Validation of a fornix depth measurer: a putative tool for the assessment of progressive cicatrising conjunctivitis

Background/aims Documentation of conjunctival forniceal foreshortening in cases of progressive cicatrising conjunctivitis (PCC) is important in ascertaining disease stage and progression. Lower fornix shortening is often documented subjectively or semi-objectively, whereas upper forniceal obliteration is seldom quantified. Although tools such as fornix depth measurers (FDMs) have been described, their designs limit upper fornix measurement. The purpose of this study was to custom-design a FDM to evaluate the upper fornix and to assess variability in gauging fornix depth. \ud \ud Methods A polymethylmethacrylate FDM was constructed using industry-standard jewellery computer software and machinery. Two observers undertook a prospective independent evaluation of central lower fornix depth in a heterogeneous cohort of patients with clinically normal and abnormal conjunctival fornices both subjectively and by using the FDM (in mm). Upper central fornix depth was also measured. Agreement was assessed using Bland–Altman plots. \ud \ud Results Fifty-one eyes were evaluated. There was 100% intraobserver agreement to within 1 mm for each observer for lower fornix measurement. The mean difference in fornix depth loss using the FDM between observer 1 and 2 was 1.19%, with 95% confidence of agreement (±2SD) of −15% to +20%. In total, 86% (44/51) of measurements taken by the two observers agreed to within 10% of total lower fornix depth (ie, ±1 mm) versus only 63% (32/51) of the subjective measurements. Mean upper fornix difference was 0.57 mm, with 95% confidence of agreement of between −2 and + 3 mm. \ud \ud Conclusions This custom-designed FDM is well tolerated by patients and shows low intraobserver and interobserver variability. This enables repeatable and reproducible measurement of upper and lower fornix depths, facilitating improved rates of detection and better monitoring of progression of conjunctival scarring

The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.

Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies

Training Load, Injury Burden, and Team Success in Professional Rugby Union:Risk Versus Reward

CONTEXT: Individual and team injury burden and performance are 2 key considerations facing practitioners in the daily prescription of an athlete's training load. Whereas a considerable number of researchers have examined univariate relationships between training load and performance, training load and injury, or injury and performance, few investigators have examined all 3 concurrently. OBJECTIVE: To assess the association among training load, injury burden, and performance in professional rugby union. DESIGN: Descriptive epidemiology study. SETTING: The English Premiership competition. PATIENTS OR OTHER PARTICIPANTS: Individual injury and training load data, as well as team performance data, were captured during the 2015–2016 (n = 433 players) and 2016–2017 (n = 569 players) seasons. MAIN OUTCOME MEASURE(S): Data were aggregated into team average scores for each week, including weekly (acute) load, smoothed chronic load, changes in load, injury burden, and weekly performance. Linear mixed modelling techniques were used to assess the association among measures. RESULTS: Injury burden was negatively associated with performance, with a high weekly burden associated with a likely harmful (P = .01) decrease in performance. Training load measures displayed only trivial associations with performance. Only the acute:chronic workload ratio measure was clearly associated with injury burden, with a possibly harmful effect (P = .02). Both squad size and player availability were associated with only trivial changes in performance. CONCLUSIONS: Whereas no association between average training load and performance existed, associations between training load and injury burden and between injury burden and performance were clear. Further investigation using more sensitive and individualized measures of load, performance, and injury may elicit a clearer relationship and should be considered for future work

Sources of Airborne Endotoxins in Ambient Air and Exposure of Nearby Communities—A Review

Endotoxin is a bioaerosol component that is known to cause respiratory effects in exposed populations. To date, most research focused on occupational exposure, whilst much less is known about the impact of emissions from industrial operations on downwind endotoxin concentrations. A review of the literature was undertaken, identifying studies that reported endotoxin concentrations in both ambient environments and around sources with high endotoxin emissions. Ambient endotoxin concentrations in both rural and urban areas are generally below 10 endotoxin units (EU) m−3; however, around significant sources such as compost facilities, farms, and wastewater treatment plants, endotoxin concentrations regularly exceeded 100 EU m−3. However, this is affected by a range of factors including sampling approach, equipment, and duration. Reported downwind measurements of endotoxin demonstrate that endotoxin concentrations can remain above upwind concentrations. The evaluation of reported data is complicated due to a wide range of different parameters including sampling approaches, temperature, and site activity, demonstrating the need for a standardised methodology and improved guidance. Thorough characterisation of ambient endotoxin levels and modelling of endotoxin from pollution sources is needed to help inform future policy and support a robust health-based risk assessment process

Fast Bowler’s knee – anteromedial articular impingement

Purpose: To describe a series of impingement lesions found on the anterior aspect of the medial femoral condyle in international cricketers. Methods: Seven international level fast bowlers presented to our clinic with knee pain in the lead leg between 2005 and 2013. The mean age of the patients was 26.7 years (20–29 years). In all patients a careful history and examination was undertaken followed by appropriate investigations. Conservative management and arthroscopic surgery were performed on these cases. We aimed for a pain free quiet knee with resolved oedema on MRI and return to sport. Results: MRI images showed oedema in the medial femoral condyle in all patients and 4 patients also had associated cartilage loss. These 4 patients underwent arthroscopic surgery whereas the other 3 were less symptomatic and were managed conservatively. All patients returned to international cricket at an average of 6 months in the non-operative group and 8 months in the operative group. Conclusion: Anterior impingement of the anteromedial femoral condyle can be a potentially serious lesion in the fast bowler. A strong index of suspicion regarding this lesion has to be exercised when a fast bowler attends with knee pain and effusion

Distinctive Personality Traits and Neural Correlates Associated with Stimulant Drug Use Versus Familial Risk of Stimulant Dependence

BackgroundStimulant drugs such as cocaine and amphetamine have a high abuse liability, but not everyone who uses them develops dependence. However, the risk for dependence is increased for individuals with a family history of addiction. We hypothesized that individuals without a family history of dependence who have been using cocaine recreationally for several years but have not made the transition to dependence will differ in terms of personality traits and brain structure from individuals who are either dependent on stimulants or at risk for dependence.MethodsWe compared 27 individuals without a familial risk of dependence who had been using cocaine recreationally with 50 adults with stimulant dependence, their nondependent siblings (n = 50), and unrelated healthy volunteers (n = 52) who had neither a personal nor a family history of dependence. All participants underwent a magnetic resonance imaging brain scan and completed a selection of personality measures that have been associated with substance abuse.ResultsIncreased sensation-seeking traits and abnormal orbitofrontal and parahippocampal volume were shared by individuals who were dependent on stimulant drugs or used cocaine recreationally. By contrast, increased levels of impulsive and compulsive personality traits and limbic-striatal enlargement were shared by stimulant-dependent individuals and their unaffected siblings.ConclusionsWe provide evidence for distinct neurobiological phenotypes that are either associated with familial vulnerability for dependence or with regular stimulant drug use. Our findings further suggest that some individuals with high sensation-seeking traits but no familial vulnerability for dependence are likely to use cocaine but may have relatively low risk for developing dependence