Factors Influencing the Participation of Older People in Clinical Trials : Data Analysis from the MAVIS Trial

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A self-contained wind speed, direction and location system for buoys and ships in the World Ocean Circulation Experiment

Knowledge of the absolute wind velocity near the surface of the ocean is a requirement of the World Ocean Circulation Experiment (WOCE) and other large programs directed towards understanding air-sea interactions and how ocean circulation and climate are interrelated. The measurement is made possible using IMET (Improved METeorology) modules, a next generation meteorological data acquisition system developed as part of the WOCE program. An IMET system consists of a set of intelligent modules for each measurement variable, with data being recorded on a computer, typically PC-based. The IMET wind module includes a propeller for wind speed, a vane and optical encoder for wind direction, a flux gate compass for the north reference, and microprocessor-based electronics for control and data formatting. The IMET Global Positioning System (GPS) module includes a five chanel GPS receiver and microprocessor based electronics for control and data formatting. These modules, as part of the complete measurement suite, result in a self-contained system that can make accurate measurements from research ships, drifting and moored buoys, and volunteer observing ships (VOS).Funding was provided by Grant No. OCE-8709614 from the National Science Foundation

Common variation at 12q24.13 (OAS3) influences chronic lymphocytic leukemia risk

Common variation at 12q24.13 (OAS3) influences chronic lymphocytic leukemia ris

Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial

Background Treatment of chronic lymphocytic leukaemia (CLL) has seen a substantial improvement over the last few years. Combination immunochemotherapy, such as fludarabine, cyclophosphamide and rituximab (FCR), is now standard first-line therapy. However, the majority of patients relapse and require further therapy, and so new, effective, targeted therapies that improve remission rates, reduce relapses, and have fewer side effects, are required. The FLAIR trial will assess whether ibrutinib plus rituximab (IR) is superior to FCR in terms of progression-free survival (PFS). Methods/design FLAIR is a phase III, multicentre, randomised, controlled, open, parallel-group trial in patients with previously untreated CLL. A total of 754 participants will be randomised on a 1:1 basis to receive standard therapy with FCR or IR. Participants randomised to FCR will receive a maximum of six 28-day treatment cycles. Participants randomised to IR will receive six 28-day cycles of rituximab, and ibrutinib taken daily for 6 years until minimal residual disease (MRD) negativity has been recorded for the same amount of time as it took to become MRD negative, or until disease progression. The primary endpoint is PFS according to the International Workshop on CLL (IWCLL) criteria. Secondary endpoints include: overall survival; proportion of participants with undetectable MRD; response to therapy by IWCLL criteria; safety and toxicity; health-related quality of life (QoL); and cost-effectiveness. Discussion The trial aims to provide evidence for the future first-line treatment of CLL patients by assessing whether IR is superior to FCR in terms of PFS, and whether toxicity rates are favourable. Trial registration ISRCTN01844152. Registered on 8 August 2014, EudraCT number 2013-001944-76. Registered on 26 April 2013

Development of an autonomous aerosol sampler for ocean buoys and land sites

The authors have successfully designed, built and tested an aerosol sampler which is capable of collecting, in an unattended manner, a time-series set of aerosol samples (aerosol-embedded filters) from moored ocean buoys and remote areas on land. Research on aerosols, in particular, and atmospheric chemistry, in general, has not been previously attempted from buoys. Aerosols entering and leaving the ocean play an important role in climate change, ocean productivity, pollutant transport and atmospheric optics. This report discusses (1) the scientific applications of a buoy-mounted aerosol sampler, (2) the advantages of using buoys as research platforms and (3) the authors' new instrument. Also discussed are the results of a four month test of the aerosol sampler on the AEROCE (Atmosphere/Ocean Chemistry Experiment) tower in Bermuda and the results of a three month test on a buoy moored in Vineyard Sound off Woods Hole, MA USA. The direct comparison between WHOI filters and AEROCE filters from the Bermuda tower is very encouraging as the Fe concentrations of aerosols compare to within 10-15% over a wide range of values. Aerosol sampling from a buoy moored in coastal waters was successfully tested under a variety of atmospheric and oceanic conditions.Funding was provided by the National Science Foundation through Grant No. OCE-943212

Arabian Sea mixed layer dynamics experiment : mooring deployment cruise report R/V Thomas Thompson cruise number 40, 11 October-25 October 1994

An array of surface and subsurface moorings were deployed in the Arabian Sea to provide high quality time series of local forcing and upper ocean currents, temperature, and conductivity in order to investigate the dynamics of the ocean's response to the monsoonal forcing characteristic of the area. The moored array was deployed during R/V Thomas Thompson cruise number 40, One Woods Hole Oceanographic Institution (WHOI) surface mooring, two Scripps Institution of Oceanography (SIO) surface moorings and two University of Washington (UW) Profiling Current Meter moorings were deployed. The moorings were deployed for a period of one year beginning in October 1994 as part of the Office of Naval Research (ONR) funded Arabian Sea experiment. Two six month deployments were planned. The moorings were deployed at 15.5°N 61.5°E (WHOI), 15.7°N 61.3°E (SIO), 15.3°N 61.3°E (SIO), 15.7°N 61.7°E (UW), and 15.3°N 61.7°E (UW). The WHOI surface mooring was outfitted with two meteorological data collection systems. A Vector Averaging Wind Recorder (VAWR) and an IMET system made measurements of wind speed and direction, sea surface temperature, air temperature, short wave radiation, long wave radiation, barometric pressure, relative humidity and precipitation. Subsurface instrumentation included Vector Measuring Current Meters (VMCMs), Multi-Variable Moored Systems (MVMS), conductivity and temperature recorders and single point temperature recorders. Expendable bathythermograph (XBT) data and CTD data were collected while in transit to the site and between mooring locations. This report describes in a general manner the work that took place during R/V Thomas Thompson cruise number 40 which was the initial deployment cruise for this moored array. A detailed description of the WHOI surface mooring and its instrumentation is provided. Information about the XBT and CTD data collected during the cruise is also included.Funding was provided by the Office of Naval Research under Grant No. N00014-94-1-0161

De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

Predictors of Long-term Exercise Maintenance among College Aged Adults: Role of Body Image Anxiety

Background and Purpose: Participation in regular exercise is low among young adults and is contributing to a rapid increase in obesity and chronic health conditions. Enhancing motivation is a key element in exercise initiation and maintenance. The current investigation considers factors relevant to the transtheoretical model (TTM), self-determination theory (SDT), self-efficacy (SE), and body image anxiety (BIA) in relation to college students’ motivation to exercise. Design and Main Outcome Measures: In this cross sectional study, lower division college students (N=614, 64% female, 36% male) completed an online survey of exercise behavior, motivation, SE and BIA. Results: BIA was related to both controlled extrinsic (external and introjected regulations) and autonomous extrinsic (integrated regulation) SDT motivational variables, as well as intrinsic motivation. Exercise maintenance was most strongly associated with integrated regulation, a “selfdetermined” motivational state, and SE. Conclusion: The current study provides support for the central tenet of SDT indicating that intrinsic and extrinsic motivation are not mutually exclusive constructs. Helping individuals with BIA develop a more intrinsic approach to exercise is integral for fostering long-term exercise maintenance. Thus, future research should focus on developing interventions that enhance integrated regulation and SE in order to promote exercise maintenance and reduce associated BIA

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre