#infectious testing market

[pangur-and-grim]

a lot of you probably knows Belphie's story, but I'll summarize just in case.

Devon Rex cats are better for people with allergies (less shed fur + less Fel d1 protein in their saliva), so on February 16, 2024, I went the breeder route and put down a deposit. before Belphie even opened his eyes, he was mine!

every Friday, the breeder sent me a new photo. I had a broken leg, and was basically rotting in bed at that point, so it was the best part of my week. then, at 12 weeks old, I BROUGHT HIM HOME!

at first, he was so alive! like a wind-up monkey that never shut off. he dangled from the wall-hangings, savaged my feet as I walked, and used my elderly cats as jumping poles to do cool acrobatics over. but all this gradually faded.

first, he stopped playing. then he stopped climbing. then he stopped moving much at all. my vet ran tests on him and found multiple pathogens (calcivrius + mycoplasma), but the medication didn't help - he kept declining.

on September 17th, I woke up to find him swollen like a balloon. we finally had an answer: he had Feline infectious Peritonitis, aka FIP. before 2017, this would've been a death sentence. he would've kept bloating until he drowned in his own fluids. and before 2024, I would've been forced to inject him with black market drugs. but thankfully, South Tower Animal Hospital in Fergus, Ontario was doing a study on the oral medication! we drove two hours, enrolled him, and left with the GS-441524 pills.

and he went from those photos above.....to this:

I thought Belphie would die as a kitten. I'd accepted that he would never grow up. but now he gets to LIVE!

and all for the low cost of $7,553.....ahhhahaha........god.

that + a recent home disaster has wiped out my savings, but I still need to pay for Belphie's medication. to remain in this study, I need to do bloodwork monthly until Feb 2025, and he'll need daily pills until March 2025.

I've put a risograph print + enamel pin set up at greerstothers.shop. I hate asking for help, but if you'd like to support Belphie's continued treatment, please consider checking them out!

[soumyafwr]

https://carbonfacesocial.org/blogs/79307/Infectious-Disease-Testing-Market-Share-Overview-Competitive-Analysis-and-Forecast

Infectious Disease Testing Market Share, Overview, Competitive Analysis and Forecast 2031

[aishavass]

North America, followed by Europe are the largest regional markets for point of care testing for infectious diseases...

[foldingfittedsheets]

wait what the fuck go back why are there lambskin condoms at all

Yeah so, back in the day people didn’t like getting pregnant. And they didn’t have access to latex for a long time. So lambskin condoms are some of the OG contraceptives, they were better than nothin. The first iterations were made from animal intestines, there’s some debate but that was sometime in the 16th century, though some think it was much earlier.

When latex condoms hit the market in the 1850’s it would have been the death knell for lambskin except! People with latex allergies still needed an option that didn’t make them drop into anaphylaxis. Also animal condoms were still cheaper until the 1920’s. Fun fact: my friend Charlie is allergic to latex but decided to just use latex condoms anyway and got stuck hiding in a closet when the girls parents came home and forgot he had a biohazard on his penis until he started having a seizure and remembered to remove it.

Anyway! The downsides of current lambskin are numerous. First off, it feels an awful lot like wax paper which seems quite unpleasant for both partners. Additionally, it still transmits STIs, because lambskin is just… skin, and is permeable to infectious disease.

Lastly why it’s bad: Modern condoms are checked for microtears and breakage by running a small electrical current through them. That’s how we know they’re safe to prevent all the stuff. But lambskin can’t be subjected to this test, so it can’t even say it’s guaranteed to prevent pregnancy, if there’s microtearing semen are gonna get through.

But noooow there’s a baller new material called polyisoprene that can be tested for breakage, doesn’t smell bad like latex, and is hypoallergenic. They’re basically the best condom in every way, and lambskin should now bow out and stop existing.

[covid-safer-hotties]

The next pandemic is inevitable. Australia isn’t ready - Published Sept 23, 2024

(Before you Americans yell at me, It's already the 23rd in Australia. This is very late-breaking)

I thought this was a really good breakdown of the current situation given the government-approved covid denial we live in. Long, but worth a read.

By Kate Aubusson and Mary Ward

Top infectious disease and public health veterans at the nerve centre of the state’s war against COVID-19 are sounding the alarm.

NSW is less prepared today to fend off a deadly pandemic despite the lessons of COVID-19, say top infectious disease and public health veterans at the nerve centre of the state’s war against the virus.

And we won’t have another hundred years to wait.

NSW’s gold standard Test-Trace-Isolate-Quarantine and vaccination strategies will be useless if a distrusting population rejects directives, refuses to give up its freedoms again, and the goodwill of shell-shocked public health workers dries up.

A panel of experts convened by The Sydney Morning Herald called for a pandemic combat agency akin to the armed forces or fire brigades to commit to greater transparency or risk being caught off guard by the next virulent pathogen and misinformation with the potential to spread faster than any virus.

“It’s inevitable,” says Professor Eddie Holmes of the next pandemic. A world-leading authority on the emergence of infectious diseases at the University of Sydney, Holmes predicts: “We’ll have less than 100 years [before the next pandemic].

“We’re seeing a lot of new coronaviruses that are spilling over into animals that humans are interacting with,” said Holmes, the first person to publish the coronavirus genome sequence for the world to see.

“People are exposed all the time, and each time we are rolling the dice.”

The independent review of NSW Health’s response to COVID-19 opened with the same warning: “No health system or community will have the luxury of 100 years of downtime.”

Pandemic preparedness needs to be a “permanent priority”, wrote the report’s author, Robyn Kruk, a former NSW Health secretary, “rather than following the path of those that have adopted a ‘panic and forget strategy,’ allowing system preparedness to wane”.

Why we don’t have 100 years to wait for the next pandemic The World Health Organisation has declared seven public health emergencies of international concern since 2014, including the current mpox outbreak.

Climate change is turbocharging the factors that coalesce to create the perfect breeding ground for a pandemic-causing virus, including population increases, bigger cities, and better-connected global markets and migration.

“Animals will be forced into more constrained environments, and humans that rely on those environments will be again constrained in the same environments. There will be more wet markets, more live animal trade that will just increase exposure,” Holmes said.

“It was clear that we weren’t ready [for COVID],” said Jennie Musto, who, after seven years working for the World Health Organisation overseas, became NSW Health’s operations manager for the Public Health Emergency Operations Centre, the team responsible for NSW’s COVID-19 contact tracing and containment.

“Everyone had preparedness plans gathering dust on a shelf, but no one was actually ready to respond, and so everyone was on the back foot,” Musto said. “Perhaps none of us really thought this was going to happen. We were waiting 500 years.”

Who would willingly become the next doomed whistleblower? Eddie Holmes, known for his repeated assertion that SARS-CoV-2 did not come from a lab, is deeply concerned that when the next pandemic-causing virus emerges, chances are it will be covered up.

“My worry is that if the virus appeared in a small population, say, somewhere in Southeast Asia, the people involved wouldn’t blow the whistle now, given the fact that you would get blamed,” he said.

Li Wenliang, the Wuhan doctor who tried to raise the alarm about a virulent new virus, was reportedly reprimanded by police for spreading rumours and later died of COVID-19.

The global blame game, culminating in a deep distrust of China and accusations that the virus was grown in a Wuhan lab, is why Holmes believes “we’re in no better place than we were before COVID started, if not worse”.

“I work with a lot of people in China trying to keep the lines of communication open, and they’re scared, I think, or nervous about saying things that are perceived to counter national interest.”

From a vaccine perspective, our defences look strong. There have been monumental advancements in vaccine development globally, driven by mRNA technology. In Sydney this month, construction began on an RNA vaccine research and manufacturing facility.

“But the way I see it is that nothing has been done in terms of animal surveillance of outbreaks or data sharing. The [global] politics has got much, much worse,” Holmes said.

Combat force Conjoint Associate Professor Craig Dalton, a leading public health physician and clinical epidemiologist, called for a dramatic expansion of the public health workforce and the establishment of a pandemic combat force that would routinely run real-time pandemic simulations during “peacetime”.

“No one is upset with fire brigades spending most of the time not fighting fires. They train. A lot. And that’s probably how we need to move,” he said.

“We need exercise training units so that every major player in pandemic response is involved in a real-time, three to four-day pandemic response every three to five years at national, state and local [levels].”

The federal Department of Health and Aged Care recently ran a health emergency exercise focused on governance arrangements involving chief health officers and senior health emergency management officials, a spokeswoman for Health Minister Mark Butler said. The outcomes of this exercise will be tested later this year.

Dalton said desktop simulations and high-level exercises involving a handful of chiefs didn’t cut it, considering the thousands of people working across regions and states. He instead suggested an intensive training program run in the Hunter New England region before the 2009 H1N1 pandemic provided a good model.

“We were ringing people, actors were getting injections, just like a real pandemic,” said Dalton, who once ordered a burrito in a last-ditch effort to contact a restaurant exposed to COVID-19.

Our heroes have had it The expert panel was emphatic that our pandemic response cannot once again rely on the goodwill of the public health and healthcare workforce.

According to the Kruk review, what began as an emergency response ultimately morphed from a sprint into an ultra marathon and “an admirable (yet unsustainable) ‘whatever it takes’ mindset”.

They were hailed as heroes, but the toll of COVID-19 on healthcare workers was brutal. Workloads were untenable, the risk of transmission was constant, and the risk of violence and aggression (for simply wearing their scrubs on public transport in some cases) was terrifying.

“We got through this pandemic through a lot of people working ridiculous hours,” Dalton said.

“You talk to a lot of people who did that and say they could not do it again.”

Tellingly, several expert personnel who worked at the front lines or in the control centre of NSW’s pandemic defences were invited to join the Herald’s forum but declined. Revisiting this period of intense public scrutiny, culminating in online attacks and physical threats, was just too painful.

So long, solidarity Arguably, the biggest threat to our pandemic defences will be the absence of our greatest strength during COVID: the population’s solidarity and willingness to follow public health orders even when it meant forfeiting fundamental freedoms.

The public largely complied with statewide public health orders, including the stay-at-home directive that became the 107-day Delta lockdown, and other severe restrictions prevented many from being at the bedside of their dying loved ones, visiting relatives in aged care homes and attending funerals.

“My worry is that next time around when those sorts of rules come out, people may say, ‘Well, don’t worry about it.’ They relax it in the future. Why don’t we just not stick to the rules?” said Professor Nicholas Wood, associate director of clinical research and services at the National Centre for Immunisation Research and Surveillance.

“I’m not sure we quite understand whether people [will be] happy with those rules again,” he said.

Dalton was more strident.

“I tend to agree with Michael Osterholm … an eminent US epidemiologist [who] recently said the US is probably less prepared for a pandemic now than it was in 2019, mostly because the learnings by health departments in the COVID pandemic may not make a material difference if faced with a community that distrusts its public health agencies,” he said.

“If H1N1 or something else were to spill over in the next couple of years, things like masks, social distancing and lockdowns would not be acceptable. Vaccination would be rejected by a huge part of the population, and politicians might be shy about putting mandates in.”

As for the total shutdown of major industries, people will struggle to accept it unless the next pandemic poses a greater threat than COVID, said UNSW applied mathematician Professor James Wood.

The risk of the virus to individuals and their families will be weighed against the negative effects of restrictions, which are much better understood today, said Wood, whose modelling of the impact of cases and vaccination rates was used by NSW Health.

“Something like school closure would be a much tougher argument with a similar pathogen,” he said.

A previous panel of education experts convened by the Herald to interrogate pandemic decision-making in that sector was highly critical of the decision to close schools for months during NSW’s Delta lockdown.

Greg Dore, professor of infectious diseases and epidemiology at the Kirby Institute, said the public’s reluctance to adhere to restrictions again may, in part, be appropriate.

“Some of the restrictions on people leaving the country were a bit feudal and too punitive,” he said. “Other restrictions were plain stupid, [for instance] limitations on time exercising outside.”

Meanwhile, the delays to publicly recognise the benefits of face masks and the threat of airborne transmission “ate away at trust”, Dalton said.

“We shouldn’t make those mistakes again,” he said.

Transparent transgressions Uncertainty is not something politicians are adept at communicating, but uncertainty is the only constant during a pandemic of a novel virus.

Vaccines that offered potent protection against early iterations of the COVID virus were less effective against Omicron variants.

“[The public], unfortunately, got hit by a rapid sequence of changes of what was ‘true’ in the pandemic,” James Wood said.

Political distrust can be deadly if governments give the public reason to suspect they are obfuscating.

The expert panel urged NSW’s political leaders to be far more transparent about the public health advice they were given before unilaterally enforcing restrictions.

There was a clear line between public health advice and political decision-making in Victoria. The Victorian chief health officer’s written advice was routinely published online.

In NSW, that line was blurred as Chief Health Officer Kerry Chant stood beside political leaders, most notably former premier Gladys Berejiklian, at the daily press conferences.

Public health experts said that they looked for subtle cues to determine the distinction between the expert advice and the political messaging during press conferences, paying attention to body language, who spoke when and who stayed silent.

“It is fine for public health personnel to have a different view to politicians. They have different jobs. What is not OK is to have politicians saying they are acting on public health advice [when they are not],” he said.

The ‘whys’ behind the decisions being made were missing from the daily press conferences, which created “a vacuum for misinformation”, said social scientist and public health expert Professor Julie Leask at the University of Sydney.

“The communication about what you need to do came out, and it was pretty good … but the ‘why we’re doing this’ and ‘what trade-offs we’ve considered’ and ‘what dilemmas we’ve faced in making this decision’; that was not shared,” Leask said.

The infodemic In the absence of transparency, misinformation and disinformation fill the vacuum.

“We had an ‘infodemic’ during the pandemic,” said Dr Jocelyne Basseal, who worked on the COVID-19 response for WHO in the Western Pacific and leads strategic development at the Sydney Infectious Diseases Institute, University of Sydney.

“The public has been so confused. Where do we go for trusted information [when] everyone can now write absolutely anything, whether on Twitter [now called X] or [elsewhere] on the web?” Basseal said.

A systematic review conducted by WHO found misinformation on social media accounted for up to 51 per cent of posts about vaccines, 29 per cent of posts about COVID-19 and 60 per cent of posts about pandemics.

Basseal’s teenage children recently asked whether they were going into lockdown after TikTok videos about the mpox outbreak.

“There is a lot of work to be done now, in ‘peacetime’ … to get ahead of misinformation,” Basseal said, including fortifying relationships with community groups and teaching scientists – trusted and credible sources of information – how to work with media.

In addition to the Kruk review’s six recommendations to improve its pandemic preparedness, NSW Health undertook a second inquiry into its public health response to COVID-19, which made 104 recommendations.

NSW Health Minister Ryan Park said: “We are working hard to ensure the findings and recommendations from those reports are being implemented as quickly as possible.”

The expert panellists spoke in their capacity as academics and not on behalf of NSW Health or WHO.

The ‘As One System’ review into NSW Health’s COVID-19 response made six recommendations 1. Make governance and decision-making structures clearer, inclusive, and more widely understood 2. Strengthen co-ordination, communication, engagement, and collaboration 3. Enhance the speed, transparency, accuracy, and practicality of data and information sharing 4. Prioritise the needs of vulnerable people and communities most at risk, impacted and in need from day one 5. Put communities at the centre of emergency governance, planning, preparedness, and response 6. Recognise, develop and sustain workforce health, wellbeing, capability and agility.

[brainddeadd]

“Why do we keep pretending we don’t want to kiss each other?”

The sound of laughter and chatter filled the air around you as you and William Nylander walked through the bustling outdoor market. The warm evening sun cast a golden hue over the stalls, and the sweet scent of pastries wafted through the air, mixing with the laughter of families and friends enjoying the night.

You and William had been friends for a while now, your bond forged over shared interests and late-night conversations. But lately, there had been an undeniable tension between you two—something electric that made your heart race whenever he was near.

As you stopped at a stall selling handmade jewelry, William leaned in closer to get a better look. “What do you think of this one?” he asked, holding up a delicate silver bracelet.

“It’s pretty,” you replied, smiling at him. “But I think it would look even better on you.”

He laughed, the sound warm and inviting. “You think so? Maybe I should get it just for that reason.”

As he spoke, his eyes sparkled, and the playful banter continued, but the tension lingered just beneath the surface. You both picked out a few trinkets to remember the day, but every time your hands brushed against each other, a spark ignited.

Finally, unable to hold back any longer, you turned to him, your heart pounding in your chest. “William,” you started, trying to find the right words. “Why do we keep pretending we don’t want to kiss each other?”

His laughter faded, and he turned to you, surprise flickering across his features. “You feel it too?” he asked, his tone more serious now.

“Of course I do,” you replied, feeling a mix of relief and vulnerability. “It’s like this huge elephant in the room that we keep ignoring.”

He stepped a little closer, the distance between you shrinking as the laughter of the market faded into the background. “I thought I was the only one,” he confessed, his voice low. “I didn’t want to ruin our friendship, but I can’t help but think about how much I want to kiss you.”

Your heart raced at his admission, and a soft smile spread across your face. “So, why don’t we stop pretending?”

With that, William hesitated only a moment before leaning in closer, his gaze searching yours for permission. You nodded, and in an instant, his lips were on yours—soft and tentative at first, as if testing the waters.

The world around you melted away, and you melted into the kiss, feeling all the pent-up emotions and unspoken words finally come to life. As he deepened the kiss, wrapping his arms around you, you felt a sense of joy and relief wash over you. This was right.

When you finally pulled away, breathless and smiling, William brushed a strand of hair behind your ear, his eyes filled with warmth. “That was worth the wait.”

“Definitely,” you agreed, feeling giddy. “Now, let’s see what other trouble we can get into tonight.”

“Lead the way,” he said, his grin infectious as he intertwined his fingers with yours, ready to explore the rest of the evening together.

[felinefractious]

hi! love your blog, i love getting to see all these cool cat colors i didnt even know were a thing LOL like i didn’t know there was such a thing as lilac or cinnamon but theyre so pretty.

ive been looking into getting a ragdoll in the future, the ones i have met have been the sweetest cats and they’re so pretty.

ive been doing research into possible health concerns they can have, and all im really seeing is the same things your typical random little guy could have when improperly cared for and things like that. kidney disease while on a bad diet, issues with hairballs when not brushed and groomed properly due to being long haired, etc. ive seen a few places say that they’re more prone to respiratory issues and heart disease, but the latter also seems to be something that breeders work to make sure their cats are safe from? at least in my research.

i guess im basically just wondering if you know anything else that can affect ragdolls specifically, or if there’s anything horribly unethical that’s totally swept under the rug or hidden about them! additional things to research and places to look would be appreciated, i never know where to research stuff like this reliably and you seem to know where to find some good info and stuff on cat breeds :)

thank you in advance for any help you can give, i hope have a good day!!

I’m glad you enjoy the blog and are learning about some new colors!

Ragdolls are definitely cool cats and they’re a pretty health breed, one of the major things to be mindful of is that this assessment only applies to well-bred individuals from good breeders.

Common breeds mean a lot of breeders which, unfortunately, also means a lot of scammers and bad breeders.

And the Ragdoll is a very common breed so there are a lot of not so good breeders out there… and the temperament and health of these backyard bred cats is a gamble, one that can end in heartbreak.

Now with that warning out of the way the big thing to worry about with the breed is Hypertrophic Cardiomyopathy. Fortunately the mutation responsible for this condition in the breed has been identified and can be tested for. Staying on top of heart health is an absolute must for a good breeder, this means regular echocardiogram’s as well as DNA testing.

The other big ones are Polycystic Kidney Disease and Progressive Retinal Atrophy, both of which can be tested for. These are common inherited disorders in the purebred population, you’ll have a hard time finding a breed which neither of these have been documented in.

Mucopolysaccharidosis VI is a storage disease that has been documented in the Ragdoll breed but it can be tested for and I’m not sure how common it is in current breeding populations.

A breeder shouldn’t cut corners when it comes to health testing, there are several commercially available tests which look for a wide variety of inherited disorders. Optimal Selection is becoming increasingly widely used, although personally I would feel most comfortable with testing submitted through somewhere like UC Davis.

But HCM is the big big one because heart disease is a silent killer. With the other conditions clinical symptoms will be apparent but a cat with HCM could appear normal and you wouldn’t know without testing. And remember - not all cardiac cases will have a heart murmur, either!

The other thing to keep in mind with Ragdolls is they seem to be more prone to developing Feline Infectious Peritonitis. This one is a little more complicated.

FIP occurs due to mutations in the feline coronavirus, which is a common viral infection in cats. Until recently FIP was considered nearly 100% fatal but thanks to Dr. Niels Pederson we now have a promising cure. One of our patients was actually one of the original study cats and has been doing well all this time, she’s amazing to work with - like a piece of living history!

One of the big problems with the treatment is the legality of it… for a long time it was only available through the black market and could easily run you thousands of dollars. Treatment is gradually becoming available through legal venues but it depends on where you live.

Anyways, the point is that we don’t know exactly why these mutations occur in some cats and not others but there’s strong evidence that there’s a genetic component - it’s common for related cats to develop FIP, we’ve seen this multiple times with littermates. We also know that it occurs at a higher incidence in some breeds than others…

And presumably your kitten wouldn’t have been exposed to feline coronavirus at the cattery but it’s not unlikely that they would be exposed at some point in their life given they don’t reside in a bubble… and if or when this happens what are the chances it’ll become the dreaded FIP?

So mitigating this risk when purchasing from a breeder can be a little more complicated… it’s not something I think should turn you off of the breed but it is something to keep in mind - and if you look into a breeder that seems good but has a lot of reviews or reports of their graduate kittens and cats developing FIP? Probably best to keep looking.

I think that’s a pretty good summary on the breed’s health but people are always welcome to chime in!

[devoted1989]

65,000 non - human primates are used in laboratory experiments every year in the united states

Each year, more than 110 million animals - including mice, rats, dogs, cats, rabbits, hamsters, fish and birds - are killed in U.S. laboratories for chemical, drug, food, and cosmetics testing. In order for a drug to be approved in the United States, the FDA typically requires toxicity tests on one rodent species such as a mouse or rat and one nonrodent species such as a monkey or dog.

Around 65,000 non - human primates (NHP) are used every year in the United States, and around 7,000 across the European Union. No new biomedical research projects have been approved on chimpanzees in the US since 2015.

Macaques are now the most commonly used NHP - most are imported from China and Cambodia.

The huge demand for research monkeys and their rising costs have created a market for monkey smugglers.

While most macaques imported by the US are identified as captive-bred on paper, some experts believe that many of those in US labs have been trafficked from the wild as the illegal trade in wild-caught macaques is widespread. Sources state that prices vary from $5 000 - $20 000 per monkey.

NHPs are used because of their similarities to humans with respect to genetic makeup, anatomy, physiology, and behavior which make it possible to approximate the human condition.

NHPs are used in research into HIV, neurology, behavior, cognition, reproduction, Parkinson's disease, stroke, malaria, respiratory viruses, infectious disease, genetics, xenotransplantation, drug abuse, and also in vaccine and drug testing.

The NIH is the largest public source of funding for biomedical research in the United States.

Last year new U.S. law eliminated the requirement that drugs in development must undergo testing in animals before being given to participants in human trials. It allows the U.S. Food and Drug Administration (FDA) to approve new drugs without requiring animal data.

Signed in December, the law doesn't ban the testing of new drugs on animals outright. Instead it simply lifts the requirement that pharmaceutical companies use animals to test new drugs before human trials. Companies can still test drugs on animals if they choose to.

And pro-research groups are downplaying the law, saying it signals a slow turning of the tide. Jim Newman, communications director at Americans for Medical Progress, which advocates for animal research, argues non-animal technologies are still “in their infancy” and won’t be able to replace animal models for “many, many years.” The FDA still retains tremendous discretion to require animal tests, he says.

- National Institutes of Health ( https://www.ncbi.nlm.nih.gov), Science Direct, World Animal Protection, science.org, National Anti - Vivisection Society and HSUS.

Image with kind permission from The Ethic Whisper.

@theethicwhisper

[mangoshorthand]

Flesh and Blood- [Five Hargreeves x F Reader]. Ch1 (Hard Feelings Part 3)

SUMMARY: As Christmas approaches, everything between you and Five is perfect...until a destructive temporal anomaly gets in the way. Five is convinced another permutation of himself is to blame. Nothing's simple when you're in a relationship Five Hargreeves: could your loyalties be tested in a way unique to him? On to Chapter 2 >>

Chriiissstmmaaassss.

Chapter One: Another Apocalypse

It’s Saturday morning. When you left him, the bedroom window and curtains were cracked so that pale-toned winter sunlight bathed the bed in a slanting shard. The chilly air felt pleasant on your skin and clean in your lungs, warm as you both were between the bedclothes.

He was asleep with his head turned from you, the light and shadow falling on his face. The fine hairs on his neck stood on end with the cold air. He had been snoring very lightly. The rays of light and very slight breeze tangled in his hair, fluttering it occasionally. You might have wanted him to wake, yet you could also watch him sleep for hours; you could be happy here, feeling his warmth. 

But your bladder was no respecter of such sentimentality. It soon became imperative to leave the bed. After relieving yourself and taking a painkiller for a threatening headache, you’d make your way down to the kitchen and put on a pot of coffee.

You try to be quiet as you re-enter the bedroom but he stirs almost immediately.

“Mmm…coffee?” his voice is hazy.

“Yep. Good morning.”

“Morning, dear one. C’mere”

You put down the breakfast tray and rejoin him on the bed. He wraps his arms around you and you lay your head on his chest. He puts his mouth and nose against your hair and inhales. 

It's been a blissful six months since the JUICED scandal. Since you started paying the (largely symbolic) rent to Reginald's estate, you'd felt better; stronger. As a result there's a new feeling between you; you can riff, harmonize and improvise around one another like a string duo- switching who plays the base notes as needed. True, it's not as if he's been seriously tested again since the JUICED scandal but, so far, it's been...nice.

Again, the breeze plays around your entwined bodies. He’s sure he can feel the rush of serotonin as he breaths in your scent…serotonin or love; call it what you want. 

"How are you today?" he asks.

"Another headache."

"Really?" You can hear the worry in his voice.

"I took a painkiller: it's fine." then, to distract him, “How about we go out today?"

He grunts.

“Gonna need at least three coffees.”

You extract yourself from his arms and bring him over a cup. He takes a grateful sip.

“Ahhh. That’s good. Do I smell bagels?”

You hand him one plate and grab your own, sitting back down beside him with your own mug. For a few minutes, you eat and drink in companionable silence. Then, with your breakfast eaten, you turn to him.

“Shall we go Christmas shopping?”

He groans, “I think I'd rather scoop out my own testes with a grapefruit spoon.”

“I could arrange that for you?”

He grumbles. You kneel on the bed and swing one leg over him.

“Watch it!” he puts his coffee cup on the nightstand to avoid you knocking it out of his hands. 

You sit on his knee, facing him.

“Come on,” you wheedle, “we can go and get cocoa and walk in the park and go to the German markets.”

“Kill me,” he groans but he’s smiling too, bringing his hands to your hips.

“You’re the one with the huge family to buy for. Let’s get all our gifts out of the way.”

He sighs, rolling his eyes.

“Fine.”

“Yes!” you say, pumping your fist, “but you have to promise not to be surly. Ooh, and let’s go ice skating!”

“NO ice skating!”

You laugh and kiss him. He responds enthusiastically, laughing a little into your mouth.

“I gotta draw the line at ice skating but I’ll do the rest.” 

Five’s enjoying himself more than he wants to admit. Today, your joy is infectious in a way that makes you radiant. 

His Christmases since arriving home had always been participated in out of obligation. He’d only really bought gifts for his nephew- he and his brothers didn’t often exchange them, although they all got together for a meal. 

Though he’d been with you last year, you were still recovering in hospital from your encounter with Michael Monroe so hadn’t been able to go Christmas crazy...which he's just learning is natural to you.

Despite feeling slightly sick from the glühwein, this is undeniably pleasant. He even found himself fully engaged in picking out a gift for Lila, of all people. He'd even gone so far as to recommend one bracelet over another- and it was the bracelet he thought Lila would like more, too. 

Now he’s standing in a store debating the merits of various gingerbread houses. He's laden with all your shopping bags as well as his own because you keep leaving them on the floor in your excitement to make the next purchase. If he were a less cynical man, he might call this adorable rather than annoying.

While Five valiantly tries to remain cynical, it’s hard. God knows he is not an easily led man, yet he's helplessly borne along in the wake of your excitement.

"It's style over substance,"  he says, indicating the giant gingerbread house you're standing beside, "if it's gonna get eaten then it's the taste that matters. Santi will demolish whatever we buy in five minutes anyway so what's the point?"

When you look at him, you're impassioned to a point that makes him want to laugh.

"Your shitty-ass gingerbread house doesn't even have a second floor. This is a gothic revival gingerbread house. Look at the windows! Look at the little wreath on the door! Look at the roof gables!"

"You're gonna eat it, not move in....and it's ninety dollars!"

"Oh fuck off. I've seen your bank balance, Five Hargreeves. This is Christmas."

He shakes his head at the absurdity of it all.

"You know, for an atheist with criticisms of capitalism, you're pretty into this."

You pout, forcing a smile from him. Despite this, he still tries to dissuade you.

"You know it will have gone stale by Christmas, anyway.

"You think I’m stupid? I'm not saying we get one now. I'm thinking to PRE-ORDER."

You give him a look of impatient, electrified enthusiasm, shining eyes bulging out of your head, eyebrows in your hairline and corners of your mouth turning down. You look entirely mad.

And then he’s impelled to take action by something stronger than his reason.

“You want to meet me on the square in an hour?” he asks

“Why?”

He tilts his head noncommittally. 

“Maybe I’ve got…stuff to buy.”

“Hmm. Ok,” you say, grabbing him by the front of his coat, “maybe I got stuff to buy too.”

Then, you kiss him briefly on the lips.

And there's your smell, your soft lips, your smile….

He doesn’t consciously know where his feet are taking him until he’s there and staring in the window. How the hell has he come to this?

He’s not an easy man to buy for. His birthday back in October was tricky enough. He’s been experimenting more recently with clothing beyond suits...but you don’t just want to buy him a shirt or something: he's not your Dad. You find yourself in an antique bookstore with creaky floorboards. It smells strongly of furniture polish and beeswax. The mahogany counter and bookshelves shine with them.

 It’s one of those places where the salespeople don’t fully trust you unless you look like a fellow collector. The tweed-suited man eyes you with benign suspicion as you enter. He takes his feet off his desk and stands to assist rather than letting you browse and potentially damage his stock.

“Good afternoon Ma'am."

"Hi," you smile.

"Are you looking for something in particular?”

“Uh- just a Christmas gift for my partner.”

The guy retains his polite smile, but you think you see something die behind his eyes nevertheless.

“Do you have anything in mind?”

You were overjoyed with your purchase.  It had set you back a pretty penny, but it was more than worth it when you imagined his face. By the end of the encounter, the salesman had become much more unctuous. 

One of the advantages of living all but rent-free in the family compound of an eccentric dead billionaire was being able to save pretty much your whole paycheck.This was aided by the fact that said paycheck had increased significantly a couple of months ago. 

You'd finally achieved the promotion you privately thought you'd deserved for eighteen months. You'd like to think that the higher-ups simply noticed all your hard work but this would be optimism to the point of stupidity. You'd become a bit of an office celebrity since the JUICED scandal.

The domino mask you'd worn at the press-conference did not shield your identity from those who already knew you. You knew the news footage had been widely shared between whispering co-workers. For weeks afterwards, you'd catch people looking from you to their computers and back again. In addition, Neil from HR told a pretty convincing story about how he'd seen you meet and be driven away by 'that Hargreeves boy from the papers' in a reconditioned Corvette Stingray. 

The book you'd bought for Five was a rare find and couldn’t be more perfect for him - it was beautiful, meaningful and came with that old-book smell that you’ve come to associate with him. 

He collects voraciously, spending hours re-stitching broken bindings and restoring or replacing worn endsheets. Having lived most of his life in a ruined library where most of the books had been completely destroyed, he hoarded books on almost any subject. The older they were, the more he valued them. He's never confirmed this, but you think that perhaps his love of these aging survivors is a deeply personal identification. 

Another headache has been threatening for the last quarter of an hour, so you sit down on a bench to wait for him. Shoppers pass with the bustle of human activity. You let your head lean forward a little and close your eyes.

And then, a rushing sound and whip-like crack.

You feel a ripple like electrical wind pass through your skin. Your stomach flips as if you’ve just missed a step walking downstairs. You and many of the people around you let out little exclamations of surprise- as you look sharply up, you see people's hair and shopping bags rustle as the almost-invisible force, (whatever it is), passes. A man standing a few feet away begins to scream. His body is caught in what looks like a film of blue light into which energy courses with a thrumming that hurts your already aching head. As he yells, fights and flails to free himself, it warps and flexes with his movements. Sparks fly with a rumbling sound like thunder. 

You only have time to gasp in horror before Five blinks into being, still holding shopping bags. He raises his arms in an instinctive protective gesture, one over his own head and the other holding you back and behind him. You both watch as, in under a second, the void consumes the shrieking man and collapses in on itself with a buzz and flumping sound. Dropping the bags, Five’s hand smacks against his forehead.

“SHIT.”

People around you scream, the man who had been beside the void’s victim panics and yells:

“Kevin! KEVIN?”

Five ignores him and looks wildly around. He scans the sky, the ground, surrounding buildings and then the crowd. His body language has taken on that frenetic energy that comes over him when on the job. He pats down his own body, searching urgently.

“Pen. I need a pen. Anything.”

You pat your pockets uselessly, knowing there’s nothing there either.

“Why don’t I carry pens?”, his hand flies back to his forehead he looks around desperately, before yelling, “SHIT!” again.

“What is it?”

“I don’t…it can’t be…wait- is this stage one? No…because then I wouldn’t have asked that. Or is that what I want me to think?” he scratches his neck distractedly, his face lined with mistrust.

“Five?”

He begins to pace.

“It was me. I felt it.”

“What?”

His wild eyes find yours. He hesitates for a fraction of a second and then tells you:

“That was my power. I know the feeling. I felt it from across the street. That-” he points at the yelling man, “-was me. That was one of my temporal portals. What the hell do I think I’m doing?"

His hands come out to feel the air in front of him in the direction of the vanished portal. He draws in breath through his nose as if searching for a scent.

"It feels...like nonsense." His eyebrows contract even tighter. Again, his eyes rove your surroundings and then, finding nothing, he yells with frustration. 

“WHERE ARE YOU, ASSHOLE?” he screams into the crowded street. After a few more moments of pacing, he snatches up the bags and grabs your hand.

“Come on, if he’s going to go anywhere, it'll be the Academy.”

Back at home, you sit downstairs in the living room. Five’s rapidly filling a notebook with scribbled calculations and mutters to himself compulsively. He’s been like this all the way home, speaking in random disconnected phrases that don’t mean anything and don’t seem to answer your questions: "Doesn't work with the fifth principle" or "Is this a Dallas permutation?"

“Five"

He jerks his head as if displacing an irksome fly.

"Can you explain this more?”

He holds up a finger imperiously and continues scribbling for a few seconds before looking up at you, his pen poised above the paper as if it’s taking all his self-control to pause its track across the page.  

“I will. I promise. Just give me a few minutes. Get them all here- all of my brothers. Now. We need a meeting,” he holds your eyes for a second, clearly seeking affirmation that this satisfies you for now. 

You nod your acceptance; your appreciation of this consideration. 

Five took a lot of persuading to join the Hargreeves family group chat, but since giving in, he’s been a solid contributor. Now, as you message the group, your message appears right below one from this morning in which he joked that he used Lila’s lost razor to shave his balls. 

You: Emergency meeting asap. Five says apocalypse-level shit. @all

Diego: Fuck.

Sloane: With you in 30 minutes

Viktor: Coming. 30 minutes too.

You: @Klaus??

Lila: Try the 3rd floor bathroom.

It took you having to nearly knock the door off its hinges to get Klaus to respond . He’d been listening to headphones and seemed mildly surprised when he popped his head around the door to find you looking exasperated. When, with a towel wrapped around his waist, you and he re-enter the living room, Lila and Diego are attempting to question an impatient Five, still scribbling incomprehensible math.

“Shut UP. I’m nearly done.”

Lila matches his exasperated tone.

“The hurry the fuck up!" 

Finally, he throws the book down and stands.

“Okay: I’ll explain it to the others when they get here. We all need to be on the lookout for another me.”

Klaus and Diego let out sighs of frustrated weariness as Lila says:

“Oh great. Younger or older?”

“Your guess is as good as mine. All I know is, there’s a version of me running around making real shitty time portals to suck up Christmas shoppers."

“Why would you do that?” Diego asks, as if stung at Five’s behavior.

“I. don’t. know." the toes of one foot begin to tap, "I just know it was my power and the math on the relativity vector is nonsense.”

He runs his fingers through his hair, sweeping it out of his eyes.

 “Time travel’s a crapshoot at the best of times but this…I’d barely even call this time travel. I doubt if that guy it caught even exists anymore. He’s probably in a thousand pieces all over the twelfth and thirteenth centuries.”

He turns to you, looking at you intensely.

“You were right there. Did you see where it came from? Did you see me?”

“No,” you say, “I felt it though. I felt it ripple.”

“Are you absolutely sure? Maybe a kid in the shorts, like in the painting? Or older, with a mustache, probably in a suit?”

You cast your mind back, “No, I didn’t see you. All I saw was the guy.”

He accepts this.

“All in all- this is not good. I know things are more flexible at the Commission now but Herb’s gotta be pissed about whatever I’m doing.”

He paces again, looking down at the last few pages of his notebook.

“This could be another apocalypse, people.”

“Really,” opines Klaus, “when I just got my hair nice?”

Again, Five sits behind his father’s desk across from Herb, whiskey poured for them both. He arrived within a second after Five used his personal pneumatic pipeline to contact him. 

“I have to tell you Number Five, so far, we’re as clueless as you on this. The switchboard gave us the alert about the temporal anomaly but that’s as much as we know.”

He sips his drink, looking troubled. “Can you give me any insight on why a version of you might be running these ‘experiments’?”

“Wish I could Herb. The equations as far as I can detect them make no sense. I would have told you that I’d never try it...if I hadn’t seen it with my own eyes.”

He pushes his notebook across the desk to Herb. He scrutinizes a few pages of calculations, face the picture of confused concern. When he's seen enough, he looks back up at Five. 

“You know we may have to take action on this.”

Five meets Herb’s eyes. It’s not a threat, not aggressive; he simply says it as an uncomfortable fact. 

“Well it’s not me me. It’s different timeline me. I can promise you I don’t intend to start spitting out nonsense woodchipper time portals,"

Five placed his glass down on the desk, leaned back and sighed.

"He’s just likely to give you a lot of trouble.”

Herb just drinks his scotch, not meeting Five's eyes.

You lie in bed together that night.

“I need you to be vigilant,” says his voice, out of the dark, “the other versions of me…part of my power means we can exist almost independently of each other across different timestreams if we do the right math. At least...theoretically. I can’t answer for my motivations under different circumstances.”

“What do you mean? Vigilant?”

He sighs, “It might be a version of me that wouldn’t care if he hurt you.”

You stay silent.

“Maybe from before I met you. Or it could just be a me who’s traveled back. So you need to keep your eyes open.”

“Ok.”

“I need you to watch me closely too. If the other me gets too close, I’m going to develop paradox psychosis. I thought I felt a bit of it today- it’s what made me sure I was nearby. Problem is, the first stage of the psychosis is denial, so I won’t be much help when the time comes."

"Huh?

"You shouldn't really be around your doppelgangers. It's not good for you. There are seven stages you need to be on the look out for." He holds up his hands and counts them off on his fingers. "We have denial, itching, extreme thirst and urination, excessive gas, acute paranoia, uncontrolled perspiration and then homicidal rage."

You laugh nervously, "Sounds like your average Saturday night."

"Very funny." he says, though unamused, "If you see any of the warning signs, we’ll know I’m around. Then we can assess the situation and do what has to be done. I'll need you to keep a close eye on me. I might get...unmanageable but if I'll listen to anyone, I'll listen to you. ”

You lie there silently. Your overtaxed mind races. Homicidal rage? Versions of Five that could hurt you? He rolls over and turns to you, you feel his breath on your cheek.

“I know this is a lot to get your head around. I haven’t myself. But we’ll manage. Whatever it takes.”

Under the sheets, his hand strokes your hip.

Tag list: (please comment to be added or removed.) @dilfjohhny , @sunsunhe, @w4stedtr4sh, @nevbrooke-555, @theredvelvetbitch, @td-miley01, @five-hxrgreeves

On to Chapter 2 >> Masterpost

Alternatively, join me on A03.  Here is a link to the whole series

[bbmct]

BBMCT: Begin Medical Research at AIIMS Hospital BBMCT: Begin Medical Research at AIIMS Hospital

## BBMCT: Your Trusted Partner for Advanced Clinical Research at AIIMS Hospital British Biomedicine Clinical Trials (BBMCT) is a renowned name in the field of clinical research, offering unparalleled expertise in advancing medical therapies. Through our partnership with **AIIMS Hospital** - one of India's most prestigious healthcare institutions - we are able to deliver advanced clinical research services across a wide array of therapeutic areas. This collaboration is focused on ensuring the highest standards of scientific integrity, patient safety, and regulatory compliance, all while accelerating the development of innovative medical solutions. In this blog post, we explore how BBMCT serves as your trusted partner for clinical trials at AIIMS, highlighting the institution's strengths, advanced facilities, and our commitment to delivering reliable and scientifically robust outcomes. ### 1. **BBMCT: Begin Medical Research at AIIMS Hospital** AIIMS Hospital has long been a global leader in medical education, research, and patient care. Its world-class infrastructure and commitment to scientific excellence make it an ideal setting for conducting cutting-edge clinical trials. Through our partnership with AIIMS, BBMCT ensures that each clinical study is conducted under the highest standards of care, bringing advanced therapies closer to market. AIIMS offers a comprehensive research environment, housing various specialized departments and providing access to a vast network of clinical specialists, researchers, and medical professionals. This allows for thorough examination and testing of new treatments, ensuring that every phase of the clinical trial is executed seamlessly. ### 2. **Distinguished Institution for Clinical Research** AIIMS Hospital is internationally recognized for its significant contributions to medical research, particularly in the fields of oncology, cardiology, neurology, and infectious diseases. As a government-funded institution, AIIMS not only provides state-of-the-art medical facilities but also offers a platform for translational research that bri

[springsheep]

War of Faith Notes Ep. 1 - 10

Ep 1 -> Wei Ruo Lai's intro, stock market

shen jinzhen the sniper appears.

Shen Jinzhen meets Wei Ruolai (rickshaw), Li Qin in pastel pink is soo pretty

Wei Ruolai sneaks in through the roof hahaha

Wei Ruolai is given a coat, goes to do the exam for Central Bank

Ep 2 -> Wei Ruolai doing the test (the fire).

Wei Ruolai interview with the Shen guy.

Poor Wei Ruolai, failed the interview becuz of his background

Wei Ruolai sneaks into Shen's party, sees Shen Jinzhen playing the piano. Wei Ruolai watches from afar.

Wei Ruolai tells Shen Tunan he has solved the Kunseng riddle.

Ep 3 -> Wei Ruolai is accepted!!! yesss

Wei Ruolai don't drink too much!! Shen Jinzhen watching them. Wei Ruolai: I'm really not a communist.

Wei Ruolai eating and drinking so much hahaha, Wei Ruolai is a bit drunk, playing violin.

Wei Ruolai's friends (from the "slums") celebrate his job.

Wei Ruolai's weird grandpa friend: In the financial world, it doesn't matter who can make more money or who can make money faster, what's important is, who can live longer. You win, when you don't lose.

Congyun doesn't like Wei Ruolai... hmmm

Shen Jinzhen infiltrating a hotel to kill someone. Shen Jinzhen 好帅啊啊 wearing pink dress tsk tsk so pretty

Wei Ruolai using binoculars to monitor the stock exchange

Lin Qiao Song interrogating Li something

Wei Ruolai understands what Mr. Shen is doing (I don't grr)

Ep 4 -> that guy's name is Lin Qiaosong.

Oh no, i think the Lonely Star is Wei Ruolai's brother... Secretary Huang is evil. Wei Ruolai learning how to identify real vs fake coins.

那个姓黄的再欺负我宝贝啊。hmph

Aaaaah poor Wei Ruolan, his brother got shot and fled to his apartment and he's bleeding everywhere. Wei Ruolan is begging his brother to go to the hospital...

Aaaah poor wei ruolan... wang yibo's crying is so infectious damn it.

Wei Ruolan buries his brother. Wei Ruolan's bro is supposed to bring the gold for the Communists. Wei Ruolan after seeing the gold: =_=

#poor Wei Ruolan's bro who only lived for 4 episodes

Ep 5 -> secretary huang is a biatch

Wei Ruolan thinks of his bro. Shen Jinzhen eats with Lin QIaosong.

Wei Ruolan stops the rich guy from emptying the vault. The Zhang guy was holding him at gunpoint grrr....

Shen Tunan arrives in time to save him (I'm starting to ship these two damn it)

Wei Ruolai posts the newspaper ad, will meet the handler.. aka Shen Jinzhen...

fuckfuckfuck Lin Qiaosong cracked the code also!!!! Fuckfuck

Ep 6 -> Shen Jinzhen and Wei Ruolai pass by each other, Shen Jinzhen scolds him to save him from Lin Qiaosong.

Shen Jinzhen fails to contact Wei Ruolai with the password, Lin Qiaosong starts to suspect Shen Jinzhen

so... the bro's name is Wei Ruochuan.

Li Shengda attacks Wei Ruolai, tells him his brother is a communist.

exam time (Wei Ruolai please get good grades arghs)

Shen Tunan (to Secretary Huang): Do you want him to leave or stay?

Ep 7 -> Everyone compete against Huang Congyun. Someone needs to kick him off his high horse (someone aka my baobei ofc)

Wei Ruolai: Secretary Huang said I need to be on standby for you 24 hours, so I missed some classes...

Shen Tunan glaring at Huang guy lololol

Wei Ruolai Vs. Congyun.

Wei Ruolai is so hardworking argh

He's been studying late into the night. Wei Ruolai wins (ofc)

Li SHengda acting bitchhh Wei Ruolai nooooo don't believe himmmmmm

Noooo Wei Ruolai told him about the 20 gold bars. whyyyy

Wei Ruolai suspects Li Shengda (thank god omggg)

Li Shengda is a piece of shit.

Ep 8 -> Wei Ruolai meets the correct handler.

Wei Ruolai swears revenge for his brother.

Li Shengda is killed (finally).

Shen Jinzhen is happy.

Lin Qiaosong wants to convict Wei Ruolai of being a Communist, but LOL Wei Ruolai is prepared. He 1) called the the police to report Li Shengda before, and 2) "turned himself in" by writing a report.

Shen Tunan looks so pleased lol, Lin Qiaosong is pissed obviously.

Everything is under Wei Ruolai's control (dis boi got plans hahaha).

Shen Tunan protecting Ruolai hahaha. Shen Tunan: I'll bear the consequences.

Mr. Kang is mad at Lin Qiaosong. Poor guy... he got whipped.

aww shen tunan's wife doesn't want to leave him.

Ep 9 -> Lin Qiaosong has a wife(?) girlfriend or something. She's upset to see his wounds. (I thought this guy was single).

Wei Ruolai 真的有本事啊

Wei Ruolai has photographic memory(?) Shen Tunan is preparing to make some big moves, tells Wei Ruolai to memorize the imports and exports blablabla.

The Central Bank is making big moves (tarrifs), people protest the Central Bank.

Shen Tunan (to Wei Ruolai）： It might be dangerous by my side, are you afraid?

Wei Ruolai expressed his thoughts, Shen Tunan praised him. halfway to sucess for the tariff reform.

Wei Ruolai asks for a gun from the Qian gang.

Mr. Qian: It's okay, i'll give you an axe instead. It's made of Manganese Steel. Wei Ruolai: =_=

Wei Ruolai visits a club(???) following the Zhang guy. Wei Ruolai what are you planning...? ohno don't kill him

Wei Ruolai stole Zhang Mingquan's gun and starts writing smth? and dismantles the gun and tries it out.

Ep 10 -> Su Cishu's acting ('nonono')

The Shen family's so cuteee lol and the Shen siblings bickering hahaha

Shen Jinzhen gave her brother a bulletproof vest.

Zhang and Yu want to assassinate Shen Tunan...

fuuck Shen Tunan is late for the tariff voting event, Wei Ruolai is gonna make a speech on his behalf (to delay the voting, cuz STN isn't there yet).

Damn an angry Wei Ruolai is shuaii hahaha

Wei Ruolai is making an impromptu speech letsgooooo

Shen Tunan is shot(?) in the arm. He fainted after the voting is finished.

Shen Jinzhen and Shen Tunan's wife are worried.

[blithe--spirit]

2 Richards

In the early 80s I was working for my dad (a self-employed builder and plumber) in a big lodging-house in Paddington (West London). There were a lot of students living in the property, and one had recently vacated one of the rooms, in which I found a copy of Richard’s Bicycle Book.

I hadn’t been on a bike for about five years, but I read this tatty old paperback from cover to cover over the following couple of days, and Richard Ballantine’s enthusiasm for cycling was so infectious I was consumed with the urge to get back on the saddle as soon as possible.

Richard Ballantine

So I bought a Raleigh Ace road bike from Club Row market in East London for £79 and became a cyclist. Thank you, Richard, you changed my life for the better.

Raleigh Ace (with me on it), 1984

A couple of years later I met Richard Dyer, who bumped my enthusiasm up a few more notches by introducing me to the London To Brighton Bike Ride and once again the passion was infectious. Once my eyes were opened to this wonderful two-wheeled world, there was no looking back. My half-hearted intentions to learn to drive and pass the driving test and get a car were abandoned and have never returned.

Richard Dyer (now a transport and climate campaigner for Friends Of The Earth). This photo is from 1985, and he still rides the same bike today.

Now I’m in my sixties and have been a “serious” cyclist for nigh on forty years and still cycle every day and this is in part thanks to the two Richards above.

Richard Ballantine's contibution to the world of cycling can’t be overstated. If you ride a bicycle - in any capacity - you owe it to yourself to hunt down a copy of Richard’s Bicycle Book and any of his other fine titles.

[covid-safer-hotties]

Also preserved on our archive (Daily updates!)

By Stephani Sutherland

Gentle nasal spray vaccines against COVID, the flu and RSV are coming. They may work better than shots in the arm

Alyson Velasquez hates needles. She never liked getting shots as a kid, and her anxiety only grew as she got older. “It really ballooned in my teens and early 20s,” she says. “It became a full-blown phobia.” She would panic at the sight of a needle being brought into an exam room; more than once she passed out. Velasquez says that she took an antianxiety medication before one appointment yet still ran around the room screaming inconsolably “like I was a small child; I was 22.” After that episode Velasquez, now a 34-year-old financial planner in southern California, quit needles completely. “No vaccinations, no bloodwork. For all of my 20s it was a no-go for me,” she says.

Then COVID showed up. “It finally hit a point where it wasn’t just about me,” Velasquez says. “It felt so selfish not to do this for the greater public health and the safety of our global community.” So she got vaccinated against the SARS-CoV-2 virus in 2021, although she had to sit on her husband’s lap while he held her arms. “It was a spectacle. The poor guy at CVS ... he did ask me, ‘Are you sure you want to do this?’” She very much did. “I’m very pro-vaccine. I am a rational human. I understand the necessity of [getting] them,” she insists. But today she still struggles with each injection.

Those struggles would end, however, if all her future vaccinations could be delivered by a nasal spray. “Oh, my God, amazing!” Velasquez says.

The amazing appears to be well on its way. Vaccines delivered through the nose are now being tested for several diseases. In the U.S., early clinical trials are showing success. Two of these vaccines have generated multiple immune system responses against the COVID-causing virus in people who received them through a puff up the nose; earlier this year their makers received nearly $20 million from Project NextGen, the Biden-Harris administration’s COVID medical initiative. Researchers are optimistic that a nasal spray delivering a COVID vaccine could be ready for the U.S. as soon as 2027. Although recent efforts have focused on inoculations against SARS-CoV-2, nasal vaccines could also protect us against the flu, respiratory syncytial virus (RSV), and more.

A few nasal vaccines have been introduced in the past, but they’ve been beset by problems. The flu inoculation FluMist has not gained popularity because of debates about its effectiveness, and a different vaccine was pulled from the market decades ago because some people had serious side effects. In China and India, nasal vaccines for COVID have been approved because those countries prioritized their development during the pandemic, whereas the U.S. and other wealthy nations opted to stick with arm injections. But this new crop of vaccines takes advantage of technology that produces stronger immune responses and is safer than preparations used in the past.

In fact, immunologists say these spritzes up the nose—or inhaled puffs through the mouth—can provide faster, stronger protection against respiratory viruses than a shot in the arm. That is because the new vaccines activate a branch of the immune system that has evolved for robust, rapid responses against airborne germs. “It may be more likely to really prevent infection from getting established,” says Fiona Smaill, an infectious disease researcher at McMaster University in Ontario. Such inoculations may also help reduce the enormous inequities in vaccine access revealed by the pandemic. These formulations should be cheaper and easier to transport to poor regions than current shots.

But nasal vaccines still face technical hurdles, such as how best to deliver them into the body. And unlike injected vaccines, which scientists can measure immune responses to with blood tests alone, testing for immunity that starts in nose cells is more challenging. But researchers working in this field agree that despite the hurdles, nasal formulations are the next step in vaccine evolution.

Traditional vaccines injected through the skin and into an arm muscle provide excellent protection against viruses. They coax immune cells into making widely circulated antibodies—special proteins that recognize specific structural features on viruses or other invading pathogens, glom on to them and mark them for destruction. Other immune cells retain a “memory” of that pathogen for future encounters.

Intramuscular injection vaccines are good at preventing a disease from spreading, but they do not stop the initial infection. A nasal spray does a much better job. That’s because sprays are aimed directly at the spot where many viruses first enter the body: the nose and the tissue that lines it, called the mucosa.

Mucosa makes up much of our bodies’ internal surfaces, stretching from the nose, mouth and throat down the respiratory tract to the lungs, through the gastrointestinal tract to the anus, and into the urogenital tract. Mucosa is where our bodies encounter the vast majority of pathogenic threats, Smaill says, be it flu, COVID, or bacterial infections that attack the gut. This tough, triple-layered tissue is specialized to fight off invaders with its thick coating of secretory goo—mucus—and with a cadre of resident immune cells waiting to attack. “Mucosa is really the first line of defense against any infection we’re exposed to,” Smaill says.

Mucosal immunity not only prepares the immune system for the fight where it occurs but also offers three different types of protection—at least one more than a shot does. Nasal vaccines and shots both mobilize immune messenger cells, which gather the interlopers’ proteins and display them on their surfaces. These cells head to the lymph nodes, where they show off their captured prize to B and T cells, which are members of another part of the immune system called the adaptive arm. B cells, in turn, produce antibodies, molecules that home in on the foreign proteins and flag their owners—the invading microbes—for destruction. Killer T cells directly attack infected cells, eliminating them and the microbes inside. This provides broad protection, but it takes time, during which the virus continues to replicate and spread.

That’s why a second type of protection, offered only by the mucosal tissue, is so important. The mucosa holds cells of the innate immune system, which are the body’s “first responders.” Some of these cells, called macrophages, recognize invasive microbes as foreign and swallow them up. They also trigger inflammation—an alarm sounded to recruit more immune cells.

Another part of this localized response is called tissue-resident immunity. These cells don’t have to detect telltale signs of a pathogen and make a long journey to the infected tissue. They are more like a Special Forces unit dropped behind enemy lines where a skirmish is occurring rather than waiting for the proverbial cavalry to arrive. This localized reaction can be quite potent. Its activation is notoriously difficult to demonstrate, however, so historically it’s been hard for vaccine makers to show they’ve hit the mark. But it turns out that one type of antibody, called IgA, is a good indicator of mucosal immunity because IgAs tend to predominate in the mucosa rather than other parts of the body. In an early trial of CoviLiv, a nasal COVID vaccine produced by Codagenix, about half of participants had detectable IgA responses within several weeks after receiving two doses. That trial also showed the vaccine was safe and led to NextGen funding for a larger trial of the vaccine’s efficacy.

It’s possible an inhaled vaccine may provide yet one more layer of protection, called trained innate immunity. This reaction is a bit of a mystery: although immunologists know it exists and appears also to be produced by intramuscular injections, they can’t quite explain how it works. Immune cells associated with trained innate immunity seem to have memorylike responses, reacting quickly against subsequent infections. They also have been found to respond against pathogens entirely unrelated to the intended vaccine target. Smaill and her colleagues found that when they immunized mice with an inhaled tuberculosis vaccine and then challenged them with pneumococcal bacteria, the mice were protected. In children, there is some evidence that a tuberculosis vaccine, in the arm, generates this type of broad response against other diseases.

Akiko Iwasaki, an immunologist at Yale University who is working to develop a nasal vaccination for COVID, sees two major potential benefits to nasal immunity in addition to better, faster, more localized protection. First, attacking the virus in the nose could prevent the disease from being transmitted to others by reducing the amount of virus that people breathe out. And second, Iwasaki says, the spray may limit how deeply the infection moves into the body, so “we believe that it will also prevent long COVID.” That debilitating postinfection condition, sometimes marked by signs of entrenched viral particles, disables people with extreme fatigue, chronic pain, a variety of cognitive difficulties, and other symptoms.

Making a new vaccine is hard, regardless of how you administer it. It needs to raise an immune response that’s strong enough to protect against future invasions but not so strong that the components of that response—such as inflammation and fever—harm the host.

The lining of the nose puts up its own barriers—literal, physical ones. Because the nasal mucosa is exposed to so many irritants from the air, ranging from pet hair to pollen, the nose has multiple lines of defense against invading pathogens. Nostril hair, mucus, and features called cilia that sweep the nasal surface all aim to trap small foreign objects before they can get deeper into the body—and that includes tiny droplets of vaccine.

And lots of small foreign particles—often harmless—still make it through those defenses. So the nose has developed a way to become less reactive to harmless objects. This dampened reactivity is called immunological tolerance, and it may be the biggest hurdle to successful development of a nasal vaccine. When foreign particles show up in the bloodstream, a space that is ostensibly sterile, immune cells immediately recognize them as invaders. But mucosal surfaces are constantly bombarded by both pathogens and harmless materials. The immune system uses tolerance—a complex series of decisions carried out by specialized cells—to determine whether a substance is harmful. “This is very important because we can’t have our lungs or gastrointestinal tract always responding to nonharmful foreign entities that they encounter,” says Yale infectious disease researcher Benjamin Goldman-Israelow. For example, inflammation in the lungs would make it hard to breathe; in the gut, it would prevent the absorption of water and nutrients.

These barriers may hamper the effectiveness of a nasal flu vaccine that’s been around for a while, called FluMist in the U.S. and Fluenz in Europe. The inoculation is safe, says infectious disease scientist Michael Diamond of Washington University in St. Louis, but it faces a similar problem as do injected flu vaccines: it isn’t very effective at warding off new seasonal flu strains. This might be because flu strains are so common, and people are frequently infected by the time they are adults. Their immune systems are already primed to recognize and destroy familiar flu particles. FluMist is built from a live flu virus, so immune cells probably treat the vaccine as an invader and demolish it as soon as it shows up in the nose, before it has a chance to do any good. This preexisting immunity isn’t such an issue in children, who are less likely to have had multiple flu infections. Nasal flu vaccines are routinely used to inoculate kids in Europe.

In other vaccines, researchers often use adjuvants, special agents that attract the attention of immune cells, to boost a response. Some nasal vaccines use adjuvants to overcome tolerance, but in the nose, adjuvants can pose unique dangers. In at least one case, a nasal adjuvant led to disastrous consequences. An intranasal vaccine for influenza, licensed in Switzerland for the 2000–2001 season, used a toxin isolated from Escherichia coli bacteria as an adjuvant to provoke a reaction to the inactivated virus. No serious side effects were reported during the trial period, but once the vaccine was released, Swiss officials saw a concerning uptick in cases of Bell’s palsy, a disease that causes weakness or paralysis of the facial muscles, often leading to a drooping or disfigured face. Researchers at the University of Zurich estimated that the adjuvanted flu vaccine had increased the risk of contracting Bell’s palsy by about 20 times, and the vaccine was discontinued. “We need to be cautious about using adjuvants like that from known pathogens,” says pharmaceutical formulations scientist Vicky Kett of Queen’s University Belfast in Northern Ireland.

To get around the challenges posed by the nose, some researchers are exploring vaccines inhaled through the mouth. Smaill is working on one of them. She and her McMaster colleagues aerosolized their vaccine for COVID into a fine mist delivered by a nebulizer, from which it rapidly reaches the lungs. Experiments in mice have shown promising results, with mucosal immunity established after administration of the vaccine.

Another vaccine strategy is to use a harmless virus to carry viral genes or proteins. Researchers at the Icahn School of Medicine at Mount Sinai in New York City selected a bird pathogen, Newcastle disease virus (NDV). “It’s naturally a respiratory pathogen,” so it infects nasal cells, says Michael Egan, CEO and chief scientific officer of CastleVax, a company that formed to develop the NDV vaccine for COVID. A small early clinical trial showed the CastleVax vaccine was safe and caused robust immune responses in people. “Those results were very promising,” Egan says. People who received the vaccine also produced antibodies that indicated multitiered mucosal immunity, not simply the adaptive immunity from a shot in the arm.

Following that trial, the CastleVax project received NextGen funding, and results from a trial of 10,000 people are expected in 2026. Half of those people will receive a messenger RNA (mRNA) injection, and half will get the new NDV nasal spray. The data should show whether the new nasal vaccine can do a better job of preventing infection than the mRNA injections. Egan has high hopes. “We’re expecting to see a lot fewer breakthrough infections in people who got the vaccine up the nose by virtue of having those mucosal immune responses,” he says.

Florian Krammer, one of the Mount Sinai researchers behind the vaccine, engineered NDV particles to display a stabilized version of the spike protein that’s so prominent in SARS-CoV-2. “You end up with a particle that’s covered with spike,” he says. Spike protein in the blood­stream can raise an immune response. But the NDV vaccine works in another way, too. The virus particle can also get into cells, where it can replicate enough times to cause virus particles to emerge from the cells, provoking another immune reaction. Before moving into human trials, however, researchers had to complete clinical trials to establish that the Newcastle virus is truly harmless because the nose is close to the central nervous system—it has neurons that connect to the olfactory bulb, which is part of the brain. Those trials confirmed that it is safe for this use.

Nasal sprays aim directly at the spot where most viruses first enter the body: the nose. This type of caution is one reason a COVID nasal vaccine approved in India hasn’t been adopted by the U.S. or other countries. The inoculation, called iNCOVACC, uses a harmless simian adenovirus to carry the spike protein into the airway. The research originated in the laboratories of Diamond and some of his colleagues at Washington University at the start of the pandemic, when they tested the formulation on rodents and nonhuman primates. “The preclinical data were outstanding,” Diamond says. Around the time he and his colleagues published initial animal results in Cell in 2020, Bharat Biotech in India licensed the idea from the university. In a 2023 phase 3 clinical trial in India, the nasal vaccine produced superior systemic immunity compared with a shot.

Diamond says American drug companies didn’t pursue this approach, because “they wanted to use known quantities,” such as the mRNA vaccines, which were already proving themselves in clinical trials in 2020. As the pandemic took hold, there was little appetite to develop nasal vaccine technology to stimulate mucosal immunity while the tried-and-true route of shots in the arm was available and working. But now, four years later, an inhaled vaccine using technology similar to iNCOVACC’s is being developed for approval in the U.S. by biotech company Ocugen. Both inhaled and nasal forms of the vaccine are set to undergo clinical trials as part of Project NextGen. These new vaccines are using classical vaccine methods based on the virus rather than using new, mRNA-based technology. The mRNA preparations were developed specifically for intramuscular injections and would have to be significantly modified.

Codagenix, which is developing CoviLiv, sidestepped the need for a new viral vector or an adjuvant by disabling a live SARS-CoV-2 virus. To make it safe, scientists engineered a version of the virus with 283 mutations, alterations to its genetic code that make it hard for the virus to replicate and harm the body. Without all these genetic changes, there would be a chance the virus could revert to a dangerous, pathogenic form. But with hundreds of key mutations, “statistically, it’s basically impossible that this will revert back to a live virus in the population,” says Johanna Kaufmann, who helped to develop the vaccine before leaving Codagenix for another company earlier this year.

Because most people on the planet have now been exposed to SARS-CoV-2—in the same way they’re regularly exposed to the flu—some nasal vaccines are being designed as boosters for a preexisting immune response that is starting to wane. For example, Yale researchers Iwasaki and Goldman-Israelow are pursuing a strategy in animals deemed “prime and spike.”

The idea is to start with a vaccine injection—the “prime” that stimulates adaptive immunity—then follow it a few weeks later with a nasal puff that “spikes” the system with more viral protein, leading to mucosal immunity. In a study published in 2022 in Science, Iwasaki and her colleagues reported that they primed rodents with the mRNA vaccine developed by Pfizer and BioNTech, the same shot so many of us have received. Two weeks later some of the mice received an intranasal puff of saline containing a fragment of the SARS-CoV-2 spike protein. Because the animals had some preexisting immunity from the shot, the researchers didn’t add any adjuvants to heighten the effects of the nasal puff. Two weeks later researchers detected stronger signs of mucosal immunity in mice that had received this treatment compared with mice that got only the shot.

“Not only can we establish tissue-resident memory T cells” to fight off the virus in the nose, Iwasaki says, but the prime-and-spike method also produces those vigorous IgA antibodies in the mucosal layer. “And that’s much more advantageous because we can prevent the virus from ever infecting the host,” she notes. The study suggests that this approach might also lessen the chances of transmitting the disease to others because of the lower overall viral load. Experiments in hamsters demonstrated that vaccinated animals shed less virus, and they were less likely to contract COVID from infected cage mates that had not been vaccinated themselves.

Although most of the new vaccine strategies are aimed at COVID, nasal vaccines for other diseases are already being planned. Kaufmann, formerly of Codagenix, says the company currently has clinical trials underway for nasal vaccines against flu and RSV. CastleVax’s Egan says “we have plans to address other pathogens” such as RSV and human metapneumovirus, another leading cause of respiratory disease in kids.

Vaccines that don’t need to be injected could clear many barriers to vaccine access worldwide. “We saw with COVID there was no vaccine equity,” Smaill says. Many people in low-income countries never received a shot; they are still going without one four years after the vaccines debuted.

In part, this inequity is a consequence of the high cost of delivering a vaccine that needs to stay frozen on a long journey from manufacturing facilities in wealthy countries. Some of the nasal sprays in development don’t need deep-cold storage, so they might be easier to store and transport. And a nasal spray or an inhaled puff would be much easier to administer than a shot. No health professional is required, so people could spray it into their noses or mouths at home.

For these reasons, needle-free delivery matters to the World Health Organization. The WHO is using the Codagenix nasal spray in its Solidarity Trial Vaccines program to improve vaccine equity. The CoviLiv spray is now in phase 3 clinical trials around the world as part of this effort. “The fact that the WHO was still interested in a primary vaccination trial in the geographies it’s passionate about—that’s indicative that there is still a gap,” Kaufmann says. CoviLiv was co-developed with the Serum Institute of India, the world’s largest maker of vaccines by dose. The partnership enabled production at the high volume required for Solidarity.

The CastleVax vaccine with the NDV vector provides another layer of equity because the facilities required to make it already exist in many low- and middle-income countries. “The cool thing is that NDV is a chicken virus, so it grows very well in embryonated eggs—that’s exactly the system used for making flu vaccines,” Krammer says. For example, for a clinical trial in Thailand, “we just shipped them the seed virus, and then they produced the vaccine and ran the clinical trials,” he says. Many countries around the world have similar facilities, so they will not need to depend on pharma companies based in richer places.

Even high-income countries face barriers to vaccination, although they may be more personal than systemic. For very many people, the needle itself is the problem. Extreme phobia such as Velasquez’s is uncommon, but many people have a general fear of needles that makes vaccinations stressful or even impossible for them. For about one in 10 people needle-related fear or pain is a barrier to vaccinations, says C. Meghan McMurtry, a psychologist at the University of Guelph in Ontario. Needle fear “is present in most young kids and in about half of adolescents. And 20 to 30 percent of adults have some level of fear.” A review of studies of children showed that “concern around pain and needle fear are barriers to vaccination in about 8 percent of the general population and about 18 percent in the vaccine-hesitant population,” McMurtry adds.

Some people are wary of injected vaccines even if they’re not afraid of needles, Kett says; they see injections as too invasive even if the needle doesn’t bother them. “We’re hopeful that something administered by the nasal route would be less likely to come across some of those issues,” Kett says.

In the U.S., however, sprays and puffs won’t be available until they are approved by the Food and Drug Administration, which requires clear evidence of disease protection. As Diamond points out, standards for such evidence are well established for injections, and vaccine makers can follow the rule book: regulations point to particular antibodies and specific ways to measure them with a simple blood test. But for nasal vaccines, Iwasaki says, “we don’t have a standard way to collect nasal mucus or measure antibody titers. All these practical issues have not been worked out.”

Iwasaki is also frustrated with a restriction by the U.S. Centers for Disease Control and Prevention that stops researchers from using existing COVID vaccines in basic research to develop new nasal sprays. The rule is a holdover from 2020, when COVID injections had just been developed and were in short supply; people had to wait to get vaccinated until they were eligible based on factors such as age and preexisting conditions. “That made sense back then, but those concerns are years old; things are different now,” Iwasaki says. “Now we have excess vaccine being thrown out, and we cannot even get access to the waste, the expired vaccine.”

Today scientists want to contrast the effectiveness of nasal formulations with injections already in use. “Those comparisons are really important for convincing the FDA that this is a worthy vaccine to pursue,” Iwasaki says. But the restriction has held up studies by her company, Xanadu, slowing down work. (The CDC did not respond to a request for comment.)

Despite the bureaucratic and scientific hurdles, the sheer number of nasal vaccines now in clinical trials encourages Iwasaki and other scientists pursuing the needle-free route. They say it seems like only a matter of time before getting vaccinated will be as simple as a spritz up the nose.

Velasquez, for one, can’t wait for that day to arrive. The circumstances that finally forced her to reckon with her fear of needles (a global pandemic, the prospect of parenthood and the numerous blood tests that accompanied her pregnancy) were so much bigger than her. If not for them, she might still be avoiding shots. “So having vaccines without needles—I would get every vaccine any doctor wanted me to get, ever. It would be a complete game changer for me.”