Saudi Arabia is planning to invite Syrian President Bashar al-Assad to an Arab League summit that Riyadh is hosting in May, three sources familiar with the plans said, a move that would formally end Syria's regional isolation.
Saudi Foreign Minister Prince Faisal bin Farhan will travel to Damascus in coming weeks to hand Assad a formal invitation to attend the summit scheduled for May 19, two of the sources said.
The Saudi government's communication office and the foreign ministries of both countries did not respond to requests for comments.
Gamal Roshdy, spokesperson for the Arab League secretary general, said the organisation is not privy to every move on the bilateral level between Arab countries.
"We are not supposed to be informed in advance about the assumed visit," he added.
Assad's attendance at an Arab League summit would mark the most significant development in his rehabilitation within the Arab world since 2011, when Syria was suspended from the organisation. Assad had been boycotted by many Western and Arab states over his brutal crackdown on protests - violence that led to a protracted civil war.
Syria's return to the 22-member body would be mostly symbolic but it reflects a change in the regional approach towards the Syrian conflict. Hundreds of thousands of people have died in the war, which drew in numerous foreign powers, and splintered the country.
Last month sources told Reuters Riyadh and Damascus had reached an agreement to reopen their embassies after the Muslim holy month of Ramadan. The Saudi foreign ministry did not confirm an agreement was reached but said it was in talks with the Syrian foreign ministry to resume consular services.
One of the three sources said discussions have been ongoing for more than a year over a list of demands from Saudi Arabia for the Syrian government to meet as a condition to mend ties, including close cooperation on border security and drug trafficking.
Charles Schwab Corp. is on pace for its worst month in more than 35 years, sparking a debate among analysts as to whether the brokerage giant has been unfairly punished by investors amid growing fears about the U.S. banking sector.
Shares of the firm have plunged 34% in March, set to be their biggest drop since October 1987, the month when the biggest single-day stock market crash, dubbed Black Monday, occurred.
The rout has wiped out $47 billion in market value from Schwab, roughly equivalent to the size of Truist Financial Corp.
“There are times in markets where logic is thrown out the window and emotion takes over and I feel like this is one of those moments with Schwab,” said Adam Sarhan, founder of 50 Park Investments.
He added that the rout is a “historic buying opportunity” for the financials sector as a whole and something not seen since 2008.
Other brokerage stocks are also lower, just not as much as Schwab. Interactive Brokers Group Inc. for instance, is down about 4.5% this month.
Schwab is facing a pair of headwinds. Its banking arm, one of the largest in the U.S., is dealing with some of the same issues that plagued the now-defunct Silicon Valley Bank.
Like many of it peers, Schwab invested in long-dated bonds during a period of historically low interest rates and is stuck with losses on those investments as the Federal Reserve has increased interest rates over the last year.
Higher rates have also created another headache for Schwab, customers seeking better returns are moving their cash deposits into higher yielding assets like money-market funds within the brokerage or elsewhere. That process — often referred to as cash sorting — has put pressure on the company’s profit outlook.
“As cash sorting occurs, that effectively hurts earnings power,” said JMP Securities analyst Devin Ryan. He noted that Schwab is now paying well over 4% for deposits that it was once paying just about 0.5% for.
The pace at which customers are shifting their cash at Schwab spurred Morgan Stanley analyst Michael Cyprys to cut his rating on the stock for the first time since he began covering the brokerage company in 2016.
Still, Bank of America’s Craig Siegenthaler, who downgraded Schwab in January, remains the only analyst with a sell-equivalent rating on the stock.
Schwab is set to report its first-quarter results before the open of trading on April 17. Its shares have fallen at least 1.5% during each of its last five sessions following its earnings release.
Buying opportunities like this are very clear in hindsight, according to Sarhan. Still, “having the courage in real time is very difficult,” he said.
Artificial intelligence in some shape or form has been a part of everyday life for years, butthe meteoric rise of ChatGPT and the resulting aggressive development pace of conversational and generative AI modelsis, for the first time ever, putting the underlying technology into the hands of the general public.
However, as Statista's Florian Zandt details below, even though current large language models are primarily able to guess the best-fitting next word in a sentence based on the corpus of content they were fed, CEOs, researchers and AI experts are now urging the industry to pump the brakes on training and developing models more capable than OpenAI's GPT-4.
The company's latest large language model is currently available in a limited capacity for ChatGPT Plus subscribers and will soon be integrated into Microsoft productivity and security products.
The letter was released by the Future of Life Institute, a non-governmental organization founded in 2014 by MIT professor Max Tegmark and Skype co-founder Jaan Tallinn, among others. The Musk Foundation is a primary donor to the organization.
75 percent of Indians surveyed between September and October 2022 would place their trust in AI, followed by 67 percent of Chinese and 57 percent of South African respondents.
According to the accompanying study, respondents claimed to trust AI used in healthcare and security contexts the most compared to other possible use cases.
In certain groups of men, glucose-6-phosphate dehydrogenase (G6PD) deficiency was linked with an increased likelihood of severe COVID-19, a Veterans Affairs cohort study found.
In Black men under 65, for example, those with the common enzyme deficiency had a roughly 1.5-fold higher risk for severe illness (OR 1.47, 95% CI 1.03-2.09), reported Lavannya Pandit, MD, MS, of the Michael E. DeBakey VA Medical Center in Houston, and colleagues.
And in white men 65 and over, those with G6PD deficiency had a 3.6-fold higher likelihood of severe outcomes (OR 3.58, 95% CI 1.64-7.80), which in the study was defined as the need for hospitalization, mechanical ventilation, or intensive care, or death.
"This study is the first to present epidemiologic evidence that putatively link a biologic mechanism of impaired cellular responses in G6PD deficiency to increased COVID-19 severity," Pandit and colleagues wrote in JAMA Network Openopens in a new tab or window. "Our analysis revealed a strong association between G6PD deficiency and COVID-19 severity, modified by race and age."
In the U.S., anywhere from 4% to 7% of people are affected by G6PD deficiencyopens in a new tab or window, but that percentages rises to 10% to 14% for Black men. G6PD enzyme activity is moderated by hyperglycemia, and associations have been observed between G6PD deficiency and risk for diabetes.
One of the challenges with COVID-19 has been understanding why certain individuals experience severe, life-threatening conditions, and others don't, the researchers said. While ancestry, socioeconomic status, healthcare utilization, and comorbid conditions are all variables that have been associated with worse illness, "the contribution of biology toward disease severity has been minimally explored. As a result, despite almost 3 years of observational data, the biologic bases of susceptibility to SARS-CoV-2 infection and risks of severe outcomes after infection are largely unknown."
The findings, they concluded, highlight "the need to review and determine possible underlying inherent genetic risks, such as G6PD deficiency, prior to illness or early in treatment course as a strategy to mitigate negative outcomes."
Pandit's team examined data on 4,811 veterans in the Veterans Health Administration who had a positive COVID-19 test and had been tested for G6PD deficiency. Most (80.4%) were men, one-third were Black, 39% were white, and three-fourths were under age 65. Of those, 454 were positive for G6PD deficiency (418 men and 36 women), 68% of whom were Black men.
Although the genetic metabolic abnormality is an X-linked condition, and thus more commonly affects men, the researchers noted that hemizygous males and heterozygous females can also be affected.
In discussing why a link was only seen among the younger population of Black men in their study, Pandit and co-authors posited that "increased COVID-19 severity may not be measurable in the older Black male population possibly due to other underlying comorbidities in this population (diabetes and chronic kidney disease, for example) that may already confer a ceiling effect on severity, and that ceiling effect may not be additionally altered (increased) by G6PD deficiency."
As to the differences in risk between the white and Black groups, they suggested that it could come down to different alleles (G6PD-Mediterranean vs G6PD-A, for example), though Department of Defense testing does not universally determine genetic variants.
Limitations cited by the researchers included that comorbidity data were obtained through ICD-10 codes, which may be misclassified, and demographic factors such as race were self-identified. "Additional study is warranted by including Medicare and Medicaid information and additional confounding factors, including healthcare policy messaging, access to care, and usage of non-prescribed and prescribed medications outside of the [Veterans Health Administration]," they added.
Disclosures
This study was funded by the Department of Veterans of Affairs.
The researchers had nothing to disclose.
Primary Source
JAMA Network Open
Source Reference: opens in a new tab or windowElsea SH, et al "Association of glucose-6-phosphate dehydrogenase deficiency with outcomes in US veterans with COVID-19" JAMA Netw Open 2023; DOI: 10.1001/jamanetworkopen.2023.5626.
Drugmakers are failing to provide Europeans with the information to understand the benefits and harms of oncology medicines. That is the headline finding of a paperpublishedin The BMJ, which found patient information leaflets routinely lack details that could support informed decision-making.
The study looked at the summaries of product characteristics (SmPCs), patient information leaflets (PILs) and public summaries for 29 cancer drugs that received their first marketing authorization in Europe from 2017 to 2019. By assessing the three sources of regulated information, and comparing them to European public assessment reports, the researchers sought to understand the gaps in the information that companies provide to clinicians, patients and the public.
While nearly all SmPCs communicated full information about the number and design of the main studies, none of the PILs communicated information to patients about how drugs were studied. Similarly, 72% of the SmPCs reported whether a drug extended survival, but none of the PILs communicated information about the drug benefits that patients might expect based on study findings. The authors of the paper see the gaps as a problem.
“Our study highlights the need to improve the communication of drug benefits and related uncertainties in regulated prescription drug information in Europe. The provision of high-quality information on drug benefits and related uncertainties is especially important for patients with time-limiting conditions such as advanced cancer,” the authors wrote.
As the authors see things, when patients have “unrealistic expectations” of the benefits of a treatment and “misplaced confidence” in the strength of the evidence, informed decision-making is undermined.
The study found that scientific concerns about the reliability of evidence on drug benefits, which were raised during an assessment of almost all the drugs, were rarely communicated to clinicians or patients. And that reporting of the design of a study and its findings was sometimes inconsistent with information reported in European public assessment reports and “potentially misleading.”
After identifying the problems, the authors proposed potential solutions. Acknowledging that regulators “cannot compel companies to include information on drug benefits and evidence about uncertainties of benefits in patient package leaflets,” the authors note that “mechanism of action statements may be misunderstood as statements of effectiveness” and “this may be at odds with legal requirements for information in patient leaflets to be accurate, non-misleading, and non-promotional.”
The authors suggest regulators concentrate on ensuring that relevant, accurate and useful content is available in online lay summaries for the public. By revising the templates for public summaries, which the authors say could happen without legislation, details of a medicine's benefits could be presented as part of a “drug facts box” specific to cancer therapies and made available online.
As the biopharma industry struggles with a dire shortage of viral vectors to make cell and gene therapies, contract manufacturers are busy beefing up their capabilities.
In the latest example of biopharma’s ongoing investment in cell and gene therapy production, Sartorius has agreed to acquire French company Polyplus for 2.4 billion euros ($2.6 billion), the German CDMO said Friday.
The deal gives Sartorius additional know-how in nucleic acid delivery, including transfection reagents and plasmid DNA design, all of which are key elements in the production of viral vectors for building cell and gene therapies.
Formed in 2001, Polyplus employs about 270 people in several locations in France, Belgium, the U.S. and China. Before the Sartorius buyout, Polyplus had itself been expanding through M&A deals. In 2021, Polyplus bought Asia-Pacific-focused reagent supplier Biowire.
Besides its core transfection reagent portfolio, Polyplus in 2022 added DNA vector design capabilities through the acquisition of French startup e-Zyvec. The company in December further expanded its plasmid DNA engineering technology by taking over Belgian CDMO Xpress Biologics.
As an increasing number of cell and gene therapy programs move through clinical development, more viral vectors are needed to deliver their genetic materials into cells, Fáber noted.
In November, the FDA approved CSL’s hemophilia B gene therapy Hemgenix, which is based on an adeno-associated virus. BioMarin is prepping for a potential U.S. launch for its hemophilia A gene therapy Roctavian. Vertex and CRISPR Therapeutics’ exa-cel looks on track to become the first gene-editing therapy based on the CRISPR technology.
Already, several commercial cell and gene therapies face manufacturing bottlenecks because of the industry-wide shortage of viral vectors. Multiple myeloma CAR-T therapies by Bristol Myers Squibb and a partnership between Johnson & Johnson and Legend Biotech haven’t been able to meet demand thanks to limited supply of lentiviral vectors.
And even as biopharma companies build their internal capacity, CDMOs have also been expanding manufacturing footprints for cell and gene therapies. Chinese CDMO Pharmaron recently kicked off a more than 8,000-square-meter expansion of its viral vector and nucleic acid facility in England. In January, Vector BioMed landed in the viral vector CDMO arena with $15 million in funding.
Last year, Fujifilm picked up a cell therapy plant in California from Atara Biotherapeutics for $100 million and then bought out Shenandoah Biotechnology for the latter’s recombinant proteins used in making cell and gene therapies.
But there are also some signs of cooling in the field. After aggressive expansions, WuXi AppTec’s cell and gene therapy arm, WuXi Advanced Therapies, recently chopped about 50 jobs at its Lingang facility in Shanghai, according to Chinese media reports. The layoffs mainly affect the commercial manufacturing team and came as part of a business adjustment, WuXi said on a Chinese investor platform.
Large pharma companies such as Biogen, Novartis, GSK and AstraZeneca have recently pulled out of cell and gene therapy programs, as well.
America’s latest episode of mass homicide has sparked renewed advocacy for restrictions on gun ownership. Once again, the accompanying debate has many gun control advocates claiming the Second Amendment’s reference to a “well regulated militia” narrows the amendment’s scope if not rendering it altogether moot.
Before we examine those claims, it’s important to ensure readers have a proper general understanding of the Bill of Rights. Contrary to common misperception, these amendments do not bestow privileges upon American citizens. Rather, they are primarily a set of prohibitions against the government infringing on pre-existing human rightsall people have.
That’s evident in the language. For example, the First Amendment begins “Congress shall make no law…” This amendment isn’t awarding citizens the rights of religion, speech and assembly — it’s outlawing the government’s thwarting of those innate and universal human rights.
Similarly, the Fourth Amendment asserts that “the right of the people to be secure in their persons, houses, papers, and effects, against unreasonable searches and seizures, shall not be violated.” Again, the authors are not granting those rights, they are protecting them.
When the Bill of Rights was proposed, some feared the enumeration of a handful of rights could be misinterpreted as providing a comprehensive catalogue — and thus empowering the government to infringe on human rights not specified. That’s why they included the Ninth Amendment, asserting that “the enumeration in the Constitution, of certain rights, shall not be construed to deny or disparage others retained by the people.”
“Amendment II. A well regulated Militia, being necessary to the security of a free State, the right of the people to keep and bear Arms, shall not be infringed.”
With that understanding of the Bill of Rights in mind, we see that, via the Second Amendment, the founders explicitly asserted that there is a “right of the people to keep and bear arms.”
What about that reference to “a well regulated militia”? As we set out to scrutinize the phrase, let’s first observe that the Second Amendment contains two distinct components serving two different purposes:
An operative clause that sets out a specific prohibition against the government’s infringement on a right: …the right of the people to keep and bear Arms, shall not be infringed.
A prefatory clause that announces a purpose: A well regulated Militia, being necessary to the security of a free State…
Positioned in the prefatory clause, the “well regulated Militia” reference merely serves to provide a rationale — and not necessarily the only rationale — for the operative clause that follows.
While the Second Amendment stands apart from the others in the Bill of Rights by having a prefatory clause, such clauses were common in state constitutions of the era.
Prefatory clauses were used to help “sell” amendments to those being asked to approve them. In this case, the authors were pointing to the necessity of an armed populace as the well from which militias are drawn — militias seen as a vital safeguard against the federal government they were creating.
James Madison offered the initial draft of the Second Amendment
In particular, America’s founders were wary of the federal government’s potential to create a standing army that could be used to destroy state sovereignty and individual liberties. Seeking to “sell” the amendment to drafting committees and state ratifying conventions, it made sense for the authors to highlight the link between militias and the people’s right to bear arms.
Given their purpose — that is, to cite one or more of many possible rationales — prefatory clauses don’t rightly constrain operative clauses, particularly one as explicit as the Second Amendment’s, which pointedly recognizes a “right of the people to keep and bear arms.”
Even if the prefatory clause did have any teeth, those seeking to interpret it as tightly restricting the gun-eligible population run into yet another wall, in that militias are assembled from the citizenry at large.
Indeed, one revision of James Madison's draft of the Second Amendment drove home this point. It began, “A well regulated militia, composed of the body of the people…”
Listen to Pennsylvanian Tench Coxe, as he championed the Constitution’s ratification: “The powers of the sword are in the hands of the yeomanry of America from sixteen to sixty.” Summarizing the Second Amendment, Coxe said, “The people are confirmed by the article in their right to keep and bear their private arms.”
Multiple state constitutional provisions of the era, some of which predate the Bill of Rights, offer additional confirmation that the armed right of self-defense belongs to individuals. As one representative example, consider the language of Vermont’s 1777 Constitution: “The right of the citizens to bear arms in defense of themselves and the State shall not be questioned.”
Further disregarding the Second Amendment’s explicit enumeration of “the right of the people to bear arms,” some claim the existence of the National Guard renders the Second Amendment entirely moot, since, via the Guard, each state has a “militia” with its own arsenal of arms.
Recall, however, that the founders viewed militias as a check on the federal government’s power, with fear that the federal government might create a standing army with the potential to tyrannize the states and the people.
Thanks to the National Defense Act of 1916 and amendments in 1933, today’s National Guard is legally a part of the United States Army, with state governments exercising only limited government control. Enlistment oaths have evolved to reflect that, with National Guard soldiers promising to obey the orders of both the president of the United States and the governor.
The Guard’s military training and the selection of its officers are controlled by the federal government. Troops are subject to activation pursuant to any number of federal missions, including — as we’ve seen too often — overseas combat deployments that render them useless to the states where their citizen-soldiers live.
Clearly, under such federal control, the National Guard cannot be seen as a counterbalance against federal power, and thus does not fulfill the Second Amendment’s aspiration to enable “well-regulated militias…necessary to the security of a free state.”
Finally, no tour of the Second Amendment’s language would be complete without addressing “well regulated” as it’s applied to “militia.” Today, people often and understandably assume that descriptor refers to regulation in the modern sense of external government control. However, in the late 1700s, “well regulated” simply meant orderly, trained and disciplined — qualities that militias should aspire to.
To summarize:
The Second Amendment explicitly recognizes the existence of “a right of the people” — not just those currently in militias — “to keep and bear arms.”
Placed in a prefatory clause, the “militia” reference merely announces one rationale for the Second Amendment. Regardless of how “militia” is interpreted, its presence does not constrain the operative-clause prohibition of government infringement against the right of the people to keep and bears arms.
Today’s National Guard is part of the U.S. Army and under heavy federal control. It cannot be used by the peoples of the separate states as a counterbalance to the federal government’s standing army — and thus is not a “militia” in the sense the term is used in the Second Amendment.
