Guest editorial: Promoting cultural competency in the nursing care of LGBT patients

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Development and testing of a risk indexing framework to determine field-scale critical source areas of faecal bacteria on grassland.

This paper draws on lessons from a UK case study in the management of diffuse microbial pollution from grassland farm systems in the Taw catchment, south west England. We report on the development and preliminary testing of a field-scale faecal indicator organism risk indexing tool (FIORIT). This tool aims to prioritise those fields most vulnerable in terms of their risk of contributing FIOs to water. FIORIT risk indices were related to recorded microbial water quality parameters (faecal coliforms [FC] and intestinal enterococci [IE]) to provide a concurrent on-farm evaluation of the tool. There was a significant upward trend in Log[FC] and Log[IE] values with FIORIT risk score classification (r2 =0.87 and 0.70, respectively and P<0.01 for both FIOs). The FIORIT was then applied to 162 representative grassland fields through different seasons for ten farms in the case study catchment to determine the distribution of on-farm spatial and temporal risk. The high risk fields made up only a small proportion (1%, 2%, 2% and 3% for winter, spring, summer and autumn, respectively) of the total number of fields assessed (and less than 10% of the total area), but the likelihood of the hydrological connection of high FIO source areas to receiving watercourses makes them a priority for mitigation efforts. The FIORIT provides a preliminary and evolving mechanism through which we can combine risk assessment with risk communication to end-users and provides a framework for prioritising future empirical research. Continued testing of FIORIT across different geographical areas under both low and high flow conditions is now needed to initiate its long term development into a robust indexing tool

Seasonal persistence of faecal indicator organisms in soil following dairy slurry application to land by surface broadcasting and shallow injection

Dairy farming generates large volumes of liquid manure (slurry), which is ultimately recycled to agricultural land as a valuable source of plant nutrients. Different methods of slurry application to land exist; some spread the slurry to the sward surface whereas others deliver the slurry under the sward and into the soil, thus helping to reduce greenhouse gas (GHG) emissions from agriculture. The aim of this study was to investigate the impact of two slurry application methods (surface broadcast versus shallow injection) on the survival of faecal indicator organisms (FIOs) delivered via dairy slurry to replicated grassland plots across contrasting seasons. A significant increase in FIO persistence (measured by the half-life ofE.coliand intestinal enterococci) was observed when slurry was applied to grassland via shallow injection, and FIO decay rates were significantly higher for FIOs applied to grassland in spring relative to summer and autumn. Significant differences in the behaviour ofE.coliand intestinal enterococci over time were also observed, withE.colihalf-lives influenced more strongly by season of application relative to the intestinal enterococci population. While shallow injection of slurry can reduce agricultural GHG emissions to air it can also prolong the persistence of FIOs in soil, potentially increasing the risk of their subsequent transfer to water. Awareness of (and evidence for) the potential for &lsquo;pollution-swapping&rsquo; is critical in order to guard against unintended environmental impacts of agricultural management decisions

A Cost Comparison of Treatments of Moderate to Severe Psoriasis

This study of the efficacy and cost-effectiveness of moderate to severe psoriasis treatments compared phototherapy, oral systemic agents, and biologics from a managed health care systems perspective. A literature review was conducted to identify published studies reporting Psoriasis Area and Severity Index (PASI) percentage improvement from baseline (PASI%) for selected treatments. The researchers then calculated total annualized costs. For each treatment, annualized cost-effectiveness was calculated by dividing total annualized costs of treatment by PASI%. The costs necessary to achieve clinically meaningful outcomes (PASI50 and PASI75) were then calculated. Of 3886 articles examined, 16 studies met inclusion criteria. Oral systemic medications, UV therapy, and UV therapy combined with acitretin appear to be the most cost-effective therapies for moderate to severe psoriasis

Possibilities for Engineered Insect Tissue as a Food Source

Due to significant environmental concerns associated with industrial livestock farming, it is vital to accelerate the development of sustainable food production methods. Cellular agriculture may offer a more efficient production paradigm by using cell culture, as opposed to whole animals, to generate foods like meats, eggs, and dairy products. However, the cost-effective scale-up of cellular agriculture systems requires addressing key constraints in core research areas: (1) cell sources, (2) growth media, (3) scaffolding biomaterials, and (4) bioreactor design. Here we summarize work in the area of insect cell cultures as a promising avenue to address some of these needs. We also review current applications of insect cell culture and tissue engineering, provide an overview of insect myogenesis and discuss various properties of insect cells that indicate suitability for use in food production systems. Compared to mammalian or avian cultures, invertebrate cell cultures require fewer resources and are more resilient to changes in environmental conditions, as they can thrive in a wide range of temperature, pH and osmolarity conditions. Alterations necessary for large-scale production are relatively simple to achieve with insect cells, including immortalization, serum-free media adaptation and suspension culture. Additional benefits include ease of transfection, nutrient density, and relevance to seafood organisms. To advance insect-based tissue engineering for food purposes, it is necessary to develop methods to regulate the differentiation of insect cells into relevant cell types, characterize cell interactions with biomaterials with an eye toward 3D culture, design supportive bioreactor systems and quantify nutritional profiles of cultured biomass

Cancer cells exploit an orphan RNA to drive metastatic progression.

Here we performed a systematic search to identify breast-cancer-specific small noncoding RNAs, which we have collectively termed orphan noncoding RNAs (oncRNAs). We subsequently discovered that one of these oncRNAs, which originates from the 3' end of TERC, acts as a regulator of gene expression and is a robust promoter of breast cancer metastasis. This oncRNA, which we have named T3p, exerts its prometastatic effects by acting as an inhibitor of RISC complex activity and increasing the expression of the prometastatic genes NUPR1 and PANX2. Furthermore, we have shown that oncRNAs are present in cancer-cell-derived extracellular vesicles, raising the possibility that these circulating oncRNAs may also have a role in non-cell autonomous disease pathogenesis. Additionally, these circulating oncRNAs present a novel avenue for cancer fingerprinting using liquid biopsies

Design, Synthesis, and Evaluation of Tetrasubstituted Pyridines as Potent 5-HT2C Receptor Agonists.

A series of pyrido[3,4-d]azepines that are potent and selective 5-HT2C receptor agonists is disclosed. Compound 7 (PF-04781340) is identified as a suitable lead owing to good 5-HT2C potency, selectivity over 5-HT2B agonism, and in vitro ADME properties commensurate with an orally available and CNS penetrant profile. The synthesis of a novel bicyclic tetrasubstituted pyridine core template is outlined, including rationale to account for the unexpected formation of aminopyridine 13 resulting from an ammonia cascade cyclization.We would like to thank the EPSRC (SVL, grant nº EP/K0099494/1 and nº EP/K039520/1) for financial support.This is the accepted manuscript. The final version is available from ACS at http://pubs.acs.org/doi/abs/10.1021/ml500507v

Fast and Furious: Energetic Tradeoffs and Scaling of High-Speed Foraging in Rorqual Whales

Although gigantic body size and obligate filter feeding mechanisms have evolved in multiple vertebrate lineages (mammals and fishes), intermittent ram (lunge) filter feeding is unique to a specific family of baleen whales: rorquals. Lunge feeding is a high cost, high benefit feeding mechanism that requires the integration of unsteady locomotion (i.e., accelerations and maneuvers); the impact of scale on the biomechanics and energetics of this foraging mode continues to be the subject of intense study. The goal of our investigation was to use a combination of multi-sensor tags paired with UAS footage to determine the impact of morphometrics such as body size on kinematic lunging parameters such as fluking timing, maximum lunging speed, and deceleration during the engulfment period for a range of species from minke to blue whales. Our results show that, in the case of krill-feeding lunges and regardless of size, animals exhibit a skewed gradient between powered and fully unpowered engulfment, with fluking generally ending at the point of both the maximum lunging speed and mouth opening. In all cases, the small amounts of propulsive thrust generated by the tail were unable to overcome the high drag forces experienced during engulfment. Assuming this thrust to be minimal, we predicted the minimum speed of lunging across scale. To minimize the energetic cost of lunge feeding, hydrodynamic theory predicts slower lunge feeding speeds regardless of body size, with a lower boundary set by the ability of the prey to avoid capture. We used empirical data to test this theory and instead found that maximum foraging speeds remain constant and high (∼4 m s–1) across body size, even as higher speeds result in lower foraging efficiency. Regardless, we found an increasing relationship between body size and this foraging efficiency, estimated as the ratio of energetic gain from prey to energetic cost. This trend held across timescales ranging from a single lunge to a single day and suggests that larger whales are capturing more prey—and more energy—at a lower cost

Genotype and Phenotype in 12 additional individuals with SATB2-Associated Syndrome

SATB2-associated syndrome (SAS) is a multisystemic disorder caused by alterations of the SATB2 gene. We describe the phenotype and genotype of 12 individuals with 10 unique (de novo in 11 of 11 tested) pathogenic variants (1 splice site, 5 frameshift, 3 nonsense, and 2 missense) in SATB2 and review all cases reported in the published literature caused by point alterations thus far. In the cohort here described, developmental delay (DD) with severe speech compromise, facial dysmorphism, and dental anomalies were present in all cases. We also present the third case of tibial bowing in an individual who, just as in the previous 2 individuals in the literature, also had a truncating pathogenic variant of SATB2. We explore early genotype-phenotype correlations and reaffirm the main clinical features of this recognizable syndrome: universal DD with severe speech impediment, mild facial dysmorphism, and high frequency of craniofacial anomalies, behavioral issues, and brain neuroradiographic changes. As the recently proposed surveillance guidelines for individuals with SAS are adopted by providers, further delineation of the frequency and impact of other phenotypic traits will become available. Similarly, as new cases of SAS are identified, further exploration of genotype-phenotype correlations will be possible