First-principles calculation of the elastic dipole tensor of a point defect: Application to hydrogen in α-zirconium

The elastic dipole tensor is a fundamental quantity relating the elastic field and atomic structure of a point defect. We review three methods in the literature to calculate the dipole tensor and apply them to hydrogen in α -zirconium using density functional theory (DFT). The results are compared with the dipole tensor deduced from earlier experimental measurements of the λ tensor for hydrogen in α -zirconium. There are significant errors with all three methods. We show that calculation of the λ tensor, in combination with experimentally measured elastic constants and lattice parameters, yields dipole tensor components that differ from experimental values by only 10%–20%. There is evidence to suggest that current state-of-the-art DFT calculations underestimate bonding between hydrogen and α -zirconium

Improving Search through A3C Reinforcement Learning based Conversational Agent

We develop a reinforcement learning based search assistant which can assist users through a set of actions and sequence of interactions to enable them realize their intent. Our approach caters to subjective search where the user is seeking digital assets such as images which is fundamentally different from the tasks which have objective and limited search modalities. Labeled conversational data is generally not available in such search tasks and training the agent through human interactions can be time consuming. We propose a stochastic virtual user which impersonates a real user and can be used to sample user behavior efficiently to train the agent which accelerates the bootstrapping of the agent. We develop A3C algorithm based context preserving architecture which enables the agent to provide contextual assistance to the user. We compare the A3C agent with Q-learning and evaluate its performance on average rewards and state values it obtains with the virtual user in validation episodes. Our experiments show that the agent learns to achieve higher rewards and better states.Comment: 17 pages, 7 figure

Augmenting the 6-3-5 method with design information

This paper describes a comparative study between the 6-3-5 Method and the ICR Grid. The ICR Grid is an evolved variant of 6-3-5 intended to better integrate information into the concept generation process. Unlike a conventional 6-3-5 process where participants continually sketch concepts, using the ICR Grid (the name derived from its Inform, Create, Reflect activities and structured, grid-like output) participants are additionally required to undertake information search tasks, use specific information items for concept development, and reflect on the merit of concepts as the session progresses. The results indicate that although the quantity of concepts was lower, the use of information had a positive effect in a number of areas, principally the quality and variety of output. Although grounded in the area of product development, this research is applicable to any organisation undertaking idea generation and problem solving. As well as providing insights on the transference of information to concepts, it holds additional interest for studies on the composition and use of digital libraries

Single Gene Deletions of Orexin, Leptin, Neuropeptide Y, and Ghrelin Do Not Appreciably Alter Food Anticipatory Activity in Mice

Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA

Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

Associations between indoor temperature, self-rated health and socioeconomic position in a cross-sectional study of adults in England

Objective: Excess winter deaths are a major public health concern in England and Wales, with an average of 20 000 deaths per year since 2010. Feeling cold at home during winter is associated with reporting poor general health; cold and damp homes have greater prevalence in lower socioeconomic groups. Overheating in the summer also has adverse health consequences. This study evaluates the association between indoor temperature and general health and the extent to which this is affected by socioeconomic and household factors. / Design: Cross-sectional study. / Setting: England. / Participants: Secondary data of 74 736 individuals living in England that took part in the Health Survey for England (HSE) between 2003 and 2014. The HSE is an annual household survey which uses multilevel stratification to select a new, nationally representative sample each year. The study sample comprised adults who had a nurse visit; the analytical sample was adults who had observations for indoor temperature and self-rated health. / Results: Using both logistic and linear regression models to examine indoor temperature and health status, adjusting for socioeconomic and housing factors, the study found an association between poor health and higher indoor temperatures. Each one degree increase in indoor temperature was associated with a 1.4% (95% CI 0.5% to 2.3%) increase in the odds of poor health. After adjusting for income, education, employment type, household size and home ownership, the OR of poor health for each degree temperature rise increased by 19%, to a 1.7% (95% CI 0.7% to 2.6%) increase in odds of poor health with each degree temperature rise. / Conclusion: People with worse self-reported health had higher indoor temperatures after adjusting for household factors. People with worse health may have chosen to maintain warmer environments or been advised to. However, other latent factors, such as housing type and energy performance could have an effect

Associations between indoor temperature, self-rated health and socioeconomic position in a cross-sectional study of adults in England

Objective: Excess winter deaths are a major public health concern in England and Wales, with an average of 20 000 deaths per year since 2010. Feeling cold at home during winter is associated with reporting poor general health; cold and damp homes have greater prevalence in lower socioeconomic groups. Overheating in the summer also has adverse health consequences. This study evaluates the association between indoor temperature and general health and the extent to which this is affected by socioeconomic and household factors. / Design: Cross-sectional study. / Setting: England. / Participants: Secondary data of 74 736 individuals living in England that took part in the Health Survey for England (HSE) between 2003 and 2014. The HSE is an annual household survey which uses multilevel stratification to select a new, nationally representative sample each year. The study sample comprised adults who had a nurse visit; the analytical sample was adults who had observations for indoor temperature and self-rated health. / Results: Using both logistic and linear regression models to examine indoor temperature and health status, adjusting for socioeconomic and housing factors, the study found an association between poor health and higher indoor temperatures. Each one degree increase in indoor temperature was associated with a 1.4% (95% CI 0.5% to 2.3%) increase in the odds of poor health. After adjusting for income, education, employment type, household size and home ownership, the OR of poor health for each degree temperature rise increased by 19%, to a 1.7% (95% CI 0.7% to 2.6%) increase in odds of poor health with each degree temperature rise. / Conclusion: People with worse self-reported health had higher indoor temperatures after adjusting for household factors. People with worse health may have chosen to maintain warmer environments or been advised to. However, other latent factors, such as housing type and energy performance could have an effect