531 research outputs found

    Making sense of risk. Donor risk communication in families considering living liverdonation to a child

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    This paper contributes to the growing line of thought in bioethics that respect for autonomy should not be equated to the facilitation of individualistic self determination through standard requirements of informed consent in all healthcare contexts. The paper describes how in the context of donation for living related liver transplantation (LRLT) meaningful, responsible decision making is often embedded within family processes and its negotiation. We suggest that good donor risk communication in families promote “conscientious autonomy” and “reflective trust”. From this, the paper offers the suggestion that transplant teams and other relevant professionals have to broaden their role and responsibility for risk communication beyond proper disclosure by addressing the impact of varied psychosocial conditions on risk interpretation and assessment for potential donors and family stakeholders. In conclusion, we suggest further research questions on how professional responsibility and role-taking in risk communication should be morally understood

    Grassy–herbaceous land moderates regional climate effects on honey bee colonies in the Northcentral US

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    The lack of seasonally sustained floral resources (i.e. pollen and nectar) is considered a primary global threat to pollinator health. However, the ability to predict the abundance of flowering resources for pollinators based upon climate, weather, and land cover is difficult due to insufficient monitoring over adequate spatial and temporal scales. Here we use spatiotemporally distributed honey bee hive scales that continuously measure hive weights as a standardized method to assess nectar intake. We analyze late summer colony weight gain as the response variable in a random forest regression model to determine the importance of climate, weather, and land cover on honey bee colony productivity. Our random forest model predicted resource acquisition by honey bee colonies with 71% accuracy, highlighting the detrimental effects of warm, wet regions in the Northcentral United States on nectar intake, as well as the detrimental effect of years with high growing degree day accumulation. Our model also predicted that grassy–herbaceous natural land had a positive effect on the summer nectar flow and that large areas of natural grassy–herbaceous land around apiaries can moderate the detrimental effects of warm, wet climates. These patterns characterize multi-scale ecological processes that constrain the quantity and quality of pollinator nutritional resources. That is, broad climate conditions constrain regional floral communities, while land use and weather act to further modify the quantity and quality of pollinator nutritional resources. Observing such broad-scale trends demonstrates the potential for utilizing hive scales to monitor the effects of climate change on landscape-level floral resources for pollinators. The interaction of climate and land use also present an opportunity to manage for climate-resilient landscapes that support pollinators through abundant floral resources under climate change

    Phenotypic plasticity in normal breast derived epithelial cells

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    Background Normal, healthy human breast tissue from a variety of volunteer donors has become available for research thanks to the establishment of the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center (KTB). Multiple epithelial (K-HME) and stromal cells (K-HMS) were established from the donated tissue. Explant culture was utilized to isolate the cells from pieces of breast tissue. Selective media and trypsinization were employed to select either epithelial cells or stromal cells. The primary, non-transformed epithelial cells, the focus of this study, were characterized by immunohistochemistry, flow cytometry, and in vitro cell culture. Results All of the primary, non-transformed epithelial cells tested have the ability to differentiate in vitro into a variety of cell types when plated in or on biologic matrices. Cells identified include stratified squamous epithelial, osteoclasts, chondrocytes, adipocytes, neural progenitors/neurons, immature muscle and melanocytes. The cells also express markers of embryonic stem cells. Conclusions The cell culture conditions employed select an epithelial cell that is pluri/multipotent. The plasticity of the epithelial cells developed mimics that seen in metaplastic carcinoma of the breast (MCB), a subtype of triple negative breast cancer; and may provide clues to the origin of this particularly aggressive type of breast cancer. The KTB is a unique biorepository, and the normal breast epithelial cells isolated from donated tissue have significant potential as new research tools

    PASS2 version 4: An update to the database of structure-based sequence alignments of structural domain superfamilies

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    Accurate structure-based sequence alignments of distantly related proteins are crucial in gaining insight about protein domains that belong to a superfamily. The PASS2 database provides alignments of proteins related at the superfamily level and are characterized by low sequence identity. We thus report an automated, updated version of the superfamily alignment database known as PASS2.4, consisting of 1961 superfamilies and 10 569 protein domains, which is in direct correspondence with SCOP (1.75) database. Database organization, improved methods for efficient structure-based sequence alignments and the analysis of extreme distantly related proteins within superfamilies formed the focus of this update. Alignment of family-specific functional residues can be realized using such alignments and is shown using one superfamily as an example. The database of alignments and other related features can be accessed at http://caps.ncbs.res.in/pass2/

    The adaptation of a youth diabetes prevention program for Aboriginal children in Central Australia: community perspectives

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    This study reports on integrating community perspectives to adapt a family-focused, culturally appropriate behavioural intervention program to prevent diabetes among Aboriginal children (6-11 years) in Central Australia. A participatory action research approach was used to engage a range of service providers, cultural advisors, and family groups. Appropriateness, acceptability, content, and delivery of a prevention program within the Central Australian context were discussed through a series of workshops with twenty-five service providers and seven family groups separately. The data obtained were deductively coded for thematic analysis. Main findings included: (i) the strong need for a diabetes prevention program that is community owned, (ii) a flexible and culturally appropriate program delivered by upskilling community members as program facilitators, and (iii) consideration of social and environmental factors when implementing the program. It is recommended that a trial of the adapted prevention program for effectiveness and implementation is led by an Aboriginal community-controlled health service.Athira Rohit, Leisa McCarthy, Shiree Mack, Bronwyn Silver, Sabella Turner, Louise A. Baur, Karla Canuto, John Boffa, Dana Dabelea, Katherine A. Sauder, Louise Maple-Brown, and Renae Kirkha

    Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

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    OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72,694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, Large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), %body fat and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate-to-vigorous physical activity (MVPA), vigorous activity and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia and ponderal index, without heterogeneity (all: I-square=0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95%CI: 0.94, 0.98) respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. This article is protected by copyright. All rights reserved.Includes MRC, Wellcome Trust and NIHR

    The Kafkaesque Pursuit of ‘World Class’: Audit Culture and the Reputational Arms Race in Academia

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    Since the 1980s universities have been subjected to a seemingly continuous process of policy reforms designed to make them more economical, efficient and effective, according to yardsticks defined by governments and university managers. The pursuit of ‘excellence’, ‘international standing’ and ‘world class’ status have become key drivers of what Hazelkorn (High Educ Pol 21(2):193–215, 2008) has termed the ‘rankings arms race’ that now dominates the world of academia. These policies are changing the mission and meaning of the public university and, more profoundly, the culture of academia itself. While some authors have sought to capture and analyse these trends in terms of ‘academic capitalism’ and the ‘enterprise university model’, we suggest they might also be usefully understood theoretically as illustrations of the rise of audit culture in higher education and its effects. Drawing on ethnographic examples from the UK, Denmark and New Zealand, we ask: how are higher education institutions being reconfigured by these new disciplinary regimes of audit? How are ranking and performance indicators changing institutional behaviour and transforming academic subjectivities? What possibilities are there for alternative university futures? And what insights can anthropology offer to address these questions

    SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1-Nrf2.

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    Whether screening the metabolic activity of immune cells facilitates discovery of molecular pathology remains unknown. Here we prospectively screened the extracellular acidification rate as a measure of glycolysis and the oxygen consumption rate as a measure of mitochondrial respiration in B cells from patients with primary antibody deficiency. The highest oxygen consumption rate values were detected in three study participants with persistent polyclonal B cell lymphocytosis (PPBL). Exome sequencing identified germline mutations in SDHA, which encodes succinate dehydrogenase subunit A, in all three patients with PPBL. SDHA gain-of-function led to an accumulation of fumarate in PPBL B cells, which engaged the KEAP1-Nrf2 system to drive the transcription of genes encoding inflammatory cytokines. In a single patient trial, blocking the activity of the cytokine interleukin-6 in vivo prevented systemic inflammation and ameliorated clinical disease. Overall, our study has identified pathological mitochondrial retrograde signaling as a disease modifier in primary antibody deficiency

    Imiquimod Does not Affect Shedding of Viable Chlamydiae in a Murine Model of Chlamydia trachomatis Genital Tract Infection

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    Objective: We postulated that either oral or vaginal administration of the immune response modifier imiquimod would decrease vaginal shedding of Chlamydia trachomatis, mouse pneumonitis strain (MoPn), in a murine model. Methods: Female BALB/c mice were infected intravaginally withC. trachomatis (MoPn) and were administered imiquimod either orally (30 mg/kg) or vaginally (10 μl of 5%imiquimod cream) prior to infection and every second day after infection for a total of four doses. The course of infection was monitored by collecting cervical–vaginal swabs and isolation in HeLa 229 cell culture. To determine whether the drug affected T helper type 1 or T helper type 2 immune response polarization, immunoglobulinG(IgG) subclass antibody responses were assessed at day 56 after infection. Results: There was no significant difference in the course of infection when imiquimod-treated mice were compared with sham-treated controls, regardless of whether the drug was administered orally or vaginally. IgG subclass antibody responses, and by extension, T helper type 1 to T helper type 2 immune response polarization, were also unaffected. Conclusions: Imiquimod has no efficacy in controllingC. trachomatis (MoPn) infection in the murine model
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