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Health-care-associated infections (HAIs) cause significant morbidity and mortality globally, including in low-income and middle-income countries (LMICs). Networks of hospitals implementing standardised HAI surveillance can provide valuable data on HAI burden, and identify and monitor HAI prevention gaps. Hospitals in many LMICs use HAI case definitions developed for higher-resourced settings, which require human resources and laboratory and imaging tests that are often not available.A network of 26 tertiary-level hospitals in India was created to implement HAI surveillance and prevention activities. Existing HAI case definitions were modified to facilitate standardised, resource-appropriate surveillance across hospitals. Hospitals identified health-care-associated bloodstream infections and urinary tract infections (UTIs) and reported clinical and microbiological data to the network for analysis.26 network hospitals reported 2622 health-care-associated bloodstream infections and 737 health-care-associated UTIs from 89 intensive care units (ICUs) between May 1, 2017, and Oct 31, 2018. Central line-associated bloodstream infection rates were highest in neonatal ICUs (20 per 1000 central line days). Catheter-associated UTI rates were highest in paediatric medical ICUs (4·5 per 1000 urinary catheter days). Klebsiella spp (24·8%) were the most frequent organism in bloodstream infections and Candida spp (29·4%) in UTIs. Carbapenem resistance was common in Gram-negative infections, occurring in 72% of bloodstream infections and 76% of UTIs caused by Klebsiella spp, 77% of bloodstream infections and 76% of UTIs caused by Acinetobacter spp, and 64% of bloodstream infections and 72% of UTIs caused by Pseudomonas spp.The first standardised HAI surveillance network in India has succeeded in implementing locally adapted and context-appropriate protocols consistently across hospitals and has been able to identify a large number of HAIs. Network data show high HAI and antimicrobial resistance rates in tertiary hospitals, showing the importance of implementing multimodal HAI prevention and antimicrobial resistance containment strategies.US Centers for Disease Control and Prevention cooperative agreement with All India Institute of Medical Sciences, New Delhi.For the Hindi translation of the abstract see Supplementary Materials section.

We propose a simple mechanism for the self-replication of protocells. Our main hypothesis is that the amphiphilic molecules composing the membrane bilayer are synthesized inside the protocell through exothermic chemical reactions. The slow increase of the inner temperature forces the hottest molecules to move from the inner leaflet to the outer leaflet of the bilayer. Because of this outward translocation flow, the outer leaflet grows faster than the inner leaflet. This differential growth increases the mean curvature and amplifies any local shrinking of the protocell until it splits in two. The proposed model, based on mere laws of physics, is a step in the study of the origin of life, as well as a clue for a better understanding of cell proliferation in cancer.

Objective To assess the contribution of large and small nerve fiber alteration in erythromelalgia (EM). Methods Thirty-three EM patients were included and underwent clinical evaluation based on EM severity score, DN4, and Utah Early Neuropathy Scale (UENS) score. Neurophysiological evaluation consisted in nerve conduction studies (NCS) for large nerve fibers and specific tests for small nerve fibers: electrochemical skin conductance, cold and warm detection thresholds, and laser evoked potentials. Finally, the evaluation of vascular changes was based on the presence of clinical feature of microvascular disorders and the measurement of the Toe Pressure Index (TPI). Results While 28 patients (85%) had vascular alteration on TPI or clinical features, 23 patients (70%) had small-fiber neuropathy on neurophysiological tests, and only 10 patients (30%) had large fiber neuropathy on NCS. Regarding clinical scores, there was no difference between groups (presence or absence of large- or small-fiber neuropathy or microvascular disorder) except for a higher UENS score in patients with large fiber neuropathy. Conclusion Peripheral neuropathy, mostly involving small nerve fibers, is almost as common as microvascular changes in EM, but remains inconstant and not related to a specific neuropathic pattern or higher clinical severity. Significance The association of neuropathic and vascular factors is not systematic in EM, this syndrome being characterized by different pathophysiological mechanisms leading to a common clinical phenotype.

The eastern margin of the Tibetan Plateau is characterized by two end-member morphologies: 2–3-km-deep canyons that are juxtaposed against extensive high elevation, low relief landscapes. Past researchers have highlighted topographic evidence for mobile drainage divides in this region. Active thrusting is thought to drive river gorge incision originating from the east, but within the eastern Tibetan plateau, there is no evidence for focussed thrusting, and no significant post-Cenozoic shortening structures are evident at the surface upstream of the Three Rivers regions. In this region, researchers have attributed the evident landscape transience to different mechanisms, including upward propagation of an incision signal, regional uplift, and local uplift caused by strike-slip motion. Here, we quantify topographic metrics to document the geomorphic response to the proposed tectonic forcing. Specifically, we quantify channel steepness and identify knickpoints to assess evidence for landscape transience and potential accelerated incision triggered in eastern Tibet. We find that ksn and slope systematically increase downstream along the Tongtianhe River (TR) which bisects the study area from NW to SE and is part of the Yangtze River system, but not along adjacent main stem rivers with similar orientation, therefore ruling out the effect of a regional uplift gradient. The spatial distribution of knickpoints does not cluster along or around fault lines, which we interpret to mean that local faulting is not likely a significant factor causing the systematic variations in the topographic metrics. We find that tributaries of the TR exhibit large non-lithological channel convexities, and that the elevation of these knickpoints above the tributaries' mouth increases towards the SE, in the TR's downstream direction. This observation can be best explained by a transient signal propagating upstream along the TR. An additional large non-lithological knickpoint along the TR, as well as a strong local drainage divide disequilibrium between the TR's tributaries and adjacent basins, suggest that waves of incision, potentially set by regional uplift, are propagating up the TR but not up the adjacent major river systems (the Mekong and eastern branch of Yangtze rivers). We propose these waves of incision are the first-order driving force for river arrangements in eastern Tibet. Accordingly, we reconstruct the evolution processes of landscapes in eastern Tibet.

Spinal cord injury pain encompasses musculoskeletal and neuropathic pain. Its management is often multidisciplinary and involves specific drugs such as antidepressants and antiepileptics, and nonpharmacological treatment including psychotherapy, physical therapy and neuromodulation techniques. Recent progress in the diagnosis, assessment, and understanding of its mechanisms offers the perspective of a more rational therapeutic management, which should result in better therapeutic outcome.

Summary Background Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of β-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. Methods We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with β-lactam therapy were randomly assigned (1:1) to receive β-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. Findings Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of β-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or β-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the β-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0–84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the β-lactam group (between-group difference of 9·42%, 95% CI −0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the β-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI −0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the β-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the β-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the β-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). Interpretation Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing β-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. Funding French Ministry of Health.

Resume Objectif Cette etude decrit l’evolution du taux de tentatives de suicide chez des patients avec schizophrenie avant, puis douze mois apres qu’un de leur proche ait beneficie du programme de psychoeducation a destination des familles Profamille. Methode Etude retrospective sur 1209 participants ayant participe au programme Profamille version V3.2 sur 40 centres francais, belges et suisses. La presence de tentatives de suicide chez les patients a ete evaluee par un auto-questionnaire renseigne par le proche participant a Profamille. Une evaluation T0 explore les 12 mois precedant le debut du programme, l’evaluation T1 explore les 12 mois suivant le programme. Resultats Le taux de tentative de suicide est de 6,4 % avant Profamille, de 2,4 % 12 mois apres la fin du programme. On observe une reduction significative du taux de tentatives de suicide au cours des 12 mois (p = 0,0003) suivant Profamille. Conclusions Cette etude montre l’impact favorable de Profamille dans la reduction du taux de tentatives de suicide chez les patients avec schizophrenie. Dans la perspective d’une reduction des tentatives de suicide, nos resultats suggerent l’interet de proposer Profamille precocement, lorsque le risque est le plus important.

Neuropathic pain remains a significant unmet medical need. Several recommendations have recently been proposed concerning pharmacotherapy, neurostimulation techniques and interventional management, but no comprehensive guideline encompassing all these treatments has yet been issued. We performed a systematic review of pharmacotherapy, neurostimulation, surgery, psychotherapies and other types of therapy for peripheral or central neuropathic pain, based on studies published in peer-reviewed journals before January 2018. The main inclusion criteria were chronic neuropathic pain for at least three months, a randomized controlled methodology, at least three weeks of follow-up, at least 10 patients per group, and a double-blind design for drug therapy. Based on the GRADE system, we provide weak-to-strong recommendations for use and proposal as a first-line treatment for SNRIs (duloxetine and venlafaxine), gabapentin and tricyclic antidepressants and, for topical lidocaine and transcutaneous electrical nerve stimulation specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a second-line treatment for pregabalin, tramadol, combination therapy (antidepressant combined with gabapentinoids), and for high-concentration capsaicin patches and botulinum toxin A specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a third-line treatment for high-frequency rTMS of the motor cortex, spinal cord stimulation (failed back surgery syndrome and painful diabetic polyneuropathy) and strong opioids (in the absence of an alternative). Psychotherapy (cognitive behavioral therapy and mindfulness) is recommended as a second-line therapy, as an add-on to other therapies. An algorithm encompassing all the recommended treatments is proposed.

The major therapeutic challenge in inflammatory rheumatic diseases is the persistence of pain despite good responses to specific therapies. Central sensitization, which can be assessed clinically by psychophysical measurements, including quantitative sensory testing (QST), is a widely proposed mechanism for chronic pain. In this systematic review, we explored the scientific literature addressing quantitative sensory testing in inflammatory rheumatic diseases. We searched Pubmed and Embase for publications up to December 2021 concerning studies on quantitative sensory testing focusing on pain thresholds, temporal summation (TS) and conditioned pain modulation (CPM), in adult patients with chronic inflammatory rheumatism (e.g. rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, juvenile idiopathic arthritis). The exclusion criteria were reviews, inclusion of children and no reported pain threshold. Data quality was assessed with the National Institutes of Health (NIH) Quality Assessment tools. We identified 27 studies (18 controlled, 9 uncontrolled) including 1875 patients with inflammatory rheumatic diseases and 795 controls. A decrease in pressure pain threshold, in favor of allodynia, was found in 12 of 14 controlled studies on patients with rheumatoid arthritis and spondyloarthritis. The results of other psychophysical tests, including TS and CPM, were inconsistent due to population heterogeneity and a lack of standardization of the patients' disease duration, activity and treatment. Our review shows that pain in chronic inflammatory rheumatism is associated with pressure allodynia. However, given the heterogeneous quality and discrepant results of studies of other QST outcome measures, the hypothesis of central sensitization involvement in pain processing in these patients cannot be confirmed.

Purpose The purpose of this study was to report the clinical evaluation of a 3D-printed protective face shield designed to protect interventional radiologists from droplet transmission of the SARS-Cov-2. Materials and methods A protective face shield consisting in a standard transparent polymerizing vinyl chloride (PVC) sheet was built using commercially available 3D printers. The 3D-printed face shield was evaluated in 31 interventional procedures in terms of ability to perform the assigned intervention as usual, quality of visual comfort and tolerance using a Likert scale (from 1, as very good to 5, as extremely poor). Results The mean rating for ability to perform the assigned intervention as usual was 1.7 ± 0.8 (SD) (range: 1–4). The mean visual tolerance rating was 1.6 ± 0.7 (SD) (range: 1–4). The mean tolerability rating was 1.4 ± 0.7 (SD) (range: 1–3). Conclusion The 3D-printed protective face shield is well accepted in various interventions. It may become an additional option for protection of interventional radiologists.

Introduction: Antimicrobial-resistant HAI (Healthcare associated infection) are a global challenge due to their impact on patient outcome. Implementation of antimicrobial stewardship programmes (AMSP) is needed at institutional and national levels. Assessment of core capacities for AMSP is an important starting point to initiate nationwide AMSP. We conducted an assessment of the core capacities for AMSP in a network of Indian hospitals, which are part of the Global Health Security Agenda-funded work on capacity building for AMR-HAIs. Subjects and Methods: The Centers for Disease Control and Prevention's core assessment checklist was modified as per inputs received from the Indian network. The assessment tool was filled by twenty hospitals as a self-administered questionnaire. The results were entered into a database. The cumulative score for each question was generated as average percentage. The scores generated by the database were then used for analysis. Results and Conclusion: The hospitals included a mix of public and private sector hospitals. The network average of positive responses for leadership support was 45%, for accountability; the score was 53% and for key support for AMSP, 58%. Policies to support optimal antibiotic use were present in 59% of respondents, policies for procurement were present in 79% and broad interventions to improve antibiotic use were scored as 33%. A score of 52% was generated for prescription-specific interventions to improve antibiotic use. Written policies for antibiotic use for hospitalised patients and outpatients were present on an average in 72% and 48% conditions, respectively. Presence of process measures and outcome measures was scored at 40% and 49%, respectively, and feedback and education got a score of 53% and 40%, respectively. Thus, Indian hospitals can start with low-hanging fruits such as developing prescription policies, restricting the usage of high antibiotics, enforcing education and ultimately providing the much-needed leadership support.

Resume Introduction La retinopathie diabetique est la resultante d’interactions entre facteurs genetiques et environnementaux. Notre interet a porte sur le gene de la synthase du monoxyde d’azote endotheliale ou l’eNOS compte tenu de l’implication de cette enzyme dans les alterations fonctionnelles des microvaisseaux retiniens au cours du diabete. L’objectif est donc d’evaluer l’association du polymorphisme T786C de l’eNOS avec la retinopathie diabetique chez la population algerienne. Patients et methodes Notre etude a porte sur 110 patients diabetiques de type 1 avec et sans RD. L’analyse genetique du polymorphisme eNOS T786C a ete realisee par la technique PCR-RFLP. Nous avons egalement explore l’association entre ce polymorphisme et certaines caracteristiques cliniques et biologiques des patients avec RD. Resultats Une augmentation significative de la frequence du genotype CC est notee chez les individus sans RD (p = 0,03). Egalement une augmentation significative de la somme des frequences genotypiques TT+TC est retrouvee chez les individus avec RD (p = 0,03) et l’association entre les differents genotypes et les profils cliniques ou biologiques rapportent des taux bas du NO chez les sujets porteurs du genotype TT (p = 0,039). Conclusion Nos resultats preliminaires suggerent que le genotype CC pourrait conferer une protection a la retinopathie diabetique chez la population algerienne tandis que l’allele T serait de susceptibilite.

Due to the dynamic nature of ubiquitous computing and ambient intelligence (AmI) environments, a challenging issue that needs to be addressed is how to construct composite services that satisfy users’ requirements in terms of quality of service (QoS). In this paper, a clustering-based and QoS-aware services composition algorithm (CQCA) is proposed. To increase the composition optimality and reduce the composition time, the candidate services are first partitioned into clusters, where each cluster represents a QoS level. In addition, a new formulation of the utility function based on the use of the characteristics of the resulting clusters is proposed to remove unpromising candidate services in terms of QoS. A lexicographic optimization method is then exploited to filter out candidate services that have low QoS attributes values. Finally, a search tree is constructed to find near-to-optimal compositions. The obtained performance shows that the proposed algorithm outperforms other composition approaches by finding very near-to-optimal compositions in a reduced composition time.

The golden ratio (phi, Φ = 1.618) is a proportion that has been found in many phenomena in nature, including the cardiovascular field. We tested the hypothesis that the systolic over mean pulmonary artery pressure ratio (sPAP/mPAP) and the mean over diastolic pressure ratio (mPAP/dPAP) may match Φ in patients with pulmonary arterial hypertension (PAH) and in control patients.In the first, theoretical part of the study, we discuss why our hypothesis is consistent with three known hemodynamic features of the pulmonary circulation: (1) the 0.61 slope of the mPAP vs sPAP relationship, (2) pulmonary artery pulse pressure and mPAP have an almost 1:1 ratio, and (3) the proportional relationship among sPAP, mPAP, and dPAP. In the second part of the study, fluid-filled pressures were analyzed in 981 incident, untreated PAH and high-fidelity pressures were also analyzed in 44 historical control patients (mPAP range, 9-113 mm Hg).In PAH (non-normal distribution), median values of sPAP/mPAP and mPAP/dPAP were 1.591 (98%Φ) and 1.559 (96%Φ), respectively. In control patients (normal distribution), mean sPAP/mPAP and mPAP/dPAP were 1.572 (97%Φ) and 1.470 (91%Φ), respectively. In both PAH and control patients, this was consistent with the Φ hypothesis, assuming 1 mm Hg error in estimation of sPAP, mPAP, and dPAP on average.In PAH and in control patients, the fluctuations in sPAP and dPAP around mPAP exhibited a constant scaling factor matched to Φ. This remarkable property allows linkage of various empirical observations on pulmonary hemodynamics that were hitherto apparently unrelated. These findings warrant further confirmation in other types of pulmonary hypertension and warrant explanation.

Aim Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous group of autosomal dominantly inherited nonketotic diabetes. MODY2 or (GCK-MODY) subtype is caused by heterozygous mutations in the GCK gene coding for glucokinase. In our current study, we aim to confirm a clinically suspected GCK-MODY phenotype at molecular level and subsequently, to estimate co-segregation of the detected mutation with hyperglycemia among Algerian related subjects. Lastly, assessment of mutation effect was performed using a combination of computational tools. Methods Sixteen related subjects were implicated in this study (proband and 15 relatives). Blood samples were used for biochemical, immunological and genetic assays. The proband was screened for mutation in the GCK gene using PCR-sequencing technique. Mutation screening among proband's relatives was performed by PCR-Restriction fragment length polymorphism (PCR-RFLP) technique. Computational analysis was performed with a combination of predictive tools to assess effect of the detected mutation on glucokinase structure/function and stability. Results Genetic analysis results revealed the presence of c.253A>T (p.R85W) GCK mutation at heterozygous state in 11 subjects, while it was absent in 5 others. Biochemical analysis showed that all subjects carrying the p.R85W mutation were affected with diabetes or impaired fasting glucose (fasting glucose 6.94 ± 0.63 mmol/l, HbA1c 6.92 ± 0.77%), whereas the five non-carriers were normoglycemic (fasting glucose 5.01 ± 0.26 mmol/l, HbA1c 5.36 ± 0.17%). All computational tools predict the detected mutation to be ‘damaging’ or ‘probably damaging’ with high scores. Conclusion The p.R85W GCK mutation segregates with diabetes or IFG in a large pedigree. Clinical features of Algerian GCK-MODY patients are similar to those of other populations; in case of double diabetes the co-occurring diabetes overcomes the GCK-MODY phenotype. In silico predictions results are consistent with metabolic study.

Background: The Global Fund to Fight AIDS, Tuberculosis and Malaria is a robust vertical global health program. Other work has discussed potential synergies between various global health initiatives, but the extent to which investments from vertical programs support health security has not been investigated. We, therefore, endeavored to quantify the extent to which the budgets of this vertical program support health security. Methods: We examined budgets from the Global Fund for work in 10 countries from 2014–2020. Using the International Health Regulations Joint External Evaluation (JEE) Tool as a framework, we mapped budget items to health security capacities. We blinded researchers who independently reviewed each budget and mapped items to the JEE. We then unblinded the researchers and reviewed the budgets again until a consensus was reached regarding if an item supported health security directly, indirectly, or not at all. Findings: The budgets totaled USD 6,927,284,966, and USD 2,562,063,054 (37·0%) of this mapped to JEE capacities. USD 1,330,942,712 (19·2%) mapped directly to JEE capacities and USD 1,231,120,342 (17·8%) mapped indirectly. Laboratory systems, antimicrobial resistance, and the deployment of medical countermeasures and personnel received the greatest amount of overall budgetary support, while laboratory systems, antimicrobial resistance, and workforce development received the greatest amount of direct budgetary support. Interpretation: Over one-third of the Global Fund’s work supports health security and the Global Fund has budgeted more than USD 2,500,000,000 for activities that support health security in these 10 countries since 2014. Funding Statement: This work was funded by Resolve to Save Lives: An Initiative of Vital Strategies. Declaration of Interests: The authors have no competing interests to declare. Ethics Approval Statement: Not required.

Resume En neuro-oncologie, le nombre de patients irradies avec une esperance de vie prolongee augmente. De plus, la radiotherapie encephalique est associee a un indice therapeutique etroit. La preservation des organes a risque est liee aux techniques d’irradiation, doses et balistiques, mais aussi a la reproductibilite du traitement. L’essor de la stereotaxie et de la protontherapie accentue cette problematique. L’importance de l’utilisation de l’imagerie et du repositionnement est souvent sous-estimee en raison d’une delegation de tâches et d’une revue d’images repetitive et fastidieuse. Pourtant, la radiotherapie guidee par l’image, dans le cas des irradiations intracrâniennes, a permis d’eviter des contentions invasives pour le patient, mais aussi un gain en termes de qualite de repositionnement et de duree des recalages. Les reperes osseux crâniens et le peu de mouvements entre et pendant les fractions des volumes a irradier permettent une automatisation des repositionnements via le guidage par l’image. Neanmoins, les protocoles d’imagerie au poste de traitement sont de la responsabilite du radiotherapeute (qualite, frequence, utilisation). Cet article propose une mise au point de l’utilisation du guidage par l’image au service des irradiations encephaliques, en se focalisant sur son utilisation pour le repositionnement et ses perspectives quant a la radiotherapie adaptative.

Objectives Patients with advanced cancer often suffer from severe malnutrition and gastrointestinal obstruction. This population could benefit from home parenteral nutrition (HPN). The aim of this study was to observe the outcome of patients with advanced cancer patients who were eligible for HPN. Methods All patients in the nutrition clinic who received HPN over the past 7 y were included in the present study. We compared patients with advanced cancer with the noncancer population in terms of hospitalization rate and mortality. Results Of 221 advanced cancer patients, 153 who had no oral/enteral intake and who received HPN survived. Of these, 35% survived for 6 mo, 27% for 1 y, 18.9% survived 2 y, and 3.9% survived for the 7 y of the follow-up. Hospitalization rate was not significantly different from the noncancer population. Conclusion These results show that HPN is a relevant palliative therapy for patients with advanced cancer patients without oral or enteral feeding access.

International audience; PurposeThe objective of this study was to describe the outcome and prognostic factors for adults treated for localized myxofibrosarcoma.Methods and MaterialsWe conducted a retrospective multicenter study of 425 nonmetastatic patients who underwent surgery between January 1996 and December 2015 in French National Group and were enrolled in the Conticabase. Pathologic diagnosis was systematically reviewed by expert pathologists. The endpoints were relapse-free and metastasis-free survival. Log-rank tests and Cox models have been used to identified prognostic factors.ResultsMedian age was 66 years; 53% were males; 85% of cases occurred in limbs or superficial trunk; median size was 60 mm; 47% and 39% were grades 2 and 3, respectively; 66% had R0 resection and 34% R1 resection. Adjuvant radiation therapy was given to 65% of patients, neoadjuvant radiation therapy to 3%, neoadjuvant chemotherapy to 7%, and adjuvant chemotherapy to 13%. The median follow-up was 51 months. The 5-year local relapse–free survival was 67%; independent prognostic factors for local relapse were R1 resection (hazard ratio [HR] = 1.26; P = .001) and adjuvant radiation therapy (HR = 0.35; P = .0001) (ie, R1 resection and no adjuvant radiation therapy increase the hazard ratio). In stratified analysis, adjuvant radiation therapy was beneficial after R0 resection (P = .0020) and after R1 resection (P = .0001). The 5-year overall survival was 80%. The 5-year metastasis-free survival was 83%. Independent prognostic factors for metastatic relapse were grade 3 disease (HR = 1.975; P = .0001) and tumor size (HR = 1.006; P = .001).ConclusionsThis large series of myxofibrosarcoma confirms the high rate of local relapse. Combination of R0 resection and adjuvant radiation therapy provided the best local control. In parallel with an increasing rate of R0 resection and adjuvant radiation therapy, we observed a constant improvement in both metastatic and local relapse–free survival during the study.

The latest studies in Algeria show that the frequency of type 1 diabetes (T1D) without complications is lower than that with complications and represents a significant burden in terms of cost and treatment. For this reason, we are interested in uncomplicated type1 diabetes and risk factors that are related to polymorphisms of antioxidant enzymes in order to prevent its complications. A total of 260 blood samples of young Algerian adults were examined. The genotypic analysis of Catalase gene (CAT −262C/T, rs1001179) and the superoxide dismutase gene (MnSOD 47C/T, rs4880) was performed by real-time PCR using TaqMan technology. The genotypic distribution of the CAT −262C/T promoter gene's polymorphism showed a significant difference between control and T1D patients for the CC genotype (p = 0.009; OR = 0.30) and for the T allele (p = 0.002; OR = 2.82). In addition, the genotypic distribution of the MnSOD 47C/T gene showed an association with T1D for the CT genotype (p = 0.040; OR = 2.37). Our results revealed that polymorphisms of CAT and MnSOD may be associated with physiopathology causing the onset of T1D. Our data, suggest that the genotypic frequencies of these SNPs appear to be influenced by clinical variables and by the Arab-Berber ethnic origin of the Algerian population.

Resume Contexte/Objectifs Les etudes cliniques montrent un taux moyen de decollement des attaches orthodontiques compris entre 6 et 8 %, avec une predominance au niveau des deuxiemes premolaires mandibulaires. Les attaches preencollees sans exces de colle a eliminer permettent d’obtenir, selon leur fabricant, un faible taux de decollement, tout en assurant une mise en œuvre simplifiee. L’objectif de cette etude a ete de mesurer la resistance au decollement par cisaillement des attaches ceramiques collees en methode directe avec un systeme preencolle sans exces de colle et de la comparer a celle d’attaches preencollees d’ancienne generation et a celle d’attaches encollees manuellement sur la surface vestibulaire des deuxiemes premolaires mandibulaires. Materiel et methodes Quarante-cinq deuxiemes premolaires mandibulaires extraites pour des raisons orthodontiques ont ete reparties de facon randomisee en 3 groupes de 15 dents chacun. Dans le premier groupe les attaches etaient preencollees avec le systeme APC Flash-Free ® (3M Unitek), dans le deuxieme groupe avec le systeme APC Plus ® (3M Unitek) et dans le troisieme groupe les attaches ont ete encollees manuellement avec le composite Transbond XT ® (3M Unitek). La surface amelaire a ete preparee de la meme facon pour les 3 groupes : mordancage a l’acide orthophosphorique 36 % suivi de l’application du primer adhesif Transbond XT ® (3M Unitek). Chaque echantillon a ete soumis a des forces de cisaillement a l’aide d’une machine de test universelle LRX ® (Lloyd Instruments LTD., Fareham, Royaume-Unis) a une vitesse de 1,0 mm/min. La resistance des attaches au decollement par cisaillement a ete enregistree en megapascals (MPa) pour chaque dent. Les valeurs moyennes ont ete ensuite comparees par le test Anova a un facteur. Resultats Bien que la valeur moyenne de la resistance au decollement dans le groupe APC Flash-Free ® soit inferieure a celles des deux autres groupes, cette difference n’est pas statistiquement significative ( p = 0,276). Conclusion Dans les conditions experimentales de cette etude in vitro , la resistance au decollement des attaches preencollees avec le systeme APC Flash-Free ® est comparable aux deux autres systemes conventionnels.

Recent studies have shown that Dickkopf-related protein (DKK1) and sclerostin decrease when a complete response (CR) is obtained after chemotherapy in myeloma multiple (MM). To study variations in DKK1, sclerostin and P1NP in patients treated for MM, between complete response (CR) and relapse, we carried out a prospective study ancillary to the IFM 2009 protocol (IFM). The aim of IFM was to compare progression-free survival between patients treated with chemotherapy with or without transplantation. We selected 69 patients who reached CR and relapsed. We assayed by ELISA: DKK1, sclerostin and P1NP at 3 end points T1: CR, T2: 4 months before relapse and T3: relapse. There was a significant increase in DKK1 and sclerostin between T1, T2 and T3. (DKK1 medians (IQR): T1 = 30 pmol/l (20.4-41.1), T2 = 37.4 pmol/l (29.8-49.4), p 0.0001, T3 = 42 pmol/l (33.8-55.5), p 0.0001 sclerostin medians (IQR): T1 = 0.57 (0.47-0.69), T2 = 0.62 ng/ml (0.53-0.79), p 0.0001, T3 = n0.64 ng/ml (0.56-0.79), p = 0.005). No significant variation was detected in the levels of P1NP. No association was observed between the characteristics of the MM, or the treatment received and the variation between T1-T3 for DKK1, sclerostin or P1NP. A significant increase in DKK1 and sclerostin was observed four months before relapse.

Summary Neuropathic pain—pain caused by a lesion or disease of the somatosensory nervous system—is underdiagnosed and difficult to treat. However, development of easy-to-use questionnaires based mainly on self-reports of symptoms has improved diagnosis and management. Two types of questionnaires (screening and assessment) have been validated, and rapidly translated and revalidated in several languages, probably because of their simplicity. Screening questionnaires help clinicians to identify neuropathic pain easily, particularly in patients with complex medical conditions (eg, spinal cord injury). Their use in large-scale epidemiological studies has provided estimates of the prevalence of neuropathic pain and identified risk factors for neuropathic pain in the general population and in disorders such as diabetes. Assessment questionnaires measure neuropathic symptoms and have been used to create phenotypic profiles of patients in various neuropathic conditions. These profiles can predict treatment outcomes, and thus enable a personalised therapeutic approach. The dissemination of these questionnaires in different countries should further improve diagnosis and management worldwide and advance knowledge on the mechanisms of neuropathic pain.

Objectives First, to analyse the in vitro release of BPA and Bis-GMA from an orthodontic resin composite (Transbond XT, 3M Unitek), stored in various conditions, by gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS); then to extrapolate the data to the clinical situation. Secondly, to explore the thermal stability of Bis-GMA. Methods Cylinders of resin composite were prepared and stored according to 3 different protocols: (1) they were light-cured 20 s, then placed in artificial saliva; (2) they were light-cured 2 s, then placed in acetonitrile; (3) they were light-cured 2 s, then placed in methanol. For each group, BPA and Bis-GMA release were determined with GC/MS and/or LC/MS at least after one week. Besides, 120 brackets (10 of each type) were bonded over metal teeth, then debonded, and the weight and the surface of resin composite residues were measured. BPA and Bis-GMA release of adhesive residues were extrapolated from the data obtained with the cylinders. Besides, BPA release from a heated Bis-GMA solution was measured. Results With GC/MC, BPA was detected in all samples. With LC/MS, BPA was detected only from samples immersed in MeOH; Bis-GMA was detected, in varying amount according to the extraction media and the light-curing time. BPA was found after heating of the Bis-GMA solution. Significance Contamination risk and the heat applied in GC/MS may overestimate the BPA release from resin composite. Based on the LC/MS results, the risk of BPA release after orthodontic bonding would be more than 42 000 times lower than the TDI for a 30-kg child.

Resume Objectif Les ulceres de jambes sont dans pres de 85 % des cas de causes vasculaires. Il existe aussi des ulceres de causes non vasculaires. Leur diagnostic repose sur un faisceau d’arguments cliniques et la biopsie cutanee avec analyse anatomopathologique. Materiel et methode Etude retrospective ayant porte sur l’analyse de 143 biopsies cutanees d’ulceres de jambe. Les raisons ayant motive la biopsie etaient principalement des signes cliniques atypiques et/ou l’absence d’amelioration sous soins bien conduits au-dela de 6 mois, comme le preconise la Haute Autorite de sante. Le but de cette etude etait d’analyser les resultats de ces biopsies et de rechercher des criteres communs aux ulceres, dont la biopsie cutanee avait permis d’etablir le diagnostic d’ulcere non vasculaire. Resultats Au total, 4,9 % des biopsies cutanees permettaient d’etablir un diagnostic d’ulcere de cause non vasculaire (7/143) : 5 carcinomes cutanes (3,5 %), 1 leishmaniose cutanee (0,7 %) et 1 pyoderma gangrenosum (0,7 %). L’analyse statistique univariee revelait que les berges surelevees et le caractere hyperbourgeonnant etaient significativement plus frequemment retrouves dans ces ulceres. Tous les patients, dont la biopsie cutanee permettait un diagnostic d’ulcere non vasculaire, avaient une atteinte vasculaire associee. Conclusion Cette etude a retrouve un taux de 5 % d’ulceres de causes non vasculaires, principalement des carcinomes cutanes. Les berges surelevees et l’hyperbourgeonnement etaient les caracteres inhabituels plus frequemment retrouves dans ces ulceres. Tous les patients, dont la biopsie cutanee revelait une cause non vasculaire, avaient une atteinte vasculaire associee. Cette information confirme la necessite de realiser une biopsie cutanee y compris en presence d’une atteinte vasculaire qui n’explique pas a elle seule l’evolution de l’ulcere.

International audience; We report results from an open-label study of the safety and efficacy of transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex (DLPFC) in patients suffering from Anorexia Nervosa (AN). AN is a severe psychiatric illness associated with a high mortality rate and a severely impaired quality of life. However, only a limited number of treatments are available, and specifically, no medication is approved for AN management [ 1 ]. Usually, psychotherapeutic interventions and the management of physical complications are recommended. Lately, rTMS has emerged as a safe and somewhat effective treatment option for the treatment of AN. However, results were not conclusive [ 2 , 3 ]. A recent development of tDCS seems to be promising in depression and schizophrenia [ 4 , 5 ] and deserves to be further investigated in AN.

Summary Background Systemic vascular resistance (SVR) and total arterial compliance (TAC) modulate systemic arterial load, and their product is the time constant (Tau) of the Windkessel. Previous studies have assumed that aortic pressure decays towards a pressure asymptote (P∞) close to 0 mmHg, as right atrial pressure is considered the outflow pressure. Using these assumptions, aortic Tau values of ∼1.5 seconds have been documented. However, a zero P∞ may not be physiological because of the high critical closing pressure previously documented in vivo. Aims To calculate precisely the Tau and P∞ of the Windkessel, and to determine the implications for the indices of systemic arterial load. Methods Aortic pressure decay was analysed using high-fidelity recordings in 16 subjects. Tau was calculated assuming P∞ = 0 mmHg, and by two methods that make no assumptions regarding P∞ (the derivative and best-fit methods). Results Assuming P∞ = 0 mmHg, we documented a Tau value of 1372 ± 308 ms, with only 29% of Windkessel function manifested by end-diastole. In contrast, Tau values of 306 ± 109 and 353 ± 106 ms were found from the derivative and best-fit methods, with P∞ values of 75 ± 12 and 71 ± 12 mmHg, and with ∼80% completion of Windkessel function. The “effective” resistance and compliance were ∼70% and ∼40% less than SVR and TAC (area method), respectively. Conclusion We did not challenge the Windkessel model, but rather the estimation technique of model variables (Tau, SVR, TAC) that assumes P∞ = 0. The study favoured a shorter Tau of the Windkessel and a higher P∞ compared with previous studies. This calls for a reappraisal of the quantification of systemic arterial load.

Hydrodynamic instabilities such as Rayleigh–Taylor (RT) and Richtmyer–Meshkov (RM) instabilities usually appear in conjunction with the Kelvin–Helmholtz (KH) instability and are found in many natural phenomena and engineering applications. They frequently result in turbulent mixing, which has a major impact on the overall flow development and other effective material properties. This can either be a desired outcome, an unwelcome side effect, or just an unavoidable consequence, but must in all cases be characterized in any model. The RT instability occurs at an interface between different fluids, when the light fluid is accelerated into the heavy. The RM instability may be considered a special case of the RT instability, when the acceleration provided is impulsive in nature such as that resulting from a shock wave. In this pedagogical review, we provide an extensive survey of the applications and examples where such instabilities play a central role. First, fundamental aspects of the instabilities are reviewed including the underlying flow physics at different stages of development, followed by an overview of analytical models describing the linear, nonlinear and fully turbulent stages. RT and RM instabilities pose special challenges to numerical modeling, due to the requirement that the sharp interface separating the fluids be captured with fidelity. These challenges are discussed at length here, followed by a summary of the significant progress in recent years in addressing them. Examples of the pivotal roles played by the instabilities in applications are given in the context of solar prominences, ionospheric flows in space, supernovae, inertial fusion and pulsed-power experiments, pulsed detonation engines and Scramjets. Progress in our understanding of special cases of RT/RM instabilities is reviewed, including the effects of material strength, chemical reactions, magnetic fields, as well as the roles the instabilities play in ejecta formation and transport, and explosively expanding flows. The article is addressed to a broad audience, but with particular attention to graduate students and researchers who are interested in the state-of-the-art in our understanding of the instabilities and the unique issues they present in the applications in which they are prominent.

Pyosalpinx is a condition usually seen in a sexually active female. In literature, only a few cases have been reported in a virginal girl presenting with pyosalpinx. Herein we report a case of an 11-year-old virginal girl with pyosalpinx treated by laparoscopic drainage and antibiotics.

The stream power law, expressed as E = KAmSn — where E is erosion rate [LT − 1], K is an erodibility coefficient [T − 1L (1 − 2m)], A is drainage area [L 2], S is channel gradient [L/L], and m and n are constants — is the most widely used model for bedrock channel incision. Despite its simplicity and limitations, the model has proved useful for topographic evolution, knickpoint migration, palaeotopography reconstruction, and the determination of rock uplift patterns and rates. However, the unknown parameters K, m, and n are often fixed arbitrarily or are based on assumptions about the physics of the erosion processes that are not always valid, which considerably limits the use and interpretation of the model. In this study, we compile a unique global data set of published basin-averaged erosion rates that use detrital cosmogenic 10Be. These data (N = 1457) enable values for fundamental river properties to be empirically constrained, often for the first time, such as the concavity of the river profile (m/n ratio or concavity index), the link between channel slope and erosion rate (slope exponent n), and substrate erodibility (K). These three parameters are calculated for 59 geographic areas using the integral method of channel profile analysis and allow for a global scale analysis in terms of climatic, tectonic, and environmental settings. In order to compare multiple sites, we also normalize n and K using a reference concavity index m/n = 0.5. A multiple regression analysis demonstrates that intuitive or previously demonstrated local-scale trends, such as the correlation between K and precipitation rates, do not appear at a global scale. Our results suggest that the slope exponent is generally > 1, meaning that the relationship between erosion rate and the channel gradient is nonlinear and thus support the hypothesis that incision is a threshold controlled process. This result questions the validity of many regional interpretations of climate and/or tectonics where the unity of n is routinely assumed.

Aims Consumption of high-fat and -sugar foods drive excessive weight gain and contribute to the global obesity crisis. Time-restricted feeding (TRF) limits daily feeding to a specific time interval and has demonstrated great promise in preventing weight gain and restoring metabolic health, even when macronutrient diet composition is unaltered. However, the effectiveness of TRF with high-fat diet and liquid sucrose consumption, which disrupts eating patterns, has not been examined. Methods In this study, juvenile male rats were fed either a high-fat, high liquid sugar (HFHS) diet or control chow ad libitum for 4 weeks; then, food access was restricted to 8 hours during the dark phase for another 4 weeks. Results Although TRF reduces triglyceride levels, it does not affect fat mass or body weight gain on a HFHS diet, contradicting previous restricted-access studies using high-fat or high solid-sucrose diets. Furthermore, TRF induces bouts of excessive HFHS solid food consumption, including a pre-withdrawal surge. Additionally, on control but not HFHS diets, TRF reduces hypothalamic gene expression for ghrelin and leptin receptors. Conclusions TRF alters feeding behavior for both standard diets and HFHS diets with liquid calories, but only prevents further weight gain on standard diets. Our results emphasize curtailing high-fat foods and liquid sucrose to promote improved health outcomes and combat obesity.

Aim of the study was to investigate patient characteristics, survival rates and neurological outcome among hypothermic patients with out-of-hospital cardiac arrest (OHCA) admitted to a trauma center.A review of patients with OHCA and a core temperature ≤32°C admitted to a trauma center between 2004 and 2016.Ninety-six patients (mean temperature 25.8°C±3.9°C) were entered in the study, 37 (39%) of them after avalanche burial. 47% showed return of spontaneous circulation (ROSC) prior to hospital admission. Survival with Glasgow-Pittsburgh Cerebral Performance Category (CPC) scale 1 or 2 was achieved in 25% of all patients and was higher in non-avalanche than in avalanche cases (35.6% vs 8.1%, p=0.002). Witnessed cardiac arrest was the most powerful predictor of favourable neurological outcome (RR: 10.8; 95% Confidence Interval: 3.2-37.1; Wald: 14.3; p0.001), whereas ROSC prior to admission and body core temperature were not associated with survival with favourable neurological outcome. Cerebral CT scan pathology within 12h of admission increased the risk for unfavourable neurological outcome 11.7 fold (RR: 11.7; 95% CI: 3.1-47.5; p0.001). Favourable neurological outcome was associated lower S 100-binding protein (0.69±0.5μg/l vs 5.8±4.9μg/l, p 0.002) and neuron-specific enolase (34.7±14.2μg/l vs 88.4±42.7μg/l, p 0.004) concentrations on intensive care unit (ICU) admission.Survival with favourable neurological outcome was found in about a third of all hypothermic non-avalanche patients with OHCA admitted to a trauma center.

Background Tunnel widening after anterior cruciate ligament reconstruction (ACLR) is influenced by the surgical and fixation techniques used. Computed tomography (CT) is the most accurate image modality for assessing tunnel widening, but magnetic resonance imaging (MRI) might also be reliable for tunnel volume measurements. In the present study tunnel widening after ACLR using biodegradable interference screw fixation was compared with all-inside ACLR using button fixation, with tunnel volume changes being measured on CT and MRI scans. Study design Randomized controlled trial; Level of evidence, 2. Methods Thirty-three patients were randomly assigned to hamstring ACLR using a biodegradable interference screw or all-inside cortical button fixation. CT and MRI scanning were done at the time of surgery and six months after. Tunnel volume changes were calculated and compared. Results On CT, femoral tunnel volumes changed from the postoperative state (100%) to 119.8% with screw fixation and 143.2% with button fixation (P = 0.023). The changes in tibial tunnel volumes were not significant (113.9% vs. 117.7%). The changes in bone tunnel volume measured on MRI were comparable with those on CT only for tunnels with interference screws. Tibial tunnels with button fixation were significantly underestimated on MRI scanning (P = 0.018). Conclusions All-inside ACLR using cortical button fixation results in increased femoral tunnel widening in comparison with ACLR with biodegradable interference screw fixation. MRI represents a reliable imaging modality for future studies investigating tunnel widening with interference screw fixation.