922017 research outputs found
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How do we meaningfully involve people in primary care research from marginalised communities?
No full textPhysical activity, sedentary time and breast cancer risk: A Mendelian randomization study
No full textObjectives: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomization (MR) assesses causality by simulating randomized trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.Methods: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130,957 European-ancestry women (69,838 invasive cases), and published UK Biobank data (n=91,105-377,234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.Results: Greater genetically-predicted overall activity was associated with lower breast cancer risk, overall (OR=0.59; 95%CI 0.42-0.83 per-standard deviation [SD; ~8 milligravities acceleration]) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95%CI 0.45-0.87, ≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95%CI 1.07-2.92 per-SD [~7% time spent sedentary]), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger). Conclusion: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.<br/
The long-term influence of Open Access on the scientific and social impact of dental journal articles: An updated analysis
No full textObjectives: To investigate whether dental journal articles that are open access (OA) receive greater citation counts and higher Altmetric Attention Scores (AAS) than articles that are non-OA in the long term.Methods: Eligible dental journal articles published in 2013 were identified via PubMed, and Web of science, Unpaywall and corresponding URLs were manually checked to determine the OA status of each included article 7 years after publication. Citation counts were extracted from Web of Science and Scopus, and AAS was harvested from the Altmetric Explorer. Multivariable general linear regression analyses were performed to investigate the association between OA and citation count, as well as between OA and AAS.Results: Among the 755 included articles, 309 (40.9%) were freely available online. Among the 309 OA articles, articles available from publishers accounted for 64.4% (199/309) of all OA articles, and those available through self-archiving accounted for 56.0% (173/309). According to regression analyses, OA articles had significantly greater citation counts (P = 0.001) and AAS (P < 0.001) than non-OA articles.Conclusions/clinical significance: In the field of dentistry, about 41% of journal articles are OA 7 years after publication, and OA articles available from the publishers are more common than those from authors through self-archiving. OA articles tend to have greater scientific and social impact than non-OA articles in the long term.Keywords: open access; dentistry; bibliometrics; altmetrics; evidence-based dentistry; research wast
Differences in walking football initiation and maintenance influences across respondent characteristics: a cross-sectional survey in 50-75 year -old adults
No full textDespite health benefits gained from physical activity and sport participation, older adults are less likely to be active. This study investigates what influences 50–75-year-olds (N=439) to initiate and maintain walking football, across gender, socioeconomic status, number of health conditions and physical activity level. It also considers relationships between participant characteristics and influences, and intentions to play after a forced break (COVID-19). Results of a UK online cross-sectional survey found those with two or more health conditions rated social influences significantly higher in initiation and maintenance, than participants with no health conditions. Multiple regression analysis found a positive walking football culture and perceived use of maintenance resources contributed significantly to intentions to return to play after COVID-19 restrictions eased. Practitioners should consider providing opportunities for social connection, foster a positive walking football culture, and encourage players to utilise maintenance resources (e.g., scheduling sessions) in older adult walking football sessions.Keywords: behaviour change, soccer, physical activity, survey research, older adults<br/
Towards an atomistic understanding of polymorphism in molecular solids
No full textAbstract Understanding and controlling polymorphism in molecular solids is a major unsolved problem in crystal engineering. While the ability to calculate accurate lattice energies with atomistic modelling provides valuable insight into the associated energy scales, existing methods cannot connect energy differences to the delicate balances of intra- and intermolecular forces that ultimately determine polymorph stability ordering. We report herein a protocol for applying Quantum Chemical Topology (QCT) to study the key intra- and intermolecular interactions in molecular solids, which we use to compare the three known polymorphs of succinic acid including the recently-discovered γ form. QCT provides a rigorous partitioning of the total energy into contributions associated with topological atoms, and a quantitative and chemically intuitive description of the intra- and intermolecular interactions. The newly-proposed Relative Energy Gradient (REG) method ranks atomistic energy terms (steric, electrostatic and exchange) by their importance in constructing the total energy profile for a chemical process. We find that the conformation of the succinic acid molecule is governed by a balance of large and opposing electrostatic interactions, while the H-bond dimerisation is governed by a combination of electrostatics and sterics. In the solids, an atomistic energy balance emerges that governs the contraction, towards the equilibrium geometry, of a molecular cluster representing the bulk crystal. The protocol we put forward is as general as the capabilities of the underlying quantum-mechanical model and it can provide novel perspectives on polymorphism in a wide range of chemical systems.<br/
Stein factors for variance-gamma approximation in the Wasserstein and Kolmogorov distances
No full textWe obtain new bounds for the solution of the variance-gamma (VG) Stein equation that are of the correct form for approximations in terms of the Wasserstein and Kolmorogorov metrics. These bounds hold for all parameters values of the four parameter VG class. As an application we obtain explicit Wasserstein and Kolmogorov distance error bounds in a six moment theorem for VG approximation of double Wiener-It^o integrals
Impact of myocardial fibrosis on cardiovascular structure, function and functional status in heart failure with preserved ejection fraction
No full textMyocardial fibrosis, measured using cardiovascular magnetic resonance extracellular volume (ECV), is associated with adverse outcome in heart failure with preserved ejection fraction but the mechanisms by which myocardial fibrosis exerts this deleterious effect are unclear. We performed mediation analyses of data from the PIROUETTE (The Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial to determine whether myocardial fibrotic regression causes changes in cardiovascular function and functional status following antifibrotic therapy. Regression of myocardial fibrosis correlated with improvements in 6-minute walk test and KCCQ clinical summary score. The only outcome variable that demonstrated a treatment effect was an increase in left ventricular ejection fraction (LVEF). The estimated average causal mediation effects of myocardial ECV, absolute myocardial extracellular matrix volume and absolute myocardial cellular volume on LVEF were 6.1%, 21.5%, and 13.7% respectively, none of which were significant and therefore not mediated by myocardial fibrosis. (PIROUETTE; NCT02932566)
Cluster Model Study into the Catalytic Mechanism of α-Ketoglutarate Biodegradation by the Ethylene-Forming-Enzyme Reveals Structural Differences with Nonheme Iron Hydroxylases
No full textEthylene is an important signaling molecule in plants that triggers the growth of leaves, flowers and fruits. One of the enzymes involved in the biosynthesis of ethylene is the ethylene-forming enzyme (EFE), which is an usual nonheme iron enzyme that biodegrades α-ketoglutarate to three CO2 molecules and ethylene. As the detailed mechanism of EFE and its biosynthesis of ethylene remains controversial and particularly the function of the co-substrate L-arginine, we decided to pursue a density functional theory study on possible pathways of the enzyme leading to its ethylene biosyn-thesis and test many possible pathways and mechanisms. A large active site cluster model of 322 atoms was created that contains all features of the first- and second-coordination sphere of the active site and substrate (α-ketoglutarate) binding pockets. The calculations identify a persuccinate intermediate that triggers a bifurcation pathway in the enzyme and either reacts with a molecule of CO2 to form carbonate or forms a high-valent iron(IV)-oxo species through heterolytic dioxygen bond cleavage. Our studies show that both bifurcation pathways converge to the same intermediate again and can lead to ethylene products, although the two pathways have different kinetics. Interestingly, our studies also show that the iron(IV)-oxo itself can form carbonate and ethylene but through much higher barriers. As a matter of fact, these barriers are higher in energy than typical aliphatic hydroxylation barriers and may not be competitive with arginine hydroxylation. Inclusion of L-arginine co-substrate into the model leads to minor changes in the structure and fold and its charge and dipole moment does not seem to affect the first stage of the catalytic cycle. Moreover, key activation barriers appear little affected by the inclusion of L-arginine into the model. We, therefore, believe that L-arginine’s role is to lock α-ketoglutarate and its products into a tight binding pocket to enable its degradation and to prevent early release of CO2. Our studies show that due to distinct differences in α-ketoglutarate positioning between different arginine activating nonheme iron dioxygenases in the co-substrate binding pocket and its tighter binding in EFE, we predict that the release of CO2 is prevented in the first stage of the oxygen activation mechanism. This enables attack of CO2 on a persuccinate complex to form carbonate products leading to ethylene formation. The work gives suggestions on the engineering of EFE into a hydroxylase or improve the ethylene biosynthesis
A System Identification Procedure Using Compressive Sensing
No full textThe conventional system identification, which is a branch of machine learning, takes advantages of the whole sampling data to identify the system. To identify a system with less sampling density, compressive sensing is applied on system identification, which randomly extracts the sampling data from the system response. Hence a novel identification procedure is proposed using compressive sensing techniques. Then a second order system is selected as the system to be identified using such identification procedure. The identification performances of estimated systems are investigated from the scenario randomly extracting 10% of total sampling data to the scenario using 90% of total sampling data. Each scenario consists of three noise cases with different levels of SNRs to test the robustness of the signal recovery algorithms of compressive sensing. The results show that the system identification using compressive sensing has are relatively high identification performance and is robust to noise when using 30% or more of total sampling data
Understanding the Effect of Water Chemistry and Surface Grinding on the Stress Corrosion Cracking Initiation of Filler Metal 82
No full textStress corrosion cracking (SCC) initiation of specimens extracted from filler metal (FM) 82 weldments was investigated in high purity 288˚C water. Accelerated autoclave slow strain rate tensile (SSRT) tests were conducted at different electrochemical corrosion potentials (ECPs) by varying the water chemistry through adjusting the concentration of dissolved hydrogen and oxygen in the recirculating water. The effect of surface preparation was also investigated. Statistical characterization of SCC initiation results showed that the ground surfaces (using P600 grit) of FM 82 appeared to be more resistant to SCC initiation than the surfaces polished via oxide polishing suspension (OPS). The effect of ECP on the SCC initiation susceptibility is also discussed through statistical characterization of the observed IG cracks