284 research outputs found

    Recruitment of ethnic minority patients to a cardiac rehabilitation trial: The Birmingham Rehabilitation Uptake Maximisation (BRUM) study [ISRCTN72884263]

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    Background: Concerns have been raised about low participation rates of people from minority ethnic groups in clinical trials. However, the evidence is unclear as many studies do not report the ethnicity of participants and there is insufficient information about the reasons for ineligibility by ethnic group. Where there are data, there remains the key question as to whether ethnic minorities more likely to be ineligible (e.g. due to language) or decline to participate. We have addressed these questions in relation to the Birmingham Rehabilitation Uptake Maximisation (BRUM) study, a randomized controlled trial (RCT) comparing a home-based with a hospital-based cardiac rehabilitation programme in a multi-ethnic population in the UK. Methods: Analysis of the ethnicity, age and sex of presenting and recruited subjects for a trial of cardiac rehabilitation in the West-Midlands, UK. Participants: 1997 patients presenting post-myocardial infarction, percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Data collected: exclusion rates, reasons for exclusion and reasons for declining to participate in the trial by ethnic group. Results: Significantly more patients of South Asian ethnicity were excluded (52% of 'South Asian' v 36% 'White European' and 36% 'Other', p < 0.001). This difference in eligibility was primarily due to exclusion on the basis of language (i.e. the inability to speak English or Punjabi). Of those eligible, similar proportions were recruited from the different ethnic groups (white, South Asian and other). There was a marked difference in eligibility between people of Indian, Pakistani or Bangladeshi origin

    Phoenix: A CubeSat Mission to Study the Impact of Urban Heat Islands Within the U.S.

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    Phoenix is a student-led CubeSat mission, developed at Arizona State University (ASU), to study the effects of Urban Heat Islands in several U.S. cities through infrared remote sensing and educate students on space mission design. The spacecraft is designed using commercial off-the-shelf components (COTS) and several custom support boards developed by the student team. As such, the student team was responsible for the design, test, and validation of the spacecraft to demonstrate the capability of using COTS hardware to conduct high-fidelity science. This paper details the mission’s concept of operations, as well as the spacecraft and ground system design that was developed to complete the mission objective. In addition, it details the mission’s current status now that Phoenix has entered the operations phase, along with resources which have proved beneficial to the team while working with the spacecraft in orbit

    INDIRECT ORGANOGENESIS FROM LEAF EXPLANTS AND IN VITRO SHOOTS LTIPLICATION OF Eucalyptus benthamii X Eucalyptus dunnii

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    Os objetivos deste trabalho foram avaliar diferentes meios de cultura na organog\ueanese indireta e na multiplica\ue7\ue3o in vitro de brotos de Eucalyptus benthamii x Eucalyptus dunnii . Para organog\ueanese, explantes foliares foram excisados no sentido transversal e cultivados in vitro, sendo os seguintes fatores testados: dois meios de cultura (MS N/2 e JADS) adicionados de 0,1 \u3bcM de ANA, duas concentra\ue7\uf5es de thidiazuron (0,1 e 0,5 \u3bcM) e presen\ue7a ou n\ue3o de PVP-40 (250 mg L-1). Ap\uf3s 70 dias de cultivo foram avaliadas as porcentagens de explantes oxidados totalmente, formando calo, produzindo antocianina, formando gema, formando brota\ue7\uf5es e o n\ufamero de brota\ue7\uf5es formadas por explante regenerando. No experimento de multiplica\ue7\ue3o, brota\ue7\uf5es isoladas foram cultivadas em meio MS, JADS e WPM, adicionados de 1,11 \u3bcM de BAP. Foram realizados quatro subcultivos a cada 28 dias e em cada subcultivo foram avaliados: a porcentagem de oxida\ue7\ue3o, de explantes apresentando clorose total ou parcial, massa fresca e n\ufamero m\ue9dio de brotos por explante. O meio de cultura MS N/2 suplementado com 0,1 \u3bcM de ANA, 0,5 \u3bcM de TDZ e PVP-40 promoveu a maior taxa de organog\ueanese (8,3%). No meio de cultura MS com 1,11 \u3bcM de BAP, a taxa de multiplica\ue7\ue3o foi maior que nos outros meios, no primeiro e segundo subcultivos (9,28 e 9,24 por m\ueas), n\ue3o havendo diferen\ue7a entre os tr\ueas meios nos demais subcultivos.The aims of this research were to evaluate different culture media for indirect organogenesis and shoot multiplication of Eucalyptus benthamii x Eucalyptus dunnii . For organogenesis, leaf explants were used to test the following treatments: two culture media (MS N/2 and JADS) supplemented with 0.1 \u3bcM 1-naphthaleneacetic acid (NAA) and thidiazuron (TDZ) (0.1 or 0.5 \u3bcM), with or without PVP- 40 (250 mg L-1). The percentage of oxidized explants, callus forming explants, explants with anthocyanin, buds, shoots and the shoot number per explant were evaluated. In the multiplication experiment, isolated shoots were cultivated in MS, JADS and WPM media, all supplemented with 1.11 \u3bcM BAP. Four subcultures were carried out every 28 days. In every subculture the explant oxidation, partial or total leaf chlorosis, fresh mass and mean number of shoot per explant were evaluated. The MS N/2 medium supplemented with 0.1 \u3bcM NAA and 0.5 \u3bcM TDZ promoted the highest rate of organogenesis (8.3%) and the culture media MS supplemented with 1.11 \u3bcM BAP the multiplication rate was higher than in the other media, in the first and the second subcultures (9.28 and 9.24, respectively), without differences between the three media in the following subcultures

    Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

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    BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Improvement of the high-accuracy O 17 ( p , α ) N 14 reaction-rate measurement via the Trojan Horse method for application to O 17 nucleosynthesis

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    The ^{17}\text{O}(p,\ensuremath{\alpha})^{14}\text{N} and ^{17}\text{O}(p,\ensuremath{\gamma})^{18}\text{F} reactions are of paramount importance for the nucleosynthesis in a number of stellar sites, including red giants (RGs), asymptotic giant branch (AGB) stars, massive stars, and classical novae. In particular, they govern the destruction of 17O^{17}\text{O} and the formation of the short-lived radioisotope 18F^{18}\text{F}, which is of special interest for \ensuremath{\gamma}-ray astronomy. At temperatures typical of the above-mentioned astrophysical scenario, T=0.01T=0.01--0.1 GK for RG, AGB, and massive stars and T=0.1T=0.1--0.4 GK for a classical nova explosion, the ^{17}\text{O}(p,\ensuremath{\alpha})^{14}\text{N} reaction cross section is dominated by two resonances: one at about ERcm=65{E}_{R}^{cm}=65 keV above the 18F^{18}\text{F} proton threshold energy, corresponding to the EX=5.673{E}_{X}=5.673 MeV level in 18F^{18}\text{F}, and another one at ERcm=183{E}_{R}^{cm}=183 keV (EX=5.786({E}_{X}=5.786 MeV). We report on the indirect study of the ^{17}\text{O}(p,\ensuremath{\alpha})^{14}\text{N} reaction via the Trojan Horse method by applying the approach recently developed for extracting the strength of narrow resonance at ultralow energies. The mean value of the strengths obtained in the two measurements was calculated and compared with the direct data available in literature. This value was used as input parameter for reaction-rate determination and its comparison with the result of the direct measurement is also discussed in the light of the electron screening effect

    Genotyping with a 198 Mutation Arrayed Primer Extension Array for Hereditary Hearing Loss: Assessment of Its Diagnostic Value for Medical Practice

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    Molecular diagnostic testing of individuals with congenital sensorineural hearing loss typically begins with DNA sequencing of the GJB2 gene. If the cause of the hearing loss is not identified in GJB2, additional testing can be ordered. However, the step-wise analysis of several genes often results in a protracted diagnostic process. The more comprehensive Hereditary Hearing Loss Arrayed Primer Extension microarray enables analysis of 198 mutations across eight genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5, MTRNR1 and MTTS1) in a single test. To evaluate the added diagnostic value of this microarray for our ethnically diverse patient population, we tested 144 individuals with congenital sensorineural hearing loss who were negative for biallelic GJB2 or GJB6 mutations. The array successfully detected all GJB2 changes previously identified in the study group, confirming excellent assay performance. Additional mutations were identified in the SLC26A4, SLC26A5 and MTRNR1 genes of 12/144 individuals (8.3%), four of whom (2.8%) had genotypes consistent with pathogenicity. These results suggest that the current format of this microarray falls short of adding diagnostic value beyond the customary testing of GJB2, perhaps reflecting the array's limitations on the number of mutations included for each gene, but more likely resulting from unknown genetic contributors to this phenotype. We conclude that mutations in other hearing loss associated genes should be incorporated in the array as knowledge of the etiology of hearing loss evolves. Such future modification of the flexible configuration of the Hereditary Hearing Loss Arrayed Primer Extension microarray would improve its impact as a diagnostic tool

    COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo

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    Collagen XXV alpha 1 (COL25A1) is a collagenous type II transmembrane protein purified from senile plaques of Alzheimer’s disease (AD) brains. COL25A1 alleles have been associated with increased risk for AD in a Swedish population. COL25A1 is specifically expressed in neurons and binds to aggregated Aβ in vitro. However, its contribution to the pathogenesis of AD and in vivo function are unknown. Here, we report that over-expression of COL25A1 in transgenic mice increases p35/p25 and β-site APP-cleaving enzyme 1 (BACE1) levels, facilitates intracellular aggregation and extracellular matrix deposits of Aβ, and causes synaptophysin loss and astrocyte activation. COL25A1 mice displayed reduced anxiety-like behavior in elevated plus maze and open field tests and significantly slower swimming speed in Morris water maze. In stable cell lines, motifs in noncollagenous domains of COL25A1 were important for the induction of BACE1 expression. These findings demonstrate that COL25A1 leads to AD-like pathology in vivo. Modulation of COL25A1 function may represent an alternative therapeutic intervention for AD

    Expression of coxsackie and adenovirus receptor distinguishes transitional cancer states in therapy-induced cellular senescence

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    Therapy-induced cellular senescence describes the phenomenon of cell cycle arrest that can be invoked in cancer cells in response to chemotherapy. Sustained proliferative arrest is often overcome as a contingent of senescent tumor cells can bypass this cell cycle restriction. The mechanism regulating cell cycle re-entry of senescent cancer cells remains poorly understood. This is the first report of the isolation and characterization of two distinct transitional states in chemotherapy-induced senescent cells that share indistinguishable morphological senescence phenotypes and are functionally classified by their ability to escape cell cycle arrest. It has been observed that cell surface expression of coxsackie and adenovirus receptor (CAR) is downregulated in cancer cells treated with chemotherapy. We show the novel use of surface CAR expression and adenoviral transduction to differentiate senescent states and also show in vivo evidence of CAR downregulation in colorectal cancer patients treated with neoadjuvant chemoradiation. This study suggests that CAR is a candidate biomarker for senescence response to antitumor therapy, and CAR expression can be used to distinguish transitional states in early senescence to study fundamental regulatory events in therapy-induced senescence

    Cellular dissection of psoriasis for transcriptome analyses and the post-GWAS era

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    Abstract Background Genome-scale studies of psoriasis have been used to identify genes of potential relevance to disease mechanisms. For many identified genes, however, the cell type mediating disease activity is uncertain, which has limited our ability to design gene functional studies based on genomic findings. Methods We identified differentially expressed genes (DEGs) with altered expression in psoriasis lesions (n = 216 patients), as well as candidate genes near susceptibility loci from psoriasis GWAS studies. These gene sets were characterized based upon their expression across 10 cell types present in psoriasis lesions. Susceptibility-associated variation at intergenic (non-coding) loci was evaluated to identify sites of allele-specific transcription factor binding. Results Half of DEGs showed highest expression in skin cells, although the dominant cell type differed between psoriasis-increased DEGs (keratinocytes, 35%) and psoriasis-decreased DEGs (fibroblasts, 33%). In contrast, psoriasis GWAS candidates tended to have highest expression in immune cells (71%), with a significant fraction showing maximal expression in neutrophils (24%, P < 0.001). By identifying candidate cell types for genes near susceptibility loci, we could identify and prioritize SNPs at which susceptibility variants are predicted to influence transcription factor binding. This led to the identification of potentially causal (non-coding) SNPs for which susceptibility variants influence binding of AP-1, NF-κB, IRF1, STAT3 and STAT4. Conclusions These findings underscore the role of innate immunity in psoriasis and highlight neutrophils as a cell type linked with pathogenetic mechanisms. Assignment of candidate cell types to genes emerging from GWAS studies provides a first step towards functional analysis, and we have proposed an approach for generating hypotheses to explain GWAS hits at intergenic loci.http://deepblue.lib.umich.edu/bitstream/2027.42/109537/1/12920_2013_Article_485.pd
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