33 research outputs found

    Bullies in the Block Area: The Early Childhood Origins of Mean Behavior

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    Bullying can pose a serious threat to children's immediate and long-term health and well-being, and can have profound impacts on all children involved in bullying behaviors, whether as the one bullying others, the one being bullied, or the one witnessing bullying. At least some of the roots of bullying behaviors, and conversely the roots of positive pro-social skills, can likely be found in adverse and positive experiences during early childhood, yet the research literature on these connections is limited. The early childhood field lacks a coherent, theoretical model that identifies the factors contributing to "mean" or aggressive behavior in young children, and establishes the developmental link between this early behavior and later bullying behavior. This white paper summarizes the literature on seven key hypotheses about the roots of bullying behavior in early childhood experiences

    Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA

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    Mitochondrial transcription factor A (mtTFA/TFAM) is a nucleus-encoded, high-mobility-group-box (HMG-box) protein that regulates transcription of the mitochondrial genome by specifically recognizing light-strand and heavy-strand promoters (LSP, HSP1). TFAM also binds mitochondrial DNA in a non-sequence specific (NSS) fashion and facilitates its packaging into nucleoid structures. However, the requirement and contribution of DNA-bending for these two different binding modes has not been addressed in detail, which prompted this comparison of binding and bending properties of TFAM on promoter and non-promoter DNA. Promoter DNA increased the stability of TFAM to a greater degree than non-promoter DNA. However, the thermodynamic properties of DNA binding for TFAM with promoter and non-specific (NS) DNA were similar to each other and to other NSS HMG-box proteins. Fluorescence resonance energy transfer assays showed that TFAM bends promoter DNA to a greater degree than NS DNA. In contrast, TFAM lacking the C-terminal tail distorted both promoter and non-promoter DNA to a significantly reduced degree, corresponding with markedly decreased transcriptional activation capacity at LSP and HSP1 in vitro. Thus, the enhanced bending of promoter DNA imparted by the C-terminal tail is a critical component of the ability of TFAM to activate promoter-specific initiation by the core mitochondrial transcription machinery

    The Neural Correlates of the Clock-Drawing Test in Healthy Aging

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    Importance: The clock-drawing test (CDT) is an important neurocognitive assessment tool, widely used as a screening test for dementia. Behavioral performance on the test has been studied extensively, but there is scant literature on the underlying neural correlates.Purpose: To administer the CDT naturalistically to a healthy older aging population in an MRI environment, and characterize the brain activity associated with test completion.Main Outcome and Measure: Blood-oxygen-level dependent (BOLD) functional MRI was conducted as participants completed the CDT using novel tablet technology. Brain activity during CDT performance was contrasted to rest periods of visual fixation. Performance on the CDT was evaluated using a standardized scoring system (Rouleau score) and time to test completion. To assess convergent validity, performance during fMRI was compared to performance on a standard paper version of the task, administered in a psychometric testing room.Results: Study findings are reported for 33 cognitively healthy older participants aged 52–85. Activation was observed in the bilateral frontal, occipital and parietal lobes as well as the supplementary motor area and precentral gyri. Increased age was significantly correlated with Rouleau scores on the clock number drawing (R2) component (rho = -0.55, p < 0.001); the clock hand drawing (R3) component (rho = -0.50, p < 0.005); and the total clock (rho = -0.62, p < 0.001). Increased age was also associated with decreased activity in the bilateral parietal and occipital lobes as well as the right temporal lobe and right motor areas.Conclusion and Relevance: This imaging study characterizes the brain activity underlying performance of the CDT in a healthy older aging population using the most naturalistic version of the task to date. The results suggest that the functions of the occipital and parietal lobe are significantly altered by the normal aging process, which may lead to performance decrements

    2016 Research & Innovation Day Program

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    A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1003/thumbnail.jp

    2015 Research & Innovation Day Program

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    A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1002/thumbnail.jp

    Health, education, and social care provision after diagnosis of childhood visual disability

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    Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

    Changes in the V3 region of gp120 contribute to unusually broad coreceptor usage of an HIV-1 isolate from a CCR5 Delta32 heterozygote

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    AbstractHeterozygosity for the CCR5 Δ32 allele is associated with delayed progression to AIDS in human immunodeficiency virus type 1 (HIV-1) infection. Here we describe an unusual HIV-1 isolate from the blood of an asymptomatic individual who was heterozygous for the CCR5 Δ32 allele and had reduced levels of CCR5 expression. The primary virus used CCR5, CXCR4, and an unusually broad range of alternative coreceptors to enter transfected cells. However, only CXCR4 and CCR5 were used to enter primary T cells and monocyte-derived macrophages, respectively. Full-length Env clones had an unusually long V1/V2 region and rare amino acid variants in the V3 and C4 regions. Mutagenesis studies and structural models suggested that Y308, D321, and to a lesser extent K442 and E444, contribute to the broad coreceptor usage of these Envs, whereas I317 is likely to be a compensatory change. Furthermore, database analysis suggests that covariation can occur at positions 308/317 and 308/321 in vivo. Y308 and D321 reduced dependence on the extracellular loop 2 (ECL2) region of CCR5, while these residues along with Y330, K442, and E444 enhanced dependence on the CCR5 N-terminus compared to clade B consensus residues at these positions. These results suggest that expanded coreceptor usage of HIV-1 can occur in some individuals without rapid progression to AIDS as a consequence of changes in the V3 region that reduce dependence on the ECL2 region of CCR5 by enhancing interactions with conserved structural elements in G-protein-coupled receptors

    Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

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    An amendment to this paper has been published and can be accessed via the original article

    Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

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    In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

    Patient and stakeholder engagement learnings: PREP-IT as a case study

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