A teenager who tested positive for avian flu is in critical condition with acute respiratory distress according to Provincial Health Officer Dr. Bonnie Henry.

1. Magnus Carlsen returns to Kolkata after almost five years at Tata Steel India Rapid and Blitz 2024  ChessBase India
2. "It's Chaotic": Chess World No. 1 Magnus Carlsen Reveals Why He Does Not Play In India  NDTV Sports
3. King Carlsen hails growth of Indian chess, praises Praggnanandhaa's fighting spirit  Telegraph India
4. Tata Steel Chess set for a Carlsen-Pragg opening  Hindustan Times
5. Tata Steel Chess India Rapid & Blitz 2024: Schedule, Venue, Players, Tickets, Prize Money  Firstpost

1. Netflix's The Great Indian Kapil Show: Navjot Singh Sidhu is back after 5 years of exit, Archana Puran Singh says, 'He’s taken over my...'  Firstpost
2. Did you know! Navjot Singh Sidhu was ousted from The Kapil Sharma Show for this reason  The Times of India
3. Navjot Singh Sidhu makes a roaring comeback; Archana Puran Singh worried about her The Great Indian Kapil Show throne  Hindustan Times
4. The Great Kapil Sharma Show: Navjot Sidhu shares his fast-track fatherhood plan. Kapil’s response is too f  The Economic Times
5. Navjot Singh Sidhu shares BTS pics from The Great Indian Kapil's show set with Archana Puran Singh and...  Moneycontrol

1. Security beefed up at Ram temple in Ayodhya after Pannun's threat message  The Times of India
2. Security beefed up around Ram Mandir in Ayodhya after Gurpatwant Pannun’s ‘threat’  Hindustan Times
3. Pannun Announces New Dates Of Temple Attacks In Canada, India Terms Threats ‘Terror Acts’: Intel Sources  News18
4. Khalistani terrorist Pannun warns of ‘shaking Ayodhya's foundations’  The Economic Times
5. Security beefed up in Ayodhya after Khalistan`s threat  Zee News

1. Bulldozer justice: SC lays down pan-India guidelines for demolition of properties, says Executive can’t become judge and accused, convicts have certain rights  The Hindu
2. "House Embodies Hope": Supreme Court Demolishes 'Bulldozer Justice' Idea  NDTV
3. Unconstitutional to demolish house without following due process merely because they are involved in a crime: SC  The Indian Express
4. Supreme Court on bulldozer action: ‘No demolition without following guidelines, 15-day notice’  Hindustan Times
5. Bulldozer justice: Executive can't become judge, demolish house of accused, SC says  The Times of India

Tickets for the event will go on sale on November 10, 2024, via BookMyShow

Music director and singer Adnan Sami said he was saddened by the demise of “one of the greatest Sarangi Maestros that the entire Indian subcontinent has ever witnessed”.

The launch event will see the YouTubers partnering with Ajey Nagar, known as CarryMinati, for a special fan interaction in Mumbai

The actor, who stars in the upcoming film ‘The Sabarmati Report’, based on the 2002 Godhra train burning incident, emphasised his secular credentials while saying that his perspective on the state of the nation has shifted in the last ten years

Calgary Flames right-winger Anthony Mantha will miss the rest of the NHL season with a knee injury, the team announced Monday.

AthletesCAN in partnership with CBC Sports presents the Most Trending Moment Award as part of the 47th Canadian Sport Awards.

15 years on, Winamp "still lives"—but mismanagement blunted its llama-whipping.

The addition of Discover to LabX’s portfolio strengthens its position as a leading voice in science and research media, bringing one of the most recognized science publications into its family.

QUEENSLAND’S water contamination crisis has deepended, following alarming test results which show chemical levels up 425 times the accepted maximum exposure limits.

Mumbai (AFP) Nov 2, 2024
Indian security forces killed three suspected militants in two separate firefights in disputed Kashmir, the army and a senior police official said Saturday. Muslim-majority Kashmir has been divided between rivals India and Pakistan since their independence from British rule in 1947 and is home to a long-running insurgency. The first firefight broke out after Indian troops moved to check

New Delhi (AFP) Nov 5, 2024
The toxic smog season in India's capital has just begun, but those unable to escape cancer-causing poisonous fumes say the hazardous impact on health is already taking its toll. New Delhi regularly ranks among the world's most polluted capitals, with a melange of factory and vehicle emissions exacerbated by agricultural fires blanketing the city each winter, stretching from mid-October until

New Delhi (AFP) Nov 7, 2024
Sweeping aside thick toxic scum, thousands of Hindu devotees ignored court warnings Thursday against bathing in the sacred but sewage-filled Yamuna river, a grim display of environmental degradation in India's capital. Thousands celebrated the festival of Chhath Puja for the Hindu sun god Surya, entering the stinking waters to pray as the evening rays set in the sky. A parliamentary repo

Barsana, India (AFP) Nov 8, 2024
Venerated as incarnations of Hindu deities, India's sacred cows are also being touted as agents of energy transition by a government determined to promote biogas production to cut its dependence on coal. It is an understatement to say that Nakul Kumar Sardana is proud of his new plant at Barsana, in India's northern Uttar Pradesh state. Firstly, says the vice-president of a biomass joint

New Delhi (AFP) Nov 8, 2024
India's capital unveiled plans Friday to fly special drones to clear pollution from its smog-choked skies - a plan derided by experts as another "band-aid" solution to a public health crisis. New Delhi and the surrounding metropolitan area, home to more than 30 million people, consistently tops world rankings for air pollution in winter. The smog is blamed for thousands of premature de

Paris, France (SPX) Nov 03, 2024
ESA's Proba-3 mission, designed to create a solar eclipse in space, is leaving Europe to head to its Indian launch site. The mission's two spacecraft, designed to align precisely in orbit so one will block the Sun for the other, have departed from Redwire Space's facilities in Kruibeke, Belgium. The pair will be transported to the Satish Dhawan Space Centre near Chennai, India, to prepare for th

Le Parti Québécois misera sur sa présidente, Catherine Gentilcore, pour tenter de ravir la circonscription de Terrebonne à la CAQ.

Labour Minister Steven MacKinnon has sent labour disputes at ports in Quebec and British Columbia to binding arbitration and has ordered people back to work after the disputes reached what he called a "total impasse."

A Canada Border Services Agency superintendent is speaking out after being targeted by the Indian government with allegations of murder and terrorism — allegations Canadian authorities say are not backed by any evidence.

SYDNEY FC headed to Barker College last week to promote their upcoming school holiday bootcamps which they hope will uncover the next Ronaldo.

Les fromages vendus en portions individuelles sont des plus pratiques pour l’école et le bureau.

The office of the Additional Director General of Foreign Trade (CLA DGFT) has announced an Export Obligation Discharge Certificate (EODC) Camp scheduled from November 11 to 22, 2024. The camp is

Public Sector Enterprises Selection Board (PSEB) is seeking qualified candidates for the post of managing director at the Karnataka Antibiotics & Pharmaceuticals Limited (KAPL) in Bengaluru. The candidate will be

The Federation of Pharmaceutical Entrepreneurs (FOPE) has identified potential opportunities for Indian pharmaceutical companies to expand in Australia. Further, the India─Australia Economic Cooperation and Trade

The Embassy of India in Iraq has extended an invitation to Indian businesses to participate in the "Medico Expo," officially known as the Erbil International Health Exhibition. This prestigious event, set to be the

Indian pharma and biotech companies are confident that under the new US President Donald Trump, its strengths in high quality generics manufacture and export will continue to command respect. This view is

Whilst the timeline set for adhering to the revised Schedule M of the Drugs and Cosmetics Act ends on December 31 for pharmaceutical companies with a turnover of less than Rs. 250 crore, the union ministry's

The Indian healthcare industry is looking to invest further in computational infrastructure as data integration frameworks and regulatory compliance are pivotal to ensure intelligent clinical support

The Indian pharmaceutical industry is advocating for enhanced fire safety measures and improved insurance coverage for employees working in pharmaceutical facilities.

FDA’s mission is “at risk” because of inadequate funding. So says Alliance for a Stronger FDA President Diane Dorman, testifying before the FDA Science Board. Her remarks come 5 years after the Science Board made a similar declaration, concluding that decades of underfunding had left FDA without the resources to fulfill its mandate and make science-based decisions. Congress responded with more monies for the agency, but since then the FDA’s workload has increased even faster. The current threat to FDA comes from two sources: four major new laws to implement since 2009; and changes in the environment in which FDA operates, notably acceleration of globalization and increasing scientific complexity. Ms. Dorman’s remarks are reprinted below. If you care about FDA, FDA Matters urges you to read her testimony, go to the Alliance’s site (www.StrengthenFDA.org) and join.

At a time when FDA’s responsibilities continue to grow rapidly, the agency has been caught in an across-the-board reduction (sequester) in federal discretionary spending, effective March 2, 2013. Although Congress may yet reverse course and restore money to affected federal agencies, this is not considered a high probability. Altogether, FDA will lose about $209 million between now and September 30, 2013. This will reduce inspections, slow drug and device approvals, and restrict implementation of the Food Safety Modernization Act and other recent legislation. Because of the many questions about the process and outcome, this is FDA Matters’ primer on the sequester of FDA funds.

The FDA doesn’t care about the First Amendment rights of the companies it regulates. It cares even less about the “free speech” rights of those companies’ sales and marketing representatives. And why should the agency care? One of FDA’s primary missions is to protect the public health and safety of the American people from illegal, adulterated and misbranded products. Doing so involves restraining food, drug, device and cosmetics companies from committing fraudulent and deceptive acts that are not protected by companies’ commercial free speech rights. Nonetheless, FDA Matters envisions opportunities for FDA and industry to broaden permissible product communications. The key is understanding history, not constitutional law.

The General Pharmaceutical Council has said it is “double, treble, quadruple-checking” for any “flexibility” that would allow all overseas candidates to sit the March 2021 registration assessment exam in their countries of residence.

The General Pharmaceutical Council has said most candidates living in countries with a two-hour or more time difference from the UK will be able to apply to sit the registration assessment at home.

By Mike Cloonan, CEO of Sionna Therapeutics, as part of the From The Trenches feature of LifeSciVC An insightful piece on this blog following the JPM healthcare conference noted the “refreshing burst of enthusiasm” in the biotech sector. It’s true

The post Lessons From A Private Funding Round: Science, Relationships, And Experience appeared first on LifeSciVC.

PDUFA V commitments signal a strong commitment to tolerance of open debate in the face of uncertainty.

I can admit to a rather powerful lack of enthusiasm when reading about interpersonal squabbles. It’s even worse in the scientific world: when I read about debates getting mired in personal attacks I tend to simply stop reading and move on to something else.

However, the really interesting part of this week’s meeting of an FDA joint Advisory Committee to discuss the controversial diabetes drug Avandia – at least in the sense of likely long-term impact – is not the scientific question under discussion, but the surfacing and handling of the raging interpersonal battle going on right now inside the Division of Cardiovascular and Renal Products. So I'll have to swallow my distaste and follow along with the drama.

Two words that make us mistrust Duke:  Anil Potti Christian Laettner

Not that the scientific question at hand – does Avandia pose significant heart risks? – isn't interesting. It is. But if there’s one thing that everyone seems to agree on, it’s that we don’t have good data on the topic. Despite the re-adjudication of RECORD, no one trusts its design (and, ironically, the one trial with a design to rigorously answer the question was halted after intense pressure, despite an AdComm recommendation that it continue).  And no one seems particularly enthused about changing the current status of Avandia: in all likelihood it will continue to be permitted to be marketed under heavy restrictions. Rather than changing the future of diabetes, I suspect the committee will be content to let us slog along the same mucky trail.

The really interesting question, that will potentially impact CDER for years to come, is how it can function with frothing, open dissent among its staffers. As has been widely reported, FDA reviewer Tom Marciniak has written a rather wild and vitriolic assessment of the RECORD trial, excoriating most everyone involved. In a particularly stunning passage, Marciniak appears to claim that the entire output of anyone working at Duke University cannot be trusted because of the fraud committed by Duke cancer researcher Anil Potti:

I would have thought that the two words “Anil Potti” are sufficient for convincing anyone that Duke University is a poor choice for a contractor whose task it is to confirm the integrity of scientific research. 

(One wonders how far Marciniak is willing to take his guilt-by-association theme. Are the words “Cheng Yi Liang” sufficient to convince us that all FDA employees, including Marciniak, are poor choices for deciding matter relating to publicly-traded companies? Should I not comment on government activities because I’m a resident of Illinois (my two words: “Rod Blagojevich”)?)

Rather than censoring or reprimanding Marciniak, his supervisors have taken the extraordinary step of letting him publicly air his criticisms, and then they have in turn publicly criticized his methods and approach.

I have been unable to think of a similar situation at any regulatory agency. The tolerance for dissent being displayed by FDA is, I believe, completely unprecedented.

And that’s the cliffhanger for me: can the FDA’s commitment to transparency extend so far as to accommodate public disagreements about its own approval decisions? Can it do so even when the disagreements take an extremely nasty and inappropriate tone?

• Rather than considering that open debate is a good thing, will journalists jump on the drama and portray agency leadership as weak and indecisive?
• Will the usual suspects in Congress be able to exploit this disagreement for their own political gain? How many House subcommittees will be summoning Janet Woodcock in the coming weeks?

I think what Bob Temple and Norman Stockbridge are doing is a tremendous experiment in open government. If they can pull it off, it could force other agencies to radically rethink how they go about crafting and implementing regulations. However, I also worry that it is politically simply not a viable approach, and that the agency will ultimately be seriously hurt by attacks from the media and legislators.

Where is this coming from?

As part of its recent PDUFA V commitment, the FDA put out a fascinating draft document, Structured Approach to Benefit-Risk Assessment in Drug Regulatory Decision-Making. It didn't get a lot of attention when first published back in February (few FDA documents do). However, it lays out a rather bold vision for how the FDA can acknowledge the existence of uncertainty in its evaluation of new drugs. Its proposed structure even envisions an open and honest accounting of divergent interpretations of data:

When they're frothing at the mouth, even Atticus doesn't let them publish a review

A framework for benefit-risk decision-making that summarizes the relevant facts, uncertainties, and key areas of judgment, and clearly explains how these factors influence a regulatory decision, can greatly inform and clarify the regulatory discussion. Such a framework can provide transparency regarding the basis of conflicting recommendations made by different parties using the same information.

(Emphasis mine.)

Of course, the structured framework here is designed to reflect rational disagreement. Marciniak’s scattershot insults are in many ways a terrible first case for trying out a new level of transparency.

The draft framework notes that safety issues, like Avandia, are some of the major areas of uncertainty in the regulatory process. Contrast this vision of coolly and systematically addressing uncertainties with the sad reality of Marciniak’s attack:

In contrast to the prospective and highly planned studies of effectiveness, safety findings emerge from a wide range of sources, including spontaneous adverse event reports, epidemiology studies, meta-analyses of controlled trials, or in some cases from randomized, controlled trials. However, even controlled trials, where the evidence of an effect is generally most persuasive, can sometimes provide contradictory and inconsistent findings on safety as the analyses are in many cases not planned and often reflect multiple testing. A systematic approach that specifies the sources of evidence, the strength of each piece of evidence, and draws conclusions that explain how the uncertainty weighed on the decision, can lead to more explicit communication of regulatory decisions. We anticipate that this work will continue beyond FY 2013.

I hope that work will continue beyond 2013. Thoughtful, open discussions of real uncertainties are one of the most worthwhile goals FDA can aspire to, even if it means having to learn how to do so without letting the Marciniaks of the world scuttle the whole endeavor.

This new 10-minute TEDMED talk is getting quite a bit of attention:


 (if embedded video does not work, try the TED site itself.)

In it, Roger Stein claims to have created an approach to advancing drugs through clinical trials that will "fundamentally change the way research for cancer and lots of other things gets done".

Because the costs of bringing a drug to market are so high, time from discovery to marketing is so long, and the chances of success of any individual drug are so grim, betting on any individual drug is foolish, according to Stein. Instead, risks for a large number of potential assets should be pooled, with the eventual winners paying for the losers.

To do this, Stein proposes what he calls a "megafund" - a large collection of assets (candidate therapies). Through some modeling and simulations, Stein suggests some of the qualities of an ideal megafund: it would need in the neighborhood of $3-15 billion to acquire and manage 80-150 drugs. A fund of this size and with these assets would be able to provide an equity yield of about 12%, which would be "right in the investment sweet spot of pension funds and 401(k) plans".

Here's what I find striking about those numbers: let's compare Stein's Megafund to everyone's favorite Megalosaurus, the old-fashioned Big Pharma dinosaur sometimes known as Pfizer:

	Megafund (Stein)	Megalosaurus (Pfizer)
Funding	$3-15 billion	$9 billion estimated 2013 R&D spend
Assets	80-150	81 (in pipeline, plus many more in preclinical)
Return on Equity	12% (estimated)	9.2% (last 10 years) to 13.2% (last 5)

Since Pfizer's a dinosaur, it can't possibly compete with the sleek, modern Megafund, right? Right?

These numbers look remarkably similar. Pfizer - and a number of its peers - are spending Megafund-sized budget each year to shepherd through a Megafund-sized number of compounds. (Note many of Pfizer's peers have substantially fewer drugs in their published pipelines, but they own many times more compounds - the pipeline is just the drugs what they've elected to file an IND on.)

What am I missing here? I understand that a fund is not a company, and there may be some benefits to decoupling asset management decisions from actual operations, but this won't be a tremendous gain, and would presumably be at least partially offset by increased transaction costs (Megafund has to source, contract, manage, and audit vendors to design and run all its trials, after all, and I don't know why I'd think it could do that any more cheaply than Big Pharma can). And having a giant drug pipeline's go/no go decisions made by "financial engineers" rather than pharma industry folks would seem like a scenario that's only really seen as an upgrade by the financial engineers themselves.
A tweet from V.S. Schulz pointed me to a post on Derek Lowe's In the Pipeline blog. which lead to a link to this paper by Stein and 2 others in Nature Biotechnology from a year and a half ago. The authors spend most of their time differentiating themselves from other structures in the technical, financial details rather than explaining why megafund would work better at finding new drugs. However, they definitely think this is qualitatively different from existing pharma companies, and offer a couple reasons. First,

[D]ebt financing can be structured to be more “patient” than private or public equity by specifying longer maturities; 10- to 20-year maturities are not atypical for corporate bonds. ... Such long horizons contrast sharply with the considerably shorter horizons of venture capitalists, and the even shorter quarterly earnings cycle and intra-daily price fluctuations faced by public companies.

I'm not sure where this line of though is coming from. Certainly all big pharma companies' plans extend decades into the future - there may be quarterly earnings reports to file, but that's a force exerted far more on sales and marketing teams than on drug development. The financing of pharmaceutical development is already extremely long term.

Even in the venture-backed world, Stein and team are wrong if they believe there is pervasive pressure to magically deliver drugs in record time. Investors and biotech management are both keenly aware of the tradeoffs between speed and regulatory success. Even this week's came-from-nowhere Cinderella story, Intercept Pharmaceuticals, was founded with venture money over a decade ago - these "longer maturities" are standard issue in biotech. We aren't making iPhone apps here, guys.

Second,

Although big pharma companies are central to the later stages of drug development and the marketing and distributing of approved drugs, they do not currently play as active a role at the riskier preclinical and early stages of development

Again, I'm unsure why this is supposed to be so. Of Pfizer's 81 pipeline compounds, 55 are in Phase 1 or 2 - a ratio that's pretty heavy on early, risky project, and that's not too different from industry as a whole. Pfizer does not publish data on the number of compounds it currently has undergoing preclinical testing, but there's no clear reason I can think of to assume it's a small number.

So, is Megafund truly a revolutionary idea, or is it basically a mathematical deck-chair-rearrangement for the "efficiencies of scale" behemoths we've already got?

[Image: the world's first known dino, Megalosaurus, via Wikipedia.]

As the coronavirus pandemic grips the world, the opioid epidemic continues to affect millions of Americans. Several states are developing innovative ways to tackle this public health issue. In this episode, we speak with Beth Connolly, who leads Pew’s research on substance use disorders, and Louisiana Representative Paula Davis, who helped ensure effective treatment in her state.

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

This SAS Usage Note illustrates fitting a model containing a spline effect in PROC GLIMMIX. It discusses the spline basis output, the interpretation of the output, how to use the spline model to make predictions, and how to use the LSMEANS and ESTIMATE statements to compute quantities of interest.

TORONTO — A teenager is in critical condition in a British Columbia children's hospital, sick with Canada's first presumptive human case of avian influenza. "This was a healthy teenager prior to this, so no underlying conditions," said provincial health officer Bonnie Henry in a news conference on Tuesday (Nov 12). "It just reminds us that in young people this is a virus that can progress and cause quite severe illness and the deterioration that I mentioned was quite rapid." British Columbia health officials said on Saturday the province had detected Canada's first human case of H5 bird flu in a teenager.

KOLKATA — A court in the eastern state of West Bengal began the trial on Monday (Nov 11) of a police volunteer accused of raping and murdering a doctor at a government hospital in August, a case that sparked outrage over the lack of safety for women in India. The woman's body was found in a classroom at the R.G. Kar Medical College and Hospital in the state capital Kolkata on Aug 9, the federal police said. They also said they had arrested a police volunteer, Sanjay Roy, for the crime.

My first editor, Rukun Advani, once described himself as ‘a composite hybrid of the Indian and the Anglo-European’, who sought to reconcile ‘within himself those varying cultural influences which chauvinistic nationalists could only see as contradictions.’ This self-characterization I might avow as my own. One mark of the Anglo-European in me is that, unlike members [...]

‘If Mumbai attack suspects arrested in Pakistan are freed, India is at fault'

U.S. feared another LeT attack in India in mid-2009, and sought Pakistan's help to ‘disrupt and prevent' it