4,156 research outputs found

    The Stage of Publication as a Fair Use Factor: Harper & Row, Publishers, Inc. v. Nation Enterprises

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    Predicting Risk of End-Stage Liver Disease in Antiretroviral-Treated HIV/Hepatitis C Virus-Coinfected Patients

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    Background. End-stage liver disease (ESLD) is an important cause of morbidity among HIV/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods. We conducted a retrospective cohort study among 6,016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results. Among 6,016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 \u3e3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions. Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients

    Effect of maternal Schistosoma mansoni infection and praziquantel treatment during pregnancy on Schistosoma mansoni infection and immune responsiveness among offspring at age five years.

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    INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. METHODS: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. RESULTS: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. CONCLUSION: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease

    Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves

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    peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. Results There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups. Conclusion Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak

    Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications

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    Background: “Residual skin surface components” (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of “normal” RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. Methods: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatography–atmospheric pressure chemical ionisation–mass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. Results: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. Conclusions: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.Peer reviewedFinal Published versio
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