Shifts to global development : is this a reframing of power, agency and progress?

This special section on global development has been developed from a conference roundtable event run by the Development Geographies Research Group of the Royal Geographical Society. In this special section, we (some of the committee) introduce the four papers and their critical contributions to emerging debates. These extend early work on how the “global” is being made, focusing on the projects of multilateral development agencies and state institutions to examine how (and whether) the rebranding of “international development” as “global development” constitutes a shift in thinking and practice. Together, the papers draw our attention to the considerable opportunities and implications that this reframing offers, while highlighting that critical attention is required as to how that framing is deployed and by whom. They reveal disparity between global development as a much-needed reframing of power, agency, and progress and global development as produced by mainstream development actors and interventions, necessitating more critical research into how this normative agenda is adopted and enacted in dominant policy and practice.PostprintPeer reviewe

Ross River Virus Disease Reemergence, Fiji, 2003–2004

We report 2 clinically characteristic and serologically positive cases of Ross River virus infection in Canadian tourists who visited Fiji in late 2003 and early 2004. This report suggests that Ross River virus is once again circulating in Fiji, where it apparently disappeared after causing an epidemic in 1979 to 1980

Identification of a potent and selective LAPTc inhibitor by RapidFire-Mass Spectrometry, with antichagasic activity

Background: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and leads to ~10,000 deaths each year. Nifurtimox and benznidazole are the only two drugs available but have significant adverse effects and limited efficacy. New chemotherapeutic agents are urgently required. Here we identified inhibitors of the acidic M17 leucyl-aminopeptidase from T. cruzi (LAPTc) that show promise as novel starting points for Chagas disease drug discovery.Methodology/Principal findings: A RapidFire-MS screen with a protease-focused compound library identified novel LAPTc inhibitors. Twenty-eight hits were progressed to the dose-response studies, from which 12 molecules inhibited LAPTc with IC50 &lt; 34 μM. Of these, compound 4 was the most potent hit and mode of inhibition studies indicate that compound 4 is a competitive LAPTc inhibitor, with Ki 0.27 μM. Compound 4 is selective with respect to human LAP3, showing a selectivity index of &gt;500. Compound 4 exhibited sub-micromolar activity against intracellular T. cruzi amastigotes, and while the selectivity-window against the host cells was narrow, no toxicity was observed for un-infected HepG2 cells. In silico modelling of the LAPTc-compound 4 interaction is consistent with the competitive mode of inhibition. Molecular dynamics simulations reproduce the experimental binding strength (-8.95 kcal/mol), and indicate a binding mode based mainly on hydrophobic interactions with active site residues without metal cation coordination.Conclusions/Significance: Our data indicates that these new LAPTc inhibitors should be considered for further development as antiparasitic agents for the treatment of Chagas disease.</p

Review of the comparative susceptibility of microbial species to photoinactivation using 380-480 nm violet-blue light

Antimicrobial violet-blue light is an emerging technology designed for enhanced clinical decontamination and treatment applications, due to its safety, efficacy and ease of use. This systematised review was designed to compile the current knowledge on the antimicrobial efficacy of 380-480 nm light on a range of healthcare and food related pathogens including vegetative bacteria, bacterial endospores, fungi and viruses. Data was compiled from 79 studies, with the majority focussing on wavelengths in the region of 405 nm. Analysis indicated that Gram positive and negative vegetative bacteria are the most susceptible organisms, whilst bacterial endospores, viruses and bacteriophage are the least. Evaluation of the dose required for a 1 log10 reduction of key bacteria compared to population, irradiance and wavelength indicated that microbial titre and light intensity had little effect on the dose of 405 nm light required, however linear analysis indicated organisms exposed to longer wavelengths of violet-blue light, may require greater doses for inactivation. Additional research is required to ensure this technology can be used effectively, including: investigating inactivation of multidrug-resistant organisms, fungi, viruses and protozoa; further knowledge about the photodynamic inactivation mechanism of action; the potential for microbial resistance; and the establishment of a standardised exposure methodology

Routine Surveillance Data as a Resource for Planning Integration of NTD Case Management

Background: There is a high burden of morbidity due to neglected tropical diseases. To help address this, the World Health Organization recommends integration of case management (CM). Here, we present a practical framework designed to identify areas that could benefit from an integrated CM strategy in Ghana. We also investigated the accessibility of primary health care (PHC) to CM cases, and the impact of this on morbidity at diagnosis. Methods: Routinely detected cases of Buruli ulcer (BU) and leprosy, and suspected lymphedema identified through morbidity surveys during mass drug administration campaigns in Ghana in 2014 were remotely georeferenced. We estimated distances from cases’ home communities to the nearest primary healthcare facility (PHC), and compared rates of reported disease, completeness of clinical information, and risk of more severe morbidity, relative to PHC accessibility. Results: We georeferenced communities of 295/350 reported leprosy cases, 240/333 BU cases, and 1,557/2383 instances of lymphedema. Overlap of these diseases was predominantly around Accra and in the Upper East Region. Rates of reported disease appeared higher in populations with higher accessibility to PHC, and leprosy cases living further from PHC had a higher risk of disability at diagnosis. Conclusions: This investigation demonstrates the feasibility and value of using routinely collected data to map CM-NTDs at low cost. The maps presented are intended to provide a resource for planning the implementation of integrated CM for NTDs in Ghana. This approach could be easily implemented by national health services in other endemic countries in the future

Aerosol-induced brucellosis increases TLR-2 expression and increased complexity in the microanatomy of astroglia in rhesus macaques

Brucella melitensis, a bacterial pathogen and agent of epizootic abortion causes multiple pathologies in humans as well as a number of agriculturally important animal species. Clinical human brucellosis manifests as a non-specific, chronic debilitating disease characterized by undulant fever, arthropathies, cardiomyopathies and neurological sequelae. These symptoms can occur acutely for a few weeks or persist for months to years. Within the brain, endothelial and glial cells can be infected leading to downstream activation events including matrix metalloprotease (MMP) and cytokine secretion and Toll-like receptor (TLR) signaling. These events are likely to lead to tissue remodeling, including morphologic changes in neuronal and glial cells, which are linked to neurological complications including depressive behavior, immune activation and memory loss. Our hypothesis was that B. melitensis infection and neurobrucellosis would lead to activation of astrocytes through upregulation of TLR2 and stimulate concurrent changes in the microanatomy. All six animals were infected via inhalation route. TLR2 expression was approximately doubled in white matter astrocytes of infected rhesus macaques. There was also a 50% increase in the number of astrocytes per unit area in subcortical white matter tracts suggesting increased innate immune activation. This coincided with dramatic increases in the length and complexity of the cell arbor of hypertrophic astrocytes in both cortical gray and white matter. Thus, aerosol-induced brucellosis results in dramatically increased innate immune activation of astrocytes in the absence of widespread neuroinflammation

On the asymmetry of biological frequency distributions

The long-standing problem of determining whether the skewness in a sample frequency distribution is the manifestation of the intermixing of disparate groups characterizable by a normal mixture distribution or the manifestation of non-mixture, skew-producing determinants is discussed. Biometrical tools for modeling and quantifying the significance of the skewness in a trait of interest that invite interpretations other than those formed in mixtures or “subgroups” are elaborated. Statistical methods for testing whether a normal mixture distribution better characterizes a set of data than the proposed (or any other) skewed, single-population-oriented models are offered. The power of these tests is examined through Monte Carlo experimentation. A brief application in hypertension research demonstrates some of the problems and methods discussed in the paper.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38499/1/1370070605_ftp.pd

Landscape-level controls on dissolved carbon flux from diverse catchments of the circumboreal

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 26 (2012): GB0E02, doi:10.1029/2012GB004299.While much of the dissolved organic carbon (DOC) within rivers is destined for mineralization to CO2, a substantial fraction of riverine bicarbonate (HCO3−) flux represents a CO2 sink, as a result of weathering processes that sequester CO2 as HCO3−. We explored landscape-level controls on DOC and HCO3− flux in subcatchments of the boreal, with a specific focus on the effect of permafrost on riverine dissolved C flux. To do this, we undertook a multivariate analysis that partitioned the variance attributable to known, key regulators of dissolved C flux (runoff, lithology, and vegetation) prior to examining the effect of permafrost, using riverine biogeochemistry data from a suite of subcatchments drawn from the Mackenzie, Yukon, East, and West Siberian regions of the circumboreal. Across the diverse catchments that we study, controls on HCO3− flux were near-universal: runoff and an increased carbonate rock contribution to weathering (assessed as riverwater Ca:Na) increased HCO3− yields, while increasing permafrost extent was associated with decreases in HCO3−. In contrast, permafrost had contrasting and region-specific effects on DOC yield, even after the variation caused by other key drivers of its flux had been accounted for. We used ionic ratios and SO4 yields to calculate the potential range of CO2 sequestered via weathering across these boreal subcatchments, and show that decreasing permafrost extent is associated with increases in weathering-mediated CO2 fixation across broad spatial scales, an effect that could counterbalance some of the organic C mineralization that is predicted with declining permafrost.Funding for this work was provided through NSF-OPP-0229302 and NSF-OPP-0732985. Additional support to S.E.T. was provided by an NSERC Postdoctoral Fellowship.2013-02-2

Problem drug use the public health imperative: what some of the literature says

<p>Abstract</p> <p>Background</p> <p>With more than 200,000 problem drug users is contact with structured treatment services in England the public health imperative behind drug treatment is great. Problem drug use for many is a chronic and relapsing condition, where "cure" is often neither a reasonable or appropriate expectation and it can further be argued that in these circumstances problem drug use is no different from any number of chronic and enduring health conditions that are managed in the health care system and therefore should be conceptualised as such.</p> <p>Discussion</p> <p>A public health approach to drug treatment emphasises the need for drug users in or accessing treatment, to reduce their harmful drug use, reduce drug use related risks such as sepsis and overdose and stay alive for longer. However a public health perspective in relation to problem drug use isn't always either apparent or readily understood and to that end there is still a significant need to continue the arguments and debate that treatment and interventions for problem and dependent drug users need to extend beyond an individualistic approach. For the purposes of discussion in this article public and population health will be used interchangeably.</p> <p>Summary</p> <p>A recognition and acceptance that a public and population health approach to the management of problem drug users is sound public health policy also then requires a long term commitment in terms of staffing and resources where service delivery mirrors that of chronic condition management.</p