Le niveau de compréhension de l’anglais des étudiants en médecine peut être amélioré. Résultats d’une stratégie d’évaluation systématique

Objectives To describe the level of English of a population of medical students and the improvement after the implementation of systematic assessment that all students achieve a minimal level. Population and methods For the past 5 years, all medical students in our medical school have been taking the Test of English for International Communication (TOEIC). The baseline population (students entering second year in 2004) had no specific obligation. After 2004, a score above 600 was mandatory for graduation. Teaching was oriented towards training for the TOEIC and the number of hours was more important for low-level students. Results The mean score has increased from 618 ± 146 in 2004, to 687 ± 94, 717 ± 97, 733 ± 96 and 731 ± 104 for the next four years. The proportion of students who do not achieve a score of 550 (B1 level of the European framework) has decreased from 30 to 0%. Discussion Improving the level of English of French medical students is possible, if this is made a priority. The objective, as set in engineering studies, that all medical students reach a B2 level would require national guidelines

Clinico-pathological considerations in a 48-years-old female with acute kidney injury: is it lupus nephritis, ANCA-associated vasculitis or something else?

BACKGROUND: The value of ANCA positivity in the setting of systemic lupus erythematous and their pathogenicity remains uncertain. CASE PRESENTATION: We report the case of a 48-year-old female with rapidly progressive kidney failure, arthro-myalgia and weight loss. Auto-immune screening showed anti-dsDNA antibodies, complement consumption and triple ANCA positivity. A first kidney biopsy done at presentation highlighted class IV-G glomerulonephritis with elective extra-capillary involvement and mainly C1q glomerular deposition at immunofluorescence study. After three months of a regimen combining steroids and cyclophosphamide, a second biopsy was performed and showed class IV-G glomerulonephritis with mainly endocapillary proliferation. CONCLUSION: This case is atypical in view of immunological profile and kidney histopathological presentation and evolution and gives rise to discussion in view of recent data on ANCA value in lupus nephritis, and suggests that different auto-immune pathways may be involved in lupus nephritis

Modeling soil organic carbon dynamics in temperate forests with Yasso07

In a context of global changes, modeling and predicting the dynamics of soil carbon stocks (CSs) in forest ecosystems are vital but challenging. Yasso07 is considered to be one of the most promising models for such a purpose. We examine the accuracy of its prediction of soil carbon dynamics over the whole French metropolitan territory at a decennial timescale. We used data from 101 sites in the RENECOFOR network, which encompasses most of the French temperate forests. These data include (i) the quantity of above-ground litterfall from 1994 to 2008, measured yearly, and (ii) the soil CSs measured twice at an interval of approximately 15 years (once in the early 1990s and around 2010). We used Yasso07 to simulate the annual changes in carbon stocks (ACCs; in tC&thinsp;ha−1&thinsp;yr−1) for each site and then compared the estimates with actual recorded data. We carried out meta-analyses to reveal the variability in litter biochemistry in different tree organs for conifers and broadleaves. We also performed sensitivity analyses to explore Yasso07's sensitivity to annual litter inputs and model initialization settings. At the national level, the simulated ACCs (+0.00±0.07&thinsp;tC&thinsp;ha−1&thinsp;yr−1, mean&thinsp;±&thinsp;SE) were of the same order of magnitude as the observed ones (+0.34±0.06&thinsp;tC&thinsp;ha−1&thinsp;yr−1). However, the correlation between predicted and measured ACCs remained weak (R2&lt;0.1). There was significant overestimation for broadleaved stands and underestimation for coniferous sites. Sensitivity analyses showed that the final estimated CS was strongly affected by settings in the model initialization, including litter and soil carbon quantity and quality and also by simulation length. Carbon quality set with the partial steady-state assumption gave a better fit than the model with the complete steady-state assumption. With Yasso07 as the support model, we showed that there is currently a bottleneck in soil carbon modeling and prediction due to a lack of knowledge or data on soil carbon quality and fine-root quantity in the litter.</p

Survey on solar X-ray flares and associated coherent radio emissions

The radio emission during 201 X-ray selected solar flares was surveyed from 100 MHz to 4 GHz with the Phoenix-2 spectrometer of ETH Zurich. The selection includes all RHESSI flares larger than C5.0 jointly observed from launch until June 30, 2003. Detailed association rates of radio emission during X-ray flares are reported. In the decimeter wavelength range, type III bursts and the genuinely decimetric emissions (pulsations, continua, and narrowband spikes) were found equally frequently. Both occur predominantly in the peak phase of hard X-ray (HXR) emission, but are less in tune with HXRs than the high-frequency continuum exceeding 4 GHz, attributed to gyrosynchrotron radiation. In 10% of the HXR flares, an intense radiation of the above genuine decimetric types followed in the decay phase or later. Classic meter-wave type III bursts are associated in 33% of all HXR flares, but only in 4% they are the exclusive radio emission. Noise storms were the only radio emission in 5% of the HXR flares, some of them with extended duration. Despite the spatial association (same active region), the noise storm variations are found to be only loosely correlated in time with the X-ray flux. In a surprising 17% of the HXR flares, no coherent radio emission was found in the extremely broad band surveyed. The association but loose correlation between HXR and coherent radio emission is interpreted by multiple reconnection sites connected by common field lines.Comment: Solar Physics, in pres

Models of human core transcriptional regulatory circuitries

A small set of core transcription factors (TFs) dominates control of the gene expression program in embryonic stem cells and other well-studied cellular models. These core TFs collectively regulate their own gene expression, thus forming an interconnected auto-regulatory loop that can be considered the core transcriptional regulatory circuitry (CRC) for that cell type. There is limited knowledge of core TFs, and thus models of core regulatory circuitry, for most cell types. We recently discovered that genes encoding known core TFs forming CRCs are driven by super-enhancers, which provides an opportunity to systematically predict CRCs in poorly studied cell types through super-enhancer mapping. Here, we use super-enhancer maps to generate CRC models for 75 human cell and tissue types. These core circuitry models should prove valuable for further investigating cell-type–specific transcriptional regulation in healthy and diseased cells.United States. National Institutes of Health (HG002668

Mycolactone as Analgesic: Subcutaneous Bioavailability Parameters

is the bacillus responsible for Buruli ulcer, an infectious disease and the third most important mycobacterial disease worldwide, after tuberculosis and leprosy. infection is a type of panniculitis beginning mostly with a nodule or an oedema, which can progress to large ulcerative lesions. The lesions are caused by mycolactone, the polyketide toxin of . Mycolactone plays a central role for host colonization as it has immunomodulatory and analgesic effects. On one hand, mycolactone induces analgesia by targeting type-2 angiotensin II receptors (ATR), causing cellular hyperpolarization and neuron desensitization. Indeed, a single subcutaneous injection of mycolactone into the mouse footpad induces a long-lasting hypoesthesia up to 48 h. It was suggested that the long-lasting hypoesthesia may result from the persistence of a significant amount of mycolactone locally following its injection, which could be probably due to its slow elimination from tissues. To verify this hypothesis, we investigated the correlation between hypoesthesia and mycolactone bioavailability directly at the tissue level. Various quantities of mycolactone were then injected in mouse tissue and hypoesthesia was recorded with nociception assays over a period of 48 h. The hypoesthesia was maximal 6 h after the injection of 4 μg mycolactone. The basal state was reached 48 h after injection, which demonstrated the absence of nerve damage. Surprisingly, mycolactone levels decreased strongly during the first hours with a reduction of 70 and 90% after 4 and 10 h, respectively. Also, mycolactone did not diffuse in neighboring skin tissue and only poorly into the bloodstream upon direct injection. Nevertheless, the remaining amount was sufficient to induce hypoesthesia during 24 h. Our results thus demonstrate that intact mycolactone is rapidly eliminated and that very small amounts of mycolactone are sufficient to induce hypoesthesia. Taken together, our study points out that mycolactone ought to be considered as a promising analgesic

Fidélité, équité et impact des mini entretiens multiples dans le processus de sélection des étudiants en santé en France

Context: The University of Angers (UA) created the PluriPASS cursus that replaced the PACES (première année commune aux études de santé/First year of common health studies) and introduced multiple mini-interviews (MMIs) in the selection process of students in France. This study is designed to evaluate MMI reliability, fairness and impact. Topics/materials/methods: Some 294 students attended the MMIs in June 2016. The MMIs were made up of four stations evaluating six competences. The following criteria (age, gender, novice/repeater, scholarship, parents’ socio-professional category, bachelor’s degree with honors, time of the evaluation and scenario) were examined using both univariate and multivariate analysis. The impact of the MMIs was evaluated following the limited-ranges method. Outcome: Cronbach’s alpha coefficients for the 6 evaluated competences ranged from 0.612 to 0.935. Males ranked better overall with MMIs (+ 27.4 pts; CI95% = [9,2; 45,7]). Students who were got their bachelor’s degree with high honors (“Très Bien” distinction, higher than 16/20) also had a better overall score (+ 30.41 pts ; CI95% = [14.75; 46.12]). There were no differences with respect to the other socio-demographic variables, and none regarding the different scenarios considered. Following the MMI follow-ups, 53 different students were excluded from the ranking in a study path. Conclusion: As part of the PluriPASS testing, MMIs were found to be coherent as well as educationally and selectively interesting. However, they require particular consideration to ensure fairness, both during implementation and in future research studies

Colorectal neuroendocrine carcinomas and adenocarcinomas share oncogenic pathways. A clinico-pathologic study of 12 cases

OBJECTIVE: Neuroendocrine carcinomas (NECs) are rare neoplasms with an increasing incidence. Oncogenetic pathways of colorectal NEC are still poorly understood, and no treatment standards are available for these rare tumors. METHODS: We analyzed retrospectively the clinical records and histology of 12 patients with colorectal NEC. KRAS and BRAF mutations were investigated after the dissection of exoendocrine and neuroendocrine components. ALK alterations and EML4-ALK transcripts were detected by in-situ hybridization and determination of fusion transcripts, respectively. RESULTS: At the time of diagnosis, the mean age of the patients was 60 years (40-79) and 10 patients had synchronous metastases. A transient response occurred in two patients and one patient treated with cisplatin-etoposide or fluoropyrimidine-oxaliplatin, respectively. Tumor progression-related death occurred in 11 of 12 patients. Ten tumors contained an exocrine component, accounting for 5-70% of the tumor, and the other two contained an amphicrine component. BRAF/KRAS mutations were found in six of 10 tumors, corresponding to BRAF(V600E) (n=2) or KRAS(G12D) (n=2), KRAS(G12V) or KRAS(G13D). DNA was obtained from both exocrine and endocrine components in seven cases, and the BRAF/KRAS status was identical in all cases. Split of the ALK locus was detected in a minority of tumor cells in two of eight cases, but EML4-ALK transcripts were absent. CONCLUSION: The association of an exocrine component in all cases and the similar profile of BRAF/KRAS mutations indicate that colorectal NEC may correspond to a high-grade transformation of colorectal carcinoma. New chemotherapy regimens using targeted therapies should be assessed in these tumors

Pre-transplant CD45RC expression on blood T cells differentiates patients with cancer and rejection after kidney transplantation

Background Biological biomarkers to stratify cancer risk before kidney transplantation are lacking. Several data support that tumor development and growth is associated with a tolerant immune profile. T cells expressing low levels of CD45RC preferentially secrete regulatory cytokines and contain regulatory T cell subset. In contrast, T cells expressing high levels of CD45RC have been shown to secrete proinflammatory cytokines, to drive alloreactivity and to predict acute rejection (AR) in kidney transplant patients. In the present work, we evaluated whether pre-transplant CD45RClow T cell subset was predictive of post-transplant cancer occurrence. Methods We performed an observational cohort study of 89 consecutive first time kidney transplant patients whose CD45RC T cell expression was determined by flow cytometry before transplantation. Post-transplant events including cancer, AR, and death were assessed retrospectively. Results After a mean follow-up of 11.1±4.1 years, cancer occurred in 25 patients (28.1%) and was associated with a decreased pre-transplant proportion of CD4+CD45RChigh T cells, with a frequency below 51.9% conferring a 3.7-fold increased risk of post-transplant malignancy (HR 3.71 [1.24–11.1], p = 0.019). The sensibility, specificity, negative predictive and positive predictive values of CD4+CD45RChigh&lt;51.9% were 84.0, 54.7, 89.8 and 42.0% respectively. Confirming our previous results, frequency of CD8+CD45RChigh T cells above 52.1% was associated with AR, conferring a 20-fold increased risk (HR 21.7 [2.67–176.2], p = 0.0004). The sensibility, specificity, negative predictive and positive predictive values of CD8+CD45RChigh&gt;52.1% were 94.5, 68.0, 34.7 and 98.6% respectively. Frequency of CD4+CD45RChigh T cells was positively correlated with those of CD8+CD45RChigh (p&lt;0.0001), suggesting that recipients with high AR risk display a low cancer risk. Conclusion High frequency of CD45RChigh T cells was associated with AR, while low frequency was associated with cancer. Thus, CD45RC expression on T cells appears as a double-edged sword biomarker of promising interest to assess both cancer and AR risk before kidney transplantation