Comparison of two interferon-gamma release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB) in testing for latent tuberculosis infection among HIV-infected adults.

There is currently no 'gold standard' for diagnosis of latent tuberculosis infection (LTBI), and both the tuberculin skin test and interferon-gamma release assays (IGRAs) are used for diagnosis; the latter have a higher sensitivity than tuberculin skin tests for diagnosis of LTBI in HIV-infected individuals with lower CD4 counts. No evidence base exists for selection of IGRA methodology to identify LTBI among human immunodeficiency virus-infected patients in the UK. We prospectively evaluated two commercially available IGRA methods (QuantiFERON-TB Gold In Tube [QFG] and T-SPOT.TB) for testing LTBI among HIV-infected patients potentially nosocomially exposed to an HIV-infected patient with 'smear-positive' pulmonary tuberculosis. Among the exposed patients median CD4 count was 550 cells/µL; 105 (90%) of 117 were receiving antiretroviral therapy, of who 104 (99%) had an undetectable plasma HIV load. IGRAs were positive in 12 patients (10.3%); QFG positive in 11 (9.4%) and T-SPOT.TB positive in six (5.1%); both IGRAs were positive in five patients (4.3%). There was one indeterminate QFG and one borderline T-SPOT.TB result. Concordance between the two IGRAs was moderate (κ = 0.56, 95% confidence interval = 0.27-0.85). IGRAs were positive in only 4 (29%) of 14 patients with previous culture-proven tuberculosis. No patient developed tuberculosis during 20 months of follow-up

Cost performance and risk in the construction of offshore and onshore wind farms

This article investigates the risk of cost overruns and underruns occurring in the construction of 51 onshore and offshore wind farms commissioned between 2000 and 2015 in 13 countries. In total, these projects required about $39 billion in investment and reached about 11 GW of installed capacity. We use this original dataset to test six hypotheses about construction cost overruns related to (i) technological learning, (ii) fiscal control, (iii) economies of scale, (iv) configuration, (v) regulation and markets and (vi) manufacturing experience. We find that across the entire dataset, the mean cost escalation per project is 6.5$63 million per windfarm, although 20 projects within the sample (39%) did not exhibit cost overruns. The majority of onshore wind farms exhibit cost underruns while for offshore wind farms the results have a larger spread. Interestingly, no significant relationship exists between the size (in total MWor per individual turbine capacity) of a windfarm and the severity of a cost overrun. Nonetheless, there is an indication that the risk increases for larger wind farms at greater distances offshore using new types of turbines and foundations. Overall, the mean cost escalation for onshore projects is 1.7% and 9.6% for offshore projects, amounts much lower than those for other energy infrastructure

Interleukin-1ß mRNA expression in ischemic rat cortex

Background and Pur pose: Interleukin-1ß is a proinftammatory cytokine produced by blood-borne and resident brain inftammatory cells. The present study was conducted to determine if interleukin-1ß mRNA was produced in the brain of rats subjected to permanent focal ischemia. Methods: Rat interleukin-1ß cDNA, synthesized from stimulated rat peritoneal macrophage RNA by reverse transcription and polymerase chain reaction and c10ned in plasmid Bluescript KS+, was used to evaluate the expression of interleukin-1ß mRNA in cerebral cortex from spontaneously hypertensive rats and normotensive rats subjected to permanent middle cerebral artery occlusion. Interleukin-1ß mRNA was quantified by Northern blot analysis and compared with rat macrophage RNA standard. To correct for gel loading, blots were also analyzed with cyclophilin cDNA, which encodes an abundant, conserved protein that was unchanged by the experimental conditions. Results: Interleukin-1ß mRNA produced in the ischemic zone was significantly increased from 6 hours to 120 hours, with a maximum of211±24% ofinterleukin-1ß reference standard, ie, 0.2 ng stimulated rat macrophage RNA, mRNA compared with the level in nonischemic cortices (4±2%) at 12 hours after ischemia (P<.OI; n=6). Interleukin-1ß mRNA at 12 hours after ischemia was markedly elevated in hypertensive rats over levels found in two normotensive rat strains. Neurological deficits were also apparent only in the hypertensive rats. Conclusions: Brain interleukin-1ß mRNA is elevated acutely after permanent focal ischemia and especially in hypertensive rats. These data suggest that this potent proinflammatory and procoagulant cytokine might have a role in brain damage following ischemia

Spatial housing economics: a survey

This introduction to the Virtual Special Issue surveys the development of spatial housing economics from its roots in neo-classical theory, through more recent developments in social interactions modelling, and touching on the role of institutions, path dependence and economic history. The survey also points to some of the more promising future directions for the subject that are beginning to appear in the literature. The survey covers elements hedonic models, spatial econometrics, neighbourhood models, housing market areas, housing supply, models of segregation, migration, housing tenure, sub-national house price modelling including the so-called ripple effect, and agent-based models. Possible future directions are set in the context of a selection of recent papers that have appeared in Urban Studies. Nevertheless, there are still important gaps in the literature that merit further attention, arising at least partly from emerging policy problems. These include more research on housing and biodiversity, the relationship between housing and civil unrest, the effects of changing age distributions - notably housing for the elderly - and the impact of different international institutional structures. Methodologically, developments in Big Data provide an exciting framework for future work

The ongoing need for rates: can physiology and omics come together to co-design the measurements needed to understand complex ocean biogeochemistry?

The necessity to understand the influence of global ocean change on biota has exposed wide-ranging gaps in our knowledge of the fundamental principles that underpin marine life. Concurrently, physiological research has stagnated, in part driven by the advent and rapid evolution of molecular biological techniques, such that they now influence all lines of enquiry in biological oceanography. This dominance has led to an implicit assumption that physiology is outmoded, and advocacy that ecological and biogeochemical models can be directly informed by omics. However, the main modeling currencies are biological rates and biogeochemical fluxes. Here, we ask: how do we translate the wealth of information on physiological potential from omics-based studies to quantifiable physiological rates and, ultimately, to biogeochemical fluxes? Based on the trajectory of the state-of-the-art in biomedical sciences, along with case-studies from ocean sciences, we conclude that it is unlikely that omics can provide such rates in the coming decade. Thus, while physiological rates will continue to be central to providing projections of global change biology, we must revisit the metrics we rely upon. We advocate for the co-design of a new generation of rate measurements that better link the benefits of omics and physiology

Building capacity without disrupting health services: public health education for Africa through distance learning

The human resources crisis in Africa is especially acute in the public health field. Through distance education, the School of Public Health of the University of the Western Cape, South Africa, has provided access to master's level public health education for health professionals from more than 20 African countries while they remain in post. Since 2000, interest has increased overwhelmingly to a point where four times more applications are received than can be accommodated. This home-grown programme remains sensitive to the needs of the target learners while engaging them in high-quality learning applied in their own work contexts

Investigating hyper-vigilance for social threat of lonely children

The hypothesis that lonely children show hypervigilance for social threat was examined in a series of three studies that employed different methods including advanced eye-tracking technology. Hypervigilance for social threat was operationalized as hostility to ambiguously motivated social exclusion in a variation of the hostile attribution paradigm (Study 1), scores on the Children’s Rejection-Sensitivity Questionnaire (Study 2), and visual attention to socially rejecting stimuli (Study 3). The participants were 185 children (11 years-7 months to 12 years-6 months), 248 children (9 years-4 months to 11 years-8 months) and 140 children (8 years-10 months to 12 years-10 months) in the three studies, respectively. Regression analyses showed that, with depressive symptoms covaried, there were quadratic relations between loneliness and these different measures of hypervigilance to social threat. As hypothesized, only children in the upper range of loneliness demonstrated elevated hostility to ambiguously motivated social exclusion, higher scores on the rejection sensitivity questionnaire, and disengagement difficulties when viewing socially rejecting stimuli. We found that very lonely children are hypersensitive to social threat

Structured illumination microscopy combined with machine learning for the high throughput analysis of virus structure

Optical super-resolution microscopy techniques enable high molecular specificity with high spatial resolution and constitute a set of powerful tools in the investigation of the structure of supramolecular assemblies such as viruses. Here, we report on a new methodology which combines Structured Illumination Microscopy (SIM) with machine learning algorithms to image and classify the structure of large populations of biopharmaceutical viruses with high resolution. The method offers information on virus morphology that can ultimately be linked with functional performance. We demonstrate the approach on viruses produced for oncolytic viriotherapy (Newcastle Disease Virus) and vaccine development (Influenza). This unique tool enables the rapid assessment of the quality of viral production with high throughput obviating the need for traditional batch testing methods which are complex and time consuming. We show that our method also works on non-purified samples from pooled harvest fluids directly from the production line

Individual variation in levels of haptoglobin-related protein in children from Gabon

Background: Haptoglobin related protein (Hpr) is a key component of trypanosome lytic factors (TLF), a subset of highdensity lipoproteins (HDL) that form the first line of human defence against African trypanosomes. Hpr, like haptoglobin (Hp) can bind to hemoglobin (Hb) and it is the Hpr-Hb complexes which bind to these parasites allowing uptake of TLF. This unique form of innate immunity is primate-specific. To date, there have been no population studies of plasma levels of Hpr, particularly in relation to hemolysis and a high prevalence of ahaptoglobinemia as found in malaria endemic areas. Methods and Principal Findings: We developed a specific enzyme-linked immunosorbent assay to measure levels of plasma Hpr in Gabonese children sampled during a period of seasonal malaria transmission when acute phase responses (APR), malaria infection and associated hemolysis were prevalent. Median Hpr concentration was 0.28 mg/ml (range 0.03-1.1). This was 5-fold higher than that found in Caucasian children (0.049 mg/ml, range 0.002-0.26) with no evidence of an APR. A general linear model was used to investigate associations between Hpr levels, host polymorphisms, parasitological factors and the acute phase proteins, Hp, C-reactive protein (CRP) and albumin. Levels of Hpr were associated with Hp genotype, decreased with age and were higher in females. Hpr concentration was strongly correlated with that of Hp, but not CRP

Temperature responses of Rubisco from Paniceae grasses provide opportunities for improving C3 photosynthesis.

Enhancing the catalytic properties of the CO2-fixing enzyme Rubisco is a target for improving agricultural crop productivity. Here, we reveal extensive diversity in the kinetic response between 10 and 37 °C by Rubisco from C3 and C4 species within the grass tribe Paniceae. The CO2 fixation rate (kcatc) for Rubisco from the C4 grasses with nicotinamide adenine dinucleotide (NAD) phosphate malic enzyme (NADP-ME) and phosphoenolpyruvate carboxykinase (PCK) photosynthetic pathways was twofold greater than the kcatc of Rubisco from NAD-ME species across all temperatures. The declining response of CO2/O2 specificity with increasing temperature was less pronounced for PCK and NADP-ME Rubisco, which would be advantageous in warmer climates relative to the NAD-ME grasses. Modelled variation in the temperature kinetics of Paniceae C3 Rubisco and PCK Rubisco differentially stimulated C3 photosynthesis relative to tobacco above and below 25 °C under current and elevated CO2. Amino acid substitutions in the large subunit that could account for the catalytic variation among Paniceae Rubisco are identified; however, incompatibilities with Paniceae Rubisco biogenesis in tobacco hindered their mutagenic testing by chloroplast transformation. Circumventing these bioengineering limitations is critical to tailoring the properties of crop Rubisco to suit future climates