Wednesday, January 11, 2023

Less than four in 100 men accepted to be sperm donors

Peer-Reviewed Publication

UNIVERSITY OF SHEFFIELD


Less than four in 100 men accepted to be sperm donors

  • An international team of researchers mapped the outcome of over 11,700 men who applied to be sperm donors in Denmark and the US
  • Less than four in 100 men end of the process and have samples frozen and released for treatments
  • Over half of the men who applied to be donors withdrew from the programme before having samples released and nearly a fifth of applicants were rejected because of a health issue or because they were a carrier for a genetic disease
  • Four in 10 donor candidates initially agreed to be identifiable, and it was more common for applicants in Denmark to agree to waive their anonymity than applicants in the US
  • The UK relies heavily on imported sperm from donors in the US and Denmark

Less than four in 100 men who apply to be sperm donors reach the end of the process and have samples frozen and released for treatments, according to a new study.

A European team of researchers led by the University of Sheffield, worked with the world’s largest sperm banks, Cryos International, to map the outcome of over 11,700 men who applied to be sperm donors.

The findings, published in the journal Human Reproduction, show that over half of the men (54.91 per cent) who applied to be donors at Cryos in Denmark and the US withdrew from the programme before having samples released for use.

Nearly a fifth of applicants (17.41 per cent) were rejected because of a health issue or because they were a carrier for a genetic disease or had an infectious disease which could not be treated.

The data also showed just over one in 10 of the applicants (11.71 per cent) failed a screening questionnaire about their lifestyle and another one in 10 (11.20 per cent) were rejected because their sperm quality was not good enough.

Lead author of the study, Professor Allan Pacey, Professor of Andrology and Head of the Department of Oncology and Metabolism at the University of Sheffield, said: “To our knowledge this is the largest study of sperm donor applicants outside China and given that the UK relies so heavily on imported sperm from the USA and Denmark it is important for us to understand the recruitment processes there and reassure ourselves that they are safe as well as see if there is anything we can do to improve them.”

Recent figures from the Human Fertilisation and Embryology Authority have shown that more than half of the new sperm donors registered in the UK were from imported sperm, mostly from sperm banks like Cryos in the US and Denmark.

Since 2006 it has been illegal in the UK to use sperm from donors who are unwilling to be identified to any people born from their donations. Therefore, in the new study, Professor Pacey and the team looked at how many of the donors at Cryos agreed to be identifiable compared to those that did not.

They found that more than four in 10 donor candidates (41.27 per cent) initially agreed to be identifiable, and it was more common for applicants in Denmark to agree to waive their anonymity than applicants in the USA.

Interestingly, the team found that as the screening and donation process continued (men donate regularly for many months) more of the donors who initially wanted to be anonymous, agreed to become identifiable.

Professor Pacey added: “The study with Cryos highlights how hard it is to become a sperm donor. It’s not like blood donation where once it’s done you can have a cup of tea and go home. Sperm donation is a regular commitment with lots of screening and regular testing as well as life-long implications for the donor if any children are born from their sample.

“What’s particularly fascinating is that more donors, who initially wanted to remain anonymous, were willing to be identifiable as the screening and donation process continued. This is particularly good news for patients in the UK undergoing fertility treatment, as it is a legal requirement for sperm donors to be identifiable to any children born from their donations.”

Dr Anne-Bine Skytte, Medical Director at Cryos International said: “We are very grateful to Professor Pacey and the team for their in depth analysis of sperm donors which has already been very valuable in helping Cryos look at its recruitment process and try to make them more efficient.

“If we can recruit donors more easily then this will help keep costs down for patients in the UK and elsewhere who often buy donor sperm with their own money because it’s not funded by the NHS.”

To be accepted as a sperm donor in the UK, men must be aged between 18 and 45 years old and be fit and healthy with good sperm quality. Donors undergo a range of screening tests for genetic conditions and infectious diseases as well as an analysis of their family medical history.

UK guidelines for sperm donor recruitment are published by the British Fertility Society and the recruitment and use of sperm donors in infertility treatments regulated by the Human Fertilisation and Embryology Authority.

Any males in the UK interested to donate sperm should contact their local licenced clinic or sperm bank (further details can be found here)

View the full paper: An analysis of the outcome of 11,712 men applying to be sperm donors in Denmark and the USA by Pacey, AA et al. Human Reproduction Journal: doi:10.1093/humrep/deac264

 

Plastic pollution in the oceans is an equity issue, says new UW-led report


Reports and Proceedings

UNIVERSITY OF WASHINGTON

Marine Plastics 

IMAGE: THIS ILLUSTRATION, BY SEATTLE-BASED ARTIST MARI SHIBUYA, DEPICTS HOW PLASTIC WASTE OF DIFFERENT SIZES CAN TRAVEL THROUGH THE MARINE ENVIRONMENT TO END UP IN FISH, ON BEACHES, OR INSIDE PEOPLE’S BODIES. view more 

CREDIT: MARI SHIBUYA

Many people are aware of plastic pollution in the oceans. Photos of turtles or seabirds entangled in plastic garbage first went viral in the 1990s, and the Great Pacific Garbage Patch is now the focus of highly publicized cleanup efforts.

Less recognized is how marine plastic waste affects human populations, and the unequal burden on different communities. A report, “Towards an Equitable Approach to Marine Plastics Pollution,” outlines the current situation and attempts to address the problem.

“We all benefit from plastics, but some people are paying more of the external costs in terms of the environmental damage, well-being issues and just horrendous scenes that they must live with in places they call home,” said project leader Yoshitaka Ota, a University of Washington professor of practice in marine and environmental affairs and director of The Nippon Foundation Ocean Nexus Center.

Increasingly, the greenhouse gases causing climate change are seen as an issue in which some countries produce most of the pollution while other countries or groups are more at risk from the long-term consequences. Plastic pollution, this report argues, is a similar issue for coastal communities.

The report, published in late November, includes 31 authors from nine countries. It incorporates case studies and analyses from around the world as well as larger, overarching recommendations for change.

The authors conclude that coastal communities most affected by marine plastic pollution should be better represented in drafting potential solutions. A free, virtual event in March will bring together stakeholders from around the world to draw up a road map for an equity-focused path to address marine plastics.

The Ocean Nexus Center was founded in 2019 as a 10-year initiative based in UW EarthLab that includes more than 20 member universities and organizations around the world. Its mission is to bring together equity and justice in the oceans on a global scale.

The recently published report covers topics such as:

  • A call to replace the term “plastic litter” with “plastic pollution.” The word “litter” frames the issue on a small scale that can be addressed with better waste collection, disposal or recycling, rather than broader industry-wide changes to production.
  • A discussion of the rise in plastic waste during the COVID-19 pandemic, through masks, gloves, face shields and a resurgence of single-use and individually wrapped products.
  • Chapters that provide place-based case studies, including interviews with local residents about their experiences with marine plastics. Locations include a fishing community in Ghana, coastal mangrove forests in Ecuador, and an island in southern Japan that includes both tourists and local residents.
  • Two analyses of waste cleanup programs — Washington state’s Marine Debris Action Plan and the “Fishing for Litter” program in the Netherlands.
  • A section with multiple authors focused on the island of Aotearoa, New Zealand. Maori perspectives have been disregarded in efforts to address marine plastic pollution, authors write, despite the greater impact and importance of marine environments for Maori people’s livelihood and culture.
  • A review of international rules for plastic waste disposal — a patchwork of regulations including the Basel Convention, a nonbinding agreement that the U.S. has not signed.
  • A critique of Coca-Cola Co.’s “World Without Waste” initiative as an example of industry-backed solutions to marine plastic pollution that focus on individual consumers, rather than bigger, more permanent solutions that could reduce plastic waste.

“Coca-Cola is the world’s biggest producer of plastic waste, and it serves as a case study of how multinational corporations engage in waste reduction and corporate social responsibility,” said lead author Jessica Vandenberg, a UW postdoctoral researcher in marine and environmental affairs who wrote the analysis of Coca-Cola’s initiative.

“As we highlight in the report, one of the key actions we see as imperative for addressing marine plastic pollution is refocusing the problem as one of plastics production, rather than as an issue of waste management,” Vandenberg said.

Mari Shibuya, a Seattle-based artist, created digital watercolor paintings that appear throughout the document. The report is funded by The Nippon Foundation and is intended to be an accessible, comprehensive summary of the issue that can be read by policymakers, educators and other audiences, Ota said.

The March event will bring together audiences to implement the report’s main recommendations. Visit The Nippon Foundation Ocean Nexus Center website to find forthcoming event details.

 

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For more information, contact Ocean Nexus marketing and communications lead Ariel Wang at arielyw@uw.edu, Ota at yota1@uw.edu or Vandenberg at jvandenb@uw.edu (note: Vandenberg is currently a visiting scholar at Wageningen University & Research in the Netherlands, on Central European Time).


Evidence about gun policies grows and supports laws to reduce violence

Reports and Proceedings

RAND CORPORATION

There is now supportive evidence that child-access-prevention laws reduce firearm homicides and self-injuries among youth, and that shall-issue concealed-carry laws and stand-your-ground laws increase levels of firearm violence, according to a new RAND Corporation report.

 

The findings are part of a new report updating RAND’s Science of Gun Policy research synthesis, which reviewed the existing scientific literature to assess the strength of available evidence about the effects of 18 commonly discussed gun policies on a range of outcomes, including injuries and deaths, mass shootings, defensive gun use, and participation in hunting and sport shooting.

 

Several other policies are now found by RAND to have moderate scientific evidence of effects, the second highest evidence rating used by the researchers. These include private-seller background-check requirements, which appear to decrease total homicides; laws setting the minimum age to purchase firearms at 21, which appear to decrease suicides among young people; and state laws prohibiting individuals subject to domestic-violence restraining orders from possessing firearms, which appear to decrease intimate-partner homicides.

 

The conclusions build on prior work by the RAND team that had already identified supportive evidence for two laws. Specifically, in the last update to this report in 2020, the team identified supportive evidence that child access prevention laws reduce intentional and unintentional firearm injuries and deaths among children, and that stand-your-ground laws increase firearm homicides. (Supportive is the project’s highest level of evidence for a policy.)

 

Overall, the updated report found that for eight gun policies, the new research results incorporated into the review were sufficient to upgrade previous conclusions to a higher level of evidence.

 

Three of those strengthened findings are for child-access prevention, concealed-carry and stand-your-ground laws. Other areas with upgraded evidence ratings compared to the prior RAND report include limited evidence that bans on high-capacity magazines may reduce mass shootings and mass shooting fatalities; that surrender laws, in combination with prohibitions related to violent offenses, may reduce firearm-related intimate-partner homicides; and that more restrictive background check laws may reduce firearm homicides.

 

“While the state of research about gun policies is less well developed than in many other areas of social science, there is a growing body of evidence that provides suggestive evidence about the effects of several frequently discussed policies,” said Rosanna Smart, lead author of the new analysis and an economist at RAND, a nonprofit, nonpartisan research organization.

 

“More than 45,000 Americans died by gun violence in 2020, and our hope is that by highlighting where scientific evidence is accumulating, we can help build consensus around a shared set of facts established through a transparent and impartial review process,” Smart said. “In so doing, we also mean to highlight areas where more and better information could make important contributions to establishing fair and effective gun policies.”

 

The updated version of the project identified 152 studies that investigated the causal effects of gun polices on any of the targeted outcomes, 29 more than the previous edition of the project released in 2020.

 

Across the 18 classes of policies studied, only child-access-prevention laws, shall-issue concealed carry laws and stand-your-ground laws had any evidence of effects that were classified as supportive for a particular conclusion.

 

These three policies aim to affect how legal gun owners can legally store, carry or use their firearms. They differ from many of the other policies considered by the project that primarily affect the acquisition of new firearms (such as background checks or waiting periods) or that are designed to affect a relatively small proportion of gun owners (such as prohibitions that target domestic violence offenders).

 

Based on the report’s findings, RAND researchers recommend that states without child-access prevention laws consider adopting them as a strategy to reduce total and firearm suicides, unintentional firearm injuries and deaths, and firearm homicides among youth. (In 2020, firearm-related injuries surpassed motor vehicle crashes as the leading cause of death among children and adolescents aged 1 to 19.)

 

RAND researchers say that while shall-issue concealed-carry laws and stand-your-ground laws were adopted on the belief that they would reduce violent victimization either by deterring violent crime or by reducing barriers to victims defending themselves, a growing body of scientific evidence suggests these laws have the opposite effect.

 

As such, the RAND report recommends that states with stand-your-ground laws consider repealing or amending them as a strategy for reducing firearm homicides. States with shall-issue or permitless-carry laws should consider whether other regulations, either through requirements implemented as part of the permitting process or as through other aspects of law (such as rules that may prevent firearm theft), might ensure the effects of concealed-carry laws are aligned with public safety.

 

In total, the report makes 19 recommendations about gun policies that policymakers might consider to reduce firearm violence, as well as ways to improve available evidence about the effects of such policies.

 

“Although the base of evidence has grown since our first edition of this report in 2018, there remain a surprisingly large number of firearm policy effects for which we have no studies, or available studies are inconclusive,” said Andrew Morral, co-author of the report and leader of  the RAND Gun Policy in America project. “This does not mean that these policies are ineffective; they might well be quite effective. Instead, this reflects shortcomings in the contributions that scientific study has been able to contribute to policy debates in these areas.”

 

The United States has a large stock of privately owned guns in circulation, estimated to be somewhere between 265 million and 393 million firearms.

 

More than 45,000 Americans die annually from deliberate and unintentional gun injuries, just over half of which are suicides. Another 50,000 to 150,000 Americans per year receive care in a hospital for a nonfatal gun injury.

 

Support for the RAND Gun Policy in America project was provided by Arnold Ventures. The report, “The Science of Gun Policy: A Critical Synthesis of Research Evidence on the Effects of Gun Policies in the United States [Third Edition],” is available at www.rand.org. Other authors of the project are Rajeev Ramchand, Amanda Charbonneau, Jhacova Williams, Sierra Smucker, Samantha Cherney and Lea Xenakis.

 

The RAND Social and Economic Well-Being division seeks to actively improve the health, and social and economic well-being of populations and communities throughout the world.

Children near airports may be exposed to dangerous levels of lead

Peer-Reviewed Publication

OXFORD UNIVERSITY PRESS USA

A new paper in PNAS Nexus, published by Oxford University Press, finds that children living near one California airport have higher lead levels in their blood. Since leaded gasoline is still used by piston-engine aircraft all around the United States, it appears children are still being exposed to toxic lead levels. This is despite policymakers’ efforts to reduce lead exposure since the 1970s.

Over the last four decades, the blood lead levels of children in the United States declined significantly due to policies that removed lead from paint, plumbing, food cans, and automotive gasoline. Scientists generally agree that the phase-out of tetraethyl lead from automotive gasoline under provisions of the Clean Air Act of 1970 was the most effective of these policies.

But leaded gasoline hasn’t disappeared entirely. It remains a standard part of aviation gasoline and is used by an estimated 170,000 piston-engine aircraft nationwide. Today, the use of lead-formulated aviation gasoline accounts for as much as two-thirds of lead emissions in the United States.

The U.S. Environmental Protection Agency estimates that four million people reside within half a mile of an airport servicing piston-engine planes. About 600 elementary or secondary schools are located near such facilities.

Researchers analyzed the blood lead levels of children under six years of age over a 10-year period (from 2011 to 2020) who lived near one such airport–Reid-Hillview Airport in Santa Clara County, California. The researchers found the probability that a child living near Reid-Hillview Airport had a blood lead level that exceeded the California Department of Public Health-defined threshold of 4.5 micrograms per decilitre increased the closer the child lived to the airport. The researchers also note that the blood lead levels were much higher when children live East (downwind) of the airport and find that child blood levels increase with piston-engine aircraft traffic and quantities of leaded aviation gasoline sold at the airport.

For children living a mile or more away from the airport, the probability of a blood sample that exceeded the threshold is 21.4% lower than for children living within a half mile of the airport. With respect to geographic direction, children residing east of the airport were 2.18 times more likely to present a blood lead level above the threshold of concern.  Adding to the evidence that exposure to aviation gasoline is a health risk to children, the researchers find that the blood lead levels of children residing within a half mile of the airport are especially responsive to an increase in piston-engine aircraft traffic. 

“Across an ensemble of tests, we find consistent evidence that the blood lead levels of children residing near the airport are pushed upward by the deposition of leaded aviation gasoline,” said the paper’s lead author, Sammy Zahran. “This indicates we should support policy efforts to limit aviation lead emissions to safeguard the welfare of at-risk children.”       

The paper “Leaded Aviation Gasoline Exposure Risk and Child Blood Lead Levels” is available (at midnight on January 10th) at: https://academic.oup.com/pnasnexus/article-lookup/doi/10.1093/pnasnexus/pgac285.

Direct correspondence to: 
Sammy Zahran
Professor and Associate Chair of Economics
Colorado State University
Fort Collins, Colorado
Sammy.Zahran@colostate.edu

To request a copy of the study, please contact:
Daniel Luzer 
daniel.luzer@oup.com

What if sodium in packaged foods was reduced for an entire continent?

A new study in the journal Hypertension speculates on the health impact of less salt in Australia’s packaged foods

Peer-Reviewed Publication

AMERICAN HEART ASSOCIATION

Research Highlights:

  • Reformulating packaged foods available in Australia to contain less sodium may save about 1,700 lives per year, according to a new study.
  • Using the World Health Organization’s (WHO) recommendations for reducing the population’s sodium intake, the researchers estimate following the WHO sodium guidance may also prevent nearly 7,000 annual diagnoses of heart disease, kidney disease and stomach cancer in Australia.

Embargoed until 4 a.m. CT/5 a.m. ET Tuesday, January 10, 2023

DALLAS, January 10, 2023 — Reformulating packaged foods in Australia to contain less sodium might save about 1,700 lives per year and prevent nearly 7,000 annual diagnoses of heart disease, kidney disease and stomach cancer, according to new research published today in Hypertension, an American Heart Association journal.

High sodium intake increases blood pressure, risk of heart disease and stroke, chronic kidney disease and stomach cancer. To reduce the incidence of these conditions, the World Health Organization (WHO) recommends reducing the population-wide average sodium intake by 30% by 2025, which limits total daily sodium intake per person to about 2 grams (g), or 2,000 milligrams (mg), per day. The U.S. Department of Agriculture’s Dietary Guidelines for Americans recommends that healthy adults limit sodium to less than 2,300 mg per day. Current daily sodium intake in the U.S. is estimated at 3,400 mg/day per person.

Most sodium in people’s diets comes from processed and packaged foods. The American Heart Association estimates that 75% or more of daily sodium intake in the U.S. is from processed/packaged foods and restaurant foods. Reducing sodium in packaged foods through product reformulation programs is considered by WHO as a “best buy” to prevent diseases related to high sodium intake. In 2021, the WHO released guidance for sodium levels in food categories that are the biggest contributors to sodium intake such as processed meats, bread and sauces. For example, the WHO benchmark for lunch meat is 540 mg of sodium per 100 g of product, and bread is 330 mg of sodium per 100 g of product. Many countries have implemented reformulation programs for processed foods; however, they may be poorly monitored and include fewer food categories than recommended by the WHO.

The Australian government established a voluntary reformulation program for 27 packaged food categories. The WHO benchmarks, however, include 58 packaged food categories.

“We had previously modeled the potential impact of the Australian program,” said the study’s co-lead author Kathy Trieu, M.P.H., Ph.D., lead author of the study and senior research fellow in food policy at The George Institute for Global Health, and a senior lecturer at the University of New South Wales, both in Sydney, Australia. “In this study, we wanted to estimate the potential number of additional premature deaths, new cases of disease and years lived with disability that may be averted with the WHO sodium benchmarks, which are above and beyond the Australian government’s sodium reformulation targets.”

In their previous study, Trieu and colleagues found that Australia’s plan reduced average sodium intake by 107 mg per day per person and may avert about 500 deaths, 1,900 new cases of cardiovascular disease, chronic kidney disease and stomach cancer (combined), and 7,355 disability-adjusted life years (DALYs) in Australia each year. DALYs are a measure of years of healthy life lost due to illness or premature death.

They applied the same statistical model to estimate the potential impact of extending the Australian plan to include all 58 packaged food categories in the WHO benchmarks. The model used national data from 2011-2012 on sodium intake, food composition and sales for the targeted food categories. The researchers first estimated the reduction in sodium intake that may occur if the WHO targets were met. Then, using published statistics on the relationship between sodium intake and high blood pressure, they calculated the potential effect of sodium reduction on rates of cardiovascular disease and chronic kidney disease. High blood pressure is a major risk factor for both conditions.

The impact on stomach cancer was calculated using risk estimates derived from published studies of sodium and stomach cancer. The analysis determined the potential number of deaths, new cases of disease and DALYs that may be avoided by following the WHO guidance.

The analyses estimated that implementing the WHO sodium targets in Australia may result in:

  • An average of 404 mg per day reduction in sodium for adults;
  • Approximately 1,770 fewer deaths from cardiovascular disease, kidney disease and stomach cancer each year, with most of the impact on deaths due to avoiding deaths from cardiovascular disease (1,450 of the total).
  • About 4,500 fewer new cases of cardiovascular disease, 2,050 fewer new cases of kidney disease and 350 fewer new cases of stomach cancer per year; and
  • A total of 25,670 fewer DALYs from the three conditions.

“Our findings indicate that compliance with WHO benchmarks compared with Australia’s current sodium targets may result in substantial health gains and prevent more than three times as many deaths and new cases of disease each year,” said Trieu, adding that the greater impact of the WHO benchmarks may be explained by both including more packaged food products and stricter sodium targets.

Study limitations include the use of national nutrition survey data that was collected in 2011-12 and based on a single 24-hour diet recall to estimate food consumption, therefore, this data may not reflect current sodium intake. In addition, estimates of disease burden may be less accurate than estimates of more easily measured outcomes such as death. Also, there may be other ways in addition to blood pressure that sodium reduction affects cardiovascular and kidney disease.

Co-authors are Daisy Coyle, Ph.D.; Emalie Rosewarne, M. Nutrition & Diet; Maria Shahid, M.P.H.; Rain Yamamoto, Ph.D.; Chizuru Nishida, Ph.D.; Bruce Neal, Ph.D.; Feng He, Ph.D.; Matti Marklund, Ph.D.; and Jason Wu, Ph.D. Authors’ disclosures are listed in the manuscript.

The study was funded by an Australian National Health and Medical Research Council Partnership Project.

Studies published in the American Heart Association’s scientific journals are peer-reviewed. The statements and conclusions in each manuscript are solely those of the study authors and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Association’s overall financial information are available here

Additional Resources:

About the American Heart Association

The American Heart Association is a relentless force for a world of longer, healthier lives. We are dedicated to ensuring equitable health in all communities. Through collaboration with numerous organizations, and powered by millions of volunteers, we fund innovative research, advocate for the public’s health and share lifesaving resources. The Dallas-based organization has been a leading source of health information for nearly a century. Connect with us on heart.orgFacebookTwitter or by calling 1-800-AHA-USA1.

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Disclaimer: AAAS and EurekAlert! are not responsible for the accura

University of Toronto scientists use machine learning to fast-track drug formulation development

New study demonstrates the potential for machine learning to accelerate the development of innovative drug delivery technologies

Peer-Reviewed Publication

UNIVERSITY OF TORONTO - LESLIE DAN FACULTY OF PHARMACY

Experts in pharmaceutical sciences and machine learning are working to accelerate new drug formulation 

IMAGE: [LEFT TO RIGHT] CHRISTINE ALLEN AND ALÁN ASPURU-GUZIK FROM THE UNIVERSITY OF TORONTO ARE COMBINING EXPERTISE IN PHARMACEUTICAL SCIENCES, AI AND MACHINE LEARNING TO DEVELOP NEW DRUG FORMULATIONS FASTER. view more 

CREDIT: STEVE SOUTHON

TORONTO, January 10, 2023 [Embargo 10 a.m. London Time] – Scientists at the University of Toronto have successfully tested the use of machine learning models to guide the design of long-acting injectable drug formulations. The potential for machine learning algorithms to accelerate drug formulation could reduce the time and cost associated with drug development, making promising new medicines available faster.

The study was published today in Nature Communications and is one of the first to apply machine learning techniques to the design of polymeric long-acting injectable drug formulations.

The multidisciplinary research is led by Christine Allen from the University of Toronto’s department of pharmaceutical sciences and Alán Aspuru-Guzik, from the departments of chemistry and computer science. Both researchers are also members of the Acceleration Consortium, a global initiative that uses artificial intelligence and automation to accelerate the discovery of materials and molecules needed for a sustainable future.

“This study takes a critical step towards data-driven drug formulation development with an emphasis on long-acting injectables,” said Christine Allen, professor in pharmaceutical sciences at the Leslie Dan Faculty of Pharmacy, University of Toronto. “We’ve seen how machine learning has enabled incredible leap-step advances in the discovery of new molecules that have the potential to become medicines. We are now working to apply the same techniques to help us design better drug formulations and, ultimately, better medicines.”

Considered one of the most promising therapeutic strategies for the treatment of chronic diseases, long-acting injectables (LAI) are a class of advanced drug delivery systems that are designed to release their cargo over extended periods of time to achieve a prolonged therapeutic effect. This approach can help patients better adhere to their medication regimen, reduce side effects, and increase efficacy when injected close to the site of action in the body. However, achieving the optimal amount of drug release over the desired period of time requires the development and characterization of a wide array of formulation candidates through extensive and time-consuming experiments. This trial-and-error approach has created a significant bottleneck in LAI development compared to more conventional types of drug formulation.

“AI is transforming the way we do science. It helps accelerate discovery and optimization. This is a perfect example of a ‘Before AI’ and an ‘After AI’ moment and shows how drug delivery can be impacted by this multidisciplinary research,” said Alán Aspuru-Guzik, professor in chemistry and computer science, University of Toronto who also holds the CIFAR Artificial Intelligence Research Chair at the Vector Institute in Toronto.

To investigate whether machine learning tools could accurately predict the rate of drug release, the research team trained and evaluated a series of eleven different models, including multiple linear regression (MLR), random forest (RF), light gradient boosting machine (lightGBM), and neural networks (NN). The data set used to train the selected panel of machine learning models was constructed from previously published studies by the authors and other research groups.

“Once we had the data set, we split it into two subsets: one used for training the models and one for testing. We then asked the models to predict the results of the test set and directly compared with previous experimental data. We found that the tree-based models, and specifically lightGBM, delivered the most accurate predictions,” said Pauric Bannigan, research associate with the Allen research group at the Leslie Dan Faculty of Pharmacy, University of Toronto.

As a next step, the team worked to apply these predictions and illustrate how machine learning models might be used to inform the design of new LAIs, the team used advanced analytical techniques to extract design criteria from the lightGBM model. This allowed the design of a new LAI formulation for a drug currently used to treat ovarian cancer. “Once you have a trained model, you can then work to interpret what the machine has learned and use that to develop design criteria for new systems,” said Bannigan. Once prepared, the drug release rate was tested and further validated the predictions made by the lightGBM model. “Sure enough, the formulation had the slow-release rate that we were looking for. This was significant because in the past it might have taken us several iterations to get to a release profile that looked like this, with machine learning we got there in one,” he said. 

The results of the current study are encouraging and signal the potential for machine learning to reduce reliance on trial-and-error testing slowing the pace of development for long-acting injectables. However, the study’s authors identify that the lack of available open-source data sets in pharmaceutical sciences represents a significant challenge to future progress. “When we began this project, we were surprised by the lack of data reported across numerous studies using polymeric microparticles,” said Allen. “This meant the studies and the work that went into them couldn’t be leveraged to develop the machine learning models we need to propel advances in this space,” said Allen. “There is a real need to create robust databases in pharmaceutical sciences that are open access and available for all so that we can work together to advance the field,” she said.

To promote the move toward the accessible databases needed to support the integration of machine learning into pharmaceutical sciences more broadly, Allen and the research team have made their datasets and  code and available on the open-source platform Zenodo.

“For this study our goal was to lower the barrier of entry to applying machine learning in pharmaceutical sciences,” said Bannigan. “We’ve made our data sets fully available so others can hopefully build on this work. We want this to be the start of something and not the end of the story for machine learning in drug formulation.”

 

 

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Media Contact:
Kate Richards
Leslie Dan Faculty of Pharmacy, University of Toronto
kate.richards@utoronto.ca
(416) 978 - 7117
 

About the Leslie Dan Faculty of Pharmacy, University of Toronto
The Leslie Dan Faculty of Pharmacy at the University of Toronto is Canada's top-ranked faculty of pharmacy, offering cutting-edge undergraduate and graduate programs. We are globally recognized for impactful pharmaceutical sciences research and fostering expert and innovative clinical practice. Our scientific research focuses on the role of pharmacists in the health care system, and the full scope of drug discovery and delivery. We advance education programs that develop leaders in science and clinical practice and work to strengthen the link between research, education, and patient care.

 

About the Acceleration Consortium, University of Toronto
Based at the University of Toronto, the Acceleration Consortium (AC) is a global community of academia, government, and industry who are accelerating the discovery of materials and molecules needed for a sustainable future, from renewable energy and biodegradable plastics to resistance evasive antibiotics. The AC builds self-driving labs that combine artificial intelligence (AI), robotics, and advanced computing to radically reduce the time and cost of bringing these materials to market.

Low concern and political distrust behind vaccine-resistance, new study finds


Peer-Reviewed Publication

UNIVERSITY OF KENT

With a return to the workplace and school, the UK Health Security Agency recently warned that cases of flu and COVID-19 are expected to soar throughout January. Currently, it is estimated that one in eight NHS beds are taken up by flu and COVID-19 patients – yet 22 million vaccines for these viruses have not been used.

A new paper, looking at the psychological reasons for people’s unwillingness to accept the COVID-19 vaccine, reveals two key factors to be people’s lack of concern for the consequences of contracting the virus together with their lack of faith in the government's actions.

Since the outbreak of the coronavirus pandemic in 2020, substantial efforts have been directed toward the development of effective vaccines.

The success of national vaccination campaigns is considered central to finally containing the virus and finding a way out of the pandemic. Yet, as seen this January with 9 million people who are still due to take a COVID-19 booster jab, and 13 million unused free flu shots, vaccine efficacy and safety are not enough to determine the success of these campaigns - vaccine acceptance among the public is also key. This is why it is so crucial to understand psychological reasons for vaccine hesitancy.

The study, conducted by Professor Dominic Abrams from the School of Psychology at the University of Kent, and Dr Fanny Lalot (University of Kent and University of Basel), tested the theory that COVID-19 vaccine hesitancy is a result of ‘distrustful complacency’ – a dangerous combination of low concern and low trust. The psychologists hypothesized that either concern or political trust should be sufficient to motivate people to get vaccinated, as the presence of one can compensate for the absence of the other. The absence of both concern and trust, however, ‘distrustful complacency’, would undermine that motivation, resulting in greater vaccine hesitancy.

Across two studies, 9,695 respondents from different parts of Britain reported their level of concern about COVID-19, their trust in the UK government, and their intention to accept or refuse the vaccine. Across the studies, respondents with both low trust and low concern were 26%–29% more hesitant to receive the vaccine, compared to those with both high trust and high concern.

The study showed that people who accept the vaccine do so because they are highly concerned about the consequences of the pandemic - for themselves and for others. Others do so because they trust the political institutions responsible for enacting the vaccination program. However, those who, for whatever reasons, do not trust these institutions and are also not concerned about the virus are much likelier to be hesitant about vaccination.

Professor Abrams said ‘Vaccines save lives but only if people are willing to take them. Our evidence shows that science and politics are powerfully interconnected. For scientific knowledge to make its contribution, people need to trust that politicians are using the evidence and advising wisely.’

Dr Lalot added ‘The importance of finding the same connection between trust, concern and vaccination intentions amongst White British, Muslim, and Black respondents, and generally across all nations in Britain. This underlines the importance of psychological perceptions regardless of demographic factors.’

ENDS

The paper ‘Distrustful Complacency and the COVID-19 Vaccine: How Concern and Political Trust Interact to Affect Vaccine Hesitancy’ is published on Wiley Online Library. The research is funded by Nuffield Foundation, and is part of a collaborative project ‘Beyond Us and Them’, between University of Kent and Belong – The Cohesion and Integration Network.

Dominic Abrams is a Professor of Social Psychology and the Director of the Centre for the Study of Group Processes in the School of Psychology at the University of Kent. He was recently awarded an OBE for services to social science in the New Year’s Honours list. His research examines all aspects of relations between different social groups and the behaviour of groups in general. Professor Abrams has extensive experience in the areas of equality and human rights, prejudice, discrimination, social attitudes and social change across the life course.

Dr Fanny Lalot is a postdoctoral researcher at the University of Basel and honorary scholar at the University of Kent. Her research interests revolve around social influence and behaviour change, motivation and goal systems, identity, group systems, and social and political trust.

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The University of Kent is a leading UK university producing world-class research, rated internationally excellent and leading the way in many fields of study. Our 20,000 students are based at campuses and centres in Canterbury, Medway, Brussels and Paris.  

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