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Contexte. Les publications de médecine générale progressent dans tous les pays, en particulier ceux dont le système de santé est structuré autour des soins premiers. Aucune donnée n’était disponible pour les publications du secteur académique de médecine générale français. Objectif. Décrire les caractéristiques des publications scientifiques du secteur académique de médecine générale entre 2011 et 2018. Méthode. Un double recueil des publications a été réalisé chaque année entre 2011 et 2018 : un autoquestionnaire a été adressé à chaque département de médecine générale qui devait déclarer ses publications ; une requête PubMed® a été réalisée pour trouver les publications dont un auteur était affilié au secteur académique de médecine générale. Les caractéristiques de chaque publication ont été recherchées. Résultats. Parmi les 1 645 publications recensées, 911 provenaient de revues indexées dans PubMed®. D’après la CISP-2, les publications indexées concernaient principalement la thématique « générale et non spécifiée » (26,9 %) suivie par les thématiques « psychologique » (13 %) et « circulatoire » (9,1 %). Entre 2011 et 2018, la médiane des facteurs d’impact variait entre 0,899 et 2,302. La part des publications avec un premier auteur variait entre 55,9 et 73,9 %, celle avec un dernier auteur affilié au secteur académique variait entre 23,5 et 39,2 %. Conclusion. Les publications ont progressé entre 2011 et 2018, suivant ainsi la tendance internationale. Le secteur académique de médecine générale français témoigne ainsi de sa structuration.

Compte tenu de leur mécanisme d’action, les inhibiteurs du cotransporteur sodium-glucose de type 2 (iSGLT2) étaient des médicaments initialement destinés à traiter l’hyperglycémie chronique des patients diabétiques de type 2, ce qui finalement était une erreur de cible. Les résultats observés sur des critères secondaires lors des premiers essais randomisés chez les patients diabétiques ont conduit l’industrie pharmaceutique à évaluer avec succès ces principes actifs dans l’insuffisance cardiaque (avec fraction d’éjection ventriculaire gauche réduite ou préservée) et dans la maladie rénale chronique, avec ou sans diabète. La récente décision de l’Agence nationale de sécurité du médicament d’étendre la primoprescription des iSGLT2 à tous les médecins ait de la médecine générale et de ses praticiens les acteurs incontournables de leur bon usage, au service de la santé de milliers de patients. Le bon usage doit tenir compte des bénéfices cliniques établis et des risques encourus. Cet article a donc pour objectif de fournir au lecteur une information factuelle et objective sur les résultats des essais cliniques ayant évalué les ISGLT2 dans leurs nouvelles indications. Sa finalité est de favoriser une décision médicale partagée entre un médecin et un patient loyalement et clairement informés.

Contexte. La consommation d’antibiotiques (ATB) en médecine ambulatoire en France reste l’une des plus élevées d’Europe malgré une baisse entre 2000 et 2008 et trois plans « antibiotiques ». La ligne téléphonique CoTéPrAgmatique (Conseil téléphonique en prescription antibiotiqueCTPA) dédiée aux médecins généralistes (MG) d’Île-de-France (IDF) a été mise en place d’avril 2013 à mars 2015 sur les financements FIR (fonds d’intervention régionaux) de l’ARS. L’objectif général de la ligne était d’améliorer la pertinence des prescriptions d’ATB en répondant aux questionnements des MG sur ce sujet en situation de soins. Objectifs. décrire le fonctionnement et les résultats de la ligne CTPA. Méthode. Étude transversale descriptive rétrospective à partir des fiches de recueil des appels de la ligne CTPA entre avril 2013 et mars 2015 avec analyse descriptive du nombre d’appels, des familles de pathologies, des conseils donnés, de l’ATB déjà en cours. Les analyses univariées et multivariées multiniveaux ont concerné les facteurs associés au conseil de non-prescription ATB. Résultats. Fin mars 2015, la ligne avait comptabilisé 517 appels, dont 36 % concernant l’appareil urinaire et 23 % les infections respiratoires hautes et basses (IRH, IRB). Un conseil de non-prescription ATB était donné dans 39,3 % des cas, les facteurs associés à ce conseil étaient les appels concernant les IRH, avec un odds ratio (OR) de 2,62 (IC95 =1,31-5,27), les infections autres (OR = 3,30; IC95 = 1,44-7,55) et l’absence d’ATB en cours (OR = 1,81; IC95 = 1,18-2,79). Conclusion. Malgré un nombre d’appels modeste, la ligne a atteint ses objectifs. Le développement d’un projet global intégrant le conseil téléphonique et d’autres outils existants bénéficiant d’une communication institutionnelle semble une perspective crédible afin de diminuer la prescription inappropriée d’antibiotiques.

La médecine générale (MG) est une discipline avec des contenus spécifiques de formation, de recherche et de pratique clinique. Elle se caractérise par son contexte de soins premiers et des fondements scientifiques internationalement reconnus. Une liste des familles de situations prévalentes et le référentiel des compétences ont été publiés et fondent les choix de formation. Le portfolio est un des outils adéquats décrits dans la littérature pour évaluer le niveau de compétence. Il contient différents travaux d’écriture et les réflexions critiques à propos de situations cliniques rencontrées, formalisant l’apprentissage qui en a été retiré1...

Contexte. Les médecins généralistes (MG) se mobilisent pour permettre à ceux qui le désirent d’être vaccinés contre la COVID-19. Ils sont sollicités pour répondre aux nombreuses questions des patients, notamment sur la possibilité de survenue d’une grave allergie post-vaccinale. Objectif. Fournir une synthèse des connaissances pour aider le MG à répondre aux questions des patients et de leur entourage sur la vaccination contre la COVID-19 notamment en cas d’antécédents allergiques. Méthodes. Une revue narrative de la littérature a été menée jusqu’à la date du 21 janvier 2021, à l’aide des données de synthèse des autorités de santé françaises et internationales et des principales sociétés savantes internationales d’allergologie. Les recommandations sur la prise en charge des anaphylaxies ont été ajoutées a posteriori. Résultats. Les réactions anaphylactiques liées au vaccin à ARNm sont très rares. Les antécédents d’allergie ou d’anaphylaxie ne constituent pas en général une contre-indication à la vaccination sauf de manière absolue en cas de réaction systémique après la première dose du vaccin et d’antécédent d’anaphylaxie à l’un des composants du vaccin. Une réaction localisée à la première dose ne contre-indique pas la réalisation de la deuxième dose. Conclusion. Les données colligées à ce jour sont rassurantes : les anaphylaxies liées au vaccin à ARNm sont comparables aux autres vaccins. Les personnes aux antécédents d’allergies, y compris d’anaphylaxies (hormis au vaccin lui-même ou à l’un de ses composants), peuvent recevoir le vaccin anti-COVID. Le rapport bénéfices/risques en cas d’antécédents allergiques est à ce jour en faveur de la vaccination. Ces informations permettent d’aider les médecins et les patients à faire un choix plus éclairé et rationnel dans le cadre de la décision partagée.

Background: BSMO 2014-01 is a published prospective phase 2 study evaluating the efficacy of neoadjuvant EC and PC in the treatment of TNBC patients. (1) The addition of weekly carboplatin to neoadjuvant paclitaxel and dose-dense EC lead to a pathologic complete response (pCR) of 54%, comparable to prior studies. A secondary endpoint was to correlate pCR to homologous recombination (HR) and DNA damaging repair (DDR) deficiency due to germline mutations. Methods: Sixty-three patients (pts) of which nine already identified with a BRCA 1/2 mutation were considered. Peripheral blood was collected in 52 pts after obtaining informed consent for a broad genomic DNA analysis. Whole Exome Sequencing was performed, and only rare variants (M.A.F. Citation Format: Christel Fontaine, Vincent Renard, Heidi Van den Bulck, Peter Vuylsteke, Philippe Glorieux, Catherine Dopchie, Lore Decoster, Ahmad Awada, Hans Wildiers, Sylvie De Brakeleer, Erik Teugels, Jacques De Grève. Evaluation of germline whole exome sequencing of early breast cancer patients with triple negative breast cancer (TNBC) included in a prospective study of neoadjuvant chemotherapy (NAC) with epirubicin and cyclophosphamide (EC) and carboplatin-paclitaxel (PC) (BSMO 2014-01) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-05.

Background: BSMO 2014-01 is a completed prospective phase 2 study evaluating the efficacy of neoadjuvant EC and PC. One of the secondary endpoints was the correlation of sTIL with response, pCR and survival. We also assessed the relationship between sTIL and TLS in the diagnostic biopsies. Methods: Stromal TIL (sTIL) were evaluated on H&E stained tumor biopsies before the start of the NAC according to the criteria described by Salgado et al(1). Scores were defined as "low" or "high" if lymphocytic infiltration in the stroma around the tumor was ≤ 10% or > 10%. TLS are ectopic lymph node-like structures recently identified in breast cancer. TLS were counted using a dual IHC stain for CD3 (T cells) and CD20 (B cells) and categorized as "little" if the TLS occupied < 10% or "moderate to abundant" if they occupied ≥ 10% of the adjacent tissue. The correlation between sTIL and pathologic parameters was analyzed using the chi-square test; DFS and OS between the groups was estimated by using the log-rank test. Results: So far we could quantify the number of sTIL in 38 out of 63 TNBC pts treated with neoadjuvant EC-PC. Twenty eight pts had a high sTIL score and 10 pts had a low sTIL score. The high-sTIL group (19/28) achieved a numerical higher pathologic complete remission (pCR) rate than the low-sTIL group (5/10) (p=0.3); both groups had a comparable disease free survival of 28.6 mths and 26.7 mths respectively (p=0.7). The overall survival was similar:29 mths and 27.8 mths respectively (p=0.8). Stromal TLS were identified in 10 out 23 samples available for this analysis and we could demonstrate a positive correlation between high levels of sTIL and high levels of moderate to abundant TLS(CD3) in the adjacent tissue in six out of the ten samples in which TLS were present (p=0.1). Conclusion: These preliminary results could not confirm the results published by Denkert et al earlier this year(2). A trend for correlation of the presence of high sTIL with moderate to abundant levels of TLS was found. Analysis on the remaining samples of all patients included in the study and correlation with outcome is ongoing and these completed results will be presented. (1)Assessing Tumor-infiltrating lymphocytes in solid tumors. Hendry S, Salgado R et al. Adv Anat Pathol 2017; 235-251. (2)Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer. Denkert C et al. Lancet Oncol 2018; 40-50. Citation Format: Fontaine C, Van den Eynden G, de Wind R, Boisson A, Renard V, Van den Bulck H, Vuylsteke P, Glorieux P, Dopchie C, Decoster L, De Grève J, Awada A, Wildiers H, Willard-Gallo K. Evaluation of stromal tumor-infiltrating lymphocytes (sTIL) and tertiary lymphoid structures (TLS) in early breast cancer patients with triple negative breast cancer(TNBC) included in a prospective study of neoadjuvant chemotherapy (NAC) with Epirubicin and cyclophosphamide (EC) and carboplatin-paclitaxel (PC) (BSMO 2014-01) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-47.

Background: While the introduction of checkpoint inhibitors (CPIs) as standard of care treatment for various tumor types has led to considerable improvements in clinical outcome, the majority of patients still fail to respond. Preclinical data suggest that stereotactic body radiotherapy (SBRT) could work synergistically with CPIs by acting as an in situ cancer vaccine, thus potentially increasing response rates and prolonging disease control. Though SBRT administered concurrently with CPIs has been shown to be safe, evidence of its efficacy from large randomized trials is still lacking. The aim of this multicenter randomized phase II trial is to assess whether SBRT administered concurrently with CPIs could prolong progression-free survival as compared to standard of care in patients with advanced solid tumors. Methods/design: Ninety-eight patients with locally advanced or metastatic disease will be randomized in a 1:1 fashion to receive CPI treatment combined with SBRT (Arm A) or CPI monotherapy (Arm B). Randomization will be stratified according to tumor histology (melanoma, renal, urothelial, head and neck squamous cell or non-small cell lung carcinoma) and disease burden (≤ or > 3 cancer lesions). The recommended SBRT dose is 24Gy in 3 fractions, which will be administered to a maximum of 3 lesions and is to be completed prior to the second or third CPI cycle (depending on CPI treatment schedule). The study’s primary endpoint is progression-free survival as per iRECIST. Secondary endpoints include overall survival, objective response, local control, quality of life and toxicity. Translational analyses will be performed using blood, fecal and tissue samples. Discussion: The CHEERS trial will provide further insights into the clinical and immunological impact of SBRT when combined with CPIs in patients with advanced solid tumors. Furthermore, study results will inform the design of future immuno-radiotherapy trials. Trial registration: Clinicaltrials.gov identifier: NCT03511391. Registered 17 April 2018., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction: Overall prognosis of early TNBC remains inferior to that of other breast cancer subtypes. Neoadjuvant platinum added to taxanes-anthracycline regimen has been reported to potentially improve pathologic complete response (pCR) and survival in TNBC pts. Aim: To report the final results of the efficacy and toxicity of the addition of weekly Cp to P and dose dense (dd) EC on the pCR rate in an open-label phase II study in stage II/III TNBC pts. Patients and methods: In the BSMO study sixty three pts received dd P (80mg/m2/wk) concurrent with Cp (AUC=2) for 12 weeks, added to bi-weekly E (90mg/m2) and C (600mg/m2) for 4 cycles, followed by surgery and radiotherapy. The primary endpoint was pCR in the breast and axilla. Additionally actual drug dosing and toxicities were registered. A correlative assessment of germline mutations in HRD genes is ongoing. Pts were monitored for clinical response by magnetic resonance and mammography, and also for relapse free survival and time to treatment failure. The study sample size has been calculated according to the optimal Simon's two-stage design method. The target sample size was 63 patients with 80% power to detect a pCR rate of > or=47% (α= 0.05). Results: Sixty three eligible pts with operable, non-inflammatory stage II/III TNBC were included. Most pts were between 40 and 59 yrs old and had clinical stage II disease. Forty percent were clinically node + and 68% were G3. Seventy three percent received breast conserving surgery. Sixty percent (38 out of 63 pts) achieved a pCR breast/axilla. Sixteen percent (10pts) missed three or more doses of wP, whereas at least 1 EC cycle was skipped in 19% (12pts). Sixty five percent had G3/4 neutropenia. Investigator reported febrile neutropenia occurred in 18 pts (28.5%) of which more than eighty percent during the EC part despite primary prophylaxis. Thrombocytopenia G3/4 was noticed in 10 pts (16%). Only four pts (6%) developed grade 3 peripheral neuropathy. Conclusion: The addition of weekly carboplatinum to neoadjuvant paclitaxel and ddEC is feasible and a pCR rate in the breast and axilla as high as 60% compares nicely with the results achieved with the similar 3 weekly carboplatinum arm of the CALBG 40603 trial. Febrile neutropenia rate was higher than the 3-weekly carboplatin arm in CALGB40603 trial, but occurred mainly during the EC part, while other toxicities are comparable. Future research could focus on this combination in the reverse sequence (first ECdd), which may lead to a better global haematological profile. Citation Format: Fontaine C, Cappoen N, Renard V, Van Den Bulck H, Vuylsteke P, Glorieux P, Dopchie C, Decoster L, De Grève J, Awada A, Wildiers H. Final results of weekly (w) neoadjuvant carboplatin (Cp) added to paclitaxel (P) followed by epirubicin (E) and cyclophosphamide (C) in triple negative breast cancer (TNBC) patients (pts): A BSMO breast cancer task force phase II study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-09.

Background: TALAPRO-1 enrolled patients (pts) with RECIST1.1-measurable disease, progressive mCRPC, and tumor DDRalt (tDDRalt) considered sensitizing to PARP inhibitors (ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C). Pts had received ≥1 taxane-based chemotherapy and progressed on ≥1 novel hormonal therapy. The primary endpoint was objective response rate (ORR per RECIST1.1; central review). Exploratory ad hoc biomarker analyses assessed germline/somatic origin and zygosity of tDDRalt and associations with antitumor activity. Data cutoff was Sept 4, 2020. Methods: Tumor tissue was tested using FoundationOne®, and saliva using an Ambry CustomNext-Cancer panel. Known/likely pathogenic tDDRalt variants were categorized as germline (also present in saliva), somatic (not present in saliva), or unknown origin (ATR and FANCA not in germline panel). tDDRalt zygosity was assessed using somatic-germline-zygosity (SGZ). Categorization was limited to short variants. Results: 128 pts were enrolled and 127 received ≥1 TALA dose (safety population). Of 52 enrolled tumor DDR-deficient pts evaluable for both germline and tumor DDR mutations and associated comparisons, 27 (52%) had ≥1 tDDRalt of germline origin, 24 (46%) of somatic origin, and 2 (4%) of unknown origin. One pt had both germline and somatic tDDRalt. The most common tDDRalt were BRCA2 (14 germline; 10 somatic) and ATM (4 germline; 7 somatic). ORR was 25.9% (7/27) in pts with tDDRalt of germline origin and 9.1% (2/22) in pts with only somatic tDDRalt (P = 0.159, 2-sided Fisher's exact test). ORR was 50.0% (7/14) in pts with tumor BRCA2alt of germline origin and 20.0% (2/10) in pts with somatic BRCA2alt (not significantly different; P = 0.210). Overall, of 77 pts in the safety population evaluable for SGZ, tDDRalt were predicted to be with loss of heterozygosity (LOH) in 16 (20.8%) pts, heterozygous in 17 (22.1%) pts and with zygosity unknown in 44 (57.1%) pts. ORR in tumors categorized as tDDRalt with LOH was 43.8% (7/16) and for those categorized as heterozygous tDDRalt was 11.8% (2/17) (odds ratio [95% CI] 5.83 [0.811-65.84]; P = 0.057). Conclusions: In this heavily pretreated mCRPC population, based on this retrospective ad hoc exploratory subgroup analysis, pts with germline and/or homozygous tDDRalt appeared to be numerically most likely to respond to TALA. Potential reasons include gene-specific imbalances in origin/zygosity of alterations and/or sensitivity to TALA. Further investigation in larger data sets is warranted. Citation Format: Johann S. de Bono, A. Douglas Laird, Niven Mehra, Philippe Barthelemy, Remy Delva, Tanya Dorff, Umberto Basso, Adam Stirling, Jean-Pascal Machiels, Herlinde Dumez, Vincent Renard, Julia Hopkins, Lee A. Albacker, Hsiang-Chun Chen, Marielena Mata, Nicola Di Santo, Cynthia Healy, Inge M. van Oort, Giorgio Scagliotti, Karim Fizazi. TALAPRO-1 final data: Talazoparib (TALA) monotherapy in men with DNA damage response alterations (DDRalt) and metastatic castration-resistant prostate cancer (mCRPC): Exploration of DDRalt germline/somatic origin and zygosity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT027.

Introduction: Triple negative breast cancer (TNBC) remains a challenging disease with dismal prognosis. Platinum analogs have not yet shown to improve long term outcome in this setting, but are associated with increased pathological complete response rate (pCR) at the cost of higher toxicity. Aim: To further increase or maintain the high pCR rate with platinum containing schedules while decreasing toxicity by administering low dose weekly carboplatin instead of high-dose 3 weekly carboplatin as in CALGB 40603.(1) Patients and methods: We evaluated the tolerability and the impact of the addition of weekly carboplatin (CP) to paclitaxel (P) and dose dense epirubicin-cyclofosfamide (EC) on pCR in an open-label multicenter phase II study in stage II/III TNBC patients (pts). Sixty three pts received dose dense paclitaxel (P:80mg/m2/wk) concurrent with carboplatin (CP: AUC=2) for 12 wks, followed by two-weekly epirubicin (E:90mg/m2) and cyclophosphamide (C:600mg/m2) for 4 cycles. The primary endpoint is pCR in the breast and axilla. Additionally treatment deliveryand adverse events are recorded. A correlative assessment of germline mutations in homologous recombination (HR) genes is planned. Pts are monitored for response by magnetic resonance and mammography and also for relapse free survival and time to treatment failure. The study size sample has been calculated according to the optimal Simon's two-stage design method. The target sample size was 63 patients with 80% power to detect a pCR rate of ≥47% (α= 0.05). Results: Accrual to the study is completed with 63 eligible pts with operable, noninflammatory stage II and III TNBC included. Most patients were between 40 and 60 yrs old and were clinical stageT2 tumors. Half of the pts were clinically node + and 70% were G3. Sixty six percent had breast conserving surgery. Sixteen out of 26 (61.5%) of the currently evaluable pts achieved a pCR rate in the breast and axilla. The other ongoing patients have not yet reached this endpoint. Four out of 21 evaluable pts that completed the chemotherapy missed two or more doses of CP due to neutropenia(NP) G3/4(2), general deterioration G3(1) and polyneuropathy(PNP) G3(1) and seven pts needed one dose reduction of P and/or CP due to NP G3-4 (3-2) and PNP G2(1) and one abdominal infection. Conclusion: These preliminary data suggest that the addition of weekly carboplatinum to neoadjuvant paclitaxel and EC is feasible and has a promising pCR rate in the breast and axilla as high as 61.5% in early TNBC pts. More mature toxicity and outcome data and correlation with genome analysis will be presented. (1) Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once per week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603(Alliance) Sikov WM et al. J Clin Oncol 33:13-21; 2014. Citation Format: Fontaine C, Cappoen N, Renard V, Vuylsteke P, Van Den Bulck H, Glorieux P, t'Kint de Roodenbeke D, Dopchie C, Decoster L, Vanacker L, De Grève J, Awada A, Wildiers H. Neoadjuvant weekly carboplatin and paclitaxel followed by dose dense epirubicin and cyclophosphamide in triple negative breast cancer patients: A single arm phase II study from the Belgian Society of Medical Oncology [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-06.

The screening of patients who are at-risk drinkers, which means exceeding the thresholds defined by health authorities or associated with a specific situation (taking psychotropic drugs, having an organic pathology, driving a vehicle, drinking during pregnancy), represents a major issue in primary care. Few studies have offered perspective from the patients' standpoint. The main purpose of this study was to describe general practitioners at-risk drinking screening from their patients point of view. The secondary objective was to identify the factors associated with perception of satisfactory general practitioner knowledge about alcohol consumption.A quantitative cross-sectional study was launched in 9 general practitioner offices over 6 months. Patients older than 18 were recruited to answer a questionnaire blinded from their general practitioner, indicating the level of their alcohol consumption and their perception regarding their general practitioner's screening methods. Descriptive, univariate and multivariate logistic regression analyses were performed.All in all, 445 patients were analyzed. Sixty-two at-risk drinkers were screened (13.9 %). Most of the patients declared they had not been interviewed about their alcohol consumption by their general practitioner either during initial consultations (86.1 %) or over time (83.3 %). Only 4.2 % of patients had previously initiated discussion about their consumption. Patients were not ashamed to talk about alcohol (99.2 %) and found their general practitioner to be competent on this topic (100 %). In multivariate analysis, independent factors associated with a good general practitioner knowledge about their patients' current consumption were the questions put forward by their general practitioner about alcohol consumption during their first visit (P0.001) and during subsequent visits (P0.001).This study showed a low general practitioner screening rate of their patients' at-risk drinking. Only a minority of patients, including at-risk drinkers, declared that their general practitioner was aware of their level of alcohol consumption. Screening could be improved by being systematized during initial consultations and regularly scheduled during subsequent visits, especially in at-risk situations.

AIM: To evaluate the pCR rate and toxicity of the addition of weekly carboplatin (Cp) to paclitaxel (wP) and dose-dense (dd) epirubicin/cyclophosphamide (EC) in an open-label phase II study in TNBC patients. METHODS: Patients were included if they had stage II and III TNBC and received wP (80 mg/m2/week) concurrent with weekly Cp (AUC = 2) for 12 weeks, followed by bi-weekly epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) plus granulocyte colony-stimulating factor (G-CSF) for four cycles, followed by surgery. The primary endpoint was the rate of pCR [(ypT0/isypN0)]. Secondary endpoints included safety and drug delivery. RESULTS: Sixty-three eligible patients were included. Median age was 51 years (range 29-74); 88.9% had stage II disease, 46% were clinically node positive, and 77.8% had grade 3 tumors. Fifty-four percent achieved a pCR. Twelve percent missed two or more doses of wP, whereas at least two cycles of EC were missed in 9.5%. The rate of tolerance without delays or dose reductions is very low (16%). Sixty-two percent had G3/4 neutropenia. Febrile neutropenia occurred in 18 patients of which more than eighty percent occurred during EC despite primary prophylaxis with G-CSF. Thrombocytopenia grade 3/4 was noticed in 11 pts. Three patients developed grade 3 peripheral neuropathy. CONCLUSION: The addition of weekly carboplatin to neoadjuvant paclitaxel and dd EC leads to a pCR rate comparable to prior studies (54%). However, hematological toxicity and febrile neutropenia rate was unexpectedly high. Future investigations could focus on reversing the sequence, which may lead to better hematological tolerability.

La pandémie a mis à l’épreuve notre pays. Les décisions sont difficiles à prendre lorsqu’il faut gérer ce qui s’apparente à une catastrophe et lorsque les données scientifiques sont à l’origine pauvres et changeantes. Comme dans toute situation de crise, les défauts des systèmes et des organisations se révèlent alors au grand jour. Je ne parle pas ici des défauts du miroir médiatique qui sème et accroît la confusion en invitant moult experts médicaux autoproclamés à répandre leurs opinions hétéroclites, ou à inventer de nouveaux gourous qui, forts de leur fatuité, s’ingénient à réduire le débat scientifique à une autopromotion débridée. Les défauts du système de santé français sont plus profonds et plus structurels. Ils procèdent d’un hospitalocentrisme renouvelé, qui est d’autant plus décalé que la crise démontre qu’il est à l’évidence inadapté à la situation. L’article de J.S. Cadwallader et coll. dans ce numéro montre de manière éclatante qu’un raisonnement épidémiologique prenant en compte les soins de première ligne (soins premiers/primaires) aurait pu aboutir à une prise de conscience beaucoup plus concrète et réelle de l’ampleur de l’épidémie, et à une prédiction plus anticipée de l’ampleur de la vague hospitalière. Il permet de réfléchir à l’inadéquation de l’organisation et des moyens dévolus à la recherche, complètement axés sur les soins tertiaires sans tenir compte de la nature des questions de recherche qui concernent la prise en charge des patients en première ligne. Un système de santé devrait marcher sur ses deux jambes, entre soins de première ligne et soins de troisième ligne, avec une deuxième ligne qui permet une interface. Une logique organisationnelle cohérente a été très bien résumée dans le manifeste pour un système de santé organisé, publié par toutes les composantes de la médecine générale réunies au sein du Collège de la discipline1. Ces préconisations s’appuient sur les données scientifiques internationales2. Malheureusement, l’épidémie n’a pas réduit le déséquilibre du système de santé, rien n’est fait pour réduire le handicap de la première ligne. Il est frappant de considérer que, malgré la ritournelle du « virage ambulatoire », la part des dépenses de santé relatives à la médecine de première ligne poursuit sa diminution constante depuis des années. Quant à la recherche en soins premiers, elle n’est toujours pas structurellement financée, alors que l’argent peut être utilisé avec faste pour financer des études dont les publications prouvent qu’elles servent plus l’intérêt médiatique de leurs auteurs que celui des patients. Pourquoi la réponse à la crise sanitaire est-elle pensée comme militaire, ne prenant en compte que la troisième ligne sans tenir compte de l’offre de soins existant en première ligne, qui s’est organisée et était prête à se mobiliser ? Pourquoi les projets de recherche sont financés en écrasante majorité pour le secteur de troisième ligne ? Pourquoi ceux relatifs à la première ligne, là où les données seraient si importantes à connaître, doivent-ils avoir l’agrément d’une kyrielle de comités successifs et l’aval des responsables de la troisième ligne avant de pouvoir éventuellement voir le jour… sauf évidemment si l’épidémie est finie entre-temps. La recherche en médecine générale doit apporter au système de santé et aux patients les réponses qui leur font cruellement défaut. La crise liée à la Covid a démontré jusqu’à quel point des opinions désolantes pouvaient fleurir en l’absence de ces réponses, désorientant les patients, les médias et l’ensemble de la société. Il est temps de permettre au système de première ligne, et notamment aux médecins généralistes, de structurer l’organisation et le financement d’une recherche universitaire indépendante du système hospitalier.

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Aims Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer. Methods Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m2 once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo. PFS was the primary end-point; key secondary end-points were objective response rate (ORR) and duration of response (DOR). Owing to PLD shortages, enrolment was paused for 13 months; the study was subsequently truncated. Results Two hundred twenty-three patients were enrolled. Median PFS was 7.6 months (95% CI, 7.2–9.0) in the trebananib arm and 7.2 months (95% CI, 4.8–8.2) in the placebo arm, with a hazard ratio of 0.92 (95% CI, 0.68–1.24). However, because the proportional hazards assumption was not fulfilled, the standard Cox model did not provide a reliable estimate of the hazard ratio. ORR in the trebananib arm was 46% versus 21% in the placebo arm (odds ratio, 3.43; 95% CI, 1.78–6.64). Median DOR was improved (trebananib, 7.4 months [95% CI, 5.7–7.6]; placebo, 3.9 months [95% CI, 2.3–6.5]). Adverse events with a greater incidence in the trebananib arm included localised oedema (61% versus 32%), ascites (29% versus 9%) and vomiting (45% versus 33%). Conclusions Trebananib demonstrated anticancer activity in this phase 3 study, indicated by improved ORR and DOR. Median PFS was not improved. No new safety signals were identified. Trial registration: ClinicalTrials.gov , NCT01281254

Resume Introduction L’obtention de la certification conjointe ISO 9001 et 13485 du processus de sterilisation sur notre CHU a conduit a developper une approche statistique des controles realises sur les produits sterilises. Objectifs Determiner une methode statistique adaptee a la production de sterilisation et etablir un plan de controles des unites sterilisees. Tester ce plan de controles pour evaluer son applicabilite et le consolider afin d’integrer les resultats comme indicateurs qualite. Methode Les produits sterilises ont ete repartis par gamme de produits selon le type d’emballage (sachets pelables, conteneurs de sterilisation et emballages souples). La norme AFNOR NFX 06-022 a ete utilisee pour calculer la taille de chaque echantillon a controler. La mise en place du plan de controles par echantillonnage a ete evaluee pendant huit semaines a raison d’une journee de controles par semaine. Resultats Une fois par semaine, les controles visaient 80 sachets, 50 conteneurs et 13 emballages souples. Le temps moyen cumule consacre aux controles etait de 67,5 ± 21,9 minutes par jour. Sur une periode de huit semaines, les controles ont porte sur 649 sachets, 400 conteneurs et 104 emballages souples. Quarante-trois (6,6 %) sachets et un (0,2 %) conteneur etaient non conformes. L’analyse des causes des non-conformites a revele un defaut de pratiques professionnelles. Un rappel des bonnes pratiques de conditionnement et de liberation des produits a permis de reduire les non-conformites. Discussion/conclusion Un plan de controles par echantillonnage selon la norme NFX 06-022 est tout a fait applicable au controle des produits fabriques en sterilisation. Cette demarche permet de s’integrer parfaitement aux exigences de notre referentiel ISO de certification.

The clinical impact of ET-743 (trabectedin; Yondelis) in women with leiomyosarcoma and undifferentiated uterine sarcoma in patients previously treated with chemotherapy is investigated. Current data show a clinical benefit in 2/5 patients, of which 1 had a partial remission during 9 months. Pooling the treatment outcomes with literature data, a response in 5 (38%) of 13 patients and a clinical benefit in 7 (54%) of 13 patients for all high-grade uterine sarcomas is calculated. When only uterine leiomyosarcomas are concerned, response rate is 5 (45%) of 11 patients with a clinical benefit in 7 (64%) of 11 patients. These results on the use of ET-743 in uterine sarcoma patients support the conductance of larger trials.

Convection-enhanced delivery using carboplatin in brainstem glioma models was reported to prolong survival. Functional impairment is of additional importance to evaluate the value of local chemotherapy. We established a neurological scoring system for the rat brainstem glioma model.In 46 male Fisher rats stereotactically 10(5) F-98 cells were implanted at 1.4-mm lateral to midline and at the lambdoid suture using guided screws. Following 4 days local delivery was performed using Alzet pumps (1 microl/h over 7 days) with either vehicle (5% dextrose) or carboplatin via one or two cannulas, respectively. All rats were subsequently tested neurologically using a specified neurological score. In 38 animals survival time was recorded. Representative MR imaging were acquired in eight rats, respectively, at day 12 after implantation. HE staining was used to evaluate tumor extension.Neurological scoring showed significantly higher impairment in the high dose carboplatin group during the treatment period. Survival was significantly prolonged compared to control animals in the high dose carboplatin-one cannula group as well as in both low dose carboplatin groups (18.6 +/- 3 versus 26.3 +/- 9, 22.8 +/- 2, 23.6 +/- 2 days; p0.05). Overall neurological grading correlated with survival time. MR imaging showed a focal contrast enhancing mass in the pontine brainstem, which was less exaggerated after local chemotherapy. Histological slices visualized decreased cellular density in treatment animals versus controls.Local chemotherapy in the brainstem glioma model showed significant efficacy for histological changes and survival. Our neurological grading enables quantification of drug and tumor-related morbidity as an important factor for functional performance during therapy.

Femtosecond degenerate four-wave mixing (fs-DFWM) experiments in CO2 exhibit a strong background due to plasma produced at high intensity (≥20 TW/cm2), when significant molecular alignment is likely to arise. This perturbing phenomenon renders the measurements of alignment very difficult. It is shown that the plasma contribution can be avoided by employing perpendicular polarizations for the two pump pulses. The effect is explained on the basis of the different diffraction angles between signals produced by molecular alignment and plasma. Copyright © 2007 John Wiley & Sons, Ltd.

The work is devoted to interaction-induced magnetoresistance in a two-dimensional electron gas in a Si/SiGe heterostructure. Several types of magnetoresistance behavior are discussed including a magnetoresistance that changes sign with temperature. The data is analyzed using the recent theory of interaction-induced magnetoresistance for arbitrary transport regime and any type of disorder potential.

Amounts of fission-generated platinoids, as recovered from high-level liquid radioactive wastes, could considerably supplement amounts of metals claimed from natural sources. Of particular interest are fission palladium and rhodium, which can be decontaminated from other fission products to a non-hazardous level. What remains is intrinsic radioactivity which is weak in fission palladium, and which in fission rhodium decays to an acceptable level after 30 years. The intrinsic radioactivity should not play a negative role when fission platinoids are applied to nuclear technology. Some non-nuclear applications of fission platinoids may be possible, if irradiation and contamination of personnel as well as uncontrolled release of the platinoids, are avoided.

In the present work we study the electron transport properties of small (≈ 100 nm) ring interferometers fabricated by the local anodic oxidation of a AlGaAs / GaAs heterostructures containing 2D electron gas. Owing to the small size of the rings the Aharonov-Bohm (AB) oscillations in them can be observed at temperatures as high as 9 K. It has been found that the temperature dependence of AB oscillations amplitude in these rings is sensitive to the modification of the microscopic potential realization resulting from thermal recycling of the structure.

We report the first observation of the metal–insulator transition (MIT) in a two-dimensional electron gas (2DEG) in a Si/SiGe heterostructure at zero field. We have performed an analysis of the temperature dependence of conductivity and magnetoresistance of our sample on the metallic side of the transition using recent theories.

We observed a giant positive quasi-classical magnetoresistance (MR) of high mobility 2D electron gas in AlGaAs/GaAs heterostructure. The MR is non-saturating and increases with the magnetic field as ρ xx ∼ B α ( α =0.9–1.2). In antidot lattice a non-monotonic behavior is observed. We show that the MR in both cases is well described by the recently advanced theory by Polyakov et al. (Phys. Rev. B 64 (2001) 205306) where non-saturating positive MR and non-monotonic MR in antidot lattice is predicted as the consequence of concurrent existence of short- and long-range scattering.

Commensurability peaks in new kind of two-dimensional (2D) systems with artificial scatterers—2D electron gas in the array of diffusive and thermalizing scatterers (it was AuGeNi alloy dots)—was studied experimentally. It is shown that the position and the amplitude of these peaks are completely described by the model of pin-ball electron trajectories.

We report magnetotransport properties of electrons in a new kind of two-dimensional electron system (2DES)-a narrow single quantum well with electron density so large that the electrons splash out of the well. We show that the system is a two-component 2D electron gas consisting of very low mobility (μ = × 10 3 cm 2 V - 1 s - 1 ) main part of the electrons and very small fraction (about 1% of all) of the electrons with much higher (10 times) mobility. The anomalous behavior of the magnetoresistance ρ x x and Hall resistance ρ x y of this system was observed. The sharp change of the transport properties at the moment of overfilling of the quantum well gives the possibility to determine the value of the band offset ΔE c on the interface Al 0 . 3 Ga 0 . 7 As/GaAs using the results of the self-consistent calculation of the energy diagram of the studied structure. As the result we have obtained ΔE c = (0.18-0.20)eV. This value is significantly less than the well-known ΔE c = 0.24 eV found in optical experiments.

We evaluated the diagnostic sensitivity of quantitative sensory testing (QST), using the CASE IV system, in 14 patients with clinically diagnosed small-fiber neuropathy and normal traditional electrodiagnostic studies. All patients had at least 1 abnormal threshold, 13 patients had abnormal heat-pain thresholds, 8 had abnormal cold thresholds, and 7 had abnormal vibration thresholds. QST is therefore highly effective in documenting dysfunction in small fiber neuropathy patients.

The state of radiorhodium in liquid waste from processing of spent nuclear fuel was analyzed in detail by ESR and NMR spectroscopy on several nuclei. The most probable oxidation state of rhodium in nitric acid solutions is +3. Three procedures for preparing nitric acid solutions of rhodium were studied. The composition of Rh(III) complexes in these solutions is similar but not identical. The method for identifying the ionic composition of similar objects was proposed. The speciation of rhodium in nitric acid solutions with the acid concentration ranging from 2×10- 2 to 15 M was studied. Polynuclear oligomers with (μ-ONO2)2 bridges, mainly tetramers, are formed in solutions with CRh > 2 M, [NO3 -] ≥ 8 M, and [H+] ≥ 0.7 M. At CRh = (1-2)×10- 2, [NO3 -] = 1-4 M, and [H+] = 0.4-4 M, the (μ-OH, μ-ONO2) dimer and trimer prevail; at [NO3 -] < 1 M and [H+] < 0.2 M, the (μ-OH, μ-ONO2) dimer dominates. No Rh(III) aqua ion and no monomeric nitrate complexes were detected in the quasiequilibrium system at any concentrations of the components. In nitrate-nitrite solutions, both “subnitrated” (μ-OH, μ-ONO2) Rh(III) oligomers and mononuclear Rh(III) nitroaqua complexes exist. The equilibrium between these species is attained very slowly and depends on the equilibrium concentration of nitrite anion. Forecast was given on isolation of rhodium from nitric acid solutions of SNF by extraction, ion-exchange, electrolytic, and precipitation procedures.

The rate of the reaction 2Rh(H2O)63+ + XeF2 = 2Rh(OH)3+ + Xe + 2HF + 4H+ + 6H2O is described by the second-order equation -d[Rh(III)]/dt = k1[Rh(III)][XeF2], where k1 = 15.4±0.8 l mol-1 min-1 at 17.8°C and the solution ionic strength μ = 2. The activation energy of the reaction is E1 = 60.6±1.0 kJ mol-1. This reaction is complicated by the parallel hydrolysis reaction 2XeF2 + 2H2O = 2Xe + O2 + 4HF. The reaction mechanism includes a slow stage of H atom transfer from Rh(H2O)63+ to XeF2 molecule with formation of XeF. radical as an intermediate. The subsequent stages of Rh(H2O)5(OH)3+ hydrolysis and reduction of XeF· radical to Xe proceed rapidly.

In order to use low-level fission palladium in technology, the paladium must be purified to a high degree with respect to foreign radionuclides with close chemical properties—ruthenium, antimony, and silver. The results of a simulation of an optimized two-cycle extraction scheme for extracting and refining palladium on the basis of one extractant—an aromatic solution of petroleum sulfides: first cycle with nitrate and second cycle with chloride system—are examined. The behavior of trace concentrations of silver is investigated and it is shown that total deep removal of silver from palladium of not less than 4.107–40 in the first cycle and 106 in the second cycle with a small number of extraction, washing, and reextraction steps can be attained. 2 figures, 3 tables, 6 references.

Reinforcement with muscle, cotton, fibrin glue, or some other material is an alternative to clipping in some intracranial aneurysms1; the surgeon must balance the need to create local inflammation (to reinforce the arterial wall) with the risk that the inflammation will spread and damage adjacent structures. Wrapping of clinoidal aneurysms, in particular, rarely may produce delayed and severe visual loss or ocular motor dysfunction.2–7 The clinical course and potential outcome of damage to the visual pathway, ocular motor tracts, or both remains controversial, as does the optimum management when visual loss occurs. We present the case of a patient who developed severe bilateral visual loss and neuroimaging evidence of inflammation in the paraclinoid and suprasellar regions 2 months after wrapping of bilateral clinoidal aneurysms with cotton and fibrin glue, but who recovered visual function and whose neuroimaging appearance improved after treatment with systemic corticosteroids. A 61 year old woman underwent magnetic resonance imaging (MRI) and angiography after experiencing a minor stroke. The studies revealed aneurysms of the clinoidal portion of both internal carotid arteries. Endovascular treatment was unsuccessful. Accordingly, craniotomy was performed. As neither aneurysm could be clipped, both were wrapped with cotton gauze saturated with fibrin glue. The patient did well postoperatively until 2 months after surgery, when she noted blurred vision in the right eye. An incomplete left …

International audience; Contexte. La qualité des soins est devenue une exigence sociétale. L'OMS a défini des objectifs d'efficacité des processus d'apprentissage. Les savoirs disciplinaires acquis sont insuffisants pour agir professionnellement lors des situations réelles de soin. Un troisième cycle de médecine générale professionnalisant doit former aux compétences indispensables du médecin généraliste (MG). Pour basculer des méthodes pédagogiques centrées sur l'enseignement vers l'approche centrée sur les apprentissages dans une logique de compétence, il est nécessaire de définir et décrire ces compétences. Objectifs. Définir et décrire précisément les compétences du MG. Méthode. Consensus d'experts. Un groupe de recherche national a été créé, issu de plusieurs départements de médecine générale, dont les membres se réunissaient trimestriellement. Chacun des membres avait pour tâche de coordonner les recherches d'un groupe régional autour d'une compétence. Le groupe national a travaillé en recherchant un consensus à partir des données proposées par les groupes régionaux et des données de la littérature. Résultat. Six compétences génériques transversales ont été décrites, recouvrant la totalité des tâches et fonctions du médecin généraliste. Une définition précise de chaque compétence et une description des capacités les constituant a été réalisée. Une représentation graphique a été proposée pour en faciliter l'appropriation. Conclusion. Selon les données de la littérature, il faut décrire préalablement les compétences pour envisager un parcours de développement de ces dernières. C'est ce qu'ont tenté de faire les différentes disciplines qui ont publié un référentiel de compétences. Le travail rapporté ici se poursuivra par la recherche de niveaux de compétence et d'indicateurs de ces niveaux. Ces travaux permettront d'envisager l'élaboration d'outils d'évaluation et de certification des compétences.

International audience; Contexte. Les tâches et fonctions des médecins généralistes sont connues et publiées. Les six compétences permettant de les réaliser efficacement sont décrites. Il manque encore la description d'un modèle de développement de ces compétences et des indicateurs de niveau. La littérature propose de commencer par faire élaborer un parcours théorique par les experts de la discipline puis de le faire valider en l'utilisant avec les étudiants. Objectifs. Décrire des niveaux pour les compétences à acquérir au cours du troisième cycle de médecine générale. Méthodes. Consensus non formalisé d'experts. Un groupe de recherche national issu de plusieurs départements de médecine générale a été créé. Ses membres se sont réunis trimestriellement. Chacun des membres avait pour tâche de coordonner les recherches d'un groupe régional autour d'une compétence. Le groupe national a travaillé en recherchant un consensus à partir des données proposées par les groupes régionaux et les données de la littérature. Résultats. Trois niveaux ont été décrits dans le troisième cycle de médecine générale : novice, intermédiaire et compétent. Pour chacune des six compétences, les trois niveaux ont été déclinés en descripteurs à l'issue de leur analyse. Chaque descripteur a lui-même été explicité par plusieurs indicateurs. Conclusion. Ce travail a permis de décrire précisément trois niveaux de compétences attendus au cours du cursus de DES de médecine générale. Dans chaque niveau, des descriptions des attributs ont été proposées. Elles pourront permettre aux départements de médecine générale de créer des outils d'évaluation des internes.

The experimentally determined total purification factors for palladium relative to silver (first cycle 102, second cycle >103) and rhodium and ruthenium (first cycle >104, second cycle >10) are greater than 105. In connection with the insufficient sensitivity of the atomic absorption method for monitoring and the relatively high value from the control run, we could not determine the true values of the purification factors in some operations of the second extraction cycle and for precipitation of palladosammine. The noted chemical aspects of the behavior of precious metals in extraction systems with petroleum sulfides lead to an estimate of the purification factors for palladium at the 108 level. In particular, the total purification factors increase by 10–100 times when the extraction is carried out in both cycles with W:O=10:1 (F=(W:O)/Dj, where j is the component to be separated [10]). Larger-scale laboratory testing of the proposed flow diagram for recovery and refining of palladium using Ag, Pd, Ru, Rh, and Sb will allow us to experimentally confirm that such estimates are realistic.

Degradation of tetrachloroethene (perchloroethylene, PCE) was investigated by combining the metabolic abilities of anaerobic bacteria, capable of reductive dechlorination of PCE, with those of aerobic methanotrophic bacteria, capable of co-metabolic degradation of the less-chlorinated ethenes formed by reductive dechlorination of PCE. Anaerobic communities reductively dechlorinating PCE, trichloroethene (TCE) and dichloroethenes were enriched from various sources. The maximum rates of dechlorination observed for various chloroethenes in these batch enrichments were: PCE to TCE (341 mu mol l(-1) day(-1)), TCE to cis-dichloroethene (159 mu mol l(-1) day(-1)), cis-dichloroethene to chloroethene (99 mu mol l(-1) day(-1)) and trans-dichloroethene to chloroethene (22 mu mol l(-1) day(-1)). A mixture of these enrichments was inoculated into an anoxic fixed-bed upflow column. In this column PCE was converted mainly into cis-1,2-dichloroethene, small amounts of TCE and chloroethene, and chloride. Enrichments of aerobic methanotrophic bacteria were grown in an oxic fixed-bed downflow column. Less-chlorinated ethenes, formed in the anoxic column, were further metabolized in this oxic methanotrophic column. On the basis of analysis of chloride production and the disappearance of chlorinated ethenes it was demonstrated that complete degradation of PCE was possible by combining these two columns. Operation of the two-column system under various process conditions indicated that the sensitivity of the methanotrophic bacteria to chlorinated intermediates represented the bottle-neck in the sequential anoxic/oxic degradation process of PCE.

Multibeam bathymetry and gravity data have been obtained along an ∼800-km-long section of the Mid-Atlantic Ridge from just south of the Hayes fracture zone at 33°N to the northern edge of the Azores Platform near 40°N. A three-dimensional analysis of these gravity and topography data, combined with results from earlier seismic refraction studies in this area, reveal two different scales of crustal heterogeneity. A systematic, along-axis, segment-scale (λ 8–9 km) near the middle of spreading segments and the thinnest crust (

The high affinity immunoglobulin E receptor (Fc epsilon RI) and the B and T cell antigen receptors (TCR) are multimeric complexes containing subunits with cytoplasmic antigen recognition activation motifs (ARAMs). The presence of multiple motifs may be a way to amplify a single signal or provide independent activation modules. Here we have compared the signaling capacity of the same Fc epsilon RI gamma motif in the context of two different receptors, Fc epsilon RI and TCR/CD3, simultaneously reconstituted on the surface of the same zeta-deficient T cell line. Both reconstituted receptors mediate early (phosphorylation) and late (interleukin [IL]-2 release) signals. Mutation of the two tyrosine residues of ARAM gamma alters early signaling by both receptors, but the set of substrates phosphorylated via ARAM gamma is different for each receptor and is thus dependent on the receptor context. Furthermore, the mutations prevent Fc epsilon RI- but not TCR/CD3-mediated IL-2 release. These data demonstrate that ARAM gamma is necessary for allowing both receptors to phosphorylate the complete set of substrates, and that the CD3 complex, unlike the Fc epsilon RI beta chain, contains activation modules capable of compensating for the absence of a functional ARAM gamma in generating late signals such as IL-2 release.

International audience; Le système de santé français est actuellement en pleine évolution afin de répondre aux enjeux actuels de qualité et de coût des soins. Parallèlement, la médecine générale connaît un gain accru d'attention de la part des institutions nationales.Ce document reflète l'analyse de l'organisation des soins primaires en France par un groupe d'experts réuni sous l'égide du Collège national des généralistes enseignants. À partir d'une revue de la littérature, il présente les définitions retenues pour les soins primaires et la médecine générale dans le monde et en France. Dans un deuxième temps, il expose les missions qui leur sont dévolues et aborde la question de leur efficience. Enfin, il dresse le constat des initiatives actuelles dans ce champ du soin en France.

The article summarizes experiments performed on the extraction of palladium from spent nuclear fuels. Palladium extraction from high-level nitric acid solutions was performed using diesel fuels and petroleum sulfides. Petroleum sulfide extraction systems with aromatic solvents provided the highest selectivity for palladium. Experimental results for refinement of palladium after extraction are also summarized. 14 refs., 4 tabs.