CEA Valduc

CEA designs, develops, and manufactures targets, especially equation of state targets, to be experimented on the LMJ (Laser MegaJoule) facility. For this type of target, the dimensional properties of the components must be perfectly known. However, conventional instruments can have limitations in their capabilities to measure thickness and flatness for the thinnest membranes. To overcome this situation, dedicated equipment has been developed using two chromatic confocal probes. This development required studying all sources of measurement errors and implementing specific procedures to reduce them. Applications are shown to demonstrate the capabilities and performances of this instrument.

Abstract. Marine sediments can be used to reconstruct the evolution of seawater [SO42-] and δ34S over time, two key parameters that contribute to refine our understanding of the sulfur cycle and thus of Earth's redox state. δ34S evolution can be measured from carbonates, barites and sulfate evaporites. [SO42-] variations can be reconstructed using fluid inclusions in halites, a method that only allows a low-resolution record. Reconstruction of the past sulfur cycle could be improved if carbonates allowed the tracking of both seawater δ34S and [SO42-] variations in a sole, continuous sedimentary repository. However, most primary carbonates formed in the ocean are biogenic, and organisms tend to overprint the geochemical signatures of their carbonates through a combination of processes often collectively referred to as vital effects. Hence, calibrations are needed to allow seawater δ34S and [SO42-] reconstructions based on biogenic carbonates. Because foraminifera are important marine calcifiers, we opted to focus on calcite synthesized by individuals of rosalinid benthic foraminifera cultured in the laboratory under controlled conditions, with varying seawater [SO42-] (ranging from 0 to 180 mM). Our experimental design allowed us to obtain foraminiferal asexual reproduction over several generations. We measured bulk carbonate-associated sulfate (CAS) content and sulfur isotopic composition (δ34SCAS) on samples of tens to hundreds of specimens from a selection of culture media, where [SO42-] varied from 5 to 60 mM. Increasing or decreasing [SO42-] with respect to modern-day seawater concentration (28 mM) impacted foraminiferal population size dynamics and the total amount of bioprecipitated carbonate. Foraminiferal CAS concentration increased proportionally with [SO42-] concentration from 5 mM up to 28 mM and then showed a plateau from 28 to 60 mM. The existence of a threshold at 28 mM is interpreted as the result of a control on the precipitation fluid chemistry that foraminifera exert on the carbonate precipitation loci. However, at high seawater sulfate concentrations (> 40 mM) the formation of sulfate complexes with other cations may partially contribute to the non-linearity of the CAS concentration in foraminiferal tests at high increases in [SO42-]. Yet, despite the significant effect of seawater [SO42-] on foraminiferal reproduction and on CAS incorporation, the isotopic fractionation between CAS and seawater remains stable through varying seawater [SO42-]. Altogether, these results illustrate that CAS in biogenic calcite could constitute a good proxy for both seawater [SO42-] and δ34S and suggests that sulfate likely plays a role in foraminiferal biomineralization and biological activity.

Younger survivors of breast cancer frequently report more treatment-related symptoms, mostly related to the menopausal transition. To assess factors associated with chemotherapy-related amenorrhea (CRA) and to evaluate its association with long-term quality of life (QOL). The prospective, longitudinal Cancer Toxicities Study, a multicenter French cohort study, includes women with a diagnosis of stage I to III breast cancer and collects data approximately yearly after diagnosis. The current study reports outcomes up to 4 years after diagnosis for participants enrolled from 2012 to 2017. Participants included premenopausal women younger than 50 years treated with chemotherapy and not receiving adjuvant ovarian function suppression. Data analysis was performed from September 2021 to June 2023. Clinical, socioeconomic, tumor, and treatment characteristics assessed at diagnosis (for the analysis of factors associated with CRA) and persistent CRA (for the QOL analysis). The main outcome of interest was CRA at year 1 (Y1), year 2 (Y2), and year 4 (Y4) after diagnosis. Generalized estimating equations assessed associations of exposure variables with CRA. In the QOL analysis, QOL at Y4 (assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BR23) was the outcome of interest. Multivariable random-effect mixed models assessed the association of persistent CRA (ie, never recovering menses after treatment) with QOL. Among 1636 women, the mean (SD) age at diagnosis was 42.2 (5.6) years. Overall, 1242 of 1497 women (83.0%) reported CRA at Y1, 959 of 1323 women (72.5%) reported it at Y2, and 599 of 906 women (66.1%) reported it at Y4. Older age vs 18 to 34 years (adjusted odds ratio [OR] for 35 to 39 years, 1.84 [95% CI, 1.32 to 2.56]; adjusted OR for 40 to 44 years, 5.90 [95% CI, 4.23 to 8.24]; and adjusted OR for ≥45 years, 21.29 [95% CI, 14.34 to 31.61]) and receipt of adjuvant tamoxifen (adjusted OR, 1.97 [95% CI, 1.53 to 2.53]) were associated with higher likelihood of CRA. In the QOL analysis, 416 of 729 women (57.1%) had persistent CRA. However, late menses recovery among women aged 18 to 34 years with no menses at Y2 were reported by 11 of 21 women (52.4%) between Y2 and Y4. Persistent CRA was associated with worse insomnia (mean difference vs recovery at any time, 9.9 points [95% CI, 3.2 to 16.5 points]; P = .004), systemic therapy-related adverse effects (mean difference, 3.0 points [95% CI, 0.2 to 5.8 points]; P = .04), and sexual functioning (mean difference, -9.2 points [95% CI, -14.3 to -4.1 points]; P < .001) at Y4. In this cohort study of premenopausal women with breast cancer, persistent CRA was common, although some women recovered menses late, and was associated with worse long-term QOL. This study can help inform risk communication, personalized counseling, and early supportive care referrals for such patients.

Fatores afetam o desempenho da fabricação e montagem de estruturas metálicas. Nesse ramo, utilizam largamente a chapa dobrada no aço ASTM A36 e CSN Civil-300 para obter juntas soldadas com qualidade e dois elementos precisam ter baixa variabilidade com limites confiáveis: corrosão e microdureza na junta soldada. Focando, a microdureza e corrosão no perfil dobrado U100x50x3,0 mm e 2,7 mm de espessuras, utilizou-se o processo de soldagem GMAW com proteção gasosa de 75%Ar-25%CO2, arames-eletrodos AWS ER70S-3 e AWS ER70S-6, e parâmetros de soldagem, que permitiram constante densidade de corrente nas juntas soldadas. Analisaram-se a corrosão, utilizando o método de aceleração por névoa salina e a microdureza pela medição de seus valores. Os resultados mostraram que a corrosão no aço CSN Civil-300 obteve a menor perda de massa de 0.0018 mm/ano e a microdureza nessas uniões evidenciou redução média de 13% usando o metal de adição AWS ER70S-3.

3515 Background: Hepatic arterial infusion (HAI) of chemotherapy (CTx) has been proposed as a potential treatment to decrease the risk of hepatic recurrence after resection of colorectal liver metastases (CRLM). Randomized controlled trials (RCTs) led to controversial results and meta-analyses are inconclusive. We conducted a comparative phase II RCT to assess the efficacy of adjuvant HAI oxaliplatin with concomitant intravenous (IV) CTx in pts at high risk of hepatic recurrence (≥4 resected CRLM). Methods: Pts who underwent curative-intent surgery of at least 4 CRLM after preoperative IV CTx were randomly assigned (1:1) to receive adjuvant IV fluorouracil/leucovorin (LV5FU2) combined with oxaliplatin (85mg/m2) by HAI (HAI-IV arm) or IV route (IV arm) every 2 weeks, for at least 3 months to achieve a minimal duration of perioperative CTx of 6 months. The primary endpoint was the hepatic recurrence free survival (h-RFS). Secondary endpoints included the feasibility of delivering at least 4 CTx cycles, toxicity (NCI-CTCAE 4.0) including HAI catheter-related complications, RFS, overall survival (OS) and recurrence pattern. 108 randomized pts were required to detect a gain in 18-month h-RFS from 30% to 50% with a one-sided α risk of 10% and 95% power. The primary endpoint was analyzed with a Cox regression model, with adjustment for stratification factors (tumor response to preoperative CTx and number of resected CRLM). The study was prematurely stopped after randomization of 99 pts due to recruitment issues and HAI catheters market withdrawal. Results: Between Jun 2015 and Dec 2020, 99 pts (median age, 62; median number of CRLM, 5) were randomly assigned in HAI-IV arm (50 pts) or IV arm (49 pts). After a median follow-up of 56 months, the intent-to-treat analysis showed a significantly longer h-RFS in the HAI-IV arm compared to the IV arm (median 25 [16-37] vs 12 months [8-21]; HR 0.598 [95%CI 0.379-0.944], p = 0.027). 5-year h-RFS was 32% [19-45] in the HAI-IV arm vs 13% [4-27] in the IV arm, respectively. Median and 5-year OS were 74 months [51-74] and 60% [43-74] in the HAI-IV arm vs 54 months [37-69] and 46% [29-61] in the IV arm (HR 0.551 [0.299-1.015], p = 0.056). The median number of postoperative CTx cycles was 6 in both groups with 86% and 78% of patients having received at least 4 cycles in HAI-IV and IV arms (p = 0.7), respectively. Grade 3-4 toxicity rate was 58% in the HAI-IV arm vs 31% in the IV arm (p = 0.01). Overall, nine pts (18%) experienced HAI-related complications. No toxic death occurred in both arms. Conclusions: Despite a higher but acceptable toxicity, combination of HAI oxaliplatin with IV LV5FU2 significantly improved h-RFS after curative resection of CRLM in high-risk patients. This combined treatment should be considered as a valid option for these patients. Clinical trial information: NCT02494973 .

Correction to: British Journal of Cancer, published online 16 November 2020 The original version of this article contained an error in an affiliation. Upon careful review of the paper, the authors noticed that the affiliation for Goran Malenkovic was not written correctly. The authors only submitted the following affiliation Gynecologic Oncology Department Clinic for Operative Oncology, Institute of Oncology of Vojvodina, Serbia but they missed to notice that the Faculty of Medicine Novi Sad, University of Novi Sad, Serbia should also be in the affiliation.

&lt;div&gt;Abstract&lt;p&gt;The protein tyrosine phosphatase PTPL1/PTPN13, the activity of which is decreased through allelic loss, promoter methylation, or somatic mutations in some tumors, has been proposed as a tumor suppressor gene. Moreover, our recent clinical study identified PTPL1 expression level as an independent prognostic indicator of a favorable outcome for patients with breast cancer. However, how PTPL1 can affect tumor aggressiveness has not been characterized. Here, we first show that PTPL1 expression, assessed by immunohistochemistry, is decreased in breast cancer and metastasis specimens compared with nonmalignant tissues. Second, to evaluate whether PTPL1 plays a critical role in breast cancer progression, RNA interference experiments were performed in poorly tumorigenic MCF-7 breast cancer cells. PTPL1 inhibition drastically increased tumor growth in athymic mice and also enhanced several parameters associated with tumor progression, including cell proliferation on extracellular matrix components and cell invasion. Furthermore, the inhibition of Src kinase expression drastically blocked the effects of PTPL1 silencing on cell growth. In PTPL1 knockdown cells, the phosphorylation of Src on tyrosine 419 is increased, leading to the activation of its downstream substrates Fak and p130cas. Finally, substrate-trapping experiments revealed that Src tyrosine 419 is a direct target of the phosphatase. Thus, by identification of PTPL1 as the first phosphatase able to inhibit Src through direct dephosphorylation in intact cells, we presently describe a new mechanism by which PTPL1 inhibits breast tumor aggressiveness. Cancer Res; 70(12); 5116–26. ©2010 AACR.&lt;/p&gt;&lt;/div&gt;