Controlling Catalyst Bulk Reservoir Effects for Monolayer Hexagonal Boron Nitride CVD.

Highly controlled Fe-catalyzed growth of monolayer hexagonal boron nitride (h-BN) films is demonstrated by the dissolution of nitrogen into the catalyst bulk via NH3 exposure prior to the actual growth step. This "pre-filling" of the catalyst bulk reservoir allows us to control and limit the uptake of B and N species during borazine exposure and thereby to control the incubation time and h-BN growth kinetics while also limiting the contribution of uncontrolled precipitation-driven h-BN growth during cooling. Using in situ X-ray diffraction and in situ X-ray photoelectron spectroscopy combined with systematic growth calibrations, we develop an understanding and framework for engineering the catalyst bulk reservoir to optimize the growth process, which is also relevant to other 2D materials and their heterostructures.S.C. and R.W. acknowledge funding from EPSRC (Doctoral training award). R.S.W. acknowledges a Research Fellowship from St. John’s College, Cambridge and a EU Marie Skłodowska-Curie Individual Fellowship (Global) under grant ARTIST (no. 656870) from the European Union’s Horizon 2020 research and innovation programme. B.C.B. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 656214 - 2DInterFOX. B.C.B and J.C.M. acknowledge support from the Austrian Science Fund (FWF): P25721-N20 and the Austrian Research Promotion Agency (FFG): 848152 - GraphenMoFET. A.C.-V. acknowledges the Conacyt Cambridge Scholarship and Roberto Rocca Fellowship. S.H. acknowledges funding from ERC grant InsituNANO (no. 279342). We acknowledge the European Synchrotron Radiation Facility (ESRF) for provision of synchrotron radiation facilities at the BM20/ROBL beamline. We acknowledge the Helmholtz-Zentrum-Berlin Electron storage ring BESSY II for provision of synchrotron radiation at the ISISS beamline. We thank the ESRF and BESSY staff for continued support of our experiments and valuable discussion.This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/acs.nanolett.5b0458

Mental states as macrostates emerging from brain electrical dynamics

Psychophysiological correlations form the basis for different medical and scientific disciplines, but the nature of this relation has not yet been fully understood. One conceptual option is to understand the mental as “emerging” from neural processes in the specific sense that psychology and physiology provide two different descriptions of the same system. Stating these descriptions in terms of coarser- and finer-grained system states (macro- and microstates), the two descriptions may be equally adequate if the coarse-graining preserves the possibility to obtain a dynamical rule for the system. To test the empirical viability of our approach, we describe an algorithm to obtain a specific form of such a coarse-graining from data, and illustrate its operation using a simulated dynamical system. We then apply the method to an electroencephalographic recording, where we are able to identify macrostates from the physiological data that correspond to mental states of the subject

Suppression of HBV by Tenofovir in HBV/HIV Coinfected Patients: A Systematic Review and Meta-Analysis

Background:Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains.Methods:A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine.Results:Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare.Interpretation:TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

Reduced-Intensity/Reduced-Toxicity Conditioning Approaches Are Tolerated in XIAP Deficiency but Patients Fare Poorly with Acute GVHD

X-linked inhibitor of apoptosis (XIAP) deficiency is an inherited primary immunodeficiency characterized by chronic inflammasome overactivity and associated with hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD). Allogeneic hematopoietic cell transplantation (HCT) with fully myeloablative conditioning may be curative but has been associated with poor outcomes. Reports of reduced-intensity conditioning (RIC) and reduced-toxicity conditioning (RTC) regimens suggest these approaches are well tolerated, but outcomes are not well established. Retrospective data were collected from an international cohort of 40 patients with XIAP deficiency who underwent HCT with RIC or RTC. Thirty-three (83%) patients had a history of HLH, and thirteen (33%) patients had IBD. Median age at HCT was 6.5 years. Grafts were from HLA-matched (n = 30, 75%) and HLA-mismatched (n = 10, 25%) donors. There were no cases of primary graft failure. Two (5%) patients experienced secondary graft failure, and three (8%) patients ultimately received a second HCT. Nine (23%) patients developed grade II-IV acute GVHD, and 3 (8%) developed extensive chronic GVHD. The estimated 2-year overall and event-free survival rates were 74% (CI 55-86%) and 64% (CI 46-77%), respectively. Recipient and donor HLA mismatch and grade II-IV acute GVHD were negatively associated with survival on multivariate analysis with hazard ratios of 5.8 (CI 1.5-23.3, p = 0.01) and 8.2 (CI 2.1-32.7, p < 0.01), respectively. These data suggest that XIAP patients tolerate RIC and RTC with survival rates similar to HCT of other genetic HLH disorders. Every effort should be made to prevent acute GVHD in XIAP-deficient patients who undergo allogeneic HCT

Disrupted-in-Schizophrenia 1 (DISC1) Overexpression and Juvenile Immune Activation Cause Sex-Specific Schizophrenia-Related Psychopathology in Rats

Synaptic pruning is a critical refinement step during neurodevelopment, and schizophrenia has been associated with overpruning of cortical dendritic spines. Both human studies and animal models implicate disrupted-in-schizophrenia 1 (DISC1) gene as a strong susceptibility factor for schizophrenia. Accumulating evidence supports the involvement of DISC1 protein in the modulation of synaptic elimination during critical periods of neurodevelopment and of dopamine D2-receptor-mediated signaling during adulthood. In many species, synaptic pruning occurs during juvenile and adolescent periods and is mediated by microglia, which can be over-activated by an immune challenge, giving rise to overpruning. Therefore, we sought to investigate possible interactions between a transgenic DISC1 model (tgDISC1) and juvenile immune activation (JIA) by the bacterial cell wall endotoxin lipopolysaccharide on the induction of schizophrenia-related behavioral and neurochemical disruptions in adult female and male rats. We examined possible behavioral aberrations along three major symptom dimensions of schizophrenia including psychosis, social and emotional disruptions, and cognitive impairments. We detected significant gene–environment interactions in the amphetamine-induced locomotion in female animals and in the amphetamine-induced anxiety in male animals. Surprisingly, gene–environment interactions improved social memory in both male and female animals. JIA alone disrupted spatial memory and recognition memory, but only in male animals. DISC1 overexpression alone induced an improvement in sensorimotor gating, but only in female animals. Our neurochemical analyses detected sex- and manipulation-dependent changes in the postmortem monoamine content of animals. Taken together, we here report sex-specific effects of environment and genotype as well as their interaction on behavioral phenotypes and neurochemical profiles relevant for schizophrenia

Effective Immunological Guidance of Genetic Analyses Including Exome Sequencing in Patients Evaluated for Hemophagocytic Lymphohistiocytosis

We report our experience in using flow cytometry-based immunological screening prospectively as a decision tool for the use of genetic studies in the diagnostic approach to patients with hemophagocytic lymphohistiocytosis (HLH). We restricted genetic analysis largely to patients with abnormal immunological screening, but included whole exome sequencing (WES) for those with normal findings upon Sanger sequencing. Among 290 children with suspected HLH analyzed between 2010 and 2014 (including 17 affected, but asymptomatic siblings), 87/162 patients with "full" HLH and 79/111 patients with "incomplete/atypical" HLH had normal immunological screening results. In 10 patients, degranulation could not be tested. Among the 166 patients with normal screening, genetic analysis was not performed in 107 (all with uneventful follow-up), while 154 single gene tests by Sanger sequencing in the remaining 59 patients only identified a single atypical CHS patient. Flow cytometry correctly predicted all 29 patients with FHL-2, XLP1 or 2. Among 85 patients with defective NK degranulation (including 13 asymptomatic siblings), 70 were Sanger sequenced resulting in a genetic diagnosis in 55 (79%). Eight patients underwent WES, revealing mutations in two known and one unknown cytotoxicity genes and one metabolic disease. FHL3 was the most frequent genetic diagnosis. Immunological screening provided an excellent decision tool for the need and depth of genetic analysis of HLH patients and provided functionally relevant information for rapid patient classification, contributing to a significant reduction in the time from diagnosis to transplantation in recent years

Enhancing precision in human neuroscience

Human neuroscience has always been pushing the boundary of what is measurable. During the last decade, concerns about statistical power and replicability - in science in general, but also specifically in human neuroscience - have fueled an extensive debate. One important insight from this discourse is the need for larger samples, which naturally increases statistical power. An alternative is to increase the precision of measurements, which is the focus of this review. This option is often overlooked, even though statistical power benefits from increasing precision as much as from increasing sample size. Nonetheless, precision has always been at the heart of good scientific practice in human neuroscience, with researchers relying on lab traditions or rules of thumb to ensure sufficient precision for their studies. In this review, we encourage a more systematic approach to precision. We start by introducing measurement precision and its importance for well-powered studies in human neuroscience. Then, determinants for precision in a range of neuroscientific methods (MRI, M/EEG, EDA, Eye-Tracking, and Endocrinology) are elaborated. We end by discussing how a more systematic evaluation of precision and the application of respective insights can lead to an increase in reproducibility in human neuroscience