Assessment of progressive collapse in multi-storey buildings

Accepted versio

The Wellbeing In Place Perceptions Scale: Structure, Validity, Reliability and Correlates during COVID times.

The influence of place-based factors on the physical and mental health of residents is well established and acknowledged within the population health approach to addressing health and wellbeing inequalities. The COVID-19 pandemic brought to the fore the issues that global communities face. The current UK policy context of ‘levelling up’ represents these concerns and the need to address them. This research examines perceptions of community wellbeing and its determinants as collected within a city region of the North West Coast of England during COVID restrictions between June and August 2020. The paper aims to establish the structure, construct validity and reliability of a new measure of community wellbeing - the Wellbeing in Place Perceptions Scale. Further, it aims to examine how this measure of community wellbeing correlated with symptoms of common mental health as reported by residents of this relatively disadvantaged city region during this unprecedented time. Results indicate that the WIPPS has a reliable and valid structure, correlating significantly with another widely used measure of sense of community and with the Index of Multiple Deprivation. Its relationship to self-reported common mental distress is also clear. Though in need of replication and longitudinal testing, the findings reported here on this new measure remind us that individual and place-based factors combine to influence wellbeing and that community needs to have an increasingly influential role to sustainably prevent future mental health challenges

Reduction of nucleosome assembly during new DNA synthesis impairs both major pathways of double-strand break repair

Assembly of new chromatin during S phase requires the histone chaperone complexes CAF-1 (Cac2p, Msi1p and Rlf2p) and RCAF (Asf1p plus acetylated histones H3 and H4). Cells lacking CAF-1 and RCAF are hypersensitive to DNA-damaging agents, such as methyl methanesulfonate and camptothecin, suggesting a possible defect in double-strand break (DSB) repair. Assays developed to quantitate repair of defined, cohesive-ended break structures revealed that DSB-induced plasmid:chromosome recombination was reduced ∼10-fold in RCAF/CAF-1 double mutants. Recombination defects were similar with both chromosomal and plasmid targets in vivo, suggesting that inhibitory chromatin structures were not involved. Consistent with these observations, ionizing radiation-induced loss of heterozygosity was abolished in the mutants. Nonhomologous end-joining (NHEJ) repair proficiency and accuracy were intermediate between wild-type levels and those of NHEJ-deficient yku70 and rad50 mutants. The defects in NHEJ, but not homologous recombination, could be rescued by deletion of HMR-a1, a component of the a1/alpha2 transcriptional repressor complex. The findings are consistent with the observation that silent mating loci are partially derepressed. These results demonstrate that defective assembly of nucleosomes during new DNA synthesis compromises each of the known pathways of DSB repair and that the effects can be indirect consequences of changes in silenced chromatin structure

The Effect of Preterm Birth on Thalamic and Cortical Development

Preterm birth is a leading cause of cognitive impairment in childhood and is associated with cerebral gray and white matter abnormalities. Using multimodal image analysis, we tested the hypothesis that altered thalamic development is an important component of preterm brain injury and is associated with other macro- and microstructural alterations. T1- and T2-weighted magnetic resonance images and 15-direction diffusion tensor images were acquired from 71 preterm infants at term-equivalent age. Deformation-based morphometry, Tract-Based Spatial Statistics, and tissue segmentation were combined for a nonsubjective whole-brain survey of the effect of prematurity on regional tissue volume and microstructure. Increasing prematurity was related to volume reduction in the thalamus, hippocampus, orbitofrontal lobe, posterior cingulate cortex, and centrum semiovale. After controlling for prematurity, reduced thalamic volume predicted: lower cortical volume; decreased volume in frontal and temporal lobes, including hippocampus, and to a lesser extent, parietal and occipital lobes; and reduced fractional anisotropy in the corticospinal tracts and corpus callosum. In the thalamus, reduced volume was associated with increased diffusivity. This demonstrates a significant effect of prematurity on thalamic development that is related to abnormalities in allied brain structures. This suggests that preterm delivery disrupts specific aspects of cerebral development, such as the thalamocortical system

Open letter from UK based academic scientists to the secretaries of state for digital, culture, media and sport and for health and social care regarding the need for independent funding for the prevention and treatment of gambling harms

First paragraph: Dear secretaries of state, As leading academic scientists studying gambling behaviours and its harms, we are writing to express our concern about the continuing support shown for the voluntary system of funding treatment, prevention and research in Great Britain. We feel compelled to write to you following the Betting and Gaming Council’s (BGC) recent announcement (17 June 2020) that five of its operators will now allocate the long awaited increase in funding for prevention and treatment, first promised on 2 August 2019, to GambleAware rather than the charity Action Against Gambling Harms. Irrespective of which organisation funds are given to, the BGC’s announcement exemplifies the longstanding weakness of a funding system that allows the gambling industry to regulate the availability and distribution of vital funds to address gambling harms across our communities. As we outline below, the continuance of this arrangement produces several negative effects that undermine the collective effort to reduce harms from gambling. It is also our belief that funds for research into gambling harms and their reduction should primarily be distributed through recognised independent organisations, such as UK Research and Innovation. We hereby urge you, as the secretaries of state with responsibilities for addressing gambling harms, to implement a statutory levy to fund effective prevention and treatment of gambling harms that is free both from industry influence and the perception of industry influence...... [Read more in the article]Additional co-authors: Carolyn Downs, Simon Dymond, Emanuele Fino, Elizabeth Goyder, Cindy Gray, Mark Griffiths, Peter Grindrod, Lee Hogan, Alice Hoon, Richard James, Bev John, Jill Manthorpe, Jim McCambridge, David McDaid, Martin McKee, Sally McManus, Antony Moss, Caroline Norrie, David J Nutt, Jim Orford, Rob Pryce, Gerda Reith, Amanda Roberts, Emmett Roberts, Gareth Roderique-Davies, Jim Rogers, Robert D Rogers, Stephen Sharman, John Strang, Richard Tunney, John Turner, Robert West, David Zendl

Comparison of RBE values of high- LET α-particles for the induction of DNA-DSBs, chromosome aberrations and cell reproductive death

<p>Abstract</p> <p>Background</p> <p>Various types of radiation effects in mammalian cells have been studied with the aim to predict the radiosensitivity of tumours and normal tissues, e.g. DNA double strand breaks (DSB), chromosome aberrations and cell reproductive inactivation. However, variation in correlations with clinical results has reduced general application. An additional type of information is required for the increasing application of high-LET radiation in cancer therapy: the Relative Biological Effectiveness (RBE) for effects in tumours and normal tissues. Relevant information on RBE values might be derived from studies on cells in culture.</p> <p>Methods</p> <p>To evaluate relationships between DNA-DSB, chromosome aberrations and the clinically most relevant effect of cell reproductive death, for ionizing radiations of different LET, dose-effect relationships were determined for the induction of these effects in cultured SW-1573 cells irradiated with gamma-rays from a Cs-137 source or with α-particles from an Am-241 source. RBE values were derived for these effects. Ionizing radiation induced foci (IRIF) of DNA repair related proteins, indicative of DSB, were assessed by counting gamma-H2AX foci. Chromosome aberration frequencies were determined by scoring fragments and translocations using premature chromosome condensation. Cell survival was measured by colony formation assay. Analysis of dose-effect relations was based on the linear-quadratic model.</p> <p>Results</p> <p>Our results show that, although both investigated radiation types induce similar numbers of IRIF per absorbed dose, only a small fraction of the DSB induced by the low-LET gamma-rays result in chromosome rearrangements and cell reproductive death, while this fraction is considerably enhanced for the high-LET alpha-radiation. Calculated RBE values derived for the linear components of dose-effect relations for gamma-H2AX foci, cell reproductive death, chromosome fragments and colour junctions are 1.0 ± 0.3, 14.7 ± 5.1, 15.3 ± 5.9 and 13.3 ± 6.0 respectively.</p> <p>Conclusions</p> <p>These results indicate that RBE values for IRIF (DNA-DSB) induction provide little valid information on other biologically-relevant end points in cells exposed to high-LET radiations. Furthermore, the RBE values for the induction of the two types of chromosome aberrations are similar to those established for cell reproductive death. This suggests that assays of these aberrations might yield relevant information on the biological effectiveness in high-LET radiotherapy.</p

Short-term salivary acetaldehyde increase due to direct exposure to alcoholic beverages as an additional cancer risk factor beyond ethanol metabolism

<p>Abstract</p> <p>Background</p> <p>An increasing body of evidence now implicates acetaldehyde as a major underlying factor for the carcinogenicity of alcoholic beverages and especially for oesophageal and oral cancer. Acetaldehyde associated with alcohol consumption is regarded as 'carcinogenic to humans' (IARC Group 1), with sufficient evidence available for the oesophagus, head and neck as sites of carcinogenicity. At present, research into the mechanistic aspects of acetaldehyde-related oral cancer has been focused on salivary acetaldehyde that is formed either from ethanol metabolism in the epithelia or from microbial oxidation of ethanol by the oral microflora. This study was conducted to evaluate the role of the acetaldehyde that is found as a component of alcoholic beverages as an additional factor in the aetiology of oral cancer.</p> <p>Methods</p> <p>Salivary acetaldehyde levels were determined in the context of sensory analysis of different alcoholic beverages (beer, cider, wine, sherry, vodka, calvados, grape marc spirit, tequila, cherry spirit), without swallowing, to exclude systemic ethanol metabolism.</p> <p>Results</p> <p>The rinsing of the mouth for 30 seconds with an alcoholic beverage is able to increase salivary acetaldehyde above levels previously judged to be carcinogenic in vitro, with levels up to 1000 μM in cases of beverages with extreme acetaldehyde content. In general, the highest salivary acetaldehyde concentration was found in all cases in the saliva 30 sec after using the beverages (average 353 μM). The average concentration then decreased at the 2-min (156 μM), 5-min (76 μM) and 10-min (40 μM) sampling points. The salivary acetaldehyde concentration depends primarily on the direct ingestion of acetaldehyde contained in the beverages at the 30-sec sampling, while the influence of the metabolic formation from ethanol becomes the major factor at the 2-min sampling point.</p> <p>Conclusions</p> <p>This study offers a plausible mechanism to explain the increased risk for oral cancer associated with high acetaldehyde concentrations in certain beverages.</p