Residual confounding after adjustment for age: a minor issue in breast cancer screening effectiveness

Residual confounding, after adjustment for age, is the major criticism of observational studies on breast cancer screening effectiveness. We developed realistic scenarios for the prevalence and strength of risk factors on screened and not screened groups, and explored the impact of residual confounding bias. Our results demonstrate that residual confounding bias is a minor issue in screening programme evaluations

Engineering the isobutanol biosynthetic pathway in Escherichia coli by comparison of three aldehyde reductase/alcohol dehydrogenase genes

Biofuels synthesized from renewable resources are of increasing interest because of global energy and environmental problems. We have previously demonstrated production of higher alcohols from Escherichia coli using a 2-keto acid-based pathway. Here, we have compared the effect of various alcohol dehydrogenases (ADH) for the last step of the isobutanol production. E. coli has the yqhD gene which encodes a broad-range ADH. Isobutanol production significantly decreased with the deletion of yqhD, suggesting that the yqhD gene on the genome contributed to isobutanol production. The adh genes of two bacteria and one yeast were also compared in E. coli harboring the isobutanol synthesis pathway. Overexpression of yqhD or adhA in E. coli showed better production than ADH2, a result confirmed by activity measurements with isobutyraldehyde

Relationship between cardiovascular risk factors and biomarkers with necrotic core and atheroma size: a serial intravascular ultrasound radiofrequency data analysis

We explored the impact of patient demographics, anthropometric measurements, cardiovascular risk factors, and soluble biomarkers on necrotic core and atheroma size in patients with coronary disease. The IBIS-2 trial enrolled 330 patients. In the multivariate analysis, at baseline, creatinine had a positive, whereas baseline mean lumen diameter and myeloperoxidase had a negative, independent association with percentage of necrotic core (PNC); while age, glomerular filtration rate <60, HbA1c, previous PCI or CABG and baseline % diameter stenosis were positively, and acute coronary syndromes (ACS) were negatively associated with baseline percentage atheroma volume (PAV). The variables associated with a decrease in PNC from baseline were darapladib, ACS and a large content of NC at baseline, while variables associated with an increase in PNC were previous stroke and % diameter stenosis at baseline. Those variables associated with a decrease in PAV from baseline were waist circumference, statin use, CD40L and baseline PAV, while the only variable associated with an increase in PAV was baseline diastolic blood pressure. Treatment with darapladib was associated with a decrease in necrotic core, but was not associated with a decrease in percentage atheroma volume. On the contrary, statin use was only associated with a decrease in percentage atheroma volume

Assessing the Quality of Goal Setting in Behavioural Support for Smoking Cessation and its Association with Outcomes

BACKGROUND: Smoking cessation behavioural support can be effective but practitioners differ markedly in effectiveness, possibly due to variation in the quality of delivery of key behaviour change techniques, such as goal setting (i.e. setting a quit date). OBJECTIVES: This study aimed to (i) develop a reliable method for assessing the quality of practitioners' support in setting quit dates and (ii) assess whether quality predicts initiation of abstinence as a first step to quitting. METHODS: A scale for scoring the quality of goal setting was developed from national guidance documents and applied to 85 transcribed behavioural support sessions. Inter-rater reliability was assessed. Associations between quality scores and quit attempts were assessed. RESULTS: The 10-item scale produced had good inter-rater reliability (Kappa = 0.68). Higher quality goal setting was associated with increased self-reported quit attempts (p < .001; OR = 2.60, 95 % CI 1.54-4.40). The scale components 'set a clear quit date' (χ (2) (2, N = 85) = 22.3, p < .001) and 'within an appropriate timeframe' (χ (2) (2, N = 85) = 15.5, p < .001) were independently associated with quit attempts. CONCLUSIONS: It is possible to reliably assess the quality of goal setting in smoking cessation behavioural support. Higher quality of goal setting is associated with greater likelihood of initiating quit attempts

Rhabdovirus Matrix Protein Structures Reveal a Novel Mode of Self-Association

The matrix (M) proteins of rhabdoviruses are multifunctional proteins essential for virus maturation and budding that also regulate the expression of viral and host proteins. We have solved the structures of M from the vesicular stomatitis virus serotype New Jersey (genus: Vesiculovirus) and from Lagos bat virus (genus: Lyssavirus), revealing that both share a common fold despite sharing no identifiable sequence homology. Strikingly, in both structures a stretch of residues from the otherwise-disordered N terminus of a crystallographically adjacent molecule is observed binding to a hydrophobic cavity on the surface of the protein, thereby forming non-covalent linear polymers of M in the crystals. While the overall topology of the interaction is conserved between the two structures, the molecular details of the interactions are completely different. The observed interactions provide a compelling model for the flexible self-assembly of the matrix protein during virion morphogenesis and may also modulate interactions with host proteins

The Role of Practitioner Resilience and Mindfulness in Effective Practice: A Practice-Based Feasibility Study.

A growing body of literature attests to the existence of therapist effects with little explanation of this phenomenon. This study therefore investigated the role of resilience and mindfulness as factors related to practitioner wellbeing and associated effective practice. Data comprised practitioners (n = 37) and their patient outcome data (n = 4980) conducted within a stepped care model of service delivery. Analyses employed benchmarking and multilevel modeling to identify more and less effective practitioners via yoking of therapist factors and nested patient outcomes. A therapist effect of 6.7 % was identified based on patient depression (PHQ-9) outcome scores. More effective practitioners compared to less effective practitioners displayed significantly higher levels of mindfulness as well as resilience and mindfulness combined. Implications for policy, research and practice are discussed

Mutations in mitochondrial DNA causing tubulointerstitial kidney disease

Tubulointerstitial kidney disease is an important cause of progressive renal failure whose aetiology is incompletely understood. We analysed a large pedigree with maternally inherited tubulointerstitial kidney disease and identified a homoplasmic substitution in the control region of the mitochondrial genome (m.547A>T). While mutations in mtDNA coding sequence are a well recognised cause of disease affecting multiple organs, mutations in the control region have never been shown to cause disease. Strikingly, our patients did not have classical features of mitochondrial disease. Patient fibroblasts showed reduced levels of mitochondrial tRNA$^{Phe}$, tRNA$^{Leu1}$ and reduced mitochondrial protein translation and respiration. Mitochondrial transfer demonstrated mitochondrial transmission of the defect and in vitro assays showed reduced activity of the heavy strand promoter. We also identified further kindreds with the same phenotype carrying a homoplasmic mutation in mitochondrial tRNA$^{Phe}$ (m.616T>C). Thus mutations in mitochondrial DNA can cause maternally inherited renal disease, likely mediated through reduced function of mitochondrial tRNA$^{Phe}$.This study was supported by a Wellcome Trust Senior Investigator Award to PHM [19710], by the National Institute for Health Research Cambridge and Imperial Biomedical Research Centres, and a Medical Research Council Clinical Training Fellowship awarded to TMC. The core facilities at CIMR were funded by a Wellcome Trust strategic award [100140]. PFC is a Wellcome Trust Senior Fellow in Clinical Science [101876/Z/13/Z] within the Medical Research Council Mitochondrial Biology Unit [MC_UP_1501/2]. CMG was supported by The Swedish Medical Research Council and The Knut and Alice Wallenberg Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Pharmacotherapeutic intervention in impulsive preschool children: The need for a comprehensive therapeutic approach

Impulsive and aggressive behaviour symptoms often are serious problems in children, even already at preschool age. Thus, effective treatment approaches are requested. In this comment pharmacotherapeutic treatment approaches, first of all risperidone, their limitations and alternative psychotherapeutic approaches are outlined

Incorporating field wind data to improve crop evapotranspiration parameterization in heterogeneous regions

Accurate parameterization of reference evapotranspiration ( ET0) is necessary for optimizing irrigation scheduling and avoiding costs associated with over-irrigation (water expense, loss of water productivity, energy costs, and pollution) or with under-irrigation (crop stress and suboptimal yields or quality). ET0 is often estimated using the FAO-56 method with meteorological data gathered over a reference surface, usually short grass. However, the density of suitable ET0 stations is often low relative to the microclimatic variability of many arid and semi-arid regions, leading to a potentially inaccurate ET0 for irrigation scheduling. In this study, we investigated multiple ET0 products from six meteorological stations, a satellite ET0 product, and integration (merger) of two stations’ data in Southern California, USA. We evaluated ET0 against lysimetric ET observations from two lysimeter systems (weighing and volumetric) and two crops (wine grapes and Jerusalem artichoke) by calculating crop ET ( ETc) using crop coefficients for the lysimetric crops with the different ET0. ETc calculated with ET0 products that incorporated field-specific wind speed had closer agreement with lysimetric ET, with RMSE reduced by 36 and 45% for grape and Jerusalem artichoke, respectively, with on-field anemometer data compared to wind data from the nearest station. The results indicate the potential importance of on-site meteorological sensors for ET0 parameterization; particularly where microclimates are highly variable and/or irrigation water is expensive or scarce