Incident Tuberculosis during Antiretroviral Therapy Contributes to Suboptimal Immune Reconstitution in a Large Urban HIV Clinic in Sub-Saharan Africa

Antiretroviral therapy (ART) effectively decreases tuberculosis (TB) incidence long-term, but is associated with high TB incidence rates in the first 6 months. We sought to determine the incidence and the long-term effects of TB during ART on HIV treatment outcome, and the risk factors for incident TB during ART in a large urban HIV clinic in Uganda.Routinely collected longitudinal clinical data from all patients initiated on first-line ART was retrospectively analysed. 5,982 patients were included with a median baseline CD4+ T cell count (CD4 count) of 117 cells/mm(3) (interquartile range [IQR]; 42, 182). In the first 2 years, there were 336 (5.6%) incident TB events in 10,710 person-years (py) of follow-up (3.14 cases/100 pyar [95% CI 2.82-3.49]); incidence rates at 0-3, 3-6, 6-12 and 12-24 months were 11.25 (9.58-13.21), 6.27 (4.99-7.87), 2.47 (1.87-3.36) and 1.02 (0.80-1.31), respectively. Incident TB during ART was independently associated with baseline CD4 count of <50 cells/mm(3) (hazard ratio [HR] 1.84 [1.25-2.70], P = 0.002) and male gender (HR 1.68 [1.34-2.11], P<0.001). After two years on ART, the patients who had developed TB in the first 12 months had a significantly lower median CD4 count increase (184 cells/mm(3) [IQR; 107, 258, n = 118] vs 209 cells/mm(3) [124, 309, n = 2166], P = 0.01), a larger proportion of suboptimal immune reconstitution according to two definitions (increase in CD4 count <200 cells/mm(3): 57.4% vs 46.9%, P = 0.03, and absolute CD4 count <200 cells/mm(3): 30.4 vs 19.9%, P = 0.006), and a higher percentage of immunological failure according to the WHO criteria (13.6% vs 6.5%, P = 0.003). Incident TB during ART was independently associated with poor CD4 count recovery and fulfilling WHO immunological failure definitions.Incident TB during ART occurs most often within 3 months and in patients with CD4 counts less than 50 cells/mm(3). Incident TB during ART is associated with long-term impairment in immune recovery

Search for Exotic Strange Quark Matter in High Energy Nuclear Reactions

We report on a search for metastable positively and negatively charged states of strange quark matter in Au+Pb reactions at 11.6 A GeV/c in experiment E864. We have sampled approximately six billion 10% most central Au+Pb interactions and have observed no strangelet states (baryon number A < 100 droplets of strange quark matter). We thus set upper limits on the production of these exotic states at the level of 1-6 x 10^{-8} per central collision. These limits are the best and most model independent for this colliding system. We discuss the implications of our results on strangelet production mechanisms, and also on the stability question of strange quark matter.Comment: 21 pages, 9 figures, to be published in Nuclear Physics A (Carl Dover memorial edition

Scoliosis: density-equalizing mapping and scientometric analysis

<p>Abstract</p> <p>Background</p> <p>Publications related to scoliosis have increased enormously. A differentiation between publications of major and minor importance has become difficult even for experts. Scientometric data on developments and tendencies in scoliosis research has not been available to date. The aim of the current study was to evaluate the scientific efforts of scoliosis research both quantitatively and qualitatively.</p> <p>Methods</p> <p>Large-scale data analysis, density-equalizing algorithms and scientometric methods were used to evaluate both the quantity and quality of research achievements of scientists studying scoliosis. Density-equalizing algorithms were applied to data retrieved from ISI-Web.</p> <p>Results</p> <p>From 1904 to 2007, 8,186 items pertaining to scoliosis were published and included in the database. The studies were published in 76 countries: the USA, the U.K. and Canada being the most productive centers. The Washington University (St. Louis, Missouri) was identified as the most prolific institution during that period, and orthopedics represented by far the most productive medical discipline. "BRADFORD, DS" is the most productive author (146 items), and "DANSEREAU, J" is the author with the highest scientific impact (h-index of 27).</p> <p>Conclusion</p> <p>Our results suggest that currently established measures of research output (i.e. impact factor, h-index) should be evaluated critically because phenomena, such as self-citation and co-authorship, distort the results and limit the value of the conclusions that may be drawn from these measures. Qualitative statements are just tractable by the comparison of the parameters with respect to multiple linkages. In order to obtain more objective evaluation tools, new measurements need to be developed.</p

Evidence for functional state transitions in intensively-managed soil ecosystems

Soils are fundamental to terrestrial ecosystem functioning and food security, thus their resilience to disturbances is critical. Furthermore, they provide effective models of complex natural systems to explore resilience concepts over experimentally-tractable short timescales. We studied soils derived from experimental plots with different land-use histories of long-term grass, arable and fallow to determine whether regimes of extreme drying and re-wetting would tip the systems into alternative stable states, contingent on their historical management. Prior to disturbance, grass and arable soils produced similar respiration responses when processing an introduced complex carbon substrate. A distinct respiration response from fallow soil here indicated a different prior functional state. Initial dry:wet disturbances reduced the respiration in all soils, suggesting that the microbial community was perturbed such that its function was impaired. After 12 drying and rewetting cycles, despite the extreme disturbance regime, soil from the grass plots, and those that had recently been grass, adapted and returned to their prior functional state. Arable soils were less resilient and shifted towards a functional state more similar to that of the fallow soil. Hence repeated stresses can apparently induce persistent shifts in functional states in soils, which are influenced by management history

Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity

TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations

Mind the gap: sentencing, rehabilitation and civic purgatory

This article discusses the relationships and tensions between the sentencing, statutory supervision and legal rehabilitation of lawbreakers under UK legislation. It does so with reference to both the Rehabilitation of Offenders Act 1974, which allows some criminal records to become ‘spent’ after a set period of time, and the Offender Rehabilitation Act 2014, which was designed to significantly expand statutory supervision arrangements. The article also demonstrates how, post-supervision, many former lawbreakers are cast into a state of ‘civic purgatory’, before suggesting that a more fully integrated approach to rehabilitation is required

When we should worry more: Using cognitive bias modification to drive adaptive health behaviour

A lack of behavioural engagement in health promotion or disease prevention is a problem across many health domains. In these cases where people face a genuine danger, a reduced focus on threat and low levels of anxiety or worry are maladaptive in terms of promoting protection or prevention behaviour. Therefore, it is possible that increasing the processing of threat will increase worry and thereby enhance engagement in adaptive behaviour. Laboratory studies have shown that cognitive bias modification (CBM) can increase or decrease anxiety and worry when increased versus decreased processing of threat is encouraged. In the current study, CBM for interpretation (CBM-I) is used to target engagement in sun protection behaviour. The goal was to investigate whether inducing a negative rather than a positive interpretation bias for physical threat information can enhance worry elicited when viewing a health campaign video (warning against melanoma skin cancer), and consequently lead to more adaptive behaviour (sun protection). Participants were successfully trained to either adopt a positive or negative interpretation bias using physical threat scenarios. However, contrary to expectations results showed that participants in the positive training condition reported higher levels of worry elicited by the melanoma video than participants in the negative training condition. Video elicited worry was, however, positively correlated with a measure of engagement in sun protection behaviour, suggesting that higher levels of worry do promote adaptive behaviour. These findings imply that more research is needed to determine under which conditions increased versus decreased processing of threat can drive adaptive worry. Various potential explanations for the current findings and suggestions for future research are discussed

C-Jun N-terminal kinase (JNK) isoforms play differing roles in otitis media

BACKGROUND: Innate immunity and tissue proliferation play important roles in otitis media (OM), the most common disease of childhood. CJUN terminal kinase (JNK) is potentially involved in both processes. RESULTS: Genes involved in both innate immune and growth factor activation of JNK are upregulated during OM, while expression of both positive and negative JNK regulatory genes is altered. When compared to wildtypes (WTs), C57BL/6 mice deficient in JNK1 exhibit enhanced mucosal thickening, with delayed recovery, enhanced neutrophil recruitment early in OM, and delayed bacterial clearance. In contrast, JNK2(−/−) mice exhibit delayed mucosal hyperplasia that eventually exceeds that of WTs and is slow to recover, delayed recruitment of neutrophils, and failure of bacterial clearance. CONCLUSIONS: The results suggest that JNK1 and JNK2 play primarily opposing roles in mucosal hyperplasia and neutrophil recruitment early in OM. However, both isoforms are required for the normal resolution of middle ear infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-014-0046-z) contains supplementary material, which is available to authorized users

Dynamical Mean-Field Theory

The dynamical mean-field theory (DMFT) is a widely applicable approximation scheme for the investigation of correlated quantum many-particle systems on a lattice, e.g., electrons in solids and cold atoms in optical lattices. In particular, the combination of the DMFT with conventional methods for the calculation of electronic band structures has led to a powerful numerical approach which allows one to explore the properties of correlated materials. In this introductory article we discuss the foundations of the DMFT, derive the underlying self-consistency equations, and present several applications which have provided important insights into the properties of correlated matter.Comment: Chapter in "Theoretical Methods for Strongly Correlated Systems", edited by A. Avella and F. Mancini, Springer (2011), 31 pages, 5 figure

Immune reconstitution inflammatory syndrome from Penicillium marneffei in an HIV-infected child: a case report and review of literature

<p>Abstract</p> <p>Backgrounds</p> <p>Disseminated <it>Penicillium marneffei </it>infection is one of the most common HIV-related opportunistic infections in Southeast Asia. Immune reconstitution inflammatory syndrome (IRIS) is a complication related to antiretroviral therapy (ART)-induced immune restoration. The aim of this report is to present a case of HIV-infected child who developed an unmasking type of IRIS caused by disseminated <it>P. marneffei </it>infection after ART initiation.</p> <p>Case presentation</p> <p>A 14-year-old Thai HIV-infected girl presented with high-grade fever, multiple painful ulcerated oral lesions, generalized non-pruritic erythrematous skin papules and nodules with central umbilication, and multiple swollen, warm, and tender joints 8 weeks after ART initiation. At that time, her CD4⁺cell count was 7.2% or 39 cells/mm³. On admission, her repeated CD4⁺cell count was 11% or 51 cells/mm³and her plasma HIV-RNA level was < 50 copies/mL. Her skin biopsy showed necrotizing histiocytic granuloma formation with neutrophilic infiltration in the upper and reticular dermis. Tissue sections stained with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Grocott methenamine silver (GMS) stain revealed numerous intracellular and extracellular, round to oval, elongated, thin-walled yeast cells with central septation. The hemoculture, bone marrow culture, and skin culture revealed no growth of fungus or bacteria. Our patient responded well to intravenous amphotericin B followed by oral itraconazole. She fully recovered after 4-month antifungal treatment without evidence of recurrence of disease.</p> <p>Conclusions</p> <p>IRIS from <it>P. marneffei </it>in HIV-infected people is rare. Appropriate recognition and properly treatment is important for a good prognosis.</p