First-principles theory of the luminescence lineshape for the triplet transition in diamond NV centre

In this work we present theoretical calculations and analysis of the vibronic structure of the spin-triplet optical transition in diamond nitrogen-vacancy centres. The electronic structure of the defect is described using accurate first-principles methods based on hybrid functionals. We devise a computational methodology to determine the coupling between electrons and phonons during an optical transition in the dilute limit. As a result, our approach yields a smooth spectral function of electron-phonon coupling and includes both quasi-localized and bulk phonons on equal footings. The luminescence lineshape is determined via the generating function approach. We obtain a highly accurate description of the luminescence band, including all key parameters such as the Huang-Rhys factor, the Debye-Waller factor, and the frequency of the dominant phonon mode. More importantly, our work provides insight into the vibrational structure of nitrogen vacancy centres, in particular the role of local modes and vibrational resonances. In particular, we find that the pronounced mode at 65 meV is a vibrational resonance, and we quantify localization properties of this mode. These excellent results for the benchmark diamond nitrogen-vacancy centre provide confidence that the procedure can be applied to other defects, including alternative systems that are being considered for applications in quantum information processing

A global fit of top quark effective theory to data

In this paper we present a global fit of beyond the Standard Model (BSM) dimension six operators relevant to the top quark sector to currently available data. Experimental measurements include parton-level top-pair and single top production from the LHC and the Tevatron. Higher order QCD corrections are modelled using differential and global K-factors, and we use novel fast-fitting techniques developed in the context of Monte Carlo event generator tuning to perform the fit. This allows us to provide new, fully correlated and model-independent bounds on new physics effects in the top sector from the most current direct hadron-collider measurements in light of the involved theoretical and experimental systematics. As a by-product, our analysis constitutes a proof-of-principle that fast fitting of theory to data is possible in the top quark sector, and paves the way for a more detailed analysis including top quark decays, detector corrections and precision observables.Comment: Additional references and preprint code added. Minor error in generation of plots fixed, no conclusions affecte

Results from TopFitter

We discuss a global fit of top quark BSM couplings, phrased in the model-independent language of higher-dimensional effective operators, to the currently available data from the LHC and Tevatron. We examine the interplay between inclusive and differential measurements, and the complementarity of LHC and Tevatron results. We conclude with a discussion of projections for improvement over LHC Run II.Comment: 5 pages, 4 figures, proceedings of the 9th International Workshop on the CKM Unitarity Triangle, 28 November - 3 December 2016, Tata Institute for Fundamental Research (TIFR), Mumbai, Indi

A Systematic Review and Meta-Analysis of Crossover Studies Comparing Physiological, Perceptual and Performance Measures Between Treadmill and Overground Running

Background Treadmills are routinely used to assess running performance and training parameters related to physiological or perceived effort. These measurements are presumed to replicate overground running but there has been no systematic review comparing performance, physiology and perceived effort between treadmill and overground running. Objective The objective of this systematic review was to compare physiological, perceptual and performance measures between treadmill and overground running in healthy adults.MethodsAMED (Allied and Contemporary Medicine), CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, SCOPUS, SPORTDiscus and Web of Science databases were searched from inception until May 2018. Included studies used a crossover study design to compare physiological (oxygen uptake [VO-2], heart rate [HR], blood lactate concentration [La]), perceptual (rating of perceived exertion [RPE] and preferred speed) or running endurance and sprint performance (i.e. time trial duration or sprint speed) outcomes between treadmill (motorised or non-motorised) and overground running. Physiological outcomes were considered across submaximal, near-maximal and maximal running intensity subgroups. Meta-analyses were used to determine mean difference (MD) or standardised MD (SMD) 95% confidence intervals. Results Thirty-four studies were included. Twelve studies used a 1% grade for the treadmill condition and three used grades >1%. Similar (V) over dotO(2) but lower La occurred during submaximal motorised treadmill running at 0% ((V) over dot O-2 MD: -0.55 0.93mL/kg/min; La MD: -1.26 +/- 0.71mmol/L) and 1% ((V) over dotO(2) MD: 0.37 +/- 1.12mL/kg/min; La MD: -0.52 +/- 0.50mmol/L) grade than during overground running. HR and RPE during motorised treadmill running were higher at faster submaximal speeds and lower at slower submaximal speeds than during overground running. (V) over dotO(2) (MD: -1.25 +/- 2.09mL/kg/min) and La (MD: -0.54 +/- 0.63mmol/L) tended to be lower, but HR (MD: 0 +/- 1bpm), and RPE (MD: -0.4 +/- 2.0units [6-20 scale]) were similar during near-maximal motorised treadmill running to during overground running. Maximal motorised treadmill running caused similar (V) over dotO(2) (MD: 0.78 +/- 1.55mL/kg/min) and HR (MD: -1 +/- 2bpm) to overground running. Endurance performance was poorer (SMD: -0.50 +/- 0.36) on a motorised treadmill than overground but sprint performance varied considerably and was not significantly different (MD: -1.4 +/- 5.8km/h). Conclusions Some, but not all, variables differ between treadmill and overground running, and may be dependent on the running speed at which they are assessed. Protocol registration (PROSPERO International Prospective Register of Systematic Reviews)

Beyond synthesis: Augmenting systematic review procedures with practical principles to optimise impact and uptake in educational policy and practice

Whilst systematic reviews, meta-analyses and other forms of synthesis are often constructed as sitting proudly atop the hierarchy of research evidence, their limited impact on educational policy and practice has been criticised. In this article, we analyse why systematic reviews do not benefit users of evidence more consistently and suggest how review teams can optimise the impact of their work. We introduce the Beyond Synthesis Impact Chain (BSIC), an integrated framework of practical strategies for enhancing the impact of systematic reviews. Focusing upon examples from health professions education, we propose that review teams can optimise the impact of their work by employing strategies that 1) focus on practical problems and mindful planning in collaboration with users; 2) ensure reviews are relevant and syntheses reflexively account for users’ needs; and 3) couch reports in terms that resonate with users’ needs and increase access through targeted and strategic dissemination. We argue that combining practical principles with robust and transparent procedures can purposefully account for impact, and foster the uptake of review evidence in educational policy and practice. For systematic review teams, this paper offers strategies for enhancing the practical utility and potential impact of systematic reviews and other forms of synthesis

Is Motorized Treadmill Running Biomechanically Comparable to Overground Running? A Systematic Review and Meta-Analysis of Cross-Over Studies

Background Treadmills are often used in research, clinical practice, and training. Biomechanical investigations comparing treadmill and overground running report inconsistent findings. Objective This study aimed at comparing biomechanical outcomes between motorized treadmill and overground running. Methods Four databases were searched until June 2019. Crossover design studies comparing lower limb biomechanics during non-inclined, non-cushioned, quasi-constant-velocity motorized treadmill running with overground running in healthy humans (18-65 years) and written in English were included. Meta-analyses and meta-regressions were performed where possible. Results 33 studies (n = 494 participants) were included. Most outcomes did not differ between running conditions. However, during treadmill running, sagittal foot-ground angle at footstrike (mean difference (MD) − 9.8° [95% confidence interval: − 13.1 to − 6.6]; low GRADE evidence), knee flexion range of motion from footstrike to peak during stance (MD 6.3° [4.5 to 8.2]; low), vertical displacement center of mass/pelvis (MD − 1.5 cm [− 2.7 to − 0.8]; low), and peak propulsive force (MD − 0.04 body weights [− 0.06 to − 0.02]; very low) were lower, while contact time (MD 5.0 ms [0.5 to 9.5]; low), knee flexion at footstrike (MD − 2.3° [− 3.6 to − 1.1]; low), and ankle sagittal plane internal joint moment (MD − 0.4 Nm/kg [− 0.7 to − 0.2]; low) were longer/higher, when pooled across overground surfaces. Conflicting findings were reported for amplitude of muscle activity. Conclusions Spatiotemporal, kinematic, kinetic, muscle activity, and muscle-tendon outcome measures are largely comparable between motorized treadmill and overground running. Considerations should, however, particularly be given to sagittal plane kinematic differences at footstrike when extrapolating treadmill running biomechanics to overground running

Analysis of host response to bacterial infection using error model based gene expression microarray experiments

A key step in the analysis of microarray data is the selection of genes that are differentially expressed. Ideally, such experiments should be properly replicated in order to infer both technical and biological variability, and the data should be subjected to rigorous hypothesis tests to identify the differentially expressed genes. However, in microarray experiments involving the analysis of very large numbers of biological samples, replication is not always practical. Therefore, there is a need for a method to select differentially expressed genes in a rational way from insufficiently replicated data. In this paper, we describe a simple method that uses bootstrapping to generate an error model from a replicated pilot study that can be used to identify differentially expressed genes in subsequent large-scale studies on the same platform, but in which there may be no replicated arrays. The method builds a stratified error model that includes array-to-array variability, feature-to-feature variability and the dependence of error on signal intensity. We apply this model to the characterization of the host response in a model of bacterial infection of human intestinal epithelial cells. We demonstrate the effectiveness of error model based microarray experiments and propose this as a general strategy for a microarray-based screening of large collections of biological samples

Unraveling the directional link between adiposity and inflammation: a bidirectional mendelian randomization approach

<b>Context</b>: Associations between adiposity and circulating inflammation markers are assumed to be causal, although the direction of the relationship has not been proven. <b>Objective</b>: The aim of the study was to explore the causal direction of the relationship between adiposity and inflammation using a bidirectional Mendelian randomization approach. <b>Methods</b>: In the PROSPER study of 5804 elderly patients, we related C-reactive protein (CRP) single nucleotide polymorphisms (SNPs) (rs1800947 and rs1205) and adiposity SNPs (FTO and MC4R) to body mass index (BMI) as well as circulating levels of CRP and leptin. We gave each individual two allele scores ranging from zero to 4, counting each pair of alleles related to CRP levels or BMI. <b>Results</b>: With increasing CRP allele score, there was a stepwise decrease in CRP levels (P for trend < 0.0001) and a 1.98 mg/liter difference between extremes of the allele score distribution, but there was no associated change in BMI or leptin levels (P ≥ 0.89). By contrast, adiposity allele score was associated with 1) an increase in BMI (1.2 kg/m2 difference between extremes; P for trend 0.002); 2) an increase in circulating leptin (5.77 ng/ml difference between extremes; P for trend 0.0027); and 3) increased CRP levels (1.24 mg/liter difference between extremes; P for trend 0.002). <b>Conclusions</b>: Greater adiposity conferred by FTO and MC4R SNPs led to higher CRP levels, with no evidence for any reverse pathway. Future studies should extend our findings to other circulating inflammatory parameters. This study illustrates the potential power of Mendelian randomization to dissect directions of causality between intercorrelated metabolic factors

Acetylcholine receptors (muscarinic) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Muscarinic acetylcholine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Muscarinic Acetylcholine Receptors [45]) are GPCRs of the Class A, rhodopsin-like family where the endogenous agonist is acetylcholine. In addition to the agents listed in the table, AC-42, its structural analogues AC-260584 and 77-LH-28-1, N-desmethylclozapine, TBPB and LuAE51090 have been described as functionally selective agonists of the M1 receptor subtype via binding in a mode distinct from that utilized by non-selective agonists [243, 242, 253, 155, 154, 181, 137, 11, 230]. There are two pharmacologically characterised allosteric sites on muscarinic receptors, one defined by it binding gallamine, strychnine and brucine, and the other defined by the binding of KT 5720, WIN 62,577, WIN 51,708 and staurosporine [161, 162]