1,467 research outputs found

    Performance of LED-Based Fluorescence Microscopy to Diagnose Tuberculosis in a Peripheral Health Centre in Nairobi.

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    Sputum microscopy is the only tuberculosis (TB) diagnostic available at peripheral levels of care in resource limited countries. Its sensitivity is low, particularly in high HIV prevalence settings. Fluorescence microscopy (FM) can improve performance of microscopy and with the new light emitting diode (LED) technologies could be appropriate for peripheral settings. The study aimed to compare the performance of LED-FM versus Ziehl-Neelsen (ZN) microscopy and to assess feasibility of LED-FM at a low level of care in a high HIV prevalence country

    Visualization of Shared Genomic Regions and Meiotic Recombination in High-Density SNP Data

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    A fundamental goal of single nucleotide polymorphism (SNP) genotyping is to determine the sharing of alleles between individuals across genomic loci. Such analyses have diverse applications in defining the relatedness of individuals (including unexpected relationships in nominally unrelated individuals, or consanguinity within pedigrees), analyzing meiotic crossovers, and identifying a broad range of chromosomal anomalies such as hemizygous deletions and uniparental disomy, and analyzing population structure.We present SNPduo, a command-line and web accessible tool for analyzing and visualizing the relatedness of any two individuals using identity by state. Using identity by state does not require prior knowledge of allele frequencies or pedigree information, and is more computationally tractable and is less affected by population stratification than calculating identity by descent probabilities. The web implementation visualizes shared genomic regions, and generates UCSC viewable tracks. The command-line version requires pedigree information for compatibility with existing software and determining specified relationships even though pedigrees are not required for IBS calculation, generates no visual output, is written in portable C++, and is well-suited to analyzing large datasets. We demonstrate how the SNPduo web tool identifies meiotic crossover positions in siblings, and confirm our findings by visualizing meiotic recombination in synthetic three-generation pedigrees. We applied SNPduo to 210 nominally unrelated Phase I / II HapMap samples and, consistent with previous findings, identified six undeclared pairs of related individuals. We further analyzed identity by state in 2,883 individuals from multiplex families with autism and identified a series of anomalies including related parents, an individual with mosaic loss of chromosome 18, an individual with maternal heterodisomy of chromosome 16, and unexplained replicate samples.SNPduo provides the ability to explore and visualize SNP data to characterize the relatedness between individuals. It is compatible with, but distinct from, other established analysis software such as PLINK, and performs favorably in benchmarking studies for the analyses of genetic relatedness

    Deceptive body movements reverse spatial cueing in soccer

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    This article has been made available through the Brunel Open Access Publishing Fund.The purpose of the experiments was to analyse the spatial cueing effects of the movements of soccer players executing normal and deceptive (step-over) turns with the ball. Stimuli comprised normal resolution or point-light video clips of soccer players dribbling a football towards the observer then turning right or left with the ball. Clips were curtailed before or on the turn (-160, -80, 0 or +80 ms) to examine the time course of direction prediction and spatial cueing effects. Participants were divided into higher-skilled (HS) and lower-skilled (LS) groups according to soccer experience. In experiment 1, accuracy on full video clips was higher than on point-light but results followed the same overall pattern. Both HS and LS groups correctly identified direction on normal moves at all occlusion levels. For deceptive moves, LS participants were significantly worse than chance and HS participants were somewhat more accurate but nevertheless substantially impaired. In experiment 2, point-light clips were used to cue a lateral target. HS and LS groups showed faster reaction times to targets that were congruent with the direction of normal turns, and to targets incongruent with the direction of deceptive turns. The reversed cueing by deceptive moves coincided with earlier kinematic events than cueing by normal moves. It is concluded that the body kinematics of soccer players generate spatial cueing effects when viewed from an opponent's perspective. This could create a reaction time advantage when anticipating the direction of a normal move. A deceptive move is designed to turn this cueing advantage into a disadvantage. Acting on the basis of advance information, the presence of deceptive moves primes responses in the wrong direction, which may be only partly mitigated by delaying a response until veridical cues emerge

    Teleology and Realism in Leibniz's Philosophy of Science

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    This paper argues for an interpretation of Leibniz’s claim that physics requires both mechanical and teleological principles as a view regarding the interpretation of physical theories. Granting that Leibniz’s fundamental ontology remains non-physical, or mentalistic, it argues that teleological principles nevertheless ground a realist commitment about mechanical descriptions of phenomena. The empirical results of the new sciences, according to Leibniz, have genuine truth conditions: there is a fact of the matter about the regularities observed in experience. Taking this stance, however, requires bringing non-empirical reasons to bear upon mechanical causal claims. This paper first evaluates extant interpretations of Leibniz’s thesis that there are two realms in physics as describing parallel, self-sufficient sets of laws. It then examines Leibniz’s use of teleological principles to interpret scientific results in the context of his interventions in debates in seventeenth-century kinematic theory, and in the teaching of Copernicanism. Leibniz’s use of the principle of continuity and the principle of simplicity, for instance, reveal an underlying commitment to the truth-aptness, or approximate truth-aptness, of the new natural sciences. The paper concludes with a brief remark on the relation between metaphysics, theology, and physics in Leibniz

    El papel social del militar en el postconflicto colombiano

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    En el presente ensayo se pretende argumentar diferentes dinámicas del conflicto interno en Colombia que llevó a que de manera temprana las Fuerzas Militares del país asumieran funciones de seguridad civil, desarrollando su estructura y doctrina en torno a las necesidades de la lucha contra los grupos armados al margen de la ley y en defensa de la sociedad y las instituciones, de esta manera relegó a un segundo plano su rol clásico de defensa de las fronteras nacionales frente a potenciales amenazas externas. Así pues es necesario mirar en primera instancia como El ordenamiento constitucional, legal y jurídico del Estado moderno prevé y justifica la creación y existencia de las fuerzas militares FFMM- cuya misión fundamental es la defensa de la soberanía con respecto y frente a otras naciones del mundo (defensa nacional externa). Así mismo, la defensa nacional interna está asignada al cuerpo de policía, al margen y de manera totalmente separada de las FFMMPregrad

    Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the R6/2 Mouse Model of HD

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    Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6/2 mouse model of HD expresses a mutant version of exon 1 HTT and develops motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Despite the vast number of studies that have been performed on this model, the association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood. In an attempt to link these factors, we have performed longitudinal assessments of behavior (rotarod, open field, passive avoidance) and of regional brain abnormalities determined through magnetic resonance imaging (MRI) (whole brain, striatum, cortex, hippocampus, corpus callosum), as well as an end-stage histological assessment. Detailed correlative analyses of these three measures were then performed. We found a gender-dependent emergence of motor impairments that was associated with an age-related loss of regional brain volumes. MRI measurements further indicated that there was no striatal atrophy, but rather a lack of striatal growth beyond 8 weeks of age. T2 relaxivity further indicated tissue-level changes within brain regions. Despite these dramatic motor and neuroanatomical abnormalities, R6/2 mice did not exhibit neuronal loss in the striatum or motor cortex, although there was a significant increase in neuronal density due to tissue atrophy. The deposition of the mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the brain. End-stage histopathological assessments were not found to be as robustly correlated with the longitudinal measures of brain atrophy or motor impairments. In conclusion, modeling pre-manifest and early progression of the disease in more slowly progressing animal models will be key to establishing which changes are causally related. © 2013 Rattray et al

    SNPs Occur in Regions with Less Genomic Sequence Conservation

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    Rates of SNPs (single nucleotide polymorphisms) and cross-species genomic sequence conservation reflect intra- and inter-species variation, respectively. Here, I report SNP rates and genomic sequence conservation adjacent to mRNA processing regions and show that, as expected, more SNPs occur in less conserved regions and that functional regions have fewer SNPs. Results are confirmed using both mouse and human data. Regions include protein start codons, 3′ splice sites, 5′ splice sites, protein stop codons, predicted miRNA binding sites, and polyadenylation sites. Throughout, SNP rates are lower and conservation is higher at regulatory sites. Within coding regions, SNP rates are highest and conservation is lowest at codon position three and the fewest SNPs are found at codon position two, reflecting codon degeneracy for amino acid encoding. Exon splice sites show high conservation and very low SNP rates, reflecting both splicing signals and protein coding. Relaxed constraint on the codon third position is dramatically seen when separating exonic SNP rates based on intron phase. At polyadenylation sites, a peak of conservation and low SNP rate occurs from 30 to 17 nt preceding the site. This region is highly enriched for the sequence AAUAAA, reflecting the location of the conserved polyA signal. miRNA 3′ UTR target sites are predicted incorporating interspecies genomic sequence conservation; SNP rates are low in these sites, again showing fewer SNPs in conserved regions. Together, these results confirm that SNPs, reflecting recent genetic variation, occur more frequently in regions with less evolutionarily conservation
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