Different modes of variation for each BG lineage suggest different functions.

Mammalian butyrophilins have various important functions, one for lipid binding but others as ligands for co-inhibition of αβ T cells or for stimulation of γδ T cells in the immune system. The chicken BG homologues are dimers, with extracellular immunoglobulin variable (V) domains joined by cysteines in the loop equivalent to complementarity-determining region 1 (CDR1). BG genes are found in three genomic locations: BG0 on chromosome 2, BG1 in the classical MHC (the BF-BL region) and many BG genes in the BG region just outside the MHC. Here, we show that BG0 is virtually monomorphic, suggesting housekeeping function(s) consonant with the ubiquitous tissue distribution. BG1 has allelic polymorphism but minimal sequence diversity, with the few polymorphic residues at the interface of the two V domains, suggesting that BG1 is recognized by receptors in a conserved fashion. Any phenotypic variation should be due to the intracellular region, with differential exon usage between alleles. BG genes in the BG region can generate diversity by exchange of sequence cassettes located in loops equivalent to CDR1 and CDR2, consonant with recognition of many ligands or antigens for immune defence. Unlike the mammalian butyrophilins, there are at least three modes by which BG genes evolve.Wellcome Trust (Grant IDs: RG49834 (Studentship), 089305 and a Senior Investigator Award), Biotechnology and Biological Sciences Research Council (Studentship)This is the final version of the article. It first appeared from The Royal Society via http://dx.doi.org/10.1098/rsob.16018

Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial

Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12+0-27+6 weeks' gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol- (200-1800 mg/d) or nifedipine-modified release (20-80 mg/d). Analysis included 112 women (98%) who completed the study (labetalol n=55, nifedipine n=57). Maximum blood pressure after randomization was 161/101 mm Hg with labetalol versus 163/105 mm Hg with nifedipine (mean difference systolic: 1.2 mm Hg [-4.9 to 7.2 mm Hg], diastolic: 3.3 mm Hg [-0.6 to 7.3 mm Hg]). Mean blood pressure was 134/84 mm Hg with labetalol and 134/85 mm Hg with nifedipine (mean difference systolic: 0.3 mm Hg [-2.8 to 3.4 mm Hg], and diastolic: -1.9 mm Hg [-4.1 to 0.3 mm Hg]). Nifedipine use was associated with a 7.4-mm Hg reduction (-14.4 to -0.4 mm Hg) in central aortic pressure, measured by pulse wave analysis. No difference in treatment effect was observed in black women (n=63), but a mean 4 mm Hg reduction (-6.6 to -0.8 mm Hg; P=0.015) in brachial diastolic blood pressure was observed with labetalol compared with nifedipine in non-black women (n=49). Labetalol and nifedipine control mean blood pressure to target in pregnant women with chronic hypertension. This study provides support for a larger definitive trial scrutinizing the benefits and side effects of first-line antihypertensive treatment. CLINICAL TRIAL REGISTRATION: URL: https://www.isrctn.com. Unique identifier: ISRCTN40973936

Land degradation and climate change: opportunities for building climate resilience in agriculture

Land degradation and climate change pose enormous risks to global food security. Land degradation increases the vulnerability of agroecological systems to climate change and reduces the effectiveness of adaptation options. Yet these interactions have largely been omitted from climate impact assessments and adaptation planning. We examine how land degradation can influence climate-change impacts and the adaptive capacity of crop and livestock producers across agroecological systems. We then present novel strategies for climate-resilient agriculture that support opportunities to integrate responses to these challenges. Forward-looking, climate-resilient agriculture requires: (1) incorporation of land degradation processes, and their linkages with adaptive capacity, into adaptation planning; (2) identification of key vulnerabilities to prioritize adaptation responses; (3) improved knowledge exchange across local to global scales to support strategies for developing the adaptive capacity of producers; and (4) innovative management and policy options that provide multiple “wins” for land, climate, and biodiversity, thus enabling global development and food security goals to be achieved

Biallelic CPAMD8 variants are a frequent cause of childhood and juvenile open-angle glaucoma

Purpose: Developmental abnormalities of the ocular anterior segment in some cases can lead to ocular hypertension and glaucoma. CPAMD8 is a gene of unknown function recently associated with ocular anterior segment dysgenesis, myopia, and ectopia lentis. We sought to assess the contribution of biallelic CPAMD8 variants to childhood and juvenile open-angle glaucoma. Design: Retrospective, multicenter case series. Participants: A total of 268 probands and their relatives with a diagnosis of childhood or juvenile open-angle glaucoma. Methods: Patients underwent a comprehensive ophthalmic assessment, with DNA from patients and their relatives subjected to genome, exome, or capillary sequencing. CPAMD8 RNA expression analysis was performed on tissues dissected from cadaveric human eyes. Main outcome measures: Diagnostic yield within a cohort of childhood and juvenile open-angle glaucoma, prevalence and risk of ophthalmic phenotypes, and relative expression of CPAMD8 in the human eye. Results: We identified rare (allele frequency -5) biallelic CPAMD8 variants in 5.7% (5/88) of probands with childhood glaucoma and 2.1% (2/96) of probands with juvenile open-angle glaucoma. When including family members, we identified 11 individuals with biallelic variants in CPAMD8 from 7 unrelated families. Nine of these individuals were diagnosed with glaucoma (9/11, 81.8%), with a mean age at diagnosis of 9.22±14.89 years, and all individuals with glaucoma required 1 or more incisional procedures to control high intraocular pressure. Iris abnormalities were observed in 9 of 11 individuals, cataract was observed in 8 of 11 individuals (72.7%), and retinal detachment was observed in 3 of 11 individuals (27.3%). CPAMD8 expression was highest in neural crest-derived tissues of the adult anterior segment, suggesting that CPAMD8 variation may cause malformation or obstruction of key drainage structures. Conclusions: Biallelic CPAMD8 variation was associated with a highly heterogeneous phenotype and in our cohorts was the second most common inherited cause of childhood glaucoma after CYP1B1 and juvenile open-angle glaucoma after MYOC. CPAMD8 sequencing should be considered in the investigation of both childhood and juvenile open-angle glaucoma, particularly when associated with iris abnormalities, cataract, or retinal detachment

Measuring Coverage in MNCH:A Validation Study Linking Population Survey Derived Coverage to Maternal, Newborn, and Child Health Care Records in Rural China

Accurate data on coverage of key maternal, newborn, and child health (MNCH) interventions are crucial for monitoring progress toward the Millennium Development Goals 4 and 5. Coverage estimates are primarily obtained from routine population surveys through self-reporting, the validity of which is not well understood. We aimed to examine the validity of the coverage of selected MNCH interventions in Gongcheng County, China.We conducted a validation study by comparing women's self-reported coverage of MNCH interventions relating to antenatal and postnatal care, mode of delivery, and child vaccinations in a community survey with their paper- and electronic-based health care records, treating the health care records as the reference standard. Of 936 women recruited, 914 (97.6%) completed the survey. Results show that self-reported coverage of these interventions had moderate to high sensitivity (0.57 [95% confidence interval (CI): 0.50-0.63] to 0.99 [95% CI: 0.98-1.00]) and low to high specificity (0 to 0.83 [95% CI: 0.80-0.86]). Despite varying overall validity, with the area under the receiver operating characteristic curve (AUC) ranging between 0.49 [95% CI: 0.39-0.57] and 0.90 [95% CI: 0.88-0.92], bias in the coverage estimates at the population level was small to moderate, with the test to actual positive (TAP) ratio ranging between 0.8 and 1.5 for 24 of the 28 indicators examined. Our ability to accurately estimate validity was affected by several caveats associated with the reference standard. Caution should be exercised when generalizing the results to other settings.The overall validity of self-reported coverage was moderate across selected MNCH indicators. However, at the population level, self-reported coverage appears to have small to moderate degree of bias. Accuracy of the coverage was particularly high for indicators with high recorded coverage or low recorded coverage but high specificity. The study provides insights into the accuracy of self-reports based on a population survey in low- and middle-income countries. Similar studies applying an improved reference standard are warranted in the future

A randomised trial into the effect of an isolated hip abductor strengthening programme and a functional motor control programme on knee kinematics and hip muscle strength

Background: Dynamic knee valgus and internal femoral rotation are proposed to be contributory risk factors for patellofemoral pain and anterior cruciate ligament injuries. Multimodal interventions including hip abductor strengthening or functional motor control programmes have a positive impact of pain, however their effect on knee kinematics and muscle strength is less clear. The aim of this study was to examine the effect of isolated hip abductor strengthening and a functional motor control exercise on knee kinematics and hip abductor strength. Methods: This prospective, randomised, repeated measures design included 29 asymptomatic volunteers presenting with increase knee valgus and femoral internal rotation. Participants completed either isolated hip abductor strengthening or a functional motor control exercise for 5 weeks. Knee kinematics were measured using inertial sensors during 2 functional activities and hip abductor strength measured using a load cell during isometric hip abduction. Results: There were no significant differences in dynamic knee valgus and internal rotation following the isolated hip abductor or functional motor control intervention, and no significant differences between the groups for knee angles. Despite this, the actual magnitude of reduction in valgus was 10° and 5° for the functional motor control group and strengthening group respectively. The actual magnitude of reduction in internal rotation was 9° and 18° for the functional motor control group and strengthening group respectively. Therefore there was a tendency towards clinically significant improvements in knee kinematics in both exercise groups. A statistically significant improvement in hip abductor strength was evident for the functional motor control group (27% increase; p = 0.008) and strengthening group (35% increase; p = 0.009) with no significant difference between the groups being identified (p = 0.475). Conclusions: Isolated hip strengthening and functional motor control exercises resulted in non-statistically significant changes in knee kinematics, however there was a clear trend towards clinically meaningful reductions in valgus and internal rotation. Both groups demonstrated similar significant gains in hip abductor strength suggesting\ud either approach could be used to strengthen the hip abductors

Interfacility Helicopter Ambulance Transport of Neurosurgical Patients: Observations, Utilization, and Outcomes from a Quaternary Level Care Hospital

The clinical benefit of helicopter transport over ground transportation for interfacility transport is unproven. We sought to determine actual practice patterns, utilization, and outcomes of patients undergoing interfacility transport for neurosurgical conditions.We retrospectively examined all interfacility helicopter transfers to a single trauma center during 2008. We restricted our analysis to those transfers leading either to admission to the neurosurgical service or to formal consultation upon arrival. Major exclusion criteria included transport from the scene, death during transport, and transport to any area of the hospital other than the emergency department. The primary outcome was time interval to invasive intervention. Secondary outcomes were estimated ground transportation times from the referring hospital, admitting disposition, and discharge disposition. Of 526 candidate interfacility helicopter transfers to our emergency department in 2008, we identified 167 meeting study criteria. Seventy-five (45%) of these patients underwent neurosurgical intervention. The median time to neurosurgical intervention ranged from 1.0 to 117.8 hours, varying depending on the diagnosis. For 101 (60%) of the patients, estimated driving time from the referring institution was less than one hour. Four patients (2%) expired in the emergency department, and 34 patients (20%) were admitted to a non-ICU setting. Six patients were discharged home within 24 hours. For those admitted, in-hospital mortality was 28%.Many patients undergoing interfacility transfer for neurosurgical evaluation are inappropriately triaged to helicopter transport, as evidenced by actual times to intervention at the accepting institution and estimated ground transportation times from the referring institution. In a time when there is growing interest in health care cost containment, practitioners must exercise discretion in the selection of patients for air ambulance transport--particularly when it may not bear influence on clinical outcome. Neurosurgical evaluation via telemedicine may be one strategy for improving air transport triage

Going to sleep in the supine position is a modifiable risk factor for late pregnancy stillbirth; findings from the New Zealand multicentre stillbirth case-control study

Objective: Our objective was to test the primary hypothesis that maternal non-left, in particular supine going-to-sleep position, would be a risk factor for late stillbirth (≥28 weeks of gestation). Methods: A multicentre case-control study was conducted in seven New Zealand health regions, between February 2012 and December 2015. Cases (n=164) were women with singleton pregnancies and late stillbirth, without congenital abnormality. Controls (n=569) were women with on-going singleton pregnancies, randomly selected and frequency matched for health region and gestation. The primary outcome was adjusted odds of late stillbirth associated with self-reported going-to-sleep position, on the last night. The last night was the night before the late stillbirth was thought to have occurred or the night before interview for controls. Going to- sleep position on the last night was categorised as: supine, left-side, right-side, propped or restless. Multivariable logistic regression adjusted for known confounders. Results: Supine going-to-sleep position on the last night was associated with increased late stillbirth risk (adjusted odds ratios (aOR) 3.67, 95% confidence interval (CI) 1.74 to 7.78) with a population attributable risk of 9.4%. Other independent risk factors for late stillbirth (aOR, 95% CI) were: BMI (1.04, 1.01 to 1.08) per unit, maternal age ≥40 (2.88, 1.31 to 6.32), birthweight <10th customised centile (2.76, 1.59 to 4.80), and <6 hours sleep on the last night (1.81, 1.14 to 2.88). The risk associated with supine-going-to sleep position was greater for term (aOR 10.26, 3.00 to 35.04) than preterm stillbirths (aOR 3.12, 0.97 to 10.05). Conclusions: Supine going-to-sleep position is associated with a 3.7 fold increase in overall late stillbirth risk, independent of other common risk factors. A public health campaign encouraging women not to go-to-sleep supine in the third trimester has potential to reduce late stillbirth by approximately 9%

Advancing the argument for validity of the Alberta Context Tool with healthcare aides in residential long-term care

<p>Abstract</p> <p>Background</p> <p>Organizational context has the potential to influence the use of new knowledge. However, despite advances in understanding the theoretical base of organizational context, its measurement has not been adequately addressed, limiting our ability to quantify and assess context in healthcare settings and thus, advance development of contextual interventions to improve patient care. We developed the Alberta Context Tool (the ACT) to address this concern. It consists of 58 items representing 10 modifiable contextual concepts. We reported the initial validation of the ACT in 2009. This paper presents the second stage of the psychometric validation of the ACT.</p> <p>Methods</p> <p>We used the <it>Standards for Educational and Psychological Testing </it>to frame our validity assessment. Data from 645 English speaking healthcare aides from 25 urban residential long-term care facilities (nursing homes) in the three Canadian Prairie Provinces were used for this stage of validation. In this stage we focused on: (1) advanced aspects of internal structure (e.g., confirmatory factor analysis) and (2) relations with other variables validity evidence. To assess reliability and validity of scores obtained using the ACT we conducted: Cronbach's alpha, confirmatory factor analysis, analysis of variance, and tests of association. We also assessed the performance of the ACT when individual responses were aggregated to the care unit level, because the instrument was developed to obtain unit-level scores of context.</p> <p>Results</p> <p>Item-total correlations exceeded acceptable standards (> 0.3) for the majority of items (51 of 58). We ran three confirmatory factor models. Model 1 (all ACT items) displayed unacceptable fit overall and for five specific items (1 item on <it>adequate space for resident care </it>in the Organizational Slack-Space ACT concept and 4 items on use of electronic resources in the Structural and Electronic Resources ACT concept). This prompted specification of two additional models. Model 2 used the 7 scaled ACT concepts while Model 3 used the 3 count-based ACT concepts. Both models displayed substantially improved fit in comparison to Model 1. Cronbach's alpha for the 10 ACT concepts ranged from 0.37 to 0.92 with 2 concepts performing below the commonly accepted standard of 0.70. Bivariate associations between the ACT concepts and instrumental research utilization levels (which the ACT should predict) were statistically significant at the 5% level for 8 of the 10 ACT concepts. The majority (8/10) of the ACT concepts also showed a statistically significant trend of increasing mean scores when arrayed across the lowest to the highest levels of instrumental research use.</p> <p>Conclusions</p> <p>The validation process in this study demonstrated additional empirical support for construct validity of the ACT, when completed by healthcare aides in nursing homes. The overall pattern of the data was consistent with the structure hypothesized in the development of the ACT and supports the ACT as an appropriate measure for assessing organizational context in nursing homes. Caution should be applied in using the one space and four electronic resource items that displayed misfit in this study with healthcare aides until further assessments are made.</p