Identifying pathways of exposure to highway pollutants in great crested newt (Triturus cristatus) road mitigation tunnels: Exposure pathways of highway pollutants to Triturus cristatus

Road mitigation tunnels are increasingly deployed for amphibians but very little is known about chemical pollution in such schemes. We assessed pollution pressures associated with road runoff at a major great crested newt mitigation scheme in England. Sediments and waters in the mitigation system were analysed for major physico-chemical parameters, trace metals and total petroleum hydrocarbons and compared to a nearby reference site. Seven out of eight tested metals including copper, zinc, lead and iron were in significantly greater concentrations in the tunnels than at a reference site and at environmentally significant concentrations. Water samples also exhibited elevated concentrations of aluminium and chromium and occasionally extreme alkaline pH associated with leaching of portlandite in tunnel cements. High conductivity values in waters and sediments corresponding with seasonal de-icing salt application were also apparent. The study highlights the potential pollutant pressures for amphibians associated with large-scale urban development and road mitigation schemes

Food on the Move: Gendered Representation, Cultural Sustainability, and Culinary Practices of Gullah Women

Food on the Move: Gendered Representation, Cultural Sustainability, and Culinary Practices of Gullah Women connects Gullah women and foodways with processes of migration, cultural heritage, sustainability, and memory. Drawing on women’s studies, history, anthropology, literature, film, and food studies, this interdisciplinary project looks at the preparation and presentation of food as an integral part of a sustained Gullah culture. Using Julie Dash’s Daughters of the Dust alongside contemporary imaginaries of the senses, the work discusses how movement of peoples into and out of the Sea Islands of South Carolina complicates the relationship between the sensory, particularly taste, memory and home. Most importantly, through food-centered stories combined with analyses of cookbooks and other culinary notations, this dissertation examines the vital role women have played in maintaining Gullah culinary history and the dissemination and sustenance of Gullah culture. It enhances not only our understanding of Gullah culture but also of the processes of social and cultural changes necessary to sustain it. This work argues that the Gullah Geechee National Heritage Corridor is a critical site for cultural sustainability particularly in regard to food. Food becomes a site for mapping the traditions, pressures, changes, adaptations, and resistances within a particular racial-ethnic community as it encounters dominant cultures, as well as a site of creativity, pleasure, and survival

The serotonin transporter promotes a pathological estrogen metabolic pathway in pulmonary hypertension via cytochrome P450 1B1 pulmonary circulation

Pulmonary arterial hypertension (PAH) is a devastating vasculopathy that predominates in women and has been associated with dysregulated estrogen and serotonin signaling. Overexpression of the serotonin transporter (SERT+) in mice results in an estrogen-dependent development of pulmonary hypertension (PH). Estrogen metabolism by cytochrome P450 1B1 (CYP1B1) contributes to the pathogenesis of PAH, and serotonin can increase CYP1B1 expression in human pulmonary arterial smooth muscle cells (hPASMCs). We hypothesized that an increase in intracellular serotonin via increased SERT expression may dysregulate estrogen metabolism via CYP1B1 to facilitate PAH. Consistent with this hypothesis, we found elevated lung CYP1B1 protein expression in female SERT+ mice accompanied by PH, which was attenuated by the CYP1B1 inhibitor 2,3',4,5'-tetramethoxystilbene (TMS). Lungs from female SERT+ mice demonstrated an increase in oxidative stress that was marked by the expression of 8-hydroxyguanosine; however, this was unaffected by CYP1B1 inhibition. SERT expression was increased in monocrotaline-induced PH in female rats; however, TMS did not reverse PH in monocrotaline-treated rats but prolonged survival. Stimulation of hPASMCs with the CYP1B1 metabolite 16α-hydroxyestrone increased cellular proliferation, which was attenuated by an inhibitor (MPP) of estrogen receptor alpha (ERα) and a specific ERα antibody. Thus, increased intracellular serotonin caused by increased SERT expression may contribute to PAH pathobiology by dysregulation of estrogen metabolic pathways via increased CYP1B1 activity. This promotes PASMC proliferation by the formation of pathogenic metabolites of estrogen that mediate their effects via ERα. Our studies indicate that targeting this pathway in PAH may provide a promising antiproliferative therapeutic strategy

A quantile-based g-computation approach to addressing the effects of exposure mixtures

Exposure mixtures frequently occur in data across many domains, particularly in the fields of environmental and nutritional epidemiology. Various strategies have arisen to answer questions about mixtures, including methods such as weighted quantile sum (WQS) regression that estimate a joint effect of the mixture components.We demonstrate a new approach to estimating the joint effects of a mixture: quantile g-computation. This approach combines the inferential simplicity of WQS regression with the flexibility of g-computation, a method of causal effect estimation. We use simulations to examine whether quantile g-computation and WQS regression can accurately and precisely estimate effects of mixtures in common scenarios. We examine the bias, confidence interval coverage, and bias-variance tradeoff of quantile g-computation and WQS regression, and how these quantities are impacted by the presence of non-causal exposures, exposure correlation, unmeasured confounding, and non-linear effects. Quantile g-computation, unlike WQS regression allows inference on mixture effects that is unbiased with appropriate confidence interval coverage at sample sizes typically encountered in epidemiologic studies and when the assumptions of WQS regression are not met. Further, WQS regression can magnify bias from unmeasured confounding that might occur if important components of the mixture are omitted. Unlike inferential approaches that examine effects of individual exposures, methods like quantile g-computation that can estimate the effect of a mixture are essential for understanding effects of potential public health actions that act on exposure sources. Our approach may serve to help bridge gaps between epidemiologic analysis and interventions such as regulations on industrial emissions or mining processes, dietary changes, or consumer behavioral changes that act on multiple exposures simultaneously.Comment: Main manuscript (3 figures, 4 tables, 7000 words) + appendi

Factors Influencing Dietetic Interns\u27 Dietary Habits During Supervised Practice

Supervised practice is a prerequisite to becoming a registered dietitian. Research suggests that environmental and social factors may affect dietary choices. This focus group research aimed to gather opinions from dietetic interns to understand what factors related to supervised practice, if any, affected their dietary habits. Qualitative data were collected via seven recorded virtual focus groups in which trained moderators facilitated a discussion using a series of controlled questions. Participants, dietetic interns (n = 42) who were currently completing or had completed their supervised practice within the previous six months, attended one of seven virtual focus groups. Each focus group had five to eight participants. Transcripts were separately coded by two trained researchers using a grounded theory approach to identify themes and subthemes. Researchers discussed any disagreements in coding and established a consensus. Elements related to the dietetic internship were observed to influence participants’ dietary choices. Main themes included time, finances, food access and availability, physical and mental effects, non-supervised practice factors, and social factors. Dietetic programs and preceptors should explore ways to raise interns’ awareness and minimize the potential negative impacts of these factors on interns’ dietary habits to improve their overall internship experience

Identification of novel small molecule inhibitors of adenovirus gene transfer using a high throughput screening approach

Due to many favourable attributes adenoviruses (Ads) are the most extensively used vectors for clinical gene therapy applications. However, following intravascular administration, the safety and efficacy of Ad vectors are hampered by the strong hepatic tropism and induction of a potent immune response. Such effects are determined by a range of complex interactions including those with neutralising antibodies, blood cells and factors, as well as binding to native cellular receptors (coxsackie adenovirus receptor (CAR), integrins). Once in the bloodstream, coagulation factor X (FX) has a pivotal role in determining Ad liver transduction and viral immune recognition. Due to difficulties in generating a vector devoid of multiple receptor binding motifs, we hypothesised that a small molecule inhibitor would be of value. Here, a pharmacological approach was implemented to block adenovirus transduction pathways. We developed a high throughput screening (HTS) platform to identify the small molecule inhibitors of FX-mediated Ad5 gene transfer. Using an in vitro fluorescence and cell-based HTS, we evaluated 10,240 small molecules. Following sequential rounds of screening, three compounds, T5424837, T5550585 and T5660138 were identified that ablated FX-mediated Ad5 transduction with low micromolar potency. The candidate molecules possessed common structural features and formed part of the one pharmacophore model. Focused, mini-libraries were generated with structurally related molecules and in vitro screening revealed novel hits with similar or improved efficacy. The compounds did not interfere with Ad5:FX engagement but acted at a subsequent step by blocking efficient intracellular transport of the virus. In vivo, T5660138 and its closely related analogue T5660136 significantly reduced Ad5 liver transgene expression at 48 h post-intravenous administration of a high viral dose (1 × 10<sup>11</sup> vp/mouse). Therefore, this study identifies novel and potent small molecule inhibitors of the Ad5 transduction which may have applications in the Ad gene therapy setting

Effectiveness of a structured, framework-based approach to implementation: the Researching Effective Approaches to Cleaning in Hospitals (REACH) Trial

BACKGROUND: Implementing sustainable practice change in hospital cleaning has proven to be an ongoing challenge in reducing healthcare associated infections. The purpose of this study was to develop a reliable framework-based approach to implement and quantitatively evaluate the implementation of evidence-based practice change in hospital cleaning. DESIGN/METHODS: The Researching Effective Approaches to Cleaning in Hospitals (REACH) trial was a pragmatic, stepped-wedge randomised trial of an environmental cleaning bundle implemented in 11 Australian hospitals from 2016 to 2017. Using a structured multi-step approach, we adapted the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to support rigorous and tailored implementation of the cleaning bundle intervention in eleven diverse and complex settings. To evaluate the effectiveness of this strategy we examined post-intervention cleaning bundle alignment calculated as a score (an implementation measure) and cleaning performance audit data collected using ultraviolet (UV) gel markers (an outcome measure). RESULTS: We successfully implemented the bundle and observed improvements in cleaning practice and performance, regardless of hospital size, intervention duration and contextual issues such as staff and organisational readiness at baseline. There was a positive association between bundle alignment scores and cleaning performance at baseline. This diminished over the duration of the intervention, as hospitals with lower baseline scores were able to implement practice change successfully. CONCLUSION: Using a structured framework-based approach allows for pragmatic and successful implementation of clinical trials across diverse settings, and assists with quantitative evaluation of practice change. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12615000325505, registered on 4 September 2015

Structural changes in gill DNA reveal the effects of contaminants on Puget Sound fish.

Structural differences were identified in gill DNA from two groups of English sole collected from Puget Sound, Washington, in October 2000. One group was from the industrialized Duwamish River (DR) in Seattle and the other from relatively clean Quartermaster Harbor (QMH). Chemical markers of sediment contamination [e.g., polynuclear aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs)] established that the DR was substantially more contaminated than QMH. The levels of these chemicals in the sediments of both sites were consistent with levels of cytochrome P450 1A (CYP1A) expression in the gills of English sole from the same sites. Structural differences in gill DNA between the groups were evinced via statistical models of Fourier transform-infrared (FT-IR) spectra. Marked structural damage was found in the gill DNA of the DR fish as reflected in differences in base functional groups (e.g., C-O and NH2) and conformational properties (e.g., arising from perturbations in vertical base stacking interactions). These DNA differences were used to discriminate between the two fish groups through principal components analysis of mean FT-IR spectra. In addition, logistic regression analysis allowed for the development of a "DNA damage index" to assess the effects of contaminants on the gill. The evidence implies that environmental chemicals contribute to the DNA changes in the gill. The damaged DNA is a promising marker for identifying, through gill biopsies, contaminant effects on fish

AACP Special Taskforce White Paper on Diversifying Our Investment in Human Capital

The 2015-2017 American Association of Colleges of Pharmacy (AACP) Special Taskforce on Diversifying our Investment in Human Capital was appointed for a two-year term, due to the rigors and complexities of its charges. This report serves as a white paper for academic pharmacy on diversifying our investment in human capital. The Taskforce developed and recommended a representation statement that was adapted and adopted by the AACP House of Delegates at the 2016 AACP Annual Meeting. In addition, the Taskforce developed a diversity statement for the Association that was adopted by the AACP Board of Directors in 2017. The Taskforce also provides recommendations to AACP and to academic pharmacy in this white paper

Resilient Soils for Resilient Farms: An Integrative Approach to Assess, Promote and Value Soil Health for Small- and Medium-Size Farms

Our team was a collaborative group of academic, extension and doctoral student researchers who met internally and conducted an IRB-approved survey that engaged with myriad stakeholders. The result was a clear trifecta on relative timing of soil health initiatives: 1) Stakeholders (91%) embrace soil health and believe soil health should be the top priority for UVM research and outreach. 2) Existing policy demands farmers assess elements of soil health every two years for nutrient management plans. 3) Only a subset of desired metrics is available at commercial laboratories, most soil analyses are sent out of state to Maine or New York, and most data are privately held instead of deposited into public databases. Together, these three findings indicate that soil health be a central focus of UVM\u27s ARS program. Yet, due to attrition, there are no longer any UVM faculty dedicated to updating the 30-year-old soil recommendations upon which regulations rely. There is opportunity for university-government-community partnerships and expanded employment opportunities in Vermont if collaborative resources were assigned to soil health