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A 68-year-old man with a medical history of hypertension was admitted to the emergency department for diffuse abdominal pain preceded by bloody diarrhea. Upon admission, neurological examination was normal, but he suddenly developed a left-sided hemiparesis. After a normal brain computed tomography, intravenous thrombolysis was administered for a suspicion of ischemic stroke. In the first laboratory investigations, hemoglobin was 16.9 g/dL, platelets 121 × 109/L (150–450), and serum creatinine 1.17 mg/dL. By the second hospital day, the platelet level dropped to 79 × 109/L, with haptoglobin at 0.12 g/L, 3% schistocytes, and normal ADAMTS13 activity (57%). Serum creatinine increased to 1.84 mg/dL with oliguria. The suspicion of thrombotic microangiopathy was supported by the identification of Shiga toxin genes stx1 and stx2 on a rectal swab and the isolation of an eaeA-negative Shiga toxin-producing E. coli O113:H4. The patient presented a generalized tonic-clonic seizure, and orotracheal intubation was required for decreased consciousness. Plasma exchange therapy was started, and eculizumab was given 6 days after symptoms onset. Brain magnetic resonance imaging (MRI) on day 13 showed symmetric hyperintensities within basal ganglia that disappeared on a second MRI on day 37. At 2-month follow-up, the patient had made a complete neurological and renal recovery and eculizumab therapy was stopped.

O estudo foi resultado da realização do curso de extensão Uso do Plano de Gerenciamento de Resíduos Sólidos (PGRS) nas organizações, realizado por mestrandos do “Filiação Institucional”, em plataforma digital no mês de novembro de 2020. Teve como objetivo capacitar os gestores das organizações públicas e privadas para o gerenciamento e o descarte de resíduos sólidos de maneira correta e responsável, além de mostrar como o destino incorreto destes resíduos pode impactar o meio ambiente, nas três esferas do tripé da sustentabilidade. Trata-se de um estudo qualitativo, com coleta de dados por meio de levantamento documental, observação participante e questionário aplicado aos participantes do curso. Como resultado obteve-se que PNRS é uma legislação que embora esteja em vigor há algum tempo ainda é pouco conhecida e explorada pela população e principalmente pelos empresários. A NBR 10004 tange sobre os resíduos sólidos e a sua classificação, já o PGRS é o plano de resíduos sólidos que deve ser aplicado pelas empresas sendo ele importância relevante para o desempenho da atividade socioambiental da empresa. A logística reversa desempenha um importante papel no complemento da aplicação das normas relacionadas aos resíduos sólidos auxiliando no devido descarte e tratamento destes resíduos de forma a contribuir com as práticas ambientais. O curso contribui com a disseminação de informações sobre os resíduos sólidos desde a sua classificação até o seu descarte e ressaltou a aplicabilidade do PGRS dentro das organizações.

El artículo estudia el universo total de sentencias de Justicia y Paz que, entre los años 2010 y junio de 2021, han reconocido la existencia de un patrón de macrocriminalidad de violencia basada en género, a fin de analizar las formas en las cuales la violencia sexual ha sido abordada en esta experiencia de justicia transicional. El artículo explora cuatro criterios que han tenido en cuenta los tribunales sobre la violencia sexual, para concluir su configuración, o no, como parte de un patrón de violencia de género: 1. La reiteración; 2. La planificación o política; 3. Las finalidades; 4. La motivación de género. Encontramos que, pese a que existe una normativa sobre los criterios para determinar un patrón de macrocriminalidad, al ponerla en marcha para estudiar los asuntos de género, las posiciones de los tribunales no solo son diversas, sino en muchas ocasiones contradictorias. A partir de este estudio el artículo pone en evidencia la importancia de explicitar los motivos de género del patrón y unificar criterios en las iniciativas de justicia transicional, a fin de garantizar adecuadamente los derechos de las víctimas.

A study aimed at evaluating the seasonal variation of Vibrio and Salmonella in the developed groundwater used for drinking water in the commune of Ntui, Center Region of Cameroon was conducted from January to July 2021. The microorganisms sought were Aerobic Heterotrophic Mesophilic Bacteria (BHAM), bacteria of the Vibrio and Salmonella genera. These bacteria were isolated from ten (10) groundwater points by the surface spreading technique on ordinary agar for BHAMs and that of filter membranes on Thiosulfate Citrate Bile Sucrose (TCBS) and Salmonella-Shigella (SS) media. for Vibrio and Salmonella respectively. Some abiotic parameters such as temperature, pH, among others were evaluated using the usual techniques.The results show that some physico-chemical parameters such as temperature vary relatively between the sampling points. There is a slightly acidic average pH of 6.86 ± 0.57 U.C which is therefore a function of the lateritic soils crossed by the waters. Bacteriological analyzes revealed that these waters have a high and varied bacterial load. Densities of pathogenic bacteria reached an average of 80 CFU/100mL for Vibrio and 7.4.102 CFU/100mL for Salmonella. The most represented bacterial species identified were Vibrio cholerae and Salmonella enterica. These germs can be the cause of cholera and typhoid epidemics in this municipality. Significant correlations (P

A study aimed at evaluating the seasonal variation of Vibrio and Pseudomonas in groundwater in the city of Ombessa, Center region of Cameroon was conducted from January to July 2021. The microorganisms sought were Aerobic Mesophilic Bacteria BHAMs, bacteria of the Vibrio and Pseudomonas genera. These bacteria were isolated from 10 groundwater points by the surface spreading technique for BHAM and the membrane filter method for Vibrio and Pseudomonas. Plate count agar was used for BHAMs, TCBS medium for Vibrio and Cetrimide agar for Pseudomonas. Some abiotic parameters such as temperature, pH, were measured using the usual techniques. The data obtained was analyzed using the appropriate software. Correlation and comparison tests between the variables were carried out. It shows that the water studied has a pH of 5.94 UC to 7.9 UC, the content of dissolved O2 reached 5 mg/L, and there are positive and significant correlations between the density of isolated bacteria and the levels of physicochemical variables. Two species of the genus Pseudomonas (aeruginosa and fluorescens) and four of the genus Vibrio (cholerea, alginolyticus, vulnificus and parahaemolyticus) were isolated, with variable abundance rates ranges from 194 to 898 CFU/100mL for Pseudomonas and from 58 to 683 CFU/100mL for Vibrio. The presence of these germs in groundwater can be explain by the proximity of sources of pollution. This water would be unfit for human consumption without prior treatment according to the World Health Organization standard.

The introduction of new water supply techniques in the Deccan region of India helped make water a crucial factor in local warfare. Improved water supply and conservation influenced military networks, especially at sites located on the strategic frontiers between local polities. Water management also served residential complexes within fortified sites and agricultural improvements in the surrounding arid landscape. This survey of the Naldurg Fort, overlooking a lofty gorge on the Bhima River in the modern state of Maharashtra, examines how builders in the sixteenth and seventeenth centuries dammed available water to service a strategic frontier military garrison, thereby creating a refreshing environment for a pleasure palace and garden. All photographs and the survey are by Nicolas Morelle.

Joint models of longitudinal process and time-to-event data have recently gained attention, notably to provide individualized dynamic predictions. In the presence of competing risks, models published mostly involve cause-specific hazard functions jointly estimated with a linear or generalized linear model. Here we propose to extend the modeling to full parametric joint estimation of a nonlinear mixed-effects model and a subdistribution hazard model. We apply this approach on 6046 patients admitted in intensive care unit (ICU) for sepsis with daily Sequential Organ Failure Assessment (SOFA) score measurements. The joint model is built on a randomly selected training set of two thirds of patients and links the current predicted SOFA measurement to the instantaneous risks of ICU death and discharge from ICU, both adjusted on the patient age. Stochastic Approximation Expectation Maximization algorithm in Monolix is used for estimation. SOFA evolution is significantly associated with both risks: 0.37, 95% confidence interval (CI) = [0.35, 0.39] for the risk of death and -0.38, 95% CI = [-0.39, -0.36] for the risk of discharge. A simulation study, inspired from the real data, shows the good estimation properties of the parameters. We assess on the validation set the added value of modeling the longitudinal SOFA follow-up for the prediction of death compared with a model that includes only SOFA at baseline. Time-dependent receiver operating characteristic area under the curve and Brier scores show that when enough longitudinal individual information is available, joint modeling provides better predictions. The methodology can easily be applied to other clinical applications because of the general form of the model.

International audience; Background: in patients with ST-segment elevation myocardial infarction and multivessel disease, percutaneous coronary intervention for non-culprit lesions is superior to treatment of the culprit lesion alone. The optimal timing for non-infarct-related artery revascularization - immediate versus staged - has not been investigated adequately. Aim: we aimed to assess clinical outcomes at 1 year in patients with ST-segment elevation myocardial infarction with multivessel disease using immediate versus staged non-infarct-related artery revascularization. Methods: outcomes were analysed in patients from the randomized FLOWER-MI trial, in whom, after successful primary percutaneous coronary intervention, non-culprit lesions were assessed using fractional flow reserve or angiography during the index procedure or during a staged procedure during the initial hospital stay, ≤5 days after the index procedure. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction and unplanned hospitalization with urgent revascularization at 1 year. Results: among 1171 patients enrolled in this study, 1119 (96.2%) had complete revascularization performed during a staged procedure, and 44 (3.8%) at the time of primary percutaneous coronary intervention. During follow-up, a primary outcome event occurred in one of the patients (2.3%) with an immediate strategy and in 55 patients (4.9%) with a staged strategy (adjusted hazard ratio 1.44, 95% confidence interval 0.39-12.69; P=0.64). Conclusions: staged non-infarct-related artery complete revascularization was the strategy preferred by investigators in practice in patients with ST-segment elevation myocardial infarction with multivessel disease. This strategy was not superior to immediate revascularization, which, in the context of this trial, was used in a small proportion of patients. Further randomized studies are needed to confirm these observational findings.

Background There is limited evidence that fractional flow reserve (FFR) is effective in guiding therapeutic strategy in multivessel coronary artery disease (CAD) beyond prespecified percutaneous coronary intervention or coronary graft surgery candidates. Objectives The FUTURE (FUnctional Testing Underlying coronary REvascularization) trial aimed to evaluate whether a treatment strategy based on FFR was superior to a traditional strategy without FFR in the treatment of multivessel CAD. Methods The FUTURE trial is a prospective, randomized, open-label superiority trial. Multivessel CAD candidates were randomly assigned (1:1) to treatment strategy based on FFR in all stenotic (≥50%) coronary arteries or to a traditional strategy without FFR. In the FFR group, revascularization (percutaneous coronary intervention or surgery) was indicated for FFR ≤0.80 lesions. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events at 1 year. Results The trial was stopped prematurely by the data safety and monitoring board after a safety analysis and 927 patients were enrolled. At 1-year follow-up, by intention to treat, there were no significant differences in major adverse cardiac or cerebrovascular events rates between groups (14.6% in the FFR group vs 14.4% in the control group; hazard ratio: 0.97; 95% confidence interval: 0.69-1.36; P = 0.85). The difference in all-cause mortality was nonsignificant, 3.7% in the FFR group versus 1.5% in the control group (hazard ratio: 2.34; 95% confidence interval: 0.97-5.18; P = 0.06), and this was confirmed with a 24 months’ extended follow-up. FFR significantly reduced the proportion of revascularized patients, with more patients referred to exclusively medical treatment (P = 0.02). Conclusions In patients with multivessel CAD, we did not find evidence that an FFR-guided treatment strategy reduced the risk of ischemic cardiovascular events or death at 1-year follow-up. (Functional Testing Underlying Coronary Revascularisation; NCT01881555 )

Background Several cases of idiopathic nephrotic syndrome (INS) relapse following the administration of coronavirus disease 2019 (COVID-19) vaccines have recently been reported, raising questions about the potential relationship between the immune response to COVID-19 vaccination and INS pathogenesis. Methods We performed a retrospective multicentre survey describing the clinical and biological characteristics of patients presenting a relapse of INS after COVID-19 vaccination, with an assessment of outcome under treatment. Results We identified 25 patients (16 men and 9 women) presenting a relapse within 1 month of a COVID-19 vaccine injection. The glomerular disease was of childhood onset in half of the patients and most patients (21/25) had received at least one immunosuppressive drug in addition to steroids for frequently relapsing or steroid-dependent nephrotic syndrome (NS). All patients were in a stable condition at the time of injection and 11 had no specific treatment. In five patients, the last relapse was reported >5 years before vaccine injection. The Pfizer-BioNTech (BNT162b2) vaccine was used in 80% of the patients. In 18 cases, INS relapse occurred after the first injection, a mean of 17.5 days after vaccination. A second injection was nevertheless administered in 14 of these patients. Five relapses occurred after administration of the second dose and two relapses after the administration of the third dose. All but one of the patients received steroids as first-line treatment, with an additional immunosuppressive agent in nine cases. During follow-up, complete remission was achieved in 21 patients, within 1 month in 17 cases. Only one patient had not achieved at least partial remission after 3 months of follow-up. Conclusions This case series suggests that, in rare patients, COVID-19 vaccination may trigger INS relapse that is generally easy to control. These findings should encourage physicians to persuade their patients to complete the COVID-19 vaccination schedule.

Diabetes mellitus (DM) predisposes patients to acute myocardial infarction (AMI) and acute heart failure (AHF).To assess correlates of AHF occurring at the early stage of AMI and synergism between early AHF and DM on 5-year mortality.FAST-MI 2005 and 2010 included 7839 consecutive patients admitted for AMI.Overall, 2151 patients (27.4%) had a history of diabetes mellitus (DM), of whom 629 (29.2%) were on insulin. Patients with versus without DM were older (mean age: 70.0 vs. 64.7years; P0.001), with more comorbidities and more severe coronary artery disease. Early AHF (pulmonary oedema or cardiogenic shock) was the most frequent in-hospital complication (12.5%) and was twice as frequent in patients with versus without DM (20.2% vs. 9.6%; adjusted odds ratio: 1.66, 95% confidence interval [CI]: 1.43-1.94; P0.001). Among in-hospital survivors, patients with DM without AHF and those with AHF without DM had 50% increases in 5-year mortality (adjusted hazard ratio [aHR]: 1.50, 95% CI: 1.32-1.69 and aHR: 1.46, 95% CI: 1.23-1.74; both P0.001) versus patients without DM or AHF; with the risk among those with DM and AHF being doubled (aHR: 1.97, 95% CI: 1.66-2.34; P0.0001).Early AHF is the most frequent complication of AMI and is twice as common in patients with versus without DM. After adjustment, early AHF and DM are associated with reduced 5-year survival with synergistic effects in patients with both conditions.https://clinicaltrials.gov (NCT00673036 and NCT01237418).

Branched glycerol dialkyl glycerol tetraethers (brGDGTs) are bacterial lipids that have been largely used as environmental proxies in continental paleorecords. Another group of related lipids, branched glycerol monoalkyl glycerol tetraethers (brGMGTs), has recently been proposed as a potential paleotemperature proxy. Nevertheless, the sources and environmental dependencies of both brGDGTs and brGMGTs along the river-sea continuum are still poorly understood, complicating their application as paleoenvironmental proxies in aquatic settings. In this study, the sources of brGDGTs and brGMGTs and the potential factors controlling their distributions are explored across the Seine River basin (NW France), which encompasses the freshwater to seawater continuum. To this aim, brGDGTs and brGMGTs were analyzed in soils, Suspended Particulate Matter (SPM) and sediments (n=237) collected all along this basin, from land to sea. Both types of compounds are shown to be produced in situ, in freshwater as well as saltwater. Redundancy analysis further shows that both salinity and nitrogen loadings dominantly control the brGDGT distributions. Furthermore, the relative abundance of 6-methyl vs. 5-methyl brGDGTs (IR6Me ratio), Total Nitrogen (TN), δ15N and chlorophyll a concentration co-vary in the upstream area, suggesting that 6-methyl brGDGTs are preferentially produced under low-salinity and high-productivity conditions. In contrast with brGDGTs, brGMGT distribution appear to be primarily regulated by salinity, with a distinct influence on the individual homologues. Salinity is positively correlated with homologues H1020a and H1020b, and negatively correlated with compounds H1020c, H1034b, and H1034c. This suggests that bacteria thriving in freshwater preferentially produce compounds H1020c, H1034b, and H1034c, whereas bacteria primarily growing in saltwater appear to be predominantly responsible for the production of homologues H1020a and H1020b. Based on the abundance ratio of the freshwater-derived compounds (H1020c, H1034b, and H1034c) vs. saltwater-derived homologues (H1020a and H1020b), a novel proxy, Riverine Index (RIX) is proposed to trace riverine organic matter inputs, with high values (>0.5) indicating higher riverine contribution. As RIX relies on compounds that are specifically produced in certain settings (freshwater or saltwater), this index has potential to serve as a powerful proxy for riverine runoff in modern samples as well as in paleorecords.

Time lapse showing cell aggregation during neurosphere formation in control condition.

Supplementary figures providing additionnal information concerning: - The cells glycome before and after PST3.1a treatment as measured by mass spectrometry (Supp. Figure 1) or Glycoprofile (Supp. Figure 2) - The absence of effect of PST3.1a on O-Glycosylation (Supp. Figure 3) - Western blot quantifications (Supp. Figure 4) - The inhibition of cell invasion in matrigel by PST3.1a (Supp. Figure 5) - The absence of cytotoxicity on non-proliferating PBMC cells (Supp. Figure 6).

Time lapse showing cell aggregation during neurosphere formation in PST3.1a-treated condition. In this condition, less cell aggregation is visible as compared to the control condition.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and accounts for a significant proportion of all primary brain tumors. Median survival after treatment is around 15 months. Remodeling of N-glycans by the N-acetylglucosamine glycosyltransferase (MGAT5) regulates tumoral development. Here, perturbation of MGAT5 enzymatic activity by the small-molecule inhibitor 3-hydroxy-4,5-bis-benzyloxy-6-benzyloxymethyl-2-phenyl2-oxo-2λ5-[1,2]oxaphosphinane (PST3.1a) restrains GBM growth. In cell-based assays, it is demonstrated that PST3.1a alters the β1,6-GlcNAc N-glycans of GBM-initiating cells (GIC) by inhibiting MGAT5 enzymatic activity, resulting in the inhibition of TGFβR and FAK signaling associated with doublecortin (DCX) upregulation and increase oligodendrocyte lineage transcription factor 2 (OLIG2) expression. PST3.1a thus affects microtubule and microfilament integrity of GBM stem cells, leading to the inhibition of GIC proliferation, migration, invasiveness, and clonogenic capacities. Orthotopic graft models of GIC revealed that PST3.1a treatment leads to a drastic reduction of invasive and proliferative capacity and to an increase in overall survival relative to standard temozolomide therapy. Finally, bioinformatics analyses exposed that PST3.1a cytotoxic activity is positively correlated with the expression of genes of the epithelial–mesenchymal transition (EMT), while the expression of mitochondrial genes correlated negatively with cell sensitivity to the compound. These data demonstrate the relevance of targeting MGAT5, with a novel anti-invasive chemotherapy, to limit glioblastoma stem cell invasion. Mol Cancer Res; 15(10); 1376–87. ©2017 AACR.

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P = 1.1 × 10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3-8.2], P = 2.1 × 10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1-2635.4], P = 3.4 × 10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3-8.4], P = 7.7 × 10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10-5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60years old.

Bio-telemetry from small tags attached to animals is one of the principal methods for studying the ecology and behaviour of wildlife. The field has constantly evolved over the last 80 years as technological improvement enabled a diversity of sensors to be integrated into the tags (e.g., GPS, accelerometers, etc.). However, retrieving data from tags on free-ranging animals remains a challenge since satellite and GSM networks are relatively expensive and or power hungry. Recently a new class of low-power communication networks have been developed and deployed worldwide to connect the internet of things (IoT). Here, we evaluated one of these, the Sigfox IoT network, for the potential as a real-time multi-sensor data retrieval and tag commanding system for studying fauna across a diversity of species and ecosystems. We tracked 312 individuals across 30 species (from 25 g bats to 3 t elephants) with seven different device concepts, resulting in more than 177,742 successful transmissions. We found a maximum line of sight communication distance of 280 km (on a flying cape vulture [Gyps coprotheres]), which sets a new documented record for animal-borne digital data transmission using terrestrial infrastructure. The average transmission success rate amounted to 68.3% (SD 22.1) on flying species and 54.1% (SD 27.4) on terrestrial species. In addition to GPS data, we also collected and transmitted data products from accelerometers, barometers, and thermometers. Further, we assessed the performance of Sigfox Atlas Native, a low-power method for positional estimates based on radio signal strengths and found a median accuracy of 12.89 km (MAD 5.17) on animals. We found that robust real-time communication (median message delay of 1.49 s), the extremely small size of the tags (starting at 1.28 g without GPS), and the low power demands (as low as 5.8 µAh per transmitted byte) unlock new possibilities for ecological data collection and global animal observation., ANIMAL BIOTELEMETRY, 11 (1)

BackgroundEndometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting.MethodsThe panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to ResultsConsensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities.ConclusionDespite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments.

IntroductionSpondylarthritis (SpA) development in HLA-B27/human β2-microglobulin transgenic rat (B27-rat) is correlated with altered conventional dendritic cell (cDC) function that promotes an inflammatory pattern of CD4+T cells, including a biased expansion of pro-inflammatory Th17 population and imbalance of regulatory T cells cytokine profile. Transcriptomic analysis revealed that cDCs from B27-rats under express IL-27, an anti-inflammatory cytokine which induces the differentiation of IL-10+ regulatory T cells and inhibits Th17 cells.MethodsHere, we first investigated whether in vitro addition of exogenous IL-27 could reverse the inflammatory pattern observed in CD4+ T cells. Next, we performed preclinical assay using IL-27 to investigate whether in vivo treatment could prevent SpA development in B27-rats.Resultsin vitro addition of IL-27 to cocultures of cDCs and CD4+ T cell subsets from B27-rats reduced IL-17 and enhanced IL-10 production by T cells. Likewise, IL-27 inhibited the production of IL-17 by CD4+ T cells from SpA patients. Interestingly, in vivo treatment with recombinant IL-27 starting before SpA onset, inhibited SpA development in B27-rats through the suppression of IL-17/TNF producing CD4+ T cells.DiscussionOverall, our results reveal a potent inhibitory effect of IL-27 and highlight this cytokine as a promising new therapeutic target in SpA, especially for SpA patients non responders to currently approved biotherapies.

Background The initial management of patients with sarcoma is a critical issue. We used the nationwide French National Cancer Institute-funded prospective sarcoma database NETSARC to report the management and oncologic outcomes in adolescents and young adults (AYAs) patients with sarcoma at the national level. Patients and methods NETSARC database gathers regularly monitored and updated data from patients with sarcoma. NETSARC was queried for patients (15–30 years) with sarcoma diagnosed from 2010 to 2017 for whom tumor resection had been performed. We reported management, locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) in AYA treated in French reference sarcoma centers (RSC) and outside RSC (non-RSC) and conducted multivariable survival analyses adjusted for classical prognostic factors. Results Among 3,227 patients aged 15–30 years with sarcoma diagnosed between 2010 and 2017, the study included 2,227 patients with surgery data available, among whom 1,290 AYAs had been operated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed including pre-treatment biopsy (RSC: 85.9%; non-RSC 48.1%), pre-treatment imaging (RSC: 86.8%; non-RSC: 56.5%) and R0 margins (RSC 57.6%; non-RSC: 20.2%) (p Conclusions This study highlights the importance for AYA patients with sarcoma to be managed in national sarcoma reference centers involving multidisciplinary medical teams with paediatric and adult oncologists.

Supplemental Material, sj-pdf-2-ptd-10.1177_0896860820982218 for ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification, measurement, interpretation and rationale for intervention by Johann Morelle, Joanna Stachowska-Pietka, Carl Öberg, Liliana Gadola, Vincenzo La Milia, Zanzhe Yu, Mark Lambie, Rajnish Mehrotra, Javier de Arteaga and Simon Davies in Peritoneal Dialysis International

Supplemental Material, sj-pdf-1-ptd-10.1177_0896860820982218 for ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification, measurement, interpretation and rationale for intervention by Johann Morelle, Joanna Stachowska-Pietka, Carl Öberg, Liliana Gadola, Vincenzo La Milia, Zanzhe Yu, Mark Lambie, Rajnish Mehrotra, Javier de Arteaga and Simon Davies in Peritoneal Dialysis International

Additional file 1: Supplementary Methods. Fig S1. Luciferase assay on HEK293T cells transfected with the pGL4.32 luciferase reporter construct and an expression vector for Renilla luciferase together with no vector (mock), EV, WT, or 4 TLR7 variants found in our cohort. After 24 h, transfected cells were left untreated or were treated by incubation with 1 μg/mL R848 for 24 h. These data were established from two independent experiments. The y-axis represents NF-κB transcriptional activity as a percentage of the WT. The x-axis indicates the alleles used for transfection. Fig S2. Age distribution as boxplot and violin plot of the critical COVID-19 cases according to the carrier status of pLOF/bLOF at 15 type I IFN-related loci. Mean age of the patients for each category is shown in red. T-test was used to compare the means, showing a significant difference between non-carriers and carriers of heterozygous or homozygous/hemizygous variants (P = 2.2 × 10−6) and between heterozygous carriers and homozygous/hemizygous carriers (P = 0.008). Fig S3. Empirical power of our sample to detect an association at the 2.5 × 10−6 exome-wide significance threshold for various relative risks and proportion of carriers of at least one disease causing variant in the general population (PD), as estimated by simulation study (N = 1000 replicates).

Supplemental Material, sj-pdf-3-ptd-10.1177_0896860820982218 for ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification, measurement, interpretation and rationale for intervention by Johann Morelle, Joanna Stachowska-Pietka, Carl Öberg, Liliana Gadola, Vincenzo La Milia, Zanzhe Yu, Mark Lambie, Rajnish Mehrotra, Javier de Arteaga and Simon Davies in Peritoneal Dialysis International

La pandemie actuelle doit faire reflechir a la menace NRBC (nucleaire, radiologique, biologique ou chimique) dont les risques biologiques. Il serait judicieux d’anticiper ce type de danger et de se doter des moyens pour eviter de se trouver sans ressources pour se proteger. Cet effort doit se faire dans une cooperation internationale, car il y va de la sante de la population.

Although indispensable, radiation exposure during cardiac catheterization procedures can cause specific radiation-induced diseases. These affect the patient but also the interventional cardiologist. Exposure to high or repeated radiation doses causes deterministic effects. Moreover, even low-dose exposure, especially when repeated, produces a risk of stochastic effets. In that respect, it is crucial to improve the radiation safety of cardiac angiography and interventions, to promote radiation protection and to maintain this exposure « As Low As Reasonably Achievable ». Thus, there is a necessity to spread knowledge about safety standards and recommandations to reduces the dose among interventionalists. Data collection and comparaison of practices are precious to this quality improvement process. For the year 2020, France-PCI registry had collected dosimetric datas related to 55 783 coronary angiographic and interventional procedures from 30 centers in France. Mean fluoroscopy time was 4,4 minutes for diagnostic procedures. Mean PDS was 1 767cGy.Cm2 and mean Air Kerma de 257Gy. Coronary percutaneous angioplasty procedures were related to approximately two to three times higher mean exposures. Mean exposure related to chronic coronary total occlusion treatment procedures was also two times higher than exposure related to non-CTO interventions. These data also highlighted wide disparities between centers.

The most appropriate criteria and timing for palliative care referral remain a critical issue, especially in patients with metastatic breast cancer for whom long-term chemosensibility and survival are observed. We aimed to compare the impact of early palliative care including formal concertation with oncologists on decision for an additional line of chemotherapy compared with usual oncology care.This randomized prospective study enrolled adult women with metastatic breast cancer and visceral metastases with a 3rd- or 4th-line chemotherapy (CT). Patients received usual oncology care with a palliative care consultation only upon patient or oncologist request (standard group, S) or were referred to systematic palliative care consultation including a regular concertation between palliative care team and oncologists (early palliative care group, EPC). The primary endpoint was the rate of an additional CT (4th or 5th line) decision. Quality of life, symptoms, social support and satisfaction were self-evaluated at 6 and 12 months, at treatment discontinuation or 3 months after discontinuation.From January 2009 to November 2012, two authorized cancer centers included 98 women (EPC: 50; S: 48). Thirty-seven (77.1%, 95%CI 62.7-88%) patients in the EPC group had a subsequent chemotherapy prescribed and 36 (72.0%, 95%CI 57.5-83.8%) in the S group (p = 0.646). No differences in symptom control and global quality of life were observed, but less deterioration in physical functioning was reported in EPC (EPC: 0 [- 53-40]; S: - 6; 7 [- 60 to - 20]; p = 0.027). Information exchange and communication were significant improved in EPC (exchange, EPC: - 8.3 [- 30 to + 7]; S: 0.0 [- 17 to + 23]; p = 0.024; communication, EPC: 12.5 [- 8 to - 37]; S: 0.0 [- 21 to + 17]; p = 0.004).EPC in metastatic breast cancer patients did not impact the prescription rate of additional chemotherapy in patients a 3rd- or 4th-line chemotherapy for metastatic breast cancer; however, EPC may contribute to alleviate deterioration in physical functioning, while facilitating communication.ClinicalTrial.gov identifier: NCT00905281, May 20, 2009.

The use of georeferenced information on the presence of a species to predict its distribution across a geographic area is one of the most common tools in management and conservation. The collection of high-quality presence-absence data through structured surveys is, however, expensive, and managers usually have more abundant low-quality presence-only data collected by citizen scientists, opportunistic observations, and culling returns for game species. Integrated Species Distribution Models (ISDMs) have been developed to make the most of the data available by combining the higher-quality, but usually less abundant and more spatially restricted presence-absence data, with the lower quality, unstructured, but usually more extensive and abundant presence-only data. Joint-likelihood ISDMs can be run in a Bayesian context using INLA (Integrated Nested Laplace Approximation) methods that allow the addition of a spatially structured random effect to account for data spatial autocorrelation. These models, however, have only been applied to simulated data so far. Here, for the first time, we apply this approach to empirical data, using presence-absence and presence-only data for the three main deer species in Ireland: red, fallow and sika deer. We collated all deer data available for the past 15 years and fitted models predicting distribution and relative abundance at a 25 km2 resolution across the island. Models’ predictions were associated to spatial estimate of uncertainty, allowing us to assess the quality of the model and the effect that data scarcity has on the certainty of predictions. Furthermore, we validated the three species-specific models using independent deer hunting returns. Our work clearly demonstrates the applicability of spatially-explicit ISDMs to empirical data in a Bayesian context, providing a blueprint for managers to exploit unused and seemingly unusable data that can, when modelled with the proper tools, serve to inform management and conservation policies.

En terrain trouble Boussole en Corée du Nord se traduit par « aiguille indiquant le nord » mais en Corée du Sud, par « aiguille indiquant le Sud » apprend-on dans Faire du terrain en Corée du Nord. Ecrire autrement les sciences sociales, édité par l’Atelier des cahiers en 2021 (p. 274). Cette traduction, me semble-t-il, peut introduire l’impression de désorientation qui découle de sa lecture. Cet ouvrage collectif dirigé par Valérie Gelézeau, géographe, et Benjamin Joineau, anthropologue, ras...

BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2],P=2.1×10−4). Adding the recently reportedTYK2COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4];P=3.4×10−3). When these 14 loci andTLR7were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0],P=4.7×10−7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9],P=0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years;P=1.68×10−5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

The present work concerns the intermetallic compound (IMC) existing in the Ag-Sn system and its potential use in electronics as attachment materials allowing the adhesion of the chip to the substrate forming the power module. First, we present the synthesis protocol in polyol medium of a compound with the chemical formula Ag

Foams are relevant in many food products and food production processes. During the bottling of beverages, foam can severely impair the process as overflowing foam causes underfilled bottles and poses a high contamination risk. Consequently, the filling speed is limited by the foaming properties of the beverage. Several filling experiments with different juices were executed to improve the understanding of the influence of flow and material properties on the foaming behavior. The foam evolution in time was evaluated using a convolutional neural network (CNN) to detect visible foam regions in video recordings of the experiments. The use of image data has the advantage that its acquisition is noninvasive and no supplementary sensor hardware with direct product contact has to be installed into the process. The CNN was able to detect image regions that contain foam with errors of only a few millimeters. The detection worked for different juice colors, regardless of the lighting and noise in the image. Based on the filling speed, viscosity, surface tension, and density, the foaming behavior during the filling process was modeled with a recurrent neural network (RNN). The RNN was able to predict the foam height evolution with average errors below five millimeters. Both models are easily transferable to new use cases by retraining the networks.