Category: Medical Research & Technology

Categories : General Interest Medical Research & TechnologyTags :

Glenda Gray’s Fierce Fight for Science, the COVID-19 Ruckus, and the Bathroom Row about HIV Drugs

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Professor Glenda Gray, internationally known for her research in HIV vaccines and interventions to prevent transmission of HIV from mother to child, received the country’s highest honour, the Order of Mapungubwe, in 2013. (Photo: Biénne Huisman/Spotlight)

By Biénne Huisman

After a decade at the helm of the country’s primary health research funder, Professor Glenda Gray will focus again on doing the science. She tells Spotlight’s Biénne Huisman about her childhood, her passion for research, administering multi-million dollar grants, and a heated argument in the bathroom with an ANC bigwig.

Professor Glenda Gray, the first woman president and chief executive of South Africa’s Medical Research Council (SAMRC), has among others been described as outspoken, credible and tenacious. After a decade at the helm of the SAMRC, Gray retains her reputation for fearlessly speaking truth to power.

“Heading the SAMRC was definitely the best job of my life,” says Gray. “But I am excited about my future, it’s time for another best job. After ten years of doing science administration, it’s time to get back and do the science.”

Perhaps Gray’s fierce spirit was honed in her childhood, growing up in Boksburg on the East Rand, “on the wrong side of the tracks”. She laughs, remembering how American cable news channel ABC sub-titled her first TV interview, due to her strong “East Rand accent”.

Investing in research

From a childhood of counting cents, these days Gray administers multi-million dollar grants and passionately makes the case for greater investment in scientific research.

She says that while South Africa’s health department has competing priorities, ideally it should double or triple its allocation to research.

“We spend a lot of time trying to show the Department of Health how important science is. And so while there is commitment from them, they’re so busy worrying about services; healthcare workers, doctors, hospitals falling down, no equipment, no cancer treatment. And so, sometimes science is seen as esoteric and a luxury.”

Speaking to Spotlight during her lunch break at an SAMRC event in Cape Town, Gray adds: “Science gives you evidence to reduce morbidity and mortality. All the things that change people’s lives; like covid vaccines, ARVs, mother to child transmission interventions, typically these stem from research. And so, you can only improve outcomes if you fund research. Currently, the SAMRC gets around R750 million from government a year; in my view, around R2 to 3 billion a year is needed to really make profound investments in research.”

Supplementing the funding from the government, the SAMRC has scores of international funders and collaborators, such as the United States National Institutes for Health. One concern with such international donor funding is that local research may end up pandering to agendas set abroad.

Gray rejects this suggestion. “We [the SAMRC] always fund the ten most common causes of mortality and morbidity in South Africa. So the funders who work with us have to agree on funding what we deem our priorities.”

One of these priorities is transformation. “So I spent ten years of my life changing who we funded, where we funded, how we funded; changing the demographics of the SAMRC, creating an executive management committee that was diverse, and being able to attract a great black scientist [Professor Ntobeko Ntusi] to take over from me,” says Gray.

While having passed the public mantle onto Ntusi in July, the paediatrician and renowned HIV vaccinologist, named one of Time magazine’s 100 most influential people in 2017, will continue her HIV vaccine research. Gray is heading a major USAID funded study aimed at “galvanising African scientists, mostly women, into discovering and making an HIV vaccine.” She also holds tenure as a distinguished professor at the University of the Witwatersrand’s Infectious Diseases and Oncology Research Institute.

Give and take

Speaking to Spotlight, Gray reflects on managing the political side of the SAMRC – the intersection between politics and science: “As the president of the MRC, you have to be very brave and you have to be able to speak truth to power. Sometimes it’s hard, and sometimes it’s easy.”

This, she says, is a dance of give and take: “The relationship has to be flexible. Because, sometimes scientists are wrong and politicians are right. Sometimes politicians are wrong and scientists are right. And sometimes both are wrong, and sometimes both are right. And our egos can get in the way. You know: ‘Oh, you took me off the MAC [Ministerial Advisory Committee], now I’m not going to help you’. That’s not the right attitude to have…”

COVID-19 lockdown ruckus

Gray served on the Department of Health’s COVID-19 MAC at the height of the pandemic. In May 2020, she caused a ruckus for breaking away from the committee’s more measured counsel, turning to the press to criticise government’s lockdown regulations as “unscientific”.

She said the hard lockdown was causing unemployment and unnecessary hardship and malnourishment in poor families. Later as the hard lockdown started to lift, she spoke out against government’s continuation of restrictions on school going, the sale of certain foods and clothes like open-toe footwear, and the limits on outdoor exercise. “It’s almost as if someone is sucking regulations out of their thumb and implementing rubbish, quite frankly,” she told journalists at the time.

Then health minister Dr Zweli Mkhize rebuked Gray’s claims and sidelined her in the MAC before excluding her from a newly constituted MAC in September. The acting Director-General of Health, Anban Pillay, wrote to the SAMRC board urging them to investigate Gray’s conduct. As the fray deepened, the SAMRC board failed to back Gray. The council’s boardwas was acting in a “sycophantic manner aimed at political appeasement”, lamented a guest editorial published in the South African Medical Journal.

Despite this public falling-out, the following year, in February 2021, Gray worked with Mkhize to bring vaccines to South Africa’s healthcare workers.

“So basically at that stage government didn’t have a vaccine programme, and I bailed them out,” she tells Spotlight.

In February 2021, results from a clinical trial showed that the Oxford AstraZeneca COVID-19 vaccine – then intended for rollout in South Africa – performed poorly in preventing mild to moderate illness caused by the Beta variant of SARS-CoV-2, which was dominant at the time.

Gray says she was approached by Mkhize about an alternative vaccine – to which she responded by facilitating the procurement of 500 000 doses of the Johnson & Johnson vaccine through personal connections. These were officially rolled out to healthcare workers on February 17, when President Cyril Ramaphosa received his jab at the Khayelitsha District Hospital. Spotlight previously reported in more detail on the procurement of those first 500 000 doses.

“The vaccines arrived in Johannesburg at about midnight,” Gray recalls. “Then the plane with the president’s vaccine touched down in Cape Town at 12:20pm; and we had to rush it to Khayelitsha to have him vaccinated at one o’clock”.

A bathroom row with a minister

Gray is no stranger to fighting for policies and treatments based on scientific evidence. She recalls an altercation with former health minister Nkosazana Dlamini-Zuma in a bathroom at the presidential residence in Pretoria (Mahlamba Ndlopfu) in the late 1990s – the era of AIDS-denialism under then President Thabo Mbeki.

“Thabo Mbeki had a national AIDS plan and they were about to publish it. So there was a meeting; we were presenting, and we had data that mother to child transmission interventions were affordable, or that it was actually cheaper to give ARVs to a pregnant woman, than to treat a child who is HIV positive. But they kept on saying it was unaffordable, and that they wouldn’t be doing it. And then, when I saw Dlamini-Zuma in the bathroom, I got into a fight with her and said: ‘but it is affordable!’”

Early years in Boksburg

One of six children born to a “maverick father”, whip-smart but taken to getting involved in crazy schemes, and a mother who later in life became a Baptist minister, Gray says they grew up poor.

“My parents would often run out of money in the middle of the month, having to scrounge for food, borrow milk or buy on the book (credit arrangements). So I know what it’s like to be on the other side of privilege.”

Gray relays how neighbours would drop by at her childhood home to borrow cups of sugar, to spy on their family – as, during apartheid, her father would entertain friends of colour.

Gray matriculated from Boksburg High School in 1980. The next year she enrolled for medical school at Wits, working part-time to pay her way: “I worked at an ABC shoe store, Joshua Door, selling furniture, making Irish coffees at Ster Kinekor, waitressing…”

In 1993, as HIV exploded across the country; pregnant with her first child, Gray watched her own stomach expand while treating HIV-positive expectant mothers at Chris Hani Baragwanath Hospital. “In those days, there were no ARVs for children,” she recalls. “And so women had to navigate this joy of a new life, with the fact that death was looming over them.”

Today, Gray has three children and lives in Kenilworth in Cape Town.

Commenting on her reputation for standing up to pressure, she smiles. “My tongue has gotten me into trouble. How do I feel about that? I just want to make sure that as scientists we let politicians and society know the data and the evidence. I feel passionate about translating science, I feel passionate about evidence. I feel passionate about science changing the world.”

Republished from Spotlight under a Creative Commons licence.

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Categories : Medical Research & Technology NeurologyTags :

Looking Ahead after 100 Years of EEG: Experts’ Predictions

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Cognionics, founded by bioengineering alumnus Mike Yu Chi, has developed a wearable EEG headset that’s comparable to state of the art laboratory equipment. Credit: UC San Diego

Since the first recording in July 1924, human electroencephalography (EEG) has been integral to our understanding of brain function and dysfunction: most significantly in the clinical diagnosis of epilepsy, where the analysis of the EEG signal meant that a condition previously seen as a personality disorder was quickly redefined as a disorder of brain activity. 

Now, a century on, more than 500 experts from around the globe have been asked to reflect on the impact of this groundbreaking methodology, as well as on the challenges and priorities for the future. 

A survey led by University of Leeds academics, saw respondents – with 6685 years of collective experience – presented with possible future developments for EEG, ranging from those deemed ‘critical to progress’ to the ‘highly improbable,’ and asked to estimate how long it might be before they were achieved. The results are published in the journal Nature Human Behaviour.   

Futuristic innovations 

The list features an array of fascinating, futuristic innovations that experts believe could be achieved within a generation. This includes using EEG to enhance cognitive performance; early detection of learning disabilities; widespread use as a lie detector; and use as a primary communication tool for those with severe motor disabilities and locked-in syndrome. 

Real-time, reliable diagnosis of brain abnormalities such as seizures or tumours is believed to be just 10-14 years away, while the probability of reading the content of dreams and long-term memories is judged to be more than 50 years away by some experts, but dismissed by many as closer to science fiction than reality.  

It may be surprising to many that, according to the survey, within a generation we could all be carrying around our own, personal, portable EEG. 

The paper’s co-author Dominik Welke, Research Fellow in Leeds’ School of Psychology, said: “They could really become something like a smartphone: where almost everybody has access to them and can use them daily – ideally improving their life by providing meaningful insight into physiological factors.” 

He added: “One such positive, potential future use of EEG technology could be vigilance control for drivers or pilots. These work-safety systems could assist the user in identifying if they were falling asleep, then wake them up or tell the co-pilot they need to take over.” 

They could really become something like a smartphone: where almost everybody has access to them and can use them daily

Dominik Welke, Research Fellow at the University

The hardware involved in recording EEG is relatively basic, remaining unchanged – in principle – since it was first used by psychiatrist Hans Berger in Germany on July 6, 1924. What has drastically changed since then is the analysis of – and what we can do with – the now digitally-recorded data. 

Consisting of just electrodes and an amplifier, EEG systems are becoming increasingly cheap to produce, as well as more portable and user-friendly. Coupled with its non-invasive nature, there is little to prevent it from becoming more accessible to a wider audience.  

Reducing health inequalities 

While the prospect of EEG technology being widely used in gaming and VR – predicted to be only around 20 years away – will thrill gamers, the truly exciting possibility for scientists and clinicians is that this increasing accessibility will allow them to engage with communities traditionally excluded from EEG research, crucially, in low-income countries that cannot afford more complex imaging technology. 

Advances in AI-driven automation are also expected to improve and speed up analysis of complicated data.  

Dr Welke said: “Looking ahead to the future: from the hardware side, it’s comparatively cheap and easy to produce, and from the analysis and software side, with these new computing technologies, all the puzzle pieces are there to really roll out EEG to a very large user base. 

“As opposed to other methods out there – such as MRI, or implanted devices – EEG has the potential to make neuroimaging available to all the people in the world.”  

I think that EEG, when combined with technologies such as AI and virtual reality, could radically transform the ways in which we interact with machines, and in doing so, play an extremely important role in science and society over the next 100 years

Faisal Mushtaq, Professor of Cognitive Science and the Director of the Centre for Immersive Technologies at the University

The paper’s lead author, Faisal Mushtaq, Professor of Cognitive Science and the Director of the Centre for Immersive Technologies at the University, said: “Nearly all the data we currently have on the human brain comes from a very small segment of the world’s population. There is a growing recognition that this is hampering our ability to generalise findings and improve global brain health.

“EEG stands out as the most cost-effective and logistically feasible neuroimaging tool for worldwide use across diverse settings. This would help build a neuroscience that is inclusive and representative of the global population.  

He added: “Our partners at the Global Brain Consortium are laying the foundations for increasing reach in this way and I expect this will unlock new opportunities for groundbreaking discoveries on the mechanisms of brain function.” 

Ethical questions 

Alongside the optimism that emerging technologies are opening exciting new possibilities for EEG, the experts consulted also sounded a note of caution, with concerns that ranged from a lack of adherence to agreed standards and protocols to ethical questions created by novel commercial applications and the lure of ‘neuroenhancement’. 

Dr Welke said: “I’m sure some of the multi-national tech companies might be very interested in rolling out EEG or other neuroimaging technology, just to get more information on their users that hints at their preferences and emotions 24 hours a day. But should it be used in this way?  

“There are obvious concerns around cognitive freedom and mental privacy. This feeds back into the importance of ‘responsibility’ – the fact that new ways of using a technology are also likely to raise new ethical questions.” 

Another objective of the survey was to identify the priorities of the EEG community for guiding future efforts. Participants rated how important major developments and advancements in various domains of EEG research would be to their work. 

Professor Mushtaq said: “I think that EEG, when combined with technologies such as AI and virtual reality, could radically transform the ways in which we interact with machines, and in doing so, play an extremely important role in science and society over the next 100 years.

“But to ensure this, the neuroscience community—from academic, clinical and industry settings—must commit to promoting robust, ethical, inclusive, and sustainable practices that will help realise its enormous potential.” 

The work was conducted by more than 90 authors, ranging from early career researchers to eminent figures in the field, collectively known as the EEG100 consortium.  

It started out as a partnership between #EEGManyLabs – an international network of researchers from more than 30 countries assessing the replicability of the results of some of the most important and influential EEG experiments of psychological phenomena – and the Global Brain Consortium, a diverse network of brain researchers, clinicians and institutions committed to achieving improved and more equitable health outcomes worldwide. 

The paper’s last author, Pedro Antonio Valdés-Sosa, Director of China Cuba Laboratory for Neurotechnology at the University of Electronic Science and Technology of China/Cuban Neuroscience Center, said: “In several countries, including Cuba, we have demonstrated that EEG can mass-screen some nervous system disorders at a population level. This technology is especially appropriate when resources are limited, as they are in disengaged groups worldwide.

“There are hurdles to overcome to employ EEG at a global scale, but by doing so, we can hopefully improve millions more lives.” 

Dr Sadhana Sharma, Head of Bioscience for Health Strategy at the Biotechnology and Biological Sciences Research Council (BBSRC) – which funded the paper’s lead authors – said: “EEG technology has the potential to transform our day-to-day activities and how we diagnose and treat neurological conditions in the future, ensuring that insights into brain health are accessible to diverse populations worldwide.

“As we embrace developments in bioscience, our focus remains on fostering interdisciplinary collaborations that drive ethical, equitable and impactful advancements in brain science on a global scale.” 

Source: University of Leeds

Categories : Cardiovascular Disease Medical Research & TechnologyTags :

A Cuffless Smartphone App that Can Measure Blood Pressure

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Photo by Ivan Samkov on Pexels

Researchers at the University of Pittsburgh are pioneering a new approach to blood pressure monitoring, using the devices we carry with us every day. Ramakrishna Mukkamala, professor of bioengineering at Pitt’s Swanson School of Engineering, is passionate about developing accessible blood pressure (BP) detection tools. Instead of designing a new medical device to monitor BP, Mukkamala decided to take advantage of the sensors readily available in smartphones and figure out how to detect blood pressure with them. 

“The most significant thing you can do to reduce your risk of cardiovascular disease is to lower high blood pressure through lifestyle changes, but in underserved populations, many people don’t have access to blood pressure cuffs, regular doctor’s appointments, or even know it’s a problem,” Mukkamala said. “But they do have smartphones.”

Mukkamala’s team harnessed tools already built into most smartphones, like motion-sensing accelerometers, front cameras, and touch sensors to build an Android smartphone application that can measure an individual’s pulse pressure. The user performs a hand-raising motion while holding the smartphone to make a measurement. The results of the project, published in Scientific Reports, demonstrate a promising new technology that could uniquely help reduce the burden of systolic hypertension globally, particularly in underserved populations. 

Designing blood pressure technology for a touchscreen 

Turning a smartphone into a monitoring device is no easy task, as Vishaal Dhamotharan, graduate student in the Cardiovascular Health Tech Laboratory, found out through multiple iterations of app development. Because smartphones don’t have force sensing tools, a crucial element of the project was figuring out how to replicate the effects of a traditional blood pressure exam using only a cell phone, which the team solved by using a familiar force – gravity.

“Because of gravity, there’s a hydrostatic pressure change in your thumb when you raise your hands up above your heart, and using the phone’s accelerometer, you’re able to convert that into the relative change in pressure.” Dhamotharan said. 

By pairing this hand-raising motion with guided thumb maneuvers on the smartphone, the team was able to calculate each participant’s pulse pressure, the difference between systolic and diastolic numbers. For example, an individual with a BP measurement of 120/80 has a pulse pressure of 40. For Sanjeev Shroff, collaborator and bioengineering department chair, this publication is a promising advancement for blood pressure measurement devices. 

“Development of a cuffless blood pressure measurement device that does not require any external calibration is the holy grail – such a device currently does not exist,” Shroff said. “The research work reported in this publication is an important step in the right direction, and is also encouraging for additional work aimed at obtaining systolic, diastolic, and mean pressures.”

Although pulse pressure isn’t typically used in cardiovascular disease monitoring, the study revealed its significance as a metric for detecting hypertension, according to Céderick Landry, assistant professor at the University of Sherbrooke and former postdoctoral researcher in the lab. 

“Guidelines typically require doctors to measure both systolic and diastolic blood pressure, and pulse pressure is just the difference between the two.” Landry said. “We showed that if you only have access to pulse pressure, it’s still very correlated with hypertension, so part of our challenge now is changing the mentality on how to best measure things.”

Hypertension management within reach

This app could bring blood pressure monitoring software to any smartphone owner, enabling consistent self-monitoring and easy sharing of results with healthcare providers. This innovation is especially promising for managing hypertension, which can often be lowered through lifestyle changes such as reducing salt intake, quitting smoking and exercising regularly. 

“This app would be really useful in low-income settings where people may not even have existing access to blood pressure tools.” Dhamotharan said. “Being able to measure blood pressure more frequently would allow an individual to track any significant changes in blood pressure, monitor for hypertension, and be able to manage their conditions with that knowledge.” 

“The research is here – we just need some help making the technology better.” Landry said. “This is the first method of its kind, and even better, it’s something that we can start implementing right now.”

Source: University of Pittsburgh

Categories : Medical Research & TechnologyTags :

Researchers Attempted to Emulate a Clinical Trial Using Data from Real Patients

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Photo by National Cancer Institute on Unsplash

The method can be used to explore treatment effects in people underrepresented in clinical trials

Researchers used real-world clinical data to attempt to emulate a randomised controlled trial testing the effectiveness of two blood thinners, apixaban and warfarin, to prevent stroke in patients with non-valvular atrial fibrillation. The study, led by Emma Maud Powell at the London School of Hygiene and Tropical Medicine, UK, and publishing August 29th in the open-access journal PLOS Medicine, provides a method to explore the effects of treatments in patients who are underrepresented or excluded from clinical trials.

Patients experiencing atrial fibrillation – a potentially dangerous medical condition in which the upper chambers of the heart beat irregularly – will often be prescribed blood thinners such as apixaban or warfarin to prevent a stroke. However, these treatment recommendations are based on results from randomized controlled trials, and it is unknown if they are applicable to populations of patients who were not included in the trial or present only in very low numbers.

In the new study, researchers used routinely collected health data from patients in the United Kingdom to attempt to emulate a previous randomized controlled trial that compared the effectiveness of apixaban and warfarin. They attempted to emulate the patient eligibility, selection and analysis approaches as the previous trial. They found that patients prescribed apixaban had similar outcomes to patients prescribed warfarin, but unlike the previous trial, they did not find that apixaban was superior. The researchers observed the differences in results may have been linked to higher quality of warfarin control, sub-optimal dosing of apixaban, and differences in the ethnicity of patients and use of concomitant medications compared with the clinical trial population.

Overall, the study established that using an existing randomised controlled trial (the reference trial) as a guide for the design of observational analysis of real patient data is an effective and valid way to estimate the treatment effects and risks of blood thinners given to patients with atrial fibrillation. The methods developed in this study can be used to investigate the effects of these medications in patient groups that are excluded from or underrepresented in these clinical trials, such as the elderly, those with multiple conditions and people with a higher risk of bleeding. This method can also help medical researchers to understand whether results from randomized controlled trials are transferable to “real-world” practices, and provides a framework that can be adapted to investigate treatment effects for other conditions.

The authors add, “Our study aimed to emulate a reference trial in oral anticoagulants in patients with atrial fibrillation using routinely collected UK healthcare data. Reference-trial informed design provides a framework for the study of treatment effects in patient groups excluded from or under-represented in trials.”

Provided by PLOS

Categories : Genetics Medical Research & TechnologyTags :

Scientists Develop a Way to Turbocharge Genetic Therapy

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Source: Pixabay CC0

Gene therapy, the idea of fixing faulty genes with healthy ones, has held immense promise. But a major hurdle has been finding a safe and efficient way to deliver those genes.

Now, researchers at the University of Hawaiʻi’s John A. Burns School of Medicine (JABSOM) have made a significant breakthrough in gene editing technology that could revolutionise how we treat genetic diseases. Their new method offers a faster, safer, and more efficient way to deliver healthy genes into the body, potentially leading to treatments for hundreds of conditions.

Current methods can fix errors in genes, but they can also cause unintended damage by creating breaks in the DNA. Additionally, they struggle to insert large chunks of genetic material such as whole genes.

The new technique, developed by Dr Jesse Owens along with his team Dr Brian Hew, Dr Ryuei Sato and Sabranth Gupta, from JABSOM’s Institute for Biogenesis Research and Cell and Molecular Biology Department, addresses these limitations. They used laboratory evolution to generate a new super-active integrase capable of inserting therapeutic genes into the genome at record-breaking efficiencies.

“It’s like having a “paste” function for the human genome,” said Dr Owens. “It uses specially engineered ‘integrases’ to carefully insert healthy genes into the exact location needed, without causing breaks in the DNA. This method is much more efficient, with success rates of up to 96% in some cases.”

“This could lead to faster and more affordable treatments for a wide range of diseases, potentially impacting hundreds of conditions with a single faulty gene,” said Dr. Owens.

Faster treatment development and a broader application

The implications of this research extend beyond gene therapy. The ability to efficiently insert large pieces of DNA has applications in other areas of medicine.

When making cell lines to produce therapeutic proteins, the gene encoding the protein is usually randomly inserted into the genome, and it rarely lands in a location in the genome that is good for production. This is like searching for a needle in a haystack. Additionally, finding a cell with the gene inserted correctly and producing the desired protein can take many months.

Instead of searching for a needle in a haystack, Dr Owens’ technique makes a stack of needles. It delivers the gene directly to the desired location, significantly speeding up the development process.

“JABSOM takes pride in nurturing talented researchers like Jesse Owens, whose work has the power to create a global impact,” said Sam Shomaker, dean of the University of Hawaiʻi John A. Burns School of Medicine. “This research, conducted in our lab in the middle of the Pacific, has the potential to significantly improve the way we treat genetic diseases.”  

Dr Owens’ team is exploring how this technique could accelerate the development and manufacture of biologics and advanced therapies such as antibodies. Currently, finding the right cell line for efficient production can be a time-consuming process. However, Dr Owens’ new genome engineering tool can reduce the cell line development timeline and accelerate the manufacture of life-saving therapeutics. 

Source: University of Hawaii at Manoa

Categories : IT in Healthcare Medical Research & TechnologyTags :

New, Inexpensive Medical Computers that Run on Air

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Closeup of the pneumatic logic sensing device. (William Grover/UCR)

Medical engineers have developed a new, air-powered computer sets off alarms when certain medical devices fail. The invention is a more reliable and lower-cost way to help prevent blood clots and strokes – all without electronic sensors. 

Described in a paper in the journal Device, the computer not only runs on air, but also uses air to issue warnings. It immediately blows a whistle when it detects a problem with the lifesaving compression machine it is designed to monitor.

Intermittent pneumatic compression (IPC) devices are pneumatic leg sleeves that periodically squeeze a patient’s legs to increase blood flow. This prevents clots that lead to blocked blood vessels, strokes, or death. Typically, these machines are powered and monitored by electronics.

“IPC devices can save lives, but all the electronics in them make them expensive. So, we wanted to develop a pneumatic device that gets rid of some of the electronics, to make these devices cheaper and safer,” said William Grover, associate professor of bioengineering at UC Riverside and corresponding paper author.

Pneumatics move compressed air from place to place. Emergency brakes on freight trains operate this way, as do bicycle pumps, tire pressure gauges, respirators, and IPC devices. It made sense to Grover and his colleagues to use one pneumatic logic device to control another and make it safer.

This type of device operates in a similar way to electronic circuits, by making parity bit calculations. “Let’s say I want to send a message in ones and zeroes, like 1-0-1, three bits,” Grover said. “Decades ago, people realized they could send these three bits with one additional piece of information to make sure the recipient got the right message.” 

That extra piece of information is called a parity bit. The bit is a number – 1 if the message contains an odd number of ones, and 0 if the message contains an even number of ones. Should the number one appear at the end of a message with an even number of bits, then it is clear the message was flawed. Many electronic computers send messages this way. 

An air-powered computer uses differences in air pressure flowing through 21 tiny valves to count the number of ones and zeroes. If no error in counting has occurred, then the whistle doesn’t blow. 

If it does blow, that’s a sign the machine requires repairs. Grover and his students, in a video demonstrating the air computer, are shown damaging an IPC device with a knife, rendering it unusable. Seconds later, the whistle blows.

“This device is about the size of a box of matches. It replaces a handful of sensors as well as a computer,” Grover said. “So, we can reduce costs while still detecting problems in a device. And it could also be used in high humidity or high temperature environments that aren’t ideal for electronics.”

The IPC device monitoring is only one application for air computing. For his next project, Grover would like to design a device that could eliminate the need for a job that kills people every year: moving around grain at the top of tall silos. 

Tall buildings full of corn or wheat, grain silos are a common sight in the Midwest. Often times, a human has to go inside with a shovel to break up the grains and even out the piles inside. 

“A remarkable number of deaths occur because the grain shifts and the person gets trapped. A robot could do this job instead of a person. However, these silos are explosive, and a single electric spark could blow a silo apart, so an electronic robot may not be the best choice,” Grover said. “I want to make an air-powered robot that could work in this explosive environment, not generate any sparks, and take humans out of danger.” 

Air-powered computing is an idea that has been around for at least a century. People used to make air-powered pianos that could play music from punched rolls of paper. After the rise of modern computing, engineers lost interest in pneumatic circuits.

“Once a new technology becomes dominant, we lose awareness of other solutions to problems,” Grover said. “One thing I like about this research is that it can show the world that there are situations today when 100-plus-year-old ideas can still be useful.”

Source: University of California Riverside

Categories : Medical Research & TechnologyTags :

Systematic Biases on Race and Gender at Play in Clinical Trials

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Photo by National Cancer Institute on Unsplash

Randomized controlled trials, or RCTs, are believed to be the best way to study the safety and efficacy of new treatments in clinical research. However, a recent study from Michigan State University found that people of colour and white women are significantly underrepresented in RCTs due to systematic biases. 

The study, published in the Journal of Ethnicity in Substance Abuse, reviewed 18 RCTs conducted over the last 15 years that tested treatments for post-traumatic stress and alcohol use disorder. The researchers found that despite women having double the rates of post-traumatic stress and alcohol use disorder than men, and people of colour having worse chronicity than white people, most participants were white (59.5%) and male (about 78%). 

“Because RCTs are the gold standard for treatment studies and drug trials, we rarely ask the important questions about their limitations and failings,” said Nicole Buchanan, co-author of the study and professor in MSU’s Department of Psychology. “For RCTs to meet their full potential, investigators need to fix barriers to inclusion. Increasing representation in RCTs is not simply an issue for equity, but it is also essential to enhancing the quality of our science and meeting the needs of the public that funds these studies through their hard-earned tax dollars.”

The researchers found that the design and implementation of the randomised controlled trials contributed to the lack of representation of people of colour and women. This happened because trials were conducted in areas where white men were the majority demographic group and study samples almost always reflected the demographic makeup where studies occurred. Additionally, those designing the studies seldom acknowledged race or gender differences, meaning they did not intentionally recruit diverse samples.

Furthermore, the journals publishing these studies did not have regulations requiring sample diversity, equity or inclusion as appropriate to the conditions under investigation.

“Marginalized groups have unique experiences from privileged groups, and when marginalised groups are poorly included in research, we remain in the dark about their experiences, insights, needs and strengths,” said Mallet Reid, co-author of the study and doctoral candidate in MSU’s Department of Psychology. “This means that clinicians and researchers may unknowingly remain ignorant to how to attend to the trauma and addiction challenges facing marginalised groups and may unwittingly perpetuate microaggressions against marginalised groups in clinical settings or fail to meet their needs.”

Source: Michigan State University

Categories : Medical Research & TechnologyTags :

New Approach Accurately Identifies Medications’ Toxicity to the Liver

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The current method for assessing medication-related liver injury does not accurately reflect some medications’ toxicity to the liver, according to a new study led by University of Pennsylvania researchers. Hepatotoxicity classification has historically been determined by counting individual reported cases of acute liver injury (ALI). Instead, the researchers used real-world health care data to measure rates of ALI within a population and uncovered that some medications’ levels of danger to the liver are being misclassified. Their paper was published in JAMA Internal Medicine.

“From a clinical standpoint, knowing the rate of severe ALI after starting a medication in real-world data will help determine which patients should be monitored more closely with liver-related laboratory tests during treatment,” said senior author Vincent Lo Re, MD, MSCE, an associate professor of Medicine and Epidemiology. “Incidence rates of severe ALI can be a valuable tool for determining a medication’s toxicity to the liver and when patients should be monitored, since incidence rates provide a truer, real-world look at this toxicity. Case reports did not accurately reflect observed rates of ALI because they do not consider the number of persons exposed to a medication, and cases of drug-induced liver injury are often underreported.”

Within the study, 17 different medications had rates that exceeded five severe ALI events per 10 000 person-years. The team determined that 11 of these medications were in lower categories of hepatoxicity by case counts that were likely not reflective of their true risk, since their incidence rates revealed higher levels of toxicity. One of the medications that fell into this group was metronidazole, an antimicrobial that can be used to treat infections in the reproductive or gastrointestinal systems, as well as some dermatological conditions.

Incidence rates, the number of new cases of a disease within a time period divided by the number of people at risk for the disease, are a key measure for examining health in a population because they give a more complete picture than simple counting. For instance, a medication with 60 reports of liver injury would be considered the most hepatotoxic through the traditional method, using the raw number of reported liver injury cases. However, if that medication had 60 observed severe ALI events and was used by five million people, the incidence rate would be very low and likely point to the medication not being dangerous to the liver. However, if 60 severe ALI events were observed within a population of 1,000 patients, it would reflect a higher, potentially more important, rate of injury.

To determine incidence rates, Lo Re and his team, including lead author Jessie Torgersen, MD, MHS, MSCE, an assistant professor of Medicine, examined electronic medical record data on almost 8 million people provided by the United States Veterans Health Administration that had been compiled from 2000 through 2021. Each person did not have pre-existing liver or biliary disease when they began taking any of the 194 medications that were studied. Each of those medications were analysed due to suspicion that they could cause harm to the liver, since each had more than four published reports of liver toxicity associated with their use.

On the other side of the hepatotoxicity coin, the researchers found eight medications that were classified as the most hepatotoxic based on the number of published case reports, but should actually be in the least liver-toxic group, with incidence rates of less than one severe ALI event per 10 000 person-years. For example, rates of severe ALI for statin medications, often used for high cholesterol, were in the group that had fewer than one event per 10 000 person-years.

“The systematic approach that we developed enables successful measurement of the rates of liver toxicity after starting a medication,” Lo Re said. “It wasn’t surprising that the case report counts did not accurately reflect observed rates of severe acute liver injury given the inherent limitations with case reports.”

With these findings, the researchers hope that there might soon be mechanisms established within electronic medical records to alert clinicians to closely monitor the liver-related laboratory tests of patients who start a medication with a high observed rate of severe ALI.

“Importantly, our approach offers a method to allow regulatory agencies and the pharmaceutical industry to systematically investigate reports of drug-induced ALI in large populations,” Lo Re said.

Source: University of Pennsylvania

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Sonic ‘Tweezers’ can Manipulate Objects inside the Body

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Photo by Pawel Czerwinski on Unsplash

In 2018, Arthur Ashkin won the Nobel Prize in Physics for inventing optical tweezers: laser beams that can be used to manipulate microscopic particles. While useful for many biological applications, optical tweezers require extremely controlled, static conditions to work properly.

“Optical tweezers work by creating a light ‘hotspot’ to trap particles, like a ball falling into a hole. But if there are other objects in the vicinity, this hole is difficult to create and move around,” says Romain Fleury, head of the Laboratory of Wave Engineering in EPFL’s School of Engineering.

Fleury and postdoctoral researchers Bakhtiyar Orazbayev and Matthieu Malléjac have spent the last four years trying to move objects in uncontrolled, dynamic environments using soundwaves. In fact, the team’s method – wave momentum shaping – is entirely indifferent to an object’s environment or even its physical properties. All the information that’s required is the object’s position, and the soundwaves do the rest.

“In our experiments, instead of trapping objects, we gently pushed them around, as you might guide a puck with a hockey stick,” Fleury explains.

The unconventional method, funded by the Swiss National Science Foundation (SNSF) Spark program, has been published in Nature Physics in collaboration with researchers from the University of Bordeaux in France, Nazarbayev University in Kazakhstan, and the Vienna University of Technology in Austria.

Very simple, very promising

If soundwaves are the hockey stick in Fleury’s analogy, then a floating object like a ping-pong ball is the puck. In the lab’s experiments, the ball was floating on the surface of a large tank of water, and its position was captured by an overhead camera. Audible soundwaves emitted from a speaker array at either end of the tank directed the ball along a pre-determined path, while a second array of microphones ‘listened’ to the feedback, called a scattering matrix, as it bounced off of the moving ball. This scattering matrix, combined with the camera’s positional data, allowed the researchers to calculate in real time the optimal momentum of the soundwaves as they nudged the ball along its path.

“The method is rooted in momentum conservation, which makes it extremely simple and general, and that’s why it’s so promising,” Fleury says.

He adds that wave momentum shaping is inspired by the optical technique of wavefront shaping, which is used to focus scattered light, but this is the first application of the concept to moving an object. What’s more, the team’s method is not limited to moving spherical objects along a path: they also used it to control rotations, and to move more complex floaters like an origami lotus.

Mimicking conditions inside the body

Once the scientists succeeded in guiding a ping-pong ball, they performed additional experiments with both stationary and moving obstacles designed to add inhomogeneity to the system. Successfully navigating the ball around these scattering objects demonstrated that wave momentum shaping could perform well even in dynamic, uncontrolled environments like a human body. Fleury adds that sound is a particularly promising tool for biomedical applications, as it is harmless and noninvasive.

“Some drug delivery methods already use soundwaves to release encapsulated drugs, so this technique is especially attractive for pushing a drug directly toward tumour cells, for example.”

Source: Ecole Polytechnique Fédérale de Lausanne

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Ancient Medicinal Minerals Inspire New Tissue Repair Technology

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Photo by MJ RAHNAMA

For centuries, civilizations have used naturally occurring, inorganic materials for their perceived healing properties. Egyptians thought green copper ore helped eye inflammation, the Chinese used cinnabar for heartburn, and Native Americans used clay to reduce soreness and inflammation.

Today, researchers at Texas A&M University are still discovering ways that inorganic materials can be used for healing.

In two recently published articles, Dr Akhilesh Gaharwar, a Tim and Amy Leach Endowed Professor in the Department of Biomedical Engineering, and Dr Irtisha Singh, assistant professor in the Department of Cell Biology and Genetics, uncovered new ways that inorganic materials can aid tissue repair and regeneration.

The first article, published in Acta Biomaterialia, explains that cellular pathways for bone and cartilage formation can be activated in stem cells using inorganic ions. The second article, published in Advanced Science, explores the usage of mineral-based nanomaterials, specifically 2D nanosilicates, to aid musculoskeletal regeneration.

“These investigations apply cutting-edge, high-throughput molecular methods to clarify how inorganic biomaterials affect stem cell behavior and tissue regenerative processes,” Singh said.

The ability to induce natural bone formation holds promise for improvements in treatment outcomes, patient recovery times and the reduced need for invasive procedures and long-term medication.

“Enhancing bone density and formation in patients with osteoporosis, for example, can help mitigate the risks of fractures, lead to stronger bones, improve quality of life and reduce healthcare costs,” Gaharwar said. “These insights open up exciting prospects for developing next-generation biomaterials that could provide a more natural and sustainable approach to healing.”

Gaharwar said the newfound approach differs from current regeneration methods that rely on organic or biologically derived molecules and provides tailored solutions for complex medical issues.

“One of the most significant findings from our research is the ability of these nanosilicates to stabilise stem cells in a state conducive to skeletal tissue regeneration,” he said. “This is crucial for promoting bone growth in a controlled and sustained manner, which is a major challenge in current regenerative therapies.”

Gaharwar recently received a grant for his work in using inorganic biomaterials in conjunction with 3D bioprinting techniques to design custom bone implants for reconstructive injuries.

“In reconstructive surgery, particularly for craniofacial defects, induced bone growth is crucial for restoring both function and appearance, vital for essential functions like chewing, breathing and speaking,” he said. “Inducing bone formation has several critical applications in orthopaedics and dentistry.”

“This approach not only bridges ancient practices with modern scientific methods but also minimises the use of protein therapeutics, which carry risks of inducing abnormal tissue growth and cancerous formations,” Gaharwar said. “Collectively, these findings elucidate the potential of inorganic biomaterials to act as powerful mediators in tissue engineering and regenerative strategies, marking a significant step forward in the field.”

Source: Texas A&M University