Étude exploratoire portant sur le support des directions d'entreprises aux équipes virtuelles de projet

Les équipes virtuelles de projet sont de plus en plus populaires dans les entreprises d'aujourd'hui. Cet état de fait est le fruit d'une adaptation à laquelle doivent faire face les organisations pour rencontrer les nouvelles exigences de l'environnement qui sont engendrées par l'internationalisation des marchés et le développement des nouvelles technologies de l'information et des communications. S'il existe un bon nombre de publications sur les dynamiques propres à l'équipe virtuelle, peu d'auteurs se sont réellement intéressés à la notion de support organisationnel aux équipes virtuelles, qui oeuvrent dans un contexte spécifique de gestion de projet. Pour pallier ce manque de connaissances, cette recherche se concentre sur le support de la direction comme facteur-clé de succès de l'équipe virtuelle de projet. Plus précisément, elle tentera de découvrir comment la direction soutient ses équipes virtuelles de projet et d'identifier les principaux systèmes et mécanismes de support qui sont mis en place par l'organisation. Cette recherche s'appuie sur des données qualitatives. Deux études de cas ont été réalisées auprès d'entreprises oeuvrant dans le secteur des technologies. Pour chacune des entreprises participantes, des entrevues en profondeurs ont été réalisées avec différents acteurs impliqués dans un projet déterminé. Par la suite, une analyse interne a été réalisée pour chacun des cas à partir des entrevues. Une analyse comparative a permis de faire ressortir les similitudes et les différences entre les deux organisations. Les résultats sont ensuite discutés et des tendances générales de support organisationnel aux équipes virtuelles de projet sont identifiées. Finalement, les contributions théoriques et pratiques ainsi que les limites et pistes de recherche futures de cette recherche sont exposées. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Gestion de projet, Équipe virtuelle, Support organisationnel

Activity of EGFR Tyrosine Kinase Inhibitors in NSCLC With Refractory Leptomeningeal Metastases

International audienc

Molecular Level Characterization of the Structure and Interactions in Peptide-Functionalized Metal-Organic Frameworks

We use density functional theory, newly parameterized molecular dynamics simulations, and last generation N-15 dynamic nuclear polarization surface enhanced solid-state NMR spectroscopy (DNP SENS) to understand graft-host interactions and effects imposed by the metal-organic framework (MOF) host on peptide conformations in a peptide-functionalized MOF. Focusing on two grafts typified by MIL-68-proline (-Pro) and MIL-68-glycine-proline (-Gly-Pro), we identified the most likely peptide conformations adopted in the functionalized hybrid frameworks. We found that hydrogen bond interactions between the graft and the surface hydroxyl groups of the MOF are essential in determining the peptides conformation(s). DNP SENS methodology shows unprecedented signal enhancements when applied to these peptide-functionalized MOFs. The calculated chemical shifts of selected MIL-68-NH-Pro and MIL-68-NH-Gly-Pro conformations are in a good agreement with the experimentally obtained (NNMR)-N-15 signals. The study shows that the conformations of peptides when grafted in a MOF host are unlikely to be freely distributed, and conformational selection is directed by strong host-guest interactions

Systematic Review of topotecan (Hycamtin) in relapsed small cell lung cancer

Background: To undertake a systematic review of the available data for oral and intravenous topotecan in adults with relapsed small cell lung cancer (SCLC) for whom re-treatment with the first line regimen is not considered appropriate. Methods: We searched six databases from 1980 up to March 2009 for relevant trials regardless of language or publication status. Relevant studies included any randomised trial of any chemotherapeutic treatment against any comparator in this licensed indication. Where possible we used apposite quantitative methods. Where meta-analysis was considered unsuitable for some or all of the data, we employed a narrative synthesis method. For indirect comparisons we used the method of Bucher et al., where available data allowed it, otherwise we used narrative descriptions. Results: Seven unique studies met the inclusion criteria, four of which could be used in our analyses. These included one study comparing oral topotecan plus best supportive care (BSC) to BSC alone, one study comparing intravenous topotecan to cyclophosphamide, adriamycin and vincristine (CAV), and two studies comparing oral topotecan with intravenous topotecan. All four studies appear to be well conducted and with low risk of bias. Oral topotecan plus BSC has advantages over BSC alone in terms of survival (hazard ratio = 0.61; 95% CI, 0.43 to 0.87) and quality of life (EQ-5 D difference: 0.15; 95% CI, 0.05 to 0.25). Intravenous topotecan was at least as effective as CAV in the treatment of patients with recurrent small-cell lung cancer and resulted in improved quality-of-life with respect to several symptoms. CAV was associated with significantly less grade 4 thrombocytopenia compared with IV topotecan (risk ratio = 5.83; 95% CI, 2.35 to 14.42). Survival (hazard ratio = 0.98; 95% CI, 0.77 to 1.25) and response (pooled risk ratio = 1.04; 95% CI, 0.58 to 1.85) data were similar for the oral and IV topotecan groups. Symptom control was also very similar between the trials and between the oral and IV groups. Toxicity data showed a significant difference in favour of oral topotecan for neutropenia (pooled risk ratio = 0.65; 95% CI, 0.47 to 0.89). Indirect evidence showed that oral topotecan was at least as good as or better than CAV on all outcomes (survival, response rates, toxicities, and symptoms) that allowed indirect comparisons, with the only exception being grade four thrombocytopenia which occurred less often on CAV treatment. Conclusions: Concerning topotecan both the oral and intravenous options have similar efficacy, and patient preference may be a decisive factor if the choice would be between the two formulations. The best trial evidence for decision making, because it was tested versus best supportive care, exists for oral topotecan. Indirectly, because we have two head-to-head comparisons of oral versus intravenous topotecan, and one comparison of intravenous topotecan versus CAV in similar patients as in the trial against best supportive care, one might infer that IV topotecan and CAV could also be superior to best supportive care, and that oral topotecan has similar effects to CAV with possibly better symptom control. From the evidence discussed above, it is evident that oral topotecan has similar efficacy to IV topotecan (direct comparison) and CAV (indirect comparison). There is no further evidence base of direct or possible indirect comparisons for other comparators than CAV of either oral or IV topotecan

PLoS One

Compared to the general population, HIV-infected patients are at higher risk of developing non-AIDS-defining cancers. Chronic HCV infection has also been associated with a higher risk than that of the general population of developing cancers other than hepatocarcinoma. Evaluation of the impact of HCV-related factors on non-AIDS-defining and non HCV-liver (NANL) related cancers among HIV/HCV co-infected patients are scarce. The aim of this study was to identify the impact of HIV/HCV clinical characteristics on NANL related cancers in a large cohort of HIV/HCV-coinfected patients followed from 2005 to 2017. Cox proportional hazards models with delayed entry were used to estimate factors associated with NANL related cancer. Among 1391 patients followed for a median of 5 years, 60 patients developed NANL related cancers, yielding an incidence rate of 8.9 per 1000 person-years (95% CI, [6.6-11.1]). By final multivariable analysis, after adjustment for sex, tobacco or alcohol consumption, baseline CD4 cell count and HCV sustained viral response (SVR), age and a longer duration since HIV diagnosis were independently associated with a higher risk of NANL related cancer (aHR for each additional year 1.10, 95% CI 1.06-1.14, p<0.0001 and 1.06, 95% CI 1.01-1.11, p = 0.02, respectively). Duration of HCV infection, cirrhosis, HCV viral load, genotype and SVR were not associated with the occurrence of NANL related cancer. Among HIV/HCV-coinfected patients, age and the duration of HIV infection were the only characteristics found to be associated with the occurrence of NANL related cancer. In contrast, no association was observed with any HCV-related variables

The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): Early findings, 2006-2010

<p>Abstract</p> <p>Background</p> <p>In France, it is estimated that 24% of HIV-infected patients are also infected with HCV. Longitudinal studies addressing clinical and public health questions related to HIV-HCV co-infection (HIV-HCV clinical progression and its determinants including genetic dimension, patients' experience with these two diseases and their treatments) are limited. The ANRS CO 13 HEPAVIH cohort was set up to explore these critical questions.</p> <p>To describe the cohort aims and organization, monitoring and data collection procedures, baseline characteristics, as well as follow-up findings to date.</p> <p>Methods</p> <p>Inclusion criteria in the cohort were: age > 18 years, HIV-1 infection, chronic hepatitis C virus (HCV) infection or sustained response to HCV treatment. A standardized medical questionnaire collecting socio-demographic, clinical, biological, therapeutic, histological, ultrasound and endoscopic data is administered at enrolment, then every six months for cirrhotic patients or yearly for non-cirrhotic patients. Also, a self-administered questionnaire documenting socio-behavioral data and adherence to HIV and/or HCV treatments is administered at enrolment and yearly thereafter.</p> <p>Results</p> <p>A total of 1,175 patients were included from January 2006 to December 2008. Their median age at enrolment was 45 years and 70.2% were male. The median CD4 cell count was 442 (IQR: 304-633) cells/μl and HIV RNA plasma viral load was undetectable in 68.8%. Most participants (71.6%) were on HAART. Among the 1,048 HIV-HCV chronically co-infected patients, HCV genotype 1 was predominant (56%) and cirrhosis was present in 25%. As of January, 2010, after a median follow-up of 16.7 months (IQR: 11.3-25.3), 13 new cases of decompensated cirrhosis, nine hepatocellular carcinomas and 20 HCV-related deaths were reported, resulting in a cumulative HCV-related severe event rate of 1.9/100 person-years (95% CI: 1.3-2.5). The rate of HCV-related severe events was higher in cirrhotic patients and those with a low CD4 cells count, but did not differ according to sex, age, alcohol consumption, CDC clinical stage or HCV status.</p> <p>Conclusion</p> <p>The ANRS CO 13 HEPAVIH is a nation-wide cohort using a large network of HIV treatment, infectious diseases and internal medicine clinics in France, and thus is highly representative of the French population living with these two viruses and in care.</p

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Evaluation environnementale des perspectives de valorisation en BTP de scories de première fusion de plomb et de zinc.

Cette recherche s\u27inscrit dans la problématique de l\u27évaluation environnementale de matériaux poreux de BTP contenant des déchets. Le cas de deux scories de première fusion de plomb et de zinc, utilisées en substitut partiel au sable dans trois matériaux (béton, sable-ciment et sable-bitume) a été étudié. La méthodologie utilisée, basée sur la prénorme ENV 12-920, prend en compte les propriétés du matériau et les conditions du scénario, elle a 4 niveaux: (1) description du scénario (2) détermination de l\u27influence des paramétres pertinents sur le comportement à la lixiviation du matériau (3) description de modèles de comportement environnemental (4) validation in situ des modèles. De manière générale, le relargage du plomb et du zinc des scories contenues dans les matériaux étudiés, est fortement liée à l\u27évolution du pH près de l\u27interface, celui-ci étant le résultat des interactions matériau-scénario. Ainsi, le niveau de relargage des polluants lors de tests de lixiviation peut être évalué à l\u27aide du te