Alu element in the RNA binding motif protein, X-linked 2 (RBMX2) gene found to be linked to bipolar disorder

Objective We have used long-read single molecule, real-time (SMRT) sequencing to fully characterize a similar to 12Mb genomic region on chromosome Xq24-q27, significantly linked to bipolar disorder (BD) in an extended family from a genetic sub-isolate. This family segregates BD in at least four generations with 24 affected individuals. Methods We selected 16 family members for targeted sequencing. The selected individuals either carried the disease haplotype, were non-carriers of the disease haplotype, or served as married-in controls. We designed hybrid capture probes enriching for 5-9Kb fragments spanning the entire 12Mb region that were then sequenced to screen for candidate structural variants (SVs) that could explain the increased risk for BD in this extended family. Results Altogether, 201 variants were detected in the critically linked region. Although most of these represented common variants, three variants emerged that showed near-perfect segregation among all BD type I affected individuals. Two of the SVs were identified in or near genes belonging to the RNA Binding Motif Protein, X-Linked (RBMX) gene family-a 330bp Alu (subfamily AluYa5) deletion in intron 3 of the RBMX2 gene and an intergenic 27bp tandem repeat deletion between the RBMX and G protein-coupled receptor 101 (GPR101) genes. The third SV was a 50bp tandem repeat insertion in intron 1 of the Coagulation Factor IX (F9) gene. Conclusions Among the three genetically linked SVs, additional evidence supported the Alu element deletion in RBMX2 as the leading candidate for contributing directly to the disease development of BD type I in this extended family.Peer reviewe

Implementation of evidence-based practice for benign paroxysmal positional vertigo: DIZZTINCT– A study protocol for an exploratory stepped-wedge randomized trial

Abstract Background Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder, and accounts for 8% of individuals with moderate or severe dizziness. BPPV patients experience substantial inconveniences and disabilities during symptomatic periods. BPPV therapeutic processes – the Dix-Hallpike Test (DHT) and the Canalith Repositioning Maneuver (CRM) – have an evidence base that is at the clinical practice guideline level. The most commonly used CRM is the modified Epley maneuver. The DHT is the gold standard test for BPPV and the CRM is supported by numerous randomized controlled trials and systematic reviews. Despite this, BPPV care processes are underutilized. Methods/design This is a stepped-wedge, randomized clinical trial of a multi-faceted educational and care-process-based intervention designed to improve the guideline-concordant care of patients with BPPV presenting to the emergency department (ED) with dizziness. The unit of randomization and target of intervention is the hospital. After an initial observation period, the six hospitals will undergo the intervention in five waves (two closely integrated hospitals will be paired). The order will be randomized. The primary endpoint is measured at the individual patient level, and is the presence of documentation of either the Dix-Hallpike Test or CRM. The secondary endpoints are referral to a health care provider qualified to treat dizziness for CRM and 90-day stroke rates following an ED dizziness visit. Formative evaluations are also performed to monitor and identify potential and actual influences on the progress and effectiveness of the implementation efforts. Discussion If this study safely increases documentation of the DHT/CRM, this will be an important step in implementing the use of these evidenced-based processes of care. Positive results will support conducting larger-scale follow-up studies that assess patient outcomes. The data collection also enables evaluation of potential and actual influences on the progress and effectiveness of the implementation efforts. Trial registration ClinicalTrials.gov, ID: NCT02809599 . The record was first available to the public on 22 June 2016 prior to the enrollment of the first patients in October 2016.https://deepblue.lib.umich.edu/bitstream/2027.42/146751/1/13063_2018_Article_3099.pd

Shocked Molecular Gas in the Supernova Remnants W 28 and W 44: Near-infrared and millimeter-wave observations

High resolution millimeter-wave and near-infrared observations of the supernova remnants W28 and W44 reveal extensive shocked molecular gas where supernova blast waves are propagating into giant molecular clouds. New CO observations were carried out with the IRAM 30-m and ARO 12-m telescopes, and the near-infrared observations were with Palomar 200-inch telescope. The near-infrared observations reveal shocked H2 emission from both supernova remnants, showing intricate networks of filaments on arcsec scales, following the bright ridges of the radio shells. The CO and CS linewidths, indicative of the shock speed, are 20-30 km/s. Both the near-infrared and millimeter-wave emission are attributed to shocks into gas with density >1e3 cm-3. Individual shock structures are resolved in the H2 emission, with inferred edge-on shock thickness ~1e17 cm, consistent with non-dissociative shocks into gas densities of 1e3-1e4 cm-3. Bright 1720 MHz OH masers are located within the shocked H2 gas complexes and highlight only localized areas where the conditions for masing are optimal. The Halpha and X-ray emission, have morphologies very different from the radio. We find a detailed correlation of the radio and H2 emission for some long filaments, indicating cosmic ray acceleration or re-acceleration due to the shocks into moderately dense gas. The different morphologies of these two remnants at different wavelengths is explained by a highly nonuniform structure for giant molecular clouds.Comment: ApJ, in press; several figures in jpg for

Giant breast tumors: Surgical management of phyllodes tumors, potential for reconstructive surgery and a review of literature

<p>Abstract</p> <p>Background</p> <p>Phyllodes tumors are biphasic fibroepithelial neoplasms of the breast. While the surgical management of these relatively uncommon tumors has been addressed in the literature, few reports have commented on the surgical approach to tumors greater than ten centimeters in diameter – the giant phyllodes tumor.</p> <p>Case presentation</p> <p>We report two cases of giant breast tumors and discuss the techniques utilized for pre-operative diagnosis, tumor removal, and breast reconstruction. A review of the literature on the surgical management of phyllodes tumors was performed.</p> <p>Conclusion</p> <p>Management of the giant phyllodes tumor presents the surgeon with unique challenges. The majority of these tumors can be managed by simple mastectomy. Axillary lymph node metastasis is rare, and dissection should be limited to patients with pathologic evidence of tumor in the lymph nodes.</p

Monsoons: global energetics and local physics as drivers of past, present and future monsoons

Global constraints on momentum and energy govern the structure of the zonal mean tropical circulation and rainfall. The continental-scale monsoon systems are also facets of a momentum- and energy-constrained global circulation, but their modern and paleo variability deviates substantially from that of the longitudinal mean through mechanisms neither fully understood nor well simulated. A framework grounded in global constraints yet encompassing the complexities of monsoon dynamics is needed to identify the causes of mismatch between theory, models, and observations and, ultimately, improve regional climate projection. In a first step towards this goal, disparate regional processes must be distilled into gross measures of energy flow in and out of continents and from the surface to the tropopause, so that monsoon dynamics may be coherently diagnosed across modern and paleo observations and across idealized and comprehensive simulations. Accounting for zonal asymmetries in the circulation, land/ocean differences in surface fluxes, and the character of convective systems, such a monsoon framework would integrate our understanding at all relevant scales: from the fine details of how moisture and energy are lifted in the updrafts of thunderclouds, up to the global circulations

Observed controls on resilience of groundwater to climate variability in sub-Saharan Africa

Groundwater in sub-Saharan Africa supports livelihoods and poverty alleviation1,2, maintains vital ecosystems, and strongly influences terrestrial water and energy budgets. Yet the hydrological processes that govern groundwater recharge and sustainability—and their sensitivity to climatic variability—are poorly constrained4. Given the absence of firm observational constraints, it remains to be seen whether model-based projections of decreased water resources in dry parts of the region4 are justified. Here we show, through analysis of multidecadal groundwater hydrographs across sub-Saharan Africa, that levels of aridity dictate the predominant recharge processes, whereas local hydrogeology influences the type and sensitivity of precipitation–recharge relationships. Recharge in some humid locations varies by as little as five per cent (by coefficient of variation) across a wide range of annual precipitation values. Other regions, by contrast, show roughly linear precipitation–recharge relationships, with precipitation thresholds (of roughly ten millimetres or less per day) governing the initiation of recharge. These thresholds tend to rise as aridity increases, and recharge in drylands is more episodic and increasingly dominated by focused recharge through losses from ephemeral overland flows. Extreme annual recharge is commonly associated with intense rainfall and flooding events, themselves often driven by large-scale climate controls. Intense precipitation, even during years of lower overall precipitation, produces some of the largest years of recharge in some dry subtropical locations. Our results therefore challenge the ‘high certainty’ consensus regarding decreasing water resources in such regions of sub-Saharan Africa. The potential resilience of groundwater to climate variability in many areas that is revealed by these precipitation–recharge relationships is essential for informing reliable predictions of climate-change impacts and adaptation strategies

A View from the Past Into our Collective Future: The Oncofertility Consortium Vision Statement

Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future

Effects of Training and Competition Load on Neuromuscular Recovery, Testosterone, Cortisol, and Match Performance During a Season of Professional Football

Introduction: Training load and other measures potentially related to match performance are routinely monitored in team-sport athletes. The aim of this research was to examine the effect of training load on such measures and on match performance during a season of professional football.Materials and Methods: Training load was measured daily as session duration times perceived exertion in 23 A-League football players. Measures of exponentially weighted cumulative training load were calculated using decay factors representing time constants of 3–28 days. Players performed a countermovement jump for estimation of a measure of neuromuscular recovery (ratio of flight time to contraction time, FT:CT), and provided a saliva sample for measurement of testosterone and cortisol concentrations 1-day prior to each of 34 matches. Match performance was assessed via ratings provided by five coaching and fitness staff on a 5-point Likert scale. Effects of training load on FT:CT, hormone concentrations and match performance were modeled as quadratic predictors and expressed as changes in the outcome measure for a change in the predictor of one within-player standard deviation (1 SD) below and above the mean. Changes in each of five playing positions were assessed using standardization and magnitude-based inference.Results: The largest effects of training were generally observed in the 3- to 14-day windows. Center defenders showed a small reduction in coach rating when 14-day a smoothed load increased from −1 SD to the mean (-0.31, ±0.15; mean, ±90% confidence limits), whereas strikers and wide midfielders displayed a small increase in coach rating when load increased 1 SD above the mean. The effects of training load on FT:CT were mostly unclear or trivial, but effects of training load on hormones included a large increase in cortisol (102, ±58%) and moderate increase in testosterone (24, ±18%) in center defenders when 3-day smoothed training load increased 1 SD above the mean. A 1 SD increase in training load above the mean generally resulted in substantial reductions in testosterone:cortisol ratio.Conclusion: The effects of recent training on match performance and hormones in A-League football players highlight the importance of position-specific monitoring and training