HCV triple therapy in co-infection HIV/HCV is not associated with a different risk of developing major depressive disorder.

INTRODUCTION Hepatitis C (HCV) treatment options have changed with the development of direct activity antivirals (DAAs) and the availability of triple therapies have improved HCV cure rates. A common neuropsychiatric side effect of pegylated-interferon and ribavirin treatment is major depressive disorder (MDD), however little is known about such adverse events with protease inhibitor-based triple therapy. The aim of this study was to assess the rate of MDD in co-infected HIV HCV patients undergoing different HCV treatments. METHODS All participants were co-infected HIV HCV attending the Royal Sussex County Hospital Brighton hepatology outpatient clinic between 2010 and 2014. Participants were assessed for DSM-IV MDD and depression severity (using the Hamilton depression scale (HAMD)) at baseline and monthly after treatment initiation. HIV and HCV stages, genotype, reinfection and standard demographic variables were recorded. Influence of HCV stage (acute vs. chronic) and type of treatment (classic vs triple), emergence of MDD and clearance outcomes were analyzed using repeated measures and logistic regression models. RESULTS Fifty participants with a mean age of 42.65 years (SD=10.32) were included; most were male (98%). The majority had contracted HCV genotype 1 (64%) or 4 (26%). The HCV stage and treatment groups were matched for age and depression at baseline. No significant differences were found on virological outcomes considering HCV stage and treatment. From baseline to SVR, there was a significant increase in HAMD scores, F(4,36)=10.09, p<.001; this was not significantly influenced by HCV stage, F(4,35)=0.54, p=.708 or HCV treatment group, F(4,35)=0.60, p=.664. Those with chronic HCV were more likely to transition to MDD than acute infection (OR 7.77, 95% CI 2.04-29.54, p=.003). No differences were found for depression emergence by HCV treatment group (OR 0.83, 95% CI 0.22-3.13, p=.787). CONCLUSIONS HCV triple therapy was not associated with a different risk of emergence of MDD versus classic treatment. MDD should be assessed before therapy initiation and monitored throughout treatment for any HCV treatment regime. Future research could usefully clarify mechanisms of MDD emergence and risk factors for this

Bypass Aware Instruction Scheduling for

Since register files suffer from some of the highest power densities within processors, designers have investigated several architectural strategies for register file power reduction, including “On Demand RF Read ” where the register file is read only if the operand value is not available from the bypasses. However, we show in this paper that significant additional reductions in the register file power consumption can be obtained by scheduling instructions so that they transfer the operands via bypasses, rather than reading from the register file. Such instruction scheduling requires the compiler to be cognizant of the bypasses in the processor pipeline. In this paper, we develop several bypass aware instruction scheduling heuristics varying in time complexity, and study their effectiveness on the Intel XScale processor pipeline running MiBench benchmarks. Our experimental results show additional power consumption reductions of up to 26 % and on average 12 % over and above the register file power reduction achieved through existing techniques

Correlative and dynamic imaging of the hatching biology of Schistosoma japonicum from eggs prepared by high pressure freezing

Background: Schistosome eggs must traverse tissues of the intestine or bladder to escape the human host and further the life cycle. Escape from host tissues is facilitated by secretion of immuno-reactive molecules by eggs and the formation of an intense strong granulomatous response by the host which acts to exclude the egg into gut or bladder lumens. Schistosome eggs hatch on contact with freshwater, but the mechanisms of activation and hatching are poorly understood. In view of the lack of knowledge of the behaviour of egg hatching in schistosomes, we undertook a detailed dynamic and correlative study of the hatching biology of Schistosoma japonicum. Methodology/Principal Findings: Hatching eggs of S. japonicum were studied using correlative light and electron microscopy (EM). The hatching behaviour was recorded by video microscopy. EM preparative methods incorporating high pressure freezing and cryo-substitution were used to investigate ultrastructural features of the miracidium and extra-embryonic envelopes in pre-activated and activated eggs, and immediately after eggshell rupture. Lectin cytochemistry was performed on egg tissues to investigate subcellular location of specific carbohydrate groups. Conclusions/Significance: The hatching of S. japonicum eggs is a striking phenomenon, whereby the larva is liberated explosively while still encapsulated within its sub-shell envelopes. The major alterations that occur in the egg during activation are scission of the outer envelope-eggshell boundary, autolysis of the cellular inner envelope, and likely hydration of abundant complex and simple polysaccharides in the lacunal space between the miracidial larva and surrounding envelopes. These observations on hatching provide insight into the dynamic activity of the eggs and the biology of schistosomes within the host