Interannual Variability in the Large-Scale Dynamics of the South Asian Summer Monsoon

This study identifies coherent and robust large-scale atmospheric patterns of interannual variability of the South Asian summer monsoon (SASM) in observational data. A decomposition of the water vapor budget into dynamic and thermodynamic components shows that interannual variability of SASM net precipitation (P − E) is primarily caused by variations in winds rather than in moisture. Linear regression analyses reveal that strong monsoons are distinguished from weak monsoons by a northward expansion of the cross-equatorial monsoonal circulation, with increased precipitation in the ascending branch. Interestingly, and in disagreement with the view of monsoons as large-scale sea-breeze circulations, strong monsoons are associated with a decreased meridional gradient in the near-surface atmospheric temperature in the SASM region. Teleconnections exist from the SASM region to the Southern Hemisphere, whose midlatitude poleward eddy energy flux correlates with monsoon strength. Possible implications of these teleconnection patterns for understanding SASM interannual variability are discussed

Community Resilience Management : Reflections and Strategies from Corporate Sustainability

Creating community resilience is a daunting task, both in scope and application, therefore it is useful to examine related efforts to inform our strategy. Sustainability, specifically corporate sustainability, has developed through similar challenges and provides insight into the possible trajectory of community resilience management. We find that both concepts reflect similar origins, developmental paths and merging goals at a scale that can be systematically managed. Therefore, we describe four strategies from corporate sustainability management that can be applied to community resilience 1) consider the community context while implementing an increasingly broad view of responsibility; 2) integrate and engage across constructs; 3) employ strategic approaches including performance measurement and assessment of progress; 4) communicate with and engage stakeholders; In doing this, we can leverage our efforts, experience, and successes to transform scorecards into strategies, programs into processes, results into sustained performance and engagement into capable, robust and resilient communities

Understanding the Support Needs of Minority Women with Heart Disease

Background. Cardiovascular disease (CVD) affects minority women disproportionately. WomenHeart: The National Coalition for Women with Heart Disease sought to determine effective ways to support non-Caucasian women with CVD. We surveyed women of color living with CVD to understand their unique CVD-related support needs. Methods. 514 non-white women (100 Hispanic, 180 African American, 104 Asian, 107 Indigenous, 23 multiracial) with CVD from 46 states responded to a 55-question survey (online/telephone, English/Spanish) 8/28/15 through 9/11/15. Results. Among respondents not currently attending support groups, 80% were interested in attending support groups. Of WomenHeart services, respondents were most interested in online message boards. Among new services, respondents were most interested in a support group with a medical expert facilitator. Women with tachycardia wanted a support group with others with the same condition. Those with cardiomyopathy preferred to meet most frequently. Respondents most preferred a monthly support group with flexible membership. Community venues were the most popular location for support groups. Indigenous populations had the lowest CVD knowledge and self-efficacy levels, were most likely to prefer a support group with women of their own race, and wished to meet with their groups most frequently. Multiracial women were most likely to have never been told about clinical trials and were least interested in support groups. Hispanics had the least social support. Conclusions. Minority women with CVD indicated interest in support groups. They may benefit from referrals to tailored support group types, including online platforms facilitated by medical experts, and to cardiac rehabilitation and clinical trials

Pharmacokinetics in neonatal prescribing: evidence base, paradigms and the future

Paediatric patients, particularly preterm neonates, present many pharmacological challenges. Due to the difficulty in conducting clinical trials in these populations dosing information is often extrapolated from adult populations. As the processes of absorption, distribution, metabolism and excretion of drugs change throughout growth and development extrapolation presents risk of over or underestimating the doses required. Information about the development these processes, particularly drug metabolism pathways, is still limited with weight based dose adjustment presenting the best method of estimating pharmacokinetic changes due to growth and development. New innovations in pharmacokinetic research, such as population pharmacokinetic modelling, present unique opportunities to conduct clinical trials in these populations improving the safety and effectiveness of the drugs used. More research is required into this area to ensure the best outcomes for our most vulnerable patients

Cell cycle progression or translation control is not essential for vesicular stomatitis virus oncolysis of hepatocellular carcinoma.

The intrinsic oncolytic specificity of vesicular stomatitis virus (VSV) is currently being exploited to develop alternative therapeutic strategies for hepatocellular carcinoma (HCC). Identifying key regulators in diverse transduction pathways that define VSV oncolysis in cancer cells represents a fundamental prerequisite to engineering more effective oncolytic viral vectors and adjusting combination therapies. After having identified defects in the signalling cascade of type I interferon induction, responsible for attenuated antiviral responses in human HCC cell lines, we have now investigated the role of cell proliferation and translation initiation. Cell cycle progression and translation initiation factors eIF4E and eIF2Bepsilon have been recently identified as key regulators of VSV permissiveness in T-lymphocytes and immortalized mouse embryonic fibroblasts, respectively. Here, we show that in HCC, decrease of cell proliferation by cell cycle inhibitors or siRNA-mediated reduction of G(1) cyclin-dependent kinase activities (CDK4) or cyclin D1 protein expression, do not significantly alter viral growth. Additionally, we demonstrate that translation initiation factors eIF4E and eIF2Bepsilon are negligible in sustaining VSV replication in HCC. Taken together, these results indicate that cellular proliferation and the initiation phase of cellular protein synthesis are not essential for successful VSV oncolysis of HCC. Moreover, our observations indicate the importance of cell-type specificity for VSV oncolysis, an important aspect to be considered in virotherapy applications in the future

Wolbachia Utilizes Host Microtubules and Dynein for Anterior Localization in the Drosophila Oocyte

To investigate the role of the host cytoskeleton in the maternal transmission of the endoparasitic bacteria Wolbachia, we have characterized their distribution in the female germ line of Drosophila melanogaster. In the germarium, Wolbachia are distributed to all germ cells of the cyst, establishing an early infection in the cell destined to become the oocyte. During mid-oogenesis, Wolbachia exhibit a distinct concentration between the anterior cortex and the nucleus in the oocyte, where many bacteria appear to contact the nuclear envelope. Following programmed rearrangement of the microtubule network, Wolbachia dissociate from this anterior position and become dispersed throughout the oocyte. This localization pattern is distinct from mitochondria and all known axis determinants. Manipulation of microtubules and cytoplasmic Dynein and Dynactin, but not Kinesin-1, disrupts anterior bacterial localization in the oocyte. In live egg chambers, Wolbachia exhibit movement in nurse cells but not in the oocyte, suggesting that the bacteria are anchored by host factors. In addition, we identify mid-oogenesis as a period in the life cycle of Wolbachia in which bacterial replication occurs. Total bacterial counts show that Wolbachia increase at a significantly higher rate in the oocyte than in the average nurse cell, and that normal Wolbachia levels in the oocyte depend on microtubules. These findings demonstrate that Wolbachia utilize the host microtubule network and associated proteins for their subcellular localization in the Drosophila oocyte. These interactions may also play a role in bacterial motility and replication, ultimately leading to the bacteria's efficient maternal transmission

py4DSTEM: a software package for multimodal analysis of four-dimensional scanning transmission electron microscopy datasets

Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full 2D image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields and other sample-dependent properties. However, extracting this information requires complex analysis pipelines, from data wrangling to calibration to analysis to visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail, and present results from several experimental datasets. We have also implemented a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open source HDF5 standard. We hope this tool will benefit the research community, helps to move the developing standards for data and computational methods in electron microscopy, and invite the community to contribute to this ongoing, fully open-source project

HPA axis related genes and response to psychological therapies: genetics and epigenetics

Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Results Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Conclusions Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner