A field trial of a reusable, hollow, cast-in-situ pile

This paper describes the concept and field testing of a hollow, cast-in-situ, rotary bored pile foundation 1200 mm diameter and 30 m deep. The aim of the foundation is to allow large-diameter piles to be constructed using less concrete than in an equivalent conventional solid pile, and with a view to allowing reuse at a later date. Reuse is made possible because the hollow core of the pile allows access for inspection after demolition of an existing structure. The new piles may also allow modification to enhance load capacity by augering through the base and extending their length. In addition, the piles are better suited than conventional piles for use as ‘energy piles' to allow environmentally friendly heating and cooling. The geotechnical performance of the hollow test pile was comparable with that of a conventional solid pile constructed during the same trial. Details of construction are given, including lessons learned

The role of defensive information processing in population-based colorectal cancer screening uptake

BACKGROUND: Internationally, colorectal cancer screening participation remains low despite the availability of home-based testing and numerous interventions to increase uptake. To be effective, interventions should be based on an understanding of what influences individuals’ decisions about screening participation. This study investigates the association of defensive information processing (DIP) with fecal immunochemical test (FIT)–based colorectal cancer screening uptake. METHODS: Regression modeling of data from a cross-sectional survey within a population-based FIT screening program was conducted. The survey included the seven subdomains of the McQueen DIP measure. The primary outcome variable was the uptake status (screening user or nonuser). Multivariable logistic regression was used to estimate the odds ratio (OR) for screening nonuse by DIP (sub)domain score, with adjustments made for sociodemographic and behavioral factors associated with uptake. RESULTS: Higher scores (equating to greater defensiveness) on all DIP domains were significantly associated with lower uptake in the model adjusted for sociodemographic factors. In the model with additional adjustments for behavioral factors, the suppression subdomains of “deny immediacy to be tested” (OR, 0.53; 95% confidence interval [CI], 0.43–0.65; p < .001) and “self-exemption” (OR, 0.80; 95% CI, 0.68–0.96; p < .001) independently predicted nonuse of FIT-based screening. CONCLUSIONS: This is the first study outside the United States that has identified DIP as a barrier to colorectal cancer screening uptake, and it is the first focused specifically on FIT-based screening. The findings suggest that two suppression barriers, namely denying the immediacy to be tested and self-exempting oneself from screening, may be promising targets for future interventions to improve uptake

Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres.

Dominant mutations in TPM3, encoding α-tropomyosin(slow), cause a congenital myopathy characterized by generalized muscle weakness. Here, we used a multidisciplinary approach to investigate the mechanism of muscle dysfunction in 12 TPM3-myopathy patients. We confirm that slow myofibre hypotrophy is a diagnostic hallmark of TPM3-myopathy, and is commonly accompanied by skewing of fibre-type ratios (either slow or fast fibre predominance). Patient muscle contained normal ratios of the three tropomyosin isoforms and normal fibre-type expression of myosins and troponins. Using 2D-PAGE, we demonstrate that mutant α-tropomyosin(slow) was expressed, suggesting muscle dysfunction is due to a dominant-negative effect of mutant protein on muscle contraction. Molecular modelling suggested mutant α-tropomyosin(slow) likely impacts actin–tropomyosin interactions and, indeed, co-sedimentation assays showed reduced binding of mutant α-tropomyosin(slow) (R168C) to filamentous actin. Single fibre contractility studies of patient myofibres revealed marked slow myofibre specific abnormalities. At saturating [Ca(2+)] (pCa 4.5), patient slow fibres produced only 63% of the contractile force produced in control slow fibres and had reduced acto-myosin cross-bridge cycling kinetics. Importantly, due to reduced Ca(2+)-sensitivity, at sub-saturating [Ca(2+)] (pCa 6, levels typically released during in vivo contraction) patient slow fibres produced only 26% of the force generated by control slow fibres. Thus, weakness in TPM3-myopathy patients can be directly attributed to reduced slow fibre force at physiological [Ca(2+)], and impaired acto-myosin cross-bridge cycling kinetics. Fast myofibres are spared; however, they appear to be unable to compensate for slow fibre dysfunction. Abnormal Ca(2+)-sensitivity in TPM3-myopathy patients suggests Ca(2+)-sensitizing drugs may represent a useful treatment for this condition

Systems biology approaches applied to regenerative medicine

Systems biology is the creation of theoretical and mathematical models for the study of biological systems, as an engine for hypothesis generation and to provide context to experimental data. It is underpinned by the collection and analysis of complex datasets from different biological systems, including global gene, RNA, protein and metabolite profiles. Regenerative medicine seeks to replace or repair tissues with compromised function (for example, through injury, deficiency or pathology), in order to improve their functionality. In this paper, we will address the application of systems biology approaches to the study of regenerative medicine, with a particular focus on approaches to study modifications to the genome, transcripts and small RNAs, proteins and metabolites

Exploring common stressors in physical education

Daily stressors, or hassles, refer to the everyday environmental demands that constitute a threat or challenge, or exceed an individual’s biological or psychological capacities (Cohen et al., 1995). Increasing evidence suggests that daily stressors have a significant impact on adolescents’ educational outcomes, for example, performance, wellbeing and negative attitudes toward school, however there is limited research examining the concept of common stressors in PE lessons. As early-adolescence is a developmental period associated with decreased engagement in PE, it is important to identify the environmental stressors that may be associated with increased disengagement. The study comprised 54 secondary school students and six PE teachers from five schools in the English Midlands. Semi-structured focus groups were conducted and a thematic analysis was applied to interview transcripts. Three higher order themes were identified from the data: the social environment, the physical and organisational environment, and the performance environment. Common stressors within the social environment included, interpersonal transactions between peers, differences in effort levels during PE, and working outside one’s peer group. Stressors within the physical and organisational environment consisted of, environmental situations within the changing facilities and the availability of activities. Finally, performance environment stressors included, situations involving the difficult acquisition of physical skills, and situations where physical appearance and physical competencies were exposed. The study extends previous findings by identifying potentially threatening and frustrating, environmental demands that have not been identified in the previous literature. The current study is the first to explore the typical stressors that are experienced by students in PE