Conservation genetics and population monitoring of the Alpine Salamander (Salamandra Atra) :

SUMMARYIn the context of the biodiversity crisis, amphibians are experiencing the most severe worldwide decline of all vertebrates and are in urgent need of better management. Efficient conservation strategies rely on sound knowledge of the species biology and of the genetic and demographic processes that might impair their welfare. Nonetheless, these processes are poorly understood in amphibians. Delineating population boundaries remains consequently problematic for these species, while it is of critical importance to define adequate management units for conservation. In this study, our attention focused on the alpine salamander (Salamandra atra), a species that deserves much interest in terms of both conservation biology and evolution. This endemic alpine species shows peculiar life-history traits (viviparity, reduced activity period, slow maturation) and has a slow population turnover, which might be problematic for its persistence in a changing environment. Due to its elusive behaviour (individuals spend most of their time underground and are unavailable for sampling), dynamic processes of gene and individuals were poorly understood for that species. Consequently, its conservation status could hardly be reliably assessed. Similarly the fire salamander (Salamandra salamandra) also poses special challenges for conservation, as no clear demarcation of geographical populations exists and dispersal patterns are poorly known. Through a phylogeographic analysis, we first studied the evolutionary history of the alpine salamander to better document the distribution of the genetic diversity along its geographical range. This study highlighted the presence of multiple divergent lineages in Italy together with a clear genetic divergence between populations from Northern and Dinaric Alps. These signs of cryptic genetic differentiation, which are not accounted for by the current taxonomy of the species, should not be neglected for further definition of conservation units. In addition, our data supported glacial survival of the species in northern peripheral glacial réfugia and nunataks, a pattern rarely documented for long-lived species. Then, we evaluated the level of gene flow between populations at the local scale and tested for asymmetries in male versus female dispersal using both field-based (mark-recapture) and genetic approaches. This study revealed high level of gene flow between populations, which stems mainly from male dispersal. This corroborated the idea that salamanders are much better dispersers than hitherto thought and provided a well- supported example of male-biased dispersal in amphibians. In a third step, based on a mark- recapture survey, we addressed the problem of sampling unavailability in alpine salamanders and evaluated its impact on two monitoring methods. We showed that about three quarters of individuals were unavailable for sampling during sampling sessions, a proportion that can vary with climatic conditions. If not taken into account, these complexities would result in false assumptions on population trends and misdirect conservation efforts. Finally, regarding the daunting task of delineating management units, our attention was drawn on the fire salamander. We conducted a local population genetic study that revealed high levels of gene flow among sampling sites. Management units for this species should consequently be large. Interestingly, despite the presence of several landscape features often reported to act as barriers, genetic breaks occurred at unexpected places. This suggests that landscape features may rather have idiosyncratic effects on population structure. In conclusion, this work brought new insights on both genetic and demographic processes occurring in salamanders. The results suggest that some biological paradigms should be taken with caution when particular species are in focus. Species- specific studies remain thus fundamental for a better understanding of species evolution and conservation, particularly in the context of current global changes.RESUMEDans le contexte de la crise de la biodiversité actuelle, les amphibiens subissent le déclin le plus important de tous les vertébrés et ont urgemment besoin d'une meilleure protection. L'établissement de stratégies de conservation efficaces repose sur des connaissances solides de la biologie des espèces et des processus génétiques et démographiques pouvant menacer leur survie. Ces processus sont néanmoins encore peu étudiés chez les amphibiens.Dans cette étude, notre attention s'est portée sur la salamandre noire (Salamandra atra), une espèce endémique des Alpes dont les traits d'histoire de vie atypiques (viviparité, phase d'activité réduite, lent turnover des populations) pourraient la rendre très vulnérable face aux changements environnementaux. Par ailleurs, en raison de son comportement cryptique (les individus passent la plupart de leur temps sous terre) la dynamique des gènes et des individus est mal comprise chez cette espèce. Il est donc difficile d'évaluer son statut de conservation de manière fiable. La salamandre tachetée {Salamandra salamandra), pour qui il n'existe aucune démarcation géographique apparente des populations, pose également des problèmes en termes de gestion. Dans un premier temps, nous avons étudié l'histoire évolutive de la salamandre noire afin de mieux décrire la distribution de sa diversité génétique au sein de son aire géographique. Cela a permis de mettre en évidence la présence de multiples lignées en Italie, ainsi qu'une nette divergence entre les populations du nord des Alpes et des Alpes dinariques. Ces résultats seront à prendre en compte lorsqu'il s'agira de définir des unités de conservation pour cette espèce. D'autre part, nos données soutiennent l'hypothèse d'une survie glaciaire dans des refuges nordiques périglaciaires ou dans des nunataks, fait rarement documenté pour une espèce longévive. Nous avons ensuite évalué la différentiation génétique des populations à l'échelle locale, ce qui a révélé d'important flux de gènes, ainsi qu'une asymétrie de dispersion en faveur des mâles. Ces résultats corroborent l'idée que les amphibiens dispersent mieux que ce que l'on pensait, et fournissent un exemple robuste de dispersion biaisée en faveur des mâles chez les amphibiens. Nous avons ensuite abordé le problème de Γ inaccessibilité des individus à la capture. Nous avons montré qu'environ trois quarts des individus sont inaccessibles lors des échantillonnages, une proportion qui peut varier en fonction des conditions climatiques. Ignoré, ce processus pourrait entraîner une mauvaise interprétation des fluctuations de populations ainsi qu'une mauvaise allocation des efforts de conservation. Concernant la définition d'unités de gestion pour la salamandre tachetée, nous avons pu mettre en évidence un flux de gènes important entre les sites échantillonnés. Les unités de gestion pour cette espèce devraient donc être étendues. Etonnamment, malgré la présence de nombreuses barrières potentielles au flux de gènes, les démarcations génétiques sont apparues à des endroits inattendus. En conclusion, ce travail a apporté une meilleure compréhension des processus génétiques et démographiques en action chez les salamandres. Les résultats suggèrent que certains paradigmes biologiques devraient être considérés avec précaution quand il s'agit de les appliquer à des espèces particulières. Les études spécifiques demeurent donc fondamentales pour une meilleure compréhension de l'évolution des espèces et leur conservation, tout particulièrement dans le contexte des changements globaux actuels.

A study on the expressive power of some fragments of the modal µ-Calculus

Résumé Le μ-calcul est une extension de la logique modale par des opérateurs de point fixe. Dans ce travail nous étudions la complexité de certains fragments de cette logique selon deux points de vue, différents mais étroitement liés: l'un syntaxique (ou combinatoire) et l'autre topologique. Du point de vue syn¬taxique, les propriétés définissables dans ce formalisme sont classifiées selon la complexité combinatoire des formules de cette logique, c'est-à-dire selon le nombre d'alternances des opérateurs de point fixe. Comparer deux ensembles de modèles revient ainsi à comparer la complexité syntaxique des formules as¬sociées. Du point de vue topologique, les propriétés définissables dans cette logique sont comparées à l'aide de réductions continues ou selon leurs positions dans la hiérarchie de Borel ou dans celle projective. Dans la première partie de ce travail nous adoptons le point de vue syntax¬ique afin d'étudier le comportement du μ-calcul sur des classes restreintes de modèles. En particulier nous montrons que: (1) sur la classe des modèles symétriques et transitifs le μ-calcul est aussi expressif que la logique modale; (2) sur la classe des modèles transitifs, toute propriété définissable par une formule du μ-calcul est définissable par une formule sans alternance de points fixes, (3) sur la classe des modèles réflexifs, il y a pour tout η une propriété qui ne peut être définie que par une formule du μ-calcul ayant au moins η alternances de points fixes, (4) sur la classe des modèles bien fondés et transitifs le μ-calcul est aussi expressif que la logique modale. Le fait que le μ-calcul soit aussi expressif que la logique modale sur la classe des modèles bien fondés et transitifs est bien connu. Ce résultat est en ef¬fet la conséquence d'un théorème de point fixe prouvé indépendamment par De Jongh et Sambin au milieu des années 70. La preuve que nous donnons de l'effondrement de l'expressivité du μ-calcul sur cette classe de modèles est néanmoins indépendante de ce résultat. Par la suite, nous étendons le langage du μ-calcul en permettant aux opérateurs de point fixe de lier des occurrences négatives de variables libres. En montrant alors que ce formalisme est aussi ex¬pressif que le fragment modal, nous sommes en mesure de fournir une nouvelle preuve du théorème d'unicité des point fixes de Bernardi, De Jongh et Sambin et une preuve constructive du théorème d'existence de De Jongh et Sambin. RÉSUMÉ Pour ce qui concerne les modèles transitifs, du point de vue topologique cette fois, nous prouvons que la logique modale correspond au fragment borélien du μ-calcul sur cette classe des systèmes de transition. Autrement dit, nous vérifions que toute propriété définissable des modèles transitifs qui, du point de vue topologique, est une propriété borélienne, est nécessairement une propriété modale, et inversement. Cette caractérisation du fragment modal découle du fait que nous sommes en mesure de montrer que, modulo EF-bisimulation, un ensemble d'arbres est définissable dans la logique temporelle Ε F si et seulement il est borélien. Puisqu'il est possible de montrer que ces deux propriétés coïncident avec une caractérisation effective de la définissabilité dans la logique Ε F dans le cas des arbres à branchement fini donnée par Bojanczyk et Idziaszek [24], nous obtenons comme corollaire leur décidabilité. Dans une deuxième partie, nous étudions la complexité topologique d'un sous-fragment du fragment sans alternance de points fixes du μ-calcul. Nous montrons qu'un ensemble d'arbres est définissable par une formule de ce frag¬ment ayant au moins η alternances si et seulement si cette propriété se trouve au moins au n-ième niveau de la hiérarchie de Borel. Autrement dit, nous vérifions que pour ce fragment du μ-calcul, les points de vue topologique et combina- toire coïncident. De plus, nous décrivons une procédure effective capable de calculer pour toute propriété définissable dans ce langage sa position dans la hiérarchie de Borel, et donc le nombre d'alternances de points fixes nécessaires à la définir. Nous nous intéressons ensuite à la classification des ensembles d'arbres par réduction continue, et donnons une description effective de l'ordre de Wadge de la classe des ensembles d'arbres définissables dans le formalisme considéré. En particulier, la hiérarchie que nous obtenons a une hauteur (ωω)ω. Nous complétons ces résultats en décrivant un algorithme permettant de calculer la position dans cette hiérarchie de toute propriété définissable.

European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring.

Given the increasing use of ambulatory blood pressure monitoring (ABPM) in both clinical practice and hypertension research, a group of scientists, participating in the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability, in year 2013 published a comprehensive position paper dealing with all aspects of the technique, based on the available scientific evidence for ABPM. The present work represents an updated schematic summary of the most important aspects related to the use of ABPM in daily practice, and is aimed at providing recommendations for proper use of this technique in a clinical setting by both specialists and practicing physicians. The present article details the requirements and the methodological issues to be addressed for using ABPM in clinical practice, The clinical indications for ABPM suggested by the available studies, among which white-coat phenomena, masked hypertension, and nocturnal hypertension, are outlined in detail, and the place of home measurement of blood pressure in relation to ABPM is discussed. The role of ABPM in pharmacological, epidemiological, and clinical research is also briefly mentioned. Finally, the implementation of ABPM in practice is considered in relation to the situation of different countries with regard to the reimbursement and the availability of ABPM in primary care practices, hospital clinics, and pharmacies.

Power laws and scaling of rain events and dry spells in the Catalonia region

We analyze the statistics of rain-event sizes, rain-event durations, and dry-spell durations in a network of 20 rain gauges scattered in an area situated close to the NW Mediterranean coast. Power-law distributions emerge clearly for the dryspell durations, with an exponent around 1.50 ± 0.05, although for event sizes and durations the power-law ranges are rather limited, in some cases. Deviations from power-law behavior are attributed to finite-size effects. A scaling analysis helps to elucidate the situation, providing support for the existence of scale invariance in these distributions. It is remarkable that rain data of not very high resolution yield findings in agreement with self-organized critical phenomena.

Clinical benefits of an adherence monitoring program in the management of secondary hyperparathyroidism with cinacalcet: results of a prospective randomized controlled study.

BACKGROUND/AIMS: One of the causes of uncontrolled secondary hyperparathyroidism (sHPT) is patient's poor drug adherence. We evaluated the clinical benefits of an integrated care approach on the control of sHPT by cinacalcet. METHODS: Prospective, randomized, controlled, multicenter, open-label study. Fifty hemodialysis patients on a stable dose of cinacalcet were randomized to an integrated care approach (IC) or usual care approach (UC). In the IC group, cinacalcet adherence was monitored using an electronic system. Results were discussed with the patients in motivational interviews, and drug prescription adapted accordingly. In the UC group, drug adherence was monitored, but results were not available. RESULTS: At six months, 84% of patients in the IC group achieved recommended iPTH targets versus 55% in the UC group (P = 0.04). The mean cinacalcet taking adherence improved by 10.8% in the IC group and declined by 5.3% in the UC group (P = 0.02). Concomitantly, the mean dose of cinacalcet was reduced by 7.2 mg/day in the IC group and increased by 6.4 mg/day in the UC group (P = 0.03). CONCLUSIONS: The use of a drug adherence monitoring program in the management of sHPT in hemodialysis patients receiving cinacalcet improves drug adherence and iPTH control and allows a reduction in the dose of cinacalcet.

Field Monitoring of Cypermethrin Residual Effect on the Mortality Rates of the Phlebotomine Sand Fly Lutzomyia longipalpis in the State of Paraíba, Brazil

In a visceral leishmaniasis endemic locality of northeast of Brasil where all settlements were treated with cypermethrin, a follow-up of Lutzomyia longipalpis populations was carried out by regular collections. The residual effect of the insecticide was studied using biological assays on three different types of walls. The results showed that the insecticides had an effect on intradomiciliar Lu. longipalpis populations limited to two months, and had no significant effect on peridomiciliar vector populations. The mortality rates of the tested sandflies were variable according to the type of wall. The decreasing of the insecticide effect was marked since the 3rd month, and mortality rates were identical whatever the type of wall since the 4th month. Unsufficient residual effect was detected after the 4th month.

Suivi thérapeutique des concentrations d'inhibiteurs de tyrosine kinase et d'autres médicaments oncologiques = Therapeutisches Drug-Monitoring der Konzentration von Tyrosinkinase-Inhibitoren und anderen Onkologika

Les médicaments anticancéreux sont souvent caractérisés par une importante variabilité pharmacocinétique interindividuelle, des relations entre concentration et réponse clinique et une marge thérapeutique étroite. Pourtant, le suivi thérapeutique des concentrations de ces médicaments (TDM) est encore rare en oncologie. Les bases scientifiques justifiant un TDM des nouvelles thérapies ciblées orales sont encore très hétérogènes. Cependant, d'assez solides évidences existent pour l'imatinib et certaines apparaissent progressivement pour d'autres composés. A côté de cela, le TDM est aussi pratiqué dans des situations spécifiques de traitement par certaines chimiothérapies conventionnelles. Des efforts considérables restent toutefois à réaliser pour mieux caractériser la pharmacocinétique de ces médicaments, pour préciser leurs relations concentration-effet et pour conduire des études prospectives randomisées évaluant le bénéfice clinique de l'approche TDM en oncologie.

An approximate solution method for boundary layer flow of a power law fluid over a flat plate

The work in this paper deals with the development of momentum and thermal boundary layers when a power law fluid flows over a flat plate. At the plate we impose either constant temperature, constant flux or a Newton cooling condition. The problem is analysed using similarity solutions, integral momentum and energy equations and an approximation technique which is a form of the Heat Balance Integral Method. The fluid properties are assumed to be independent of temperature, hence the momentum equation uncouples from the thermal problem. We first derive the similarity equations for the velocity and present exact solutions for the case where the power law index n = 2. The similarity solutions are used to validate the new approximation method. This new technique is then applied to the thermal boundary layer, where a similarity solution can only be obtained for the case n = 1.

Ambulatory Blood Pressure and Adherence Monitoring: Diagnosing Pseudoresistant Hypertension.

A small proportion of the treated hypertensive population consistently has a blood pressure greater than 140/90 mm Hg despite a triple therapy including a diuretic, a calcium channel blocker, and a blocker of the renin-angiotensin system. According to guidelines, these patients have so-called resistant hypertension. The prevalence of this clinical condition is higher in tertiary than primary care centers and often is associated with chronic kidney disease, diabetes, obesity, and sleep apnea syndrome. Exclusion of pseudoresistant hypertension using ambulatory or home blood pressure monitoring is a crucial step in the investigation of patients with resistant hypertension. Thus, among the multiple factors to consider when investigating patients with resistant hypertension, ambulatory blood pressure monitoring should be performed very early. Among other factors to consider, physicians should investigate patient adherence to therapy, assess the adequacy of treatment, exclude interfering factors, and, finally, look for secondary forms of hypertension. Poor adherence to therapy accounts for 30% to 50% of cases of resistance to therapy depending on the methodology used to diagnose adherence problems. This review discusses the clinical factors implicated in the pathogenesis of resistant hypertension with a particular emphasis on pseudoresistance, drug adherence, and the use of ambulatory blood pressure monitoring for the diagnosis and management of resistant hypertension.

Uranium reserve, nuclear fuel cycle delusion, CO2 emission from the sea, and electricity supply: reflections after the fuel meltdown of Fukushima nuclear power units

The Great Tohoku-Kanto earthquake and resulting tsunami has brought considerable attention to the issue of the construction of new power plants. We argue in this paper, nuclear power is not a sustainable solution to energy problems. First, we explore the stock of uranium-235 and the different schemes developed by the nuclear power industry to exploit this resource. Second, we show that these methods, fast breeder and MOX fuel reactors, are not feasible. Third, we show that the argument that nuclear energy can be used to reduce CO2 emissions is false: the emissions from the increased water evaporation from nuclear power generation must be accounted for. In the case of Japan, water from nuclear power plants is drained into the surrounding sea, raising the water temperature which has an adverse affect on the immediate ecosystem, as well as increasing CO2 emissions from increased water evaporation from the sea. Next, a short exercise is used to show that nuclear power is not even needed to meet consumer demand in Japan. Such an exercise should be performed for any country considering the construction of additional nuclear power plants. Lastly, the paper is concluded with a discussion of the implications of our findings.

Application of detection probabilities to the design of amphibian monitoring programs in temporary ponds

Failure to detect a species in an area where it is present is a major source of error in biological surveys. We assessed whether it is possible to optimize single-visit biological monitoring surveys of highly dynamic freshwater ecosystems by framing them a priori within a particular period of time. Alternatively, we also searched for the optimal number of visits and when they should be conducted. We developed single-species occupancy models to estimate the monthly probability of detection of pond-breeding amphibians during a four-year monitoring program. Our results revealed that detection probability was species-specific and changed among sampling visits within a breeding season and also among breeding seasons. Thereby, the optimization of biological surveys with minimal survey effort (a single visit) is not feasible as it proves impossible to select a priori an adequate sampling period that remains robust across years. Alternatively, a two-survey combination at the beginning of the sampling season yielded optimal results and constituted an acceptable compromise between sampling efficacy and survey effort. Our study provides evidence of the variability and uncertainty that likely affects the efficacy of monitoring surveys, highlighting the need of repeated sampling in both ecological studies and conservation management.

Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care : A statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.

Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.