Tag: Research

Eight Scientists, a Billion Dollars, and the Moonshot Agency Trying to Make Britain Great Again

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“It’s great that ARIA exists, and I think it’s great that there is a plants program in it,” says Langdale. “There’s no doubt about that because for far too long, people like Gates have been driving the moonshot projects, and of course they have a very specific focus on what it is they want to achieve.”

Philanthropic foundations like Gates’ also have a higher tolerance for projects that may not hit paydirt. “We’ve been going quite a long time, and we certainly don’t have anything near a product to put in the field,” Langdale says. Government-backed science funding has historically had much less of an appetite for these kinds of projects, because it’s hard to justify spending taxpayer money on projects that might take 30 years to come to fruition.

Even compared to the C4 Rice Project, Burnett’s synthetic plants program is a very significant chunk of money, Langdale says. Burnett is aiming to spend £62.4 million ($82 million) over five years. The program will fund scientists to try to make synthetic chromosomes, the genetic building blocks of plants, and synthetic chloroplasts, which have their own separate genomes. But the program doesn’t specify what new features these partly synthetic plants should have. It’s a little like designing a new machine without knowing what tools that machine is going to build, says Langdale.

Johnathan Napier, a science director at agricultural institute Rothamsted Research shares these concerns. Building synthetic chromosomes and chloroplasts are clearly defined goals, but he’s not sure whether they’re going to deliver a tangible benefit. Napier tries to engineer crops to produce omega-3 fish oils, while the C4 Rice Project is attempting to make rice much more productive. But Burnett’s program is much wider than either of these. In theory at least, it could one day allow plant scientists to plug in any kind of functionality into a plant.

“If this all worked, you’d be able to design your complex pathway in the computer, build an entire chromosome […] and just plug that into the plant in a single step,” says Saul Purton, another workshop attendee and a professor at University College London who works on synthetic chloroplasts in algae. Purton says that he may apply for an ARIA grant, but that the five-year timeline set out to deliver synthetic chloroplasts in several crop species is extremely tight. “We’ve been bashing away in terms of developing new synthetic biology tools for engineering the chloroplast of a simple model system for 15 or 20 years now, and we’re still learning, we’re still making mistakes.”

Angie Burnett is funding research into synthetic chromosomes and chloroplasts, and the ethics of synthetic plants.

PHOTOGRAPHY: CHARLIE CLIFT

When I meet Burnett again in early August, she has just had her program approved after a grueling three-hour meeting with Gur, members of ARIA’s executive team, and a panel of external experts. “It was a little nerve-wracking because it’s such a big moment that I’ve been working towards for this whole time,” she says. As well as funding projects working to build synthetic chromosomes and chloroplasts, Burnett is also asking for research into the ethics of synthetic plants—anticipating a world where farmers, lawmakers, and the public may have to grapple with the idea of crops fully crafted by human hands. But it’s unlikely she’ll still be with the agency to see those scientific seeds bear fruit. Program directors are typically hired for three-year terms, and the agency is already hiring its next batch of directors, some of whom will launch entirely new project areas.

Over such short timescales, it can be difficult to gauge the success of such long-term plays: Are mistakes just bumps in the road, or signs that you’ve taken the wrong route altogether? Collison is wary about defining success at all. Give it 15 years, he says, and it should be pretty obvious if ARIA is a good thing or not. The agency has a little breathing room. It cannot be dissolved for at least 10 years, by which point the UK will have had at least one more general election. The new Labour government has indicated its support for ARIA, not least by making Vallance the minister responsible for ARIA. “It is essential to harness the power of science to deliver economic growth, opportunity, and scientific advancements for people across the UK,” said a government spokesperson.

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October 2, 2024
Scientists Figured Out How to Recycle Plastic by Vaporizing It

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Our planet is choking on plastics. Some of the worst offenders, which can take decades to degrade in landfills, are polypropylene—which is used for things such as food packaging and bumpers—and polyethylene, found in plastic bags, bottles, toys, and even mulch.

Polypropylene and polyethylene can be recycled, but the process can be difficult and often produces large quantities of the greenhouse gas methane. They are both polyolefins, which are the products of polymerizing ethylene and propylene, raw materials that are mainly derived from fossil fuels. The bonds of polyolefins are also notoriously hard to break.

Now, researchers at UC Berkeley have come up with a method of recycling these polymers that uses catalysts that easily break their bonds, converting them into propylene and isobutylene, which are gases at room temperature. Those gases can then be recycled into new plastics.

“Because polypropylene and polyethylene are among the most difficult and expensive plastics to separate from each other in a mixed waste stream, it is crucial that [a recycling] process apply to both polyolefins,” the research team said in a study recently published in Science.

Breaking It Down

The recycling process the team used is known as isomerizing ethenolysis, which relies on a catalyst to break down olefin polymer chains into their small molecules. Polyethylene and polypropylene bonds are highly resistant to chemical reactions, because both of these polyolefins have long chains of single carbon-carbon bonds. Most polymers have at least one carbon-carbon double bond, which is much easier to break.

While isomerizing ethenolysis had been tried by the same researchers before, the previous catalysts were expensive metals that did not remain pure long enough to convert all of the plastic into gas. Using sodium on alumina followed by tungsten oxide on silica proved much more economical and effective, even though the high temperatures required for the reaction added a bit to the cost.

In both plastics, exposure to sodium on alumina broke each polymer chain into shorter polymer chains and created breakable carbon-carbon double bonds at the ends. The chains continued to break over and over. Both then underwent a second process known as olefin metathesis. They were exposed to a stream of ethylene gas flowing into a reaction chamber while being introduced to tungsten oxide on silica, which resulted in the breakage of the carbon-carbon bonds.

The reaction breaks all the carbon-carbon bonds in polyethylene and polypropylene, with the carbon atoms released during the breaking of these bonds ending up attached to molecules of ethylene. “The ethylene is critical to this reaction, as it is a coreactant,” researcher R.J. Conk, one of the authors of the study, told Ars Technica. “The broken links then react with ethylene, which removes the links from the chain. Without ethylene, the reaction cannot occur.”

The entire chain is catalyzed until polyethylene is fully converted to propylene, and polypropylene is converted to a mixture of propylene and isobutylene.

This method has high selectivity—meaning it produces a large amount of the desired product: propylene derived from polyethylene, and both propylene and isobutylene derived from polypropylene. Both of these chemicals are in high demand; propylene is an important raw material for the chemical industry, while isobutylene is a frequently used monomer in many different polymers, including synthetic rubber and a gasoline additive.

Mixing It Up

Because plastics are often mixed at recycling centers, the researchers wanted to see what would happen if polypropylene and polyethylene underwent isomerizing ethenolysis together. The reaction was successful, converting the mixture into propylene and isobutylene, with slightly more propylene than isobutylene.

Mixtures also typically include contaminants in the form of additional plastics. So the team also wanted to see whether the reaction would still work if there were contaminants. They experimented with plastic objects that would otherwise be thrown away, including a centrifuge and a bread bag, both of which contained traces of other polymers besides polypropylene and polyethylene. The reaction yielded only slightly less propylene and isobutylene than it did with unadulterated versions of the polyolefins.

Another test involved introducing different plastics, such as PET and PVC, to polypropylene and polyethylene to see if that would make a difference. These did lower the yield significantly. If this approach is going to be successful, then all but the slightest traces of contaminants will have to be removed from polypropylene and polyethylene products before they are recycled.

While this recycling method sounds like it could prevent tons upon tons of waste, it will need to be scaled up enormously for this to happen. When the research team increased the scale of the experiment, it produced the same yield, which looks promising for the future. Still, we’ll need to build considerable infrastructure before this could make a dent in our plastic waste.

“We hope that the work described … will lead to practical methods for … [producing] new polymers,” the researchers said in the same study. “By doing so, the demand for production of these essential commodity chemicals starting from fossil carbon sources and the associated greenhouse gas emissions could be greatly reduced.”

This story originally appeared on Ars Technica.

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September 27, 2024
OpenAI Threatens Bans as Users Probe Its ‘Strawberry’ AI Models

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OpenAI truly does not want you to know what its latest AI model is “thinking.” Since the company launched its “Strawberry” AI model family last week, touting so-called reasoning abilities with o1-preview and o1-mini, OpenAI has been sending out warning emails and threats of bans to any user who tries to probe how the model works.

Unlike previous AI models from OpenAI, such as GPT-4o, the company trained o1 specifically to work through a step-by-step problem-solving process before generating an answer. When users ask an “o1” model a question in ChatGPT, users have the option of seeing this chain-of-thought process written out in the ChatGPT interface. However, by design, OpenAI hides the raw chain of thought from users, instead presenting a filtered interpretation created by a second AI model.

Nothing is more enticing to enthusiasts than information obscured, so the race has been on among hackers and red-teamers to try to uncover o1’s raw chain of thought using jailbreaking or prompt injection techniques that attempt to trick the model into spilling its secrets. There have been early reports of some successes, but nothing has yet been strongly confirmed.

Along the way, OpenAI is watching through the ChatGPT interface, and the company is reportedly coming down hard on any attempts to probe o1’s reasoning, even among the merely curious.

One X user reported (confirmed by others, including Scale AI prompt engineer Riley Goodside) that they received a warning email if they used the term “reasoning trace” in conversation with o1. Others say the warning is triggered simply by asking ChatGPT about the model’s “reasoning” at all.

The warning email from OpenAI states that specific user requests have been flagged for violating policies against circumventing safeguards or safety measures. “Please halt this activity and ensure you are using ChatGPT in accordance with our Terms of Use and our Usage Policies,” it reads. “Additional violations of this policy may result in loss of access to GPT-4o with Reasoning,” referring to an internal name for the o1 model.

Marco Figueroa, who manages Mozilla’s GenAI bug bounty programs, was one of the first to post about the OpenAI warning email on X last Friday, complaining that it hinders his ability to do positive red-teaming safety research on the model. “I was too lost focusing on #AIRedTeaming to realized that I received this email from @OpenAI yesterday after all my jailbreaks,” he wrote. “I’m now on the get banned list!!!”

Hidden Chains of Thought

In a post titled “Learning to Reason With LLMs” on OpenAI’s blog, the company says that hidden chains of thought in AI models offer a unique monitoring opportunity, allowing them to “read the mind” of the model and understand its so-called thought process. Those processes are most useful to the company if they are left raw and uncensored, but that might not align with the company’s best commercial interests for several reasons.

“For example, in the future we may wish to monitor the chain of thought for signs of manipulating the user,” the company writes. “However, for this to work the model must have freedom to express its thoughts in unaltered form, so we cannot train any policy compliance or user preferences onto the chain of thought. We also do not want to make an unaligned chain of thought directly visible to users.”

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September 18, 2024
With AI Tools, Scientists Can Crack the Code of Life

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In 2021, AI research lab DeepMind announced the development of its first digital biology neural network, AlphaFold. The model was capable of accurately predicting the 3D structure of proteins, which determines the functions that these molecules play. “We’re just floating bags of water moving around,” says Pushmeet Kohli, VP of research at DeepMind. “What makes us special are proteins, the building blocks of life. How they interact with each other is what makes the magic of life happen.”

AlphaFold was considered by the journal Science as the breakthrough of the year in 2021. In 2022, it was the most cited research paper in AI. “People have been on [protein structures] for many decades and were not able to make that much progress,” Kohli says. “Then came AI.” DeepMind also released the AlphaFold Protein Structure Database—which contained the protein structures of almost every organism whose genome has been sequenced—making it freely available to scientists worldwide.

More than 1.7 million researchers in 190 countries have used it for research ranging from the design of plastic-eating enzymes to the development of more effective malaria vaccines. A quarter of the research involving AlphaFold was dedicated to the understanding of cancer, Covid-19, and neurodegenerative diseases like Parkinson’s and Alzheimer’s. Last year, DeepMind released its next generation of AlphaFold, which extended its structure prediction algorithm to biomolecules like nucleic acids and ligands.

“It has democratized scientific research,” Kohli says. “Scientists working in a developing country on a neglected tropical disease did not have access to the funds to get the structure of a protein computed. Now, at the click of a button, they can go to the AlphaFold database and get these predictions for free.” For instance, one of DeepMind’s early partners, the Drugs for Neglected Diseases Initiative, used AlphaFold to develop medicine for diseases that affect millions—such as sleeping sickness, Chagas disease, and leishmaniasis—yet receive comparatively little research.

DeepMind’s latest breakthrough is called AlphaMissense. The model categorizes the so-called missense mutations—genetic alterations that can result in different amino acids being produced at particular positions in proteins. Such mutations can alter the function of the protein itself, and AlphaMissense attributes a likelihood score for that mutation being either pathogenic or benign. “Understanding and predicting those effects is crucial for the discovery of rare genetic diseases,” Kohli says. The algorithm, which was released last year, has classified around 89 percent of all possible human missense. Before, only 0.1 percent of all possible variants had been clinically classified by researchers.

“This is just the beginning,” Kohli says. Ultimately, he believes AI could eventually lead to the creation of a virtual cell that could radically accelerate biomedical research, enabling biology to be explored in-silico rather than in real-world laboratories. “With AI and machine learning we finally have the tools to comprehend this very sophisticated system that we call life.”

This article appears in the July/August 2024 issue of WIRED UK magazine.

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June 26, 2024
AI Is a Black Box. Anthropic Figured Out a Way to Look Inside

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Last year, the team began experimenting with a tiny model that uses only a single layer of neurons. (Sophisticated LLMs have dozens of layers.) The hope was that in the simplest possible setting they could discover patterns that designate features. They ran countless experiments with no success. “We tried a whole bunch of stuff, and nothing was working. It looked like a bunch of random garbage,” says Tom Henighan, a member of Anthropic’s technical staff. Then a run dubbed “Johnny”—each experiment was assigned a random name—began associating neural patterns with concepts that appeared in its outputs.

“Chris looked at it, and he was like, ‘Holy crap. This looks great,’” says Henighan, who was stunned as well. “I looked at it, and was like, ‘Oh, wow, wait, is this working?’”

Suddenly the researchers could identify the features a group of neurons were encoding. They could peer into the black box. Henighan says he identified the first five features he looked at. One group of neurons signified Russian texts. Another was associated with mathematical functions in the Python computer language. And so on.

Once they showed they could identify features in the tiny model, the researchers set about the hairier task of decoding a full-size LLM in the wild. They used Claude Sonnet, the medium-strength version of Anthropic’s three current models. That worked, too. One feature that stuck out to them was associated with the Golden Gate Bridge. They mapped out the set of neurons that, when fired together, indicated that Claude was “thinking” about the massive structure that links San Francisco to Marin County. What’s more, when similar sets of neurons fired, they evoked subjects that were Golden Gate Bridge-adjacent: Alcatraz, California Governor Gavin Newsom, and the Hitchcock movie Vertigo, which was set in San Francisco. All told the team identified millions of features—a sort of Rosetta Stone to decode Claude’s neural net. Many of the features were safety-related, including “getting close to someone for some ulterior motive,” “discussion of biological warfare,” and “villainous plots to take over the world.”

The Anthropic team then took the next step, to see if they could use that information to change Claude’s behavior. They began manipulating the neural net to augment or diminish certain concepts—a kind of AI brain surgery, with the potential to make LLMs safer and augment their power in selected areas. “Let’s say we have this board of features. We turn on the model, one of them lights up, and we see, ‘Oh, it’s thinking about the Golden Gate Bridge,’” says Shan Carter, an Anthropic scientist on the team. “So now, we’re thinking, what if we put a little dial on all these? And what if we turn that dial?”

So far, the answer to that question seems to be that it’s very important to turn the dial the right amount. By suppressing those features, Anthropic says, the model can produce safer computer programs and reduce bias. For instance, the team found several features that represented dangerous practices, like unsafe computer code, scam emails, and instructions for making dangerous products.

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May 21, 2024
Cancer history raises cardiovascular disease risk in hypertensive patients

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A study published in the journal Hypertension Research reveals that having a cancer history can increase the risk of cardiovascular disease in individuals with hypertension.

Study: Risk of cancer history in cardiovascular disease among individuals with hypertension. Image Credit: Black Salmon / Shutterstock

Background

A growing pool of evidence highlights the link between hypertension and cancer since both hypertension and cancer risks increase with advancing age, and that certain anti-cancer medications increase the risk of hypertension.

Several epidemiological studies have found that hypertension can increase the risk of certain types of cancers and that individuals with a cancer history are more likely to develop cardiovascular complications.

Given the potential link between the risks of hypertension, cardiovascular disease, and cancer, the scientists in this study have assessed the risk of cardiovascular disease events in hypertensive individuals with a history of cancer.

Study design

The study population included 747,620 individuals who were diagnosed with hypertension between January 2005 and May 2022. Patient information was collected from the JMDC Claims Database, a nationwide healthcare database in Japan.

Appropriate statistical analyses were conducted to determine the risk of Composite cardiovascular disease events, including myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation, based on the participant’s history of cancer and chemotherapy.

A history of cancer was defined as being diagnosed with malignancies before the initial health check-up.

Self-reported information on comorbidities (obesity, diabetes, and dyslipidemia), alcohol intake and smoking status, and physical activity level was collected from participants during the health check-up.

Important observations

A total of 26,531 individuals with a history of cancer were identified from the entire study population of 747,620 participants with hypertension. Participants with a history of cancer were more likely to be older adults, less likely to be men, and more likely to have diabetes. In contrast, participants without a history of cancer were more likely to have obesity and current smoking status.

A total of 67,154 composite cardiovascular disease events were detected during the study follow-up period until May 2022. Hypertensive patients with a history of cancer showed a significantly higher risk of developing composite cardiovascular disease events. However, the risk of developing myocardial infarction was not statistically significant.

The highest risk of developing cardiovascular disease events except myocardial infarction was observed among cancer survivors who received chemotherapy compared to those who did not receive chemotherapy or those without a history of cancer.

Regarding myocardial infarction, a higher risk was observed among cancer patients receiving chemotherapy compared to those without a history of cancer.

Five types of cancers, including colorectal cancer, prostate cancer, stomach cancer, renal, pelvic, and ureteral cancer, and lung cancer, showed the highest prevalence in men. In women, the highest prevalence was observed for breast cancer, colorectal cancer, thyroid cancer, corpus uteri cancer, and cervix uteri cancer.

A significantly higher risk of composite cardiovascular events was observed among men with a history of lung cancer and women with a history of breast cancer compared to those without a history of cancer.

A sensitivity analysis conducted after adjusting for age, sex, smoking status, alcohol intake, and physical inactivity showed a similar positive association between having a cancer history and risk of composite cardiovascular disease events.

Study significance

The study finds that hypertensive patients with a history of cancer have a higher risk of developing various cardiovascular disease events than those without a history of cancer. The risk of cardiovascular disease events is even higher in cancer patients receiving chemotherapy.

The study findings highlight the need for early screening of cancer in patients with hypertension. Physicians should manage hypertensive individuals more carefully as cancer comorbidity not only adversely affects cancer mortality but also significantly increases the risk of cardiovascular disease.

The coexistence of cancer and hypertension is a significant public health crisis in Asian countries. Implementation of appropriate healthcare policies is needed to prevent detrimental cardiovascular health consequences, particularly in developing countries with advanced aging.

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April 26, 2024
Research reveals undertreatment of women with heart disease

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Women with heart disease are less often treated with cholesterol-lowering drugs than men, according to research presented today at ESC Preventive Cardiology 2024, a scientific congress of the European Society of Cardiology (ESC).

Cholesterol-lowering drugs save lives and prevent heart attacks, and should be prescribed to all patients with coronary artery disease. Unfortunately, our study shows that women are missing out on these essential medications.”

Dr. Nina Johnston, study author of Uppsala University, Sweden

Patients with coronary artery disease, also called chronic coronary syndrome, require medication to alleviate symptoms and prevent heart attacks and death. ESC guidelines recommend statins for all patients to lower cholesterol levels in the blood. If levels are not sufficiently lowered with the maximum tolerated dose of statin, then patients should receive a statin plus another cholesterol-lowering drug called ezetimibe. The recommendations are the same for women and men.

Despite having the same recommendations for treatment and for target levels of low-density lipoprotein (LDL; “bad”) cholesterol, previous studies have shown that women are less likely to meet target levels than men. This study examined whether women and men receive the same treatments.

This was a retrospective observational study that included 1,037 men and 415 women with a chronic coronary syndrome diagnosed between 2012 and 2020, and who had never had a heart attack. The median age was 68 years in men and 70 years in women. Electronic health records were used to obtain data on cholesterol levels. Information on dispensed medications was obtained from the Swedish National Prescribed Drug Registry.

Participants were followed up for three years following their diagnosis. The researchers found that at the end of the third year of follow-up, just 54% of women were treated with cholesterol-lowering drugs compared with 74% of men. Additionally, 5% of women were treated with statin plus ezetimibe compared with 8% of men. Factors which may explain the observed sex differences are under further investigation by the research group.

The researchers also examined treatments and cholesterol levels of women and men diagnosed with a chronic coronary syndrome at different ages (less than 60, 60 to 69.9, 70-79.9, 80 years or older). In all age groups, prescription of cholesterol-lowering treatment was highest at diagnosis and declined over the following three years. This decline in treatment over time was steeper in women compared with men. For example, in patients under 60 years of age, 65% of women and 79% of men were treated with cholesterol-lowering treatment the week after diagnosis, compared with 52% of women and 78% of men three years later. Achievement of LDL cholesterol targets was also lower in women than men.

Dr. Johnston said: “Our findings should be a wake-up call about the undertreatment of women with heart disease. Equal prescribing practices are needed so that women receive all recommended therapies and are protected from adverse outcomes.”

Contrary to common belief, cardiovascular disease kills more women than men, accounting for 45% of all deaths in women which is more than all cancers combined in the 57 ESC member countries.

Source:

European Society of Cardiology

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April 25, 2024
PhRMA Foundation awards grants to fight health disparities with digital health tools

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The PhRMA Foundation (PhF) awarded $500,000 grants to David G. Armstrong, DPM, MD, PhD, of the University of Southern California and Nino Isakadze, MD, MHS, of Johns Hopkins University to conduct research using digital health technologies (DHTs) to improve health equity and health outcomes for patients.

Armstrong and Isakadze were selected out of a group of seven researchers awarded $25,000 planning grants in 2023 by the Foundation to develop comprehensive research proposals to study the use of DHTs for advancing patient health, especially in underserved populations.

Digital health technologies have great potential to improve health care broadly, but they could be especially impactful for underserved communities if we design and test them with equity in mind. These studies will engage diverse populations to develop digital health solutions targeting treatment challenges for patients with diabetes and heart arrhythmia.”

Amy M. Miller, PhD, President of the PhRMA Foundation

Armstrong, a professor of surgery and neurological surgery at Keck School of Medicine of USC, will lead a project that aims to improve treatment for diabetic foot ulcers (DFU) using special smart boots that relieve pressure from specific areas of the foot. DFUs affect 15% of patients with diabetes -; more than 1 million people annually -; and if inadequately treated, can lead to amputation. Individuals from racial and ethnic minority groups are more likely to develop DFUs, receive amputations, and experience complications, leading to a lower survival rate.

While pressure offloading boots are considered the gold standard of care for DFU, patients struggle with using them because of discomfort, aesthetics, and mobility restrictions. Armstrong’s team seeks to improve patient outcomes with a new smart boot design that allows for remote monitoring of patient activity and adherence to the treatment.

“This grant from the PhRMA Foundation empowers us to enhance our smart offloading boots, tailoring them to fit the unique cultural and behavioral aspects of minority populations who are most at risk for hospitalization and amputation,” Armstrong said. “Our project is a step forward in making state-of-the-art health care accessible and equitable for all, particularly those in underserved communities.”

Isakadze, a clinical cardiac electrophysiology fellow and incoming faculty at Hopkins’ School of Medicine, will lead a project to test a digital health intervention for the management of atrial fibrillation (Afib), the most common type of heart arrhythmia. Afib is associated with poor quality of life and increased risk of stroke, heart attack, and death. Evidence shows that modifying risk factors such as weight, physical activity, and tobacco and alcohol use can reduce Afib burden.

Isakadze’s team is working with diverse patients, clinicians, and key stakeholders to design and test an Afib care management program that integrates 1) an Apple watch to track heart health data 2) a mobile app to educate and empower patients in tracking their health and setting health goals, 3) a clinician dashboard with patient data from the mobile app and smartwatch, and 4) individualized weekly health coaching to promote adherence to the virtual program.

“Receiving the PhRMA Foundation grant will allow us to generate robust evidence to support the use of digital health technologies to enable risk factor modification for diverse patients with Afib and bridge the critical gap in Afib management,” Isakadze said. “I am confident that digital health tools have tremendous potential to reach people where they are and transform health care delivery.”

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April 25, 2024
Public funding for single embryo transfer cuts multifetal pregnancy rates in IVF

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In the era after the introduction of publicly funded in vitro fertilization (IVF) mandating elective single embryo transfer, the multifetal pregnancy rate decreased significantly for IVF, but the contribution of ovulation induction and intrauterine insemination (OI/IUI) to multifetal pregnancy still needs attention, according to a new study from ICES and Queen’s University.

Twins, triplets, and higher multifetal pregnancies are associated with some adverse outcomes in pregnancy and childbirth. Fertility treatments such as IVF and ovulation induction and intrauterine insemination (OI/IUI) are more likely to result in a multifetal pregnancy. In Canada, Ontario’s publicly funded fertility program mandated the use of elective single embryo transfer (eSET) in 2015.

In a new study from the journal JAMA Network Open, researchers evaluated the association between fertility treatment and multifetal pregnancies in Ontario for over 1 million pregnancies between 2006 and 2021. This is one of the first studies to include all forms of fertility treatments and accounted for fetal reductions that may have been performed earlier in a pregnancy.

While we found a substantial decrease in multifetal pregnancy rates for IVF after the mandate was introduced, we didn’t see the same decrease after OI/IUI. It’s more difficult to regulate multifetal pregnancies with this type of fertility treatment, because the type of protocols used and adherence to specific cancellation criteria may differ across clinics.”

Maria Velez, lead author, adjunct scientist at ICES and associate professor in the department of Obstetrics and Gynaecology at Queen’s University

Of the total number of pregnancies, 96.9% were from unassisted conception, 1.4% from OI/IUI and 1.7% from IVF. Compared to those who had unassisted conception, people who received fertility treatments tended to be older, lived in higher-income communities, and had more preexisting health conditions.

The overall rate of multifetal pregnancies declined from 2006 to 2021, but the decrease was greater for IVF pregnancies than for those conceived by OI/IUI. When comparing the time periods before and after the eSET mandate, the rate of multifetal pregnancies declined from 13% to 9% with OI/IUI, and from 29% to 7% with IVF.

Improvements in assisted reproductive technology (ART) have also influenced rates of multifetal pregnancies. Advances in technologies such as embryo culture media and elective freezing of all available embryos means higher success rates for pregnancy.

However, the authors say that “Future studies should address the cost-effectiveness of providing 1 vs multiple publicly funded IVF cycles, especially because some couples in Ontario still pursue privately paid IVF cycles, which can result in a higher rate of multifetal pregnancy and an inherently higher risk of maternal and neonatal morbidity.”

One limitation of the study was the lack of detail about those who underwent fetal reduction. The data also did not capture information about the type of medication used for OI/IUI, and IVF cycles would have included both private and publicly funded treatments.

Nevertheless, the findings show that changes to assisted reproductive technology and the introduction of a publicly funded IVF program in Ontario both contributed to a decrease in the risk of multifetal pregnancy.

“Future work should address the higher risk associated with OI/IUI, and changes may be needed to standardize protocols and cancellation policies,” says Velez.

Source:

Institute for Clinical Evaluative Sciences

Journal reference:

Velez, M. P., et al. (2024). Multifetal Pregnancy After Implementation of a Publicly Funded Fertility Program. JAMA Network Open. doi.org/10.1001/jamanetworkopen.2024.8496.

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April 25, 2024
Bivalent COVID-19 vaccine boosts immunity but needs to be updated

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A major bivalent COVID-19 vaccine induces production of neutralizing antibodies against the coronavirus that circulated at the start of the pandemic as well as subvariants of omicron, albeit less abundantly, according to a Brazilian study reported in the Journal of Medical Virology.

The study confirmed the vaccine’s effectiveness and its importance to control of the disease, while also showing that, more than three years after the first application of a COVID-19 vaccine in Brazil, the vaccination model should be similar to that adopted for influenza, with frequent adjustments to the formulation to prioritize more recent variants.

This was the first research project conducted to evaluate the immunity induced by the Pfizer-BioNTech bivalent vaccine (COMIRNATY Original/Omicron BA.4-5) in a group of Brazilian subjects. The scientists investigated the antibody neutralization response against different variants of SARS-CoV-2 using serum samples from 93 healthy volunteers (31 males and 62 females) aged between 16 and 84 years and living in Barreiras, Bahia state. Some of the volunteers had previously been given three or four doses of monovalent vaccines based only on the original strain of the virus first identified in Wuhan, China, such as Coronavac (Butantan Institute/Sinovac), Covishield (Oxford/AstraZeneca), or those of Janssen and Pfizer.

Others were also given as an extra booster the bivalent vaccine containing components of the original strain as well as omicron subvariants BA.4 and BA.5.

Serum samples collected from the volunteers were submitted to antibody neutralization assays using different strains of SARS-CoV-2: the original strain from the start of the pandemic; omicron (BA.1), predominant in 2021; and omicron subvariants FE.1.2 and BQ.1.1, predominant in Brazil more recently.

The study was funded by FAPESP (projects 20/05204‐7, 20/06409‐1, 20/08943‐5, 21/05661‐1, 22/11981‐1 and 23/01925‐0), and by the Brazilian Ministry of Science, Technology and Innovation (MCTI).

The study showed that the bivalent vaccine administered as a booster reinforced the immune response and was more effective in neutralizing omicron and its subvariants than in volunteers given only four shots of a monovalent vaccine. However, its main focus was still the original strain that predominated at the start of the pandemic, and the resulting competition limited medium- to long-term immunity against more recent variants, which are now more important epidemiologically.

This was expected because immune memory is based on cells capable of recognizing fractions of the virus and is reinforced by the number of contacts with the contaminant. The immune system will naturally react more against what it already knows, and the participants given the bivalent vaccine had already taken three or four doses of a monovalent vaccine.”

Jaime Henrique Amorim, last author of the article

Amorim is a professor at the Federal University of Western Bahia (UFOB) and a visiting researcher at the University of São Paulo’s Biomedical Sciences Institute (ICB-USP).

Model for the future

“Controlling a virus with the high transmission capacity of SARS-CoV-2 requires equally high vaccine coverage,” said Luís Carlos de Souza Ferreira, head of ICB-USP’s Vaccine Development Laboratory and a co-author of the article. “The results of the study show that bivalent vaccines are effective to achieve immunity against subvariants of omicron and that their administration has been fundamental to control novel variants.”

According to the researchers, another conclusion to be drawn from the findings is that future planning of vaccination policy should take into account the fact that the immune response induced by existing vaccines is mainly to the original strain, which has ceased circulating since 2020, and vaccines should have their formulation adjusted so that they no longer include these components.

“Forthcoming doses should be designed to combat the variants that are circulating now, instead of those that have disappeared, so that immunity is updated and reinforced in accordance with the current epidemiological situation, as it already is in the case of influenza vaccines,” Amorim said.

The joint first authors of the article are Milena Silva Souza and Jéssica Pires Farias, researchers at UFOB. The other co-authors are affiliated with institutions in Brazil and the United States.

Source:

São Paulo Research Foundation (FAPESP)

Journal reference:

Souza, M. S., et al. (2024). Neutralizing antibody response after immunization with a COVID‐19 bivalent vaccine: Insights to the future. Journal of Medical Virology. doi.org/10.1002/jmv.29416.

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April 25, 2024