A cross sectional study of requests for knee radiographs from primary care

<p>Abstract</p> <p>Background</p> <p>Knee pain is the commonest pain complaint amongst older adults in general practice. General Practitioners (GPs) may use x rays when managing knee pain, but little information exists regarding this process. Our objectives, therefore, were to describe the information GPs provide when ordering knee radiographs in older people, to assess the association between a clinical diagnosis of osteoarthritis (OA) and the presence of radiographic knee OA, and to investigate the clinical content of the corresponding radiologists' report.</p> <p>Methods</p> <p>A cross sectional study of GP requests for knee radiographs and their matched radiologists' reports from a local radiology department. Cases, aged over 40, were identified during an 11-week period. The clinical content of the GPs' requests and radiologists' reports was analysed. Associations of radiologists' reporting of i) osteoarthritis, ii) degenerative disease and iii) individual radiographic features of OA, with patient characteristics and clinical details on the GPs' requests, were assessed.</p> <p>Results</p> <p>The study identified 136 cases with x ray requests from 79 GPs and 11 reporting radiologists. OA was identified clinically in 19 (14%) of the requests, and queried in another 31 (23%). The main clinical descriptor was pain in 119 cases (88%). Radiologists' reported OA in 22% of cases, and the features of OA were mentioned in 63%. Variation in reporting existed between radiologists. The commonest description was joint space narrowing in 52 reports (38%). There was an apparent although non significant increase in the reporting of knee OA when the GP had diagnosed or queried it (OR 1.95; 95% CI 0.76, 5.00).</p> <p>Conclusion</p> <p>The features of radiographic OA are commonly reported in those patients over 40 whom GPs send for x ray. If OA is clinically suspected, radiologists appear to be more likely to report its presence. Further research into alternative models of referral and reporting might identify a more appropriate imaging policy in knee disorders for primary care.</p

The Repertoire and Dynamics of Evolutionary Adaptations to Controlled Nutrient-Limited Environments in Yeast

The experimental evolution of laboratory populations of microbes provides an opportunity to observe the evolutionary dynamics of adaptation in real time. Until very recently, however, such studies have been limited by our inability to systematically find mutations in evolved organisms. We overcome this limitation by using a variety of DNA microarray-based techniques to characterize genetic changes—including point mutations, structural changes, and insertion variation—that resulted from the experimental adaptation of 24 haploid and diploid cultures of Saccharomyces cerevisiae to growth in either glucose, sulfate, or phosphate-limited chemostats for ∼200 generations. We identified frequent genomic amplifications and rearrangements as well as novel retrotransposition events associated with adaptation. Global nucleotide variation detection in ten clonal isolates identified 32 point mutations. On the basis of mutation frequencies, we infer that these mutations and the subsequent dynamics of adaptation are determined by the batch phase of growth prior to initiation of the continuous phase in the chemostat. We relate these genotypic changes to phenotypic outcomes, namely global patterns of gene expression, and to increases in fitness by 5–50%. We found that the spectrum of available mutations in glucose- or phosphate-limited environments combined with the batch phase population dynamics early in our experiments allowed several distinct genotypic and phenotypic evolutionary pathways in response to these nutrient limitations. By contrast, sulfate-limited populations were much more constrained in both genotypic and phenotypic outcomes. Thus, the reproducibility of evolution varies with specific selective pressures, reflecting the constraints inherent in the system-level organization of metabolic processes in the cell. We were able to relate some of the observed adaptive mutations (e.g., transporter gene amplifications) to known features of the relevant metabolic pathways, but many of the mutations pointed to genes not previously associated with the relevant physiology. Thus, in addition to answering basic mechanistic questions about evolutionary mechanisms, our work suggests that experimental evolution can also shed light on the function and regulation of individual metabolic pathways

The Role of Emotional Reactivity, Self-regulation, and Puberty in Adolescents\u27 Prosocial Behaviors

This study was designed to examine the roles of emotional reactivity, self-regulation, and pubertal timing in prosocial behaviors during adolescence. Participants were 850 sixth graders (50% female, Mean age = 11.03, SD = .17) who were followed up at age 15. In hierarchical regression models, measures of emotional reactivity, self-regulation, pubertal timing and their interactions were used to predict (concurrently and over time) adolescents’ prosocial behaviors in the home and with peers. Overall, the findings provide evidence for pubertal and temperament based predictors of prosocial behaviors expressed in different contexts. Self-regulation was positively related to both forms of prosocial behavior, concurrently and longitudinally. Emotional reactivity showed moderately consistent effects, showing negative concurrent relations to prosocial behavior with peers and negative longitudinal relations (four years later) to prosocial behavior at home. Some curvilinear effects of temperament on prosocial behaviors were also found. Effects of pubertal timing were found to interact with gender, such that boys who were early maturers showed the highest levels of prosocial behavior at home concurrently. Discussion focuses on the role of temperament-based mechanisms in the expression of prosocial behaviors in different contexts in adolescence

Inactivation of Staphylococcal Phenol Soluble Modulins by Serum Lipoprotein Particles

Staphylococcus aureus virulence has been associated with the production of phenol soluble modulins (PSM). PSM are known to activate, attract and lyse neutrophils. However, the functional characterizations were generally performed in the absence of human serum. Here, we demonstrate that human serum can inhibit all the previously-described activities of PSM. We observed that serum can fully block both the cell lysis and FPR2 activation of neutrophils. We show a direct interaction between PSM and serum lipoproteins in human serum and whole blood. Subsequent analysis using purified high, low, and very low density lipoproteins (HDL, LDL, and VLDL) revealed that they indeed neutralize PSM. The lipoprotein HDL showed highest binding and antagonizing capacity for PSM. Furthermore, we show potential intracellular production of PSM by S. aureus upon phagocytosis by neutrophils, which opens a new area for exploration of the intracellular lytic capacity of PSM. Collectively, our data show that in a serum environment the function of PSM as important extracellular toxins should be reconsidered

Reciprocal Sign Epistasis between Frequently Experimentally Evolved Adaptive Mutations Causes a Rugged Fitness Landscape

The fitness landscape captures the relationship between genotype and evolutionary fitness and is a pervasive metaphor used to describe the possible evolutionary trajectories of adaptation. However, little is known about the actual shape of fitness landscapes, including whether valleys of low fitness create local fitness optima, acting as barriers to adaptive change. Here we provide evidence of a rugged molecular fitness landscape arising during an evolution experiment in an asexual population of Saccharomyces cerevisiae. We identify the mutations that arose during the evolution using whole-genome sequencing and use competitive fitness assays to describe the mutations individually responsible for adaptation. In addition, we find that a fitness valley between two adaptive mutations in the genes MTH1 and HXT6/HXT7 is caused by reciprocal sign epistasis, where the fitness cost of the double mutant prohibits the two mutations from being selected in the same genetic background. The constraint enforced by reciprocal sign epistasis causes the mutations to remain mutually exclusive during the experiment, even though adaptive mutations in these two genes occur several times in independent lineages during the experiment. Our results show that epistasis plays a key role during adaptation and that inter-genic interactions can act as barriers between adaptive solutions. These results also provide a new interpretation on the classic Dobzhansky-Muller model of reproductive isolation and display some surprising parallels with mutations in genes often associated with tumors

Staphylococcus aureus infection dynamics

Staphylococcus aureus is a human commensal that can also cause systemic infections. This transition requires evasion of the immune response and the ability to exploit different niches within the host. However, the disease mechanisms and the dominant immune mediators against infection are poorly understood. Previously it has been shown that the infecting S. aureus population goes through a population bottleneck, from which very few bacteria escape to establish the abscesses that are characteristic of many infections. Here we examine the host factors underlying the population bottleneck and subsequent clonal expansion in S. aureus infection models, to identify underpinning principles of infection. The bottleneck is a common feature between models and is independent of S. aureus strain. Interestingly, the high doses of S. aureus required for the widely used "survival" model results in a reduced population bottleneck, suggesting that host defences have been simply overloaded. This brings into question the applicability of the survival model. Depletion of immune mediators revealed key breakpoints and the dynamics of systemic infection. Loss of macrophages, including the liver Kupffer cells, led to increased sensitivity to infection as expected but also loss of the population bottleneck and the spread to other organs still occurred. Conversely, neutrophil depletion led to greater susceptibility to disease but with a concomitant maintenance of the bottleneck and lack of systemic spread. We also used a novel microscopy approach to examine abscess architecture and distribution within organs. From these observations we developed a conceptual model for S. aureus disease from initial infection to mature abscess. This work highlights the need to understand the complexities of the infectious process to be able to assign functions for host and bacterial components, and why S. aureus disease requires a seemingly high infectious dose and how interventions such as a vaccine may be more rationally developed

Unilateral Exoskeleton Imposes Significantly Different Hemispherical Effect in Parietooccipital Region, but Not in Other Regions

In modern society, increasing people suffering from locomotor disabilities need an assistive exoskeleton to help them improve or restore ambulation. When walking is assisted by an exoskeleton, brain activities are altered as the closed-loop between brain and lower limbs is affected by the exoskeleton. Intuitively, a unilateral exoskeleton imposes differential effect on brain hemispheres (i.e., hemispherical effect) according to contralateral control mechanism. However, it is unclear whether hemispherical effect appears in whole hemisphere or particular region. To this end, we explored hemispherical effect on different brain regions using EEG data collected from 30 healthy participants during overground walking. The results showed that hemispherical effect was significantly different between regions when a unilateral exoskeleton was employed for walking assistance and no significance was observed for walking without the exoskeleton. Post-hoc t-test analysis revealed that hemispherical effect in the parietooccipital region significantly differed from other regions. In the parietooccipital region, a greater hemispherical effect was observed in beta band for exoskeleton-assisted walking compared to walking without exoskeleton, which was also found in the source analysis. These findings deepen the understanding of hemispherical effect of unilateral exoskeleton on brain and could aid the development of more efficient and suitable exoskeleton for walking assistance

Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.Peer reviewe