823 research outputs found

    Comparative Analysis of Acid Sphingomyelinase Distribution in the CNS of Rats and Mice Following Intracerebroventricular Delivery

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    Niemann-Pick A (NPA) disease is a lysosomal storage disorder (LSD) caused by a deficiency in acid sphingomyelinase (ASM) activity. Previously, we reported that biochemical and functional abnormalities observed in ASM knockout (ASMKO) mice could be partially alleviated by intracerebroventricular (ICV) infusion of hASM. We now show that this route of delivery also results in widespread enzyme distribution throughout the rat brain and spinal cord. However, enzyme diffusion into CNS parenchyma did not occur in a linear dose-dependent fashion. Moreover, although the levels of hASM detected in the rat CNS were determined to be within the range shown to be therapeutic in ASMKO mice, the absolute amounts represented less than 1% of the total dose administered. Finally, our results also showed that similar levels of enzyme distribution are achieved across rodent species when the dose is normalized to CNS weight as opposed to whole body weight. Collectively, these data suggest that the efficacy observed following ICV delivery of hASM in ASMKO mice could be scaled to CNS of the rat

    Experiments in lifelog organisation and retrieval at NTCIR

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    Lifelogging can be described as the process by which individuals use various software and hardware devices to gather large archives of multimodal personal data from multiple sources and store them in a personal data archive, called a lifelog. The Lifelog task at NTCIR was a comparative benchmarking exercise with the aim of encouraging research into the organisation and retrieval of data from multimodal lifelogs. The Lifelog task ran for over 4 years from NTCIR-12 until NTCIR-14 (2015.02–2019.06); it supported participants to submit to five subtasks, each tackling a different challenge related to lifelog retrieval. In this chapter, a motivation is given for the Lifelog task and a review of progress since NTCIR-12 is presented. Finally, the lessons learned and challenges within the domain of lifelog retrieval are presented

    Investigating hyper-vigilance for social threat of lonely children

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    The hypothesis that lonely children show hypervigilance for social threat was examined in a series of three studies that employed different methods including advanced eye-tracking technology. Hypervigilance for social threat was operationalized as hostility to ambiguously motivated social exclusion in a variation of the hostile attribution paradigm (Study 1), scores on the Children’s Rejection-Sensitivity Questionnaire (Study 2), and visual attention to socially rejecting stimuli (Study 3). The participants were 185 children (11 years-7 months to 12 years-6 months), 248 children (9 years-4 months to 11 years-8 months) and 140 children (8 years-10 months to 12 years-10 months) in the three studies, respectively. Regression analyses showed that, with depressive symptoms covaried, there were quadratic relations between loneliness and these different measures of hypervigilance to social threat. As hypothesized, only children in the upper range of loneliness demonstrated elevated hostility to ambiguously motivated social exclusion, higher scores on the rejection sensitivity questionnaire, and disengagement difficulties when viewing socially rejecting stimuli. We found that very lonely children are hypersensitive to social threat

    Saddlepoint tests for quantile regression

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    Quantile regression is a flexible and powerful technique which allows us to model the quantiles of the conditional distribution of a response variable given a set of covariates. Regression quantile estimators can be viewed as M-estimators and standard asymptotic inference is readily available based on likelihood-ratio, Wald, and score-type test statistics. However these statistics require the estimation of the sparsity function s(α) = [g(G−1(α))]−1, where G and g are the cumulative distribution function and the density of the regression errors, respectively, and this can lead to nonparametric density estimation. Moreover the asymptotic χ2 distribution for these statistics can provide an inaccurate approximation of tail probabilities and this can lead to inaccurate P-values, especially for moderate sample sizes. Alternative methods which do not require the estimation of the sparsity function include rank techniques and resampling methods to obtain confidence intervals, which can be inverted to test hypotheses. These are typically more accurate than the standard M-tests. In this article we show how accurate tests can be obtained by using a nonparametric saddlepoint test statistic. The proposed statistic is asymptotically χ2 distributed, does not require the specification of the error distribution, and does not require the estimation of the sparsity function. The validity of the method is demonstrated through a simulation study, which shows both the robustness and the accuracy of the new test compared to the best available alternatives

    Mainshocks are aftershocks of conditional foreshocks: How do foreshock statistical properties emerge from aftershock laws

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    The inverse Omori law for foreshocks discovered in the 1970s states that the rate of earthquakes prior to a mainshock increases on average as a power law ~ 1/(t_c-t)^p' of the time to the mainshock occurring at t_c. Here, we show that this law results from the direct Omori law for aftershocks describing the power law decay ~ 1/(t-t_c)^p of seismicity after an earthquake, provided that any earthquake can trigger its suit of aftershocks. In this picture, the seismic activity at any time is the sum of the spontaneous tectonic loading and of the activity triggered by all preceding events weighted by their corresponding Omori law. The inverse Omori law then emerges as the expected (in a statistical sense) trajectory of seismicity, conditioned on the fact that it leads to the burst of seismic activity accompanying the mainshock. The often documented apparent decrease of the b-value of the GR law at the approach to the main shock results straightforwardly from the conditioning of the path of seismic activity culminating at the mainshock. In the space domain, we predict that the phenomenon of aftershock diffusion must have its mirror process reflected into an inward migration of foreshocks towards the mainshock. In this model, foreshock sequences are special aftershock sequences which are modified by the condition to end up in a burst of seismicity associated with the mainshock.Comment: Latex document of 35 pages, 10 figure

    Tibet, the Himalaya, Asian monsoons and biodiversity - In what ways are they related?

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    Prevailing dogma asserts that the uplift of Tibet, the onset of the Asian monsoon system and high biodiversity in southern Asia are linked, and that all occurred after 23 million years ago in the Neogene. Here, spanning the last 60 million years of Earth history, the geological, climatological and palaeontological evidence for this linkage is reviewed. The principal conclusions are that: 1) A proto-Tibetan highland existed well before the Neogene and that an Andean type topography with surface elevations of at least 4.5 km existed at the start of the Eocene, before final closure of the Tethys Ocean that separated India from Eurasia. 2) The Himalaya were formed not at the start of the India-Eurasia collision, but after much of Tibet had achieved its present elevation. The Himalaya built against a pre-existing proto-Tibetan highland and only projected above the average height of the plateau after approximately 15 Ma. 3) Monsoon climates have existed across southern Asia for the whole of the Cenozoic, and probably for a lot longer, but that they were of the kind generated by seasonal migrations of the Inter-tropical Convergence Zone. 4) The projection of the High Himalaya above the Tibetan Plateau at about 15 Ma coincides with the development of the modern South Asia Monsoon. 5) The East Asia monsoon became established in its present form about the same time as a consequence of topographic changes in northern Tibet and elsewhere in Asia, the loss of moisture sources in the Asian interior and the development of a strong winter Siberian high as global temperatures declined. 6) New radiometric dates of palaeontological finds point to southern Asia's high biodiversity originating in the Paleogene, not the Neogene

    Development of aggression subtypes from childhood to adolescence:a group-based multi-trajectory modelling perspective

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    The persistence of elevated subtypes of aggression beginning in childhood have been associated with long-term maladaptive outcomes. Yet it remains unclear to what extent there are clusters of individuals following similar developmental trajectories across forms (i.e., physical and indirect) and functions (i.e., proactive and reactive) of aggression. We aimed to identify groups of children with distinct profiles of the joint development of forms and functions of aggression and to identify risk factors for group membership. A sample of 787 children was followed from birth to adolescence. Parent and teacher reports, and standardised assessments were used to measure two forms and two functions of aggressive behaviour, between six and 13 years of age along with preceding child, maternal, and family-level risk-factors. Analyses were conducted using a group-based multi-trajectory modelling approach. Five trajectory groups emerged: non-aggressors, low-stable, moderate-engagers, high-desisting, and high-chronic. Coercive parenting increased membership risk in the moderate-engagers and high-chronic groups. Lower maternal IQ increased membership risk in both high-desisting and high-chronic groups, whereas maternal depression increased membership risk in the high-desisting group only. Never being breastfed increased membership risk in the moderate-engagers group. Boys were at greater risk for belonging to groups displaying elevated aggression. Individuals with chronic aggression problems use all subtypes of aggression. Risk factors suggest that prevention programs should start early in life and target mothers with lower IQ. Strategies to deal with maternal depression and enhance positive parenting while replacing coercive parenting tactics should be highlighted in programming efforts

    Seek Help from Teachers or Fight Back? Student Perceptions of Teachers’ Actions during Conflicts and Responses to Peer Victimization

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    Previous research has shown that teachers’ actions when addressing conflict on school grounds can shape adolescent perceptions regarding how well the school manages victimization. Our objective in this study was to determine how these perceptions influenced the likelihood that adolescent students would react to victimization scenarios by either seeking help from school authority or physically fighting back. Vignettes describing two events of victimization were administered to 148 ethnic minority adolescents (Latino, African American, and Asian backgrounds; 49% female) attending an urban high school with high rates of conflict. Positive perceptions of teachers’ actions during conflicts—assessed via a questionnaire tapping how teachers manage student conflicts both generally and in a specific instance of strife—predicted a greater willingness to seek help from school authority, which in turn negatively predicted self-reported aggressive responses to the victimization scenarios. Path analysis established the viability of this indirect effect model, even when we controlled for sex, beliefs about the acceptability of aggression, and previous levels of reactive aggression. Adolescents’ perceptions of teachers’ actions during conflicts are discussed in relation to social information processing models, improving student–teacher relations, and decreasing aggression at schools
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