Forecasting neuromuscular recovery after anterior cruciate ligament injury: Athlete recovery profiles with generalized additive modeling

A retrospective analysis of longitudinally collected athlete monitoring data wasconducted to generate a model of neuromuscular recovery after anterior cruciateligament (ACL) injury and reconstruction (ACLR). Neuromuscular testing data in-cluding countermovement jump (CMJ) force‐time asymmetries and knee extensorstrength (maximum voluntary contractionext) asymmetries (between‐limb asymmetryindex—AI) were obtained from athletes with ACLR using semitendinosus (ST) au-tograft (n= 29; AI measurements: n= 494), bone patellar tendon bone autograft(n= 5; AI measurements:n= 88) and noninjured controls (n= 178; AI measurements:n= 3188). Explosive strength measured as the rate of torque development was alsocalculated. CMJ force‐time asymmetries were measured over discrete movementphases (eccentric deceleration phase, concentric phase). Separate additive mixedeffects models (additive mixed effects model [AMM]) were fit for each AI with amain effect for the surgical technique and a smooth term for the time since surgery(days). The models explained between 43% and 91% of the deviance in neuro-muscular recovery after ACLR. The mean time course was generated from the AMM.Comparative neuromuscular recovery profiles of an athlete with an acceleratedprogression and an athlete with a delayed progression after a serious multiligamentinjury were generated. Clinical Significance: This paper provides a new perspectiveon the utility of longitudinal athlete monitoring including routine testing to developmodels of neuromuscular recovery after ACLR that can be used to characterizeindividual progression throughout rehabilitation

The co-evolutionary relationship between energy service companies and the UK energy system: Implications for a low-carbon transition

The Energy Service Company (ESCo) business model is designed to reward businesses by satisfying consumers' energy needs at less cost and with fewer carbon emissions via energy demand management and/or sustainable supply measures. In contrast, the revenue of the incumbent Energy Utility Company (EUCo) model is coupled with the sale of units of energy, which are predominantly sourced from fossil fuels. The latter is currently dominant in the UK. This paper addresses two questions. First, why has the ESCo model traditionally been confined to niche applications? Second, what role is the ESCo model likely to play in the transition to a low-carbon UK energy system? To answer these, the paper examines the core characteristics of the ESCo model, relative to the EUCo model. The paper then examines how ESCos have co-evolved with the various dimensions of the energy system (i.e. ecosystems, institutions, user practices, technologies and business models) to provide insight into how ESCos might help to shape the future UK energy system. We suggest that institutional and technological changes within the UK energy system could result in a more favourable selection environment for ESCos, consequently enabling the ESCo model to proliferate at the expense of the EUCo model. © 2013 Elsevier Ltd

Spectrum of Neutral Helium in Strong Magnetic Fields

We present extensive and accurate calculations for the excited state spectrum of spin-polarized neutral helium in a range of magnetic field strengths up to $10^{12}$ G. Of considerable interest to models of magnetic white dwarf stellar atmospheres, we also present results for the dipole strengths of the low lying transitions among these states. Our methods rely on a systematically saturated basis set approach to solving the Hartree--Fock self-consistent field equations, combined with an ``exact'' stochastic method to estimate the residual basis set truncation error and electron correlation effects. We also discuss the applicability of the adiabatic approximation to strongly magnetized multi-electron atoms.Comment: 19 pages, 7 figures, 10 table

Enhanced ultrafast X-ray diffraction by transient resonances

Diffraction-before-destruction imaging with single ultrashort X-ray pulses has the potential to visualise non-equilibrium processes, such as chemical reactions, at the nanoscale with sub-femtosecond resolution in the native environment without the need of crystallization. Here, a nanospecimen partially diffracts a single X-ray flash before sample damage occurs. The structural information of the sample can be reconstructed from the coherent X-ray interference image. State-of-art spatial resolution of such snapshots from individual heavy element nanoparticles is limited to a few nanometers. Further improvement of spatial resolution requires higher image brightness which is ultimately limited by bleaching effects of the sample. We compared snapshots from individual 100 nm Xe nanoparticles as a function of the X-ray pulse duration and incoming X-ray intensity in the vicinity of the Xe M-shell resonance. Surprisingly, images recorded with few femtosecond and sub-femtosecond pulses are up to 10 times brighter than the static linear model predicts. Our Monte-Carlo simulation and statistical analysis of the entire data set confirms these findings and attributes the effect to transient resonances. Our simulation suggests that ultrafast form factor changes during the exposure can increase the brightness of X-ray images by several orders of magnitude. Our study guides the way towards imaging with unprecedented combination of spatial and temporal resolution at the nanoscale

The effect of octopaminergic compounds on the behaviour and transmission of Gyrodactylus

Background: The high transmission potential of species belonging to the monogenean parasite genus Gyrodactylus, coupled with their high fecundity, allows them to rapidly colonise new hosts and to increase in number. One gyrodactylid, Gyrodactylus salaris Malmberg, 1957, has been responsible for devastation of Altantic salmon (Salmo salar L.) populations in a number of Norwegian rivers. Current methods of eradicating G. salaris from river systems centre around the use of non-specific biocides, such as rotenone and aluminium sulphate. Although transmission routes in gyrodactylids have been studied extensively, the behaviour of individual parasites has received little attention. Specimens of Gyrodactylus gasterostei Gläser, 1974 and G. arcuatus Bychowsky, 1933, were collected from the skin of their host, the three-spined stickleback (Gasterosteus aculeatus L.), and permitted to attach to the substrate. The movements of individual parasites were recorded and analysed. Results: The behaviour patterns of the two species were similar and parasites were more active in red light and darkness than in white light. Four octopaminergic compounds were tested and all four inhibited the movements of parasites. Treatment ultimately led to death at low concentrations (0.2 μM), although prolonged exposure was necessary in some instances. Conclusions: Octopaminergic compounds may affect the parasite's ability to locate and remain on its host and these or related compounds might provide alternative or supplementary treatments for the control of G. salaris infections. With more research there is potential for use of octopaminergic compounds, which have minimal effects on the host or its environment, as parasite-specific treatments against G. salaris infections

Through a Glass, Darkly:The CIA and Oral History

This article broaches the thorny issue of how we may study the history of the CIA by utilizing oral history interviews. This article argues that while oral history interviews impose particular demands upon the researcher, they are particularly pronounced in relation to studying the history of intelligence services. This article, nevertheless, also argues that while intelligence history and oral history each harbour their own epistemological perils and biases, pitfalls which may in fact be pronounced when they are conjoined, the relationship between them may nevertheless be a productive one. Indeed, each field may enrich the other provided we have thought carefully about the linkages between them: this article's point of departure. The first part of this article outlines some of the problems encountered in studying the CIA by relating them to the author's own work. This involved researching the CIA's role in US foreign policy towards Afghanistan since a landmark year in the history of the late Cold War, 1979 (i.e. the year the Soviet Union invaded that country). The second part of this article then considers some of the issues historians must confront when applying oral history to the study of the CIA. To bring this within the sphere of cognition of the reader the author recounts some of his own experiences interviewing CIA officers in and around Washington DC. The third part then looks at some of the contributions oral history in particular can make towards a better understanding of the history of intelligence services and the CIA

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

Discovery of a Small-Molecule Probe for V-ATPase Function

Lysosomes perform a critical cellular function as a site of degradation for diverse cargoes including proteins, organelles, and pathogens delivered through distinct pathways, and defects in lysosomal function have been implicated in a number of diseases. Recent studies have elucidated roles for the lysosome in the regulation of protein synthesis, metabolism, membrane integrity, and other processes involved in homeostasis. Complex small-molecule natural products have greatly contributed to the investigation of lysosomal function in cellular physiology. Here we report the discovery of a novel, small-molecule modulator of lysosomal acidification derived from diversity-oriented synthesis through high-content screening

I am hiQ—a novel pair of accuracy indices for imputed genotypes

Background: Imputation of untyped markers is a standard tool in genome-wide association studies to close the gap between directly genotyped and other known DNA variants. However, high accuracy with which genotypes are imputed is fundamental. Several accuracy measures have been proposed and some are implemented in imputation software, unfortunately diversely across platforms. In the present paper, we introduce Iam hiQ, an independent pair of accuracy measures that can be applied to dosage files, the output of all imputation software. Iam (imputation accuracy measure) quantifies the average amount of individual-specific versus population-specific genotype information in a linear manner. hiQ (heterogeneity in quantities of dosages) addresses the inter-individual heterogeneity between dosages of a marker across the sample at hand. Results: Applying both measures to a large case–control sample of the International Lung Cancer Consortium (ILCCO), comprising 27,065 individuals, we found meaningful thresholds for Iam and hiQ suitable to classify markers of poor accuracy. We demonstrate how Manhattan-like plots and moving averages of Iam and hiQ can be useful to identify regions enriched with less accurate imputed markers, whereas these regions would by missed when applying the accuracy measure info (implemented in IMPUTE2). Conclusion: We recommend using Iam hiQ additional to other accuracy scores for variant filtering before stepping into the analysis of imputed GWAS data