Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Sleep, metabolism and aging

Aging is a multidimensional process of physical, psychological, and social changes. Understanding how we sleep and how this dynamic process evolves across life span will help to identify normal developmental aspects of sleep over time and to create strategies to increase awareness of sleep disturbances and their early management. In normal sleepers from HypnoLaus cohort, we evaluated the effects of age and gender on both subjective and objective sleep measurements. Our results indicate that normal aging is not accompanied by sleep complaints, and when they exist suggest the presence of underlying comorbidities. Polysomnographic data revealed that slow wave sleep was more affected with age in men, and age affected differently NREM and REM spectral power densities. Both sleep structure and spectral analysis profiles may constitute standards to delineate pathological changes in sleep, both for aging women and men. Another important aspect in the management of sleep and its disorders is a detailed characterization of sleep-inducing medications. Gamma-hydroxybutyrate (GHB) is an inhibitory neurotransmitter derivative of GABA, but its mode of action and the range of effects are not well understood. Several properties, as growth hormone stimulation in humans and the development of weight loss in treated patients suggest an unexplored metabolic effect. In different experiments we assessed the effects of acute, short term and chronic GHB administration on central (cerebral cortex) and peripheral (liver) biochemical processes involved in the metabolism of the drug, as well as the effects of the drug on metabolism in C57BL/6J, GABAB knock-out and obese (ob/ob) mice. We showed that GHB treatment affects weight gain in C57BL/6J and GABAB knock-out mice. Metabolomic analysis indicated large central and peripheral metabolic changes induced by GHB with important relevance to its therapeutic use. -- Le vieillissement est un processus multidimensionnel accompagné par de multiples changements dans les domaines physique, psychologique et social. Comprendre comment nous dormons et comment ce processus dynamique évolue sur la durée de vie nous aidera à identifier les aspects normaux du développement du sommeil au fil du temps, et à créer des stratégies pour accroître la connaissance et compréhension des troubles du sommeil et leur prise en charge précoce. Chez les sujets normaux de la cohorte HypnoLaus nous avons évalué les effets de l'âge et du sexe sur les mesures subjectives et objectives du sommeil. Nos résultats indiquent que le vieillissement normal ne s'accompagne pas de troubles du sommeil, et quand ils existent ceux-ci suggèrent la présence de comorbidités sous-jacentes. Les données polysomnographiques ont révélé que le sommeil profond était plus affecté avec l'âge chez les hommes. De plus, nous avons montré comment l'âge modifie la composition spectrale du sommeil lent et paradoxal. La structure du sommeil et les profils d'analyse spectrale peuvent donc constituer des standards permettant de définir les changements pathologiques du sommeil chez les personnes âgées. Parmi les aspects importants de la gestion du sommeil et de ses troubles, la caractérisation détaillée des médicaments hypnotiques utilisés est essentielle. L'acide gamma-hydroxybutyrique (GHB) est un acide gras à courte chaîne dérivé du GABA, principal neurotransmetteur inhibiteur du cerveau, mais son mode d'action et tous ses effets sont toujours largement méconnus. Plusieurs propriétés, comme la stimulation de la sécrétion de l'hormone de croissance chez l'homme et le développement d'une perte de poids chez les patients traités suggèrent un effet métabolique inexploré. Dans différentes expériences, nous avons évalué les effets d'une exposition aiguë, à court terme et chronique de GHB sur les processus biochimiques centraux (cortex cérébral) et périphériques (foie) impliqués dans le métabolisme du médicament. Nous avons aussi évalué les effets du médicament sur le métabolisme des souris C57BL/6J, GABAB KO et obèses (ob/ob). Nos résultats ont montré que le GHB diminue le gain de poids chez les souris C57BL/6J et GABAB KO. L'analyse métabolomique a indiqué des changements importants induits par GHB au niveau central et périphérique, et ces effets sont importants pour son utilisation thérapeutique.

Principal curves and principal oriented points

Principal curves have been defined Hastie and Stuetzle (JASA, 1989) assmooth curves passing through the middle of a multidimensional dataset. They are nonlinear generalizations of the first principalcomponent, a characterization of which is the basis for the principalcurves definition.In this paper we propose an alternative approach based on a differentproperty of principal components. Consider a point in the space wherea multivariate normal is defined and, for each hyperplane containingthat point, compute the total variance of the normal distributionconditioned to belong to that hyperplane. Choose now the hyperplaneminimizing this conditional total variance and look for thecorresponding conditional mean. The first principal component of theoriginal distribution passes by this conditional mean and it isorthogonal to that hyperplane. This property is easily generalized todata sets with nonlinear structure. Repeating the search from differentstarting points, many points analogous to conditional means are found.We call them principal oriented points. When a one-dimensional curveruns the set of these special points it is called principal curve oforiented points. Successive principal curves are recursively definedfrom a generalization of the total variance.

Measuring subcompositional incoherence

Subcompositional coherence is a fundamental property of Aitchison s approach to compositional data analysis, and is the principal justification for using ratios of components. We maintain, however, that lack of subcompositional coherence, that is incoherence, can be measured in an attempt to evaluate whether any given technique is close enough, for all practical purposes, to being subcompositionally coherent. This opens up the field to alternative methods, which might be better suited to cope with problems such as data zeros and outliers, while being only slightly incoherent. The measure that we propose is based on the distance measure between components. We show that the two-part subcompositions, which appear to be the most sensitive to subcompositional incoherence, can be used to establish a distance matrix which can be directly compared with the pairwise distances in the full composition. The closeness of these two matrices can be quantified using a stress measure that is common in multidimensional scaling, providing a measure of subcompositional incoherence. The approach is illustrated using power-transformed correspondence analysis, which has already been shown to converge to log-ratio analysis as the power transform tends to zero.

An enhanced concave program relaxation for choice network revenue management

The network choice revenue management problem models customers as choosing from an offer-set, andthe firm decides the best subset to offer at any given moment to maximize expected revenue. The resultingdynamic program for the firm is intractable and approximated by a deterministic linear programcalled the CDLP which has an exponential number of columns. However, under the choice-set paradigmwhen the segment consideration sets overlap, the CDLP is difficult to solve. Column generation has beenproposed but finding an entering column has been shown to be NP-hard. In this paper, starting with aconcave program formulation based on segment-level consideration sets called SDCP, we add a class ofconstraints called product constraints, that project onto subsets of intersections. In addition we proposea natural direct tightening of the SDCP called ?SDCP, and compare the performance of both methodson the benchmark data sets in the literature. Both the product constraints and the ?SDCP method arevery simple and easy to implement and are applicable to the case of overlapping segment considerationsets. In our computational testing on the benchmark data sets in the literature, SDCP with productconstraints achieves the CDLP value at a fraction of the CPU time taken by column generation and webelieve is a very promising approach for quickly approximating CDLP when segment consideration setsoverlap and the consideration sets themselves are relatively small.

Pollen storages in nests of bees of the genera Partamona, Scaura and Trigona (Hymenoptera, Apidae)

Bees and angiosperms established a mutualistic relationship along the evolutionary time. The aim of this study is to contribute for the understanding of this relation analyzing pollen stored by stingless bees colonies distributed along the Rio Negro. Fourteen species of Meliponini from the genera Partamona, Scaura, and Trigona were studied with regard to the content of pollen pots. The pollen material was removed from the pollen pots, homogenized, and prepared according to the usual acetolysis technique. The overlap of the trophic niche and the grouping of species by similarity of niches was calculated. The identification revealed 78 pollen types belonging to 36 families, being 37 types attractive and 16 considered as promoters of a temporary specialization event. With the results, it was possible to indicate a list of important plants for meliponiculture in the Amazon.

Hesperioidea e Papilionoidea (Lepidoptera) coligidos em expedição aos Rios Nhamundá e Abacaxis, Amazonas, Brasil: novos subsídios para o conhecimento da biodiversidade da Amazônia Brasileira

Hesperioidea e Papilionoidea (Lepidoptera) coligidos em expedição aos Rios Nhamundá e Abacaxis, Amazonas, Brasil: novos subsídios para o conhecimento da biodiversidade da Amazônia Brasileira. Objetivando um aprimoramento do conhecimento da lepidopterofauna diurna da Amazônia brasileira, este estudo lista 180 taxa coligidos em cinco pontos distintos de dois afluentes do Rio Amazonas, envolvendo as áreas de endemismo Guiana e Rondônia. As coletas foram passivas e ativas e as diferentes localidades comparadas através de análise de Escalonamento Multidimensional Não-Métrico (NMDS).

Origin of samples of Cannabis sativa through insect fragments associated with compacted hemp drug in South America

Origin of samples of Cannabis sativa through insect fragments associated with compacted hemp drug in South America. Insects associated with a seizure of Cannabis sativa L. may indicate the origin of the illicit drug. Nevertheless, no work regarding this subject has been previously published for South America. In the present investigation, seven kilograms of vegetal material (C. sativa) were inspected for insect fragments. Three species were identified and used to test the origin of the seizure of cannabis plant material: Euschistus heros (Fabricius, 1794), Thyanta perditor (Fabricius, 1794) (Heteroptera, Pentatomidae), and Cephalotes pusillus (Klug, 1824) (Hymenoptera, Formicidae). These insect species restricted the geographic origin of the drug to the Neotropical region, and their distribution patterns showed an overlap of the State of Mato Grosso (Brazil), Argentina, and Paraguay. Based on this information, two of the three major C. sativa growing areas in South America were excluded: (1) the Colombian territory and (2) northeastern Brazil.

Weighted Euclidean biplots

We construct a weighted Euclidean distance that approximates any distance or dissimilarity measure between individuals that is based on a rectangular cases-by-variables data matrix. In contrast to regular multidimensional scaling methods for dissimilarity data, the method leads to biplots of individuals and variables while preserving all the good properties of dimension-reduction methods that are based on the singular-value decomposition. The main benefits are the decomposition of variance into components along principal axes, which provide the numerical diagnostics known as contributions, and the estimation of nonnegative weights for each variable. The idea is inspired by the distance functions used in correspondence analysis and in principal component analysis of standardized data, where the normalizations inherent in the distances can be considered as differential weighting of the variables. In weighted Euclidean biplots we allow these weights to be unknown parameters, which are estimated from the data to maximize the fit to the chosen distances or dissimilarities. These weights are estimated using a majorization algorithm. Once this extra weight-estimation step is accomplished, the procedure follows the classical path in decomposing the matrix and displaying its rows and columns in biplots.

Cumulative frequency-dependent selective episodes allow for rapid morph cycles and rock-paper-scissors dynamics in species with overlapping generations.

Rock-paper-scissors (RPS) dynamics, which maintain genetic polymorphisms over time through negative frequency-dependent (FD) selection, can evolve in short-lived species with no generational overlap, where they produce rapid morph frequency cycles. However, most species have overlapping generations and thus, rapid RPS dynamics are thought to require stronger FD selection, the existence of which yet needs to be proved. Here, we experimentally demonstrate that two cumulative selective episodes, FD sexual selection reinforced by FD selection on offspring survival, generate sufficiently strong selection to generate rapid morph frequency cycles in the European common lizard Zootoca vivipara, a multi-annual species with major generational overlap. These findings show that the conditions required for the evolution of RPS games are fulfilled by almost all species exhibiting genetic polymorphisms and suggest that RPS games may be responsible for the maintenance of genetic diversity in a wide range of species.

Dung beetle (Coleoptera, Scarabaeidae) assemblage of a highly fragmented landscape of Atlantic forest: from small to the largest fragments of northeastern Brazilian region

Human activities in tropical forests are the main causes of forest fragmentation. According to historical factor in deforestation processes, forest remnants exhibit different sizes and shapes. The aim of the present study was to evaluate the dung beetle assemblage on fragments of different degree of sizes. Sampling was performed during rainy and dry season of 2010 in six fragments of Atlantic forest, using pitfall traps baited with excrement and carrion. Also, we used two larger fragments as control. We used General Linear Models to determine whether the fragments presented distinguished dung beetle abundance and richness. Analysis of Similarities and Non-Metric Multidimensional Scaling were used to determine whether the dung beetle assemblage was grouped according to species composition. A total of 3352 individuals were collected and 19 species were identified in the six fragments sampled. Dung beetle abundance exhibited a shift according to fragment size; however, richness did not change among fragments evaluated. Also, fragments sampled and the two controls exhibited distinct species composition. The distinction on abundance of dung beetles among fragments may be related to different amount of resource available in each one. It is likely that the dung beetle richness did not distinguish among the different fragments due to the even distribution of the mammal communities in these patches, and consequent equal dung diversity. We conclude that larger fragments encompass higher abundance of dung beetle and distinct species. However, for a clearer understanding of effects of fragmentation on dung beetles in Atlantic forest, studies evaluating narrower variations of larger fragments should be conducted.

Discovering Historic Iowa Transportation Milestones, February 1999

In studying and forming an understanding of Iowa’s transportation history, we must surely develop a reverence for the lifestyles which preceded ours. Achieving a greater understanding of our past, we are better prepared to plan our future as we say farewell to the 20th century and move forward into the 21st. In the words of Oliver Wendell Holmes: “I believe the greatest thing in this world is not so much where we stand as in what direction we are moving... and the further backward you can look, the farther forward you can see.” To help Iowans gain a better understanding of our state’s rich transportation past, the Iowa Department of Transportation has produced a collection of materials including this booklet, the 1999-2000 Iowa Transportation Map, a video entitled A History of Iowa’s Rivers, Roads, Rails and Runways, and a traveling photo exhibit. In addition, Iowa is fortunate to have many local organizations, and the state-owned museum and historic sites, working to preserve the history of our state. Listed in the back section of this booklet are the addresses and descriptions of many sites that offer visitors an opportunity to see a wide range of transportation- related artifacts. The information and photographs are organized in time sequence. However, you will note that many of the transportation eras overlap. The booklet begins with Iowa’s pre-settlement era and concludes with the historic highway and transit program that was signed into law by President Clinton in 1998. As you can imagine, condensing this much Iowa history into a booklet-sized resource was a monumental challenge. Making selections and abbreviating the information resulted in some difficult editorial choices. However, we hope this publication will inspire readers to learn more about our rich, rewarding past and to visit and experience some of Iowa’s historic sites.

Municipalismo e desenvolvimento local

O desenvolvimento era considerado um processo de forte pendor económico, mas ao longo dos anos vem sofrendo diversas interpretações e conceituações, incorporando experiências e lições ao longo do processo. No mundo predominava a visão marcadamente economicista, visão essa que tem vindo a evoluir, no sentido de conceber o desenvolvimento tendo o homem como ponto de partida e de chegada. Ao conceito de desenvolvimento associa-se a perspetiva qualitativa e global das modificações inter-relacionadas, isto é, para que se possa falar de desenvolvimento deverão ocorrer progressos económicos mas também melhorias sociais e culturais (é um fenómeno multidimensional). Cabo Verde ascende à independência numa situação de grande vulnerabilidade e pobreza extrema. Era imprescindível a construção de um Estado e criar as condições básicas para o processo endógeno de desenvolvimento. Relativamente à organização administrativa do território, a pais estava dividido em municípios à frente dos quais foi colocado um delegado do Governo central. Após a independência de Cabo verde, registou-se um acumular de experiências e de reflexões sobre a problemática das autarquias locais que justificam a adoção de um novo sistema de normas e princípios disciplinadores dessa matéria. O município do Porto Novo apesar dos ganhos consideráveis desde a independência, o Concelho continua carecendo de infraestruturas básicas. Com efeito, a dimensão do Concelho, abrangendo mais de metade da ilha de Santo Antão entra em contraponto com a dispersão geográfica da população e a consequente necessidade de disseminação de infraestruturas. O reforço do municipalismo em Cabo Verde é ainda uma responsabilidade tanto política como técnica e um imperativo do desenvolvimento económico. (Dr. MANUEL VARELA NEVES).

Hospital de día de enfermedades respiratorias: Impacto sobre la tasa de ingresos hospitalarios por exacerbaciones de la enfermedad pulmonar obstructiva crónica.

Las exacerbaciones de la enfermedad pulmonar obstructiva crónica (EA-EPOC) constituyen una de las principales causas de hospitalización y de asistencia a los Servicios de Urgencias, lo cual les confiere ser las responsables de una gran carga sobre el sistema sanitario. En nuestro estudio hemos evaluado el impacto de un modo asistencial alternativo (los hospitales de día de enfermedades respiratorias -HDER-) sobre la tasa de ingresos durante las EA-EPOC. Los resultados muestran que la atención en los HDER puede disminuir el número de ingresos en comparación con los Servicios de Urgencias a partir de un modelo de atención continuada y multidimensional.

Compositional and structural variabilities of Mg-rich iron oxide spinels from tuffite

Maghemite (γFe2O3) from tuffite is exceptionally rich in Mg, relatively to most of those reportedly found in other mafic lithosystems. To investigate in detail the compositional and structural variabilities of this natural magnetic iron oxide, sets of crystals were isolated from samples collected at different positions in a tuffite weathering mantle. These sets of crystal were individually powdered and studied by X-ray diffractometry, Mössbauer spectroscopy, magnetization measurements and chemical analysis. Lattice parameter of the cubic cell (a0) was found to vary from 0.834(1) to 0.8412(1) nm. Lower a0-values are characteristic of maghemite whereas higher ones are related to a magnetite precursor. FeO content ranges up to 17 mass % and spontaneous magnetization ranges from 8 to 32 J T-1 kg-1. Zero-field room temperature Mössbauer spectra are rather complex, indicating that the hyperfine field distributions due to Fe3+ and mixed valence Fe3+/2+ overlap. The structural variabilities of the (Mg, Ti)-rich iron oxide spinels is essentially related to the range of chemical composition of its precursor (Mg, Ti)-rich magnetite, and probably to the extent to which it has been oxidized during transformation in soil.