Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct ...patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.
Recently, piezoelectric thin films including zinc oxide (ZnO) and aluminium nitride (AlN) have found a broad range of lab-on-chip applications such as biosensing, particle/cell concentrating, ...sorting/patterning, pumping, mixing, nebulisation and jetting. Integrated acoustic wave sensing/microfluidic devices have been fabricated by depositing these piezoelectric films onto a number of substrates such as silicon, ceramics, diamond, quartz, glass, and more recently also polymer, metallic foils and bendable glass/silicon for making flexible devices. Such thin film acoustic wave devices have great potential for implementing integrated, disposable, or bendable/flexible lab-on-a-chip devices into various sensing and actuating applications. This paper discusses the recent development in engineering high performance piezoelectric thin films, and highlights the critical issues such as film deposition, MEMS processing techniques, control of deposition/processing parametres, film texture, doping, dispersion effects, film stress, multilayer design, electrode materials/designs and substrate selections. Finally, advances in using thin film devices for lab-on-chip applications are summarised and future development trends are identified.
Essentials
Microbe‐dependent production of trimethylamine N‐oxide (TMAO) contributes to thrombosis risk.
The impact of host flavin monooxygenase 3 (FMO3) modulation on platelet function is unknown.
...Genetic manipulation of FMO3 in mice alters systemic TMAO levels and thrombosis potential.
Genetic manipulation of FMO3 is associated with alteration of gut microbial community structure.
Summary
Background
Gut microbes play a critical role in the production of trimethylamine N‐oxide (TMAO), an atherogenic metabolite that impacts platelet responsiveness and thrombosis potential. Involving both microbe and host enzymatic machinery, TMAO generation utilizes a metaorganismal pathway, beginning with ingestion of trimethylamine (TMA)‐containing dietary nutrients such as choline, phosphatidylcholine and carnitine, which are abundant in a Western diet. Gut microbial TMA lyases use these nutrients as substrates to produce TMA, which upon delivery to the liver via the portal circulation, is converted into TMAO by host hepatic flavin monooxygenases (FMOs). Gut microbial production of TMA is rate limiting in the metaorganismal TMAO pathway because hepatic FMO activity is typically in excess.
Objectives
FMO3 is the major FMO responsible for host generation of TMAO; however, a role for FMO3 in altering platelet responsiveness and thrombosis potential in vivo has not yet been explored.
Methods
The impact of FMO3 suppression (antisense oligonucleotide‐targeting) and overexpression (as transgene) on plasma TMAO levels, platelet responsiveness and thrombosis potential was examined using a murine FeCl3‐induced carotid artery injury model. Cecal microbial composition was examined using 16S analyses.
Results
Modulation of FMO3 directly impacts systemic TMAO levels, platelet responsiveness and rate of thrombus formation in vivo. Microbial composition analyses reveal taxa whose proportions are associated with both plasma TMAO levels and in vivo thrombosis potential.
Conclusions
The present studies demonstrate that host hepatic FMO3, the terminal step in the metaorganismal TMAO pathway, participates in diet‐dependent and gut microbiota‐dependent changes in both platelet responsiveness and thrombosis potential in vivo.
Background
This study aimed to compare sequential treatment by transcatheter arterial chemoembolization (TACE) and percutaneous radiofrequency ablation (RFA) with partial hepatectomy for ...hepatocellular carcinoma (HCC) within the Milan criteria.
Methods
In a randomized clinical trial, patients with HCC within the Milan criteria were included and randomized 1 : 1 to the partial hepatectomy group or the TACE + RFA group. The primary outcome was overall survival and the secondary outcome was recurrence‐free survival.
Results
Two hundred patients were enrolled. The 1‐, 3‐ and 5‐year overall survival rates were 97·0, 83·7 and 61·9 per cent for the partial hepatectomy group, and 96·0, 67·2 and 45·7 per cent for the TACE + RFA group (P = 0·007). The 1‐, 3‐ and 5‐year recurrence‐free survival rates were 94·0, 68·2 and 48·4 per cent, and 83·0, 44·9 and 35·5 per cent respectively (P = 0·026). On Cox proportional hazard regression analysis, HBV‐DNA (hazard ratio (HR) 1·76; P = 0·006), platelet count (HR 1·00; P = 0·017) and tumour size (HR 1·90; P < 0·001) were independent prognostic factors for recurrence‐free survival, and HBV‐DNA (HR 1·61; P = 0·036) was a risk factor for overall survival. The incidence of complications in the partial hepatectomy group was higher than in the TACE + RFA group (23·0 versus 11·0 per cent respectively; P = 0·024).
Conclusion
For patients with HCC within the Milan criteria, partial hepatectomy was associated with better overall and recurrence‐free survival than sequential treatment with TACE and RFA. Registration number: ACTRN12611000770965 (http://www.anzctr.org.au/).
Partial hepatectomy better
The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This ...mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ̃ confidence level, using a low-background, 14.6-kilogram CsINa scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.
Abstract
Topological superconductors (TSCs) are unconventional superconductors with bulk superconducting gap and in-gap Majorana states on the boundary that may be used as topological qubits for ...quantum computation. Despite their importance in both fundamental research and applications, natural TSCs are very rare. Here, combining state of the art synchrotron and laser-based angle-resolved photoemission spectroscopy, we investigated a stoichiometric transition metal dichalcogenide (TMD), 2M-WS
2
with a superconducting transition temperature of 8.8 K (the highest among all TMDs in the natural form up to date) and observed distinctive topological surface states (TSSs). Furthermore, in the superconducting state, we found that the TSSs acquired a nodeless superconducting gap with similar magnitude as that of the bulk states. These discoveries not only evidence 2M-WS
2
as an intrinsic TSC without the need of sensitive composition tuning or sophisticated heterostructures fabrication, but also provide an ideal platform for device applications thanks to its van der Waals layered structure.
The functional relevance of the B-cell receptor (BCR) and the evolution of protein kinases as therapeutic targets have recently shifted the paradigm for treatment of B-cell malignancies. Inhibition ...of p110δ with idelalisib has shown clinical activity in chronic lymphocytic leukemia (CLL). The dynamic interplay of isoforms p110δ and p110γ in leukocytes support the hypothesis that dual blockade may provide a therapeutic benefit. IPI-145, an oral inhibitor of p110δ and p110γ isoforms, sensitizes BCR-stimulated and/or stromal co-cultured primary CLL cells to apoptosis (median 20%, n=57; P<0.0001) including samples with poor prognostic markers, unmutated IgVH (n=28) and prior treatment (n=15; P<0.0001). IPI-145 potently inhibits the CD40L/IL-2/IL-10 induced proliferation of CLL cells with an IC50 in sub-nanomolar range. A corresponding dose-responsive inhibition of pAKT(Ser473) is observed with an IC50 of 0.36 nM. IPI-145 diminishes the BCR-induced chemokines CCL3 and CCL4 secretion to 17% and 37%, respectively. Pre-treatment with 1 μM IPI-145 inhibits the chemotaxis toward CXCL12; reduces pseudoemperipolesis to median 50%, inferring its ability to interfere with homing capabilities of CLL cells. BCR-activated signaling proteins AKT(Ser473), BAD(Ser112), ERK(Thr202/Tyr204) and S6(Ser235/236) are mitigated by IPI-145. Importantly, for clinical development in hematological malignancies, IPI-145 is selective to CLL B cells, sparing normal B- and T-lymphocytes.
The gut microbiome is associated with diverse diseases
, but a universal signature of a healthy or unhealthy microbiome has not been identified, and there is a need to understand how genetics, ...exposome, lifestyle and diet shape the microbiome in health and disease. Here we profiled bacterial composition, function, antibiotic resistance and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We correlated these to 241 host and environmental factors, including physical and mental health, use of medication, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is shaped primarily by the environment and cohabitation. Only around 6.6% of taxa are heritable, whereas the variance of around 48.6% of taxa is significantly explained by cohabitation. By identifying 2,856 associations between the microbiome and health, we find that seemingly unrelated diseases share a common microbiome signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, with numerous early-life and current factors being significantly associated with microbiome function and composition. Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.
Severe air pollution episodes have been frequent in China during the recent years. While high emissions are the primary reason for increasing pollutant concentrations, the ultimate cause for the most ...severe pollution episodes has remained unclear. Here we show that a high concentration of particulate matter (PM) will enhance the stability of an urban boundary layer, which in turn decreases the boundary layer height and consequently cause further increases in PM concentrations. We estimate the strength of this positive feedback mechanism by combining a new theoretical framework with ambient observations. We show that the feedback remains moderate at fine PM concentrations lower than about 200 μg m(-3), but that it becomes increasingly effective at higher PM loadings resulting from the combined effect of high surface PM emissions and massive secondary PM production within the boundary layer. Our analysis explains why air pollution episodes are particularly serious and severe in megacities and during the days when synoptic weather conditions stay constant.
Shifts in ecosystem phenology play an important role in the definition of inter-annual variability of net ecosystem carbon uptake. A good estimate at the global scale of ecosystem phenology, mainly ...that of photosynthesis or gross primary productivity (GPP), may be provided by vegetation indices derived from MODIS satellite image data.
However, the relationship between the start date of a growing (or greening) season (SGS) when derived from different vegetation indices (VI's), and the starting day of carbon uptake is not well elucidated. Additionally, the validation of existing phenology data with in-situ measurements is largely missing. We have investigated the possibility to use different VI's to predict the starting day of the growing season for 28 FLUXNET sites as well as MODIS data. This analysis included main plant functional types (PFT's).
Of all VI's taken into account in this paper, the NDVI (Normalized Difference Vegetation Index) shows the highest correlation coefficient for the relationship between the starting day of the growing season as observed with MODIS and in-situ observations. However, MODIS observations elicit a 20–21days earlier SGS date compared to in-situ observations. The prediction for the NEE start of the growing season diverges when using different VI's, and seems to depend on the amplitude for carbon and VI and on PFT. The optimal VI for estimation of a SGS date was PFT-specific — for example the WRDVI for cropland, but the MODIS NDVI performed best when applied as an estimator for Net Ecosystem Exchange and when considering all PFT's pooled.
•MODIS VI's show a higher correlation with SGSNEE compared to in-situ VI's.•The MODIS NDVI matches best with SGSNEE.•Specific VI's can be applied improving a SGSNEE estimate specific for a PFT.
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