Impacts of a weakened AMOC on precipitation over the Euro-Atlantic region in the EC-Earth3 climate model

Given paleoclimatic evidence that the Atlantic Meridional Overturning Circulation (AMOC) may affect the global climate system, we conduct model experiments with EC-Earth3, a state-of-the-art GCM, to specifically investigate, for the first time, mechanisms of precipitation change over the Euro-Atlantic sector induced by a weakened AMOC. We artificially weaken the strength of the AMOC in the model through the release of a freshwater anomaly into the Northern Hemisphere high latitude ocean, thereby obtaining a similar to 57% weaker AMOC with respect to its preindustrial strength for 60 model years. Similar to prior studies, we find that Northern Hemisphere precipitation decreases in response to a weakened AMOC. However, we also find that the frequency of wet days increases in some regions. By computing the atmospheric moisture budget, we find that intensified but drier storms cause less precipitation over land. Nevertheless, changes in the jet stream tend to enhance precipitation over northwestern Europe. We further investigate the association of precipitation anomalies with large-scale atmospheric circulations by computing weather regimes through clustering of geopotential height daily anomalies. We find an increase in the frequency of the positive phase of the North Atlantic Oscillation (NAO+), which is associated with an increase in the occurrence of wet days over northern Europe and drier conditions over southern Europe. Since a similar to 57% reduction in the AMOC strength is within the inter-model range of projected AMOC declines by the end of the twenty-first century, our results have implications for understanding the role of AMOC in future hydrological changes

Physics of Neutron Star Crusts

The physics of neutron star crusts is vast, involving many different research fields, from nuclear and condensed matter physics to general relativity. This review summarizes the progress, which has been achieved over the last few years, in modeling neutron star crusts, both at the microscopic and macroscopic levels. The confrontation of these theoretical models with observations is also briefly discussed.Comment: 182 pages, published version available at <http://www.livingreviews.org/lrr-2008-10

Advances in the therapy of Alzheimer's disease: Targeting amyloid beta and tau and perspectives for the future

Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD

Assessment of Equine Autoimmune Thrombocytopenia (EAT) by flow cytometry

RATIONALE: Thrombocytopenia is a platelet associated process that occurs in human and animals as result of i) decreased production; ii) increased utilization; iii) increased destruction coupled to the presence of antibodies, within a process know as immune-mediated thrombocytopenia (IMT); or iv) platelet sequestration. Thus, the differentiation of the origin of IMT and the development of reliable diagnostic approaches and methodologies are important in the clarification of IMT pathogenesis. Therefore, there is a growing need in the field for easy to perform assays for assessing platelet morphological characteristics paired with detection of platelet-bound IgG. OBJECTIVES: This study is aimed to develop and characterize a single color flow cytometric assay for detection of platelet-bound IgG in horses, in combination with flow cytometric assessment of platelet morphological characteristics. FINDINGS: The FSC and SSC evaluation of the platelets obtained from the thrombocytopenic animals shows several distinctive features in comparison to the flow cytometric profile of platelets from healthy animals. The thrombocytopenic animals displayed i) increased number of platelets with high FSC and high SSC, ii) a significant number of those gigantic platelets had strong fluorescent signal (IgG bound), iii) very small platelets or platelet derived microparticles were found significantly enhanced in one of the thrombocytopenic horses, iv) significant numbers of these microplatelet/microparticles/platelet-fragments still carry very high fluorescence. CONCLUSIONS: This study describes the development and characterization of an easy to perform, inexpensive, and noninvasive single color flow cytometric assay for detection of platelet-bound IgG, in combination with flow cytometric assessment of platelet morphological characteristics in horses

Particulate Matter (PM) Research Centers (1999–2005) and the Role of Interdisciplinary Center-Based Research

Objective: The U.S. Environmental Protection Agency funded five academic centers in 1999 to address the uncertainties in exposure, toxicity, and health effects of airborne particulate matter (PM) identified in the “Research Priorities for Airborne Particulate Matter” of the National Research Council (NRC). The centers were structured to promote interdisciplinary approaches to address research priorities of the NRC. In this report, we present selected accomplishments from the first 6 years of the PM Centers, with a focus on the advantages afforded by the interdisciplinary, center-based research approach. The review highlights advances in the area of ultrafine particles and traffic-related health effects as well as cardiovascular and respiratory effects, mechanisms, susceptibility, and PM exposure and characterization issues. Data sources and synthesis: The collective publications of the centers served as the data source. To provide a concise synthesis of overall findings, authors representing each of the five centers identified a limited number of topic areas that serve to illustrate the key accomplishments of the PM Centers program, and a consensus statement was developed. Conclusions: The PM Centers program has effectively applied interdisciplinary research approaches to advance PM science

Sociodemographic and Disease Correlates of Body Image Distress among Patients with Systemic Sclerosis

Body image concerns are infrequently studied in systemic sclerosis (SSc), even though significant visible disfigurement is common. The objective of this study was to identify sociodemographic and disease-related correlates of dissatisfaction with appearance and social discomfort among people with SSc.SSc patients came from the 15-center Canadian Scleroderma Research Group Registry. Sociodemographic information was based on patient self-report. Disease characteristics were obtained via physician examinations. The Brief-SWAP was used to assess dissatisfaction with appearance and social discomfort. Structural equation models were conducted with MPlus to determine the relationship of dissatisfaction with appearance and social discomfort with age, sex, education, marital status, race/ethnicity, disease duration, skin involvement, telangiectasias, skin pigmentation changes, and hand contractures.A total of 489 SSc patients (432 female, 57 male) were included. Extent of skin involvement was significantly associated with both dissatisfaction with appearance and social discomfort (standardized regression coefficients = 0.02, p = 0.001; 0.02, p = 0.020, respectively), as was skin involvement in the face (0.18, p = 0.016; 0.23, p = 0.006, respectively). Greater social discomfort was robustly associated with younger age (-0.017, p<0.001) and upper-body telangiectasias (0.32, p = 0.021). Dissatisfaction with appearance was associated with hand contractures (0.07, p = 0.036).This study found that dissatisfaction with appearance and social discomfort were associated with numerous disfiguring characteristics of SSc, in addition to age. These results underline that there are multiple factors contributing to body image distress in SSc, as well as the need to attend to both disease and social contexts in understanding the impact of disfigurement among patients

Conditional Inactivation of Brca1, p53 and Rb in Mouse Ovaries Results in the Development of Leiomyosarcomas

Epithelial ovarian cancer (EOC) is thought to arise in part from the ovarian surface epithelium (OSE); however, the molecular events underlying this transformation are poorly understood. Germline mutations in the BRCA1 tumor suppressor gene result in a significantly increased risk of developing EOC and a large proportion of sporadic EOCs display some sort of BRCA1 dysfunction. To generate a model in which Brca1-mediated transformation can be studied, we previously inactivated Brca1 alone in murine OSE, which resulted in an increased accumulation of premalignant changes, but no tumor formation. In this study, we examined tumor formation in mice with conditionally expressed alleles of Brca1, p53 and Rb, alone or in combination. Intrabursal injection of adenovirus expressing Cre recombinase to inactivate p53 resulted in tumors in 100% of mice. Tumor progression was accelerated in mice with concomitant inactivation of Brca1 and p53, but not Rb and p53. Immunohistologic analyses classified the tumors as leiomyosarcomas that may be arising from the ovarian bursa. Brca1 inactivation in primary cultures of murine OSE cells led to a suppression of proliferation that could be rescued by concomitant inactivation of p53 and/or Rb. Brca1-deficient OSE cells displayed an increased sensitivity to the DNA damaging agent cisplatin, and this effect could be modulated by inactivation of p53 and/or Rb. These results indicate that Brca1 deficiency can accelerate tumor development and alter the sensitivity of OSE cells to chemotherapeutic agents. Intrabursal delivery of adenovirus intended to alter gene expression in the ovarian surface epithelium may, in some strains of mice, result in more rapid transformation of adjacent cells, resulting in leiomyosarcomas

Mechanical and Assembly Units of Viral Capsids Identified via Quasi-Rigid Domain Decomposition

Key steps in a viral life-cycle, such as self-assembly of a protective protein container or in some cases also subsequent maturation events, are governed by the interplay of physico-chemical mechanisms involving various spatial and temporal scales. These salient aspects of a viral life cycle are hence well described and rationalised from a mesoscopic perspective. Accordingly, various experimental and computational efforts have been directed towards identifying the fundamental building blocks that are instrumental for the mechanical response, or constitute the assembly units, of a few specific viral shells. Motivated by these earlier studies we introduce and apply a general and efficient computational scheme for identifying the stable domains of a given viral capsid. The method is based on elastic network models and quasi-rigid domain decomposition. It is first applied to a heterogeneous set of well-characterized viruses (CCMV, MS2, STNV, STMV) for which the known mechanical or assembly domains are correctly identified. The validated method is next applied to other viral particles such as L-A, Pariacoto and polyoma viruses, whose fundamental functional domains are still unknown or debated and for which we formulate verifiable predictions. The numerical code implementing the domain decomposition strategy is made freely available

Ethnic discrimination prevalence and associations with health outcomes: data from a nationally representative cross-sectional survey of secondary school students in New Zealand

<p>Abstract</p> <p>Background</p> <p>Reported ethnic discrimination is higher among indigenous and minority adult populations. There is a paucity of nationally representative prevalence studies of ethnic discrimination among adolescents. Experiencing ethnic discrimination has been associated with a range of adverse health outcomes. NZ has a diverse ethnic population. There are health inequalities among young people from Māori and Pacific ethnic groups.</p> <p>Methods</p> <p>9107 randomly selected secondary school students participated in a nationally representative cross-sectional health and wellbeing survey conducted in 2007. The prevalence of ethnic discrimination by health professionals, by police, and ethnicity-related bullying were analysed. Logistic regression was used to examine the associations between ethnic discrimination and six health/wellbeing outcomes: self-rated health status, depressive symptoms in the last 12 months, cigarette smoking, binge alcohol use, feeling safe in ones neighbourhood, and self-rated school achievement.</p> <p>Results</p> <p>There were significant ethnic differences in the prevalences of ethnic discrimination. Students who experienced ethnic discrimination were less likely to report excellent/very good/good self-rated general health (OR 0.51; 95% CI 0.39, 0.65), feel safe in their neighbourhood (OR 0.48; 95% CI 0.40, 0.58), and more likely to report an episode of binge drinking in the previous 4 weeks (OR 1.77; 95% CI 1.45, 2.17). For all these outcomes the odds ratios for the group who were 'unsure' if they had experienced ethnic discrimination were similar to those of the 'yes' group.</p> <p>Ethnicity stratified associations between ethnic discrimination and the depression, cigarette smoking, and self-rated school achievement are reported. Within each ethnic group participants reporting ethnic discrimination were more likely to have adverse outcomes for these three variables. For all three outcomes the direction and size of the association between experience of ethnic discrimination and the outcome were similar across all ethnic groups.</p> <p>Conclusions</p> <p>Ethnic discrimination is more commonly reported by Indigenous and minority group students. Both experiencing and being 'unsure' about experiencing ethnic discrimination are associated with a range of adverse health/wellbeing outcomes. Our findings highlight the progress yet to be made to ensure that rights to be free from ethnic discrimination are met for young people living in New Zealand.</p