Systematic review of topical treatments for fungal infections of the skin and nails of the feet

OBJECTIVE: To identify and synthesise the evidence for efficacy and cost effectiveness of topical treatments for superficial fungal infections of the skin and nails of the feet. DESIGN: Systematic review. INTERVENTIONS: Topical treatments for superficial fungal infections. MAIN OUTCOME MEASURES: Cure confirmed by culture and microscopy for skin and by culture for nails in patients with clinically diagnosed fungal infections. RESULTS: Of 126 trials identified in 121 papers, 72 (57.1%) met the inclusion criteria. Placebo controlled trials yielded pooled relative risks of failure to cure skin infections: allylamines (0.30, 95% confidence interval 0.24 to 0.38); azoles (0.54, 0.42 to 0.68); undecenoic acid (0.28, 0.11 to 0.74); and tolnaftate (0.46, 0.17 to 1.22). Although meta-analysis of 11 trials comparing allylamines and azoles showed a relative risk of failure to cure of 0.88 (0.78 to 0.99) in favour of allylamines, there was evidence of language bias. Seven reports in English favoured allylamines (0.79, 0.69 to 0.91), but four reports in foreign languages showed no difference between the two drugs (1.01, 0.90 to 1.13). Neither trial of nail infections showed significant differences between alternative topical treatments. CONCLUSIONS: Allylamines, azoles, and undecenoic acid were efficacious in placebo controlled trials. There are sufficient comparative trials to judge relative efficacy only between allylamines and azoles. Allylamines cure slightly more infections than azoles but are much more expensive than azoles. The most cost effective strategy is first to treat with azoles or undecenoic acid and to use allylamines only if that fails

Medium range structural order in amorphous tantala spatially resolved with changes to atomic structure by thermal annealing

Amorphous tantala (a-Ta2O5) is an important technological material that has wide ranging applications in electronics, optics and the biomedical industry. It is used as the high refractive index layers in the multi-layer dielectric mirror coatings in the latest generation of gravitational wave interferometers, as well as other precision interferometers. One of the current limitations in sensitivity of gravitational wave detectors is Brownian thermal noise that arises from the tantala mirror coatings. Measurements have shown differences in mechanical loss of the mirror coatings, which is directly related to Brownian thermal noise, in response to thermal annealing. We utilise scanning electron diffraction to perform Fluctuation Electron Microscopy (FEM) on Ion Beam Sputtered (IBS) amorphous tantala coatings, definitively showing an increase in the medium range order (MRO), as determined from the variance between the diffraction patterns in the scan, due to thermal annealing at increasing temperatures. Moreover, we employ Virtual Dark-Field Imaging (VDFi) to spatially resolve the FEM signal, enabling investigation of the persistence of the fragments responsible for the medium range order, as well as the extent of the ordering over nm length scales, and show ordered patches larger than 5 nm in the highest temperature annealed sample. These structural changes directly correlate with the observed changes in mechanical loss.Comment: 22 pages, 5 figure

Childhood IQ and marriage by mid-life: the Scottish Mental Survey 1932 and the Midspan Studies

The study examined the influence of IQ at age 11 years on marital status by mid-adulthood. The combined databases of the Scottish Mental Survey 1932 and the Midspan studies provided data from 883 subjects. With regard to IQ at age 11, there was an interaction between sex and marital status by mid-adulthood (p = 0.0001). Women who had ever-married achieved mean lower childhood IQ scores than women who had never-married (p < 0.001). Conversely, there was a trend for men who had ever-married to achieve higher childhood IQ scores than men who had never-married (p = 0.07). In men, the odds ratio of ever marrying was 1.35 (95% CI 0.98–1.86&#59; p = 0.07) for each standard deviation increase in childhood IQ. Among women, the odds ratio of ever marrying by mid-life was 0.42 (95% CI 0.27–0.64; p = 0.0001) for each standard deviation increase in childhood IQ. Mid-life social class had a similar association with marriage, with women in more professional jobs and men in more manual jobs being less likely to have ever-married by mid-life. Adjustment for the effects of mid-life social class and height on the association between childhood IQ and later marriage, and vice versa, attenuated the effects somewhat, but suggested that IQ, height and social class acted partly independently

Decision support and the effectiveness of web-based delivery and information tailoring for bowel cancer screening : an exploratory study

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females throughout the developed world. Population screening using fecal occult blood tests (FOBTs) facilitates early detection and greater chance of survival, but participation rates are low. We developed a Web-based decision tool to provide information tailored to an individual&rsquo;s decision stage for CRC screening and attitude toward screening utilizing the Preventive Health Model (PHM) and Precaution Adoption Process Model (PAPM) as theoretical frameworks for screening behavior. We describe the practical steps employed in the tool&rsquo;s design and the subsequent conduct of an exploratory study.Objective: To design a decision tool for CRC screening and conduct an exploratory study among average-risk men and women to (1) test the impact of message type (tailored vs non-tailored) and message delivery modality (Web-based vs paper-based) on attitudes toward screening and screening uptake, and (2) investigate the acceptability of the decision tool and relevance of materials.Methods: Participants (n = 100), recruited from a population sample of men and women aged 50-76 residing in urban Adelaide, Australia, were randomly assigned to a control group or one of 4 interventions: (1) Web-based and tailored information, (2) paper-based and tailored information, (3) Web-based and non-tailored (generic) information, or (4) paper-based and non-tailored information. Participation was augmented by snowball recruitment (n = 19). Questionnaires based on PHM variables were administered pre- and post-intervention. Participants were given the opportunity to request an FOBT. Following the intervention, participants discussed the acceptability of the tool.Results: Full data were available for 87.4% (104/119) of participants. Post-intervention, perceived susceptibility scores for individuals receiving tailored information increased from mean 10.6 (SD 2.1) to mean 11.8 (SD 2.2). Scores on self-efficacy increased in the tailored group from mean 11.7 (SD 2.0) to mean 12.6 (SD 1.8). There were significant time x modality x message effects for social influence and salience and coherence, reflecting an increase in these scores for tailored Web-based participants only; social influence scores increased from mean 11.7 (SD 2.6) to mean 14.9 (SD 2.3), and salience and coherence scores increased from mean 16.0 (SD 2.2) to mean 17.7 (SD 2.1). There was no greater influence of modality or message type on movement toward a decision to screen or screening uptake, indicating that neither tailored messages nor a Web modality had superior effect. Overall, participants regarded tailored messages positively, but thought that the Web tool lacked &ldquo;media richness.&rdquo;Conclusions: This exploratory study confirms that tailoring on PHM predictors of CRC screening has the potential to positively address attitudes toward screening. However, tailoring on these variables did not result in significantly increased screening uptake. Future research should consider other possible psychosocial influences. Mode of delivery did not affect outcomes, but as a delivery medium, the Web has economic and logistical advantages over paper.<br /

Characterising the vertical separation of shale-gas source rocks and aquifers across England and Wales (UK)

Shale gas is considered by many to have the potential to provide the UK with greater energy security, economic growth and jobs. However, development of a shale gas industry is highly contentious due to environmental concerns including the risk of groundwater pollution. Evidence suggests that the vertical separation between exploited shale units and aquifers is an important factor in the risk to groundwater from shale gas exploitation. A methodology is presented to assess the vertical separation between different pairs of aquifers and shales that are present across England and Wales. The application of the method is then demonstrated for two of these pairs—the Cretaceous Chalk Group aquifer and the Upper Jurassic Kimmeridge Clay Formation, and the Triassic sandstone aquifer and the Carboniferous Bowland Shale Formation. Challenges in defining what might be considered criteria for ‘safe separation’ between a shale gas formation and an overlying aquifer are discussed, in particular with respect to uncertainties in geological properties, aquifer extents and determination of socially acceptable risk levels. Modelled vertical separations suggest that the risk of aquifer contamination from shale exploration will vary greatly between shale–aquifer pairs and between regions and this will need to be considered carefully as part of the risk assessment and management for any shale gas development

Enhancing the Value of Rural Towns through Ecosystem Interventions:A report for the Local Enterprise Partnerships of Lancashire and Cumbria, to inform ecosystem approaches to place-based policy

This in-depth case study of a Rural Hub Town delivers new evidence for place makers, with insights that have resonance across the 182 Hub Towns in England. As the UK government performs its ‘pivot to towns’ through multiple strands of place-based policy, we need to better understand these critical sites. Hub Towns, as identified by DEFRA and the ONS, play a critical role at the nexus of urban and rural economies and society, and need to be better studied and understood. We break new ground by unpacking the ways in which economy, culture and environment can come together to support thriving communities and economic growth in Hub Towns. Building on a robust core of academic research, we draw together a substantial body of data including 49 interviews with key stakeholders in a single town, along with public engagement data (collected by the District Council) constituting the comments and feedback from 1,663 individuals and organisations. By studying the entire rural town ecosystem, we reveal how Place Value is created. Furthermore, we propose two economic, one cultural, and one environment related intervention that each deliver significant, cascading benefits through the town and its rural hinterland. Taken together, these interventions represent a cohesive approach to Rural Hub Town development, applicable in this site, whilst offering a start point for ecosystem-level research and policy making across the other Hub Towns

Intergenerational social mobility and mid-life status attainment: influences of childhood intelligence, childhood social factors, and education

We examined the influences of childhood social background, childhood cognitive ability, and education on intergenerational social mobility and social status attainment at midlife. The subjects were men born in 1921 and who participated in the Scottish Mental Survey of 1932 and thereafter in the Midspan Collaborative study in Scotland between 1970 and 1973. In logistic regression analyses, childhood cognitive ability and height were associated with upward and downward change from father's social class to participant's social class at mid-life. Education significantly influenced upward social mobility. Number of siblings had no significant effect on social mobility. These effects were also examined after adjusting for the other variables. In structural equation modelling analyses, father's social class and childhood cognitive ability influenced social status attainment at midlife, with education and occupational status in young adulthood as partially mediating factors. It was noteworthy that childhood cognitive ability related more strongly to occupation in midlife than to first occupation. These data add to the relatively few studies that track the process of status attainment in adulthood, they provide information from a new geographical setting, and they contain information from a greater proportion of the lifecourse than do most existing studies

Therapeutic targeting of integrin αvβ6 in breast cancer

BACKGROUND: Integrin ?v?6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of ?v?6 has yet to be elucidated in breast cancer.METHODS: Protein expression of integrin subunit beta6 (?6) was measured in breast cancers by immunohistochemistry (n &gt; 2000) and ITGB6 mRNA expression measured in the Molecular Taxonomy of Breast Cancer International Consortium dataset. Overall survival was assessed using Kaplan Meier curves, and bioinformatics statistical analyses were performed (Cox proportional hazards model, Wald test, and Chi-square test of association). Using antibody (264RAD) blockade and siRNA knockdown of ?6 in breast cell lines, the role of ?v?6 in Human Epidermal Growth Factor Receptor 2 (HER2) biology (expression, proliferation, invasion, growth in vivo) was assessed by flow cytometry, MTT, Transwell invasion, proximity ligation assay, and xenografts (n ? 3), respectively. A student's t-test was used for two variables; three-plus variables used one-way analysis of variance with Bonferroni's Multiple Comparison Test. Xenograft growth was analyzed using linear mixed model analysis, followed by Wald testing and survival, analyzed using the Log-Rank test. All statistical tests were two sided.RESULTS: High expression of either the mRNA or protein for the integrin subunit ?6 was associated with very poor survival (HR = 1.60, 95% CI = 1.19 to 2.15, P = .002) and increased metastases to distant sites. Co-expression of ?6 and HER2 was associated with worse prognosis (HR = 1.97, 95% CI = 1.16 to 3.35, P = .01). Monotherapy with 264RAD or trastuzumab slowed growth of MCF-7/HER2-18 and BT-474 xenografts similarly (P &lt; .001), but combining 264RAD with trastuzumab effectively stopped tumor growth, even in trastuzumab-resistant MCF-7/HER2-18 xenografts.CONCLUSIONS: Targeting ?v?6 with 264RAD alone or in combination with trastuzumab may provide a novel therapy for treating high-risk and trastuzumab-resistant breast cancer patients.<br/