Prediction of Childhood Asthma Using Conditional Probability and Discrete Event Simulation

Abstract: Asthma prevalence in children and adolescents in Spain is 10-17%. It is the most common chronic illness during childhood. Prevalence has been increasing over the last 40 years and there is considerable evidence that, among other factors, continued exposure to cigarette smoke results in asthma in children. No statistical or simulation model exist to forecast the evolution of childhood asthma in Europe. Such a model needs to incorporate the main risk factors that can be managed by medical authorities, such as tobacco (OR = 1.44), to establish how they affect the present generation of children. A simulation model using conditional probability and discrete event simulation for childhood asthma was developed and validated by simulating realistic scenario. The parameters used for the model (input data) were those found in the bibliography, especially those related to the incidence of smoking in Spain. We also used data from a panel of experts from the Hospital del Mar (Barcelona) related to actual evolution and asthma phenotypes. The results obtained from the simulation established a threshold of a 15-20% smoking population for a reduction in the prevalence of asthma. This is still far from the current level in Spain, where 24% of people smoke. We conclude that more effort must be made to combat smoking and other childhood asthma risk factors, in order to significantly reduce the number of cases. Once completed, this simulation methodology can realistically be used to forecast the evolution of childhood asthma as a function of variation in different risk factors.

Methods for Estimating Annual Exceedance-Probability Discharges for Streams in Iowa, Based on Data through Water Year 2010, TR-519, 2013

A statewide study was performed to develop regional regression equations for estimating selected annual exceedance- probability statistics for ungaged stream sites in Iowa. The study area comprises streamgages located within Iowa and 50 miles beyond the State’s borders. Annual exceedanceprobability estimates were computed for 518 streamgages by using the expected moments algorithm to fit a Pearson Type III distribution to the logarithms of annual peak discharges for each streamgage using annual peak-discharge data through 2010. The estimation of the selected statistics included a Bayesian weighted least-squares/generalized least-squares regression analysis to update regional skew coefficients for the 518 streamgages. Low-outlier and historic information were incorporated into the annual exceedance-probability analyses, and a generalized Grubbs-Beck test was used to detect multiple potentially influential low flows. Also, geographic information system software was used to measure 59 selected basin characteristics for each streamgage. Regional regression analysis, using generalized leastsquares regression, was used to develop a set of equations for each flood region in Iowa for estimating discharges for ungaged stream sites with 50-, 20-, 10-, 4-, 2-, 1-, 0.5-, and 0.2-percent annual exceedance probabilities, which are equivalent to annual flood-frequency recurrence intervals of 2, 5, 10, 25, 50, 100, 200, and 500 years, respectively. A total of 394 streamgages were included in the development of regional regression equations for three flood regions (regions 1, 2, and 3) that were defined for Iowa based on landform regions and soil regions. Average standard errors of prediction range from 31.8 to 45.2 percent for flood region 1, 19.4 to 46.8 percent for flood region 2, and 26.5 to 43.1 percent for flood region 3. The pseudo coefficients of determination for the generalized leastsquares equations range from 90.8 to 96.2 percent for flood region 1, 91.5 to 97.9 percent for flood region 2, and 92.4 to 96.0 percent for flood region 3. The regression equations are applicable only to stream sites in Iowa with flows not significantly affected by regulation, diversion, channelization, backwater, or urbanization and with basin characteristics within the range of those used to develop the equations. These regression equations will be implemented within the U.S. Geological Survey StreamStats Web-based geographic information system tool. StreamStats allows users to click on any ungaged site on a river and compute estimates of the eight selected statistics; in addition, 90-percent prediction intervals and the measured basin characteristics for the ungaged sites also are provided by the Web-based tool. StreamStats also allows users to click on any streamgage in Iowa and estimates computed for these eight selected statistics are provided for the streamgage.

Conservation of the Eurasian Lynx (Lynx lynx) in a fragmented landscape - habitat models, dispersal and potential distribution

Abstract: The expansion of a recovering population - whether re-introduced or spontaneously returning - is shaped by (i) biological (intrinsic) factors such as the land tenure system or dispersal, (ii) the distribution and availability of resources (e.g. prey), (iii) habitat and landscape features, and (iv) human attitudes and activities. In order to develop efficient conservation and recovery strategies, we need to understand all these factors and to predict the potential distribution and explore ways to reach it. An increased number of lynx in the north-western Swiss Alps in the nineties lead to a new controversy about the return of this cat. When the large carnivores were given legal protection in many European countries, most organizations and individuals promoting their protection did not foresee the consequences. Management plans describing how to handle conflicts with large predators are needed to find a balance between "overabundance" and extinction. Wildlife and conservation biologists need to evaluate the various threats confronting populations so that adequate management decisions can be taken. I developed a GIS probability model for the lynx, based on habitat information and radio-telemetry data from the Swiss Jura Mountains, in order to predict the potential distribution of the lynx in this mountain range, which is presently only partly occupied by lynx. Three of the 18 variables tested for each square kilometre describing land use, vegetation, and topography, qualified to predict the probability of lynx presence. The resulting map was evaluated with data from dispersing subadult lynx. Young lynx that were not able to establish home ranges in what was identified as good lynx habitat did not survive their first year of independence, whereas the only one that died in good lynx habitat was illegally killed. Radio-telemetry fixes are often used as input data to calibrate habitat models. Radio-telemetry is the only way to gather accurate and unbiased data on habitat use of elusive larger terrestrial mammals. However, it is time consuming and expensive, and can therefore only be applied in limited areas. Habitat models extrapolated over large areas can in turn be problematic, as habitat characteristics and availability may change from one area to the other. I analysed the predictive power of Ecological Niche Factor Analysis (ENFA) in Switzerland with the lynx as focal species. According to my results, the optimal sampling strategy to predict species distribution in an Alpine area lacking available data would be to pool presence cells from contrasted regions (Jura Mountains, Alps), whereas in regions with a low ecological variance (Jura Mountains), only local presence cells should be used for the calibration of the model. Dispersal influences the dynamics and persistence of populations, the distribution and abundance of species, and gives the communities and ecosystems their characteristic texture in space and time. Between 1988 and 2001, the spatio-temporal behaviour of subadult Eurasian lynx in two re-introduced populations in Switzerland was studied, based on 39 juvenile lynx of which 24 were radio-tagged to understand the factors influencing dispersal. Subadults become independent from their mothers at the age of 8-11 months. No sex bias neither in the dispersal rate nor in the distance moved was detected. Lynx are conservative dispersers, compared to bear and wolf, and settled within or close to known lynx occurrences. Dispersal distances reached in the high lynx density population - shorter than those reported in other Eurasian lynx studies - are limited by habitat restriction hindering connections with neighbouring metapopulations. I postulated that high lynx density would lead to an expansion of the population and validated my predictions with data from the north-western Swiss Alps where about 1995 a strong increase in lynx abundance took place. The general hypothesis that high population density will foster the expansion of the population was not confirmed. This has consequences for the re-introduction and recovery of carnivores in a fragmented landscape. To establish a strong source population in one place might not be an optimal strategy. Rather, population nuclei should be founded in several neighbouring patches. Exchange between established neighbouring subpopulations will later on take place, as adult lynx show a higher propensity to cross barriers than subadults. To estimate the potential population size of the lynx in the Jura Mountains and to assess possible corridors between this population and adjacent areas, I adapted a habitat probability model for lynx distribution in the Jura Mountains with new environmental data and extrapolated it over the entire mountain range. The model predicts a breeding population ranging from 74-101 individuals and from 51-79 individuals when continuous habitat patches < 50 km2 are disregarded. The Jura Mountains could once be part of a metapopulation, as potential corridors exist to the adjoining areas (Alps, Vosges Mountains, and Black Forest). Monitoring of the population size, spatial expansion, and the genetic surveillance in the Jura Mountains must be continued, as the status of the population is still critical. ENFA was used to predict the potential distribution of lynx in the Alps. The resulting model divided the Alps into 37 suitable habitat patches ranging from 50 to 18,711 km2, covering a total area of about 93,600 km2. When using the range of lynx densities found in field studies in Switzerland, the Alps could host a population of 961 to 1,827 residents. The results of the cost-distance analysis revealed that all patches were within the reach of dispersing lynx, as the connection costs were in the range of dispersal cost of radio-tagged subadult lynx moving through unfavorable habitat. Thus, the whole Alps could once be considered as a metapopulation. But experience suggests that only few disperser will cross unsuitable areas and barriers. This low migration rate may seldom allow the spontaneous foundation of new populations in unsettled areas. As an alternative to natural dispersal, artificial transfer of individuals across the barriers should be considered. Wildlife biologists can play a crucial role in developing adaptive management experiments to help managers learning by trial. The case of the lynx in Switzerland is a good example of a fruitful cooperation between wildlife biologists, managers, decision makers and politician in an adaptive management process. This cooperation resulted in a Lynx Management Plan which was implemented in 2000 and updated in 2004 to give the cantons directives on how to handle lynx-related problems. This plan was put into practice e.g. in regard to translocation of lynx into unsettled areas. Résumé: L'expansion d'une population en phase de recolonisation, qu'elle soit issue de réintroductions ou d'un retour naturel dépend 1) de facteurs biologiques tels que le système social et le mode de dispersion, 2) de la distribution et la disponibilité des ressources (proies), 3) de l'habitat et des éléments du paysage, 4) de l'acceptation de l'espèce par la population locale et des activités humaines. Afin de pouvoir développer des stratégies efficaces de conservation et de favoriser la recolonisation, chacun de ces facteurs doit être pris en compte. En plus, la distribution potentielle de l'espèce doit pouvoir être déterminée et enfin, toutes les possibilités pour atteindre les objectifs, examinées. La phase de haute densité que la population de lynx a connue dans les années nonante dans le nord-ouest des Alpes suisses a donné lieu à une controverse assez vive. La protection du lynx dans de nombreux pays européens, promue par différentes organisations, a entraîné des conséquences inattendues; ces dernières montrent que tout plan de gestion doit impérativement indiquer des pistes quant à la manière de gérer les conflits, tout en trouvant un équilibre entre l'extinction et la surabondance de l'espèce. Les biologistes de la conservation et de la faune sauvage doivent pour cela évaluer les différents risques encourus par les populations de lynx, afin de pouvoir rapidement prendre les meilleuresmdécisions de gestion. Un modèle d'habitat pour le lynx, basé sur des caractéristiques de l'habitat et des données radio télémétriques collectées dans la chaîne du Jura, a été élaboré afin de prédire la distribution potentielle dans cette région, qui n'est que partiellement occupée par l'espèce. Trois des 18 variables testées, décrivant pour chaque kilomètre carré l'utilisation du sol, la végétation ainsi que la topographie, ont été retenues pour déterminer la probabilité de présence du lynx. La carte qui en résulte a été comparée aux données télémétriques de lynx subadultes en phase de dispersion. Les jeunes qui n'ont pas pu établir leur domaine vital dans l'habitat favorable prédit par le modèle n'ont pas survécu leur première année d'indépendance alors que le seul individu qui est mort dans l'habitat favorable a été braconné. Les données radio-télémétriques sont souvent utilisées pour l'étalonnage de modèles d'habitat. C'est un des seuls moyens à disposition qui permette de récolter des données non biaisées et précises sur l'occupation de l'habitat par des mammifères terrestres aux moeurs discrètes. Mais ces méthodes de- mandent un important investissement en moyens financiers et en temps et peuvent, de ce fait, n'être appliquées qu'à des zones limitées. Les modèles d'habitat sont ainsi souvent extrapolés à de grandes surfaces malgré le risque d'imprécision, qui résulte des variations des caractéristiques et de la disponibilité de l'habitat d'une zone à l'autre. Le pouvoir de prédiction de l'Analyse Ecologique de la Niche (AEN) dans les zones où les données de présence n'ont pas été prises en compte dans le calibrage du modèle a été analysée dans le cas du lynx en Suisse. D'après les résultats obtenus, la meilleure mé- thode pour prédire la distribution du lynx dans une zone alpine dépourvue d'indices de présence est de combiner des données provenant de régions contrastées (Alpes, Jura). Par contre, seules les données sur la présence locale de l'espèce doivent être utilisées pour les zones présentant une faible variance écologique tel que le Jura. La dispersion influence la dynamique et la stabilité des populations, la distribution et l'abondance des espèces et détermine les caractéristiques spatiales et temporelles des communautés vivantes et des écosystèmes. Entre 1988 et 2001, le comportement spatio-temporel de lynx eurasiens subadultes de deux populations réintroduites en Suisse a été étudié, basé sur le suivi de 39 individus juvéniles dont 24 étaient munis d'un collier émetteur, afin de déterminer les facteurs qui influencent la dispersion. Les subadultes se sont séparés de leur mère à l'âge de 8 à 11 mois. Le sexe n'a pas eu d'influence sur le nombre d'individus ayant dispersés et la distance parcourue au cours de la dispersion. Comparé à l'ours et au loup, le lynx reste très modéré dans ses mouvements de dispersion. Tous les individus ayant dispersés se sont établis à proximité ou dans des zones déjà occupées par des lynx. Les distances parcourues lors de la dispersion ont été plus courtes pour la population en phase de haute densité que celles relevées par les autres études de dispersion du lynx eurasien. Les zones d'habitat peu favorables et les barrières qui interrompent la connectivité entre les populations sont les principales entraves aux déplacements, lors de la dispersion. Dans un premier temps, nous avons fait l'hypothèse que les phases de haute densité favorisaient l'expansion des populations. Mais cette hypothèse a été infirmée par les résultats issus du suivi des lynx réalisé dans le nord-ouest des Alpes, où la population connaissait une phase de haute densité depuis 1995. Ce constat est important pour la conservation d'une population de carnivores dans un habitat fragmenté. Ainsi, instaurer une forte population source à un seul endroit n'est pas forcément la stratégie la plus judicieuse. Il est préférable d'établir des noyaux de populations dans des régions voisines où l'habitat est favorable. Des échanges entre des populations avoisinantes pourront avoir lieu par la suite car les lynx adultes sont plus enclins à franchir les barrières qui entravent leurs déplacements que les individus subadultes. Afin d'estimer la taille de la population de lynx dans le Jura et de déterminer les corridors potentiels entre cette région et les zones avoisinantes, un modèle d'habitat a été utilisé, basé sur un nouveau jeu de variables environnementales et extrapolé à l'ensemble du Jura. Le modèle prédit une population reproductrice de 74 à 101 individus et de 51 à 79 individus lorsque les surfaces d'habitat d'un seul tenant de moins de 50 km2 sont soustraites. Comme des corridors potentiels existent effectivement entre le Jura et les régions avoisinantes (Alpes, Vosges, et Forêt Noire), le Jura pourrait faire partie à l'avenir d'une métapopulation, lorsque les zones avoisinantes seront colonisées par l'espèce. La surveillance de la taille de la population, de son expansion spatiale et de sa structure génétique doit être maintenue car le statut de cette population est encore critique. L'AEN a également été utilisée pour prédire l'habitat favorable du lynx dans les Alpes. Le modèle qui en résulte divise les Alpes en 37 sous-unités d'habitat favorable dont la surface varie de 50 à 18'711 km2, pour une superficie totale de 93'600 km2. En utilisant le spectre des densités observées dans les études radio-télémétriques effectuées en Suisse, les Alpes pourraient accueillir une population de lynx résidents variant de 961 à 1'827 individus. Les résultats des analyses de connectivité montrent que les sous-unités d'habitat favorable se situent à des distances telles que le coût de la dispersion pour l'espèce est admissible. L'ensemble des Alpes pourrait donc un jour former une métapopulation. Mais l'expérience montre que très peu d'individus traverseront des habitats peu favorables et des barrières au cours de leur dispersion. Ce faible taux de migration rendra difficile toute nouvelle implantation de populations dans des zones inoccupées. Une solution alternative existe cependant : transférer artificiellement des individus d'une zone à l'autre. Les biologistes spécialistes de la faune sauvage peuvent jouer un rôle important et complémentaire pour les gestionnaires de la faune, en les aidant à mener des expériences de gestion par essai. Le cas du lynx en Suisse est un bel exemple d'une collaboration fructueuse entre biologistes de la faune sauvage, gestionnaires, organes décisionnaires et politiciens. Cette coopération a permis l'élaboration du Concept Lynx Suisse qui est entré en vigueur en 2000 et remis à jour en 2004. Ce plan donne des directives aux cantons pour appréhender la problématique du lynx. Il y a déjà eu des applications concrètes sur le terrain, notamment par des translocations d'individus dans des zones encore inoccupées.

The normal distribution in some constrained sample spaces

Phenomena with a constrained sample space appear frequently in practice. This is the case e.g. with strictly positive data, or with compositional data, like percentages or proportions. If the natural measure of difference is not the absolute one, simple algebraic properties show that it is more convenient to work with a geometry different from the usual Euclidean geometry in real space, and with a measure different from the usual Lebesgue measure, leading to alternative models which better fit the phenomenon under study. The general approach is presented and illustrated using the normal distribution, both on the positive real line and on the D-part simplex. The original ideas of McAlister in his introduction to the lognormal distribution in 1879, are recovered and updated

The genomic distribution of intraspecific and interspecific sequence divergence of human segmental duplications relative to human/chimpanzee chromosomal rearrangements

Background: It has been suggested that chromosomal rearrangements harbor the molecular footprint of the biological phenomena which they induce, in the form, for instance, of changes in the sequence divergence rates of linked genes. So far, all the studies of these potential associations have focused on the relationship between structural changes and the rates of evolution of single-copy DNA and have tried to exclude segmental duplications (SDs). This is paradoxical, since SDs are one of the primary forces driving the evolution of structure and function in our genomes and have been linked not only with novel genes acquiring new functions, but also with overall higher DNA sequence divergence and major chromosomal rearrangements.Results: Here we take the opposite view and focus on SDs. We analyze several of the features of SDs, including the rates of intraspecific divergence between paralogous copies of human SDs and of interspecific divergence between human SDs and chimpanzee DNA. We study how divergence measures relate to chromosomal rearrangements, while considering other factors that affect evolutionary rates in single copy DNA. Conclusion: We find that interspecific SD divergence behaves similarly to divergence of single-copy DNA. In contrast, old and recent paralogous copies of SDs do present different patterns of intraspecific divergence. Also, we show that some relatively recent SDs accumulate in regions that carry inversions in sister lineages.

Error probability in synchronous digital circuits due to power supply noise

This paper presents a probabilistic approach to model the problem of power supply voltage fluctuations. Error probability calculations are shown for some 90-nm technology digital circuits.The analysis here considered gives the timing violation error probability as a new design quality factor in front of conventional techniques that assume the full perfection of the circuit. The evaluation of the error bound can be useful for new design paradigms where retry and self-recoveringtechniques are being applied to the design of high performance processors. The method here described allows to evaluate the performance of these techniques by means of calculating the expected error probability in terms of power supply distribution quality.

The Omega model: from bankruptcy to occupation times in the red

Ruin occurs the first time when the surplus of a company or an institution is negative. In the Omega model, it is assumed that even with a negative surplus, the company can do business as usual until bankruptcy occurs. The probability of bankruptcy at a point of time only depends on the value of the negative surplus at that time. Under the assumption of Brownian motion for the surplus, the expected discounted value of a penalty at bankruptcy is determined, and hence the probability of bankruptcy. There is an intrinsic relation between the probability of no bankruptcy and an exposure random variable. In special cases, the distribution of the total time the Brownian motion spends below zero is found, and the Laplace transform of the integral of the negative part of the Brownian motion is expressed in terms of the Airy function of the first kind.

Using species richness and functional traits predictions to constrain assemblage predictions from stacked species distribution models

Aim: Modelling species at the assemblage level is required to make effective forecast of global change impacts on diversity and ecosystem functioning. Community predictions may be achieved using macroecological properties of communities (MEM), or by stacking of individual species distribution models (S-SDMs). To obtain more realistic predictions of species assemblages, the SESAM framework suggests applying successive filters to the initial species source pool, by combining different modelling approaches and rules. Here we provide a first test of this framework in mountain grassland communities. Location: The western Swiss Alps. Methods: Two implementations of the SESAM framework were tested: a "Probability ranking" rule based on species richness predictions and rough probabilities from SDMs, and a "Trait range" rule that uses the predicted upper and lower bound of community-level distribution of three different functional traits (vegetative height, specific leaf area and seed mass) to constraint a pool of environmentally filtered species from binary SDMs predictions. Results: We showed that all independent constraints expectedly contributed to reduce species richness overprediction. Only the "Probability ranking" rule allowed slightly but significantly improving predictions of community composition. Main conclusion: We tested various ways to implement the SESAM framework by integrating macroecological constraints into S-SDM predictions, and report one that is able to improve compositional predictions. We discuss possible improvements, such as further improving the causality and precision of environmental predictors, using other assembly rules and testing other types of ecological or functional constraints.

5C.09: Heritability of renal function parameters and electrolyte levels in the Swiss population

OBJECTIVE: Electrolytes handling by the kidney is essential for volume and blood pressure (BP) homeostasis but their distribution and heritability are not well described. We estimated the heritability of kidney function as well as of serum and urine concentrations, renal clearances and fractional excretions for sodium, chloride, potassium, calcium, phosphate and magnesium in a Swiss population-based study. DESIGN AND METHOD: Nuclear families were randomly selected from the general population in Switzerland. We estimated glomerular filtration rate (eGFR) using the CKD-EPI and MDRD equations. Urine was collected separately during day and night over 24-hour. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including as covariates in the model: age, sex, body mass index and study center. RESULTS: The 1128 participants (537 men and 591 women from 273 families), had mean (sd) age of 47.4(17.5) years, body mass index of 25.0 (4.5) kg/m2 and CKD-EPI of 98.0(18.5) mL/min/1.73 m2. Heritability estimates (SE) were 46.0% (0.06), 48.0% (0.06) and 18.0% (0.06) for CKD-EPI, MDRD and 24-hour creatinine clearance (P < 0.05), respectively. Heritability [SE] of serum concentration was highest for calcium (37%[0.06]) and lowest for sodium (13%[0.05]). Heritabilities [SE] of 24-h urine concentrations and excretions, and of fractional excretions were highest for calcium (51%[0.06], 44%[0.06] and 51%[0.06], respectively) and lowest for potassium (11%[0.05], 10%[0.05] and 16%[0.06], respectively). All results were statistically different from zero.(Figure is included in full-text article.) CONCLUSIONS: : Serum and urine levels, urinary excretions and renal handling of electrolytes, particularly calcium, are heritable in the general adult population. Identifying genetic variants involved in electrolytes homeostasis may provide useful insight into the pathophysiological mechanisms involved in common chronic diseases such as kidney diseases, hypertension and diabetes.

Microtubule Associated Protein 1b (MAP1B) Is a Marker of the Microtubular Cytoskeleton in Podocytes but Is Not Essential for the Function of the Kidney Filtration Barrier in Mice.

Podocytes are essential for the function of the kidney glomerular filter. A highly differentiated cytoskeleton is requisite for their integrity. Although much knowledge has been gained on the organization of cortical actin networks in podocyte's foot processes, less is known about the molecular organization of the microtubular cytoskeleton in primary processes and the cell body. To gain an insight into the organization of the microtubular cytoskeleton of the podocyte, we systematically analyzed the expression of microtubule associated proteins (Maps), a family of microtubules interacting proteins with known functions as regulator, scaffold and guidance proteins. We identified microtubule associated protein 1b (MAP1B) to be specifically enriched in podocytes in human and rodent kidney. Using immunogold labeling in electron microscopy, we were able to demonstrate an enrichment of MAP1B in primary processes. A similar association of MAP1B with the microtubule cytoskeleton was detected in cultured podocytes. Subcellular distribution of MAP1B HC and LC1 was analyzed using a double fluorescent reporter MAP1B fusion protein. Subsequently we analyzed mice constitutively depleted of MAP1B. Interestingly, MAP1B KO was not associated with any functional or structural alterations pointing towards a redundancy of MAP proteins in podocytes. In summary, we established MAP1B as a specific marker protein of the podocyte microtubular cytoskeleton.

Distribution of monocarboxylate transporters in the peripheral nervous system suggests putative roles in lactate shuttling and myelination.

Lactate, a product of glycolysis, has been shown to play a key role in the metabolic support of neurons/axons in the CNS by both astrocytes and oligodendrocytes through monocarboxylate transporters (MCTs). Despite such importance in the CNS, little is known about MCT expression and lactate function in the PNS. Here we show that mouse MCT1, MCT2, and MCT4 are expressed in the PNS. While DRG neurons express MCT1, myelinating Schwann cells (SCs) coexpress MCT1 and MCT4 in a domain-specific fashion, mainly in regions of noncompact myelin. Interestingly, SC-specific downregulation of MCT1 expression in rat neuron/SC cocultures led to increased myelination, while its downregulation in neurons resulted in a decreased amount of neurofilament. Finally, pure rat SCs grown in the presence of lactate exhibited an increase in the level of expression of the main myelin regulator gene Krox20/Egr2 and the myelin gene P0. These data indicate that lactate homeostasis participates in the regulation of the SC myelination program and reveal that similar to CNS, PNS axon-glial metabolic interactions are most likely mediated by MCTs.

The regional distribution of unemployment. What do micro-data tell us?

Regional disparities in unemployment rates are large and persistent. The literature provides evidence of their magnitude and evolution, as well as evidence of the role of certain economic, demographic and environmental factors in explaining the gap between regions of low and high unemployment. Most of these studies, however, adopt an aggregate approach and so do not account for the individual characteristics of the unemployed and employed in each region. This paper, by drawing on micro-data from the Spanish wave of the Labour Force Survey, seeks to remedy this shortcoming by analysing regional differentials in unemployment rates. An appropriate decomposition of the regional gap in the average probability of being unemployed enables us to distinguish between the contribution of differences in the regional distribution of individual characteristics from that attributable to a different impact of these characteristics on the probability of unemployment. Our results suggest that the well-documented disparities in regional unemployment are not just the result of regional heterogeneity in the distribution of individual characteristics. Non-negligible differences in the probability of unemployment remain after controlling for this type of heterogeneity, as a result of differences across regions in the impact of the observed characteristics. Among the factors considered in our analysis, regional differences in the endowment and impact of an individual’s education are shown to play a major role.

Emergent geomorphic-vegetation interactions on a subalpine alluvial fan

Following perturbation, an ecosystem (flora, fauna, soil) should evolve as a function of time at a rate conditioned by external variables (relief, climate, geology). More recently, biogeomorphologists have focused upon the notion of co-development of geomorphic processes with ecosystems over very short through to very long (evolutionary) timescales. Alpine environments have been a particular focus of this co-development. However, work in this field has tended to adopt a simplified view of the relationship between perturbation and succession, including: how the landform and ecosystem itself conditions the impact of a perturbation to create a complex spatial response impact; and how perturbations are not simply ecosystem destroyers but can be a significant source of ecosystem resources. What this means is that at the within landform scale, there may well be a complex and dynamic topographic and sedimentological template that co-develops with soil, flora and fauna. Here, we present and test a conceptual model of this template for a subalpine alluvial fan. We combine detailed floristic inventory with soil inventory, determination of edaphic variables and analysis of historical aerial imagery. Spatial variation in the probability of perturbation of sites on the fan surface was associated with down fan variability in the across-fan distribution of fan ages, fan surface channel characteristics and fan surface sedimentology. Floristic survey confirmed that these edaphic factors distinguished site floristic richness and plant communities up until the point that the soil-vegetation system was sufficiently developed to sustain plant communities regardless of edaphic conditions. Thus, the primary explanatory variable was the estimated age of each site, which could be tied back into perturbation history and its spatial expression due to the geometry of the fan: distinct plant communities were emergent both across fan and down fan, a distribution maintained by the way in which the fan dissipates potentially perturbing events.

An analytic approach to distribution logistics strategic management

Logistics management is increasingly being recognised by many companies to be of critical concern. The logistics function includes directly or indirectly many of the new areas for achieving or maintaining competitive advantage that companies have been forced to develop due to increasing competitive pressures. The key to achieving a competitive advantage is to manage the logistics function strategically which involves determining the most cost effective method of providing the necessary customer service levels from the many combinations of operating procedures in the areas of transportation, warehousing, order processing and information systems, production, and inventory management. In this thesis, a comprehensive distribution logistics strategic management process is formed by integrating the periodic strategic planning process with a continuous strategic issues management process. Strategic planning is used for defining the basic objectives for a company and assuring co operation and synergy between the different functions of a company while strategic issues management is used on a continuous basis in order to deal with environmental and internal turbulence. The strategic planning subprocess consists of the following main phases: (1) situational analyses, (2) defining the vision and strategic goals for the logistics function, (3) determining objectives and strategies, (4) drawing up tactical action plans, and (5) evaluating the implementation of the plans and making the needed adjustments. The aim of the strategic issues management subprocess is to continuously scan the environment and the organisation for early identification of the issues having a significant impact on the logistics function using the following steps: (1) the identification of trends, (2) assessing the impact and urgency of the identified trends, (3) assigning priorities to the issues, and (4) planning responses to the, issues. The Analytic Hierarchy Process (AHP) is a systematic procedure for structuring any problem. AHP is based on the following three principles: decomposition, comparative judgements, and synthesis of priorities. AHP starts by decomposing a complex, multicriteria problem into a hierarchy where each level consists of a few manageable elements which are then decomposed into another set of elements. The second step is to use a measurement methodology to establish priorities among the elements within each level of the hierarchy. The third step in using AHP is to synthesise the priorities of the elements to establish the overall priorities for the decision alternatives. In this thesis, decision support systems are developed for different areas of distribution logistics strategic management by applying the Analytic Hierarchy Process. The areas covered are: (1) logistics strategic issues management, (2) planning of logistic structure, (3) warehouse site selection, (4) inventory forecasting, (5) defining logistic action and development plans, (6) choosing a distribution logistics strategy, (7) analysing and selecting transport service providers, (8) defining the logistic vision and strategic goals, (9) benchmarking logistic performance, and (10) logistic service management. The thesis demonstrates the potential of AHP as a systematic and analytic approach to distribution logistics strategic management.

The normal distribution in some constrained sample spaces

Phenomena with a constrained sample space appear frequently in practice. This is the case e.g. with strictly positive data, or with compositional data, like percentages or proportions. If the natural measure of difference is not the absolute one, simple algebraic properties show that it is more convenient to work with a geometry different from the usual Euclidean geometry in real space, and with a measure different from the usual Lebesgue measure, leading to alternative models which better fit the phenomenon under study. The general approach is presented and illustrated using the normal distribution, both on the positive real line and on the D-part simplex. The original ideas of McAlister in his introduction to the lognormal distribution in 1879, are recovered and updated