13,966 research outputs found

    Identifying and responding to people with mild learning disabilities in the probation service

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    It has long been recognised that, like many other individuals, people with learningdisabilities find their way into the criminal justice system. This fact is not disputed. Whathas been disputed, however, is the extent to which those with learning disabilities arerepresented within the various agencies of the criminal justice system and the ways inwhich the criminal justice system (and society) should address this. Recently, social andlegislative confusion over the best way to deal with offenders with learning disabilities andmental health problems has meant that the waters have become even more muddied.Despite current government uncertainty concerning the best way to support offenders withlearning disabilities, the probation service is likely to continue to play a key role in thesupervision of such offenders. The three studies contained herein aim to clarify the extentto which those with learning disabilities are represented in the probation service, toexamine the effectiveness of probation for them and to explore some of the ways in whichprobation could be adapted to fit their needs.Study 1 and study 2 showed that around 10% of offenders on probation in Kent appearedto have an IQ below 75, putting them in the bottom 5% of the general population. Study 3was designed to assess some of the support needs of those with learning disabilities in theprobation service, finding that many of the materials used by the probation service arelikely to be too complex for those with learning disabilities to use effectively. To addressthis, a model for service provision is tentatively suggested. This is based on the findings ofthe three studies and a pragmatic assessment of what the probation service is likely to becapable of achieving in the near future

    Study on the concordance between different SNP‐genotyping platforms in sheep

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    .Different SNP genotyping technologies are commonly used in multiple studies to perform QTL detection, genotype imputation, and genomic predictions. Therefore, genotyping errors cannot be ignored, as they can reduce the accuracy of different procedures applied in genomic selection, such as genomic imputation, genomic predictions, and false-positive results in genome-wide association studies. Currently, whole-genome resequencing (WGR) also offers the potential for variant calling analysis and high-throughput genotyping. WGR might overshadow array-based genotyping technologies due to the larger amount and precision of the genomic information provided; however, its comparatively higher price per individual still limits its use in larger populations. Thus, the objective of this work was to evaluate the accuracy of the two most popular SNP-chip technologies, namely, Affymetrix and Illumina, for high-throughput genotyping in sheep considering high-coverage WGR datasets as references. Analyses were performed using two reference sheep genome assemblies, the popular Oar_v3.1 reference genome and the latest available version Oar_rambouillet_v1.0. Our results demonstrate that the genotypes from both platforms are suggested to have high concordance rates with the genotypes determined from reference WGR datasets (96.59% and 99.51% for Affymetrix and Illumina technologies, respectively). The concordance results provided in the current study can pinpoint low reproducible markers across multiple platforms used for sheep genotyping data. Comparing results using two reference genome assemblies also informs how genome assembly quality can influence genotype concordance rates among different genotyping platforms. Moreover, we describe an efficient pipeline to test the reliability of markers included in sheep SNP-chip panels against WGR datasets available on public databases. This pipeline may be helpful for discarding low-reliability markers before exploiting genomic information for gene mapping analyses or genomic predictionS

    Biocontrol as a key component to manage brown rot on cherry

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    Brown rot, caused by Monilinia spp., is one of the most important diseases in stone fruits worldwide. Brown rot can cause blossom wilts and fruit rots in the orchard as well as latent infections of fruit, leading to post-harvest fruit decaying. Current control methods rely on scheduled spraying of fungicides. However, the continuing pressure to reduce fungicide use has seen an increase in research into alternative management methods, such as biological control. NIAB EMR recently identified two microbes that significantly reduced sporulation of Monilinia laxa under laboratory conditions. These two isolates were a bacterial species Bacillus subtilis (B91) and yeast-like fungus Aureobasidium pullulans (Y126) and are currently being formulated into commercial products. We are investigating how to optimise the use of these two potential biocontrol products in practice, in terms of suppressing Monilinia sporulation on overwintered mummies and preventing infection of blossoms and fruits. When applied to mummified fruits in winter Y126’s population was stable through the winter but at a low concentration. The B91 survived a little longer with the population reaching that of the control group by week 4. Neither Biological control (BCA) treatments had an affected the population of M. laxa when compared to the control treatment of sterile distilled water. The interaction time between the BCAs and M. laxa showed the longer the interaction time the lower the spore count of M. laxa. Another study was performed looking into the ability of our BCAs to colonise and survive on blossoms. B91 did not survive well on blossoms but could survive on fruits. However, its antagonistic compounds need to be in relatively high concentration to be effective against M. laxa. Therefore, it is best used as a fungicide, ensuring the antagonistic compounds are at a high concentration when applied in the field. Y126 can persist throughout the season and was marginally, though not statistically significantly, more effective at long term reduction in M. laxa. This could be because Y126 works through competition, therefore the interaction time with the pathogen could be important for efficacy and something worth investigating further. The difference between the BCAs highlights the need to understand each BCA’s ecology to ensure maximum efficacy. In a latent infection experiment, we inoculated trees with M. laxa and then treated them with the two biocontrol isolates two weeks before harvest. Post-harvest disease development was assessed after four days of storage in 2019 and two weeks in 2020. There was a significant reduction in rot incidence (p < 0.001) of 29% (Y126) and 27% (B91) in 2019 and 62 % (Y126) and 80 % (B91) in 2020 when the harvested fruit was stored at cold store levels. With new products to be introduced into the environment, it's important to understand the effects they may have on the plant's microbiome. Using next-generation sequencing techniques, we looked at the impact B91 and Y126 has on the blossom and cherry microbiomes. There was a treatment effect in both the bacterial and fungal communities on the blossom and ripe cherry. But the biggest variability was between blocks (Geographical effect) and between the years in which we experimented (p < 0.0001). This research will assist in the development of management strategies, especially spray timings for brown rot on stone fruit, integrating BCAs with other management practices

    Incentivising research data sharing : a scoping review

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    Background: Numerous mechanisms exist to incentivise researchers to share their data. This scoping review aims to identify and summarise evidence of the efficacy of different interventions to promote open data practices and provide an overview of current research. Methods: This scoping review is based on data identified from Web of Science and LISTA, limited from 2016 to 2021. A total of 1128 papers were screened, with 38 items being included. Items were selected if they focused on designing or evaluating an intervention or presenting an initiative to incentivise sharing. Items comprised a mixture of research papers, opinion pieces and descriptive articles. Results: Seven major themes in the literature were identified: publisher/journal data sharing policies, metrics, software solutions, research data sharing agreements in general, open science ‘badges’, funder mandates, and initiatives. Conclusions: A number of key messages for data sharing include: the need to build on existing cultures and practices, meeting people where they are and tailoring interventions to support them; the importance of publicising and explaining the policy/service widely; the need to have disciplinary data champions to model good practice and drive cultural change; the requirement to resource interventions properly; and the imperative to provide robust technical infrastructure and protocols, such as labelling of data sets, use of DOIs, data standards and use of data repositories

    Metabolic and nutritional triggers associated with increased risk of liver complications in SARS-CoV-2

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    Obesity, diabetes, cardiovascular and respiratory diseases, cancer and smoking are risk factors for negative outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can quickly induce severe respiratory failure in 5% of cases. Coronavirus disease-associated liver injury may occur during progression of SARS-CoV-2 in patients with or without pre-existing liver disease, and damage to the liver parenchyma can be caused by infection of hepatocytes. Cirrhosis patients may be particularly vulnerable to SARS-CoV-2 if suffering with cirrhosis-associated immune dysfunction. Furthermore, pharmacotherapies including macrolide or quinolone antibiotics and steroids can also induce liver damage. In this review we addressed nutritional status and nutritional interventions in severe SARS-CoV-2 liver patients. As guidelines for SARS-CoV-2 in intensive care (IC) specifically are not yet available, strategies for management of sepsis and SARS are suggested in SARS-CoV-2. Early enteral nutrition (EN) should be started soon after IC admission, preferably employing iso-osmolar polymeric formula with initial protein content at 0.8 g/kg per day progressively increasing up to 1.3 g/kg per day and enriched with fish oil at 0.1 g/kg per day to 0.2 g/kg per day. Monitoring is necessary to identify signs of intolerance, hemodynamic instability and metabolic disorders, and transition to parenteral nutrition should not be delayed when energy and protein targets cannot be met via EN. Nutrients including vitamins A, C, D, E, B6, B12, folic acid, zinc, selenium and ω-3 fatty acids have in isolation or in combination shown beneficial effects upon immune function and inflammation modulation. Cautious and monitored supplementation up to upper limits may be beneficial in management strategies for SARS-CoV-2 liver patients

    Exploring the effects of spinal cord stimulation for freezing of gait in parkinsonian patients

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    Dopaminergic replacement therapies (e.g. levodopa) provide limited to no response for axial motor symptoms including gait dysfunction and freezing of gait (FOG) in Parkinson’s disease (PD) and Richardson’s syndrome progressive supranuclear palsy (PSP-RS) patients. Dopaminergic-resistant FOG may be a sensorimotor processing issue that does not involve basal ganglia (nigrostriatal) impairment. Recent studies suggest that spinal cord stimulation (SCS) has positive yet variable effects for dopaminergic-resistant gait and FOG in parkinsonian patients. Further studies investigating the mechanism of SCS, optimal stimulation parameters, and longevity of effects for alleviating FOG are warranted. The hypothesis of the research described in this thesis is that mid-thoracic, dorsal SCS effectively reduces FOG by modulating the sensory processing system in gait and may have a dopaminergic effect in individuals with FOG. The primary objective was to understand the relationship between FOG reduction, improvements in upper limb visual-motor performance, modulation of cortical activity and striatal dopaminergic innervation in 7 PD participants. FOG reduction was associated with changes in upper limb reaction time, speed and accuracy measured using robotic target reaching choice tasks. Modulation of resting-state, sensorimotor cortical activity, recorded using electroencephalography, was significantly associated with FOG reduction while participants were OFF-levodopa. Thus, SCS may alleviate FOG by modulating cortical activity associated with motor planning and sensory perception. Changes to striatal dopaminergic innervation, measured using a dopamine transporter marker, were associated with visual-motor performance improvements. Axial and appendicular motor features may be mediated by non-dopaminergic and dopaminergic pathways, respectively. The secondary objective was to demonstrate the short- and long-term effects of SCS for alleviating dopaminergic-resistant FOG and gait dysfunction in 5 PD and 3 PSP-RS participants without back/leg pain. SCS programming was individualized based on which setting best improved gait and/or FOG responses per participant using objective gait analysis. Significant improvements in stride velocity, step length and reduced FOG frequency were observed in all PD participants with up to 3-years of SCS. Similar gait and FOG improvements were observed in all PSP-RS participants up to 6-months. SCS is a promising therapeutic option for parkinsonian patients with FOG by possibly influencing cortical and subcortical structures involved in locomotion physiology

    Unraveling the effect of sex on human genetic architecture

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    Sex is arguably the most important differentiating characteristic in most mammalian species, separating populations into different groups, with varying behaviors, morphologies, and physiologies based on their complement of sex chromosomes, amongst other factors. In humans, despite males and females sharing nearly identical genomes, there are differences between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides the genome with a distinct hormonal milieu, differential gene expression, and environmental pressures arising from gender societal roles. This thus poses the possibility of observing gene by sex (GxS) interactions between the sexes that may contribute to some of the phenotypic differences observed. In recent years, there has been growing evidence of GxS, with common genetic variation presenting different effects on males and females. These studies have however been limited in regards to the number of traits studied and/or statistical power. Understanding sex differences in genetic architecture is of great importance as this could lead to improved understanding of potential differences in underlying biological pathways and disease etiology between the sexes and in turn help inform personalised treatments and precision medicine. In this thesis we provide insights into both the scope and mechanism of GxS across the genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits through the calculation of sex-specific heritability, genetic correlations, and sex-stratified genome-wide association studies (GWAS). We further investigated whether sex-agnostic (non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we studied the potential functional role of sex differences in genetic architecture through sex biased expression quantitative trait loci (eQTL) and gene-level analyses. Overall, this study marks a broad examination of the genetics of sex differences. Our findings parallel previous reports, suggesting the presence of sexual genetic heterogeneity across complex traits of generally modest magnitude. Furthermore, our results suggest the need to consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms

    How to Be a God

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    When it comes to questions concerning the nature of Reality, Philosophers and Theologians have the answers. Philosophers have the answers that can’t be proven right. Theologians have the answers that can’t be proven wrong. Today’s designers of Massively-Multiplayer Online Role-Playing Games create realities for a living. They can’t spend centuries mulling over the issues: they have to face them head-on. Their practical experiences can indicate which theoretical proposals actually work in practice. That’s today’s designers. Tomorrow’s will have a whole new set of questions to answer. The designers of virtual worlds are the literal gods of those realities. Suppose Artificial Intelligence comes through and allows us to create non-player characters as smart as us. What are our responsibilities as gods? How should we, as gods, conduct ourselves? How should we be gods
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