73 research outputs found

    The Urban Environment and Childhood Asthma (URECA) birth cohort study: design, methods, and study population

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    <p>Abstract</p> <p>Background</p> <p>The incidence and morbidity of wheezing illnesses and childhood asthma is especially high in poor urban areas. This paper describes the study design, methods, and population of the Urban Environment and Childhood Asthma (URECA) study, which was established to investigate the immunologic causes of asthma among inner-city children.</p> <p>Methods and Results</p> <p>URECA is an observational prospective study that enrolled pregnant women in central urban areas of Baltimore, Boston, New York City, and St. Louis and is following their offspring from birth through age 7 years. The birth cohort consists of 560 inner-city children who have at least one parent with an allergic disease or asthma, and all families live in areas in which at least 20% of the population has incomes below the poverty line. In addition, 49 inner-city children with no parental history of allergies or asthma were enrolled. The primary hypothesis is that specific urban exposures in early life promote a unique pattern of immune development (impaired antiviral and increased Th2 responses) that increases the risk of recurrent wheezing and allergic sensitization in early childhood, and of asthma by age 7 years. To track immune development, cytokine responses of blood mononuclear cells stimulated <it>ex vivo </it>are measured at birth and then annually. Environmental assessments include allergen and endotoxin levels in house dust, pre- and postnatal maternal stress, and indoor air nicotine and nitrogen dioxide. Nasal mucous samples are collected from the children during respiratory illnesses and analyzed for respiratory viruses. The complex interactions between environmental exposures and immune development will be assessed with respect to recurrent wheeze at age 3 years and asthma at age 7 years.</p> <p>Conclusion</p> <p>The overall goal of the URECA study is to develop a better understanding of how specific urban exposures affect immune development to promote wheezing illnesses and asthma.</p

    IPCC reasons for concern regarding climate change risks

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    The reasons for concern framework communicates scientific understanding about risks in relation to varying levels of climate change. The framework, now a cornerstone of the IPCC assessments, aggregates global risks into five categories as a function of global mean temperature change. We review the framework's conceptual basis and the risk judgments made in the most recent IPCC report, confirming those judgments in most cases in the light of more recent literature and identifying their limitations. We point to extensions of the framework that offer complementary climate change metrics to global mean temperature change and better account for possible changes in social and ecological system vulnerability. Further research should systematically evaluate risks under alternative scenarios of future climatic and societal conditions

    Immunological aspects in chronic lymphocytic leukemia (CLL) development

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    Chronic lymphocytic leukemia (CLL) is unique among B cell malignancies in that the malignant clones can be featured either somatically mutated or unmutated IGVH genes. CLL cells that express unmutated immunoglobulin variable domains likely underwent final development prior to their entry into the germinal center, whereas those that express mutated variable domains likely transited through the germinal center and then underwent final development. Regardless, the cellular origin of CLL remains unknown. The aim of this review is to summarize immunological aspects involved in this process and to provide insights about the complex biology and pathogenesis of this disease. We propose a mechanistic hypothesis to explain the origin of B-CLL clones into our current picture of normal B cell development. In particular, we suggest that unmutated CLL arises from normal B cells with self-reactivity for apoptotic bodies that have undergone receptor editing, CD5 expression, and anergic processes in the bone marrow. Similarly, mutated CLL would arise from cells that, while acquiring self-reactivity for autoantigens—including apoptotic bodies—in germinal centers, are also still subject to tolerization mechanisms, including receptor editing and anergy. We believe that CLL is a proliferation of B lymphocytes selected during clonal expansion through multiple encounters with (auto)antigens, despite the fact that they differ in their state of activation and maturation. Autoantigens and microbial pathogens activate BCR signaling and promote tolerogenic mechanisms such as receptor editing/revision, anergy, CD5+ expression, and somatic hypermutation in CLL B cells. The result of these tolerogenic mechanisms is the survival of CLL B cell clones with similar surface markers and homogeneous gene expression signatures. We suggest that both immunophenotypic surface markers and homogenous gene expression might represent the evidence of several attempts to re-educate self-reactive B cells

    Housing: An Under-Explored Influence on Children’s Well-Being and Becoming

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    Research on housing has tended to focus on adult outcomes, establishing relationships between housing and a number of aspects of health and well-being. Research exploring the influence of housing on children has been more limited, and has tended to focus on adult concerns around risk behaviours, behavioural problems and educational attainment. While these outcomes are important, they neglect the impact of housing on children’s lives beyond these concerns. There are a number of reasons to believe that housing would play an important role in children’s well-being more broadly. Family stress and strain models highlight how housing difficulties experienced by adults may have knock on effects for children, while Bronfenbrenner’s ecological approach to human development emphasises the importance of children’s experiences of their environments, of which the home is among the most important. This paper summaries the existing evidence around housing and child outcomes, predominantly educational and behavioural outcomes, and argues for the extension of this work to consider the impact of housing on children’s lives more broadly, especially their subjective well-being
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