La crise de productivité en recherche pharmaceutique : identification d'un paradoxe stratégique par la dynamique des systèmes

Ce mémoire repose sur la notion que l'industrie pharmaceutique mondiale traverse une sévère \ud « crise » de productivité (Wood Mackenzie, 2003 ; Van Arnum, 2003; Banerjee et al., 2001 ; Bolten et DeGregorio, 2002; Graves et Langowitz, 1996). Depuis les dernières années, l'industrie a peu innové en nouveaux médicaments commercialisés annuellement. Pourtant, les investissements n'ont cessé de croître, passant de 1,3 milliard de dollars U.S. en 1977, à 32,1 milliards de dollars U.S. en 2002 (PhRMA, 2004). La diminution du nombre d'approbations de nouveaux médicaments, combinée à l'augmentation croissante des dépenses en R-D, ont eu pour effet d'augmenter substantiellement le coût moyen de production estimé d'un nouveau médicament. Les données disponibles montrent l'émergence d'une nouvelle structure de coûts. Celle-ci semble avoir provoqué un changement dans la perception des grandes firmes au sujet de la taille minimale efficace (TME) permettant de conserver un avantage concurrentiel; puisque dès le début des années 1990, d'importantes vagues de fusions et d'acquisitions furent constatées dans ce secteur. Malgré la consolidation de l'industrie, les données disponibles montrent que la productivité continue de décroître. Face à cette situation, plusieurs universitaires et acteurs de l'industrie se sont penchés sur les causes possibles de cette \ud « crise » de productivité (James, 1994; Drews et Ryser, 1996; Christensen, 1997). Cependant, aucun chercheur ne s'est intéressé à l'apport d'une modélisation structurelle par rétroaction de ces difficultés. De la revue de la littérature semble émerger un cercle vicieux stratégique (nommé \ud « paradoxe stratégique ») qui permet de montrer que les stratégies déployées par les grandes firmes de l'industrie pourraient ne pas produire les résultats escomptés à moyen et long terme. Appuyée par une collecte de données exhaustive, cette recherche propose une modélisation par la dynamique des systèmes du « pipeline » d'études cliniques, de fabrication et de commercialisation des 14 meneurs de l'industrie mondiale. L'objectif de la recherche consiste à analyser et à comprendre les diverses influences et rétroactions entre les variables et leurs impacts sur l'état de ce système. L'analyse des comportements du modèle a permis d'illustrer, par la simulation, le « choc global » du paradoxe stratégique sur la productivité. Sommairement, le modèle montre que les stratégies mises en place pour contrer la crise de productivité auraient des répercussions inattendues sur l'état du système. Les stratégies déployées contribueraient, de fait, à entretenir les difficultés associées à la productivité et ainsi à accentuer la « crise » actuelle. La simulation de divers scénarios permet d'évaluer et d'exposer de manière systémique les causes possibles de ce paradoxe. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Industrie de la recherche pharmaceutique, Dynamique des systèmes, Modélisation, Crise de productivité, Paradoxe stratégique, Fusions et acquisitions (F-A)

The Role of Footwear, Foot Orthosis and Training-Related Strategies in the Prevention of Bone Stress Injuries: A Systematic Review and Meta-Analysis

International Journal of Exercise Science 16(3): 721-743, 2023. Objective: To evaluate the effectiveness of footwear, foot orthoses and training-related strategies to prevent lower extremity bone stress injury (BSI). Design: Systematic review and meta-analysis. Data sources: Four bibliographic databases (from inception until November 2021): Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and CINAHL. Eligibility criteria: Randomised controlled trials (RCTs) that assessed the risk of developing a BSI when using particular footwear, foot orthoses or training-related strategies such as muscle strengthening, stretching, and mechanical loading exercises. Results: Eleven studies were included in this systematic review. When wearing foot orthoses, the risk ratio of developing a BSI on any lower extremity bone is 0.47 (95% CI 0.26 to 0.87; p = 0.02). When doing pre-exercise dynamic stretching, the risk ratio of suffering a tibial BSI is 1.06 (95% CI 0.67 to 1.68; p = 0.79). No meta-analyses could be performed for footwear or training-related strategies. The quality of evidence for all these results is low considering the high risk of bias in each study, the low number of studies and the low number of cases in each study. Conclusion: This systematic review reveals the lack of high-quality studies in BSI prevention. Based on studies at high risk of bias, foot orthoses could potentially help prevent BSIs in the military setting. It is still unknown whether footwear and training-related strategies have any benefits. It is crucial to further investigate potential BSI prevention strategies in women and athletes. Research is also needed to assess the influence of running shoes and loading management on BSI incidence

Near Infrared Observations of GQ Lup b Using the Gemini Integral Field Spectrograph NIFS

We present new JHK spectroscopy (R ~ 5000) of GQ Lup b, acquired with the near-infrared integral field spectrograph NIFS and the adaptive optics system ALTAIR at the Gemini North telescope. Angular differential imaging was used in the J and H bands to suppress the speckle noise from GQ Lup A; we show that this approach can provide improvements in signal-to-noise ratio (S/N) by a factor of 2 - 6 for companions located at subarcsecond separations. Based on high quality observations and GAIA synthetic spectra, we estimate the companion effective temperature to Teff = 2400 +/- 100 K, its gravity to log g = 4.0 +/- 0.5, and its luminosity to log(L/L_s) = -2.47 +/- 0.28. Comparisons with the predictions of the DUSTY evolutionary tracks allow us to constrain the mass of GQ Lup b to 8 - 60 MJup, most likely in the brown dwarf regime. Compared with the spectra published by Seifahrt and collaborators, our spectra of GQ Lup b are significantly redder (by 15 - 50%) and do not show important Pa\beta emission. Our spectra are in excellent agreement with the lower S/N spectra previously published by McElwain and collaborators.Comment: 34 pages, 10 figures, accepted for publication in Ap

Center of Mass Compensation during Gait in Hip Arthroplasty Patients: Comparison between Large Diameter Head Total Hip Arthroplasty and Hip Resurfacing

Objective. To compare center of mass (COM) compensation in the frontal and sagittal plane during gait in patients with large diameter head total hip arthroplasty (LDH-THA) and hip resurfacing (HR). Design. Observational study. Setting. Outpatient biomechanical laboratory. Participants. Two groups of 12 patients with LDH-THA and HR recruited from a larger randomized study and 11 healthy controls. Interventions. Not applicable. Main Outcome Measures. To compare the distance between the hip prosthetic joint center (HPJC) and the COM. The ratio (RHPJC-COM) and the variability (CVHPJC-COM) were compared between groups. Hip flexor, abductor, and adductor muscle strength was also correlated between groups while radiographic measurements were correlated with the outcome measures. Results. In the frontal plane, HR shows less variability than healthy controls at push-off and toe-off and RHPJC-COM is correlated with the muscle strength ratios (FRABD) at heel contact, maximal weight acceptance, and mid stance. In the sagittal plane, LDH-THA has a higher RHPJC-COM than healthy controls at push-off, and CVHPJC-COM is significantly correlated with FRFLEX. Conclusions. One year after surgery, both groups of patients, LDH-THA and HR, demonstrate minor compensations at some specific instant of the gait cycle, in both frontal and sagittal planes. However, their locomotion pattern is similar to the healthy controls

Neutral modelling of agricultural landscapes by tessellation methods—Application for gene flow simulation.

International audienceNeutral landscape models are not frequently used in the agronomical domain, whereas they would be very useful for studying given agro-ecological or physical processes. Contrary to ecological neutral landscape models, agricultural models have to represent and manage geometrical patches and thus should rely on tessellation methods. We present a three steps approach that aimed at simulating such landscapes. Firstly, we characterized the geometry of three real field patterns; secondly, we generated simulated field patterns with two tessellation methods attempting to control the value of some of the observed characteristics and, thirdly, we evaluated the simulated field patterns. For this evaluation, we considered that good simulated field patterns should capture characteristics of real landscapes that are important for the targeted agro-ecological process. Real landscapes and landscapes simulated using either a Voronoi or a rectangular tessellation were thus compared when used as input data within a gene flow model. The results showed that neither tessellation method captured field shapes correctly, thus leading to over or (small) under estimation of gene flow. The Voronoi tessellation, though, performed better than the rectangular tessellation. Possible research directions are proposed to improve the simulated patterns, including the use of post processing, the control of cell orientation or the implementation of other tessellation techniques

Staphylococcus aureus Bloodstream Infection and Endocarditis―A Prospective Cohort Study

Equipe CHU UB (EA) Pôle MERS CT3 Hors Enjeu The VIRSTA Study Group : Clinical centres: Besançon: Catherine Chirouze, Elodie Curlier, Cécile Descottes-Genon, Bruno Hoen, Isabelle Patry, Lucie Vettoretti. Dijon: Pascal Chavanet, Jean-Christophe Eicher, Sandrine Gohier-Treuvelot, Marie-Christine Greusard, Catherine Neuwirth, André Péchinot, Lionel Piroth. Lyon: Marie Célard, Catherine Cornu, François Delahaye, Malika Hadid, Pascale Rausch. Montpellier: Audrey Coma, Florence Galtier, Philippe Géraud, Hélène Jean-Pierre, Vincent Le Moing, Catherine Sportouch, Jacques Reynes. Nancy: Nejla Aissa, Thanh Doco- Lecompte, François Goehringer, Nathalie Keil, Lorraine Letranchant, Hepher Malela, Thierry May, Christine Selton-Suty. Nîmes: Nathalie Bedos, Jean-Philippe Lavigne, Catherine Lechiche, Albert Sotto. Paris: Xavier Duval, Emila Ilic Habensus, Bernard Iung, Catherine Leport, Pascale Longuet, Raymond Ruimy. Rennes: Eric Bellissant, Pierre-Yves Donnio, Fabienne Le Gac, Christian Michelet, Matthieu Revest, Pierre Tattevin, Elise Thebault. Coordination and statistical analyses: François Alla, Pierre Braquet, Marie-Line Erpelding, Laetitia Minary, Sarah Tubiana. Centre National de Référence des staphylocoques: Michèle Bès, Jérôme Etienne, Anne Tristan, François Vandenesch. Sponsor CHU de Montpellier: Sandrine Barbas, Christine Delonca, Virginie Sussmuth, Anne Verchère. Alain Makinson reviewed the manuscript for English correctness.International audienceOBJECTIVES: To update the epidemiology of S. aureus bloodstream infection (SAB) in a high-income country and its link with infective endocarditis (IE).METHODS: All consecutive adult patients with incident SAB (n = 2008) were prospectively enrolled between 2009 and 2011 in 8 university hospitals in France. RESULTS: SAB was nosocomial in 54%, non-nosocomial healthcare related in 18% and community-acquired in 26%. Methicillin resistance was present in 19% of isolates. SAB Incidence of nosocomial SAB was 0.159/1000 patients-days of hospitalization (95% confidence interval [CI] 0.111-0.219). A deep focus of infection was detected in 37%, the two most frequent were IE (11%) and pneumonia (8%). The higher rates of IE were observed in injecting drug users (IE: 38%) and patients with prosthetic (IE: 33%) or native valve disease (IE: 20%) but 40% of IE occurred in patients without heart disease nor injecting drug use. IE was more frequent in case of community-acquired (IE: 21%, adjusted odds-ratio (aOR) = 2.9, CI = 2.0-4.3) or non-nosocomial healthcare-related SAB (IE: 12%, aOR = 2.3, CI = 1.4-3.5). S. aureus meningitis (IE: 59%), persistent bacteremia at 48 hours (IE: 25%) and C-reactive protein > 190 mg/L (IE: 15%) were also independently associated with IE. Criteria for severe sepsis or septic shock were met in 30% of SAB without IE (overall in hospital mortality rate 24%) and in 51% of IE (overall in hospital mortality rate 35%).CONCLUSION: SAB is still a severe disease, mostly related to healthcare in a high-income country. IE is the most frequent complication and occurs frequently in patients without known predisposing condition

GENEXP, un logiciel pour simuler des paysages agricoles

National audienceDans cet article, nous présentons un simulateur de paysages agricoles bidimensionnels, GenExP, qui engendre des découpages parcellaires à partir des paramètres statistiques de paysages réels, en utilisant une géométrie algorithmique classique. L'originalité de GenExP est d'être couplé d'une part avec le logiciel R -- qui autorise les paramétrages et traitements statistiques des parcellaires générés -- et d'autre part avec le logiciel de fouille de données CarottAge -- afin d'intégrer des successions de culture construites à partir de bases de données agricoles. Finalement, GenExP fournit des cartes pluriannuelles de paysages agricoles, qui peuvent être utilisées dans le cadre de nombreuses applications. Ainsi, les résultats des logiciels Mapod et GeneSys, qui sont utilisés par les agronomes et écologues pour simuler la dispersion des pollens et des graines d'OGM à l'échelle d'une ou quelques parcelles, peuvent être étendus dans le temps et l'espace et permettre une meilleure estimation des risques