La Roumanie et la coopération autour de la mer Noire

L'intérêt manifeste de la Roumanie pour le projet turc de coopération économique entre pays de la mer Noire tient avant tout à sa position géopolitique qui l'a toujours poussée à jouer un rôle d'intermédiaire entre l'Orient et l'Occident. Cependant, les avis restent très partagés quant au degré d'implication dans ce projet. D'une part, les partisans d'une intégration régionale dans le cadre de la ZCEMN, avec des partenaires proches, d'autre part, les défenseurs de la priorité à la candidature à la CEE

Identification of Prognostic Molecular Features in the Reactive Stroma of Human Breast and Prostate Cancer

Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value

Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial.

BACKGROUND: Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%). METHODS AND FINDINGS: This randomized controlled trial included children (0.5-10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥ 99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7 g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥ 99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI -7, 5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥ 99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI -12, 1; p = 0.24). Delayed parasite clearance was associated with the N86YPfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms. A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner. CONCLUSIONS: A simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201102000277177

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Gene expression profiling of the stromal reaction to invasive human breast and prostate cancer

Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and a deeper knowledge of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, for discovering potential therapeutic targets, and for finding a stromal signature that may predict clinical outcome. To selectively address stromal gene expression changes during cancer progression, oligo-based Affymetrix microarray technology was used to analyze laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma in comparison to their normal counterparts. Statistical analysis of the gene expression profile of breast and prostate stroma revealed genes differentially expressed in tumor stroma compared to normal stroma together with genes common to the stromal reaction in both tumor types. Several up and downregulated genes were validated by quantitative real-time RT-PCR and one common upregulated gene, periostin (POSTN), was validated by immunohistochemistry. The tumor-specific stromal genes as well as common stromal genes were observed to cluster breast and prostate cancer patients into two groups with statistically different clinical outcome. Univariate Cox analysis identified the genes whose expression level was most strongly associated with patient survival. Taken together, these observations provide evidence of the implication of the tumor microenvironment in tumor progression and its survival-predictive value

La Roumanie et la coopération autour de la mer Noire

Planche Anne. La Roumanie et la coopération autour de la mer Noire. In: CEMOTI, n°15, 1993. La zone de coopération économique des pays riverains de la Mer Noire. pp. 121-147

Du syndicalisme officiel à Solidarité : les chemins difficiles d'une libération

Nicole Fratellini, Thomas Lowit, Anne Planche From official trade-unions to solidarity There is not one but quite a few different forms of trade-unionism. The polish example leaves no doubt on this bit of evidence. The rupture introduced by Solidarity — an indépendant and self determinated union based, for the first time, on the right to associate — takes on it's full meaning only in reference to the official union model prevailing before august 1980. After having clearly explicited this model, the authors show how a " revo¬ lution " gave birth for fifteen months to an entirely new type of what could be called " control " unionism. Their analysis is all the more convincing that it stands on a broad knowledge of power structure in eastern socialist countries.Il existe non pas un mais des syndicalismes. On le savait déjà mais l'exemple polonais vient rappeler cette évidence avec force. La rupture qu'introduit l'avènement de Solidarité — syndicat indépendant et autogéré — et l'entrée en scène d'un véritable droit d'association pour les travailleurs polonais ne prend tout son sens qu'en référence au modèle du syndicat officiel d'avant août 1980. C'est à l'exploitation de ce modèle puis à celle de la «révolution» qui a donné naissance pour quinze mois à un nouveau type de syndicalisme de contrôle que s'attachent les auteurs de cet article. Leur analyse est d'autant plus fouillée qu'elle s'appuie sur une connaissance approfondie des formes spécifiques du pouvoir dans les pays de l'Est.Lowit Thomas, Planche Anne, Fratellini Nicole. Du syndicalisme officiel à Solidarité : les chemins difficiles d'une libération. In: Sociologie du travail, 24ᵉ année n°3, Juillet-septembre 1982. Lutte sociale en Pologne. pp. 293-308