The phase 3 VISION trial demonstrated that [¹⁷⁷Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]–positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor–signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [¹⁷⁷Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [¹⁷⁷Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using t testing of proportions and survival analyses. Results: In total, 117 patients with mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA RRs (42% vs. 46%; P = 0.50) and OS (median: 15.1 vs. 15.3 mo; P > 0.05). Conclusion: Patients with PSMA-positive mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.

[¹⁷⁷Lu]Lu-PSMA-617 was approved by the U.S. Food and Drug Administration for patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC). Since the time of regulatory approval, however, real-world data have been lacking. This study investigated the efficacy, safety, and outcome predictors of [¹⁷⁷Lu]Lu-PSMA-617 at a major U.S. academic center. Methods: Patients with mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 at the Johns Hopkins Hospital outside clinical trials were screened for inclusion. Patients who underwent [¹⁷⁷Lu]Lu-PSMA-617 and had available outcome data were included in this study. Outcome data included prostate-specific antigen (PSA) response (≥50% decline), PSA progression-free survival (PFS), and overall survival (OS). Toxicity data were evaluated according to the Common Terminology Criteria for Adverse Events version 5.03. The study tested the association of baseline circulating tumor DNA mutational status in homologous recombination repair, PI3K alteration pathway, and aggressive-variant prostate cancer–associated genes with treatment outcome. Baseline PSMA PET/CT images were analyzed using SelectPSMA, an artificial intelligence algorithm, to predict treatment outcome. Associations with the observed treatment outcome were evaluated. Results: All 76 patients with PSMA-positive mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 met the inclusion criteria. A PSA response was achieved in 30 of 74 (41%) patients. The median PSA PFS was 4.1 mo (95% CI, 2.0–6.2 mo), and the median OS was 13.7 mo (95% CI, 11.3–16.1 mo). Anemia of grade 3 or greater, thrombocytopenia, and neutropenia were observed in 9 (12%), 3 (4%), and 1 (1%), respectively, of 76 patients. Transient xerostomia was observed in 23 (28%) patients. The presence of aggressive-variant prostate cancer–associated genes was associated with a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P = 0.040). No other associations were observed between circulating tumor DNA mutational status and treatment outcomes. Eighteen of 71 (25%) patients classified by SelectPSMA as nonresponders had significantly lower rates of PSA response than patients classified as likely responders (6% vs. 51%; P < 0.001), a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P < 0.001), and a shorter OS (median, 6.3 vs. 14.5 mo; P = 0.046). Conclusion: [¹⁷⁷Lu]Lu-PSMA-617 offered in a real-world setting after regulatory approval in the United States demonstrated antitumor activity and a favorable toxicity profile. Artificial-intelligence–based analysis of baseline PSMA PET/CT images may improve patient selection. Validation of these findings on larger cohorts is warranted.

BACKGROUND AND PURPOSE:

Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees.

MATERIALS AND METHODS:

This prospective study was conducted between March 2023 and October 2023. Medical students and resident trainees were asked to identify intracranial hemorrhage and large-vessel occlusion in 100 noncontrast head CTs and 100 head CTAs, respectively. One group received diagnostic aid simulating artificial intelligence for intracranial hemorrhage only (n = 26); the other, for large-vessel occlusion only (n = 28). Primary outcomes included accuracy, sensitivity, and specificity for intracranial hemorrhage/large-vessel occlusion detection without and with aid. Study interpretation time was a secondary outcome. Individual responses were pooled and analyzed with the t test; differences in continuous variables were assessed with ANOVA.

RESULTS:

Forty-eight participants completed the study, generating 10,779 intracranial hemorrhage or large-vessel occlusion interpretations. With diagnostic aid, medical student accuracy improved 11.0 points (P < .001) and resident trainee accuracy showed no significant change. Intracranial hemorrhage interpretation time increased with diagnostic aid for both groups (P < .001), while large-vessel occlusion interpretation time decreased for medical students (P < .001). Despite worse performance in the detection of the smallest-versus-largest hemorrhages at baseline, medical students were not more likely to accept a true-positive artificial intelligence result for these more difficult tasks. Both groups were considerably less accurate when disagreeing with the artificial intelligence or when supplied with an incorrect artificial intelligence result.

CONCLUSIONS:

This study demonstrated greater improvement in diagnostic accuracy with artificial intelligence for medical students compared with resident trainees. However, medical students were less likely than resident trainees to overrule incorrect artificial intelligence interpretations and were less accurate, even with diagnostic aid, than the artificial intelligence was by itself.

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library, which can then be used for biopanning using multiple display methods. This protocol describes selection from affibody libraries using display on Staphylococcus carnosus. Display of affibodies on staphylococci is very efficient and straightforward because of the single cell membrane and the use of a construct with a constitutive promoter. The workflow involves display of affibody libraries on the surface of S. carnosus cells, followed by screening and selection of binders using fluorescence-activated cell sorting (FACS). The transformation of DNA libraries into S. carnosus is less efficient and more complicated than for Escherichia coli. Because of this, staphylococcal display is suitable for affinity maturation or other protein-engineering efforts that are not dependent on very high diversity, and thus magnetic-activated cell sorting (MACS) is often not required before FACS. However, MACS is an option, and MACS procedures used for E. coli can easily be adapted for use in S. carnosus if needed.

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library, which can then be used for selection via multiple display methods. This protocol describes selection from affibody libraries by Escherichia coli cell surface display. With this method, high-diversity libraries of 10¹¹ can be displayed on the cell surface. The method involves two steps for selection of binders from high-diversity libraries: magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS). MACS is used first to enrich the library in target-binding clones and to decrease diversity to a size that can be effectively screened and sorted in the flow cytometer in a reasonable time (typically <10⁷ cells). The protocol is based on methodology using an AIDA-I autotransporter for display on the outer membrane, but the general procedures can also be adjusted and used for other types of autotransporters or alternative E. coli display methods.

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library. This is then followed by amplification of the library, which can then be used for biopanning using multiple methods. This protocol describes amplification of affibody libraries, followed by biopanning using phage display and analysis of the selection output. The general procedure is mainly for selection of first-generation affibody molecules from large naive (unbiased) libraries, typically yielding affibody hits with affinities in the low nanomolar range. For selection from affinity maturation libraries with the aim of isolating variants of even higher affinities, the procedure is similar, but parameters such as target concentration and washing are adjusted to achieve the proper stringency.

Affibody molecules are small (6-kDa) affinity proteins folded in a three-helical bundle and generated by directed evolution for specific binding to various target molecules. The most advanced affibody molecules are currently tested in the clinic, and data from more than 300 subjects show excellent activity and safety profiles. The generation of affibody molecules against a particular target starts with the generation of an affibody library, which can then be used for panning using multiple methods and selection systems. This protocol describes the molecular cloning of DNA-encoded affibody libraries to a display vector of choice, for either phage, Escherichia coli, or Staphylococcus carnosus display. The DNA library can come from different sources, such as error-prone polymerase chain reaction (PCR), molecular shuffling of mutations from previous selections, or, more commonly, from DNA synthesis using various methods. Restriction enzyme-based subcloning is the most common strategy for affibody libraries of higher diversity (e.g., >10⁷ variants) and is described here.

Affibody molecules are small, robust, and versatile affinity proteins currently being explored for therapeutic, diagnostic, and biotechnological applications. Surface-exposed residues on the affibody scaffold are randomized to create large affibody libraries from which novel binding specificities to virtually any protein target can be generated using combinatorial protein engineering. Affibody molecules have the potential to complement—or even surpass—current antibody-based technologies, exhibiting multiple desirable properties, such as high stability, affinity, and specificity, efficient tissue penetration, and straightforward modular extension of functional domains. It has been shown in both preclinical and clinical studies that affibody molecules are safe, efficacious, and valuable alternatives to antibodies for specific targeting in the context of in vivo diagnostics and therapy. Here, we provide a general background of affibody molecules, give examples of reported applications, and briefly summarize the methodology for affibody generation.

HBO's Casey Bloys was asked about the Game of Thrones author's spicy take on House of the Dragon season two.

In August, fellow reporter Jason Patinkin and I crossed on foot from northern Uganda into rebel-held South Sudan. Over the course of four days, we walked more than 40 miles through the bush, escorted by rebel soldiers, to shed light on one of the world’s most underreported conflicts.

Reporting on South Sudan’s war, which began in 2013, has always been a challenge due to the risk and logistical hurdles associated with accessing remote areas where fighting takes place. But over the past year, covering the war and its humanitarian fallout has become particularly difficult. Since the beginning of this year, South Sudan’s government has banned at least 20 foreign journalists in an apparent effort to silence reporters who had a track record of critically reporting on the government.

This systematic crackdown on the foreign press (South Sudanese journalists have long risked imprisonment and death for doing their work) coincided with two important developments. In November 2016, the United Nations warned that the violence being committed against civilians in the southern region of Equatoria risked spiraling into genocide. Then, in February, the UN declared a man-made famine, warning that 100,000 people were at risk of starving to death as a result of civil war.

Journalists seeking to cover these events were left with two equally unsavory options: self-censorship or a risky trip to rebel-held parts of the country. Only a handful of journalists have attempted the latter since fighting escalated in July last year. For us, this was our second embed with the rebels this year.

We set off from a town in northern Uganda at five in the morning, bouncing along a bumpy dirt track towards the South Sudan border. Crammed into our four-wheel drive were rebel commander Martin Abucha, a dual American and South Sudanese citizen who we planned to profile for our PBS NewsHour Weekend segment, a couple of guides, and several duffle bags stuffed with our tents, sleeping bags, emergency medical kits and provisions to last us four days.

Just as the sun began to rise above a distant range of hills that we aimed to cross later that day, our car came to a halt in front of a stream. Because of the rainy reason, it carried more water than usual. It was time to disembark and start walking, or “footing,” as South Sudanese tend to call it.

We took off our shoes and waded through the stream’s chilly waters. This was the first of a many rivers we’d have to cross along the way, either on foot or in small flimsy canoes dug out from tree trunks. Each time, we dreaded the idea of falling in with our camera gear.

The first part of our journey in northern Uganda felt very much like a hike through a national park. Passing beautiful landscapes and idyllic farming villages, one could almost forget we were headed into a war zone — but we were about to get a reality check.

We had just crossed into South Sudan when out of nowhere, two dozen armed men popped out of the tall grass and surrounded us at gunpoint.

“Stop! Who are you and where are you going?” a soldier called out in Juba Arabic from his hideout no more than 20 yards away, pointing his AK47 at us. Another one next to him had a rocket-propelled grenade propped on his shoulder, also unequivocally aiming it in our direction.

Instinctively, we threw our hands in the air and exchanged a baffled glance. Had we accidentally bumped into government soldiers? Or perhaps we had come onto the “wrong” rebels? Abucha’s group, called the Sudan People’s Liberation Army In Opposition, is the biggest but not the only armed group in Equatoria, an area rife with rival militia and bandits who exploit the security vacuum left by war.

To our relief, and only after Abucha answered a series of questions, this routine security check quickly gave way to a warm welcome. The platoon would be our escort for the next four days as we trekked to their base and to Loa, Abucha’s hometown.

Keeping up with the rebels was no easy task. Given the country’s pervasive lack of basic infrastructure, South Sudanese grow up walking for dozens of miles just to go about their daily lives. For sedentary Westerners, keeping the target pace of “two meters per second” (around five miles an hour) proved challenging amid 90-degree temperatures, all while filming and plowing our way through dense, itchy elephant grass.

The upside of the cumbersome terrain was that it kept us safe. During our four-day trip, we didn’t cross a single road, instead walking along a dizzying network of narrow bush paths the rebels seemed to know like the backs of their hands. An unwanted encounter with government troops, who tended to stick to roads and move around in vehicles as opposed to on foot, was highly unlikely.

The closest we got to government-controlled area was a visit to Loa, located just two kilometers away from a main road frequently patrolled by government soldiers. We couldn’t stay long, but the hour we spent on the ground offered us a glimpse into what villages must look like in many parts of Equatoria: burned mud huts, looted schools and clinics, fallow fields and – most strikingly – no civilians.

The war has had a devastating impact on South Sudanese communities like the one in Loa, but much of it has remained out of the limelight of international media. Our four-day venture into rebel-held South Sudan offered us a rare opportunity to report ground truths, and we are thankful for that.

The post Column: Why reporting from South Sudan is so difficult — and critically needed appeared first on PBS NewsHour.

The accountancy firm has opened a new office in the Scottish town

Inflexion Games are closing their UK office, laying off staff and restructuring their main Canadian studio after failing to find commercial success with their Victorian fantasy survival game Nightingale. Reportedly, at least 22 people have been let go.

Read more

A US standards agency has issued new guidance saying organisations shouldn’t require users to change their passwords periodically – advice that is backed up by decades of research

Local officials are beginning to certify the results of this year's presidential election in a process that, so far, has been playing out quietly, in stark contrast to the tumultuous certification period four years ago that followed then-President Donald Trump's loss.

President-elect Donald Trump on Tuesday announced that Tesla founder Elon Musk and businessman Vivek Ramaswamy will a new Department of Government Efficiency, a White House office given the task of cutting the federal budget.

As many as 115 Post Office Branches and hundreds of jobs could be at risk following a strategic review held by Post Office Chairman Nigel Railton.

President-elect Trump announced that billionaire Elon Musk and former GOP presidential candidate Vivek Ramaswamy will lead the Department of Government Efficiency.

Montana public health officials are investigating an outbreak of infections caused by Salmonella. The Cascade City-County Health Department in Great Falls is reporting that six students at Sacajawea and Valley View elementary schools have tested positive for the pathogen. A staff member at another school has also tested positive. There... Continue Reading

When it’s time to make stuffing, whether it’s for Thanksgiving or any other meal, you have a decision to make. Do you make homemade stuffing or go for the shortcut and buy Stove Top? It comes down to the ease of making something right out of a box versus the satisfaction of making the perfect […]

A man from Eugene, Oregon, pleaded guilty to federal hate crimes on Tuesday after he spray-painted antisemitic graffiti on a synagogue in 2023 and 2024.

The business secretary Jonathan Reynolds has called for a change of culture at the Post Office, as he gave evidence to the inquiry into the Horizon scandal.

President-elect Donald Trump has made many selections to lead his administration as his transition gets underway, ranging from chief of staff to head of the Environmental Protection Agency (EPA). At the same time, a number of crucial positions have yet to be filled just one week removed from the landslide election.

The post Donald Trump’s Administration Takes Shape After 15 Official or Expected Picks appeared first on Breitbart.

President-elect Donald Trump announced he has picked Tesla CEO and X owner Elon Musk and entrepreneur and former Republican presidential candidate Vivek Ramaswamy to "lead the Department of Government Efficiency."

The post Donald Trump Selects Elon Musk, Vivek Ramaswamy to ‘Lead the Department of Government Efficiency’ appeared first on Breitbart.

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

Credit the franchise's popularity, sure—but also its ludicrous file sizes.

The announcement was made in a video unveiled at Disney’s D23 event in Brazil, featuring the returning stars in a reveal

NPR's Juana Summers talks with Cindy Nava, a Democrat, who will be joining the New Mexico state senate in Albuquerque. She is one of the millions of "Dreamers" who are protected by DACA.

President-elect Trump announced a "Department of Government Efficiency," or DOGE, that will be led by Tesla CEO Elon Musk and entrepreneur Vivek Ramaswamy, focused on shrinking the federal government.

Amazon is reportedly developing smart glasses for its delivery drivers, according to sources who spoke to Reuters. These glasses are intended to cut “seconds” from each delivery because, well, productivity or whatever. Sources say that they are an extension of the pre-existing Echo Frames smart glasses and are known by the internal code Amelia.

These seconds will be shaved off in a couple of ways. First of all, the glasses reportedly include an embedded display to guide delivery drivers around and within buildings. They will allegedly also provide drivers with “turn-by-turn navigation” instructions while driving. Finally, wearing AR glasses means that drivers won’t have to carry a handheld GPS device. You know what that means. They’ll be able to carry more packages at once. It’s a real mitzvah.

I’m being snarky, and for good reason, but there could be some actual benefit here. I’ve been a delivery driver before and often the biggest time-sink is wandering around labyrinthine building complexes like a lost puppy. I wouldn’t have minded a device that told me where the elevator was. However, I would not have liked being forced to wear cumbersome AR glasses to make that happen.

To that end, the sources tell Reuters that this project is not an absolute certainty. The glasses could be shelved if they don’t live up to the initial promise or if they’re too expensive to manufacture. Even if things go smoothly, it’ll likely be years before Amazon drivers are mandated to wear the glasses. The company is reportedly having trouble integrating a battery that can last a full eight-hour shift and settling on a design that doesn’t cause fatigue during use. There’s also the matter of collecting all of that building and neighborhood data, which is no small feat.

Amazon told Reuters that it is “continuously innovating to create an even safer and better delivery experience for drivers” but refused to comment on the existence of these AR glasses. "We otherwise don’t comment on our product roadmap,” a spokesperson said.

The Echo Frames have turned out to be a pretty big misfire for Amazon. The same report indicates that the company has sold only 10,000 units since the third-gen glasses came out last year.

This article originally appeared on Engadget at https://www.engadget.com/big-tech/amazon-reportedly-wants-drivers-to-wear-ar-glasses-for-improved-efficiency-until-robots-can-take-over-174910167.html?src=rss

President-elect Donald Trump has named Elon Musk as the leader of a new “Department of Government Efficiency," that will “dismantle Government Bureaucracy, slash excess regulations, cut wasteful expenditures, and restructure Federal Agencies.” The Tesla CEO and owner of X will spearhead the effort along with former presidential candidate Vivek Ramaswamy, Trump announced in a statement on Truth Social.

The scope of the role isn’t exactly clear. Trump’s press release said that “the Department of Government Efficiency will provide advice and guidance from outside of Government, and will partner with the White House and Office of Management & Budget to drive large scale structural reform, and create an entrepreneurial approach to Government never seen before.” It also stated that “their work will conclude no later than July 4, 2026.”

Musk shared the news on X, but didn’t indicate how the role might impact his obligations at his various other companies. Musk, who poured millions of dollars into Super Pac boosting Trump’s campaign, has previously talked about his desire to work with Trump to cut government spending. He did, however, joke about potential "merch" for the operation. "Republican politicians have dreamed about the objectives of 'DOGE' for a very long time," Trump's statement said. 

This article originally appeared on Engadget at https://www.engadget.com/big-tech/elon-musk-will-lead-a-new-department-of-government-efficiency-donald-trump-says-015521217.html?src=rss

Donald Trump a indiqué mardi qu’il comptait nommer Elon Musk à la tête d’un ministère nouvellement créé de l’«efficacité gouvernementale»

Don’t trust yourself to stop nibbling? Shut those tempting treats away in a time-locked safe.

Le film québécois a devancé plusieurs grandes productions hollywoodiennes

In an effort to strengthen the regulatory activities for medical devices in the country, the Union health ministry has framed and finalised rules regulating the method of recruitment to various posts under the Central

In this episode you can hear Olivia Friett, editor of Medical Plastics News talk to Erik Haines, managing director at Guidepoint Qsight where we will discuss Qsight Prospector, a data-driven sales intelligence programme.

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

By adopting a contingent workforce model and investing in the right data tools to power better informed decision-making and talent strategy, healthcare organizations can begin to address staffing challenges and turn their talent goals into reality. 

The post Closing Staffing Gaps in Healthcare by Utilizing Diverse Pipelines of Contingent Talent appeared first on MedCity News.

Neurogene’s Rett syndrome gene therapy has preliminary data supporting safety and efficacy of the one-time treatment. But a late-breaking report of a serious complication in a patient who received the high dose sent shares of the biotech downward.

The post Neurogene Gene Therapy Shows Signs of Efficacy in Small Study, But an Adverse Event Spooks Investors appeared first on MedCity News.

The Food and Drug Administration published a concept paper in early January that describes a preliminary proposal for how the agency will ensure that companies developing antibiotics for administration to animals establish defined, evidence-based durations of use for all medically important antibiotics.

WASHINGTON — US President-elect Donald Trump said on Nov 12 that Elon Musk and former Republican presidential hopeful Vivek Ramaswamy will lead the newly created Department of Government Efficiency. Musk and Ramaswamy "will pave the way for my Administration to dismantle Government Bureaucracy, slash excess regulations, cut wasteful expenditures, and restructure Federal Agencies", Trump said in a statement. Trump said their work would conclude by July 4, 2026, adding that a smaller and more efficient government would be a "gift" to the country on the 250th anniversary of the signing of the Declaration of Independence. Businessman and former Republican presidential candidate Vivek Ramaswamy attends Donald Trump's campaign event sponsored by conservative group Turning Point Action, in Las Vegas, Nevada, US, Oct 24, 2024. PHOTO: Reuters file The appointments reward two Trump supporters from the private sector.

TAIPEI — Taiwanese businessman Robert Tsao said on Nov 11 that he would sue in a Taiwan court senior Chinese officials over sanctions they had placed on him, saying he was seeking to counter China's intimidation of lawful activity. China, which claims Taiwan as its own territory, said in October it would punish and sanction Tsao, the retired founder of chipmaker United Microelectronics Corp (UMC), for alleged criminal and pro-Taiwan independence activities. China's Taiwan Affairs Office said the "Black Bear Academy" that Tsao has helped fund was seeking to incite separatism that would endanger cross-strait ties. Tsao, one of Taiwan's richest men who has pledged to provide millions to two civilian defence training programmes, told a press conference that China was threatening the lawful holding of political views in Taiwan and his personal safety. The lawsuit will be lodged in a Taipei court against Song Tao, head of China's Taiwan Affairs Office, and also the office's spokesman Chen Binhua. Taiwan courts have no jurisdiction in China and senior Chinese officials do not visit the island.

The estranged DMK M.P. spoke about party's corrupt image & predicted its downfall; criticised ‘freebies'; praised Rahul Gandhi; was ‘very downbeat' about United Progressive Alliance's electoral prospects

Dec 3, 2022

Recent guest speaker at the Future of Diplomacy Project, Ricardo Zuniga, the Principal Deputy Assistant Secretary and Special Envoy for the Northern Triangle in the Bureau of Western Hemisphere Affairs at the U.S. Department of State, was quoted in Folha de Sao Paulo describing Brazil as "a great multilateral actor and has a long legacy of involvement in peace processes, in the search for multilateral solutions to one of the most complex security problems."

Herman Miller 'Living Beats Dying' video

Virtual tour of 350 Fifth, a new 20-story office building in one of the top-ranked U.S. cities for sustainable buildings. Pt. 1 Pittsburgh-Gateway to the World & 350 Fifth Urban Genius.