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The theoretical and empirical links between bullying behavior and male sexual violence perpetration
Bullying experiences and male sexual violence (SV) perpetration are major public health problems, and while extant literature suggests that they may share some developmental correlates, there is no established empirical link between being a perpetrator or victim of bullying and SV perpetration in the literature. Nonetheless, some SV prevention programs in the U.S. include bullying prevention components for elementary and middle-school aged children. Research is needed to test the hypothesized links between bullying experiences and SV perpetration to determine whether bullying prevention programs are likely to prevent SV perpetration. The purpose of this paper is to present results from a review of research on each of these topics and to discuss the potential shared and unique risk and protective factors within a social-ecological framework. The paper concludes with suggested directions for future research
Preliminary report on the design of a constraint-based musical planner
This work described in this paper forms part of a wider research project, described in Holland (1989), to find ways of using artificial intelligence methods to encourage and facilitate music composition by musical novices. This paper focusses on the key component of a knowledge-based tutoring system under development to help novices learn to compose and analyse musically 'sensible' chord sequences. This key component is a constraint-based musical planner dubbed 'PLANC'. The musical planner (together with its set of musical 'plans') can be used to construct and analyse chord sequences in terms of musical strategies that can be understood and made use of by complete musical novices. PLANC can generate a class of musically 'interesting' chord sequences that include the chord sequences of many well known existing pieces of music, as well as generating a large space of new 'interesting' sequences. The design of the planner draws on a characterisation of creativity due to Johnson-Laird (1988). The planner is psychologically plausible , though not intended as a detailed cognitive model. An overview of the structure of PLANC is presented, and its suitability for use in a tutoring system is considered. The design of the planner is criticised. Each of the main components of PLANC is analysed: plan variables, constraints, value generators and methods. Much of the 'knowledge' used in PLANC consists of informal musical knowledge: three appendices analyse the different kinds of informal knowledge used. The applicability and value of similar constraint-based mechanisms in intelligent tutors in a wide range of other open-ended domains is considere
Defining thalamic nuclei and topographic connectivity gradients in vivo.
The thalamus consists of multiple nuclei that have been previously defined by their chemoarchitectual and cytoarchitectual properties ex vivo. These form discrete, functionally specialized, territories with topographically arranged graduated patterns of connectivity. However, previous in vivo thalamic parcellation with MRI has been hindered by substantial inter-individual variability or discrepancies between MRI derived segmentations and histological sections. Here, we use the Euclidean distance to characterize probabilistic tractography distributions derived from diffusion MRI. We generate 12 feature maps by performing voxel-wise parameterization of the distance histograms (6 feature maps) and the distribution of three-dimensional distance transition gradients generated by applying a Sobel kernel to the distance metrics. We use these 12 feature maps to delineate individual thalamic nuclei, then extract the tractography profiles for each and calculate the voxel-wise tractography gradients. Within each thalamic nucleus, the tractography gradients were topographically arranged as distinct non-overlapping cortical networks with transitory overlapping mid-zones. This work significantly advances quantitative segmentation of the thalamus in vivo using 3T MRI. At an individual subject level, the thalamic segmentations consistently achieve a close relationship with a priori histological atlas information, and resolve in vivo topographic gradients within each thalamic nucleus for the first time. Additionally, these techniques allow individual thalamic nuclei to be closely aligned across large populations and generate measures of inter-individual variability that can be used to study both basic function and pathological processes in vivo
Identification of valid reference genes for the normalization of RT qPCR gene expression data in human brain tissue
<p>Abstract</p> <p>Background</p> <p>Studies of gene expression in post mortem human brain can contribute to understanding of the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Quantitative real-time PCR (RT qPCR) is often used to analyse gene expression. The validity of results obtained using RT qPCR is reliant on accurate data normalization. Reference genes are generally used to normalize RT qPCR data. Given that expression of some commonly used reference genes is altered in certain conditions, this study aimed to establish which reference genes were stably expressed in post mortem brain tissue from individuals with AD, PD or DLB.</p> <p>Results</p> <p>The present study investigated the expression stability of 8 candidate reference genes, (ubiquitin C [UBC], tyrosine-3-monooxygenase [YWHAZ], RNA polymerase II polypeptide [RP II], hydroxymethylbilane synthase [HMBS], TATA box binding protein [TBP], β-2-microglobulin [B2M], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], and succinate dehydrogenase complex-subunit A, [SDHA]) in cerebellum and medial temporal gyrus of 6 AD, 6 PD, 6 DLB subjects, along with 5 matched controls using RT qPCR (TaqMan<sup>® </sup>Gene Expression Assays). Gene expression stability was analysed using geNorm to rank the candidate genes in order of decreasing stability in each disease group. The optimal number of genes recommended for accurate data normalization in each disease state was determined by pairwise variation analysis.</p> <p>Conclusion</p> <p>This study identified validated sets of mRNAs which would be appropriate for the normalization of RT qPCR data when studying gene expression in brain tissue of AD, PD, DLB and control subjects.</p
Climate warming, marine protected areas and the ocean-scale integrity of coral reef ecosystems
Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution
of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the
associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local
management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef
fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions
and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the
1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites
and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure,
diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale
integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales,
with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas
still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance.
This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should
be integrated into existing management frameworks and combined with policies to improve system-wide resilience to
climate variation and change
Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases.
The gold standard for a definitive diagnosis of Parkinson disease (PD) is the pathologic finding of aggregated α-synuclein into Lewy bodies and for Alzheimer disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinicopathologic-based nosology is the assumption that pathologic protein aggregation at autopsy reflects pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated α-synuclein in SNCA gene multiplication or aggregated β-amyloid in APP mutations), their near universality at postmortem in sporadic PD and AD suggests they may alternatively represent common outcomes from upstream mechanisms or compensatory responses to cellular stress in order to delay cell death. These 3 conceptual frameworks of protein aggregation (pathogenic, epiphenomenon, protective) are difficult to resolve because of the inability to probe brain tissue in real time. Whereas animal models, in which neither PD nor AD occur in natural states, consistently support a pathogenic role of protein aggregation, indirect evidence from human studies does not. We hypothesize that (1) current biomarkers of protein aggregates may be relevant to common pathology but not to subgroup pathogenesis and (2) disease-modifying treatments targeting oligomers or fibrils might be futile or deleterious because these proteins are epiphenomena or protective in the human brain under molecular stress. Future precision medicine efforts for molecular targeting of neurodegenerative diseases may require analyses not anchored on current clinicopathologic criteria but instead on biological signals generated from large deeply phenotyped aging populations or from smaller but well-defined genetic-molecular cohorts
Urban Heat Island and Vulnerable Population. The Case of Madrid
The Urban Heat Island effect shows the differences among temperatures in urban areas and the surrounding rural ones. Previous studies have demonstrated that temperature differences could be up to 8 °C during the hottest periods of summer in Madrid , and that it varies according to the urban structure. Associated to this effect, the impact of temperature increase over dwelling indoor thermal comfort seems to double cooling energy demand . In Madrid, fuel poor households already suffering from inadequate indoor temperatures can face important overheating problems and, as a consequence, relevant health problems could become more frequent and stronger. This poses an increment in mortality rates in risk groups that should be evaluated. This research is aimed at establishing the geospatial connection between the urban heat island and the most vulnerable population living in the city of Madrid. Hence, those areas most in need for an urban intervention can be detected and prioritized
Diagnostic and prognostic prediction using gene expression profiles in high-dimensional microarray data
Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study.
ObjectiveTo assess the efficacy and safety of enzyme replacement therapy (ERT) with BMN 110 (elosulfase alfa) in patients with Morquio A syndrome (mucopolysaccharidosis IVA).MethodsPatients with Morquio A aged ≥5 years (N = 176) were randomised (1:1:1) to receive elosulfase alfa 2.0 mg/kg/every other week (qow), elosulfase alfa 2.0 mg/kg/week (weekly) or placebo for 24 weeks in this phase 3, double-blind, randomised study. The primary efficacy measure was 6-min walk test (6MWT) distance. Secondary efficacy measures were 3-min stair climb test (3MSCT) followed by change in urine keratan sulfate (KS). Various exploratory measures included respiratory function tests. Patient safety was also evaluated.ResultsAt week 24, the estimated mean effect on the 6MWT versus placebo was 22.5 m (95 % CI 4.0, 40.9; P = 0.017) for weekly and 0.5 m (95 % CI -17.8, 18.9; P = 0.954) for qow. The estimated mean effect on 3MSCT was 1.1 stairs/min (95 % CI -2.1, 4.4; P = 0.494) for weekly and -0.5 stairs/min (95 % CI -3.7, 2.8; P = 0.778) for qow. Normalised urine KS was reduced at 24 weeks in both regimens. In the weekly dose group, 22.4 % of patients had adverse events leading to an infusion interruption/discontinuation requiring medical intervention (only 1.3 % of all infusions in this group) over 6 months. No adverse events led to permanent treatment discontinuation.ConclusionsElosulfase alfa improved endurance as measured by the 6MWT in the weekly but not qow dose group, did not improve endurance on the 3MSCT, reduced urine KS, and had an acceptable safety profile
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