53 research outputs found

    US local action on heat and health: are we prepared for climate change?

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    OBJECTIVES: Global climate change is increasing the frequency of heat waves, hot weather, and temperature variability, which contribute to mortality and illness. Baseline information on local efforts to reduce heat vulnerability, including public advisories; minimizing greenhouse gas emissions; and mitigating urban heat islands, is lacking. METHODS: We designed a survey about local government programs to prevent health problems and reduce heat exposure during heatwaves and administered it to 285 US communities. RESULTS: Of 70 respondents, 26 indicated that excessive heat events are a significant issue for the local government; 30 had established preventive programs. Local government leadership and public health impacts of heat were cited most frequently as extremely important determinants of preventive programs, followed by implementation costs, economic impacts of hot weather, and greenhouse gas emissions mitigation. Cool paving materials and vegetated roofs were common heat mitigation strategies. Fact sheets and case studies were desired guidance for protecting communities during hot weather. CONCLUSIONS: New partnerships and financial resources are needed to support more widespread local action to prevent adverse health consequences of climate change and promote environmental sustainability.http://deepblue.lib.umich.edu/bitstream/2027.42/78375/1/ONeillJackman2010_IJPH.pd

    Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

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    Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis

    Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci

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    PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

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    Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

    Task specific training and functional hand splinting for children with cerebral palsy or brain injury

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    Cerebral palsy and brain injury are common conditions of childhood that can have devastating effects on a child’s ability to use their hands. Occupational therapists use a range of treatment modalities to address difficulties with hand function in this population. Hand splints and task specific training are two treatment options that may be used. There is a lack of evidence to support hand splinting, whilst task specific training is supported by high level evidence in children with neurological conditions. In practice, these treatments may be provided in isolation or concurrently. There is currently limited evidence exploring the benefits of combining hand splints with task specific training. AIM The aim of this research was to explore the efficacy of functional hand splints and task specific training. The task specific training approach utilised was the Cognitive Orientation to daily Occupational Performance (CO-OP) Approach. METHODS This research used quantitative and qualitative methods to explore the research question. A systematic review with meta analyses was conducted to explore the current evidence regarding hand splints and upper limb task specific training. A study protocol was then devised and two concurrent randomised controlled trials completed exploring (a) the immediate effect of a hand splint, and (b) the use of a functional hand splint, compared to and combined with the CO-OP Approach. Parent interviews were conducted exploring the experience of undertaking CO-OP with their child with cerebral palsy or brain injury. Secondary analyses of RCT results were conducted to explore individual characteristics of children who responded best to CO-OP. RESULTS Meta-analyses investigating non-functional upper limb splints found a small positive effect of splints compared to no splints (SMD=0.81), although benefits were reduced 2 to 3 months after splint wearing stopped (SMD=0.35). Results of the RCT showed that functional hand splints did not lead to improvements in grasp and release immediately following application, compared to no splint (p=0.348). Participating in CO-OP was more effective than receiving a splint and practicing goals at home (GAS p=0.010). Functional hand splints did not add benefit when combined with CO-OP (COPM p=0.807). CO-OP was shown to lead to goal achievement for children with cerebral palsy or brain injury, and parents perceived CO-OP to be a beneficial treatment option for their child. CONCLUSIONS CO-OP may be an effective task specific training option for children with cerebral palsy or brain injury. There may be little benefit to prescribing functional hand splints concurrently with task specific training. There remains a lack of evidence to guide the use of upper limb splinting in this population

    Critical Life-Cycle Decision Making for Projects under Uncertainty

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    In this paper, we first describe how critical life-cycle decisions are made for projects facing significant uncertainties. The key differentiating aspect of our approach from the traditional net present value approach is regarding the timing of such decisions. For example, our emphasis is on the effective dates for the commencement and expiration (i.e., a window of opportunity) for possible actions regarding a project, which is clearly above and beyond a single shot decision of investment or no investment. Our approach is based on elementary stochastic optimal control methods, which often afford closed-form solutions on critical timing information such as the expected remaining life of a project under significant uncertainties. These analytic solutions provide managerial insights and economic implications that are simply absent in numerical results under particular sets of parameter values. We next show how we integrate our approach in a traditional engineering economy course utilizing a short, self-contained module of a few lectures. The context of the lectures is the decisions by wind farms to exit and/or enter. For this module, we administer pre- and post- tests as well as self-efficacy surveys. In addition, focus groups are utilized to obtain immediate feedback in an interactive manner. The results from the assessment of outcomes and the self-efficacy surveys, as well as the feedback from focus groups are presented. Finally, subsequent steps towards improved teaching and learning in life-cycle decision making for projects under uncertainty are outlined.This is a proceeding from the ASEE Annual Conference & Exposition (2016): doi:10.18260/p.26598. Posted with permission.</p

    Survey of Saturn’s magnetopause and bow shock positions over the entire Cassini mission: boundary statistical properties, and exploration of associated upstream conditions

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    The Cassini spacecraft orbited the planet Saturn from July 2004 to September 2017, and its varied orbital trajectory took it across the magnetopause and bow shock boundaries multiple times, at varying radial distances, local times, latitudes, and phases of the solar cycle. Here we present a comprehensive list of these boundary crossings, derived primarily using data from the Cassini magnetometer instrument, with cross‐validation against the electron spectrometer data where available. There are a multitude of scientific avenues for exploitation of this list. In this work, we examine the variability in boundary location and use the crossing times in concert with models of the bow shock and magnetopause to infer the upstream solar wind dynamic pressure at the times of crossings. This analysis allows us to understand the limitations of the Cassini trajectory for studying boundary physics under a range of solar wind driving conditions. In addition, rapid traversals of the magnetosheath are used to estimate the range of speeds of boundary motion

    Parents experience of undertaking an intensive Cognitive Orientation to daily Occupational Performance (CO-OP) group for children with cerebral palsy

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    Purpose: The purpose of this study was to explore the experience of parents of children with cerebral palsy (CP) who participated in an intensive cognitive orientation to daily occupational performance (CO-OP) group program addressing child chosen goals. Method: Participants were six parents of children with CP who participated in a CO-OP upper limb task-specific training program. Parents participated in semi-structured interviews conducted via phone. A grounded theory approach was used. Interviews were transcribed verbatim and coded to identify categories and overarching themes of the parent experience of CO-OP. Results: The theory of CO-OP for children with CP was one of offering a unique and motivating learning experience for both the child and the parent, differing from other therapeutic approaches that families had previously been involved in. Five categories were identified: the unique benefits of CO-OP; the importance of intensity; the child’s motivation; challenging the parent role; and the benefits and challenges of therapy within a group context. Conclusion: Parents felt that CO-OP was a worthwhile intervention that leads to achievement of goals involving upper limb function and had the capacity to be transferred to future goals. Intensity of therapy and a child’s motivation were identified as important factors in improvements. Further studies using quantitative research methods are warranted to investigate the benefits of CO-OP for children with neurological conditions. Implications for rehabilitation The cognitive orientation to daily occupational performance (CO-OP) is a promising upper limb cognitive motor training intervention for children with cerebral palsy. In a small sample, parents perceived that CO-OP leads to achievement of upper limb goals. Intensity of therapy, the child’s motivation and the parents’ ability to “step-back” were identified as important to the success of CO-OP

    Analysis of 2′-phosphotransferase (Tpt1p) from Saccharomyces cerevisiae: Evidence for a conserved two-step reaction mechanism

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    Tpt1p is an essential protein responsible for the 2′-phosphotransferase step of tRNA splicing in Saccharomyces cerevisiae, in which the splice junction 2′-phosphate of ligated tRNA is transferred to NAD to form mature tRNA and ADP-ribose 1″-2″ cyclic phosphate. We showed previously that Tpt1p is a member of a family of functional 2′-phosphotransferases found in eukaryotes, eubacteria, and archaea, that the Escherichia coli protein (KptA) is highly specific for 2′-phosphorylated RNAs despite the lack of obvious natural substrates, and that KptA acts on a trinucleotide substrate through an intermediate in which RNA is ADP-ribosylated at the 2′-phosphate. This mechanism is similar to a proposed mechanism of NAD-dependent histone deacetylases. We present evidence here that this mechanism is conserved in S. cerevisiae, and we identify residues important for the second step of the reaction, during which the intermediate is resolved into products. We examined 21 Tpt1 protein variants mutated in conserved residues or blocks of residues and show that one of them, Tpt1 K69A/R71S protein, accumulates large amounts of intermediate with trinucleotide substrate due to a very slow second step. This intermediate can be trapped on beads when formed with biotin-NAD. We also show that Tpt1 K69A/R71S protein forms an intermediate with the natural ligated tRNA substrate and demonstrate that, as expected, this mutation is lethal in yeast. The high degree of conservation of these residues suggests that the entire Tpt1p family is involved in a similar two-step chemical reaction
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