The MRC trial of assessment and management of older people in the community: objectives, design and interventions [ISRCTN23494848].

BACKGROUND: The benefit of regular multidimensional assessment of older people remains controversial. The majority of trials have been too small to produce adequate evidence to inform policy. Despite the lack of a firm evidence base, UK primary care practitioners (general practitioners) are required to offer an annual health check to patients aged 75 years and over. DESIGN: Cluster-randomised factorial trial in primary care comparing a package of assessments (i) universal versus targeted assessment and (ii) management by the primary care team (PC) or a multidisciplinary geriatric assessment team (GM). The unit of randomization is the general practice. METHODS: Older people aged 75 and over eligible for the over 75s health check and excluding those in nursing homes or terminally ill were invited to participate. All participants receive a brief assessment covering all areas of the over 75s check. In the universal arm all participants also receive a detailed health and social assessment by a study nurse while in the targeted arm only participants with a pre-determined number and range of problems at the brief assessment go on to have the detailed assessment. The study nurse follows a standard protocol based on results and responses in the detailed assessment to make referrals to (i) the randomised management team (PC or GM) (ii) other medical services, health care workers or agencies (iii) emergency referrals to the GP. The main outcomes are mortality, hospital and institutional admissions and quality of life. 106 practices and 33,000 older people have been recruited to the trial

A Trade-Off between Somatosensory and Auditory Related Brain Activity during Object Naming But Not Reading.

The parietal operculum, particularly the cytoarchitectonic area OP1 of the secondary somatosensory area (SII), is involved in somatosensory feedback. Using fMRI with 58 human subjects, we investigated task-dependent differences in SII/OP1 activity during three familiar speech production tasks: object naming, reading and repeatedly saying "1-2-3." Bilateral SII/OP1 was significantly suppressed (relative to rest) during object naming, to a lesser extent when repeatedly saying "1-2-3" and not at all during reading. These results cannot be explained by task difficulty but the contrasting difference between naming and reading illustrates how the demands on somatosensory activity change with task, even when motor output (i.e., production of object names) is matched. To investigate what determined SII/OP1 deactivation during object naming, we searched the whole brain for areas where activity increased as that in SII/OP1 decreased. This across subject covariance analysis revealed a region in the right superior temporal sulcus (STS) that lies within the auditory cortex, and is activated by auditory feedback during speech production. The tradeoff between activity in SII/OP1 and STS was not observed during reading, which showed significantly more activation than naming in both SII/OP1 and STS bilaterally. These findings suggest that, although object naming is more error prone than reading, subjects can afford to rely more or less on somatosensory or auditory feedback during naming. In contrast, fast and efficient error-free reading places more consistent demands on both types of feedback, perhaps because of the potential for increased competition between lexical and sublexical codes at the articulatory level

DNMTs are required for delayed genome instability caused by radiation

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited - Copyright @ 2012 Landes Bioscience.The ability of ionizing radiation to initiate genomic instability has been harnessed in the clinic where the localized delivery of controlled doses of radiation is used to induce cell death in tumor cells. Though very effective as a therapy, tumor relapse can occur in vivo and its appearance has been attributed to the radio-resistance of cells with stem cell-like features. The molecular mechanisms underlying these phenomena are unclear but there is evidence suggesting an inverse correlation between radiation-induced genomic instability and global hypomethylation. To further investigate the relationship between DNA hypomethylation, radiosensitivity and genomic stability in stem-like cells we have studied mouse embryonic stem cells containing differing levels of DNA methylation due to the presence or absence of DNA methyltransferases. Unexpectedly, we found that global levels of methylation do not determine radiosensitivity. In particular, radiation-induced delayed genomic instability was observed at the Hprt gene locus only in wild-type cells. Furthermore, absence of Dnmt1 resulted in a 10-fold increase in de novo Hprt mutation rate, which was unaltered by radiation. Our data indicate that functional DNMTs are required for radiation-induced genomic instability, and that individual DNMTs play distinct roles in genome stability. We propose that DNMTS may contribute to the acquirement of radio-resistance in stem-like cells.This study is funded by NOTE, BBSRC and the Royal Society Dorothy Hodgkin Research Fellowship

Development of a reliable and reproducible phantom manufacturing method using silica microspheres in silicone

Optically scattering phantoms composed of silica microspheres embedded in an optically clear silicone matrix were manufactured using a previously developed method. Multiple problems, such as sphere aggregation, adsorption to the cast, and silicone shrinkage, were, however, frequently encountered. Solutions to these problems were developed and an improved method, incorporating these solutions, is presented. The improved method offers excellent reliability and reproducibility for creating phantoms with uniform scattering coefficient. We also present evidence of decreased sphere aggregation

Discrete element models of soil-geogrid interaction

Geogrids are the geosynthetics of choice for soil reinforcement applications. To evaluate the efficiency of geogrid reinforcement, several methods are used including field tests, laboratory tests and numerical modeling. Field studies consume long period of time and conducting these investigations may become highly expensive because of the need for real-size structures. Laboratory studies present also significant difficulties: large-size testing machines are required to accommodate realistic geogrid designs. The discrete element method (DEM) may be used as a complementary tool to extend physical testing databases at lower cost. Discrete element models do not require complex constitutive formulations and may be fed with particle scale data (size, strength, shape) thus reducing the number offree calibration parameters. Discrete element models also are well suited to problems in which large displacements are present, such as geogrid pullout. This paper reviews the different approaches followed to model soil-geogrid interaction in DEM and presents preliminary results from pull-out conditions.Peer ReviewedPostprint (author's final draft

Expansive cement couplers - a means of pre-tensioning fibre reinforced plastic tendons

Fibre reinforced plastics describes a group of materials composed of inorganic or organic fibres embedded in a resin matrix. frps are strong, non-magnetic, light-weight and for the most part, non-corrodable. There is great scope for the use of frps as concrete reinforcement and the high strength of the materials is conducive to prestressed applications. However, finding a suitable method of anchoring the tendons without inducing stress concentrations in the fibres has been identified as a problem. The current paper investigates the potential for the use of expansive cement couplers as a means of pretensioning frp tendons. An experimental study was carried out on couplers to join steel reinforcing bars and then extended to include the coupling of frp materials to steel prestress wire

Psychological, psychophysical, and ergogenic effects of music in swimming

OBJECTIVES: Existing work using dry land exercise-related activities has shown that the careful application of music can lead to a range of benefits that include enhanced affect, lower perceived exertion, greater energy efficiency, and faster time trial performances. The purpose of this study was to assess the psychological, psychophysical, and ergogenic effects of asynchronous music in swimming using a mixed-methods approach. DESIGN: A mixed-model design was employed wherein there was a within-subjects factor (two experimental conditions and a control) and a between-subjects factor (gender). The experimental component of the study was supplemented by qualitative data that were analysed using inductive content analysis. METHODS: Twenty six participants (Mage = 20.0 years, age range: 18–23 years) underwent a period of habituation with Speedo Aquabeat MP3 players prior to the experimental phase. They were then administered two experimental trials (motivational and oudeterous music at 130 bpm) and a no-music control, during which they engaged in a 200-m freestyle swimming time trial. RESULTS: Participants swam significantly faster when exposed to either music condition relative to control (p = .022, ηp2=.18). Moreover, the music conditions were associated with higher state motivation (p = .016, ηp2=.15) and more dissociative thoughts (p = .014, ηp2=.16). CONCLUSIONS: Findings supported the hypothesis that the use of asynchronous music during a high-intensity task can have an ergogenic effect; this was in the order of 2% when averaged out across the two experimental conditions. The use of music, regardless of its motivational qualities, resulted in higher self-reported motivation as well as more dissociative thoughts

Numerical evaluation of shear strength of CFS shear wall panels for different height-to-width ratios

This paper presents a numerical evaluation of the shear strength of Cold Formed Steel Shear Wall Panels (CFS-SWPs) having 1.33:1 and 1:1 height-to-width aspect ratios with 0.76 mm steel plate sheathing thickness and 1:4,  1.33:1 and 1:1  height-to-width aspect ratios with 0.46 mm steel plate sheathing thickness, which are not provided by AISI S400. For this purpose, shell finite element (FE) models, validated with test results, are completed in ABAQUS v2018 with nonlinear geometry, material and connection. A good agreement is achieved between experimental and numerical results in terms of shear strength-lateral displacement and failure modes.It is concluded that, for a fixed height-to-width aspect ratio, the shear strength of SWPs having different screws spacing varying from 50.4 mm up to 152.4 can be assessed by interpolation using this FE method. However, by interloping the shear strength from 4:1 to 1:1 height-to-width aspect ratio, the shear strength can be underestimated; hence, it is more economical for practicing engineers to use the shear strength assessed by this proposed FE method for 1.33:1 and 1:1 height-to-width aspect ratios. Moreover, the effect of the sheathing thickness having 0.46 mm is evaluated and proposed as it lacks in data provided by the code (i.e., AISI S400)

Systemic Therapy for Hereditary Breast Cancers.

Approximately 5% to 10% of all breast cancers are hereditary; many of which are caused by pathogenic variants in genes required for homologous recombination, including BRCA1 and BRCA2. Here we discuss systemic treatment for such breast cancers, including approved chemotherapeutic approaches and also targeted treatment approaches using poly-(ADP ribose) polymerase inhibitors. We also discuss experimental approaches to treating hereditary breast cancer, including new small molecule DNA repair inhibitors and also immunomodulatory agents. Finally, we discuss how drug resistance emerges in patients with hereditary breast cancer, how this might be delayed or prevented, and how biomarker-adapted treatment is molding the future management of hereditary breast cancer