The effect of health care expenditures on survival in locally advanced and metastatic Non Small Cell Lung Cancer

Context: The significant survival benefit of chemotherapy over best supportive care for locally advanced and metastatic NSCLC has been amply demonstrated in the literature. However, there is no clear evidence of the impact of the type of chemotherapy or of a superiority of combination chemotherapy over single-agent chemotherapy.Objective: The present study empirically examines, in real-life practise and using multiple proxies, the impact of health care expenditures on overall survival in locally advanced and metastatic NSCLC in order to guide medical decision-making.Methods: Disease characteristics, the resources used, the costs of treatment and survival data were retrospectively collected from the records of 175 patients treated between 2000 and 2004 at Léon Bérard Regional Cancer Center (Lyon, France). Survival data were modelled using multivariate Cox models and controlled for endogeneity with the instrumental variable method.Results: The median survival for the whole cohort was 289 days. The average total cost of treatment reached €35,160. Survival was significantly shorter for patients with stage IV disease, poor performance status, and past or concomitant cardiovascular disease and/or diabetes, for current smokers, and for patients with adenocarcinoma compared to large cell carcinoma. Survival duration was not significantly associated with the total cost of treatment per day of hospitalisation, the number of chemotherapy drugs administered, nor inpatient length of stay.Conclusion: Higher care expenditures do not appear to improve survival for patients with locally advanced or metastatic NSCLC. Hence, maintaining patient quality of life and tailoring therapy to stage, histology and comorbidities appears to be the less bad choice.Cost; NSCLC; Oncology; Survival

The effect of health care expenditures on survival in locally advanced and metastatic Non Small Cell Lung Cancer

Working Paper GATE 2009-03Context: The significant survival benefit of chemotherapy over best supportive care for locally advanced and metastatic NSCLC has been amply demonstrated in the literature. However, there is no clear evidence of the impact of the type of chemotherapy or of a superiority of combination chemotherapy over single-agent chemotherapy.Objective: The present study empirically examines, in real-life practise and using multiple proxies, the impact of health care expenditures on overall survival in locally advanced and metastatic NSCLC in order to guide medical decision-making.Methods: Disease characteristics, the resources used, the costs of treatment and survival data were retrospectively collected from the records of 175 patients treated between 2000 and 2004 at Léon Bérard Regional Cancer Center (Lyon, France). Survival data were modelled using multivariate Cox models and controlled for endogeneity with the instrumental variable method.Results: The median survival for the whole cohort was 289 days. The average total cost of treatment reached €35,160. Survival was significantly shorter for patients with stage IV disease, poor performance status, and past or concomitant cardiovascular disease and/or diabetes, for current smokers, and for patients with adenocarcinoma compared to large cell carcinoma. Survival duration was not significantly associated with the total cost of treatment per day of hospitalisation, the number of chemotherapy drugs administered, nor inpatient length of stay.Conclusion: Higher care expenditures do not appear to improve survival for patients with locally advanced or metastatic NSCLC. Hence, maintaining patient quality of life and tailoring therapy to stage, histology and comorbidities appears to be the less bad choice

Assessment of sub-shelf melting parameterisations using the ocean–ice-sheet coupled model NEMO(v3.6)–Elmer/Ice(v8.3)

Oceanic melting beneath ice shelves is the main driver of the current mass loss of the Antarctic ice sheet and is mostly parameterised in stand-alone ice-sheet modelling. Parameterisations are crude representations of reality, and their response to ocean warming has not been compared to 3-D ocean–ice-sheet coupled models. Here, we assess various melting parameterisations ranging from simple scalings with far-field thermal driving to emulators of box and plume models, using a new coupling framework combining the ocean model NEMO and the ice-sheet model Elmer/Ice. We define six idealised one-century scenarios for the far-field ocean ranging from cold to warm, and representative of potential futures for typical Antarctic ice shelves. The scenarios are used to constrain an idealised geometry of the Pine Island glacier representative of a relatively small cavity. Melt rates and sea-level contributions obtained with the parameterised stand-alone ice-sheet model are compared to the coupled model results. The plume parameterisations give good results for cold scenarios but fail and underestimate sea level contribution by tens of percent for warm(ing) scenarios, which may be improved by adapting its empirical scaling. The box parameterisation with five boxes compares fairly well to the coupled results for almost all scenarios, but further work is needed to grasp the correct number of boxes. For simple scalings, the comparison to the coupled framework shows that a quadratic as opposed to linear dependency on thermal forcing is required. In addition, the quadratic dependency is improved when melting depends on both local and non-local, i.e. averaged over the ice shelf, thermal forcing. The results of both the box and the two quadratic parameterisations fall within or close to the coupled model uncertainty. All parameterisations overestimate melting for thin ice shelves while underestimating melting in deep water near the grounding line. Further work is therefore needed to assess the validity of these melting parameteriations in more realistic set-ups

Fun at Antarctic grounding lines: Ice-shelf channels and sediment transport

Meltwater beneath the polar ice sheets drains, in part, through subglacial conduits. Landforms created by such drainages are abundant in areas formerly covered by ice sheets during the last glacial maximum. However, observations of subglacial conduit dynamics under a contemporary ice sheet are lacking. We present results from ice-penetrating radar to infer the existence of subglacial conduits upstream of the grounding line of Roi Baudouin Ice Shelf, Antarctica. The conduits are aligned with ice-shelf channels, and underlain by esker ridges formed from sediment deposition due to reduced water outflow speed near the grounding line. In turn, the eskers modify localice flow to initiate the bottom topography of the ice-shelf channels, and create small surface ridges extending onto the shelf. Relict features on the shelf are interpreted to indicate a history of these interactions and variability of past subglacial drainages. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation, and ice-shelf stability. To investigate the role of sediment transport beneath ice sheets further, we model the sheet-shelf system ofthe Ekstömisen catchment, Antarctica. A 3D finite element model (Elmer/ICE) is used to solve the transients full Stokes equation for isotropic, isothermal ice with a dynamic grounding line. We initialize the model with surface topography from the TanDEM-X satellites and by inverting simultaneously for ice viscosity and basaldrag using present-day surface velocities. Results produce a flow field which is consitent with sattelite and on-site observations. Solving the age-depth relationship allows comparison with radar isochrones from airborne data, and gives information about the atmospheric/dynamic history of this sector. The flow field will eventually be used to identify potential sediment sources and sinks which we compare with more than 400 km of seismic profiles collected over the floating ice shelves and the grounded ice sheet

ANKRD26 is a new regulator of type I cytokine receptor signaling in normal and pathological hematopoiesis

Sustained ANKRD26 expression associated with germline ANKRD26 mutations causes thrombocytopenia 2 (THC2), an inherited platelet disorder associated with a predisposition to leukemia. Some patients also present with erythrocytosis and/or leukocytosis. Using multiple human-relevant in vitro models (cell lines, primary patients’ cells and patient-derived induced pluripotent stem cells) we demonstrate for the first time that ANKRD26 is expressed during the early steps of erythroid, megakaryocyte and granulocyte differentiation, and is necessary for progenitor cell proliferation. As differentiation progresses, ANKRD26 expression is progressively silenced, to complete the cellular maturation of the three myeloid lineages. In primary cells, abnormal ANKRD26 expression in committed progenitors directly affects the proliferation/differentiation balance for the three cell types. We show that ANKRD26 interacts with and crucially modulates the activity of MPL, EPOR and G-CSFR, three homodimeric type I cytokine receptors that regulate blood cell production. Higher than normal levels of ANKRD26 prevent the receptor internalization that leads to increased signaling and cytokine hypersensitivity. These findings afford evidence how ANKRD26 overexpression or the absence of its silencing during differentiation is responsible for myeloid blood cell abnormalities in patients with THC2

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

Publisher Correction: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

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La vulgarisation du dérèglement climatique par deux groupements de citoyens : la Fresque du Climat et les Citoyens pour le Climat

Si la menace que représente le dérèglement climatique d’origine anthropique a été identifiée depuis les années 1970 par certains climatologues, la prise de conscience de ses enjeux par la population ne se manifeste que depuis très récemment. Nés de ces préoccupations, des groupements de citoyens se sont formés avec la volonté de sensibiliser à cette problématique par la vulgarisation de ses fondements scientifiques. Nous sommes partis à la rencontre de deux d’entre eux : l’association de la Fresque du Climat et le collectif des Citoyens pour le Climat. Après une mise en contexte par les récits historiques de la connaissance du dérèglement climatique, de la vulgarisation scientifique et des mobilisations environnementales, nous décrivons tout d’abord les origines sociales des militants qui constituent ces groupements, puis nous analysons et comparons leurs approches fort différentes de vulgarisation pour les mêmes fondements scientifiques. Enfin, nous explorons les ressorts du passage de la connaissance à l’action, qui dans le cas du dérèglement climatique peut être freiné par des aspects psychosociaux et culturel mais aussi catalysé par les émotions

Approche numérique par éléments discrets 3D de la sollicitation d'un écoulement granulaire sur un obstacle

The analysis of impact pressure by granular flows on obstacles requires an investigation of the drag coefficient. However, in the bibliography, experimental studies cannot reach inner flow properties, in spite of their consideration in its computation. Therefore, in this thesis we propose to determine this coefficient through three dimensional numerical tools, carried out with the discrete element method (DEM), and validated through experimental studies. The experiments consist in a laboratory canal, fully modelled by the DEM. The local contact law includes a normal elastic, hysteretic behaviour with a tangential sliding criterion. The full model validation is deduced from the similarity between experimental and numerical results of the flow's physical parameters and of the impact loading against the obstacle. This validation is obtained without any important calibration of the numerical parameters. Then, the full model is optimized, in terms of time computation and number of studies possibilities, as a granular launcher, in which is only considered the flow-obstacle interaction zone. The flow properties: velocity, thickness, density, are controlled because taken as initial numerical parameters. The effect of flow characteristics, like the Froude number, grains' mean size, or the shape and size of the obstacle, on the drag coefficient, is then analyzed. Finally, further micromechanical investigations are performed to study the effect of an adhesion and cohesion added in the local behaviour.L'analyse de la pression exercée par un écoulement granulaire sur un obstacle nécessite la connaissance du coefficient de traînée. Néanmoins, les études bibliographiques expérimentales ne fournissent pas les données internes de l'écoulement intervenant dans son calcul. C'est pourquoi, nous proposons la détermination du coefficient de traînée par l'application d'outils numériques tridimensionnels, basés sur la méthode des éléments discrets (MED), et validés par des études expérimentales. L'expérience est un canal d'écoulement de laboratoire, intégralement modélisé par la MED. Les lois locales de contact intègrent un comportement normal élastique, hystérétique associé à un critère de glissement tangentiel. La validation du modèle intégral repose sur la similarité entre les résultats expérimentaux et numériques des paramètres physiques de l'écoulement et de l'effort d'impact sur l'obstacle. Cette validation est obtenue sans calibration importante des paramètres numériques. Le modèle intégral est ensuite optimisé, en termes de temps de calcul et de possibilités d'études, sous la forme d'un canon granulaire, dans lequel n'est simulée que la zone d'interaction entre l'écoulement et l'obstacle. Les propriétés de l'écoulement : vitesse, épaisseur, densité, sont contrôlées car intégrées en tant que paramètres initiaux numériques. L'influence de caractéristiques associées à l'écoulement, comme le nombre de Froude, à la taille des grains, ou à la forme et la taille de l'obstacle, sur le coefficient de traînée, est alors analysée. Enfin, une extension micromécanique est proposée dans l'analyse de l'influence d'une adhésion et d'une cohésion intégrées aux lois locales de contact