Gambling and Canada: The Best Online Casino Games – The Garnette Report

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Gambling and Canada: The Best Online Casino Games

We dont know what the future holds for us, but one thing is for sure: online casinos are the next big thing. Although casinos have been present for quite some time now, the online version has just showed up and made its way to the market recently worldwide, and Canada was not an exception. Since it was observed that people loved the convenience of playing from home, more and more investors have invested in online casinos and now we basically have them in every corner of the digital world.

But with all this presence online, one might ask, what is this hype about? Well, while casinos that have a physical location might not be present in every city in Canada for example, online casinos make it into every home. As a result, there are more and more users that can entertain themselves playing at a casino. Now the question rises, there are plenty of websites that promote real money online casino in Canada, what games are leading the list of being the best ones in those online casinos? Lets find out together!

Oh, the good ol blackjack. Yes, thats right, blackjack is also leading this list. I am saying also because it is widely known that blackjack is the game that is played mostly in the casino world. That means, it is also a favorite in brick-and-mortar casinos.

The game has a deck of 52 cards and the idea is that you and the rest of the players are presented two each time. If the value of the cards you are presented is 21, then that is blackjack, and you win. If it is less or more, then you get to choose what you do next. There are two options on what you can do; you can continue to draw other cards until you get what you want, or you can stay with what you have. Then, this goes on rounds with all the people playing.

Roulette is another classic that people just love, and we could say that it is almost standing next to blackjack on this list. Btw, the games name derives from French and it basically means wheel in English, which denotes the revolving wheel in the game.

Initially, in roulette all of the players place their bets on whether they are going for the red or the black numbers. In the revolving wheel that we mentioned previously, there are different numbers some of which are colored red and the others with black. What happens is that the dealer in this case throws a small ball into the revolving wheel and whatever lands on, it determines who the winners are. The best for roulette can start as small as $5 and then as the game carries on, the bet also rises.

Third on this list is baccarat which is also known as baccara. This game is present in every casino; be it in real life or online. Similar to blackjack, baccarat is also a game played with cards.

As stated above, baccarat uses a set of cards and different from blackjack where multiple people can pay, in baccarat there are only two people and those are the player and the banker. There are some coups involved in baccara where three options are available, the banker, the player or a tie. Then, the cards are presented facing up by the dealer for both the banker and the player. Finally, whichever hand sums up to the total of nine wins, it wins.

This list is then finalized by slots which are very different from the rest of the games here, yet a global favorite. Slots for many people appear to be an easy and entertaining way of getting into the mood for playing.

Slot machines have a machine of number generation inside of them. Each of the numbers has a symbol which shows up on the screen. For example, there are 7s, diamonds, cherries, lemons, berries or bells, which by the way is the most common symbol which either gives you a jackpot or a bonus round. Then once you turn on the machine, you get a different combination of symbols, and you can go around playing slots for as long as you want.

Conclusion

And that concludes our list! So, in this article we saw which games are the most popular ones in online casinos in Canada and also briefly showed how they are played. We are excited to see what online casinos, often referred to as this next big thing, have in store for us in the future and whether this list will change overtime with more and more users involved.

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Gambling and Canada: The Best Online Casino Games - The Garnette Report

The Intersection of Rugby Players and Online Gambling: A Closer … – Rugby Observer

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Rugby and online gambling do not appear to be two activities that have much in common if anything at all. However, when you dig deep beneath the surface, it becomes possible to notice some similarities that do exist.

Rugby players are known to enjoy playing casino games, with some often opting to play at online casinos. It can provide them with a level of anonymity, as they can stay out of the limelight, especially if they are athletes who may play at the highest levels of the sport. They may even opt for No KYC Casinos as a means of remaining private and being able to enjoy a quick session whenever they want to enjoy and entertain themselves away from the training field and the pitch.

Both activities require individuals to be disciplined in what they do, with things like strategies and game management being crucial. Matches require the athletes to be able to manage the clock and execute certain strategies that are required to try and best their opponent. Many of these skills are needed with casino games, too. Discipline, concentration, focus, and patience are all transferable skills between the two activities, as are decision-making and critical thinking. It is almost impossible for any sport to challenge football when it comes to betting, but wagering on rugby can do its best to compete.

Football is renowned worldwide as the biggest sport, with billions of people enjoying it. Many like to bet on it because of their love for the game. With matches being played globally and at any given moment, it is also one of the most accessible, offering various opportunities through various markets.

Nonetheless, rugby betting can offer the same experiences, albeit on a smaller scale than football. Competitive leagues are played in various countries, with many tournaments also being played domestically and continentally.

International tournaments are also huge, with the Rugby World Cup, Six Nations, and Tests between two countries often being extremely competitive. In truth, these are perhaps the events that receive more attention from bettors, as sports enthusiasts will be more prepared to support and wager on nations compared to the clubs, especially if they have no real passion or interest in the sport at a club level.

These matches continue to offer markets in the same ways football matches have, with traditional final result odds and player props all possible to find.

It would appear unlikely that rugby betting will ever become as popular as football betting, but there is always a chance that the gap between them shortens. With sport offering the same types of bets, the only reason the sport is perhaps not as widely bet on as football is the number of people who actually enjoy the sport.

Sportsbooks can do their best to try and help make rugby betting more attractive by offering certain bonuses or promotions. However, with billions enjoying football, it might be a tireless task to make rugby betting more popular than it already is.

It is possible to argue that online gambling can provide rugby players with several benefits when games are played. Players can keep their brains active and healthy, which can translate onto the field through the decisions that they are able to make. Certain online gambling games can also have a positive impact on focus and concentration, while also providing them with the ability to be able to create strategies that they can execute.

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The Intersection of Rugby Players and Online Gambling: A Closer ... - Rugby Observer

Gambling securely: A look at the technology behind online casino … – Times of Malta

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In the vast landscape of online casinos, where the thrill of a bet meets the convenience of the digital realm, ensuring a secure gaming environment is paramount. As players navigate through the virtual corridors of blackjack tables, slot machines and poker rooms, the unseen guardian ensuring a safe experience is the sophisticated technology underpinning online casino security. This exploration will explore four intriguing aspects that shed light on the high-tech fortress protecting your bets.

At the heart of every secure online casino lies a robust encryption system, the digital guardian of your sensitive information. It's not merely a technological buzzword; it's the impregnable fortress that shields your financial transactions, personal details and gameplay history from prying eyes. Top online gambling establishments, including the ones reviewed ononline-casinos.es, use advanced encryption protocols, such as the industry-standard SSL (Secure Socket Layer). This technology creates an encrypted tunnel between your device and the casino's servers.

Imagine this encryption as an intricate lock and your data as a precious gem in a virtual safe. Even if a cyber marauder were to intercept the data during transmission, the encryption renders it unreadable and useless. It's a technological dance of complex algorithms and keys, ensuring that your online gambling experience is not only thrilling but also impenetrable to cyber threats.

In the dynamic world of online security, the humble password is no longer the lone sentinel standing guard. Two-factor authentication (2FA) emerges as the unsung hero, adding an extra layer of defence against unauthorized access. While the password remains your first defence, 2FA introduces a second step, typically involving a temporary code sent to your mobile device or email.

This additional layer of verification not only fortifies your account against potential breaches but also adds a touch of real-world security to the virtual realm. It's akin to having a second key to your digital kingdom, ensuring that even if one key is stolen, the other remains securely in your possession. As the saying goes, luck favours the prepared, and in online gambling, preparation includes a sturdy two-factor shield.

The tech landscape has evolved beyond passwords and codes, introducing biometric security to online casinos. Imagine logging into your casino account without a password but with the touch of your fingertip. Biometric authentication, such as fingerprint and facial recognition, adds a touch of sophistication to the security dance.

In an era where smartphones unlock at a glance, online casinos are embracing this technology to enhance user experience and security simultaneously. It's not just about convenience; it's about making sure that the person placing the bets is who they claim to be. Biometric security is the high-tech bouncer ensuring that only the rightful account owner gains access to the exciting world of online gambling.

Anti-fraud systems are the digital detectives safeguarding the integrity of online casino games. These systems utilize advanced algorithms and machine learning to analyze behaviour patterns, identifying anomalies that might indicate fraudulent activity. From detecting suspicious transactions to identifying collusive play in poker rooms, these systems operate silently, preserving the fairness and security of the online casino environment.

Anti-fraud measures are not just about protecting the casino but about ensuring a fair and enjoyable experience for every player. By swiftly identifying and neutralizing potential threats, these systems contribute to the overall trustworthiness of online casinos, fostering an environment where players can focus on the thrill of the game without worrying about foul play.

As online casinos continue to shape the future of gambling, the technology safeguarding these digital arenas becomes increasingly sophisticated. Encryption, two-factor authentication, biometric security, and anti-fraud systems collectively form an impregnable fortress, ensuring that players can indulge in the excitement of online gambling without compromising security. In this digital age, where luck is just a spin away, the robust technology behind online casino security ensures that your bets remain your own, and the thrill of the game is the only uncertainty you need to embrace.

Disclaimer: Play responsibly. Players must be over 18. For help visit https://www.gamcare.org.uk/

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Gambling securely: A look at the technology behind online casino ... - Times of Malta

Simone de Beauvoir, Hannah Arendt, Simone Weil and Ayn Rand … – The Conversation Indonesia

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The actual impulse of astonishment that sparks all philosophising is honest bafflement that other people live as they do, writes Wolfram Eilenberger in his new book, The Visionaries.

Its a wild ride through ten of the worst years in the 20th century, spanning the period from 1933, the year Hitler was appointed Chancellor of Germany, to 1943 and the thick of the second world war. Its told through the occasionally intersecting lives of four brilliant young women philosophers: Simone de Beauvoir and Simone Weil (both French), Russian-American Ayn Rand, and German-Jewish Hannah Arendt, who spent time exiled in France and New York.

Though very different, they all experienced themselves as having been placed fundamentally differently in the world from how other people had been. Eilenberger writes:

All of them were tormented from an early age by the same questions: What could it be that makes me so different? What is it that I clearly cant understand and experience like all the others? Am I really driving down the freeway of life in the wrong direction or is it not perhaps the mass of wildly honking people coming toward me flashing their lights?

I had thought myself reasonably schooled in the writings of these women, but discovered how little I actually knew about them their early work and their jobs, who they knew and loved or loathed, and how the broken stick of 1930s Europe shaped the possibilities for their lives and thought.

Review: The Visionaries: Arendt, Beauvoir, Rand, Weil, and the salvation of philosophy Wolfram Eilenberger, trans Shaun Whiteside (Allen Lane)

The Visionaries traces the gradual unfolding of their systems of thought, including how they changed their minds in response to the radically changed situations they found themselves in.

It builds, to some extent, on Eilenbergers earlier volume, Time of the Magicians: Wittgenstein, Benjamin, Cassirer, Heidegger, and the Decade That Reinvented Philosophy, which followed four brilliant young men who transformed European philosophy in the agonised decade following the first world war.

Both books weave the work of the philosophers with social history, biography, accounts of the cultural and economic environment, and depictions of the quarrels and agreements, friendships and passions that characterised their communities.

The Visionaries opens at the end of 1943. Each character is a very young woman, only in her thirties. But each is already possessed of a trained mind, formidable intelligence and a determination to make sense of life, the universe, and everything.

Beauvoir is writing her first philosophical essay, is about to publish her first novel and has a play in the works. Weil has been asked by occupied Frances shadow government to draw up plans and scenarios for the political reconstruction of France (after her offer to go to the front to die for her ideals was refused).

Rand is awaiting the publication of her debut book, The Fountainhead, a philosophical manifesto masquerading as a novel. And exactly ten years after being driven out of Hitlers Germany, Hannah Arendt is figuring out her next steps, reflecting that in these dark times:

One only had to find the courage in oneself to open ones eyes keep them open to perceive the abysses of ones own time with an alert mind.

After this opening chapter, the narrative jumps back a decade to 1933, and then progresses year by year, back to where it began.

First, we meet Simone de Beauvoir, who with her life partner Jean-Paul Sartre is associated with existentialism (though Eilenberger writes that she avoids the term). Existentialism argues each individual is a free agent, capable of crafting their own identity and existence through acts of the will.

By 1943, Beauvoir was wrestling with one of existentialisms core precepts: how individuals can achieve their best possible lives. She asked, why would someone even attempt this? After all, everything we do comes to nothing because of times inexorable progress and our inevitable death so why do anything at all?

At that stage, her answer is that we should do something because we are in the world as acting creatures, and therefore should grasp our freedom to act while we are able.

Read more: What makes a good life? Existentialists believed we should embrace freedom and authenticity

Simone Weil, whom we meet next, is pretty much the polar opposite of Beauvoir. Indeed, late in the volume Eilenberger notes:

If we compare Weils Notebooks with Beauvoirs diaries and writings from the same time [19411942], we have the extremely strange impression of a telepathic contact between two minds resonating tensely at either end of an infinite piece of string.

Where Beauvoir sees herself as comparatively separate from society, Weil had, as Beauvoir wrote, a heart that could beat right across the world. Despite her physical fraility (and probable anorexia), Weil was possessed by enormous passion and empathy. The wellbeing of everyone else in the world absorbed her thoughts and actions during her short life (she died in 1943).

For years, Weil kept from her wages precisely the minimum sum assigned to unemployed factory workers on state support, while the rest she donate[d] to needy or feeling comrades. And she directed her obedient parents to use their unoccupied apartment to house refugees it once hosted a meeting between exiled communist leader Leon Trotsky and the new high command of the world revolution.

Born into a Jewish family, Weil veered into a passionate and ascetic Christianity. For her, the point of being alive was to disappear into a future of nonbeing, confident that Supernatural love alone creates reality and that our meaning, if one can call it that, is to dissolve into a vessel for Gods will.

This is not a matter of acting, in Beauvoirs terms, but of leaving the world of authenticity and safety in favour of some notion of the divine. (Perhaps unsurprisingly, Weils often brilliant work has attracted less attention than that of her fellow characters in this book.)

Read more: Guide to the Classics: Simone Weils The Need for Roots

Ayn Rand comes next: her familys home and possessions were expropriated in the 1917 October Revolution, on the grounds they were representatives of the Jewish bourgeoisie. They fled to Crimea, then lived in poverty when they returned to St Petersburg (now named Petrograd) in 1921.

The Russian jackboot she escaped was at least as violent as that of the Nazis as Simone Weil too argues in her 1933 discussion about the structural similarity between newly fascist Germany and Stalins Soviet Union.

Rand made it to the United States in 1926, and began a career as a thinker and writer who named her philosophical position objectivism. Where Weil aimed to change the whole world through divine engagement, and Beauvoir perceived freedom as the freedom to act within a community, Rand insisted on:

the concept of man as a heroic being, with his own happiness as the moral purpose of his life, with productive achievement as his noblest activity, and reason as his only absolute.

For man, read Rand. Her most famous character, the architect Howard Roark, the protagonist of The Fountainhead, was after all based on herself. Roark, whose real-life admirers include Donald Trump, was a mouthpiece for objectivism: for reason, for facts, but never for compassion or empathy.

Like an early Margaret Thatcher, Rand built an entire worldview based on there being no society only self-focused, self-seeking individuals, capable of determining who and what they are, in perfect freedom.

Read more: Atlas Shrugged: Ayn Rand's hero burns the world down when he doesn't get his way. Her fans run the world should we worry?

Hannah Arendt, with her mother, had fled Germany in 1933 after they were arrested and interrogated by the Gestapo. For some years, she lived as an exile in France, later escaping to the United States.

Her initial writings explored the uncertainty of freedom in a world where events can strip the individual of identity, of nationality, of freedom and even of life.

Her perspectives differ markedly from both existentialism and objectivism: Eilenberger observes that, for Arendt, self-creation is always contingent on social and cultural conditions, from which no individual can fully escape. It is, she argued poignantly, political power, not self-determination, that sets the limits of our being.

In her case, this was the power of the Nazi machine, which destroyed so many members of her community and which she had so narrowly escaped. Her philosophical concerns were, therefore, far from either individual self-realisation or self-abnegation.

Rather, she was concerned with what an individuals responsibility might be in the face of overwhelming social, political and economic realities.

Read more: The book that changed me: Hannah Arendt's Eichmann in Jerusalem and the problem of terrifying moral complacency

These, in brief, are the four philosophers who galvanised the salvation of philosophy. The lines and turns of their thinking were unpacked and reframed through much of what was going on in the salons of their twenties, or the writings of their thirties.

They were deeply connected, through reading, through shared intellectual concerns, and in some cases through personal relationships, with the great philosophers who preceded them all the way back to Plato in the fourth century BCE and with their contemporaries.

Simone de Beauvoir, for example, was intimately connected to Jean-Paul Sartre in life and work. Ludwig Wittgensteins ethical and intellectual struggles with religion closely parallel Weils own (though there is little evidence they knew each other). Walter Benjamin was Arendts friend throughout their period of exile (and later was the subject of her writings).

Martin Heidegger was the most intertwined with these philosophers. His writings influenced both Weils and Beauvoirs work, particularly into the nature of being, and of human consciousness.

He had also been Arendts teacher (and lover) at university; and though they were on opposite sides of the political divide Heidegger became a Nazi in 1933, the same year Arendt was arrested by the Gestapo Arendt reconnected with him in 1949, and remained his friend.

Read more: Heidegger in ruins? Grappling with an anti-semitic philosopher and his troubling rebirth today

The four women are complex characters, and not always likeable, being neither straightforward, nor straightforwardly admirable. Beauvoir, for example, declined to join a 1934 general workers strike on the grounds she was not part of society. She wrote: The existence of Otherness remained a danger to me. In fact, Otherness was such a danger that at this point, she claimed to identify with no one but Sartre.

Interestingly though, she records a sharp criticism offered her by Simone Weil in a discussion they had about care of the Other, and what matters in the world. For Weil, the most important thing is to feed all the starving people of the earth. For Beauvoir, what matters is:

not to make men happy, but to find the reason for their existence. [Weil] looked me up and down: Its easy to see youve never been hungry, she snapped. Our relations ended right there []

Fair point. Or maybe not all that fair, since by the mid-1930s, Beauvoir was less inclined to consider the world a universe only of Beauvoir-plus-Sartre. Instead, she was beginning to take a more other-oriented, and more sensibly pragmatic, stance.

Perhaps this was motivated by the fact the Beauvoir-plus-Sartre unit had become a polyamorous group, incorporating a worryingly young group of people who participated in their sexual and intellectual lives. The philosophers ease with this complicated sexual engagement, which they characterised as family, did not meet social norms.

Beauvoir was the subject of a year-long investigation, following complaints by the mother of one of the young people that she seduced her students and then passed them on to Sartre. This crime of incitement to debauchery was not proven, for lack of evidence. At the same time, Sartre was sulking about his unsatisfying professional life, and insatiably sexually engaging with (it seems) pretty well anyone who entered his orbit.

Read more: Sex, lies and Hegel: did the intimate lives of philosophers shape their ideas?

I would imagine such experiences exposed Beauvoir to the limitations of both her philosophy and her capabilities. Certainly, such an awareness seems present in her explanation of why she and Sartre declined to join so many of their circle in travelling to Spain to serve in the war against Franco: that they were more likely to be a nuisance rather than a help.

In evidence of this, she pointed out that Weil had gone to Spain to serve in the military, but when the infantry sensibly refused to arm her, Weil instead worked in the kitchens. (Her war ended when she stepped into a pot of boiling oil and was sent back to France to recover.)

Weils passion for others often made her a nuisance rather than a help. She identified strongly with the concept, at least, of the common people, but usually got things wrong. Despite her deeply fragile health, she took a sabbatical from her job as a philosophy teacher to work in a metals factory. This, she thought, would be real life. Eilenberger gently teases this aspiration, but at the same time he notes her action:

stands in a respectable tradition of philosophical experiments whose declared objective was to turn ones back on a presumably alienated world [] Like the Buddha fleeing the temple, or Diogenes in his barrel, or of course Thoreau building his hut on Walden Pond.

It was not an obviously useful experiment. Weil was a hopeless factory worker, causing herself injury, messing up the production line, and worsening her always-frail physical health. She was a hopeless social activist too. After her failure to solve the problems of the Spanish Civil War, and as France edged ever closer to war with Germany, she began developing suites of well-argued and utterly impractical solutions, all of which were rejected.

Arendt seems to have had a much stronger practical streak than did Weil, and a much clearer sense both of the complexities of being a human among other humans, and of the limitations on the fantasies of freedom, than either Beauvoir or Rand.

While she was still living as a refugee in France, she was developing an understanding of what it is to be a pariah: considering how to preserve the only freedom pariahs have the capacity to think for themselves. She was also wondering about what love means.

Read more: Friday essay: Rai Gaita and the moral power of conversation

Reading through this decade, and through the thinking that propelled the four women then, I had to keep reminding myself how dire their living conditions were.

For the three Europeans, the looming dread of war and the nailing down of any freedom or opportunity framed their lives. Ayn Rand may have been far from Hitlers reach, but she was unable to free her parents from the Great Terror of Stalinist Russia, she was having only uncertain success in her writing, and she lived with an unsatisfying husband.

Throughout all this, the Europeans at least sharpened and nuanced their understanding of what it is to be human, the point of being alive, what freedom means, and where our responsibilities lie. In doing so, they laid down some of the intellectual and ethical foundations that have inflected much of the 20th century, and into our time. (Ayn Rands writings, on the other hand, provided a textbook for the US Tea Party efficacious work, no doubt, but not work I can applaud.)

By the end of the book, I found I had changed my mind about the four women primarily in the form of a significantly elevated appreciation for Simone de Beauvoir and an enhanced sympathy for Simone Weil. (I retained my confirmed enthusiasm for Arendt, and my equally confirmed disdain for Rand.)

I also discovered a substantial admiration for the skill of the author and his translator. The clarity of voice, the respect paid to readers and to the four main subjects, and the little glimpses of humour (and larger glimpses of empathy) have left me a fan of this work.

Readers who are not fans of philosophy shouldnt fear the book will tangle them in the weeds of impenetrable lines of thought: its philosophy is made highly accessible. And the human stories, with all their tragedies, irritations and delights, are luminously and empathically crafted.

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Simone de Beauvoir, Hannah Arendt, Simone Weil and Ayn Rand ... - The Conversation Indonesia

Exclusive Event: Ayn Rand Speaking about Her Life – New Ideal

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Join us for a presentation of intriguing audio excerpts from Ayn Rands in-depth 196061 biographical recollections.

Mark your calendar: On December 9 we will host a special year-end celebration with Tal Tsfany, president and CEO of the Ayn Rand Institute, who will showcase the Institutes successes, followed by an exclusive presentation of Ayn Rands biographical recollections.

These 196061 audio recordings provide an extraordinary window into Rands life, work, and achievements in her own words. At the event, well share a thirty-minute selection curated from nearly forty hours of original audio, housed at the Ayn Rand Archives.

This online event part of our monthly ARI Member Roundtable series is open to supporters who donate $25 or more per month ($300+ year). They will receive an invitation with details on how to join the Zoom space.

Please become an ARI donor or increase your support today to attend this special event.

After the audio presentation, well open breakout rooms hosted by ARI staff and scholars. At the end of our program, youre welcome to stay for the free-form hangout. The Roundtable will last approximately ninety minutes; the hangout will remain open for another hour.

(This audio selection premiered in July at a private event for Benefactors and members of Atlantis Legacy, our planned giving program.)

Join us on Saturday, December 9, at 1:00 pm ET / 10:00 am PT.

If you value the ideas presented here, please become an ARI Member today.

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Exclusive Event: Ayn Rand Speaking about Her Life - New Ideal

Childfree Woman Wants To Divorce Husband Over Wanting … – Romper

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Is there some weird new guy code about dating that says you should just...never bring up the fact that you have kids? A dad went viral on Reddits popular Am I The A**hole? community earlier this year for refusing to tell his dates he had children until at least a year into being together. Well if you thought that was bad, a new post is taking AITA by storm, in which one woman says her husband of approximately one year is just now telling her he has two kids, and that he suddenly wants custody of them. Now, she considering getting divorced.

In the Reddit post, the 27-year-old woman explains that she has been married to her 33-year-old husband for roughly a year. She describes herself as vehemently childfree, saying she has been sterilized and made it very clear she has no interest in bearing or caring for any children. Fair enough, maam! All was seemingly well until her husband surprised her with some news: hes actually a father of two, a 10-year-old son and 7-year-old daughter. And now, he wants to file for 50/50 custody of the kids.

The idea to fight for custody came about because the couple shares a bank account for bills, but keeps separate savings and fun money accounts. He pays regular child support, however, it dips into his fun money and he wants to be able to have fun like I am, she writes. The poster describes herself as having amazing pay for very few working hours as a honeymoon planner. Her husband works 12- and 16-hour shifts as a nurse, so she expects to be the one caring for the children should he actually be granted custody. She said she wants a divorce. He says shes an a**hole for not helping him save money. And Reddit has no mercy on him.

The comments on this post make one thing clear: no one thinks this dude is even a halfway decent dad.

He only wants 50/50 custody of his own children because itll reduce his child support and give him some fun money. Hes a f*cking loser, says one. How on earth has this guy been hanging out with his kids for the entirety of his marriage without his wife finding out? Or has he just been paying the child support and not actually developing any kind of relationship with them? And now he wants 50-50 custody, its ridiculous, adds another. (One person replied to this by saying, Easy. He didnt. This guy is a sad excuse for a father.)

There are also plenty of comments in support of the poster, with more than one saying the dad in this equation was just looking for a sugar mama all along. Dont you love being pressured to step up and take someone elses responsibility? jokes one commenter. Your husband lied to you and probably married you with the intention of saddling you with his children. Get out of this marriage whether or not he fights for custody. He is a liar and a manipulator, and your entire marriage is built on sand, says another. Harsh, but this seems to be the consensus.

Whether the poster goes through with the divorce because her husband lied, doesnt care about her wish to be child-free, ignored his own children for years, or just wants them now for selfish reasons, Redditors agree: its time to throw the whole man in the trash.

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Childfree Woman Wants To Divorce Husband Over Wanting ... - Romper

Professors collaborate with NASA to lower cost of space travel – The Baylor Lariat

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By Kobe Baker | Reporter

In collaboration with teams at NASA, Purdue University, the University of New Hampshire and Astroport, three Baylor professors are working to make space travel more affordable.

The Baylor professors on the project are Dr. Trevor Fleck, assistant professor of mechanical engineering; Dr. Paul Allison, professor of mechanical engineering; and Dr. J. Brian Jordon, professor of mechanical engineering.

Jordon said the project uses technology with a combination of human-made materials and lunar resources to create devices needed to travel in space.

I think the long-term goal was then to shrink down the scale of the machine into a footlocker-type thing that can be sent into space, Jordon said.

Additionally, Fleck said the teams are trying to ensure that the process does not sacrifice the performance of what they are creating.

The fundamental science were trying to establish is understanding the entire relationship so that an engineer can go design something with this, process them with these materials and have some idea of how its going to perform when they use that part, Fleck said.

The scale of the project requires constant communication from all of the teams at NASA, Astroport and the three universities.

I think there are natural challenges in working with multiple institutions, but theres some really good people, Jordon said. Weve got some really good colleagues at the other institutions and in the private company that were collaborating with.

Fleck said the teams have found community through the project, bringing in many different backgrounds while working toward a common goal.

Its kind of meeting with the community through conferences and establishing those relationships and finding unique problems we can collaborate on, Fleck said.

Fleck said that with large national research teams like this one, more expert perspectives are available to give insight into a project.

Whenever researchers collaborate, you get to go after these bigger projects and solve these bigger problems that need to be overcome, Fleck said.

Fleck, Allison and Jordon dont have a set estimate of how much money the project will save, although sending a satellite into space can currently cost anywhere from $50 million to $400 million for an individual launch.

Part of this research will identify what is the return on investment the savings that can be obtained through doing these types of manufacturing approaches, Allison said.

In September, Fleck, Allison and Jordon also received a $3 million grant from the National Science Foundation, and they said they hope to use the funds to bring in a variety of graduate and undergraduate students to aid them in their research.

Part of the reason were excited is we get to introduce new students to this technology field and expose them to things they may not have an opportunity to, Jordon said. And exposing undergrad students to research in our lab, we hope they get bit by the research bug.

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Professors collaborate with NASA to lower cost of space travel - The Baylor Lariat

After Starfield, I thought I was done with large-scale space travel, but … – PC Gamer

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I never fully wrote off Star Citizen as a scam to sell expensive fake ships to credulous fans of Wing Commander, but neither have I ever been convinced that it will actually achieve a 1.0 release someday. I don't think this latest trailer has changed my mind on that point, but it has made me glad that Star Citizen exists as an idea, purely because it is so mesmerising to watch.

To be honest, "trailer" doesn't really do this video justice. It's a 25-minute showcase of the game's bespoke Star Engine tech, and by proxy a chance for Roberts Space Industries to exhibit the scale of the game. And it's the most I've been interested in Star Citizen for ages, despite recent events demonstrating that exploring simulated universes is never as exciting as it seems.

The trailer kicks off with a crucial note: "Everything you are about to see has been captured in engine as one continuous shot without loading screens. Distance between planets has been compressed for the sake of brevity." Then there's a performative orchestral tune-up, before the trailer's soaring soundtrack kicks in.

Instantly, we're off, barrelling through the cosmos. After a few seconds, we arrive at the first planet, microTech Stanton IV, where the Star Engine shows off those most coveted of features, fully explorable planets and seamless transition from space to ground without a loading screen in sight. Take that, Starfield! Right between the eyes.

The trailer spends a while floating around Stanton IV, showing off an incredibly detailed city complete with fully operating rail system, glistening icy mountains, and lush forests. Then we're off again, arriving at a silhouetted ring planet, where the trailer dives into those icy halos to showcase the engine's "real-time large scale asteroid belt generation and rendering". Then we pop over to a gas giant for a look at my favourite bit of ostentatious-sounding tech, "Volumetric clouds at a gas giant scale." We also see the impressive "Floating Cloud City" Orison, which in typical Star Citizen fashion looks absolutely massive.

There are plenty more technical whizzbangs shown off in the second half of the trailer. A spaceship engulfed in flames showcases the game's "Dynamic fire simulation based on voxel grids", while a bleak Hebridean planet forms the stage for the game's "Hierarchical object container technology for outposts and points of interest," which I'm guessing means procedurally generated small settlements. Weirdly, it ends with a closeup of a sweaty man's face, although I can't deny how realistic those salty beads look.

In short, the trailer achieves what it sets out to do, namely wowing with its scale, and making me want to play an open-universe space-game underpinned by this tech. That's despite the fact that I got excited about No Man's Sky and Starfield for the exact same reasons, and both of them ultimately left me cold. This I suppose is the ultimate question: Can Star Citizen turn all this flashy technology into a game that's fun to play? I tried the playable Alpha years ago, and it certainly seemed to have more mechanical grit than either Starfield or NMS. But it was also far too janky to be fun.

Either way, I thoroughly enjoyed kicking back and zooming through Star Citizen's universe for 25 minutes, and it reignited my desire for a space sim which merges that galactic scale and seamless spaceflight with a game that's actually fun to play. I remain doubtful about whether that's actually possible, but I'm also happy that, after all these years, Roberts Space Industries is still trying to make it happen.

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After Starfield, I thought I was done with large-scale space travel, but ... - PC Gamer

Short-term benefits of smoking cessation | COPD – Dove Medical Press

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Introduction

Refrain from smoking is the main therapeutic intervention effective in curbing and reducing the patients respiratory functional decline. It is reported in the COPD guidelines.13 The main consequence of a long-time cigarette exposure is airflow limitation involving both large and small airways.4 A major component of bronchial obstruction is represented by small airways which is characterized by inflammation of bronchioles and airway wall narrowing.

The evolution of the disease can be influenced by the presence of exacerbations that correlate with the degree of obstruction, influencing mortality.5,6

The purpose of the present study is to point out the benefit of quit smoking on respiratory functional and metabolic parameters.

From April to December 2021, 120 patients who referred to a smoking cessation outpatients service were recruited and retrospectively analyzed. The setting was a university hospital, at the outpatient anti-smoking center of the pulmonology operating unit.

Exclusion criteria were: patients who were taking oral steroid therapy or bronchodilators were ruled out as well as patients with severe comorbidities.

Inclusion criteria were the following: patients smokers for at least 20 pack-years who were not taking neither therapy for lipid metabolism nor bronchodilators. The expected duration of the smoking cessation program was six months The assessment was done at baseline and at one month after smoking cessation. Data management was by the physicians attached to the smoke-free center and an expert statistician.

Smoking cessation program was accomplished through motivational counselling along with a drug that reduces addiction. It was varenicline that acts as a partial agonist on 42 nicotinic-acetylcholine receptor. Counselling was also applied consisting of a psycho-behavioural analysis by identifying the stage of change according to the transtheoretical approach. Smoking abstinence was achieved as the eCO value was less than 7 ppm.

Several tests and questionnaires were being administered: the test for nicotine dependence (FTND) (range 02 no dependence, 34 low, 57 moderate, 810 high dependence), the questionnaire COPD assessment test, CAT (range 040),7 the questionnaire for detection of dyspnea, mMRC (range 04).8 The Wests test for the assessment of motivation to quit was also performed. The spirometry (Jaeger system masterscreen, Germany) was performed according to the ERS-ATS guidelines.

Post-bronchodilation values were obtained by inhaling 400 g of salbutamol.9 A smokerlyzer device was used for eCO detection (Bedfont, USA).10 Each patient underwent a 6 min walking test (WT) with walking distance detection (NoninMed Inc., Plymouth,MN, USA).11 Finally, a venous blood sample was taken for detection of cholesterol, HDL and vitamin D total level. The time of detection was at baseline and at one month after smoking cessation.

The study was approved by Sapienza Ethic Committee. Each patient provided the consent to the study. The patients were informed about the purpose of the study. Our study complies with the Declaration of Helsinki.

Data are represented as mean SD or median interquartile range as appropriate.

Data comparison before and after smoking cessation was performed by the Wilcoxon signed rank test.

The statistical significance value was set at p<0.05. SPSS 24.0 for windows was the statistical program used for the analysis of data (Chicago, Il).

The baseline values are shown in Table 1: the mean age is 62 years.

Table 1 Demographic Baseline Data

Males were prevalent: 65 versus 55. Hypertension was the main comorbidity.

At baseline smoking exposure was major than 20 pack-years which represent the cutoff about the risk of developing COPD. The mean daily consumption of cigarettes exceeded the packet. The Fagestroms test indicates a moderate level of nicotine dependence.

By contrast, the Wests test revealed a high motivation and therefore a good probability to achieve smoking cessation. The mean value of body mass index was in the normal range. Finally the average of CAT value (152.5) indicates a moderate increase of the risk of exacerbation.

In Table 2 we can find the variation of the parameters one month after smoking cessation from baseline. No significant differences between different genders were detected.

Table 2 Differences Among Baseline and at the Follow-Up One Month After Quit. Gender: 55 Females, 65 Males

A significant increase of the main obstruction parameters was observed. Notably FEV 1 absolute value in litres was significantly increased (p<0.02), as well as indices of capacity and volume such as FVC were increased.

An index of peripheral airway obstruction such as the FEF 25/75% of predicted was also increased in a short time (p<0.05) as an expression of reduced inflammation. The six minute walking test results show that a significant increase of the walking distance was obtained along with a reduction of heart rate (p<0.05). This goes hand in hand with improved respiratory symptoms and exercise tolerance. In fact the other parameter of respiratory symptoms,CAT, decreased (p<0.01) whereas mMRC test which refers to the extent of dyspnea improved by 0.5 (p<0.0.05).

The main index of smoking exposure, as a tobacco combustion product, such as exhaled CO was reduced (p<0.02).

Regarding metabolic parameters and molecules examined on peripheral venous blood, the data show an improvement. In particular, an important decrease of total cholesterol had been achieved without the use of specific drugs, as well as vitamin D levels had been raised (Respectively p<0.02, p<0.01).

The purpose of this study was to highlight the effects of smoking cessation in the short term, not only on clinical and respiratory function indices but also on metabolic indices and in particular on the level of macromolecules important for many of our functions, such as cholesterol and vitamin D. To our knowledge it is the first study that highlights the rapid benefits of smoking cessation therapy on symptoms and metabolism-expressing molecules. Our findings suggest that smoking cessation confirms its efficacy on respiratory obstruction parameters. Its effectiveness is also extended to the effect of reducing the level of a cholesterol, which when in excess, increases the risk of heart and vascular disease. Similar studies highlighted that cigarette smoke increases the level of fatty acids and glycerol.12

In previous studies a higher concentration of high-density lipoprotein cholesterol (HDL-C) in ex-smokers than smokers has consistently been observed.13 Our findings suggest that there is a recovery of HDL and total cholesterol levels by quitting smoking.

We know that smoke exposure is the main cause of COPD that is the third cause of mortality and it is closely smoke-related. Under the continuous stimulus of tobacco smoke, large and small airways are affected by inflammation and structural remodeling.14,15

In the present study, the effects of smoking cessation on respiratory function in the short time are shown and an improvement of all considered parameters was achieved in both large and small airways.

We know that long-term smoking patients experience a respiratory function decline, furthermore there is an association of bronchial obstruction with nicotine metabolism rate.16

Chronic inflammation of the airways causes COPD, which in turn is characterized by flow limitation that occurs in the small and large bronchial branches.15

Lung function decline is closely related to age and smoking habit leading to symptoms worsening, conversely smoking cessation allow an improvement of functional and clinical parameters.17,18

Our findings provide novel insights in the clinical approach and evolution of bronchial obstruction highlighting a benefit in lipid metabolism, too.

As we know small airways are involved in smoke-induced inflammation by an alteration of the basal cells differentiation.1921

With regard to smoking cessation therapy, the first-line treatment of smoking cessation, aside from replacement therapy, is represented by varenicline which increases the percentage of quit smoking.22 The latter showed its efficacy both as a brief treatment and as a maintenance treatment.23

Smoking can affect the lungs local immune defenses by reducing them, and at the same time it can alter the local bacterial flora by increasing the pathogenic power of microorganisms. This ultimately promotes exacerbations in COPD patients.24

Regarding the effects of smoking on metabolism, it is associated with an increase of triglycerides and cholesterol lipoproteins, due to the interference of cigarette smoking with cytochrome enzyme system involved in lipid, cholesterol metabolism and its transport.25

Cigarette smoking promotes an altered level of cholesterol and lipoproteins26,27 and we demonstrated that after smoking cessation the levels improve without any therapeutic supplement. Finally, the increased level of vitamin D after smoking cessation suggests that smoking reduces bowel absorption of the vitamin and conversely smoking cessation leads to a fast improvement of its level.28

The study has some limitations mainly due to the small sample of patients, however it lends itself as a basis for further clinical and biological studies.

Smoking cessation confirms its efficacy leading to an improvement of all respiratory functional parameters including symptoms and obstruction parameters in the short time. It also affects lipid metabolism leading to a decrease of total cholesterol and at the same time it brings about an increase of HDL cholesterol level. Patients who quit benefit about their quality of life, by reducing dyspnea, and other respiratory symptoms, eventually preventing bronchitis exacerbations.

The authors would like to acknowledge and thank all the patients who agreed to take part in this research. The abstract of this paper took its cue from the abstract that was presented at the XXIV National Congress of Italian Pulmonology as a poster presentation talk with interim findings. The posters abstract was published in Poster Abstracts in Journal Respiration Hyperlink https://doi.org/10.1159/000531211 with DOI: 10.1159/000531211.

Professor Giuseppe Tonini reports on advisory board for Molteni, MSD, Novartis, Roche, and Pharmamar, outside the submitted work. The authors report no other conflicts of interest in this work.

1. Lareau SC, Fahy B, Meek P, Wang A. Chronic obstructive pulmonary disease (COPD). Am J Respir Crit Care Med. 2019;199:1P2.

2. Global Initiative for Chronic Obstructive Lung Disease Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease Global Initiative for Chronic Obstructive Lung Disease; 2020.

3. Pezzuto A, Spoto C, Vincenzi B, Tonini G. Short-term effectiveness of smoking-cessation treatment on respiratory function and CEA level. J Comp Eff Res. 2013;2:335343.

4. Song Q, Zhao YY, Zeng YQ, et al. The characteristics of airflow limitation and future exacerbations in different GOLD groups of COPD patients. Int J Chronic Obstr Pulm Dis. 2021;16:14011412.

5. Suissa S, DellAniello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;6:957963.

6. Seemungal TA, Hurst JR, Wedzicha JA. Exacerbation rate, health status and mortality in COPD--a review of potential interventions. Int J Chron Obstruct Pulmon Dis. 2009;4:203223. doi:10.2147/copd.s3385

7. Jones PW, Tabberer M, Chen WH. Creating scenarios of the impact of COPD and their relationship to COPD Assessment Test (CAT) scores. BMC Pulm Med. 2011;11:42. doi:10.1186/1471-2466-11-42

8. Hayata A, Minakata Y, Matsunaga K, Nakanishi M, Yamamoto N. Differences in physical activity according to mMRC grade in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:22032208.

9. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166:111117.

10. Deveci S, Deveci F, Aik Y, Ozan A. The measurement of exhaled carbon monoxide in healthy smokers and non smokers. Respir Med. 2004;98:551556.

11. Laszlo G. Standardization of lung function testing: helpful guidance from the ATS/ERS Task Force. Thorax. 2006;61:744746.

12. Kershbaum A, Bellet S, Dickstein ER, Feinbergl J. Effect of cigarette smoking and nicotine on serum free fatty acids based on a study in the human subject and the experimental animal. Circ Res. 1961;9:631638. doi:10.1161/01.res.9.3.631.

13. Forey BA, Fry JS, Lee PN, Thornton AJ, Coombs KJ. The effect of quitting smoking on HDL-cholesterol - a review based on within-subject changes. Biomark Res. 2013;1(1):26. doi:10.1186/2050-7771-1-26.

14. Mirza S, Clay RD, Koslow MA. Scanlon PD2 COPD Guidelines: a Review of the 2018 GOLD Report. Mayo Clin Proc. 2018;93:14881502.

15. Rennard SI, Vestbo J. Natural histories of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:878883. doi:10.1513/pats.200804-035QC

16. Pezzuto A, Lionetto L, Ricci A, Simmaco M, Borro M. Inter-individual variation in CYP2A6 activity and chronic obstructive pulmonary disease in smokers: perspectives for an early predictive marker. Biochim Biophys Acta Mol Basis Dis. 2021;1867(1):165990.

17. Maci E, Comito F, Frezza AM, Tonini G, Pezzuto A. Lung nodule and functional changes in smokers after smoking cessation short-term treatment. Cancer Investig. 2014;32:388393.

18. Pezzuto A, Stellato M, Catania G, et al. Short term benefit of smoking cessation along with glycopyrronium on lung function and respiratory symptoms in mild COPD patients: a retrospective study. J Breath Res. 2018;12:046007.

19. Polosa R. Cessation of smoking in COPD: a reality check. Intern Emerg Med. 2021;16:20292030. doi:10.1007/s11739-021-02740-w

20. Wohnhaas CT, Gindele JA, Kiechle T, et al. Cigarette smoke specifically affects small airway epithelial cell populations and triggers the expansion of inflammatory and squamous differentiation associated basal cells. Int J Mol Sci. 2021;22(14):7646. doi:10.3390/ijms22147646.

21. Churg A, Tai H, Coulthard T, Wang R, Wright JL. Cigarette smoke drives small airway remodeling by induction of growth factors in the airway wall. Am J Respir Crit Care Med Churg. 2006;174(12):13271334. doi:10.1164/rccm.200605-585OC.

22. Tashkin DP. Smoking cessation in COPD: confronting the challenge. Intern Emerg Med. 2021;16:545547.

23. Tonstad S, Tnnesen P, Hajek P, Williams KE, Billing CB, Reeves KR, for the Varenicline Phase 3 Study Group. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA. 2006;296:6471.

24. Ghosh B, Gaike AH, Pyasi K, et al. Bacterial load and defective monocyte-derived macrophage bacterial phagocytosis in biomass smoke-related COPD. Eur Respir J. 2019;53(2):1702273. doi:10.1183/13993003.02273-2017.

25. Vicol C, Buculei I, Melinte OE, et al. The lipid profile and biochemical parameters of COPD patients in relation to smoking status. Biomedicines. 2022;10(11):2936. doi:10.3390/biomedicines10112936.

26. Freyberg J, Landt EM, Afzal S, Nordestgaard BG, Dahl M. Low-density lipoprotein cholesterol and risk of COPD: Copenhagen general population study. ERJ Open Res. 2023;9(2):004962022.

27. He BM, Zhao SP, Peng ZY. Effects of cigarette smoking on HDL quantity and function: implications for atherosclerosis. J Cell Biochem. 2013;114(11):24312436.

28. Zhang C, Zhu Z.Associations among vitamin D, tobacco smoke, and hypertension: a cross-sectional study of the NHANES 2001-2016 by Wu et al. Hypertens Res. 2023;46(6):1615.

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Short-term benefits of smoking cessation | COPD - Dove Medical Press

Key protein in blood vessel’s growth identified – Science Daily

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Blood vessels are responsible of the appropriate and efficient delivery of nutrients and oxygen to the whole body. To do so, they must grow and branch to reach every cell in a process called angiogenesis. The precise regulation of the sprouting and pruning of blood vessels is complex and partly unknown, but endothelial cells, those lining the inner part of the vessels, are known to play an important role.

The growth and proliferation of endothelial cells is promoted by a protein known as mTORC1. Controlling its activity is important to organise a coherent branching of blood vessels and alterations in this process may lead to vascular malformations.

New research from the Mariona Graupera's lab (Josep Carreras Leukaemia Research Institute), published yesterday at the top journal Science Signaling, has just found that PI3K-C2b, a family member of the PI3K kinases, is responsible of the mTORC1 fine tuning through its inhibition. In a series of experiments using mice models and human cells, researchers found that animals with an inactive form of PI3K-C2a displayed aberrantly enlarged blood vessels. Similarly, when PI3K-C2b was transiently inactivated, endothelial cells appeared larger than usual. Both effects correlated with an increased expression of mTORC1 and were restored upon its external repression.

The findings are important since mutations in components of the PI3K family of proteins are frequent in patients with congenital vascular disorders. Understanding the link between one and the other may be useful to find new therapeutic targets in the future.

The present work was a collaborative initiative including researchers from the Josep Carreras Leukaemia Research Institute, the CNIO, the Universittsmedizin Berlin, the Max Delbrck Center for Molecular Medicine in the Helmholtz Association and the University College London. Funders of the project were the Spanish Ministry for Science and Innovation, the PTEN Foundation, "La Caixa" Foundation, the Spanish Association Against Cancer and the BBVA Foundation.

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Key protein in blood vessel's growth identified - Science Daily

Why you should be vaccinated even if you have had COVID-19 – EurekAlert

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image:

Top: A person is infected by the Alpha variant of SARS-CoV-2. Within a few weeks, antibodies are made that protect the person against the Alpha variant as well as Beta and Gamma variants which are very similar to the Alpha variant. Bottom: A person who (1) has recovered from COVID-19 and who (2) has received mRNA vaccine with components of the Alpha variant develops a strong immune response within a few weeks. The antibodies that are made in the body protect against the Alpha variant, the closely related Beta and Gamma variants as well as the more distantly related Delta and Omicron variants. People who have recovered from COVID-19 and then received the mRNA vaccine are also protected against new variants of SARS-CoV-2. Ill: Gerda Kaynova

Credit: Gerd Kaynova

Vaccines help boost the production of antibodies, providing effective protection against serious illness and death, says Mona Hyster Fenstad.

Fenstad is a senior consultant at the blood bank at St. Olavs Hospital in Trondheim.

We are already well into autumn, and the COVID-19 virus is rife all over Norway. The Norwegian Institute of Public Health recommends people in risk groups to get vaccinated.

They point out that elderly people in particular will be vulnerable to serious illness if they are infected with COVID-19. However, since the vast majority of us have already had COVID-19 at least once, do we really need to think about getting vaccinated?

Yes, say the scientists.

The saying what doesnt kill you makes you stronger is not true in this context. The inflammation that occurs in the body during infections such as influenza, COVID-19 and pneumonia can be harmful. Especially for people with heart or lung disease, or where other risk factors are involved, says Fenstad.

Fenstand and her international colleagues have recently published a study that looked at the effect of vaccination on people who became ill with COVID-19 before vaccines were available. This work has been closely linked to the search for antibodies that can be used as medicine against COVID-19.

At the beginning of 2020, the World Health Organization (WHO) asked scientists and therapists around the world to look for treatments for COVID-19. Among the treatments proposed was convalescent plasma therapy, which uses plasma from blood donors who have recovered from the illness. Along with colleagues from NTNU (the Norwegian University of Science and Technology), we chose to take a closer look at how the antibodies in this plasma were able to neutralize new virus variants that emerged, says Fenstad.

While big pharmaceutical companies were working hard to develop vaccines and medicines, scientists had already begun to look at the use of blood plasma from COVID-19 patients as a possible treatment.

Many of these patients had large amounts of antibodies in their blood. Plasma containing these antibodies was therefore given to seriously ill patients to help them fight the virus. It turned out that convalescent plasma therapy was primarily effective in patients who had immunodeficiencies, says Fenstad.

We were looking for so-called super-neutralizers, people who develop specific antibodies that effectively neutralize different variants of SARS-CoV-2, says Denis Kainov, a professor in NTNUs Department of Clinical and Molecular Medicine who was part of the research team.

These antibodies were eventually cultivated and cloned, and then turned into medicines used to fight COVID-19.

In Norway, the first COVID-19 outbreak occurred in February 2020. The first Alpha variant was quickly followed by new, mutated variants named Beta and Delta. Omicron, which is currently the prevailing variant, was first reported in late 2021.

By April 2020, blood banks across Norway had begun collecting blood plasma from patients who had recovered from COVID-19. At St. Olavs Hospital, 72 patients were selected for a more detailed study of the antibodies in their blood plasma.

It turned out that half of these patients had serum containing antibodies that effectively neutralized the Beta variant, says Kainov.

Kainov has been searching for active substances to use in the treatment of COVID-19 and other viral diseases.

He is now looking for antibodies that could provide wider protection, including against new COVID-19 variants that might emerge.

They noticed that four patients had antibodies that effectively neutralized the COVID-19 variant that was dominant in Trondheim at the time.

We followed up by taking new samples from these patients and found that their antibodies also neutralized other COVID-19 variants. In fact, they were also effective on new virus variants, says Kainov.

The conclusion is thus that it is a good idea to get vaccinated even if you have already had COVID-19 and even if the virus has mutated since the vaccine was made.

Out of the four patients, the scientists picked the one whose antibodies had been least effective against the Omicron variant. This patient had received their first vaccine dose four months after recovering from COVID-19. The efficacy of the vaccine was striking.

The vaccine boosted the production of immune cells and antibodies against all tested variants of the virus, including Omicron, says Kainov.

Kainovs colleagues in Estonia could then proceed with blood plasma from the patient, cloning and cultivating antibodies that neutralised COVID-19 viruses on a wide scale.

The results have also provided the scientists with useful knowledge about the effect of the vaccine on convalescents.

When it comes to vaccines, it is always a race. The virus is always one step ahead, and the vaccines and medicines will never be completely up to date, Fenstad said

Our study is an in-depth study of just one patient, and it constitutes only a tiny piece of research in this field. However, large studies in other countries confirm our findings. Vaccines boost the production of antibodies that are also effective against new variants of the virus, she said.

The finding demonstrate that it is a good idea to get vaccinated even if you have already had COVID-19 and even if the virus has mutated since the vaccine was made. It may not prevent you from being reinfected, but it will provide protection against serious illness and death.

When you get sick with COVID-19, you develop antibodies, but the effects of these diminish and are gone after six to nine months. This is why people can get infected again and again by new variants of SARS-CoV-2. The virus mutates to avoid the immune response we have developed through previous infections or vaccines, says Kainov.

That is why vaccination is important now that we are heading towards winter.

The studies we have conducted here on COVID-19 patients are extremely important, because there will be new outbreaks of the virus. Almost seven million people have died from COVID-19. We must avoid getting into the same situation again, says Kainov.

Reference: Mona Hyster Fenstad et al.:Boosted production of antibodies that neutralized different SARS-CoV-2 variants in a COVID-19 convalescent following messenger RNA vaccination a case study.International Journal of Infectious Diseases. Volum 137, December 2023 https://doi.org/10.1016/j.ijid.2023.10.011

International Journal of Infectious Diseases

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Boosted production of antibodies that neutralized different SARS-CoV-2 variants in a COVID-19 convalescent following messenger RNA vaccination - a case study

1-Nov-2023

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Why you should be vaccinated even if you have had COVID-19 - EurekAlert

Multidisciplinary Collaboration and Molecular Testing Are Integral to … – OncLive

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Lyudmila A. Bazhenova, MD

With the integration of neoadjuvant, adjuvant and perioperative chemoimmunotherapy approaches into the nonsmall cell lung cancer (NSCLC) treatment paradigm, it is increasingly vital for clinicians to accurately identify patients with unresectable disease displaying key oncogenic drivers, such as EGFR and ALK mutations, before deciding on a therapeutic approach, according to Lyudmila A. Bazhenova, MD.

Its important to highlight that [genetic] testing is necessary for patients [with unresectable lung cancer], and remember that the phase 3 PACIFIC trial [(NCT02125461) regimen] is the standard of care [SOC] right now in this space, Bazhenova said regarding a recent OncLive Institutional Perspectives in Cancer webinar on lung cancer, which she chaired.

In an interview with OncLive, Bazhenova, who is a medical oncologist and professor of medicine at the University of California San Diego (UCSD) Moores Cancer Center in California, expanded on key topics in lung cancer that were discussed by her colleagues at UCSD Health. This included key considerations when navigating the use of perioperative immunotherapy for patients with or without oncogenically-driven lung cancers, the importance of collaboration between oncologists and other specialists when deciding on a treatment plan, and the need for increased and earlier implementation of biomarker testing in all patients with lung cancer.

Bazhenova: 2023 has been a very busy year in lung cancer and several important publications have been presented. Many [of the emerging agents presented] do not have FDA approvals yet, so its hard to apply these data to current practice. However, it is important to be aware of what agents are coming down the lineonce they are FDA approved, we can utilize that treatment modality.

Its important to know which cancers are resectable and which are unresectable. It is very important to work with your multidisciplinary team to make that decision. [Clinicians should not] forget that durvalumab [Imfinzi] is the SOC for patients with unresectable disease. I would not consider durvalumab for patients with oncogenic drivers, especially EGFR and ALK mutations.

The challenge with this approach is the fact that there is no consensus because we have options for our patients. You can give them adjuvant, neoadjuvant or perioperative immunotherapy. We do not have any randomized trials telling us what the right thing to do is, so whatever works [at a given clinicians] institution is appropriate. At UCSD, we are believers in neoadjuvant and perioperative immunotherapy, so thats what we offer our patients. Again, like with unresectable disease, multidisciplinary care is vital. Clinicians should make sure to discuss [the patients situation] with a radiation oncologist as well as surgeon and determine a treatment plan in the beginning once all the specialists have evaluated the patient.

For patients with EGFR mutations and ALK rearrangements, we know that immunotherapy generally does not work very well. For those patients, I would not consider neoadjuvant chemoimmunotherapy or adjuvant immunotherapy. Those patients will generally go to surgery. One could consider neoadjuvant chemotherapy if theyre dealing with a stage III cancer where this approach would be appropriate. After the completion of neoadjuvant treatment, it is important to make sure that [clinicians] offer those patients adjuvant osimertinib [Tagrisso], which is currently FDA approved.

Although adjuvant alectinib [Alecensa] has not yet been FDA approved, the phase 3 ALINA trial [NCT03456076] is very important. I hope that adjuvant alectinib will eventually become an FDA-approved option. It is also important to make sure that clinicians test patients for those abnormalities; ideally, one would want to test patients before selecting a neoadjuvant approach because your decision depends on the presence or absence of given mutations.

At UCSD, we have the [phase 2 TRUST-II study (NCT04919811)] with taletrectinib for ROS1rearranged lung cancer. The preliminary efficacy [data] showed a high response rate [with the agent] and responses appear to be durable. The interesting fact about taletrectinib is that it does not inhibit trkB. So the adverse effect profile is different, and in my opinion better, than the safety profile of entrectinib (Rozlytrek) and repotrectinib (Augtyro).

My main message is biomarkers, biomarkers, biomarkers! [Clinicians should] make sure that patients are being tested for molecular abnormalities and should understand the difference between DNA testing and RNA testing. [We should understand] the additional benefit that RNA testing brings, especially for patients with gene fusions, which are common in lung cancer.

[Lastly], we need to know the issues surrounding cell-free DNA. Its a great tool for patients, but approximately 30% of cell-free DNA tests will produce a false negative. If an oncologist performs a liquid biopsy and didnt discover the mutation, it is not appropriate to stop there. We want to make sure that tissue next-generation sequencing is being performed so we dont miss patients who display oncogenic drivers.

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Multidisciplinary Collaboration and Molecular Testing Are Integral to ... - OncLive

SBU Crime Watch: Nov. 18 Nov. 24 The Statesman – Stony Brook Statesman

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A map of Stony Brook University marked with the locations of crimes that occurred on campus from Saturday, Nov 18. to Friday, Nov 24. ILLUSTRATED BY BRITTNEY DIETZ/THE STATESMAN

All reports are taken directly from the University Police Department and cannot be independently verified by The Statesman.

On Saturday, Nov. 18, there was a report of missing kitchen scissors last seen on Oct. 30 in Chapin Hall. The case was closed by investigation.

On Monday, Nov. 20, a patient struck another patient in Stony Brook University Hospital. The case was closed after the victim refused to cooperate.

On Monday, Nov. 20, there was a report of a phone scam in the Centers for Molecular Medicine. The case was closed and referred to another agency.

On Tuesday, Nov. 21, there was a report of a missing pair of jeans and dorm key in the Walter J. Hawrys Campus Recreation Center. The case is still open.

On Tuesday, Nov. 21, a dispute was reported between a motorist and pedestrian in a motor vehicle accident at Circle Road and Engineering Drive. An MV-104 was completed, and no injuries were reported. The case was closed after the victim refused to cooperate, and there was a student referral.

On Wednesday, Nov. 22, a social media scam was reported in Greeley Hall. The case is still open, and the victim was transported to the Comprehensive Psychiatric Emergency Program.

On Wednesday, Nov. 22, there was a report of a vehicle driving through a gate arm, damaging the Stony Brook University Hospital parking garage. The case is still open.

On Thursday, Nov. 23, a patient slapped a staff member on the arm in Stony Brook University Hospital. The case was closed after the victim refused to cooperate.

On Friday, Nov. 24, a patient struck three employees in Stony Brook University Hospital. The case was closed after the victims refused to cooperate.

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SBU Crime Watch: Nov. 18 Nov. 24 The Statesman - Stony Brook Statesman

New CT, MR scanners and AI top GE HealthCare highlights at … – AuntMinnie

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CHICAGO -- GE HealthCare (GEHC) brought new CT and MRI scanners and a range of AI software applications to McCormick Place for RSNA 2023.

CT

In CT, GEHCshined the spotlight on its Revolution Ascend scanner, which was first introduced at ECR in March. With onsite detector upgrades, Ascend can be upgraded from a 20-mm coverage system for routine scanning to a 40-mm coverage system that delivers better low-contrast detectability, according to the vendor.

The scanner also comes with True Enhance DL, an AI-based application that generates deep learning-based monochromatic-like images from a single-energy x-ray acquisition. This capability is designed to increase contrast resolution and is especially useful for challenging oncology exams, GEHC said.

GE HealthCare's new Revolution Ascend CT scanner.

GEHC also pointed to upgrades for its Revolution Apex scanner, including ECG-less Cardiac for acquiring cardiac images without the need for an ECG signal or trace. Whats more, GEHC has launched Tube Watch, which uses digital twin technology to remotely monitor and predict tube failures or potential issues in Apexs x-ray generation chain.

In addition, the vendor said that its TrueFidelity DL software is available on both Apex and Ascend. Based on a deep neural network, TrueFidelity DL is designed to generate high-definition, low-noise CT images. TrueFidelity DL features for the lung and extremity are available exclusively, however, on the Apex.

Both Apex and Ascend come with GEHCs Effortless Workflow CT workflow automation software and Smart Subscription services for easy software updates.

In photon-counting CT technology developments, GEHC said that researchers at Stanford Medicine have begun scanning human subjects using its photon-counting CT prototype. The research will produce technical feedback to assist GEHC in assessing the systems reconstruction methods, image presentation workflow, and clinical benefits for specific pathologies and disease types.

MRI

GEHC unveiled Signa Champion, a 1.5-tesla, wide-bore scanner that features AI-supported workflow features such as the firms AIR Recon DL image reconstruction software and Sonic DL software for accelerating image acquisition. The company also highlighted the patient comfort benefits of Champions wide bore and short scan times. Notably, Champion has the smallest footprint and is the most power-efficient among GEHCs wide-bore systems.

GE HealthCare's Signa Champion 1.5-tesla scanner.

Via a partnership with Brazilian automation technology provider Ionic Health, GEHC has also added remote scanning capability as part of anew version of its Digital Expert Access software. Ionic Healths nCommand Lite technology, which is currently pending U.S. Food and Drug Administration (FDA) 510(k) clearance, is designed to support vendor-agnostic remote scanning capabilities

As a result of the new technology, remote clinical users can currently initiate a scan on GEHCs MR devices from inside or outside the radiology suite or at any clinical facility, according to the firm.

Informatics/AI

GEHC featured App Orchestrator, an AI application orchestration platform for facilitating integration of multiple third-party apps into existing workflow. App Orchestrator is compatible with most major PACS, according to the company.

The company also unveiled Theranostics Pathway Manager Tile, an application designed to aid in coordinating the theranostics care pathway, as well as identifying and tracking potential theranostics candidates. Its available on GEHCs Command Center Software Platform.

GEHC also introduced version 2.0 of its Imaging 360 for Operations platform. The latest release supports operational analytics, remote scan assistance, protocol management, dose management, and scheduling.

Interventional

In image-guided surgery activities, GEHC showcased two new AI applications previously presented at ECR 2023. Embo Assist AI automatically segments vascular structures to facilitate embolization workflow planning, while Liver Assist Virtual Parenchyma 3D provides AI-based virtual parenchymography.

Interact Touch is a new feature for GEHCs Allia image-guided surgery platform that enables clinicians to control up to three different third-party devices including Avvigo+ multimodality guidance system from Boston Scientific -- through one single touch panel.

GEHC has also added an interventional augmented reality (AR) application via a partnership with MediView for OmnifyXR Interventional Suite, which allows users to simultaneously display up to four customized holographic projections of liver imaging. 3D volume images can also be displayed in AR for improved anatomy visualization.

In addition, the company said it has continued its collaboration with Centerline Biomedical for its Intra-Operative Positioning System (IOPS) and has also partnered with Proximie to incorporate real-time collaboration and access to data insights.

Molecular imaging

In molecular imaging, GEHC emphasized the launch of its Precision DL for PET/CT imaGEHC processing software, which is now available on its Omni Legend PET/CT scanner.

GEHC has also brought its Effortless Workflow technology to its molecular imaging portfolio. Available on GEHCs Omni PET/CT and StarGuide SPECT/CT scanners, the AI-based Effortless Workflow service automates patient positioning and suggests protocols to enable time savings for molecular imaging studies, according to the firm.

In theranostics developments, GEHC has formed a collaboration with cancer treatment center BAMF Health to provide its PETtrace Solid Target gallium production platform; Omni Legend; Signa PET/MR AIR scanner; StarGuide SPECT/CT scanner; and software such as Precision DL, AIR Recon DL, and Q.Thera AI.

GEHC also displayed its Signa PET/MR AIR system, which was introduced at the annual Society of Nuclear Medicine and Molecular Imaging (SNMMI) conference in June.

Ultrasound

In ultrasound developments, GEHC discussed the addition of Caption Guidance AI software to its Venue family of point-of-care ultrasound systems. With Caption Guidance, even healthcare providers without specialized training or experience can perform cardiac ultrasound exams and acquire diagnostic-quality cardiac images, according to the vendor.

GEHC acquired caption guidance developer Caption Health earlier this year and said it plans to integrate the software into other ultrasound systems in its portfolio, including handheld units.

GE also introduced bkActive, an ultrasound system that provides real-time surgical visualization and improved control over procedures supporting surgeons and clinicians in urology, neurosurgery, hepato-pancreato-biliary surgeries, colorectal and pelvic floor surgeries, and laparoscopic surgeries. The system was developed by GEHC company BK Medical.

Other ultrasound scanners on display included GEHCs Logiq E10, Fortis, Invenia ABUS 2.0, Vscan AIR SL, and Voluson Expert systems. The company also showed its Vivid series of cardiovascular ultrasound scanners.

Additionally, GE pointed to its Verisound suite of ultrasound software applications, including Verisound Reporting, Verisound Fleet Management, Verisound Collaboration, and Vscan Digital Tools.

Meanwhile, a new version of GEs ViewPoint software, 6.14, enables data to be distributed directly from the ultrasound scanner to populate reports.

Womens imaging

GEHC introduced MyBreastAI Suite, an AI platform that currently integrates three AI applications from partner iCAD, including the following: ProFound AI for DBT, PowerLook Density Assessment, and SecondLook for 2D Mammography.

To help practices start a new contrast-enhanced mammography program, GEHC has launched Pristina Bright, which combines SenoBright HD, Pristina Serena, and Serena Bright with an education program that provides dedicated onsite support, CME-accredited self-assessment, and access to a user club to collaborate with experts around the globe, the firm said.

X-ray

In radiologys oldest modality, GEHC once again emphasized Definium 656 HD, an overhead tube suspension system with the highest weight capacity in the companys fixed x-ray portfolio. At RSNA 2023, the firm announced upgrades to Definium 656 HD aimed at improving image quality and consistency, reducing acquisition errors, and streamlining workflows.

The company also debuted Precision CRF, a fluoroscopy system featuring an overhead tube suspension, digital detectors, intelligence exposure control, and image processing software. It supports both radiography and fluoroscopic imaging.

Another introduction, Definium Pace, is a fixed x-ray system available at a value price point, according to GEHC. It comes with a range of automation and enhanced workflow features, the company said.

In other news, GE announced that users of its legacy AMX 200, 220, or 240 systems can now be upgraded to an AMX fixed-column configuration, as well as a modern user interface and software functionalities.

Pharmaceutical diagnostics

The company pointed to a recent study that validated the use of AI models for predicting patient response to therapy. In research presented at the Society for Immunotherapy of Cancer in San Diego in November, the AI models yielded 70%-80% accuracy for predicting treatment response.

Cardiology

In cardiology, GEHC introduced CardioVision for AFib, a software tool for management of patients with atrial fibrillation. The software automatically compiles longitudinal data for disease progression from multiple data sources and generates therapy recommendations based on guidelines, according to the vendor.

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New CT, MR scanners and AI top GE HealthCare highlights at ... - AuntMinnie

Daniel Muoz and Francis Miller named interim directors of the … – VUMC Reporter

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Daniel Muoz, MD, MPA

by Matt Batcheldor

Daniel Muoz, MD, MPA, associate professor of Medicine, and Francis Miller, MD, professor of Medicine, have been named interim directors of the Division of Cardiovascular Medicine at Vanderbilt University Medical Center. Their appointments are effective Dec. 1.

Muoz, also the executive director of Vanderbilt Heart and Vascular Institute (VHVI), will be responsible for clinical affairs. Miller, a physician-scientist investigator in the Division of Cardiovascular Medicine and chief of Cardiology at the VA Tennessee Valley Healthcare System, will be responsible for academic affairs.

Muoz and Miller will assume the directorship duties of Jane Freedman, MD, professor of Medicine, who has been named to serve as interim chair of the Department of Medicine and physician-in-chief for VUMC, also effective Dec. 1.

Muoz graduated from Princeton University with a bachelors degree in Economics. He went on to receive his medical degree from Johns Hopkins University and his masters degree in Public Administration from Harvard Universitys John F. Kennedy School of Government in 2005. He continued to serve in the Johns Hopkins Hospital and Health System, where he completed his residency in 2008, chief residency in 2010 and cardiology fellowship in 2011. After completing a research fellowship at Duke University, he came to Vanderbilt for further subspecialty training, after which he joined the faculty in 2013.

In his decade on the VUMC faculty, Muoz has served in various leadership roles, including medical director of the Cardiovascular Intensive Care Unit (CVICU), medical director for Quality at VHVI and as interim division co-director for Clinical Affairs from 2020-2021.

Muoz currently serves as an attending physician in the CVICU, where he is known as an effective teacher and a skilled clinician. His outpatient practice is focused on the realms of preventive and general cardiology.

His research has focused on developing innovative strategies for lowering cardiovascular risk and improving patient outcomes in high-risk primary prevention settings. This includes widely recognized work with the polypill in underserved areas of the rural South. This research, published in The New England Journal of Medicine, demonstrated that a polypill approach to the management of hypertension and cholesterol could effectively improve these measurements of cardiovascular health in an underserved population.

Miller obtained his bachelors degree in Biology and a medical degree from the University of Iowa. He completed an internal medicine residency at the University of Texas Southwestern Medical Center in Dallas before returning to the University of Iowa for a cardiology fellowship. He remained at the University of Iowa as a faculty member, rising to professor before relocating to Duke University and the Durham VA Medical Center in 2016 as a professor of Medicine. In 2020, Miller became the chief of Cardiology at the Salisbury VA Medical Center and a professor at Wake Forest University. He joined VUMC and VA Tennessee Valley Healthcare System in 2022.

Miller has served on several national committees, including as a member of the board of directors of the Federation of American Societies for Experimental Biology, committee chair for the Society for Redox Biology and Medicine, chair of an oversight advisory committee for the American Heart Association, and president of the American Federation for Medical Research.

He has contributed to several editorial boards and study sections. and is a deputy editor of Circulation Research. His research has been funded by the National Institute of Health, National Science Foundation, Department of Defense, Department of Veterans Affairs, and American Heart Association.

The central goal of Millers research is to understand the molecular and cellular roles of reactive oxygen species in cardiovascular disease. His work on NADPH oxidases in the blood vessels has received international recognition.

As a practicing cardiologist, he strives to unite findings in the research lab with human disease. His current research has resulted in several patents using synthetic RNA ligands as novel therapies. Miller is an avid supporter of the physician-scientist and has received awards for house staff teaching and mentorship of graduate students.

I am delighted with Drs. Muoz and Millers appointments to serve as joint interim directors of the Division of Cardiovascular Medicine, Freedman said. I am confident that their expertise and experience in academic, clinical and educational affairs will support the division during an exciting time of ongoing growth and expansion.

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School of Medicine’s Kim lab secures more than $3 million from … – Wayne State University

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At left is Hyeong-Reh Kim, Ph.D., with her lab members in the School of Medicine Department of Pathology.

The National Cancer Institute has awarded the Wayne State University School of Medicine $3,032,353 over five years to fund a study that holds the potential to introduce a new class of drugs tailored for patients with therapy-resistant cancers.

Professor of Pathology Hyeong-Reh Kim, Ph.D., is the principal investigator on the project, A novel AR degrader in castrate-resistant prostate cancer.

The goal is to develop a new class of drugs that effectively degrade both wild-type androgen receptor (AR) proteins and AR variants in prostate cancer. The Kim laboratory has been working to uncover the molecular and cellular mechanisms underlying human cancer progression and metastasis, to identify therapeutic targets and to develop novel therapeutics for patients with therapy-resistant cancers, including advanced head and neck cancers and castrate-resistant metastatic prostate cancer.

The receptors for androgens, the group of male sex hormones, play a critical role in all stages of prostate cancer. While many prostate cancer patients initially respond to hormone therapies, significant numbers of patients develop castrate-resistant prostate cancer.

Clinical studies have shown that castrate-resistant prostate cancer often involves androgen receptor variants that lack the ligand binding domain, making this hormone receptor constitutively active and resistant to hormone therapy.

The innovations in our study include the development of a new therapeutic platform usingautophagy-targetingchimera (AUTOTAC)for oncoprotein degradation, she said.This novel therapeutic platform is composed of a target-binding small molecule linked to an autophagy ligand. The AUTOTAC brings the targeted oncoprotein to the protein degradation machinery, involving autophagosome and lysosome, leading to the efficient removal of oncoproteins.

Using a natural ligand or a synthetic small molecule that binds the protein of interest, the AUTOTAC can be utilized for the removal of unwanted proteins. Our study will help establish the foundation for arevolutionary drug development platform in a wide array of human diseases, Dr. Kim added.

In collaboration with Radiation Oncology Professor Harold Kim, M.D., and Associate Professor Joseph Rakowski, Ph.D., and the new Barber Integrative Metabolic Research Team, the Kim laboratory is engaged in the development of radiosensitizers utilizing the AUTOTACplatform or inducers of lipolysis.

This is a truly collaborative project involving many co-investigators, including Dr. Yong Tae Kwon at Seoul National University; and Drs. Elisabeth Heath (Oncology), Seongho Kim (Oncology), Dongping Shi (Pathology), Michael Cher (Urology), Lisa Polin (Oncology) and Sijana Dzinic (Oncology) at the Wayne State University School of Medicine. In my laboratory, Drs. Abdo Najy and Tri Pham, Alaleh Zamiri, M.D. a Ph.D. student and Jenna Poole will work on this project. We hope to recruit more student and post-doctoral fellows to work on this project, Dr. Kim said.

The number for this National Institute of Health award is R01CA282040.

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School of Medicine's Kim lab secures more than $3 million from ... - Wayne State University

NOT-AR-23-022: Request for Information on Themes for the NIAMS … – National Institutes of Health (.gov)

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Request for Information on Themes for the NIAMS Strategic Plan for Fiscal Years 2025-2029

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supports research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. NIAMS is updating its Strategic Plan to help guide the research, training, and information dissemination programs it supports between fiscal years 2025 through 2029. The new Plan will focus on cross-cutting thematic research opportunities that position the Institute to make a difference in the lives of all Americans.Because public input is a crucial step in this effort, the Institute issued a Request for Information (NOT-AR-22-023) and hosted a meeting attended by approximately 160 researchers, patient representatives, and staff from other Federal entities to gain insight into topics that could be included in the new Strategic Plan.

Through this Request for Information, NIAMS invites feedback from researchers in academia and industry, health care professionals, patient advocates and health advocacy organizations, scientific or professional organizations, Federal agencies, and other interested members of the public on the Institutes distillation of the input received to date. Professional societies and patient organizations are strongly encouraged to submit a single response that reflects the views of their entire membership.

Please provide your perspective on the following potential cross-cutting themes, examples, and bold aspirations. NIAMS is particularly interested in suggestions for additional or alternative:

Examples:

Bold Aspirations:

Examples:

Bold Aspiration:

Note: Efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare should be considered for NIAMS-funded research projects whenever possible.

Examples:

Bold Aspirations:

Examples:

Bold Aspiration:

Note: Consistent with the note under Health disparities and health equity, studies of lifestyle factors and environmental exposures should include efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare whenever possible.

Examples:

Bold Aspiration:

Note: Consistent with the note under Health disparities and health equity, clinical and epidemiologic research should include efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare whenever possible.

Examples:

Bold Aspiration:

Examples:

Bold Aspiration:

Note: Training and workforce efforts are essential for the pursuit of all cross-cutting thematic research areas in the new NIAMS Strategic Plan.

Examples:

Bold Aspiration:

Examples:

Bold Aspirations:

Responses to this RFI must be submitted electronically at https://rfi.grants.nih.gov/?s=654a7bc81e7ccb6f7d03d792.

Responses must be received by Monday, January 1, 2024.

Responses to this RFI are voluntary. Do not include any proprietary, classified, confidential, trade secret, or sensitive information in your response. The responses will be reviewed by NIAMS staff, leadership, and Advisory Council members. Individual feedback will not be provided to any respondent. NIAMS will use the information submitted in response to this RFI at its discretion and will not provide comments to any respondents submission. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted.The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.

This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers to provide support for any ideas identified in response to it. The Government will not pay for the preparation of any information submitted or for the Governments use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Governments use of such information.

We look forward to your input and hope that you will share this RFI document with your colleagues.

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A novel targeted molecular therapy for drug-resistant biliary tract … – EurekAlert

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image:

When human biliary tract cancer cells are transfected with miR-451a, cell proliferation within the cell aggregates is inhibited. Researchers from Okayama University Hospital, Japan, show this occurs due to the suppression of PI3K/AKT pathway, partially through the downregulation of MIF.

Credit: Dr. Koichiro Tsutsumi from Okayama University Hospital, Japan

Biliary tract cancers (BTCs) including cholangiocarcinoma (CCA) and gallbladder cancer (GBC) are becoming more prevalent globally. An effective chemotherapeutic agent for the treatment of BTCs is gemcitabine. Other novel molecular targeted drugs have also been developed; however, they are only effective at treating a few cases of BTCs. In addition, very few drugs are effective against GEM-resistant BTCs. While surgery is the best option for the treatment of BTCs, many patients are diagnosed late, due to a lack of symptoms. Another challenge for physicians treating BTCs is identifying an appropriate treatment approach due to the complexity of the hepatobiliary-pancreatic system. Therefore, developing novel treatment strategies for BTCs, especially for GEM-resistant BTCs, is the need of the hour.

Nucleic acid-based therapies built around microRNAs (miRNAs) are the next frontier of cancer treatment. miRNAs play a role in gene expression, and their dysregulation is believed to contribute to cancer pathogenesis. Now, researchers from Japan are exploring the prospects of microRNA-451a (miR-451a), a miRNA identified in gallbladder tissue, as a viable targeted nucleic acid BTC therapy. The team, led by Assistant Professor Koichiro Tsutsumi, along with Dr. Taisuke Obata and Dr. Motoyuki Otsuka, all from the Department of Gastroenterology Okayama University Hospital, Japan, recently uncovered the mechanism of miR-451as antineoplastic effects. Their findings were published in Molecular Therapy: Nucleic Acids on 28 October 2023.

Apart from gemcitabine, very few effective drugs are available for the treatment of BTCs. Therefore, there is an urgent need for new therapies. Additionally, we dont know a lot about the miRNA targets that can be used to improve the prognosis of BTCs, especially in the context of resistance to GEM, explains Dr. Tsutsumi while discussing his motivation behind this research. The team had evidence from previous experiments that miR-451a was downregulated in patients with GBC, and they decided to build on other research that showed that the miRNA inhibited cell proliferation when introduced into human GBC cells. They transfected miR-451a into GBC, gemcitabine-resistant GBC (GR-GBC), and gemcitabine-resistant CCA (GR-CCA) cells to understand its effects on tumor progression. They also studied the gene expression profile in these three groups following transfection, to gauge how cell-signaling pathways were altered by miR-451a.

Under experimental conditions that mimicked those of the cancer environment, we found that miR-451a significantly diminished cell proliferation, induced cell death, and reduced the occurrence of chemoresistant cell types in GBC, GR-CCA, and GR-GBC cells, says Dr. Tsutsumi. He adds, One of the factors known to promote metastasis and chemoresistance was the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. This pathway was suppressed partially through the downregulation of macrophage migration inhibitory factor (MIF) after the transfection of miR-451a. These findings underpin miR-451as use as a replacement therapy for GEM-resistant BTCs. miR-451as effects at the molecular level were reflected in 2D or 3D cell culture experiments where GR-CCA and GR-GBC cells were rendered less viable following treatment.

Dr. Tsutsumi is looking to the future, and the group is planning future studies to evaluate the effective delivery of miR-451a and validate its clinical application. He concludes, Nucleic acid-based treatments are not mature enough to be considered first-line treatments for BTCs, so chemotherapy and immunotherapy still have their place. However, given miR-451as antineoplastic activity against GEM-resistant BTCs, I anticipate them to be mainstream alternatives with further developments.

About Okayama University, Japan As one of the leading universities in Japan, Okayama University aims to create and establish a new paradigm for the sustainable development of the world. Okayama University offers a wide range of academic fields, which become the basis of integrated graduate schools. This not only allows us to conduct the most advanced and up-to-date research, but also provides an enriching educational experience. Website: https://www.okayama-u.ac.jp/index_e.html

About Assistant Professor Koichiro Tsutsumi from Okayama University, Japan Dr. Koichiro Tsutsumi is an Assistant Professor in the Department of Gastroenterology at Okayama University Hospital. He earned his Doctor of Medicine from Tohoku University in 2001, and Doctor of Philosophy from Okayama University in 2013. His research explores themes across gastroenterology, tumor diagnostics and therapeutics. Dr. Tsutsumi has published over 120 peer-reviewed articles since 2003 and received the Japanese Biliary Society International Exchange Encouragement Award in 2016.

Molecular Therapy Nucleic Acids

Experimental study

Cells

MicroRNA-451a inhibits gemcitabine-refractory biliary tract cancer progression by suppressing the MIF-mediated PI3K/AKT pathway

28-Oct-2023

The authors declare no competing interests.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Understanding the Vaginal Microbiome’s Impact on Health and … – Inside Precision Medicine

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Researchers at the University of California (UC) San Diego School of Medicine have made significant discoveries in understanding the complex relationship between bacterial vaginosis and adverse sexual and reproductive health outcomes.

Bacterial vaginosis, a common condition affecting nearly 29 percent of women between the ages of 14 and 49 in the United States, has long been associated with pregnancy loss, preterm birth, postsurgical infections, pelvic inflammatory disease, and sexually transmitted infections. Reporting in Science Translational Medicine, researchers are now shedding light on the mechanisms by which certain bacterial species disrupt the delicate balance of the vaginal microbiome, leading to these severe health complications.

Bacterial vaginosis is known to be linked to pregnancy loss, preterm birth, postsurgical infections, pelvic inflammatory disease, and sexually transmitted infections, emphasized Warren G. Lewis, an assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at UC San Diego School of Medicine. The study not only highlights the severity of the conditions associated with bacterial vaginosis but also provides a deeper understanding of its underlying molecular mechanisms.

The researchers analyzed epithelial cells that line the vagina as crucial players in the interaction between bacteria and the human body. These cells are densely coated with sugar chains known as glycans, which play pivotal roles in cell biology and disease. The team discovered that in bacterial vaginosis, specific bacteria release enzymes called sialidases, which partially dismantle protective glycan molecules on the surface of epithelial cells. Remarkably, they were able to induce a bacterial-vaginosis-like state in normal epithelial cells by treating them directly with sialidase enzymes produced in the laboratory.

Amanda Lewis, a professor in the Department of Obstetrics, Gynecology & Reproductive Sciences, said, The fact that we were able to replicate some of the effects of bacterial vaginosis suggests that we may be on the right track to finding a common cellular origin for the various complications associated with this condition. According to the researchers, this breakthrough opens the door to potential diagnostic advancements, as studying the surface of vaginal epithelial cells at such a detailed biochemical level could aid in identifying subsets of individuals at the greatest risk for negative health outcomes, including recurrence.

While the study provides a blueprint of the glycans present on vaginal epithelial cells, Warren Lewis acknowledges that further research is needed to fully comprehend the functions of glycans in the vaginal epithelium and how bacterial vaginosis impacts these functions. As this research progresses, clinicians are urging individuals with vaginas to be vigilant about the symptoms of bacterial vaginosis and to refrain from practices such as douching or using scented products, which may exacerbate microbial imbalances.

In unraveling the complexities of the vaginal microbiome, this research not only contributes to our understanding of bacterial vaginosis but also holds the promise of more effective diagnostics and targeted interventions for individuals at risk. The authors believe that the implications of this study reach beyond gynecology, touching on broader aspects of reproductive health and paving the way for innovative approaches to tackle related complications.

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Honorary doctorate for Kelly Chibale in Switzerland – University of Cape Town News

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Leading University of Cape Town (UCT) scholar and scientist Professor Kelly Chibale has been awarded an honorary doctorate from the Faculty of Science at the University of Basel, Switzerland a world-leading research university and one of the oldest in Europe.

Professor Chibale was one of seven scholars who received honorary doctorates during the Dies Academicus ceremony in Basel on 24November. But his was the only one awarded by the universitys Faculty of Science.

The annual Dies Academicus celebration is held in St Martins Church on the last Friday of each November and commemorates the opening of the university on 4April1460 at the Basel Minster. The ceremony is also an occasion to honour early-career researchers for their achievements through awards sponsored by companies, foundations or associations.

The University of Basel is the oldest university in Switzerland; its goal is to remain one of the best research universities worldwide and to make important contributions to research and social development through scientific knowledge and innovation.

Exceptional and inspiring

Chibale is a South African National Research Foundation A-rated scholar and holds the Neville Isdell Chair in African-centric Drug Discovery and Development at UCT. He isthe founder and director of H3D, UCTs drug discovery and development centre based in the Department of Chemistry and the Institute of Infectious Disease and Molecular Medicine (IDM).

The commendation for his honorary doctorate reads: At the Dies Academicus of the University of Basel, the faculties award honorary doctorates to outstanding personalities in science or society. I am delighted to inform you that the Faculty of Science has decided to award you with this years honorary doctorate.

It is to honour your exceptional and inspiring curriculum vitae, your outstanding academic achievements and last, but not least, your continuous and ongoing support of the Swiss Tropical and Public Health Institute, an associate Institute of the University of Basel.

It continues: Professor Kelly Chibale [is] one of the most influential scientists in the research and development of new drugs for malaria, tuberculosis and understudied tropical diseases. The researcher, who is currently working in South Africa, was part of the Next Generation Scientist program run by Novartis and the University of Basel for over a decade.

Speaking to UCT News after the event, Chibale said, The ceremony at a packed church was movingly symbolic as a church is a place of worship for me. I was there in the church worshiping, thanking, and giving glory to God for being the source of this award given to me.

The celebratory banquet that followed was out of this world and the largest I have ever attended.

After the event, Chibale presented a Novartis public lecture titled Fostering drug discovery in Africa at the breathtakingly impressive Novartis Pavillon.

It was a fantastic day of celebrations with my Swiss friends. In the process I boosted the economy of Switzerland with the many Swiss chocolate gifts I was presented with by my Swiss friends who in turn boosted the South African economy with the South African wine I took to Switzerland for them.

With the Royal Society Africa Prize and Schmidt Futures AI2050 Senior Fellowship, the two other individual awards already received this year, this honorary doctorate is like icing on the cake. An individual award like this is also an opportunity for me to thank my present and past team members (both in my academic group and H3D), as well as research and funding partners because as the saying goes, It takes a village to raise a child.

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Honorary doctorate for Kelly Chibale in Switzerland - University of Cape Town News