1,262 research outputs found

    Room-temperature Polymerisation Of Ethylene On A Tio2 (anatase) Surface; Infrared Spectroscopic Evidence For An Alkylidene-ti4+ Polymer End-group And For A 'hydrogen-bonding' Type Of Interaction Of Ch Bonds Of The Polymer Chain With The Oxide Surface

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    An infrared spectroscopic study of the spontaneous polymerisation of ethylene on a sulphate-containing TiO2 (anatase) sample shows evidence for an alkylidene surface end-group of the polymer and for substantial perturbation of CH2 groups of the polymer chain by interaction with the oxide surface.2112581259DARPA; Defense Advanced Research Projects Agency; NSF; Defense Advanced Research Projects Agenc

    Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice

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    Evaluating presentation formats of local climate change in community planning with regard to process and outcomes

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    This study synthesizes two evaluations of a local climate change planning process in a rural town in British Columbia (Canada), which was supported through landscape visualizations. First, the impact of the visualizations, based on scientific environmental modeling and presented in three different presentation formats, verbal/visual presentation, posters and a virtual globe, was evaluated with regard to immediate impacts during the process. Second, the long-term impacts on decision-making and actual outcomes were evaluated in a retrospective evaluation 22 months after the end of the initial planning process. Two results are highlighted: according to the quantitative pre-/post-questionnaires, the visualizations contributed to increased awareness and understanding. Most importantly, the retrospective evaluation indicated that the process informed policy, operational and built changes in Kimberley, in which the landscape visualizations played a role. The post interviews with key decision-makers showed that they remembered most of the visualizations and some decision-makers were further using them, particularly the posters. The virtual globe seemed to be not a "sustainable" display format suitable for formal decision-making processes such as council meetings though. That may change with the further mainstreaming of visualization technologies or mobile devices. Until then, we recommend using display formats that can be re-used following a specific planning event such as an Open House, to ensure on-going support for effective decision-making over the longer-term

    Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor

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    Some residues in the cystic fibrosis transmembrane conductance regulator (CFTR) channel are the site of more than one CFTR variant that cause cystic fibrosis. Here, we investigated the function of S1159F and S1159P, two variants associated with different clinical phenotypes, which affect the same pore-lining residue in transmembrane segment 12 that are both strongly potentiated by ivacaftor when expressed in CFBE41o− bronchial epithelial cells. To study the single-channel behaviour of CFTR, we applied the patch-clamp technique to Chinese hamster ovary cells heterologously expressing CFTR variants incubated at 27°C to enhance channel residence at the plasma membrane. S1159F- and S1159P-CFTR formed Cl− channels activated by cAMP-dependent phosphorylation and gated by ATP that exhibited thermostability at 37°C. Both variants modestly reduced the single-channel conductance of CFTR. By severely attenuating channel gating, S1159F- and S1159P-CFTR reduced the open probability (Po) of wild-type CFTR by ≥75% at ATP (1 mM); S1159F-CFTR caused the greater decrease in Po consistent with its more severe clinical phenotype. Ivacaftor (10–100 nM) doubled the Po of both CFTR variants without restoring Po values to wild-type levels, but concomitantly, ivacaftor decreased current flow through open channels. For S1159F-CFTR, the reduction of current flow was marked at high (supersaturated) ivacaftor concentrations (0.5–1 μM) and voltage-independent, identifying an additional detrimental action of elevated ivacaftor concentrations. In conclusion, S1159F and S1159P are gating variants, which also affect CFTR processing and conduction, but not stability, necessitating the use of combinations of CFTR modulators to optimally restore their channel activity

    Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease

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    BACKGROUND: There is growing support for a biopsy avoidant approach to diagnose coeliac disease in both children and adults, using a serological diagnosis instead. AIMS: To assess the diagnostic accuracy of serological tests for coeliac disease in adults and children. METHODS: Seven electronic databases were searched between January 1990 and August 2020. Eligible diagnostic studies evaluated the accuracy of serological tests for coeliac disease against duodenal biopsy. Risk of bias assessment was performed using QUADAS-2. Bivariate random-effects meta-analyses were used to estimate serology sensitivity and specificity at the most commonly reported thresholds. RESULTS: 113 studies (n = 28,338) were included, all in secondary care populations. A subset of studies were included in meta-analyses due to variations in diagnostic thresholds. Summary sensitivity and specificity of immunoglobulin A (IgA) anti-tissue transglutaminase were 90.7% (95% confidence interval: 87.3%, 93.2%) and 87.4% (84.4%, 90.0%) in adults (5 studies) and 97.7% (91.0%, 99.4%) and 70.2% (39.3%, 89.6%) in children (6 studies); and of IgA endomysial antibodies were 88.0% (75.2%, 94.7%) and 99.6% (92.3%, 100%) in adults (5 studies) and 94.5% (88.9%, 97.3%) and 93.8% (85.2%, 97.5%) in children (5 studies). CONCLUSIONS: Anti-tissue transglutaminase sensitivity appears to be sufficient to rule out coeliac disease in children. The high specificity of endomysial antibody in adults supports its use to rule in coeliac disease. This evidence underpins the current development of clinical guidelines for a serological diagnosis of coeliac disease. Studies in primary care are needed to evaluate serological testing strategies in this setting

    The accommodative ciliary muscle function is preserved in older humans

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    Presbyopia, the loss of the eye’s accommodation capability, affects all humans aged above 45–50 years old. The two main reasons for this to happen are a hardening of the crystalline lens and a reduction of the ciliary muscle functionality with age. While there seems to be at least some partial accommodating functionality of the ciliary muscle at early presbyopic ages, it is not yet clear whether the muscle is still active at more advanced ages. Previous techniques used to visualize the accommodation mechanism of the ciliary muscle are complicated to apply in the older subjects, as they typically require fixation stability during long measurement times and/or to have an ultrasound probe directly in contact with the eye. Instead, we used our own developed method based on high-speed recording of lens wobbling to study the ciliary muscle activity in a small group of pseudophakic subjects (around 80 years old). There was a significant activity of the muscle, clearly able to contract under binocular stimulation of accommodation. This supports a purely lenticular-based theory of presbyopia and it might stimulate the search for new solutions to presbyopia by making use of the remaining contraction force still presented in the aging eye

    Present Limits to Heat-Adaptability in Corals and Population-Level Responses to Climate Extremes

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    Climate change scenarios suggest an increase in tropical ocean temperature by 1–3°C by 2099, potentially killing many coral reefs. But Arabian/Persian Gulf corals already exist in this future thermal environment predicted for most tropical reefs and survived severe bleaching in 2010, one of the hottest years on record. Exposure to 33–35°C was on average twice as long as in non-bleaching years. Gulf corals bleached after exposure to temperatures above 34°C for a total of 8 weeks of which 3 weeks were above 35°C. This is more heat than any other corals can survive, providing an insight into the present limits of holobiont adaptation. We show that average temperatures as well as heat-waves in the Gulf have been increasing, that coral population levels will fluctuate strongly, and reef-building capability will be compromised. This, in combination with ocean acidification and significant local threats posed by rampant coastal development puts even these most heat-adapted corals at risk. WWF considers the Gulf ecoregion as “critically endangered”. We argue here that Gulf corals should be considered for assisted migration to the tropical Indo-Pacific. This would have the double benefit of avoiding local extinction of the world's most heat-adapted holobionts while at the same time introducing their genetic information to populations naïve to such extremes, potentially assisting their survival. Thus, the heat-adaptation acquired by Gulf corals over 6 k, could benefit tropical Indo-Pacific corals who have <100 y until they will experience a similarly harsh climate. Population models suggest that the heat-adapted corals could become dominant on tropical reefs within ∼20 years

    Comparison of Multiparametric Magnetic Resonance Imaging and Targeted Biopsy with Systematic Biopsy Alone for the Diagnosis of Prostate Cancer: A Systematic Review and Meta-analysis

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    This is the final version. Available from JAMA Network via the DOI in this record. Importance: The current diagnostic pathway for patients with suspected prostate cancer (PCa) includes prostate biopsy. A large proportion of individuals who undergo biopsy have either no PCa or low-risk disease that does not require treatment. Unnecessary biopsies may potentially be avoided with prebiopsy imaging. Objective: To compare the performance of systematic transrectal ultrasonography-guided prostate biopsy vs prebiopsy biparametric or multiparametric magnetic resonance imaging (MRI) followed by targeted biopsy with or without systematic biopsy. Data Sources: MEDLINE, Embase, Cochrane, Web of Science, clinical trial registries, and reference lists of recent reviews were searched through December 2018 for randomized clinical trials using the terms "prostate cancer" and "MRI." Study Selection: Randomized clinical trials comparing diagnostic pathways including prebiopsy MRI vs systematic transrectal ultrasonography-guided biopsy in biopsy-naive men with a clinical suspicion of PCa. Data Extraction and Synthesis: Data were pooled using random-effects meta-analysis. Risk of bias was assessed using the revised Cochrane tool. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. All review stages were conducted by 2 reviewers. Main Outcomes and Measures: Detection rate of clinically significant and insignificant PCa, number of biopsy procedures, number of biopsy cores taken, and complications. Results: Seven high-quality trials (2582 patients) were included. Compared with systematic transrectal ultrasonography-guided biopsy alone, MRI with or without targeted biopsy was associated with a 57% (95% CI, 2%-141%) improvement in the detection of clinically significant PCa, a 33% (95% CI, 23%-45%) potential reduction in the number of biopsy procedures, and a 77% (95% CI, 60%-93%) reduction in the number of cores taken per procedure. One trial showed reduced pain and bleeding adverse effects. Systematic sampling of the prostate in addition to the acquisition of targeted cores did not significantly improve the detection of clinically significant PCa compared with systematic biopsy alone. Conclusions and Relevance: In this meta-analysis, prebiopsy MRI combined with targeted biopsy vs systematic transrectal ultrasonography-guided biopsy alone was associated with improved detection of clinically significant PCa, despite substantial heterogeneity among trials. Prebiopsy MRI was associated with a reduced number of individual biopsy cores taken per procedure and with reduced adverse effects, and it potentially prevented unnecessary biopsies in some individuals. This evidence supports implementation of prebiopsy MRI into diagnostic pathways for suspected PCa.National Institute for Institute for Health Research (NIHR)Cancer Research U
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