Numerical study of the impact of land use modification on local rainfall over Manila, A

Includes bibliographical references

“Tales and Adventures”: G.A. Henty’s Union Jack and the Competitive World of Publishing for Boys in the 1880s’

In the competitive publishing environment of the late nineteenth century, writers and magazines had to distinguish themselves carefully from potential rivals. This article examines how G.A. Henty’s quality boys’ weekly, Union Jack (1880-83), attempted to secure a niche in the juvenile publishing market by deliberately distinguishing itself from other papers as a literary, imperialist and “healthy” publication. The article explores the design and marketing techniques of the magazine, its status as a fiction paper, the high calibre of its contributors, and its aggressive rhetoric in targeting an exclusively masculine audience. It argues that while Union Jack was marketed as a niche publication, it eventually failed to distinguish itself sufficiently to survive in an extremely competitive environment

Protocol for a Trial Assessing the Impacts of School-Based WaSH Interventions on Children’s Health Literacy, Handwashing, and Nutrition Status in Low- and Middle-Income Countries

Diarrhea, soil-transmitted helminth infection and malnutrition are leading causes of child mortality in low- and middle-income countries (LMICs). To reduce the prevalence of these diseases, effective interventions for adequate water, sanitation, and hygiene (WaSH) should be implemented. This paper describes the design of a cluster-randomized controlled trial that will compare the efficacy of four school-based WaSH interventions for improving children’s health literacy, handwashing, and nutrition. Interventions consisted of (1) WaSH policy reinforcement; (2) low-, medium-, or high-volume health education; (3) hygiene supplies; and (4) WaSH facilities (e.g., toilets, urinals, handwashing basins) improvements. We randomly allocated school clusters from the intervention arm to one of four groups to compare with schools from the control arm. Primary outcomes were: children’s health literacy, physical growth, nutrition status, and handwashing prevalence. Secondary outcomes were: children’s self-reported health status and history of extreme hunger, satisfaction with WaSH facilities, and school restrooms’ WaSH adequacy. We will measure differences in pre- and post-intervention outcomes and compare these differences between control and intervention arms. This research protocol can be a blueprint for future school-based WaSH intervention studies to be conducted in LMICs. Study protocols were approved by the ethics committees of the University of Bonn, Germany, and the University of the Philippines Manila. This trial was retroactively registered, ID number: DRKS00021623

The Impact of HIV, an Antiretroviral Programme and Tuberculosis on Mortality in South African Platinum Miners, 1992–2010

HIV and tuberculosis (TB) are the most common causes of death in South Africa. Antiretroviral therapy (ART) programmes should have had an impact on mortality rates. This study describes the impact of HIV, a Wellness (HIV/ART) programme and TB on population-wide trends in mortality and causes of death among South African platinum miners, from before the HIV epidemic into the ART era

Inhibiting ex-vivo Th17 responses in Ankylosing Spondylitis by targeting Janus kinases

Treatment options for Ankylosing Spondylitis (AS) are still limited. The T helper cell 17 (Th17) pathway has emerged as a major driver of disease pathogenesis and a good treatment target. Janus kinases (JAK) are key transducers of cytokine signals in Th17 cells and therefore promising targets for the treatment of AS. Here we investigate the therapeutic potential of four different JAK inhibitors on cells derived from AS patients and healthy controls, cultured in-vitro under Th17-promoting conditions. Levels of IL-17A, IL-17F, IL-22, GM-CSF and IFN gamma were assessed by ELISA and inhibitory effects were investigated with Phosphoflow. JAK1/2/3 and TYK2 were silenced in CD4+ T cells with siRNA and effects analyzed by ELISA (IL-17A, IL-17F and IL-22), Western Blot, qPCR and Phosphoflow. In-vitro inhibition of CD4+ T lymphocyte production of multiple Th17 cytokines (IL-17A, IL-17F and IL-22) was achieved with JAK inhibitors of differing specificity, as well as by silencing of JAK1-3 and Tyk2, without impacting on cell viability or proliferation. Our preclinical data suggest JAK inhibitors as promising candidates for therapeutic trials in AS, since they can inhibit multiple Th17 cytokines simultaneously. Improved targeting of TYK2 or other JAK isoforms may confer tailored effects on Th17 responses in AS

Comprehensive Genotyping in Two Homogeneous Graves' Disease Samples Reveals Major and Novel HLA Association Alleles

BACKGROUND: Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [P(Bc)]  = 1.17 x 10⁻²), DPB1*05:01 (OR  = 2.34, P(Bc) = 2.58 x 10⁻¹⁰), DQB1*03:02 (OR  = 0.62, P(Bc)  = 1.97 x 10⁻²), DRB1*15:01 (OR  = 1.68, P(Bc) = 1.22 x 10⁻²) and DRB1*16:02 (OR  = 2.63, P(Bc)  = 1.46 x 10⁻⁵) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. CONCLUSIONS/SIGNIFICANCE: These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis

Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND

Re-imagining management education in post-WWII Britain: Views from government and business

This paper explores the role of government and business in establishing two business schools in Britain in the 1960s. Partly in response to the Robbins Report of 1963, business leaders and politicians re-imagined management education and formed a new type of management education institution to operate alongside and ultimately compete a variety of other methods of management preparation. These two groups collaborated to create the London Graduate School of Business and Manchester Business School as national centers of excellence for management education. Using both archival and published sources, the paper’s contribution is to analyze perspectives expressed by businesspeople and political advocates involved with the business school project. It concludes that these advocates sought to create a body of educated, productive, yet socially-minded managers to lead Britain forward into the next phase of its economic development

Données histophysiologiques sur le développement post-embryonnaire d'un insecte Trichoptère (Phryganea varia Fab.)

Par l'application conjointe des techniques de la cytochimie et de l'analyse par spectographie des rayons X, la présence de divers cations (Ca, Mg, Mn, Zn et Fe) a été décelée dans de nombreux organes de P. varia. Ces éléments peuvent être liés à des MPSA (glandes salivaires), associés à des pigments (oeil, hypoderme) ou constituer des concrétions de phosphates (mésentéron, tissu adipeux, tubes de Malpighi). La distribution et l'abondance des métaux ainsi que l'évolution des teneurs en produits de réserves ont été envisagées au cours du développement post-embryonnaire et comparées aux données obtenues dans divers ordres d'Insectes terrestres. La vie en milieu aquatique a pour conséquences une absence d'accumulation de potassium et de déchets puriques. Il semble que la formation de sels minéraux soit nécessaire à certains échanges ioniques chez cet Insecte qui n'a pas à résoudre de problème de l'économie de l'eau pendant une grande partie de sa vie