from the world's big
Duke University researchers might have solved a half-century old problem.
- Duke University researchers created a hydrogel that appears to be as strong and flexible as human cartilage.
- The blend of three polymers provides enough flexibility and durability to mimic the knee.
- The next step is to test this hydrogel in sheep; human use can take at least three years.
Duke researchers have developed the first gel-based synthetic cartilage with the strength of the real thing. A quarter-sized disc of the material can withstand the weight of a 100-pound kettlebell without tearing or losing its shape.
Photo: Feichen Yang.<p>That's the word from a team in the Department of Chemistry and Department of Mechanical Engineering and Materials Science at Duke University. Their <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/adfm.202003451" target="_blank">new paper</a>, published in the journal<em> </em>Advanced Functional Materials, details this exciting evolution of this frustrating joint.<br></p><p>Researchers have sought materials strong and versatile enough to repair a knee since at least the 1970s. This new hydrogel, comprised of three polymers, might be it. When two of the polymers are stretched, a third keeps the entire structure intact. When pulled 100,000 times, the cartilage held up as well as materials used in bone implants. The team also rubbed the hydrogel against natural cartilage a million times and found it to be as wear-resistant as the real thing. </p><p>The hydrogel has the appearance of Jell-O and is comprised of 60 percent water. Co-author, Feichen Yang, <a href="https://today.duke.edu/2020/06/lab-first-cartilage-mimicking-gel-strong-enough-knees" target="_blank">says</a> this network of polymers is particularly durable: "Only this combination of all three components is both flexible and stiff and therefore strong." </p><p> As with any new material, a lot of testing must be conducted. They don't foresee this hydrogel being implanted into human bodies for at least three years. The next step is to test it out in sheep. </p><p>Still, this is an exciting step forward in the rehabilitation of one of our trickiest joints. Given the potential reward, the wait is worth it. </p><p><span></span>--</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
An algorithm may allow doctors to assess PTSD candidates for early intervention after traumatic ER visits.
- 10-15% of people visiting emergency rooms eventually develop symptoms of long-lasting PTSD.
- Early treatment is available but there's been no way to tell who needs it.
- Using clinical data already being collected, machine learning can identify who's at risk.
The psychological scars a traumatic experience can leave behind may have a more profound effect on a person than the original traumatic experience. Long after an acute emergency is resolved, victims of post-traumatic stress disorder (PTSD) continue to suffer its consequences.
In the U.S. some 30 million patients are annually treated in emergency departments (EDs) for a range of traumatic injuries. Add to that urgent admissions to the ED with the onset of COVID-19 symptoms. Health experts predict that some 10 percent to 15 percent of these people will develop long-lasting PTSD within a year of the initial incident. While there are interventions that can help individuals avoid PTSD, there's been no reliable way to identify those most likely to need it.
That may now have changed. A multi-disciplinary team of researchers has developed a method for predicting who is most likely to develop PTSD after a traumatic emergency-room experience. Their study is published in the journal Nature Medicine.
70 data points and machine learning
Image source: Creators Collective/Unsplash
Study lead author Katharina Schultebraucks of Columbia University's Department Vagelos College of Physicians and Surgeons says:
"For many trauma patients, the ED visit is often their sole contact with the health care system. The time immediately after a traumatic injury is a critical window for identifying people at risk for PTSD and arranging appropriate follow-up treatment. The earlier we can treat those at risk, the better the likely outcomes."
The new PTSD test uses machine learning and 70 clinical data points plus a clinical stress-level assessment to develop a PTSD score for an individual that identifies their risk of acquiring the condition.
Among the 70 data points are stress hormone levels, inflammatory signals, high blood pressure, and an anxiety-level assessment. Says Schultebraucks, "We selected measures that are routinely collected in the ED and logged in the electronic medical record, plus answers to a few short questions about the psychological stress response. The idea was to create a tool that would be universally available and would add little burden to ED personnel."
Researchers used data from adult trauma survivors in Atlanta, Georgia (377 individuals) and New York City (221 individuals) to test their system.
Of this cohort, 90 percent of those predicted to be at high risk developed long-lasting PTSD symptoms within a year of the initial traumatic event — just 5 percent of people who never developed PTSD symptoms had been erroneously identified as being at risk.
On the other side of the coin, 29 percent of individuals were 'false negatives," tagged by the algorithm as not being at risk of PTSD, but then developing symptoms.
Image source: Külli Kittus/Unsplash
Schultebraucks looks forward to more testing as the researchers continue to refine their algorithm and to instill confidence in the approach among ED clinicians: "Because previous models for predicting PTSD risk have not been validated in independent samples like our model, they haven't been adopted in clinical practice." She expects that, "Testing and validation of our model in larger samples will be necessary for the algorithm to be ready-to-use in the general population."
"Currently only 7% of level-1 trauma centers routinely screen for PTSD," notes Schultebraucks. "We hope that the algorithm will provide ED clinicians with a rapid, automatic readout that they could use for discharge planning and the prevention of PTSD." She envisions the algorithm being implemented in the future as a feature of electronic medical records.
The researchers also plan to test their algorithm at predicting PTSD in people whose traumatic experiences come in the form of health events such as heart attacks and strokes, as opposed to visits to the emergency department.
An article in Journal of Bioethical Inquiry raises questions about the goal of these advocacy groups.
- Two-thirds of American consumer advocacy groups are funded by pharmaceutical companies.
- The authors of an article in Journal of Bioethical Inquiry say this compromises their advocacy.
- Groups like the National Alliance on Mental Illness act more like lobbyists than patient advocates.
The Corruption That Brought Prozac to Market — Robert Whitaker, Journalist<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="bea9cff2b25efc18b663a011a679ba16"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/UyaJExxFPAE?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Consumer-oriented groups gained steam over the ensuing decades. Their efforts helped inspire the 1938 Food, Drug, and Cosmetic Act after over 100 people (mostly children) died from a sanctioned drug, Sulfanilamide. If not for the hard work of these advocates, this case might have been overlooked.</p><p>Early efforts also focused on the food industry, which was increasingly using chemical preservatives. The origin of Consumer Reports can be found in the consumer advocacy movement. Both the food and drug industries were getting a free pass to experiment on citizens with few repercussions.</p><p>These movements provided a social foundation for important advocacy work in the second half of the century. Female-led groups evolved to focus on women's reproductive rights, AIDS, and mental health. As the authors write, these groups struck a balance between working <em>with</em> and <em>against</em> current trends. Sometimes you need to craft legislation with officials; at other times, you have to rage against the machine with everything you've got. </p><p>Advocacy marked an important turning point in public health (and culture in general). These groups were tired of placating to a medical model that treated the male body as the standard. This wasn't limited to anatomy. As I <a href="https://bigthink.com/coronavirus/pandemic-warnings-rp-eddy" target="_self">wrote about last week</a>, a high-profile 1970s-era conference about the role of women on Wall St featured no women on stage. You can imagine what reproductive health looked like during that time. </p><p>Advocacy groups made real impact in public health. Then the money began pouring in. </p><p style="margin-left: 20px;">"These groups were funded largely by individual donations with some foundation support, but in the late 1980s, newer women's health groups moved to professionalize, effectively splitting the women's health movement."</p><p>A number of groups resist corporate ties to this day, such as the National Women's Heath Network and Breast Cancer Action. Too often, however, groups argue that their existence depends on corporate funding. This can lead to uncomfortable compromises. </p><p>An estimated two-thirds of patient advocacy groups in America accept funds from the pharmaceutical industry. Pharma companies gave <a href="https://link.springer.com/content/pdf/10.1007/s11673-019-09956-8.pdf" target="_blank">at least $116 million</a> to such groups in 2015 alone.</p><p>For example, over a three-year period, the National Alliance on Mental Illness (NAMI), which was founded by two mothers whose sons suffered from schizophrenia, received nearly $12 million from 18 pharmaceutical companies. The largest donor was Prozac manufacturer, Eli Lilly. By 2008, three-quarters of NAMI's budget was funded by the pharmaceutical industry. It gets worse:</p><p style="margin-left: 20px;">"An Eli Lilly executive was even 'on loan' to NAMI, paid by Eli Lilly, while he worked out of the NAMI office on 'strategic planning.'"</p>
A customer waiting for his medication at the Headache Bar in a pharmacy in Sydney, Australia. Among the items on sale are 'Paigees with Chlorophyll' and Alka Seltzer on tap.
Photo by Dennis Rowe/BIPs/Getty Images<p>This influx of cash skews public understanding of drugs. It also influences advocates to overlook real problems caused by pharmaceutical interventions, especially when it comes to mental health.<br></p><p>For a real-world example, consider how Xanax came to market. As journalist Robert Whitaker <a href="https://www.youtube.com/watch?v=2e829xdb4AA" target="_blank">explains</a>, an <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463502/?page=1" target="_blank">initial study</a> was conducted to determine efficacy in treating panic attacks. After four weeks, Xanax was outperforming placebo, which is common with benzodiazepines over short-term usage. But it wasn't a four-week study; it was a 14-week study.</p><p>At the end of eight weeks, there was no difference in efficacy between Xanax and placebo.</p><p>At the conclusion of the study after 14 weeks, the placebo outperformed Xanax. By a lot.</p><p>Why is Xanax still prescribed for panic attacks? Because the pharmaceutical company, Upjohn, only published the four-week data. The 14-week data was not in its favor. Nearly forty years later, over <a href="https://www.statista.com/statistics/781816/alprazolam-sodium-prescriptions-number-in-the-us/" target="_blank">25 million</a> Americans receive a prescription despite its <a href="https://drugabuse.com/xanax/effects-use/" target="_blank">long list</a> of side effects and addictive profile. </p><p>As the authors note, many consumers are not aware of how advocacy groups are funded.</p><p style="margin-left: 20px;">"An international study of groups in the United States, United Kingdom, Australia, Canada, and South Africa found that the extent of relationships with industry was inadequately disclosed in websites that addressed ten health conditions: cancer, heart disease, diabetes, asthma, cystic fibrosis, epilepsy, depression, Parkinson's disease, osteoporosis, and rheumatoid arthritis."</p><p>That's a tangled web of relationships. Pharmaceutical industry funding negatively impacts the work advocacy groups should be focused on: protecting us. NAMI, for example, claims that as a "natural ally" to the pharmaceutical industry, it helps consumers access "all scientifically proven treatments." When the industry ignores evidence of long-term damage caused by its treatments, you have to wonder what's being advocated. </p><p>Although, as the authors conclude, that question is easy to answer. </p><p style="margin-left: 20px;">"Instead of drawing insights from patient experience to set organizational agendas and challenge industry agendas, today's groups are silent on high prices and drug harms, oppose efforts to regulate these basic rights, and demand access to drugs that challenge the safety and effectiveness."</p><p><span></span>--</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
Innovative drugs are sometimes held up due to old-fashioned human biases.
- When new drugs are similar to popular drugs on the market, FDA approval takes up to 75 percent longer.
- Texas McCombs Professor Francisco Polidoro Jr. reviewed 291 drugs over a 35-year period.
- Polidoro believes that potential coronavirus treatments or vaccines could help the FDA improve upon this longstanding bias.
Why vaccines are absolutely necessary | Larry Brilliant | Big Think<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="7f681e7e08a6ac9cea06ae50e6bbd7b5"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/ffiw6K3rjiU?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>That leaves us in a bind: our brain simultaneously seeks novelty and is resistant to change. Installing a new app on your phone is easy. Discovering a cheaper phone that performs better than your current brand brings with it layers of anxiety. This low-stakes example is amplified when the same cognitive process plays out in life-or-death situations, as is the case in drug development.</p><p>Polidoro begins his article with one question: "How does knowledge about different technologies that exist in a domain affect the time it takes for regulatory agencies to review an innovation in that domain?" While drug discovery and development typically produces a high failure rate around the world, the FDA approves "the vast majority of new drug applications." This makes the agency an ideal case study for his question. </p><p>Polidoro focuses his research on the time between submission of a new drug application and FDA approval. Clinical trials have been conducted; the drug has met certain criteria. While we assume FDA approval implies that the drug works, journalist Robert Whitaker <a href="https://bigthink.com/mind-brain/antidepressants-dangers" target="_self">recently explained to Big Think</a> that the process is not so clear-cut. </p><p style="margin-left: 20px;">"Let's say you have a drug that provides a relief of symptoms in 20 percent of people. In placebo it's 10 percent. How many people in that study do not benefit from the drug? Nine out of 10. How many people are exposed to the adverse effects of the drug? 100 percent. They'll pass that drug because it meets this small standard of benefit over placebo. And they're not subtracting the risk; they're just warning of the risk."</p><p>These data points shed light on the FDA's thought process: a drug only needs to perform better than placebo <em>and</em> the agency approves most new drugs. Inherent biases are already on display. Polidoro writes that innovative drugs are subject to another: new drugs take 75 percent longer to be approved when going up against popular pre-existing drugs. </p>
This picture taken on May 23, 2020 shows a laboratory technician holding a dose of a COVID-19 novel coronavirus vaccine candidate ready for trial on monkeys at the National Primate Research Center of Thailand at Chulalongkorn University in Saraburi.
Photo by Mladen Antonov/AFP via Getty Images<p>From a consumer perspective, this might make sense: if other drugs already perform the same function, why flood the market with new drugs? Of course, this has to be measured on a case-by-case basis. If the pre-existing drug has numerous side effects, and a new drug minimizes risk, you'd want that on the shelves sooner than later.</p><p>However, the reverse is also true, especially when patents are considered. Pharmaceutical companies are notorious for attempting to extend patents by changing a single molecule. Even such a seemingly small change can produce negative effects downstream. While the clinical trial threshold appears to be high, it's impossible to gauge long-term effects of any drug. We don't have decades to wait before releasing a drug to market. </p><p>Polidoro <a href="https://medium.com/texas-mccombs/new-era-requires-new-approach-to-drug-approvals-b814eae9418" target="_blank">describes</a> the trend succinctly: </p><p style="margin-left: 20px;">"Regulators search for solutions in the neighborhood of what they already know. They have a harder time when the next big thing emerges."</p><p>He expects the pipeline to approval for COVID-19 treatments or vaccines to run more smoothly than with past examples. The urgency will allow regulators to be less cautious in the hopes of helping the greatest number of people, a trend that could set a new precedent. "It may be more complicated for them at first," he concludes, "but in the long run, we will all be better off."</p><p>The scientific process will always be beholden to human habits. For now, it's the best process we have. Time will tell if Polidoro's optimism pans out. </p><p>--</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
In spite of a government mandate, females are often treated as afterthoughts in scientific research.
- A new study finds that though more females are included in experiments, sex-specific data often goes un-analyzed.
- Only about a third of studies analyzed published participant breakdown by sex.
- Some researchers say considering females more fully as research subjects is logistically too challenging.
In 2016, the National Institutes of Health (NIH) issued a directive that scientists receiving NIH funding must consider sex as a biological variable in pre-clinical research on vertebrate animals and human cells and tissues. According to a new study published in eLife that looked at over 700 journal articles, the number of women included as participants in pre-clinical research has jumped from 28 percent in 2009 to 49 percent in 2019. However, it's also unfortunately still the case that few studies actually consider sex as a biological influence that may potentially affect outcomes, and that data from women participants continues to be simply combined with data from men.
Study co-author Nicole C. Woitowich of Northwestern University's Feinberg School of Medicine tells INSIDE Higher Ed, "In the last 10 years, there has been a major in increase in sex inclusion, but it's still not where it's needs to be."
What's missing in current research
Image source: Hush Naidoo/Unsplash
Woitowich and others see two particularly problematic aspects to the continuing disregard of sex as a meaningful biological research variable.
First, female-specific data is rarely considered in study conclusions, despite the fact that it may have implications for women's health. According to L. Syd M Johnson of SUNY Update Medical University, who was not involved with the study, "This becomes highly problematic both scientifically and ethically, because women, children, and the elderly also need medical care, and they shouldn't be treated as if they have adult, male bodies. When they are excluded from research, and from the reported results, treatment for them becomes, effectively, off-label.
Second, Woitowich tells INSIDE Higher Ed it's, "troublesome to me as a scientist [that] a little under one-third [of studies] did not even report the number of males and females used as subjects." This makes it impossible for scientists to replicate the results. "If I don't have all the information," Woitowich says, "I'm left guessing."
On top of that, Woitowich laments that too much of the female-focused research that is undertaken is what's been called "bikini science," research surrounding issues related to female reproductive organs.
Why is this happening?
Image source: Image Point Fr/Shutterstock
"Many scientists, I don't even know if this is on their radar," says Woitowich. She proposes, therefore, that in the short term it may be the research gatekeepers — the funding entities, journal editors, and peer reviewers — who will have to step up and demand more inclusive science. She expresses surprise that they aren't already doing more to enforce the NIH's mandate. In the longer term, training for medical students should include a fuller awareness of the role that can be played by sex differences in research.
In a 2014 letter to the journal Nature, Janine A. Clayton and Francis S. Collins of the NIH admitted the problem even extends to female researchers. Noting that roughly half of the scientists doing NIH-funded research are women: "There has not been a corresponding revolution in experimental design and analyses in cell and animal research — despite multiple calls to action."
Another possible explanation
Image source: Ousa Chea/Unsplash
There are some researchers who feel that a greater inclusion of women and their data in studies would unnecessarily complicate the problems inherent in designing research and getting it funded.
In a 2015 letter to the journal Science, a group of researchers wrote that sex considerations added an additional investigational layer to research, one that was often irrelevant to the purpose of a research project. They asserted that, "nonhypothesis-driven documentation of sex differences in basic laboratory research is more likely to introduce conceptual and empirical problems in research on sex and gender than bring new clarity to differences in men's and women's health outcomes."
The writers also suggested that sex may be less of a biological variable than gender and weight. If, for example, women are more likely to be taking multiple pharmaceuticals than men and tend to be lighter in weight, these factors may be more influential on experiment outcomes than sex. Reluctant to commit to considering sex as a variable, they suggested instead two generalized studies to determine if it should be, writing, "we see a stronger empirical basis for directed funding initiatives in two areas: scientific validation of preclinical models for studying human sex differences, and human studies of the interaction of sex- and gender-related variables in producing health outcomes that vary by sex."
Image source: Valeriy Lebedev/Shutterstock
A 2019 analysis by Harvard University's GenderSci Lab found that basic science researchers, "repeated again and again that their experiments were in large part constrained by practicalities of various sorts. These practicalities were often used to explain why they don't or can't account for sex in their research," says the lab's Annika Gompers. Among the practicalities noted were the acquisition of study materials such as cells from deceased patients, test animals, fat from cosmetic surgery patients, and so on. Gompers said researchers often simply work with what they can get.
She adds, "While my participants recognize that considering sex can be important for the generalizability of results, in practice it is often impractical if not impossible to incorporate sex as a variable into biomedical research. Such a finding is consistent with scholars who have long looked at science as practice and observed how practicalities — as mundane as the availability of materials — are often central to the reduction of complexity into 'doable problems.'"
As far as sample composition goes, the choice of subjects may have to do with researchers wanting to avoid the constraints and costs of the safety regulations that accompany studies of pregnant women, women of child-bearing age whom may become pregnant, children, and the elderly.
Finally, though it may be that having enough females in a sample to draw valid conclusions would likely require larger participant cohorts. Woitowich's co-author, Smith College's Anneliese Beery, says that fears of doubled sample sizes are overblown, asserting that such increases in participant numbers would be "not actually necessary."
Avoiding wasted research opportunities
One of the authors of that Science letter was Harvard's Sarah S. Richardson, who suggests a sort of middle path, though it does give researchers license to ignore the NIH requirement as they see fit. Richardson proposes something she calls "sex contextualism," which is the "simple view that the definition of sex and sex-related variables, and whether they are relevant in biological research, depends on the research context."
Science journalist Angela Saini agrees , saying, "While it's valuable to include a broad spectrum of people in studies, it doesn't necessarily follow that the sex differences will be significant or important. So disaggregating for sex, while useful sometimes, doesn't always matter."
The above points, however, don't seem to acknowledge the potential for findings important specifically to female health, and seem more concerned with protecting the efficacy of studies that benefit males.
In any event, Woitowich finds that things are progressing more slowly than the NIH and others may have hoped. While Beery says it's "exciting to see increased inclusion of female subjects across so many different fields of biology," there are potentially meaningful scientific insights being lost. The disinclination toward fully collecting and analyzing female data for research experiments "means we are still missing out on the opportunity to understand when there are sex differences and losing statistical power when sex differences go unnoticed."