‘Game Changer’ also stars Kiara Advani, Anjali, Samuthirakani, SJ Suryah, Srikanth and Sunil

For our last full controller review on TouchArcade, I’ve been using the Victrix Pro BFG Tekken 8 Rage Art Edition …

Continue reading "Victrix Pro BFG Tekken 8 Rage Art Edition Controller Review – Customizable, Comfortable, but Lacking in Ways"

Replay our October 15 chat on, “Finding certainty in IT when the world is uncertain.”

Join Sean Gallagher, Dell's Ivan Nekrasov, and me today, January 21, at 3:15pm Eastern!

Apple has a history of eye-popping price tags, but the company is reaching new heights with a product that isn't even a gadget. After Apple Music unveiled a list of the 100 best albums of all time earlier this year, the streaming service is releasing a companion coffee table book. You can grab one of the 1,500 copies for a cool $450.

I find these endeavors to rank and quantify art hilarious, because music is subjective and personal by nature. But people do love to debate their own artistic opinions, so if that's your jam there's plenty to dig into with Apple Music's assessment. (And before you ask, the top spot was claimed by The Miseducation of Lauryn Hill.) This particular countdown was assembled by "Apple Music’s team of experts alongside an exclusive group of artists including Maren Morris, Pharrell Williams, J Balvin, Charli XCX, Mark Hoppus, Honey Dijon and Nia Archives, as well as songwriters, producers and industry professionals," according to the book listing.

I'm sure this limited-run hardcover will be very beautiful, and maybe the liner notes analyzing each entry are deeply insightful. But I also wonder who would bother to buy it. If you are one of those 1,500 people who wants one, the book is due to start shipping in January.

This article originally appeared on Engadget at https://www.engadget.com/entertainment/music/the-coffee-table-book-of-apple-musics-best-100-albums-will-set-you-back-450-193018825.html?src=rss

Un mois après la mystérieuse disparition d’un comptable sans histoire de Saint-Jean-sur-Richelieu, le corps de l’homme de 68 ans a été retrouvé.

Donald Trump va nommer la représentante Elise Stefanik, républicaine du nord de l’État de New York, ambassadrice des États-Unis à l’ONU.

The Department of Pharmaceuticals (DoP) has upheld the retail price fixation of National Pharmaceutical Pricing Authority (NPPA) for Mumbai─based Aristo Pharmaceuticals for its multivitamin tablets with

The Subject Expert Committee (SEC), which advises the national drug regulator on approval of new drugs and clinical trials, has recommended grant of market authorisation for Dr Reddy's Laboratories' Siponimod

The decade following passage of FDAAA has been one of easing standards for drug approvals in the US, most notably with the advent of “breakthrough” designation created by FDASIA in 2012 and the 21st Century Cures Act in 2016.

Although, as of this writing, there is no nominee for FDA Commissioner, it appears to be safe to say that the current administration intends to accelerate the pace of deregulation, mostly through further lowering of approval requirements. In fact, some of the leading contenders for the position are on record as supporting a return to pre-Kefauver-Harris days, when drug efficacy was not even considered for approval.

Build a better mouse model, and pharma will beat a path to your door - no laws needed.

In this context, it is at least refreshing to read a proposal to increase efficacy standards. This comes from two bioethicists at McGill University, who make the somewhat-startling case for a higher degree of efficacy evaluation before a drug begins any testing in humans.

We contend that a lack of emphasis on evidence for the efficacy of drug candidates is all too common in decisions about whether an experimental medicine can be tested in humans. We call for infrastructure, resources and better methods to rigorously evaluate the clinical promise of new interventions before testing them on humans for the first time.

The author propose some sort of centralized clearinghouse to evaluate efficacy more rigorously. It is unclear what they envision this new multispecialty review body’s standards for green-lighting a drug to enter human testing. Instead they propose three questions:

• What is the likelihood that the drug will prove clinically useful?
• Assume the drug works in humans. What is the likelihood of observing the preclinical results?
• Assume the drug does not work in humans. What is the likelihood of observing the preclinical results?

These seem like reasonable questions, I suppose – and are likely questions that are already being asked of preclinical data. They certainly do not rise to the level of providing a clear standard for regulatory approval, though perhaps it’s a reasonable place to start.

The most obvious counterargument here is one that the authors curiously don’t pick up on at all: if we had the ability to accurately (or even semiaccurately) predict efficacy preclinically, pharma sponsors would already be doing it. The comment notes: “More-thorough assessments of clinical potential before trials begin could lower failure rates and drug-development costs.” And it’s hard not to agree: every pharmaceutical company would love to have even an incrementally-better sense of whether their early pipeline drugs will be shown to work as hoped.

The authors note

Commercial interests cannot be trusted to ensure that human trials are launched only when the case for clinical potential is robust. We believe that many FIH studies are launched on the basis of flimsy, underscrutinized evidence.

However, they do not produce any evidence that industry is in any way deliberately underperforming their preclinical work, merely that preclinical efficacy is often difficult to reproduce and is poorly correlated with drug performance in humans.

Pharmaceutical companies have many times more candidate compounds than they can possibly afford to put into clinical trials. Figuring out how to lower failure rates – or at least the total cost of failure - is a prominent industry obsession, and efficacy remains the largest source of late-stage trial failure. This quest to “fail faster” has resulted in larger and more expensive phase 2 trials, and even to increased efficacy testing in some phase 1 trials. And we do this not because of regulatory pressure, but because of hopes that these efforts will save overall costs. So it seems beyond probable that companies would immediately invest more in preclinical efficacy testing, if such testing could be shown to have any real predictive power. But generally speaking, it does not.

As a general rule, we don’t need regulations that are firmly aligned with market incentives, we need regulations if and when we think those incentives might run counter to the general good. In this case, there are already incredibly strong market incentives to improve preclinical assessments. Where companies have attempted to do something with limited success, it would seem quixotic to think that regulatory fiat will accomplish more.

(One further point. The authors try to link the need for preclinical efficacy testing to the 2016 Bial tragedy. This seems incredibly tenuous: the authors speculate that perhaps trial participants would not have been harmed and killed if Bial had been required to produce more evidence of BIA102474’s clinical efficacy before embarking on their phase 1 trials. But that would have been entirely coincidental in this case: if the drug had in fact more evidence of therapeutic promise, the tragedy still would have happened, because it had nothing at all to do with the drug’s efficacy.

This is to some extent a minor nitpick, since the argument in favor of earlier efficacy testing does not depend on a link to Bial. However, I bring it up because a) the authors dedicate the first four paragraphs of their comment to the link, and b) there appears to be a minor trend of using the death and injuries of that trial to justify an array of otherwise-unrelated initiatives. This seems like a trend we should discourage.)

[Update 2/23: I posted this last night, not realizing that only a few hours earlier, John LaMattina had published on this same article. His take is similar to mine, in that he is suspicious of the idea that pharmaceutical companies would knowingly push ineffective drugs up their pipeline.]

Kimmelman, J., & Federico, C. (2017). Consider drug efficacy before first-in-human trials Nature, 542 (7639), 25-27 DOI: 10.1038/542025a

In the spirit of the Halloween season, IEEE Spectrum presents a pair of stories that—although grounded in scientific truth rather than the macabre—were no less harrowing for those who lived them. In today’s installment, Robert Langer had to push back against his field’s conventional wisdom to pioneer a drug-delivery mechanism vital to modern medicine.

Nicknamed the Edison of Medicine, Robert Langer is one of the world’s most-cited researchers, with over 1,600 published papers, 1,400 patents, and a top-dog role as one of MIT’s nine prestigious Institute Professors. Langer pioneered the now-ubiquitous drug delivery systems used in modern cancer treatments and vaccines, indirectly saving countless lives throughout his 50-year career.

But, much like Edison and other inventors, Langer’s big ideas were initially met with skepticism from the scientific establishment.

He came up in the 1970s as a chemical engineering postdoc working in the lab of Dr. Judah Folkman, a pediatric surgeon at the Boston Children’s Hospital. Langer was tasked with solving what many believed was an impossible problem—isolating angiogenesis inhibitors to halt cancer growth. Folkman’s vision of stopping tumors from forming their own self-sustaining blood vessels was compelling enough, but few believed it possible.

Langer encountered both practical and social challenges before his first breakthrough. One day, a lab technician accidentally spilled six months’ worth of samples onto the floor, forcing him to repeat the painstaking process of dialyzing extracts. Those months of additional work steered Langer’s development of novel microspheres that could deliver large molecules of medicine directly to tumors.

In the 1970s, Langer developed these tiny microspheres to release large molecules through solid materials, a groundbreaking proof-of-concept for drug delivery.Robert Langer

Langer then submitted the discovery to prestigious journals and was invited to speak at a conference in Michigan in 1976. He practiced the 20-minute presentation for weeks, hoping for positive feedback from respected materials scientists. But when he stepped off the podium, a group approached him and said bluntly, “We don’t believe anything you just said.” They insisted that macromolecules were simply too large to pass through solid materials, and his choice of organic solvents would destroy many inputs. Conventional wisdom said so.

Nature published Langer’s paper three months later, demonstrating for the first time that non-inflammatory polymers could enable the sustained release of proteins and other macromolecules. The same year, Science published his isolation mechanism to restrict tumor growth.

Langer and Folkman’s research paved the way for modern drug delivery.MIT and Boston Children’s Hospital

Even with impressive publications, Langer still struggled to secure funding for his work in controlling macromolecule delivery, isolating the first angiogenesis inhibitors, and testing their behavior. His first two grant proposals were rejected on the same day, a devastating blow for a young academic. The reviewers doubted his experience as “just an engineer” who knew nothing about cancer or biology. One colleague tried to cheer him up, saying, “It’s probably good those grants were rejected early in your career. Since you’re not supporting any graduate students, you don’t have to let anyone go.” Langer thought the colleague was probably right, but the rejections still stung.

His patent applications, filed alongside Folkman at the Boston Children’s Hospital, were rejected five years in a row. After all, it’s difficult to prove you’ve got something good if you’re the only one doing it. Langer remembers feeling disappointed but not crushed entirely. Eventually, other scientists cited his findings and expanded upon them, giving Langer and Folkman the validation needed for intellectual property development. As of this writing, the pair’s two studies from 1976 have been cited nearly 2,000 times.

As the head of MIT’s Langer Lab, he often shares these same stories of rejection with early-career students and researchers. He leads a team of over 100 undergrads, grad students, postdoctoral fellows, and visiting scientists, all finding new ways to deliver genetically engineered proteins, DNA, and RNA, among other research areas. Langer’s reputation is further bolstered by the many successful companies he co-founded or advised, like mRNA leader Moderna, which rose to prominence after developing its widely used COVID-19 vaccine.

Langer sometimes thinks back to those early days—the shattered samples, the cold rejections, and the criticism from senior scientists. He maintains that “Conventional wisdom isn’t always correct, and it’s important to never give up—(almost) regardless of what others say.”

Modern innovation typically occurs one step-improvement at a time. Some clients initially question whether their new application of an existing technology is patentable. Usually, the answer is ‘yes.’ Under U.S. law (and most other jurisdictions), an innovation to an existing technology is patentable so long as at least one claim limitation is novel and non-obvious....… Continue Reading

NEW YORK – Moves by major US fast-food chains to temporarily scrub fresh onions off their menus on Oct 24, after the vegetable was named as the likely source of an E. coli outbreak at McDonald’s, laid bare the recurring nightmare for restaurants: Produce is a bigger problem for restaurants to keep free of contamination than beef. Onions are likely the culprit in the McDonald’s E. coli outbreak across the Midwest and some Western states that has sickened 49 people and killed one, the US Department of Agriculture said late on Oct 23. The company pulled the Quarter Pounder off its menu at one-fifth of its 14,000 US restaurants. In past years, beef patties dominated the dockets of food-borne-illness lawyers, before US federal health regulators cracked down on beef contamination after an E. coli outbreak linked to Jack in the Box burgers hospitalised more than 170 people across states and killed four. As a result, beef-related outbreaks became much rarer, experts say.

As a group of friends circled a hearse, chants were heard. Then, they stopped and bowed to the portrait displayed at the front of the vehicle. This was not a typical Buddhist funeral, but rather the unconventional birthday celebration of a funeral director, reported Shin Min Daily News. According to the Chinese evening daily, a video circulating online showed the friends chanting a birthday song. The hearse's interior had been decorated with balloons and a birthday banner, with the man even laying inside for photos. The clip garnered criticism from netizens, with some deeming it overboard and disrespectful to the funeral industry. In an interview with Shin Min, director of Xin An Funeral Services Chen Weisong (transliteration) explained that he had celebrated his birthday at the company's premises with his friends and family last week. Halfway through the performances by singers, his employees and business partners had surprised him with the birthday-themed hearse bearing his portrait. Chen told 8world he was not angry and did not think it was taboo. "I was too embarrassed to turn down their gesture," he said. 

NOTA continues to be salient in Naxalite areas, but its share has fallen in recent elections

Nov 17, 2022

The speakers included Yale Law School professor Harold H. Koh ’75, and Patrick W. Pearsall, Director of the International Claims and Reparations Project at Columbia Law School. Koh and Pearsall discussed their experiences representing Ukraine in legal proceedings against Russia before the International Court of Justice.

Feb 2, 2024

Jacqueline L. Hazelton's Bullets not Ballots: Success in Counterinsurgency Warfare (Cornell University Press, 2021) is the subject of a Roundtable Review.

Jul 8, 2024

The July 2024 update to our database on the U.S. government investments in energy research, development, demonstration, and deployment (ERD3) through the U.S. Department of Energy.

Mar 18, 2024

Harvard Kennedy School hosted Jahi Wise, Senior Adviser to the Administrator of the U.S. Environmental Protection Agency, to discuss the design and implementation of the Greenhouse Gas Reduction Fund, a historic investment in American clean energy technology finance.

Algiz-RT7 rugged tablet product presentation

Every bottle of Bellucci starts in a family grove.

The McKnight Center for the Performing Arts at Oklahoma State University named in honor of visionary gift

Special guests helped celebrate the opening of Ondori Asian Kitchen, a distinctive new dining concept at The Orleans Hotel and Casino, on March 2, 2016.

Laura Dern, Kellie Pickler, Valerie Harper Among Notable Voices Kicking Off National Women�s Lung Health Week

Tailoring Anti-Aging Treatments To Patients' Needs

Safe Handling of Raw Produce and Fresh-Squeezed Fruit and Vegetable Juices

Gout as a Serious Health Issue

Help Kids Defeat the Mouth Monsters

Government of IndiaMinistry of FinanceDepartment of RevenueCentral Board of Indirect Taxes and CustomsNotification No. 73/2024-CUSTOMS (N.T.)New Delhi, 30th October, 202408 Kartika,1946 (SAKA)S.O. .

Our new online platform and summit will help students learn more about product inclusion and equity.

Amazon's Children's Day Store is now open, featuring an array of products specially discounted for the occasion, including top-selling Android tablets ideal for e-learning. With price reductions of up to 75% on select items such as headphones, tablets, and kids' smartwatches,

Over the next few weeks and months, you'll see social media posts discussing how companies cannot offer holiday bonuses or will have to cut employees due to Trump's tariffs (proposed or enacted).

 

Some of these stories may be fiction or cautionary tales that illustrate the price the average American pays for a politician's decision.

 

But I can 100% tell you this is a reality many business owners in the manufacturing sector now face.

 

If you aren't aware of how tariffs work, it's relatively simple. The company importing the goods from a foreign country pays the fee. If a company has to pay 20%, 60%, or 200% more to bring that item into the United States, who ultimately bears that cost? The American people.

 

Over the last few days, I have been talking at length with my factory representatives, figuring out how much of an item I need to order now to offset any expanded costs later. In addition, we are looking at where we can move manufacturing to outside of China (hard mode, not a lot of places outside of China or Europe produce boardgame components at the scale our industry uses).

 

I've been speaking with my shipping representatives about the increasing freight costs we expect to see with a rise in tariffs. We're already paying extreme freight prices, which will only go up as demand increases. The last time tariffs were levied on Chinese manufactured goods, freight costs went up.

 

Now I am in a position that forces me to examine how much we may need to raise prices if the most extreme of the proposed tariffs goes into effect.

 

I'm also trying to do right by my staff. But I can only do so much, you know? How long can business owners incur these costs, protect our staff, and not have consumers pay through the nose? Can I accept breaking even for the time being to keep my people employed and our games affordable? But what happens when the company starts losing money?

 

Many CEOs and business owners are staring down this reality right now. This isn't just a theoretical exercise. We have to plan for the worst.

 

So, what do I plan to do about this? I will be even more present in my local and state business associations that have direct links to policy makers in D.C. I will take every opportunity to speak directly to those who have a say in this new administration about why this isn't good for the economy. I'm just a tiny player in the world of manufacturing. But I do know the power of my voice. And more importantly, I know the power your voice holds as well.

 

You can start putting pressure on your elected (or newly elected) officials by writing, calling, or contacting them through their open channels (many of them love social media). Tell them you do not want these proposed tariffs, and let them know how these cost increases will impact you. Hold them to their promises. Make your voice heard. 

We are all in this together. 

– Meredith Placko

Warehouse 23 News: A Great Deal Of Adventure!

Excitement is in the cards with the Decks of Destiny for The Fantasy Trip. This collection of resources and reference material contains adversaries, rumors, combat options, and more to make your games of TFT fast and furious. Download this set today from Warehouse 23!

Google DeepMind has been using its AI watermarking method on Gemini chatbot responses for months – and now it’s making the tool available to any AI developer

Experiments where vampire bats were made to run on a treadmill have revealed how they extract energy from protein in their latest blood meal

Yay could have had the conversation entirely within their head, but they were trying to impress Roko

Politicians say we're living in dangerous times, and Trump is a lot less willing than Biden to pay for Europe's defence.

Hospitals in England will be ranked on care and finances, so patients can look for good service.

Britain's para-cyclists put in a strong performance at the World Championships in Los Angeles but the competition is improving.

Malta's Commissioner for Revenue has announced an extension to the deadline for applying for fiscal unity for the 2020 year of assessment.

Hong Kong tabled the Inland Revenue (Amendment) (Miscellaneous Provisions) Bill 2021 in parliament on March 24.

Highlights: TRIUMEQ is a fixed dose combination of Abacavir, Dolutegravir and Lamivudine for the treatment of ped

The Government of the Cayman Islands has published legislation in its Official Gazette to introduce a regulatory regime for virtual asset service providers (VASPs).

The European Commission has committed to tabling a proposal for a digital tax in October, whether or not an international agreement surfaces from OECD-led talks on new international tax rules for the world's largest firms.

Highlights: AWAK Technologies' wearable peritoneal dialysis (PD) device could allow kidney patients to perform

Highlights: Onions are packed with antioxidants and may lower blood sugar levels in diabetics Sweet potato

Hong Kong tabled the Inland Revenue (Amendment) (Miscellaneous Provisions) Bill 2021 in parliament on March 24.

Highlights: India introduces the Aarogya Maitri Aid Cube, a portable hospital designed for swift deployment in

Actionable information from earth observation data will enable better water management for African governments, communities and companies.

The post IWMI project enables fast access to petabytes of analysis-ready water data in Africa first appeared on International Water Management Institute (IWMI).

As climate change continues to drive up summer temperatures, a decade-long study from Spain has uncovered a startling revelation: on the hottest days,