Whole-brain functional hypoconnectivity as an endophenotype of autism in adolescents.

Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives.The authors wish to thank the participants and their families for their participation and the autism support organisations who assisted with recruitment. We thank colleagues at the Brain Mapping Unit for methodological discussions and thank Meng-Chuan Lai, Amber Ruigrok and Richard Bethlehem for the same. Data collection was funded by a Clinical Scientist Fellowship from the UK Medical Research Council (MRC) (G0701919) to MDS. LRC was supported by the Gates Cambridge Scholarship Trust. The study was conducted in associated with the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Cambridgeshire, and Peterborough National Health Service (NHS) Foundation Trust. The present analysis was funded by a NARSAD Young Investigator award (to MR) and by the Isaac Newton Trust (to MR); RJFY is additionally supported by a Rubicon Fellowship from the Netherlands Organisation for Scientific Research. The Brain Mapping Unit (MR, RLM, RJFY, JS and ETB) is part of the Behavioural & Clinical Neuroscience Institute, which is funded by the MRC and the Wellcome Trust. High performance computing facilities were supported by the NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.nicl.2015.07.01

OXYGEN REACTIVE POLYMERS FOR TREATMENT OF TRAUMATIC BRAIN INJURY

Methods and compositions for treating traumatic brain injury . The methods and compositions utilize a multi - functional oxygen reactive polymer ( ORP ) that includes repeating units that include a reactive oxygen species ( ROS ) scavenging group and a polyalkylene oxide group . For theranostic applications , the oxygen reactive polymer fur ther includes a diagnostic group

Carfilzomib, Pomalidomide, and Dexamethasone As Second-line Therapy for Lenalidomide-refractory Multiple Myeloma

This phase 2 trial investigated reinduction with carfilzomib, pomalidomide, and dexamethasone (KPd) and continuous pomalidomide/dexamethasone in patients at first progression during lenalidomide maintenance. The second objective was to evaluate high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) at first progression. Patients were eligible who had progressive disease according to International Myeloma Working Group (IMWG) criteria. Treatment consisted of 8 cycles carfilzomib (20/36 mg/m2), pomalidomide (4 mg) and dexamethasone. Patients without prior transplant received HDM/ASCT. Pomalidomide 4 mg w/o dexamethasone was given until progression. One hundred twelve patients were registered of whom 86 (77%) completed 8 cycles of KPd. Thirty-five (85%) eligible patients received HDM/ASCT. The median time to discontinuation of pomalidomide w/o dexamethasone was 17 months. Best response was 37% ≥ complete response, 75% ≥ very good partial response, 92% ≥ partial response, respectively. At a follow-up of 40 months median PFS was 26 and 32 months for patients who received KPd plus HDM/ASCT and 17 months for patients on KPd (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.37-1.00, P = 0.051). PFS was better after longer duration of prior lenalidomide (HR 3.56, 95% CI 1.42-8.96, P = 0.035). Median overall survival (OS) was 67 months. KPd-emerging grade 3 and 4 adverse events included hematologic (41%), cardiovascular (6%), respiratory (3%), infections (17%), and neuropathy (2%). KPd followed by continuous pomalidomide is an effective and safe triple drug regimen in second-line for patients previously exposed to bortezomib and/or refractory to lenalidomide

Regional versus remote atmosphere‐ocean drivers of the rapid projected intensification of the East Australian Current

Like many western boundary currents, the East Australian Current extension is projected to get stronger and warmer in the future. The CMIP5 multi‐model mean (MMM) projection suggests up to 5°C of warming under an RCP85 scenario by 2100. Previous studies employed Sverdrup balance to associate a trend in basin wide zonally integrated wind stress curl (resulting from the multi‐decadal poleward intensification in the westerly winds over the Southern Ocean) with enhanced transport in the EAC extension. Possible regional drivers are yet to be considered. Here, we introduce the NEMO‐OASIS‐WRF coupled regional climate model as a framework to improve our understanding of CMIP5 projections. We analyse a hierarchy of simulations in which the regional atmosphere and ocean circulations are allowed to freely evolve subject to boundary conditions that represent present day and CMIP5 RCP8.5 climate change anomalies. Evaluation of the historical simulation shows an EAC extension that is stronger than similar ocean‐only models and observations. This bias is not explained by a linear response to differences in wind stress. The climate change simulations show that regional atmospheric CMIP5 MMM anomalies drive 73% of the projected 12 Sv increase in EAC extension transport whereas the remote ocean boundary conditions and regional radiative forcing (greenhouse gases within the domain) play a smaller role. The importance of regional changes in wind stress curl in driving the enhanced EAC extension is consistent with linear theory where the NEMO‐OASIS‐WRF response is closer to linear transport estimates compared to the CMIP5 MMM