189 research outputs found

    Why Do Humans Imagine Robots?

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    This project analyzes why people are intrigued by the thought of robots, and why they choose to create them in both reality and fiction. Numerous movies, literature, news articles, online journals, surveys, and interviews have been used in determining the answer

    The Role of MAPK in Drug-Induced Kidney Injury

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    This paper focuses on the role that mitogen-activated protein kinases (MAPKs) play in drug-induced kidney injury. The MAPKs, of which there are four major classes (ERK, p38, JNK, and ERK5/BMK), are signalling cascades which have been found to be broadly conserved across a wide variety of organisms. MAPKs allow effective transmission of information from the cell surface to the cytosolic or nuclear compartments. Cross talk between the MAPKs themselves and with other signalling pathways allows the cell to modulate responses to a wide variety of external stimuli. The MAPKs have been shown to play key roles in both mediating and ameliorating cellular responses to stress including xenobiotic-induced toxicity. Therefore, this paper will discuss the specific role of the MAPKs in the kidney in response to injury by a variety of xenobiotics and the potential for therapeutic intervention at the level of MAPK signalling across different types of kidney disease

    The development and validation of a dashboard prototype for real-time suicide mortality data

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    Data visualisation is key to informing data-driven decision-making, yet this is an underexplored area of suicide surveillance. By way of enhancing a real-time suicide surveillance system model, an interactive dashboard prototype has been developed to facilitate emerging cluster detection, risk profiling and trend observation, as well as to establish a formal data sharing connection with key stakeholders via an intuitive interface. Individual-level demographic and circumstantial data on cases of confirmed suicide and open verdicts meeting the criteria for suicide in County Cork 2008-2017 were analysed to validate the model. The retrospective and prospective space-time scan statistics based on a discrete Poisson model were employed via the R software environment using the "rsatscan" and "shiny" packages to conduct the space-time cluster analysis and deliver the mapping and graphic components encompassing the dashboard interface. Using the best-fit parameters, the retrospective scan statistic returned several emerging non-significant clusters detected during the 10-year period, while the prospective approach demonstrated the predictive ability of the model. The outputs of the investigations are visually displayed using a geographical map of the identified clusters and a timeline of cluster occurrence. The challenges of designing and implementing visualizations for suspected suicide data are presented through a discussion of the development of the dashboard prototype and the potential it holds for supporting real-time decision-making. The results demonstrate that integration of a cluster detection approach involving geo-visualisation techniques, space-time scan statistics and predictive modelling would facilitate prospective early detection of emerging clusters, at-risk populations, and locations of concern. The prototype demonstrates real-world applicability as a proactive monitoring tool for timely action in suicide prevention by facilitating informed planning and preparedness to respond to emerging suicide clusters and other concerning trends

    The Cognitive Ageing, Nutrition and Neurogenesis trial: Design and progress

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    Introduction: Cohort studies indicate that long-chain n-3 polyunsaturated fatty acids and flavonoids may improve cognition and reduce dementia risk. The neuroprotective effects of these dietary components indicate that they are likely to be additive and potentially synergistic. Methods: The Cognitive Ageing, Nutrition and Neurogenesis trial hypothesizes that an intervention comprising long-chain n-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid) and cocoa flavan-3-ols (n-3 FLAV) will mitigate the cognitive decline anticipated to naturally occur over 1 year in older adults with mild cognitive impairment or subjective memory impairment. A double-blinded, placebo-controlled parallel design is used. Two hundred fifty-nine adults (aged ≥55 years) with mild cognitive impairment or subjective memory impairment were recruited and randomized to a control or n-3 FLAV group (1.5 g docosahexaenoic acid + eicosapentaenoic acid and 500 mg n-3 FLAV daily) for 12 months. Cognitive performance was measured three times over the 1-year intervention, at 0 (baseline), 3, and 12 months. The primary end point is hippocampus-sensitive cognitive function (e.g., number of false-positives on the Picture Recognition Task of the Cognitive Drug Research test battery). Secondary outcomes include additional cognitive measures, brain atrophy and blood flow (assessed by magnetic resonance imaging), vascular function, circulating biomarkers of cardiovascular and cognitive health, gut microflora speciation and metabolism, red blood cell fatty acid status, and urine flavan-3-ol metabolites. The intervention arms were matched for sex and apolipoprotein E4 status to allow retrospective exploratory analysis of the impact of these variables on response to intervention.  Results: Screening began in 2015, with all baseline visits completed in March 2017. The intervention was finished in March 2018.  Discussion: Cognitive Ageing, Nutrition and Neurogenesis aims to identify an effective diet-based intervention to prevent or delay cognitive impairment in cognitively at-risk individuals, which could ultimately contribute to a reduced population burden of dementia

    Post-depositional fracturing and subsidence of pumice flow deposits: Lascar Volcano, Chile

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    Unconsolidated pyroclastic flow deposits of the 1993 eruption of Lascar Volcano, Chile, have, with time, become increasingly dissected by a network of deeply penetrating fractures. The fracture network comprises orthogonal sets of decimeter-wide linear voids that form a pseudo-polygonal grid visible on the deposit surface. In this work, we combine shallow surface geophysical imaging tools with remote sensing observations and direct field measurements of the deposit to investigate these fractures and their underlying causal mechanisms. Based on ground penetrating radar images, the fractures are observed to have propagated to depths of up to 10 m. In addition, orbiting radar interferometry shows that deposit subsidence of up to 1 cm/year occurred between 1993 and 1996 with continued subsidence occurring at a slower rate thereafter. In situ measurements show that 1 m below the surface, the 1993 deposits remain 5°C to 15°C hotter, 18 years after emplacement, than adjacent deposits. Based on the observed subsidence as well as estimated cooling rates, the fractures are inferred to be the combined result of deaeration, thermal contraction, and sedimentary compaction in the months to years following deposition. Significant environmental factors, including regional earthquakes in 1995 and 2007, accelerated settling at punctuated moments in time. The spatially variable fracture pattern relates to surface slope and lithofacies variations as well as substrate lithology. Similar fractures have been reported in other ignimbrites but are generally exposed only in cross section and are often attributed to formation by external forces. Here we suggest that such interpretations should be invoked with caution, and deformation including post-emplacement subsidence and fracturing of loosely packed ash-rich deposits in the months to years postemplacement is a process inherent in the settling of pyroclastic material

    Genetic Mapping and Exome Sequencing Identify Variants Associated with Five Novel Diseases

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    The Clinic for Special Children (CSC) has integrated biochemical and molecular methods into a rural pediatric practice serving Old Order Amish and Mennonite (Plain) children. Among the Plain people, we have used single nucleotide polymorphism (SNP) microarrays to genetically map recessive disorders to large autozygous haplotype blocks (mean = 4.4 Mb) that contain many genes (mean = 79). For some, uninformative mapping or large gene lists preclude disease-gene identification by Sanger sequencing. Seven such conditions were selected for exome sequencing at the Broad Institute; all had been previously mapped at the CSC using low density SNP microarrays coupled with autozygosity and linkage analyses. Using between 1 and 5 patient samples per disorder, we identified sequence variants in the known disease-causing genes SLC6A3 and FLVCR1, and present evidence to strongly support the pathogenicity of variants identified in TUBGCP6, BRAT1, SNIP1, CRADD, and HARS. Our results reveal the power of coupling new genotyping technologies to population-specific genetic knowledge and robust clinical data

    Does transition from an unstable labour market position to permanent employment protect mental health? Results from a 14-year follow-up of school-leavers

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    <p>Abstract</p> <p>Background</p> <p>Having secure employment, in contrast to being unemployed, is regarded as an important determinant of health. Research and theories about the negative health consequences of unemployment indicated that transition from unemployment to a paid job could lead to improved health. The objective of this study was to test the hypothesis that obtaining permanent employment after being in an unstable labour market position protects mental health.</p> <p>Methods</p> <p>A 14-year follow-up of all graduates from compulsory school in an industrial town in northern Sweden was performed at ages 16, 18, 21 and 30 years. Complete data on the cohort were collected for 1044 individuals with the aid of a comprehensive questionnaire. The response rate was 96.4%. The health measurement used in this study was the psychological symptoms analysed by multivariate logistic regression. Those who obtained permanent employment were the focus of the analysis. This group consisted of people who were in an unstable labour market position for a year or more between the ages of 25 and 29, and who had acquired a permanent job one year before and at the time of the investigation.</p> <p>Results</p> <p>After controlling for gender as well as for an indicator of health-related selection, possible confounders and mediators, an association was found between the lower probability of psychological symptoms and obtaining permanent employment (OR = 0.35, 95% CI 0.19–0.63) as well as having permanent employment (OR = 0.22, 95% CI 0.10–0.51).</p> <p>Conclusion</p> <p>Our findings suggest that transition from an unstable labour market position to permanent employment could be health-promoting, even after controlling for possible confounders and mediators, as well as for an indicator of health-related selection. However, as there are few studies in the field, there is a need for more longitudinal studies in order to further analyse the relationship and to examine possible explanations. The policy implication of our study is that the transformation of unstable labour market positions into permanent employment could contribute to better public health.</p

    Structure of the germline genome of Tetrahymena thermophila and relationship to the massively rearranged somatic genome

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    The germline genome of the binucleated ciliate Tetrahymena thermophila undergoes programmed chromosome breakage and massive DNA elimination to generate the somatic genome. Here, we present a complete sequence assembly of the germline genome and analyze multiple features of its structure and its relationship to the somatic genome, shedding light on the mechanisms of genome rearrangement as well as the evolutionary history of this remarkable germline/soma differentiation. Our results strengthen the notion that a complex, dynamic, and ongoing interplay between mobile DNA elements and the host genome have shaped Tetrahymena chromosome structure, locally and globally. Non-standard outcomes of rearrangement events, including the generation of short-lived somatic chromosomes and excision of DNA interrupting protein-coding regions, may represent novel forms of developmental gene regulation. We also compare Tetrahymenas germline/soma differentiation to that of other characterized ciliates, illustrating the wide diversity of adaptations that have occurred within this phylum.</p

    The Determinants of young Adult Social well-being and Health (DASH) study: diversity, psychosocial determinants and health.

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    Purpose: The Determinants of young Adult Social well-being and Health longitudinal study draws on life-course models to understand ethnic differences in health. A key hypothesis relates to the role of psychosocial factors in nurturing the health and well-being of ethnic minorities growing up in the UK. We report the effects of culturally patterned exposures in childhood. Methods: In 2002/2003, 6643 11–13 year olds in London, ~80 % ethnic minorities, participated in the baseline survey. In 2005/2006, 4782 were followed-up. In 2012–2014, 665 took part in a pilot follow-up aged 21–23 years, including 42 qualitative interviews. Measures of socioeconomic and psychosocial factors and health were collected. Results: Ethnic minority adolescents reported better mental health than White British, despite more adversity (e.g. economic disadvantage, racism). It is unclear what explains this resilience but findings support a role for cultural factors. Racism was an adverse influence on mental health, while family care and connectedness, religious involvement and ethnic diversity of friendships were protective. While mental health resilience was a feature throughout adolescence, a less positive picture emerged for cardio-respiratory health. Both, mental health and cultural factors played a role. These patterns largely endured in early 20s with family support reducing stressful transitions to adulthood. Education levels, however, signal potential for socio-economic parity across ethnic groups

    Mitochondrial division inhibitor-1 is neuroprotective in the A53T-α-synuclein rat model of Parkinson’s disease

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    Alpha-synuclein (α-syn) is involved in both familial and sporadic Parkinson’s disease (PD). One of the proposed pathogenic mechanisms of α-syn mutations is mitochondrial dysfunction. However, it is not entirely clear the impact of impaired mitochondrial dynamics induced by α-syn on neurodegeneration and whether targeting this pathway has therapeutic potential. In this study we evaluated whether inhibition of mitochondrial fission is neuroprotective against α-syn overexpression in vivo. To accomplish this goal, we overexpressed human A53T-α- synuclein (hA53T-α-syn) in the rat nigrostriatal pathway, with or without treatment using the small molecule Mitochondrial Division Inhibitor-1 (mdivi-1), a putative inhibitor of the mitochondrial fission Dynamin-Related Protein-1 (Drp1). We show here that mdivi-1 reduced neurodegeneration, α-syn aggregates and normalized motor function. Mechanistically, mdivi-1 reduced mitochondrial fragmentation, mitochondrial dysfunction and oxidative stress. These in vivo results support the negative role of mutant α-syn in mitochondrial function and indicate that mdivi-1 has a high therapeutic potential for PD
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