Body

London, May 14, 2018
-- Very obese women should actually lose weight during pregnancy in order to have a healthy baby, contrary to current recommendations, according to a new study in the journal Heliyon. The researchers behind the study, from Centre Hospitalier Universitaire Sud Réunion in France, say the current guidelines for weight gain in pregnancy should be adjusted for better outcomes in underweight and very obese women and their babies.

The new study reveals the optimal weight gain for women that would give them a balanced risk of having a very small or very large baby. The findings will enable healthcare providers to give their patients more personalized recommendations. The team has developed an online calculator that can advise women on their ideal weight gain for the safest birth outcome, based on the research.

“The results of our research provide a solution to the conundrum affecting the 135 million pregnancies per year on this planet,” said lead author Dr. Pierre-Yves Robillard. “Women want to know what their optimal weight gain should be to have their baby as safely as possible, and their maternity care providers want to know what advice they can give women throughout their pregnancy. While our results show the recommendations are fine for women in the normal weight range, we have shown they are not ideal for very underweight and very overweight women.”

There is a strong link between the weight of mother and baby: very underweight mothers tend to have smaller babies – called small for gestational age (SGA) babies – and morbidly obese mothers tend to have more large for gestational age (LGA) babies. These babies are at higher risk of conditions like heart attacks, hypertension, obesity and diabetes as adults than babies born at normal weight.

In order to ensure babies have the safest births and healthiest lives possible, there are guidelines recommending the ideal weight gain during pregnancy based on body mass index (BMI). These guidelines, set by the US Institute of Medicine in 2009, have been subject to some controversy: in countries where women are generally smaller, such as Japan and Korea, healthcare providers have suggested the weight gain at the lower end of the spectrum is not sufficient. With the increasing burden of obesity in many countries, it has been suggested that very obese women should in fact lose weight during pregnancy.

To test these claims, Dr. Robillard and the team carried out a 16.5-year observational study. They recorded the pre-pregnancy BMI, weight gain, and weight of the baby of 52,092 women who gave birth at full term. The first finding was that only women with a normal BMI had a balanced risk of having an SGA or LGA baby (both 10 percent risk); they call this crossing point the Maternal Fetal Corpulence Symbiosis (MFCS).

They then looked at how this MFCS shifted with BMI and weight gained during pregnancy. They pinpointed for each BMI category what the optimal weight gain should be for a balanced risk of having an SGA and LGA baby. This revealed that although the current recommendations are correct for women with a normal BMI, they are not correct for underweight or obese women.

According to the study, a woman with a BMI of 17 should gain about 22kg instead of the recommended 12.5-18kg. An obese woman with a BMI of 32 should gain 3.6 kg instead of the recommended 5-9kg. And a very obese women with a BMI of 40 should actually lose 6kg.

“We were surprised to find such a linear connection between BMI, weight gain and MFCS,” said Dr. Robillard. “The results will greatly facilitate an individualized approach when advising women about their optimal weight gain during pregnancy without having to put them into fixed categories – using the equation we uncovered, it’s possible to give specific advice based on the exact BMI of the woman.”

The results have already led to an online calculator in which a woman can enter their height and weight to get a specific recommendation for her optimal weight gain, based on the research results. This could be developed into an app for women and their healthcare providers.

Notes for editorsThe article is “Relationship between pre-pregnancy maternal BMI and optimal weight gain in singleton pregnancies” by Pierre-Yves Robillard et al. (https://doi.org//10.1016/j.heliyon.2018.e00615). The article appears in Heliyon (May 2018), published by Elsevier.

This study is published open access and can be downloaded by following the DOI link above.

In online coverage of this paper, please mention the journal Heliyon and link to the paper at https://www.heliyon.com/article/e00615/

About Heliyon Heliyon is an open access journal from Elsevier that publishes robust research across all disciplines. The journal's team of experts ensures that each paper meeting their rigorous criteria is published quickly and distributed widely. Led by Dr. Claudia Lupp, the editorial team consists of over 900 active researchers who review papers on their merit, validity, and technical and ethical soundness. All published papers are immediately and permanently available on both Heliyon.com and ScienceDirect.

About Elsevier
Elsevier is a global information analytics business that helps institutions and professionals advance healthcare, open science and improve performance for the benefit of humanity. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support and professional education, including ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, more than 38,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX Group, a global provider of information and analytics for professionals and business customers across industries. http://www.elsevier.com

Media contactVictoria HowardElsevier+1 215 239 3589v.howard@elsevier.com

Journal

Heliyon

DOI

10.1016/j.heliyon.2018.e00615

Gout, a painful inflammatory arthritis, is not associated with an increased risk of fracture, according to a large study led by Keele University, and published in CMAJ (Canadian Medical Association Journal).

These results contrast with those of previous studies, which found higher risk of fracture in people with gout.

Gout is the most common form of inflammatory arthritis, caused by the buildup of urate crystals in a joint. It can result in severe pain and swelling in joints, most often the base of the big toe but also in other joints. In the United Kingdom, 2.4% of adults are afflicted.

There is some evidence that chronic inflammation may increase the risk of fracture.

Researchers from Keele University conducted a study in the UK using a large primary care database. They included 31 781 patients with gout who were matched to 122961 controls and followed them for between 6.8 and 13.6 years until the first diagnosis of a fracture. The rate of fracture was similar in people with and without gout. In addition, medication to lower urate levels in people with gout did not appear to benefit or adversely affect the long-term risk of fractures.

"Our use of a nationally representative cohort should enable our study findings to be generalizable not only to the UK but also to other countries with similar health care systems," writes Dr. Zoe Paskins, Arthritis Research UK Primary Care Centre, Keele University, Staffordshire, UK.

The study was funded by the National Institute for Health Research (NIHR) School for Primary Care Research in the UK.

"Risk of fragility fracture among patients with gout and the effect of urate-lowering therapy" is published May 14, 2018.

Effective intervention can reduce medication overuse in Residential Aged Care Facilities (RACF's), the latest University of Tasmania research shows.

Led by The Wicking Dementia Research and Education Centre's Dr Juanita Westbury, the research published in the Medical Journal of Australia (MJA) today focuses on the results of the RedUSe (Reducing Use of Sedatives) intervention aimed at reducing the use of psychotropic medications (mainly antipsychotic and benzodiazepine medications) in RACFS around the country.

The research was conducted in 150 Australian RACF's in six states and the ACT.

Dr Westbury's research initially showed around two thirds of RACF residents were prescribed psychotropic medications to manage high rates of sleep disturbance, anxiety, depression and the behavioural and psychological symptoms of dementia.

"For at least two decades, concerns have been raised about inappropriate psychotropic prescribing in Australian residential aged care facilities, due to their modest therapeutic benefits and high risks," Dr Westbury said.

"These medications aren't effective in many cases and can lead to many side effects including a higher risk of falls, pneumonia and stroke."

After an initial trial in Tasmania, Dr Westbury introduced The RedUSe multi-strategic intervention nationally to more than 12,000 aged care residents.

During the project, each RACF's sedative medication use was measured initially, then at three months and finally at six months. Nursing and care staff attended training sessions on psychotropic medication and residents taking these medicines were reviewed by nursing staff, pharmacists and their GP.

Initial or 'baseline statistics' of the research published recently in the Australian & New Zealand Journal of Psychiatry showed that although regular antipsychotic use in Australian RACFs had gone down in the last five years, the routine use of benzodiazepines to treat anxiety, agitation and sleeplessness, had increased.

The use of sedating antidepressants and prescribing of psychotropic medication on an 'as needed' basis had also increased.

Following the introduction of RedUSe, statistics showed a significant reduction of the use of psychotropic medication in RACF's.

"Under RedUSe approximately 40% of residents had their antipsychotic or benzodiazepine medication ceased completely or their dosage reduced," Dr Westbury said.

"Furthermore, substitution to sedating antidepressants did not occur and the issuing on an 'as needed' basis of antipsychotics and benzodiazepines declined significantly."

RedUSe aims to ensure that sedative medication is used appropriately and is reviewed frequently in the aged care setting through strategies including education of nursing staff, promotion of evidence-based guidelines, and drug audits of aged care home medication use.

Dr Westbury said she had received an overwhelmingly positive response to the project from staff at RACFs around the country.

"We were approached by more than 300 RACFS from around Australia to be a part of this project. They were interested in any staff education or project developed to address this issue," she said.

The key recommendations of Dr Westbury's research included making RedUSe available to all Australian RACFs in the future and for the program to be offered as part of the Federally funded 'Quality Use of Medicines' program for community pharmacists.

The research also recommended the provision of national training for RACF staff to manage behavioural and psychological symptoms of dementia and in alternatives to medication for the treatment of these symptoms.

Dr Westbury is a researcher at the University of Tasmania's College of Health and Medicine, Wicking Dementia Research and Education Centre.

Montreal, May 11 2018 -- Historically, our view of host defense against infection was that we must eliminate pathogens to eradicate disease. However, this perspective has recently been challenged as scientists have taken a lesson from plant biologists about an ancient strategy involving the ability to "tolerate" rather than "resist" infection to maintain health. This concept, referred to as "disease toler-ance", provides an opportunity to develop new strategies that mitigate the consequences of infection.

Since the discovery of Mycobacterium tuberculosis, or Mtb, (the bacteria causing TB) over a century ago, great progress has been made in defining strategies that facilitate elimination of the bacteria. For instance, the discovery of antibiotics was a major breakthrough in the treatment of active TB. However, greater than 90 per cent of TB-infected individuals tolerate the bacteria without any treatment.

Dr. Maziar Divangahi, a pulmonary immunologist at the Research Institute of the McGill University Health Centre (RI-MUHC) and a professor of Medicine at McGill University in Montreal, has been try-ing to explain why the vast majority of people infected with Mtb can tolerate the infection without developing disease. Clinicians refer to this condition as "latent tuberculosis", and it affects a quarter of the global population. "TB is a perfect example of disease tolerance," says Dr. Divangahi who is also the associate director of the Translational Research in Respiratory Diseases Program at the RI-MUHC and a member of the McGill International TB Centre.

Dr. Divangahi's team found that rather than fighting to resist the pathogen, the body's tolerance to Mtb is the key mechanism for preventing the spread of the infection. More surprisingly, they found that having excessive levels of T cells, which are known as soldiers of our immune system, could cause more harm than good.

"We always thought that having more T cells would provide better protection against TB. Instead, we found that it could imbalance disease tolerance causing extensive tissue damage and ultimately killing the host," says Dr. Divangahi, lead author of the study published today in Science Immunology, who is the also the associate director of the Meakins-Christie Laboratories.

Disease tolerance versus host resistance

Our body's defense system is divided into two arms: one is resistance, which aims to eliminate the pathogen, while the other is tolerance, which is designed to control the tissue damage caused by the infection.

"While disease tolerance is an established field of research in simple organisms such as plants, our un-derstanding of this host defense strategy in humans is very limited," says Dr. Divangahi.

Although, immunologists and vaccinologists have made progress in the study of host resistance to infectious diseases, little is known about the mechanisms of disease tolerance in humans.

A key protein in disease tolerance

Dr. Divangahi's team determined that a protein in the mitochondria called cyclophilin D (CypD) acts as a key checkpoint for T cell activation. Through collaboration with Dr. Russell Jones from McGill University, who is an international expert in T cell biology, they identified that CypD is required for controlling T cell metabolism. "T cells are traditionally considered to be important in eliminating Mtb," says Dr. Divangahi. "However, we found that increasing T cell activation in mice by eliminating a metabolic checkpoint unexpectedly compromised host survival without any impact on the growth of Mtb."

"In contrast to conventional thinking, we show that T cells are essential for regulating the body's toler-ance to Mtb infection," explains one of the study's first authors, Dr. Nargis Khan, who is currently a postdoctoral fellow in Dr. Divangahi's lab at the RI-MUHC.

Giving the widespread drug resistance to various Mtb strains the limited pipeline of effective antibiotics and the lack of an efficient vaccine, alternative approaches to treat TB are urgent. "If we could understand the mechanisms of 'natural immunity' that controls TB in 90-95 per cent of infected individuals," says Dr. Divangahi,"we will able to design a novel therapy or vaccine to substantially reduce the world wide burden of this ancient disease."

A study published in the BMJ Open journal shows that even moderate coffee consumption during pregnancy, one to two cups per day, is related to a risk of overweight or obesity in school age children. It has not been clearly shown if caffeine is the direct cause of the overweight, but the relationship, alone, has caused researchers to encourage increased caution.

"There may be good cause to increase the restriction of the recommended maximum of three cups of coffee per day. Caffeine is not a medicine that needs to be consumed," says Verena Sengpiel, Associate Professor in obstetrics and gynecology at Sahlgrenska Academy, Sweden, and specialist physician at the Department of Obstetrics and Gynecology at Sahlgrenska University Hospital.

Researchers at Sahlgrenska Academy, in collaboration with the Norwegian Institute of Public Health, studied information on 50 943 pregnant women, in one of the world's largest health surveys of pregnant women, the Norwegian Mother and Child Cohort Study (MoBa).

The results show that children born to mothers who consumed caffeine during pregnancy are at greater risk of being overweight at preschool and school ages. Children were followed until eight years of age. Being overweight in childhood has previously been linked to increased risk of cardiovascular disease and Type 2 diabetes later in life.

For example, at age five, the share of children who were overweight or obese was five percent greater in the group whose mothers had the highest caffeine consumption in the study, compared to those whose mothers had the lowest caffeine consumption.

The association between caffeine consumption during pregnancy and the risk of excess growth and overweight or obesity in children could also be seen in women who had followed the recommended amount for pregnant women. According to the National Food Agency, Sweden, pregnant women should not consume more than 300 milligrams of caffeine per day, which is equivalent to three cups of coffee (1.5 dl each) or six mugs of black tea (2 dl each).

The results of the current study are supported by at least two other studies; however, these included significantly fewer subjects and fewer sources of caffeine. This time, coffee, tea, chocolate, energy drinks and other sources were included.

"In the Nordic countries, coffee is the primary source, while, women in, for example, England receive the greatest amount of caffeine from black tea. If you look at mothers in the younger age group, it comes from energy drinks. We included different sources in the study and found a similar association between caffeine consumption from these different sources and children's growth," says Verena Sengpiel.

In general, the gestational environment is viewed as being important in the turning off and on of genes and metabolic programming for the duration of life. Previous animal studies, where embryos were exposed to caffeine in the womb, were also followed by excess growth and cardiometabolic disease in the offspring.

"Even if more studies are needed before we can say what this finding really means, caffeine is a substance that you can choose to reduce consumption of or completely refrain from during pregnancy," notes Verena Sengpiel.

Young Latina women who have experienced racial or ethnic discrimination are less satisfied overall with their contraceptive care, which could affect their access to more effective contraceptives, a new study from Oregon State University has found.

The findings indicate that experiences of discrimination, inside or outside medical settings, can have a dramatic effect on women's comfort using reproductive health services, said Lisa Oakley, the study's lead author and a post-doctoral researcher in OSU's College of Public Health and Human Sciences.

"It is a positive finding that three-quarters of the women in our study reported being satisfied with their contraceptive care, but among the quarter that reported being unsatisfied, their experience with discrimination and its negative effects on satisfaction could severely affect their contraceptive use experience," Oakley said. "That's really important because a lack of access to effective birth control contributes to increased rates of unintended pregnancy."

The study was published recently in the journal Women's Health Issues. Co-authors are S. Marie Harvey, associate dean and distinguished professor OSU's College of Public Health and Human Sciences and Daniel López-Cevallos, assistant professor of ethnic studies in OSU's College of Liberal Arts.

Harvey received funding from the Centers for Disease Control and Prevention for the research, which was part of a larger Latino Health project focused on the social and cultural factors related to contraceptive use, risky sexual behavior and HIV prevention among young adult Latinos living in rural Oregon.

The researchers' goal in the latest research was to better understand the factors that may affect Latinas' satisfaction with contraceptive services. In all 211 women, ages 18-25, participated in the study, which included surveys and interviews. About 40 percent were born in the U.S. and about 60 percent were born outside the U.S. Among the foreign-born, the average length of U.S. residency was 8.4 years, with a range of less than six months to 24 years.

Initially, the researchers found experiences of discrimination, medical mistrust and structural barriers to care, such as trouble with childcare or getting time off work to see a doctor, were associated with low satisfaction. But when considering all of these influences together, they found that everyday instances of discrimination were the largest influence on women's satisfaction.

It's particularly critical for young women of reproductive age to have access to effective contraceptives to prevent unintended pregnancies, Harvey said. The most effective methods of birth control, including hormonal pills or implantable devices, can only be obtained through a medical provider.

"The causes of unintended pregnancy are broad, but one reason is a lack of access to birth control," she said. "Those who lack access are at higher risk of becoming pregnant, regardless of the individual's behavior. It's a systemic issue."

The researchers found that most of the women in the study, about 83 percent, had seen a health care provider for birth control services in the past, and of those, nearly 90 percent reported receiving birth control services in the past year.

About 75 percent of the women reported being very or extremely satisfied with their birth control services. Among the remaining women, the most significant reason for dissatisfaction was perceived racial or ethnic discrimination.

The perceived discrimination cited by women in the study represents discrimination occurring in everyday experiences such as going to the bank, buying groceries or finding a place to live, Oakley said. It is rooted in the larger environment and culture of a community, but impacts individuals' satisfaction with health care.

"Ensuring health care providers have culturally-responsive staff and reducing other barriers to access, such as child care, transportation and unemployment, can help women feel more satisfied with their overall care," she said. "And satisfaction with care helps to ensure that women will continue to seek medical care, including contraceptives."

"However, because everyday discrimination was the key driver of women's dissatisfaction in this study, it is important to look outside the health care system and into the larger community to identify spaces where discrimination and cultural competence can be addressed," Oakley added.

The study helps researchers understand Latinos' health care experiences in non-traditional but fast-growing settlement areas such as rural Oregon, where Latino populations have grown significantly but the systems to support them have not kept pace, said López-Cevallos.

"Latinos in these areas may not have access to societal supports and resources such as health care that are found in more traditional settlement areas," he said. "They also may be exposed to more discrimination than in areas that do not have a history of Latino settlement. Those early, negative experiences can have a long-term impact on their lives and their decisions about health care."

(Geneva, 11 May, 2018) An international research team has today reported the first results of a study investigating the natural history of progressive familial intrahepatic cholestasis (PFIC) - a rare genetic liver disease that predominantly affects children. Most alarmingly, the team reported that, by the age of 10 years, approximately half of the children with two different forms of PFIC had already received a liver transplant.

The study1 presented today at the 51st Annual Congress of the European Society for Paediatric Gastroenterology Hepatology and Nutrition, was undertaken by the NAPPED (NAtural course and Prognosis of PFIC and Effect of biliary Diversion) Consortium - an international study group whose aim is to characterise globally the natural history of two types of PFIC: PFIC1 (FIC1 protein deficiency) and PFIC2 (BSEP protein deficiency). These conditions result from inherited genetic mutations that lead to impaired bile flow through the liver (cholestasis), resulting in the accumulation of bile, progressive liver damage and, potentially, end-stage liver disease and death2. Children with PFIC may benefit from medical treatment with ursodeoxycholic acid (UDCA) or from surgical biliary diversion techniques, however, many children require a liver transplant at a young age2.

"PFIC1 and PFIC2 are very rare conditions and, because of this, very little is known about their natural history, the impact of different genetic mutations on phenotype, and the overall effectiveness of the treatment options available," said Daan van Wessel from the University Medical Center Groningen in The Netherlands, who presented the study findings in Geneva today. "The NAPPED Consortium, which involves 28 specialist centres across the world, hopes to better define the natural course of disease, the outcomes of different treatment options, and, hopefully, find biomarkers that can help target treatment for these conditions more effectively."

The study involved a retrospective analysis of data from 42 children with PFIC1 and 184 children with PFIC2. Children in the PFIC1 group attended their first specialist centre at a median age of 6 months (range: 0 months to 201 months); and 33% of these had already received UDCA treatment. Children in the PFIC2 group attended their first specialist centre at a median age of 9 months (range: 0 months to 195 months) and 47% had received UDCA. By the age of 5 years, 27% and 36% of children with PFIC1 and PFIC2, respectively, had already received a liver transplant and, by 10 years of age, 49% and 52% of children, respectively, had been transplanted.

The results of this study also shed important new light on the benefits of surgical biliary diversion in children with PFIC - a procedure used to reduce the amount of bile entering the liver2. Although the procedure did not appear to reduce the need for liver transplantation in children with PFIC1, among those with mild or moderately severe PFIC2 mutations, surgical biliary diversion led to a 63% increase in the percentage of children surviving with their own livers compared with those who did not have the procedure (hazard ratio: 0.37; 95% confidence interval: 0.24-0.68; p=0.001).

"This study has demonstrated for the first time that surgical biliary diversion is a highly effective treatment option for children with mild or moderate PFIC2 mutations. Present data on PFIC1 are still inconclusive, but we expect to assess the value of surgical biliary diversion for PFIC1 shortly, based on the ongoing collection of patients' data" said Daan van Wessel. "We hope this information will help healthcare professionals to inform the children and their parents about their possible prognosis and enable clinicians to select treatment options more rationally based on the evidence. The current data also provide strong support for the recent development of oral drugs that accomplish similar effects as surgical biliary diversion" he adds.

Working overtime may negatively influence nurses' collaboration with fellow nurses and physicians, finds a new study by researchers at NYU Rory Meyers College of Nursing.

The study, published in the Journal of Nursing Administration, showed that a third of nurses work beyond their scheduled shift, the average of which is nearly 12 hours.

"One in three nurses reported working longer than scheduled. This appears to be a chronic problem
for nurses - one that extends an already long work day and appears to interfere with collaboration," said Chenjuan Ma, PhD, an assistant professor at NYU Meyers and the study's lead author.

Collaboration among healthcare professionals is critical for quality care and patient safety. Previous studies have shown that patients receive superior care and have better outcomes in hospitals where nurses collaborate well with other healthcare providers. In fact, a study published May 2 in the International Journal of Nursing Studies by Ma and her colleagues finds that both collaboration between nurses and physicians and collaboration among nurses are significantly associated with patient safety outcomes.

However, nurses frequently work long shifts, irregular hours, and unexpected overtime, putting them at risk for fatigue and sleep deprivation. Fatigue and sleep issues can lead to impaired emotional, social, and cognitive processing, which could, in turn, hurt nurses' ability to collaborate. This study sought to evaluate how shift length and working overtime impact nurses' perceptions of collaboration with other care providers, specifically with other nurses and physicians.

The researchers used 2013 survey data from the National Database of Nursing Quality Indicators, analyzing responses from 24,013 nurses in 957 units from 168 U.S. hospitals. Collaboration on a unit was measured using the nurse-nurse interaction scale (RN-RN Scale) and nurse-physician interaction scale (RN-MD Scale). Shift pattern was measured in three ways: average shift length, average overtime, and the proportion of nurses on a unit who worked overtime.

The average shift length was 11.88 hours across the five types of nursing units measured, suggesting that 12-hour shifts are the predominant shift schedule for hospital nurses. Critical care and step-down units had slightly but significantly longer average shift lengths - both 12.17 hours - compared to other units (medical, surgical, and medical-surgical).

On average, nurses worked 24 minutes longer than their scheduled shift. A third (33 percent) of the nurses on a unit reported working longer than initially scheduled and 35 percent of nurses said that the amount of overtime needed from nurses on their unit increased over the past year.

The researchers did not find a significant relationship between average shift length and collaboration, meaning that longer scheduled shifts did not necessarily lead to less collaboration. However, after controlling for shift length, unit, and hospital characteristics, they found that collaboration suffered in nursing units with longer overtime shifts and more nurses working overtime.

One hour of overtime was associated with a 0.17 decrease on the RN-RN scale and was marginally associated with a 0.13 decrease on the RN-MD Scale. In other words, a 0.17 decrease from the mean score on the RN-RN scale suggests that a unit's rank on the RN-RN score would drop from the 50th percentile to roughly the 30th percentile.

"Our research suggests that the more overtime hours nurses work, resulting in extended periods of wakefulness, the greater difficulty they have in collaborating effectively," said Amy Witkoski Stimpfel, PhD, RN, assistant professor at NYU Meyers and the study's coauthor.

The researchers provided suggestions for nurses, nurse managers, and hospital administrators for sustaining good collaboration between healthcare professionals. Most importantly, they recommend using overtime as minimally as possible. However, given that longer shifts are the norm and completely eliminating overtime may not be possible, they also suggest offering fatigue management training and education, as well as training to help nurses and physicians communicate effectively and respectfully.

"Our findings support policies that limit the amount of overtime worked by nurses. In practice, nurse managers should monitor the amount of overtime being worked on their unit and minimize the use of overtime," Ma said.

Investigators at Children's Hospital Los Angeles have determined that in children receiving gadolinium as a contrast agent to enhance MRI examinations, signal changes attributed solely to deposition of this material in the brain are not dependent on the amount of gadolinium administered but rather these changes are seen in association with other factors such as the presence of brain tumors and treatment using brain irradiation. Results of the study were just published in the journal, Radiology.

Gadolinium is used as a contrast agent to enhance the visibility of specific anatomic structures as well as to identify certain pathological conditions. MRI images are often described in terms of "signal intensity", or the brightness of specific structures -- conveying information about the content of the tissue. In neuroradiology, MRIs are useful for identifying and monitoring brain tumors.

In 2014, a sentinel paper was published that reported gadolinium deposition in the brains of patients experiencing repeat, enhanced MRI. Most of these patients required imaging due to brain tumors. As a result of this and subsequent studies, gadolinium deposition was considered dose dependent - meaning the more contrast material a patient was exposed to - the greater deposition in the brain.

"In my practice, I was not seeing this phenomenon - MRI signal changes previously identified were not happening equally to patients receiving the same amount of gadolinium," said Benita Tamrazi, MD, a neuroradiologist at Children's Hospital Los Angeles and first author on the recently published study. "I saw increased MRI signal changes in the patients receiving radiation for brain tumors, independent of the dose of gadolinium."

This observation led Tamrazi to undertake her own study of patients treated at CHLA between 2000 through 2015, who received gadolinium at least 4 times. The 145 evaluable patients were separated into groups - patients with primary brain tumors (structural changes) and patients with neuroblastoma without disease in the brain (no structural changes). The primary brain tumor group was further divided into the following treatment groups:

Radiation +/- chemotherapy

Chemotherapy alone

No therapy

Tamrazi found that MR signal intensity changes presumed to be entirely secondary to gadolinium deposition in the brain were much more significant in patients who had primary brain tumors treated with radiation, independent of the dose of gadolinium they received. She suggests more research is needed to determine if brain tumor treatment with radiation enhances gadolinium deposition independent of the dose administered.

"There are a lot of unknowns regarding gadolinium deposition in the brain," said Tamrazi. "Understanding that the process is not dose dependent and that other factors are at play, such as structural changes of the brain with tumors and radiation, will hopefully help us learn more about the underlying mechanism of deposition and ultimately identify any possible clinical implications of deposition."

Scientists have identified a mutation that gives cancer cells resistance to the breakthrough cancer treatment olaparib and other PARP inhibitors.

The study findings could help predict which patients will develop resistance to PARP inhibitors and allow doctors to alter treatment at the earliest possible opportunity.

A team at The Institute of Cancer Research, London, used gene editing to identify a specific mutation in the PARP1 protein that prevents PARP inhibitors from working.

Testing for this mutation could add another level of personalisation to an already targeted treatment - helping guide decisions about whether to use PARP inhibitors in the first place, and when to switch to other drugs, such as platinum-based therapies.

The research was funded by Cancer Research UK and Breast Cancer Now, and is published today (Thursday) in the journal Nature Communications.

PARP1 is crucial for the repair of damaged DNA and is an important target for olaparib and other PARP inhibitors. These drugs are especially effective in patients who already have weaknesses in DNA repair because of inherited errors in the BRCA genes - a discovery that was made at the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR).

The scientists used new 'CRIPSR-Cas9' gene editing technology to generate mutations in small, targeted sections of the PARP1 gene, and tagged the mutant protein with a fluorescent protein so their effects could be tracked.

This approach allowed the researchers to observe the effect of specific mutations on PARP1 and on the sensitivity of cancer cells to PARP inhibitors, such as olaparib and talazoparib.

Olaparib is available on the NHS for women with ovarian cancer who have inherited BRCA mutations, and is currently being evaluated for breast cancer. It was the first ever cancer drug to be approved that is targeted against an inherited genetic fault.

The study identified specific PARP1 mutations which disrupt the ability of the protein to bind to DNA, which means PARP inhibitors can no longer trap them at the site of DNA damage.

The researchers found that, contrary to their original predictions, cancer cells with certain mutations in the BRCA1 gene could survive this loss of PARP1's DNA repair function - making them resistant to PARP inhibitors.

It is thought that in these cases the BRCA1 gene retains some function, providing some residual ability to repair DNA despite the loss of PARP1.

The scientists emphasised that further research needs to be carried out to examine more PARP1 mutations in patients as only one example in humans was found in this study.

The team is looking to apply this same gene editing approach to study how resistance arises to other drugs, and if it is possible to predict how quickly this resistance will progress.

Study author Dr Stephen Pettitt, Staff Scientist in Cancer Genomics at The Institute of Cancer Research, London, said:

"PARP inhibitors are hugely exciting new drugs which are especially effective in women with BRCA mutations - but unfortunately as with many other treatments it is common for cancer cells to eventually develop resistance.

"Our study has discovered one of the reasons why resistance to PARP inhibitors such as olaparib might occur. Testing for the mutations we have identified could offer even more personalised treatment for women with breast and ovarian cancer, by allowing doctors to judge whether and for how long olaparib should be used."

Study leader Professor Chris Lord, Professor of Cancer Genomics at The Institute of Cancer Research, London, said:

"The evolution of cancers into drug resistant forms is a major challenge we face in getting cancer treatments to work. Studies like this can tell us how and why drug resistance occurs, and give us new ways of predicting the likely response to new-style targeted drugs.

"We hope our research will help doctors use the best drug right from the outset, respond quickly to early signs of resistance, and work out the best ways to combine treatments to overcome drug resistance."

Professor Charles Swanton, Cancer Research UK's chief clinician, said:

"This ambitious study using state-of-the-art molecular technologies shows new ways in which tumours become resistant to PARP inhibitors, a family of drugs discovered and developed by Cancer Research UK funded scientists. Importantly, this resistance may influence the success of future treatment options, so increasing our understanding of how resistance occurs means we may be able to design even better therapies and predict how well a patient may respond to future treatment."

Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, which helped to fund the study, said:

"It is incredibly promising that this study has pinpointed genetic mutations that may lead to resistance to PARP inhibitors, which could help us ensure we maximise the use of this pioneering class of drugs.

"Resistance to breast cancer drugs is a major hurdle that we must overcome if we are to stop women dying from this devastating disease. It is vital that we understand exactly how and when cancer cells begin to adapt to and resist treatment, so that we can remain one step ahead of often elusive cancer cells.

"Identifying specific mutations that indicate how likely breast cancer cells are to develop resistance to PARP inhibitors could help guide their use in the clinic. This important finding could in future allow clinicians to determine who would benefit most from these drugs, or to track when they are becoming less effective and when a change of treatment might be appropriate.

"Studies like this, which build on the development of PARP inhibitors as a brand new treatment option for some women with breast cancer, could help take us a step closer to an even more personalised approach to treating the disease."

Older Americans are often at a high risk for obstructive sleep apnea, yet this illness remains vastly underdiagnosed, a new study finds.

University of Michigan researchers found evidence that more than half (56 percent) of persons ages 65 and older have a high risk of OSA, a sleep disorder in which the throat collapses during sleep, causing the patient to repeatedly stop breathing for periods of 10 seconds or longer throughout the night.

But only 8 percent of these individuals have been tested for OSA, a disorder that is associated with significant health risks. An overnight sleep study is necessary to diagnose OSA.

"It appears most older adults who are at risk for obstructive sleep apnea may not be getting referred for overnight sleep studies, and we may be missing an important chance for treatment," says co-first author Tiffany Braley, M.D., M.S., assistant professor of neurology at Michigan Medicine.

'Almost always confirmed'

The data, published in the Journal of the American Geriatrics Society, come from 1,052 Medicare beneficiaries who completed a series of sleep questions and other surveys as part of the National Health and Aging Trends Study (NHATS). The NHATS sample is representative of more than seven million Americans.

"We see that OSA was rarely evaluated, but when it was, it was almost always confirmed, as nearly all -- 94 percent -- of those at risk and tested for OSA were diagnosed," says co-first author Galit Levi Dunietz, Ph.D., MPH, postdoctoral research fellow in sleep epidemiology at Michigan Medicine's Sleep Disorders Center. "This suggests an opportunity to increase the evaluation among older Americans."

The NHATS survey questions about sleep resembled STOP-Bang, a popular questionnaire used in the clinical setting to evaluate common OSA risk factors. The survey evaluated whether respondents were at an advanced age, snored, were overweight, were male, had high blood pressure and felt fatigued.

Among the 94 percent of those who received a diagnosis after being deemed at risk and given a sleep study, 82 percent of respondents' physicians prescribed the first-line treatment. Continuous Positive Airway Pressure, or CPAP, sends pressurized air through the nose or nose and mouth to the throat, keeping it from collapsing during sleep.

"It was good to see a high treatment rate after diagnosis, so the main concern is the underdiagnosis of OSA," Dunietz says.

More research needed

"We know that OSA is quite common, yet often underdiagnosed in adults in the U.S.," Braley says. "But most of the data available are from younger or middle-aged patients."

In the young and middle-aged populations, OSA is linked to significant health risks and can worsen quality of life. But in addition to a lack of data on the prevalence of OSA in the older population, Braley says more research is needed to confirm whether the consequences are the same for OSA in older adults.

"This is an important first step in getting to the heart of question: What is the national scope of OSA, and our ability to recognize it, in all age groups?" she says.

"If we can assume that older adults are subject to the same risks of OSA as middle-aged adults, then missing a diagnosis could ultimately lead to a higher risk of conditions like hypertension, stroke, heart disease, diabetes and depression, as well as cognitive impairment, which is especially important for older individuals. These conditions have serious impact, and lead to expensive medical care."

And some older patients may not realize their snoring, sleepiness, tiredness and other symptoms of OSA could be because of something other than normal aging. Those who are already dealing with health conditions such as obesity, diabetes, stroke, a previous heart attack and high blood pressure are more likely to experience OSA as well.

"The results of this study are impressive," says co-author Ronald Chervin, M.D., M.S., professor of neurology and director of the Sleep Disorders Centers at Michigan Medicine. "They amount to estimates, but even so, they help to quantify the magnitude of the challenge.

"We already know that untreated sleep apnea costs billions each year, with decreased work productivity, impaired quality of life and increased medical costs. We still need to learn more about the impact of OSA in older persons more specifically, but the findings of this study suggest a huge, untapped opportunity to improve lives in older years, and perhaps medical costs as well, through more effective diagnosis, and then treatment, of OSA."

WEST LAFAYETTE, Ind. -- A solid can serve as a medium for heat and sound wave interactions just like a fluid does for thermoacoustic engines and refrigerators - resulting in leak-free machines that can stay operating longer.

Leaky systems have limited how engineers design thermoacoustic devices that rely on the interplay between temperature oscillations and sound waves. Researchers at Purdue and the University of Notre Dame have demonstrated for the first time that thermoacoustics could theoretically occur in solids as well as fluids, recently presenting their findings at the 175th Meeting of the Acoustical Society of America.

"Although still in its infancy, this technology could be particularly effective in harsh environments, such as outer space, where strong temperature variations are freely available and when system failures would endanger the overall mission," said Fabio Semperlotti, Purdue assistant professor of mechanical engineering.

Thermoacoustics has been an established and well-studied phenomenon in fluids - whether as a gas or liquid - for centuries. "Applying heat to a fluid enclosed in a duct or cavity will cause the spontaneous generation of sound waves propagating in the fluid itself," said Carlo Scalo, an assistant professor of mechanical engineering at Purdue. "This results in so-called singing pipes, or thermoacoustics machines."

While fluids have been historically used for these systems, the extra step of building something to contain the fluids and prevent leaks is cumbersome. This led the researchers to consider solids as a replacement.

"Properties of solids are more controllable, which could make them potentially better suited to these applications than fluids. We needed to first verify that this phenomenon could theoretically exist in solid media," said Haitian Hao, Purdue graduate research assistant in mechanical engineering.

Thermoacoustics enables either waste heat or mechanical vibrations to be converted into other useful forms of energy. For refrigerators, sound waves generate a temperature gradient of hot and cold. The vibrating motion makes cold areas colder and hot areas hotter.

Engines use an opposite process: a temperature gradient provided by waste heat leads to mechanical vibrations.

Solid state thermoacoustics initially seemed unlikely, since solids are somewhat more "stable" than fluids and tend to dissipate mechanical energy more readily, making it harder for heat to generate sound waves.

The researchers developed a theoretical model demonstrating that a thin metal rod can exhibit self-sustained mechanical vibrations if a temperature gradient is periodically applied to segments of the rod. This balanced unwanted mechanical energy dissipation and showed that, like fluids, solids contract when they cool down and expand when they heat up. If the solid contracts less when cooled and expands more when heated, the resulting motion will increase over time.

Solids can also be engineered to achieve the needed properties for achieving high thermoacoustics performance. "Fluids do not allow us to do this," Semperlotti said.

Extreme temperature differences in space would be perfect for generating mechanical vibrations that are then converted to electrical energy on spacecraft.

"A solid state device would use the sun as its heat source and radiation towards deep space as its cold source," Semperlotti said. "These systems could operate indefinitely, given that they do not have any part in motion or fluid that could leak out."

Researchers still need to complete an experimental setup to validate this design idea and better understand the thermoacoustics of solids as discovered through mathematical calculations and modeling.

"Possible applications and performance of these devices are still in the realm of pure speculation at this point," Semperlotti said. "But the phenomenon exists and it has the potential to open some remarkable directions for the design of thermoacoustic devices."

In a study of mice, National Institutes of Health-funded researchers describe a new circuit involved in fine-tuning the brain's decision either to hide or confront threats. The study, published in Nature, was partially funded by the NIH's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.

"Being able to manipulate specific circuits can uncover surprising relationships between brain areas and provide great insight into how the sensory, emotional, and behavioral centers work together to drive reactions," said Jim Gnadt, Ph.D., program director at the NIH's National Institute of Neurological Disorders and Stroke (NINDS) and a team lead for the BRAIN Initiative. "The tools and technologies developed through the BRAIN Initiative have made studies such as this one possible."

A team of researchers led by Andrew Huberman, Ph.D., professor of neurobiology and of ophthalmology at Stanford University in California, investigated the role of the ventral midline thalamus (vMT) in determining how animals respond to visual threats. The thalamus is a brain region that acts as a relay station, taking in sensory information, such as what is seen and heard, and sorting out where in the brain to send that information.

Dr. Huberman and his colleagues showed that the vMT was activated when mice were confronted with a threat, specifically a black circle that grew larger on top of their cage, mimicking the experience of something looming over them. When faced with the looming threat, the mice spent most of the time freezing or hiding and very little time rattling their tails, which is typically an aggressive response.

To further investigate the role of vMT, Dr. Huberman's team used state-of-the-art tools, including designer drugs that allowed specific circuits to be turned on and off. Although inactivating the vMT had no effect on freezing and hiding, it eliminated the tail rattling response. Turning on the vMT increased the number of tail shaking responses and caused the mice to move around more and spend less time hiding or freezing.

Dr. Huberman's group also discovered that the vMT sends information primarily to two brain areas: the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC). These circuits turned out to be critical in determining how the mice reacted to a visual threat. Turning on the circuit that projected to the BLA caused more freezing responses, while activating the mPFC circuit increased tail shaking responses.

"Dr. Huberman's work is opening a new area of vision research with the looming threat model, helping us understand how circuitry in the brain works from sensation to behavior," said Thomas Greenwell, Ph.D., program director at the NIH's National Eye Institute, which co-funded the study.

Dr. Huberman and his team showed that activation of the vMT increased arousal, a state of heightened alertness. Mice preferred spending more time in a room where they received vMT activation, suggesting that turning on that brain circuit made them feel good. Although there may have been a difference in response to the visual threat, either tail shaking or freezing, the underlying positive feeling was the same for both types of reactions.

"This study may help explain why acts of courage, such as standing up for yourself or for a cause, or a physical challenge can feel empowering. Experiencing that good feeling can also make it more likely to respond to future threats in a similar way," said Dr. Huberman. "Although our study was done in mice, learning more about the vMT may provide some insight into conditions such as generalized anxiety disorder and post-traumatic stress disorder and we are now pursuing study of the human vMT for that reason."

Future research is needed to increase understanding of ways in which the vMT circuit affects behavior and how to develop treatments that can target specific parts of this system.

DENVER -Significant disparities in the quality of end-of-life lung cancer care were found among racial-ethnic minorities, with higher odds of experiencing potentially preventable medical encounters during end-of-life as compared with non-Hispanic whites.

Lung cancer is the leading cause of cancer-related deaths in the world today. Despite advances in lung cancer detection, there is a lack of lung cancer screening programs as well as technology limitations that result in more than 60% of patients with lung cancer being diagnosed in later stages (III-IV). Therefore, survival is still very poor, with only 18% of these patients surviving beyond 5 years. Given the high mortality of lung cancer, end-of-life care is crucial for improving the quality of life in advanced stage lung cancer patients. Lung cancer mortality and end-of-life cancer care burden is higher among minorities due to their higher lung cancer risk, diagnosis at later stages, and higher odds of receiving inappropriate treatment strategies. In addition, minorities often receive poor quality and more aggressive care near death, in the form of care being administered in emergency rooms (ER), intensive care units (ICU), and inpatient facilities. Minorities are also less likely to receive hospice care during end-of-life. Given these disparities, it is important to understand the effect of race-ethnicity on the type and quality of end-of-life care for all lung cancer patients and to develop guidelines to standardize end-of-life care.

A group of investigators led by researchers from The University of Texas Health Science Center at Houston School of Public Health conducted a retrospective analysis to examine racial-ethnic disparities in the quality of lung cancer end-of-life care. The study used Surveillance Epidemiology and End Result (SEER) data containing newly diagnosed lung cancer patients between 1992 and 2011 linked to Medicare claims from 1991 to 2013. Patients 66 years and older who were diagnosed with stage I-IV lung cancer, and who died on or before December 31, 2013, were included in the study. Patients were divided and analyzed as two separate cohorts, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Poor quality of care was measured using three themes: 1) potentially preventable medical encounters (such as ER, ICU and inpatient stays, and deaths in acute care settings), 2) delayed hospice referral, and 3) aggressive chemotherapy during end-of-life. Logistic regression analyses were performed to estimate racial-ethnic disparities in the adjusted odds of receiving poor quality end-of-life care.

The results of the study were published in the Journal of Thoracic Oncology., the official journal of the International Association for the Study of Lung Cancer (IASLC). The study identified 154,498 NSCLC patients and 27,834 SCLC patients who died on or before December 31, 2013. Eighty-four percent of the NSCLC and 88% of the SCLC patients were non-Hispanic (NH) white. Among patients surviving less than 1 month after diagnosis, statistically significant racial-ethnic differences in poor quality end-of-life care were minimal. However, among patients surviving 1 to 7 months after diagnosis, NH blacks and Hispanics had a higher proportion of preventable medical encounters in the last month of life as compared to NH whites. Hospice care initiation during the last 3 days of life was similar among all race-ethnicities surviving 1 to 7 months, with marginally lower rates of delayed hospice referral among NH blacks with NSCLC. Aggressive chemotherapy in the last month of life was less common among NH blacks as compared to NH whites, however, a higher proportion of NH blacks and Hispanics received overall aggressive care near end-of-life. The racial-ethnic differences in quality of end-of-life care for patients surviving more than 7 months after diagnosis were similar to the differences in patients surviving 1 to 7 months.

The authors comment that, "This is the first study that uses two decades of nationally representative SEER-Medicare data to examine racial-ethnic disparities in lung cancer end-of-life care. Our study found that aggressive end-of-life care management was increasing over time among lung cancer patients, with increase in the rates of potentially preventable medical encounters, delayed hospice referral, and aggressive chemotherapy provision during end-of-life. Our study also found considerable racial-ethnic disparities in end-of-life care quality. In particular, our study found that the racial-ethnic minorities (NH blacks and Hispanics) had higher odds of experiencing potentially preventable medical encounters in the last month of life as compared with NH whites. Notably, NH blacks had 20 to 40% higher odds of having ER visits, hospital stays, ICU visits, death in an acute care setting, and overall provision of aggressive care as compared with NH whites. Nevertheless, the odds of delayed hospice referral or aggressive chemotherapy provision were lower in NH blacks as compared with NH whites. Our findings may indicate continued lack of access and care disparity among the minorities during the earlier phases of cancer care, which might precipitate potentially preventable utilizations during end-of life. These findings indicate the need to examine the access of minority populations to appropriately trained providers during all phases of cancer care and their geographic access to hospice care. In addition, identifying patient-level reasons for racial-ethnic disparities will help develop educational and patient navigational interventions to reduce access barriers and facilitate informed patient-level decision-making during end-of-life."

TUCSON, Ariz. - Recent headlines have cast suspicion on social network analysis, which can mine data from the internet to target advertisements or potentially influence elections.

But what if we could use those same tools not for the economic or political gain of a few, but for the health of all humankind? Scientists now can harness the tools of social network analysis to understand connections among genes, an advance that someday could lead to medical advancements.

Megha Padi, PhD, director of the UA Cancer Center Bioinformatics Shared Resource and an assistant professor of molecular and cellular biology, developed a computer algorithm called ALPACA that reveals which gene networks are activated in a diseased cell -- an approach that could lead to better treatments for various diseases. The results were published online April 19 in the open-access Nature Partner journal Systems Biology and Applications.

Cancer researchers usually focus on specific genes when comparing healthy cells to tumor cells, an approach that does not completely explain what occurs behind the scenes to cause cancer.

"You can get a list of the parts in your car, but you won't understand what makes the car run until you understand how all the parts are connected to each other," Dr. Padi said.

Likewise, it is essential to study how genes work together as part of a larger network, so Dr. Padi is analyzing these gene communities in the same way one would examine a social network composed of connections among people who know one another.

Dr. Padi is the first author on the study, in collaboration with John Quackenbush, PhD, director of the Center for Cancer Computational Biology at Dana-Farber Cancer Institute. The study was conducted when she was a postdoctoral fellow at Dana-Farber; Dr. Padi joined the UA in January 2018.

Genes in a community, like people in a social network, talk to one another. In a healthy cell, gene communities function like factory workers, cooperating to process raw materials into goods the cell needs to thrive. In a diseased cell, miscommunication along the "assembly line" results in defective products. Tracking how genes' conversations change over time might provide clues how cancer arises. These conversations can be analyzed using tools developed to study social networks.

"A classic example is a phone network," said Dr. Padi. "I'm calling my mom, my mom may be calling my sister, my sister's calling me, and I may call you, but you won't call my mom. Natural communities are formed, like your work community and family community."

Dr. Quackenbush added, "In the same way, we see that gene regulatory networks form communities. The pattern of 'conversations' within the communities change between healthy and diseased individuals. ALPACA is the first method to understand how the cell's 'social network' is reorganized in disease, which might provide clues how cancer forms."

To uncover cancer's causes, the challenge is to find the differences between gene communities in healthy cells compared to diseased cells, rather than the differences between individual genes. But comparing gene communities is easier said than done, as the genetics underlying cancer can have tens of thousands of interacting components to sort through. Drawing a diagram of these interactions results in what researchers call a "hairball."

"To make a map that humans can understand, scientists need computers to figure out the subtle ways in which this 'hairball' goes awry in tumor cells," Dr. Padi said.

One of the next steps is to identify drug candidates that can be further investigated in the laboratory.

"We'd like to use what we have learned to develop new strategies that can help prevent or cure disease," said Dr. Quackenbush.

Dr. Padi is particularly interested in using ALPACA to find novel treatments for people whose cancers fail to respond to currently available treatments. By contrasting cancers that cannot be treated with drugs, known as chemoresistant tumors, with chemosensitive tumors, those that can be treated with drugs, researchers may be able to zero in on a community of "bad guys" -- genetic pathways that might be targeted with customized drugs.

ALPACA's incorporation of social network analysis is an innovative use of tools most commonly associated with marketing, not medical research.

"Network scientists usually ask questions like how information is being spread through Twitter or other communication channels," Dr. Padi said. "We're asking completely different questions, like how networks function in different types of tumors. This type of research is rare because not many people work on both those fields at the same time."