331 research outputs found

    The BMSLSS: Measurement Invariance and Latent Mean Differences Across Black and White Early Adolescents

    Get PDF
    The Brief Measure of Students’ Life Satisfaction Scale (BMSLSS; Seligson, Huebner, & Valois, 2003) is a widely used brief self-report measure of child and adolescent Life Satisfaction (LS). Although acceptable reliability and validity have been demonstrated for the BMSLSS across various youth samples, few cross-cultural comparisons have been performed. Specifically, no studies to date have examined measurement invariance of the BMSLSS across diverse samples of racial groups in the US. The current study explored measurement invariance across Black and White middle school students (N = 1484) from four schools in a southeastern U.S. state through use of multi-group confirmatory factor analysis (MGCFA). Findings provided preliminary support for use of the BMSLSS with Black and White youth, both individually and in comparative research regarding early adolescent LS. Specifically, results supported configural and metric invariance but problems were indicated in the examination of full scalar invariance. Thus, a partial scalar invariance model was identified and demonstrated adequate model fit. Latent mean analyses across the full and partial scalar invariance models indicated that White students reported higher LS scores than Black students. These findings suggest the need for further studies of the generalizability of the findings and the possible determinants of racial differences in the LS of U.S. youth

    An X-ray Mini-survey of Nearby Edge-on Starburst Galaxies II. The Question of Metal Abundance

    Get PDF
    (abbreviated) We have undertaken an X-ray survey of a far-infrared flux limited sample of seven nearby edge-on starburst galaxies. Here, we examine the two X-ray-brightest sample members NGC 253 and M 82 in a self-consistent manner, taking account of the spatial distribution of the X-ray emission in choosing our spectral models. There is significant X-ray absorption in the disk of NGC 253. When this is accounted for we find that multi-temperature thermal plasma models with significant underlying soft X-ray absorption are more consistent with the imaging data than single-temperature models with highly subsolar abundances or models with minimal absorption and non-equilibrium thermal ionization conditions. Our models do not require absolute abundances that are inconsistent with solar values or unusually supersolar ratios of the alpha-burning elements with respect to Fe (as claimed previously). We conclude that with current data, the technique of measuring abundances in starburst galaxies via X-ray spectral modeling is highly uncertain. Based on the point-like nature of much of the X-ray emission in the PSPC hard-band image of NGC 253, we suggest that a significant fraction of the ``extended'' X-ray emission in the 3-10 keV band seen along the disk of the galaxy with ASCA and BeppoSAX (Cappi et al.) is comprised of discrete sources in the disk, as opposed to purely diffuse, hot gas. This could explain the low Fe abundances of ~1/4 solar derived for pure thermal models.Comment: (accepted for publication in the Astrophysical Journal

    Very Extended X-ray and H-alpha Emission in M82: Implications for the Superwind Phenomenon

    Full text link
    We discuss the properties and implications of a 3.7x0.9 kpc region of spatially-coincident X-ray and H-alpha emission about 11.6 kpc to the north of the galaxy M82 previously discussed by Devine and Bally (1999). The PSPC X-ray spectrum is fit by thermal plasma (kT=0.80+-0.17 keV) absorbed by only the Galactic foreground column density. We evaluate the relationship of the X-ray/H-alpha ridge to the M82 superwind. The main properties of the X-ray emission can all be explained as being due to shock-heating driven as the superwind encounters a massive ionized cloud in the halo of M82. This encounter drives a slow shock into the cloud, which contributes to the excitation of the observed H-alpha emission. At the same time, a fast bow-shock develops in the superwind just upstream of the cloud, and this produces the observed X-ray emission. This interpretation would imply that the superwind has an outflow speed of roughly 800 km/s, consistent with indirect estimates based on its general X-ray properties and the kinematics of the inner kpc-scale region of H-alpha filaments. The gas in the M82 ridge is roughly two orders-of-magnitude hotter than the minimum "escape temperature" at this radius, so this gas will not be retained by M82. (abridged)Comment: 24 pages (latex), 3 figures (2 gif files and one postscript), accepted for publication in Part 1 of The Astrophysical Journa

    Coordinated oncogenic transformation and inhibition of host immune responses by the PAX3-FKHR fusion oncoprotein

    Get PDF
    Tumors have evolved elaborate mechanisms for evading immune detection, such as production of immunoinhibitory cytokines and down-regulation of major histocompatibility complex (MHC) expression. We have studied PAX3-FKHR as an example of an oncogenic fusion protein associated with an aggressive metastatic cancer. We show that PAX3-FKHR alters expression of genes that are normally regulated by Janus kinase/signal transducer and activator of transcription (STAT) signaling pathways. This occurs as a result of a specific interaction between PAX3-FKHR and the STAT3 transcription factor, which results in a dramatic reduction in tumor MHC expression, and an alteration in local cytokine concentrations to inhibit surrounding inflammatory cells and immune detection. Collectively, these data show that an oncogenic transcription factor can promote tumor growth and tissue invasion while inhibiting local inflammatory and immune responses. This is the first time that an immunomodulatory role has been described for an oncogenic fusion protein

    Selective Role of the Catalytic PI3K Subunit p110β in Impaired Higher Order Cognition in Fragile X Syndrome

    Get PDF
    SummaryDistinct isoforms of the PI3K catalytic subunit have specialized functions in the brain, but their role in cognition is unknown. Here, we show that the catalytic subunit p110β plays an important role in prefrontal cortex (PFC)-dependent cognitive defects in mouse models of Fragile X syndrome (FXS), an inherited intellectual disability. FXS is caused by loss of function of the fragile X mental retardation protein (FMRP), which binds and translationally represses mRNAs. PFC-selective knockdown of p110β, an FMRP target that is translationally upregulated in FXS, reverses deficits in higher cognition in Fmr1 knockout mice. Genetic full-body reduction of p110β in Fmr1 knockout mice normalizes excessive PI3K activity, restores stimulus-induced protein synthesis, and corrects increased dendritic spine density and behavior. Notably, adult-onset PFC-selective Fmr1 knockdown mice show impaired cognition, which is rescued by simultaneous p110β knockdown. Our results suggest that FMRP-mediated control of p110β is crucial for neuronal protein synthesis and cognition

    Aducanumab anti-amyloid immunotherapy induces sustained microglial and immune alterations

    Get PDF
    Aducanumab, an anti-amyloid immunotherapy for Alzheimer\u27s disease, efficiently reduces Aβ, though its plaque clearance mechanisms, long-term effects, and effects of discontinuation are not fully understood. We assessed the effect of aducanumab treatment and withdrawal on Aβ, neuritic dystrophy, astrocytes, and microglia in the APP/PS1 amyloid mouse model. We found that reductions in amyloid and neuritic dystrophy during acute treatment were accompanied by microglial and astrocytic activation, and microglial recruitment to plaques and adoption of an aducanumab-specific pro-phagocytic and pro-degradation transcriptomic signature, indicating a role for microglia in aducanumab-mediated Aβ clearance. Reductions in Aβ and dystrophy were sustained 15 but not 30 wk after discontinuation, and reaccumulation of plaques coincided with loss of the microglial aducanumab signature and failure of microglia to reactivate. This suggests that despite the initial benefit from treatment, microglia are unable to respond later to restrain plaque reaccumulation, making further studies on the effect of amyloid-directed immunotherapy withdrawal crucial for assessing long-term safety and efficacy

    The Discovery of a Potent, Selective, and Peripherally Restricted Pan-Trk Inhibitor (PF-06273340) for the Treatment of Pain

    Get PDF
    The neurotrophin family of growth factors, comprised of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4), is implicated in the physiology of chronic pain. Given the clinical efficacy of anti-NGF monoclonal antibody (mAb) therapies, there is significant interest in the development of small molecule modulators of neurotrophin activity. Neurotrophins signal through the tropomyosin related kinase (Trk) family of tyrosine kinase receptors, hence Trk kinase inhibition represents a potentially “druggable” point of intervention. To deliver the safety profile required for chronic, nonlife threatening pain indications, highly kinase-selective Trk inhibitors with minimal brain availability are sought. Herein we describe how the use of SBDD, 2D QSAR models, and matched molecular pair data in compound design enabled the delivery of the highly potent, kinase-selective, and peripherally restricted clinical candidate PF-06273340

    One size doesn’t fit all: methodological reflections in conducting community-based behavioural science research to tailor COVID-19 vaccination initiatives for public health priority populations

    Get PDF
    BACKGROUND: Promoting the uptake of vaccination for infectious diseases such as COVID-19 remains a global challenge, necessitating collaborative efforts between public health units (PHUs) and communities. Applied behavioural science can play a crucial role in supporting PHUs' response by providing insights into human behaviour and informing tailored strategies to enhance vaccination uptake. Community engagement can help broaden the reach of behavioural science research by involving a more diverse range of populations and ensuring that strategies better represent the needs of specific communities. We developed and applied an approach to conducting community-based behavioural science research with ethnically and socioeconomically diverse populations to guide PHUs in tailoring their strategies to promote COVID-19 vaccination. This paper presents the community engagement methodology and the lessons learned in applying the methodology. METHODS: The community engagement methodology was developed based on integrated knowledge translation (iKT) and community-based participatory research (CBPR) principles. The study involved collaboration with PHUs and local communities in Ontario, Canada to identify priority groups for COVID-19 vaccination, understand factors influencing vaccine uptake and co-design strategies tailored to each community to promote vaccination. Community engagement was conducted across three large urban regions with individuals from Eastern European communities, African, Black, and Caribbean communities and low socioeconomic neighbourhoods. RESULTS: We developed and applied a seven-step methodology for conducting community-based behavioural science research: (1) aligning goals with system-level partners; (2) engaging with PHUs to understand priorities; (3) understanding community strengths and dynamics; (4) building relationships with each community; (5) establishing partnerships (community advisory groups); (6) involving community members in the research process; and (7) feeding back and interpreting research findings. Research partnerships were successfully established with members of prioritized communities, enabling recruitment of participants for theory-informed behavioural science interviews, interpretation of findings, and co-design of targeted recommendations for each PHU to improve COVID-19 vaccination uptake. Lessons learned include the importance of cultural sensitivity and awareness of sociopolitical context in tailoring community engagement, being agile to address the diverse and evolving priorities of PHUs, and building trust to achieve effective community engagement. CONCLUSION: Effective community engagement in behavioural science research can lead to more inclusive and representative research. The community engagement approach developed and applied in this study acknowledges the diversity of communities, recognizes the central role of PHUs, and can help in addressing complex public health challenges
    • …
    corecore