The Evaluation of a Rapid In Situ HIV Confirmation Test in a Programme with a High Failure Rate of the WHO HIV Two-Test Diagnostic Algorithm

BACKGROUND: Concerns about false-positive HIV results led to a review of testing procedures used in a Médecins Sans Frontières (MSF) HIV programme in Bukavu, eastern Democratic Republic of Congo. In addition to the WHO HIV rapid diagnostic test algorithm (RDT) (two positive RDTs alone for HIV diagnosis) used in voluntary counselling and testing (VCT) sites we evaluated in situ a practical field-based confirmation test against western blot WB. In addition, we aimed to determine the false-positive rate of the WHO two-test algorithm compared with our adapted protocol including confirmation testing, and whether weakly reactive compared with strongly reactive rapid test results were more likely to be false positives. METHODOLOGY/PRINCIPAL FINDINGS: 2864 clients presenting to MSF VCT centres in Bukavu during January to May 2006 were tested using Determine HIV-1/2 and UniGold HIV rapid tests in parallel by nurse counsellors. Plasma samples on 229 clients confirmed as double RDT positive by laboratory retesting were further tested using both WB and the Orgenics Immunocomb Combfirm HIV confirmation test (OIC-HIV). Of these, 24 samples were negative or indeterminate by WB representing a false-positive rate of the WHO two-test algorithm of 10.5% (95%CI 6.6-15.2). 17 of the 229 samples were weakly positive on rapid testing and all were negative or indeterminate by WB. The false-positive rate fell to 3.3% (95%CI 1.3-6.7) when only strong-positive rapid test results were considered. Agreement between OIC-HIV and WB was 99.1% (95%CI 96.9-99.9%) with no false OIC-HIV positives if stringent criteria for positive OIC-HIV diagnoses were used. CONCLUSIONS: The WHO HIV two-test diagnostic algorithm produced an unacceptably high level of false-positive diagnoses in our setting, especially if results were weakly positive. The most probable causes of the false-positive results were serological cross-reactivity or non-specific immune reactivity. Our findings show that the OIC-HIV confirmation test is practical and effective in field contexts. We propose that all double-positive HIV RDT samples should undergo further testing to confirm HIV seropositivity until the accuracy of the RDT testing algorithm has been established at programme level

Inhibition of Hypoxia-Inducible Factor-1α (HIF-1α) Protein Synthesis by DNA damage inducing agents

10.1371/journal.pone.0010522PLoS ONE55

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

Psychological adjustment and quality of life in children and adolescents following open-heart surgery for congenital heart disease: a systematic review

BACKGROUND: Children with congenital heart defects (CHD) requiring open-heart surgery are a group at high risk for health-related sequelae. Little consensus exists regarding their long-term psychological adjustment (PA) and health-related quality of life (QoL). Thus, we conducted a systematic review to determine the current knowledge on long-term outcome in this population. METHODS: We included randomized controlled trials, case control, or cohort studies published between 1990-2008 evaluating self- and proxy-reported PA and QoL in patients aged between two and 17 years with a follow-up of at least two years after open heart surgery for CHD. RESULTS: Twenty-three studies assessing psychological parameters and 12 studies assessing QoL were included. Methodological quality of the studies varied greatly with most studies showing a moderate quality. Results were as follows: (a) A considerable proportion of children experienced psychological maladjustment according to their parents; (b) studies on self-reported PA indicate a good outcome; (c) the studies on QoL suggest an impaired QoL for some children in particular for those with more severe cardiac disease; (d) parental reports of psychological maladjustment were related to severity of CHD and developmental delay. CONCLUSION: A significant proportion of survivors of open-heart surgery for CHD are at risk for psychological maladjustment and impaired QoL. Future research needs to focus on self-reports, QoL data and adolescents

Placental miR-340 mediates vulnerability to activity based anorexia in mice

Anorexia nervosa is characterised by self-starvation but its etiology is not completely understood. Here the authors describe how prenatal stress can induce activity-based anorexia in the offspring during early adulthood by upregulating miR-340 expression in the placenta that affects expression of nutrient transporters

Using high-resolution LiDAR data to quantify the three-dimensional structure of vegetation in urban green space

The spatial arrangement and vertical structure of vegetation in urban green spaces are key factors in determining the types of benefits that urban parks provide to people. This includes opportunities for recreation, spiritual fulfilment and biodiversity conservation. However, there has been little consideration of how the fine-scale spatial and vertical structure of vegetation is distributed in urban parks, primarily due to limitations in methods for doing so. We addressed this gap by developing a method using Light Detection and Ranging (LiDAR) data to map, at a fine resolution, tree cover, vegetation spatial arrangement, and vegetation vertical structure. We then applied this method to urban parks in Brisbane, Australia. We found that parks varied mainly in their amount of tree cover and its spatial arrangement, but also in vegetation vertical structure. Interestingly, the vertical structure of vegetation was largely independent of its cover and spatial arrangement. This suggests that vertical structure may be being managed independently to tree cover to provide different benefits across urban parks with different levels of tree cover. Finally, we were able to classify parks into three distinct classes that explicitly account for both the spatial and vertical structure of tree cover. Our approach for mapping the three-dimensional vegetation structure of urban green space provides a much more nuanced and functional description of urban parks than has previously been possible. Future research is now needed to quantify the relationships between vegetation structure and the actual benefits people derive from urban green space.</p

Intracellular Ion Channel CLIC1: Involvement in Microglia-Mediated β-Amyloid Peptide(1-42) Neurotoxicity

Microglia can exacerbate central nervous system disorders, including stroke and chronic progressive neurodegenerative diseases such as Alzheimer disease. Mounting evidence points to ion channels expressed by microglia as contributing to these neuropathologies. The Chloride Intracellular Channel (CLIC) family represents a class of chloride intracellular channel proteins, most of which are localized to intracellular membranes. CLICs are unusual in that they possess both soluble and integral membrane forms. Amyloid beta-peptide (A beta) accumulation in plaques is a hallmark of familial Alzheimer disease. The truncated A beta(25-35) species was shown previously to increase the expression of CLIC1 chloride conductance in cortical microglia and to provoke microglial neurotoxicity. However, the highly pathogenic and fibrillogenic full-length A beta(1-42) species was not examined, nor was the potential role of CLIC1 in mediating microglial activation and neurotoxicity by other stimuli (e.g. ligands for the Toll-like receptors). In the present study, we utilized a two chamber Transwell (TM) cell culture system to allow separate treatment of microglia and neurons while examining the effect of pharmacological blockade of CLIC1 in protecting cortical neurons from toxicity caused by A beta(1-42)- and lipopolysaccaride-stimulated microglia. Presentation of A beta(1-42) to the upper, microglia-containing chamber resulted in a progressive loss of neurons over 3 days. Neuronal cell injury was prevented by the CLIC1 ion channel blockers IAA-94 [(R(+)-[(6,7-dichloro-2-cyclopentyl-2,3-dihydro-2-methyl-1-oxo-1H-inden-5yl)-oxy] acetic acid)] and niflumic acid (2-{[3-(trifluoromethyl)phenyl]amino}nicotinic acid) when presented to the upper chamber only. Incubation of microglia with lipopolysaccharide plus interferon-gamma led to neuronal cell injury which, however, was insensitive to inhibition by the CLIC1 channel blockers, suggesting a degree of selectivity in agents leading to CLIC1 activation