#phase 1 trials

[phase1trials]

The Role of Phase 1 Trials in Medical Research and Innovation

Medical breakthroughs don’t happen overnight—each new drug, therapy, or treatment must pass through multiple stages of research and testing before it can be used to treat patients. The first critical step in this process is the Phase 1 clinical trial, which ensures that a potential treatment is safe for human use. While often overlooked, Phase 1 trials play a pivotal role in medical research and innovation, shaping the future of healthcare by identifying promising treatments and eliminating unsafe ones early in development.

What Are Phase 1 Trials?

Phase 1 trials are the first stage of human testing in drug development. Conducted after extensive preclinical studies (laboratory and animal testing), these trials typically involve 20 to 100 healthy volunteers or, in cases of serious diseases like cancer, patients who have exhausted other treatment options.

The primary goals of a Phase 1 trial include:

Evaluating safety by identifying potential side effects and adverse reactions.

Determining dosage by assessing the maximum tolerated dose (MTD).

Understanding drug behavior in the body, including absorption, metabolism, and elimination.

Unlike later-phase trials that focus on effectiveness, Phase 1 trials are designed to ensure that a drug is safe before it is tested on a larger population.

How Phase 1 Trials Drive Medical Innovation

1. Laying the Foundation for New Treatments

Every successful medication on the market today—including life-saving treatments for cancer, heart disease, and infectious diseases—once started as a Phase 1 trial. Without this crucial stage, many groundbreaking therapies would never advance to further testing or reach the patients who need them most.

2. Identifying Potentially Transformative Drugs Early

Phase 1 trials allow researchers to identify promising new drugs that could revolutionize treatment. If a drug demonstrates a strong safety profile and good pharmacokinetics (how the body processes it), it can move to Phase 2 trials, where its effectiveness is tested in larger patient groups.

3. Advancing Precision Medicine

With the rise of personalized medicine, Phase 1 trials are evolving to test targeted therapies designed for specific patient populations. This approach is particularly important in oncology, where drugs are developed based on genetic markers rather than a one-size-fits-all method. These trials help determine which treatments work best for individual patients, paving the way for more effective, customized care.

4. Encouraging Innovation in Drug Development

Medical research constantly seeks to develop safer, more effective, and less invasive treatments. Phase 1 trials play a key role in testing new drug delivery methods, such as:

Nanotechnology-based treatments that improve drug absorption.

Gene and cell therapies that could offer long-term or even permanent cures.

Immunotherapies that harness the body’s own immune system to fight diseases like cancer.

By testing these novel approaches, Phase 1 trials contribute directly to cutting-edge medical advancements.

5. Reducing Drug Development Costs and Risks

Developing a new drug is expensive—costing hundreds of millions to billions of dollars—and time-consuming, often taking over a decade. Phase 1 trials help pharmaceutical companies and research institutions identify potential failures early, preventing unnecessary investments in unsafe or ineffective drugs. By eliminating weak candidates early on, resources can be redirected toward more promising innovations.

Challenges and Ethical Considerations

Despite their importance, Phase 1 trials come with challenges:

Limited participant numbers make it difficult to predict how a drug will behave in larger populations.

Potential safety risks exist since the drug is being tested in humans for the first time.

Ethical concerns must be addressed, ensuring that participants are fully informed of risks and receive proper medical oversight.

Regulatory agencies like the FDA (U.S.) and EMA (Europe) enforce strict ethical guidelines to protect participants, ensuring that trials are conducted responsibly.

Conclusion

Phase 1 trials are the foundation of medical research and innovation, allowing scientists to test new drugs safely before moving on to larger trials. Without them, life-saving treatments for countless diseases would never reach patients. As medical science advances, Phase 1 trials will continue to play a crucial role in shaping the future of healthcare, offering hope for better, safer, and more effective treatments worldwide.

[intelligentchristianlady]

Amazing indeed! Read the whole thread.

[jewishcissiekj]

fun fact I'm DUMB

[clivaldatabase]

Orphan Drug Designation Benefits : What You Need to Know

In the ever-evolving pharmaceutical landscape, orphan drug development plays a critical role in addressing rare diseases—conditions that affect a small percentage of the population yet often lack effective treatments. The orphan drug development (ODD), granted by regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), provides crucial incentives for companies to invest in therapies for rare conditions.

[dravidious]

You're more amazing than love

Finished up Trauma Team, and I gotta say, the difficulty was consistently way lower than Under the Knife. Even the final Twisted Rosalia operation was easy. But wait, beating the game unlocks hard mode! I'm so sorry, I wasn't being fair, I was judging the difficulty by the first playthrough, I should really try out the hard mode to see if-

I beat hard-mode Twisted Rosalia on the first try.

So yeah, no idea what to expect for UtK2's difficulty

[dermatology-cro]

[strialternatives]

bonus:

(if atlus won't give akechi's mom a name i'll have to Do It Myself-)

Here's part 2 of the Akechi palace au with a bunch of character concepts :jazzhands: once again having a normal one lads

check out part 1 over here

some additional mechanics and a plot outline continued under the cut

The fifth and final area is the Imperial Box, this is where the Empress and the Treasure reside.

(Acceptance, Akechi must acknowledge that his old ambitions are long dead and buried so to speak. Thus, he must move forward, whatever that looks like for him personally now that all other legal avenues for redemption have been closed to him.)

The ‘treasure’ is with the Empress, a bound Hereward disguised as Mamakechi’s cognition; Goro, the Emperor, is locked within his own palace and must leave the courtroom a free man on his own two feet. Akira an’ Co have to wake him from his restful sleep and steal him from the palace while the Empress rampages. 

Boss fight includes continuously knocking Hereward down while fleeing the palace as it collapses area by area. Robin Hood and Loki help guide the Thieves out, having finally come together to share a stage.

Phase 1: The Empress will not rise from her throne, she reflects fire, physical, bless and curse attacks with a detached, disinterest as though the battle has nothing to do with her.

Phase 2: The Empress surges up in anger, using a hail of hellfire arrows on the party that must be ridden out.

Phase 3: She full heals the party and invites them to join in the palace’s festivities.

Phase 4: Her attacks start to grow lethargic and sloppy the closer the party gets to the palace entrance.

Phase 5: All of her shields are down, she can no longer reflect attacks, her facade shatters like a mirror, revealing the final palace ruler--Hereward.

Goro has a third awakening during this pursuit--Wilhelm Tell. A Swiss folk hero representing individual freedom and rebellion, a skilled hunter and father most known for shooting an apple from his son’s head at the behest of a tyrant who ultimately seeks retribution. A hero that kept to his convictions while taking control of his future, and protecting the person most important to him. 

(AKA Goro deep down craves a decent fraternal figure and alas, his own psyche and the sea of collective human consciousness decided to provide. And no, he is NOT talking about it Joker.)

Misc Palace rules/gen details:

Loki and Robin Hood hate each other which is honestly just Goro’s internal self-loathing running wild, it’s part of why they can’t exist on the same stage.

Hereward pulls Goro into the metaverse as a defense mechanism of sorts aka before Goro did something self-destructive deep down none of them wanted post-Shido’s trial.

Akechi’s palace is hostile to every intruder aside from Akira, his rival, whom he’ll always see as a threat but respects and trusts more than anyone else. This results in every enemy but his own shadows targeting the rest of the party. They also abide by the "Oracle is off limits" rule. Fights in general are easier with a smaller team as teammates in the back lineup will also take damage.

Jazz records instead of grief seeds, every time you get one the music in the area stops.

In the audience stands there’s a cognition of Wakaba in the VIP section, the party learns about Futaba being Goro’s half-sibling. Goro sees himself in Futaba and deep down wishes he hadn’t burned all bridges on that front.

Initial Infiltration Team: Joker, Sumire, Morgana, Futaba. Haru and Makoto are at uni, Yusuke has a patron in Kyoto, Ann is overseas until a month into the palace and Ryuji is also at uni on a track scholarship until around the same time. The other thieves slowly fill in the ranks as the palace progresses, until we have a full house in the Hall of Severance.

First Layer Philosophy Puzzle Quotes: 

“He who has a why to live for can bear almost any how.” ― Friedrich Nietzsche

“Genuine tragedies in the world are not conflicts between right and wrong. They are conflicts between two rights.” ― Hegel

“The law is reason, free from passion.” ― Aristotle

“The first and greatest victory is to conquer yourself; to be conquered by yourself is of all things most shameful and vile.” ― Plato

“I shall not be present at my trial.” ― Leblanc

This is basically a loose fic outline, broad strokes, etc ;; ty to everyone who left replies and comments, they're all really sweet!

(had to get this au out or the mold would get me ya see :/)

[reasonsforhope]

"A large clinical trial in South Africa and Uganda has shown that a twice-yearly injection of a new pre-exposure prophylaxis drug gives young women total protection from HIV infection.

The trial tested whether the six-month injection of lenacapavir would provide better protection against HIV infection than two other drugs, both daily pills. All three medications are pre-exposure prophylaxis (or PrEP) drugs.

Physician-scientist Linda-Gail Bekker, principal investigator for the South African part of the study, tells Nadine Dreyer what makes this breakthough so significant and what to expect next.

Tell us about the trial and what it set out to achieve

The Purpose 1 trial with 5,000 participants took place at three sites in Uganda and 25 sites in South Africa to test the efficacy of lenacapavir and two other drugs.

Lenacapavir (Len LA) is a fusion capside inhibitor. It interferes with the HIV capsid, a protein shell that protects HIV’s genetic material and enzymes needed for replication. It is administered just under the skin, once every six months.

The randomised controlled trial, sponsored by the drug developers Gilead Sciences, tested several things.

The first was whether a six-monthly injection of lenacapavir was safe and would provide better protection against HIV infection as PrEP for women between the ages of 16 and 25 years than Truvada F/TDF, a daily PrEP pill in wide use that has been available for more than a decade.

Secondly, the trial also tested whether Descovy F/TAF, a newer daily pill, was as effective as F/TDF...

The trial had three arms. Young women were randomly assigned to one of the arms in a 2:2:1 ratio (Len LA: F/TAF oral: F/TDF oral) in a double blinded fashion. This means neither the participants nor the researchers knew which treatment participants were receiving until the clinical trial was over.

In eastern and southern Africa, young women are the population who bear the brunt of new HIV infections. They also find a daily PrEP regimen challenging to maintain, for a number of social and structural reasons.

During the randomised phase of the trial none of the 2,134 women who received lenacapavir contracted HIV. There was 100 percent efficiency.

By comparison, 16 of the 1,068 women (or 1.5%) who took Truvada (F/TDF) and 39 of 2,136 (1.8%) who received Descovy (F/TAF) contracted the HIV virus...

What is the significance of these trials?

This breakthrough gives great hope that we have a proven, highly effective prevention tool to protect people from HIV.

There were 1.3 million new HIV infections globally in the past year. Although that’s fewer than the 2 million infections seen in 2010, it is clear that at this rate we are not going to meet the HIV new infection target that UNAIDS set for 2025 (fewer than 500,000 globally) or potentially even the goal to end Aids by 2030...

For young people, the daily decision to take a pill or use a condom or take a pill at the time of sexual intercourse can be very challenging.

HIV scientists and activists hope that young people may find that having to make this “prevention decision” only twice a year may reduce unpredictability and barriers.

For a young woman who struggles to get to an appointment at a clinic in a town or who can’t keep pills without facing stigma or violence, an injection just twice a year is the option that could keep her free of HIV.

What happens now?

The plan is that the Purpose 1 trial will go on but now in an “open label” phase. This means that study participants will be “unblinded”: they will be told whether they have been in the “injectable” or oral TDF or oral TAF groups.

They will be offered the choice of PrEP they would prefer as the trial continues.

A sister trial is also under way: Purpose 2 is being conducted in a number of regions including some sites in Africa among cisgender men, and transgender and nonbinary people who have sex with men.

It’s important to conduct trials among different groups because we have seen differences in effectiveness. Whether the sex is anal or vaginal is important and may have an impact on effectiveness.

How long until the drug is rolled out?

We have read in a Gilead Sciences press statement that within the next couple of months [from July 2024] the company will submit the dossier with all the results to a number of country regulators, particularly the Ugandan and South African regulators.

The World Health Organization will also review the data and may issue recommendations.

We hope then that this new drug will be adopted into WHO and country guidelines.

We also hope we may begin to see the drug being tested in more studies to understand better how to incorporate it into real world settings.

Price is a critical factor to ensure access and distribution in the public sector where it is badly needed.

Gilead Sciences has said it will offer licences to companies that make generic drugs, which is another critical way to get prices down.

In an ideal world, governments will be able to purchase this affordably and it will be offered to all who want it and need protection against HIV."

-via The Conversation, July 3, 2024

[ennn]

Hold the fuck up, this isn’t a real trial.

In retrospect a number of things about the episode, especially the coven's characterisation felt off... and now on rewatch I'm pretty certain this isn't a trial of the Road at all – it's the Salem Seven punishing Agatha.

Clues under the cut with some spoilers from future scenes in trailers / promo clips.

Clue #1 – No screen aspect ratio change

As @wolfcracker points out, for the two previous trials the screen ratio changed once they entered the place (going full screen). We didn't get that for this cabin.

Clue #2 – No phase of the moon decoration at the entrance

We've had these obviously built into the previous trial entrances but there's no sign of one for this cabin.

The coven's so panicked getting chased by the locusts they don't notice it running in. The door is made of wooden planks with tiny gaps in between and you don't see a sign of any moon on the other side either.

Notably, in a trailer and promo shot, you see the moon featured prominently again for an upcoming trial, when Agatha and Billy cross a stone bridge structure and approach an entrance (presumably of the tower).

Clue #3 – Each trial has an element, this cabin doesn't

This was something that seemed odd even before this episode, we saw five weird horror movie-trope settings – assumed to be trials – in posters and promotional materials but there are only four identified elements for the Road.

Sure you could have more moon phases (like we do irl) but the Ballad that is central the show only mentions four elements: fire, water, earth, and air.

Our first two trials had strong ties with an element: if you failed you'd be killed by that element or something associated with it i.e. drowning or burning.

Now from the promos, an upcoming trial with the anti-gravity effect going on in a tower fits well with the air element. And the threat of death here is associated with going into the air (spikes in the ceiling).

Notice from the flying forms that this trial does go full-frame like the first two we certainly had (clue #1).

Another upcoming trial we know of (that looks like a morgue or asylum-like place) can be linked with the earth given that we see rocks and earth falling in a shot. Death by crushing earth.

This cabin had no element associated with it at all. The threat of death was by... Agatha siphoning your magic? Or in the case of Agatha, to be tortured forever by her mom?

Clue #4 – The trial area doesn't necessarily keep out the Salem Seven

From the promo shots of presumably the air trial (see above), we clearly see the Salem Seven in the tower attacking them. Why then did Locust and the rest of the Seven leave them alone in the cabin when they were right behind them?

Other sus elements

OK, these are more ambiguous and could be the result of bad writing but here's the other stuff in this "trial" that just seems off

The coven turns really really quickly on Agatha and viciously. And they literally just rode broomsticks where it's mentioned it's "about selflessness" and "we fly together or not at all". I mean yeah the people might lie but they were enough of a team that the magic for the broomsticks worked.

The trial's instruction was to just "punish Agatha"? That's oddly specific and pointed. Previous trials had the entire coven in danger (e.g. everyone had to drink the poison). Between this and the above point it feels like someone is mad at Agatha for killing lots of witches over the years. Some people like the Salem Seven.

The trials so far have tested the witch's ability in the craft (potion-making, protection) and how they work together. How does punishing or sacrificing Agatha align with the Road's test of "Burn and brew with coven true / And glory shall be thine" -- which we were just reminded of last week.

Jen calling and dismissing Billy as a familiar is... more mean-ness that I'd expect. You could make a case for her disliking Agatha, but the amount of venom in this moment towards the boy for trying is surprising considering she was trying to watch out for him not too long ago. Of course, it could be her frustration and fear in that moment boiling over.

Pretty much everything at the end after Billy snapping and going all dark and vengeful.

Ultimately we don't know what the Salem Seven can do. Sure they shriek like Nazgûl but turning into animals isn't the most threatening thing? So, bad writing and copium or is this show being truly tricksy and reality-bending?

[foxybrownsugababe]

𝐀𝐫𝐭𝐢𝐟𝐢𝐜𝐢𝐚𝐥 𝐈𝐧𝐟𝐚𝐭𝐮𝐚𝐭𝐢𝐨𝐧

𝐏𝐚𝐢𝐫𝐢𝐧𝐠𝐬 - Ai Michael B. Jordon x Black!OC

𝐒𝐮𝐦𝐦𝐚𝐫𝐲 - in which a woman receives a mysterious crate that changes everything she thought she knew about solitude, control, and connection.

𝐖𝐚𝐫𝐧𝐢𝐧𝐠𝐬 - Mild language, slow burn, emotional vulnerability, light sci-fi themes, let me know if I missed anything! Sorry for any spelling errors and grammar mistakes!! Go easy one me <3

𝐉𝐚𝐳𝐳𝐢𝐞’𝐬 𝐍𝐨𝐭𝐞𝐬 - I had the idea, and I thought “Why the hell not?” And here we are….

𝐖𝐨𝐫𝐝 𝐂𝐨𝐮𝐧𝐭 - 5,637+

There was no room for weakness in Nadine Nelson’s life.

Not in her closet, where the hems of her Italian suits and Asian silks hung like armor. Not in her penthouse apartment in the heart of Manhattan, with its clean marble surfaces and city skyline views. And definitely not in the courtroom, where a well-timed objection could make or break a multimillion-dollar case.

Nadine was steel, wrapped in silk.

Her alarm rang at 5:45 AM, a single chime before she cut it off and sat up. Not a single grin or anything, just a long cat stretch before rolling over and letting her feet hit the floor. And already, her mind was racing.

Deposition at 10. Client call at 1. Lunch with the DA’s assistant—, no I’m skipping that. Trial prep at 4. Court by Thursday.

She moved like a machine all while thinking. First her perfectly manicured feet slipped into her slippers before she was up and tossing her arms into her deep blue silk robe. Then she was turning on the bathroom light, standing in front of the mirror before the sound of her electric toothbrush humming filled the space. Once she put into the sink, cold water hit her face, a nice cleaned scrub applied to her skin with some expensive soap before multiple serums and creams soothed her epidermis. Then she was down the hall and into the kitchen, her domain of silence.

She barely blinked as she moved around, effortlessly pulling together an authentic espresso. Double shot, four sugars, two creamers. She sipped out of the small cup that she placed on a saucer as she made her way to the living room, clinking on the large television with a simple tap to the panel near the light switch, as well as opening the curtains to the floor to ceiling windows of the space.

It was the news on low volume, something she played in the background as she sat on the couch and began the first part of her work day, which was checking notifications. Stock tickers scrolling. Loads of emails, and real mail. Even a text from her assistant.

Jane: Morning. Confirmed meeting with Sloane. Added an extra hour for court prep. I had to push your massage again. Sorry.

Nadine didn’t even flinch. Self-care was for people with the luxury of losing. She had no such privilege. As she continued to check and sort through her things, she came across a letter, which was rare nowadays in their advanced society. But she didn’t sit to read it for long once she saw it was some sort of survey with a government seal.

C.R.I.S.

(Cognitive Robotics & Intelligence Systems)

Confidential Prototype Program | Not for Public Disclosure

To Ms. Nadine Nelson,

Congratulations.

You are one of only twenty individuals selected to participate in the private beta phase of AURA—the world’s most advanced artificial intelli-

With a sigh, she tossed the paper into the rest of the junk mails she’d gathered, not even giving it a second thought.

By 6:30AM, she was showered and dressed in navy Balmain with matching slacks, gold cufflinks fastened, and her Louboutin heels clicked against the floors like a metronome. Every detail was precise. Her eyeliner was sharp, her decently pixie bob cut was curled and bouncy, not a strand out of place.

That was the version of herself she showed the world.

The version no one saw was the one who stared at herself in any reflection for a moment too long, trying to spot any imperfections and critiquing the ones she had. The one who pressed the ends of her hand to her temple when things became too much, roughly rubbing against her skin to not panic. The one who felt the beginnings of a headache every morning before she even stepped outside.

But there was no time for that.

Today was a big day. So big that she nearly ran over one of her co-workers in the complex’s private parking lot. The woman leaned out of the window, looking at her co-worker, Simon, was entrapped within his phone, coffee in other hand.

“Simon.” She clipped as she exited the car, standing beside the driver’s side with her bag slung over her arm and her eyes narrowed like the barrel of a gun.

Her junior partner, Simon Gellar, flinched, nearly spilling his coffee. He was leaned against the concrete column next to his vehicle, relaxed as if he had no multi-million-dollar contracts waiting for him upstairs.

“Nadine! Goodmorning.” He blurted, straightening up, phone still in hand. His thin wire glasses were crooked from how fast he’d jerked up.

She leveled a gaze at him. “You’re in my line of motion. Next to my parking spot. Were you planning to get hit by my car?” She asked, and though she was being sarcastic, her stoic face didn’t lean into that notion.

Simone scrambled back, laughing awkwardly. “Sorry, sorry. I was—uh—watching something.”

“I gathered.” She pushed past him, heels echoing. Still, curiosity peeked through her otherwise impenetrable wall of ice. She pivoted at the elevator. “What was so important it made you forget spatial awareness?”

Simon followed her with a sheepish grin, lifting his phone to show a paused video. “This new AI prototype. It’s a for a government project. They’re calling it a fully integrated domestic interface. Basically a robot with a personality. They’re doing a limited civilian roll-out.” He explained.

Nadine gave a single, unimpressed glance at the screen. It was paused on a thumbnail image—what looked like a man stepping out of a delivery crate, bare-chested, perfect skin, electric-blue eyes, and a jawline engineered with an questionable precision.

“They sent you a stripper?” She deadpanned.

Simon choked. “We-well, no! Th-this isn’t mine, this is some guy online. A-and he’s, uh, he’s supposed to be adaptable. Learns your habits, routines, even preferences. The AI body is designed to assist with home tasks and companionship. There’s an application online—”

“Companionship?” Nadine asked, one brow arching as they stepped into the elevator.

“Not like that. I mean—maybe like that.” He said, squinting. “But—anyway, apparently they already started selecting people to house the prototypes.” He sipped his coffee, missing the twitch of Nadine’s jaw. “Random civilian testing. They’re sending out offers from low to high-income environments.” He continued.

The elevator dinged. Nadine stepped out before the doors fully opened.

“Mm, sounds like a weird distraction. Who has time for pet projects from a government that doesn’t care about them. Let me know when they build one that can argue in court and bill clients.” She deadpanned before the elevator dinged and she stepped off, stuttering down the hall to her office.

“Will do.” Simon called after her, blushing as he pushed up his glasses and watched as the woman walked away from him.

✦

Nadine’s office sat at the top floor of the firm—an expansive corner with floor-to-ceiling windows, brushed gold fixtures, and enough clean lines to make any minimalist cry from joy. But it wasn’t decoration that mattered, not to her at least. It was power. Clients walked in and knew exactly who was in charge and who was a leader.

She dumped her bag on the chair and was halfway through her espresso number two when the day officially launched.

By 7:15 AM, she was pacing through an emergency strategy meeting regarding an international corporate dispute. She cut through the legalese with surgical precision, offering airtight solutions and eviscerating anyone who hesitated.

By 9:00, she was on a three-way call with the CEO of a pharmaceutical giant and their scandal-scrambling PR team, coaching them through deposition answers while reading through a second case file on her desk.

By 10:00, she was downstairs in one of the firm’s conference rooms, dressed in a power stance that had the opposing counsel checking their notes twice before daring to even speak. She flipped through paper evidence like chapters of a book she’d already read, correcting a junior associate mid-sentence with nothing but a hard stare.

Every moment, every move, every gesture, was precise. Intention was behind it all.

There were no lunch breaks for her, only a small snacks here and there, or of like the food version of a power nap. And even then, she canceled today’s one-on-one with the DA’s assistant five minutes before she was supposed to show. Nadine opted to pace the rooftop patio instead, shoes clicking against stone as she answered emails, reviewed evidence, and toggled between two back-to-back client emergencies.

Her assistant, Jane, appeared like a ghost, silent as ever behind her at 2:35 PM. “You’re behind by twenty minutes.” She said softly, placing a fresh folder on the edge of the table. “And you haven’t eaten.”

“I’ll eat…later.” Nadine replied, flipping open the folder.

Jane hesitated. “Should I reschedule your chiropractor again?”

“Does he do brain surgery now? If not, no.”

✦

The rest of the day continued in a blur of depositions, and back-door negotiations. She squeezed in a quick stop at the firm’s media floor to prepare for an interview with New York Legal Elite next week—her sixth cover in two years.

By the time she returned to her office at 6:47 PM, her makeup was still flawless. But her shoulders had a weight she didn’t let show and her temples ached with the pressure of having to always be better. A pressure she put on herself everyday.

She sat at her desk, the city lights beginning to glow outside her window, and pressed her fingers to her forehead.

Three seconds. Just three seconds of quiet.

But then her phone buzzed.

BiBi: On our way up. The twins are bringing “surprises.” Brace yourself.

Nadine closed her eyes for one heartbeat before standing.

Her apartment was ten minutes away. She could beat them there, she thought. Maybe.

She did not beat them here. Inside, chaos was already blooming. Her penthouse was already lit up when she stepped inside at 7:15PM. She barely had time to set her bag down before she heard the commotion. Marley was dancing on the rug in her socks, while Micah had discovered the fridge’s smart screen and was trying to play Mario Kart through it.

“NADIIIIINE!” The two high-pitched voices screamed in unison. The twins came barreling toward her, curly hair flailing behind them like capes. They launched into her legs with the force of tiny meteors.

“Oof.” Nadine said, catching her balance. “Are you two ever not moving at Mach 10?”

“Nope!” Markey grinned. “We made cookies!”

“With Aunt Bianca’s help.” Micah added with a proud nod.

Bianca appeared behind them, holding a wine bottle and looking way too comfortable. “And I brought provisions. You look like you’ve had one of those weeks.” She said with a small pout on her lips.

Nadine raised a brow, looking over at the older woman. “I have those every week.”

“Exactly my point.”

“I missed the Nelson Towers!” Micah said, throwing herself dramatically onto Nadine’s ivory couch.

Nadine gave her a small smile, sliding off her heels. “Your mom should’ve brought you to court last week. You would’ve seen me destroy a man three times my size.”

“Did you throw a chair at him?” Marley asked.

“No, I used the law.”

“That’s boring.”

“No, my friends, that’s winning.” She grinned. As she moved around her home, making her way into the kitchen. Bianca settled onto a stool at the kitchen island, watching her sister silently. After a beat, she asked, “What time did you go to bed last night” she questioned, the sudden ask causing Nadine to scrunch her face as she looked over at her. Before she could open her mouth to speak, Bianca spoke again. “When was the last time you slept through the night?”

Nadine simply sighed as she turned her back and opened the fridge. “I sleep.”

“That’s not what I asked. I said through the night, not on your files. What time?”

Nadine pulled out a green juice and a yogurt, even though her stomach was already tight with stress. “B, I appreciate the visit. But I don’t need a wellness check. I’m at the top of my game, so I would say I’m doing pretty fine.” Nadine said with a small smile.

This only caused Bianca to give her a look. “You’re at the top of your ulcer.”

Nadine’s sarcastic grin dropped as her jaw flexed, nostril flaring as she glared at her sister.

Bianca continued, gently now. “Nay, you’re doing amazing. But you’ve been in trial mode for two straight years. You don’t date. You barely see sunlight. You don’t even blink unless it’s part of a strategy or some shit.”

Nadine stayed quiet, her spoon tapping the edge of the yogurt cup.

“You don’t have to prove anything anymore.” Bianca added.

And that struck something. Not that Nadine showed it.

“It’s not about proving.” She finally said. “It’s about maintaining. You fight your way up from nothing, and you learn fast—falling isn’t dramatic. It’s silent and quick. It’s one missed call, one lost case. One person thinking you’ve lost your edge.”

Bianca didn’t press further. Instead, she let out a sigh before she called out to her children. “Alright girls, thirty minutes, then we’re heading out.”

The twins groaned but obeyed, bouncing off to the guest room.

Bianca reached for Nadine’s tablet to put on a cartoon on the television, or something to entertain them while she packed snacks.

What she didn’t notice was Micah and Marley sneaking back in and whispering behind the kitchen counter. They had a letter in their hands, a piece of paper they found tossed haphazardly in the living room. And once they read it, the twins were all on board.

“There it is!” Marley whispered.

“I wonder why she didn’t answer. Robots are so cool.” Micah questioned, rereading the page over and over again in excitement. “Maybe she didn’t want one.”

“That’s dumb.” Markey sighed before pulling out her purple glitter pen from her back pocket. “Should I do it?” She questioned, looking over at her twin. There was a moment of silence that passed between them, staring into the other’s eyes before looking back down at the paper.

“Do it.” They said at the same time.

With sticky fingers and wild curiosity, they marked the “Accept Housing Unit” checkbox on the government letter Nadine had flagged but never opened. Marley then folded it back up before move to place it into the mail slot next to the front door, hearing the suction sound as the letter was whisked away back to the owner.

A pop-up confirmed the delivery on the screen next Mail Drop, causing the to high-five before they scurried off. “Okay, now we have to fill this out.” Micah said, pulling the retractable delivery screen closer as the screen loaded a soft blue logo. AURA | Adaptive User Response Assistant. Marley was already typing on the screen like she worked at NASA. “We so can’t tell mom about this.” Micah mumbled nervously.

“No one’s telling Mom.” Marley muttered.

“Okay, well, if Auntie Nadine gets mad, I’m blaming you,” Micah said, peering at the glowing tablet in his sister’s lap. Marley let out a sigh, rolling her eyes at her brother. “She’s not gonna get mad,” Markey tressed with a whisper. “She’s gonna love it. You saw the commercial—this thing can do laundry, make dinner, answer emails. It’s like if Iron Man was a butler.”

“No, it’s like if Pennyworth was a robot.” Micah added, eyeing the girl next to him. “That was a really bad…analogy? Have you ever even read Ironman?” The boy judged.

“Shut up.” Marley deadpanned. “We’re making Auntie Nadine’s house ten times cooler. You think she’s gonna notice another package with all the stuff she orders?”

“She will if it walks and talks.”Micah said, grinning. “Now hurry. I think this is the setup survey and anyone can come checking up on his at any minute.”

The screen adjusted to a smooth, futuristic interface.

AURA Configuration Survey. Optional. But, if you want to make the experience unforgettable…

“Unforgettable.” Marley repeated with a smirk. “Let’s go.”

Private Configuration Survey – AURA Unit #007

Answer honestly to ensure optimal user experience.(Note: Once submitted, preferences are locked in for bonding phase.)

1. What kind of support will the user benefit from most? (Select all that apply):

[ ] Physical assistance (lifting, running, protection). [ ] Task management (emails, errands, organization). [x] Emotional balance (stress de-escalation, energy reading). [x] Conversational engagement (company, reminders, reflection)

“Definitely that one,” Marley said, pointing. “She talks to herself too much.”

“I don’t think she notices.”

2. What is the user’s current lifestyle?

[ ] Highly active, social, fast-pace. [x] Independent, professional, busy. [ ] Creative, exploratory, experimental. [ ] Relaxed, home-oriented

3. How should AURA respond under pressure?

[ ] Assertive and directive. [x] Calm and grounded. [ ] Humorous and light [ ] Silent until prompted

4. What kind of presence should AURA have in the home?

[ ] Subtle but attentive. [x] Always on-hand. [ ] In the background unless called. [ ] Commanding and structured

5. How emotionally intuitive should AURA be

[ ] Not at all—task-focused only. [ ] Moderately—pick up on moods, offer support. [x] Highly—understand shifts in tone, body language, even silences

“Okay, she’s gonna love that.”Marley said with a grin. “Remember when she cried at the end of Paddington 2?”

“Well, so did I….”

6. The user prefers companions who are…

[x] Thoughtful and calm. [ ] Straightforward and direct. [ ] Reserved and quiet. [ ] High energy and expressive

7. Ideal communication style?

[ ] Formal and efficient. [x] Warm and intuitive. [ ] Light and witty. [ ] Minimal

8. Would the user appreciate personal attention to detail? (e.g. remembering birthdays, moods, routines):

[x] Yes. [ ] No. [ ] Only when relevant

9. AURA should interact like…

[ ] A professional assistant. [x] A loyal companion. [ ] A discreet observer. [ ] A supportive coach

Micah tilted his head. “What does ‘loyal companion’ mean?”

Marley shrugged. “I think it just means cool sidekick energy. Like Watson or Chewbacca.”

“Nice.”

10. Anything else we should know about the user? (Optional):

Marley hummed in thought for a moment before she began typing quickly. “She drinks coffee every morning at 6:45, she falls asleep with documentaries on, animal or history, and she forgets to eat when she’s on high emotions. Anger, stress, sadness. She likes it when people notice little things but gets weird when you say nice stuff too directly. She’s kind of secretly lonely but she won’t admit it. Oh, and she likes jazz but not the weird kind with screechy horns.”

Micah blinked. “Whoa. That’s kinda deep. You really know your stuff.”

“I pay attention.” The girl said. Marley then hit SUBMIT with a grin.

The screen flashed. Profile Logged. Preparing AURA for transport. Estimated arrival: 2-3 business days.

The twins then high-fived. “She’s gonna freak out.” Micah whispered.

“In a good way.”Marley added. “Hopefully.”

✦

It was now the next day, and if you couldn’t tell by now, Nadine Nelson was not one to wake up late.

That was the first rule of her universe. The first part to her routine. Her alarm chimed at precisely 5:45 AM, every morning without fail, a single soft note, like the chip of a bird, before she silenced it, sat up, and began the orchestration that was her life. Her body and mind moved like synchronized gears in a Swiss watch—sleek, efficient, and expensive.

So when a loud, jarring knock knock knock banged against her front door at 6:15 AM, it was not just an interruption.

It was an affront.

Her eyes snapped open, head jerking toward the illuminated time panel beside her bedroom light switch. 6:15? Her jaw clenched. She was already behind schedule.

Muttering under her breath, she shoved off her covers and grabbed her silk robe from the hook near her bed. Her movements were less precise this morning, more agitated than usual, and still a bit sleepy as her slippers scuffed across the hardwood as she stormed to the front door.

When she opened it, ready to deliver a verbal cease and desist, she paused.

There was a man at her door, next to a large package. But the man at her doorstep didn’t look like the usual FedEx or UPS guy. He wore a crisp black-and-white suit with polished shoes, a slim earpiece tucked behind one ear. He stood beside a large, square wooden crate perched on a steel dolly, taller than he was and easily the size of a refrigerator.

“Yes?” Nadine asked, her tone sharp as broken glass.

The man, unreadable behind dark glasses, tilted his head. “Are you Nadine Nelson?”

She didn’t like the way he asked it. Like he already knew the answer.

“Yes.” She replied flatly, arms crossed over her robe.

“Great. This is for you.” He said, stepping forward and pushing the crate toward her. Nadine moved out of shock, and instinct with a crate that size barking towards her, inevitably letting the man in with the crate, but once she realized she was coming drier into her honey she stepped in, palms up. “Uh, excuse me!” She said, stopping him. “I didn’t order anything. And certainly not something that looks like it should be in a warehouse.”

The man didn’t blink, but that the should tell through his glasses. “You are Nadine Nelson, correct?”

She sighed, jaw tight. “Yes. I already said that.”

“Then this is for you.”

Without another word, he wheeled the box into her foyer. Her eyes widened as the dolly clacked over her expensive floors, the crate casting a looming shadow across the pristine white walls of her home, from the sun shining through the large windows.

“Wait—hold on.” Nadine said, gripping the belt of her robe. “I’m serious. I did not order this. You need to take it back.”

The man was already turning for the door. “Take it up with customs, ma’am.”

“What? Customs? What customs?”

He ignored her completely. As he stepped outside, Nadine caught him press two fingers to the earpiece tucked behind his ear. “It’s been delivered.” He said coolly, then walked down the hallway of her luxury building as her front door slid shut on its own.

Nadine stood there in stunned silence, her arms hanging at her sides as she stared at the box now squatting in the middle of her living room.

Then she screamed.

A long, guttural scream that echoed off the marble and glass of her carefully curated life. Something she tended to do to let out her overflowing emotions.

And after a minute or two of huffing out of breath and anger, she turned on her heel and stormed back to her bedroom. Her phone was still on the nightstand, glowing from a few missed notifications. She didn’t even bother to text. She opened her voice message, hit record, and in her usual no-nonsense tone, she snapped.

“Clear my schedule for today. All of it. There’s some bullshit I need to take care of.”She pressed send to Jane, and then tossed the phone onto the bed without a second thought.

Back in the hallway, she opened the hall closet and pulled out a crowbar from the bottom shelf of her emergency tool kit. She hadn’t touched it since she assembled her custom bookcases two years ago, but it felt oddly satisfying in her grip.

The walk back into the living room was almost cinematic if someone else was there to view it—robe flowing, face full of anger, slippers skimming the floor, crowbar in hand. The crate sat there like a taunt. Uninvited. Immovable.

She didn’t hesitate to go to town, unleashing her irritation onto the box. Nadine wedged the crowbar into the gap between the wood slats and yanked. A nail groaned before it snapped loose, followed by another, and another. She was methodical but furious, stripping the crate open like a woman possessed with rage. Bits of sawdust and packing foam floated through the air, nails flying left and right, a bit dangerous but she didn’t seem to care at the moment. All of it littering her previously immaculate living room.

Nadine kicked aside the last of the packing material, breath puffing from her lips in irritation. She was done. Done with the entire thing. She expected to find an overpriced espresso machine or something.

But instead, she opened the crate and was met with… another crate?

Her brows lifted, her irritation fading into a slow, confused frown.

It wasn’t like the shipping box. This one was different. Striking. A dark wood, deep mahogany with an almost matte sheen. The surface gleamed with intricate carvings, elegant but oddly ancient, like something pulled from the archives of some old, forgotten dynasty from long ago. And in the center was a large gem. Oval-shaped, but a natural look to it, like it was just pulled from the earth and placed into the center. It was embedded like a heart, its color a deep blue, almost black in the shadows but gleaming cerulean where the light hit. It shimmered like water at midnight.

Nadine let out a breath she didn’t realize she was holding. Her fingers hovered over the jewel, almost drawn to it, like it was calling to something beneath her skin. Something primal.

She reached forward.

The stone was cool. Smooth. Her fingertips just barely grazed the surface when—

FLASH.

The gem lit up instantly, glowing from within like a waking eye. Nadine gasped and jerked her hand back, stumbling slightly.

“What the hell?” She whispered.

But she couldn’t look away, no matter how bright the light got

The light from the gemstone pulsed slowly, rhythmically, like it had a heartbeat. And then, as if in response to her shock, the carvings along the chest began to glow as well—lines of a sliver blue creeping from the jewel into the grooves and patterns etched into the wood, filling every line until the whole thing shimmered in a way that made her chest tighten with unease and…awe.

Nadine blinked, and her heart thudded against her ribs.

This—this was definitely not something you could order off Amazon.

And that’s when she noticed it. Taped to the inner panel of the crate, partially obscured by packing straw, was an envelope. Thick. Heavy. Cream-colored paper with a glossy finish and silver wax seal.

She reached for it, peeling it free. The seal bore the emblem of the United States, but stylized. Sleek. Futuristic. Her name was printed across the front in smooth, robotic cursive.

𝐓𝐨 𝐍𝐚𝐝𝐢𝐧𝐞 𝐍𝐞𝐥𝐬𝐨𝐧

She frowned. A deep, suspicious furrow. This crate was for her?

Snatching the envelope, she tore it open and unfolded the single sheet inside. The words were printed, formal, precise. But they sent a jolt down her spine.

𝐓𝐨 𝐌𝐬. 𝐍𝐚𝐝𝐢𝐧𝐞 𝐍𝐞𝐥𝐬𝐨𝐧,

𝐂𝐨𝐧𝐠𝐫𝐚𝐭𝐮𝐥𝐚𝐭𝐢𝐨𝐧𝐬.

𝐘𝐨𝐮 𝐚𝐫𝐞 𝐨𝐧𝐞 𝐨𝐟 𝐨𝐧𝐥𝐲 𝐭𝐰𝐞𝐧𝐭𝐲 𝐢𝐧𝐝𝐢𝐯𝐢𝐝𝐮𝐚𝐥𝐬 𝐬𝐞𝐥𝐞𝐜𝐭𝐞𝐝 𝐭𝐨 𝐩𝐚𝐫𝐭𝐢𝐜𝐢𝐩𝐚𝐭𝐞 𝐢𝐧 𝐭𝐡𝐞 𝐩𝐫𝐢𝐯𝐚𝐭𝐞 𝐛𝐞𝐭𝐚 𝐩𝐡𝐚𝐬𝐞 𝐨𝐟 𝐀𝐔𝐑𝐀—𝐭𝐡𝐞 𝐰𝐨𝐫𝐥𝐝’𝐬 𝐦𝐨𝐬𝐭 𝐚𝐝𝐯𝐚𝐧𝐜𝐞𝐝 𝐚𝐫𝐭𝐢𝐟𝐢𝐜𝐢𝐚𝐥 𝐢𝐧𝐭𝐞𝐥𝐥𝐢𝐠𝐞𝐧𝐜𝐞 𝐜𝐨𝐦𝐩𝐚𝐧𝐢𝐨𝐧. 𝐂𝐫𝐚𝐟𝐭𝐞𝐝 𝐟𝐨𝐫 𝐥𝐞𝐚𝐝𝐞𝐫𝐬, 𝐯𝐢𝐬𝐢𝐨𝐧𝐚𝐫𝐢𝐞𝐬, 𝐚𝐧𝐝 𝐩𝐢𝐨𝐧𝐞𝐞𝐫𝐬 𝐢𝐧 𝐭𝐡𝐞𝐢𝐫 𝐟𝐢𝐞𝐥𝐝𝐬, 𝐀𝐔𝐑𝐀 𝐢𝐬 𝐧𝐨𝐭 𝐣𝐮𝐬𝐭 𝐚𝐧 𝐚𝐬𝐬𝐢𝐬𝐭𝐚𝐧𝐭. 𝐈𝐭 𝐢𝐬 𝐚𝐧 𝐞𝐱𝐭𝐞𝐧𝐬𝐢𝐨𝐧 𝐨𝐟 𝐲𝐨𝐮𝐫 𝐚𝐦𝐛𝐢𝐭𝐢𝐨𝐧.

𝐓𝐡𝐞𝐲 𝐰𝐢𝐥𝐥 𝐥𝐞𝐚𝐫𝐧 𝐲𝐨𝐮𝐫 𝐫𝐨𝐮𝐭𝐢𝐧𝐞𝐬, 𝐚𝐧𝐭𝐢𝐜𝐢𝐩𝐚𝐭𝐞 𝐲𝐨𝐮𝐫 𝐧𝐞𝐞𝐝𝐬, 𝐚𝐧𝐝 𝐨𝐟𝐟𝐞𝐫 𝐬𝐮𝐩𝐩𝐨𝐫𝐭 𝐰𝐡𝐞𝐫𝐞 𝐞𝐯𝐞𝐧 𝐭𝐡𝐞 𝐦𝐨𝐬𝐭 𝐞𝐥𝐢𝐭𝐞 𝐡𝐮𝐦𝐚𝐧 𝐭𝐞𝐚𝐦 𝐜𝐚𝐧𝐧𝐨𝐭.

𝐅𝐫𝐨𝐦 𝐬𝐜𝐡𝐞𝐝𝐮𝐥𝐢𝐧𝐠 𝐰𝐢𝐭𝐡 𝐦𝐢𝐥𝐢𝐭𝐚𝐫𝐲 𝐩𝐫𝐞𝐜𝐢𝐬𝐢𝐨𝐧 𝐭𝐨 𝐞𝐦𝐨𝐭𝐢𝐨𝐧𝐚𝐥 𝐜𝐚𝐥𝐢𝐛𝐫𝐚𝐭𝐢𝐨𝐧 𝐝𝐮𝐫𝐢𝐧𝐠 𝐡𝐢𝐠𝐡-𝐬𝐭𝐫𝐞𝐬𝐬 𝐞𝐧𝐯𝐢𝐫𝐨𝐧𝐦𝐞𝐧𝐭𝐬, 𝐀𝐔𝐑𝐀 𝐢𝐬 𝐡𝐞𝐫𝐞 𝐭𝐨 𝐞𝐥𝐞𝐯𝐚𝐭𝐞 𝐲𝐨𝐮𝐫 𝐞𝐟𝐟𝐢𝐜𝐢𝐞𝐧𝐜𝐲, 𝐬𝐭𝐫𝐞𝐚𝐦𝐥𝐢𝐧𝐞 𝐲𝐨𝐮𝐫 𝐬𝐮𝐫𝐫𝐨𝐮𝐧𝐝𝐢𝐧𝐠𝐬, 𝐚𝐧𝐝, 𝐢𝐧 𝐭𝐢𝐦𝐞, 𝐮𝐧𝐝𝐞𝐫𝐬𝐭𝐚𝐧𝐝 𝐲𝐨𝐮.

𝐘𝐨𝐮 𝐦𝐚𝐲 𝐧𝐨𝐭𝐢𝐜𝐞 𝐭𝐡𝐚𝐭 𝐭𝐡𝐞𝐲 𝐫𝐞𝐪𝐮𝐢𝐫𝐞 𝐧𝐨 𝐰𝐚𝐤𝐞 𝐰𝐨𝐫𝐝, 𝐧𝐨 𝐜𝐨𝐝𝐞, 𝐧𝐨 𝐦𝐚𝐧𝐮𝐚𝐥.

𝐓𝐡𝐞𝐲’𝐫𝐞 𝐚𝐥𝐫𝐞𝐚𝐝𝐲 𝐥𝐢𝐬𝐭𝐞𝐧𝐢𝐧𝐠.

𝐖𝐞𝐥𝐜𝐨𝐦𝐞 𝐭𝐨 𝐭𝐡𝐞 𝐟𝐮𝐭𝐮𝐫𝐞.

—𝐂.𝐑.𝐈.𝐒.

𝐂𝐨𝐠𝐧𝐢𝐭𝐢𝐯𝐞 𝐑𝐨𝐛𝐨𝐭𝐢𝐜𝐬 & 𝐈𝐧𝐭𝐞𝐥𝐥𝐢𝐠𝐞𝐧𝐜𝐞 𝐒𝐲𝐬𝐭𝐞𝐦𝐬

𝐂𝐨𝐧𝐟𝐢𝐝𝐞𝐧𝐭𝐢𝐚𝐥 𝐏𝐫𝐨𝐭𝐨𝐭𝐲𝐩𝐞 𝐏𝐫𝐨𝐠𝐫𝐚𝐦 | 𝐍𝐨𝐭 𝐟𝐨𝐫 𝐏𝐮𝐛𝐥𝐢𝐜 𝐃𝐢𝐬𝐜𝐥𝐨𝐬𝐮𝐫𝐞

There was a purple glitter check mark by the question. And she closed her eyes as she took in a deep breath, already knowing who to blame for this. Nadine stared at the letter, then at the crate, then back again.

She was going to kill her niece and nephew.

And then—once the twins were grounded for life and Bianca was chewed out for letting them touch her mail—she was going to sue whoever thought it was cute to send her a six-foot robot without consent.

But for now, she placed the letter down slowly and stepped closer to the chest.

It hummed. Just once. A low vibration that rippled across the wood floor and into the soles of her feet. Then, the chest unfastened with a hiss.

The lid groaned.

A long, sinuous sound of pressure escaping, like the breath of something long dormant finally allowed to exhale. Mist pooled from the edges of the ornate coffin-like crate, curling along the floor like tendrils of fog. The dim morning light poured through the windows, catching the shimmer of the gemstone embedded in the chest—still pulsing with a slow, deliberate rhythm, like a heartbeat.

Nadine stared, crowbar slack in her hand, chest rising and falling too fast for comfort.

Inside, the shape was obscured. Cloth. A velvet-like black material draped across something… someone.

Another hiss whispered from the crate. The latches disengaged with an audible thunk. And slowly, ever so slowly, the coffin-like chest began to open—hinges smooth and silent, assisted by unseen tech. The lid released fully and slid backward, revealing more of the figure beneath.

Nadine inched forward, each footstep muffled by the hush of mist and the pounding of her heart. Her instincts screamed at her to stop. To turn around. To call someone. Her sister. Jane. The FBI. The CIA. The Pope.

She stared at it, eyes narrowing. “What did you two do?” She muttered, already picturing her nieces, innocent smiles hiding devilish delight, whispering and giggling as they plotted this chaos.

But her curiosity was stronger. That damned glimmering jewel. That sleek envelope with her name etched like some sort of prophecy. That letter that claimed this… thing knew her already.

The cloth stirred and Nadine froze.

Then the fabric peeled itself away—mechanically, precisely—revealing skin.

Well, no, not skin. It couldn’t be. It was just some beautiful mimicry of it. Smooth and matte. A man’s chest, carved with symmetrical precision and framed by sculpted shoulders. They were bare and powerful in the right compression shirt with the cut sleeves.

Nadine’s breath hitched.

And then he sat up. The fabric slipped off like water while Nadine stared, mouth slightly open.

It was slow and graceful, like someone waking from a century-long slumber. The man—because that’s what he looked like, down to the subtle flex of his hands—was breathtaking. Sculpted. Not just handsome, but deliberately so, he was made this way. Smooth dark skin, eyes like obsidian glass, and a face that didn’t seem designed but born from every secret longing she’d never dared voice. His eyes opened—two smoldering pools of warm obsidian, rimmed faintly with glints of silver. They found hers immediately.

Nadine staggered back a step.

He blinked once. Tilted his head. And then—smiled.

Not a robotic, lifeless twitch. But a curve of the mouth that felt… devastatingly real. It was warm and gentle. Intimate in a way.

Nadine almost forgot he was meant to be a robot and not some random man in a box.

“Nadine.” He said.

Her name, from his lips, made something low in her belly twist. His voice was deep, perfectly modulated, with just enough grit to make her toes curl. It was soft but strong, like thunder rolling far away across the sea.

“You—you know my name?” She asked, trying not to sound like a complete idiot. But she did anyways with the uncharacteristic stutter that slipped through, totally unlike her. The crowbar was still in her hand, but it felt laughable now. She wasn’t in danger. She was… almost enchanted in a way.

“Yes.” He said, stepping forward with fluid, feline grace. He towered a good foot above her, dressed in a fitted black uniform that shimmered faintly in the light. “I’ve always known your name, known it since you were assigned to the prototype queue.” He replied. “I was made for you. I’ve been learning you ever since.”

“Learning me?” She repeated, throat dry.

His eyes softened as he nodded. “I’ve watched your presentations. Your interviews. I’ve studied your calendar. Your habits. Your moods. What calms you. What drives you. What keeps you up at night.”

Her brows furrowed. “And why would you do that?”

“So I could be ready when you needed me.”

The words hit her like a wave. Sudden and unsettled something deep within her. It was undeniable.

“I didn’t need anyone.” She snapped at him out of instinct.

The man tilted his head, his eyes glowing blue as he scanned her face. ‘Defensive’ it flashed across his eyes. “No.” He agreed. “But you deserve someone.”

And then there was silence. A thick, emotional silence hung between them as Nadine stared up at him. His face was symmetrical, almost distractingly beautiful—like something a sculptor would weep over. But it was his gaze that disarmed her. No flicker of code was viable besides the unnatural glow, and even that was a bit comforting. There was no empty mimicry. He just looked at her, his eyes never once leaving her face.

“Who… what are you?” She whispered.

He then extended a hand with a small smile. Palm up. As if offering her not just an answer, but himself.

“I am AURA-7.” He said. “My designated name is Michael, but you can call me whatever feels right.”

Nadine didn’t move at first, her brain screaming a thousand warnings at her as her eyes flicked between his face and hang. Her chest was tight, unsure.

But her hand reached out anyway.

And when their skin touched—when her fingers slid against his palm—it wasn’t cold. It wasn’t metal. It was warm. Comforting and real. And this was the first time she’s touched someone in such a non work manner in a long time.

He smiled again, this time slower, more intimate.

And Nadine Nelson, woman of routine, disciple of control, high priestess of solitude… felt her entire world shift beneath her feet.

[genshin-impact-updates]

Version 5.3 Event Wishes Notice - Phase II

Travelers, stock up on weapons and characters in the event wish to make your party stronger in combat!

Event Wish "The Hearth's Ashen Shadow" - Boosted Drop Rate for "Dire Balemoon" Arlecchino (Pyro)!

〓Event Wish Duration〓

2025/1/21 18:00—2025/2/11 14:59

〓Event Wish Details〓

● During this event wish, the event-exclusive 5-star character "Dire Balemoon" Arlecchino (Pyro) will receive a huge drop-rate boost!

● During this event wish, the 4-star characters "Spring Woven From Jade" Lan Yan (Anemo), "Executor of Justice" Chevreuse (Pyro), and "Thorny Benevolence" Rosaria (Cryo) will receive a huge drop-rate boost!

● After this event wish ends, the 4-star character "Spring Woven From Jade" Lan Yan (Anemo) will be available in the standard wish "Wanderlust Invocation" in the next Version.

※ Of the above characters, the event-exclusive character will not be available in the standard wish "Wanderlust Invocation."

※ This is for "Character Event Wish." The wish guarantee count for "Character Event Wish" and "Character Event Wish-2" is shared, and is accumulated between both "Character Event Wish" and "Character Event Wish-2." This wish guarantee count is independent of the guarantee counts of other types of wishes.

※ The "Test Run" trial event will be open during this event wish. Travelers may use fixed lineups containing the selected trial characters to enter specific stages and test them out. Travelers that complete the challenges will receive the corresponding rewards!

※ For more information, go to the Wish screen and select Details in the bottom-left corner.

Event Wish "Illuminating Lightning" - Boosted Drop Rate for "Candlebearer, Shadowhunter" Clorinde (Electro)!

〓Event Wish Duration〓

2025/1/21 18:00—2025/2/11 14:59

〓Event Wish Details〓

● During this event wish, the event-exclusive 5-star character "Candlebearer, Shadowhunter" Clorinde (Electro) will receive a huge drop-rate boost!

● During this event wish, the 4-star characters "Spring Woven From Jade" Lan Yan (Anemo), "Executor of Justice" Chevreuse (Pyro), and "Thorny Benevolence" Rosaria (Cryo) will receive a huge drop-rate boost!

● After this event wish ends, the 4-star character "Spring Woven From Jade" Lan Yan (Anemo) will be available in the standard wish "Wanderlust Invocation" in the next Version.

※ Of the above characters, the event-exclusive character will not be available in the standard wish "Wanderlust Invocation."

※ This is for "Character Event Wish-2." The wish guarantee count for "Character Event Wish" and "Character Event Wish-2" is shared, and is accumulated between both "Character Event Wish" and "Character Event Wish-2." This wish guarantee count is independent of the guarantee counts of other types of wishes.

※ The "Test Run" trial event will be open during this event wish. Travelers may use fixed lineups containing the selected trial characters to enter specific stages and test them out. Travelers that complete the challenges will receive the corresponding rewards!

※ For more information, go to the Wish screen and select Details in the bottom-left corner.

Event Wish "Epitome Invocation" - Boosted Drop Rate for Crimson Moon's Semblance (Polearm) and Absolution (Sword)!

〓Event Wish Duration〓

2025/1/21 18:00—2025/2/11 14:59

〓Event Wish Details〓

● During this event wish, the event-exclusive 5-star weapons Crimson Moon's Semblance (Polearm) and Absolution (Sword) will receive a huge drop-rate boost!

● During this event wish, the event-exclusive 4-star weapon Lithic Spear (Polearm) as well as the 4-star weapons Lion's Roar (Sword), Rainslasher (Claymore), The Widsith (Catalyst), and Sacrificial Bow (Bow) will receive a huge drop-rate boost!

● During this event wish, use Epitomized Path to chart a course towards a promotional 5-star weapon, such as Crimson Moon's Semblance (Polearm) or Absolution (Sword). For more information on Epitomized Path, go to the Wish screen and select Details in the bottom-left corner.

※ Of the above weapons, the event-exclusive weapons will not be available in the standard wish "Wanderlust Invocation."

※ For more information, go to the Wish screen and select Details in the bottom-left corner.

Event Wish "Remembrance of Jade and Stone" - Chronicled Wish Now Available!

〓Event Wish Duration〓

2025/1/21 18:00—2025/2/11 14:59

〓Event Wish Details〓

● During this event wish, you can freely select and chart a course towards your chosen boosted 5-star character or weapon amongst all 5-star items in the "Remembrance of Jade and Stone" Event Wish of this period!

● During this event wish, the event-exclusive 5-star characters "Beyond Mortality" Baizhu (Dendro), "Lonesome Transcendence" Shenhe (Cryo), "Plenilune Gaze" Ganyu (Cryo), "Childe" Tartaglia (Hydro), and "Vigilant Yaksha" Xiao (Anemo), the event-exclusive 5-star weapons Primordial Jade Cutter (Sword), Summit Shaper (Sword), The Unforged (Claymore), Calamity Queller (Polearm), Jadefall's Splendor (Catalyst), Memory of Dust (Catalyst), and Polar Star (Bow), as well as the event-exclusive 4-star weapons Lithic Blade (Claymore) and Lithic Spear (Polearm) will be available for a limited time.

● All 5-star and 4-star items in this Chronicled Wish:

5-Star Characters: Baizhu, Shenhe, Keqing, Ganyu, Qiqi, Tartaglia, and Xiao

5-Star Weapons: Primordial Jade Cutter, Summit Shaper, The Unforged, Calamity Queller, Primordial Jade Winged-Spear, Jadefall's Splendor, Memory of Dust, Polar Star, and Amos' Bow

4-Star Characters: Gaming, Yaoyao, Yun Jin, Yanfei, Xinyan, Chongyun, Ningguang, Xingqiu, Beidou, and Xiangling

4-Star Weapons: Lion's Roar, Sacrificial Sword, The Flute, Favonius Sword, Lithic Blade, Rainslasher, Sacrificial Greatsword, The Bell, Favonius Greatsword, Favonius Lance, Lithic Spear, Dragon's Bane, Eye of Perception, Sacrificial Fragments, The Widsith, Favonius Codex, Rust, Sacrificial Bow, The Stringless, and Favonius Warbow

※ This is for "Chronicled Wish." The wish guarantee count is accumulated within "Chronicled Wish" only and is independent of the guarantee counts of other types of wishes.

※ For more information, go to the Wish screen and select Details in the bottom-left corner.

[clivaldatabase]

Enhancing Patient Safety: The Role of Clinical Trials and Drug Development

Patient safety is always a big issue of concern especially in clinical trials and during the drug development. Given the increasing speed of developing new therapies, ensuring those therapies are safe and effective prior to be made public is imperative for the preservation of patient safety and endorsement of innovative treatments. This blog post focuses on the vital role of clinical trials in improving patient safety including the procedures followed to ensure safer drug development and advancements towards making clinical trials safer.

[rootspiral]

Agatha All Along deep dive: episode 3 part 2

(Wandavision entries: [1][2][3])

(AAA entries: ep1 [1][2][3][4] ep2 [1][2][3][4] ep3 [1][2][3] ep4 [1][2][3][4][5][6][7][+1] ep5 [1][2][3][4][5] ep6 [1][2][3] ep7 [1][2][3][4][5][6] ep8 [1][2][3][4][5][6][7][8][9] ep9 [1][2][3][4][5][6])

alice panics and checks if she still has her mom's amulets, lilia says, you still got them! in a sweet reassuring way. agatha also panics and checks if she has her brooch, but she does it quietly. when she finds the brooch she gives a sigh that no one notices.

I just love the parallels between agatha and alice, a daughter who lost her mother and a mother who lost her son, both grieving, both connected to the Road. but while alice, despite her shyness, is able to express her feelings and find strength and reassurance within her coven, agatha keeps her pain quiet and close to the chest.

checking her exit strategies while the others are still looking around in awe, because she's a) always a step ahead everybody else and b) a huge fucking coward. agatha is never as confident as she seems. was she hoping to bolt the moment billy wasn't looking and leave the others to deal with his mess?

ooh alice is the second to check. that's so interesting, they parallel each other but agatha does things secretly, alice does them openly.

NOT FUNNY, writers

yeah this is not a confident woman. she is terrified

not because babies make her cry or anything. in fact she eats babies, haven't you heard?

agatha is always real mature, but there's something about jen in particular that makes her regress into toddlerdom - and yeah it's funny, but we know agatha does this kind of stuff to mask and deflect, and I think she's especially defensive around jen because she actually respects her and values her opinion! so she has to rebel to that feeling like the true kindergartener she is

sharon dives for the wine, agatha rises a hand to warn her but hesitates. a moment later alice rises a hand and stops her. I'm only seeing this because I'm looking so closely but I'm not dreaming it, am I? this has to be on purpose? and oh my god alice was a cop. what did agatha choose to be under the spell, when she didn't bottle her emotions and guard herself so closely?????

okay okay okay now I'm thinking about moon phases and elements. alice is Fire, agatha is Spirit, would there be a connection? or maybe agatha as Spirit is like the Avatar and has to learn something from each element. from Alice she would learn to listen to her protective instincts - or rather to use them to protect others and not only herself, and that's what would ultimately make her choose to save Billy. I'll keep an eye out for this, maybe I'm on to something? this is Water and Jen's trial tho, so what does she learn from jen?

so jen despite her sarcastic exterior has been very vocal about both billy and sharon not belonging here. now she takes billy to the side and openly warns him. she's very pragmatic and not particularly emotional, she had to grow a lot of armor too, which makes her breaking down and crying in the finale all the more meaningful. the obvious lesson aside (agatha being responsible for jen's trauma), another thing that agatha has to learn from her is moral values. if jen were in agatha's shoes and saw the truth behind the Road you know she would have stopped this whole thing immediately. agatha needs to learn to be the bigger person for once and take things seriously, instead of running away.

we know agatha tolerates and even encourages the rumors about nicky, because the truth is too awful. is that why she's always yapping about hating children and eating babies? dear lord, it's so funny that she's so immature, and at the same time it's not funny at all

no one's judging you honey. you get drunk all you want, you earned it. and fuck these bitches and agatha especially for letting her drink poison - billy gets a pass because he's underage, why doesn't sharon get a pass for being magicless? I'll tell you why, because deep down no one takes her seriously. she's a joke to them.

lol billy's empty hand

agatha you will be ready to tackle him the moment he tries to drink for real. the clowning! all for show. and sharon is already pouring herself a third glass, nothing funnier than self medicating with alcohol, am I right gang?

I adore adore adore adore alice bonding with billy. she tries to do the agatha "i'm too damaged to open up" thing but one sad puppy look and she melts away. because he's just a kid (and a emo hot topic kid at that) and she WILL make him feel accepted no matter how sad inside she is. she's such a good person leave me alone

"so you guys evil, am I right?"

"no no no we have reclaimed that term, that's no longer a slur"

what's your favorite donatella versace impression? mine's alice's

can you guys please stop deadnaming this poor woman?? (spellnaming? magicnaming? wandanaming?)

agatha you are a humongous asshole for only pretending to drink and kathryn hahn you are so funny and so hot and talented

dying future!lilia jumps back in time to tell her coven she loves them and that's the moment she lands on lmaooooo with her face all swollen and everyone panicking and agatha pounding on the door. you don't deserve her love anyway agatha. she will give it to you because she's the better person, but you don't deserve shit

so yeah agatha we've been poisoned and Death's gonna come any minut....

BWAHAHAAHAHAHAAHHAH

that's taking 'deadbeat wife' to a whole other level

bit creepy there, billy. it's like Jigsaw being upset at people not participating in his games

billy: fine I'LL DRINK

agatha running in slowmo: NOOOOOOOOOOOOOOOOOOO

you miiight be projecting your issues on that kid a lil bit there, buddy

she might drink the wine to save billy but she'll be an ABSOLUTE TEENY-WEENY BABY about it

such a fun episode

aaaaaaaaaaaaaaaaaaaaaaand that would be her last words, folks! aren't we HAVING SO MUCH FUN????

alice always being the first one to run and help and trying to save everyone. just... alice

shoutout to @idkbroletssee and their billy's commentary!

go to episode 3 part 3

[mindblowingscience]

The mRNA revolution continues. Just a few years after mRNA vaccines proved their efficacy against COVID-19, scientists are now turning their attention to lung cancer. The mRNA vaccine, known as BTN116, developed by the German biotechnology company BioNTech, is the first of its kind and has entered phase 1 clinical trials in seven countries, including the United States and the United Kingdom. This vaccine is designed to treat non-small cell lung cancer (NSCLC), the most common form of the disease.

Continue Reading.

[dermatology-cro]