Structural basis of initial RNA polymerase II transcription

Several RNA polymerase II–nucleic acid crystal structures reveal the transition of the initiating polymerase from the open complex (OC) state to the initially transcribing complex (ITC) containing several RNA nucleotides

Refusing to Endorse. A must Explanation for Pejoratives.

In her analysis of pejoratives, Eva Picardi rejects a too sharp separation between descriptive and expressive content. I reconstruct some of her arguments, endorsing Eva’s criticism of Williamson’s analysis of Dummett and developing a suggestion by Manuel Garcia Carpintero on a speech act analysis of pejoratives. Eva’s main concern is accounting for our instinctive refusal to endorse an assertion containing pejoratives because it suggests a picture of reality we do not share. Her stance might be further developed claiming that uses of pejoratives not only suggest, but also promote a wrong picture of reality. Our refusal to endorse implies rejecting not only a wrong picture of reality but also a call for participation to what that picture promotes

The influence of risk factors associated with captive rearing on post-release survival in translocated cirl buntings Emberiza cirlus in the UK

Population decline resulting from agricultural intensification led to contraction of the range of the cirl bunting Emberiza cirlus in the UK to a small area of south Devon. As part of the UK Biodiversity Action Plan for the species, a project to re-establish a population in suitable habitat in Cornwall was undertaken during 2006–2011, in which chicks were removed from the nest in Devon, hand-reared and then delayed-released. The survival of the birds to four time points in the year after release was analysed in relation to the effect of rearing factors, using a multivariable logistic regression model. Individuals with higher body weight at capture were more likely to survive to 1 January and 1 May in the year following release, and individuals released in June and July were more likely to survive than those released in August. Individuals released in 2006 and 2011 had a higher survival rate than those released during 2007–2010. Timing of capture, time spent at each stage in captivity, medication and the detection of parasites in the brood had no significant effect. Immunosuppressive disease, weather factors and predator activity may have led to some of the observed differences in survival. This analysis provides evidence with which to plan future translocation projects for cirl buntings and other passerine birds

Y4 receptor knockout rescues fertility in ob/ob mice

Hypothalamic neuropeptide Y (NPY) has been implicated in the regulation of energy balance and reproduction, and chronically elevated NPY levels in the hypothalamus are associated with obesity and reduced reproductive function. However, it is not known which one of the five cloned Y receptors mediates these effects. Here we show that crossing the Y4 receptor knockout mouse (Y4−/−) onto the ob/ob background restores the reduced plasma testosterone levels of ob/ob mice as well as the reduced testis and seminal vesicle size and morphology to control values. Fertility in the sterile ob/ob mice was greatly improved by Y4 receptor deletion, with 100% of male and 50% of female Y4−/−,ob/ob double knockout mice producing live offspring. Development of the mammary ducts and lobuloalveoli was significantly enhanced in pregnant Y4−/− and Y4−/−,ob/ob females. Consistent with the improved fertility and enhanced mammary gland development, gonadotropin releasing hormone (GnRH) expression was significantly increased in Y4−/− and Y4−/−,ob/ob animals. Y4−/− mice displayed lower body weight and reduced white adipose tissue mass accompanied by increased plasma levels of pancreatic polypeptide (PP). However, Y4 deficiency had no beneficial effects to reduce body weight or excessive adiposity of ob/ob mice. These data suggest that central Y4 receptor signaling specifically inhibits reproductive function under conditions of elevated central NPY-ergic tonus

Breast cancer teams: the impact of constitution, new cancer workload, and methods of operation on their effectiveness

National guidance and clinical guidelines recommended multidisciplinary teams (MDTs) for cancer services in order to bring specialists in relevant disciplines together, ensure clinical decisions are fully informed, and to coordinate care effectively. However, the effectiveness of cancer teams was not previously evaluated systematically. A random sample of 72 breast cancer teams in England was studied (548 members in six core disciplines), stratified by region and caseload. Information about team constitution, processes, effectiveness, clinical performance, and members' mental well-being was gathered using appropriate instruments. Two input variables, team workload (P=0.009) and the proportion of breast care nurses (P=0.003), positively predicted overall clinical performance in multivariate analysis using a two-stage regression model. There were significant correlations between individual team inputs, team composition variables, and clinical performance. Some disciplines consistently perceived their team's effectiveness differently from the mean. Teams with shared leadership of their clinical decision-making were most effective. The mental well-being of team members appeared significantly better than in previous studies of cancer clinicians, the NHS, and the general population. This study established that team composition, working methods, and workloads are related to measures of effectiveness, including the quality of clinical care

Patterns and impact of hypoglycemia, hyperglycemia, and glucose variability on inpatients with insulin-treated cystic fibrosis-related diabetes

Introduction: Mortality in patients with cystic fibrosis-related diabetes (CFRD) is higher than that in patients with cystic fibrosis without diabetes. Hypoglycemia, hyperglycemia, and glucose variability confer excess mortality and morbidity in the general inpatient population with diabetes. Methods: We investigated patterns of hypoglycemia and the association of hypoglycemia, hyperglycemia, and glucose variability with mortality and readmission rate in inpatients with CFRD. All capillary blood glucose (CBG) readings (measured using the Abbott Precision web system) of patients with insulin-treated CFRD measured within our health board between January 2009 and January 2015 were. Frequency and timing of hypoglycemia (<4 mmol/L) and was recorded. The effect of dysglycemia on readmission and mortality was investigated with survival analysis. Results: Sixty-six patients were included. A total of 22,711 CBG results were included in the initial analysis. Hypoglycemia was common with 1433 episodes (6.3%). Hypoglycemia ascertainment was highest between 2400 and 0600 h. Hypoglycemia was associated with a significantly higher rate of readmission or death over the 3.5-year follow-up period (P = 0.03). There was no significant association between hyperglycemia or glucose variability and the rate of readmission and mortality. Conclusion: Among inpatients with CFRD hypoglycemia is common and is associated with an increased composite endpoint of readmission and death. As with previously reported trends in general inpatient population this group shows a peak incidence of hypoglycemic during the night

Accuracy of hands v. household measures as portion size estimation aids

Accurate estimation of food portion size is critical in dietary studies. Hands are potentially useful as portion size estimation aids; however, their accuracy has not been tested. The aim of the present study was to test the accuracy of a novel portion size estimation method using the width of the fingers as a 'ruler' to measure the dimensions of foods ('finger width method'), as well as fists and thumb or finger tips. These hand measures were also compared with household measures (cups and spoons). A total of sixty-seven participants (70 % female; age 32·7 (sd 13·7) years; BMI 23·2 (sd  3·5) kg/m(2)) attended a 1·5 h session in which they estimated the portion sizes of forty-two pre-weighed foods and liquids. Hand measurements were used in conjunction with geometric formulas to convert estimations to volumes. Volumes determined with hand and household methods were converted to estimated weights using density factors. Estimated weights were compared with true weights, and the percentage difference from the true weight was used to compare accuracy between the hand and household methods. Of geometrically shaped foods and liquids estimated with the finger width method, 80 % were within ±25 % of the true weight of the food, and 13 % were within ±10 %, in contrast to 29 % of those estimated with the household method being within ±25 % of the true weight of the food, and 8 % being within ±10 %. For foods that closely resemble a geometric shape, the finger width method provides a novel and acceptably accurate method of estimating portion size

The Relative Importance of Different Trophic Pathways for Secondary Exposure to Anticoagulant Rodenticides

Secondary exposure of predators to anticoagulant rodenticides, and in particular second generation anticoagulant rodenticides (SGARs), is a global phenomenon. The widespread and large-scale nature of this exposure has attracted considerable concern, although the consequences in terms of likelihood of poisoning of individuals and resultant impacts on populations are not well characterised. Secondary exposure of predators may as rise from once or more of: (i) eating contaminated commensal rodents subject to control (target species are typically rats and house mice); (ii) consumption of contaminated non-target small mammals (such as Peromyscus, Microtus, and Apodemus species) that encounter and feed on what are rodent-attractive baits; (iii) consumption of non-rodent vertebrate and invertebrate prey that may also incidentally encounter and eat baits. We hypothesised that predators feeding primarily on target species may be most at risk of exposure to SGARs while those predominantly taking non-mammalian prey may be at least risk. We tested this hypothesis by comparing exposure, determined from the presence and magnitude of SGAR liver residues, in red kites (Milvus milvus), which feeds extensively on rats, in barn owls (Tyto alba), kestrels (Falco tinnunculus), and tawny owls (Strix aluco) that feed widely on non-target small mammals, and in sparrowhawks (Accipiter nisus) that feed predominantly on small birds. We found that the scale and magnitude of exposure was broadly consistent with our hypothesis, and that controlling for age in the analysis could be important as older birds can accumulate residues with age. However, exposure in kestrels was typically greater than that in barn owls and tawny owls, despite what is thought to be a general similarity among the species in their diets. We discuss the relative importance of trophic pathways relative to other factors that may drive secondary exposure in predators, and confirm that species that feed on rats or other target species may be at most risk of exposure and poisoning