Culture

In recent years, the market for direct-to-consumer genetic testing has exploded. The number of people who used at-home DNA tests more than doubled in 2017, most of them in the U.S. About 1 in 25 American adults now know where their ancestors came from, thanks to companies like AncestryDNA and 23andMe.

As the tests become more popular, these companies are grappling with how to store all the accumulating data and how to process results quickly. A new tool called TeraPCA, created by researchers at Purdue University, is now available to help. The results were published in the journal Bioinformatics.

Despite people's many physical differences (determined by factors like ethnicity, sex or lineage), any two humans are about 99 percent the same genetically. The most common type of genetic variation, which contribute to the 1% that makes us different, are called single nucleotide polymorphisms, or SNPs (pronounced "snips").

SNPs occur nearly once in every 1,000 nucleotides, which means there are about 4 to 5 million SNPs in every person's genome. That's a lot of data to keep track of for even one person, but doing the same for thousands or millions of people is a real challenge.

Most studies of population structure in human genetics use a tool called Principal Component Analysis (PCA), which analyzes a huge set of variables and reduces it to a smaller set that still contains most of the same information. The reduced set of variables, known as principal factors, are much easier to analyze and interpret.

Typically, the data to be analyzed is stored in the system memory, but as datasets get bigger, running PCA becomes infeasible due to the computation overhead and researchers need to use external applications. For the largest genetic testing companies, storing data is not only expensive and technologically challenging, but comes with privacy concerns. The companies have a responsibility to protect the extremely detailed and personal health data of thousands of people, and storing it all on their hard drives could make them an attractive target for hackers.

Like other out-of-core algorithms, TeraPCA was designed to process data too large to fit on a computer's main memory at one time. It makes sense of large datasets by reading small chunks of it at a time.

"In 2017, I met some people from the big genetic testing companies and I asked them what they were doing to run PCA. They were using FlashPCA2, which is the industry standard, but they weren't happy with how long it was taking," said Aritra Bose, a Ph.D. candidate in computer science at Purdue. "To run PCA on the genetic data of a million individuals and as many SNPs with FlashPCA2 would take a couple of days. It can be done with TeraPCA in five or six hours."

The new program cuts down on time by making approximations of the top principal components. Rounding to three or four decimal places yields results just as accurate as the original numbers would, Bose said.

"People who work in genetics don't need 16 digits of precision - that won't help the practitioners," he said. "They need only three to four. If you can reduce it to that, then you can probably get your results pretty fast."

Timing for TeraPCA also was improved by making use of several threads of computation, known as "multithreading." A thread is sort of like a worker on an assembly line; if the process is the manager, the threads are hardworking employees. Those employees rely on the same dataset, but they execute their own stacks.

Today, most universities and large companies have multithreading architectures, but FlashPCA2 doesn't leverage it. For tasks like analyzing genetic data, Bose thinks that's a missed opportunity.

"We thought we should build something that leverages the multithreading architecture that exists right now, and our method scales really well," he said. "TeraPCA scales linearly with the number of threads you have. FlashPCA2 doesn't do this, which means it would take very long to reach your desired accuracy."

Compared to FlashPCA2, TeraPCA performs similarly or better on a single thread and significantly better with multithreading, according to the paper. The code is available now on GitHub.

The performance of different prosthetic implant combinations used in patients undergoing hip and knee replacements in England and Wales over the last 14 years have, for the first time, been directly compared in two new studies. The University of Bristol findings, published in the BMJ Open today [Tuesday 30 April], reveal substantial variability in the performance of different joint replacements, and the number of patients requiring a second surgery.

Using data from the the largest joint replacement register in the world -- the National Joint Registry (NJR) for England, Wales, Northern Ireland and the Isle of Man, researchers from Bristol's Musculoskeletal Research Unit and Wrightington Hospital, assessed 4,442 different hip implants used in 797,178 hip replacements, and 449 different types of knee implants used in 947,686 knee replacements between 1 April 2003 and 31 December 2016.

Failure estimates (the number of procedures requiring a second surgery) of each hip or knee implant brand were compared to the best performing hip or knee implant in the ten years following surgery. The large data set allowed the analysis to be performed for men and women of different ages.

Two thresholds were used for defining the performance of an implant, the first being that implants were at least 100 per cent worse (double the failure rate) than the benchmark implant, the second being that they were at least 20 per cent worse than the benchmark implant.

In analyses of hip replacements at ten years following surgery, it was found that of the 26 implant combinations, with enough data to enable analysis, one had at least a 100 per cent higher risk of revision than the benchmark implant and 11 others had at least 20 per cent higher risk. For knee replacements of the 27 that could be compared at ten years, two implants had at least 100 per cent higher risk of revision and 16 had at least 20 per cent higher risk of revision. Separate analyses of men and women and of different ages illustrate that some implants perform well in some groups, but not others.

Kevin Deere, Senior Research Associate from Bristol's Musculoskeletal Research Unit and lead author on the studies, commented: "We have shown that commonly used hip and knee replacements can have excellent results with very low failure rates. However, there is variation in performance and many implants have been used in too few cases to allow meaningful comparison."

Adrian Sayers, the studies' senior author from Bristol's Musculoskeletal Research Unit in the Bristol Medical School; Translational Health Sciences (THS), added: "This is first time that all the different implant combinations used in England and Wales in the last 14 years have been directly compared, and results are available to everyone. This gives patients the opportunity to discuss with their surgeon the choice of implants they intend to use and see how they perform in comparison to other implants. This research will empower patients and surgeons and help in the decision-making process."

Martyn Porter, hip surgeon and previous President of the British Orthopaedic Association, said: "The data produced by this study is very powerful. It allows patients, surgeons and others interested in the care of patients undergoing joint replacement to have a contemporary and relevant reference for comparison of revision rates. Whilst the rate of revision is only one of the metrics by which the success of joint replacement is judged, it is one that is often important to patients. This data is the beginning of a discussion that patients can have with their surgeon around the type of joint replacement that they might have."

Increased stress during university examinations is associated with eating a poorer quality diet including less fruit and vegetables and more fast food, according to an observational study being presented at this year's European Congress on Obesity (ECO) in Glasgow, UK (28 April-1 May).

"Stress has long been implicated in poor diet. People tend to report overeating and comfort eating foods high in fat, sugar, and calories in times of stress. Our findings looking at the eating habits of students during exam periods confirm this stress-induced dietary deterioration hypothesis", says Dr Nathalie Michels from Ghent University in Belgium who led the research.

"A healthy diet is needed for optimal academic and mental performance. Unfortunately, our findings suggest that students have difficulties eating healthily and find themselves adopting bad eating habits, which over a few weeks can considerably affect your overall health and be difficult to change."

The results are based on an anonymous online survey of 232 students (aged 19-22 years) recruited from Ghent University and other universities in Belgium. Before and after the month-long examination period in January 2017, respondents were asked to disclose their perceived stress and complete questionnaires that assessed changes to their dietary patterns and various psychosocial factors.

The researchers investigated the relationship between exam stress and change in dietary quality, and whether these associations were modified by psychosocial factors such as eating behaviour (emotional/external/restrained), food choice motive, taste preference, reward/punishment sensitivity, impulsivity, coping strategies, sedentary behaviour, and social support.

During the month-long exam period, participants found it harder to stick to a healthy diet, and only a quarter fulfilled the WHO recommended 400g of fruit and vegetables a day. What is more, students reporting higher levels of stress tended to snack more often.

The findings suggest that emotional eaters (who eat in response to negative emotions), external eaters (who eat in response to the sight or smell of food), sweet/fat lovers, people who are highly motivated by health (with health as a food choice motive), sensitive to reward and punishment, highly sedentary, and with higher stress levels are at greatest risk of making unhealthy food choices during this stressful time.

"To fight against stress-induced eating, prevention strategies should integrate psychological and lifestyle aspects including stress management (eg, emotion regulation training, mindfulness, yoga), nutritional education with techniques for self-effectiveness, awareness of eating-without-hunger, and creating an environment that stimulates a healthy diet and physical activity", says Dr Michels.

The authors acknowledge that their findings show observational differences, so no firm conclusions can be drawn about cause and effect. They point to several limitations including that dietary patterns were based on self-reported data which may have introduced information and recall bias; and that most (92%) of the participants were women, who tend to prefer sweet and fatty food as comfort items, which may limit the generalisability of the results to men. Finally, given the small sample size, further research is needed.

The discovery, published today in Nature Communications by researchers from La Trobe University and the University of Queensland, provides details on how proteins in the outer membrane of bacteria - the bacteria's 'superglue' - are able to stick to and populate parts of the human body.

This new information paves the way for the development of innovative treatments for preventing and curing infections, in what could be a significant step forward for new anti-microbial development.

The study focused on UpaB - the superglue protein of a pathogen known to cause urinary tract infections within 50 per cent of women within their lifetime.

Similar proteins are found in the outer membrane of other pathogens responsible for infections ranging from life-threatening food poisoning to whooping cough, meningitis, typhus fever and chlamydia.

Lead researcher at La Trobe University, Dr Begoña Heras, said the study provides unprecedented fundamental science that could inform future solutions to the world health crisis in antibiotic resistance.

"The knowledge we now have on this bacteria's protein gives us the ability to block the bacteria sticking to different parts of the human body," said Dr Heras.

"Antibiotic resistance is an urgent, global problem and this information gives us an important opportunity to develop new anti-microbial treatments. Naturally, this is the next step for this research."

La Trobe researcher Dr Jason Paxman added that there is a flip-side to these bacterial proteins in that they could be harnessed for good.

"There is nothing like these bacterial proteins in modern medicine; bacteria have had thousands of years to develop these adhesive proteins," Dr Paxman explained.

"These findings could open up new opportunities such as delivering targeted therapies to parts of the human body, which could even help in the fight against cancer down the line."

Repeated exposure to alcohol advertising in sport - either at venues or during media coverage of matches - can have long-term effects on drinking attitudes, according to a new international study.

Researchers from the Parisien Laboratory of Social Psychology, the University Grenoble of Alpes (France) and Monash University found a positive and casual link between alcohol sponsorship and alcohol-related attitudes, as well as the specific brand being advertised.

The study, titled "How alcohol advertising and sponsorship works - effects through indirect measures", was published today (Tuesday, 30 April, 2019) in Drug and Alcohol Review.

The alcohol industry accounts for roughly 20% of all sport sponsorships internationally. This is despite evidence showing that direct alcohol sponsorship of sport is associated with more hazardous drinking, and that large numbers of children are exposed to alcohol messages while watching sport.

"What we showed is that alcohol advertising and sponsorship not only send a message directly encouraging people to drink, but tends to implicitly and/or unconsciously associate a product, like beer, within a specific context of going to the football or watching a sports match on television," said the study's co-author, Professor Kerry O'Brien, from Monash University's School of Social Sciences.

Study lead Dr Oulmann Zerhouni reported that: "We also found that exposing people to an alcohol brand, and more strongly to a mainstream alcohol brand, leads to more positive attitudes towards alcohol more generally.

"Our results suggest that alcohol advertising and sponsorship exposure may change attitudes in an automatic fashion, because it doesn't require an individual to cognitively process the advertising stimuli."

As part of the study, 109 students from France were exposed to 10 minutes of a rugby match featuring one of three sponsorship conditions: a globally renowned beer; a domestic beer; or motor oil.

Researchers tested whether incidental exposure to alcohol marketing messages influenced their evaluation of brands and alcohol in general, and whether these decision-making processes occurred naturally. Alcohol consumption immediately following the experiment wasn't analysed.

"We found evidence to suggest that the more popular the brand of alcohol, the greater the influence in changes to participants' drinking attitudes. This wasn't the case when the alcohol brand was relatively unknown, or if the sponsorship was unrelated to alcohol, in this case motor oil," Dr Zerhouni said.

Because sports fans are repeatedly exposed to alcohol advertising and sponsorship when watching sport, Professor O'Brien said this was likely to have a long-term effect on their drinking that needed to be understood and addressed.

"This is especially important for countries that allow alcohol marketing in sport programming during the day, when we know hundreds of thousands of children are watching," he said.

A study of more than 300,000 individuals in Denmark, presented at this year's European Congress on Obesity in Glasgow, Scotland (28 April-1 May), reveals that heavier and taller children are at greater risk than their average-sized peers of developing renal cell carcinoma (RCC) as adults.

RCC is the most common form of kidney cancer found in adults. Although it often occurs in men between the ages of 50 and 70, the cancer can be diagnosed throughout adulthood. Medical experts don't know the exact causes of RCC.

"We know that overweight in adulthood is associated with an increased risk of RCC. We also know that cancers take many years to develop. We therefore had a theory that already being overweight in childhood would increase the risk of RCC later in life," explains lead author Dr Britt Wang Jensen.

To tease out the relationships between childhood body size and the risk of RCC in adulthood, Dr. Jensen, of the Center for Clinical Research and Prevention at Bispebjerg and Frederiksberg Hospital and her colleagues used data from the Copenhagen School Health Records Register (CSHRR). The CSHRR is an electronic data base of health examination information with data from 372,636 children born in Copenhagen in the years 1930 to 1989 (and aged 30 to 89 years now). It contains serial measurements of height and weight as well as birth weight from 1942 onwards reported by the parents.

In their study the researchers included 301,422 individuals (152,573 men) from the CSHRR, born from 1930 to1985. The weights and heights were measured at annual school health examinations at the ages 7-13 years, and body mass index (BMI) was used to categorise the children as normal-weight or overweight, based on age- and sex- specific cut-offs suggested by the International Obesity Task Force. Cases of RCC were identified by linkage to the Danish Cancer Registry.

To analyse the data, the researchers used a statistical technique known as Cox proportional hazards regression. The procedure relates several factors or exposures -- considered simultaneously -- to measure the risk of an outcome, in this case, the risk of developing RCC.

During a median of 32 years of observation, 1,010 individuals (680 men) were diagnosed with RCC. Among men and women significant and positive associations were observed between childhood BMI and height, respectively, and RCC risk. When comparing two 13-year old children with one z-score difference in BMI (equivalent to 5.9 kg for boys and 6.8 kg for girls), but with similar height, the heaviest boy or girl had, in each case, a 14% higher risk of RCC than the leaner child. For height, a one z-score difference in two 13-year old children (equivalent to 8.0 cm for boys and 6.9 cm for girls) was associated with a 12% increased risk of RCC later in life for the taller boy or girl.

Compared to children with a normal-weight at 7 and 13 years, children with overweight at both ages did not have increased risks of RCC, whereas children with normal-weight at 7 years and overweight at 13 years had a 67% greater risk of developing this cancer. Compared to children with an average height at 7 and 13 years, children who were 0.5 z-score taller than average at age 7 years (equivalent to 2.6 cm for boys and girls) and remain taller than average until age 13 years have a 6% increased risk of RCC. Children who grew from average to above average height (0.5 z-score change is equivalent to 4.0 cm additional growth in height for boys and 3.5 cm for girls) had an 8% increased risk of RCC.

The authors say: "We have found in other studies that childhood height is positively associated with several cancer forms. Therefore, we did expect to find that tall children have a higher risk of RCC than average-sized children."

They conclude: "Our findings that heavier and taller children have increased risks of RCC opens the door to new ways to explore the causes of kidney cancer."

BALTIMORE - A new study aims to validate the pediatric version of Sequential Organ Failure Assessment score in the emergency department (ED) setting as a predictor of mortality in all patients and patients with suspected infection. Findings from the study will be presented during the Pediatric Academic Societies (PAS) 2019 Meeting, taking place on April 24 - May 1 in Baltimore.

In adult Sepsis-3, sepsis is defined as a Sequential Organ Failure Assessment (SOFA) score greater than or equal to 2 plus suspected infection. A pediatric version (pSOFA) was derived among pediatric intensive care unit (PICU) patients.

"Our study is the first evaluation of pSOFA and Sepsis-3 outside of the PICU setting in a broad, multi-centered cohort of children seeking emergency care," said Frances Balamuth, MD, PhD, MSCE, one of the authors of the study. "We found that hospital mortality is a very rare outcome in this setting due to the diverse population that seek care in the ED and differentiating it from prior areas of pSOFA study. We found that pSOFA in the ED has face validity in that we observed increasing mortality with increasing pSOFA scores in both the ED population overall, and in those with sepsis according to Sepsis-3 definitions. Interestingly, we found that an ED pSOFA score of greater than or equal to 2 had poor sensitivity for predicting in hospital death, and not surprisingly had better test characteristics in those with suspected infection compared to the ED population overall."

This study involved a retrospective observational study in seven U.S. children's hospitals using the Pediatric Emergency Care Applied Research Network (PECARN) Registry from January 1, 2012 through -March 31, 2018. It included all ED visits for patients less than 18 years.

There were 3,087,746 ED visits during the study period. The pSOFA scores ranged from 0 to 14, with median (IQR) of 0 (0, 0). There were 88,916 (2.9%) visits with pSOFA greater than or equal to 2. Visits with pSOFA greater than or equal to 2 had increased risk of death (RR 31.8 (95% CI 28.5, 35.7) and longer median length of stay (LOS) (116 [41, 358] versus 41 [20, 85] hours, p

The study evaluated the pSOFA score in a large, multicenter sample of pediatric ED visits. The pSOFA greater than or equal to 2 was uncommon but associated with increased mortality. The pSOFA had fair discrimination for in-hospital mortality among all ED visits; and improved discrimination among patients with suspected infection.

Dr. Balamuth continued, "Because the pSOFA score incorporates laboratory values as components of the score, and many children in the ED setting appropriately do not undergo laboratory testing, the pSOFA score likely has limited utility in improving initial clinician sensitivity for mortality risk in children with possible infections. Additional risk stratification tools are needed that are specifically designed for improving sensitivity for the 'needle in the haystack' problem of finding pediatric severe sepsis in the emergency setting."

Dr. Balamuth will present findings from "Validation of the Pediatric Sequential Organ Failure Assessment Score and Evaluation of Sepsis-3 Definitions in the Pediatric Emergency Department" on Sunday, April 28 at 3:30 p.m. EDT. Reporters interested in an interview with Dr. Balamuth should contact PAS2019@piercom.com. Please note that only the abstracts are being presented at the meeting. In some cases, the researchers may have additional data to share with media.

The PAS 2019 Meeting brings together thousands of pediatricians and other health care providers to improve the health and well-being of children worldwide. For more information about the PAS 2019 Meeting, please visit http://www.pas-meeting.org.

BALTIMORE - A new systematic review provides a succinct summary of the scientific evidence for and/or against causal associations for 47 adverse events following immunization (AEFI). Findings from the study will be presented during the Pediatric Academic Societies (PAS) 2019 Meeting, taking place on April 24 - May 1 in Baltimore.

"Health care providers desire objective and clear information on a broad range of vaccine safety issues to assist them in answering patient questions," said Matthew Dudley, PhD, MSPH, one of the authors of the study. "There have been no recent comprehensive reviews on AEFI, and previous reviews were not written for providers or the public. This systematic review provides an update to the scientific evidence assessing possible causal associations of AEFI compiled in the 2012 report from the Institute of Medicine (IOM) and the 2014 report from the Agency for Healthcare Research and Quality (AHRQ), along with clear causality conclusions intended for health care providers."

The review found that for 12 of the 47 AEFI studied, a causal relationship has been established with at least one vaccine currently routinely recommended to the general population in the U.S. These 12 confirmed adverse reactions are: anaphylaxis, arthralgia/arthritis (mild, acute and transient, not chronic), deltoid bursitis (when vaccine is administered improperly), disseminated varicella infection (in immune deficient individuals for whom the varicella vaccine is contraindicated), encephalitis, febrile seizures, Guillain-Barré Syndrome, hepatitis (in immune deficient individuals for whom the varicella vaccine is contraindicated), herpes zoster, immune thrombocytopenic purpura, meningitis and syncope. Most of these adverse reactions are rare.

For the other 35 AEFIs, the evidence does not support a causal relationship with vaccines recommended for routine use in the U.S. In particular, the evidence shows a clear lack of association between certain vaccines and AEFIs: influenza vaccines do not cause asthma, childhood vaccines do not cause autism, vaccines do not cause diabetes, vaccines given to immunocompetent persons do not cause hepatitis, influenza vaccines do not cause MS in adults, and DTP and hepatitis B vaccines do not cause Sudden Infant Death Syndrome (SIDS).

Dr. Dudley added, "Although vaccines currently recommended for the general population in the U.S. do cause some adverse reactions, vaccines have an excellent safety profile overall and provide protection against infectious diseases to individuals and the general population."

Dr. Dudley will present findings from "The State of Vaccine Safety Science: Systematic Reviews of the Evidence" on Monday, April 29 at 10:30 a.m. EDT. Reporters interested in an interview with Dr. Dudley should contact PAS2019@piercom.com. Please note that only the abstracts are being presented at the meeting. In some cases, the researchers may have additional data to share with media.

The PAS 2019 Meeting brings together thousands of pediatricians and other health care providers to improve the health and well-being of children worldwide. For more information about the PAS 2019 Meeting, please visit http://www.pas-meeting.org.

Obesity and emotional problems, such as feelings of low mood and anxiety, tend to develop hand-in-hand from as young as age 7 years, according to new research being presented at this year's European Congress on Obesity (ECO) in Glasgow, UK (28 April-1 May).

The analysis of a large nationally representative sample of over 17,000 children in the UK finds that regardless of their socioeconomic status, girls and boys with obesity at age 7 were at greater risk of emotional problems at age 11, which in turn, predicted high body mass index (BMI) at 14 years of age.

While the study did not investigate the reasons why obesity and emotional problems develop together during childhood, the researchers say that a range of factors are likely to be involved.

"Children with higher BMI may experience weight-related discrimination and poor self-esteem, which could contribute to increased depressive symptoms over time (as has been shown in adults), while depression may lead to obesity through increased emotional eating of high-calorie comfort foods, poor sleep patterns, and lethargy", explains Dr Charlotte Hardman from the University of Liverpool, UK, who co-led the study. "Our findings highlight the importance of early interventions that target both weight and mental health and minimise negative outcomes later in childhood."

Adolescence is a key developmental period for both obesity and emotional problems. But how they relate to each other over time is unclear, and little research has focused on the onset and co-occurrence of these disorders through childhood and adolescence.

Lower socioeconomic status is strongly associated with both obesity and poor mental health, but it is unknown whether the association between these two health outcomes is merely a function of shared socioeconomic disadvantage.

In this study, researchers used statistical modelling to assess associations between obesity and emotional problems in 17,215 children born in the UK between 2000 and 2002, who are taking part in the Millennium Cohort Study--a nationally representative, UK birth cohort study of over 19,000 individuals born at the start of the millennium.

Information on children's height and weight (BMI) were collected at ages 3, 5, 7, 11 and 14 years, and parents filled in a questionnaire on their children's emotional problems such as feelings of low mood and anxiety. The researchers adjusted for a range of factors known to affect both obesity and mental health including gender, ethnicity, socioeconomic status, and behavioural problems, as well as parents' mental health.

Rates of obesity and emotional problems increased gradually throughout childhood and adolescence. Almost 8% (814/10,767 children with available data) of young people were obese by the age of 14, and around twice that number were reported to have had feelings of low mood and anxiety (1369/10,123).

By adolescence, around a fifth (137/693) of those with obesity also had high levels of emotional distress.

The analysis found that obesity and emotional problems tended to occur together in mid-childhood and adolescence between the 7 and 14 years of age, but not in early childhood (3 to 5 years of age).

On average, girls had higher BMIs and emotional symptoms than boys from 7 to 14 years of age, but co-occurrence and development of obesity and emotional problems were similar in both girls and boys.

After taking socioeconomic status into account, the association between BMI and emotional problems was reduced slightly, suggesting that socioeconomic disadvantage may partly explain the link between children's obesity and poor mental health.

"The shared socioeconomic risk in the development of obesity and poor mental ill-health could be explained by numerous factors. For instance, socioeconomically deprived areas tend to have poorer access to healthy food and green spaces, which may contribute to increased obesity and emotional problems, and compound the effects of family-level socioeconomic disadvantage", says Dr Praveetha Patalay from University College London, UK who co-led the research.

"As both rates of obesity and emotional problems in childhood are increasing, understanding their co-occurrence is an important public health concern, as both are linked with poor health in adulthood. The next steps are to understand the implications of their co-occurrence and how to best intervene to promote good health."

The authors acknowledge that their findings show observational associations, so conclusions about cause and effect cannot be drawn. They point to several limitations, including unmeasured confounding, parent report, and the attrition rate that may have influenced the results.

BALTIMORE - A new study measures the impact state-run, prescription drug monitoring programs (PDMPs), pain clinic legislation and opioid prescribing guidelines have on opioid exposures among children. Findings from the study will be presented during the Pediatric Academic Societies (PAS) 2019 Meeting, taking place on April 24 - May 1 in Baltimore.

"The U.S. remains in the throes of an opioid epidemic born out of the overzealous prescribing of opioids over the past two decades and with national guidelines and monitoring programs primarily focused on adult populations, there is limited information on the effects of opioid policies on opioid exposures and poisonings in children," said Michael Toce, MD, one of the authors of the study. "We investigated the effects of state-level PDMPs, pain clinic legislation and mandatory opioid prescribing limits on pediatric opioid exposures reported to U.S. Poison Control Centers. Our results indicate that these policies--though designed primarily for adults--are associated with significant reductions in opioid exposures among children."

The study analyzed opioid exposures reported to the National Poison Data System (NPDS) for children less than 20 years of age between 2005 and 2017. The NPDS database is maintained by the American Association of Poison Control and collects data on exposures reported to 55 poison control centers across the U.S. Then, the authors conducted a state-level interrupted time series analysis to examine the impact of PDMPs, pain clinic legislation and opioid prescribing guidelines have on the rate of opioid exposures in children per month. The primary outcome was the change in rate of pediatric opioid exposures, before and after implementation of each opioid reduction policy at the state level. Models included covariates to account for socioeconomic and demographic factors that are associated with opioid exposure.

There were 332,745 opioid exposures in children reported to the NPDS during the study period. The majority of exposures in children at or less than 4 years were unintentional (99.2%) while the majority among those 15 to 19 years were intentional (88.8%). The total number of exposures peaked in 2009. The rate of exposures per 100,000 children was highest for children less than or equal to 4 years of age, followed by children 15 to 19 years of age. The implementation of a PDMP was associated with an overall decrease of 0.27 fewer opioid exposures per 100,000 children per month. Implementation of an opioid prescribing guideline was associated with an immediate 20% reduction in the rate of opioid exposures, but the overall effect was not statistically significant. Conversely, implementation of pain clinic legislation was associated with an immediate 22% reduction in exposures, and overall was associated with a decrease of 0.84 fewer opioid exposures per 100,000 per month.

The findings indicate that state opioid reduction policies are associated with a significant decrease in opioid exposures among children.

Dr. Toce added, "Building on this work, additional analyses will be conducted to identify policy features most protective to children so that future initiatives can further promote the public health benefits of opioid policies for pediatric populations."

Dr. Toce will present findings from "Impact of Prescription Drug Monitoring Programs on Pediatric Opioid Exposures" on Monday, April 29 at 1 p.m. EDT. Reporters interested in an interview with Dr. Toce should contact PAS2019@piercom.com. Please note that only the abstracts are being presented at the meeting. In some cases, the researchers may have additional data to share with media.

The PAS 2019 Meeting brings together thousands of pediatricians and other health care providers to improve the health and well-being of children worldwide. For more information about the PAS 2019 Meeting, please visit http://www.pas-meeting.org.

BALTIMORE - A new study shines light on pediatric opioid deaths by U.S. region, the first time a study of this nature has been conducted. Findings from the study will be presented during the Pediatric Academic Societies (PAS) 2019 Meeting, taking place on April 24 - May 1 in Baltimore.

"Although we know that nearly 10,000 children and adolescents died from opioid poisonings over the past two decades in the United States, we have little understanding of how kids in particular regions of the country have been affected by the opioid crisis," said Julie Gaither, PhD, MPH, RN, the lead author of the study. "In this study, we found that while there was a four-fold increase in pediatric deaths from opioids in the Midwest, while there was only a two-fold increase in the West. Moreover, unlike with every other region of the country, there has not been a recent upsurge in deaths from heroin and illicit fentanyl in the western states."

The study analyzed CDC mortality data--stratified by the four U.S. census regions--for children and adolescents less than 20 years of age who died from opioid poisonings between 1999 and 2016. Generalized smoothing spline Poisson regression was used to estimate mortality rates per 100,000.

Nationally, 8,986 children and adolescents died from opioid poisonings between 1999 and 2016; the pediatric mortality rate increased 268.2%, from 0.22 to 0.81 per 100,000. Mortality rates were highest in the Northeast in both 1999 and 2016 at 0.33 and 1.05, respectively, but the largest increase over time occurred in the Midwest, where rates rose by 429.4%, from 0.17 to 0.90. The smallest increase was in the West, where rates increased by 200.0%, from 0.19 to 0.57. In all regions but the West, there was a marked upswing in mortality rates between 2013 and 2016. This increase can be attributed to a recent surge in deaths from heroin and synthetic opioids (primarily illicit fentanyl) among 15 to 19-year-olds. In this group, heroin was implicated in 32.1% of all opioid deaths in the Northeast (highest proportion), compared to 18.3% in the South (lowest proportion). Similarly, synthetic opioids were implicated in 17.5% of opioid deaths in the Northeast, compared to 8.9% in the South.

In the U.S., pediatric mortality rates for opioid poisonings increased nearly 3-fold over 18 years; however, substantial variation exists in the degree to which children and adolescents in particular regions of the country were affected. Mortality rates in the Midwest increased more than 4-fold, compared to a 2-fold increase in the West. A better understanding of how fatal pediatric opioid poisonings vary geographically has the potential to aid in the development of targeted interventions to mitigate what is a growing public health problem for the young in the U.S.

Dr. Gaither added, "We are interested in finding out what is at the root of this variation, and whether there are public health policies in place in the West that are serving as safeguards for kids; and if so, how do we begin to implement them across the rest of the country?"

Dr. Gaither will present findings from "Geographic Variation in Pediatric Deaths from Prescription and Illicit Opioid Poisonings, 1999-2016" on Saturday, April 27 at 5:30 p.m. EDT. Reporters interested in an interview with Dr. Gaither should contact PAS2019@piercom.com. Please note that only the abstracts are being presented at the meeting. In some cases, the researchers may have additional data to share with media.

The PAS 2019 Meeting brings together thousands of pediatricians and other health care providers to improve the health and well-being of children worldwide. For more information about the PAS 2019 Meeting, please visit http://www.pas-meeting.org.

BALTIMORE - Text message reminders led to timely HPV vaccine series completion across a low-income, urban, minority population, according to a new study. Findings from the study will be presented during the Pediatric Academic Societies (PAS) 2019 Meeting, taking place on April 24 - May 1 in Baltimore.

"HPV vaccine is a critical cancer-protecting vaccine; yet, only half of adolescents have received their needed doses," said Melissa Stockwell, MD, MPH, FAAP, Associate Professor of Pediatrics and Population and Family Health at Columbia University Irving Medical Center, the lead author of the study. "Even among those who start the series, only three-quarters get all the doses needed for protection. In this study, we found that text message vaccine reminders are a powerful, rapid and scalable way to help encourage families to have adolescents complete their vaccine series."

In this AHRQ-funded study, eligible 9 to 17-year-olds receiving their first HPV vaccine at four affiliated community clinics in Northern Manhattan from December 2014 through December 2016 were randomized 1:1 to receive one of two types of text message vaccine reminders. Conventional messages included next dose due date and site-specific walk-in hours. Enhanced educational reminders included educational information targeted to the parent's stage of vaccine decision-making based on the transtheoretical model. The primary outcome was timely HPV vaccine series completion within 12 months (receipt of two or three doses, based on age and enrollment date, accounting for the 2016 change in CDC guidelines).

Chi-square analyses compared the intervention arms to concurrent non-enrollees who received their first vaccine dose during the study period, but who were not enrolled because they were ineligible, not able to be contacted or refused. Participants were also compared to historical controls (first dose administered 2011-2013); for this analysis adolescents from the intervention arms who only needed two doses to complete the series were removed in order to be more directly comparable. In addition, population coverage for those who received their first dose within the three years prior (2011-2013) and three years (2014-2016) during the intervention were calculated.

Overall, 956 parents of 1,264 eligible families enrolled. Adolescents were half female, and primarily Latino (89%), less than or equal to 14 years (92%), and publicly insured (94%). Two-thirds of parents were primarily Spanish speaking; 60.0% had not finished high school. Both text message arms had similarly high timely series completion rates within 12 months: educational (72.4%) versus conventional (75.7%). Those who were in any text message arm had significantly higher completion rates than non-enrollees (n= 1503)(74.1% vs 45.2%; P

Dr. Stockwell will present findings from "Impact of Text Message Reminders on HPV Vaccine Series Completion" on Monday, April 29 at 10:30 a.m. EDT. Reporters interested in an interview with Dr. Stockwell should contact PAS2019@piercom.com. Please note that only the abstracts are being presented at the meeting. In some cases, the researchers may have additional data to share with media.

The PAS 2019 Meeting brings together thousands of pediatricians and other health care providers to improve the health and well-being of children worldwide. For more information about the PAS 2019 Meeting, please visit http://www.pas-meeting.org.

BALTIMORE - Pediatricians and nurse practitioners report using several strategies to improve human papillomavirus (HPV) vaccination, yet also perceive barriers, according to a national American Academy of Pediatrics (AAP) Pediatric Research in Office Settings (PROS) network study. Findings from the study will be presented during the Pediatric Academic Societies (PAS) 2019 Meeting, taking place on April 24 - May 1 in Baltimore.

A safe and effective vaccine that prevents HPV-attributable cancers has been available since 2006. Despite demonstrated safety and effectiveness, coverage rates for the HPV vaccine remain suboptimal, and considerably lower than coverage for other adolescent vaccinations.

The study examined barriers to HPV vaccination and strategies used to improve HPV vaccination rates in a sample of pediatricians and nurse practitioners from 19 states who participate in the AAP's primary care practice-based research network. As part of the NIH-funded STOP HPV trial, the lead respondent from 47 practices recruited from the PROS research network completed an online, confidential survey in 2018. The survey measured office characteristics, standard office procedures for and communication about HPV vaccination, and use of evidence-based strategies such as performance feedback, prompts, reminder-recall, and standing orders. Proportions and medians were calculated for categorical and continuous variables, respectively.

All respondents reported more than one barrier to HPV vaccination. The most commonly reported major barrier was parent refusal or delay (over 80%). Respondents reported approximately 30% (range 5%-75%) of parents of their 11 to 12-yr-old patients due for an HPV vaccine refused and 15% (range 5%-60%) hesitated without refusing. Other major barriers reported by respondents included the time required to discuss HPV vaccination with families (17% of practitioners), low proportion of adolescents coming in for well visits (13%), lack of training in providing a strong recommendation (11%), respondents sense that others may view that HPV vaccination can wait (9%), and challenges associated with administering HPV vaccine at acute or chronic care visits (7%).

The most commonly reported strategy to improve HPV vaccination rates was use of prompts when HPV vaccination is needed (89%). Respondents also reported that their practices commonly use tools to improve communication about HPV vaccination with parents and adolescents (87%) and receive performance feedback about HPV vaccination rates (83%). Only 17% of respondents cited that their practice uses reminder-recall messages specific to the HPV vaccine.

The study concluded that respondent-perceived barriers to HPV vaccination remain. Practices are already using a wide variety of strategies to improve delivery of this vaccine, yet room for improvement remains. Alexander Fiks, MD, FAAP, MSCE, the senior author on the abstract, primary care pediatrician at Children's Hospital of Philadelphia, PROS Director and associate director of the Center for Pediatric Clinical Effectiveness and researcher at PolicyLab, added: "The ongoing STOP HPV trial will test the effectiveness of distinct strategies, alone or in combination, to overcome barriers to vaccination and, if effective, may ultimately minimize the burden of HPV-related disease."

Margaret Wright, PhD, one of the authors of the study, will present findings from "Pediatric Practitioners Report Using Strategies to Improve HPV Vaccination, yet Barriers Persist: Results from the National AAP Pediatric Research in Office Settings (PROS) Network" on Monday, April 29 at 10:30 a.m. EDT. Reporters interested in an interview with Dr. Fiks should contact PAS2019@piercom.com.

The PAS 2019 Meeting brings together thousands of pediatricians and other health care providers to improve the health and well-being of children worldwide. For more information about the PAS 2019 Meeting, please visit http://www.pas-meeting.org.

LA JOLLA, CA--A family of cancer suppressive proteins, known as TET proteins, help regulate gene activity via their influence on chromosomal architecture. However, until now it wasn't entirely clear how genes were activated by TET proteins to make sure that cells perform their normal functions efficiently.

The team of La Jolla Institute for Immunology investigator Anjana Rao, Ph.D, addresses that question in the April 26, 2019, issue of the journal Science Immunology. They report that genetic deletion, or mutation, of TET2 and TET3 in mouse B cells damps down the generation of functional IgG antibodies, decreasing the effectiveness of immune responses.

Moreover, they identify a B cell gene that becomes aberrantly silenced in the absence of TET2 and TET3, highlighting how critical "epigenetic" control of gene expression is for healthy immune cell function and hinting at why TET loss promotes oncogenesis.

DNA can be loosely or tightly coiled--tight coiling silences genes buried within chromosomal twists, while gene expression proceeds as coils unwind and DNA becomes more accessible. This process is influenced by TET proteins, which modify the chemical structure of DNA by altering a methyl group attached to C, one of the four DNA bases A, C, T and G. This so-called "epigenetic regulation" by altering DNA accessibility or structure is a major strategy that cells use to switch genes on and off.

"Previously people knew that TET proteins were involved in suppressing cancer," says study-co-author Chan-Wang Jerry Lio, Ph.D., one of the study's two co-first authors. "But it was difficult to tease out what the normal function of TET genes was because mice developed cancer so rapidly when we deleted them."

The new study circumvents this issue by using an alternate "conditional knock-out" strategy in which experimenters deleted TET2 and TET3 in mature B cells at a time point of their choice in experimental mice. Five days later, they removed the mouse's B cells and performed a battery of molecular tests to compare their activity with B cells derived from normal mice in which TET2 and TET3 remained intact.

A critical difference was that when stimulated by an experimental pathogen, mutant B cells that lacked TET2 and TET3 produced an overabundance of a class of antibody called IgM, whereas normal control B cells churned out more effective antibodies classified as IgG or "gamma globulin".

"Antibodies come in different 'flavors'", explains Vipul Shukla, Ph.D., the study's other co-first author. "The standard flavor (IgM) does a poor job of activating other immune cells. So once a normal B cell encounters a pathogen, it tries to convert IgM antibodies to a more beneficial flavor to mount an effective immune response."

That "beneficial" flavor, known to immunologists as IgG, constitutes ~75% of all antibodies found in normal human serum and is what you received if you ever got an immunity-boosting gamma globulin shot.

Healthy B cells have no problem converting IgM to IgG using an innate gene editing trick called "class switching", in which protein tools snip out IgM-specific regions in a DNA strand and then paste in analogous IgG DNA sequences. That maneuver creates recombined genes that express IgG antibodies, which unlike IgM, are capable of neutralizing pathogens, helping other cells recognize invaders (including cancer cells), and maintaining an organism's well-being.

And that is where TET comes in. Rao's group found that mutant B cells lacking TET2 and TET3 flip this switch only poorly and instead remain stuck making IgM antibodies because they lack the requisite DNA splicing tool. Specifically, mutant cells lacking TET2 and TET3 do not make enough of a protein called AID, which actually executes the IgM-to-IgG splicing trick, simply because TET2 and TET3 were not available to demethylate and hence enhance expression of the AID gene. In mutant cells lacking TET2 and TET3, the AID gene likely remains methylated, inaccessible and silent, allowing IgM antibodies to predominate.

An inability to perform class switching has clinical consequences: patients who inherit mutations in the AID gene (which in humans is called AICDA) suffer an immune deficiency called hyper IgM syndrome, in which their B cells can't make the normal conversion of IgM to IgG antibodies. Those individuals are more vulnerable to severe infection and to malignancy.

TET genes have not yet been implicated in hyper IgM syndrome. But the revelation that the AID gene is a TET target makes unquestionable immunological sense to Lio in this context. "TET2 is the most frequently mutated gene in blood cancers including diffuse large B cell lymphomas, which suggests that it restrains cancer progression in normal B cells" he says. "More importantly, the full activity of TET proteins requires vitamin C. Our study may explain how a healthy diet may enhance our immune response."

Shukla concurs. "TET proteins are often inhibited in cancers, including cancers derived from B cells addressed here," he says. "An important rationale for this paper was to identify the normal function of TET proteins so that we better understand why cancers develop when TET genes are restrained."

COLUMBUS, Ohio - If you believe that great scientists are most creative when they're young, you are missing part of the story.

A new study of winners of the Nobel Prize in economics finds that there are two different life cycles of creativity, one that hits some people early in their career and another that more often strikes later in life.

In this study, the early peak was found for laureates in their mid-20s and the later peak for those in their mid-50s.

The research supports previous work by the authors that found similar patterns in the arts and other sciences.

"We believe what we found in this study isn't limited to economics, but could apply to creativity more generally," said Bruce Weinberg, lead author of the study and professor of economics at The Ohio State University.

"Many people believe that creativity is exclusively associated with youth, but it really depends on what kind of creativity you're talking about."

Weinberg did the study with David Galenson, professor of economics at the University of Chicago. Their study appears in a special issue of the journal De Economist.

In the study, the Nobel Prize winners who did their most groundbreaking work early in their career tended to be "conceptual" innovators.

These type of innovators "think outside the box," challenging conventional wisdom and tend to come up with new ideas suddenly. Conceptual innovators tend to peak early in their careers, before they become immersed in the already accepted theories of the field, Weinberg said.

But there is another kind of creativity, he said, which is found among "experimental" innovators. These innovators accumulate knowledge through their careers and find groundbreaking ways to analyze, interpret and synthesize that information into new ways of understanding.

The long periods of trial and error required for important experimental innovations make them tend to occur late in a Nobel laureate's career.

"Whether you hit your creative peak early or late in your career depends on whether you have a conceptual or experimental approach," Weinberg said.

The researchers took a novel, empirical approach to the study, which involved 31 laureates. They arranged the laureates on a list from the most experimental to most conceptual.

This ranking was based on specific, objective characteristics of the laureates' single most important work that are indicative of a conceptual or experimental approach.

For example, conceptual economists tend to use assumptions, proofs and equations and have a mathematical appendix or introduction to their papers.

Experimental economists rely on direct inference from facts, so their papers tended to have more references to specific items, such as places, time periods and industries or commodities.

After classifying the laureates, the researchers determined the age at which each laureate made his most important contribution to economics and could be considered at his creative peak.

They did this through a convention of how academics rate the value and influence of a research paper. A paper is more influential in the field when other scientists mention - or cite - the paper in their own work. So the more citations a paper accumulates, the more influential it is.

Weinberg and Galenson used two different methods to calculate at which age the laureates were cited most often and thus were at the height of their creativity.

The two methods found that conceptual laureates peaked at about either 29 or 25 years of age. Experimental laureates peaked when they were roughly twice as old - at about 57 in one method or the mid-50s in the other.

Most other research in this area has studied differences in peak ages of creativity between disciplines, such as physics versus medical sciences. These studies generally find small variations across disciplines, with creativity peaking in the mid-30s to early 40s in most scientific fields.

"These studies attribute differences in creative peaks to the nature of the scientific fields themselves, not to the scientists doing the work," Weinberg said.

"Our research suggests than when you're most creative is less a product of the scientific field that you're in and is more about how you approach the work you do."