Consolidation whole abdomen irradiation following adjuvant carboplatin-paclitaxel based chemotherapy for advanced uterine epithelial cancer: feasibility, toxicity and outcomes.

BACKGROUND: To evaluate feasibility and preliminary outcomes associated with sequential whole abdomen irradiation (WAI) as consolidative treatment following comprehensive surgery and systemic chemotherapy for advanced endometrial cancer. METHODS: We conducted a retrospective analysis of patients treated at our institution from 2000 to 2011. Inclusion criteria were stage III-IV endometrial cancer patients with histological proof of one or more sites of extra-uterine abdomen-confined disease, treated with WAI as part of multimodal therapy. Endpoints were feasibility, acute toxicity, late effects, recurrence-free survival (RFS) and overall survival (OS). Twenty patients were identified. Chemotherapy consisted of 3 to 6 cycles of a platinum-paclitaxel regimen in 18 patients. WAI was delivered using conventional technique to a median total dose of 27.5 Gy. RESULTS: No grade 4 toxicities occurred during chemotherapy or radiotherapy. No radiation dose reduction was necessary. Three patients developed small bowel obstruction, all in the context of recurrent intraperitoneal disease. Kaplan-Meier estimates and 95% confidence intervals for RFS and OS at one year were 63% (38-80%) and 83% (56-94%) and at 3 years 57% (33-76%) and 62% (34-81%), respectively. On univariate Cox analysis, stage IVB and serous papillary (SP) histology were found to be statistically significantly (at the p = 0.05 level) associated with worse RFS and OS. The peritoneal cavity was the most frequent site of initial failure. CONCLUSIONS: Consolidative WAI following chemotherapy is feasible and can be performed without interruption with manageable acute and late toxicity. Patients with endometrioid adenocarcinoma, especially stage FIGO III, had favorable outcomes possibly meriting prospective evaluation of the addition of WAI following chemotherapy in selected patients. Patients with SP do poorly and do not routinely benefit from this approach.

Averting inflammation by targeting the cytokine environment.

Cytokines are key instigators and regulators of immune responses and therefore hold great potential as targets for new therapeutic strategies. However, the selection of which cytokines to target, and in particular the identification of which cytokines regulate the rate-limiting steps of disease pathways, is crucial to the success of such strategies. Moreover, balancing the need for ablating pathological inflammatory responses and simultaneously maintaining the ability to control infectious agents is a key consideration. Recent advances in our understanding of cytokine networks, as well as technical progress in blocking cytokines in vivo, are likely to be a source for new drugs that can control chronic inflammatory diseases.

Does the working environment influence health care professionals' values, meaning in life and religiousness? Palliative care units compared with maternity wards.

CONTEXT: Increased altruism, self-transcendence, and quests for meaning in life (MiL) have been found in palliative care (PC) patients and their families who experience the finiteness of life. Similar changes were observed in healthy subjects who were experimentally confronted with their mortality. OBJECTIVES: The study investigated how daily experiences of the transitoriness of life influence PC health care professionals' (HCPs) values, MiL, and religiousness. METHODS: In a cross-sectional study, the Schwartz Value Survey, the Schedule for Meaning in Life Evaluation, and the Idler Index of Religiosity were used to investigate personal values, MiL, and private religiousness. HCPs working in PC (confronted with death) were compared with a control group of HCPs working at maternity wards (MWs) using multivariate models. Differences were considered to be statistically significant at P < 0.05. RESULTS: Seventy PC- and 70 MW-HCPs took part in the study (response rate 74.0%). No differences between the groups were found in overall MiL satisfaction scores. PC-HCPs were significantly more religious than MW-HCPs; they listed spirituality and nature experience more often as areas in which they experience MiL. Furthermore, hedonism was more important for PC-HCPs, and they had higher scores in openness-to-change values (stimulation and self-direction). MW-HCPs were more likely to list family as a MiL area. They assigned more importance to health and scored higher in conservation values (conformity and security). Duration of professional experience did not influence these results. CONCLUSION: Basic differences in values, MiL, and religiousness between PC-HCPs and MW-HCPs might have influenced the choice of working environment because no effect of job duration was observed. Longitudinal research is needed to confirm this hypothesis.

Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited.

Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases.

Innovative implementation by non-state actors in environment-related areas : towards a positive implementation gap ?

This contribution (presented in the first International Conference on Public Policy (ICPP) in Grenoble in June 2013) explores the phenomena of innovation in action ("innovative implementation"). To do so, we operationalize "innovative implementation" as a strategy by which (coalitions of) non-state actors seek to develop ad hoc solutions to address a given environmental issue, going beyond what is provided for in formal policy designs. Following an inductive research strategy, we elaborate a conceptual framework whose main advantage is to bring the actors and their coalition (in all their diversity) back in the analysis. More concretely, we state that perceiving implementation as broader 'social interaction processes' (De Boer & Bressers 2011) within which actors play strategic 'games' (Bardach 1977, Scharpf 1997) opens interesting lines of research to better account for their innovative and strategic behaviours. In a second step, we apply this framework to three strategies of innovative implementation in different contexts, and identify on this basis empirical regularities in the individual pathways related to the emergence and success (or failure) of these strategies.

Collective decision making in a heterogeneous environment: Lasius niger colonies preferentially forage at easy to learn locations

Many ants forage in complex environments and use a combination of trail pheromone information and route memory to navigate between food sources and the nest. Previous research has shown that foraging routes differ in how easily they are learned. In particular, it is easier to learn feeding locations that are reached by repeating (e.g. left-left or right-right) than alternating choices (left-right or right-left) along a route with two T-bifurcations. This raises the hypothesis that the learnability of the feeding sites may influence overall colony foraging patterns. We studied this in the mass-recruiting ant Lasius niger. We used mazes with two T-bifurcations, and allowed colonies to exploit two equidistant food sources that differed in how easily their locations were learned. In experiment 1, learnability was manipulated by using repeating versus alternating routes from nest to feeder. In experiment 2, we added visual landmarks along the route to one food source. Our results suggest that colonies preferentially exploited the feeding site that was easier to learn. This was the case even if the more difficult to learn feeding site was discovered first. Furthermore, we show that these preferences were at least partly caused by lower error rates (experiment 1) and greater foraging speeds (experiment 2) of foragers visiting the more easily learned feeder locations. Our results indicate that the learnability of feeding sites is an important factor influencing collective foraging patterns of ant colonies under more natural conditions, given that in natural environments foragers often face multiple bifurcations on their way to food sources.

Sensing the light environment in plants: photoreceptors and early signaling steps.

Plants must constantly adapt to a changing light environment in order to optimize energy conversion through the process of photosynthesis and to limit photodamage. In addition, plants use light cues for timing of key developmental transitions such as initiation of reproduction (transition to flowering). Plants are equipped with a battery of photoreceptors enabling them to sense a very broad light spectrum spanning from UV-B to far-red wavelength (280-750nm). In this review we briefly describe the different families of plant photosensory receptors and the mechanisms by which they transduce environmental information to influence numerous aspects of plant growth and development throughout their life cycle.

Studying social interactions through immersive virtual environment technology: Virtues, pitfalls, and future challenges

Thegoalofthepresentreviewistoexplainhowimmersivevirtualenvironmenttechnology(IVET)canbeusedforthestudyofsocialinteractionsandhowtheuseofvirtualhumansinimmersivevirtualenvironmentscanadvanceresearchandapplicationinmanydifferentfields.Researchersstudyingindividualdifferencesinsocialinteractionsaretypicallyinterestedinkeepingthebehaviorandtheappearanceoftheinteractionpartnerconstantacrossparticipants.WithIVETresearchershavefullcontrolovertheinteractionpartners,canstandardizethemwhilestillkeepingthesimulationrealistic.Virtualsimulationsarevalid:growingevidenceshowsthatindeedstudiesconductedwithIVETcanreplicatesomewell-knownfindingsofsocialpsychology.Moreover,IVETallowsresearcherstosubtlymanipulatecharacteristicsoftheenvironment(e.g.,visualcuestoprimeparticipants)orofthesocialpartner(e.g.,his/herrace)toinvestigatetheirinfluencesonparticipants'behaviorandcognition.Furthermore,manipulationsthatwouldbedifficultorimpossibleinreallife(e.g.,changingparticipants'height)canbeeasilyobtainedwithIVET.Besidetheadvantagesfortheoreticalresearch,weexplorethemostrecenttrainingandclinicalapplicationsofIVET,itsintegrationwithothertechnologies(e.g.,socialsensing)andfuturechallengesforresearchers(e.g.,makingthecommunicationbetweenvirtualhumansandparticipantssmoother).

Assessing the use of very high resolution data to predict species distribution in a mountain environment

Nowadays, Species Distribution Models (SDMs) are a widely used tool. Using different statistical approaches these models reconstruct the realized niche of a species using presence data and a set of variables, often topoclimatic. There utilization range is quite large from understanding single species requirements, to the creation of nature reserve based on species hotspots, or modeling of climate change impact, etc... Most of the time these models are using variables at a resolution of 50km x 50km or 1 km x 1 km. However in some cases these models are used with resolutions below the kilometer scale and thus called high resolution models (100 m x 100 m or 25 m x 25 m). Quite recently a new kind of data has emerged enabling precision up to lm x lm and thus allowing very high resolution modeling. However these new variables are very costly and need an important amount of time to be processed. This is especially the case when these variables are used in complex calculation like models projections over large areas. Moreover the importance of very high resolution data in SDMs has not been assessed yet and is not well understood. Some basic knowledge on what drive species presence-absences is still missing. Indeed, it is not clear whether in mountain areas like the Alps coarse topoclimatic gradients are driving species distributions or if fine scale temperature or topography are more important or if their importance can be neglected when balance to competition or stochasticity. In this thesis I investigated the importance of very high resolution data (2-5m) in species distribution models using either very high resolution topographic, climatic or edaphic variables over a 2000m elevation gradient in the Western Swiss Alps. I also investigated more local responses of these variables for a subset of species living in this area at two precise elvation belts. During this thesis I showed that high resolution data necessitates very good datasets (species and variables for the models) to produce satisfactory results. Indeed, in mountain areas, temperature is the most important factor driving species distribution and needs to be modeled at very fine resolution instead of being interpolated over large surface to produce satisfactory results. Despite the instinctive idea that topographic should be very important at high resolution, results are mitigated. However looking at the importance of variables over a large gradient buffers the importance of the variables. Indeed topographic factors have been shown to be highly important at the subalpine level but their importance decrease at lower elevations. Wether at the mountane level edaphic and land use factors are more important high resolution topographic data is more imporatant at the subalpine level. Finally the biggest improvement in the models happens when edaphic variables are added. Indeed, adding soil variables is of high importance and variables like pH are overpassing the usual topographic variables in SDMs in term of importance in the models. To conclude high resolution is very important in modeling but necessitate very good datasets. Only increasing the resolution of the usual topoclimatic predictors is not sufficient and the use of edaphic predictors has been highlighted as fundamental to produce significantly better models. This is of primary importance, especially if these models are used to reconstruct communities or as basis for biodiversity assessments. -- Ces dernières années, l'utilisation des modèles de distribution d'espèces (SDMs) a continuellement augmenté. Ces modèles utilisent différents outils statistiques afin de reconstruire la niche réalisée d'une espèce à l'aide de variables, notamment climatiques ou topographiques, et de données de présence récoltées sur le terrain. Leur utilisation couvre de nombreux domaines allant de l'étude de l'écologie d'une espèce à la reconstruction de communautés ou à l'impact du réchauffement climatique. La plupart du temps, ces modèles utilisent des occur-rences issues des bases de données mondiales à une résolution plutôt large (1 km ou même 50 km). Certaines bases de données permettent cependant de travailler à haute résolution, par conséquent de descendre en dessous de l'échelle du kilomètre et de travailler avec des résolutions de 100 m x 100 m ou de 25 m x 25 m. Récemment, une nouvelle génération de données à très haute résolution est apparue et permet de travailler à l'échelle du mètre. Les variables qui peuvent être générées sur la base de ces nouvelles données sont cependant très coûteuses et nécessitent un temps conséquent quant à leur traitement. En effet, tout calcul statistique complexe, comme des projections de distribution d'espèces sur de larges surfaces, demande des calculateurs puissants et beaucoup de temps. De plus, les facteurs régissant la distribution des espèces à fine échelle sont encore mal connus et l'importance de variables à haute résolution comme la microtopographie ou la température dans les modèles n'est pas certaine. D'autres facteurs comme la compétition ou la stochasticité naturelle pourraient avoir une influence toute aussi forte. C'est dans ce contexte que se situe mon travail de thèse. J'ai cherché à comprendre l'importance de la haute résolution dans les modèles de distribution d'espèces, que ce soit pour la température, la microtopographie ou les variables édaphiques le long d'un important gradient d'altitude dans les Préalpes vaudoises. J'ai également cherché à comprendre l'impact local de certaines variables potentiellement négligées en raison d'effets confondants le long du gradient altitudinal. Durant cette thèse, j'ai pu monter que les variables à haute résolution, qu'elles soient liées à la température ou à la microtopographie, ne permettent qu'une amélioration substantielle des modèles. Afin de distinguer une amélioration conséquente, il est nécessaire de travailler avec des jeux de données plus importants, tant au niveau des espèces que des variables utilisées. Par exemple, les couches climatiques habituellement interpolées doivent être remplacées par des couches de température modélisées à haute résolution sur la base de données de terrain. Le fait de travailler le long d'un gradient de température de 2000m rend naturellement la température très importante au niveau des modèles. L'importance de la microtopographie est négligeable par rapport à la topographie à une résolution de 25m. Cependant, lorsque l'on regarde à une échelle plus locale, la haute résolution est une variable extrêmement importante dans le milieu subalpin. À l'étage montagnard par contre, les variables liées aux sols et à l'utilisation du sol sont très importantes. Finalement, les modèles de distribution d'espèces ont été particulièrement améliorés par l'addition de variables édaphiques, principalement le pH, dont l'importance supplante ou égale les variables topographique lors de leur ajout aux modèles de distribution d'espèces habituels.

Adjusting for the environment in DEA: a comparison of alternative models based on empirical data

Due to the existence of free software and pedagogical guides, the use of Data Envelopment Analysis (DEA) has been further democratized in recent years. Nowadays, it is quite usual for practitioners and decision makers with no or little knowledge in operational research to run their own efficiency analysis. Within DEA, several alternative models allow for an environmental adjustment. Four alternative models, each user-friendly and easily accessible to practitioners and decision makers, are performed using empirical data of 90 primary schools in the State of Geneva, Switzerland. Results show that the majority of alternative models deliver divergent results. From a political and a managerial standpoint, these diverging results could lead to potentially ineffective decisions. As no consensus emerges on the best model to use, practitioners and decision makers may be tempted to select the model that is right for them, in other words, the model that best reflects their own preferences. Further studies should investigate how an appropriate multi-criteria decision analysis method could help decision makers to select the right model.

Geospatial approach for defining the Wildland-Urban Interface in the Alpine environment

Problems related to fire hazard and fire management have become in recent decades one of the most relevant issues in the Wildland-Urban Interface (WUI), that is the area where human infrastructures meet or intermingle with natural vegetation. In this paper we develop a robust geospatial method for defining and mapping the WUI in the Alpine environment, where most interactions between infrastructures and wildland vegetation concern the fire ignition through human activities, whereas no significant threats exist for infrastructures due to contact with burning vegetation. We used the three Alpine Swiss cantons of Ticino, Valais and Grisons as the study area. The features representing anthropogenic infrastructures (urban or infrastructural components of the WUI) as well as forest cover related features (wildland component of the WUI) were selected from the Swiss Topographic Landscape Model (TLM3D). Georeferenced forest fire occurrences derived from the WSL Swissfire database were used to define suitable WUI interface distances. The Random Forest algorithm was applied to estimate the importance of predictor variables to fire ignition occurrence. This revealed that buildings and drivable roads are the most relevant anthropogenic components with respect to fire ignition. We consequently defined the combination of drivable roads and easily accessible (i.e. 100 m from the next drivable road) buildings as the WUI-relevant infrastructural component. For the definition of the interface (buffer) distance between WUI infrastructural and wildland components, we computed the empirical cumulative distribution functions (ECDF) of the percentage of ignition points (observed and simulated) arising at increasing distances from the selected infrastructures. The ECDF facilitates the calculation of both the distance at which a given percentage of ignition points occurred and, in turn, the amount of forest area covered at a given distance. Finally, we developed a GIS ModelBuilder routine to map the WUI for the selected buffer distance. The approach was found to be reproducible, robust (based on statistical analyses for evaluating parameters) and flexible (buffer distances depending on the targeted final area covered) so that fire managers may use it to detect WUI according to their specific priorities.