A Prospective Longitudinal Study of the Clinical Outcomes from Cryptococcal Meningitis following Treatment Induction with 800 mg Oral Fluconazole in Blantyre, Malawi

Introduction: Cryptococcal meningitis is the most common neurological infection in HIV infected patients in Sub Saharan Africa, where gold standard treatment with intravenous amphotericin B and 5 flucytosine is often unavailable or difficult to administer. Fluconazole monotherapy is frequently recommended in national guidelines but is a fungistatic drug compromised by uncertainty over optimal dosing and a paucity of clinical end-point outcome data. Methods: From July 2010 until March 2011, HIV infected adults with a first episode of cryptococcal meningitis were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients were treated with oral fluconazole monotherapy 800 mg daily, as per national guidelines. ART was started at 4 weeks. Outcomes and factors associated with treatment failure were assessed 4, 10 and 52 weeks after fluconazole initiation. Results: Sixty patients were recruited. 26/60 (43%) died by 4 weeks. 35/60 (58.0%) and 43/56 (77%) died or failed treatment by 10 or 52 weeks respectively. Reduced consciousness (Glasgow Coma Score ,14 of 15), moderate/severe neurological disability (modified Rankin Score .3 of 5) and confusion (Abbreviated Mental Test Score ,8 of 10) were all common at baseline and associated with death or treatment failure. ART prior to recruitment was not associated with better outcomes. Conclusions: Mortality and treatment failure from cryptococcal meningitis following initiation of treatment with 800 mg oral fluconazole is unacceptably high. To improve outcomes, there is an urgent need for better therapeutic strategies and point-of-care diagnostics, allowing earlier diagnosis before development of neurological deficit

The utilisation of health research in policy-making: Concepts, examples and methods of assessment

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies

Identification of Herbig Ae/Be Stars in the Small Magellanic Cloud

Protoplanetary disks orbiting intermediate-mass stars, Herbig Ae/Be stars, that have formed in a metal-poor environment may evolve differently than their Galactic cousins. A study of the planet-formation process in such an environment requires identification and characterization of a sample of candidates. We have observed several stars in the Small Magellanic Cloud, a nearby metal-poor dwarf galaxy, that have optical spectral properties of Herbig Ae/Be stars, including strong Hα emission, blue continuum excess, and spectral types ranging from early G to B. Infrared spectra of these sources from the Spitzer Space Telescope show strong excess emission indicating the presence of silicate dust, molecular and atomic gas, and polycyclic aromatic hydrocarbons. We present an analysis of the likelihood that these candidates are Herbig Ae/Be stars. This identification is the necessary first step to future investigations that will examine the role of metallicity in the evolution of protoplanetary disks

European American Stratification in Ovarian Cancer Case Control Data: The Utility of Genome-Wide Data for Inferring Ancestry

We investigated the ability of several principal components analysis (PCA)-based strategies to detect and control for population stratification using data from a multi-center study of epithelial ovarian cancer among women of European-American ethnicity. These include a correction based on an ancestry informative markers (AIMs) panel designed to capture European ancestral variation and corrections utilizing un-thinned genome-wide SNP data; case-control samples were drawn from four geographically distinct North-American sites. The AIMs-only and genome-wide first principal components (PC1) both corresponded to the previously described North or Northwest-Southeast axis of European variation. We found that the genome-wide PCA captured this primary dimension of variation more precisely and identified additional axes of genome-wide variation of relevance to epithelial ovarian cancer. Associations evident between the genome-wide PCs and study site corroborate North American immigration history and suggest that undiscovered dimensions of variation lie within Northern Europe. The structure captured by the genome-wide PCA was also found within control individuals and did not reflect the case-control variation present in the data. The genome-wide PCA highlighted three regions of local LD, corresponding to the lactase (LCT) gene on chromosome 2, the human leukocyte antigen system (HLA) on chromosome 6 and to a common inversion polymorphism on chromosome 8. These features did not compromise the efficacy of PCs from this analysis for ancestry control. This study concludes that although AIMs panels are a cost-effective way of capturing population structure, genome-wide data should preferably be used when available

Deep-Inelastic Inclusive ep Scattering at Low x and a Determination of alpha_s

A precise measurement of the inclusive deep-inelastic e^+p scattering cross section is reported in the kinematic range 1.5<= Q^2 <=150 GeV^2 and 3*10^(-5)<= x <=0.2. The data were recorded with the H1 detector at HERA in 1996 and 1997, and correspond to an integrated luminosity of 20 pb^(-1). The double differential cross section, from which the proton structure function F_2(x,Q^2) and the longitudinal structure function F_L(x,Q^2) are extracted, is measured with typically 1% statistical and 3% systematic uncertainties. The measured partial derivative (dF_2(x,Q^2)/dln Q^2)_x is observed to rise continuously towards small x for fixed Q^2. The cross section data are combined with published H1 measurements at high Q^2 for a next-to-leading order DGLAP QCD analysis.The H1 data determine the gluon momentum distribution in the range 3*10^(-4)<= x <=0.1 to within an experimental accuracy of about 3% for Q^2 =20 GeV^2. A fit of the H1 measurements and the mu p data of the BCDMS collaboration allows the strong coupling constant alpha_s and the gluon distribution to be simultaneously determined. A value of alpha _s(M_Z^2)=0.1150+-0.0017 (exp) +0.0009-0.0005 (model) is obtained in NLO, with an additional theoretical uncertainty of about +-0.005, mainly due to the uncertainty of the renormalisation scale.Comment: 68 pages, 24 figures and 18 table

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Cranial Growth and Variation in Edmontosaurs (Dinosauria: Hadrosauridae): Implications for Latest Cretaceous Megaherbivore Diversity in North America

The well-sampled Late Cretaceous fossil record of North America remains the only high-resolution dataset for evaluating patterns of dinosaur diversity leading up to the terminal Cretaceous extinction event. Hadrosaurine hadrosaurids (Dinosauria: Ornithopoda) closely related to Edmontosaurus are among the most common megaherbivores in latest Campanian and Maastrichtian deposits of western North America. However, interpretations of edmontosaur species richness and biostratigraphy have been in constant flux for almost three decades, although the clade is generally thought to have undergone a radiation in the late Maastrichtian. We address the issue of edmontosaur diversity for the first time using rigorous morphometric analyses of virtually all known complete edmontosaur skulls. Results suggest only two valid species, Edmontosaurus regalis from the late Campanian, and E. annectens from the late Maastrichtian, with previously named taxa, including the controversial Anatotitan copei, erected on hypothesized transitional morphologies associated with ontogenetic size increase and allometric growth. A revision of North American hadrosaurid taxa suggests a decrease in both hadrosaurid diversity and disparity from the early to late Maastrichtian, a pattern likely also present in ceratopsid dinosaurs. A decline in the disparity of dominant megaherbivores in the latest Maastrichtian interval supports the hypothesis that dinosaur diversity decreased immediately preceding the end Cretaceous extinction event

Understanding How Social Entrepreneurs Fit into the Tourism Discourse

This chapter discusses how social entrepreneurs fit into the existing tourism discourse. It examines four areas of literature in particular, tourism entrepreneurs, sustainability, destination development and intrapreneurship, and analyzes how introducing the concept of social entrepreneurs into these discussions is useful, and contributes to our understanding. Furthermore the paper illustrates that as social entrepreneurs are relevant to a broad range of issues in the tourism literature this should prevent the development of research silos where social entrepreneurship scholars seek out their own vein of research. The nexus of common ground and interests, as displayed in this chapter, should enhance the development of research, thought and understanding of social entrepreneurs within the field as a whole The key argument is that research on social entrepreneurs is not just relevant for those interested in entrepreneurs it also effects our thinking on issues such as destination development, relationships between stakeholders, tourism policy and sustainability. The chapter concludes with a wide range of questions for further research

Importance of lysosomal cysteine proteases in lung disease

The human lysosomal cysteine proteases are a family of 11 proteases whose members include cathepsins B, C, H, L, and S. The biology of these proteases was largely ignored for decades because of their lysosomal location and the belief that their function was limited to the terminal degradation of proteins. In the past 10 years, this view has changed as these proteases have been found to have specific functions within cells. This review highlights some of these functions, specifically their roles in matrix remodeling and in regulating the immune response, and their relationship to lung diseases

Transitions in bacterial communities along the 2000 km salinity gradient of the Baltic Sea

Salinity is a major factor controlling the distribution of biota in aquatic systems, and most aquatic multicellular organisms are either adapted to life in saltwater or freshwater conditions. Consequently, the saltwater–freshwater mixing zones in coastal or estuarine areas are characterized by limited faunal and floral diversity. Although changes in diversity and decline in species richness in brackish waters is well documented in aquatic ecology, it is unknown to what extent this applies to bacterial communities. Here, we report a first detailed bacterial inventory from vertical profiles of 60 sampling stations distributed along the salinity gradient of the Baltic Sea, one of world's largest brackish water environments, generated using 454 pyrosequencing of partial (400 bp) 16S rRNA genes. Within the salinity gradient, bacterial community composition altered at broad and finer-scale phylogenetic levels. Analogous to faunal communities within brackish conditions, we identified a bacterial brackish water community comprising a diverse combination of freshwater and marine groups, along with populations unique to this environment. As water residence times in the Baltic Sea exceed 3 years, the observed bacterial community cannot be the result of mixing of fresh water and saltwater, but our study represents the first detailed description of an autochthonous brackish microbiome. In contrast to the decline in the diversity of multicellular organisms, reduced bacterial diversity at brackish conditions could not be established. It is possible that the rapid adaptation rate of bacteria has enabled a variety of lineages to fill what for higher organisms remains a challenging and relatively unoccupied ecological niche