Studies have suggested involvement of interleukin 17 (IL-17) in autoimmune diseases, although its effect on B cell biology has not been clearly established. Here we demonstrate that IL-17 alone or in combination with B cell-activating factor controlled the survival and proliferation of human B cells and their differentiation into immunoglobulin-secreting cells. This effect was mediated mainly through the nuclear factor-kappaB-regulated transcription factor Twist-1. In support of the relevance of our observations and the potential involvement of IL-17 in B cell biology, we found that the serum of patients with systemic lupus erythematosus had higher concentrations of IL-17 than did the serum of healthy people and that IL-17 abundance correlated with the disease severity of systemic lupus erythematosus.

BackgroundAntibodies directed against haemagglutinin, measured by the haemagglutination inhibition (HI) assay are essential to protective immunity against influenza infection. An HI titre of 1:40 is generally accepted to correspond to a 50% reduction in the risk of contracting influenza in a susceptible population, but limited attempts have been made to further quantify the association between HI titre and protective efficacy.MethodsWe present a model, using a meta-analytical approach, that estimates the level of clinical protection against influenza at any HI titre level. Source data were derived from a systematic literature review that identified 15 studies, representing a total of 5899 adult subjects and 1304 influenza cases with interval-censored information on HI titre. The parameters of the relationship between HI titre and clinical protection were estimated using Bayesian inference with a consideration of random effects and censorship in the available information.ResultsA significant and positive relationship between HI titre and clinical protection against influenza was observed in all tested models. This relationship was found to be similar irrespective of the type of viral strain (A or B) and the vaccination status of the individuals.ConclusionAlthough limitations in the data used should not be overlooked, the relationship derived in this analysis provides a means to predict the efficacy of inactivated influenza vaccines when only immunogenicity data are available. This relationship can also be useful for comparing the efficacy of different influenza vaccines based on their immunological profile.

CARDIAC IMAGINGC oronary CT angiography (CCTA) is currently recommended for the assessment of many cardiovascular diseases, including coronary artery disease (CAD) evaluation (1). CCTA is particularly important for its high negative predictive value for CAD in a low-and intermediaterisk acute chest pain population, with a high sensitivity and specificity for CAD in a low-and intermediate-risk chronic coronary syndrome population (2-5). This had been made possible by the recent technical evolution of the CT systems and the existence of large-scale validation cohort studies (6,7). However, conventional CCTA still has a limited spatial resolution and soft-tissue contrast, which impairs its diagnostic performance for small arteries (ie, ,2 mm) and high-contrast (eg, stent, calcification) and low-contrast (eg, noncalcified plaque) tasks, and carries the risks of relatively high x-ray dose delivery.Over the past 5 years, photon-counting CT (PCCT) technology has emerged in the field of CT imaging. Compared with conventional CT, this new modality has better spatial resolution and soft-tissue contrast and reduced noise, blooming, and beam-hardening artifacts (8). This is because of new energy-resolving detectors, called photon-counting Background. Spatial resolution, soft-tissue contrast, and dose-efficient capabilities of photon-counting CT (PCCT) potentially allow a better quality and diagnostic confidence of coronary CT angiography (CCTA) in comparison to conventional CT. Purpose:To compare the quality of CCTA scans obtained with a clinical prototype PCCT system and an energy-integrating detector (EID) dual-layer CT (DLCT) system. Materials and Methods:In this prospective board-approved study with informed consent, participants with coronary artery disease underwent retrospective electrocardiographically gated CCTA with both systems after injection of 65-75 mL of 400 mg/mL iodinated contrast agent at 5 mL/sec. A prior phantom task-based quality assessment of the detectability index of coronary lesions was performed. Ultra-high-resolution parameters were used for PCCT (1024 matrix, 0.25-mm section thickness) and EID DLCT (512 matrix, 0.67-mm section thickness). Three cardiac radiologists independently performed a blinded analysis using a five-point quality score (1 = insufficient, 5 = excellent) for overall image quality, diagnostic confidence, and diagnostic quality of calcifications, stents, and noncalcified plaques. A logistic regression model, adjusted for radiologists, was used to evaluate the proportion of improvement in scores with the best method.Results: Fourteen consecutive participants (12 men; mean age, 61 years 6 17) were enrolled. Scores of overall quality and diagnostic confidence were higher with PCCT images with a median of 5 (interquartile range [IQR], 2) and 5 (IQR, 1) versus 4 (IQR, 1) and 4 (IQR, 3) with EID DLCT images, using a mean tube current of 255 mAs 6 0 versus 349 mAs 6 111 for EID DLCT images (P , .01). Proportions of improvement with PCCT images for quality of calcification, stent, and non...

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Introduction:Direct measurement of antiretroviral treatment (ART) program indicators essential for evidence-based planning and evaluation – especially HIV incidence, population viral load, and ART eligibility – is rare in sub-Saharan Africa.Design/methods:To measure key indicators in rural western Kenya, an area with high HIV burden, we conducted a population survey in September to November 2012 via multistage cluster sampling, recruiting everyone aged 15–59 years living in 3330 randomly selected households. Consenting individuals were interviewed and tested for HIV at home. Participants testing positive were assessed for CD4+ cell count and viral load, and their infections classified as either recent or long term based on Limiting Antigen Avidity assays. HIV-negative participants were tested by nucleic acid amplification to detect acute infections.Results:Of 6833 household members eligible for the study, 6076 (94.7% of all women and 81.0% of men) agreed to participate. HIV prevalence and incidence were 24.1% [95% confidence interval [CI] 23.0–25.2] and 1.9 new cases/100 person-years (95% CI 1.1–2.7), respectively. Among HIV-positive participants, 59.4% (95% CI 56.8–61.9) were previously diagnosed, 53.1% (95% CI 50.5–55.7) were receiving care, and 39.7% (95% CI 37.1–42.4) had viral load less than 1000 copies/ml. Applying 2013 WHO recommendations for ART initiation increased the proportion of ART-eligible people from 60.0% (based on national guidelines in place during the survey; 95% CI 57.3–62.7) to 82.0% (95% CI 79.5–84.5). Among HIV-positive people not receiving ART, viral load increased with decreasing CD4+ cell count (500–749 vs. ≥750 cells/μl, adjusted mean difference, 0.40 log10 copies/ml, 95% CI 0.20–0.60, P < 0.01).Conclusion:This study demonstrates how population-level data can help optimize HIV programs. Based on these results, new regional programs are prioritizing diagnosis and expanding ART eligibility, key steps to reach undetectable viral load.

IntroductionThe antiretroviral therapy (ART) programme supported by Médecins Sans Frontières in the rural Malawian district of Chiradzulu was one of the first in sub-Saharan Africa to scale up ART delivery in 2002. After more than a decade of continuous involvement, we conducted a population survey to evaluate the cascade of care, including population viral load, in the district.MethodsA cross-sectional household-based survey was conducted between February and May 2013. Using a multistage cluster sampling method, we recruited all individuals aged 15 to 59 years living in 4125 randomly selected households. Each consenting individual was interviewed and tested for HIV at home. All participants who tested positive had their CD4 count and viral load measured. The LAg-Avidity assay was used to distinguish recent from long-term infections. Viral suppression was defined as a viral load below 1000 copies/mL.ResultsOf 8271 individuals eligible for the study, 7269 agreed to participate and were tested for HIV (94.1% inclusion for women and 80.3% for men). Overall HIV prevalence and incidence were 17.0% (95% CI 16.1 to 17.9) and 0.39 new cases per 100 person-years (95% CI 0.0 to 0.77), respectively. Coverage at the other steps along the HIV care cascade was as follows: 76.7% (95% CI 74.4 to 79.1) had been previously diagnosed, 71.2% (95% CI 68.6 to 73.6) were under care and 65.8% (95% CI 62.8 to 68.2) were receiving ART. Finally, the proportion of participants who were HIV positive with a viral load ≤1000 copies/mL reached 61.8% (95% CI 59.0 to 64.5).ConclusionsThis study demonstrates that a high level of population viral suppression and low incidence can be achieved in high HIV prevalence and resource-limited settings.

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