irispublishersmedicaljournals - Tumblr blog

[irispublishersmedicaljournals]

Iris Publishers - Happy Easter

[irispublishersmedicaljournals]

Iris Publishers - Happy Easter

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

Turning Back the Clock: The Effect of the COVID-19 Response in Sub-Saharan Africa and Other Low- Income Countries

Authored by Sanghvi Reema

Introduction

The COVID-19 pandemic has affected everyone across the world, either through the disease itself or with our response to the disease as healthcare professionals, for the better part of a year. In the matter of a few months, it managed to spread from its little corner of the world to a true pandemic. In response to this global pandemic many affluent nations have instituted lockdown procedures to protect their population, a practice that has been adopted by many low to low- middle income countries (LMICs) as well.

Unfortunately, this pandemic does not take place in a vacuum, and individuals can have more than one condition with resultant needs outside their homes. This becomes readily apparent when considering someone receiving medical treatment for a disease such as HIV or TB, who may struggle keeping their treatment appointments. It also can restrict patients who rely on public transportation to reach hospitals or clinics, for example, pregnant women attempting to see their obstetrician or when going into labor. A lockdown of this magnitude and duration, while bothersome in wealthy countries, can be catastrophic in LMICs. In addition to access to medical care, this lockdown can also have an effect on a family’s financial stability. Many work in the informal economy even a day without work could lead to an inability to place food on the table [1].

Many individuals in these countries live in overcrowded spaces, leading to local outbreaks within a community. Enforcement of the lockdown has also seen an increase in violence towards those violating the order. In this review we will examine the literature, with a few firsthand accounts as well, of how the pandemic is currently being handled. We will examine the multitude of effects these policies are having on the local populace, particularly in Sub-Saharan Africa, the socioeconomic impact it is having, and hopefully elicit agreed upon recommendations for how national health agencies could create an individualized approach to their own COVID-19 response. We will also highlight areas that would benefit from additional research in the coming months to years.

Background

As of August 2020, there had been over 19 million confirmed cases of COVID-19 and 716 thousand deaths worldwide. By the end of 2020 this jumped to 81.9 million cases and 1.8 million deaths [2]. Through 2020 a little less than half of these cases occurred in the Americas, the United States leading with 19.6 million cases and 341 thousand deaths [3]. By contrast, all of Africa has 1.9 million cases with 42 thousand deaths. This all translates to 86.6 deaths per 100,000 in the Americas and only 4.2 per 100,000 in Africa. It is also important to point out that, for example, in the country of Malawi the average age is 17 with only 6.6% of the population over the age of 60 [4]. In comparison, in the United States the median age is 38.5 with 16.9% greater than the age of 65, in the United Kingdom the median age is 40.6 with 18.5% greater than the age of 65, and in Japan the median age is 48.6 with 29.2% over the age of 65 [5]. This should be an important consideration seeing that advanced age is a significant risk factor for morbidity and mortality due to this disease. The response to this pandemic is constantly changing based on recommendations from the various international health organizations. As areas are hit harder by the disease, restrictions there may increase and vice versa. Nations have adopted their own policies in how to combat this pandemic from quarantining the sick to full on lockdown. It has been speculated and even shown that minimizing interactions within a population, along with better hygiene practices, can slow the spread of disease, the so-called flattening of the curve. This is of course a good thing for health care systems, and the more well-developed nations have benefited from this practice. The problem lies when considering how this could affect the developing world [6].

Many LMICs have also adopted these lockdown policies while their health care systems are significantly lacking compared to wealthier countries. There is evidence that non-COVID-19 deaths (such as cancer deaths, measles, women dying in labor) are increasing due to disruption in health services [6]. It has been postulated that lives lost to lockdown could potentially exceed those saved from COVID-19. In Africa patients rely on their national health services or non- government organizations (NGOs) for HIV and TB treatment programs which can face interruptions in access to treatment. Other potentially fatal unintended consequences of lockdown include hunger, food insecurity, and violence [4].

Some sources question the feasibility of the high-income country model in LMICs, stating that this blueprint could negatively affect the economy and food systems, access to education and routine clinical services, the burden of vaccine-preventable diseases, and could even be counterproductive with regards to COVID-19 spread due to lockdowns causing out-migration from cities [7]. In India, many informal workers live in outlying villages while working in large city centers [8]. When the lockdown was put into effect, public transportation shut down almost overnight and these individuals, deprived of their livelihood, were left with no other options but to walk for days, sometimes covering hundreds of miles, risking death just to escape the city and return home to their families.

COVID-19 Compared to other Pandemics

While not the focus of this review, it is still important to look back briefly at some other pandemics we have encountered. COVID-19 is unfortunately just the latest pandemic faced by humanity, with notable predecessors such as the H1N1 swine flu of 2009-2010, the related coronavirus SARS pandemic of 2002, the 1918 Spanish flu, and of course The Black Death of the 14th century [9]. The swine flu, while viral like SARS-CoV-2, has an interesting difference in that some of the older population had some immunity, likely due to infection from a similar strain decades before. This made 62-85% of swine flu fatalities in patients less than 65 [10]. COVID-19 is also more highly transmittable with a Ro of 1.6-2.6 [11] while the swine flu was 1.4- 1.6 [10]. The 2002 SARS pandemic was also caused by a coronavirus, SARS-CoV, also originating in China. These have a similar transmission and patient presentation with most fatalities in the elderly over 65, however COVID-19 does appear more infectious with more fatalities to date.

SARS was eventually eradicated through surveillance, isolation, and quarantine [12]. It is apparent with these few examples that these various pandemics share a lot of similarities and some notable differences. For example, The Black Death was caused by a bacterium while the others on this list are caused by viruses. However, one similarity shared between all these pandemics is the disproportional impact they have on vulnerable populations such as the old, the sick, and the poor. A lesson learned from these prior pandemics is the effectiveness of surveillance and quarantine. However, as the rest of this review will illustrate, it is important not to just quarantine an entire community. We must first consider the full effect it will have on the populace and ensure steps have been taken to address the aptly named lockdown effect.

Coexisting Conditions Requiring Regular Treatment

As mentioned earlier, COVID-19 does not exist in a vacuum. Individuals can and do have more than one condition affecting their overall health. In sub-Saharan Africa tuberculosis, malaria, and HIV/ AIDS had been a large focus of NGOs and national healthcare systems, and prior to the emergence of SARS-CoV-2 they had been working diligently to combat these diseases. They were accomplishing this by working to lower active and new infections now and in the coming years. These plans are now directly being jeopardized by the emergence of this new pandemic. Various reports are showing disruption of healthcare services, diversion of the workforce, and travel/supply chain disruption, all due to the COVID-19 response and various lockdowns [13]. The WHO notes that during the recent Ebola outbreak in west Africa there was an increase in other disease morbidity and mortality with the sudden increase in demand for health services [14]. The importance of ensuring continued access to care for these diseases, especially during the currently year-long COVID-19 pandemic, cannot be understated. It is also pertinent to note that while TB, malaria, and HIV/AIDS are well known in this region, other infection prevention campaigns are also affected. For example, according to a special report in Nature [15], measles rates have been declining for the past 40 years but due to concerns for COVID-19 over 20 countries have suspended vaccination campaigns and measles rates are projected to rise. This is especially concerning in a country like the Democratic Republic of the Congo as it has the greatest single nation outbreak of measles in decades, with an estimated 6,500 child deaths from 2019-20, and as of March 2020 projections are continuing to rise [15]. One highimpact scenario predicts 84 immunization preventable deaths in children in Africa for everyone excess COVID- 19 death attributed to infection acquired during routine vaccine clinic visits, which are shut down in the interest of quarantining [16]. However, in this review we will focus on tuberculosis, malaria, and HIV/AIDS as examples of the effect COVID-19 is having on combating other diseases.

Tuberculosis

Tuberculosis (TB) is a well-known bacterial infection seen worldwide with well documented treatment and prevention strategies. While seen across the world, around 20 countries, especially in Africa, south Asia, and south-east Asia, are collectively known as high-burden countries that make up 54% of the global TB burden [17]. The Stop TB Partnership performed a rapid assessment and modeling analysis of the impact COVID-19 and the associated lockdown are expected to have on TB in the coming months to years. Looking across 16 high-burden countries they noted at least 40% of TB facilities being utilized for COVID-19 responses [17]. In India they have noticed a decrease by 80% of daily TB notifications during the lockdown contributed to people avoiding or being unable to reach medical care, laboratory delays, and stoppage of case finding actives [17]. They note not only lack of access to testing but also lack of medicines with no time for hospitals to prepare in advance for curfews and lack of patient transportation [17]. The modeling report was focused on three countries in particular; India, Kenya, and Ukraine; with their results extrapolated to a global level. When looking at the estimated impact over the next 5 years the study showed upwards of 10.7% increase in cases and a 16% increase of deaths between 2020-2025 when considering a 3-month lockdown with 10-month recovery of services [18]. They also estimated for every month of lockdown they expect over 600,000 more cases and over 125,000 more deaths; with every month of recovery, they expect over 400,000 more cases and over 80,000 more deaths [18]. In summary they have determined a setback of 5-8 years in the fight against TB due to the increase in incidence and deaths due to the COVID-19 pandemic [18]. This illustrates the importance of ensuring continued access to care for patients with TB living and receiving treatment within locked down communities. TB requires months of antibiotic treatments, access and transportation to regular medical care, and timely recognition of new cases; all things directly impacted by a lockdown. While no one expected nor was prepared for such a lockdown steps need to be taken to ensure continued access to TB treatment throughout this pandemic.

Malaria

The case incidence rate of malaria has decreased by 30% from 2000 to 2018 while the case mortality has decreased by 60% over the same period, the majority of which has occurred in sub- Saharan Africa, the area of the world that accounts for 90% of global malaria cases [14]. The WHO had previously developed a modeling framework detailing the normalized malaria incidence per person year from 2016 to 2030, a model they used as the basis of their COVID-19 model. Prior to developing their model, they determined the primary disruptions in intervention secondary to the COVID-19 response to be distribution of insecticide treated nets, indoor residual spraying, seasonal malaria chemoprevention, and access to malaria diagnosis and treatment. They then looked at 9 different possible scenarios with differences in reduction of net campaigns, distribution, and available effective treatment. Examples of some of these scenarios include scenario 1 in which they assumed no net campaigns and continuous net distribution decreased by 25%. In scenario 4, only effective antimalarial treatment was assumed to be reduced by 25%. Finally, in scenario 9 they assumed no net campaigns and a 75% reduction in net distribution and effective treatment. The remaining six scenarios fell along a spectrum similar to these three. While considering possible effect, in scenario 9 they concluded that every country in sub-Saharan Africa would see at least 20% increase in malaria deaths in 2020 compared to 2018, with the highest being greater than 200% increase in malaria deaths specifically in Guinea Bissau and Uganda [14]. In addition, the WHO published recommendations for malaria intervention in the setting of COVID-19 with guidance for vector control, case management, chemoprevention, and other extraordinary interventions [19]. Malaria is a prime example of a disease that has seen great reductions in recent years and, prior to the emergence of COVID-19, continued improvement was expected. The WHO model looks at nine different scenarios that could play out in the coming months, all of which illustrate an increase in both malaria cases and mortality in the setting of COVID-19. Much like the other diseases analyzed in this paper, the importance of continued access to malaria care by healthcare systems needs to be maintained. Fortunately, in the case of malaria, the WHO has published comprehensive recommendations that can help guide healthcare systems in developing their COVID-19 response with regards to malaria, which can be found on the WHO website at https://www. who.int/publications/m/item/tailoring-malaria-interventions-inthe- covid-19-response.

HIV/AIDS

COVID-19 may be our current pandemic, but the HIV/AIDS pandemic was here long before COVID-19 and will continue to plague society after it is gone. There is not a corner of the world that has not experienced HIV/AIDS to some degree. It is the most wellknown pandemic prior to the one we currently find ourselves in, and it is also probably the best studied. Researchers have spent decades studying and developing therapies against HIV/AIDS while various national and international organizations have spent time and money combating this disease. As of 2018, there were 37.9 million people living with HIV, according to UNAIDS two-thirds of those live in sub- Saharan Africa [20]. The WHO and UNAIDS used 5 existing HIV models to determine the potential effect that disruptions of access to care due to the COVID-19 pandemic will have on prevention and treatment. The various models examined how disruptions in specific HIV related services would affect incidence and mortality over both and 1- and 5-year period. Some of the services they considered were condom availability, suspension of HIV testing, no new anti- retroviral therapy (ART) initiation, stoppage of viral load testing and adherence counseling services, ART interruption, and others [20]. Across the models they found a 1.87 – 2.80-fold increase in HIV related deaths after only a six-month interruption of antiretroviral drug supply [20]. For example, in Kenya there were an estimated 25,000 HIV-related deaths in 2018. The five models examined saw an increase of 32,000 – 58,000 excess HIV-related deaths over 1 year as compared to 2018 data [20], with similar trends in all other African nations. The total sub- Saharan Africa excess HIV deaths over 1 year after a 6-month interruption ranged from 471,000-673,000 based on the model examined [20]. During the current COVID-19 pandemic it is important to prioritize where the time and resources should go concerning HIV/AIDS. Based on the results in this study it appears that the most important service to ensure reduced interruptions is ART. Maintaining as many HIV/ AIDS related services as possible, such as prevention and testing, are also important yet ART interruption would have the largest effect. Therefore, it is important for healthcare systems and NGOs in sub-Saharan Africa to ensure continued access to anti-retroviral medications during this COVID-19 pandemic.

Effects on Pregnancy and Women’s Health

There is no question that while we all have the potential for exposure to SARS-CoV-2 there are certain populations that we consider at greater risk for infection and disease course. As previously mentioned, the poor, the sick, and the old all fall into that category. However, there is increasing evidence that some women should be considered at greater risk as well. While pregnancy is the most obvious contributor to this claim, things such as employment opportunities, domestic violence, and access to sexual and reproductive health (including pregnancy, family planning, and availability of contraception) all play a role. One report looking at 118 LMICs estimate a worse-case scenario of 1,157,000 additional child deaths and 56,700 additional maternal deaths over the first six months due to disruptions in access to routine healthcare and food security [21]. Per the UN policy brief it is known that women are 25% more likely to live in poverty globally compared to men [22] and are also 1/3rd more likely than men to work in a sector now closed due to lockdown. This includes non-food retail, restaurants and hotels, childcare, arts and leisure, and personal care [23]. There is also the concern of domestic violence. The UN believes that the number of women and girls subjected to sexual and/or physical violence is expected to increase in the setting of the lockdown. At the time of publishing in April 2020 there was a documented increase of domestic violence in France of 30% and Argentina of 25% since lockdown a month prior [22]. The Center for Global Development documented nine pathways based on published literature linking pandemics to increased violence against women and children including quarantines and social isolation, reduced health service availability and access to first responders, and inability of women to temporarily escape abusive partners to name a few [23].

With regards to a woman’s sexual and reproductive health it is believed that COVID-19 will cause disruptions in access to care and availability of family planning and contraceptive services. Per UN News, in 114 LMICs there are approximately 450 million women using various forms of contraception, anticipating that six months of lockdown would lead to 47 million without access to contraception and 7 million unintended pregnancies [25]. There is evidence of this during the outbreak of the HIV pandemic, where women’s access to reproductive health care and family planning services was limited [26]. Pregnancy also places women and their fetuses at high-risk. It is well established that physiological changes during pregnancy increases risk of infection, in general, and dominance of the T helper cell type 2 system during pregnancy decreases a woman’s defense against viral infections such as SARS-CoV-2, as viral defense is primarily T helper cell type 1 dominant [27]. While complications during pregnancy seem to be less serious when compared to SARS and MERS there is still a 2% risk of miscarriage, 10% risk of intrauterine growth restriction, and 39% increase of preterm birth seen with COVID-19, however, a mild fever is the most common symptom [27]. With regards to vertical transmission there is limited data. In a study looking at close to 50 neonates born to COVID-19 positive mothers, two tested positive while the others did not [27]. Most of these mothers became infected during the third trimester. While data is limited, one case report of a severe case of COVID-19 in a 41-year-old G3P2 at 33 weeks gestation is worth mentioning. The mother presented with 4 days of mild symptoms that then progressed to respiratory failure requiring mechanical ventilation on day 5. She was nasal swab positive for SARS-CoV-2 and negative on serology.

The mother then underwent Cesarean delivery with no delayed cord clamping or skin-to-skin. The neonate was intubated and at 16 hours had a positive nasal swab for SARS-CoV-2, required mechanical ventilation for 12 hours, and then had mild symptoms requiring supplemental oxygen on day six of life [28]. Data is limited with regards to vertical transmission, so it is not entirely clear whether it is occurring or not. However, the vulnerability of both mother and fetus/neonate place both individuals in a highrisk group requiring increased precautions. Protecting women’s access to healthcare services and certain other protections must be prioritized, without lapses, during this and future pandemics. Maintaining reporting pathways and protections to those facing abuse is imperative, along with financial protections to those facing poverty due to the lockdown. While not specific just to women’s health, many countries’ lockdowns affect and even shutdown public transportation, making it difficult if not impossible to get to a healthcare institution, even if the clinic is open. While data is limited, there are firsthand accounts and news reports out of countries like Uganda of women in labor dying while attempting to reach hospitals by foot due to lack of ambulances and public transport [7].

Pregnant women face the increased risk of infection, not just for themselves, but for their fetuses as well. Steps must be taken by healthcare teams to protect the mother from infection and should she become infected further precautions to protect the healthcare team and neonate are necessary. Personal protective equipment (PPE) for both the mother and team, particularly during delivery, are vital. Women with active infection requiring supplemental oxygen should wear a surgical mask over the nasal canula and care should be taken to prevent cross-contamination via the gas delivery system [27]. N95 use can also be used to lower risk of infection, particularly in pregnant healthcare workers; however, teams should consider the reduced tidal volume and minute ventilation secondary to N95 use, particularly during the second and third trimester [27], and alternative protections should be considered. Finally, beyond protecting patients and healthcare teams, plans need to be established ahead of time to ensure access and transportation for these services. PPE and pregnancy precautions are of course best left to the obstetric team and the patient and are not the focus of this review. However, they do serve to illustrate the importance of preparation, having the infrastructure and equipment in place ahead of time, and ensuring accessibility to obstetric services for women, especially during a pandemic such as this.

Vaccination Campaign

It is currently difficult to assess the worldwide vaccination campaign, as this has only just begun in December 2020 with the first wave of vaccines stretching into January 2021. The Pfizer and Moderna vaccines are two of the more commonly administered in western countries such as the United States. However, even now, it is apparent that there will be a delay in access to this life saving, and potentially pandemic ending, therapy in LMICs. In fact, it is predicted that at least 90% of people in 67 low-income countries have little chance of vaccination in 2021, the source citing vaccine hoarding by wealthier nations [29]. Storage and shelf life make it difficult for healthcare systems to transport, store, and administer these vaccines as well, putting an additional burden and obstacle to be overcome by less robust healthcare systems. For example, the Pfizer vaccine requires storage between -80 to -60˚C, while the Moderna vaccine can be stored a little warmer at -25 to -15˚C [30]. Even when there is availability and storage arrangements have been made, cost can play a large role in accessibility. For example, in South Africa, Pfizer offered a discounted rate per dose to make purchasing the vaccine more affordable. Unfortunately, even at a discounted rate, the cost was still prohibitive [31]. There is also the concern for new viral variants emerging, such as the UK variant and South African variant. The South African variant is notable for its large number of mutations and has been noted to be more contagious than prior strains [32]. While concerning, it is important to note per a Moderna press release, that while they are noting a 6-fold reduction in neutralizing titers, levels remain above those thought to be protective [33]. While promising, South Africa itself has received supplies of the Johnson & Johnson, Pfizer, and AstraZeneca vaccines as of February 2021. While initially thought to cover this new variant, campaign roll out has been put on hold due to disappointing results covering the South African variant [34].

While there is much working against access to vaccinations in LMICs, there is some good news as well. With regards to cost, AstraZeneca has promised to deliver vaccines, not for profit, throughout the pandemic. Their vaccine is also stated to be stable between 2-8˚C, making it more easily stored and distributed [31]. There is also concern for hesitancy with regards to vaccines. For example, in Western Europe, a 2018 survey showed only 59% of participants believing vaccines to be safe [35]. This is in stark contrast to LMICs, where 95% of participants in South Asia and 92% of participants in East Africa believe vaccines to be safe [35]. Fortunately, the WHO, The Coalition for Epidemic Preparedness Innovations (CEPI), and The Global Alliance for Vaccines and Immunizations (GAVI) have seen the need for vaccination worldwide and have taken steps to ensure access to the COVID-19 vaccine to the global poor, developing a program called COVAX. In the setting of this pandemic, COVAX aims for equitable access to all countries of the world, with plans to offer doses to at least 20% of the population, diverse and actively manage vaccine portfolios, ensure timely vaccine delivery, strive for the end of the acute phase of the pandemic, and to help rebuild economies [36]. While some of this is promising news for LMICs, it is important to remember that they continue to face struggles in availability and will likely not start seeing significant relief until 2022. Of note, even though most individuals in East Africa and South Asia believe vaccines to be safe, with access to programs like COVAX, they remain at significant risk when their leaders believe otherwise. In Tanzania, President Magufuli and other government officials have spoken out about the safety of these vaccines, going so far as to claim Tanzania to be a “COVID-19-free country” [37]. Going beyond simply questioning vaccine safety, Tanzania, Burundi, Eritrea, and Madagascar, are African nations that have all chosen to opt out of COVAX support at this time.

Conclusion

This is just a small example of considerations that need to be made by healthcare systems in the setting of a pandemic. Unfortunately, COVID-19 is not the first and will not be the last pandemic we have faced. The hope is that with each new disease/ outbreak we learn more and our response and capabilities continue to improve as we strive to ensure access to care for all. Services such as preventative vaccinations and disease-specific treatments must be maintained without lapses in care. In sub-Saharan Africa programs and services combating HIV/AIDS, malaria, and TB must be supported and not overlooked by local and international healthcare services. We must also ensure access to women’s health services and obstetric care. Beyond simply ensuring continuity of care for these patients, we must also examine the socioeconomic effect our pandemic response places on a country. Continuing healthcare services does not help anyone if public transportation shuts down or is severely limited. Quarantine and lockdown may ensure social distancing but at what cost to a mother and child in an abusive household? In countries like the United States with a robust healthcare system these issues are less of a concern, but in many LMICs with limited resources, they are often forced to choose where to allocate resources between pandemic response and continued access to necessary services. In addition to resource allocation to combat the pandemic directly, considerations need to be made to ensure equitable access to vaccination for all people of the world with special attention paid to LMICs and the global poor. In fact, concerning the global poor, poverty levels have now begun to rise for the first time since 1998 [38]. Estimates of where we will end up vary, with initial estimates placing the global poverty level back around 2017 levels. However, more recent numbers are far worse, stating a reversal of greater than 10 years improvements on global poverty.

To read more about this article: https://irispublishers.com/ctcms/fulltext/turning-back-the-clock-the-effect-of-the-covid-19-response-in-sub-saharan-africa.ID.000543.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

Active Filtering and Exchange of Indoor Air by Means of Mobile Air Conditioners to Avoid Infection by The SARS Cov-2 Virus

Authored by Sebastian König

Introduction

In not actively ventilated rooms such as in schools, air exchange is insufficient, particularly during win- ter. Under the presence of COVID-19 or to reduce the CO2 concentration, the air must be filtered and refreshed as well as possible. A tracer clearance experiment using a mobile air conditioner e.g. from KRONE Kälte + Klima VertriebsmbH Germany is supposed to determine to what extent. In Szabadi [1]. the air exchange rate [n] = 1/h is introduced as a measure of air exchange. The exhaust volume flow [dV/dt] ⩒ = m3/h is related to room volume [V] = m3. The air exchange rate n is a multiple of the room volume. Reference values are n = 3/h <= n <= 6/h. The air conditioner in (Figure 1) comprises an air recirculation (5) and an active air exchange (6). The recirculation may also filter and cool the air. Here, the air filter rate [f] = 1/h serves as a measure. Both measures must be considered according to [1].

Setup

A mobile air conditioner (1) in (Figure 2) actively recirculates (2) and refreshes (3) the air of the room. A ventilator (4) supports recirculation. The recirculation of air (5) in (Figure 1) also cools an dehumidifies and filters the air. The second air exchange (6) suck in the room air and blows it out of the window. The air conditioner

GREE GPC-12-AL-R290 [2] comes with a recirculation volume flow of ⩒ = 360 m3/h and is optimized for rooms up to floor area of 22m2an air exchange rate of n ≈ 16/h. The conducted measurements show effectiveness also in bigger rooms. Disco fog (EUROLITE smoke fluid -X EXTREM A2) served as a tracer replacing the aerosol. The relative fog density is measured indirectly via relative light transmission T = 0T=0%...100% alternativly 0%<=T<=100% with measuring instrument TRDA 2.0 [3]. In a seminar room of V = 220 m³ Figure 3, an active operating mode without refrigeration and without dehumidification is used (Figure 1& 2).

Result

Figure 4 shows the plot of the tracer clearance process by relative light transmission as a function of 83 minutes the fog is removed completely whence n = 360 m3/h /220 m3 = 1, 6/h. After t < 10 s without fog (which is T˳ = 100%) the room is filled with fog. The light transmission goes down Figure 4 shows the plot of the tracer clearance process by relative light transmission as a function of two T < 10%. At the same time the air filter rate f = 2/h has effect. As example for lecture rooms, n ≥ 8/h is required. This is accomplished by stationary air conditioners. the step response of a simple mathematical model with just one-time constant τ and a normalized light transmission T˳= 100% is plotted in red in Figure

To read more about this article: https://irispublishers.com/ctcms/fulltext/active-filtering-and-exchange-of-indoor-air-by-means-of-mobile-air-conditioners.ID.000542.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

A Long Non-coding RNA and its Potential Role in Human Myeloid Leukemia

Authored by David Reisman

Introduction

Over the past decade, long non-coding RNAs (lncRNAs) have been discovered to function as regulators of gene expression and numerous biological processes. They are transcribed from loci throughout the genomes of most eukaryotes [1-7]. and reports indicate that many lncRNAs are involved in the regulation of pluripotency and differentiation [8-14]. Although the mechanisms by which these lncRNAs function are still being explored, one model that has emerged states that nuclear lncRNAs modulate gene expression through interactions with histone modifying proteins and/or transcription factors [6-7, 12, 15-18].

Other lncRNAs function in the cytoplasm [19-21]. Lnc-MD1, for example, is a muscle-specific lncRNA that regulates muscle differentiation by binding to microRNAs (miRNA) and limiting their availability to regulate gene expression [9]. Another lncRNA, TINCR, is induced during epidermal differentiation and interacts with a number of differentiation-specific mRNAs to regulate their stability [10]. These, and other results, demonstrate that lncRNAs can act to regulate genes required for cell differentiation through multiple mechanisms [13, 21- 23]. Furthermore, enhanced expression of some lncRNAs have been shown to contribute to certain cancers as well. SAMMSON for example, is a lncRNA expressed at elevated levels in melanomas and its inhibition resulted in decreased viability of human melanoma-derived cells [24]. Likewise, numerous lncRNAs, including the one we describe here have been implicated in contributing to acute myeloid leukemia [25-28].

Identification of a lncRNA transcribed from exon 1 of the p53 gene

A few years ago, as described below, we identified a lncRNA, designated as lncRNAp53Int1, that exhibits enhanced expression in myeloid leukemias, that functions to maintain the proliferative state of leukemic cells [25]. To date, our findings indicate that lncRNAp53Int1 functions in the cytoplasm, and through interactions with as yet unidentified RNA molecules or proteins, contributes to oncogenic transformation by suppressing the differentiation of myeloid progenitor cells. Inhibiting its activity or the activity of its targets is predicted to lead to differentiation and cessation of proliferation.

lncRNAp53int1 is linked to the differentiation of human myeloid leukemia cells

A number of years ago, we identified a transcription unit located in the 1st intron of the human p53 tumor suppressor gene that encoded a RNA transcript that had no identifiable open reading frame for protein synthesis [28]. This transcript was later classified as a lncRNA [19, 30-31] and is listed as GC17M015273 in the GeneCard Human Gene Database (http://www.genecards.org) and NONHSAG020729 in NONCODE v4 (http://www.noncode. org). The lncRNAp53Int1 transcript is approximately 1125 nucleotides in length, is polyadenylated, and contains no introns. While there appears to be no functional or regulatory relationship to p53 itself, the abundance of this lncRNA is significantly reduced during differentiation of human myeloid leukemia cells [25]. We hypothesize that lncRNAp53Int1 plays a crucial role in maintenance of the undifferentiated proliferative state in myeloid leukemia. That lncRNAp53Int1 is expressed in immature cell types is supported by lncRNA expression data collated in various publicly available databases. Although expressed in a variety of human tissues, tissues found to express the highest levels of lncRNAp53Int1 include those that contain proliferative and immature cell types such as lymph node, foreskin fibroblasts and umbilical endothelial cells.

Potential Therapeutics

 Myeloid leukemias are characterized by genetic alterations that lead to a complete or partial block at various stages of myeloid differentiation and subsequent proliferation of myeloid progenitor cells [32-36]. That lncRNAp53Int1 appears to block differentiation of human myeloid leukemia cells is noteworthy because the ability to induce differentiation of acute myeloid leukemias is used as one therapeutic strategy [34, 37-40]. The discovery of a regulatory role for lncRNAp53Int1 in leukemia cell differentiation and the ultimate identification of its cellular targets could provide researchers with new pathways to target in the development of novel therapeutics for acute myeloid leukemias [41-42]. Silencing this lncRNA or one or more of its interacting molecules could potentially lead to an effective way to inhibit proliferation through the induction of terminal differentiation

To read more about this article: https://irispublishers.com/ctcms/fulltext/a-long-non-coding-rna-and-its-potential-role-in-human-myeloid-leukemia.ID.000541.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

Plasma Biochemical Parameters of The Blood of Captive Adult Male and Female Black-Necked Pheasants (Phasianus colchicus), Gray Partridge (Perdix perdix) and Chukar Partridge (Alectoris chukar) in Bulgaria

Authored by Slavko Naskov Nikolov

Introduction

The Black-necked pheasants or Southern Caucasus pheasants (Phasianus col. colchicus), Gray partridge (Perdix perdix) and Chukar partridge (Alectoris chukar) are birds from the order Galliformes, family Phasianidae and native to Europe and Asia. They have been widely introduced as game birds and are one of the world’s most hunted birds [1-2]. Over the last few years, industrial pheasant farms have been developed as a new agricultural activity for commercial production of meat in Europe, and the number of the pheasant population reared each year has increased exponentially [3-4]. Although it is well known that plasma biochemistry is important for medical diagnosis of disease in several bird species, limited information is available for pheasants, partridges [5-6] and chukars [7]. There are studies have reported the values of biochemical parameters in pheasants [8-9], and the knowledge of plasma chemistry parameters in pheasants, partridges and chukars still remains incomplete [10]. Therefore, accurate and useful biochemical analyses are needed. In general, blood examination is performed for several reasons as a screening procedure to assess general health [11]. Because the clinical signs of illness in birds are frequently subtle, clinical chemistry is necessary to evaluate cellular damage [12].

Materials and methods

Game birds were allocated in breeding aviaries. The birds were fed a proprietary pellet formulated for pheasants (HL-TopMix OOD Company, Bulgaria) ad libitum and had access to fresh water at all times. The adult animals were 52-54-week-old оn the reproduction season: Black-necked pheasants allocated in families with one male and seven females; Gray partridges in pair; Chukars in families with one male and four females. All the birds were vaccinated against Newcastle disease virus 4 months before blood sampling and were free from any endoparasites or ectoparasites. Blood samples were collected from the ulnar wing vein (vena cutanea ulnaris superficialis) from 36 adult birds: pheasants (6 male and 6 female), Gray partridges (6 male and 6 female) and Chukars (6 male and 6 female). The birds were selected randomly from breeding aviaries. Approximately 0.5-1.0 ml of whole blood was obtained from each bird and immediately placed into blood collection tubes that contained heparin. Samples were processed within 1-3 hours after collection. The plasma biochemical parameters: Total protein, Albumin, Glucose and Total bilirubin were measured using a standard automatic biochemical analyzer (BS-120, Mindray, China). We were got Permission to use animals in experiments №280 aviary-bred wild birds issued by Bulgarian food safety agency. The data were processed with IBM SPSS Statistics (SPSS-Inc., 2019, SPSS Reference Guide 26 SPSS, Chicago, USA) using descriptive statistics with frequency distribution tables. Males and females were analyzed separately as sex may affect the parameters studied. All values were expressed as mean ± standard error, and P≤0.05 was determined as statistically significant.

Results

The mean values of selected plasma biochemical parameters for adult male and female Black-necked pheasants were determined (Table 1). The overall biochemical blood values including Total protein, Albumin, Glucose, and Total bilirubin values were 47.89±1.87, 22.47±0.71, 23.97±1.43 and 4.55±0.25, respectively. All these parameters between adult male and female Black-necked pheasants were no significant (p>0.05).

The mean values of selected plasma biochemical parameters for adult male and female Gray partridges were determined (Table 2). Significant differences in plasma Glucose and Total bilirubin were found among both males and females’ values were 20.04±0.78 and 10.99±1.52, respectively. The other blood parameters Total protein, Albumin showed no significant differences between the male and female adult Gray partridges’ values were 53.72±1.55 and 21.66±0.78, respectively.

Discussion

The mean values of selected plasma biochemical parameters Total protein, Albumin, Glucose, and Total bilirubin for adult male and female Black-necked pheasants were compared/similar to Common pheasants [9-10] and Ring-necked pheasants [12-13]: The results for Total protein (g/l) 49.20±6.800 in Common pheasants [10], significantly approach our values 47.89±1.87 in Black-necked pheasants. The Total protein was found in males 37.50±2.0 and in females 43.00±6.2 [12], similar to males 46.3±0.5 females 36.9±0.7 [13] with Ring-necked pheasants were of lower values, from our results for male 46.47±2.71 and female 49.32±2.68 Black-necked pheasants. Most likely this was due to the fact that our pheasants were studied during the breeding season, unlike other authors. The data in laying Common pheasant hens for the values of Total protein 38.6±1.39 and 41.5±1.55 [9] were close to our Black-necked pheasant hens.

Albumin levels (g/l) in male 28.1±0.4 and female 22.6±0.5 Ring-necked pheasants [13] were elevated in male pheasants compared to our data in male 23.42±1.15 Black-necked pheasants. However, in laying Common pheasant hens were 20.4±0.79 at the initial period and 22.8±1.07 at the end of laying (Hrabcakova et al. 2014), were relatively close to the values obtained by us for females 21.51±0.72 Black-necked pheasants.

Glucose (mmol/l) data were similar 20.08±1.87 in Common pheasants [10] to our results 22.47±0.71 in Black-necked pheasants. The results of Glucose in males 12.9±2.17 and females 12.6±1.96 [12]; and male 12.043±58 and female 11.15±61 [13] Ring-necked pheasants were twice lower than our results obtained male 21.03±1.53 and female 26.91±1.77 Black-necked pheasants, which may be due to the fact that the birds were out of the reproductive season. [9] established Glucose levels in Common pheasant hens in the initial laying period of 20.4±0.26 and at its end 20.8±0.33, which was close to our data of 26.91±1.77 in Blacknecked pheasant hens. Nazifi et al. 2011 found higher values of Total bilirubin (μmol/l) in males 8.03±1.02 and significantly higher values in females 15.73±0.34 mature Ring-necked pheasants, in contrast to our data in males 5.15±0.29 and females 3.94±0.19 mature Black-necked pheasants. The difference may be due to the fact that his research received in the off-breeding season for birds.

The mean values of selected plasma biochemical parameters: Total protein and Glucose for adult male and female Gray partridges; Albumin and Total bilirubin together with Chukar partridges were compared to Gray partridges [6,10], Chukars [7] and Ring-necked pheasants [12]: Total protein (g/l) in Gray partridges 38.62±7.99 was much lower than our studies 53.72±1.55, the same trend was observed by sex male 36.52± 5.36 and female 40.76±9.59 [6], respectively our values for Total protein at male 55.82±1.79 and female 51.63±2.37 Gray partridges. While the results for Total protein 45.60±7.086 at Gray partridges [10] were closer to our values.

Albumin values (g/l) in males 23.9±0.221 and females 24.8±0.095 Chukar partridges (Farooq et al. 2019) differ slightly from our data in males 22.62±1.23 and females 20.7±0.88 Gray partridges, but are significantly close to our data male 23.23±0.77 and female 21.40±0.59 Chukar partridges, the difference was most likely determined by latitude and diet. Plasma levels of Glucose (mmol/l) 18.90±2.60 in Gray partridges [6] were quite close to the levels measured by us 20.04±0.78 in the same species, respectively male 18.78±0.61 and female 21.29±1.28 Gray partridges. They were even closer to our Glucose values of 19,260±2,000 in Gray partridges [10].

Our data on Total bilirubin values (μmol/l) at male 12.71±2.42 and female 9.28±1.77 Gray partridges were higher than those at male 7.77±0.29 and female 7.57±0.60 Chukar partridges, data compared to male 8.03 ± 1.02 and female 15.73±0.34 Ring-necked pheasants [12], showed that male pheasants had a closer value of Total bilirubin than those of Chukars, and data of female pheasants with Gray partridges.

The mean values of selected plasma biochemical parameters Total protein and Glucose for adult male and female Chukar partridges were compared to the same species of bird [7,10], Gray partridges [6,10] and Red-legged partridges [5]: The data for Total protein (g/l) 45.70±4.62 for Chukar partridges [10] were lower than our values of 60.66±3.23 for the same species. Total protein values at 80.5±0.372 male and 102.8±2.19 female Chukar partridges (Farooq et al. 2019) were significantly higher than our data at male 56.60±5.92 and female 64.72±2.08 Chukars, which may be due to the difference in latitude (between Pakistan and Bulgaria) or using a different anticoagulant (EDTA or Heparin). While the data in males 38.0±0.5 and females 51.0±0.9 Red-legged partridges (Alectoris rufa) [5] were closer to our data, in particular to female Chukars.

Plasma levels of Glucose (mmol/l) 20,040±1,702 in Chukar partridges [7] and 22.64±61.26 Red-legged partridges (Alectoris rufa) [5] were slightly higher than our 19.27±0.64 in Chukar partridges, this deviation may be due to the time of counting the blood samples, the type of anticoagulant and the preliminary consumption of food by game birds.

To read more about this article: https://irispublishers.com/ctcms/fulltext/plasma-biochemical-parameters-of-the-blood-of-captive.ID.000540.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Thanksgiving Day

Wishing You A Happy Thanksgiving Day!!!

It’s time to wish on the occasion of Thanksgiving Day for everyone on behalf of Current Trends in Clinical & Medical Sciences (CTCMS). We Wish you Happy Thanksgiving Day to you and your family!!!

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

Pharmacoeconomic Evaluation of Novel Oral Anticoagulants in Patients with Cardiovascular Diseases: A Systematic Review

Authored by Ahmed Ibrahim Nouri

Introduction

For decades, the oral anticoagulant warfarin remained the gold standard of medical management for many cardiovascular diseases and main pharmacological agents for the prophylaxis of venous thromboembolism [1]. Among these cardiovascular patients, the vitamin K antagonists are especially beneficial to patients with venous thromboembolism and for the prevention of stroke. In terms of clinical consideration, warfarin displays several limitations and disadvantages. The narrow therapeutic window and vast drugdrug and drug-food interactions properties of warfarin render it clinically difficult to use [2]. Precise dose adjustment and frequent dose monitoring are of utmost importance because inappropriate dose can lead to many adverse clinical events. Warfarin over-dose will increase the risk of serious bleeding while under-dose will not produce the therapeutic outcomes desired, for example stroke prevention [3].

Novel oral anticoagulants (NOACs) are becoming more important in clinical uses due to the limitations of warfarin mentioned above. NOACs can be divided into direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and direct thrombin inhibitors (dabigatran). In terms of bleeding risk, NOACs display a significantly lower risk of intracranial and intracerebral bleeding than warfarin [4]. NOACs display evidence that they are at least as effective as warfarin if not superior to warfarin in the clinical treatment of patients with systemic embolism and as a prophylaxis for stroke in atrial fibrillation patients [5-6].

Even though NOACs show a superior performance in clinical uses compared to warfarin, but the main drawback on prescribing NOACs to patients instead of warfarin is due to the high daily costs. The rising clinical importance of NOACs, as well as their higher cost, impose a question on the pharmacoeconomic performance of the NOACs. There are numerous studies done in many countries to evaluate the pharmacoeconomic profile of the NOACs.

The aim of this systematic review is to evaluate the pharmacoeconomic performance of four novel oral anticoagulants, rivaroxaban, apixaban, edoxaban and dabigatran usage in patients with cardiovascular diseases (deep vein thrombosis, pulmonary embolism, atrial fibrillation and stroke).

Methodology

A search was conducted in Google Scholar, Embase, Cochrane Library, Medline, CINAHL and Science Direct using search algorithms to identify relevant pharmacoeconomic publications of novel oral anticoagulants in patients with cardiovascular diseases. Processes throughout systematic review were carried out using Preferred Reporting Items for Systematic Reviews and Meta- Analysis (PRISMA) statement. The search identified publications with the keywords pharmacoeconomic, cost-effectiveness, novel oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, cardiovascular diseases, stroke, atrial fibrillation, deep vein thrombosis or pulmonary embolism. Both cost studies and economic evaluation of novel oral anticoagulants were considered.

While cost studies estimate expenses associated with a particular treatment for cardiovascular diseases, economic evaluations assess both health costs and benefits associated with a drug against its comparator(s). Economic evaluations usually include cost-effectiveness analyses, cost-utility analyses, and cost-benefit analyses depending on how health benefits [natural units, quality-adjusted-life-years (QALYs)] and monetary terms are measured. QALYs incorporated both morbidity (as the quality of life) and mortality. Cost-effectiveness analyses looks at a single quantified effectiveness measure of the cost per unit. There are many variations in cost-effectiveness analyses that can be considered; cost consequence and cost-minimization analyses, with comparing cost outcomes due to health benefits. Economic evaluation in health care consider the resources consumed by patients, productivity losses, health sector and other sectors as well. A treatment is usually considered cost-effective if the incremental cost-effectiveness ratio (ICER) is below the commonly used threshold for the given country. Various threshold are available such as $50,000 per QALY in the United States and $20,000-$100,000 per QALY in Canada.

The title and/or abstract of articles published between 2008 and 2018 pertaining to novel oral anticoagulants were searched for the keywords. “Grey” literature (ie, material that can be referenced, but is not published in peer-reviewed, indexed medical journals) was not examined and not included in this review. From the review questions, the author concluded that the question is a therapy question. Hence, the best evidence would be a randomized controlled trial, cohort study, and case-control. Abstracts were included when all of the following were true: cost-effectiveness of different novel oral anticoagulants on patients with cardiovascular diseases and published from 2008 to 2018. Articles published in English language only were accepted; those that did not meet the pre-stated criteria were excluded. Different types of novel oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban) used in patients with cardiovascular diseases were included in this review. Articles that have not mentioned novel oral anticoagulants were excluded. Patients with cardiovascular diseases (stroke, deep vein thrombosis, pulmonary embolism and atrial fibrillation); any gender; any age and any severity of cardiovascular diseases were included in this review. Populations were not restricted to one country or place. All papers around the world will be examined and reviewed.

For data extraction, data extracted from included studies using data extraction from guided by standardized extraction data tool by Cochrane Collaboration. The extracted data assured to match with the review question and fulfill the review objectives. A table was used to present details of the characteristic of included studies, such as author, country, year of study; interventions, sample and study design. Data on study design, inputs, results and authors’ conclusions were extracted

To read more about this article: https://irispublishers.com/ctcms/fulltext/pharmacoeconomic-evaluation-of-novel-oral-anticoagulants-in-patients.ID.000539.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

The Psychology of Phenomenological Structuralism

Authored by Paul Mocombe C

Introduction

This work highlights the psychology behind Paul C. Mocombe’s theory of phenomenological structuralism. The author posits a cognitive developmental psychology that is tied to the theory’s emergent logico-metaphysical materialist account regarding the formation, constitution, and perpetuation of the multiverse, consciousness, society, and the individual.

Paul C. Mocombe’s structurationist theory of phenomenological structuralism, building on and synthesizing a form of M-theory with, mathematical elements of univon multiverse hypothesis, the quantum computation of ORCH-OR theory, Black Hole Big Bang Theory (BHBBT), structurationism, and the multiverse ideas of Haitian ontology/epistemology and quantum mechanics abductively posits that spacetime is fundamental; and consciousness is an emergent fifth force of nature, a field of consciousness (the consciousness field-CF) composed of an emergent quantum material substance/energy, psychion, the phenomenal property, qualia or informational content, of which is recycled/replicated/ entangled/superimposed throughout the multiverse and becomes embodied via the microtubules of neurons of brains and aggregate matter of multiple worlds to constitute mind. Mind (composed of the personal and collective unconscious, and the sense-experience of the emerging ego held together by the brain’s electromagnetic field generated by the periodic discharge of neurons), in turn, is manifested in simultaneous, entangled, superimposed, and interconnecting material resource frameworks, multiple worlds, as praxis or practical consciousness of organic life, the content of which in-turn becomes the phenomenal properties, qualia, of material (subatomic particle energy, psychion) consciousness that is recycled/replicated/entangled/superimposed via the consciousness field throughout the multiverses upon matter disaggregation. In other words, existence precedes essence; but essence is emergent and eternal, and comes to constitute a fifth force of nature, a field of consciousness for Being production (the consciousness field), through the phenomenal properties, qualia (personal and collective unconscious), of neuronal subatomic particles, psychion, which are recycled/replicated/superimposed/ entangled throughout the multiverse and give human actors their initial (essential) practical consciousness that they organize and reproduce in replicated, entangled, and superimposed material resource frameworks. On this physics Mocombe builds his systemic philosophy, sociology, and psychology called, phenomenological structuralism. This work highlights the (cognitive) developmental psychology within Mocombe’s theory of phenomenological structuralism.

Background of the Problem

From Freud to Erickson, Vygotsky, and Kholberg developmental psychologists attempt to describe, explain, and highlight how cognition, affect, and practical activities change or develop throughout a person’s lifespan in order to optimize development and assist them in their practical situations. For the most part, the field focuses on the dialectical relationship between normative development, which highlight objective patterns of change and development; and idiographic development, which explores individual variations in patterns of development. The problem in the field to date is that developmental psychologists do a better job describing development as opposed to explaining how the changes they have observed in relation to normative processes and individual variations occur. In this work, I describe and explain how human psychological development and individuation unfolds within Paul C. Mocombe’s theory of phenomenological structuralism.

Within Mocombe’s theory of phenomenological structuralism the psychological assumptions are that human psychological development emerges from consciousness, which is an emergent fifth force of nature, a field of consciousness or consciousness field. Consciousness is an emergent fifth force of nature, a field of consciousness or the consciousness field, composed of an emergent quantum material substance/energy, psychion, the phenomenal property, qualia or informational content, of which is recycled/ replicated/entangled/superimposed throughout the multiverse and becomes embodied via the microtubules of neurons of brains and multiple worlds to constitute mind. Mind, composed of the personal and collective unconscious, and the emerging senseexperiences of the ego, qualia, held together or given uniformity and integrated as an I via the electromagnetic field of the brain is manifested in simultaneous, entangled, superimposed, and interconnecting material resource frameworks, multiple worlds, as praxis or practical consciousness of organic life, the content of which in-turn becomes the phenomenal properties, qualia, of material (subatomic particle energy, psychion) consciousness that is recycled/replicated/entangled/superimposed throughout the multiverses upon matter disaggregation. In other words, existence precedes essence; but essence is emergent and eternal, and comes to constitute a fifth force of nature, a field of consciousness for Being production, through the phenomenal properties, qualia (personal and collective unconscious sense experiences of past, present, and future existences), of neuronal subatomic particles, psychion, which are recycled/replicated/superimposed/entangled throughout the multiverse and give human actors their initial (essential and unconscious) practical consciousness that they organize and reproduce in replicated, entangled, and superimposed material resource frameworks.

The brain is a receiver of consciousness from an emergent consciousness field of the multiverse (Figure 1). This consciousness field theory, CFT, differs from [1]. conscious electromagnetic (EM) information (CEMI) field theory, which posits “that the seat of consciousness is simply the brain’s EM field” (pg. 5), in that for me, the EM field of the brain is not the seat of consciousness; instead, it (the brain’s EM field) serves more like a glue, which holds and integrates consciousness, which emerges from its on field, together. In other words, consciousness emerges out of a field composed of subatomic particles, psychions, which have phenomenal properties (qualia) and become embodied in the neurons of brains that constitute an electromagnetic field during their firing that holds the psychions together as an individuated consciousness in order to experience objective reality. McFadden’s attempt to hold on to dualism by substituting spirit in the matter/spirit argument with the EM field of the brain is tautological. That is holding on to energy and matter to give a dualist account of consciousness is not a dualist account; instead, it is an incomplete materialist account. My consciousness field theory (CFT) completes McFadden’s materialist account regarding the nature and origins of consciousness by arguing for a physics that views consciousness as an emergent fifth force of nature with its own field.

On this physics, Mocombe builds his systemic philosophy, sociology, and psychology called phenomenological structuralism by tying the emergence of the field of consciousness, the consciousness field, composed of psychions to human sociological and psychological development and experiences, which constitute the phenomenal properties (qualia) of the psychions, which form the tripartite structure (ego, personal and collective unconscious) of the emerging human mind manifested as their practical activities. Psychologically speaking, in other words, the field of consciousness or consciousness field is the basis for psychological development. The field is an emergent fifth force of nature composed of the psychion, which is the energy substance that constitutes and transmits the ego essence of an individual person to the microtubules of neurons of brains (Figure 1). The ego essence, psychion, is composed of all of the personal and collective sense experiences (personal and collective unconscious of the ego), the phenomenal properties or qualia, of the individual person, which becomes embodied in the microtubules of neurons in the brain as a result of matter aggregation across multiple simultaneous existing past/present/future worlds/universes. The structure of the mind, in the end, is composed of the ego and the personal and collective unconscious, which becomes embodied, as the qualia of psychions, via the microtubules of neurons of the aggregated brain and its EM field across replicated simultaneous past/present/future worlds of the multiverse. The EM field’s “source is the electrical dipoles within the neuronal membranes caused by the motion of ions in and out of those membranes during action potentials and synaptic potentials. The periodic discharge of neurons-firing or action potentials- generates EMF waves that propagate out of the neuron and into the surrounding inter-neuronal spaces where they overlap and combine to generate the brain’s global EM field that is routinely measured by brain scanning techniques such as electroencephalography (EEG) and magnetoencephalography (MEG)” (McFadden, 2020, pg. 5). The EM field integrates and holds together, like a glue, the ego essence, individuated consciousness of being, their psychion, which emerges out of its own (emergent) force, the consciousness field. The ego, in other words, is the (material) essence, psychion, of the individual being. It is a composite of their past/present/future experiences, which emerge as the personal and collective unconscious, i.e., qualia, of the ego. The latter two as such are the past/present/future biological and sociological sense experiences of the ego over all of its lived experiences across the multiverse. Following matter disaggregation, the psychion, either collapses unto other versions of itself still in existence in the multiverse or returns to the consciousness field. The individual, doing embodiment, only becomes aware of itself as an ego with personal and collective tastes that individuates them from other objects and persons when they encounter conflict, throughout their lifespan, in becoming and being-in-worlds constituted via five (sociological) systems, i.e., mode of production, language, ideology, ideological apparatuses, and communicative discourse.

The individual being, whose mechanical brain and electromagnetic field, is initially constituted as superimposed, entangled, recycled, and embodied subatomic particles, psychion, of multiple worlds of the multiverse, which have their own predetermined form of understanding and cognition, phenomenal properties, qualia, based on previous or simultaneous senseexperiences as aggregated matter (this is akin to what the Greek philosopher Plato refers to when he posits knowledge as recollection of the Soul; and Nietzsche’s idea of eternal recurrence). Again, the individual’s actions are not necessarily determined by the embodiment and drives (qualia or phenomenal properties) of these recycled (replicated)/entangled/superimposed subatomic particles in the neurons of the brain. It is conflict and an individual’s stance, ready-to-hand, unready-to-hand, and present-at-hand, when the subatomic particles become aggregated matter or embodied, which determines whether are not they become aware, present-at-hand, of the subatomic particle drives and choose to recursively reorganize and reproduce the content of the drives as their practical consciousness.

This desire to reproduce the (essence) cognition and understanding of the (phenomenal properties/qualia) drives of the recycled/replicated/entangled/superimposed subatomic particles, however, may be limited by the structuring structure (chemical, biological, and physiological drives) of the aggregated body and brain of the individual subject. That is to say, the second origins and basis of an individual’s actions are the structuring drives and desires, for food, clothing, shelter, social interaction, and sex, of the aggregated body and brain, which the subatomic particles constitute and embody. In other words, the aggregated body and brain is preprogrammed with its own (chemical, biological, and physiological) forms of sensibility, understanding, and cognition, structuring structure, by which it experiences being-in-a-world as aggregated embodied subatomic particles. These bodily forms of sensibility, understanding, and cognition, such as the drive and desire for food, clothing, shelter, social interaction, linguistic communication, and sex, are tied to the material embodiment and survival of the embodied individual actor, and may or may not supersede or conflict with the desire and drive of an individual to recursively (re) organize and reproduce the structuring structure of the superimposed, entangled, and recycled (phenomenal properties of) subatomic particles. If these two initial (unconscious) structuring structures are in conflict, the individual moves from the ready-to-hand to the unready-to-hand stance or analytics where they may begin to reflect upon and question their being-in-theworld prior to acting. Hence just as in the case of the structuring structure of the subatomic particles it is an individual being’s analytics vis-à-vis the drives of its body and brain in relation to the impulses/drives of the subatomic particles, which determines whether or not they become driven by the desire to solely fulfill the material needs of their body and brain at the expense of the drives/ desires of the subatomic particles or the social class language game of the material resource framework they find their existence unfolding in.

The social class language game, and its differentiating effects, an individual find their existence unfolding in is the third structuring structure, which attempts to determine the actions of individual beings as they experience being-in-a-world as embodied subatomic particles. The aggregated individual finds themselves objectified and unfolding (Being) within a material resource framework controlled by the actions of other bodies, which presuppose their existence, via the actions of their bodies (practical consciousness), language, communicative discourse, ideology, and ideological apparatuses stemming from how they satisfy the desires of their bodies and subatomic particle drives (means and mode of production). What is aggregated and reified as a social class language game by those in power positions via and within its mode of production, language, ideology, ideological apparatuses, and communicative discourse attempts to interpellate and subjectify other beings to its interpretive frame of satisfying their bodily needs, fulfilling the impulses of their subatomic particles, and organizing a material resource framework at the expense of all others, and becomes a third form of structuring individual action based on the mode of production and how it differentiates individual actors.

That is to say, an individual’s interpellation, subjectification, and differentiation within the social class language game that presupposes their being-in-a-world attempts to determine their actions or practical consciousness via the reified language, ideology, etc., of the social class language game, the meaning of which can be deferred via the communicative discourse of the individual actors allowing them to form social groups or heterogeneous communities tied to the dominant social order because of their control of the materials of the material resource framework. Hence, the deferment of meaning in ego-centered communicative discourse of the language and ideology of a social class language game is the final means of determining an individual’s action or practical consciousness outside of, and in relation to, its stance, i.e., analytics, vis-à-vis the drives of subatomic particles, drives and desires (anatomy and physiology) of the body and brain, and structural reproduction and differentiation.

The interaction of all four elements or structuring processes in relation to the (mental) stance of the transcendental ego of the individual actor is the basis for human action, praxis/practical consciousness, and cognition/mind in a world. However, in the end, consequently, the majority of practical consciousness will be a product of an individual actor’s embodiment and the structural reproduction and differentiation of a social class language game given 1) the determinant nature of embodiment, (anatomical and physiological) form of understanding and sensibility of the body and brain amidst, paradoxically, the indeterminacy of impulses of embodied subatomic particles and the neuronal processes involved in ego-centered communicative discourse; and 2) the consolidation of power of those who control the material resource framework wherein a society, the social class language game, is ensconced and the threat that power (consolidated and constituted via the actions of bodies, mode of production, language, ideology, ideological apparatuses, and communicative discourse) poses to the ontological security of an aggregated individual actor who chooses (or not) either ready-to-hand or present-at-hand to recursively reorganize and reproduce the ideals of the society as their practical consciousness. Lastly, the entire lived experiences (across the multiverses) of the individual being is recorded as the phenomenal properties, qualia, essence, of the psychions that constitute the field of consciousness, which is an emerging fifth force of nature.

Theory and Methods

Against philosophical dualism and idealism [2-4]. philosophy and structurationist sociology, phenomenological structuralism, which attempts to resolve the structure/agency problematic of the social sciences, is a logico-metaphysical materialist philosophy, which posits that we live in a material multiverse composed of brute facts, which human consciousness reifies as ideas, concepts, and theories via language and the abstractions of space/time geometry and mathematics (Mocombeian nominalism) in order to experience, understand, and be in the world for our survival: hence the emergence of religion, science, and the scientific process. For [1], quantum superposition, entanglement, wave-function realism, and evidence in Haitian Vodou of psychic phenomena and spirit possession, which represent ancestors from a parallel world, Vilokan, of the earth’s of which we ought to pattern our behaviors and structures, are grounding proofs for the acceptance of the multiple worlds hypothesis of quantum mechanics. Within the latter hypothesis, the understanding is that “each possibility in a superposition evolves to form its own universe, resulting in an infinite multitude of [(replicated)] coexisting ‘parallel’ worlds. The stream of consciousness of the observer is supposed somehow to ‘split’, so that there is one in each of the worlds-at least in those worlds for which the observer remains alive and conscious. Each instance of the observer’s consciousness experiences a separate independent world and is not directly aware of any of the other worlds” [5]. It is within this multiple world hypothesis, physics, that Mocombe constitutes his understanding of the emergence of the material multiverse, the notion of consciousness in each of the universes according to his theory of phenomenological structuralism, and human psychological development.

For Mocombe, consciousness, like the material multiverse, is emergent; an emergent fifth force of nature, a field of consciousness or consciousness field composed of a quantum material substance/ energy, psychion (which constitutes a “field of consciousness), the phenomenal properties, qualia, of which are recycled/ replicated/entangled/superimposed throughout the multiverse and becomes embodied via the microtubules of neurons of brains and their electromagnetic field. It (consciousness), held together and integrated by the brain’s electromagnetic field, is manifested in simultaneous, entangled, superimposed, and interconnecting material resource frameworks as mind or embodied praxis or practical consciousness, the sense-experiences in-turn become the phenomenal properties (informational content), qualia, of material (subatomic particle energy, psychion) consciousness that is recycled/entangled/superimposed throughout the multiverses following matter disaggregation. In other words, existence precedes essence; but essence is emergent and eternal, and comes to constitute a fifth force of nature, a field of consciousness or consciousness field for Being production, through the phenomenal properties, qualia, of neuronal subatomic particles, psychions, which are recycled/replicated/superimposed/entangled throughout the multiverse and give human actors their initial (essential) practical consciousness embodied and recursively organized and reproduced as the personal and collective unconscious praxis of an individuated ego-essence held together and integrated by the brains EM field.

Be that as it may, the essentialist assumptions inherent in this logico-metaphysical materialist view are that:

• Thought precedes language as a result of qualia, informational content or phenomenal properties (personal and collective unconscious), of psychions (ego-essence), which become embodied as a result of matter aggregation.

• Languages of heterogeneous speech communities are emergent in the cerebral cortex of the embodied brain and attempt to capture the nature of reality as such through syntax or generative grammar and the language games of those who control the resources of a material resource framework.

• The signs (signifier and signified) of the language games of those who control the resources of a material resource framework are arbitrary.

• Two linguistic systems emerge and dominate heterogeneous speech communities, the ordinary language of a speech community and the language of science/religion, which (via the-present-at-hand stance, observation, experimentation, and abstraction or idealization) attempts to capture the nature of reality as such (the idealization of brute facts) by which members of speech communities must recursively reorganize and reproduce their being-in-the-world through their generative grammar and speech acts.

• Ordinary languages are conventional and rule governed based on the rules of the social class language game (personal and collective unconscious) of those who control the resources of a material resource framework and not necessarily the language of science/religion, which is also rule-governed but in relation to its abstractions about the nature of reality as such.

Hence in phenomenological structuralism the reading is that consciousness is the by-product or evolution of subatomic particles, psychions, unfolding, as qualia (subjective and collective informational content), with increasing levels of abstraction within an evolutionary material resource framework enframed by the mode of production, language, ideology, ideological apparatuses, and communicative discourse, i.e., social class language game, of bodies (who control the material resource framework) recursively reorganizing and reproducing the language and ideals (conventions) of the latter factors as their practical consciousness or activity. Within this perspective, thought precedes language as a result of conflict and the phenomenal properties, qualia, of embodied subatomic particles, which direct action in an emergent material world via impulses or drives of past/present/ future sense-experiences (personal and collective unconscious). (Ordinary) language is an emergent system generated from an innate structure of the embodied brain in order so that we can be in the world, communicate, and do things with the other things and beings we experience the world with for our survival. Thus, in phenomenological structuralism the understanding is that the structure of reality determines language (via its generative grammar) and how we ought to live and do things in the world for our survival amidst the internal thought processes (essences) of phenomenal properties, qualia, of psychions of individuals. However, the (ordinary) language, and its usage, i.e., social class language game (personal and collective unconscious), of those who control the material resource frameworks of the world conceals that relationship (the relationship between the individual and the structure of reality as such) via their mode of production, language, ideologies, ideological apparatuses, and communicative discourse (ordinary language), which is evolutionary. In other words, like the Wittgensteinian position of the Tractatus, Mocombe’s theory of phenomenological structuralism assumes that there is a uniform (grammatical/syntactical) structure to language determined by the logical-empirical structure of (quantum and physical) reality. The grammatical structure of linguistic utterances and sentences attempt to capture the subjects, objects, and states of affairs of that reality and how we ought to live in it and among them for our survival. In being-in-the-world with others, this logicalgrammatical structure, however, is concealed by the evolution and developmental knowledge, and its usage (practical activity), of those who control the material resource framework of the world via the stage of development of their language, ideology, ideological apparatuses, social relations of production, and communicative discourse (ordinary language/collective unconscious). Be that as it may, the latter comes to constitute an evolutionary social class language whose linguistic systemicity and usage comes to determine our conception of reality, and the classes, categories, and forms of life we belong to and interact in and with, which depending on its stage of development and relation to the True nature of reality as such as idealized by science/religion, is either accepted or constantly deferred by those individuals in its speech community who are marginalized or not represented in its evolutionarily developed linguistic systemicity. The latter process under the guise “language game,” language as a tool, is what Wittgenstein captures in his second treatise on language as developed in the Philosophical Investigations.

That is, the classes and categories created by the dominant social class language game of a material resource framework, in their efforts to capture the logical-grammatical structure of reality and how we ought to live within it, constitute reified classes, categories, and forms of life, “language games,” whose meanings and praxes as defined by the dominant social class language game are either accepted or deferred by those individuals classified in them (based on their 1) qualia, 2) drives of the body, or 3) their abilities to defer meaning in ego-centered communicative discourse). The latter may in-turn seek to reify their form of life that they are marginalized for, or categorized in, as a distinct alternative practical consciousness or heterogeneous community to that of the dominant order thereby undermining the attempted universality of the logical-grammatical structure of the dominant order for notions of diversity, intersectionality, etc.

So in Mocombe’s theory of phenomenological structuralism, Ludwig Wittgenstein’s two theories of language and meaning must be read as one philosophy as opposed to two, one supported by analytical philosophy and the other by postmodernism/poststructuralism. We have a plethora of (ordinary) language games (classes, forms of life, and categories), heterogeneous speech communities, in the world, which structures our language, because of the ability to defer meaning in ego-centered communicative discourse and the developmental stage of the human mind and body vis-à-vis the actual structure of reality. The language of science, like its predecessor religion, attempts (via observation, experimentation, and idealization) to capture the “True” logicalempirical structure of (quantum and physical) reality, and how we ought to live within it, amidst the (ordinary) utterances and practical consciousnesses of the masses given their abilities to defer meaning in ego-centered communicative discourse and the classes, categories, and forms of life they are classed in/with by the dominant social class language game as they attempt to be in the world via their (ordinary) language, which following matter disaggregation the content of which becomes the personal and collective unconscious of the ego.

To formulate the basic premise of this physic and metaphysic, I adopt from the “membrane theory” model of Lisa Randall and Raman Sundrum (1999) the assertion, in keeping with the logic of Haitian Vodou, that there might be an additional dimension on the cosmological scale, the scale described by general relativity, which gives rise to four dimensional multiverses within it. That is to say, our universe is embedded in a vastly bigger five-dimensional space (the four-dimensional space of relativity, plus a fifth dimension for the subatomic forces including consciousness), a kind of super-universe. Within this super-space, our universe is just one of a whole array of co-existing universes (Haitian Vodou only accounts for our universe and its parallel), each a separate fourdimensional bubble within a wider arena of five-dimensional space where consciousness (a subatomic force) is recycled/replicated/ entangled/superimposed between the phenomenal properties/ informational contents of the species of the five-dimensional superspace, i.e., superverses, and their four-dimensional multiverses (Figure 2).

The origins of consciousness and the multiverse within this phenomenal structural paradigm is material and emergent, and not the product of a supreme creator or god. For this position, I build on the mathematics of [6]. in his “univon multiverse hypothesis.” Unlike Gauthier, who holds on to God or a supreme creator to account for the origins and nature of consciousness within the multiverse, I do not. According to [6] model, identical univon quantum particles, produced from a univon quantum field, created not only our universe but also many other identically finetuned universes in a multiverse. The univon, also called a cosmic quantum, is composed of a helically circulating superluminal primordial information quantum (sprinq). [(The univon is the quantum particle of a conscious cosmic quantum field having both physical and mental potentialities. Quantum fields may be composed of cosmic ectoplasm or mind-stuff, which according to yoga philosophy is a subtle vibrational substance formed from consciousness by a cosmic creative power, that takes the form of objects within a cosmic mind)].

The physical [(and mind-stuff)] constants carried in the information content of each univon’s sprinq are exactly the same in all univons and in all sprinqs, though sprinqs express different fundamental particle attributes in different environments. The univon is radioactive. The decay of a univon into less energetic products is the starting point (t=0) of its created universe. The univon’s sprinq rapidly multiplies itself into different quantum fields and particles, leading very quickly to the early universe’s exponentially rapid inflationary period and then to the Big Bang, which produces abundant relic dark matter particles of the universe as well as the less abundant ordinary matter. Univons made many other [(entangling)] equally fine-tuned universes with identical fundamental forces and constants…. (pgs. 1-3).

In my metaphysical materialistic model, which differs in language and the need for a “cosmic mind,” the “univon” is the cosmological scale described by Einstein constituted by the forces, constants, particles, etc., sprinqs in Gauthier’s hypothesis and phenomenal properties or qualia in my model, of the multiverses, with gravity and the psychionic force of consciousness emergent forces following matter aggregation, evolution, and disaggregation, which give rise to inflation, big bangs, and additional (entangled) universes with similar (replicated) informational (physical and mental) content. Hence, the mathematics for both models are the same as seen in Figures 1 and 2, which is adopted from [6].

I tie this physical model to Black Hole Big Bang Theory (BHBBT)-the understanding “that matter from a mother universe collapses into a black hole. The singularity of this black hole is at a single point in space with respect to anyone in the mother universe. But, because of the reversal of time and space for anyone inside the daughter universe, that point in space r=0 become their initial point in time, t=0. Hence, what was a singularity in space is now a singularity in time, just like the Big Bang. This means that any matter falling in from the mother universe will disappear from that universe and emerge at the initial t=0 point of the daughter universe thoroughly scrambled. Not only that, but what emerges at the Big Bang is not just the matter that was there at the black hole’s formation but all matter that ever fell into it.” [7]-and Mocombe’s structuration theory, phenomenological structuralism, to explain the emergence and constitution of the multiverses, consciousness, minds, and society in them (Figure 3,4).

Structurationism and Phenomenological Structuralism

To the aforementioned physical and metaphysical processes (the brute fact that we are a product of a multiverse that has always existed, which is entangled, superimposed, and replicated via black holes), I add the psychology and sociology of Mocombeian structuration theory to account for the emergence of human action and its relation to consciousness in the determinism of the multiverses and the constitution of societies. Structurationist sociology synthesizes structure and agency via the concept of praxis or practical consciousness; accounting for human agency or practical consciousness via the actions associated with (societal) structural reproduction and differentiation within a particular material resource framework [8-9]. This latter factor, however, does not account for the moments or movements, which escape from the compound of socially constructed identifications, which for Mocombe is epiphenomenal. Building on structurationist sociology in relation to the physics and metaphysics of phenomenological structuralism, Mocombe argues that the “moments, or movements, which escape from the compound of socially constructed identifications” are the product of an individual actors’ (mental) stance/analytics (Martin Heidegger’s term) vis-à-vis three types of structures/systems of signification amidst the practical consciousness associated with societal structural reproduction and differentiation (the social system), which is a tertiary process: 1) the (chemical, biological, and physiological) drives (forms of sensibility and understanding) of the body and brain (the biological system), 2) impulses or phenomenal properties of residual past/present/future consciousnesses or recycled/replicated/entangled/superimposed subatomic/chemical particles, psychions, encapsulated in and as the neuronal energies and qualia of the brain via microtubules (the physical system), 3) and actions or practical consciousnesses resulting from the deferment of meaning in ego-centered linguistic and symbolic communicative discourse (the linguistic system). Our ability to perform the latter, defer meaning in ego-centered communicative discourse, is what gives us as a species the illusion of choice and free-will amidst the aforementioned determining structures the second of which is tied to our connection to the (physical) multiverse and its constitution.

Generally speaking, consciousnesses, actions (practical consciousness), learning, and development within Mocombe’s phenomenological structural ontology are the product of the embodiment of the phenomenal properties, qualia, of recycled/ replicated/entangled/superimposed subatomic neuronal energies/ chemicals, psychion, of the multiverse objectified in the space-time of multiverses via the aggregated body and the microtubules of the neurons of the brain and its EM field. Once objectified and embodied the phenomenal properties, qualia, of the neuronal energies/ chemicals, psychion, encounter the space-time of physical worlds via a transcendental subject of consciousnesses (the aggregation of a universal-self, the ego-essence with phenomenal properties, replicated, superimposed, and entangled across the multiple worlds of the multiverse) held together and integrated by the brain’s EM field and the drives and sensibilities of the aggregated body and brain in reified structures of signification, language, ideology, ideological apparatuses, and communicative discourse defined and determined by other beings that control the resources (economics), and modes of distributing them, of the material world required for physical survival in space-time.

The Heideggerian (mental) stances/analytics, “ready-to-hand,” “unready-to-hand,” and “present-at-hand,” which emerge as a result of conflict between the embodied transcendental ego (qualia) vis-à-vis its different (structuring) systems, 1) the sensibilities and (chemical, biological, and physiological) drives of the body and brain, 2) drives/impulses of embodied residual memories or phenomenal properties of past/present/future recycled/ entangled/superimposed subatomic/chemical particles, 3) the actions produced via the body in relation to the indeterminacy/ deferment of meaning of linguistic and symbolic signifiers as they appear to individuated consciousnesses in ego-centered communicative discourse, 4) and the dialectical and differentiating effects, i.e., structural reproduction and differentiation, of the structures of signification, social class language game, of those who control the economic materials (and their distribution, i.e., mode of production) of a world are the origins of practical consciousnesses. All four types of actions, the drives and sensibilities of the body and brain, drives or phenomenal properties of embodied recycled/replicated/entangled/superimposed past/present/ future consciousnesses, structural reproduction/differentiation stemming from the mode of production, and deferential actions arising from the deferment of meaning in ego-centered communicative discourse via the present-at-hand stance/analytic, exist in the material world with the social class language game, i.e., the physical, mental, emotional, ideological, etc. 5) powers of those who control the material resource framework as the causative agent for individual behaviors. In other words, our (mental) stances in consciousness vis-à-vis the conflict (or lack thereof) between the (chemical, biological, and physiological) drives and sensibilities of the body and brain, (societal) structural reproduction and differentiation, drives (personal and collective unconscious) of embodied past/present/future consciousnesses of recycled/entangled/superimposed subatomic/chemical particles, and deferential actions arising as a result of the deferment of meaning in ego-centered communicative discourse determines the practical consciousness we want to recursively reorganize and reproduce in the material world. The power, power positions, and power relations of those who control (via the mode of production, language, ideology, ideological apparatuses, and communicative discourse) the resources (and their distribution, i.e., mode of production) of a material resource framework, and the threat it poses to the ontological security of an actor, in the end determines what actions and identities are allowed to organize and reproduce in the material world without the individual actor/agent facing marginalization or death.

It is Being’s (mental) stance/analytic, “ready-to-hand,” “unready-to-hand,” and “present-at-hand,” in consciousness vis-àvis the conflict, or lack thereof, between the (chemical, biological, and physiological) drives and sensibilities of the aggregated body and brain, drives/impulses (phenomenal properties) of residual past/present/future consciousnesses of recycled/replicated/ entangled/superimposed subatomic particles, alternative practices which arise as a result of phenomenological meditation and deferment of meaning, along with the differentiating logic or class divisions of the social relations of production, which produces the variability of actions and practices in cultures, social structures, or social systems and gives us the illusion of free-will. All four types of actions are always present and manifested in a social structure to some degree contingent upon the will and desires of the economic social class, power elites, which controls the material resource framework through its body (practical consciousness), language/ symbols, ideology, ideological apparatuses, and social relations of production. They choose, amidst the class division of the social relations of production, what other meaning constitutions and practices manifest themselves in the material world without facing alienation, marginalization, domination, or death.

Hence, we never experience the things-in-themselves of the world culturally and historically in consciousness. We experience them structurally or relationally, the structure of the conjuncture of the mode of production, its language, ideology, ideological apparatuses, etc., and our (mental) stances/analytics, ready-tohand, unready-to-hand, present-at-hand, vis-à-vis these things as they appear to and in consciousness determine our practical consciousness or behaviors.

We initially know, experience, and utilize the things of and in consciousness in the preontological ready-to-hand mode, which is structural and relational. That is, our bodies encounter, know, experience, and utilize the things of the world in consciousness, intersubjectively, via their representation as objects of knowledge, truth, usage, and experience enframed and defined in the relational logic and practices or language game (Wittgenstein’s term) of the institutions or ideological apparatuses of the other beings-ofthe- material resource framework whose historicity comes before our own and gets reified in and as the actions of their bodies, language, ideology, ideological apparatuses, mode of production, and communicative discourse. This is the predefined phenomenal structural, i.e., ontological, world we and our bodies are thrown-in in coming to be-in-the-world. How an embodied-hermeneuticallystructured Being as such solipsistically view, experience, understand, act, and utilize the predefined objects of knowledge, truth, and experienced defined by others and their conditions of possibilities in consciousness in order to formulate their practical consciousness is albeit indeterminate. Martin Heidegger in Being in Time is accurate, however, in suggesting that three stances or modes of encounter (Analytic of Dasein), “presence-at-hand,” “readiness-to-hand,” and “un-readiness-to-hand,” characterizes our views of the things of consciousness represented intersubjectively via bodies, language, ideology, and communicative discourse, and subsequently determine our practical consciousness or social agency. In “ready-to-hand,” which is the preontological mode of human existence thrown in the world, we accept and use the things in consciousness with no conscious experience of them, i.e., without thinking about them or giving them any meaning or signification outside of their intended usage. Heidegger’s example is that of using a hammer in hammering.

We use a hammer without thinking about it or giving it any other condition of possibility outside of its intended usage as defined by those whose historicity presupposes our own. In “present-at-hand,” which, according to Heidegger, is the stance of science, we objectify the things of consciousness and attempt to determine and reify their meanings, usage, and conditions of possibilities as the nature of reality as such. Hence the hammer is intended for hammering by those who created it as a thing solely meant as such. The “unreadyto- hand” outlook is assumed when something goes wrong in our usage of a thing of consciousness as defined and determined by those who adopt a “present-at-hand” view. As in the case of the hammer, the unready-to-hand view is assumed when the hammer breaks and we must objectify it, by then assuming a present-athand position, and think about it in order to either reconstitute it as a hammer, or give it another condition of possibility. Any other condition of possibility that we give the hammer outside of its initial condition of possibility which presupposed our historicity becomes relational, defined in relation to any of its other conditions of possibilities it may have been given by others we exist in the world with who either ready-to-hand, unready-to-hand, or present-athand attempts to maintain the social class language game of power. In the ready-to-hand stance the latter unconsciously practices and attempts to reproduce the social class language game of power by discriminating against and marginalizing any other conditions of possibilities of their social class language as determined by those in ideological power positions [10-20].

They may move to the unready-to-hand stance in response to those who they encounter that attempts, present-at-hand, to alter the nature of the dominant social class language game they recursively reorganize and reproduce as outlined by those in power positions who are present-at-hand of the dominant social class language game. In either case, not all beings achieve the present-at-hand stance. The latter is the stance of science and ideologies, which are tautologies when they profess that their stances represent the nature of reality as such, and those in power positions, who choose, among a plethora of alternative presentat- hand social class language games, what alternative practical consciousnesses outside of their social class language game that are allowed to manifest in the material world.

The Evolution of Consciousness, Individual Psychology, and Mind within Phenomenological Structuralism

Hence, as outlined above, phenomenological structuralism posits consciousness to be the by-product or evolution of subatomic particles, psychion, with phenomenal properties, qualia, embodied and unfolding (out of an emergent consciousness field) with increasing levels of abstraction within entangled, replicated, and superimposed material resource frameworks enframed by the mode of production, language, ideology, ideological apparatuses, and communicative discourse (i.e., social class language game) of bodies recursively reorganizing and reproducing the ideals of the latter factors as their practical consciousness. That is to say, the logical consequence regarding the evolution and constitution of the multiverses, and their contents, based on the assumptions of superposition, action-at-a-distance, wave-function realism, phenomenal properties, and panpsychism of quantum mechanics, for Mocombe, is similar to the intersecting worlds theory highlighted in Haitian Vodou, which parallels the physics, “membrane theory,” of Lisa Randall and Raman Sundrum (1999). The proposal in keeping with the logic of Haitian Vodou and the “brane theory” of Randall and Sundrum is that there might be an additional dimension on the cosmological scale, the scale described by general relativity, which gives rise to four dimensional multiverses within it. That is to say, our universe is embedded in a vastly bigger five-dimensional space (the four-dimensional space of relativity, plus a fifth dimension for the subatomic forces including consciousness), a kind of superuniverse. Within this super-space, our universe is just one of a whole array of co-existing, entangled, and superimposed universes (Haitian Vodou only accounts for our universe and its parallel), each a separate four-dimensional bubble, which share the same informational contents via black holes (BHBBT), within a wider arena of five-dimensional space where consciousness (a subatomic force, i.e., psychion, and it’s phenomenal properties, qualia) emerges and is recycled/replicated/entangled/superimposed between the five-dimensional super-space, i.e., superverses, and their multiverses.

For Mocombe the multiverses originated, from the superuniverses, either by fiat or quantum fluctuation. They are bosonic forces that were brought forth together with fermion counterparts. They are also the primeval pan-psychic fields, stemming from the superimposed and entangled super-verses, whose fermion can be called a psychion, a particle of consciousness or protoconsciousness. These have evolved together with the four forces of nature, electromagnetic force; gravity; the strong nuclear force; and weak nuclear force, in our universe, which in turn produced atoms, molecules, and aggregated life endowed (embodied) with the recycled/replicated/entangled/superimposed consciousness and phenomenal properties, qualia or informational content, of the primeval pan-psychic fields, psychion (the fifth force of nature), of the superverses and their multiverses. In other words, the superverses with entangled and superimposed (via black holes) multiverses share the same informational content. So, the hypothesis here is that one (original) superverse created a universe, and its informational content is entangled and superimposed on top of another superverse with the informational content of the previous universe emerging and replicating in it via black holes. Hence, what you have are layers of multiverses and superverses, superimposed and entangled, whose informational contents are shared or recycled and replicated via black holes, which organize and structure the multiverses similarly. As such, the basic idea for this Black Hole Big Bang Theory (BHBBT) is that quantum fluctuation and big bangs are constantly occurring and producing the same worlds, superimposed and entangled, ad infinitum. So, when physicists look out to the cosmic microwave background (CMB), they are looking at the remnant from an early stage of our universe, which came forth from its older version a layer above it, and so on ad infinitum (see Figure 3). Put more concretely, the physicists are in a superverse, of our universe, in our milky-way galaxy, looking out to the black hole of a milky-way galaxy from the superverse/multiverse above us.

Within these same worlds or multiverses, subatomic particles, via the Higgs boson particle, give/gave rise to carbon atoms, molecules and chemistry, which give/gave rise to DNA, biological organisms, neurons and nervous systems, which aggregate/aggregated into bodies and brains that give/gave rise to the embodiment of preexisting consciousness of the subatomic particles, bodies, and languages from entangled/superimposed multiverses. In human beings, the indeterminate behavior of superimposed, entangled, and replicated subatomic neuronal energies that produced the plethora of consciousnesses and languages in the neocortex of brains gave rise to ideologies, which in turn gave rise to ideological apparatuses and societies (sociology) under the social class language game or language, ideology, and ideological apparatuses of those who organize and control the material resources (and their distribution) required for physical (embodied) survival in a particular resource framework. In other words, existence precedes essence; but essence is emergent and eternal, and comes to constitute a fifth force of nature, a field of consciousness or consciousness field for Being production, through the phenomenal properties, qualia, of neuronal subatomic particles, psychions, which are recycled/replicated/superimposed/ entangled throughout the multiverse and give human actors their initial (essential) practical consciousness among the structuring structure of the drives of the biological body, a social structure or social class language game, and the ability to defer meaning in egocentered communicative discourse.

So contrary to Karl Marx’s materialism which posits human consciousness to be the product of material conditions, the logic here is a structural Marxist one in the Althusserian sense. That is, the aggregated, atomic, mature human being is a body and neuronal drives that never encounters the (ontological) material world directly. Instead, they encounter the (ideological) world via structures of signification, which structures the world or a particular part of it through the body, language, ideology, ideological apparatuses, and communicative discourse, i.e., social class language game, of those whose power, power positions, and power relations dictate how the resources of that framework are to be gathered, used, and distributed (means and mode of production).

Hence in the end, societal and subject constitution, mind organizing and reproducing consciousness as praxis, is a product of conflict and an individual’s mental stance, i.e., analytics, vis-àvis three structures/systems of signification and the ability to defer meaning in ego-centered communicative discourse stemming from the social class language game (i.e., language, symbols, ideology, ideological apparatuses, and communicative discourse) of those who control the mode of production of a material resource framework. It is the ready-to-hand drives of the body and brain, ready-to-hand and present-at-hand manifestation of past/present/ future recycled residual consciousnesses/subatomic particles, the present-at-hand phenomenological meditation and deferment of meaning that occurs in embodied consciousness via language, ideology, and communicative discourse as reflected in diverse individual practices, within the ready-to-hand, unready-to-hand, and present-at-hand differentiating logic or class divisions of the social relations of production, which produces the variability of actions and practices in cultures, social structures, or social systems. All four types of actions, the (chemical, biological, and physiological) drives/impulses of the body and residual past consciousnesses of subatomic particles, structural reproduction/differentiation, and actions resulting from the deferment of meaning in ego-centered communicative discourse, are always present and manifested in a social structure (which is the reified ideology via ideological apparatuses, their social class language game, of those who control a material resource framework) to some degree contingent upon the will and desires of the economic social class that controls the material resource framework through the actions of their bodies (practical consciousness), language, symbols, ideology, ideological apparatuses, and social relations of production. They choose, amidst the class division of the social relations of production, “the structure of the conjuncture,” (Marshall Sahlins’s term) what other meaning constitutions and practices are allowed to manifest themselves without the Beings of that practice facing alienation, marginalization, domination, or death.

Hence psychological speaking, the individual being is initially constituted as superimposed, entangled, recycled, and embodied subatomic particles, psychion, of multiple worlds of the multiverse, which have their own predetermined form of understanding and cognition, phenomenal properties, qualia (personal and collective unconscious), based on previous or simultaneous experiences of multiword as aggregated matter (this is akin to what the Greek philosopher Plato refers to when he posits knowledge as recollection of the Soul; and Nietzsche’s idea of eternal recurrence). The psychions, which have informational content, qualia, are embodied and integrated in the microtubules of neurons of brains and their electromagnetic field, which holds together and integrates consciousness as an ego-essence that initially drives practical consciousness/activity unconsciously (Figure 1). Again, the individual’s actions are not necessarily determined by the embodiment and drives of these recycled (replicated)/entangled/ superimposed subatomic particles and their informational content (qualia, personal and collective unconscious). It is conflict and an individual’s stance, ready-to-hand, unready-to-hand, and presentat- hand, when the subatomic particles become aggregated matter or embodied, and throughout their life-cycle, which determines whether are not they become aware, present-at-hand (third person perspective), of the subatomic particle drives and choose to recursively reorganize and reproduce the content of the drives as their practical consciousness [21-39].

This desire to reproduce the cognition and understanding of the (personal and collective unconscious) drives of the recycled/ replicated/entangled/superimposed subatomic particles, psychions, however, may be limited by the structuring structure of the aggregated body and brain of the individual subject. That is to say, the second origins and basis of an individual’s actions are the structuring drives and desires, for food, clothing, shelter, social interaction, and sex, of the aggregated body and brain, which the subatomic particles constitute and embody. In other words, the aggregated body and brain is preprogrammed with its own (chemical, biological, and physiological) developing forms of sensibility, understanding, and cognition, structuring structure, by which it experiences being-in-a-world as aggregated embodied subatomic particles with phenomenal properties (personal and collective unconscious).

These bodily forms of sensibility, understanding, and cognition, such as the drive and desire for food, clothing, shelter, social interaction, linguistic communication, and sex, are tied to the material embodiment and survival of the embodied individual actor, and may or may not supersede or conflict with the desire and drive of an individual to recursively (re) organize and reproduce the structuring structure of the superimposed, entangled, and recycled (phenomenal properties, personal and collective unconscious, of) subatomic particles. If these two initial structuring structures are in conflict, anytime throughout the lifecycle, the individual moves from the ready-to-hand to the unready-to-hand stance or analytics where they may begin to reflect upon and question their being-in-the-world prior to acting. Hence just as in the case of the structuring structure of the subatomic particles it is an individual being’s analytics vis-à-vis the drives of its body and brain in relation to the impulses/drives (personal and collective unconscious) of the subatomic particles, which determines whether or not they become driven by the desire to solely fulfill the material needs of their body and brain at the expense of the drives/desires of the subatomic particles or the social class language game of the material resource framework they find their existence unfolding in.

The social class language game (the institutionalized personal and collective unconscious of those who control a material resource framework), and its differentiating effects, an individual find their existence unfolding in is the third structuring structure, which attempts to determine the actions of individual beings as they experience being-in-the-world as embodied subatomic particles. The aggregated individual finds themselves objectified and unfolding (developing) within a material resource framework controlled by the actions of other bodies, which presuppose their existence, via the actions of their bodies (practical consciousness), language, communicative discourse, ideology, and ideological apparatuses stemming from how they satisfy the desires of their bodies and subatomic particle drives (means and mode of production). What is aggregated as a social class language game by those in power positions via and within its mode of production, language, ideology, ideological apparatuses, and communicative discourse attempts to interpellate and subjectify other beings to its interpretive frame of satisfying their bodily needs, fulfilling the impulses of their subatomic particles, and organizing a material resource framework at the expense of all others, and becomes a third form of structuring individual action based on the mode of production and how it differentiates individual actors.

That is to say, an individual’s interpellation, subjectification, and differentiation within the social class language game that presupposes their being-in-a-world attempts to determine their actions or practical consciousness via the reified language, ideology, etc., of the social class language game, the meaning of which can be deferred via the communicative discourse of the individual actors allowing them to form social groups or heterogeneous communities tied to the dominant social order because of their control of the materials of the material resource framework. Hence, the deferment of meaning in ego-centered communicative discourse of the language and ideology of a social class language game is the final means of determining an individual’s action or practical consciousness outside of, and in relation to, its stance, i.e., analytics, vis-à-vis the drives of subatomic particles, drives and desires (anatomy and physiology) of the body and brain, and structural reproduction and differentiation. The (mental) stance of the transcendental ego and the ability to defer meaning in egocentered communicative discourse within a social class language game are what accounts for the feeling or illusion of free-will.

In other words, whereas the practical consciousness of the transcendental ego stemming from the impulses of embodied subatomic particles are indeterminant as with its neuronal processes involved with the constitution of meaning in ego-centered communicative discourse (Albeit physicists are in the process of exploring the nature, origins, and final states of subatomic particles, and neuroscientists are attempting to understand the role of neuronal activities in developing the transcendental ego and whether or not it continues to exist after death). The form of the understandings and sensibilities of the body and brain are determinant as with structural reproduction and differentiation of the mode of production, and therefore can be mapped out by neuroscientists, biologists, and sociologists to determine the nature, origins, and directions of societal constitution and an individual actor’s practical consciousness unfolding/developing.

To read more about this article: https://irispublishers.com/ctcms/fulltext/the-psychology-of-phenomenological-structuralism.ID.000538.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

Transition from Junior to Senior Residency in Emergency Medicine: Requirements, Challenges and Recommendations

Authored by Fatimah Lateef

Introduction

In Singapore, Emergency Medicine (EM) residency training according to the ACGME-I guidelines commenced in 2010. It provides structured and formative post-graduate training in EM. It aims to inculcate the fundamental knowledge, skills and humanistic qualities that make up the foundations of EM practice. (1) Residents will develop an expected level of clinical maturity, judgment and technical skills required to practice and also have the ability to incorporate ongoing updates and new knowledge as well as skills during their career. The training is for 5 years; 3 years in junior residency and 2, in senior residency. There are three sponsoring institutions in Singapore: National Healthcare Group, National University Health System and Singapore Health (Singhealth) Services, with the latter usually taking in the higher numbers of residents each year. As the demand for Emergency Physicians increase, with the opening of new government and restructured hospitals, the intake for each of the institution has been increasing gradually [1,2].

During the residency training, there are regular weekly training and teaching sessions. Some are institution specific whilst the others are planned at the national level (that means residents from all three programs come together for the session). There are assessments at strategic intervals and multiple key performance indicators these residents have to fulfill. The transition from junior to senior residency can be a significant and major milestone in the lives of these residents. They must meet certain minimum standard and criteria which have been set by the program and be versatile and capable of running the resuscitation room and the emergency department eventually. This transition in their medical life cycle can indeed be very stressful and uncertain, as they move on from being supervised to a supervising status [1,3,4].

The Domains and their Challenges

As residents’ transition from junior to senior residency, their job scope, job performance and range of responsibilities given to them as well as the expectations pertaining to their performance evolve. Some may need time to adjust to these new responsibilities and roles they need to fulfill. Based on the observations made over the last 10 years, feedback from core faculty at Clinical Competency Committee meetings and review of residents’ performance, certain challenges have been noted in the various domains of training. [1,4] The following section shares some of these observations.

Medical Knowledge and Patient Care

This domain is a fundamental which residents need to develop. The greater their range of exposures and experiential learning, the better will be their pattern recognition capabilities. This can vary across the residents entering senior residency. They must get used to managing patients with complex issues and multi-faceted problems. Therefore, for those with gaps in this domain, one on one training and supervision, using simulation-based learning as well as case-based discussions can be conducted. Senior residents are more independent in managing patients. They need not consult and review with faculty for all the cases they provide consultation. This also means a certain level of confidence must have been attained. The junior residency does have a strong emphasis on competencybased training and skills acquisition and by the time they reach senior residency level, they should be familiar and comfortable with all the requirements, provided they have satisfied the guidelines and met the minimum numbers for their logs [1,5-7]. Their clinical reasoning process must be sound. [6] In managing patients with common range of presentations, they should be able to anticipate the potential problems and complications. Recognition of the ill or deteriorating patient is also a necessary skill. When on duty, they need to demonstrate more adaptive capabilities and leadership, besides just being able to technically manage patients, one at a time [8]. Awareness of the available resources they can tap on as well as how to mobilize these when needed, for example in the situation of upsurge, is important. Their situational awareness capabilities must have been sharpening, from the many postings they would have gone through. At the same time, skills in interprofessional practice and systems-based practice are also highly necessary in view of the team-based work as well as collaborative practice in ED management of patients. Being able to execute all these seamlessly, is a rather big challenge, but in most programs, these senior residents are not left alone. They will be able to consult with faculty and attending. Supervision can be either in the form of direct supervision or indirect supervision, as appropriate for each resident.

Communications

Communications represent the cornerstone of practice. It can be the element that “make or break” an EP-patient or EP-others relationship. They have to communicate with other colleagues in the ED, both doctors and nurses, prehospital care providers such as paramedics, other discipline doctors, administrative staff and even make telephone calls as needed to other providers, perhaps also from other institutions. Today, expectations from patients and their families are very high, in terms of the care delivery, correspondence and professionalism of healthcare providers. Similarly, our residents will have to measure up and perform accordingly as well [4,7].

As a senior resident, one has to be dynamic and adaptable in their communications responses in the ED. Things and action are moving fast and knowing what to say or ‘not to say’ under these circumstances can be crucial. Besides the verbal, the non-verbal communications skills play an important role as well. The people who work with the senior residents will provide 360 degrees feedback on their performance and a significant weightage and influence of this is based on their communications skills [7,9].

The senior residents can be called upon to handle any communications issue the junior residents may not be able to handle. Thus, they must be versatile, be able to think fast, make the appropriate “damage control” explanation and conversations. There will also be occasions to make end of life decisions, with patients and family members. Not forgetting also, the documentation and typing or writing skills. These may be involved in patient record keeping and a high degree of vigilance and astuteness is needed. Of all the skills, good and effective communications capabilities is one of the most pertinent one [9,10].

Leadership

The senior resident will start to take on more and more leadership roles. They will be supervising junior residents, leading resuscitation teams and will be consulted by colleagues and nurses in the event of doubts and uncertainties. They will be acting like the faculty (the faculty is around to be consulted and to supervise as well) and will also need to educate others on the job. Any opportunities to teach younger colleagues can be grabbed during “embedded learning”. They will hold the senior doctor/ faculty on-call telephone and have to discuss regarding transfers and acceptance of patients from other institutions. They will be the role model on the shift, they may be the one doing the debriefing after challenging cases and act as the coordinator, who can re-allocate manpower to the different areas according to patient load and needs [8,9]. This means their situational awareness of how the ED is on their shift is spot-on and up to date. These roles that they have to fulfill can be daunting for a resident who has just stepped into senior residency year. They need to be proactive, adapt quickly, take charge and perform. It is a challenging role indeed and under the trained eye of the senior faculty, it is not difficult to pick up those who falter and non- performers [8, 11].

Academic and Scholarly Activities

Senior residency is still a training phase. Residents will continue to perform clinical work, be supervised accordingly, teach, conduct research and publish papers in peer-reviewed journals.

They also have to attend the EMCC (Emergency Medicine Core Curriculum) weekly training, make presentations, attend conferences and many more. This is also similar to the lifelong continuing education they will have to go through. Senior residency is also the period when residents begin to realize which is/ are their areas of interest for sub-specialization eg. emergency cardiovascular care, trauma and disaster, pediatric emergency medicine, toxicology etc. From senior residency onwards, they can begin to establish themselves and their niche areas of research and interest as well [1,4,11].

Advocacy

With the more adaptive leadership roles and views, senior residents now become aware of many other issues, which are spinoffs and may have either direct or indirect links with healthcare and health promotion. By now, they have to see the bigger picture of healthcare in their countries, region and the world [8].

Initiatives such as patient safety, quality care and standards, risk management, population determinants of health and healthcare will come to be on their radar. Some senior residents will find their passion in some of these areas and become advocates. They may then make representation of these topics to senior management, to non –governmental (NGOs) or even governmental agencies. They start to become advocates for change and for equality [1,11-12]. For example the author herself was an elected Member of Parliament in Singapore for 15 years, whilst she continued with her practice as an EP. During these periods, she championed multiple healthcare related issues and asked the relevant questions in Parliament, changed policies, brought on new guidelines and practices. Others will find the appropriate channels to make the necessary representations, which they come across in the course of their work at the frontline.

Senior residents will also begin to form collaboration with different groups and different disciplines. They will realize the importance of inter-professional collaborative practice. They will represent Emergency Medicine in some of these collaborations. They may even begin to be approached to be representatives on boards of NGOs and other relevant organizations. They may begin to speak up on a variety of topics and themes which appeal to them [4,7].

Professionalism

This is not something new or only founded during senior residency. It is a follow through from the earlier training years. However now, their commitments and performance are closing up towards that of a faculty or attending. The judgment of their level of professionalism is multi-factorial and multi-faceted, incorporating elements such as good and upright clinical practice, ethics, integrity, camaraderie with colleagues, teamwork and partnerships, knowledge and confidence, amongst others. This is also where they begin to be more aware of their strengths and weaknesses in some of these areas [12,13].

The Challenges

Besides medical knowledge and patient care domains which tend to be more technical, leadership, professionalism, role as educator and assessor or advocacy are not formally taught as didactic topics. There may be some topics such as “residents as teachers” incorporated into the curriculum, but even with this it may only cover the topic superficially. Residents will learn and acquire these capabilities by observing their seniors, by trial and error, by immersion and other informal platforms of exposure. This, they will have to do, amidst the time constraints and competing demands and priorities in the ED. Residents will try to find their own ways of coping and going through this [14-16] Some do this very well whilst others may struggle and may need more time. Supervisors will need to keep a keen eye on them and advise or intervene appropriately, in a timely fashion.

The use of dedicated supervising shifts can be useful but not many EDs can afford to grant residents and faculty, this time. Role modelling can be useful provided the appropriate faculty are available to help nurture and inculcate correct principles and values. To get around this, some centers come up with checklists on the topics and skills senior residents need to know and be trained in. In Singapore we use The Education Portfolio and The Administration Portfolio to help guide the senior residents on what capabilities, experiential learning and exposure they need to have under these categories. The Education Portfolio emphasizes on their involvement in small group teaching, large group learning activities, direct observation supervision, mentoring and coaching students and junior residents and even education involving the public, nursing colleagues and others [1]. Feedback must also be gotten for these involvements. Their personalized supervisor faculty will guide them and help with direction/ goals setting. For the Administration Portfolio, they are required to accomplish activities such as doing a root cause analysis, handling medication errors, risk management incident in the ED, handling complaints and even disaster and mass casualty responses [1,14].

One of the useful initiatives for residents in training is to receive feedback. To be useful, the feedback from faculty should be specific, timely and targeted, with specific examples. Generic feedback such as ‘keep up the good work’, ‘need to read more’, ‘need to show more confidence in talking to patients’ may not have significant impact on the resident. Instead comments such as “resident is able to come up with a good set of differential diagnoses when discussing chest pain. He is able to read the electrocardiograph confidently to ensure acute coronary syndrome is being ruled out’, may be more useful. Constructive feedback is encouraged. It can be difficult to provide negative feedback, but there are techniques to deliver this in which faculty can be trained. At times, the resident may not have insight into the problem, habit or working model that he/she has [14-16] Here is where the faculty need to assist with very concise, targeted inputs, with sound and concrete examples to illustrate the points. It is also similar to promoting the more conscious practice of medicine [17].

The EM senior resident has to go through a significant range of experiences and activities, and some may not be able to keep up. Thus, case by case review by their supervisors as well as the Clinical Competency Committee is conducted. Some may require a period of remediation, set with focused and targeted goals to complete the gaps in which ever domains they may lack [18].

Recommendations

Understanding the issues related with transitioning from junior to senior residency in EM is important, if we want to facilitate the process and assist our residents through this milestone in their medical lifecycle. The following are recommendations which can be implemented:

• To create awareness of the transition milestones to both faculty and residents. This is to encourage them to communicate more about it, share their concerns, fears and suggestions and have the faculty, together with the resident, come up with a specified targeted game plan for each resident. Focused group discussions can also be conducted for residents in their third year of junior residency, in preparation for the ‘big jump’

• Incorporating some formal sessions on “how to supervise and assess junior residents/ colleagues can be very helpful

• Having dedicated ‘partnership shifts’ or ‘piggy-back shifts’ where the third-year residents can closely work with their personal supervisors and get detailed targeted feedback on their performance. These can be very useful as a form of on the job training, utilizing an apprentice-ship model. This helps to better prepare the resident for the transition

• The use of ‘shift cards’ is something we utilize at SingHealth, from the first year of residency training. This is a summarized report at the end of each shift, given to the resident by the faculty in-charge. It covers inputs in all the following domains: medical knowledge, patient care, professionalism, communications, evidence-based practice and systems-based practice. These shift cards are kept and compiled so the resident and faculty supervisor can review at regular intervals and assess their performance and the need for interventions.

• Case-based discussions are also very useful. The faculty will take the resident through a medical case and discuss all the relevant points/ domains. They will assist the resident through reflection as well.

• Orientation to the various resources that senior residents need to know and utilize

• Allowing gradual enhancement of the repertoire of privileges given to the resident, which may commence from the second half of their third year

• The option to use simulation where relevant to help get feedback points across or strengthen areas of weakness.

• Ensuring faculty and supervisors to residents attend sessions on how to give effective feedback

• Faculty can be a trusted friend to the resident besides just as a mentor/ supervisor. This way they can open up and share their deepest thoughts and concerns, which may be holding them back.

Conclusion

Senior residents have to integrate the continued development of their clinical acumen, with becoming a medical educator as well as an assessor. Their job scope has a broad spectrum and can be challenging; with the need to ace Medical Knowledge, Patient Care, Practice-based Learning, Professionalism, Communications and Systems-based Practice as core competencies. It is essential that planning and conceptualizing of the pathway be done to customize and facilitate the journey of our residents. This journey does not end there; because they will continue to incorporate new skills and knowledge during their careers and maintain their physical and psychological wellness.

To read more about this article: https://irispublishers.com/ctcms/fulltext/transition-from-junior-to-senior-residency-in-emergency-medicine-requirements.ID.000537.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

Vaccination Contribution to World Health: History, Current and Future

Authored by Ebtsam M Es Kadys

Introduction

Stimulating and activating the immune system against infectious diseases, by selecting vaccines in order to prepare the immune system, and this stimulation is called immune responses, which in turn provide acquired immunity to the disease against which the vaccine has been immunized, which usually consists of the microbe or its derivatives after weakening or destroying it. Vaccines may be prophylactic (to prevent or mitigate the effects of a potential infection by a natural or wild pathogen) or preventive (e.g. cancer vaccines under investigation) [1].

The inventions of Edward Jenner, which began with his popular 1796 [2] by using cowpox material to establish immunity to smallpox, rapidly spread the disease. At the beginning of the 19th century, Jenner’s vaccine technique spread rapidly across the world, sponsored by preferred governments to a measure that could minimize the devastating effects of epidemics on their populations [3]. During the next 200 years, his process underwent scientific and technological changes and eventually led to the eradication of smallpox.

The development of vaccines has increased significantly since the middle of the twentieth century, including the manufacture of virus vaccines in terms of development and innovations such as the polio vaccine and the triple vaccine (measles - German measles - parotid). This development was done by DNA and it is considered one of the most recent applications in the production and development of vaccines.

Main text

The different vaccine industry depends on the method of combating disease-causing germs and viruses by stimulating and stimulating the immune system. The response depends on the technology and approach of the vaccine, as there are four groups in the vaccine industry which are: polysaccharide, and conjugate vaccines. Subunit, recombinant, Live-attenuated vaccines, Inactivate vaccines.

Live-attenuated vaccines: In this type of vaccine, the microbe that causes the disease is used after it is weakened or destroyed, and this vaccine is given an effective and long-term immune response, and this immune protection is done by using one or two doses of this type of vaccine. Live vaccines are used to protect against: measles, mumps, rubella, rotavirus, smallpox, chickenpox, and yellow fever.

Inactivated vaccines: This type of vaccine does not provide good immunity like live vaccines, and this leads to the need for multiple doses of vaccination to obtain continuous immunity against the disease and among these diseases are hepatitis, influenza, polio and rabies.

Subunit, recombinant, polysaccharide, and conjugate vaccines: These types of vaccines use only part of the microbe, such as protein, sugars or capsid, as they target the main parts of the microbe which leads to a strong immune response. One of the negative aspects of this type is the need for multiple doses of the vaccine which use for immunized against Hepatitis B, Whooping cough, Shingles, Haemophilus influenzae type b disease, Human papillomavirus,, Pneumococcal disease, and Meningococcal disease.

Toxoid vaccines: Toxoid vaccines through converting the toxin into an toxoid in order to get rid of the toxicity of the vaccine, As the toxoid affects the immune part of the microbe and not the microbe itself which leads to the need for many doses (booster doses) of the vaccine in order to obtain permanent or continues protection. Toxoid vaccines are used to guard against: tetanus and diphtheria, diphtheria toxoid occur by cross linked the A-B fragments of diphtheria toxin.

Emerging outbreaks of toxigenic cutaneous diphtheria associated with conflict and failing healthcare systems: The crisis threatens to devastate the world’s health-care system with significant morbidity and mortality implications. While emergency immunization programs are vital measures in the current situation to monitor and prevent outbreaks of infectious diseases in the long term. Diphtheria is also an issue with inadequate immunization coverage in a number of low-income countries. Several outbreaks in Sub-Saharan Africa were recorded e.g. Nigeria and Madagascar since 2000 [4]. Recently in South-East Asia the diphtheria outbreaks such as the 2012-2013 People’s Democratic Republic of Lao [5] and 2015 and 2016 in India [6]. In 2017 there was a diphtheria outbreak among the Pemon ethnic group Amerindians in Wonken, Venezuela [7]. Last but not least, the recent ongoing diphtheria outbreak in Yemen2019 exposed the increasing number of cases of diphtheria and deaths as well as the recent shortages of antitoxin diphtheria and cases leading to immunization coverage failure [8]. WHO European region reported the shortages of diphtheria antitoxin, the Strategic Advisory Group of Experts (SAGE) on immunization called for a review of the evidence available and the need to reexamine the current recommendation. Now let’s get to know about this illness, its causes, symptoms and ways of defending us against it.

Diphtheria

It is a serious bacterial infection caused by the bacteria Corynebacterium diphtheria [Figure1]. Diphtheria causes the back of the throat to have thick covering. This can lead to breathing difficulties, heart failure, paralysis and even death. The average diphtheria case-fatality is 5-10 percent. Corynebacterium diphtheria has 4 subspecies (gravis, mitis, belfanti and intermedius). One of the most common dangers of diphtheria is respiratory infection, and it also affects the pharynx and tonsils. In severe cases, pseudo-obstructive membranes form in the respiratory system, and complications of diphtheria are myocarditis and neuritis. Diphtheria may occur in a cutaneous form, resulting in indolent skin infection.

Diphtheria toxin: It is an exotoxin which is secreted by the pathogenic causing diphtheria Corynebacterium diphtheriae. A prophage (a virus that has itself inserted into the host bacterium’s genome) encodes the toxin gene. It is responsible for the Diphtheria symptoms. By 1888 the poison was isolated, in the year 1923 a vaccine was made. Diphtheria toxin (DT) contains three structural domains, each with a distinct biological function involved in cell poisoning: cell-surface binding and internalization into endosomes, crossing of the endosome membrane into the cytosol, and preventing the synthesis of cell proteins.

Pathogenicity of Diphtheria Toxin: Diphtheria toxin is a protein that contains 535 residual amino acids. It is synthesized as a single polypeptide, but it is proteolyzed in its active form to two polypeptide chains connected by a disulfide bond. The fragment C-terminal B (345 residues) contains the transmembrane and receptor binding domains, and the fragment N-terminal A (190 residues) contains the catalytic domain [Figure 2]. On the cell surface, diphtheria toxin binds to the precursor of the heparinbinding epidermal growth factor, and the complex of toxin-receptors undergoes endocytosis mediated by receptors. Next, the A fragment is translocated into the cytosol across the endocytic membrane. The catalytic domain, once in the cytosol, catalyzes the transition of adenosine diphosphate (ADP) ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor 2, inhibits protein synthesis and results in cell death [9].

Nature and Pathogenicity of Microorganisms: Diphtheria toxin is a part of the so-called bifunctional toxins A–B. Fragmentart A is the enzyme activity responsible for halting protein synthesis in the target cell, while Fragment B is related to the cell receptor as it prevents the transfer of Fragment A into the cytosol Portion B accounts for the cell and species specificity of the A–B toxins. Fragment B of diphtheria toxin deals with a heparin-binding precursor of epidermal growth factor, which is an essential hormone for cell growth and differentiation. Uptake of diphtheria toxin is done through endocytosis mediated by the receptor. Endocytic vesicle acidification induces a conformation of the enclosed holotoxin, allowing Fragment A subunit of the diphtheria toxin to traverse the membrane and reach its cytoplasmic target. The A subunit of diphtheria toxin catalyzes the elongation factor-2 (EF-2) ribosylation of ADP and inactivates it [Figure 3].

The tox gene is encoded by a phage and is controlled by the DtxR (diphtheria toxin repressor gene )suppressor protein, which forms an iron complex, DtxR-Fe that binds DNA and restrains the expression of tox [Figure 4].Therefore, diphtheria toxin is only synthesized under low iron conditions, indicating that iron release from target cells can be stimulated [10,11].

Diphtheria Vaccination: Four forms of vaccines used today to protect against diphtheria and other diseases as well: Vaccines for diphtheria and tetanus (DT), diphtheria, tetanus, and acellular pertussis (DTaP), tetanus and diphtheria (Td), tetanus, diphtheria, and acellular pertussis (Tdap). Babies and kids under the age of 7 receive DTaP or DT while older kids and adults receive Tdap and Td.

Passive and active immunization: Passive immunization of equine origin through diphtheria antitoxin (DAT) is highly effective in the treatment of diphtheria though it is not a substitute for active immunization using diphtheria toxoid. Nonetheless, antitoxin is an effective diphtheria medication, and can reduce morbidity as well as mortality. Should be administered diphtheria antitoxin (DAT) as soon as possible after the initiation of the disease, once the toxin has reached the host cells the antitoxin is unaffected. You will administer the entire therapeutic dose at one time. The recommended amount of antitoxin ranges from 20,000 to120,000 units with larger amounts recommended for individuals with severe local lesions and longer periods since the onset. New approaches include developing monoclonal antibodies to diphtheria toxin or developing recombinant modified toxin receptor molecules to bind toxin to diphtheria. To date, however, no monoclonal diphtheria toxin antibody has been approved for clinical use, so treatment is still based on DAT. The toxoid to diphtheria is used for successful immunization. Diphtheria vaccines are based on the toxoid diphtheria, a modified bacterial toxin that causes defensive antitoxin. immunization with DT by combination the diphtheria toxoid with tetanus toxoid as DT (for use < 7 years of age) or Td (for use < 7 years of age) or as DT(a)(w) P or TdaP with tetanus and pertussis vaccine (acellular= a, wholecell= w). Diphtheria toxoid associated with other vaccine antigens such as polio (IPV), hepatitis B, and type b Haemophilus influenzae.

The efficacy of diphtheria antitoxin antisera

The antigen binding with the corresponding Abs determines the basis for evaluating vaccines, therapeutic antisera, and human and population immune functions. Composition of the antigen produced, aside from assay types, Abs complex interaction is mainly determined by reactant heterogeneity, interaction specificity, and reactant concentration. These interactions were widely used in many assays, in which one of the reactants was calculated by the arbitrary set-end stage. A variety of methods are commonly used to titrate diphtheria antitoxins, including both in vivo and in vitro assays. While in vivo study has the advantage of testing the Abs, which essentially neutralizes the toxin, it is relatively costly and repeatable. Several complementary quantitation assays have been developed for DT and antitoxins [12,13]. The total Abs content and the Abs avidity have not been precisely calculated for any of those measures. Although the measured traits could be very distinct in different assays, the determined titers were found to be satisfactory in various applications. The heterogeneity of contributing factors was essentially largely overlooked. Abs ‘avidity was recognized as an effective vector in restraining the defense against various diseases [14].

Avidity as a criterion for the efficacy of the vaccine against diphtheria: The term avidity refers to how closely it binds an antibody to their antigen. Affinity refers to the strength of the bond between an antibody and its antigen. However, several isotypes of antibodies are multivalent, and bind to several antigens. The strength of this overall partnership is the covetousness of avidity. Antibodies (Abs) avidity to diphtheria toxin (DT), toxoids (DTo) and the diphtheria toxin binding site (DTBS) were investigated in sera from guinea broad vaccinated with specific DTo during 2004. Measuring avidity by the thiocyanate method showed that when maturing, Abs maturation trends to the corresponding DTo were not quite different. In the DTBS affinity variations of up to 20 folds were observed as calculated by the tissue culture technique and expressed as equilibrium constant (K). Abs ‘avidity to either the corresponding DTo or the DT could not be correlated with the vaccine’s effectiveness, while the vaccine’s efficacy could be measured by its association with the DTBS. This can be represented in any procedure in terms of measuring precision. The thiocyanate procedure measures the average avidity to complex antigens with multiple epitopes while the tissue culture procedure allows the DTBS affinity of Abs to be determined. It is concluded that the priority in testing new vaccines should involve measuring the avidity of Abs to the known protective epitome [15].

Defense against different pathogens depends mainly on antibodies, where each antibody is specific to a certain antigen to reach maximum effect and this is the major part of humoral immunity. A research to determine the relevance and reliability of the non-functional Enzyme-Linked Immunosorbent Assay (ELISA) for potency testing of diphtheria toxoid-containing combination vaccines was initiated in January 2000 [16]. According to conventional antibody standard, a strong enzyme-linked immunosorbent assay (ELISA) was proven to identify the quantity of anti-diphtheria antibodies in human serum, researches showed very accurate results where recovery have reached up to 97.06 %. The ELISA test mentioned for the quantitation of diphtheria antitoxin is a valuable tool for evaluating immunological defense against diphtheria and could be particularly useful for population studies, since it is economical and practical for large-scale routine purposes.

A quick hexavalent bead-based method was developed by [17] to improve preclinical assessment of serological immune responses to the individual components of DTP combination vaccines diphtheria, tetanus, and pertussis (DTP). The sensitivities of the mouse DTP avidity multiplex immunoassay (MIA) per antigen were comparable to those of the six individual in-house avidity ELISAs, and strong correlations of the IgG concentrations obtained for all antigens tested by both methods were shown. The normal and active mouse DTP MIAs were reproducible for all antigens, with strong variability (CV) intra- and inter-assay coefficients. Ultimately, a retrospective study of the production and avidity maturation of differentIgG antibodies in mice demonstrated the utility of the assay. They conclude that the hexaplex mouse DTP MIA is a reliable, responsive and high-throughput alternative for ELISA in preclinical vaccine studies to investigate the quantity and quality of serological responses to DTP antigens [18]. Estimate avidity by a Modified ELISAs by using chaotropic agents and calculating the degree to which they interfere with the interaction between the antigen and the antibody. The idea behind the test is the greater an interaction’s avidity the less sensitive it is to the effects of the chaotropic agent. The test was highly reproducible and identified a wide variety of avidities for antibodies. Consequently, a GuHCl-modified ELISA is an appropriate approach which can be used within a clinical trial setting to evaluate HPV-specific antibody avidity indices.

Conclusion

Diphtheria is mainly regulated by vaccination, and by high immunization coverage ensures adequate herd immunity. The initiation of diphtheria outbreaks represents insufficient coverage of the vaccine. This epidemic was likely the result of the reintroduction by contaminated migrants passing through mining districts and poor vaccination levels of previously eradicated diseases [19]. In addition to several outbreaks, thousands of cases of diphtheria are still recorded annually from many countries in Asia and Africa. Changes in diphtheria epidemiology have been identified across the globe. Toxigenic Corynebacterium is prevalent. Highlights the need for effective clinical and epidemiological investigations with a view to rapid diagnosis and care of sick persons and public health. Additional studies for new assays and limits are needed to increase the current level of vaccine potency. These attempts to improve assays are expected to stimulate the production of the diphtheria vaccine and lead to self- of the vaccine.

To read more about this article: https://irispublishers.com/ctcms/fulltext/vaccination-contribution-to-world-health-history.ID.000536.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

Progress and Challenges in Clinical AAV Gene Therapy for Neurological and Neuromuscular Disorders

Authored by Megan Baird, Maura Schwartz, Kathrin Meyer and Nicolas Wein

Introduction

Adeno-associated viruses (AAV) are small, replicationdefective, nonenveloped viruses from the family Parvoviridae. First discovered in the mid-1960s, AAV was thought to be a contaminant in adenovirus cultures [1,2]. Over the next 15-20 years, studies to understand basic AAV biology began, characterizing AAV elements such as genome composition and configuration [1,2]. AAV contains a linear single-stranded DNA genome containing approximately 4.7 kilobases [2,3]. As AAV is non-integrating and has a low immunogenic profile, it has become an attractive candidate for viral mediated gene therapies following the unfortunate death of Jesse Gelsinger in 1999. Jesse’s death was caused by immune complications triggered by an adenoviral based gene therapy. Despite the hesitation and fear that resulted from this event, the advent of recombinant AAV (rAAV), showing a lower immunogenic profile compared to adenoviruses, was able to propel the field forward. The first rAAV clinical trial was initiated in 1995 as a treatment for cystic fibrosis [4]. In the early 2000s, new AAV subtypes (serotypes) with the capability to infect various tissues and cell types were discovered in primates, leading to an expansion of the AAV in vivo gene delivery toolbox [2]. The intent of this mini review is to give a brief overview of current Food and Drug Administration (FDA) approved AAV gene therapies as well as to highlight additional AAV vectors currently in clinical trials for neurological and neuromuscular disorders. Due to large number of clinical trials, the mini review will only focus on selected programs for which interim data has been made public, as well as on showcasing different gene therapy methods including not only classic gene replacement strategies but also gene expression (mRNA) modulation [5,6]. Moreover, we will shortly discuss the limitations and current hurdles of AAV based therapeutics.

FDA approved AAV Gene Therapies

RPE65 mutation-associated retinal dystrophy: Fifty-two years after the initial discovery of AAV, the FDA approved the first gene replacement strategy for treatment of a monogenic disorder [7,8]. Voretigene neparvovec-rzyl, or Luxturna, was approved in December 2017 to treat patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy [9]. RPE65 is essential for regeneration of the visual pigment necessary for photoreceptor mediated vision [10]. Without regeneration, the unconverted pigment builds up within the retinal pigment epithelium, blocks the visual cycle, and leads to visual impairment especially in lowlight conditions [10]. Luxturna prevents and partially reverses vision loss by restoring expressing of the RPE65 gene delivered to the retinal pigment epithelium via subretinal injection of AAV2 [8,10]. 55% of patients treated in the initial clinical trial were able to navigate an obstacle course at 2 light levels darker compared to testing prior to treatment [8]. The approval of Luxturna demonstrated safety, utility, and effectiveness of AAV mediated gene replacement strategies. However, the site of administration served as an advantage in this case since the eye is an immune-privileged site [11]. For gene therapies targeted to organs outside the eye, the innate immune response can become a greater obstacle.

Spinal Muscular Atrophy: The first intravenous (IV) delivered AAV9 gene therapy was approved by the FDA in 2019 for treatment of infants below 2 years of age suffering from Spinal Muscular Atrophy [9]. Loss of the SMN1 gene is detrimental to motor neuron survival and leads to whole body muscle weakness [12]. Death typically occurs by two years of age due to respiratory failure [13]. Onasemnogene abeparvovec-xioi (Zolgensma) is an AAV9 based gene therapy that contains the coding sequence of the SMN protein [14]. Treatment allowed SMA patients to achieve new motor milestones, like sitting without assistance, and successfully prevents early death [15]. The first treated patients are now five years of age [15]. Zolgensma’s market approval was a landmark success for the SMA field and solidified the idea for translation of AAV based gene replacement strategies as an effective option for other neuromuscular disorders. Additional clinical trials are currently testing Onasemnogene abeparvovec-xioi in older patients using intrathecal delivery of the vector into the cerebrospinal fluid (CSF). To date, Voretigene neparvovec-rzyl and Onasemnogene abeparvovec-xioi are the only FDA approved AAV gene therapies on the market, but over 100 clinical trials are currently ongoing using different AAVs and delivery routes for a wide range of diseases.

Selected ongoing clinical trials for neurological and neuromuscular disorders with published interim data

Batten disease: Batten Disease encompasses a number of neuronal ceroid lipofuscinoses (NCL) disorders which mostly affect children [16]. Mutations in CLN genes generally result in accumulation of lipofuscin granules in neuronal cells and lead to blindness, regression in cognitive and intellectual ability, seizures, loss of motor function, and early death [16]. Nationwide Children’s Hospital (Columbus, OH, USA) developed gene therapy approaches for Batten Disease CLN6 and CLN3 which were later licensed by Amicus Therapeutics. Both Phase I/II gene replacement clinical trials are currently ongoing [17]. For CLN6 Batten Disease, AAV9. CLN6 (AT-GTX-501) is injected directly at a dose of 1.5e13vg/kg into the cerebrospinal fluid (CSF) via lumbar intrathecal delivery [17]. As of November 2020, efficacy data from the 24-month follow-up visit has been reported for eight children [18]. Compared to subjects from the natural history study, who had a mean rate of decline of 2.4 points over 24 months, treated patients had a mean rate of decline of only 0.6 points on the Hamburg motor and language scale [18]. Amicus also reported safety data that showed treatment was well-tolerated [18]. The treatment for CLN3 Batten Disease with AAV9.CLN3 (AT-GTX-502) began in late 2018, but sufficient interim data has yet to be reported [19]. In addition to these therapies, several ongoing or upcoming clinical studies are being dedicated to treatment of CLN2 Batten Disease, including those from Weill Cornell Medical School (AAVrh10.CLN2), Spark Therapeutics (SPK-1001), and REGENXBIO (RGX-181) [20-22].

Duchenne muscular dystrophy (DMD): DMD is an X-linked recessive disorder characterized by severe muscle weakness and loss of ambulation affecting children around the ages of 8-13 [23]. The disease later progresses to respiratory complications, cardiac abnormalities, and eventual death [23]. The disorder is caused by mutations in the DMD gene, which encodes the dystrophin protein [23]. Without dystrophin, the plasma membrane (sarcolemma) of muscle cells becomes unstable which leads to muscle degeneration and myofiber loss [24]. Unfortunately, the DMD mRNA is too big and therefore cannot be packaged into AAV vectors [25]. However, in 1990, a researchers described a milder form of muscular dystrophy in patients expressing a truncated form of the protein that still had functional properties [25]. As a result, researchers began developing truncated dystrophin proteins, termed micro and mini dystrophin, that could be packaged into AAV and still have therapeutic effects [25]. Three micro-dystrophin constructs are currently being tested in clinical trials: Sarepta Therapeutics (rAAVrh74; SRP-9001), Pfizer (AAV9), and Biosciences (AAV9) [26-28]. All constructs were delivered intravenously and in varying doses ranging from 5e13 vg/kg to 2e14vg/kg [23,29,30]. Overall, the treatments were well tolerated with the exception of the Biosciences trial, which was placed on hold several times due to concerns of severe complement activation [23,29-31]. However, all treatments were shown to be efficacious with reports of decreased creatine kinase (CK) levels and improvements in North Star Ambulatory Assessment scores [23,29-31]. Notably, the efficacy seems to be dose-dependent with 74.3% - 95.8% of muscle fibers expressing the new dystrophin protein after delivery of 2e14vg/kg micro-dystrophin in Sarepta’s trial [9,23].

In addition to the micro- and mini-dystrophin trials, another AAV clinical trial for DMD was initiated this year, taking advantage of the modularity of this giant protein using mRNA exon skipping technology. This approach can be used to treat a subpopulation of DMD patients in which exon 2 of the gene is duplicated. The AAV9 therapeutic vector contains a small RNA that binds to the dystrophin messenger RNA (mRNA) and alters mRNA splicing to promote exon exclusion. Exon duplications encompass approximately 10-15% of disease-causing mutations in DMD, with exon 2 being the most commonly duplicated exon (~1-2% of DMD patients) [32,33]. Exclusion of exon 2 results in production of either mRNA containing a single copy of exon 2 and production of normal dystrophin protein; or mRNA with no copies of exon 2, resulting in a highly functional shorter isoform of the dystrophin protein [34]. The phase I/II clinical trial is currently ongoing using IV injection of 3e13 vg/kg with this vector for treatment of DMD patients carrying exon 2 duplications. The primary outcome measure is safety and secondary outcomes include monitoring change in dystrophin expression and changes in exon 2 inclusion in the mRNA transcript of dystrophin [35]. Interim data from 3 months post injection was recently presented at the World Muscle Society meeting showing reduction of creatine kinase levels as well as increased dystrophin protein expression in treated patients.

X-linked myotubular myopathy (XLMTM): Mutations in the MTM1 gene, encoding myotubularin, causes XLMTM which results in extreme muscle weakness, respiratory failure, and death [36]. Audentes Therapeutics is conducting a Phase I/II clinical trial investigating the treatment of patients less than five years of age with an AAV8.hMTM1 (AT132) construct delivered intravenously [37]. A low dose (1e14vg/kg) and a high dose (3e14vg/kg) were delivered [37]. As of May 2019, safety and efficacy data was available for six patients given the low dose and four patients given the high dose [38]. All patients showed improved motor function including the ability to sit unassisted, raise self to stand, and walk with or without support [38]. In addition, time of ventilator assistance was decreased with most patients becoming fully independent [38]. These milestones persisted to over 1-year post treatment and were consistent with increased expression of myotubularin in muscle biopsies [38]. Based on these initial highly promising results, the 3e14vg/kg dose was chosen for the confirmatory phase [38]. To date, a total of 17 patients received the high dose, which unfortunately led to severe side effects and death in three patients. Preliminary findings indicate that the immediate cause of death was sepsis. Although the exact mechanisms that led to these deaths remain unknown, the patients who suffered severe side effects were amongst the older and heavier patients, therefore receiving an overall larger dose of viral vector since dosing is calculated by kilogram body weight. Moreover, the patients had pre-existing hepatobiliary disease, which could have increased their sensitivity to the treatment since the liver is highly targeted by AAVs [39,40].

Limb girdle muscular dystrophy (LGMD): Limb Girdle Muscular Dystrophies (LGMD) are a distinct class of muscular dystrophies with 34 identified variants, each showing significant phenotypic heterogeneity [41]. LGMD Type 2E (LGMD2E) is a childhood to adolescent onset LGMD characterized by progressive weakness in the pelvic-girdle and shoulder-girdle muscles, typically resulting from mutations in the beta-sarcoglycan gene (SGCB) [42]. Sarepta Therapeutics has an ongoing AAV-mediated gene replacement clinical trial for the treatment of patients with LGMD2E [43]. In this trial, cohort 1 patients, 4-15 years of age with a confirmed beta-sarcoglycan gene mutation in both alleles, received a single IV injection of AAVrh74 containing human SGCB cDNA under the control of the muscle specific MHCK7 promoter (AAVrh74.MHCK7. SGCB) at the dose of 5e13vg/kg [43,44]. Muscle biopsies taken 3 months post-treatment from 3 patients show an average of 51% SGCB positive muscle fibers, a 90% reduction in CK levels, and restoration of the sarcoglycan complex to the membrane [25,44]. At the 90-day patient follow-up, 2 patients had elevated liver enzymes as a side effect of the AAV treatment, which resolved with supplemental steroid treatment [44]. Cohort 2 patient dosing will be based on results from cohort 1 patients and may be escalated [43].

Parkinson’s disease (PD): Parkinson’s Disease (PD) is an adult-onset neurodegenerative disease with motor and cognitive impairment resulting from the loss of striatal dopaminergic neurons in the substantia nigra of the brain. In PD, motor impairment manifests as bradykinesia, tremor, and rigidity. Non-motor impairments include cognitive, mood, and behavioral dysfunction, sleep disturbance, pain, and autonomic disturbances [45]. The most effective pharmacological treatment for PD is levodopa, a dopamine precursor amino acid, but as the disease progresses, the benefits of levodopa treatment decline due to the loss of Aromatic L-Amino Acid Decarboxylase (AADC), an enzyme that converts levodopa to dopamine [46]. Neurocrine Biosciences, in collaboration with University of California San Francisco, Feinstein Institute for Medical Research, Oregon Health and Science University, and Voyager Therapeutics, recently completed a clinical trial safety study of AADC gene therapy as a treatment for PD [47]. In this study, fifteen patients received bilateral putamen injections of AAV2 containing AADC cDNA (VY-AADC01) at the dose of 7.5e11vg (n=5), 1.5e12vg (n=5), or 4.7e12vg (n=5) [47]. Results from this study show a dose dependent putaminal coverage of VY-AADC01 expression and dose dependent increases in AADC activity, as well as a reduction of ant parkinsonism medications at 6 months [46]. The Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) was used to evaluate changes in motor and non-motor complications and showed clinically meaningful dose-dependent improvements at 12 months and increased Quality of Life measurements even with reductions in dopaminergic medications [46,47]. A Phase II clinical study (NCT03562494) has been recently initiated, sponsored by Neurocrine Biosciences in collaboration with Voyager Therapeutics and is currently recruiting [48].

Amyotrophic lateral sclerosis (ALS): ALS is an adult-onset neurodegenerative disease characterized by progressive loss of motor neurons in the brain and spinal cord. As there is currently no cure, the disease is always fatal with patients succumbing to death within 2-5 years of symptom onset. In July 2020, The New England Journal of Medicine published results from a compassionate-use patient study for the treatment of familial ALS. The study was conducted at University of Massachusetts and Massachusetts General Hospital and included treatment of two patients with SOD1- mediated ALS [49]. The gene therapy construct contains a microRNA sequence that reduces expression of the superoxide dismutase 1 (SOD1) protein. Mutated forms of this protein cause approximately 2% of all ALS cases. Two patients were intrathecally injected with AAVrh10-miR-SOD1 at the dose of 4.2e14 vector genomes [49]. Patient 1 experienced an adverse inflammatory response to the viral vector causing severe pain which decreased over time but was not resolved [49]. Patient 1 had transient improvements in the strength of his right leg after treatment, but no change in vital capacity, and succumbed to the disease 15.6 months post treatment [49]. The gene therapy treatment led to a 90% reduction of SOD1 protein in the post-mortem lumbosacral spinal cord of Patient 1 but there was no change in SOD1 levels in the cerebrospinal fluid with treatment [49]. Western Immunoblot analysis of SOD1 protein in the spinal cord showed no differences in the cervical spinal cord, though there was a reduction in SOD1 enzyme activity [49]. For Patient 2, a more rigorous immunosuppressive regimen was used to reduce chances of a strong inflammatory response and the patient did not have increased hepatic aminotransferase levels or sensory dysfunction following treatment [49]. As patient 2 has a milder form of the disease and a slower disease progression, additional data on the disease course is expected to be collected over time.

Conclusion

The field of AAV mediated gene therapy has grown exponentially over the last decade, with a massive increase in publications, preclinical studies, and ongoing or completed clinical trials [2]. Though many results so far are exciting, these clinical studies also underline challenges the field is still attempting to overcome. In all the aforementioned trials, pre-existing immunity, measured in form of antibodies, were designated as exclusion criteria. This is a significant barrier to treatment for patients in need, and much of the field is dedicated to finding strategies that can temporarily evade or dampen the immune response of patients that have been naturally exposed to AAV viruses [9,50]. These strategies, such as the use of immunomodulatory enzymes, plasmapheresis, or modified AAV capsids, may also be useful in the event patients need a second administration of vector to maintain expression of the transgene in cell types that continue to divide and therefore might lose the AAV construct over time [9]. For the treatment of neurological and neuromuscular diseases, choosing an appropriate route of administration is vital to the success of a therapy. Local routes of delivery, such as direct brain injections, allow for sufficient local targeting but increase the risk of injury at the site of injection [51]. Several of the described studies are currently utilizing IV delivery of AAV constructs capable of targeting muscles but also brain and spinal cord. The caveat of IV delivery is that high doses are required for sufficient transduction of target cell types, especially in the central nervous system (CNS). As a result, several studies have reported serious adverse events related to liver toxicity, an organ that is highly targeted with IV delivery [39,52,53]. Alternatively, CSF delivery via intrathecal (IT) route offers several advantages over IV delivery for neurological disorders because it allows for sufficient transduction of neuronal cell types with a lower required dose, thereby limiting immunogenic response and liver targeting [54]. The CSF delivery route could potentially lead to toxicity in other organs, as a recent study performed in non-human primates suggests this route may induce dorsal root ganglion (DRG) pathology [55]. To date, DRG pathology or clinical signs thereof have not been reported in patients dosed intrathecally in the ongoing Batten disease trials or the clinical trials currently conducted with Zolgensma for older patients (NCT03381729). Another consideration is when to dose patients for maximal therapeutic effect. In general, it seems the highest benefit is achieved in patients that are dosed early in disease progression with as few symptoms as possible, as symptom reversion seems to be more challenging. The currently ongoing clinical trials and newly initiated studies will be highly informative and will help advance the exciting field of AAV gene therapy further

To read more about this article: https://irispublishers.com/ctcms/fulltext/progress-and-challenges-in-clinical-aav-gene-therapy-for-neurological-and-neuromuscular-disorders.ID.000535.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

Specification A Model for Study of Harassment Agenda

Authored by Cruz Garcia Lirios

Introduction

A review of the literature regarding the study of Internet harassment alludes to variables such as; stalking, stashing, trolling, sexting and bullying. Each one explains the origin, development and consolidation of asymmetric relationships that are not necessarily related to other economic, political, social, cultural or educational differences, but being cross-cutting they increase the gap between victims, stalkers, spectators and promoters [1]. In this way, a review and discussion is necessary to highlight their relationships and guide their composition towards the exploration, explanation and prediction of the behavior of the actors involved in harassment through electronic technologies, devices and networks [2]. However, the literature consulted has focused on the relationship between perpetrators and victims without considering the mediating or moderating role of viewers, promoters or apologists for Internet harassment [3].

In the hegemonic analysis of the differences between bullies and victims, preponderant indicators have been found: bullying, trolling, stashing, sexting or stalking, but a partial and unidirectional analysis between the variables inhibits the observation of bullying as an extensive system of economic differences, political, social, cultural or educational among the parties involved [4]. It is about the establishment of a diversified agenda in its composition and extension, as well as heterogeneous among its actors. Therefore, the analysis of the relationships between the indicators of Internet harassment opens the discussion around the construction of a common agenda for stakeholders in which the victim and perpetrator are passive and active, specifying their function from the environment and electronic resources with which they have more than a pathology related to the violent, situational or dispositional nature of the parties involved [5]

Studies of Harassment Agenda

The specification of the model is based on the assumptions of the Theory of Reasoned Action, the Theory of Planned Behavior, the Theory of Self-efficacy, the Theory of Technology Acceptance, the Theory of Electronic Consumption and the Theory of the Dissemination of Innovations according to which the perceptions of utility, ease, risk, control, efficiency and compatibility directly and indirectly determine the use of a technology or electronic device. L a relationship between perceptual factors and cyberbullying direct (hypothesis 1). Or indirect through the perception of effectiveness (hypothesis 2) and / or the perception of ease (hypothesis 3). Direct relationships are estimated by multiple regressions in which seven perceptual variables simultaneously affect cyberbullying. This is because it is considered that an interrelation between the perceptual variables would affect the predictive power of each one over cyberbullying [6]

The perception of control, as established by the Theory of Planned Behavior, is a factor that, when associated with the intensive use of a technology, mainly affects the planning of an information device [7]. However, being a general perception, as established by the Theory of Reasoned Action, its predictive power is reduced to its minimum expression since it requires its association with another perceptual factor such as efficiency or ease of use [8].

In this way, the perception of utility, according to the Theory of Acceptance of Technology, influences to a greater extent if it is linked to the perception of ease of use, but it diminishes its impact if it is related to the perception of risk according to the Theory. of Electronic Consumption. This logic applies to each of the perceptual variables and their probable link between them when anticipating the effects of cyberbullying [9]. For its part, the perception of compatibility is more influential on the use of technology as predicated by the Theory of the Diffusion of Innovations since the relationship with another perception would be a difficult system to get along with lifestyle and intensive use of technology [10].

In the case of risk perception, the Theory of Electronic Consumption indicates that its power is more incisive on the use of an electronic device if the uncertainty or mistrust is not reduced by a perceptual factor of control or utility [11]. Finally, in the case of the perception of efficiency, the Theory of Self-efficacy warns that it has a greater impact on the use of technology if it is associated with the achievement of achievements which is very close to the perception of utility. That is why the indirect effect of perceived efficiency will be greater than its direct bearing on the use of technology [12].

In indirect relationships, the effects of perceptual variables obey the same logic of interrelation and determination, but unlike direct relationships, measurement errors have an influence on the estimation of an exogenous variable on an endogenous variable or mediator before predict the effects of their association on cyberbullying [13]

Both systems, direct routes and indirect pathways, to be included in the specification model try to predict the cyberbullyng considering different edges of interrelation between perceptual variables that the state of knowledge warns as fundamental but have only been able to establish by routes direct their predictive power.

Interrelationship between perceived usefulness, compatibility, control, harassment and impact risk by perceptions of effectiveness and ease, to cyberbullying shall conform to the observed data.

Method

A documentary study was carried out with sources indexed to international repositories such as Dialnet, Latindex, Publindex, Redalyc and Scielo, considering the period from 2010 to 2018, as well as the inclusion of key words. The information was processed based on the Delphi technique, which considers rounds of synthesis, qualification, discussion and integration of the differences between expert judges of the topics with the purpose of structuring criteria for the interpretation of an expert agenda that is compared with the agenda extracted from the literature review [14].

The synthesis of the data to be discussed in the first round was obtained from the literature review, highlighting the indicators: stalking, trolling, stashing, sextint and bullying , but without including reasoning about the relationships in order that the judges will evaluate the content , assigned -1 for content unfavorable to bullying, 0 for unlinked content and +1 for favorable content. The data were processed in the analysis package for social sciences (SPSS for its acronym in English version 17), frequencies and d were estimated and from them hypotheses were established to specify the model.

Results

The contribution of the present work to the state of the question lies in the specification of a model in which two agendas were compared, one of experts who warn asymmetric relationships between the parties involved in the harassment but disconnected from the literature consulted which highlights the prevalence of lifestyles prone to risk and because of harassment.

Final considerations

Harassment in times of discussion opens up regarding its measurement because, given the diversity of components, the weighting of its dimensions and indicators becomes more complex, and a balance between definitions and their features is essential [15].

In the present work it has been argued that pre-existing differences between the actors involved such as the perpetrators, the victims, the spectators and the promoters, although it is a reflection of their economic, political, social, cultural or educational asymmetries, is also the establishment of an agenda that has focused its attention on axes and topics of discussion such as the harassment seen from pathologies that emerge in the interrelation. [16] warns that harassment is collateral and simultaneous to the use of the Internet itself, since the development of capacities, skills and information resources potentiates harassment not mediated by a technology, device or digital network.

Precisely, in this reflective line, this work highlights the relationships between the variables subtracted from a first review of the literature and specified in the qualification of expert judges. García, Hernández, Aguilar and [17] demonstrated that the intensive use of electronic devices and networks increases Internet user harassment in relation to other determinants that allude to expectations of achievement, identity, usefulness, ease and risk.

In effect, the situational factor combined with the dispositional factor, or, the intensive use of the internet added to the skills and knowledge explain the harassment, but only a type of harassment more oriented to the processing of information as a resource for the ridicule of a potential victim more than the observation of relationships between the interested parties, as is the case of those who search, store, document, process and disseminate information related to bullying [18-20]. The construction of an integral model is necessary in which, once the relationships between the variables are specified, it is possible to contrast the hypotheses in order to contribute to the state of the question.

To read more about this article: https://irispublishers.com/ctcms/fulltext/specification-a-model-for-study-of-harassment-agenda.ID.000534.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

Ongoing COVID-19 Clinical Trials: A Pharmacological Perspective on Pneumonia

Authored by Prof. Dr. Amani E Khalifa

Introduction

Coronavirus disease 2019; the current pandemic, is a newly emerged viral pneumonia that was named COVID-19 by the WHO on February 11th, 2020 [1]. The causative agent of this viral pneumonia is the SARS-CoV-2 which was found to be closely similar to SARS-CoV with about 80% sequence identity [2]. Although the pathogenesis of COVID-19 disease including the mechanisms of antigen presentation is poorly understood, the high similarity between SARS-CoV-2 and SARS-CoV was reflected in the clinical course of the disease where the virus typically attacks the lungs in certain vulnerable populations in three phases; viral replication, immune hyper-reactivity, and pulmonary destruction [3].

Clinical studies of COVID-19 disease

The database registry of “ClinicalTrials.gov” run by the United States National Library of Medicine at the National Institutes of Health includes all privately and publically funded clinical studies conducted in 211 countries around the world. Observational and interventional studies from Egypt (148 studies) and the rest of the world (4019 studies) are taking place [4]. Among such running clinical trials is our team’s principal investigation of the roles of Egyptian pharmacists in combating this disease that is available at: https://clinicaltrials.gov/ct2/show/NCT04374513

Specifically, “Clinicaltrials.gov” database registry classified the overall listed clinical studies related to COVID-19 into many categories according to the targeted condition. Three categories are most prominent; one major category targeting the COVID-19 disease condition in general including mild, moderate and/or severe disease with or without evidence of pneumonia, another category of clinical studies targeting confirmed COVID-19 pneumonia, and a third category targeting COVID-19 associated ARDS, with some overlap that might exist among these categories. Among the updated total of 4019 studies on COVID-19 generally, the refined search strategy yielded only 747 on pneumonia in COVID-19 [5].

From a pharmacological point of view, it is important to focus on the second category of clinical studies targeting COVID-19 pneumonia rather than COVID-19 associated ARDS or the broad COVID-19 disease categories for many reasons. First, the majority of COVID-19 patients exhibit mild to moderate symptoms, and only 15% of patients progress to severe pneumonia cases within which about 5% eventually develop ARDS, septic shock, and/or multiple organ failure [3,6]. So, the disease can be tolerated by most patients with a positive outcome of viral load reduction/ clearance, followed by receding of inflammation and in this population, the benefit/risk ratio of any pharmacological intervention may not be ethically justified and may also negatively affect their otherwise capable immune system function. The category of clinical trials targeting the COVID-19 disease condition in general including mild, moderate, and/or severe disease, therefore may expose many cases to unneeded and unknown risk due to the medications’ side effects/toxicities in this novel disease. Also, the same pharmacological interventions may not be appropriate for all levels of disease severity given the reported multistage pathophysiology of CoVs discussed earlier. On the other hand, patients experiencing ARDS develop overwhelming lung hyper-inflammatory cytokine storm and acute respiratory failure; a critical and late condition in the course of COVID-19 disease that might not allow for a completely successful intervention. Therefore, in clinical trials targeting COVID-19 associated ARDS, reaching a safe and effective pharmacotherapy would be utterly difficult. Besides, treatment before the onset of ARDS could be a wise decision since the overall prognosis of ARDS is poor, with mortality rates of approximately 40% [7], and even if patients survive, they might face other life-long physical and psychological consequences after exhausting their economic and national healthcare systems.

It is also important to focus on the second category of clinical studies targeting COVID-19 pneumonia rather than COVID-19 associated ARDS or the broad COVID-19 disease category since the available clinical data indicates that the majority of COVID-19 patients had pneumonia while only small percentage had ARDS. In a Chinese cohort of 1,099 patients with COVID-19, 93.6% were hospitalized, 91.1% had pneumonia, 5.3% were admitted to the ICU, 3.4% had ARDS and only 0.5% had acute kidney injury [8]. In addition, a retrospective study that included 357 patients with ARDS who chronic kidney disease or acute kidney injury before ARDS presentation did not have reported that pneumonia was the cause of ARDS in 83% of patients [9]. Therefore, safe and effective treatment for COVID-19 pneumonia is necessary, particularly if targeted to the cases with potential bad prognosis whose immune system could not otherwise overcome such illness without intervention (Figure 1).

To read more about this article: https://irispublishers.com/ctcms/fulltext/ongoing-covid-clinical-trials-a-pharmacological-perspective-on-pneumonia.ID.000533.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

Satisfaction and Knowledge of Elderly Patients Towards Their Multiple Medications Usage

Authored by SM Alqallaf

Although multiple drug use or polypharmacy might be considered appropriate as in cases of concomitant diseases or in complex medical conditions, the inappropriate polypharmacy or major polypharmacy is a very common problem around the globe [1-4]. An example of that is a German study which reported the use of more than 5 medications in 26.7% of elderly patients and this doubles (54%) when including over the counter medications [1]. Nevertheless, the number of medications that constitutes polypharmacy is not fully agreed. However, WHO (2004) defined Polypharmacy as “the administration of many drugs at the same time or the administration of an excessive number of drugs “WHO 2004. Hence, polypharmacy term has been used to describe a patient’s use of multiple drugs and is used also more generally to describe unnecessary drug prescription [3,5].

The main reason for the problem of inappropriate polypharmacy is the growing elderly population with its accompanying pathophysiological changes and the advancement in healthcare services [6-8]. Age-related changes involves all body organs / systems and necessitates special considerations in drug prescribing in the elderly [9]. These changes might affect drugs’ pharmacokinetics parameters and might result in potential drugdrug interactions [9,10]. Other causes for the polypharmacy include visiting multiple physicians, the use of complex drug treatment and the occurrence of drugs’ side effects which might be interpreted as a newly existing disease [6,11,12]. Another genuine reason is the psychosocial factor such as the use of traditional remedies or herbs which was reported in 30 % of German adults [6,8].

he evidence for the negative impact of polypharmacy on the patients’ health is well established, even with the intake of as few as four medications at any given time [5,13]. One main complication is the exposure to potentially inappropriate medications with what it carries of an increase in the incidence of serious adverse drug reactions and interactions [2,6,13-16]. In Sweden, fatal adverse drug reactions represented approximately 3 % of all deaths in elderly patients [15]. Non-fatal adverse drug reactions secondary to polypharmacy represents a significant cause of emergency department visits and hospital admission in the elderly [7,14-16]. A study indicated that 12 % of hospital admissions in elderly are related to adverse drug reactions [14]. These patients were found to be at increased risk of rehospitalization [17]. Another complication of polypharmacy is the under-prescribing of recommended drugs; which is known as ‘‘treatment risk paradox’’ [6]. Polypharmacy is also associated with an increase in the risk of geriatric syndromes such as delirium, falls, incontinence and behavioral disturbances [14-16]. Other consequences of polypharmacy are higher mortality rate, greater health-care cost and increased medication errors [6, 14-18]. Additionally, multiple medication use carries the risk of poor adherence which is a multi-factorial problem [14]. Factors that might worsen the problem of poor adherence in patients with multiple medications include dosing schedule confusion, inadequate medication education / counselling, poor patient’s memory, poor hand dexterity with difficult to open packages and it might intentional trying to avoid adverse drug reactions [6].

The aim of this study is to determine the satisfaction and knowledge of elderly patients in Bahrain towards their multiple medication’s usage. Another aim is to discover the prevalence of inappropriate polypharmacy among elderly patients in Bahrain.

Methods

A systematic review of the literature was performed using several medical engines including the National Library of Medicine’s PubMed database, Science Direct and Google Scholars (limited to English language). The terms used in the search were polypharmacy, multiple medication use, polypharmacy and elderly, inappropriate medication frequency, medication errors with polypharmacy. The search profile included comprehensive lists of various clinical studies that were conducted in different world areas for statistically relevant information about polypharmacy. Data of these studies were eventually compared with the analysis of the current study. A cross sectional survey was carried out aiming at exploring the prevalence of the problem of inappropriate polypharmacy. Using a standardized questionnaire, 100 Bahraini patients aged 55 to more than 75 years were interviewed in different. Because of the limited time available for completing the study being part of an educational course, convenience sampling was used and therefore the study may not be sufficiently representative of the entire population. The Inclusion criteria were patients aged more than 55 years. No exclusion criteria were put. Both genders were enrolled, in which fifty-five males and forty-five females were interviewed. Participants answered 14 questions regarding drugs taken, pattern of using each drug and patients’ personal, social and medical history in addition to their satisfaction with their treatment regimen. The survey was pilot tested on 10 subjects to improve questions, clarity and quality of data collection. Full demographic data was collected for all subjects, including age, gender, and education Table 1.

A summary score of percentage correct answers was finally created. The data was analyzed using Microsoft Excel program for statistical analysis. Since the study is cross-sectional, descriptive statistical analysis was conducted. This study was approved by the Pharmacy Program Ethics Committees. Data was collected from participants who provided verbal consent.

Results

Demographic data

Demographical data of the participants are shown in Table 1. The male patients were 55 %, while the rest were female. The majority (49 %) of patients were 55 - 64 years age, 31 % were 65- 75 years and the rest (20%) were more than 75 years. Illiterate patients were 15 %, patients with elementary, intermediate and secondary school certificates were 18%, 16% and 33% respectively, while patients with university degrees were 18%. The results showed that the majority of participants suffered from diabetes (87%), hypertension (84%) and hyperlipidemia (83%). Furthermore, some of the participants suffered from heart disease (38 %), thyroid gland disorders (32%) and other chronic disease such as gout, glaucoma, depression, asthma and rheumatoid arthritis (Figure 1).

To read more about this article: https://irispublishers.com/ctcms/fulltext/satisfaction-and-knowledge-of-elderly-patients-towards-their-multiple-medications-usage.ID.000532.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - Current Trends in Clinical & Medical Sciences (CTCMS)

A Latent Growth Model Evaluation of the Comprehensive, Integrated HIV Prevention Program Effect on Excessive Alcohol Risk Awareness and Excessive Alcohol Consumption Risk

Authored by Meya YB Mongkuo

It has been almost four decades when HIV infection became a severe public health problem. Since then, infectious disease experts worldwide have been working without finding a vaccine to immune people from the disease. So the focus has shifted from developing a vaccine to identifying the most effective evidence-based prevention strategies to slow the spread of the disease. In 2017 an estimated 5.1 million or 14.8% of young adults aged 18 to 25 were diagnosed with substance use disorder [1,2]. Other researchers have focused on identifying evidence-based risk and protective factors and prevention strategies to slow the disease [3-8]. Research has found excessive alcohol consumption destabilize the normal functioning of virtually all vital organs that regulate behavior, including the nervous system, the immune system, the digestive system, the endocrine system, and the circulatory system [3,9]. These hormones control metabolism and energy levels, electrolyte balance, growth and development, reproduction, responses to and appropriate coping with changes in the internal and external environments, such as changes in temperature and the electrolyte composition of body fluids, and response to stress, anxiety, and injury [3,5-8,10].

Both acute and chronic alcohol consumption induces hormonal disturbance of the endocrine system that disrupts the body’s ability to maintain homeostasis leading to various disorders, including cardiovascular diseases, reproductive deficits, immune dysfunction, certain cancers, bone disease, and psychological and behavioral disorders. Research has also found that indulgence in excessive alcohol consumption does not only harm the hypothalamicpituitary- adrenal (HPA) axis, but practically all the hormonal systems of the body, including the hypothalamic-pituitary-gonadal (HPG) axis Sakar DK, Gibbs DM [5], the hypothalamic-pituitarythyroid (HPT) axis [11], hypothalamic-pituitary-growth hormone/ insulin-like growth factor-1 (GH/IGF-1) axis [13-15], and the hypothalamic-posterior pituitary (HPP) axis [3,4,17-19].

A recent review of studies on youth and adolescents also suggests that hypothalamic-pituitary-adrenal (HPA) axis dysfunction and exposure to stress are critical components that interact to convey risk for developing attention deficit disorder (AUD) [20]. For example, several randomized clinical trials (RCT) have found that excessive alcohol consumption harms the normal functioning of the nervous and endocrine systems, both of which are responsible for proper communication between various organs and cells of the body to maintain a stable internal environment or homeostasis [21- 22]. Interference of the normal functions of these communication systems sets in motion a series of adverse physiological activities, including disruption of the hormonal control of metabolism and energy levels, electrolyte balance, growth and development, and reproduction of the body. These disruptions, in turn, inhibits the body’s ability to respond to effectively and appropriately adapt to changes in body temperature or the electrolyte composition of the body’s fluids, response to stress and injury, and psychological and behavioral disorders [1, 22-24]. As for the nervous system, excessive consumption of alcohol disrupts the vital hormonal flow of the hypothalamic-pituitary-adrenal HPP axis that is responsible for cognitive brain functioning. The HPP axis includes two neuropeptides called arginine vasopressin (AVP) and oxytocin.

Other research has focused on the progressive alterations in the HPA axis function crucial for understanding the underlying brain mechanisms of substance use, including excessive alcohol consumption disorders. These studies found that in contrast to mood and affective disorders, alcohol dependence has a biphasic effect on HPA axis dynamics as a person traverses through the various phases of heavy hazardous drinking, including dependent alcohol, withdrawal, abstinence, and relapse. Generally speaking, these developmental stages seem to be mirrored by a shift between hyper- and hypo-responsiveness of the HPA axis to stressful events [25]. For example, hyper-responsiveness has been identified in people with a family history of alcoholism [8,10], a population that is at increased risk for alcohol dependence (Windle 1997). Thisfinding raises the question of whether heightened stress responsivity is clinically meaningful to the development of alcoholism. This view is supported by studies showing that cortisol responsivity correlates with the activity of the regulatory function of the nervous system called the mesolimbic dopaminergic pathway, which is a central neural reward pathway [8,26]. The transition to alcohol dependence leads to compensatory allostatic mechanisms result in injury to HPA axis function and elevation of stress peptide levels (e.g., corticotropin-releasing factor (CRF) in brain regions outside the hypothalamus. Allostasis refers to the process through which various biological processes attempt to restore homeostasis when an organism is threatened by multiple types of stress in the internal or external environment [3,27]. Allostatic responses can involve alterations in the HPA axis function, the nervous system, various signaling molecules in the body, or other systems. Allostatic changes in HPA axis function have been posited to, among other things, injure brain reward pathways, contribute to depressed mood (i.e., dysphoria) and craving, and further contribute to the maintenance of problem drinking behavior.

A close examination of the physiology of the hypothalamicpituitary- adrenal (HPA) axis reveals that the body responds to stress with automatic, allostatic processes aimed at returning critical systems to a set point within a narrow range of operation that ensures survival [3,4]. These automatic processes consist of multiple behavioral and physiological components. Perhaps the best-studied element in the stress response in humans and mammals is the activation of the HPA axis. This line of inquiry has found that the neurons in the paraventricular nucleus (PVN) of the hypothalamus release two neurohormones-CRF and arginine vasopressin (AVP)-into the blood vessels connecting the hypothalamus and the pituitary gland (i.e., hypophysial portal blood). Both hormones stimulate the anterior pituitary gland to produce and secrete adrenocorticotropic hormone (ACTH) into the general circulation. The ACTH, in turn, induces glucocorticoid synthesis and release from the adrenal glands located atop the kidneys.

The main glucocorticoid in humans is cortisol, which frequently is used as model systems to investigate the relationship between stress and alcohol use, which is corticosterone. Hypothalamic activation of the HPA axis modulated a variety of brain signaling (i.e., neurotransmitter) systems. Some of these systems have inhibitory effects (e.g., g-aminobutyric acid [GABA] and opioids), whereas others have excitatory effects (e.g., norepinephrine and serotonin) on the PVN. These effects suggest that the central nervous system (CNS) and the hormone (i.e., endocrine) system are tightly interconnected to coordinate glucocorticoid activity [28]. The HPA system carefully modulates through negative-feedback loops designed to maintain predetermined hormone levels (i.e., setpoints) and homeostasis. To this end, Hermann [28] asserts that secretion of CRF, AVP, and ACTH in part controlled by sensitive negative feedback exerted by cortisol at the level of the anterior pituitary gland, PVN, and hippocampus.

Iovino [18] suggest that there are two types of receptors for cortisol-mineralocorticoid (type-I) and glucocorticoid (type- II) receptors-both of which participate in the negative feedback mechanisms. Cortisol binds more strongly (i.e., has higher binding affinity) for the mineralocorticoid receptors (MRS)1 than the glucocorticoid receptors (GRs). Because of this difference in a critical relationship, the MRS help maintain the relatively low cortisol levels circulating in the blood during the regular daily (i.e., circadian) rhythm. Only when the cortisol concentration is high (e.g., during a stressful situation) does it bind to the GRs with lower affinity; the resulting activation of the GRs terminates the stress response. This delicate negative feedback control mechanism maintains the secretion of ACTH and cortisol within a relatively narrow bandwidth [29]. This process is a critical homeostatic mechanism because it regulates too much or too little exposure AVP secreted in response to osmotic stimuli. Also, it restricts the concentration of dissolved molecules (i.e., osmolality) in the blood fluid by retaining water in the body and constricting blood vessels [18,29]. Some AVP is released directly in the brain, and research suggests that it play an essential role in social behavior, sexual motivation and pair bonding, as well as maternal response to stress (Dorin et al. 2003; Ehrenreich et al. 2010).

Excessive alcohol consumption lowers the level of AVP to the brain leading to impaired cognitive performance (Laczi 1987). Like AVP, oxytocin is produced by both magnocellular and parvocellular neurons of the hypothalamus and functions both as a peripheral hormone and a signaling molecule in the central nervous system Buijs [30] to regulate adaption of the body to respond effectively to internal physiological and environmental changes or disruptions. Research on people with a history of excessive alcohol consumption shows that hyperresponsiveness of the stress response is mediated by the HPPA axis [8], leading to mental health problems. Research on animals found acute ethanol administration to rats increased plasma ACTH and corticosterone levels by enhancing CRF release from the hypothalamus [31-32]. Chronic alcohol consumption is associated with anxiety-producing (i.e., anxiogenic) Behavior [33]. Collectively, these studies show that excessive or chronic alcohol consumption attenuates basal ACTH and corticosterone levels and increases stressful and anxiogenic behaviors. Other studies have found an association between excessive alcohol consumption and depression among young adults [34-36].

Rate of excessive alcohol consumption in Cumberland, North Carolina

The Center for Disease Control and Prevention (CDC) reports that Cumberland County’s rate of people drinking five or more drinks of alcohol in one seating of 11.2% is higher than North Carolina State’s rate of 10.5%. Disease prevalence data and study findings suggest that our target populations have a more severe than expected alcohol abuse problem that makes them vulnerable to alcohol-related HIV infection. The CDC also estimates that Cumberland County’s rate of people drinking five or more drinks of alcohol in one seating of 11.2% is higher than North Carolina State’s rate of 10.5% [2]. The North Carolina Department of Health and Human Service (NCHHS) reports that Cumberland County continues to battle against sexually transmitted diseases. North Carolina Department of Health and Human Services reports that in 2013, there 1,339 persons living with HIV infection (PLWHI) in Cumberland County. Of this total, 866 had HIV, and 473 had AIDS. There were 158 PLWHI young adults ages 15-24 years old, representing 0.6% with a corresponding HIV infection rate of 27.7 per 100,000 population in Region 5, which includes Cumberland County. This HIV infection rate is higher than North Carolina’s rate of 25.7 per 100,000 people. Desegregating the PLWHI.rate by regionshows that the rate in Region 5, which includes Cumberland County by race/ethnicity,reveals that except for Hispanics and Asian/Pacific Islanders, the rate of PLWHI for Region 5 was higher than that of North Carolina, with the PHLI.Rate and percent of Americans of 4.9% and 189.6 per 100,000 population areseven times higher than North Carolina’s 0.7% and 175.2 per 100,000 people; African Americans were 69.4% and 710.4 per 100,000 people compared to North Carolina’s 65.4% and 857.8 per 100,000 people. This prevalence data suggest that higher than expected level of HIV infection among our target populations, and hence a need for evidence-based intervention.

Rate of HIV infection in cumberland county, north carolina

North Carolina Department of Health and Human Services report that in 2013, Cumberland County had 97 newly diagnosed HIV infections, which rank 3rd among all North Carolina Counties in newly diagnosed HIV infection rate with 26.0% HIV infections per 100,000 population (97 cases) compared to NC. rate of 15% per 100,000 people. From 1983 to 2013, Cumberland County had a cumulative number of HIV cases of 2,087, which ranks 6th out 100 Counties in North Carolina. During the same period, the County had 910 increasing cases of AIDS, which ranks 6th among the 100 counties in North Carolina. North Carolina State Center for Health Statistics (NCSCHS) reported that during the period 2007- 2011, Cumberland County’s HIV rate of infection of 27.3/100,000 population was 1.54 times higher than the State of North Carolina’s HIV infection rate of 17.7 per 100,000 people. Also, NCSCHS reported that during 2007-2011, Cumberland County’s total AIDS rate of 3.4p/100,000 population was 1.7 times higher than North Carolina State’s overall AIDS rate of 2.0 p/100,000 population and 13% higher than all its peer counties, except for one (Mecklenburg County) in the State of North Carolina.

Theoretical Framework

Theoretical approaches to prevention have three primary assumptions. First, they view prevention as a proactive process by which conditions that promote the well-being of an individual. Prevention activities empower individuals and communities to meet the challenges of life events and transitions by creating conditions and reinforcing individual and collective behaviors that lead to healthy communities and lifestyles. Second, prevention requires multiple processes on multiple levels to protect, enhance, and restore the health and well‐being of high sexual risk populations. Such as minority young adults in Cumberland County. Third, prevention involves an understanding of risk and protective factors that vary among individuals, age groups, racial and ethnic groups, communities, and geographic areas.

Theories, models, and data that allow for the explanation and understanding of sexual risk and protective factors at several levels of social aggregation-community, school, peers, family, and the individual’s characteristics-provide a rational approach to designing appropriate prevention strategies and programs. Risk factors exist in clusters rather than in isolation. Research has shown that these multiple risk factors have a synergistic effect (i.e., the interactions between these risk factors have a more significant impact than any single risk factor) alone. For example, some of the behaviors that put people at heightened risk of contracting and spreading HIV are excessive alcohol consumption, illicit substance, and tobacco use, and having sex with multiple sex partners.

The Comprehensive HIVPrevention Program (CIHPP)

CIHPP is essentially a derivative of Bronfenbrenner’s [37] ecological epistemology framework, which asserts that health risk behaviors such as excessive alcohol consumption, involves complex interactions between social and biological factors [38] March &Susser, 2006; Dalhberg& Krug, 2002; [39] Schiberner et al., 2001. This approach to health risk behavior prevention is considered the most effective evidence-informed strategy to prevent the spread of HIV and other infectious diseases among at-risk populations. This framework emanates from Jessor’s [40] problem behavior theory (PBT), which proposes interrelated concentric domains of risk factors beginning with the individual level, the neighborhood or community level, and societal level [37,39]. Specifically, the states that young adult health risk factors consist of a personality system, social environment, and behavior. The approach extends to the domain of psychosocial theory that views health risk behaviors as co-occurring [40-41] among young adults. Hence, assessing the effectiveness of prevention programs should include examining the association between externalizing problems (such as alcohol consumption) and internalizing problems (such as depression, anxiety, cognitive impairment, and disruptive behavior). Therefore, as suggested by [37], effective prevention strategies should identify and address the prevention of sexually transmitted infections among high-risk individuals and communities at all four levels (i.e., individual, interpersonal, organization, and societal).

The individual level is considered the microsystem where individuals work within their family and home environment, school and peers, work-peer networks, peer support, family support, parental mentoring, and parental involvement in health risk behaviors networks. [37,40-42]. This individual-level characteristic is nested within the broader community, consisting of community norms, attitudes regarding health risk behavior, cultural standards, gender norms, spiritual and religious norms, and ideological and political norms. The prevalence of individual-level health risk behaviors may include having multiple sex partners, having sex without condoms, having concurrence partnerships, sharing infected needles, and readily available alcohol, illicit substance, and tobacco. The prevalence of interpersonal risk behavior is social and sexual network structure (i.e., network size, density, mixing, and turnover) and compositional factors (i.e., characteristics of network members) that influence vulnerable to HIV infection and transmission such as minority young adults HIV transmission [43].

Community-level risk factors include the density of alcohol, tobacco, illicit substance and tobacco outlets, and community social and economic disadvantages, crime, and homelessness [44- 47]. Societal level sexual risk factors consist of public policies that shape the environment of the community, such as policies that promote high density of alcohol and other risky sexual behavior products outlets in poor and minority neighborhoods, leading to segmentation of drinkers in hot spots for HIV risk behaviors and HIV transmission [46]. Also, societal health risks may include institutional racism, stigma, segregation, formal and informal public policies, and religious and cultural norm [44,47].

The macro-policy level may also include the biological and physiological status of essential systems of the body that regulate behavior, including the nervous system, endocrine system, the digestive system, immune system, and renal system. The macropolicy level consists of advertisements and marketing policies related to health risk behaviors [37,39]. Hence, effective prevention strategies and procedures should include considering all these multiple interrelated spheres of influence on behavior to achieve desired health outcomes.

The ecological epidemiology framework of the comprehensive HIV prevention program germane to our study implies identifying the prevalence of HIV infection and transmission rates in the target population by conducting needs assessments of measurable constructs at each level or domain of influence, at cross-level connections at both the micro and macro levels, as well as by examining the macrosocial and microsocial or protective factors (risk regulators) that can either constrain or promote the occurrence of individual-level behavior associated with the risk of HIV infection [48]. The needs assessments, in turn, provide objective data for developing a strategic HIV prevention plan for the target population and community. So far, no research that we know of have has validated the psychometric properties of the expected outcome of CHIPP, as well as an evaluation of the desired results of this prevention intervention strategy, including an increase in excessive alcohol consumption risk awareness, decrease in excessive alcohol consumption. So far, there has been no study that we know of has determined the change in behavior in the behavior of participants over time using the latent growth curve model within the framework of structural equation modeling.

Purpose of the Study

The purpose of this study is to begin a line of inquiry to fill this gap in research by examining the effectiveness of the Comprehensive Integrated HIV Prevention Program in raising awareness and decreased the involvement of risky sexual behaviors among minority young adults. We expect that the study to provide public policymakers, stakeholders, and practitioners with reliable and valid policy-relevant information relied upon in designing efficient and effective public policies to reduce the spread of HIV infection among this vulnerable population.

Research question

This study sought to provide an empirically-ground answer to the following two research questions:

• What is the effectiveness of the comprehensive, integrated HIV prevention program in raising excessive alcohol consumption risk awareness of minority young adults?

• What is the excessiveness of the comprehensive, integrated HIV prevention program in reducing excessive alcohol consumption of minority young adults?

• Research Hypothesis

• The Comprehensive Integrated HIV Prevention Program (CIHPP) effectively increases excessive alcohol consumption risk awareness of minority young adults.

• The (CIHPP) is effective in reduces excessive alcohol consumption among minority young adults.

Materials and Method

Research design

The study used a pre-experimental One-shot latent growth curve (LGC) model case Study Design) [49-53]. Figure 1 displays a schematic representation of the design. Treatment Post-test X OT1 OT2…. OTn.

Where X is the participation level of minority young adults in the comprehensive, integrated HIV prevention program, O2 is the level of minority young adults’excessive alcohol consumption risk awareness and excessive alcohol consumption. A limitation of this type of research design is the lack of a control group. However, latent growth curve modeling within the framework of the structural equation model modulates this limitation by having six main advantages over the traditional longitudinal research design. Specifically, the LGC modeling approach to evaluating change has six important unique features that make it superior to other longitudinal procedures in assessing domain outcomes change over time. First, the method can accommodate anywhere from three to thirty waves of longitudinal data equally well. Indeed, Willett (1988,1989) has shown that the more waves of data collected, the more precise the estimated growth trajectory and higher will be the reliability of the measurement of change. Second, there is no requirement of the time between each wave of assessments to be equivalent, which suggests that the LGC modeling approach can comfortably accommodate irregularly spaced measurements with the caveat that the same set of occasions measures participants.

Third, personal change can be represented by either a linear growth or a non-linear growth trajectory, although linearity is usually assumed. The assumption is tested, and the model respecified to address curvilinearity if need be. Fourth, in contrast to traditional longitudinal methods used in measuring change, the LGC allows not only for estimating measurement error and accounts for autocorrelation but also for fluctuation across the time when the test for the assumptions of independence and homoscedasticity is untenable. Fifth, the multiple predictors of change can be included in LGC as fixed or time-varying [54]. Finally, the independence of measurement error variances and homoscedasticity of measurement can be tested by comparing nested models [54].

Participants and Procedure

Participants in this study were a random sample of minority young adults (18-24 years old) living in a high prevalent community in the southeastern United States who volunteered to participate in the study. Upon getting the Institutional Review Board’s (IRB) approval of the study questionnaire and proposal, culturally and linguistically appropriate announcements and advertisements were was send out to residents of the high HIV prevalence community through various minority young adult outlets, including social media, radio, print media, community organizations, word-ofmouth, and distribution of flyers inviting them to attend community health events and participate is a healthy living event.

Minority young adults who volunteered to participate in the study were informed that a survey would be conducted periodically over 24 months to obtain their opinion about key risky behaviors, such as excessive alcohol consumption risk awareness, excessive alcohol consumption, that may predispose people to HIV infection. The minority young adults who agreed to participate were given a linguistically and culturally appropriate consent form to read, sign, and return. The consent stated that their participation in the survey was strictly voluntary; they may either opt not to participate in the study or not provide a response to any of the statements; their identity will not appear in any report; a $30 gift card will be given to them as an incentive for fully participating in the surveys. The minority young adults who agreed to participate in the study were provided with a linguistically appropriate consent form to read, sign, and date. The consent form explained to the community residents that their participation was voluntary and that their identity would be kept strictly confidential, and their names would not appear in any report.

The survey instrument used in this study is the National Minority Substance/HIV Prevention Initiative Adult Questionnaire approved on March 15, 2016, by the United States Office of Management and Budget, containing a total of health risk-related constructs and over 56 items. The Questionnaire included over 100 constructs, 70 measurement items, and demographic information of the participants. Upon the Institutional Review Board (IRB) approval, we administered the survey to the participants who volunteered, read, and signed the consent form. We adhered to all American Psychological Association research guidelines. The survey was anonymous in that no identifying information was connected to individual participants or included in the study data set. The participants completed the study in less than 25 minutes during the HIV prevention events and returned them before leaving. A total of 518 minority young adults participated in the survey, and 498 of them completed the entire survey representing a 96 percent response rate. A small sample of the to check for internal consistency reliability of the items measuring the three constructs of interest using Cronbach’s Alpha Reliability test. The test produced five items measuring excessive alcohol risk awareness, and two items measuring excessive alcohol consumption.

Measures

The items measuring excessive alcohol consumption risk awareness and alcohol consumption were: Alcohol consumption risk awareness was measured by three items such as “How much do people harm themselves physically or in other ways when they have five or more drinks of an alcoholic beverage once or twice a week? The items were scored on an ordinal Likert Scale ranging from 0 days = 0 to 30 days = 30. Excessive alcohol consumption was measured by five items, such as, “Have you ever felt bad or guilty about your drinking? The questions were scored on an ordinal Likert Scale ranging from 0 days = 0 to 30 days = 30.

Statistical Analysis

This study used the latent growth curve modeling (LGC) within the SEM framework to evaluate the intraindividual and interindividual change of excessive alcohol consumption risk awareness and excessive alcohol consumption CIHPP participant overtime. The hierarchical levels to use in assessing invariance consist of

• Configural Invariance test to determine if the same factor structure exists in all groups.

• Metric Invariance to test whether the loading estimates are equal in all group, which allows comparisons of relationships.

• Scalar Invariance to verify whether the intercept terms for all equations are similar in all groups which allow for comparisons of means.

• Factor Covariance Invariance to test whether the covariances matrix among latent constructs is the same in all groups.

• Factor Variance Invariance to test whether the factor variances are the same in all groups.

• Error Variance Invariance to test whether error variance terms are the same in all groups.

The analytic method used to assess the psychometric properties of the National Minority SA/HIV Prevention Initiative Adult Questionnaire (NMSPIAQ) consists of four interrelated SEM procedures. First, Exploratory Factor Analysis (EFA) to assess the factorability of each factor and evaluate the internal consistency (i.e., Cronbach’s alpha) of the psychometric properties of NMSPIAQ using SPSS version 26.0. Second, single group Confirmatory Factor Analysis (CFA) of NMSPIAQ determines the construct and content validity of NMSPIAQ. Third, a series of Multi-group C.F.A. to test the invariance of NMSPIAQ across static factors groups. Fourth, Latent Growth Curve (LGC) modeling within the SEM framework using Analysis of Moment Structure (AMOS) version 26.0 to answer questions about systematic intra-individual BOP innate and inter-individual BOP innates differences in change over time of a minority young adult’s likelihood of excessive alcohol consumption. AMOS statistical software version 26.0 was used to conduct the second through the fourth analysis. A description of each of these procedures is presented below.

Exploratory factor analysis - The first phase of the data analysis involved assessing the reliability or internal consistency of the primary CIHPP outcome constructs by performing an exploratory factor analysis (EFA) to determine the meaningful factor loading structure of the items or observed variables were measuring the CIHPP outcome constructs. The EFA began by checking the assumptions necessary for proceeding with factor analysis. The check involved assessing the degree of intercorrelation of the items from both the overall and individual variables perspectives. The overall measure of intercorrelation was evaluated by

• Computing the partial correlation or anti-image correlation among the variables, with small values indicating the existence of “true” factors in the data [55].

• Performing Bartlett’s Test of Sphericity, with significant approximate chi-square (χ) indicative of significant correlation among at least some of the construct’s observed variables;

• Estimating the Kaiser-Meyer-Olkin Measure of Sampling Adequacy (MSA) value, with MSA values above .50 considered acceptable to proceed with factor analysis [55].

The variable-specific measure of intercorrelation was assessed by estimating the Kaiser-Meyer-Olkin (KMO) measure of sampling adequacy (MSA) value for each observed variable or item with values below .50 considered to be unacceptable [55-56]. The variable with the lowest MSA value was deleted, and the factor analysis was repeated. This process continued until all the observed variables had acceptable MSA values, and a decision was made to proceed with factor analysis. Principal component factor analysis applying the varimax rotation was used to reduce or organize the item pool into a smaller number of interpretable factors. The number of factors was determined by joint consideration of Cattell’s (1966) scree plot, a priori, and the percentage of factors to be extracted criteria [55]. The latent root residual (eigenvalue) criterion was considered inappropriate if the number of observed variables fells below or outside the acceptable range of 20 to 50 [55]. [57] principle of simple structure using pattern coefficients of absolute 0.35 as the lower bound of influential per factor and interpretability of the solution used to determine the final solution Lambert & Durant, 1974; [55]. After rotation, variables with crossloading and communalities lower than .50 were deleted [55].

The second step of the analysis involved reviewing the items measuring each dynamic factor by calculating the internal consistency estimates (Cronbach’s alpha) for the items representing each factor retained from the exploratory factor analysis procedure. Cronbach’s alpha of 0.6 was considered the minimum acceptable level of internal consistency for using a factor [55]. For factors with Cronbach’s alpha below this minimum benchmark, the internal consistency of the factor was improved by identifying and removing items with low item-test correlation and item-rest correlation. The factor was deleted if no improvement in the reliability score occurred.

Single group confirmatory factor analysis

After establishing the reliability of the CIHPP expected outcomes constructs, the constructs were validated by performing a single group CFA. This validation involved testing for the factorial stability of each CIHPP outcome construct. This test aimed to determine the extent to which items designed to measure each CIHPP outcome factor (i.e., latent construct) do so. Because the analysis was performed on original data and not data summary, missing data were accommodated using the full information maximum likelihood (FIML) procedure. This procedure allowed the maximum likelihood estimation to be performed on a dataset containing missing data, without any form of imputation [58]. Several indices were used to evaluate the goodness of fit of the 6-factor orthogonal CIHPP measurement model.

The guidelines for determining model fit consisted of adjusting each index cutoff values based on model characteristics as suggested by simulation research that considers different sample size, model complexity, and degree of error in the model specification as a basis for determining how various accurate indices performed [55,59]. The model’s absolute fit was assessed using chi-square statistic, χ2, with low, insignificant χ2 considered a good fit [55]. The incremental fit was evaluated using Root Mean Square Errors of Approximation (RMSEA) with a value less than 0.8 indicating a relatively good fit, along with Comparative Fit Index (CFI) and Tucker-Lewis Index (TLI) with a value of 0.97 or greater considered desirable [55, 59-60]. Convergent validity among items was determined by estimating the unstandardized factor loadings and Cronbach’s alpha with significant loadings and alpha of 0.70 or higher considered good reliability [55]. Construct validity of the model was evaluated by examining the completely standardized factor loadings with approximately factor loadings of 0.5 or higher and construct reliability (Cronbach’s alpha) equal or greater than 0.7 considered to be a good fit [55]. Also, a parametric test of the significance of each estimated (free) coefficient was performed. Insignificant loadings with low standardized loading estimates were deleted from the model.

The completely standardized loadings were examined for offending estimates to assess problems with the model, such as loadings above 1.0. Any identified offending estimates were dropped from the model. Finally, internal consistency estimates (Cronbach’s alpha) were calculated for the item representing the CIHPP outcome factor retained. Cronbach’s alpha of 0.7 was considered as a minimum acceptable level of internal consistency for retaining the factor [55]. For factors with Cronbach’s alpha below this minimum threshold, an attempt to improve the internal consistency was made by identifying and removing items with low item-test correlation and item-rest correlation (Nunnally & Bernstein, 1994). If no improvement of the reliability score occurred, the factor was deleted from the model of the construct. The likelihood that the model’s parameter estimates from the original sample will crossvalidate across in future samples was assessed by examining the [61] consistent version of the AIC (CAIC) with lower values of the hypothesized compared to the independent and saturated models considered to be an appropriate fit. The likelihood that the model cross-validates across similar-sized samples from the same population was determined by examining the Expected Cross- Validation Index (ECVI) with an ECVIvalue for the hypothesized model lower compared to both the independent and saturated models considered to represent the best fit to the data. Finally, [62] Critical N (CN) was examined to determine if the study’s sample size is sufficient to yield an adequate model fit for a χ2 test [59] with a value over 200 for both .05 and .01 CN indicative of the CIHPP outcome measurement model adequately representing the sample data [49]. The normality of the distribution of the variables in the model was assessed by Mardia’s (1970; 1974) normalized estimate of multivariate kurtosis with a value of 5 or less reflexive of normal distribution. Multivariate outliers were detected by computation of the squared Mahalanobis distance (D2) for each case with D2 values standings distinctively apart from all the other D2-values indicative of an outliers

Multi-group analysis

After validating the factorial structure of NMSPIAQ, we proceeded to conduct a series of multiple groups CFA to test the invariance of CIHPP outcome factors across static factors groups. The multiple-group analysis of this study involved performing three types of CFA. First, examining the factorial invariance of CIHPP outcome factor scales (1st Order CFA Model). Second, testing the invariance of dynamic factor mean structure. Third, testing the invariance of CIHPP factors causal structure. The central concern of measurement invariance was testing measurement equivalence across groups [63]. We conducted the test at two types of models that frequently used: first-order models and second-order models (Little,1997). These tests are the recommended procedures for testing measurement invariance across a hierarchical series of models, and their common purpose is maximizing the interpretability of the results sought at each step of the hierarchy [64].

Latent growth curve (LGC) modeling

The LGC modeling within the SEM framework was relied upon to evaluate the excessive alcohol consumption risk awareness and excessive alcohol consumption of each minority young adult periodically, including indicators of progress and regression of time-invariant predictors CIHPP outcome domains in case of the presence of heterogeneity of dynamic factor variance. Unlike like the usual “scape shots” approach of taking the status of outcome domains of interest before and after an intervention such as CIHPP time-invariant and dynamic factors, the LGC model captures the actual development of the processes and outcome domains of interest following a trajectory over time to reveal the intricacies of intra-individual and inter-individual changes of the study participants. Therefore, the approach capitalizes on the richness of continuous multi-wave data to provide a somewhat superior program evaluation approach for answering questions about systematic intra-individual and inter-individual change among minority young adult CIHPP participants during 24 months [65- 67].

The next step was to assess an increase or decline in change over time for one or more CIHPP domain of interest. A representative sample of the participants was tested systematically over time, and their status in each CIHPP domain outcome was measured on several temporal-spaced occasions based on four conditions [65]. First, the outcome variable of the domain of interest must be an interval level of measurement [68-69]. Second, while the time lag between occasions can maybe evenly or unevenly spaced, both the number and spacing of these assessments must be the same for all CIHPP participants. Third, when the focus is on individual CIHPP participants, data must be obtained for each CIHPP participant on three or more occasions, and change is structured as an LGC model, with analyses conducted using the SEM procedure. Finally, the sample size must be large (i.e., a minimum 200) enough to allow for the detection of person-level effects [65] Bootsma, 2005; Bootsma & Hoogland, 2001). Our proposed LCG model met all of these four conditions.

The basic building block of the LGC model comprised of two sub-models referred to as Level 1 model and Level 2 model [65]. Level 1 model is a within-person regression model representing an individual’s change over time of the outcome variables, which in our case are the five CIHPP outcome domains mentioned earlier. Level 2 model is the between-person model that focuses on inter-individual differences in CIHPP outcome factors change over time. Level 1 (i.e., intraindividual minority young adult change) focuses on capturing the measurement model, which is the portion of the model that incorporates only linkages between the observed variables of the measurement instrument and their underlying observed or latent construct or factor (i.e., likelihood of excessive alcohol consumption). As in any measurement model, the primary interest is the strength of the factor loading or regression paths linking the observed variable to the unobserved variable. The only parts of the model that are relevant in the modeling of intraindividual change are the regression paths linking the observed variables to the unobserved factor (both intercept and slope), the factor variances and covariances, and the related measurement errors associated with these observed variables. This part of the modeling is an ordinary factor analysis model with the following two distinctive features. First, all the loadings are fixed (i.e., there are no unknown factor loadings). Second, the pattern of fixed loadings plus the mean structure allows us to interpret the factors as intercept and slope factors. As in all factor models, the present case argues that each minority young adult’s likelihood of excessive alcohol consumption at each temporal time point (i.e., Time 1=0; Time 2=1; Time 3 = 2), are a function of three distinct components:

• A factor loading matrix of constants (1:1:1) and known time values (0:1:2) that remain invariant across all individual BOP innates, multiplied by.

• A latent growth curve vector containing particular minority young adult-specific and unknown factors called particular CIHPP participant growth parameter (Intercept, Slope), plus.

• A vector of individual minority young adult-specific and unknown errors of measurement [49]. Whereas a latent growth curve vector represents the within-person actual change in the likelihood of excessive alcohol consumption over time, the error vector represents the within-person likelihood of excessive alcohol consumption “noise” that serves to erode these actual change values [65].

Level 2 argues that, over and above the hypothesized linear change in CIHPP outcome domains over time, trajectories will necessarily vary across CIHPP participants due to differences in intercepts and slopes. Within the framework of SEM, this portion of the model reflects the “structural model” component, which in general portrays relationships among unobserved factors and postulated relations among their associated residuals. However, within the more specific LGC model, this structure is limited to the means of the Intercept and Slope factors and their related variances, which represent deviations from the means. The means carry information on individual differences in intercept and slope values. The specification of these parameters, then, makes possible the estimation of interindividual differences in change. AMOS 26.0 Graphics were used to test the latent Growth Curve Model 1 and Model 2. AMOS was also used to test the LGC. Models with static factors as a time-invariant predictor of change. This test aimed to determine if the static variable can explain statistically significant heterogeneity in the individual growth trajectories (i.e., intercept and slope) of CIHPP outcome domains as time-invariant predictors of change. Specifically, this later test aimed at answering two questions. First, “Do the CIHPP outcome domains differ for the subsets of a static factor at time 1?” second, “Do the CIHPP outcome domains change over time differ over time for a subset of a static?” The answer to these questions used the predictor “static factor,” or variable incorporated into the Level 2 (or structural) path of the model. This predictor model represented an extension of our final best-fitting multiple domain model (Model 3).

The following four new structural model components were included in the measurement models. First, the regression paths that flow from the static factors to the intercept and slope factors associated with CIHPP outcome domains are of primary interest in this predictor model as they hold the key in answering the question of whether the trajectory of CIHPP outcome domains differs for the subset groups of the static factor. Second, there is now a latent residual associated with each of the intercept and slope factors. This addition is a requirement as these factors are now dependent variables in the model due to the regression paths generated from the predictor variables of the static factors. Given that dependent variables cannot be estimated in SEM, the latent factor residuals served as proxies for the intercept and slope factors in capturing the variances. These residuals represented variation in the intercepts and slopes after all variability in their prediction by the static factors has been explained [67]. Third, the covariances link the appropriate residuals rather than the factors themselves. Finally, the means of the residuals were fixed to 0.0.

The first step in building the LGC model involved determining the direction and extent of change in outcomes of each CIHPP participant’s scores over the specified time of participation in the CIHPP programming. Following [49] protocol for determining and testing the LGC model, the shape of the growth trajectory was known in advance and the LGC assumption of modeling linearity, which states that the specified model should include the following two growth parameters: (a) an intercept representing an individual CIHPP participant’s domain outcome score on the outcome variable at time 1, and (b) slope parameters representing an individual CIHPP participant’s rate of change throughout the period. In our study, the intercept described a CIHPP participant’s CIHPP excessive alcohol consumption awareness and excessive alcohol consumption scores at the beginning of the intervention; and the slope represented the rate of change of the two constructs of interest scores over the 24-month transition. The hypothesized link between the individual growth parameter (i.e., the intercept and the slope) of levels one and level two models were considered analysis of change in the CIHPP process and outcome domains.

The first step in building the LGC model involved determining the direction and extent of change in outcomes of each CIHPP participant’s scores over the specified time of participation in the CIHPP programming. Following [49] protocol for determining and testing the LGC model, the shape of the growth trajectory was known in advance and the LGC assumption of modeling linearity, which states that the specified model should include the following two growth parameters: (a) an intercept representing an individual CIHPP participant’s domain outcome score on the outcome variable at time 1, and (b) slope parameters representing an individual CIHPP participant’s rate of change throughout the period. In our study, the intercept described a CIHPP participant’s CIHPP excessive alcohol consumption awareness and excessive alcohol consumption scores at the beginning of the intervention; and the slope represented the rate of change of the two constructs of interest scores over the 24-month transition. The hypothesized link between the individual growth parameter (i.e., the intercept and the slope) of levels one and level two models were considered analysis of change in the CIHPP process and outcome domains.

Results

The results of this study consist of estimates of mean, covariance, and variance of the latent growth curve model of two CIHPP effectiveness in raising excessive alcohol consumption risk awareness and reducing excessive alcohol consumption. The results of each of these CIHPP outcome domains are presenting below.

Effectiveness in Reducing Excessive alcohol consumption risk awareness latent growth curve model results

Mean estimate: Results of the analysis indicate that the mean estimate of excessive alcohol consumption for the intercept and the slope are statistically significant. The results reveal that the average score for excessive alcohol consumption risk awareness increased (2.863) significantly over the 24-months periods, as indicated by the value of 0.374; p = 001. (Table 1-1).

Covariance estimate: Table 1-2 shows the results of the covariance estimate between the intercept and slope factors for excessive alcohol consumption risk awareness. The results indicate that the covariance between the intercept and slope factor for excessive alcohol consumption risk awareness was statistically significant (p = .001). The positive estimate of .774 suggests that minority young adults exhibited a rate of increase in their excessive alcohol consumption awareness over the 24 months. This finding indicates that the CIHPP was effective in raising the excessive alcohol consumption risk perception of young adults under study.

Variance estimate: The variance estimate related to the intercept and slope for excessive alcohol consumption risk awareness is statistically significant (p=.001).This finding reveals substantial inter-individual differences in the original score of excessive alcohol risk perception between the young adults at the beginning of the implementation of the CIHPP and its change over time, as the young adult progressed from the beginning of the CIHPP intervention through the 24 months. Such evidence provides powerful support for further investigation of variability related to the growth trajectory. Specifically, incorporating time-invariant change into the model explains the participants’’ excessive variability of alcohol consumption risk awareness. This incorporation involves testing the latent growth curve model with the demographic or static variable as a time-invariant predictor of change [49]. This study incorporated gender in the LGC model as a predictor of growth. Table 1-3 displays the result.

Excessive alcohol consumption risk latent growth curve model results

Mean estimate: The results indicate that the mean estimate of excessive alcohol consumption risk for the intercept and the slope are statistically significant. Specifically, the findings reveal that the average score for excessive alcohol consumption (-5.016) decreased significantly over the three 6-months periods as indicated by the value of 20/662; p=001. Hence, we can conclude that CIHPP was effective in reducing excessive alcohol consumption among minority young adults. Table 2-1.Covariance estimate: The covariance between the intercept and slope factor for excessive alcohol consumption risk was not statistically significant (p= .189). The positive sign suggests that young adults exhibited a high rate of increase in their alcohol consumption over the 24 months. This finding indicates that the Comprehensive, integrated HIV prevention program was not effective in decreasing the excessive alcohol consumption of young adults under study. Table 2-2.

Variance estimate: The variance estimate related to the intercept and slope for excessive alcohol consumption risk is statistically significant (p=.001). This finding reveals substantial inter-individual differences in the original score of excessive alcohol risk perception between the young adults at the beginning of the implementation of the CIHPP and its change over time, as the young adult progressed from the beginning of the CIHPP intervention through the 24 months. Such evidence provides powerful support for further investigation of variability related to the growth trajectory. Specifically, incorporating time-invariant change into the model can explain the participant’s variability of alcohol consumption risk awareness. This incorporation involves testing the latent growth curve model with the demographic or static variable as a time-invariant predictor of change [49]. This study incorporated gender in the LGC model as a predictor of growth. Table 2-3 present the results of the variance estimate.

Regression Weight with Gender as Predictor: Gender was found not to be a statistically significant predictor of excessive alcohol consumption risk predictor of both initial status (-.001) at p = .981 and rate of change (.018) at p = .811. This finding suggests that there was no meaningful difference in excessive alcohol consumption risk between minority young adult males and females both at the beginning of CIHPP and the rate of change during the 24 months intervention period. Table 2-4. Conclusions

The Comprehensive, integrated HIV prevention program effectively raised the excessive alcohol consumption risk awareness of minority young adults under study. There is a significant interindividual difference in the original score of excessive alcohol risk perception between the young adults at the beginning of the implementation of the CIHPP and its change over time, as the young adult progressed from the beginning of the CIHPP intervention through the 24 months. Female young adult’s excessive alcohol consumption risk awareness was more significant than male minority young adults. In summation, The CIHPP effectively increased the awareness of excessive alcohol consumption risk of minority young adults. The alcohol awareness of young female adults was higher than the male minority young adult during the 24 months implementation of the CIHPP. Hence, hypothesis 1.confirmed.

Regarding excessive alcohol consumption risk, the CIHPP effectively decreased excessive alcohol consumption among minority young adults. Hence, hypothesis 2 is confirmed. There was inter-individual differences or heterogeneity in alcohol consumption among the minority young adults between minority young adult at the beginning of CIHPP intervention and through the 24 months. However, there was no meaningful difference in excessive alcohol consumption between minority young adult males and females, both at the beginning of CIHPP and the rate of change during the 24 months intervention period. In other words, the interindividual difference was not attributable to gender. Collectively, the result of this study is consistent with previous studies [38,48] March &Susser, 2006; [39,70].

Study Limitations

The study used one static variable, gender, as a predictor of excessive alcohol consumption awareness and excessive alcohol consumption risk. To more precisely evaluate interindividual change, we recommend that future studies use two or more static valuables. Also, the sample for this study was drawn from one jurisdiction, only making external validity questionable. Therefore, as a contribution to theory building, future studies two conduct the research in similar in two or more jurisdictions with similar populations. Finally, this study used a sample size of 498 minority young adults. Although this sample meets the recommended minimum threshold of a sample size of 200 for structural equation modeling [49], the sensitivity of statistical significance testing to sample size [71], we recommend that future studies should use effect size instead [72-92].

To read more about this article: https://irispublishers.com/ctcms/fulltext/a-latent-growth-model-evaluation-of-the-comprehensive-integrated-hiv-prevention-program.ID.000531.php

Indexing List of Iris Publishers: https://medium.com/@irispublishers/what-is-the-indexing-list-of-iris-publishers-4ace353e4eee

Iris publishers google scholar citations: https://scholar.google.co.in/scholar?hl=en&as_sdt=0%2C5&q=irispublishers&btnG=

[irispublishersmedicaljournals]

Iris Publishers - American Independence Day Wishes

Let’s celebrate a peaceful life in our land by remembering all national heroes who gave us freedom! Have a wonderful Independence Day!