The teaching of recent and violent conflicts as challenges for history education

This paper has been written with the support of Projects EDU2015-65088P from the DGICYT (Ministry of Education, Spain) and also the Project PICT2012-1594 from the ANPCYT (Argentina) coordinated by the autho

Transitory electrochemical masking for precision jet processing techniques

Electrochemical jet processing techniques provide an efficient method for large area surface structuring and micro-milling, where the metallurgy of the near-surface is assured and not adversely affected by thermal loading. Here, doped electrolytes are specifically developed for jet techniques to exploit the Gaussian energy distribution as found in energy beam processes. This allows up to 26% reduction in dissolution kerf and enhancements of the defined precision metric of up to 284% when compared to standard electrolytes. This is achieved through the filtering of low energy at discrete points within the energy distribution curve. Two fundamental mechanisms of current filtering and refresh rate are proposed and investigated in order to underpin the performance enhancements found using this methodology. This study aims to demonstrate that a step change in process fidelity and flexibility can be achieved through optimisation of the electrochemistry specific to jet processes

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Inverse association of NSAID use and ovarian cancer in relation to oral contraceptive use and parity

We examined the association between non-steroidal anti-inflammatory drug (NSAID) use and ovarian cancer by potential effect modifiers, parity and oral contraceptive use, in a population-based case–control study conducted in Wisconsin and Massachusetts. Women reported prior use of NSAIDs and information on risk factors in a telephone interview. A total of 487 invasive ovarian cancer cases and 2653 control women aged 20–74 years were included in the analysis. After adjustment for age, state of residence and other covariates, ever use of NSAIDs was inversely associated with ovarian cancer in never users of oral contraceptives (odds ratio (OR)=0.58, 95% confidence interval (CI) 0.42–0.80) but not for ever users (OR=0.98, 95% CI 0.71–1.35) (P-interaction=0.03). A reduced risk with NSAID use was also noted in nulliparous women (OR=0.47, 95% CI 0.27–0.82) but not among parous women (OR=0.81, 95% CI 0.64–1.04) (P-interaction=0.05). These results suggest that use of NSAIDs were beneficial to women at greatest risk for ovarian cancer

The association between Toll-like receptor 2 single-nucleotide polymorphisms and hepatocellular carcinoma susceptibility

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLR) are key innate immunity receptors participating in an immune response. Growing evidence suggests that mutations of TLR2/TLR9 gene are associated with the progress of cancers. The present study aimed to investigate the temporal relationship of single nucleotide polymorphisms (SNP) of TLR2/TLR9 and the risk of hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>In this single center-based case-control study, SNaPshot method was used to genotype sequence variants of TLR2 and TLR9 in 211 patients with HCC and 232 subjects as controls.</p> <p>Results</p> <p>Two synonymous SNPs in the exon of TLR2 were closely associated with risk of HCC. Compared with those carrying wild-type homozygous genotypes (T/T), risk of HCC decreased significantly in individuals carrying the heterozygous genotypes (C/T) of the rs3804099 (adjusted odds ratio (OR), 0.493, 95% CI 0.331 - 0.736, <it>P </it>< 0.01) and rs3804100 (adjusted OR, 0.509, 95% CI 0.342 - 0.759, <it>P </it>< 0.01). There was no significant association found in two TLR9 SNPs concerning the risk of HCC. The haplotype TT for TLR2 was associated significantly with the decreased risk of HCC (OR 0.524, 95% CI 0.394 - 0.697, <it>P </it>= 0.000). Inversely, the risk of HCC increased significantly in patients with the haplotype CC (OR 2.743, 95% CI 1.915 - 3.930, <it>P </it>= 0.000).</p> <p>Conclusions</p> <p>These results suggested that TLR2 rs3804099 C/T and rs3804100 C/T polymorphisms were closely associated with HCC. In addition, the haplotypes composed of these two TLR2 synonymous SNPs have stronger effects on the susceptibility of HCC.</p

Childhood bullying, paranoid thinking, and the misappraisal of social threat: trouble at school

Background:Experiences of bullying predict the development of paranoia in school-age adolescents. While many instances of psychotic phenomena are transitory, maintained victimization can lead to increasingly distressing paranoid thinking. Furthermore, paranoid thinkers perceive threat in neutral social stimuli and are vigilant for environmental risk. Aims:The present paper investigated the association between different forms of bullying and paranoid thinking, and the extent to which school-age paranoid thinkers overestimate threat in interpersonal situations. Methods: Two hundred and thirty participants, aged between eleven and fourteen, were recruited from one secondary school in the UK. Participants completed a series of questionnaires hosted on the Bristol Online Survey tool. All data were collected in a classroom setting in quiet and standardized conditions. Results: A significant and positive relationship was found between experiences of bullying and paranoid thinking: greater severity of bullying predicted more distressing paranoid thinking. Further, paranoid thinking mediated the relationship between bullying and overestimation of threat in neutral social stimuli. Conclusion: Exposure to bullying is associated with distressing paranoid thinking and subsequent misappraisal of threat. As paranoid thinkers experience real and overestimated threat, the phenomena may persist

Catechol-O-Methyltransferase Val158Met Polymorphism Associates with Individual Differences in Sleep Physiologic Responses to Chronic Sleep Loss

Val158Met polymorphism was a novel marker in healthy adults of differential vulnerability to chronic partial sleep deprivation (PSD), a condition distinct from total sleep loss and one experienced by millions on a daily and persistent basis. allelic frequencies were higher in whites than African Americans.-related treatment responses and risk factors for symptom exacerbation

Prediction of chronic disability in work-related musculoskeletal disorders: a prospective, population-based study

BACKGROUND: Disability associated with work-related musculoskeletal disorders is an increasingly serious societal problem. Although most injured workers return quickly to work, a substantial number do not. The costs of chronic disability to the injured worker, his or her family, employers, and society are enormous. A means of accurate early identification of injured workers at risk for chronic disability could enable these individuals to be targeted for early intervention to promote return to work and normal functioning. The purpose of this study is to develop statistical models that accurately predict chronic work disability from data obtained from administrative databases and worker interviews soon after a work injury. Based on these models, we will develop a brief instrument that could be administered in medical or workers' compensation settings to screen injured workers for chronic disability risk. METHODS: This is a population-based, prospective study. The study population consists of workers who file claims for work-related back injuries or carpal tunnel syndrome (CTS) in Washington State. The Washington State Department of Labor and Industries claims database is reviewed weekly to identify workers with new claims for work-related back injuries and CTS, and these workers are telephoned and invited to participate. Workers who enroll complete a computer-assisted telephone interview at baseline and one year later. The baseline interview assesses sociodemographic, employment-related, biomedical/health care, legal, and psychosocial risk factors. The follow-up interview assesses pain, disability, and work status. The primary outcome is duration of work disability over the year after claim submission, as assessed by administrative data. Secondary outcomes include work disability status at one year, as assessed by both self-report and work disability compensation status (administrative records). A sample size of 1,800 workers with back injuries and 1,200 with CTS will provide adequate statistical power (0.96 for low back and 0.85 for CTS) to predict disability with an alpha of .05 (two-sided) and a hazard ratio of 1.2. Proportional hazards regression models will be constructed to determine the best combination of predictors of work disability duration at one year. Regression models will also be developed for the secondary outcomes