Modeling Electric Fields in Support of a Measurement of the Neutron Electric Dipole Moment

This research focuses on calculating electric fields in support of a proposed experiment to measure the electric dipole moment (EDM) of the neutron at Las Alamos National Laboratory. The experiment will employ a very strong electric field to exert a torque on the neutrons EDM, if any exists. Field Precision software is used to calculate the theoretical electric fields in and around the central detector region of the proposed experimental setup. This research has two goals. The first is to seek out areas of high electric field in the apparatus that will cause arcing and disrupt the experiment. When these areas are found, the shapes of parts are changed to eliminate the problem. The second goal is to map the electric field in the central detector region where measurements are to be made. It is desirable to know the strength, direction, and uniformity of the electric field in this region. The results of this research will be crucial to the design and execution of the proposed experiment to measure the neutrons EDM, which will, in turn, have far reaching implications in theoretical particle physics

Genomics in cardiac metabolism

Cell biology is in transition from reductionism to a more integrated science. Large-scale analysis of genome structure, gene expression, and metabolites are new technologies available for studying cardiac metabolism in diseases known to modify cardiac function. These technologies have several limitations and this review aims both to assess and take a critical look at some important results obtained in genomics restricted to molecular genetics, transcriptomics and metabolomics of cardiac metabolism in pathophysiological processes known to alter myocardial function. Therefore, our goal was to delineate new signalling pathways and new areas of research from the vast amount of data already published on genomics as applied to cardiac metabolism in diseases such as coronary heart disease, heart failure, and ischaemic reperfusio

Infectious complications and graft outcome following treatment of acute antibody-mediated rejection after kidney transplantation: A nationwide cohort study.

Acute antibody-mediated rejection (AMR) remains a challenge after kidney transplantation (KT). As there is no clear-cut treatment recommendation, accurate information on current therapeutic strategies in real-life practice is needed. KT recipients from the multicenter Swiss Transplant Cohort Study treated for acute AMR during the first post-transplant year were included retrospectively. We aimed at describing the anti-rejection protocols used routinely, as well as patient and graft outcomes, with focus on infectious complications. Overall, 65/1669 (3.9%) KT recipients were treated for 75 episodes of acute AMR. In addition to corticosteroid boluses, most common therapies included plasmapheresis (56.0%), intravenous immunoglobulins (IVIg) (38.7%), rituximab (25.3%), and antithymocyte globulin (22.7%). At least one infectious complication occurred within 6 months from AMR treatment in 63.6% of patients. Plasmapheresis increased the risk of overall (hazard ratio [HR]: 2.89; P-value = 0.002) and opportunistic infection (HR: 5.32; P-value = 0.033). IVIg exerted a protective effect for bacterial infection (HR: 0.29; P-value = 0.053). The recovery of renal function was complete at 3 months after AMR treatment in 67% of episodes. One-year death-censored graft survival was 90.9%. Four patients (6.2%) died during the first year (two due to severe infection). In this nationwide cohort we found significant heterogeneity in therapeutic approaches for acute AMR. Infectious complications were common, particularly among KT recipients receiving plasmapheresis

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Meta-analysis of multidecadal biodiversity trends in Europe

Local biodiversity trends over time are likely to be decoupled from global trends, as local processes may compensate or counteract global change. We analyze 161 long-term biological time series (15-91 years) collected across Europe, using a comprehensive dataset comprising similar to 6,200 marine, freshwater and terrestrial taxa. We test whether (i) local long-term biodiversity trends are consistent among biogeoregions, realms and taxonomic groups, and (ii) changes in biodiversity correlate with regional climate and local conditions. Our results reveal that local trends of abundance, richness and diversity differ among biogeoregions, realms and taxonomic groups, demonstrating that biodiversity changes at local scale are often complex and cannot be easily generalized. However, we find increases in richness and abundance with increasing temperature and naturalness as well as a clear spatial pattern in changes in community composition (i.e. temporal taxonomic turnover) in most biogeoregions of Northern and Eastern Europe. The global biodiversity decline might conceal complex local and group-specific trends. Here the authors report a quantitative synthesis of longterm biodiversity trends across Europe, showing how, despite overall increase in biodiversity metric and stability in abundance, trends differ between regions, ecosystem types, and taxa.peerReviewe

Increased peri-ductal collagen micro-organization may contribute to raised mammographic density

BACKGROUND: High mammographic density is a therapeutically modifiable risk factor for breast cancer. Although mammographic density is correlated with the relative abundance of collagen-rich fibroglandular tissue, the causative mechanisms, associated structural remodelling and mechanical consequences remain poorly defined. In this study we have developed a new collaborative bedside-to-bench workflow to determine the relationship between mammographic density, collagen abundance and alignment, tissue stiffness and the expression of extracellular matrix organising proteins. METHODS: Mammographic density was assessed in 22 post-menopausal women (aged 54–66 y). A radiologist and a pathologist identified and excised regions of elevated non-cancerous X-ray density prior to laboratory characterization. Collagen abundance was determined by both Masson’s trichrome and Picrosirius red staining (which enhances collagen birefringence when viewed under polarised light). The structural specificity of these collagen visualisation methods was determined by comparing the relative birefringence and ultrastructure (visualised by atomic force microscopy) of unaligned collagen I fibrils in reconstituted gels with the highly aligned collagen fibrils in rat tail tendon. Localised collagen fibril organisation and stiffness was also evaluated in tissue sections by atomic force microscopy/spectroscopy and the abundance of key extracellular proteins was assessed using mass spectrometry. RESULTS: Mammographic density was positively correlated with the abundance of aligned periductal fibrils rather than with the abundance of amorphous collagen. Compared with matched tissue resected from the breasts of low mammographic density patients, the highly birefringent tissue in mammographically dense breasts was both significantly stiffer and characterised by large (>80 μm long) fibrillar collagen bundles. Subsequent proteomic analyses not only confirmed the absence of collagen fibrosis in high mammographic density tissue, but additionally identified the up-regulation of periostin and collagen XVI (regulators of collagen fibril structure and architecture) as potential mediators of localised mechanical stiffness. CONCLUSIONS: These preliminary data suggest that remodelling, and hence stiffening, of the existing stromal collagen microarchitecture promotes high mammographic density within the breast. In turn, this aberrant mechanical environment may trigger neoplasia-associated mechanotransduction pathways within the epithelial cell population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0664-2) contains supplementary material, which is available to authorized users

HBV DNA Integration and Clonal Hepatocyte Expansion in Chronic Hepatitis B Patients Considered Immune Tolerant

BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is characterized clinically by progression through disease phases. The first, labeled immune tolerant (IT), is perceived to lack disease activity. Here, we examined HBV-DNA integration, clonal hepatocyte expansion, HBV antigen expression and HBV-specific immunity in patients considered IT to assess whether this designation is appropriate, or if pathological changes may be present. METHODS: HBV-DNA integration, clonal hepatocyte expansion, HBsAg and HBcAg expression were studied in liver tissue from CHB patients, (age 14–39 years; median=24.5). These included 9 HBeAg(+) IT patients. Ten HBeAg(+) and 7 HBeAg(−) age-matched patients with active disease served as controls. HBV-specific T cells were quantified in paired peripheral blood lymphocytes. RESULTS: HBV antigen expression differed between the patient groups. However, unexpectedly high numbers of HBV-DNA integrations, randomly distributed across most chromosomes, were detectable in all patient groups. Patients considered IT also displayed significant clonal hepatocyte expansion, potentially in response to active HBV-specific T cell immunity. HBV-specific T cell responses were also confirmed in the periphery of these patients. CONCLUSIONS: A high level of HBV DNA integration and clonal hepatocyte expansion in patients considered IT suggests that events in hepatocarcinogenesis are underway even in the early stages of CHB. The concept that the IT phase is devoid of markers of disease progression and is immunologically inert is unsupported; instead, we propose that high replicative low inflammatory (HRLI) CHB more accurately reflects this early disease phase. The timing of therapeutic intervention to minimize further genetic damage to the hepatocyte population should be reconsidered

Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week. Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.Peer reviewe

Geosciences Roadmap for Research Infrastructures 2025 - 2028 by the Swiss Geosciences Community

This roadmap is the product of a grassroots effort by the Swiss Geosciences community. It is the first of its kind, outlining an integrated approach to research facilities for the Swiss Geosciences. It spans the planning period 2025-2028. Swiss Geoscience is by its nature leading or highly in-volved in research on many of the major national and global challenges facing society such as climate change and meteorological extreme events, environmental pol-lution, mass movements (land- and rock-slides), earth-quakes and seismic hazards, global volcanic hazards, and energy and other natural resources. It is essential to under- stand the fundamentals of the whole Earth system to pro-vide scientific guidelines to politicians, stakeholders and society for these pressing issues. Here, we strive to gain efficiency and synergies through an integrative approach to the Earth sciences. The research activities of indivi- dual branches in geosciences were merged under the roof of the 'Integrated Swiss Geosciences'. The goal is to facilitate multidisciplinary synergies and to bundle efforts for large research infrastructural (RI) requirements, which will re-sult in better use of resources by merging sectorial acti- vities under four pillars. These pillars represent the four key RIs to be developed in a synergistic way to improve our understanding of whole-system processes and me- chanisms governing the geospheres and the interactions among their components. At the same time, the roadmap provides for the required transition to an infrastructure adhering to FAIR (findable, accessible, interoperable, and reusable) data principles by 2028.The geosciences as a whole do not primarily profit from a single large-scale research infrastructure investment, but they see their highest scientific potential for ground-break-ing new findings in joining forces in establishing state-of-the-art RI by bringing together diverse expertise for the benefit of the entire geosciences community. Hence, the recommendation of the geoscientific community to policy makers is to establish an integrative RI to support the ne- cessary breadth of geosciences in their endeavor to ad-dress the Earth system across the breadth of both temporal and spatial scales. It is also imperative to include suffi-cient and adequately qualified personnel in all large RIs. This is best achieved by fostering centers of excellence in atmospheric, environmental, surface processes, and deep Earth projects, under the roof of the 'Integrated Swiss Geosciences'. This will provide support to Swiss geo-sciences to maintain their long standing and internatio- nally well-recognized tradition of observation, monitor-ing, modelling and understanding of geosciences process-es in mountainous environments such as the Alps and beyond