CTLA-4: a negative regulator of autoimmune disease.

CTLA-4, a CD28 homologue expressed on activated T cells, binds with high affinity to the CD28 ligands, B7-1 (CD80) and B7-2 (CD86). This study was designed to examine the role of CTLA-4 in regulating autoimmune disease. Murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) is a demyelinating disease mediated by PLP139-151-specific CD4+ T cells in SJL/J mice. Anti-CTLA-4 mAbs (or their F(ab) fragments) enhanced in vitro proliferation and pro-inflammatory cytokine production by PLP139-151-primed lymph node cells. Addition of either reagent to in vitro activation cultures potentiated the ability of T cells to adoptively transfer disease to naive recipients. In vivo administration of anti-CTLA-4 mAb to recipients of PLP139-151-specific T cells resulted in accelerated and exacerbated disease. Finally, anti-CTLA-4 treatment of mice during disease remission resulted in the exacerbation of relapses. Collectively, these results suggest that CTLA-4 mediates the downregulation of ongoing immune responses and plays a major role in regulating autoimmunity

Super aggressive s-ducts for air breathing rocket engines

Abstract Air breathing rocket engines require turbomachinery and ducting that is substantially lighter than that used in ground based or aerospace gas turbines. In order to reduce the weight of the axial compressor, the design of the inter-spool swan neck duct is targeted. In this paper a circumferential splitter blade is used to reduce loading and diffusion on the duct endwalls. The splitter and duct geometry are coupled and optimised together using 2D CFD. A design is selected that is 30% shorter than ducts that are currently used in aerospace gas turbines and the 3D flow features are investigated in further detail using an experimental rig and 3D CFD. This paper shows that the “splittered” duct has 3 benefits over a conventional duct design: First, separation of the endwalls is prevented even at short duct lengths, this will reduce distortion into the downstream compressor. Second, losses generated by corner separations on structural struts can be reduced by 20%, enabling short ducts to achieve high performance. Third, splittered ducts are shown to be twice as robust to uncertain inlet flow conditions as conventional ducts. This allows a designer to target high performance short designs with reduced risk.</jats:p

The Child Outcome Rating Scale: validating a four-item measure of psychosocial functioning in community and clinic samples of children aged 10-15

Psychosocial functioning is considered an important and valued outcome in relation to young people’s mental health as a construct distinct from psychiatric symptomology, especially in the light of an increasing focus on transdiagnostic approaches. Yet, the level of psychosocial functioning is rarely directly asked of young people themselves, despite the widespread recognition that the young person’s perspective is valuable and is often at odds with those of other reporters, such as parents or professionals. One possible reason for this is that the field lacks a clear agreed tool to capture this information in a non-burdensome way. To begin to address this gap, this paper describes psychometric analysis of the Child Outcome Rating Scale (CORS), a brief and highly accessible self-report measure of young people’s psychosocial functioning already used extensively by mental health professionals around the world but with only limited data on psychometric robustness. Using large community (n = 7822) and clinic (n = 2604) samples, we explore the factor structure, construct validity, internal consistency, differential item functioning, and sensitivity of the CORS. We found that the CORS stands up to psychometric scrutiny, having found satisfactory levels of reliability, validity, and sensitivity in this sample. We also found that the CORS is suitable for use with young people as old as 15 years old. That the CORS has been found to be psychometrically robust while being highly feasible (brief, simple, easy to administer) for use in busy clinical settings, combined with the fact that the CORS has already been widely adopted by clinicians and young people, suggests CORS may be an important tool for international use

Using eddy covariance to measure the dependence of air–sea CO2 exchange rate on friction velocity

Parameterisation of the air–sea gas transfer velocity of CO2 and other trace gases under open-ocean conditions has been a focus of air–sea interaction research and is required for accurately determining ocean carbon uptake. Ships are the most widely used platform for air–sea flux measurements but the quality of the data can be compromised by airflow distortion and sensor cross-sensitivity effects. Recent improvements in the understanding of these effects have led to enhanced corrections to the shipboard eddy covariance (EC) measurements. Here, we present a revised analysis of eddy covariance measurements of air–sea CO2 and momentum fluxes from the Southern Ocean Surface Ocean Aerosol Production (SOAP) study. We show that it is possible to significantly reduce the scatter in the EC data and achieve consistency between measurements taken on station and with the ship underway. The gas transfer velocities from the EC measurements correlate better with the EC friction velocity (u*) than with mean wind speeds derived from shipboard measurements corrected with an airflow distortion model. For the observed range of wind speeds (u10 N = 3–23 m s−1), the transfer velocities can be parameterised with a linear fit to u*. The SOAP data are compared to previous gas transfer parameterisations using u10 N computed from the EC friction velocity with the drag coefficient from the Coupled Ocean–Atmosphere Response Experiment (COARE) model version 3.5. The SOAP results are consistent with previous gas transfer studies, but at high wind speeds they do not support the sharp increase in gas transfer associated with bubble-mediated transfer predicted by physically based models

Air/sea DMS gas transfer in the North Atlantic: evidence for limited interfacial gas exchange at high wind speed

Shipboard measurements of eddy covariance dimethylsulfide (DMS) air–sea fluxes and seawater concentration were carried out in the North Atlantic bloom region in June/July 2011. Gas transfer coefficients (k660) show a linear dependence on mean horizontal wind speed at wind speeds up to 11 m s−1. At higher wind speeds the relationship between k660 and wind speed weakens. At high winds, measured DMS fluxes were lower than predicted based on the linear relationship between wind speed and interfacial stress extrapolated from low to intermediate wind speeds. In contrast, the transfer coefficient for sensible heat did not exhibit this effect. The apparent suppression of air–sea gas flux at higher wind speeds appears to be related to sea state, as determined from shipboard wave measurements. These observations are consistent with the idea that long waves suppress near-surface water-side turbulence, and decrease interfacial gas transfer. This effect may be more easily observed for DMS than for less soluble gases, such as CO2, because the air–sea exchange of DMS is controlled by interfacial rather than bubble-mediated gas transfer under high wind speed conditions

Is markerless, smart phone recorded two-dimensional video a clinically useful measure of relevant lower limb kinematics in runners with patellofemoral pain? A validity and reliability study.

OBJECTIVES: Investigate the validity and reliability of markerless, smart phone collected, two-dimensional (2D) video, analysed using the 'Hudl technique' application, compared to three-dimensional (3D) kinematics during running, in participants with patellofemoral pain (PFP). DESIGN: Validity/reliability study. SETTING: Biomechanics laboratory. PARTICIPANTS: Males/females with PFP (n = 21, 10 males, 11 females, age 32.1 months [±12.9]). MAIN OUTCOME MEASURES: Manually synchronised 2D and 3D measurement of peak hip adduction (HADD) and peak knee flexion (KFLEX) during running. RESULTS: 2D and 3D measures of peak KFLEX (p = 0.02, d = 1.13), but not peak HADD (p = 0.25, d = -0.27), differed significantly. Poor validity was identified for 2D measurement of peak HADD (ICC 0.06, 95% CI -0.35, 0.47) and peak KFLEX ICC 0.42, 95% CI (-0.10, 0.75). Moderate intra-rater reliability was identified for both variables (ICC 0.61-65), alongside moderate inter-rater reliability for peak KFLEX (ICC 0.71) and poor inter-rater reliability for peak HADD (ICC 0.31). CONCLUSIONS: Measurement of peak HADD and KFLEX in runners with PFP using markerless, smart phone collected 2D video, analysed using the Hudl technique Application is invalid, with poor to moderate reliability. Investigation of alternate 2D video approaches to increase precision is warranted. At present, 2D video analysis of running using Hudl Technique cannot be advocated

Implementation of routine outcome measurement in child and adolescent mental health services in the United Kingdom: a critical perspective

The aim of this commentary is to provide an overview of clinical outcome measures that are currently recommended for use in UK Child and Adolescent Mental Health Services (CAMHS), focusing on measures that are applicable across a wide range of conditions with established validity and reliability, or innovative in their design. We also provide an overview of the barriers and drivers to the use of Routine Outcome Measurement (ROM) in clinical practice

Global Diversity of the Stylasteridae (Cnidaria: Hydrozoa: Athecatae)

The history and rate of discovery of the 247 valid Recent stylasterid species are discussed and graphed, with emphasis on five historical pulses of species descriptions. A table listing all genera, their species numbers, and their bathymetric ranges are presented. The number of species in 19 oceanographic regions is mapped, the southwestern temperate Pacific (region including New Zealand) having the most species; species are cosmopolitan from the Arctic Circle to the Antarctic at depths from 0 to 2789 m. The current phylogenetic classification of the genera is briefly discussed. An illustrated glossary of 53 morphological characters is presented. Biological and ecological information pertaining to reproduction, development, commensals, and distribution is discussed. Aspects of stylasterid mineralogy and taxa of commercial value are discussed, concluding with suggestions for future work