248 research outputs found

    Oscillatory instability of radiative shocks with multiple cooling processes

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    The stand-off shock formed in the accretion flow on to a stationary wall, such as the surface of a white dwarf, may be thermally unstable, depending on the cooling processes which dominate the post-shock flow. Some processes lead to instability, while others tend to stabilize the shock. We consider competition between the destabilizing influence of thermal bremsstrahlung cooling, and a stabilizing process which is a power law in density and temperature. Cyclotron cooling and processes which are of order 1, 3/2 and 2 in density are considered. The relative efficiency and power-law indices of the second mechanism are varied, and particular effects on the stability properties and frequencies of oscillation modes are examined

    Pediatric Allergy

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    Special Consideration in Post-Secondary Institutions: Trends at a Canadian University

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    This study examined trends in the practice of granting special consideration for missed tests and late papers in colleges and universities. We analyzed a database of 4,183 special consideration requests at a large Canadian university between 1998 and 2008. Results show a growing rate of requests per enrolment between 2001 and 2007. Although university officials and faculty are concerned that request making is excessive, an in-depth investigation of request making by the number of requests per student, request rate by course difficulty, grade point average, and illness-related work absences in the general population fails to support suspicions of dishonest behaviour. Furthermore, demographic variables—aside from part-time versus full-time student status, and to a lesser degree socio-economic status—do not distinguish students who made frequent requests from those who made few. We discuss potential explanations for the increase in requests for special consideration.  Cette étude examine les tendances quant à l’octroi de dérogations pour la reprise de tests manqués ou la remise tardive de travaux académiques dans les collèges et universités. Nous avons analysé une base de données compilées entre 1998 et 2008 contenant 4 183 demandes de dérogation provenant d’une grande université canadienne. Les résultats montrent une augmentation du taux de demandes de dérogation par inscription entre 2001 et 2007. Bien que les autorités universitaires et les membres de facultés s’inquiètent que les demandes de dérogation soient excessives, une analyse poussée du nombre de requêtes par étudiant, du taux de requêtes en fonction du niveau de difficulté des cours, de la moyenne cumulative de l’étudiant, et des absences au travail liées aux conditions de santé dans la population générale ne soutient pas l’hypothèse d’un comportement malhonnête. Par ailleurs, mis à part l’opposition des statuts d’étudiants à temps partiel et à temps plein, ainsi que, dans une moindre mesure, le statut socio-économique, les variables démographiques ne permettent pas de distinguer les étudiants qui font de multiples requêtes de ceux qui en font moins. Nous discutons des potentialités expliquant l’augmentation des demandes de dérogations

    On the interaction of a thin, supersonic shell with a molecular cloud

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    Molecular clouds (MCs) are stellar nurseries, however, formation of stars within MCs depends on the ambient physical conditions. MCs, over a free-fall time are exposed to numerous dynamical phenomena, of which, the interaction with a thin, dense shell of gas is but one. Below we present results from self-gravitating, 3-D smoothed particle hydrodynamics ({\small SPH}) simulations of the problem; seven realisations of the problem have been performed by varying the precollision density within the cloud, the nature of the post-collision shock, and the spatial resolution in the computational domain. Irrespective of the type of shock, a complex network of dense filaments, seeded by numerical noise, readily appears in the shocked cloud. Segregation of the dense and rarefied gas phases also manifests itself in a bimodal distribution of gas density. We demonstrate that the power-spectrum for rarefied gas is Kolomogorov like, while that for the denser gas is considerably steeper. As a corollary to the main problem, we also look into the possibly degenerative effect of the {\small SPH} artificial viscosity on the impact of the incident shell. It is observed that stronger viscosity leads to greater post-shock dissipation, that strongly decelerates the incident shock-front and promotes formation of contiguous structure, albeit on a much longer timescale. We conclude that too much viscosity is likely to enhance the proclivity towards gravitational boundedness of structure, leading to unphysical fragmentation.On the other hand, insufficient resolution appears to suppress fragmentation. Convergence of results is tested at both extremes, first by repeating the test case with more than a million particles and then with only half the number of particles in the original test case.Comment: 15 pages, 15 figures, and 1 Table; To appear in Monthly Notices to the RA

    Down-Modulation of Cockroach (CR) Allergen-specific Th2 Cell Responses Following Subcutaneous German Cockroach Allergen Immunotherapy (SCIT)

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    Rationale: The responses of T cells to subcutaneous allergen immunotherapy (SCIT) are not fully elucidated. We conducted a functional immunological evaluation of cockroach (CR) allergen-specific CD4+ T cell reactivity in the double-blinded, placebo-controlled, multi-center CRITICAL study. Methods: Participants (8-17 years of age) with mild to moderate, well-controlled asthma received 12 months of maintenance dosing of CR SCIT (n=20) or placebo (n=26). Peripheral blood mononuclear cells (PBMC) were isolated prior to, and after 12 months of therapy. CD4+ T cell responses at baseline and after treatment were assessed using overlapping peptide pools derived from 11 well-defined CR allergens and intracellular cytokine staining for IL-4, IFNg, and IL-10 production. T cell responses were further evaluated in terms of magnitude, cytokine polarization, and allergen immunodominance. Results: Significant down-modulation of the total magnitude of CD4+ T cell responses was observed with SCIT but not placebo, with a significant change between groups (-4.46±0.82 vs. −1.81±0.72, respectively, p = 0.020). Responses were driven by a decrease in IL-4 (-4.87±0.86 vs. −1.09±0.75, p = 0.002) with unaltered IFNg and IL-10 production, reflecting a shift towards a Th1 polarization profile (1.35±0.58 vs. −0.37±0.50, in SCIT and placebo respectively, p = 0.031). The largest effects were observed against the allergens Bla g 5 and Bla g 9, which are dominantly recognized, suggesting that dominant responses are susceptible to modulation. Conclusions: Our results demonstrate a significant down-regulation of CR-specific Th2 cell responses in urban children with asthma who received SCIT, compared with those who received placebo

    The Effect of Subcutaneous German Cockroach Immunotherapy (SCIT) on Nasal Allergen Challenge (NAC) and Cockroach-specific Antibody Responses Among Urban Children and Adolescents

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    Rationale: Cockroach allergy contributes to asthma and rhinitis morbidity among many urban children. Treatment with cockroach SCIT could be beneficial. Methods: 8-17 year-old children with mild-moderate asthma from 11 urban sites participated in a randomized double-blind placebo-controlled SCIT trial using non-standardized, glycerinated German cockroach extract. Positive cockroach skin tests, cockroach-specific IgE, and nasal challenge response with total nasal symptom scores (TNSS) ≥6 or maximal sneeze scores of 3 during a graded NAC were required for enrollment. Following dose escalation, 0.4 ml of undiluted extract was targeted for maintenance dosing (∼7 mcg Bla g2/dose). The primary endpoint was change in NAC-induced mean TNSS from baseline to one year post randomization. Changes in cockroach-specific IgE (CRsIgE) and IgG4 (CRsIgG4) were also analyzed. Results: Mean TNSS did not significantly change from baseline in either group (placebo n=29, SCIT n=28). There was no significant difference in the change in mean TNSS between placebo and SCIT [−0.79±0.35 vs. −1.02±0.37, respectively, difference=0.2(−1.15, 0.70), p=0.63]. Baseline CRsIgE and CRsIgG4 didn’t differ between groups. Mean CRsIgE decreased in both groups following treatment: 3.6 to 2.3 kU/L (0.64 fold change), p=0.015 and 8.3 to 4.2 kU/L (0.51 fold change), p\u3c0.001 in placebo and SCIT respectively, but did not differ between groups [p=0.33]. Significant increases in CRsIgG4 post-treatment were observed among SCIT recipients only: 0.07 to 12.3 mg/L (176 fold change), p\u3c0.001. Conclusions: Cockroach SCIT increased CRsIgG4 levels but did not significantly alter NAC-induced TNSS responses. The extent to which NAC in these children may reflect clinical efficacy for rhinitis or asthma is uncertain

    Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children.

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    Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. Results: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. Conclusions: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes

    Inducible expression quantitative trait locus analysis of the MUC5AC gene in asthma in urban populations of children

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    BACKGROUND: Mucus plugging can worsen asthma control, lead to reduced lung function and fatal exacerbations. MUC5AC is the secretory mucin implicated in mucus plugging, and MUC5AC gene expression has been associated with development of airway obstruction and asthma exacerbations in urban children with asthma. However, the genetic determinants of MUC5AC expression are not established. OBJECTIVE: To assess single-nucleotide polymorphisms (SNPs) that influence MUC5AC expression and relate to pulmonary functions in childhood asthma. METHODS: We used RNA-sequencing data from upper airway samples and performed cis-expression quantitative trait loci (eQTL) and allele specific expression (ASE) analyses in two cohorts of predominantly Black and Hispanic urban children, a high asthma-risk birth cohort and an exacerbation-prone asthma cohort. We further investigated inducible MUC5AC eQTLs during incipient asthma exacerbations. We tested significant eQTLs SNPs for associations with lung function measurements and investigated their functional consequences in DNA regulatory databases. RESULTS: We identified two independent groups of SNPs in the MUC5AC gene that were significantly associated with MUC5AC expression. Moreover, these SNPs showed stronger eQTL associations with MUC5AC expression during asthma exacerbations, consistent with inducible expression. SNPs in one group also showed significant association with decreased pulmonary functions. These SNPs included multiple EGR1 transcription factor binding sites suggesting a mechanism of effect. CONCLUSIONS: These findings demonstrate the applicability of organ specific RNA-sequencing data to determine genetic factors contributing to a key disease pathway. Specifically, they suggest important genetic variations that may underlie propensity to mucus plugging in asthma and could be important in targeted asthma phenotyping and disease management strategies

    Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children

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    Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk and egg) in 2,759 US participants (1,315 children and 1,444 parents) from the Chicago Food Allergy Study, and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (P=5.5 × 10 -8) and rs9275596 (P=6.8 × 10 -10), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (

    Lung function, asthma symptoms, and quality of life for children in public housing in Boston: a case-series analysis

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    BACKGROUND: Children in urban public housing are at high risk for asthma, given elevated environmental and social exposures and suboptimal medical care. For a multifactorial disease like asthma, design of intervention studies can be influenced by the relative prevalence of key risk factors. To better understand risk factors for asthma morbidity in the context of an environmental intervention study, we conducted a detailed baseline evaluation of 78 children (aged 4–17 years) from three public housing developments in Boston. METHODS: Asthmatic children and their caregivers were recruited between April 2002 and January 2003. We conducted intake interviews that captured a detailed family and medical history, including questions regarding asthma symptom severity, access to health care, medication usage, and psychological stress. Quality of life was evaluated for both the child and caregiver with an asthma-specific scale. Pulmonary function was measured with a portable spirometer, and allergy testing for common indoor and outdoor allergens was conducted with skin testing using the prick puncture method. Exploratory linear and logistic regression models evaluating predictors of respiratory symptoms, quality of life, and pulmonary function were conducted using SAS. RESULTS: We found high rates of obesity (56%) and allergies to indoor contaminants such as cockroaches (59%) and dust mites (59%). Only 36% of children with persistent asthma reported being prescribed any daily controller medication, and most did not have an asthma action plan or a peak flow meter. One-time lung function measures were poorly correlated with respiratory symptoms or quality of life, which were significantly correlated with each other. In multivariate regression models, household size, body mass index, and environmental tobacco smoke exposure were positively associated with respiratory symptom severity (p < 0.10). Symptom severity was negatively associated with asthma-related quality of life for the child and the caregiver, with caregiver (but not child) quality of life significantly influenced by caregiver stress and whether the child was in the intensive care unit at birth. CONCLUSION: Given the elevated prevalence of multiple risk factors, coordinated improvements in the social environment, the built environment, and in medical management would likely yield the greatest health benefits in this high-risk population
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