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Abstract Introduction The COVID-19 pandemic generated overflow of healthcare systems in several countries. As the ethical debates focused on prioritisation for access to care with scarce medical resources, numerous recommendations were created. Late 2021, the emergence of the Omicron variant whose transmissibility was identified but whose vaccine sensitivity was still unknown, reactivated debates. Fears of the need to prioritise patients arose, particularly in France. Especially, a debate began about the role of vaccination status in the prioritisation strategy. Material and methods The Ethics Committee (EC) of the University Hospital of Bordeaux (UHB), France, identified prioritisation criteria in the literature (some recommended, such as being a healthcare worker (HCW) or having consented to research, while others were discouraged, such as age with a threshold effect or vaccination status). A survey was sent within the institution in January 2022 to explore frontline physicians' adherence to these prioritisation criteria. The decision making conditions were also surveyed. Results In 15 days, 78/165 (47.3%) frontline physicians responded, and more widely 1286/12946 (9.9%) professionals. A majority of frontline physicians were opposed to prioritising HCWs (54/75, 72%) and even more opposed to participating in research (69/76, 89.6%). Conversely, the results were very balanced for non-recommended criteria (respectively 39/77, 50.7% and 34/69 49.3% in favour for age with a threshold effect and for vaccination status). Decisions were considered to be multi-professional and multi-disciplinary for 65/76, 85.5% and 53/77, 68.8% of frontline physicians. Responders expressed opposition to extending decision-making to representatives of patients, civil society or HCWs not involved in care. Discussion Prioritisation recommendations in case of scarce medical resources were not necessarily approved by the frontline physicians, or by the other HCWs. This questions the way ethical recommendations should be communicated and discussed at a local scale, but it also questions these recommendations themselves. The article also reports the experience of seeking HCWs opinions on a sensitive ethical debate in a period of crisis.

Abstract To describe clinical outcomes of patients aged 75 years and above after partial nephrectomy (PN), and to assess independent factors of postoperative complications. We retrospectively reviewed information from our multi-institutional database. Every patient over 75 years old who underwent a PN between 2003 and 2016 was included. Peri-operative and follow up data were collected. Multivariate logistic regression was performed to determine independent predictive factors of postoperative complications. We reviewed 191 procedures including 69 (40%) open-surgery, and 122 (60%) laparoscopic procedures, of which 105 were robot-assisted. Median follow-up was 25 months. The mean age was 78 [75–88]. The American Society of Anesthesiologist’s score was 1, 2, 3 and 4 in 10.5%, 60%, 29% and 0.5% of patients respectively. The mean tumor size was 4.6 cm. Indication of PN was elective in 122 (65%) patients and imperative in 52 patients (28%). The median length of surgery was 150(± 60) minutes, and the median estimated blood loss 200 ml. The mean glomerular filtration rate was 71.5 ml/minute preoperatively, and 62 ml/min three months after surgery. The severe complications (Clavien III-V) rate was 6.2%. On multivariate analysis, the robotic-assisted procedure was an independent protective factor of medical postoperative complications (Odds Ration (OR) = 0.31 [0.12–0.80], p = 0.01). It was adjusted for age and RENAL score, robotic-assisted surgery (OR = 0.22 [0.06–0.79], p = 0.02), and tumor size (OR = 1.13 [1.02–1.26], p = 0.01), but the patients age did not forecast surgical complications. Partial nephrectomy can be performed safely in elderly patients with an acceptable morbidity, and should be considered as a viable treatment option. Robotic assistance is an independent protective factor of postoperative complications.

Background and objectives Violence against women (VAW) is widespread and can have serious physical and mental health consequences, including post-traumatic stress disorder (PTSD) and sleep disorders. Victim-survivors often face barriers in accessing specialised care, highlighting the need for a multidisciplinary response, especially in healthcare settings. The Maison des Femmes (MdF) model provides holistic support to women experiencing VAW, including medical, psychological, social and legal support. The aim of this study is to examine whether the MdF’s comprehensive intervention programme offers advantages over standard care in improving mental health indicators, such as PTSD.Method and analysis Our pragmatic quasi-experimental study uses a non-randomised controlled cluster design. The intervention group comprises women enrolled in MdFs in five French cities, while the comparison group includes women receiving usual care in sociomedical structures located geographically close to MdF centres. Our study aims to recruit 360 women (180 per group), aged 18 years or older, who have experienced intimate partner violence or sexual violence and who seek care at the study centres. The primary analysis will compare the change in PTSD Checklist for DSM-5 (PCL-5) scores over 6 months in the two groups using multivariable linear regression with propensity score adjustment. Secondary outcomes include sleep disorders, quality of life, symptoms of anxiety and depression, self-esteem, sense of safety and well-being, initiation of legal and socioprofessional proceedings, and healthcare utilisation.Ethics and dissemination The study was approved by the ‘Comité de protection des personnes Ile de France III’ (CPP Committee for the Protection of Persons Ile de France III; institutional review board on 20 December 2023; Ref no. (Numéro SI): 23.04197.000491).The results of the study will be communicated via academic publications; easily understandable briefs for a broader public; and proactive involvement with medical institutions, journalists and advocacy groups.Trial registration number NCT06226818. Version Number 1- february2024.

Most of the existing water quality models for water distribution networks assume complete mixing at junctions. Albeit few models offer the possibility to consider incomplete mixing (IM) at junctions, most of them were developed under laboratory conditions and for equal pipe size junctions. In real-world distribution networks, however, cross junctions of 150 × 100 × 150 × 100 mm or 100 × 150 × 150 × 150 mm are common, yet no model has been developed for these configurations. This paper presents a new equation to compute concentrations in cross junction outlets while considering IM for six cross junction configurations, including unequal pipe sizes and 150 mm pipes. For each cross junction configuration, mixing was studied under 25 flow scenarios in the laboratory and 40 simulated flow scenarios using OpenFOAM software. Two new flow rate ratios were selected as independent variables to compute different outlet concentrations. For two specific cross junctions with equal pipe sizes, the root-mean-squared error between the observed and simulated concentrations of the newly developed model was 0.02, while it was 0.05 and 0.07, respectively, for the AZRED IM model and the Shao et al. IM model. HIGHLIGHTS Laboratory experiments were conducted under real-world conditions with 150 mm pipes.; New principal combinations of independent variables for mixing were identified.; A single equation was developed for mixing in different cross junction configurations.; The developed model reproduces observations more accurately than the other models.;

Summary: Changes in lymphocyte production patterns occurring across human ontogeny remain poorly defined. In this study, we demonstrate that human lymphopoiesis is supported by three waves of embryonic, fetal, and postnatal multi-lymphoid progenitors (MLPs) differing in CD7 and CD10 expression and their output of CD127−/+ early lymphoid progenitors (ELPs). In addition, our results reveal that, like the fetal-to-adult switch in erythropoiesis, transition to postnatal life coincides with a shift from multilineage to B lineage-biased lymphopoiesis and an increase in production of CD127+ ELPs, which persists until puberty. A further developmental transition is observed in elderly individuals whereby B cell differentiation bypasses the CD127+ compartment and branches directly from CD10+ MLPs. Functional analyses indicate that these changes are determined at the level of hematopoietic stem cells. These findings provide insights for understanding identity and function of human MLPs and the establishment and maintenance of adaptative immunity.

IntroductionCOVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients.MethodsThis study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic.ResultsThe median age was 50.3 years (min – max; 1.0 – 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min – max; 0.0 – 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 – 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p

The performance of stormwater treatment trains and of their individual green infrastructures was evaluated near Montreal, Canada. Three treatment trains were studied: Train 1 – five bioretention cells in series with a wet retention pond; Train 2 – an infiltration trench in series with a dry detention pond; and Train 3 – Train 2 in series with a wet retention pond. A total of 47 rain events were monitored to quantity the hydrological performance, while water quality samples were taken during 24 rainfall events. During the summer, the bioretention cells led to a reduction in runoff volumes varying from 8 to 100%. Overall, the three studied treatment trains and all of the individual infrastructures, except for the dry pond, provided reductions in the mean concentrations of total suspended solids, chemical oxygen demand, total nitrogen and total phosphorous. Results also showed that the use of a train of stormwater infrastructures can be more effective to reach Quebec's legislated targets than single infrastructures, but only if the infrastructures are sequenced properly. Indeed, the addition of a dry basin at the end of Train 2 affected negatively the removal efficiency of the four studied contaminants. HIGHLIGHTS Hydrological and water quality performance of single and in-series (train) stormwater control infrastructures was assessed.; The use of a train can be more effective for removing contaminants if sequenced properly.; Adding a dry basin at the end of a train affected negatively the removal efficiency of the four studied contaminants.; The mean removal efficiency of total suspended solids was positive during the winter months.;

The application of artificial neural network (ANN) models for short-term (15 min) urban water demand predictions is evaluated. Optimization of the ANN model's hyperparameters with a genetic algorithm (GA) and use of a growing window approach for training the model are also evaluated. The results are compared to those of commonly used time series models, namely the Autoregressive Integrated Moving Average (ARIMA) model and a pattern-based model. The evaluations are based on data sets from two Canadian cities, providing 15 min water consumption records over respectively 5 years and 23 months, with a respective mean water demand of 14,560 and 887 m3/d. The GA optimized ANN model performed better than the other models, with Nash–Sutcliffe Efficiencies of 0.91 and 0.83, and relative root mean square errors of 6 and 16% for City 1 and City 2, respectively. The results of this study indicate that the optimization of the hyperparameters of an ANN model can lead to better 15 min urban water demand predictions, which are useful for many real-time control applications, such as dynamic pressure control. HIGHLIGHTS ANN models were used for short-term (15 min) urban water demand predictions.; The hyperparameters of the ANN model were optimized with a genetic algorithm for better model performance.; The results of the ANN approach were compared to an ARIMA and a pattern-based models for two different datasets.; The performance results proved GA optimized ANN model as an efficient approach for short-term UWD predictions.;

The combination of chemotherapy and broad-spectrum antibiotics induces gut microbiota (GM) dysbiosis in acute myeloid leukaemia (AML) leading to additional complications. Here, the authors report the efficacy in GM restoration and safety of autologous faecal microbiota transfer in treated AML patients in a phase II clinical trial.

Class I Human Leukocyte Antigen (HLA) evolutionary divergence (HED) is a metric which reflects immunopeptidome diversity and has been associated with immune checkpoint inhibitor responses in solid tumors. Its impact and interest in allogeneic hematopoietic stem cell transplantation (HCT) have not yet been thoroughly studied. This study analyzed the clinical and immune impact of class I and II HED in 492 acute myeloid leukemia (AML) recipients undergoing HCT. The overall cohort was divided into a training (n=338) and a testing (n=132) set. Univariate cox screening found a positive impact of a high class I HED and a negative impact of a high class II HED on both disease-free (DFS) and overall survival (OS). These results were combined in a unique marker, class I/class II HED ratio, and assessed in the testing cohort. The final multivariate cox model confirmed the positive impact of a high versus low class I/class II HED ratio on both DFS (Hazard Ratio (HR) 0.41 [95% CI 0.2-0.83]; p=0.01) and OS (HR 0.34 [0.19-0.59]; p

Funding agencies and journal editors strongly incite researchers to share and archive their data, when they don’t compel them to do so. However, the ways we archive data have a strong influence on their potential for reuse. The activity of banking data in centralised archives, with all the normalisation processes it involves, spoils them and renders impossible the profound engagement with the original research required by a fruitful reanalysis. We need to think collectively and design other archiving structures, more respectful of the research process.

One-hundred and four adults with newly diagnosed or relapsed/refractory acute myeloid leukemia (AML) were treated with fractionated doses of gemtuzumab ozogamicin (GO) at one-single French center over a 10-year period. We attempted to define predictive factors for response and survival. The overall response rate was 70% (86% in newly diagnosed and 67% in relapsed/refractory AML). Disease-free survival (DFS) and overall survival at 3 years after GO treatment was 31% and 29%, respectively. Mortality during induction was 7%. Among remitters, allogeneic hematopoietic stem cell transplantation can be performed in 33 cases (45%). DFS at 3 years was 54%. Incidences of transplant-related mortality, grade ≥ 3 acute graft-versus-host (GvH) disease, and extensive chronic GvH disease were 15%, 12%, and 27%, respectively.No sinusoidal obstruction syndromes were reported among allografted patients as among the other patients in the studied cohort. GO-based chemotherapy is a viable option for treatment of newly diagnosed and relapsed/refractory AML patients, and is a feasible schedule as a bridge to allogeneic transplant.

Torque teno virus (TTV) has been proposed as a surrogate biomarker of T-cell function in allogeneic–haematopoietic–stem-cell transplantation (allo-HSCT). Conflicting data exists regarding the value of TTV to assess the degree of immunosuppression. The aim of the present study was to investigate the correlation between TTV viral load and immune function. Using samples from a prospective cohort composed of healthy-volunteers (HV) and allo-HSCT recipients at 6 months post-transplantation, we assessed the correlation between TTV viraemia and immune cell counts or T-cell proliferation capacity post-phytohaemagglutinin stimulation. TTV viraemia was detected in 68% of HV (n = 80) and 100% of allo-HSCT recipients (n = 41; p < 0.001); it was significantly higher in allo-HSCT recipients (3.9 vs. 2.1 Log copies/mL, p < 0.001). There was no correlation between T-cell function and CD3+T-cell count (rho: 0.002) suggesting that T-cell count can normalise without full functional recovery. Furthermore, no significant correlation was observed between TTV viraemia and absolute total/subset lymphocyte counts (rho:

The strong temporal backscatter signature of rice growing above the water's surface allows for the use of synthetic aperture radar (SAR) for paddy rice crop mapping in Southern Vietnam (Mekong Delta). In Northern Vietnam (Red River Delta), rice mapping using SAR is a challenge and is rarely performed because of the complex land-use/land-cover. Nevertheless, information about rice fields is needed for hydrological simulations in river basins such as the Cau River basin. The objective of this research is to investigate the potential of RADARSAT-2 band- C in identifying rice fields over a large and fragmented land-use area. Two methods are proposed, one for each data type, adapted to the land-use/land-cover of the study area. The thresholding technique, with a statistical analysis of the temporal variation of rice backscattering, was applied to the HH like-polarized ratio of dual-pol data. The support vector machine (SVM) algorithm was applied to the full quad-pol and a single HH-polarization calculated from polarimetric data. This study demonstrates that RADARSAT-2 dual- and quad-pol data can be successfully used to identify cultivated rice fields. However, the dual-pol data seems less efficient than the quad-pol data and the SVM classification is more flexible than the thresholding technique. Between the full quad-pol and a single polarization, the overall classification accuracy shows that the results derived from the single HH polarization are 3 to 10% less accurate than those derived from the classification of full quad-pol data. The results show the usefulness of polarimetric C-band data for the identification of rice fields in Northern Vietnam.

Among immunoglobulins (Igs), IgE can powerfully contribute to antimicrobial immunity and severe allergy despite its low abundance. IgE protein and gene structure resemble other Ig classes, making it unclear what constrains its production to thousand-fold lower levels. Whether class-switched B cell receptors (BCRs) differentially control B cell fate is debated, and study of the membrane (m)IgE class is hampered by its elusive in vivo expression. Here, we demonstrate a self-controlled mIgE+ B cell stage. Primary or transfected mIgE+ cells relocate the BCRs into spontaneously internalized lipid rafts, lose mobility to chemokines, and change morphology. We suggest that combined proapoptotic mechanisms possibly involving Hax1 prevent mIgE+ memory lymphocyte accumulation. By uncoupling in vivo IgE switching from cytokine and antigen stimuli, we show that these features are independent from B cell stimulation and instead result from mIgE expression per se. Consequently, few cells survive IgE class switching, which might ensure minimal long-term IgE memory upon differentiation into plasma cells.

Although numerous factors have been found to modulate hTERT transcription, the mechanism of its repression in certain leukemias remains unknown. We show here that DEK represses hTERT transcription through its enrichment on the hTERT promoter in cells from chronic and acute myeloid leukemias, chronic lymphocytic leukemia, but not acute lymphocytic leukemias where hTERT is overexpressed. We isolated DEK from the hTERT promoter incubated with nuclear extracts derived from fresh acute myelogenous leukemia (AML) cells and from cells expressing Tax, an hTERT repressor encoded by the human T cell leukemia virus type 1. In addition to the recruitment of DEK, the displacement of two potent known hTERT transactivators from the hTERT promoter characterized both AML cells and Tax-expressing cells. Reporter and chromatin immunoprecipitation assays permitted to map the region that supports the repressive effect of DEK on hTERT transcription, which was proportionate to the level of DEK-promoter association but not with the level of DEK expression. Besides hTERT repression, this context of chromatin redistribution of DEK was found to govern about 40% of overall transcriptional modifications, including those of cancer-prone genes. In conclusion, DEK emerges as an hTERT repressor shared by various leukemia subtypes and seems involved in the deregulation of numerous genes associated with leukemogenesis.

Objectives: Low-dose cytarabine (LD-AraC) is still regarded as the standard of care in elderly patients with acute myeloid leukemia (AML) ‘unfit’ for intensive chemotherapy. In this study, we compared the efficacy of LD-AraC, in patients ≥ 70 years old, with that of intensive chemotherapy, best supportive care (BSC), or hypomethylating agents in a single institution experience. Methods: Between 2000 and 2014, 60 patients received LD-AraC at 20 mg once or twice daily by subcutaneous injection for 10 consecutive days every 4-6 weeks. 85 patients were treated by intensive chemotherapy, 34 patients by hypomethylating agents, and 43 patients only by BSC. Results: Complete remission rate with LD-AraC was 7% versus 56% with intensive chemotherapy and 21% with hypomethylating agents. Median overall survival (OS) of patients treated with LD-AraC was 9.6 months with 3-year OS of 12%. Survival with LD-AraC was better than with BSC only (P = 0.001). Although not statistically significant, intensive chemotherapy and hypomethylating agents tended to be better than LD-AraC in terms of OS (median: 12.4 months and 16.1 months, respectively). There was no clear evidence that a beneficial effect of LD-AraC was restricted to any particular subtype of patients, except for cytogenetics. Conclusions: Despite a trend in favor of intensive chemotherapy and hypomethylating agents over LD-AraC, no real significant advantage could be demonstrated, while LD-AraC showed a significant advantage comparatively to BSC. This tends to confirm that LD-AraC can still represent a baseline against which new promising agents may be compared either alone or in combination.