Alpine vegetation community patterns in the Khumbu region, Nepalese Himalaya

This is the final version. Available from Taylor & Francis via the DOI in this record. The Himalayan alpine zone (HAZ)—a high-altitude zone above approximately 4,100 m.a.s.l., is projected to experience strong eco-environmental changes with climate change. As plants expand their range in this region, other processes are likely to be impacted; for example, flows and stores of water. A first vital step in conceptualizing HAZ ecohydrology is to understand the distribution pattern of HAZ vegetation communities. Satellite remote sensing provides one means of doing so, but the often patchy distribution of alpine vegetation creates challenges when using coarse- grained satellite data whose pixels are typically coarser than the grain of vegetation pattern. Here we use fine spatial resolution satellite imagery from WorldView-2 (2 m2 per pixel) coupled with elevation model data from the Copernicus GLO-30 product to produce a land cover classification for the HAZ. Field data captured during in situ surveys in the Gokyo valley, Nepal, were used to drive and then test a random forest classifier. Grassy meadows and dwarf shrubs belonging to the Rhododendron and Juniperus families dominate the ecology of the alpine zone in this region, so we created three vegetation classes for mapping indicative major plant communities dominated by these species. We found that altitude and aspect were dominant drivers of vegetation distribution in the HAZ and that the average vegetation cover of Rhododendron spp. and Juniperus spp. reduces with increasing altitude, as expected. South- and east-facing slopes were dominated by Juniperus spp., whereas north- and west-facing slopes were dominated by Rhododendron spp., and the growth extent of Rhododendron spp. (between 4,010 and 4,820 m.a.s.l.) and meadow (between 4,010 and 4,680 m.a.s.l.) were vertically wider than that of Juniperus spp. (between 4,010 and 4,660 m.a.s.l.). Results from this study demonstrate the vegetation distribution pattern in HAZ at the plant community level and provide an impetus for further studies that seek to understand ecohydrological interactions between dwarf plants and water flows and stores in the HAZ

Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo

The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity

The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts

The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Prevalence of vancomycin-resistant Enterococcus fecal colonization among kidney transplant patients

BACKGROUND: End stage renal disease patients are at risk of Vancomycin-Resistant Enterococcus (VRE) infections. The first reports of VRE isolation were from hemodialysis patients. However, to date, VRE fecal colonization rates as well as associated risk factors in kidney transplant patients have not yet been established in prospective studies. METHODS: We collected one or two stool samples from 280 kidney transplant patients and analysed the prevalence of VRE and its associated risk factors. Patients were evaluated according to the post-transplant period: group 1, less than 30 days after transplantation (102 patients), group 2, one to 6 months after transplantation (73 patients) and group 3, more than 6 months after transplantation (105 patients). RESULTS: The overall prevalence rate of fecal VRE colonization was 13.6% (38/280), respectively 13.7% for Group 1, 15.1% for group 2 and 12.4% for group 3. E. faecium and E. faecalis comprised 50% of all VRE isolates. No immunologic variables were clearly correlated with VRE colonization and no infections related to VRE colonization were reported. CONCLUSION: Fecal VRE colonization rates in kidney transplant patients were as high as those reported for other high-risk groups, such as critical care and hemodialysis patients. This high rate of VRE colonization observed in kidney transplant recipients may have clinical relevance in infectious complications

Beliefs about weight and breast cancer: An interview study with high risk women following a 12 month weight loss intervention

This is an Version of Record of an article published by BioMed Central in Hereditary Cancer in Clinical Practice on 9 January 2015, available online: http://www.hccpjournal.com/content/13/1/1 This is an Open Access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Breast cancer is the most common cancer in the UK. Lifestyle factors including excess weight contribute to risk of developing the disease. Whilst the exact links between weight and breast cancer are still emerging, it is imperative to explore how women understand these links and if these beliefs impact on successful behaviour change. Overweight/obese premenopausal women (aged 35–45) with a family history of breast cancer (lifetime risk 17–40%) were invited to a semi-structured interview following their participation in a 12 month weight loss intervention aimed at reducing their risk of breast cancer. Interviews were carried out with 9 women who successfully achieved ≥5% weight loss and 11 who were unsuccessful. Data were transcribed verbatim and analysed using thematic analysis. Three themes were developed from the analysis. The first theme how women construct and understand links between weight and breast cancer risk is composed of two subthemes, the construction of weight and breast cancer risk and making sense of weight and breast cancer risk. The second theme - motivation and adherence to weight loss interventions - explains that breast cancer risk can be a motivating factor for adherence to a weight loss intervention. The final theme, acceptance of personal responsibility for health is composed of two subthemes responsibility for one’s own health and responsibility for family health through making sensible lifestyle choices.Beliefs about weight and breast cancer risk were informed by social networks, media reports and personal experiences of significant others diagnosed with breast cancer. Our study has highlighted common doubts, anxieties and questions and the importance of providing a credible rationale for weight control and weight loss which addresses individual concerns

Evaluation of the effects of sensory denervation on osteoblasts by 3 H-proline autoradiography

The inferior alveolar nerve was unilaterally resected in 30-day-old mice; other animals were unilaterally sham-operated. At 15, 30, 60, 90, or 150 days after surgery, the mice were injected with 2μCi of 3 H-proline (sp. act. 1.0 Ci/mM) per g of body weight and killed 15, 30, or 60 min later. Autoradiographs were prepared from 5μm decalcified sagittal sections of mandibles and grain counts made over periosteal osteoblasts mesial to the first molar. In denervated mandibles, osteoblasts incorporated less isotope compared to controls with differences being maximal at the early intervals. These differences became attenuated with time, possibly due to an intrinsic compensatory mechanism, secondary to neurotrophic regulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47675/1/441_2004_Article_BF00219365.pd