Coastal proximity and mental health among urban adults in England: The moderating effect of household income

This is the final version. Available on open access from Elsevier via the DOI in this recordAfter adjusting for covariates, self-reported general health in England is higher among populations living closer to the coast, and the association is strongest amongst more deprived groups. We explored whether similar findings were present for mental health using cross-sectional data for urban adults in the Health Survey for England (2008-2012, N ≥25,963). For urban adults, living ≤1 km from the coast, in comparison to >50 km, was associated with better mental health as measured by the GHQ12. Stratification by household income revealed this was only amongst the lowest-earning households, and extended to ≤5 km. Our findings support the contention that, for urban adults, coastal settings may help to reduce health inequalities in England.National Institute for Health Research (NIHR)European Union Horizon 202

Neighbourhood blue space, health and wellbeing: The mediating role of different types of physical activity

This is the final version. Available on open access from Elsevier via the DOI in this recordBackground: Evidence suggests that living near blue spaces such as the coast, lakes and rivers may be good for health and wellbeing. Although greater levels of physical activity (PA) may be a potential mechanism, we know little about the types of PA that might account for this. Objectives: To explore the mediating role of: a) ‘watersports’ (e.g. sailing/canoeing); b) ‘on-land outdoor PA’ in natural/mixed settings (e.g. walking/running/cycling); and, c) ‘indoor/other PA’ (e.g. gym/squash) in the relationships between residential blue space availability and health outcomes. Methods: Using data from the Health Survey for England (n = 21,097), we constructed a path model to explore whether weekly volumes of each PA type mediate any of the relationships between residential blue space availability (coastal proximity and presence of freshwater) and self-reported general and mental health, controlling for green space density and a range of socio-economic factors at the individual- and area-level. Results: Supporting predictions, living nearer the coast was associated with better self-reported general and mental health and this was partially mediated by on-land outdoor PA (primarily walking). Watersports were more common among those living within 5kms of the coast, but did not mediate associations between coastal proximity and health. Presence of freshwater in the neighbourhood was associated with better mental health, but this effect was not mediated by PA. Conclusions: Although nearby blue spaces offer potentially easier access to watersports, relatively few individuals in England engage in them and thus they do not account for positive population health associations. Rather, the benefits to health from coastal living seem, at least in part, due to participation in land-based outdoor activities (especially walking). Further research is needed to explore the mechanisms behind the relationship between freshwater presence and mental health.Kone FoundationEuropean CommissionNational Institute for Health Research (NIHR)European Union Horizon 202

How is overall survival assessed in randomised clinical trials in cancer and are subsequent treatment lines considered? A systematic review

Background: Overall survival is the “gold standard” endpoint in cancer clinical trials. It plays a key role in determining the clinical- and cost-effectiveness of a new intervention and whether it is recommended for use in standard of care. The assessment of overall survival usually requires trial participants to be followed up for a long period of time. In this time, they may stop receiving the trial intervention and receive subsequent anti-cancer treatments, which also aim to extend survival, during trial follow-up. This can potentially change the interpretation of overall survival in the context of the clinical trial. This review aimed to determine how overall survival has been assessed in cancer clinical trials and whether subsequent anti-cancer treatments are considered. Methods: Two searches were conducted using MEDLINE within OVID© on the 9th of November 2021. The first sought to identify papers publishing overall survival results from randomised controlled trials in eight reputable journals and the second to identify papers mentioning or considering subsequent treatments. Papers published since 2010 were included if presenting or discussing overall survival in the context of treating cancer. Results: One hundred and thirty-four papers were included. The majority of these were presenting clinical trial results (98, 73%). Of these, 45 (46%) reported overall survival as a (co-) primary endpoint. A lower proportion of papers including overall survival as a (co-) primary endpoint compared to a secondary endpoint were published in recent years. The primary analysis of overall survival varied across the papers. Fifty-nine (60%) mentioned subsequent treatments. Seven papers performed additional analysis, primarily when patients in the control arm received the experimental treatment during trial follow-up (treatment switching). Discussion: Overall survival has steadily moved from being the primary to a secondary endpoint. However, it is still of interest with papers presenting overall survival results with the caveat of subsequent treatments, but little or no investigation into their effect. This review shows that there is a methodological gap for what researchers should do when trial participants receive anti-cancer treatment during trial follow-up. Future research will identify the stakeholder opinions, on how this methodological gap should be addressed

Lysyl oxidases regulate fibrillar collagen remodelling in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with few effective therapeutic options. Structural remodelling of the extracellular matrix [i.e. collagen cross-linking mediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4)] might contribute to disease pathogenesis and represent a therapeutic target. This study aimed to further our understanding of the mechanisms by which LO inhibitors might improve lung fibrosis. Lung tissues from IPF and non-IPF subjects were examined for collagen structure (second harmonic generation imaging) and LO gene (microarray analysis) and protein (immunohistochemistry and western blotting) levels. Functional effects (collagen structure and tissue stiffness using atomic force microscopy) of LO inhibitors on collagen remodelling were examined in two models, collagen hydrogels and decellularized human lung matrices. LOXL1/LOXL2 gene expression and protein levels were increased in IPF versus non-IPF. Increased collagen fibril thickness in IPF versus non-IPF lung tissues correlated with increased LOXL1/LOXL2, and decreased LOX, protein expression. β-Aminoproprionitrile (β-APN; pan-LO inhibitor) but not Compound A (LOXL2-specific inhibitor) interfered with transforming growth factor-β-induced collagen remodelling in both models. The β-APN treatment group was tested further, and β-APN was found to interfere with stiffening in the decellularized matrix model. LOXL1 activity might drive collagen remodelling in IPF lungs. The interrelationship between collagen structural remodelling and LOs is disrupted in IPF lungs. Inhibition of LO activity alleviates fibrosis by limiting fibrillar collagen cross-linking, thereby potentially impeding the formation of a pathological microenvironment in IPF

A High Deuterium Abundance at z=0.7

Of the light elements, the primordial abundance of deuterium, (D/H)_p, provides the most sensitive diagnostic for the cosmological mass density parameter Omega_B. Recent high redshift (D/H) measurements are highly discrepant, although this may reflect observational uncertainties. The larger (D/H) values, which imply a low Omega_B and require the Universe to be dominated by non-baryonic matter (dynamical studies indicate a higher total density parameter), cause problems for galactic chemical evolution models since they have difficulty in reproducing the large decline down to the lower present-day (D/H). Conversely, low (D/H) values imply an Omega_B greater than derived from ^7Li and ^4He abundance measurements, and may require a deuterium abundance evolution that is too low to easily explain. Here we report the first measurement at intermediate redshift, where the observational difficulties are smaller, of a gas cloud with ideal characteristics for this experiment. Our analysis of the z = 0.7010 absorber toward 1718+4807 indicates (D/H) = 2.0 +/- 0.5 x 10^{-4} which is in the high range. This and other independent observations suggests there may be a cosmological inhomogeneity in (D/H)_p of at least a factor of ten.Comment: 6 pages, 1 figur

The effects of meteorological conditions and daylight on nature-based recreational physical activity in England

This is the final version. Available on open access from Elsevier via the DOI in this recordMeteorological conditions affect people’s outdoor physical activity. However, we know of no previous research into how these conditions affect physical activity in different types of natural environments – key settings for recreational physical activity, but ones which are particularly impacted by meteorological conditions. Using responses from four waves (2009–2013) of a survey of leisure visits to natural environments in England (n = 47,613), visit dates and locations were ascribed estimates of energy expenditure (MET-minutes) and assigned meteorological data. We explored relationships between MET-minutes in natural environments (in particular, parks, woodlands, inland waters, and coasts) and the hourly maxima of air temperature and wind speed, levels of rainfall, and daylight hours using generalised additive models. Overall, we found a positive linear relationship between MET-minutes and air temperature; a negative linear relationship with wind speed; no relation with categories of rainfall; and a positive, but non-linear relationship with daylight hours. These same trends were observed for park-based energy expenditure, but differed for visits to other natural environments: only daylight hours were related to energy expenditure at woodlands; wind speed and daylight hours affected energy expenditure at inland waters; and only air temperature was related to energy expenditure at coasts. Natural environments support recreational physical activity under a range of meteorological conditions. However, distinct conditions do differentially affect the amount of energy expenditure accumulated in a range of natural environments. The findings have implications for reducing commonly-reported meteorological barriers to both recreational physical activity and visiting natural environments for leisure, and begin to indicate how recreational energy expenditure in these environments could be affected by future climate change.National Institute for Health Research (NIHR)European Commissio

Salford postgraduate annual research conference (SPARC) 2012 proceedings

These proceedings bring together a selection of papers from the 2012 Salford Postgraduate Annual Research Conference (SPARC). They reflect the breadth and diversity of research interests showcased at the conference, at which over 130 researchers from Salford, the North West and other UK universities presented their work. 21 papers are collated here from the humanities, arts, social sciences, health, engineering, environment and life sciences, built environment and business

Single event upset studies for the ATLAS SCT and pixel optical links

Optical data transmission has been chosen for the ATLAS Pixel and SemiConductor Tracker to deliver both timing and control information to the detector modules and transmit tracking data to the remote computer room. Radiation hardness of individuals optical components and their ASICs drivers have been reported in previous papers. We will report here the Single Event Upset studies carried out on a customised optopackage using a high-energy pion beam. It will be shown that the system is sufficiently robust to SEU at the ATLAS SCT level

Mode Switching Is the Major Mechanism of Ligand Regulation of InsP3 Receptor Calcium Release Channels

The inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) plays a critical role in generation of complex Ca2+ signals in many cell types. In patch clamp recordings of isolated nuclei from insect Sf9 cells, InsP3R channels were consistently detected with regulation by cytoplasmic InsP3 and free Ca2+ concentrations ([Ca2+]i) very similar to that observed for vertebrate InsP3R. Long channel activity durations of the Sf9-InsP3R have now enabled identification of a novel aspect of InsP3R gating: modal gating. Using a novel algorithm to analyze channel modal gating kinetics, InsP3R gating can be separated into three distinct modes: a low activity mode, a fast kinetic mode, and a burst mode with channel open probability (Po) within each mode of 0.007 ± 0.002, 0.24 ± 0.03, and 0.85 ± 0.02, respectively. Channels reside in each mode for long periods (tens of opening and closing events), and transitions between modes can be discerned with high resolution (within two channel opening and closing events). Remarkably, regulation of channel gating by [Ca2+]i and [InsP3] does not substantially alter channel Po within a mode. Instead, [Ca2+]i and [InsP3] affect overall channel Po primarily by changing the relative probability of the channel being in each mode, especially the high and low Po modes. This novel observation therefore reveals modal switching as the major mechanism of physiological regulation of InsP3R channel activity, with implications for the kinetics of Ca2+ release events in cells

How antimalarial drug resistance affects post-treatment prophylaxis

Slowly eliminated antimalarial drugs suppress malaria reinfections for a period of time determined by the dose, the pharmacokinetic properties of the drug, and the susceptibility of the infecting parasites. This effect is called post-treatment prophylaxis (PTP). The clinical benefits of preventing recrudescence (reflecting treatment efficacy) compared with preventing reinfection (reflecting PTP) need further assessment. Antimalarial drug resistance shortens PTP. While blood concentrations are in the terminal elimination phase, the degree of shortening may be estimated from measurements of in-vitro susceptibility and the terminal elimination half-life. More information is needed on PTP following intermittent preventive treatments, and on the relationship between the duration of PTP and immunity, so that policy recommendations can have a firmer evidence base