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Carotid Web (CaW) is a growingly recognized cause of ischemic stroke, associated with a high recurrence risk. Several therapeutic strategies have been proposed as a tertiary prevention including carotid stenting, endarterectomy and antithrombotic medications. Among these, carotid stenting with dual-layer stent may be promising to adequately cover the focal arterial dysplasia. Our aim was to investigate the safety and efficacy of the Casper stent in the treatment of symptomatic CaW.We conducted a retrospective analysis of consecutive patients presenting with a symptomatic CaW and included in the ongoing prospective observational multicenter CAROWEB registry. The study period was January 2015 to December 2021. Inclusion criteria were CaW treated with dual-layer Casper stent. Patients treated with other types of carotid stent, endarterectomy or antithrombotic medication were excluded. Clinical and radiological initial data and outcomes were recorded.twenty-seven patients (with 28 caw) were included. median age was 52 (iqr: 46-68). median delay between index cerebrovascular event and cervical stenting was 9 days (IQR: 6-101). In all cases, the cervical carotid stenting was successfully performed. No major perioperative complication was recorded. No recurrent stroke or transient ischemic attack was observed during a median follow-up time of 272 days (IQR: 114-635). Long-term imaging follow-up was available in 25/28 (89.3%) stented CaW with a median imaging follow-up of 183 days (IQR: 107-676; range: 90-1542). No in-stent occlusion or stenosis was detected.In this study, carotid stenting with dual-layer Casper stent in the treatment of symptomatic CaW was effective regarding stroke recurrence prevention and safe, without procedural nor delayed detected adverse event. However, the optimal therapeutic approach of symptomatic CaW still needs to be explored through randomized trials.

This paper provides a laboratory workflow for single-nucleus RNA-sequencing (snRNA-seq) including a protocol for gentle nuclei isolation from fresh frozen tumor biopsies, making it possible to analyze biobanked material. To develop this protocol, we used non-frozen and frozen human bladder tumors and cell lines. We tested different lysis buffers (IgePal and Nuclei EZ) and incubation times in combination with different approaches for tissue and cell dissection; sectioning, semi-automated dissociation, manual dissociation with pestles, and semi-automated dissociation combined with manual dissociation with pestles. Our results showed a combination of IgePal lysis buffer, tissue dissection by sectioning and short incubation time was the best conditions for gentle nuclei isolation applicable for snRNA-seq, and we found limited confounding transcriptomic changes based on the isolation procedure. This protocol makes it possible to analyze biobanked material from patients with well described clinical and histopathological information and known clinical outcomes with snRNA-seq.

The follow-up of Bosniak IIF (BIIF) renal cysts is associated with significant costs, radiation, and anxiety. Recent studies have suggested a risk of malignancy and upgrading lower than previously reported. We aimed to determine their clinical outcomes and to evaluate the impact of the 2019 Bosniak classification on the diagnosis of such lesions.We identified all radiology reports with the diagnosis of a BIIF cyst at our institution between January 2000 and December 2018. Imaging was reviewed to confirm the diagnosis and determine progression based on the 2005 Bosniak classification. Radiological and clinical characteristics were established, and the 2019 Bosniak criteria were retrospectively applied.Out of 252 cysts reviewed, 55 (22%) were re-classified as BII upon revision using the 2005 Bosniak classification. A total of 181 BIIF cysts were included for final analysis. The median imaging follow-up was 50 months. 4 (2.2%) cysts progressed to BIII or BIV. Five (2.8%) patients underwent surgical interventions, with only 1 malignant pathology being reported. No malignant progression was observed after 36 months. When applied to our cohort, the 2019 Bosniak classification would have led to a 76% decrease in BIIF diagnoses, with no increase in BIII or BIV diagnoses, and identical classification of the confirmed malignant pathology.Upgrading and malignancy rates among BIIF cysts was markedly lower than traditionally reported. No patient had a significant progression beyond 36 months. More than 20% of BIIF cysts were initially overdiagnosed. The 2019 Bosniak classification may help to reduce the overdiagnosis of BIIF lesions requiring follow-up.

This study aimed to estimate the prevalence of scabies in humans in Babylon province. The study comprised a total of 740 individuals who complained of skin disorders when they visited the clinic. There were 740 cases in all, 320 women (43.2%), 282 men (38.1%), and 138 kids (18.7%). The prevalence of scabies in Babylon province was 14.32%. This study showed that males 25.5% were signifi cantly more infected than females 41.5% and children 33%. The infection with scabies in the spring season is signifi cantly higher than in the other seasons of the year, where the temperature is between 20–35ºC. In conclusion, the prevalence of scabies was signifi cantly higher in males and children than in females and the spring season was the most prevalent season for infection

This article explores the gendered securitisation of humanitarianism through the lens of Venezuelan women who fled to Brazil, as part of the largest migration flows in South America. By the end of 2022, the number of displaced Venezuelans had grown to seven million, half of whom were women and girls. Alongside humanitarian programmes, measures of migration control, policing and deterrence are now routinely implemented. This article explores the interplay between securitised policies and humanitarian programmes on the everyday experience of rights of Venezuelan migrant women and girls. We ask: what happens when migrant women reach Brazil, a supposed place of safety? Do they experience rights restitution and protection, or do they continue to be subject to everyday gendered humiliations? Building on fieldwork in Boa Vista and Manaus in 2020–2022, we explore migrant women and girls’ experiences with shelter and healthcare, two central pillars of humanitarian programmes. Contributing directly to literatures on migration management, humanitarianism and control, this article focuses on ‘the receiving end’ of securitised humanitarian practices and deploys a gender lens to reveal how securitised humanitarians reproduces disciplinary dynamics of governance and creates gendered risks and vulnerabilities that erode migrant women and girl’s rights and agency in everyday life.

Helicobacter pylori (H. pylori) infection causes chronic gastritis, peptic ulcers and gastric cancer. Although H. pylori prevalence is decreasing worldwide, regional variations exist in Europe, with the lowest infection prevalence in Northern Europe, and the highest in Eastern and Southern Europe (1). Changes in the treatment recommendations and the increasing available evidence have justified the implementation of new recommendations since last Belgian consensus in 1998 (2). Several non-H. pylori Helicobacter species (NH.PYLORI-H), colonizing the stomach of domestic animals, also have the ability to cause gastric disease in humans, although to a lesser extent. These zoonotic NH. PYLORIH are not the subject of the current recommendations.

International audience; Apathy occurs in approximately one third of people after stroke. Despite its frequency and functional consequences, the determinants of apathy have only been partially defined. The major difficulty lies in disentangling the reduction in activity due to apathy itself from those secondary to comorbidities, such as depression, sensorimotor deficits, and cognitive impairment. Here, we aimed to examine the prevalence of apathy, identify confounding sources of hypoactivity, and define its neuroimaging determinants using multivariate voxel lesion symptom-mapping (mVLSM) analyses. We assessed apathy in a subgroup (n = 325, mean age: 63.8 ± 10.5 years, 91.1% ischemic stroke) of the GRECogVASC cohort using the validated Behavioral Dysexecutive Syndrome Inventory, interpreted using GREFEX criteria, as well as confounding factors (depression, anxiety, severity of the neurological deficit, and gait disorders). mVLSM analysis was used to define neuroimaging determinants and was repeated after controlling for confounding factors. Apathy was present for 120 patients (36.9%, 95% CI: 31.7-42.2). Stepwise linear regression identified three factors associated with apathy: depressive symptoms (R2 = .3, p = .0001), cognitive impairment (R2 = .015, p = .02), and neurological deficit (R2 = .110, p = .0001). Accordingly, only 9 (7.5%) patients had apathy without a confounding factor, i.e., isolated apathy. In conventional VLSM analysis, apathy was associated with a large number of subcortical lesions that were no longer considered after controlling for confounding factors. Strategic site analysis identified five regions associated with isolated apathy: the F3 orbitalis pars, left amygdala, left thalamus, left pallidum, and mesencephalon. mVLSM analysis identified four strategic sites associated with apathy: the right corticospinal tract (R2 = .11; p = .0001), left frontostriatal tract (R2 = .11; p = .0001), left thalamus (R2 = .04; p = .0001), and left amygdala (R2 = .01; p = .013). These regions remained significant after controlling for confounding factors but explained a lower amount of variance. These findings indicate that poststroke apathy is more strongly associated with depression, neurological deficit, and cognitive impairment than with stroke lesions locations, at least using VLSM analysis.

Objective To evaluate the association between dose of skin-to-skin contact (SSC) per day and initiation time with the occurrence of deaths in newborns with weight up to 1800g. Method Multicentric cohort in five Brazilian neonatal units, including newborns with a birth weight of ≤1800g. The time of SSC was registered in individual file, by the team or family during the hospitalization. Maternal and newborn data were obtained through questionnaires applied to mothers and in medical records. Classification Tree was used for data analysis. Results The performance of the first SSC after 206h was significantly associated with death (p = 0.02). Although there was no association between SSC/day and death (p = 0.09), the number of deaths among those who performed more than 146.9 minutes/day was lower (3;1.5%) than among those who performed this practice for a shorter time (13;6.4%), a fact considered of great clinical importance. Early and late infections present statistically significant associations with the outcome. The chance of death was equal to zero when there was no early infection in the group with the longest duration of SSC. This probability was also equal to zero in the absence of late sepsis for the group with less than 146.9 minutes/day of SSC. Conclusions The first SSC before 206 hours of life is recommended in order to observe a reduction in the risk of neonatal death. Staying in SSC for more than 146.9 min/day seems to be clinically beneficial for these neonates mostly when it was associated with the absence of infection.

Purpose: To investigate the use of plasma and urine DNA mutation analysis for predicting neoadjuvant chemotherapy (NAC) response and oncological outcome in patients with muscle-invasive bladder cancer. Experimental Design: Whole-exome sequencing of tumor and germline DNA was performed for 92 patients treated with NAC followed by radical cystectomy (RC). A custom NGS-panel capturing approximately 50 mutations per patient was designed and used to track mutated tumor DNA in plasma and urine. A total of 447 plasma samples, 281 urine supernatants, and 123 urine pellets collected before, during, and after treatment were analyzed. Patients were enrolled from 2013 to 2019, with a median follow-up time of 41.3 months after RC. Results: We identified tumor DNA before NAC in 89% of urine supernatants, 85% of urine pellets, and 43% of plasma samples. Tumor DNA levels were higher in urine supernatants and urine pellets compared with plasma samples (P < 0.001). In plasma, detection of circulating tumor DNA (ctDNA) before NAC was associated with a lower NAC response rate (P < 0.001). Detection of tumor DNA after NAC was associated with lower response rates in plasma, urine supernatant, and urine pellet (P < 0.001, P = 0.03, P = 0.002). Tumor DNA dynamics during NAC was predictive of NAC response and outcome in urine supernatant and plasma (P = 0.006 and P = 0.002). A combined measure from plasma and urine supernatant tumor DNA dynamics stratified patients by outcome (P = 0.003). Conclusions: Analysis of tumor DNA in plasma and urine samples both separately and combined has a potential to predict treatment response and outcome.

Background Myocardial injury after non-cardiac surgery (MINS), based on measurement of troponin T, is associated with perioperative major adverse cardiovascular events (MACE). We therefore determined the high-sensitivity troponin I (hsTnI) thresholds associated with 30 day MACE after non-cardiac surgery. Methods We performed a nested biobank cohort study of 4553 patients from the Vascular Events in Non-Cardiac Surgery Patients Cohort Evaluation (VISION) Study. We measured hsTnI (ADVIA Centaur® hsTnI assay) on postoperative days 1 to 3 in patients ≥45 years undergoing non-cardiac surgery. An iterative Cox proportional hazard model determined peak postoperative hsTnI thresholds independently associated with MACE (i.e., death, myocardial infarction occurring on postoperative day 4 or after, non-fatal cardiac arrest, or congestive heart failure) within 30 days after surgery. Results MACE occurred in 89/4545 (2.0%) patients. Peak hsTnI values of Conclusion A peak postoperative hsTnI ≥75 ng/L was associated with >5-fold increase in the risk of 30 days MACE compared to levels Clinicaltrials.gov Registration Number: NCT00512109.

Patients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion.Consecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes.Among 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11-11.5]; p 0.048).In patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality.

Our planet is facing a variety of serious threats from climate change that are unfolding unevenly across the globe. Uncovering the spatial patterns of ecosystem stability is important for predicting the responses of ecological processes and biodiversity patterns to climate change. However, the understanding of the latitudinal pattern of ecosystem stability across scales and of the underlying ecological drivers is still very limited. Accordingly, this study examines the latitudinal patterns of ecosystem stability at the local and regional spatial scale using a natural assembly of forest metacommunities that are distributed over a large temperate forest region, considering a range of potential environmental drivers. We found that the stability of regional communities (regional stability) and asynchronous dynamics among local communities (spatial asynchrony) both decreased with increasing latitude, whereas the stability of local communities (local stability) did not. We tested a series of hypotheses that potentially drive the spatial patterns of ecosystem stability, and found that although the ecological drivers of biodiversity, climatic history, resource conditions, climatic stability, and environmental heterogeneity varied with latitude, latitudinal patterns of ecosystem stability at multiple scales were affected by biodiversity and environmental heterogeneity. In particular, α diversity is positively associated with local stability, while β diversity is positively associated with spatial asynchrony, although both relationships are weak. Our study provides the first evidence that latitudinal patterns of the temporal stability of naturally assembled forest metacommunities across scales are driven by biodiversity and environmental heterogeneity. Our findings suggest that the preservation of plant biodiversity within and between forest communities and the maintenance of heterogeneous landscapes can be crucial to buffer forest ecosystems at higher latitudes from the faster and more intense negative impacts of climate change in the future.

New biomass crop hybrids for bioeconomic expansion require yield projections to determine their potential for strategic land use planning in the face of global challenges. Our biomass growth simulation incorporates radiation interception and conversion efficiency. Models often use leaf area to predict interception which is demanding to determine accurately, so instead we use low-cost rapid light interception measurements using a simple laboratory-made line ceptometer and relate the dynamics of canopy closure to thermal time, and to measurements of biomass. We apply the model to project the European biomass potentials of new market-ready hybrids for 2020–2030. Field measurements are easier to collect, the calibration is seasonally dynamic and reduces influence of weather variation between field sites. The model obtained is conservative, being calibrated by crops of varying establishment and varying maturity on less productive (marginal) land. This results in conservative projections of miscanthus hybrids for 2020–2030 based on 10% land use conversion of the least (productive) grassland and arable for farm diversification, which show a European potential of 80.7–89.7 Mt year−1 biomass, with potential for 1.2–1.3 EJ year−1 energy and 36.3–40.3 Mt year−1 carbon capture, with seeded Miscanthus sacchariflorus × sinensis displaying highest yield potential. Simulated biomass projections must be viewed in light of the field measurements on less productive land with high soil water deficits. We are attempting to model the results from an ambitious and novel project combining new hybrids across Europe with agronomy which has not been perfected on less productive sites. Nevertheless, at the time of energy sourcing issues, seed-propagated miscanthus hybrids for the upscaled provision of bioenergy offer an alternative source of renewable energy. If European countries provide incentives for growers to invest, seeded hybrids can improve product availability and biomass yields over the current commercial miscanthus variety.

International audience; The insertion of a nasogastric (NG) tube is often a difficult experience for both patients and caregivers. This often results in a high failure rate of NG insertion. This pilot study aimed to evaluate the effectiveness, tolerance, and acceptability of hypnoanalgesia to assist self-insertion of an NG tube. Patients undergoing high-dose chemotherapy for autologous or allogeneic hematopoietic stem cell transplantation (HSCT) or acute leukemia and with high risk of aplasia were included in the study. A total of 38 patients were included during 6 consecutive months. They all achieved successful NG tube self-insertion. The NG tube remained in place during hospitalization in 32 cases for an average duration of 15 days. Six patients rejected the NG tube during vomiting but they all voluntarily attempted it again later on and succeeded. The discomfort related to NG-tube insertion was mild. This pilot study suggests that NG tube self-insertion assisted by hypnoanalgesia may be effective, well-accepted, and well-tolerated in patients. These promising findings will need further confirmation.

International audience; INTRODUCTION: Molecular profile of resected stage I-II non-small cell lung cancer (NSCLC) would help refine prognosis and personalize induction or adjuvant strategies. We sought to report the molecular profile of resected stage I-II NSCLC and analyzed the impact of epidermal growth factor receptor (EGFR) mutations on outcomes in a Western population. PATIENTS AND METHODS: Surgical cases were identified from Biomarkers France study, a nationwide prospective study including NSCLC patients screened for EGFR, HER2, KRAS, BRAF, PIK3CA, ALK alterations from 2012 to 2013. Among surgical patients, clinical charts of the largest centers were reviewed in order to analyze the prognostic impact of EGFR mutations. RESULTS: In the BMF database (n = 17.636), surgical patients (n = 854) were characterized by a higher proportion of EGFR mutations than nonsurgical patients (12.9% vs. 10.2%, P = .025), while the other molecular alterations did not differ. The proportion of EGFR mutations was 27% in women undergoing surgery. In the study group (n = 293; EGFR wild type, n = 235; usual mutation, n = 50; rare mutation, n = 8), after a median follow-up of 67 months, 215 patients (74.4%) had not relapsed. No difference was found between EGFR-mutant and EGFR-wt tumors regarding recurrence site, disease-free survival, and overall survival. The 5-year disease-free survival and overall survival after surgical resection of stage I-II EGFR-mutated tumors were 65% and 75%, respectively. CONCLUSION: In resected stage I to II NSCLC, EGFR mutations were found in 12.9% of cases, associated with a 5-year overall survival of 75%, with no impact on recurrence site, disease-free survival, and overall survival.

Plus de deux décennies après le lancement par Claire Blanche-Benveniste et son équipe, de la méthode pionnière EuRom4, rééditée et augmentée en 2011 sous le nom d’EuRom5, paraît PanromanIC, manuel d’intercompréhension entre les six langues romanes principales, à savoir, le catalan, l’espagnol, le français, l’italien, le portugais et le roumain. Les auteur·es, tou·te·s enseignant·es, universitaires et spécialistes de l’intercompréhension, y proposent une approche inductive pour découvrir les similarités entre les langues romanes, basée sur la lecture et la compréhension écrite partielle ; le titre de l’ouvrage faisant référence à la dimension globale (Pan-) du milieu roman (roman-) et à l’intercompréhension (IC) des langues qui le composent.

International audience; PURPOSE: The preferred hypothesis for the dissemination patterns of Hodgkin lymphoma (HL) is the contiguity hypothesis. However, this hypothesis is based on studies performed before the advent of [(18)F]-FDG PET/CT which is now the established reference for HL staging. This study aims to extract the dissemination patterns of HL using [(18)F]-FDG PET/CT and a probability network model. METHODS: We retrospectively analyzed [(18)F]-FDG PET/CT performed for initial staging of patients with classical HL. The HL involvement status (presence of absence) was reported for 19 supra- and infra-diaphragmatic lymph node regions and 4 extranodal regions (lung, spleen, liver, and osteo- medullary). The analysis of HL dissemination was carried out using HL involvement status for all regions through 3 distinct methods: comparison of nearby lymph node regions, correlation assessment between all regions and relationship strength between all regions using Ising network model. RESULTS: A total of 196 patients were included. Our results showed strong relationships between nearby involved lymph node regions (for example between the left pelvic and the abdominal lymph node regions (relationship strength = 0.980)) and between more distant regions (for example between right and left axillary lymph node regions (strength = 0.714)). Furthermore, involvement of the infra-diaphragmatic lymph node regions was significantly correlated with Ann Arbor stage IV (phi = 0.56, p

Few data are available on the impact of KRAS mutation in patients with advanced non-squamous non-small cell lung cancer (aNSCLC) treated with immunotherapy. This analysis assessed the impact of KRAS mutation on the efficiency of first-line pembrolizumab immunotherapy in aNSCLC patients with PD-L1 ≥ 50 %.This was a secondary analysis of the ESCKEYP study, a retrospective, national, multicenter study which included consecutively all metastatic NSCLC patients who initiated first-line treatment with pembrolizumab monotherapy from May 2017 (date of pembrolizumab availability in this indication in France) to November 22, 2019 (pembrolizumab-chemotherapy combination approval). Progression-free survival (PFS) and overall survival (OS) were calculated from the start of pembrolizumab treatment by the Kaplan-Meier method. Tumor response and PFS were assessed locally.Among the 681 non-squamous aNSCLC PD-L1 ≥ 50 % patients treated with pembrolizumab in the first line, 227 (33.0 %) had a KRAS mutation (KRAS G12C, 12.5 %; KRAS non-G12C, 20.5 %). Except among non-smokers (KRAS G12C, 0 %; KRAS non-G12C, 2.9 %; no KRAS mutation, 9.2 %), patients presented no differences in terms of sex, age, number and sites of metastatic disease at diagnosis, use of corticosteroids, use of antibiotics, and for biological factors between wild-type KRAS, KRAS G12C and non-KRAS G12C groups. Median (95 % CI) PFS in months were 7.0 (3.7-14) for KRAS G12C, 4.8 (3.4-6.7) for KRAS non-G12C and 8.5 (7.3-10.6) for wild-type KRAS genotypes (p = 0.23). Median OS were 18.4 (12.6-NR), 20.6 (11.4-NR) and 27.1 (18.7-34.2) months, respectively (p = 0.57).No difference in efficacy was observed in non-squamous aNSCLC patients treated with first-line pembrolizumab immunotherapy whether they presented a KRAS G12C, non KRAS G12C or wild-type KRAS genotype.

BACKGROUND: The functional status of immune cells in the tumor microenvironment and tumor characteristics may explain bacillus Calmette-Guérin (BCG) failure in high-risk non-muscle-invasive bladder cancer (NMIBC).OBJECTIVE: To characterize molecular correlates of post-BCG high-grade (HG) recurrence using multiomics analysis.DESIGN, SETTING, AND PARTICIPANTS: Patients with BCG-treated NMIBC (n = 156) were included in the study. Metachronous tumors were analyzed using RNA sequencing (n = 170) and whole-exome sequencing (n = 195). Urine samples were analyzed for immuno-oncology-related proteins (n = 190) and tumor-derived DNA (tdDNA; n = 187).OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was post-BCG HG recurrence. Cox regression and Wilcoxon rank-sum, t, and Fisher's exact tests were used for analyses.RESULTS AND LIMITATIONS: BCG induced activation of the immune system regardless of clinical response; however, immunoinhibitory proteins were observed in the urine of patients with post-BCG HG recurrence (CD70, PD1, CD5). Post-BCG HG recurrence was associated with post-BCG T-cell exhaustion (p = 0.002). Pre-BCG tumors from patients with post-BCG T-cell exhaustion had high expression of genes related to cell division and immune function. A high predicted post-BCG exhaustion score for pre-BCG tumors was associated with worse post-BCG HG recurrence-free survival (HGRFS; p = 0.002). This was validated in independent cohorts. Pre-BCG class 2a and 2b tumors (UROMOL2021 scheme) were associated with worse post-BCG HGRFS (p = 0.015). Post-BCG exhaustion was observed in patients with high pre-BCG neoantigen load (p = 0.017) and MUC4 mutations (p = 0.002). Finally, the absence of post-BCG tdDNA clearance identified patients at high risk of recurrence (p = 0.018). The retrospective design and partial overlap for analyses are study limitations.CONCLUSIONS: Post-BCG HG recurrence may be caused by T-cell exhaustion. Tumor subtype and pre-BCG tumor characteristics may identify patients at high risk of post-BCG HG recurrence. Urinary measurements have potential for real-time assessment of treatment response.PATIENT SUMMARY: A dysfunctional immune response to bacillus Calmette-Guérin (BCG) therapy may explain high-grade recurrences of bladder cancer.

Background and Purpose: Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH. Methods: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of Results: Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38–4.04] and 2.32/1000 patient-years [95% CI, 1.61–3.03], respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01–6.31], P =0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00–5.62], P =0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH. Conclusions: Targeting an LDL cholesterol of Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.

Aim: To explore how empowerment in chronically-ill patients could contribute to their therapeutic regimen management style. To investigate relation between chronic illness impact, therapeutic regimen management style, and the chronic disease intrusiveness´s in a person's life. Methods: A survey of 271 patients with chronic conditions administered once time with three questionnaires. From this simple (271 patients with Chronic illness.) we did nine interviews with them. Results: Regarding the socio demographic variables, age and schooling level reached statistical significance concerning individual empowerment, formally guided, and abandoned scores of the therapeutic regimen management styles. Regarding the predictive model, four multivariable linear regression models were constructed with the overall empowerment level as a dependent variable. The theoretical explanation was identified: “Facilitating decision-making according to each mindset". Conclusion: This study confirms the association between individual empowerment, the therapeutic regimen management style and the interference of chronic disease.

L’horloge à pendule inventée par Christiaan Huygens émerge comme un instrument générique au xviie siècle. En suivant les propositions sociologiques de Terry Shinn, il est possible de caractériser l’horloge de Huygens par sa généricité, sa modularité et les fondements théoriques sur lesquels repose son fonctionnement. De même, Huygens investit un espace socio-épistémique interstitiel pour produire son instrument : au croisement de l’artisanat et des pratiques savantes. La capacité de l’horloge à pendule de circuler dans le régime disciplinaire (notamment en astronomie et dans les sciences nautiques), le régime utilitaire (par sa valeur commerciale) et le régime régulatoire (par le soutien politique que reçoit l’objet) caractérise bien un régime technico-instrumental susceptible d’intégrer un instrument générique à usages multiples. The pendulum clock invented by Christiaan Huygens emerged as a generic instrument in the 17th century. Following Terry Shinn’s sociological propositions, it is possible to characterise Huygens’ clock by its genericity, its modularity, and the theoretical foundations on which its operation is based. Similarly, Huygens invested an interstitial socio-epistemic space to produce his instrument: at the crossroads of craft and academic practices. The ability of the pendulum clock to circulate in the disciplinary regime (notably in astronomy and nautical sciences), the utilitarian regime (through its commercial value) and the regulatory regime (through the political support that the object received) characterises a technico-instrumental regime capable of integrating a generic instrument with multiple uses.

We establish small energy H\"{o}lder bounds for minimizers $u_\varepsilon$ of \[E_\varepsilon (u):=\int_\Omega W(\nabla u)+ \frac{1}{\varepsilon^2} \int_\Omega f(u),\] where $W$ is a positive definite quadratic form and the potential $f$ constrains $u$ to be close to a given manifold $\mathcal N$. This implies that, up to subsequence, $u_\varepsilon$ converges locally uniformly to an $\mathcal N$-valued $W$-harmonic map, away from its singular set. We treat general energies, covering in particular the 3D Landau-de Gennes model for liquid crystals, with three distinct elastic constants. Similar results are known in the isotropic case $W(\nabla u)=\vert \nabla u\vert^2$ and rely on three ingredients: a monotonicity formula for the scale-invariant energy on small balls, a uniform pointwise bound, and a Bochner equation for the energy density. In the level of generality we consider, all of these ingredients are absent. In particular, the lack of monotonicity formula is an important reason why optimal estimates on the singular set of $W$-harmonic maps constitute an open problem. Our novel argument relies on showing appropriate decay for the energy on small balls, separately at scales smaller and larger than $\varepsilon$: the former is obtained from the regularity of solutions to elliptic systems while the latter is inherited from the regularity of $W$-harmonic maps. This also allows us to handle physically relevant boundary conditions for which, even in the isotropic case, uniform convergence up to the boundary was open., Comment: The initial proof of the energy improvement lemma 2.2 contained a gap and has been corrected in this new version

Background: Autosomal dominant polycystic kidney disease is the most frequent hereditary kidney disease and is generally due to mutations in PKD1 and PKD2 , encoding polycystins 1 and 2. In autosomal dominant polycystic kidney disease, hypertension and cardiovascular disorders are highly prevalent, but their mechanisms are partially understood. Methods: Since endothelial cells express the polycystin complex, where it plays a central role in the mechanotransduction of blood flow, we generated a murine model with inducible deletion of Pkd1 in endothelial cells ( Cdh5-Cre ERT2 ; Pkd1 fl/fl ) to specifically determine the role of endothelial polycystin-1 in autosomal dominant polycystic kidney disease. Results: Endothelial deletion of Pkd1 induced endothelial dysfunction, as demonstrated by impaired flow-mediated dilatation of resistance arteries and impaired relaxation to acetylcholine, increased blood pressure and prevented the normal development of arteriovenous fistula. In experimental chronic kidney disease induced by subtotal nephrectomy, endothelial deletion of Pkd1 further aggravated endothelial dysfunction, vascular remodeling, and heart hypertrophy. Conclusions: Altogether, this study provides the first in vivo demonstration that specific deletion of Pkd1 in endothelial cells promotes endothelial dysfunction and hypertension, impairs arteriovenous fistula development, and potentiates the cardiovascular alterations associated with chronic kidney disease.