Alternative methods to analyse the impact of HIV mutations on virological response to antiviral therapy

<p>Abstract</p> <p>Background</p> <p>Principal component analysis (PCA) and partial least square (PLS) regression may be useful to summarize the HIV genotypic information. Without pre-selection each mutation presented in at least one patient is considered with a different weight. We compared these two strategies with the construction of a usual genotypic score.</p> <p>Methods</p> <p>We used data from the ANRS-CO3 Aquitaine Cohort Zephir sub-study. We used a subset of 87 patients with a complete baseline genotype and plasma HIV-1 RNA available at baseline and at week 12. PCA and PLS components were determined with all mutations that had prevalences >0. For the genotypic score, mutations were selected in two steps: 1) p-value < 0.01 in univariable analysis and prevalences between 10% and 90% and 2) backwards selection procedure based on the Cochran-Armitage Test. The predictive performances were compared by means of the cross-validated area under the receiver operating curve (AUC).</p> <p>Results</p> <p>Virological failure was observed in 46 (53%) patients at week 12. Principal components and PLS components showed a good performance for the prediction of virological response in HIV infected patients. The cross-validated AUCs for the PCA, PLS and genotypic score were 0.880, 0.868 and 0.863, respectively. The strength of the effect of each mutation could be considered through PCA and PLS components. In contrast, each selected mutation contributes with the same weight for the calculation of the genotypic score. Furthermore, PCA and PLS regression helped to describe mutation clusters (e.g. 10, 46, 90).</p> <p>Conclusion</p> <p>In this dataset, PCA and PLS showed a good performance but their predictive ability was not clinically superior to that of the genotypic score.</p

STE-QUEST - Test of the Universality of Free Fall Using Cold Atom Interferometry

In this paper, we report about the results of the phase A mission study of the atom interferometer instrument covering the description of the main payload elements, the atomic source concept, and the systematic error sources

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Observer for LPV Singular Systems Applied to a Binary Distillation Column

In this work the application of a full-order observer to a binary distillation column, using a strategy to simplify the nonlinear model is presented. Mainly for process system, it is feasible to use differential-algebraic equations for describing the dynamical behavior of the plant. A mathematical model is an extension of the traditional chemical and physical laws (such as the laws of conservation of mass, energy, momentum, etc.) to include the time-varying parameters which can be seen as singular systems. Then, the binary distillation column model is presented as a Linear Parameter Variant (LPV) singular system. Singular systems provide special features not found in traditional systems. In that sense, the proposed model maintains the dynamics and physical properties of the plant. The applied method guarantees the regularity and the convergence of the observer system

Intradialytic parenteral nutrition for patients on hemodialysis: when, how and to whom?

Lay Summary Hemodialysis for patients with chronic kidney disease is associated with high morbidity and mortality rates as well as low quality of life. Poor nutritional status is an important predictor of these risks, so maintaining optimal nutrition in patients on hemodialysis is a critical but sometimes overlooked aspect of care. Because many patients undergoing hemodialysis cannot maintain good nutrition through daily diet or oral nutritional supplements, intravenous delivery of nutrition during hemodialysis sessions has been proposed as another way to support nutrition over time. In this review, a consensus panel of experienced clinicians reviews the available literature and provides experience-based guidance on when to use this nutritional strategy, which patients may be best suited for this approach, practical strategies for delivery, and how to monitor patients receiving this nutrition during hemodialysis.Hemodialysis is associated with high morbidity and mortality rates as well as low quality of life. Altered nutritional status and protein-energy wasting are important indicators of these risks. Maintaining optimal nutritional status in patients with hemodialysis is a critical but sometimes overlooked aspect of care. Nutritional support strategies usually begin with dietary counseling and oral nutritional supplements. Patients may not comply with this advice or oral nutritional supplements, however , or compliance may be affected by other complications of progressive chronic kidney disease. Intradialytic parenteral nutrition (IDPN) may be a possibility in these cases, but lack of knowledge on practical aspects of IDPN delivery are seldom discussed and may represent a barrier. In this review, we, as a consensus panel of clinicians experienced with IDPN, survey existing literature and summarize our views on when to use IDPN, which patients may be best suited for IDPN, and how to effectively deliver and monitor this strategy for nutritional support

Safety and Efficacy of Short Daily Hemodialysis with Physidia S3 System: Clinical Performance Assessment during the Training Period

International audienceBackground: A growing body of scientific evidence indicates that clinical outcomes of hemodialysis patients can be improved with short daily dialysis treatment. Current in-center hemodialysis machines do not fulfill the requirements needed for self-care home hemodialysis (HHD) treatment. In line with the reviviscence of home therapy, several hemodialysis devices have been developed and deployed for treatment. Physidia S3 is one of these new dialysis delivery systems featuring an appealing design and functionalities intended for daily HHD treatment. Methods: In this French multicenter proof-of-concept study enrolling 13 training centers, we report our preliminary experience with a special focus on quantifying clinical performances in short daily HHD treatment performed during the training period of the patients. Results: Among the 80 patients included in this study, a total of 249 sessions could be analyzed. Dialysis dose, estimated from weekly standardized Kt/V, was maintained at 2.22 [1.95–2.61] with a normalized protein catabolic rate of 0.93 [0.73–1.18] g/kg/24 h. Furthermore, anemia and nutritional status were adequately controlled as indicated by 11.6 ± 1.4 g/dL of hemoglobin level and 39.4 ± 5.7 g/L of serum albumin as well as electrolyte disorders. Conclusions: The safety and efficacy of the S3 therapy concept relying on a short daily hemodialysis treatment using a bagged delivery system are in total agreement with daily HHD recommendations. Clinical performances are aligned to the metabolic needs of the vast majority of HHD patients. Currently ongoing studies at home will provide further evidence and value of this therapeutic approach

Projet PRODIADOM "Promouvoir la dialyse à domicile"

(The main text is available only in French) PRODIADOM is an innovative solution designed to help professionals to develop home dialysis. By the moment only available for Peritoneal Dialysis (very soon as well for Home Haemodialysis), PRODIADOM is a very simple, practical, useful and user-friendly website. Nephrologists will find in guidelines, formations, practice-sheets, decisions-trees, decision-making process in complex situations, functional evaluations and tests in Peritoneal Dialysis, their indications and practical executions. PRODIADOM’s ambition is to become a practical reference for doctors and nurses who want to start a home dialysis program in their renal unit. Created by nephrology experts, the website access is free.PRODIADOM est une solution innovante destinée à aider les professionnels qui souhaitent développer la dialyse à domicile. Dans un premier temps disponible pour la dialyse péritonéale (bientôt disponible pour l’hémodialyse à domicile), PRODIADOM propose un site Web qui se veut simple, pratique, utile et convivial. Les praticiens pourront y trouver des formations, des guides, des fiches pratiques, des arborescences décisionnelles, des conduites à tenir face à des situations inhabituelles, des recommandations, tous les protocoles utiles pour la dialyse péritonéale, toutes les explorations fonctionnelles péritonéales courantes, avec leurs indications et leur réalisation pratique. PRODIADOM a l’ambition de devenir la référence des professionnels médicaux et paramédicaux qui souhaitent démarrer un programme de dialyse à domicile. Conçu par des experts, son accès est gratuit