A systematic review and network meta-analysis of randomized controlled trials evaluating the evidence base of melatonin, light exposure, exercise, and complementary and alternative medicine for patients with insomnia disorder

Insomnia is a prevalent disorder and it leads to relevant impairment in health-related quality of life. Recent clinical guidelines pointed out that Cognitive-Behavior Therapy for Insomnia (CBT-I) should be considered as first-line intervention. Nevertheless, many other interventions are commonly used by patients or have been proposed as effective for insomnia. These include melatonin, light exposure, exercise, and complementary and alternative medicine. Evaluation of comparable effectiveness of these interventions with first-line intervention for insomnia is however still lacking. We conducted a systematic review and network meta-analysis on the effects of these interventions. PubMed, PsycInfo, PsycArticles, MEDLINE, and CINAHL were systematically searched and 40 studies were included in the systematic review, while 36 were entered into the meta-analysis. Eight network meta-analyses were conducted. Findings support effectiveness of melatonin in improving sleep-onset difficulties and of meditative movement therapies for self-report sleep efficiency and severity of the insomnia disorder. Some support was observed for exercise, hypnotherapy, and transcranial magnetic resonance, but the number of studies for these interventions is still too small. None of the considered interventions received superior evidence to CBT-I, which should be more widely disseminated in primary care

Enhancement of the electronic contribution to the low temperature specific heat of Fe/Cr magnetic multilayer

We measured the low temperature specific heat of a sputtered $(Fe_{23\AA}/Cr_{12\AA})_{33}$ magnetic multilayer, as well as separate $1000\AA$ thick Fe and Cr films. Magnetoresistance and magnetization measurements on the multilayer demonstrated antiparallel coupling between the Fe layers. Using microcalorimeters made in our group, we measured the specific heat for $4<T<30 K$ and in magnetic fields up to $8 T$ for the multilayer. The low temperature electronic specific heat coefficient of the multilayer in the temperature range $4<T<14 K$ is $\gamma_{ML}=8.4 mJ/K^{2}g-at$. This is significantly larger than that measured for the Fe or Cr films (5.4 and $3.5 mJ/K^{2}mol$ respectively). No magnetic field dependence of $\gamma_{ML}$ was observed up to $8 T$. These results can be explained by a softening of the phonon modes observed in the same data and the presence of an Fe-Cr alloy phase at the interfaces.Comment: 20 pages, 5 figure

Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network

Using a phenome-wide association study (PheWAS) approach, we comprehensively tested genetic variants for association with phenotypes available for 70,061 study participants in the Population Architecture using Genomics and Epidemiology (PAGE) network. Our aim was to better characterize the genetic architecture of complex traits and identify novel pleiotropic relationships. This PheWAS drew on five population-based studies representing four major racial/ethnic groups (European Americans (EA), African Americans (AA), Hispanics/Mexican-Americans, and Asian/Pacific Islanders) in PAGE, each site with measurements for multiple traits, associated laboratory measures, and intermediate biomarkers. A total of 83 single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) were genotyped across two or more PAGE study sites. Comprehensive tests of association, stratified by race/ethnicity, were performed, encompassing 4,706 phenotypes mapped to 105 phenotype-classes, and association results were compared across study sites. A total of 111 PheWAS results had significant associations for two or more PAGE study sites with consistent direction of effect with a significance threshold of p<0.01 for the same racial/ethnic group, SNP, and phenotype-class. Among results identified for SNPs previously associated with phenotypes such as lipid traits, type 2 diabetes, and body mass index, 52 replicated previously published genotype-phenotype associations, 26 represented phenotypes closely related to previously known genotype-phenotype associations, and 33 represented potentially novel genotype-phenotype associations with pleiotropic effects. The majority of the potentially novel results were for single PheWAS phenotype-classes, for example, for CDKN2A/B rs1333049 (previously associated with type 2 diabetes in EA) a PheWAS association was identified for hemoglobin levels in AA. Of note, however, GALNT2 rs2144300 (previously associated with high-density lipoprotein cholesterol levels in EA) had multiple potentially novel PheWAS associations, with hypertension related phenotypes in AA and with serum calcium levels and coronary artery disease phenotypes in EA. PheWAS identifies associations for hypothesis generation and exploration of the genetic architecture of complex traits

The case for open science: rare diseases.

The premise of Open Science is that research and medical management will progress faster if data and knowledge are openly shared. The value of Open Science is nowhere more important and appreciated than in the rare disease (RD) community. Research into RDs has been limited by insufficient patient data and resources, a paucity of trained disease experts, and lack of therapeutics, leading to long delays in diagnosis and treatment. These issues can be ameliorated by following the principles and practices of sharing that are intrinsic to Open Science. Here, we describe how the RD community has adopted the core pillars of Open Science, adding new initiatives to promote care and research for RD patients and, ultimately, for all of medicine. We also present recommendations that can advance Open Science more globally

Robots and Organization Studies: Why Robots Might Not Want to Steal Your Job

A number of recent high-profile studies of robotics and artificial intelligence (or AI) in economics and sociology have predicted that many jobs will soon disappear due to automation, with few new ones replacing them. While techno-optimists and techno-pessimists contest whether a jobless future is a positive development or not, this paper points to the elephant in the room. Despite successive waves of computerization (including advanced machine learning), jobs have not disappeared. And probably won’t in the near future. To explain why, some basic insights from organization studies can make a contribution. I propose the concept of ‘bounded automation’ to demonstrate how organizational forces mould the application of technology in the employment sector. If work does not vanish in the age of AI, then poorly paid jobs will most certainly proliferate, I argue. Finally, a case is made for the scholarly community to engage with wider social justice concerns. This I term public organization studies

A phenome-wide association study (PheWAS) in the Population Architecture using Genomics and Epidemiology (PAGE) study reveals potential pleiotropy in African Americans

We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African Americans as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study. The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio- metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p<0.01 in two or more PAGE study sites for two or more phenotype classes. We further annotated these PheWAS-identified variants using publicly available functional data and local genetic ancestry. Amongst our novel findings is SPARC rs4958487, associated with increased glucose levels and hypertension. SPARC has been implicated in the pathogenesis of diabetes and is also known to have a potential role in fibrosis, a common consequence of multiple conditions including hypertension. The SPARC example and others highlight the potential that PheWAS approaches have in improving our understanding of complex disease architecture by identifying novel relationships between genetic variants and an array of common human phenotypes

Preclinical Models for Neuroblastoma: Establishing a Baseline for Treatment

Preclinical models of pediatric cancers are essential for testing new chemotherapeutic combinations for clinical trials. The most widely used genetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse. This neuroblastoma-prone mouse recapitulates many of the features of human neuroblastoma. Limitations of this model include the low frequency of bone marrow metastasis, the lack of information on whether the gene expression patterns in this system parallels human neuroblastomas, the relatively slow rate of tumor formation and variability in tumor penetrance on different genetic backgrounds. As an alternative, preclinical studies are frequently performed using human cell lines xenografted into immunocompromised mice, either as flank implant or orthtotopically. Drawbacks of this system include the use of cell lines that have been in culture for years, the inappropriate microenvironment of the flank or difficult, time consuming surgery for orthotopic transplants and the absence of an intact immune system.Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, minimally invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a "standard of care" chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents.The studies suggest that use of both the TH-NMYC model of neuroblastoma and the orthotopic xenograft model provide the optimal combination for testing new chemotherapies for this devastating childhood cancer