Similar neurocognitive outcomes after 48 weeks in HIV-1-infected participants randomized to continue tenofovir/emtricitabine + atazanavir/ritonavir or simplify to abacavir/lamivudine + atazanavir

Human immunodeficiency virus (HIV)-associated neurocognitive disorders can persist in many patients despite achieving viral suppression while on antiretroviral therapy (ART). Neurocognitive function over 48 weeks was evaluated using a Cogstate test battery assessing psychomotor function, attention, learning, and working memory in 293 HIV-1-infected, ART-experienced, and virologically suppressed adults. The ASSURE study randomized participants 1:2 to remain on tenofovir/emtricitabine (TDF/FTC) and ritonavir-boosted atazanavir (ATV/r) or simplify to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Neurocognitive z-scores were computed using demographically adjusted normative data and were classified as “impaired” (defined as either a z-score ≤ − 2 or having 2 or more standardized individual test z-scores ≤ − 1); while higher scores (equaling better performance) were classified as “normal”. By z-scores, 54.7% of participants had impaired neurocognition at baseline and 50.2% at week 48. There were no significant differences (p < 0.05) in the baseline-adjusted performance between treatment groups for any individual test or by z-score. Specific demographic and medical risk factors were evaluated by univariate analysis for impact on neurocognitive performance. Factors with p < 0.10 were evaluated by backwards regression analysis to identify neurocognition-correlated factors after accounting for treatment, assessment, and baseline. Four risk factors at baseline for impaired neurocognition were initially identified: lower CD4 nadir lymphocyte counts, higher Framingham risk scores, and interleukin-6 levels, and a history of psychiatric disorder not otherwise specified, however none were found to moderate the effect of treatment on neurocognition. In this aviremic, treatment-experienced population, baseline-adjusted neurocognitive function remained stable and equivalent over 48 weeks with both TDF/FTC + ATV/r-treated and in the ART-simplified ABC/3TC + ATV treatment groups

What are communities of practice? A comparative review of four seminal works

This paper is a comparative review of four seminal works on communities of practice. It is argued that the ambiguities of the terms community and practice are a source of the concept's reusability allowing it to be reappropriated for different purposes, academic and practical. However, it is potentially confusing that the works differ so markedly in their conceptualizations of community, learning, power and change, diversity and informality. The three earlier works are underpinned by a common epistemological view, but Lave and Wenger's 1991 short monograph is often read as primarily about the socialization of newcomers into knowledge by a form of apprenticeship, while the focus in Brown and Duguid's article of the same year is, in contrast, on improvising new knowledge in an interstitial group that forms in resistance to management. Wenger's 1998 book treats communities of practice as the informal relations and understandings that develop in mutual engagement on an appropriated joint enterprise, but his focus is the impact on individual identity. The applicability of the concept to the heavily individualized and tightly managed work of the twenty-first century is questionable. The most recent work by Wenger – this time with McDermott and Snyder as coauthors – marks a distinct shift towards a managerialist stance. The proposition that managers should foster informal horizontal groups across organizational boundaries is in fact a fundamental redefinition of the concept. However it does identify a plausible, if limited, knowledge management (KM) tool. This paper discusses different interpretations of the idea of 'co-ordinating' communities of practice as a management ideology of empowerment

Glucocorticoids regulate AKR1D1 activity in human liver in vitro and in vivo

Steroid 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates endogenous glucocorticoids and catalyses an important step in bile acid synthesis. Endogenous and synthetic glucocorticoids are potent regulators of metabolic phenotype and play a crucial role in hepatic glucose metabolism. However, the potential of synthetic glucocorticoids to be metabolised by AKR1D1 as well as to regulate its expression and activity has not been investigated. The impact of glucocorticoids on AKR1D1 activity was assessed in human liver HepG2 and Huh7 cells; AKR1D1 expression was assessed by qPCR and Western blotting. Genetic manipulation of AKR1D1 expression was conducted in HepG2 and Huh7 cells and metabolic assessments were made using qPCR. Urinary steroid metabolite profiling in healthy volunteers was performed pre- and post-dexamethasone treatment, using gas chromatography-mass spectrometry. AKR1D1 metabolised endogenous cortisol, but cleared prednisolone and dexamethasone less efficiently. In vitro and in vivo, dexamethasone decreased AKR1D1 expression and activity, further limiting glucocorticoid clearance and augmenting action. Dexamethasone enhanced gluconeogenic and glycogen synthesis gene expression in liver cell models and these changes were mirrored by genetic knockdown of AKR1D1 expression. The effects of AKR1D1 knockdown were mediated through multiple nuclear hormone receptors, including the glucocorticoid, pregnane X and farnesoid X receptors. Glucocorticoids down-regulate AKR1D1 expression and activity and thereby reduce glucocorticoid clearance. In addition, AKR1D1 down-regulation alters the activation of multiple nuclear hormone receptors to drive changes in gluconeogenic and glycogen synthesis gene expression profiles, which may exacerbate the adverse impact of exogenous glucocorticoids

The ASSURE study: HIV-1 suppression is maintained with bone and renal biomarker improvement 48 weeks after ritonavir discontinuation and randomized switch to abacavir/lamivudine+atazanavir

Objectives: HIV treatment guidelines endorse switching or simplification of antiretroviral therapy in therapy-experienced patients with suppressed viraemia; ritonavir discontinuation may also enhance tolerability and reduce long-term adverse events (AEs). This open-label, multicentre, noninferiority study enrolled HIV-1-infected, treatment-experienced adults with confirmed HIV-1 RNA≤75 HIV-1 RNA copies/mL currently receiving tenofovir/emtricitabine+atazanavir/ritonavir (TDF/FTC+ATV/r) for ≥6 months with no reported history of virological failure. Methods: Participants were randomized 1:2 to continue current treatment or switch to abacavir/lamivudine + atazanavir (ABC/3TC+ATV). Endpoints included the proportion of participants with HIV-1 RNA<50 copies/mL by time to loss of virological response (TLOVR), AEs, fasting lipids, and inflammatory, coagulation, bone and renal biomarkers. Results: After 48 weeks, 76% (152 of 199) of ABC/3TC+ATV-treated and 79% (77 of 97) of TDF/FTC+ATV/r-treated participants had HIV-1 RNA<50 copies/mL (TLOVR; P=0.564). Other efficacy analyses yielded similar results. Rates of new grade 2-4 AEs were 45% in both groups, but an excess of hyperbilirubinaemia made the rate of treatment-emergent grade 3-4 laboratory abnormalities higher with TDF/FTC+ATV/r (36%) compared with ABC/3TC+ATV (19%). Most fasting lipid levels remained stable over time; high-density lipoprotein (HDL) cholesterol increased modestly in ABC/3TC+ATV-treated participants. Bone and renal biomarkers improved significantly between baseline and week 48 in participants taking ABC/3TC+ATV and were stable in participants taking TDF/FTC+ATV/r. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups. Conclusions: The ABC/3TC+ATV treatment-switch group had similar viral suppression rates up to 48 weeks to the TDF/FTC+ATV/r comparator group, with lower rates of moderate- to high-grade hyperbilirubinaemia and improvements in bone and renal biomarkers

Bottom-Tau Unification in SUSY SU(5) GUT and Constraints from b to s gamma and Muon g-2

An analysis is made on bottom-tau Yukawa unification in supersymmetric (SUSY) SU(5) grand unified theory (GUT) in the framework of minimal supergravity, in which the parameter space is restricted by some experimental constraints including Br(b to s gamma) and muon g-2. The bottom-tau unification can be accommodated to the measured branching ratio Br(b to s gamma) if superparticle masses are relatively heavy and higgsino mass parameter \mu is negative. On the other hand, if we take the latest muon g-2 data to require positive SUSY contributions, then wrong-sign threshold corrections at SUSY scale upset the Yukawa unification with more than 20 percent discrepancy. It has to be compensated by superheavy threshold corrections around the GUT scale, which constrains models of flavor in SUSY GUT. A pattern of the superparticle masses preferred by the three requirements is also commented.Comment: 21pages, 6figure

Atomic X-ray Spectroscopy of Accreting Black Holes

Current astrophysical research suggests that the most persistently luminous objects in the Universe are powered by the flow of matter through accretion disks onto black holes. Accretion disk systems are observed to emit copious radiation across the electromagnetic spectrum, each energy band providing access to rather distinct regimes of physical conditions and geometric scale. X-ray emission probes the innermost regions of the accretion disk, where relativistic effects prevail. While this has been known for decades, it also has been acknowledged that inferring physical conditions in the relativistic regime from the behavior of the X-ray continuum is problematic and not satisfactorily constraining. With the discovery in the 1990s of iron X-ray lines bearing signatures of relativistic distortion came the hope that such emission would more firmly constrain models of disk accretion near black holes, as well as provide observational criteria by which to test general relativity in the strong field limit. Here we provide an introduction to this phenomenon. While the presentation is intended to be primarily tutorial in nature, we aim also to acquaint the reader with trends in current research. To achieve these ends, we present the basic applications of general relativity that pertain to X-ray spectroscopic observations of black hole accretion disk systems, focusing on the Schwarzschild and Kerr solutions to the Einstein field equations. To this we add treatments of the fundamental concepts associated with the theoretical and modeling aspects of accretion disks, as well as relevant topics from observational and theoretical X-ray spectroscopy.Comment: 63 pages, 21 figures, Einstein Centennial Review Article, Canadian Journal of Physics, in pres

Large-Scale Stable Isotope Alteration Around the Hydrothermal Carbonate-Replacement Cinco de Mayo Zn-Ag Deposit, Mexico

Carbonate-hosted hydrothermal deposits typically show narrow visible mineralogical and textural alteration halos, which inhibit exploration targeting. In contrast, hydrothermal modification of the country rock’s stable isotope composition usually extends far beyond the limited visible alteration. Hence, stable isotope studies should be an effective tool to aid exploration for carbonate-hosted deposits. Here we present new insight into the development of a large stable isotope alteration halo based on 910 O and C isotope analyses of carbonate veins and hydrothermally altered limestone hosting the Cinco de Mayo Pb-Zn-Ag (Au, Cu) carbonate replacement deposit (CRD), in Chihuahua, Mexico. Our results demonstrate that stable isotope alteration is consistent with reactive, magmatic fluid flow into unaltered limestone and represents a powerful tool for the characterization of these hydrothermal ore systems. Synmineralization veins are texturally and isotopically distinct from those formed during pre- and postmineralization diagenesis and fluid flow and show distinct gradients along the direction of mineralizing fluid flow: this appears to be a promising exploration vectoring tool. Downhole variations in wall-rock isotope values reveal aquifers and aquicludes and outline the principal hydrothermal flow paths. Furthermore, wall-rock δ18OVSMOW systematically decreases toward mineralization from ~23‰ to <17‰ over a distance of ~10 km, providing another vectoring tool. The extent of the stable isotope alteration halo likely reflects the overall fluid volume and areal extent of a fossil hydrothermal system, which may be expected to scale with the mineral endowment. This suggests that constraining the size, shape, and degree of isotopic alteration has direct application to mineral exploration by outlining the system and indicating the potential size of a deposit

Efficacy of menthol as an anesthetic for tambaqui (Colossoma macropomum, Characiformes: Characidae)

Anesthetics are important in fish culture to reduce handling stress and mortality. The objective of this work is to investigate menthol as an anesthetic for tambaqui. In the first series of tests, fish were exposed to various concentrations of menthol to evaluate induction time and stress responses. The second series examined the effect of exposure period to menthol at 150 mg/L on recovery time. The third assessed the best dosage for juveniles in larger tambaqui. The best concentration for surgical anesthesia is 150 mg/L. At this concentration the induction time is short, but their recovery time is significantly longer than that for lower concentrations. For biometry procedures, the best concentration is 100 mg/L. At this concentration the induction time is prolonged, but the recovery time is within the desired period. Recovery time for fish exposed to 150 mg/L is equal for 10, 20 or 30 minutes of exposure. The results confirmed that menthol is an adequate anesthetic for tambaqui.Os anestésicos são importantes na piscicultura para reduzir o estresse e a mortalidade no manejo. Este trabalho tem como objetivo determinar a eficácia do mentol para tambaqui durante o manejo. Na primeira série de testes, foi examinado o efeito da concentração de anestésico sobre indução à anestesia e o estresse de tambaqui. Na segunda série de testes, foi avaliada a recuperação dos peixes após a exposição a uma concentração de 150 mg/L de mentol por diferentes tempos. Na terceira série, foi avaliada se a melhor concentração encontrada para juvenil (150 mg/L) também era adequada para peixes maiores. A melhor concentração para uma anestesia cirúrgica foi 150 mg/L, pois o tempo de indução é rápido, porém a recuperação é significativamente mais demorada do que para as menores concentrações testadas. Para uma anestesia, com finalidade de biometria, a melhor concentração foi 100 mg/L. Nesta concentração o tempo de indução à anestesia é prolongado, porém o tempo de recuperação está dentro da faixa considerada adequada. O tempo de recuperação do tambaqui quando exposto a 150 mg/L é significativamente igual para 10, 20 e 30 minutos de anestesia. Os resultados obtidos mostram que o mentol é um anestésico eficiente para o tambaqui

Genetic, abiotic and social influences on sex differentiation in cichlid fishes and the evolution of sequential hermaphroditism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73799/1/j.1467-2979.2005.00184.x.pd