Néphrectomie partielle ou totale pour les carcinomes à cellules rénales de haut grade de Furham

Objectif : L objectif était de comparer les résultats carcinologiques sur la survie des patients présentant des carcinomes à cellules rénales de grades de Fuhrman élevés (grades 3 et 4), en fonction du type de traitement réalisé (Néphrectomie Partielle ou Néphrectomie Totale). Matériels et Méthodes : Etude rétrospective de 1999 à 2011, incluant 288 patients consécutifs présentant une masse rénale traitée chirurgicalement soit par néphrectomie partielle (NP) soit par néphrectomie totale (NT) et retrouvant un haut grade cyto-nucléaire de Fuhrman à l examen anatomopathologique de la pièce opératoire. L indication de NP ou NT dépendait de la faisabilité de l'exérèse chirurgicale basée sur la taille et la localisation de la tumeur. Les données cliniques, paracliniques, pathologiques, et thérapeutiques des deux groupes de patients ont été comparées. Des analyses comparatives de survie ont été réalisées pour la survie sans récidive, la survie spécifique et la survie globale. Résultats : Sur les 288 patients de l étude, 59 (19,4%) et 232 (80,6%) ont respectivement eu une NP et une NT. Par rapport aux patients traités par NT, les patients traités par NP étaient plus symptomatiques (79 vs 63 %, p=0,03), avec des tumeurs de taille inférieure (3,98 vs 7,65 cm, p<0,001) et un stade T tumoral moins élevé (T1a 57,1% vs 10,3% ; T2 7,1% vs 34% ; T3a 0% vs 20,2%, respectivement p<0,001 ), une extension métastatique au moment du diagnostic était moins représentée en cas de traitement par NP par rapport aux patients traités par NT (N1 1,7% vs 18,1%, p=0,002 et M1 0% vs 30,6%, p<0,001). Il n a pas été retrouvé de différence significative pour la survie sans récidive, la survie spécifique et la survie globale entre les groupes de NP et de NT en analyse multivariée. La présence de marges chirurgicales positives était un facteur de risque de mortalité spécifique et de mortalité globale de manière significative. Conclusion et Perspectives : Il n a pas été retrouvé de différence significative pour la survie sans récidive, la survie spécifique et la survie globale entre les groupes NP et NT. La stratégie chirurgicale consistant à privilégier l'indication de NP par rapport à la NT pour favoriser la préservation néphronique n'a pas lieu d'être modifiée. Une étude prospective multicentrique sur une population et un suivi plus importants avec critères d'indication de NT précis est nécessaire pour valider ces résultats. La comparaison des marges chirurgicales entre les groupe NT et NP chirurgicales est discutable.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

The changing culture of silviculture

Changing climates are altering the structural and functional components of forest ecosystems at an unprecedented rate. Simultaneously, we are seeing a diversification of public expectations on the broader sustainable use of forest resources beyond timber production. As a result, the science and art of silviculture needs to adapt to these changing realities. In this piece, we argue that silviculturists are gradually shifting from the application of empirically derived silvicultural scenarios to new sets of approaches, methods and practices, a process that calls for broadening our conception of silviculture as a scientific discipline. We propose a holistic view of silviculture revolving around three key themes: observe, anticipate and adapt. In observe, we present how recent advances in remote sensing now enable silviculturists to observe forest structural, compositional and functional attributes in near-real-time, which in turn facilitates the deployment of efficient, targeted silvicultural measures in practice that are adapted to rapidly changing constraints. In anticipate, we highlight the importance of developing state-of-the-art models designed to take into account the effects of changing environmental conditions on forest growth and dynamics. In adapt, we discuss the need to provide spatially explicit guidance for the implementation of adaptive silvicultural actions that are efficient, cost-effective and socially acceptable. We conclude by presenting key steps towards the development of new tools and practical knowledge that will ensure meeting societal demands in rapidly changing environmental conditions. We classify these actions into three main categories: reexamining existing silvicultural trials to identify key stand attributes associated with the resistance and resilience of forests to multiple stressors, developing technological workflows and infrastructures to allow for continuous forest inventory updating frameworks, and implementing bold, innovative silvicultural trials in consultation with the relevant communities where a range of adaptive silvicultural strategies are tested. In this holistic perspective, silviculture can be defined as the science of observing forest condition and anticipating its development to apply tending and regeneration treatments adapted to a multiplicity of desired outcomes in rapidly changing realities

The changing culture of silviculture

Changing climates are altering the structural and functional components of forest ecosystems at an unprecedented rate. Simultaneously, we are seeing a diversification of public expectations on the broader sustainable use of forest resources beyond timber production. As a result, the science and art of silviculture needs to adapt to these changing realities. In this piece, we argue that silviculturists are gradually shifting from the application of empirically derived silvicultural scenarios to new sets of approaches, methods and practices, a process that calls for broadening our conception of silviculture as a scientific discipline. We propose a holistic view of silviculture revolving around three key themes: observe, anticipate and adapt. In observe, we present how recent advances in remote sensing now enable silviculturists to observe forest structural, compositional and functional attributes in near-real-time, which in turn facilitates the deployment of efficient, targeted silvicultural measures in practice that are adapted to rapidly changing constraints. In anticipate, we highlight the importance of developing state-of-the-art models designed to take into account the effects of changing environmental conditions on forest growth and dynamics. In adapt, we discuss the need to provide spatially explicit guidance for the implementation of adaptive silvicultural actions that are efficient, cost-effective and socially acceptable. We conclude by presenting key steps towards the development of new tools and practical knowledge that will ensure meeting societal demands in rapidly changing environmental conditions. We classify these actions into three main categories: re-examining existing silvicultural trials to identify key stand attributes associated with the resistance and resilience of forests to multiple stressors, developing technological workflows and infrastructures to allow for continuous forest inventory updating frameworks, and implementing bold, innovative silvicultural trials in consultation with the relevant communities where a range of adaptive silvicultural strategies are tested. In this holistic perspective, silviculture can be defined as the science of observing forest condition and anticipating its development to apply tending and regeneration treatments adapted to a multiplicity of desired outcomes in rapidly changing realities

Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Monoamine oxidase A (MAO-A), a mitochondrial enzyme that degrades monoamines including neurotransmitters, is highly expressed in basal cells of the normal human prostatic epithelium and in poorly differentiated (Gleason grades 4 and 5), aggressive prostate cancer (PCa). Clorgyline, an MAO-A inhibitor, induces secretory differentiation of normal prostate cells. We examined the effects of clorgyline on the transcriptional program of epithelial cells cultured from high grade PCa (E-CA).</p> <p>Methods</p> <p>We systematically assessed gene expression changes induced by clorgyline in E-CA cells using high-density oligonucleotide microarrays. Genes differentially expressed in treated and control cells were identified by Significance Analysis of Microarrays. Expression of genes of interest was validated by quantitative real-time polymerase chain reaction.</p> <p>Results</p> <p>The expression of 156 genes was significantly increased by clorgyline at all time points over the time course of 6 – 96 hr identified by Significance Analysis of Microarrays (SAM). The list is enriched with genes repressed in 7 of 12 oncogenic pathway signatures compiled from the literature. In addition, genes downregulated ≥ 2-fold by clorgyline were significantly enriched with those upregulated by key oncogenes including beta-catenin and ERBB2, indicating an anti-oncogenic effect of clorgyline. Another striking effect of clorgyline was the induction of androgen receptor (AR) and classic AR target genes such as prostate-specific antigen together with other secretory epithelial cell-specific genes, suggesting that clorgyline promotes differentiation of cancer cells. Moreover, clorgyline downregulated EZH2, a critical component of the Polycomb Group (PcG) complex that represses the expression of differentiation-related genes. Indeed, many genes in the PcG repression signature that predicts PCa outcome were upregulated by clorgyline, suggesting that the differentiation-promoting effect of clorgyline may be mediated by its downregulation of EZH2.</p> <p>Conclusion</p> <p>Our results suggest that inhibitors of MAO-A, already in clinical use to treat depression, may have potential application as therapeutic PCa drugs by inhibiting oncogenic pathway activity and promoting differentiation.</p

The limited interest of carmakers in corporate venture capital: insights from a mature industry

A whole corpus of literature has evolved to discuss the motivation of industrial companies in creating corporate venture capital (CVC) funds. However, most studies have been limited to technology sectors that are particularly active in this domain. The present paper seeks to analyse a mature economic sector – automobiles – which should have good reason to take an interest in CVC. A panel comprising 13 of the world’s leading carmakers reveals that (1) few operate any CVC funds; (2) the ones that do tend not to be very active; and (3) investments basically correspond to strategic motivations of the kind that literature already envisions. These findings suggest that CVC studies in particular sectors should take a closer look at institutional isomorphism and consider how inter-firm relationships are organised

La valeur seuil, le pourcentage d'abaissement et la vélocité du PSA sont des facteurs prédictifs du risque de progression chez les patients ayant un cancer de prostate T1a non traité

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Marges, complications précoces et fonction rénale (évaluation du score "triade" après traitement partiel des tumeurs du rein de moins de 4 cm)

OBJECTIF. Validation du recueil et de l utilisation d un score pour l évaluation des thérapies partielles des tumeurs du rein de moins de 4cm. Le score triade est défini à partir de trois données déterminantes : 1- marges carcinologiques, 2- complications précoces, 3- préservation de la fonction rénale. MATERIELS ET METHODES. Etude uni-centrique rétrospective, entre janvier 2011 et décembre 2012, incluant 113 patients ayant eu un traitement partiel pour une tumeur du rein de moins de 4 cm par néphrectomie partielle par voie ouverte NP-O (40), par voie coelioscopique robot-assistée NP-R (57) ou par radiofréquence RF (16). La tumeur a été classée sur l imagerie pré-opératoire selon le R.E.N.A.L. score en fonction de la difficulté de l exérèse : faible (FD : 4 à 6), moyenne (MD : 7 à 9) ou haute (HD>9). Les données démographiques, anatomopathologiques (marges), d imagerie post-opératoire (RF), de la fonction rénale initiale et à 3 mois (eDFG en mL/min/1,732 selon la formule MDRD) et les complications périopératoires (classification de Dindo-Clavien en 5 scores) ont été analysées. Le score triade a été calculé pour chaque patient. La présence des 3 critères favorables (marges saines, complication de stade 0,05). Une complication majeure était observée dans 11,5 % des cas. Le groupe R.E.N.A.L. score FD présentait un taux de complications majeures plus faible que les 2 autres groupes (2,3% vs 18,4%, p=0,04). Le score triade optimal était observé dans 38% des cas et n était pas différent entre les groupes de traitement (29, 44 et 40% pour NP-O, NP-R et RF p=0,34). Le score était intermédiaire dans 50% des cas et défavorable dans 11% des cas. Le R.E.N.A.L. score n était pas différent entre les groupes de difficulté (47, 34 et 33% pour les groupes de FD, de MD et HD p=0,36). CONCLUSIONS. Le score triade est un score d évaluation clinique pertinent pour la description des tumeurs du rein de moins de 4 cm traitées partiellement. Un score triade optimal est un objectif en pratique clinique pour la prise en charge de ces tumeurs et atteignait 38% des cas. Il doit être validé dans d autres séries. Le recueil systématique prospectif des items de ce score et du R.E.N.A.L. score est déterminant pour cette évaluation.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Influence of bridge deck shape on extreme buffeting forces

peer reviewedThe design of a bridge deck with respect to wind action usually relies on a simple principle: as the average and standard deviation of aerodynamic coefficients are responsible for the buffeting excitation, minimizing them is supposed to be beneficial for extreme wind loads. Traditional bridge deck shapes are optimized in this view. Seminal developments related to the establishment of peak factors for the estimation of the extreme loads are generally attributed to Cartwright and Higgins (1956). They have been widely applied, but fail to offer an accurate model in some circumstances as they are developed within the framework of Gaussian processes. Some less restrictive formulations are discussed and compared by Floris and Iseppi (1998). The non-Gaussianity of the wind loading is indeed an important issue as it affects the extreme wind forces, i.e. those that precisely have to be taken into account for the structural design. Such discussions indicate that a skewed random process might evince, even for a skewness coefficient as small as γ_3=0.5, peak factors that are 20% to 30% higher than those obtained with Gaussian developments (e.g. based on a model proposed in (Gurley et al., 1997)). With that in mind, and being restricted to buffeting analysis, this paper proposes to supplement the traditional considerations about deck shape optimization with a discussion about the skewness of aerodynamic loading. We consider a nonlinear wind loading model in which the skewness results, in part, from the nonlinearity of aerodynamic coefficients. Actually, in a quasi-steady context, these coefficients are measured for various angles of attack on the bridge deck. This typically results in a nonlinear coefficient .vs. incidence relation, which in turn is partly responsible for the non Gaussian distribution of the aerodynamic loading. As a final objective, we endeavor at providing an estimation of the skewness of the aerodynamic loading that could be typically expected for a given bridge deck typology. In doing so, we believe the general trends that are observed in this study will help in assessing the effect of the choice of a bridge deck typology on the extreme wind force. This objective is reached in a two-step procedure. First a database analysis of several bridge decks is performed in order to provide, for three families of deck typology –box, girder, streamlined- ranges of variation of drag and lift coefficients. Then, based on a quasi-steady nonlinear aerodynamic model, these ranges are translated into skewness coefficient of aerodynamic forces

Quelles stratégies peut-on suivre en créant des fonds de Corporate Venture Capital ? Leçons à partir des constructeurs automobiles

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