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There has been an increase in the use of medications to treat attention deficit hyperactivity disorder (ADHD) in both adults and children between 2001 and 2015, according to a major observational study involving over 154 million individuals from 14 countries in Europe, North America, Asia, and Australasia, published in The Lancet Psychiatry journal. The study provides the most comprehensive analysis yet of trends in ADHD medication use.

Global estimates suggest that ADHD affects 5% to 7% of children and around 2.5% of adults. While use of ADHD medications in children and adolescents (aged 3-18 years) has gone up in all countries, the number of people using medication ranged from 0.3% in France to 6.7% among Medicaid beneficiaries in the USA in 2010. In adults, use of these drugs was less common, ranging from 0.003% in Japan to 1.5% among privately insured individuals in the USA in 2010.

The findings highlight that prescription rates are still far below diagnosis rates in many countries. Additionally, the wide and persistent disparities in use of these drugs between countries and regions, suggests marked differences in the clinical approach to treating ADHD, underscoring the need for evidence-based guidelines to be followed consistently in clinical practice so that individuals with ADHD receive optimal treatment.

ADHD is one of the most common neurodevelopmental disorders in children. However, it can be a lifelong condition and at least two-thirds of children continue to show symptoms in adulthood. A recent study published in The Lancet Psychiatry found that ADHD medications can be effective and safe treatment options for children, adolescents, and adults [2].

"What's especially important is our finding that the rates and type of drug treatment prescribed appears to depend largely on where you live," says Professor Ian Wong from The University of Hong Kong, Hong Kong, who co-led the study.

"We believe increases in the prescribing of ADHD medications reflect improved awareness of ADHD and recognition of the importance of effective treatment to avoid long-term problems. Yet, in most countries these rates are considerably lower than ADHD prevalence estimates, indicating that many cases of ADHD may be going undiagnosed and untreated--especially in nations in Asia where use is low. However, in the USA where rates of prescribing in many states already outstrip prevalence of the condition, we cannot exclude the possibility that ADHD is overdiagnosed and overmedicated. There is a need for monitoring medication safety and effectiveness in exposed populations, particularly in adults." [1]

Despite concerns over the rising use of ADHD drugs and inappropriate prescribing of medications, little was known about the trends and usage patterns in different world regions, particularly among adults, before this latest research.

The study analysed electronic patient records from 14 countries in northern Europe, western Europe, Asia and Australia, and North America to compare ADHD medication use in over 154 million individuals aged 3 years or older between 2001 and 2015 [3]. The authors note that prevalence data were not available for all countries in all years [4].

Over the study period, an average of around 2% of children (aged 3-18 years) and 0.4% of adults were given at least one prescription for an ADHD drug. Regional prevalence was highest in North America, where 4.5% of children and 1.4% of adults were using ADHD medications, and lowest in western Europe (0.7% and 0.03% respectively).

Use of these drugs in children and adults increased over the study period in all countries.

The rise in medication was most pronounced among children in Canada, with average increases of over 45% a year (from 0.2% of children using ADHD drugs in 2001 to 1.8% in 2009). In adults, growth in Japan has been faster than in other countries, with average increases of 76% a year (0.003% of adults in 2010 to 0.5% in 2015). However, despite large increases, overall medication use remains low.

Comparatively, in the USA--where medication use is high--the rate of increase has been slower than in other countries in both children (around 3% a year; 4.6% of children in 2002 to 5.6% in 2014) and adults (about 13% a year; from 0.42% of adults in 2001 to 2.1% in 2014).

In Europe, children and adults from northern regions are increasingly likely to be prescribed ADHD medications compared to their western counterparts, and especially high rates of ADHD medication use have been reached in Iceland (5% of children and 1.6% of adults in 2013).

Additionally, there were average rises in medication use of 22% a year in Finland (0.2% of children in 2005 to 1% in 2012) and 29% in Denmark (0.03% of adults in 2001 to 0.52% in 2013), while the increase in medication use among children in the UK was much slower (5% a year; 0.3% children in 2001 to 0.64% in 2014).

The types of medications prescribed also varied. Methylphenidate was the most commonly prescribed drug for ADHD in all countries in 2010--ranging from more than 90% of patients in Hong Kong, Taiwan, Canada, Finland, and Spain to less than 60% in Australia, and 45% of US Medicaid patients. The main treatment for privately insured US patients (MarketScan) was amphetamine (41%), followed by methylphenidate (34%) and lisdexamfetamine (21%).

The authors speculate that the variation in prescribing practices is likely to be due to a number of factors, including varying diagnostic practices and thresholds used to initiate treatment in individuals with ADHD, the availability and cost of medicines, and differences in regional treatment guidelines. For example, The National Institute for Health and Care Excellence in England and Wales (NICE) guidelines until recently recommended non-pharmacological treatment as the first-line treatment for children and young people aged 6 years and older; whereas medications have been recommended as first-line treatment by the American Academy of Pediatrics and the Academy of Child and Adolescent Psychiatry guidelines.

"Renewed efforts are needed to improve the consistent identification and treatment of ADHD across the international community and to develop consensus on best practices and to implement such practices", says co-author Dr Patrick Ip from The University of Hong Kong, Hong Kong, China. "Further research is needed to show the longer-term safety and effectiveness of ADHD medications to develop evidence-based guidelines, particularly in adults." [1]

The authors point to some limitations including that the data only relate to the proportion of individuals with at least one prescription in a calendar year and not to the proportion receiving treatment at any given time. They also note that for some countries, data sources with complete population coverage were not available (ie, USA, Canada, and the UK), and this may have affected the accuracy and generalisability of the results. Finally, the study examined medication use regardless of an ADHD diagnosis, so it is unclear what proportion of participants were prescribed medications for ADHD or hyperactivity symptoms in patients with other disorders such as autism.

Writing in a linked Comment, Margaret Sibley from Florida International University, Miami, Florida, USA discusses the reasons why stimulant medication prescriptions are rising globally, adding that: "There is an urgent need to refine evidence-based guidelines for stimulant medication. This mission extends beyond ADHD. Researchers should address pressing questions, including the following: which sources of cognitive dysfunction (eg, illness, sleep difficulties, stress, trauma, low intelligence quotient, high demands, or fatigue) are appropriate for stimulant prescription and under which circumstances is it appropriate to prescribe stimulants to cognitively healthy individuals (eg, weight loss or cognitive enhancement)? Resolving these issues represents an important step towards improving global stimulant medication practices."

The sky gets a new reference frame. On 30 August the International Astronomical Union adopted the International Celestial Reference Frame 3 (ICRF-3) during their general assembly in Vienna, Austria. As of 1 January 2019 this reference frame has global validity. It serves for example for the orientation of GPS systems as well as the navigation of space probes.

For any kind of positioning and navigation on Earth or in space reference frames are needed. Just like the longitudes and latitudes on the Earth's surface, the sky can be covered with a grid net. This reference frame allows for a precise positioning of objects in the sky in relation to Earth. For the establishment of this grid net "anchor points" are needed: For the Earth, there are about 50 radio telescopes and for the sky 4536 so called quasars, galaxies that circle around a black hole, serve as anchors of the grid.

Over the last 40 years, the radio telescopes, located on every continent, determined the positions of the 4536 quasars via Very Long Baseline Interferometry (VLBI), with significant contribution of the VLBI working group of GFZ section Space Geodetic Techniques. Robert Heinkelmann, head of the working group: "Based on all VLBI observations of the past 40 years we were able to calculate the exact locations of all extra galactic objects. We furthermore found a solution to compensate for the observation bias caused by the rotation of our galaxy, the Milky Way."

The last reference frame (ICRF-2) was published in 2010. Compared to that the new system improves the precision on average by a factor of 1.5. Furthermore, about 30 percent more objects were included in the calculations, and the rotation of the Milky Way was included for the first time. In addition, the results are now available in three different radio band widths which makes them available for a wide user group.

Based on the new system, the position of objects in space can be determined with a precision of a hundredth of a millionth angular degree, equivalent to spotting a tennis ball on the surface of the Moon from the Earth.

Quasars permanently emit radio waves that can be detected via the radio telescopes on Earth. Since the quasars are extremely far away from Earth (about 100 million to 10 billion light years) they can be considered as stationary in relation to Earth, even if in permanent motion. This is why they are suitable as anchor points for the celestial reference frame.

Not only positioning systems like GPS or the European pendant Galileo depend on a reference system in the sky, also changes on the surface of the Earth like the movement of plates, volcanic eruptions, sea level changes, earthquakes or changes in the position of the Earth in space are based on it. For the surface of the Earth the International Terrestrial Reference Frame (ITRF) determines every position on the Earth in a coordinate system with the centre of the Earth as the centre of the system. To measure, for example, if sea level is rising or land is sinking the reference frame on the Earth's surface needs another reference frame in the sky that it can be related to. The more precise the reference frame in the sky, the more precise an observation of changes on the surface of the Earth can be.

GALVESTON, Texas -Researchers from The University of Texas Medical Branch at Galveston found that testosterone replacement therapy may slow disease progression of chronic obstructive pulmonary disease. The paper is currently available in Chronic Respiratory Disease.

Chronic obstructive pulmonary disease, or COPD, is predicted by the World Health Organization to be the third-leading cause of illness and death internationally by 2030. Low testosterone is common in men with COPD and may worsen their condition. Men with COPD have shortness of breath and often take steroid-based medications for an extended time, both of which increase their risk of low testosterone.

"Previous studies have suggested that testosterone replacement therapy may have a positive effect on lung function in men with COPD," said Jacques Baillargeon, UTMB professor in preventive medicine and community health. "However, we are the first to conduct a large scale nationally representative study on this association."

The goal of the study was to find out whether testosterone replacement therapy reduced the risk of respiratory hospitalizations in middle-aged and older men with COPD.

Using the Clinformatics Data Mart, a database of one of the largest commercially insured populations in the U.S., Baillargeon and colleagues examined data of 450 men aged 40 to 63 with COPD who began testosterone replacement therapy between 2005 and 2014. They also used the national Medicare database to study data from 253 men with COPD aged 66 and older who initiated testosterone replacement therapy between 2008 and 2013.

"We found that testosterone users had a greater decrease in respiratory hospitalizations compared with non-users. Specifically, middle-aged testosterone replacement therapy users had a 4.2 percent greater decrease in respiratory hospitalizations compared with non-users and older testosterone replacement therapy users had a 9.1 percent greater decrease in respiratory hospitalizations compared with non-users," said Baillargeon. "The findings suggest that testosterone replacement therapy may slow the progression of disease in men with COPD."

Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets. These materials make it possible to achieve computing speeds much faster than existing devices. Conventional devices using current technologies have the unwelcome side effect of getting hot and being limited in speed. This is slowing down the progress of information technology.

The emerging field of magnon spintronics aims to use insulating magnets capable of carrying magnetic waves, known as magnons, to help solve these problems. Magnon waves are able to carry information without the disadvantage of the production of excess heat. Physicists at Johannes Gutenberg University Mainz (JGU) in Germany, in cooperation with theorists from Utrecht University in the Netherlands and the Center for Quantum Spintronics (QuSpin) at the Norwegian University of Science and Technology (NTNU) in Norway, demonstrated that antiferromagnetic iron oxide, which is the main component of rust, is a cheap and promising material to transport information with low excess heating at increased speeds. Their study has been published recently in the scientific journal Nature.

By reducing the amount of heat produced, components can continue to become smaller alongside an increased information density. Antiferromagnets, the largest group of magnetic materials, have several crucial advantages over other commonly used magnetic components based on iron or nickel. For example, they are stable and unaffected by external magnetic fields, which is a key requirement for future data storage. Additionally, antiferromagnet-based devices can be potentially operated thousands of times faster than current technologies as their intrinsic dynamics are in the terahertz range, potentially exceeding a trillion operations per second.

Fast computers with antiferromagnetic insulators are within reach

In their study, the researchers used platinum wires on top of the insulating iron oxide to allow an electric current to pass close by. This electric current leads to a transfer of energy from the platinum into the iron oxide, thereby creating magnons. The iron oxide was found to carry information over the large distances needed for computing devices. "This result demonstrates the suitability of antiferromagnets to replace currently used components," said Dr. Romain Lebrun from the JGU Institute of Physics. "Devices based on fast antiferromagnet insulators are now conceivable," he continued.

Andrew Ross, one of the lead authors of the study, added: "If you are able to control insulating antiferromagnets, they can operate without excessive heat production and are robust against external perturbations." Professor Mathias Kläui, senior author of the paper, commented on the joint effort: "I am very happy that this work was achieved as an international collaboration. Internationalization is a key aim of our research group and in particular of our Graduate School of Excellence Materials Science in Mainz and the spintronics research center Spin+X. Collaborations with leading institutions globally, like the Center for Quantum Spintronics and Utrecht University enable such exciting research."

The timing of seizures may be linked to natural rhythms in around 80% of people with epilepsy, according to the largest study of individual patients' seizure cycles including more than 1,000 people, published in The Lancet Neurology journal.

Most people's seizures occurred in a circadian (ie, 24-hour) rhythm, but some people experienced weekly and 3-weekly cycles in their seizures, and some had a combination of daily, weekly or longer cycles associated with their seizures.

While seizure patterns are known to vary over days, months and years, previous studies have been short-term or in small groups. The new study gives robust evidence of seizure cycles, showing that they are patient-specific and more common than previously thought.

"Understanding the cyclic nature of diseases is vital for treating diseases like epilepsy that continuously fluctuate in their severity," says senior author Professor Mark Cook, The University of Melbourne, Australia. "The human body is a collection of thousands of clocks, each cycling in accordance with their own pacemaker. For example, some cells can track time with millisecond accuracy, while hormonal cycles might have longer periods of hours, days or more. Combined in the body, the presence of all of these cycles has a fundamental effect on our health." [1]

The link between epileptic seizures and other natural cycles has been studied for hundreds of years, and some now-disproven historical hypotheses suggested a link between the phases of the moon and seizure rates. More recently, the possible links have included associations with stress levels, seasonal variations in sleep quality, and other biological processes involved in sleep, menstruation and hibernation.

The new study used data from a seizure tracking website and mobile phone app with which 1118 patients with epilepsy recorded and tracked their seizures, and from a small study in which 12 people with epilepsy had a device fitted that recorded the electrical activity in their brain. The authors looked at the data for seizure frequency between six hours and three months, using statistical analysis to identify trends in individual patients' seizure cycles. The study only included people who had frequent seizures.

80% (891/1118) of people using the website and mobile app and 92% (11/12) of people whose brain activity was recorded showed circadian rhythms in their seizures. Additionally, 7-21% (77-233/1118) of people using the website and mobile app showed weekly rhythms, and 14-22% (151-247/1118) of people had cycles that were longer than three weeks.

In addition, around two-thirds of people in the study (64%, 720/1118) had more than one type of cycle associated with their seizures. The authors say that the weekly cycle in seizures is particularly interesting, as the physiological cause of a weekly cycle is not as well established as a circadian rhythm, and it is debated whether this is natural or environmental.

For people with a circadian cycle to their seizures, peak time of seizures varied across the day, but more seizures occurred at about 8am and 8pm. Weekly cycles did not favour any day of the week, but more people had seizures on Tuesdays and Wednesdays.

The results were similar for men and women, and for people with different forms of epilepsy. The authors believe that the cycles drive the likelihood of the seizures, rather than epilepsy driving the cycles.

They also say that the findings could have important implications for patients by helping them to predict and manage their seizures. They note that, after further research, the findings could help guide treatment.

"The ubiquity of seizure cycles indicates that this is an important clinical phenomenon that affects most patients. This means it could be an important way to improve treatment for many people with epilepsy. Even without fully understanding the mechanisms of seizure cycles, temporal patterns can be incorporated into patient management plans, through chronotherapy - the process of scheduling medication so that drug concentrations match to times when seizures are more likely. However, the daily cycles might also be caused by peaks and troughs in drug effectiveness due to how the drug is metabolised in the body, so altering this could just alter the timings of a person's seizures. Adapting drug timings to suit weekly or monthly cycles has also not yet been explored." Explains Professor Cook. [1]

The authors note some limitations, including that the majority of the data from the study are self-reported and could be therefore biased. However, the authors note that inaccuracy would not invalidate the cycles detected if the majority of seizures reported were real, and the inaccurate ones were distributed evenly across the day.

They also note that they could only study the trends up to three months and so could not consider yearly or seasonal variations, nor the effect of holidays or daylight savings time.

Writing in a linked Comment, Professor Andreas Schulze-Bonhage, University Hospital Freiburg, Germany, says: "Ultraslow oscillations in brain excitability are so far barely understood. There is evidence emerging that such slow cycles below well-known circadian rhythms influence both, physiological functioning and disease states. It is remarkable that the group of Mark Cook found such long-lasting cycling alterations in seizure propensity over several weeks, which have also been reported in chronic psychiatric diseases."

Figures published by The BMJ today show how crowdfunding for alternative therapies for patients with terminal cancer has soared in recent years. But there are fears that huge sums are being raised for treatments that are not backed by evidence and which, in some cases, may even do then harm.

As such, there are now calls for crowdfunding sites to vet cancer appeals to help ensure that patients and their donors are not being exploited, writes freelance journalist Melanie Newman.

The figures, collected by the Good Thinking Society, a charity that promotes scientific thinking, show that since 2012 appeals on UK crowdfunding sites for cancer treatment with an alternative health element have raised £8m (€9m; $10m). Most of this was for treatment abroad.

JustGiving's own figures show more than 2,300 UK cancer related appeals were set up on its site in 2016, a sevenfold rise on the number for 2015.

While the phenomenon has allowed less well-off patients to access expensive, experimental treatments that are not funded by the NHS but have some evidence of benefit, many fear it has also opened up a new and lucrative revenue stream for cranks, charlatans, and conmen who prey on the vulnerable.

The society's project director, Michael Marshall, says: "We are concerned that so many UK patients are raising huge sums for treatments which are not evidence based and which in some cases may even do them harm."

Good Thinking now wants the crowdfunding sites to vet cancer appeals and "reject outright proposals that refer to specific drugs that have been discredited, extreme dietary regimes, intravenous vitamin C, alkaline therapy and other alternative treatments."

"If these platforms want to continue to benefit from the goodwill of their users--and, indeed, to profit from the fees they charge each of their fundraisers--they have a responsibility to ensure that they do not facilitate the exploitation of vulnerable people," says Marshall.

Edzard Ernst, professor of complementary medicine at Exeter University, supports the move, pointing out that crowdfunding organisations already reject appeals involving violence or illegal activity, such as terror attacks.

GoFundMe, the platform that features most prominently in Good Thinking's dataset, said it is already "taking proactive steps" in the US to make sure users of its site are better informed and will be doing the same globally over the coming months.

JustGiving told The BMJ, "We don't believe we have the expertise to make a judgment on this."

In contrast, some argue that the very process of searching for alternative therapies can have a positive effect. Sarah Thorp, who set up a GoFundMe account to pay for her sister Andrea Kelly's treatment at the Integrative Whole Health Clinic in Tijuana, Mexico, believes Andrea was helped as much by the feeling of being in control as by the treatments she received.

Andrea spent three weeks at the clinic at a cost of $21,000 (£16,000; €18 000) and died just over a year after she returned.

The largest sums by far in Good Thinking's dataset, allegedly accounting for £4.7m of the £8m identified, were raised for trips to the Hallwang Private Oncology Clinic in the Black Forest of southern Germany.

However, the clinic claims that some people have used Hallwang's name to raise money but have not then proceeded to treatment and, in some instances, have done so without ever contacting the clinic.

Some health professionals, including Professor Christian Ottensmeier at the University of Southampton, don't think patients should be banned from visiting such clinics, but say careful conversation with the patient about the chances, the risk, and the costs, are essential.

Others, however, such as Patricia Peat, a former oncology nurse who has advised people to go to the Hallwang after visiting the clinic herself, says she has now stopped recommending it to her clients.

The Hallwang maintains that it never gives guarantees to patients and always provides thorough information on its alternative treatment strategies, which it says are state of the art.

Finally, Michael Marshall also points to the role of the media, whose reports on people with cancer often drive donors to the crowdfunding sites and encourage others to seek the same treatment.

"These reports may look like uplifting human interest stories, but they rarely highlight the dubious and pseudoscientific nature of some of the treatments involved or just how many of the success stories actually ended in tragedy," he says. "If the media want to report on medical fundraising stories, they should seek the advice of qualified medical experts."

In a proof of concept study, scientists at Johns Hopkins report they have successfully performed 3D personalized virtual simulations of the heart to accurately identify where cardiac specialists should electrically destroy cardiac tissue to stop potentially fatal irregular and rapid heartbeats in patients with scarring in the heart. The retrospective analysis of 21 patients and prospective study of five patients with ventricular tachycardia, the researchers say, demonstrate that 3D simulation-guided procedures are worthy of expanded clinical trials.

Results of the study are described in the Sept. 3 issue of Nature Biomedical Engineering.

"Cardiac ablation, or the destruction of tissue to stop errant electrical impulses, has been somewhat successful but hampered by a lot of guesswork and variability in the way that physicians figure out which locations to zap with a catheter," says Natalia Trayanova, Ph.D., the Murray B. Sachs Professor in the Department of Biomedical Engineering at The Johns Hopkins University Schools of Engineering and Medicine. "Our new study results suggest we can remove a lot of the guesswork, standardize treatment and decrease the variability in outcomes, so that patients remain free of arrhythmia in the long term," she adds.

When a normal heart contracts to pump blood throughout the body, a wave of electrical signals flows through the heart, stimulating each cardiac cell to contract--one after the other--in a normal rhythm. After the heart contracts, it relaxes and refills with blood.

In people with ventricular tachycardia, the electrical signals in the heart's lower chambers misfire and get stuck within the fist-size organ, crippling the relaxation and refilling process and producing rapid and irregular pulses--or arrhythmias--linked to an estimated 300,000 sudden cardiac deaths in the U.S. each year.

Numerous drugs are available to treat and manage so-called infarct-related ventricular tachycardia, but side effects and limitations of the drugs have increased focus on other interventions, especially the potential of cardiac ablation that essentially "rewires" the electrical signaling that gives rise to the arrhythmias. Trayanova says current estimates indicate that cardiac ablation is successful anywhere between 50 and 88 percent of the time, but outcomes are difficult to predict.

To perform a traditional ablation, doctors thread a catheter through blood vessels to reach the heart, and use radiofrequency waves to destroy regions in the heart tissue believed to sustain and propagate erratic electrical waves. Mapping of the heart's electrical functioning with a catheter is used to locate likely problem areas, but as Trayanova notes, precise pinpointing of those tissues has been a challenge.

In a bid to locate arrhythmias more precisely, Trayanova and her research team developed 3D personalized computational models of patients' hearts based on contrast-enhanced clinical MRI images. Each heart tissue cell in the model generates electrical signals with the aid of mathematical equations representing how heart cells behave when they are healthy, or when they are semiviable when near the scar. By poking the patient's virtual heart with small electrical signals in different locations, the computer program then determines whether the heart develops an arrhythmia and the location of the tissue that perpetuates it. Using the model, Trayanova then simulates an ablation to that area of the heart and runs the computer program over and over to find multiple locations that doctors should ablate on the actual patient.

Among the experiments in the current study, Trayanova and her team used MRI images to create personalized heart models of 21 people who previously had successful cardiac ablation procedures for infarct-related ventricular tachycardia at The Johns Hopkins Hospital between 2006 and 2017. The 3D modeling of these patients correctly identified and predicted the locations where physicians ablated heart tissue. In five patients, the amount of ablated tissue identified by the 3D model was smaller overall--in some cases, more than 10 times smaller--than the area that was destroyed during the patients' procedures.

Next, the research team tested the 3D simulation to guide cardiac ablation treatments for three patients with ventricular tachycardia at the University of Utah and two patients at the University of Pennsylvania. Two patients who received the simulation-guided ablation procedure have remained free of tachycardia throughout follow-up periods of 23 and 21 months. One patient who had the simulation procedure remained free of tachycardia after two months of follow up. In two patients, the virtual heart approach predicted that tachycardias would not be inducible -- this was confirmed during the clinical procedure, so cardiac ablation was not performed.

With this prospective test, the research team demonstrated the feasibility of integrating a computer-simulated prediction into the clinical routine. The patient is scanned approximately 24 hours or less before the procedure. Then, the simulation is created and a prediction is made of where physicians should perform the ablation. Finally, the predicted set of ablation targets is imported into the mapping system before the patient's procedure so that the ablation catheter is navigated directly to the predicted targets.

The study represents the first attempt to incorporate personalized simulation predictions as part of anti-arrhythmia treatment. The researchers believe that implementing these predictions will cut down the lengthy and invasive cardiac mapping process and reduce complications experienced by patients. The technology could also reduce the need for repeat procedures through its ability to make the infarcted heart incapable of creating new arrhythmias.

"It's an exciting blend of engineering and medicine," says Trayanova.

"One of the main challenges of catheter ablation is that we are performing procedures on very sick patients with advanced heart disease who have multiple areas in their heart that could sustain arrhythmias," says Jonathan Chrispin, M.D., Robert E. Meyerhoff Assistant Professor of Medicine at the Johns Hopkins University School of Medicine, who will lead the clinical trials of this technology. "We are excited to begin testing Trayanova's approach in a prospective clinical trial. We are hopeful that it can help us achieve our overarching goal of improving quality of life for patients suffering from treatment-resistant ventricular tachycardia."

Trayanova says the results of a clinical trial are needed to validate the promise of personalized simulation guidance for infarct-related ablation treatments. Further clinical study planned at The Johns Hopkins Hospital was recently approved by the Food and Drug Administration under an investigational device exemption.

Two to three million years ago, the functional loss of a single gene triggered a series of significant changes in what would eventually become the modern human species, altering everything from fertility rates to increasing cancer risk from eating red meat.

In a new paper, published in the September 12 issue of the Proceedings of the Royal Society B, researchers at University of California San Diego School of Medicine report on studies of mice engineered to lack the same gene, called CMAH, and resulting data that suggest the lost gene may also have contributed to humanity's well-documented claim to be among the best long-distance runners in the animal kingdom.

At roughly the same time as the CMAH mutation took hold, human ancestors were transitioning from forest dwellers to life primarily upon the arid savannahs of Africa. While they were already walking upright, the bodies and abilities of these early hominids were evolving dramatically, in particular major changes in skeletal biomechanics and physiology that resulted in long, springy legs, big feet, powerful gluteal muscles and an expansive system of sweat glands able to dissipate heat much more effectively than other larger mammals.

Such changes, say scientists, helped fuel the emergence of the human ability to run long distances relatively tirelessly, allowing ancestors to hunt in the heat of the day when other carnivores were resting and to pursue prey to their point of exhaustion, a technique called persistence hunting.

"We discovered this first clear genetic difference between humans and our closest living evolutionary relatives, the chimpanzees, more than 20 years ago," said senior author Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine and co-director of the UC San Diego/Salk Center for Academic Research and Training in Anthropogeny.

Given the approximate timing of the mutation and its documented impact on fertility in a mouse model with the same mutation, Varki and Pascal Gagneux, PhD, professor of anthropology and pathology, began investigating how the genetic difference might have contributed to the origin of Homo, the genus that includes modern Homo sapiens and extinct species like Homo habilis and Homo erectus.

"Since the mice were also more prone to muscle dystrophy, I had a hunch that there was a connection to the increased long distance running and endurance of Homo," said Varki, "but I had no expertise on the issue and could not convince anyone in my lab to organize this long-shot experiment."

Ultimately, a graduate student named Jon Okerblom took up the task, building mouse running wheels and borrowing a mouse treadmill. "We evaluated the exercise capacity (of mice lacking the CMAH gene), and noted an increased performance during treadmill testing and after 15 days of voluntary wheel running," said Okerblom, the study's first author. The researchers then consulted Ellen Breen, PhD, a research scientist in the division of physiology, part of the Department of Medicine in the UC San Diego School of Medicine, who added observations that the mice displayed greater resistance to fatigue, increased mitochondrial respiration and hind-limb muscle, with more capillaries to increase blood and oxygen supply.

Taken together, Varki said the data suggest CMAH loss contributed to improved skeletal muscle capacity for oxygen utilization. "And if the findings translate to humans, they may have provided early hominids with a selective advantage in their move from trees to becoming permanent hunter-gatherers on the open range."

When the CMAH gene mutated in the genus Homo two to three million years ago, perhaps in response to evolutionary pressures caused by an ancient pathogen, it altered how subsequent hominids and modern humans used sialic acids -- a family of sugar molecules that coat the surfaces of all animal cells, where they serve as vital contact points for interaction with other cells and with the surrounding environment.

The human mutation causes loss of a sialic acid called N-glycolylneuraminic acid (Neu5Gc), and accumulation of its precursor, called N-acetylneuraminic acid or Neu5Ac, which differs by only a single oxygen atom.

This seemingly minor difference affects almost every cell type in the human body -- and has proved to be a mixed blessing. Varki and others have linked the loss of the CMAH gene and sialic acids to not just improved long-distance running ability, but also enhanced innate immunity in early hominids. Sialic acids may also be a biomarker for cancer risk.

Conversely, they have also reported that certain sialic acids are associated with increased risk of type 2 diabetes; may contribute to elevated cancer risk associated with red meat consumption; and trigger inflammation.

"They are a double-edged sword," said Varki. "The consequence of a single lost gene and a small molecular change that appears to have profoundly altered human biology and abilities going back to our origins."

New Rochelle, September 11, 2018-A novel high throughput screening (HTS) assay compatible with an ion channel biosensor component was used successfully to identify selective and active small molecule modulators of G protein-coupled receptor 119 (GPR119), a promising target for the treatment of type 2 diabetes and related metabolic disorders. The development of this cell-based HTS assay and its miniaturization are described in an article published in ASSAY and Drug Development Technologies, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the ASSAY and Drug Development Technologies website through October 11, 2018.

Patricia McDonald, Ainhoa Nieto, Virneliz Fernandez-Vega and colleagues from The Scripps Research Institute, Jupiter, FL coauthored the article entitled "Identification of Novel, Structurally Diverse, Small Molecule Modulators of GPR119."

The researchers describe the use of a HEK293 cell line to co-express the receptor of interest and the ion channel, which functions as a biosensor for cAMP. The group presented data indicating having met their goal, with more than 500,000 small molecules screened and 200 modulators of hGPR119 identified for further follow-up. They were also able to miniaturize the assay and implement it in a 1536-well plate format.

"Prof. McDonald and her team have developed an efficient and robust assay platform to identify new hits for the treatment of type 2 diabetes. The congruence of GPCR screening and development of new drugs for diabetes and other metabolic diseases is of high interest to our readers," says ASSAY and Drug Development Technologies Editor-in-Chief Bruce Melancon, PhD, Director of the Chemical Synthesis and Drug Discovery facility at the University of Notre Dame.

Research reported in this publication was supported by the National Institutes of Health under Award Number DK088125. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Gilding is the process of coating intricate artifacts with precious metals. Ancient Egyptians and Chinese coated their sculptures with thin metal films using gilding--and these golden sculptures have resisted corrosion, wear, and environmental degradation for thousands of years. The middle and outer coffins of Tutankhamun, for instance, are gold leaf gilded, as are many other ancient treasures.

In a new study, Sameh Tawfick, an assistant professor of Mechanical Science and Engineering at the University of Illinois at Urbana-Champaign, inspired by this ancient process, has added a single layer of carbon atoms, known as graphene, on top of metal leaves--doubling the protective quality of gilding against wear and tear.

The study, "Gilding with Graphene: Rapid Chemical Vapor Deposition Synthesis of Graphene on Thin Metal Leaves," is published in the journal Advanced Functional Materials. The researchers coated thin metal leaves of palladium with a single layer of graphene.

Metal leaves, or foils, offer many advantages as a scalable coating material, including their commercial availability in large rolls and their comparatively low price. By bonding a single layer of graphene to the leaves, Tawfick and his team demonstrated unexpected benefits, including enhanced mechanical resistance. Their work presents exciting opportunities for protective coating applications on large structures like buildings or ship hulls, metal surfaces of consumer electronics, and small precious artifacts or jewelry.

"Adding one more layer of graphene atoms onto the palladium made it twice as resistant to indents than the bare leaves alone," said Tawfick. "It's also very attractive from a cost perspective. The amount of graphene needed to cover the gilded structures of the Carbide & Carbon Building in Chicago, for example, would be the size of the head of a pin."

Additionally, the team developed a new technology to grow high-quality graphene directly on the surface of 150 nanometer-thin palladium leaves--in just 30 seconds. Using a process called chemical vapor deposition, in which the metal leaf is processed in a 1,100°C furnace, the bare palladium leaf acts as a catalyst, allowing the gases to react quickly.

"Chemical vapor deposition of graphene requires a very high temperature, which could melt the leaves or cause them to bead up by a process called solid state dewetting," said Kaihao Zhang, PhD candidate in MechSE and lead author of the study. "The process we developed deposits the graphene quickly enough to avoid high-temperature degradation, it's scalable, and it produces graphene of very high quality."

A new study in the Journal of Public Health indicates that adolescents who experience back pain more frequently are also more likely to smoke cigarettes, drink alcohol, and report problems like anxiety and depression.

During adolescence, the prevalence of musculoskeletal pain (pain arising from the bones, joints or muscles) in general, and back pain in particular rises steeply. Although often dismissed as trivial and fleeting, adolescent back pain is responsible for substantial health care use, school absence, and interference with day-to-day activities in some children.

The aim of this study was to determine whether adolescents who experience back pain more often were also more likely to report other health risk indicators, such as alcohol use, smoking, school absenteeism, and depression or anxiety.

Researchers used data collected from approximately 6500 teenagers. The proportion of participants reporting smoking, drinking, and missing school rose incrementally with increasing frequency of pain. For example, 14-15 year olds that experienced pain more than once a week were 2-3 times more likely to have drunk alcohol or smoked in the past month than those who rarely or never had pain. Similarly, students that experienced pain more than once a week were around twice as likely to have missed school in the previous term. The trend with anxiety and depression was less clear, although there was a marked difference between the children who reported no pain, and those who reported frequent pain.

Back pain and unhealthy behaviors not only occur together, but also track into adulthood. This means that they are responsible for current issues, and also have implications for future health. Adolescent back pain may play a role in characterizing poor overall health, and risk of chronic disease throughout life. The researchers involved with the study believe this is of concern because the developing brain may be susceptible to negative influences of toxic substances, and use in early adolescence may increase the risk of substance abuse and mental health problems in later life.

"Findings like this provide an argument that we should be including pain in the broader conversation about adolescent health," said the paper's lead author, Steven Kamper. "Unfortunately our understanding of the causes and impacts pain in this age group is quite limited, the area is badly in need of more research."

A long-established treatment used around the world to help troubled young people and their families tackle behavioural problems may not be as effective as its practitioners claim - a new study reveals.

Functional Family Therapy (FFT) is a short-term, evidence-based intervention provided at over 270 sites worldwide - mostly within the US, but also in Belgium, Ireland, The Netherlands, New Zealand, Norway, Sweden and the UK.

Researchers at the University of Birmingham recommend that greater examination of FFT is needed, after evaluating 31 existing reviews of research on the treatment's effectiveness in treating young people, aged 10 to 18.

They found that the quality of evidence in reviews was mixed and adversely affected by small sample sizes, no critical appraisal methods and a failure to examine evidence for risk of bias.

Paul Montgomery, Professor of Social Intervention in the University of Birmingham's School of Social Policy, said: "Our overview of FFT illuminates some real areas of concern around this treatment. It appears that in nearly 40 years of existence, there remain a number of unanswered questions about the effectiveness and implementation of FFT.

"FFT is intensive and costly. It may not be advisable to continue using the therapy without re-examining and testing its effects. Many reviews currently available are written by people developing and delivering FFT, demonstrating the need for independent and robust trials."

The study, published in Research on Social Work Practice, reveals that median rates of reoffending with FFT were 28 per cent; as opposed to 57 per cent for usual care. Impact on substance abuse was modest and reducing rates of out-of-home placements was not reported, despite being considered a main outcome of FFT.

Juvenile delinquency represents a major cost in many countries, with the US spending over $5.7 billion annually on incarcerating minors. In the UK, over 42 per cent of minors typically re-offend, up from ten years ago.

Family and youth dysfunction may lead to higher rates of abandonment, higher rates of alcohol and substance use, untreated mental health issues and other negative behaviours. These issues contribute to behavioural disorders resulting in higher likelihood of school drop-out, imprisonment, unemployment and anti-social activities.

FFT is designed to treat the behaviours and acting-out activities that take a toll on youth, families and communities. Additionally, FFT may be used as a re-entry programme for young people being released from institutional settings or at risk for removal from the home.

Scientists at The University of Manchester have developed the first non-antibiotic drug to successfully treat tuberculosis in animals.

The team hope the compound -developed after 10 years of painstaking research will be trialled on humans within three to four years.

The drug- which works by targeting Mycobacterium tuberculosis' defences rather than the bacteria itself - can also take out its increasingly commonly antibiotic resistant strains.

The research funded by the Medical Research Council - is published today in the Journal of Medicinal Chemistry.

Although a vaccine for TB was developed 100 years ago, one in three people across the world are thought to be infected with the infectious disease.

About 1.7 million die from the bug each year worldwide and 7.3 million people were diagnosed and treated in 2018, up from the 6.3 million in 2016.

It is most common in Africa, India and China, but on the rise in the UK with London often described as the TB capital of Europe.

Patients are forced to take a cocktail of strong antibiotics over 6 to 8 months, often enduring unpleasant side effects with a 20% risk that the disease will return.

But now The University of Manchester team's discovery has been proven effective in guinea pigs at Rutgers University in the United States.

The animals with acute and chronic TB infection were treated with the compound, which was discovered after investigating dozens of other derivatives and compounds thought to have similar properties.

Professor Lydia Tabernero is the project leader. She said: "The fact that the animal studies showed our compound, which doesn't kill the bacteria directly, resulted in a significant reduction in the bacterial burden is remarkable.

"For more than 60 years, the only weapon doctors have been able to use against TB is antibiotics. But resistance is becoming an increasingly worrying problem and the prolonged treatment is difficult and distressing for patients.

"And with current treatments, there's no guarantee the disease will be eliminated: antibiotics do not clear the infection and the risk of being infected with drug-resistant bacteria is very high.

"But by disabling this clandestine bacteria's defences we're thrilled to find a way that enhances the chances of the body's immune system to do its job, and thus eliminate the pathogen."

Mycobacterium Tuberculosis secretes molecules called Virulence Factors - the cell's secret weapon -which block out the immune response to the infection, making it difficult to treat.

The team identified one Virulence Factor called MptpB as a suitable target, which when blocked allows white blood cells to kill Mycobacterium Tuberculosis in a more efficient way

Professor Tabernero added: "The great thing about MptpB is that there's nothing similar in humans - so our compound which blocks it is not toxic to the human cells.

"Because the bacteria hasn't been threatened directly, it is less likely to develop resistance against this new agent, and this will be a major advantage over current antibiotics, for which bacteria had already become resistant.

"TB is an amazingly difficult disease to treat so we feel this is a significant breakthrough.

"The next stage of our research is to optimise further the chemical compound, but we hope Clinical trials are up to four years away."

NASA's Aqua satellite passed over the Northwestern Pacific Ocean and captured a visible image of Typhoon Mangkhut lashing Guam and the Northern Marianas Islands.

On Sept. 7 when Mangkhut formed as a tropical depression it was known as Tropical Depression 26W. On the day it formed, a tropical storm watch was posted for Enewetak. 26W then moved west toward Micronesia and strengthened into a typhoon.

On Sept. 10, the National Weather Service (NWS) in Tiyan, Guam said a Typhoon Warning remains in effect for Guam, Rota, Tinian, Saipan and adjacent coastal waters in the Mariana Islands. Guam is a U.S. island territory in Micronesia.

At 0335 UTC on Sept.10 (11:35 p.m. EDT on Sept. 9) the Moderate Resolution Imaging Spectroradiometer or MODIS instrument aboard NASA's Aqua satellite provided a visible image of Typhoon Mangkhut. Satellite imagery shows the center over the Northern Mariana Islands and a thick band of thunderstorms wrapping from south of the center to the west past Guam.

At 5 a.m. EDT on Sept. 10 (7 p.m. CHST local time), the NWS in Guam noted that "Damaging or destructive winds are now occurring. Damaging south winds of up to 105 mph with gusts to 120 mph will continue for the next few hours. Winds will gradually decrease to between 55 and 65 mph around midnight. Damaging south winds early Tuesday morning will decrease to 25 to 35 mph by the afternoon. Small craft should remain in port and well secured."

At 11 a.m. EDT (1 a.m. CHST/1500 UTC) the center of Typhoon Mangkhut was located near Latitude 14.1 degrees north and longitude 143.5 degrees east. That's about 95 miles west-northwest of Guam, 115 miles west of Rota, 155 miles west-southwest of Tinian and about 165 miles west-southwest of Saipan.

Typhoon Mangkhut is moving toward the west at 17 mph. It is expected to make a slight turn to the west-northwest with a decrease in forward speed over the next few days.Maximum sustained winds remain at 115 mph. Typhoon Mangkhut (26W) is forecast to intensify through Wednesday, Sept 12.

Typhoon force winds extend outward from the center up to 50 miles. Tropical storm force winds extend outward from the center up to 180 miles to the north and up to 120 miles to the south.

Mangkhut is forecast to move on a westerly track and move away from Guam and the Marianas while strengthening.

UCLA Samueli engineers have developed a new tool to model how magnetic materials, which are used in smartphones and other communications devices, interact with incoming radio signals that carry data. It accurately predicts these interactions down to the nanometer scales required to build state-of-the-art communications technologies.

The tool allows engineers to design new classes of radio frequency-based components that are able to transport large amounts of data more rapidly, and with less noise interference. Future use cases include smartphones to implantable health monitoring devices.

Magnetic materials can attract or repel each other based on their polar orientation--positive and negative ends attract each other, while two positives or two negatives repel. When an electromagnetic signal like a radio wave passes through such materials, a magnetic material acts like a gatekeeper, letting in the signals that are desired, but keeping out others. They can also amplify the signal, or dampen the speed and strength of the signal.

Engineers have used these gatekeeper-like effects, called "wave-material interactions," to make devices used in communications technologies for decades. For example, these include circulators that send signals in specific directions or frequency-selective limiters that reduce noise by suppressing the strength of unwanted signals.

Current design tools are not comprehensive and precise enough to capture the complete picture of magnetism in dynamic systems, such as implantable devices. The tools also have limits in the design of consumer electronics.

"Our new computational tool addresses these problems by giving electronics designers a clear path toward figuring out how potential materials would be best used in communications devices," said Yuanxun "Ethan" Wang, a professor of electrical and computer engineering who led the research. "Plug in the characteristics of the wave and the magnetic material, and users can easily model nanoscale effects quickly and accurately. To our knowledge, this set of models is the first to incorporate all the critical physics necessary to predict dynamic behavior."

The study was published in the June 2018 print issue of IEEE Transactions on Microwave Theory and Techniques.

The computational tool is based on a method that jointly solves well-known Maxwell's equations, which describe how electricity and magnetism work and the Landau-Lifshitz-Gilbert equation, which describes how magnetization moves inside a solid object.

The study's lead author Zhi Yao is a postdoctoral scholar in Wang's laboratory. Co-authors are Rustu Umut Tok, a postdoctoral scholar in Wang's laboratory, and Tatsuo Itoh, a distinguished professor of electrical and computer engineering at UCLA and the Northrop Grumman Chair in Electrical Engineering. Itoh is also Yao's co-advisor.

The team is working to improve the tool to account for multiple types of magnetic and non-magnetic materials. These improvements could lead it to become a "universal solver," able to account for any type of electromagnetic wave interacting with any type of material.

Wang's research group recently received a $2.4 million grant from the Defense Advanced Research Project Agency to expand the tool's modeling capacity to include additional material properties.