Numerical simulations of compressible Rayleigh-Taylor turbulence in stratified fluids

We present results from numerical simulations of Rayleigh-Taylor turbulence, performed using a recently proposed lattice Boltzmann method able to describe consistently a thermal compressible flow subject to an external forcing. The method allowed us to study the system both in the nearly-Boussinesq and strongly compressible regimes. Moreover, we show that when the stratification is important, the presence of the adiabatic gradient causes the arrest of the mixing process.Comment: 15 pages, 11 figures. Proceedings of II Conference on Turbulent Mixing and Beyond (TMB-2009

Medulloblastoma has a global impact on health related quality of life: Findings from an international cohort.

BackgroundUnderstanding the global impact of medulloblastoma on health related quality of life (HRQL) is critical to characterizing the broad impact of this disease and realizing the benefits of modern treatments. We evaluated HRQL in an international cohort of pediatric medulloblastoma patients.MethodsSeventy-six patients were selected from 10 sites across North America, Europe, and Asia, who participated in the Medulloblastoma Advanced Genomics International Consortium (MAGIC). The Health Utilities Index (HUI) was administered to patients and/or parents at each site. Responses were used to determine overall HRQL and attributes (ie specific subdomains). The impact of various demographic and medical variables on HRQL was considered-including molecular subgroup.ResultsThe majority of patients reported having moderate or severe overall burden of morbidity for both the HUI2 and HUI3 (HUI2 = 60%; HUI3 = 72.1%) when proxy-assessed. Self-care in the HUI2 was rated as higher (ie better outcome) for patients from Western versus Eastern sites, P = .02. Patients with nonmetastatic status had higher values (ie better outcomes) for the HUI3 hearing, HUI3 pain, and HUI2 pain, all P < .05. Patients treated with a gross total resection also had better outcomes for the HUI3 hearing (P = .04). However, those who underwent a gross total resection reported having worse outcomes on the HUI3 vision (P = .02). No differences in HRQL were evident as a function of subgroup.ConclusionsBy examining an international sample of survivors, we characterized the worldwide impact of medulloblastoma. This is a critical first step in developing global standards for evaluating long-term outcomes

Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

Rabies kills many people throughout the developing world every year. The murine monoclonal antibody (mAb) 62-71-3 was recently identified for its potential application in rabies postexposure prophylaxis (PEP). The purpose here was to establish a plant-based production system for a chimeric mouse-human version of mAb 62-71-3, to characterize the recombinant antibody and investigate at a molecular level its interaction with rabies virus glycoprotein. Chimeric 62-71-3 was successfully expressed in Nicotiana benthamiana. Glycosylation was analyzed by mass spectroscopy; functionality was confirmed by antigen ELISA, as well as rabies and pseudotype virus neutralization. Epitope characterization was performed using pseudotype virus expressing mutagenized rabies glycoproteins. Purified mAb demonstrated potent viral neutralization at 500 IU/mg. A critical role for antigenic site I of the glycoprotein, as well as for two specific amino acid residues (K226 and G229) within site I, was identified with regard to mAb 62-71-3 neutralization. Pseudotype viruses expressing glycoprotein from lyssaviruses known not to be neutralized by this antibody were the controls. The results provide the molecular rationale for developing 62-71-3 mAb for rabies PEP; they also establish the basis for developing an inexpensive plant-based antibody product to benefit low-income families in developing countries.—Both, L., van Dolleweerd, C., Wright, E., Banyard, A. C., Bulmer-Thomas, B., Selden, D., Altmann, F., Fooks, A. R., Ma, J. K.-C. Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans

Social factors and obesity: an investigation of the role of health behaviours

OBJECTIVES: This study evaluated a behavioural model of the relation between social factors and obesity, in which differences in body mass index (BMI) across sociodemographic groups were hypothesized to be attributable to social group differences in health behaviours affecting energy expenditure (physical activity, diet and alcohol consumption and weight control). METHODS: A total of 8667 adults who participated in the 1995 Australian National Health and Nutrition Surveys provided data on a range of health factors including objectively measured height and weight, health behaviours, and social factors including family status, employment status, housing situation and migration status. RESULTS: Social factors remained significant predictors of BMI after controlling for all health behaviours. Neither social factors alone, nor health behaviours alone, adequately explained the variance in BMI. Gender-specific interactions were found between social factors and individual health behaviours. CONCLUSIONS: These results suggest that social factors moderate the relation between BMI and weight-related behaviours, and that the mechanisms underlying sociodemographic group differences in obesity may vary among men and women. Additional factors are likely to act in conjunction with current health behaviours to explain variation in obesity prevalence across sociodemographic groups.<br /

Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma.

Pediatric glioblastoma (pGBM) is a lethal cancer with no effective therapies. To understand the mechanisms of tumor evolution in this cancer, we performed whole-genome sequencing with linked reads on longitudinally resected pGBM samples. Our analyses showed that all diagnostic and recurrent samples were collections of genetically diverse subclones. Clonal composition rapidly evolved at recurrence, with less than 8% of nonsynonymous single-nucleotide variants being shared in diagnostic-recurrent pairs. To track the origins of the mutational events observed in pGBM, we generated whole-genome datasets for two patients and their parents. These trios showed that genetic variants could be (i) somatic, (ii) inherited from a healthy parent, or (iii) de novo in the germlines of pGBM patients. Analysis of variant allele frequencies supported a model of tumor growth involving slow-cycling cancer stem cells that give rise to fast-proliferating progenitor-like cells and to nondividing cells. Interestingly, radiation and antimitotic chemotherapeutics did not increase overall tumor burden upon recurrence. These findings support an important role for slow-cycling stem cell populations in contributing to recurrences, because slow-cycling cell populations are expected to be less prone to genotoxic stress induced by these treatments and therefore would accumulate few mutations. Our results highlight the need for new targeted treatments that account for the complex functional hierarchies and genomic heterogeneity of pGBM. SIGNIFICANCE: This work challenges several assumptions regarding the genetic organization of pediatric GBM and highlights mutagenic programs that start during early prenatal development.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/9/2111/F1.large.jpg.Wellcome Trust Royal Societ

Five meal patterns are differently associated with nutrient intakes, lifestyle factors and energy misreporting in a sub-sample of the Malmö Diet and Cancer cohort

OBJECTIVE: Examine how meal patterns are associated with nutrient intakes, lifestyle and socioeconomic factors, and energy misreporting. DESIGN: A cross-sectional study within the Malmö Diet and Cancer (MDC) cohort. Participants reported on the overall types and frequency of meals consumed, and completed a modified dietary history, a lifestyle and socioeconomic questionnaire, and anthropometric measurements. Based on the reported intake of six different meal types, meal pattern groups were distinguished using Ward's cluster analysis. Associations between meal patterns and nutrient intakes, anthropometric, lifestyle and socioeconomic variables were examined using the chi(2)-method and analysis of variance. SUBJECTS: A sub-sample of the MDC study cohort (n=28,098), consisting of 1,355 men and 1,654 women. RESULTS: Cluster analysis identified five groups of subjects with different meal patterns in both men and women. These meal pattern groups differed regarding nutrient intakes, lifestyle and socioeconomic factors. Subjects reporting frequent coffee meals were more likely to report an 'unhealthy' lifestyle, e.g. smoking, high alcohol consumption and low physical activity, while those with a fruit pattern reported a more 'healthy' lifestyle. Women were more likely to underreport their energy intake than men, and the degree of underreporting varied between the meal pattern groups. CONCLUSIONS: The meal pattern groups showed significant differences in dietary quality and socioeconomic and lifestyle variables. This supports previous research suggesting that diet is part of a multifaceted phenomenon. Incorporation of aspects on how foods are combined and eaten into public health advices might improve their efficiency