Adapting global conservation strategies to climate change at the European scale: the otter as a flagship species

Climate change has created the need for new strategies in conservation planning that account for the dynamics of factors threatening endangered species. Here we assessed climate change threat to the European otter, a flagship species for freshwater ecosystems, considering how current conservation areas will perform in preserving the species in a climatically changed future. We used an ensemble forecasting approach considering six modelling techniques applied to eleven subsets of otter occurrences across Europe. We performed a pseudo-independent and an internal evaluation of predictions. Future projections of species distribution were made considering the A2 and B2 scenarios for 2080 across three climate models: CCCMA-CGCM2, CSIRO-MK2 and HCCPR HAD-CM3. The current and the predicted otter distributions were used to identify priority areas for the conservation of the species, and overlapped to existing network of protected areas. Our projections show that climate change may profoundly reshuffle the otter's potential distribution in Europe, with important differences between the two scenarios we considered. Overall, the priority areas for conservation of the otter in Europe appear to be unevenly covered by the existing network of protected areas, with the current conservation efforts being insufficient in most cases. For a better conservation, the existing protected areas should be integrated within a more general conservation and management strategy incorporating climate change projections. Due to the important role that the otter plays for freshwater habitats, our study further highlights the potential sensitivity of freshwater habitats in Europe to climate change.

Male sexuality-related concerns: what use of the internet?

Purpose: Although young males encounter sexually-related concerns, they are mostly absent from specialized services. Our objective is to assess whether the internet is used by boys to find answers to these types of problems and questions. Methods: In the context of a qualitative study assessing young males' barriers to access sexual and reproductive health facilities, we conducted two focus groups gathering 12 boys aged 17-20. Discussions were triggered through the presentation of four vignettes corresponding to questions posted by 17-20 year old boys and girls on an information website for adolescents (www.ciao.ch), concerning various sexual dysfunction situations. In order to avoid having to talk about their own experience, participants were asked what they would do in those cases. Results: In general, the internet was mentioned quite thoroughly as a means of searching for information through research engines and a place to address professionals for advice.Within the hierarchy of consultation possibilities, the internet was given the first place as a way to deal with these types of problems presenting many advantages: (1) the internet enables to maintain intimacy; (2) it is anonymous (use of a pseudo); (3) it avoids having to confront someone face-to-face with personal problems which can be embarrassing and challenging for one's pride; (4) it is free; and (5) it is accessible at all times. In other words, participants value the internet as a positive tool to avoid many barriers which prevent offline consultations to take place. Most participants consider the internet at least as a first step in trying to solve a problem; for instance, by better defining the seriousness of a problem and judging if it is worth consulting a doctor. However, despite the positive qualities of the internet, they do put forward the importance of having specialists answering questions, trustworthiness, and being followed-up by the same person. Participants suggested that a strategy to break down barriers for boys to consult in face-to-face settings is to have a consultation on the internet as a first step which could then guide the person to an in-person consultation if necessary. Conclusions: The internet as a means of obtaining information or consulting received high marks overall. Although the internet cannot replace an in-person consultation, the screen and the keyboard have the advantage of not involving a face-to-face encounter and raise the possibility of discussing sexual problems anonymously and in private. The internet tools together with other new technologies should continue to develop in a secure manner as a space providing prevention messages and to become an easy access door to sexual and reproductive health services for young men, which can then guide youths to appropriate resource persons. Sources of support: This study was supported by the Maurice Chalumeau Foundation, Switzerland.

Impedance boundary conditions for pseudo-spectral time-domain methods in room acoustics

The pseudo-spectral time-domain (PSTD) method is an alternative time-marching method to classicalleapfrog finite difference schemes in the simulation of wave-like propagating phenomena. It is basedon the fundamentals of the Fourier transform to compute the spatial derivatives of hyperbolic differential equations. Therefore, it results in an isotropic operator that can be implemented in an efficient way for room acoustics simulations. However, one of the first issues to be solved consists on modeling wallabsorption. Unfortunately, there are no references in the technical literature concerning to that problem. In this paper, assuming real and constant locally reacting impedances, several proposals to overcome this problem are presented, validated and compared to analytical solutions in different scenarios.

Impedance boundary conditions for pseudo-spectral time-domain methods in room acoustics

The Pseudo-Spectral Time Domain (PSTD) method is an alternative time-marching method to classical leapfrog finite difference schemes inthe simulation of wave-like propagating phenomena. It is based on the fundamentals of the Fourier transform to compute the spatial derivativesof hyperbolic differential equations. Therefore, it results in an isotropic operator that can be implemented in an efficient way for room acousticssimulations. However, one of the first issues to be solved consists on modeling wall absorption. Unfortunately, there are no references in thetechnical literature concerning to that problem. In this paper, assuming real and constant locally reacting impedances, several proposals toovercome this problem are presented, validated and compared to analytical solutions in different scenarios.

Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial.

Glioblastoma (GBM) is a morphologically heterogeneous tumor type with a median survival of only 15 months in clinical trial populations. However, survival varies greatly among patients. As part of a central pathology review, we addressed the question if patients with GBM displaying distinct morphologic features respond differently to combined chemo-radiotherapy with temozolomide. Morphologic features were systematically recorded for 360 cases with particular focus on the presence of an oligodendroglioma-like component and respective correlations with outcome and relevant molecular markers. GBM with an oligodendroglioma-like component (GBM-O) represented 15% of all confirmed GBM (52/339) and was not associated with a more favorable outcome. GBM-O encompassed a pathogenetically heterogeneous group, significantly enriched for IDH1 mutations (19 vs. 3%, p = 0.003) and EGFR amplifications (71 vs. 48%, p = 0.04) compared with other GBM, while co-deletion of 1p/19q was found in only one case and the MGMT methylation frequency was alike (47 vs. 46%). Expression profiles classified most of the GBM-O into two subtypes, 36% (5/14 evaluable) as proneural and 43% as classical GBM. The detection of pseudo-palisading necrosis (PPN) was associated with benefit from chemotherapy (p = 0.0002), while no such effect was present in the absence of PPN (p = 0.86). In the adjusted interaction model including clinical prognostic factors and MGMT status, PPN was borderline nonsignificant (p = 0.063). Taken together, recognition of an oligodendroglioma-like component in an otherwise classic GBM identifies a pathogenetically mixed group without prognostic significance. However, the presence of PPN may indicate biological features of clinical relevance for further improvement of therapy.

ILS-ESP An efficient, simple, and parameter-free algorithm for solving the permutation flow-shop problem

From a managerial point of view, the more effcient, simple, and parameter-free (ESP) an algorithm is, the more likely it will be used in practice for solving real-life problems. Following this principle, an ESP algorithm for solving the Permutation Flowshop Sequencing Problem (PFSP) is proposed in this article. Using an Iterated Local Search (ILS) framework, the so-called ILS-ESP algorithm is able to compete in performance with other well-known ILS-based approaches, which are considered among the most effcient algorithms for the PFSP. However, while other similar approaches still employ several parameters that can affect their performance if not properly chosen, our algorithm does not require any particular fine-tuning process since it uses basic "common sense" rules for the local search, perturbation, and acceptance criterion stages of the ILS metaheuristic. Our approach defines a new operator for the ILS perturbation process, a new acceptance criterion based on extremely simple and transparent rules, and a biased randomization process of the initial solution to randomly generate different alternative initial solutions of similar quality -which is attained by applying a biased randomization to a classical PFSP heuristic. This diversification of the initial solution aims at avoiding poorly designed starting points and, thus, allows the methodology to take advantage of current trends in parallel and distributed computing. A set of extensive tests, based on literature benchmarks, has been carried out in order to validate our algorithm and compare it against other approaches. These tests show that our parameter-free algorithm is able to compete with state-of-the-art metaheuristics for the PFSP. Also, the experiments show that, when using parallel computing, it is possible to improve the top ILS-based metaheuristic by just incorporating to it our biased randomization process with a high-quality pseudo-random number generator.

Solid pseudopapillary tumor of the pancreas in children : typical radiological findings and pathological correlation

Introduction : Les tumeurs solides pseudo-papillaires du pancréas (SPT) sont des tumeurs rares, d'étiopathogénie encore incertaine.Le but de notre travail était de décrire les caractéristiques radiologiques des SPT dans le groupe d'âge pédiatrique et d'étudier leur corrélation avec les études anatomopathologiques en vue d'établir un diagnostic.Patients et Méthodes : Nous avons étudié rétrospectivement trois malades pédiatriques pour lesquelles le diagnostic de tumeur solide pseudo-papillaire du pancréas a été porté à l'examen d'une pièce opératoire. Ce groupe comprenait 3 jeunes filles et femmes (âge médian: 13 ans).Résultats : La tumeur a été découverte pendant le bilan de symptômes digestifs non spécifiques. Les examens biologiques n'étaient pas informatifs. Des investigations radiologiques complètes ont été réalisées y compris les ultrasons (US), la tomodensitométrie (CT) et l'imagerie par résonance magnétique (IRM).Celles-ci ont montré de volumineuses lésions nodulaires, peu vascularisées, de compositions habituellement hétérogènes, avec des composantes kystiques et hémorragiques identifiées dans les 3 cas. Un traitement chirurgical a été pratiqué chez toute les patientes. L'étude de la pièce opératoire a montré une tumeur encapsulée dans les 3 cas. Aucune métastase n'a été mise en évidence.Conclusion : Les SPT doivent être considérées dans le diagnostic différentiel des masses pancréatiques pédiatriques, en particulier chez les adolescentes. Certaines caractéristiques radiologiques comme des masses volumineuses bien circonscrites, des lésions hétérogènes avec des zones kystiques et hémorragiques, de plus entourées d'une pseudocapsule fibreuse réactive, suggèrent fortement le diagnostic de SPT. Celui-ci devrait ensuite être confirmé par une biopsie avant que la résection chirurgicale soit effectuée. Chez les enfants, Γ écho graphie abdominale reste la méthode de première intention, suivie par l'IRM comme technique d'imagerie de choix pour évaluer les caractéristiques et l'extension de la lésion, tout en évitant l'exposition des patients aux rayonnements ionisants.

Cis-configured aziridines are new pseudo-irreversible dual-mode inhibitors of Candida albicans secreted aspartic protease 2

A series of cis-configured epoxides and aziridines containing hydrophobic moieties and amino acid esters,were synthesized as new potential inhibitors of the secreted aspartic protease 2 (SAP2) of Candida albicans. Enzyme assays revealed the N- benzyl-3-phenyl-substituted aziridines 11 and 17 as the most potent inhibitors, with second-order inhibition, rate constants (k(2)) between 56000 and 12-1000 M-1 min(-1). The compounds were shown to be pseudo-irreversible dual-mode, inhibitors: the interm ediate esterified enzyme resulting from nucleophilic ring opening was hydrolyzed and yielded amino alcohols as transition state-mimetic reversible inhibitors. The results of docking studies with the ring-closed aziridine forms of the inhibitors suggest binding modes mainly dominated by hydrophobic interactions with the S1, S1' S2, and S2' subsites of the protease, and docking studies with the processed amino alcohol forms predict additional hydrogen bonds of the new hydroxy group to the active site Asp residues. C. albicans growth assays showed the compounds to decrease SAP2-dependent growth while not affecting SAP2-independent growth.

Late Proterozoic thrust tectonics, high-pressure metamorphism and Uranium mineralization in the domes area, Lufilian arc, northwestern Zambia

The following main lithostratigraphic units have been distinguished in the Domes Area. The Kibaran basement complex composed of gneisses, migmatites with amphibolite bands and metagranites is exposed in dome structures; metamorphic features of Kibaran age have been almost completely obliterated by extensive Lufilian reactivation. The post-Kibaran cover sequence is subdivided into the Lower Roan Group consisting of well-preserved quartzites with high Mg content, talc-bearing, extremely foliated schists intercalated with pseudo-conglomerates of tectonic origin and the Upper Roan Group including dolomitic marbles with rare stromatolites, metapelites and a sequence of detrital metasediments, with local volcano-sedimentary components and interlayered banded ironstones. The sediments of the Lower Roan Group are interpreted as continental to lagoonal-evaporitic deposits partly converted into the talc-kyanite + garnet assemblage characteristic of ``white schists''. The dolomites and metapelites of the Upper Roan Group are attributed to a carbonate platform sequence progressively subsiding under terrigenous deposits, whilst the detrital metasediments and BIF may be interpreted as a basinal sequence, probably deposited on oceanic crust grading laterally into marbles. Metagabbros and metabasalts are considered as remnants of an ocean-floor-type crustal unit probably related to small basins. Alkaline stocks of Silurian age intruded the post-Kibaran cover. Significant ancestral tectonic discontinuities promoted the development of a nappe pile that underwent high-pressure metamorphism during the Lufilian orogeny and all lithostratigraphic units. Rb-Sr and K-Ar and U-Pb data indicate an age of 700 Ma for the highest grade metamorphism and 500 Ma for blocking of the K-Ar and Rb-Sr system in micas, corresponding to the time when the temperature dropped below 350-degrees-400-degrees-C and to an age of about 400 Ma for the emplacement of hypabyssal syenitic bodies. A first phase of crustal shortening by decoupling of basement and cover slices along shallow shear zones has been recognized. Fluid-rich tectonic slabs of cover sediments were thus able to transport fluids into the anhydrous metamorphic basement or mafic units. During the subsequent metamorphic re-equilibration stage of high pressure, pre-existing thrusts horizons were converted into recrystallized mylonites. Due to uplift, rocks were re-equilibrated into assemblages compatible with lower pressures and slightly lower temperatures. This stage occurs under a decompressional (nearly adiabatic) regime, with P(fluid) almost-equal-to P(lithostatic). It is accompanied by metasomatic development of minerals, activated by injection of hot fluids. New or reactivated shear zones and mylonitic belts were the preferred conduits of fluids. The most evident regional-scale effect of these processes is the intense metasomatic scapolitization of formerly plagioclase-rich lithologies. Uraninite mineralization can probably be assigned to the beginning of the decompressional stage. A third regional deformation phase characterized by open folds and local foliation is not accompanied by significant growth of new minerals. However, pitchblende mineralization can be ascribed to this phase as late-stage, short-range remobilization of previously existing deposits. Finally, shallow alkaline massifs were emplaced when the level of the Domes Area now exposed was already subjected to exchange with meteoric circuits, activated by residual geothermal gradients generally related to intrusions or rifting. Most of the superficial U-showings with U-oxidation products were probably generated during this relatively recent phase.

On the efficiency and sensitivity of a pyramidal classification algorithm

In this paper we propose a Pyramidal Classification Algorithm,which together with an appropriate aggregation index producesan indexed pseudo-hierarchy (in the strict sense) withoutinversions nor crossings. The computer implementation of thealgorithm makes it possible to carry out some simulation testsby Monte Carlo methods in order to study the efficiency andsensitivity of the pyramidal methods of the Maximum, Minimumand UPGMA. The results shown in this paper may help to choosebetween the three classification methods proposed, in order toobtain the classification that best fits the original structureof the population, provided we have an a priori informationconcerning this structure.

A neuronal gamma oscillatory signature during morphological unification in the left occipitotemporal junction.

Morphology is the aspect of language concerned with the internal structure of words. In the past decades, a large body of masked priming (behavioral and neuroimaging) data has suggested that the visual word recognition system automatically decomposes any morphologically complex word into a stem and its constituent morphemes. Yet the reliance of morphology on other reading processes (e.g., orthography and semantics), as well as its underlying neuronal mechanisms are yet to be determined. In the current magnetoencephalography study, we addressed morphology from the perspective of the unification framework, that is, by applying the Hold/Release paradigm, morphological unification was simulated via the assembly of internal morphemic units into a whole word. Trials representing real words were divided into words with a transparent (true) or a nontransparent (pseudo) morphological relationship. Morphological unification of truly suffixed words was faster and more accurate and additionally enhanced induced oscillations in the narrow gamma band (60-85 Hz, 260-440 ms) in the left posterior occipitotemporal junction. This neural signature could not be explained by a mere automatic lexical processing (i.e., stem perception), but more likely it related to a semantic access step during the morphological unification process. By demonstrating the validity of unification at the morphological level, this study contributes to the vast empirical evidence on unification across other language processes. Furthermore, we point out that morphological unification relies on the retrieval of lexical semantic associations via induced gamma band oscillations in a cerebral hub region for visual word form processing.

A pseudo-spectral method for simulating of poro-elastic seismic wave propagation in complex borehole environments

We present a novel numerical approach for the comprehensive, flexible, and accurate simulation of poro-elastic wave propagation in cylindrical coordinates. An important application of this method is the modeling of complex seismic wave phenomena in fluid-filled boreholes, which represents a major, and as of yet largely unresolved, computational problem in exploration geophysics. In view of this, we consider a numerical mesh consisting of three concentric domains representing the borehole fluid in the center, the borehole casing and the surrounding porous formation. The spatial discretization is based on a Chebyshev expansion in the radial direction, Fourier expansions in the other directions, and a Runge-Kutta integration scheme for the time evolution. A domain decomposition method based on the method of characteristics is used to match the boundary conditions at the fluid/porous-solid and porous-solid/porous-solid interfaces. The viability and accuracy of the proposed method has been tested and verified in 2D polar coordinates through comparisons with analytical solutions as well as with the results obtained with a corresponding, previously published, and independently benchmarked solution for 2D Cartesian coordinates. The proposed numerical solution also satisfies the reciprocity theorem, which indicates that the inherent singularity associated with the origin of the polar coordinate system is handled adequately.

Pharmacodynamic, pharmacokinetic and pharmacogenetic aspects of drugs used in the treatment of Alzheimer's disease.

With the aging population and its rapidly increasing prevalence, dementia has become an important public health concern in developed and developing countries. To date, the pharmacological treatment is symptomatic and based on the observed neurotransmitter disturbances. The four most commonly used drugs are donepezil, galantamine, rivastigmine and memantine. Donepezil, galantamine and rivastigmine are acetylcholinesterase inhibitors with different pharmacodynamic and pharmacokinetic profiles. Donepezil inhibits selectively the acetylcholinesterase and has a long elimination half-life (t½) of 70 h. Galantamine is also a selective acetylcholinesterase inhibitor, but also modulates presynaptic nicotinic receptors. It has a t½ of 6-8 h. Donepezil and galantamine are mainly metabolised by cytochrome P450 (CYP) 2D6 and CYP3A4 in the liver. Rivastigmine is a so-called 'pseudo-irreversible' inhibitor of acetylcholinesterase and butyrylcholinesterase. The t½ of the drug is very short (1-2 h), but the duration of action is longer as the enzymes are blocked for around 8.5 and 3.5 h, respectively. Rivastigmine is metabolised by esterases in liver and intestine. Memantine is a non-competitive low-affinity antagonist of the NMDA receptor with a t½ of 70 h. Its major route of elimination is unchanged via the kidneys. Addressing the issue of inter-patient variability in treatment response might be of special importance for the vulnerable population taking anti-dementia drugs. Pharmacogenetic considerations might help to avoid multiple medication changes due to non-response and/or adverse events. Some pharmacogenetic studies conducted on donepezil and galantamine reported an influence of the CYP2D6 genotype on the pharmacokinetics of the drugs and/or on the response to treatment. Moreover, polymorphisms in genes of the cholinergic markers acetylcholinesterase, butyrylcholinesterase, choline acetyltransferase and paraoxonase were found to be associated with better clinical response to acetylcholinesterase inhibitors. However, confirmation studies in larger populations are necessary to establish evidence of which subgroups of patients will most likely benefit from anti-dementia drugs. The aim of this review is to summarize the pharmacodynamics and pharmacokinetics of the four commonly used anti-dementia drugs and to give an overview on the current knowledge of pharmacogenetics in this field.

Fluid evolution at the Variscan front in the vicinity of the Aachen thrust

Quartz-carbonate-chlorite veins were studied in borehole samples of the RWTH-1 well in Aachen. Veins formed in Devonian rocks in the footwall of the Aachen thrust during Variscan deformation and associated fluid flow. Primary fluid inclusions indicate subsolvus unmixing of a homogenous H(2)O-CO(2)-CH(4)-(N(2))-Na-(K)-Cl fluid into a H(2)O-Na-(K)-Cl solution and a vapour-rich CO(2)-(H(2)O, CH(4), N(2)) fluid. The aqueous end-member composition resembles that of metamorphic fluids of the Variscan front zone with salinities ranging from 4 to 7% NaCl equiv. and maximum homogenisation temperatures of close to 400A degrees C. Pressure estimates indicate a burial depth between 4,500 and 8,000 m at geothermal gradients between 50 and 75A degrees C/26 MPa, but pressure decrease to sublithostatic conditions is also indicated, probably as a consequence of fracture opening during episodic seismic activity. A second fluid system, mainly preserved in pseudo-secondary and secondary fluid inclusions, is characterised by fluid temperatures between 200 and 250A degrees C and salinities of < 5% NaCl equiv. Bulk stable isotope analyses of fluids released from vein quartz, calcite, and dolomite by decrepitation yielded delta D(H2O) values from -89 to -113 aEuro degrees, delta(13)C(CH4) from -26.9 to -28.9aEuro degrees (VPDB) and delta(13)C(CO2) from -12.8 to -23.3aEuro degrees (VPDB). The low delta D and delta(13)C range of the fluids is considered to be due to interaction with cracked hydrocarbons. The second fluid influx caused partial isotope exchange and disequilibrium. It is envisaged that an initial short lived flux of hot metamorphic fluids expelled from the epizonal metamorphic domains of the Stavelot-Venn massif. The metamorphic fluid was focused along major thrust faults of the Variscan front zone such as the Aachen thrust. A second fluid influx was introduced from formation waters in the footwall of the Aachen thrust as a consequence of progressive deformation. Mixing of the cooler and lower salinity formation water with the hot metamorphic fluid during episodic fluid trapping resulted in an evolving range of physicochemical fluid inclusion characteristics.

On the existence of doubling measures with certain regularity properties

Given a compact pseudo-metric space, we associate to it upper and lower dimensions, depending only on the pseudo-metric. Then we construct a doubling measure for which the measure of a dilated ball is closely related to these dimensions.