Search

The mission of WEST (tungsten-W Environment in Steady-state Tokamak) is to explore long pulse operation in a full tungsten (W) environment for preparing next-step fusion devices (ITER and DEMO) with a focus on testing the ITER actively cooled W divertor in tokamak conditions. Following the successful completion of phase 1 (2016-2021), phase 2 started in December 2022 with the lower divertor made entirely of actively cooled ITER-grade tungsten mono-blocks. A boronization prior the first plasma attempt allowed for a smooth startup with the new divertor. Despite the reduced operating window due to tungsten, rapid progress has been made in long pulse operation, resulting in discharges with a pulse length of 100 s and an injected energy of around 300 MJ per discharge. Plasma startup studies were carried out with equatorial boron nitride limiters to compare them with tungsten limiters, while Ion Cyclotron Resonance Heating assisted startup was attempted. High fluence operation in attached regime, which was the main thrust of the first campaigns, already showed the progressive build up of deposits and appearance of dust, impacting the plasma operation as the plasma fluence increased. In total, the cumulated injected energy during the first campaigns reached 43 GJ and the cumulated plasma time exceeded 5 h. Demonstration of controlled X-Point Radiator regime is also reported, opening a promising route for investigating plasma exhaust and plasma-wall interaction issues in more detached regime. This paper summarises the lessons learned from the manufacturing and the first operation of the ITER-grade divertor, describing the progress achieved in optimising operation in a full W environment with a focus on long pulse operation and plasma wall interaction.

Abstract Background In the Lao People's Democratic Republic (Lao PDR), cervical cancer is the third leading cause of women cancer. Aims The objective of this cross‐sectional study was to compare the efficacy of careHPV™ test versus conventional Pap smear or Siriraj liquid‐based cytology in the detection of cervical cancer in women living with human immunodeficiency virus type 1 (HIV‐1). Materials & Methods Overall, 631 women consented to participate. Four cervical specimens were taken for the purpose of conventional Pap smear, Siriraj liquid‐based cytology, careHPV™ test, and HPV‐16 genotyping. The exact McNemar test was used to compare the efficacy and diagnostic performance of the tests. Results Of the 631 women with follow‐up, 331 were human papillomavirus (HPV) negative. High‐grade squamous intraepithelial lesions were found in 37 women, biopsy‐proven high‐grade cervical intraepithelial neoplasia in 50 women, and invasive carcinoma in seven women. The proportion of women with high‐grade cervical lesion or carcinoma detected after abnormal careHPV™ test was higher (6.02%; 95% confidence interval [CI]: 4.4–8.1) than that detected by conventional Pap smear (4.59%; 95% CI: 3.2–6.5). careHPV™ and HPV‐16 genotyping had, respectively, the highest sensitivity (80.8%; 95% CI: 67.4–89.5) and specificity (92.2%; 95% CI: 89.8–94.2). HPV‐16 was the most frequently detected genotype. Conclusions careHPV™ test represents a screening option in Lao PDR, particularly in women living with HIV‐1 because of higher prevalence of chronic HPV in this population.

Abstract Background One out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response. Methods In a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active (n = 72) or sham (n = 72) hf-tRNS. hf-tRNS (100–500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients’ symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3- and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcomes will include brain activity and connectivity, source monitoring performances, social cognition, other clinical (including auditory hallucinations) and biological variables, and attitude toward treatment. Discussion The results of this trial will constitute a first step toward establishing the usefulness of hf-tRNS in schizophrenia whatever the stage of the illness and the level of treatment resistance. We hypothesize a long-lasting effect of active hf-tRNS on the severity of schizophrenia symptoms as compared to sham. This trial will also have implications for the use of hf-tRNS as a preventive intervention of relapse in patients with schizophrenia. Trial registration ClinicalTrials.gov NCT02744989. Prospectively registered on 20 April 2016

Abstract Background Human cardiac stem cells expressing the W8B2 marker (W8B2+ CSCs) were recently identified and proposed as a new model of multipotent CSCs capable of differentiating into smooth muscle cells, endothelial cells and immature myocytes. Nevertheless, no characterization of ion channel or calcium activity during the differentiation of these stem cells has been reported. Methods The objectives of this study were thus to analyze (using the TaqMan Low-Density Array technique) the gene profile of W8B2+ CSCs pertaining to the regulation of ion channels, transporters and other players involved in the calcium homeostasis of these cells. We also analyzed spontaneous calcium activity (via the GCaMP calcium probe) during the in vitro differentiation of W8B2+ CSCs into cardiac myocytes. Results Our results show an entirely different electrophysiological genomic profile between W8B2+ CSCs before and after differentiation. Some specific nodal genes, such as Tbx3, HCN, ICaT, L, KV, and NCX, are overexpressed after this differentiation. In addition, we reveal spontaneous calcium activity or a calcium clock whose kinetics change during the differentiation process. A pharmacological study carried out on differentiated W8B2+ CSCs showed that the NCX exchanger and IP3 stores play a fundamental role in the generation of these calcium oscillations. Conclusions Taken together, the present results provide important information on ion channel expression and intrinsic calcium dynamics during the differentiation process of stem cells expressing the W8B2 marker.

Introduction The prognosis of first episode psychosis (FEP), which is a severe disorder, can be notably impaired by patients’ disengagement from healthcare providers. Coordinated specialty care with case management is now considered as the gold standard in this population, but there are still challenges for engagement with subsequent functional impairments. Youth-friendly and patient-centred clinical approaches are sought to improve engagement in patients with FEP. Mobile applications are widely used by young people, including patients with FEP, and can increase the youth friendliness of clinical tools. We hypothesise that a co-designed mobile application used during case management can improve functioning in patients with FEP as compared with usual case management practices.Methods and analysis A mobile case management application for planning and monitoring individualised care objectives will be co-designed with patients, caregivers and health professionals in a recovery-oriented approach. The application will be compared with usual case management practices in a multicentre, two-arm and parallel groups clinical trial. Patients will be recruited by specialised FEP teams. Impact on functioning will be assessed using the Personal and Social Performance Scale; the variation between baseline and 12 months in each group (control and active) will be the primary outcome.Ethics and dissemination This study has been approved by the Inserm Institutional Review Board IRB00003888 (Comité d’évaluation éthique de l’INSERM, reference number 20-647). The results of the study will be published in a peer-reviewed journal and presented at national and international conferences. We will also communicate the results to patients and family representatives’ associations. An optimised version of the application will be then disseminated through the French FEP network (Transition Network).Trial registration number ClinicalTrials.gov: NCT04657380

Abstract Background Traumatic exposure is a frequent issue in patients visiting emergency departments (EDs). Some patients will subsequently develop post-traumatic stress disorder (PTSD) while other will not. The problem is under-diagnosed in EDs and no standardized management is provided to prevent PTSD. Most studies focused on a particular group of trauma whereas we need a global approach to further develop interventions for detecting and treating patients at high risk. We aim to assess the prevalence of traumatic exposure and situation at high risk of further PTSD and identify pre and peri-traumatic biopsychosocial factors predisposing individuals to PTSD in the general context of EDs. Methods This comprehensive multicenter study will have two steps. The first step will be a cross-sectional study on moderate and high risk of PTSD prevalence among EDs visitors with a recent history of trauma. All patients aged 18–70 years, presenting with a recent history of trauma (

This paper analyses the Cologne attacks through identity discourses: a reaction from M. Le Pen, the extreme right-wing candidate; a speech of the member of Parliament V. Boyer and member of the right-wing party Les Républicains; two scholars who react on the media (A. Finkielkraut and D. Stoecklin); and one journalist (E. Levy), editing manager of the French on line journal Causeur. It isolates three means to interpret the event (serial data processing, predictive data processing, sequential data processing) through three linguistic phenomena: the Place Tahrir precedent, ab auctoritate quotation and phrases. These interpretations linked with political and competition issues also reveal the fictions about the migrants, the otherness and the self.

IntroductionSenticol 2 is a randomized multicenter trial in the treatment of early-stage cervical cancer patients. The aim of the Senticol 2 study was to compare the effect of sentinel-lymph-node biopsy (SLNB) to that of SLNB + pelvic lymphadenectomy (PLND), and to determine the postoperative lymphatic morbidity in the two groups. Here, we report a secondary objective of this study: the follow up.Material and MethodsIn the Senticol 2 trial, patients underwent a laparoscopy with a sentinel-node-detection procedure and were randomized into two groups, namely: Group A, in which participants received SLNB, and Group B, in which participants received SLNB + PLND. Patients with an intra-operative macroscopically suspicious lymph node, were given a frozen-section evaluation and were randomized only if the results were negative. All of the patients received follow up with a clinical examination at 1, 3, and 6 months after surgery, and then every 3–4 months after that. The median follow up was 51 months (4 years and 3 months).ResultsDisease-free survival after 4 years for the SLNB group and the SLNB + PLND group were 89.51% and 93.1% (p = 0.53), respectively. The only statistical factor associated with recurrence in the univariate analysis was the adjuvant radiotherapy. No other factors, including the age of the patients, histological type, tumor size, lymph vascular space invasion (LVSI), and positive nodal status, were significant in the univariate or multivariate analyses. The overall survival rates after 4 years in the SLNB and SLNB + PLND groups were 95.2% and 96% (p = 0.97), with five and four deaths, respectively. The univariate and multivariate analyses did not find any prognostic factors.ConclusionsThis randomized study confirmed the results of the Senticol 1 study and supports the sentinel lymph node (SLN) technique as a safe technique for use in patients with early-stage cervical cancer treated with SLNB only. Disease-free survival after 4 years was similar in patients treated with SLN biopsy and patients who underwent a lymphadenectomy.

Objective: In this subanalysis of the prospective randomized multicenter SENTICOL 2 study, we compared the quality of life (QoL), in two arms, in association with lower-limb consequences in women with early stage cervical cancer undergoing randomized sentinel lymph node (SLN) sampling alone or SLN sampling and full pelvic lymphadenectomy.Methods: 206 patients with an early stage cervical cancer and a negative SLN, were randomized. Every patient had a SLN detection based on a combination of radio-isotope (Nanocis®) and blue dye (Bleu Patenté®) injections. One hundred and One patients, the “standard” group, had complete pelvic lymphadenectomy, 105 patients, the “SLN alone” group, had SLN biopsy without lymphadenectomy. At each visit (V0: preoperative, V1: 1 month, V2: 3 months and V3: 6 months following surgery) the patients completed a Short Form Health Survey (SF36) questionnaire and another questionnaire related to leg lymphedema. SF36 scores variations (compared to the baseline values) were assessed with a standard analysis and by an evaluation of the area under the curve (AUC). Several lower-limb circumferences and signs were also determined.Results: General characteristics of the patients were well–balanced between groups. Physical function and general health dimensions of the SF36 scale were significantly improved at V1 and V2 in the “SLN alone” group. Mental health was also statistically better in the “SLN alone” group at V2. Other dimensions were similar. The two groups had similar evaluation at V3. AUC of SF36 sub-scores was also in favor of the “SLN alone” arm, but the difference was not statistically significant. The analysis about the lymphedema of the legs showed a reduced (but not significant) risk in the “SLN alone” group for the top-of-thigh and the mid-thigh perimeters. Lymphedema symptoms reported by the patients were significantly less severe in the “SLN alone” group.Conclusion: Our study demonstrates a trend for a better quality of life and less severe leg heaviness and leg fatigue when a full pelvic lymphadenectomy is avoided.

Understanding the behavior of a single particle flowing in a microchannel is a necessary step in designing and optimizing efficient microfluidic devices for the separation, concentration, counting, detecting, sorting, or mixing of particles in suspension. Although the inertial migration of spherical particles has been deeply investigated in the last two decades, most of the targeted applications involve shaped particles whose behavior in microflows is still far from being completely understood. While traveling in a channel, a particle both rotates and translates: it translates in the streamwise direction driven by the fluid flow but also in the cross-section perpendicular to the streamwise direction due to inertial effects. In addition, particles’ rotation and translation motions are coupled. Most of the existing works investigating the transport of particles in microchannels decouple their rotational and lateral migration behaviors: particle rotation is mainly studied in simple shear flows, whereas lateral migration is neglected, and studies on lateral migration mostly focus on spherical particles whose rotational behavior is simple. The aim of this review is to provide a summary of the different works existing in the literature on the inertial migration and the rotational behavior of non-spherical particles with a focus and discussion on the remaining scientific challenges in this field.

The inertial migration of particles in microchannel flows has been deeply investigated in the last two decades. In spite of numerous reports on the inertial focusing patterns in a square channel, the particle inertial focusing and longitudinal ordering processes remain unclear at high Reynolds numbers (>200) in square microchannels smaller than 100 µm in width. Thus, in this work, in situ visualization of particles flowing in square micro-channels at Reynolds numbers Re ranging from 5 to 280 has been conducted and their migration behaviors have been analyzed. The obtained results confirm that new equilibrium positions appear above a critical Re depending on the particle to channel size ratio and the particle volume fraction. It is also shown that, for a given channel length, an optimal Reynolds number can be identified, for which the ratio of particles located on equilibrium positions is maximal. Moreover, the longitudinal ordering process, i.e., the formation of trains of particles on equilibrium positions and the characterization of their length, has also been analyzed for the different flow conditions investigated in this study.

Anomalies in constitutive calcium entry (CCE) have been commonly attributed to cell dysfunction in pathological conditions such as cancer. Calcium influxes of this type rely on channels, such as transient receptor potential (TRP) channels, to be constitutively opened and strongly depend on membrane potential and a calcium driving force. We developed an optogenetic approach based on the expression of the halorhodopsin chloride pump to study CCE in non-excitable cells. Using C2C12 cells, we found that halorhodopsin can be used to achieve a finely tuned control of membrane polarization. Escalating the membrane polarization by incremental changes in light led to a concomitant increase in CCE through transient receptor potential vanilloid 2 (TRPV2) channels. Moreover, light-induced calcium entry through TRPV2 channels promoted cell migration. Our study shows for the first time that by modulating CCE and related physiological responses, such as cell motility, halorhodopsin serves as a potentially powerful tool that could open new avenues for the study of CCE and associated cellular behaviors.

El Estado colombiano, en su afán por terminar el conflicto armado interno, decide negociar e implementar procesos de justicia transicional, donde la reparación integral a las víctimas es uno de sus grandes propósitos. Las medidas para dicha reparación están formuladas de manera general, por ello se establece que la interpretación y aplicación para las comunidades étnicas debe tener en cuenta la diversidad cultural y las cosmovisiones de las diferentes poblaciones que la habitan. Para el desarrollo de este artículo, se realiza una entrevista a Ati Quigua, miembro de la comunidad indígena Ikü y Comisionada indígena para la paz, e, igualmente, a Ati Gúndiwa, perteneciente a la misma comunidad. Gracias a estas entrevistas, se encuentra que, a lo largo de la historia y por los diferentes conflictos por los que ha pasado Colombia, esta comunidad se ha visto afectada por desplazamientos, daños en su territorio ancestral y proceso de aculturación. Con base en los datos suministrados se relata la manera en que deben ser reparadas las afectaciones de la comunidad, basándose en su pensamiento ancestral.

Splenic diffuse red pulp lymphoma is an indolent small B-cell lymphoma recognized as a provisional entity in the World Health Organization 2008 classification. Its precise relationship to other related splenic B-cell lymphomas with frequent leukemic involvement or other lymphoproliferative disorders remains undetermined. We performed whole-exome sequencing to explore the genetic landscape of ten cases of splenic diffuse red pulp lymphoma using paired tumor and normal samples. A selection of 109 somatic mutations was then evaluated in a cohort including 42 samples of splenic diffuse red pulp lymphoma and compared to those identified in 46 samples of splenic marginal zone lymphoma and eight samples of hairy-cell leukemia. Recurrent mutations or losses in BCOR (the gene encoding the BCL6 corepressor) – frameshift (n=3), nonsense (n=2), splicing site (n=1), and copy number loss (n=4) – were identified in 10/42 samples of splenic diffuse red pulp lymphoma (24%), whereas only one frameshift mutation was identified in 46 cases of splenic marginal zone lymphoma (2%). Inversely, KLF2, TNFAIP3 and MYD88, common mutations in splenic marginal zone lymphoma, were rare (one KLF2 mutant in 42 samples; 2%) or absent (TNFAIP3 and MYD88) in splenic diffuse red pulp lymphoma. These findings define an original genetic profile of splenic diffuse red pulp lymphoma and suggest that the mechanisms of pathogenesis of this lymphoma are distinct from those of splenic marginal zone lymphoma and hairy-cell leukemia.

Recent studies demonstrate that early molecular response to tyrosine-kinase inhibitors is strongly predictive of outcome in chronic myeloid leukemia patients and that early response landmarks may identify patients at higher risk for transformation who would benefit from an early switch to second-line therapy. In this study, we evaluated the ability of the control gene GUS to identify relevant thresholds for known therapeutic decision levels (BCR-ABL1/ABL1IS = 10% and 0.1%). We then defined the most relevant cut-offs for early molecular response markers (transcript level at 3 months, halving time and log reduction between diagnosis and 3 months of treatment) using GUS or ABL1. We demonstrated that, although both control genes could be used (in an equivalent way) to accurately assess early molecular response, the BCR-ABL1/GUS level at diagnosis is impacted by the higher GUS copy number over-expressed in CML cells, thus negatively impacting its ability to completely replace ABL1 at diagnosis. Furthermore, we pointed out, for the first time, that it would be helpful to monitor BCR-ABL1 levels at an earlier time point than that currently performed, in order to assess response to first-line tyrosine-kinase inhibitors and consider a potential switch of therapy as early as possible. We evaluated this optimal time point as being 19 days after the start of treatment in our cohort.

It has been recently shown that DNA methyl transferase overexpression is correlated with unfavourable prognosis in human malignancies while methylation deregulation remains a hallmark that defines acute myeloid leukemia (AML). The oncogenic transcription factor EVI1 is involved in methylation deregulation and its overexpression plays a major role for predicting an adverse outcome. Moreover, the identification of DNMT3A mutations in AML patients has recently been described as a poor prognostic indicator. In order to clarify relationship between these key actors in methylation mechanisms and their potential impact on patient outcomes, we analysed 195 de novo AML patients for the expression of DNMT3A, 3B (and its non-catalytic variant 3B(NC)) and their correlations with the outcome and the expression of other common prognostic genetic biomarkers (EVI1, NPM1, FLT3ITD/TKD and MLL) in adult AML. The overexpression of DNMT3B/3B(NC) is (i) significantly correlated with a shorter overall survival, and (ii) inversely significantly correlated with event-free survival and DNMT3A expression level. Moreover, multivariate analysis showed that a high expression level of DNMT3B/3B(NC) is statistically a significant independent poor prognostic indicator. This study represents the first report showing that the overexpression of DNMT3B/3B(NC) is an independent predictor of poor survival in AML. Its quantification should be implemented to the genetic profile used to stratify patients for therapeutical strategies and should be useful to identify patients who may benefit from therapy based on demethylating agents.

Dans la vision cosmogonique de certaines communautés indiennes colombiennes, le monde est peuplé d’une symbolique féminine qui rappelle un univers protecteur, fécond, chaleureux et pur, où ce qui règne dans l’esprit humain est un sentiment de confiance et de continuité. Leur imaginaire magico-religieux contient des symboles qui font croire en un monde dans lequel les règles sont dictées par des dieux de la nature. Ces images veulent nous montrer une autre perception du monde, une autre manière d’observer la nature et le cosmos, elles nous font découvrir le besoin qu’a l’homme de retrouver l’harmonie et l’équilibre spirituel. Autrement dit, ces images sont le témoignage du besoin qu’a l’homme de retrouver son essence première et le bien-être qu’il expérimente dans le ventre de sa mère.