561 research outputs found

    Evaluation of SLC11A1 as an inflammatory bowel disease candidate gene

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    BACKGROUND: Significant evidence suggests that a promoter polymorphism withinthe gene SLC11A1 is involved in susceptibility to both autoimmune and infectious disorders. The aim of this study was to evaluate whether SLC11A1 has a role in the susceptibility to inflammatory bowel disease (IBD) by characterizing a promoter polymorphism within the gene and two short tandem repeat (STR) markers in genetic proximity to SLC11A1. METHODS: The studied population consisted of 484 Caucasians with IBD, 144 population controls, and 348 non-IBD-affected first-degree relatives of IBD patients. IBD subjects were re-categorized at the sub-disease phenotypic level to characterize possible SLC11A1 genotype-phenotype correlations. Polymorphic markers were amplified from germline DNA and typed using gel electrophoresis. Genotype-phenotype correlations were defined using case-control, haplotype, and family-based association studies. RESULTS: This study did not provide compelling evidence for SLC11A1 disease association; most significantly, there was no apparent evidence of SLC11A1 promoter allele association in the studied Crohn's disease population. CONCLUSION: Our results therefore refute previous studies that have shown SLC11A1 promoter polymorphisms are involved in susceptibility to this form of IBD

    Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity

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    Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson\u27s disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50 – 70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN − and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10 – 12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson\u27s disease

    Cardiac device implantation and device usage in Fabry and hypertrophic cardiomyopathy

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    Background: Fabry disease (FD) is a treatable X-linked condition leading to progressive cardiac disease, arrhythmia and premature death. We aimed to increase awareness of the arrhythmogenicity of Fabry cardiomyopathy, by comparing device usage in patients with Fabry cardiomyopathy and sarcomeric HCM. All Fabry patients with an implantable cardioverter defibrillator (ICD) implanted in the UK over a 17 year period were included. A comparator group of HCM patients, with primary prevention ICD implantation, were captured from a regional registry database. Results: Indications for ICD in FD varied with 72% implanted for primary prevention based on multiple potential risk factors. In FD and HCM primary prevention devices, arrhythmia occurred more frequently in FD over shorter follow-up (HR 4.2, p < 0.001). VT requiring therapy was more common in FD (HR 4.5, p = 0.002). Immediate shock therapy for sustained VT was also more common (HR 2.5, p < 0.001). There was a greater burden of AF needing anticoagulation and NSVT in FD (AF: HR 6.2, p = 0.004, NSVT: HR 3.1, p < 0.001). Conclusion: This study demonstrates arrhythmia burden and ICD usage in FD is high, suggesting that Fabry cardiomyopathy may be more ‘arrhythmogenic’ than previously thought. Existing risk models cannot be mutually applicable and further research is needed to provide clarity in managing Fabry patients with cardiac involvement

    Methods to estimate aboveground wood productivity from long-term forest inventory plots

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    Forest inventory plots are widely used to estimate biomass carbon storage and its change over time. While there has been much debate and exploration of the analytical methods for calculating biomass, the methods used to determine rates of wood production have not been evaluated to the same degree. This affects assessment of ecosystem fluxes and may have wider implications if inventory data are used to parameterise biospheric models, or scaled to large areas in assessments of carbon sequestration. Here we use a dataset of 35 long-term Amazonian forest inventory plots to test different methods of calculating wood production rates. These address potential biases associated with three issues that routinely impact the interpretation of tree measurement data: (1) changes in the point of measurement (POM) of stem diameter as trees grow over time; (2) unequal length of time between censuses; and (3) the treatment of trees that pass the minimum diameter threshold (“recruits”). We derive corrections that control for changing POM height, that account for the unobserved growth of trees that die within census intervals, and that explore different assumptions regarding the growth of recruits during the previous census interval. For our dataset we find that annual aboveground coarse wood production (AGWP; in Mg ha−1 year−1 of dry matter) is underestimated on average by 9.2% if corrections are not made to control for changes in POM height. Failure to control for the length of sampling intervals results in a mean underestimation of 2.7% in annual AGWP in our plots for a mean interval length of 3.6 years. Different methods for treating recruits result in mean differences of up to 8.1% in AGWP. In general, the greater the length of time a plot is sampled for and the greater the time elapsed between censuses, the greater the tendency to underestimate wood production. We recommend that POM changes, census interval length, and the contribution of recruits should all be accounted for when estimating productivity rates, and suggest methods for doing this.European UnionUK Natural Environment Research CouncilGordon and Betty Moore FoundationCASE sponsorship from UNEP-WCMCRoyal Society University Research FellowshipERC Advanced Grant “Tropical Forests in the Changing Earth System”Royal Society Wolfson Research Merit Awar

    Unique genomic profile of fibrolamellar hepatocellular carcinoma

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    BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary hepatic cancer that develops in children and young adults without cirrhosis. Little is known about its pathogenesis, and it can be treated only with surgery. We performed an integrative genomic analysis of a large series of patients with FLC to identify associated genetic factors. METHODS: By using 78 clinically annotated FLC samples, we performed whole-transcriptome (n = 58), single-nucleotide polymorphism array (n = 41), and next-generation sequencing (n = 48) analyses; we also assessed the prevalence of the DNAJB1-PRKACA fusion transcript associated with this cancer (n = 73). We performed class discovery using non-negative matrix factorization, and functional annotation using gene-set enrichment analyses, nearest template prediction, ingenuity pathway analyses, and immunohistochemistry. The genomic identification of significant targets in a cancer algorithm was used to identify chromosomal aberrations, MuTect and VarScan2 were used to identify somatic mutations, and the random survival forest was used to determine patient prognoses. Findings were validated in an independent cohort. RESULTS: Unsupervised gene expression clustering showed 3 robust molecular classes of tumors: the proliferation class (51% of samples) had altered expression of genes that regulate proliferation and mammalian target of rapamycin signaling activation; the inflammation class (26% of samples) had altered expression of genes that regulate inflammation and cytokine enriched production; and the unannotated class (23% of samples) had a gene expression signature that was not associated previously with liver tumors. Expression of genes that regulate neuroendocrine function, as well as histologic markers of cholangiocytes and hepatocytes, were detected in all 3 classes. FLCs had few copy number variations; the most frequent were focal amplification at 8q24.3 (in 12.5% of samples), and deletions at 19p13 (in 28% of samples) and 22q13.32 (in 25% of samples). The DNAJB1-PRKACA fusion transcript was detected in 79% of samples. FLC samples also contained mutations in cancer-related genes such as BRCA2 (in 4.2% of samples), which are uncommon in liver neoplasms. However, FLCs did not contain mutations most commonly detected in liver cancers. We identified an 8-gene signature that predicted survival of patients with FLC. CONCLUSIONS: In a genomic analysis of 78 FLC samples, we identified 3 classes based on gene expression profiles. FLCs contain mutations and chromosomal aberrations not previously associated with liver cancer, and almost 80% contain the DNAJB1-PRKACA fusion transcript. By using this information, we identified a gene signature that is associated with patient survival time

    Essential indicators for measuring site‐based conservation effectiveness in the post‐2020 global biodiversity framework

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    Abstract: Work on the post‐2020 global biodiversity framework is now well advanced and will outline a vision, goals, and targets for the next decade of biodiversity conservation and beyond. For the effectiveness of Protected areas and Other Effective area‐based Conservation Measures, an indicator has been proposed for “areas meeting their documented ecological objectives.” However, the Convention on Biological Diversity (CBD) has not identified or agreed on what data should inform this indicator. Here we draw on experiences from the assessment of protected area effectiveness in the CBD's previous strategic plan to provide recommendations on the essential elements related to biodiversity outcomes and management that need to be captured in this updated indicator as well as how this could be done. Our proposed protected area effectiveness indicators include a combination of remotely derived products for all protected areas, combined with data from monitoring of both protected area management and trends in species and ecosystems based on field observations. Additionally, we highlight the need for creating a digital infrastructure to operationalize national‐level data‐capture. We believe these steps are critical and urge the adoption of suitable protected area effectiveness indicators before the post‐2020 framework is agreed in 2021

    The impact of clinical placements on the emotional intelligence of occupational therapy, physiotherapy, speech pathology, and business students: a longitudinal study

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    Background: Emotional intelligence (EI) is a critical skill for healthcare practitioners. Minimal longitudinal research has tracked the changes in EI of therapy students over their final full-time clinical placements. Methods: The Emotional Quotient Inventory (EQ-i2.0) measured the EI of 283 therapy students and 93 business students (control group who do no clinical placements) at three time points over a 16-month period, the same period that the therapy students participated in clinical placements. Results: Analysis of the therapy students showed significant increases over the 16 months of the study in Total EI score, as well as nine other EI skills. However, large percentages of students reported declining scores in emotional expression, assertiveness, self-expression, and stress tolerance, with some students reporting low EI scores before commencing full-time extended clinical placements. Conclusions: The study contributes to new knowledge about the changing EI skills of therapy students as they complete their full-time, extended placements. Emotional intelligence in student therapists should be actively fostered during coursework, clinical placements and when first entering the workforce. University educators are encouraged to include EI content through the therapy curricula. Employers are encouraged to provide peer coaching, mentoring and workshops focused on EI skills to recent graduates
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