Stillen als wissenschaftlicher Gegenstand. Epistemologische Überlegungen zur Untersuchung einer "natürlich sozialen Tatsache am Beispiel des medizinischen Diskurses

Im gesellschaftlichen Diskurs um das Stillen ist gegenwärtig, trotz fundierter sozialwissenschaftlicher Kritik, immer noch die Position als hegemonial zu bezeichnen, die das Stillen als die beste Form der Säuglingsernährung sieht. Um die Hintergründe für die Macht dieser Position besser verstehen zu können, befragt der Aufsatz medizinische Publikationen aus über einem Jahrhundert aus der wissenschaftstheoretischen Perspektive der französischen Epistemologie und zeichnet die sich darin zeigende Wissensordnung um das Stillen nach: Wie hat sich das Stillen als wissenschaftlicher Gegenstand infolge der Verwissenschaftlichung der Medizin konstituiert? Wie wurde er im Kontext moderner Dichotomien zwischen dem Natürlichen und dem Sozialen positioniert? Welche Hierarchien wurden damit bedient, stabilisiert oder unterlaufen? Zentral für die Argumentation sind drei Erkenntnishindernisse im Sinne Gaston Bachelards, die im Untersuchungszeitraum des 19. Jahrhunderts eine Verschiebung des Gegenstands Stillen von einer natürlichen zu einer "natürlich sozialen Tatsache" erschwerten: die Hybridität der Medizin als Disziplin, die kumulative Praxis der medizinischen Forschung und ihr Fokus auf die Mutter-Kind-Dyade.Although the social sciences have over the years expressed well-founded criticism, in the contemporary public discourse in Germany breastfeeding is still considered to be the best way to feed a baby. In order to be able to better understand why this is the case, this article discusses material taken from the medical discourse in Germany during the late 19th and 20th century while exploring the potential of the epistemological concept of rupture, which originates in the French sociological tradition. The following questions will be answered: How was breastfeeding constituted as a scientific subject of research during the process of scientification of medicine? Where did this scientific subject of research end up caught between the social and the natural? What kinds of hierarchy were stabilized or subverted as a result? This line of reasoning sheds light on three epistemological obstacles which exacerbate breastfeeding shifting from being a natural to becoming a naturally social fact in the period investigated: medicine as a hybrid discipline, cumulative practices of medical research and its focus on the dyad of mother and child

Approches à base de fréquences pour la simplification lexicale

National audienceLa simplification lexicale consiste à remplacer des mots ou des phrases par leur équivalent plus simple. Dans cet article, nous présentons trois modèles de simplification lexicale, fondés sur différents critères qui font qu'un mot est plus simple à lire et à comprendre qu'un autre. Nous avons testé différentes tailles de contextes autour du mot étudié : absence de contexte avec un modèle fondé sur des fréquences de termes dans un corpus d'anglais simplifié ; quelques mots de contexte au moyen de probabilités à base de n-grammes issus de données du web ; et le contexte étendu avec un modèle fondé sur les fréquences de cooccurrences. ABSTRACT Studying frequency-based approaches to process lexical simplification Lexical simplification aims at replacing words or phrases by simpler equivalents. In this paper, we present three models for lexical simplification, focusing on the criteria that make one word simpler to read and understand than another. We tested different contexts of the considered word : no context, with a model based on word frequencies in a simplified English corpus ; a few words context, with n-grams probabilites on Web data, and an extended context, with a model based on co-occurrence frequencies. MOTS-CLÉS : simplification lexicale, fréquence lexicale, modèle de langue

Natalizumab alters the TCR repertoire after one year of treatment in four MS patients

International audiencen.

Macrophage-induced blood vessels guide Schwann cell-mediated regeneration of peripheral nerves

The peripheral nervous system has remarkable regenerative capacities in that it can repair a fully cut nerve. This requires Schwann cells to migrate collectively to guide regrowing axons across a 'bridge' of new tissue, which forms to reconnect a severed nerve. Here we show that blood vessels direct the migrating cords of Schwann cells. This multicellular process is initiated by hypoxia, selectively sensed by macrophages within the bridge, which via VEGF-A secretion induce a polarized vasculature that relieves the hypoxia. Schwann cells then use the blood vessels as "tracks" to cross the bridge taking regrowing axons with them. Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair. This study provides important insights into how the choreography of multiple cell-types is required for the regeneration of an adult tissue

Study of Ether-, Alcohol-, or Cyano-Functionalized Ionic Liquids Using Inverse Gas Chromatography

This article discusses the study of ether-, alcohol, or cyano-functionalized ionic liquids using inverse gas chromatography

POSEIDON Trial Phase 1b Results: Safety, Efficacy and Circulating Tumor DNA Response of the Beta Isoform-Sparing PI3K Inhibitor Taselisib (GDC-0032) Combined with Tamoxifen in Hormone Receptor Positive Metastatic Breast Cancer Patients.

PURPOSE: The strategy of combining endocrine therapy with PI3K-mTOR inhibition has shown promise in estrogen receptor (ER)-positive breast cancer, but new agents and combinations with a better therapeutic index are urgently needed. Taselisib is a potent, selective, beta-isoform-sparing PI3 kinase inhibitor. PATIENTS AND METHODS: 30 patients with ER-positive, metastatic breast cancer who had failed prior endocrine therapy were treated with escalating doses of taselisib (2 or 4 mg in an intermittent or continuous schedule) combined with tamoxifen 20 mg once daily in this phase 1b study using a "rolling six" design. RESULTS: Taselisib combined with tamoxifen was generally well tolerated, with treatment-emergent adverse events as expected for this class of drugs, including diarrhea (13 patients, 43%), mucositis (10 patients, 33%), and hyperglycemia (8 patients, 27%). No dose-limiting toxicities were observed. Objective responses were seen in 6 of 25 patients with RECIST-measurable disease (ORR 24%). Median time to disease progression was 3.7 months. Twelve of 30 patients (40%) had disease control for 6 months or more. Circulating tumor (ct)DNA studies using next-generation tagged amplicon sequencing identified early indications of treatment response and mechanistically relevant correlates of clinical drug resistance (e.g., mutations in KRAS, ERBB2) in some patients. CONCLUSIONS: Taselisib can be safely combined with tamoxifen at the recommended phase 2 dose of 4 mg given once daily on a continuous schedule. Preliminary evidence of antitumor activity was seen in both PIK3CA mutant and wild-type cancers. The randomized phase 2 part of POSEIDON (testing tamoxifen plus taselisib or placebo) is currently recruiting

µ-Calpain Conversion of Antiapoptotic Bfl-1 (BCL2A1) into a Prodeath Factor Reveals Two Distinct alpha-Helices Inducing Mitochondria-Mediated Apoptosis

Anti-apoptotic Bfl-1 and pro-apoptotic Bax, two members of the Bcl-2 family sharing a similar structural fold, are classically viewed as antagonist regulators of apoptosis. However, both proteins were reported to be death inducers following cleavage by the cysteine protease µ-calpain. Here we demonstrate that calpain-mediated cleavage of full-length Bfl-1 induces the release of C-terminal membrane active α-helices that are responsible for its conversion into a pro-apoptotic factor. A careful comparison of the different membrane-active regions present in the Bfl-1 truncated fragments with homologous domains of Bax show that helix α5, but not α6, of Bfl-1 induces cell death and cytochrome c release from purified mitochondria through a Bax/Bak-dependent mechanism. In contrast, both helices α5 and α6 of Bax permeabilize mitochondria regardless of the presence of Bax or Bak. Moreover, we provide evidence that the α9 helix of Bfl-1 promotes cytochrome c release and apoptosis through a unique membrane-destabilizing action whereas Bax-α9 does not display such activities. Hence, despite a common 3D-structure, C-terminal toxic domains present on Bfl-1 and Bax function in a dissimilar manner to permeabilize mitochondria and induce apoptosis. These findings provide insights for designing therapeutic approaches that could exploit the cleavage of endogenous Bcl-2 family proteins or the use of Bfl-1/Bax-derived peptides to promote tumor cell clearance

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management