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Abstract Islet transplantation is a unique paradigm in organ transplantation, since multiple donors are required to achieve complete insulin-independence. Preformed or de novo Donor Specific Antibodies (DSA) may target one or several donor islets, which adds complexity to the analysis of their impact. Adult patients with type 1 diabetes transplanted with pancreatic islets between 2005 and 2018 were included in a single-center observational study. Thirty-two recipients with available sera tested by solid-phase assays for anti-HLA antibodies during their whole follow-up were analyzed. Twenty-five recipients were islet-transplantation-alone recipients, and 7 islet-after-kidney recipients. Seven recipients presented with DSA at any time during follow-up (two with preformed DSA only, one with preformed and de novo DSA, 4 with de novo DSA only). Only islet-transplantation-alone recipients presented with de novo DSA. Three clinical trajectories were identified according to: 1/the presence of preformed DSA, 2/early de novo DSA or 3/late de novo DSA. Only late de novo DSA were associated with unfavorable outcomes, depicted by a decrease of the β-score. Islet transplantation with preformed DSA, even with high MFI values, is associated with favorable outcomes in our experience. On the contrary, de novo DSA, and especially late de novo DSA, may be associated with allograft loss.

Background: Advances in smart technology have expanded into the field of orthopedic surgery to deliver enhanced patient care. Smart technology has also raised important issues regarding protected patient information. The purpose of this study is to determine patient preferences regarding smart technology in their postarthroplasty care. Methods: Patient surveys were administered in the office setting of 2 adult reconstructive orthopedic surgeons during a 4-week period. Surveys queried patient demographics, twelve yes/no questions, five continuous agree/disagree statements, and a single free-text question. Logistic regression and statistical significance testing were performed. Results: Of the study patients, 83.6% were willing to wear a device. Women were more likely to consent to a monitoring device and have activity data collected than men (P < .05). Younger patients were more likely to consent to a device and have data collected than octogenarians. Nearly 90% of respondents indicated peace of mind with data being constantly tracked. However, 64% of respondents had hesitations about a surgically implanted device that was independent of a previous arthroplasty surgery (P < .05). Conclusions: Patients are comfortable with smart technology being involved in their postoperative care, especially younger patients and women. Older individuals, possibly with less experience using smart technology in their lives, were not as willing to wear smart devices or have their data collected. Nearly two-thirds of patients had hesitations about surgically implanted smart devices. Further investigation is needed to understand hesitations concerning smart implants as the orthopedic community enters an era of commercially available smart implants in total joint arthroplasty.

Abstract Background Bronchoalveolar lavage (BAL) is a major diagnostic tool in interstitial lung disease (ILD). Its use remains largely quantitative, usually focused on cell differential ratio. However, cellular morphological features provide additional valuable information. The significance of the “immune alveolitis” cytological profile, characterized by lymphocytic alveolitis with activated lymphocytes and macrophages in epithelioid transformation or foamy macrophages desquamating in cohesive clusters with lymphocytes, remains unknown in ILD. Our objective was to describe patients’ characteristics and diagnoses associated with an immune alveolitis profile in undiagnosed ILD. Methods We performed a monocentric retrospective observational study. Eligible patients were adults undergoing diagnostic exploration for ILD and whose BAL fluid displayed an immune alveolitis profile. For each patient, we collected clinical, radiological and biological findings as well as the final etiology of ILD. Results Between January 2012 and December 2018, 249 patients were included. Mean age was 57 ± 16 years, 140 patients (56%) were men, and 65% of patients were immunocompromised. The main etiological diagnosis was Pneumocystis pneumonia (PCP) (24%), followed by drug-induced lung disease (DILD) (20%), viral pneumonia (14%) and hypersensitivity pneumonitis (HP) (10%). All PCP were diagnosed in immunocompromised patients while HP was found in only 8% of this subgroup. DILD and viral pneumonia were also commonly diagnosed in immunocompromised patients (94% and 80%, respectively). Conclusion Our study highlights the additional value of BAL qualitative description in ILD. We suggest incorporating the immune alveolitis profile for the diagnosis and management of ILD, especially in immunocompromised patients, since it guides towards specific diagnoses.

Background: Exploring clinical trial data using alternative methods may enhance original study's findings and provide new insights. The SOAP II trial has been published more than 10 years ago; but there is still some speculation that some patients may benefit from dopamine administration for shock management. We aimed to reanalyse the trial under different approaches and evaluate for heterogeneity in treatment effect (HTE). Methods: All patients enrolled in SOAP II were eligible for reanalysis. We used a variety of methods including the win-ratio (WR), a Bayesian reanalysis stratified according to shock type, and both a risk-based and effect-based explorations for HTE. The methods were applied to different endpoints, including a hierarchy of death, new use of renal-replacement therapy (RRT), and new-onset arrhythmia; 28-day mortality; a composite endpoint (mortality, new use of RRT, and new-onset arrhythmia), and days alive and free of ICU at 28-days (DAFICU28). Results: A total of 1679 patients were included (average age was 64.9 years, 57% male, 62% with septic and 17% with cardiogenic shock). All analysis favoured norepinephrine over dopamine. Under the WR approach, dopamine had fewer wins compared to norepinephrine (WR 0.79; 95% confidence intervals [CI] 0.68–0.92; p = 0.003), evident in both cardiogenic and septic shock subgroups. The Bayesian reanalysis for type of shock showed, for dopamine, a probability of harm of 0.95 for mortality, > 0.99 probability of harm for composite endpoint, and 0.91 probability of harm for DAFICU28. The fewer DAFICU28 with dopamine was more apparent in those with cardiogenic shock (0.92). Under the risk-based HTE, there was a high probability that dopamine resulted fewer DAFICU28 in the highest quartile of predicted mortality risk. The effect-based HTE assessment model did not recommended dopamine over norepinephrine for any combination of possible modifiers including age, type of shock, presence of cardiomyopathy, and SOFA score. Receiving dopamine when the effect-based model recommended norepinephrine was associated with an absolute increase in composite endpoint of 6%. Conclusion: The harm associated with the use of dopamine for the management of shock appears to be present in both septic and cardiogenic shock patients. There was no suggestion of any subgroup in which dopamine was found to be favourable over norepinephrine. [ABSTRACT FROM AUTHOR]

Light/dark (LD) cycles are responsible for oscillations in gene expression, which modulate several aspects of plant physiology. Those oscillations can persist under constant conditions due to regulation by the circadian oscillator. The response of the transcriptome to light regimes is dynamic and allows plants to adapt rapidly to changing environmental conditions. We compared the transcriptome of Arabidopsis under LD and constant light (LL) for 3 days and identified different gene co‐expression networks in the two light regimes. Our studies yielded unforeseen insights into circadian regulation. Intuitively, we anticipated that gene clusters regulated by the circadian oscillator would display oscillations under LD cycles. However, we found transcripts encoding components of the flavonoid metabolism pathway that were rhythmic in LL but not in LD. We also discovered that the expressions of many stress‐related genes were significantly increased during the dark period in LD relative to the subjective night in LL, whereas the expression of these genes in the light period was similar. The nocturnal pattern of these stress‐related gene expressions suggested a form of "skotoprotection." The transcriptomics data were made available in a web application named Cyclath, which we believe will be a useful tool to contribute to a better understanding of the impact of light regimes on plants. [ABSTRACT FROM AUTHOR]

Rate coefficients for electron-impact dissociation of O3 + to the O+ and O2 + fragments are calculated for the new, recommended cross section data set and for various collisional conditions. Two sets of the cross section data, measured recently by different experimental groups, are used. These cross sections differ significantly with each other, but are renormalized and optimized to the coherent data base. Rate coefficients for the ozone cation fragmentation are determined using the Maxwellian and the non-thermal electron energy distribution functions (EEDF). In the case of Maxwellian distribution, mean electron energies cover the range from zero up to 2 keV. Non-thermal electron energy distribution functions are adopted from the recent electron observations by the 3-D plasma and energetic particles experiment on the WIND spacecraft. The non-thermal rates are evaluated for the mean electron energies from 4 to 80 eV. The role of the possible contribution of electron-impact dissociation of O3 + to the ozone layer depletion has been emphasized.

Abstract Background Allergic bronchopulmonary aspergillosis (ABPA) is a bronchopulmonary disease caused by a complex hypersensitivity to Aspergillus and is usually associated with underlying respiratory diseases such as asthma or cystic fibrosis. Mucus plugging can lead to segmental or lobar atelectasis, but complete lung atelectasis has been exceptionally reported in the literature, making it difficult to diagnose. The diagnosis of ABPA may however be suggested in patients without known predisposing respiratory disorder, even in the absence of other relevant radiographic findings. Case presentation We report five cases of total unilateral lung collapse secondary to ABPA in 70–81-year-old women. Two of them had a past history of ABPA, while total unilateral lung collapse was the first sign of the disease in the other three patients, contributing to the initial misdiagnosis. Flexible bronchoscopy was initially performed to remove mucus plugs from the obstructed airways but was inefficient in four cases. Corticosteroid and/or antifungal treatment was needed. Conclusion ABPA can cause total unilateral lung collapse even in patients without known underlying chronic respiratory disease, making the diagnosis difficult. Flexible bronchoscopy should be considered when lung collapse is associated with respiratory distress but corticosteroids are the mainstay treatment for ABPA.

This paper describes the extension of the previously CMIP5 based high-resolution climate projections with additional ones based on the more recent climate projections from the CMIP6 experiment. The downscaling method and data processing are the same but the reference dataset is now the ERA5-Land reanalysis (compared to ERA5 previously) allowing to increase the resolution of the new downscaled projections from 0.25° x 0.25° to 0.1°x 0.1°. The extension comprises 5 climate models and includes 2 surface variables at daily resolution: air temperature and precipitation. Three greenhouse gas emissions scenarios are available: Shared Socioeconomic Pathways with mitigation policy (SSP1-2.6), an intermediate one (SSP2-4.5), and one without mitigation (SSP5-8.5).

Chronic Lymphocytic Leukemia (CLL) is characterized by the progressive accumulation of monoclonal mature B lymphocytes. Autoimmune complications are common in CLL occurring in up to a quarter of all patients during the course of the illness. Etiology of autoimmunity in CLL is unknown but it is widely admitted that the pathogenic auto-Abs do not originate from the tumoral clone but from the non-malignant B cell pool. This indicates that the developmental scheme of non-malignant B cells could also be perturbed in CLL patients. To address this question, we have designed a B cell-centered antibody panel and used time-of-flight mass cytometry to compare the residual non-malignant B cell pool of CLL patients with the peripheral B cell pool of age-matched healthy donors. We show that the non-malignant B cell compartment of the patients is characterized by profound attrition of naïve B cells and of a population of anergized autoreactive B cells, suggesting impaired B cell lymphopoeisis as well as perturbations of the B cell tolerance checkpoints.

Release of freshwater into the oceans as a result of ice sheet melting could impact the distribution of climate-sensitive diseases. Here, the authors show that a rapid ice sheet melting in Greenland could cause an emergence of malaria in Southern Africa whilst transmission risks in West Africa may decline.

Abstract Background Single-cell RNA sequencing (scRNA-seq) has emerged has a main strategy to study transcriptional activity at the cellular level. Clustering analysis is routinely performed on scRNA-seq data to explore, recognize or discover underlying cell identities. The high dimensionality of scRNA-seq data and its significant sparsity accentuated by frequent dropout events, introducing false zero count observations, make the clustering analysis computationally challenging. Even though multiple scRNA-seq clustering techniques have been proposed, there is no consensus on the best performing approach. On a parallel research track, self-supervised contrastive learning recently achieved state-of-the-art results on images clustering and, subsequently, image classification. Results We propose contrastive-sc, a new unsupervised learning method for scRNA-seq data that perform cell clustering. The method consists of two consecutive phases: first, an artificial neural network learns an embedding for each cell through a representation training phase. The embedding is then clustered in the second phase with a general clustering algorithm (i.e. KMeans or Leiden community detection). The proposed representation training phase is a new adaptation of the self-supervised contrastive learning framework, initially proposed for image processing, to scRNA-seq data. contrastive-sc has been compared with ten state-of-the-art techniques. A broad experimental study has been conducted on both simulated and real-world datasets, assessing multiple external and internal clustering performance metrics (i.e. ARI, NMI, Silhouette, Calinski scores). Our experimental analysis shows that constastive-sc compares favorably with state-of-the-art methods on both simulated and real-world datasets. Conclusion On average, our method identifies well-defined clusters in close agreement with ground truth annotations. Our method is computationally efficient, being fast to train and having a limited memory footprint. contrastive-sc maintains good performance when only a fraction of input cells is provided and is robust to changes in hyperparameters or network architecture. The decoupling between the creation of the embedding and the clustering phase allows the flexibility to choose a suitable clustering algorithm (i.e. KMeans when the number of expected clusters is known, Leiden otherwise) or to integrate the embedding with other existing techniques.

Abstract This study aims to analyze, in a population of singletons, the potential confounding or modifying effect of noise on the relationship between fetal growth restriction (FGR) or small for gestational age (SGA) and environmental exposure to air pollution. All women with single pregnancies living in one of two medium-sized cities (Besançon, Dijon) and who delivered at a university hospital between 2005 and 2009 were included. FGR and SGA were obtained from medical records. Outdoor residential exposure to nitrogen dioxide (NO2) and particulate matter (PM10) was quantified at the mother’s address at delivery over defined pregnancy periods; outdoor noise exposure was considered to be the annual average daily noise levels in the façade of building (LAeq,24 h). Adjusted odds ratios (ORa) were estimated by multivariable logistic regressions. Among the 8994 included pregnancies, 587 presented FGR and 918 presented SGA. In the two-exposure models, for SGA, the ORa for a 10-µg/m3 increase of PM10 during the two last months before delivery was 1.18, 95%CI 1.00–1.41 and for FGR, these ORa were for the first and the third trimesters, and the two last months before delivery: 0.77 (0.61–0.97), 1.38 (1.12–1.70), and 1.35 (1.11–1.66), respectively. Noise was not associated with SGA or FGR and did not confound the relationship between air pollution and SGA or FGR. These results are in favor of an association between PM10 exposure and fetal growth, independent of noise, particularly towards the end of pregnancy, and of a lack of association between noise and fetal growth.

This paper describes a faculty development project in which four teacher educators, who were part of a larger Faculty Learning Community, used an innovative model called the Faculty Learning Lab to support each other in critical reflections about their teaching. Within the learning lab, which was guided by Knowles' adult learning theory, each faculty member invited colleagues to observe a lesson, priming their observations with a description of desired learning objectives. Learning lab members shared their noticings regarding evidence of student learning and their hypotheses about the interaction of factors that may have affected the learning. Exploratory analyses indicate that participation in this faculty mentoring project has helped participants develop a professional vision, as well as a sense of professional collegiality.