Culture

Scientists have developed a new way to understand complex genetic diseases and have identified a gene that modifies the severity of inherited kidney disease, paving the way for personalised treatments.

Experts at Newcastle University, UK, have shown that the rate of kidney disease in people with Joubert syndrome is determined by the genetic makeup of the individual and each patient may respond differently to treatment.

Joubert syndrome is a complex disorder, affecting approximately one in 80,000 newborns, causing varying degrees of physical, mental and sometimes visual impairments. It is often associated with severe kidney disease that requires dialysis and ultimately transplantation.

The study, published online in the Proceedings of the National Academy of Sciences, is the first time that an explanation has been given for the difference of disease progression in Joubert syndrome patients.

Significant breakthrough

The Newcastle research has identified a second gene called BSND - a 'modifier gene' - which determines the severity of kidney disease in patients with CEP290 mutations of Joubert syndrome.

It has been assumed that these modifier genes exist, but they have never been found before in rare genetic conditions until now.

Professor John Sayer and Dr Colin Miles, from the Translational and Clinical Research Institute, Newcastle University, led the Medical Research Council-funded research.

Professor Sayer said: "We have shown, using mouse and human DNA samples, that BSND is a modifier gene for the severity of kidney disease in Joubert syndrome.

"This is the first time that a modifier gene for inherited kidney disease has been identified, and this information will improve diagnoses and will be used to develop therapies to reduce the severity of kidney disease in affected patients.

"Our research is a major step forwards and, in the future, we may be able to offer a therapy that switches on the protective modifier gene and reduces the development of genetic kidney disease.

"This work paves the way towards personalised therapies in patients with the inherited kidney disease."

The international study used mouse models and DNA samples from patients with Joubert syndrome to progress the research.

Scientists used mouse models of disease and genetic manipulation to see how the kidney disease responded to modifier gene manipulation, cross-referenced with DNA sequencing data from patients around the world to prove the modifier gene was relevant in humans.

Challenging disease

Professor Sayer, a Consultant Nephrologist at Newcastle Hospitals NHS Foundation Trust, said: "The treatment of genetic kidney disease is challenging, as this requires both the correction of the underlying gene defect and the delivery of the treatment.

"We have shown that the kidney disease in a mouse can be dramatically changed by switching on or off a modifier gene.

"This will mean that we can use this information to carry out treatments, including genetic therapies, to lessen the effects of inherited kidney diseases, such as Joubert syndrome.

"We are testing these treatments further in our model systems before we move into patient studies."

Within the next three years, research will start to test treatment of patients with modifier genes in the hope of developing personalised treatment plans.

Patient story

Siblings Emma, 11, and Ben Buckley, eight, have Joubert syndrome and both developed kidney failure before the age of eight.

They were diagnosed with Joubert syndrome from a few months of age and both have required dialysis and a kidney transplant.

They suffer from a range of medical issues due to Joubert syndrome, including visual impairment, communication problems and developmental delay.

The two children, of Whitley Bay, North Tyneside, have been instrumental in helping further the research over the years, allowing the Newcastle scientists to study the mutation in detail.

Parents Leanne and Michael say they welcome the findings of the Newcastle University-led study as it will help to give patients a chance of preventing kidney failure in the future.

Leanne said: "It is very important that research is done into Joubert syndrome and the linked kidney damage, as this will hopefully prevent patients in the future needing a kidney transplant.

"All throughout Ben and Emma's lives, they have lived with the effects of Joubert syndrome and scientists found they had a problem with the CEP290 gene.

"Both Ben and Emma have needed dialysis and kidney transplants because of their kidney problems and I would like to hope this research will help prevent kidney failure for other affected children.

"We were happy for Ben and Emma to provide samples for the study as anything that helps further understanding into the condition is well worth doing, so it's great to see the study's positive results."

Be it autism, sickle cell or other life-disrupting health conditions, being the parent of a child with a chronic condition takes a psychological toll. For too many families, however, emotional and behavioral health support has been far too difficult to obtain.

Now, a project led by experts at Cincinnati Children's reports on the progress made since 2017, when the American Board of Pediatrics Foundation launched its "Roadmap Initiative" to increase resilience and emotional health within families of children with chronic conditions. The report, published today in Pediatrics, was co-written by parents living through this experience. It also provides a set of tools that any pediatrician can use to improve how they communicate with families about emotional well-being.

"There have been numerous successful efforts to improve the physical care of pediatric patients living with chronic conditions. We rightly celebrate our therapeutic achievements," says Tom Boat, MD, a long-time leader in pediatric medicine at Cincinnati Children's.

Boat co-authored the report in Pediatrics. He also is a member of the National Academy of Medicine, where he recently chaired a report on fostering healthy mental and emotional development.

"However, more children are living longer with disabling and life-threatening chronic disorders.

There has not been commensurate focus on enhancing emotional health and building resilience," Boat says. "But we're beginning to understand that if you don't support emotional health of children and
families, everything else is at risk for falling apart."

Parents Calling for Change

Shortfalls and limitations to the availability of mental health services in pediatric settings have been documented for many years. The Roadmap Initiative traces its roots to September, 2016, when more than 30 parents attended and addressed a meeting of the American Board of Pediatrics. Despite coping with extremely different health conditions, many of the challenges families face are universal.

"The overriding theme was of being overwhelmed, with our child's condition affecting every aspect of our lives, and everyone to whom we are connected," according to parent co-authors Diane Pickles and Stacey Lihn.

"There are multiple stressors and often a lack of consistency in daily life for families of children with chronic conditions. There are impacts on friendships and social life for children and parents, and educational impacts for children who miss school and/or have neurological impacts from their disease," the parents say. "There can be behavioral challenges, either from the child with the health issue or siblings. For parents, there is little time to exercise, eat right, or give enough attention to your other children. We feel isolated and as if our family and friends don't truly understand."

Be it the stigma that can be attached to mental health, or feelings of embarrassment or inadequacy, many parents may be afraid to say they are struggling. However, pediatricians can open doors for families simply by beginning a conversation.

LaToshia Rouse, the mother of a set of triplets born prematurely and a son with autism, recalls being shocked when a pediatrician asked her how she was doing. Now she likens the importance of mental health support for parents to the oxygen masks that drop from airplane overhead consoles during emergencies. Passengers are reminded to put their own mask on before helping their children.

"What I realize now is that until mamma has what she needs, that baby can never thrive," Rouse says.

Support for Pediatricians

The new report points out that experts have identified "resilience-based interventions" that can help families, such as strengths-based cognitive-behavioral therapy and mindfulness techniques. The co-authors also acknowledge that many pediatricians have been unaware of these resources and may also be reluctant to begin discussions that they fear may go beyond their direct expertise.

"A crucial message to all pediatricians, specialists and generalists, is that you don't have to be a mental health professional to make a difference," says Carole Lannon, MD, MPH.

Lannon is the Senior Faculty Lead of the Learning Networks Program at the James M. Anderson Center for Health Systems Excellence at Cincinnati Children's. She's also the Senior Quality Advisor for the American Board of Pediatrics.

"Parents emphasize they don't expect their pediatricians to be mental health experts. But the pediatrician's interest and support is tremendously valued," Lannon says. "Validating the stress patients and families feel can open the door to discussion."

To help more pediatricians begin such conversations, the Roadmap Initiative offers a number of free tools and resources (available at: https://www.abp.org/foundation/roadmap ). Looking ahead, teams from Cincinnati Children's and eight other children's hospitals have formed a pilot learning collaborative to test the feasibility of specific practice changes.

Boat predicts that many caregivers will find they can provide more help without being full-blown psychiatric experts.

"If we start working with families from the time of diagnosis--very early--so that they begin to understand that their resilience is important for their child, that their emotional well-being is crucial to outcomes for their child, then I think that the care team can take responsibility for partnering with families to achieve this," Boat says.

As early as 4 years old, children associate power and masculinity, even in countries considered to be more egalitarian like Norway. This is what scientists at the Institut des Sciences Cognitives Marc Jeannerod (CNRS/Université Claude Bernard Lyon 1) report, in collaboration with the Universities of Oslo (Norway), Lausanne and Neuchâtel (Switzerland), in a study published on 7 January 2020 in Sex Roles. They also show that in some situations the power-masculinity association does not manifest in girls.

We know little about how representations of power interact with gender in early childhood. Researchers at the Institut des Sciences Cognitives Marc Jeannerod (CNRS/Université Claude Bernard Lyon 1), in collaboration with the Universities of Oslo (Norway), Lausanne and Neuchâtel (Switzerland) wanted to know whether children aged 3 to 6 years old in France, Lebanon, and Norway attribute more power to masculine figures than feminine figures.

In a first experiment, they showed the children a picture with two non-gendered individuals. One of them adopted a dominant physical posture and the other a subordinate posture (See figure). First the children had to guess which of these two individuals was exerting power over the other. Next they had to assign a gender to each individual (Who is the girl? Who is the boy?). The results reveal that from 4 years old, a large majority of children consider the dominant individual to be a boy. The power-masculinity association was observed in both boys and girls, and just as much in Lebanon as in France and Norway. However it was not significant in 3-year old children.

In a second experiment, this time in children aged 4 and 5 years old all in school in France, had to imagine themselves in the picture and imagine the other person as a boy or a girl. When the children had to consider their power relation with a person of the same gender as themselves, the girls and boys both largely identified with the dominant character. But when they had to consider their power relation with a person of the opposite gender, boys identified more often with the dominant character whereas girls did not significantly identify more with one or other of the characters.

Finally, in a third experiment, children aged 4 and 5 years old in Lebanon and France watched a series of exchanges between two puppets, one representing a girl and the other a boy, behind a board1. In one case, the puppets were getting ready to play a game together and the child heard one impose their choices on the other. In the other case, one puppet had more money than the other to buy ice cream. In France and Lebanon, most of the boys thought that the puppet that imposed their choices or that had more money was the male puppet. However, the girls in both countries did not attribute the dominant position preferably to one or other gender.

These results show that children have early sensitivity to a gender hierarchy, though in some situations girls do not associate power and masculinity. The scientists now hope to find out what power forms they attribute to feminine figures and whether they legitimise the expression of gendered power.

New research has demonstrated how food producers could change the surface texture of products to change people's perceptions and promote healthy eating.

The study, led by Consumer Psychologist Dr Cathrine Jansson-Boyd of Anglia Ruskin University (ARU), investigated people's perceptions of identical biscuits with six different textures.

Published in the journal Food Quality and Preference, the research involved 88 people rating the six oat biscuits on healthiness, tastiness, crunchiness, chewiness, pleasantness and likelihood of purchase based only on their visual appearance, not on their taste or touch.

Previous studies have shown that packaging, labelling and even the texture of a cup or plate can alter people's perception of food. This new study looked at how a food product itself can be perceived differently depending on its appearance.

Oat biscuits were chosen as they can represent both a "healthy" and "unhealthy" snack. The research found that the surface texture of the oat biscuit clearly communicated to people how healthy it was likely to be and the participants viewed the biscuits that had an explicit, pronounced texture, as healthier.

However, the biscuits that had a less explicitly textured surface were perceived to be tastier, crunchier and more likely to be purchased. The study found that perceived tastiness increases as healthiness decreases, and the likelihood of purchasing the biscuit increases when perceived healthiness is low and decreases when healthiness is higher.

Therefore having a 'healthy looking' texture is considered to be a negative attribute in that it reduces perceived tastiness, a key criteria for purchasing biscuits. This has implications for producers of many different food types.

Dr Jansson-Boyd, Reader in Psychology at Anglia Ruskin University (ARU), said: "The findings are really exciting as they give food manufacturers a means to design foods that can help consumers make healthier choices.

"A sweet item, such as a biscuit, benefits from having an appearance as being less healthy as that increases the perception of tastiness and increases the likelihood of purchase. To guide healthier purchasing decisions, food producers can therefore look to use non-healthy looking, smoother textures to overcome this perception that healthy is not tasty.

"At a time when the World Health Organisation has declared that there is an obesity epidemic, it is essential to think of ways to encourage improved eating patterns. Our research provides a good starting point in how to promote healthier food products."

Researchers have found people on the brink of release from a prison sentence have lost any sense of being connected to the outside world and, as a result, become prejudiced towards wider society.

Seeing the outside world as this 'other' makes it more difficult to reintegrate and be rehabilitated, but new research has found a simple, structured conversation in the days leading up to a prisoner being released could dramatically turn their attitude and sense of belonging around.

Evangelos Mitrokostas, Visiting Fellow at the University of Portsmouth said; "For many prisoners, being incarcerated means losing more than physical freedom. It appears to also take a criminal's sense of belonging to wider society, making it doubly difficult for them to join back in or even want to, once released.

Our research looked at the rehabilitation and social behaviour of prisoners and found that inmates who were asked to reflect on their time in prison were significantly more likely to experience positive rehabilitation and social reintegration after their release."

The study was conducted in two prisons, a low and a high security facility in Chania, Greece. Researchers performed a comprehensive analysis of inmate's behaviour by asking them to take part in three tests.

This series of experiments was based on questionnaires and simple games that saw the prisoners split into two groups. Prisoners in one group were then asked to reflect on their time in prison, described by researchers as a priming intervention. The other group was not.

Evangelos explained: "Prisoners in the priming group were asked to contemplate their time spent in jail and how it had affected them. The idea behind this intervention was that inmates were driven to think about rehabilitation - the purpose of imprisonment. They often then expressed a desire or a commitment to become 'better persons' through decisions made in the experimental tests."

The results showed a strong increase in the inmates' trust and reciprocity towards those outside prison as a result of the priming intervention. Although priming had no significant effect on trust towards other inmates, it almost tripled the percentage of prisoners who trusted the outside world.

The experiments also revealed that prisoners exhibited some degree of discrimination in their behaviour. Those inmates who were not asked to reflect on their time in prison were significantly less reciprocal and less cooperative towards people outside the prison.

These findings suggest that a simple low-cost intervention based on encouraging prison inmates to reflect on their incarceration may be an effective tool to promote rehabilitation into society. This intervention could easily be integrated into counselling sessions routinely offered to prisoners by trained psychologists or social workers.

Evangelos is calling on policy makers to look again at how prisoners are rehabilitated. He said: "I believe that our findings can be very useful to policy makers who are in charge of evaluating the impact of incarceration on social behaviour and successful return to society. A simple conversation could significantly strengthen a prisoner's sense of identity and improve their chances of positive cultural reintegration."

The nucleic acids of DNA encode genetic information, while the amino acids of proteins contain the code to turn that information into structures and functions. Together, they provide the two fundamental codes underlying all of life.

Now scientists have found a way to combine these two main coding languages into a single "bilingual" molecule.

The Journal of the American Chemical Society published the work by chemists at Emory University. The synthesized molecule could become a powerful tool for applications such as diagnostics, gene therapy and drug delivery targeted to specific cells.

"Much like a translator enables communication between two people from different regions of the world, we envision that our bilingual molecule will enable us to mediate new forms of communications between nucleic acids and proteins in the cellular environment," says Jennifer Heemstra, associate professor of chemistry at Emory University and senior author of the study.

Nucleic acids store information in an "alphabet" of four bases, known as nucleotides. Peptides and proteins use an entirely different alphabet, made up of 20 different amino acids.

"The nucleic acid language is easy to speak, but kind of limited," Heemstra says. "While the protein language is incredibly complex and difficult to predict. Both of these molecules have developed exquisite properties over billions of years of evolution."

Previously synthesized molecules have focused on the properties of either nucleic acids or amino acids. The Emory researchers wanted to harness the powers of both information systems within a single molecule.

The challenge was enormous, drawing on techniques from organic chemistry, molecular and cellular biology, materials science and analytical chemistry. The researchers built a protein scaffold and then attached functioning fragments of nucleotides and amino acids to this framework.

"The two different codes needed to be synthesized separately and then brought together into the scaffold," says Colin Swenson, first author of the paper and a graduate student in Heemstra's lab.

The resulting bilingual molecule is stable, made of inexpensive materials, and highly generalizable, giving it the potential for diverse biomedical and nanotechnology applications. "It's like a programmable, universal adaptor that brings proteins and nucleic acids together," Heemstra says. "We hope that other researchers are inspired to think about different ways that it might be applied."

The Emory chemists are now exploring using the bilingual molecule for targeted drug delivery to particular cells. "It's essentially a stimuli-sensitive container," Heemstra says. "We've demonstrated that it can bind to drug molecules. And it's programmable to fall apart in the presence of specific RNA molecules that are more abundant in cancer cells."

Judo may be just the right sport to increase the physical activity level among children with autism spectrum disorder (ASD) and holds promise for reducing sedentary behavior, which is linked to obesity and diabetes, according to a new study from the University of Central Florida.

The pilot study found increases in moderate to vigorous physical activity among participants during and beyond the study period and a reduction of sedentary time, although researchers say the amount was not statistically significant. However, the children in the study were eager to continue judo lessons beyond the scope of the study and the few who did not continue failed to do so because of scheduling or transportation problems, rather than lack of interest. More research is needed to see if the reduction in sedentary time will last.

Parents also reported their children were more comfortable with social interaction and physical contact, things children diagnosed with autism struggle with in most cases. Another journal is reviewing a second paper written by the researchers focused on these aspects of the study.

"While karate, a form of martial arts, has documented benefits for the autism population related to social interaction, we hypothesized that the emphasis on mindfulness and self-defense promoted by judo would provide additional benefits for ASD youth," says Jeanette Garcia, an assistant professor in the College of Health Professions and Sciences who led the study. "Indeed, our study shows that judo not only promotes social skills, but is well accepted by this population and is a great program for reducing sedentary behavior and increasing confidence."

The study's findings were published in late December 2019 in the Journal of Autism and Developmental Disorders.

Garcia, who has a passion for helping children with autism, began the study last summer to determine if judo was a good way to get children moving. She became interested in helping these children because of the growing prevalence of children diagnosed with autism spectrum disorder. One in 59 children in the nation have been diagnosed with ASD, according to the Centers for Disease Control and Prevention.

Garcia thought judo might be a good fit because its approach held promise for addressing some of the challenges these children face, including communication deficits, high levels of anxiety, difficulties with social interaction, and preferences for structured and repetitive activities. Judo promotes social interaction, emphasizes mindfulness, and focuses on balance, strength, and coordination, while alternating between low, moderate, and high-intensity exercise.

There also is a lot of repetition to mastering techniques.

To see a video about this study click here.

How it worked

Fourteen local children, ages 8-17, were given the opportunity to participate in a 45-minute judo lesson at the university once a week for eight weeks. The class was specifically designed for children diagnosed on the autism spectrum. The student to instructor ratio was 2-1 and students from the College of Community Innovation and Education, College of Health Professions and Sciences and the Center for Autism and Related Disorders helped at each session.

Participants were separated into smaller groups based on age (8-12 and 13-17 years). And although everyone was taught a similar curriculum, any unused portions of the gym where the lessons were held were sealed off. This design helped limit distractions.

A primary judo instructor and assistant instructor, who previously worked with Garcia to offer a judo program for youth with ASD as part of a service project at a local school, taught the program. The graduate students provided encouragement to participants and assisted in demonstrating exercises to participants in a 1:1 format if needed.

The general warm?up included activities such as light jogging, stretching, and tumbling. Following the warm-up, sessions consisted of a progression of techniques that focused on safety, stability, the use of extremities, and visual cues. Individual completion of these exercises gradually transitioned to partner or small group completion as the program progressed. Each session was concluded with time allocated to practice breathing techniques and mindfulness, including participant reflection on the activities completed.

To track their time away from the judo mats, each student was given an accelerometer. The smart watch-like device measures activity and rest levels. Researchers used the device to track activity at the beginning and end of the program.

"This first cohort of students in the judo program showed positive results in achieving the desired health outcomes," Garcia says. "We will extend the study with this cohort and others to continue to assess the impact of the program. If it continues to be successful, we look forward to developing a program that schools can use to implement their own programs."

Co-authors on the study include: UCF graduate students Nicholas Leahy, Paola Rivera, and Justine Renziehausen; Judith Samuels, autism disorder specialist at the Center for Autism and Related Disabilities; Associate Professor David H. Fukuda, and UCF School of Kinesiology and Physical Therapy director Jeffrey R. Stout.

Garcia has a master's degree in psychology and a doctorate in exercise physiology, with an emphasis on public health and behavioral medicine. She also completed postdoctoral training at Harvard University before joining UCF in Fall 2016. Garcia's area of research focuses on the development and implementation of community-based health interventions to improve physical and psychosocial health in children and adolescents. She also has a strong interest in health behaviors in youth with social/emotional/behavioral disorders, primarily autism spectrum disorder, which is where most of her recent research has focused.

"I recall back in grade school and high school, kids with these disorders were always left out and made to sit on the sidelines," Garcia says. "That's the worst thing you can do for them. When I was at Harvard, we did a cycling intervention for kids with a variety of social, emotional, behavioral disorders, and I was amazed by how the youth with ASD responded to the exercises. I knew that was where I wanted to focus my attention."

Mathematicians have used a statistical technique to interrogate some of the big "what if" questions in the Second World War battle for Britain's skies.

What if the switch to bombing London had not occurred? What if a more eager Hitler had pushed for an earlier beginning to the campaign? What if Goring had focused on targeting British airfields throughout the entire period of the Battle?

These are just some of the alternative scenarios that have formed a long running debate among Second World War historians and enthusiasts over what might have affected the outcome of the battle, which took place between May and October 1940.

Mathematicians from the University of York have developed a new model to explore what the impact of changes to Luftwaffe tactics would actually have been. Their approach uses statistical modelling to calculate how the Battle might have played out if history had followed one of several alternative courses.

The researchers say that the method could now be used as a tool to investigate other historical controversies and unrealised possibilities, giving us a deeper understanding of events such as the Battle of the Atlantic (the longest continuous military campaign of the Second World War).

The statistical technique is called "weighted bootstrapping" and the computer simulation is a bit like taking a ball for the events of each day of the Battle of Britain and placing them in a lotto machine. Balls are then drawn, read and replaced to create thousands of alternative sets of days' fighting, but in a different order, and perhaps with some days appearing more than once or not at all.

The researchers then repeated the process to test out the Battle "what ifs", making some days more or less likely to be chosen, depending on how a protagonist (such as Hitler) would have changed their decisions had they been using different tactics.

Co-author of the paper, Dr Jamie Wood from the Department of Mathematics at the University of York, said: "The weighted bootstrap technique allowed us to model alternative campaigns in which the Luftwaffe prolongs or contracts the different phases of the battle and varies its targets.

"The Luftwaffe would only have been able to make the necessary bases in France available to launch an air attack on Britain in June at the earliest, so our alternative campaign brings forward the air campaign by three weeks.
We tested the impact of this and the other counterfactuals by varying the probabilities with which we choose individual days."

The results provide statistical backing to a change in tactics that several historians have argued could have brought the Luftwaffe victory in the summer of 1940: The simulations suggested that if they had started the campaign earlier and focused on bombing airfields, the RAF might have been defeated, paving the way for a German land invasion.

According to the mathematical model, the impact of these two changes would have been dramatic. Although it is impossible to estimate what the real statistical chances of an RAF victory were in July 1940, the study suggests that whatever Britain's prospects, an earlier start and a focused targeting of airfields would have shifted the battle significantly in the Germans' favour.

For example, had the likelihood of a British victory in the actual battle been 50%, these two tactical changes would have reduced it to less than 10%. If the real probability of British victory was 98%, the same changes would have reduced this to just 34%.

Co-author of the paper, Professor Niall Mackay from the Department of Mathematics at the University of York, said: "Weighted bootstrapping can provide a natural and intuitive tool for historians to investigate unrealised possibilities, informing historical controversies and debates.

"It demonstrates just how finely-balanced the outcomes of some of the biggest moments of history were. Even when we use the actual days' events of the battle, make a small change of timing or emphasis to the arrangement of those days and things might have turned out very differently.

"This technique can be used to give us a more complete understanding of just how differently events might have played out."

Existing evidence suggests pornography may negatively affect some individuals, but it does not qualify as a public health crisis, and calling it one could cause harm.

Researchers from the Boston University School of Public Health (BUSPH) have written an editorial in the American Journal of Public Health special February issue arguing against the claim that pornography is a public health crisis, and explaining why such a claim actually endangers the health of the public.

"The movement to declare pornography a public health crisis is rooted in an ideology that is antithetical to many core values of public health promotion and is a political stunt, not reflective of best available evidence," write Dr. Kimberly M. Nelson and Dr. Emily F. Rothman, both faculty in the Department of Community Health Sciences at BUSPH.

While 17 U.S. states have introduced nonbinding resolutions declaring pornography a public health crisis, the authors write that pornography does not fulfill the public health field's definition of one. Pornography use has increased steadily over time rather than spiking or reaching a tipping point; it does not "directly or imminently" lead to death, disease, property destruction, or population displacement; and it does not overwhelm local health systems.

Instead, Nelson and Rothman write, the existing evidence suggests that there may be negative health consequences for some people who use pornography, no substantial consequences for the majority, and even positive effects for some (for example, through safer sexual behaviors such as solo masturbation). Motivating people to use less extreme pornography, and less frequently, are reasonable harm reduction goals, the authors write, instead of trying to end all use. Increasing pornography literacy would also be useful, they write; Dr. Rothman and colleagues outline their pornography literacy program for Boston area adolescents in a paper in the same journal issue.

What is the harm of calling pornography a public health crisis? Nelson and Rothman argue that this mischaracterization can lead to unwarranted policy or funding shifts, rather than saving the power to mobilize the public health workforce for real crises. "Moreover, pathologizing any form of sexual behavior, including pornography use, has the potential to restrict sexual freedom and to stigmatize, which is antithetical to public health," they write.

Toronto -- Sometimes, there's the "price" and then there's the price.

Online shoppers may be pleasantly surprised to find the price of their chosen item has dropped once they've moved to the checkout phase of their purchase.

It could be because they are the beneficiary of something called a Minimum Advertised Price restraint, or MAP. That's where a manufacturer limits a seller from advertising a product below a certain price threshold. Consumers, however, may still be able to buy the product for less in store or at the moment of online checkout.

Regulatory authorities and critics concerned with anti-competitive practices have frequently considered this form of "vertical restraint" as having the same marketplace impact as a restriction that prevents a seller from selling a product below a certain price, called Resale Price Maintenance (RPM). That's a mistake, say researchers.

Using three different scenarios, Heski Bar-Isaac and John Asker illustrate that MAP has different impacts on competition and consumers than RPM, depending on market conditions. Because of MAP's greater flexibility, there are circumstances where MAP can be more beneficial than either RPM or no restrictions, and other circumstances where it is detrimental in comparison to both

"MAP allows for different prices to be out there whereas RPM doesn't," said Prof. Bar-Isaac, who is a professor of economic analysis and policy at the University of Toronto's Rotman School of Management. Prof. Asker is a professor of economics at UCLA.

The research is particularly timely given that the use of vertical restraints in e-commerce "really seems to have blossomed," said Prof. Bar-Isaac.

MAP provides more benefit to consumers who are motivated to look around for the lowest price while still allowing manufacturers to get more money out of less price-discriminating shoppers.

Its greatest benefits are seen when retailers provide an additional service to the manufacturer as part of their agreement, such as targeted product education to customers. In this scenario, everyone wins, because manufacturers and consumers benefit from the additional education, while retailers may have the opportunity to obtain higher profit margins.

However, MAP can make it easier for manufacturers to collude on wholesale prices, when retailers might add variable markups, by including a MAP agreement as part of the collusive agreement and facilitating mutual monitoring.

The differing economic impacts illustrated by the three scenarios show that it's misguided to treat MAP as carrying the same anti-competitive risks as RPM and applying a blanket policy to it, the research points out.

"There is no one-size-fits-all scenario here, so it's important to look at things on a case-by-case basis," said Prof. Bar-Isaac.

To replenish groundwater, many municipalities inject reclaimed water into depleted aquifers. The injected water has been purified by secondary wastewater treatment, and, in some cases, the water has been treated through tertiary processes and can be clean enough to drink directly.

The original water in the aquifer was chemically stable, in equilibrium with the surrounding rocks, and was slowly recharged by natural processes (water infiltration). However, when more groundwater is consumed than the natural processes can restore, engineered recharging with purified, reclaimed water is needed. Unfortunately, over time, the reclaimed water sometimes becomes contaminated.

A research team in the McKelvey School of Engineering at Washington University in St. Louis, led by Young-Shin Jun,  professor of energy, environmental and chemical engineering; and Xuanhao Wu, a doctoral student in Jun's lab, has determined how the potable water used to recharge an aquifer can become contaminated with dangerous levels of arsenic.

The research was published in Environmental Science and Technology.

In a managed aquifer recharge, "we continuously draw down the aquifer, but we never refill it enough," Jun said.

"Our population can grow quickly and our lifestyle becomes more water dependent but the natural refilling process is slow," she said. " So water management practice has engineered a way to inject water to compensate for our consumption and achieve environmental sustainability."

Keeping aquifers full is important for a few reasons. On the coasts, salty seawater can fill a depleted aquifer, creating a disastrous situation for the ecosystem and crops that the aquifer feeds. And, if the depleted zone remains empty, sinkholes can occur and the land may subside. Thus, refilling aquifers to provide drinking water is a standard practice in places from California to Florida.

But about 10 years ago, when working on managed aquifer recharge with the Environmental Protection Agency (EPA), Jun encountered a puzzling situation.

"When we injected the water, it was good," she said, "but when we withdrew it, it was bad, tainted with arsenic. What was wrong?"

It turned out that although the water being injected into the aquifer was usually clean enough to drink, it was bringing something new to the aquifer: oxygen.

"By injecting reclaimed water, we are triggering oxidative dissolution of sulfide minerals in the aquifer, which were stable at low oxygen levels," she said. In particular, she looked at arsenopyrite (FeAsS), a mineral that dissolves into iron, sulfur and, crucially, arsenic. Before the arsenic can reach problematic levels, however, another reaction takes place.

"The iron precipitates into iron oxides or hydroxides," Jun said. The arsenic adsorbs, or adheres, to the iron oxides or hydroxides, which are insoluble, keeping arsenic out of the water.

There is, however, another important factor.

Dissolved organic matter (DOM) -- compounds that contain carbon -- changes the situation drastically. "With high levels of organic compounds, we found the precipitation reaction is suppressed," Jun said. When precipitation of iron oxides or hydroxides is suppressed, the arsenic does not adsorb sufficiently. Instead, it remains available in the water.

Jun is quick to emphasize that this is more than an experimental exercise in laboratory exercise. "This is not a potential future problem," she said, noting that using reclaimed water is actual practice right now. "When thinking about water reclamation from aquifers, we need to consider the roles of organic matter," Jun said.

"We have to take into account the DOMs in injected water to make sure they do not trigger more mobilization of toxins," Jun said. "The roles of DOMs in managed aquifer recharge should be included in the predictive models. Knowing how water chemistry alters the chemical reactions in an aquifer will enable us to fully utilize the water, rather than discarding it as waste.

"Please keep in mind that there is only one kind of water in the world," she said.

"All water -- drinking water, seawater, groundwater, wastewater, stormwater, greywater, and more -- is simply 'water.' Keeping it safe and sustainable is our continuing homework."

SALT LAKE CITY - In the first-ever genome-scale analysis of the puberty process in humans, researchers at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) outline distinct and critical changes to stem cells in males during adolescence. They further outline how testosterone, and the cells that produce testosterone, impact stem cells in male reproductive organs. The researchers believe this study adds dramatically to a foundation of knowledge that may yield insights into critical areas of human health, including infertility and cellular changes that lead to cancer and other diseases.

The study, published today in the journal Cell Stem Cell, was led by Bradley Cairns, PhD, cancer researcher at HCI and professor and chair of oncological sciences at the U of U, in collaboration with colleagues Jingtao Guo, PhD, a postdoctoral fellow in the Cairns lab at HCI, James Hotaling, MD, associate professor of surgery at the U of U, and Anne Goriely, PhD, associate professor of human genetics at the University of Oxford.

Puberty spurs numerous developmental changes in humans and other mammals. Hallmarks of puberty include physical characteristics easily visible to the naked eye, like rapid growth. These physical and hormonal changes signal the process of a maturing body preparing for reproductive years.

In the testis, the male reproductive organ that makes and stores sperm and produces testosterone, puberty introduces monumental changes at a cellular and physiological level. Thanks to new genomic technologies, researchers are able to examine the expression of thousands of genes in each individual cell in an entire organ, providing unprecedented insights into cellular behavior during puberty.

Several types of cells within the testis regulate reproductive health. Like the human body that changes along the path from infancy to adulthood, these cells undergo major changes as the body matures. These cells include spermatogonial stem cells that ultimately generate sperm production, and niche cells that help form parts of the testis, such as the seminiferous tubule, a tube-like structure within which sperm is formed. In this study, researchers characterized how, just prior to puberty, spermatogonial stem cells first expand significantly in number. These stem cells progress toward meiosis, a special type of cell division that splits the number of chromosomes from the parent cell in half, and also separates the male X and Y sex chromosomes to create cells that, after fertilization of eggs and considerable subsequent development, will ultimately result in either male (Y-containing) or female (X-containing) children. Late in puberty, these stem cells commit to creating mature sperm, which includes a tail piece for motility. The researchers showed how two of the cells that form the stem cell niche and chaperone this process--the myoid cells and Leydig cells--derive from a common precursor, and mature during early puberty.

A major novel insight of this study was the first-ever genomic analysis of the testis of adult transfemales (individuals assigned male at birth, but who self-identify as female). For these individuals, gender confirmation surgery is preceded by hormone therapy that induces long-term testosterone suppression, enabling the examination of testis lacking testosterone. By using samples donated after surgery, researchers uncovered critical insights into the role of testosterone in maintaining testis development. Genomic analysis of the cells from the testis of transfemales showed that stem cells and other cells revert to earlier states of development when compared to samples from male adolescents. Thus, Cairns and his colleagues identified that testosterone is critical to maintaining the mature state of the testis: if testosterone is no longer present, the testis reverts to an earlier developmental state.

The major changes that occur in humans during puberty give rise to numerous functions in normal development, like reproductive health and fertility. But, when these processes go awry, confounding challenges can result. Infertility is a relatively common health issue. About 50 percent of the time, the underlying cause is attributed to the male reproductive functions, which often include errors that occur during puberty. The team hopes these insights into how cells develop will help yield insights into what happens when developmental issues during puberty cause changes that result in infertility.

The study also informs understanding of cancer and other diseases that arise due to errors in cellular processes. "The majority of the time, testicular cancers arise when stem cells in the testis are misregulated," said Cairns. "We want to understand how these changes can cause testicular tumors; however, we need to know what should normally happen before we can identify ways to prevent or more effectively treat these cancers."

In juveniles, cancers and reproductive health intersect via a medical process called oncofertility; that is, the study of how to retain fertility in adolescent and young adult cancer patients whose reproductive health and fertility may be impacted by their cancer, or as a result of side effects of cancer treatment. "Some chemotherapies can result in young men with cancer not being able to have children--the chemotherapy can cause changes to their stem cells," said Cairns. "My hope and expectation is that our research will provide a foundation for creating options to support the reproductive health of young men affected by cancer through a better understanding of how these stem cells survive, are supported, and develop."

A potentially big advance for neuroprostheses

Scientists discover neural activity patterns for limb movements remain stable over time

Like listening to 'cocktail party conversations' in the brain

Ultimate goal: a neuroprosthesis that translates brain signals (the activity of tens to hundreds of neurons) into a variety of movements

CHICAGO --- Once you learn a skill like tying your sneakers, you can perform it consistently over the years. This suggests the neural activity in the brain associated with the skill remains stable over time.

Thus far, though, it has been impossible to find this stable neural signal, because the electrodes necessary to monitor the brain activity see an ever-changing set of neurons.

New Northwestern Medicine findings provide an immediate way of compensating for this change in recorded neurons. Hidden in the activity patterns, scientists discovered a small set of neural "conversations" underlying the individual neurons' activity that described movements in a remarkably stable way over many months or years.

Northwestern scientists were able to record, decode and reconstruct preserved activity patterns for common movement skills from these ever-changing neurons in both motor and sensory areas of the cerebral cortex.

The findings have immediate implications for neuroprostheses, devices that bypass neurological injuries by inferring intended motor actions from a patient's brain, then using this decoded information to provide the patient voluntary control of a computer cursor, a robot limb or even their own reanimated limb.

"The study is significant because it is the first to extract or 'decode' a stable pattern of information from many neurons across the different brain areas that work together to create a movement," said lead author Lee Miller, professor of physiology at Northwestern University Feinberg School of Medicine. "Previous studies focused on the individual neurons, whose activity cannot typically be recorded for more than a few hours, and reported somewhat contradictory findings."

The challenge the scientists solved is a bit like attending a cocktail party where many people are talking to each other about politics, religion and the weather. The combined voices are impossible to follow, and listening to a single person only works until they wander away. However, by monitoring a few representative people and extracting the information related to these three different topics, one could come away from the evening with a very good running commentary of current events.

Such is the case in the cerebral cortex: one can sample several hundred neurons out of many million to find the dominant neural "conversations." By combining the simultaneous recordings from many neurons, it is possible to extract stable patterns of activity distributed across the whole population, potentially allowing for consistent control of a neuroprosthesis over long periods of time.

The study was published Jan. 6 in Nature Neuroscience.

Although there have been pre-clinical demonstrations of neuroprostheses that try to address multiple movement commands, they all have the same limitation, Miller said. The individual neurons driving the neuroprostheses change across days. This instability in the signals being recorded makes it difficult to interpret movement commands, and requires the patient and the neuroprosthesis to relearn how to move almost every day.

Other groups have developed methods to accelerate this process, but the Northwestern results suggest that it may not be necessary if one focuses on the neural conversations rather than on the individual neurons.

"Our study supports a recent model of how the brain works: by using highly distributed patterns of activity across neurons to generate behavior, rather than by carefully adjusting the activity of each individual neuron," said first author Juan Gallego, a former postdoc in Miller's lab who is now an assistant professor at Imperial College London.

Miller's final goal is to have a neuroprosthesis that translates brain signals (the activity of tens to hundreds of neurons) into a variety of movements over a long period of time. Current neuroprostheses only function particularly well for the tasks on which they have been trained.

"By accurately predicting how the subject wants to activate their many individual muscles, this future neuroprosthesis should, in principle, allow the user to perform any movement she wants," Miller said.

But challenges remain to achieve this. Scientists can currently build a mathematical model that predicts muscle activity during a given task (and Miller's team has done it for several tasks), or even during a slightly different task.

"Yet, these mathematical models fail when you test them on a very different task," Miller said. "In other words, with current methods a 'hammering nails' model may not work well when the subject is 'applying lipstick.'"

Miller's lab team is working to overcome this challenge. In preclinical studies, they are performing wireless recordings of brain signals, muscle activity and movement data. They are exploring methods from artificial intelligence to build a model that works for a much broader variety of movements than has previously been possible.

"If successful, this research will open new exciting avenues for bringing neuroprostheses from the lab to the patients' homes," Miller said.

One-fourth of children under age 8 with autism spectrum disorder -- most of them black or Hispanic -- are not being diagnosed, which is critical for improving quality of life.

The findings, published in the journal Autism Research, show that despite growing awareness about autism, it is still under-diagnosed, particularly in black and Hispanic people, said study co-author Walter Zahorodny, an associate professor at Rutgers New Jersey Medical School and director of the New Jersey Autism Study, which contributed to the research.

Researchers analyzed the education and medical records of 266,000 children who were 8 years old in 2014, seeking to determine how many of those who showed symptoms of the disorder were not clinically diagnosed or receiving services.

Of the nearly 4,500 children identified, 25 percent were not diagnosed. Most were black or Hispanic males with deficits in mental abilities, social skills and activities of daily living who were not considered disabled.

"There may be various reasons for the disparity, from communication or cultural barriers between minority parents and physicians to anxiety about the complicated diagnostic process and fear of stigma," Zahorodny said, "Also, many parents whose children are diagnosed later often attribute their first concerns to a behavioral or medical issue rather than a developmental problem."

Screening all toddlers, preschool and school-age children for autism could help reduce the disparities in diagnosis, Zahorodny said. In addition, clinicians can overcome communication barriers by using pictures and/or employing patient navigators to help families understand the diagnosis process, test results and treatment recommendations.

States can help improve access to care by requiring insurance companies to cover early intervention services when a child is first determined to be at risk rather than waiting for a diagnosis, he said.

The research was conducted through the Autism and Developmental Disabilities Monitoring Network, a surveillance program funded by the U.S. Centers for Disease Control and Prevention that tracks the prevalence of the developmental disorder in 11 states: Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee and Wisconsin.

PHILADELPHIA - Integral Molecular, the leader in discovering antibodies against multipass membrane proteins, announces lead monoclonal antibodies (MAbs) against P2X7, a structurally complex ion channel that is the target for autoimmune disorders including atopic dermatitis and glomerulonephritis. The panel of P2X7 antibodies is fully humanized and optimized, and ready to progress towards preclinical studies.

The P2X7 ion channel target is involved in regulating a population of T cells that drive multiple autoimmune diseases. However, the target has been largely refractory to antibody discovery efforts due to its complex structure.

"Despite its important role in the pathway of many diseases, there are no existing drugs against P2X7," said Ross Chambers, VP of Antibody Discovery. "Our MPS Antibody Discovery platform was built to handle complex membrane protein targets such as P2X7 and has enabled us to isolate high-affinity antibodies in the picomolar range that exhibit antagonist or rare agonist activity."

Integral Molecular's MPS Antibody Discovery platform encompasses a comprehensive technology suite that overcomes the obstacles of working with highly conserved and structurally complex membrane protein targets, including antigen engineering and presentation on Lipoparticles, immunization of divergent species, and deep screening techniques such as B-cell cloning to recover rare antibodies.

Integral Molecular will discuss its antibody assets in immune modulation, oncology, and metabolic disease at the upcoming JP Morgan Conference taking place from January 13-16, 2020 in San Francisco, California. The company is currently isolating MAbs against dozens of membrane protein targets and welcomes antibody out licensing opportunities and discovery partnerships.