Extreme population differentiation in vulnerable slavemaking ant with fragmented distribution

Understanding levels of population differentiation and inbreeding are important issues in conservation biology, especially for social Hymenoptera with fragmented and small population sizes. Isolated populations are more vulnerable to genetic loss and extinction than those with extended continuous distributions. However, small populations are not always a consequence of a recent reduction of their habitat. Thus, determining the history of population isolation and current patterns of genetic variation of a species is crucial for its conservation. Rossomyrmex minuchae is a slave-making ant with patchy distribution in South Eastern Spain and is classified as vulnerable by the IUCN. In contrast, the other three known species of the genus are presumed to show more uniform distributions. Here we investigate the genetic diversity and population structure of R. minuchae and compare it with that found in two other species of the genus: R. anatolicus and R. quandratinodum. We conclude that although genetic diversity of R. minuchae is low, there is no evidence of a recent bottleneck, suggesting a gradual and natural fragmentation process. We also show extreme population differentiation at nuclear and mitochondrial markers, and isolation by distance at a local scale. Despite some evidence for inbreeding and low genetic variation within populations, we found almost no diploid males, a finding which contrasts with that expected in inbred Hymenoptera with single locus complementary sex determination. This could mean that sex is determined by another mechanism. We argue that continued low population size means that detrimental effects of inbreeding and low genetic variation are likely in the future. We suggest that a policy of artificial gene flow aimed at increasing within population variation is considered as a management option.

Effect of an ectoparasite on reproduction in great tits.

1. The effect of a haematophageous ectoparasite, the hen flea, on quality an number of offspring was experimentally investigated in the great tit. The experiment consisted of a controlled infestation of a random sample of nests with the parasitic flea and of a regular treatment of control nests with Microwaves in order to eliminate the naturally occurring fleas. 2. To assess the effects of fleas on variables related to offspring number, we considered the number of hatchlings and fledglings, the mortality between hatching and fledging, and the hatching and fledging success. For assessment of offspring quality, we measured body mass, tarsus and wing length, and calculated the nutritional condition of, nestlings as the ratio of body mass to tarsus length. A physiological variable, the haematocrit level, was also measured. 3. Hatching success and hatchling numbers did not differ between the two experimental groups. Offspring mortality between hatching and fledging was significantly higher in the infested broods (xBAR = 0.22 chicks dead per day) than in the parasite-free broods (xBAR = 0.07 dead per day). Fledging success was 83% in the parasite-free broods, but only 53% in the infested ones. The number of fledglings in infested broods (xBAR = 3.7 fledglings +/-2.1 SD) was significantly lower than in the parasite-free (xBAR = 4.9 +/- 1.1 SD) broods. 4. Body mass of chicks in the infested broods was significantly smaller than in the parasite-free broods both 14 days and 17 days after hatching. The chicks in the infested broods reached a significantly smaller tarsus length than the ones in the parasite-free broods. Close to fledging, the nutritional condition of chicks was significantly lower in infested broods. Haematocrit levels were significantly lower in the infested broods. 5. Brood size correlated differently with body mass and condition of chicks in infested and parasite-free nests. In parasite-free broods both body mass and condition of chicks at age 17 days, i.e. close to fledging, were significantly higher in small broods than in large ones. However, in the infested broods chicks were of the same body mass and condition in large as in small broods. Therefore, in parasite-free broods fitness can potentially be gained through offspring quality or number or both, whereas in infested broods it can be gained through offspring quantity only. In other words, a trade-off between quality and number of offspring is feasible only in the absence of the parasitic hen flea. 6. These results emphasize the need to study the effects of ectoparasites on ecological, behavioural and evolutionary traits of their bird hosts. A knowledge of these effects is essential for the understanding of population dynamics, behaviour and life-history traits of the hosts.

Diffusion of influenza during the winter of 1889-90 in Switzerland

The influenza of the winter of 1889-90 was one of the first epidemics to spread all over the world. At the time, several people hypothesized that the railway was one of the main vectors of diffusion of this influenza. This hypothesis was defended in Switzerland especially by Schmid, Chief of the Swiss Office of Health, who collected an impressive body of material about the spread of the epidemic in that country. These data on influenza combined with data about the structure of the railway are used in this paper in order to test the hypothesis of a mixed diffusion process, first between communes interconnected by the railway, and secondly, between those communes and neighbouring communes. An event history analysis model taking into account diffusion effects is proposed and estimated. Results show that the hypothesis is supported if the railway network in Switzerland is not taken as a whole but if a distinction between railway companies is made.

Computational and statistical analysis of copy number variants in normal and cancer genomes

AbstractAlthough the genomes from any two human individuals are more than 99.99% identical at the sequence level, some structural variation can be observed. Differences between genomes include single nucleotide polymorphism (SNP), inversion and copy number changes (gain or loss of DNA). The latter can range from submicroscopic events (CNVs, at least 1kb in size) to complete chromosomal aneuploidies. Small copy number variations have often no (lethal) consequences to the cell, but a few were associated to disease susceptibility and phenotypic variations. Larger re-arrangements (i.e. complete chromosome gain) are frequently associated with more severe consequences on health such as genomic disorders and cancer. High-throughput technologies like DNA microarrays enable the detection of CNVs in a genome-wide fashion. Since the initial catalogue of CNVs in the human genome in 2006, there has been tremendous interest in CNVs both in the context of population and medical genetics. Understanding CNV patterns within and between human populations is essential to elucidate their possible contribution to disease. But genome analysis is a challenging task; the technology evolves rapidly creating needs for novel, efficient and robust analytical tools which need to be compared with existing ones. Also, while the link between CNV and disease has been established, the relative CNV contribution is not fully understood and the predisposition to disease from CNVs of the general population has not been yet investigated.During my PhD thesis, I worked on several aspects related to CNVs. As l will report in chapter 3, ! was interested in computational methods to detect CNVs from the general population. I had access to the CoLaus dataset, a population-based study with more than 6,000 participants from the Lausanne area. All these individuals were analysed on SNP arrays and extensive clinical information were available. My work explored existing CNV detection methods and I developed a variety of metrics to compare their performance. Since these methods were not producing entirely satisfactory results, I implemented my own method which outperformed two existing methods. I also devised strategies to combine CNVs from different individuals into CNV regions.I was also interested in the clinical impact of CNVs in common disease (chapter 4). Through an international collaboration led by the Centre Hospitalier Universitaire Vaudois (CHUV) and the Imperial College London I was involved as a main data analyst in the investigation of a rare deletion at chromosome 16p11 detected in obese patients. Specifically, we compared 8,456 obese patients and 11,856 individuals from the general population and we found that the deletion was accounting for 0.7% of the morbid obesity cases and was absent in healthy non- obese controls. This highlights the importance of rare variants with strong impact and provides new insights in the design of clinical studies to identify the missing heritability in common disease.Furthermore, I was interested in the detection of somatic copy number alterations (SCNA) and their consequences in cancer (chapter 5). This project was a collaboration initiated by the Ludwig Institute for Cancer Research and involved other groups from the Swiss Institute of Bioinformatics, the CHUV and Universities of Lausanne and Geneva. The focus of my work was to identify genes with altered expression levels within somatic copy number alterations (SCNA) in seven metastatic melanoma ceil lines, using CGH and SNP arrays, RNA-seq, and karyotyping. Very few SCNA genes were shared by even two melanoma samples making it difficult to draw any conclusions at the individual gene level. To overcome this limitation, I used a network-guided analysis to determine whether any pathways, defined by amplified or deleted genes, were common among the samples. Six of the melanoma samples were potentially altered in four pathways and five samples harboured copy-number and expression changes in components of six pathways. In total, this approach identified 28 pathways. Validation with two external, large melanoma datasets confirmed all but three of the detected pathways and demonstrated the utility of network-guided approaches for both large and small datasets analysis.RésuméBien que le génome de deux individus soit similaire à plus de 99.99%, des différences de structure peuvent être observées. Ces différences incluent les polymorphismes simples de nucléotides, les inversions et les changements en nombre de copies (gain ou perte d'ADN). Ces derniers varient de petits événements dits sous-microscopiques (moins de 1kb en taille), appelés CNVs (copy number variants) jusqu'à des événements plus large pouvant affecter des chromosomes entiers. Les petites variations sont généralement sans conséquence pour la cellule, toutefois certaines ont été impliquées dans la prédisposition à certaines maladies, et à des variations phénotypiques dans la population générale. Les réarrangements plus grands (par exemple, une copie additionnelle d'un chromosome appelée communément trisomie) ont des répercutions plus grave pour la santé, comme par exemple dans certains syndromes génomiques et dans le cancer. Les technologies à haut-débit telle les puces à ADN permettent la détection de CNVs à l'échelle du génome humain. La cartographie en 2006 des CNV du génome humain, a suscité un fort intérêt en génétique des populations et en génétique médicale. La détection de différences au sein et entre plusieurs populations est un élément clef pour élucider la contribution possible des CNVs dans les maladies. Toutefois l'analyse du génome reste une tâche difficile, la technologie évolue très rapidement créant de nouveaux besoins pour le développement d'outils, l'amélioration des précédents, et la comparaison des différentes méthodes. De plus, si le lien entre CNV et maladie a été établit, leur contribution précise n'est pas encore comprise. De même que les études sur la prédisposition aux maladies par des CNVs détectés dans la population générale n'ont pas encore été réalisées.Pendant mon doctorat, je me suis concentré sur trois axes principaux ayant attrait aux CNV. Dans le chapitre 3, je détaille mes travaux sur les méthodes d'analyses des puces à ADN. J'ai eu accès aux données du projet CoLaus, une étude de la population de Lausanne. Dans cette étude, le génome de plus de 6000 individus a été analysé avec des puces SNP et de nombreuses informations cliniques ont été récoltées. Pendant mes travaux, j'ai utilisé et comparé plusieurs méthodes de détection des CNVs. Les résultats n'étant pas complètement satisfaisant, j'ai implémenté ma propre méthode qui donne de meilleures performances que deux des trois autres méthodes utilisées. Je me suis aussi intéressé aux stratégies pour combiner les CNVs de différents individus en régions.Je me suis aussi intéressé à l'impact clinique des CNVs dans le cas des maladies génétiques communes (chapitre 4). Ce projet fut possible grâce à une étroite collaboration avec le Centre Hospitalier Universitaire Vaudois (CHUV) et l'Impérial College à Londres. Dans ce projet, j'ai été l'un des analystes principaux et j'ai travaillé sur l'impact clinique d'une délétion rare du chromosome 16p11 présente chez des patients atteints d'obésité. Dans cette collaboration multidisciplinaire, nous avons comparés 8'456 patients atteint d'obésité et 11 '856 individus de la population générale. Nous avons trouvés que la délétion était impliquée dans 0.7% des cas d'obésité morbide et était absente chez les contrôles sains (non-atteint d'obésité). Notre étude illustre l'importance des CNVs rares qui peuvent avoir un impact clinique très important. De plus, ceci permet d'envisager une alternative aux études d'associations pour améliorer notre compréhension de l'étiologie des maladies génétiques communes.Egalement, j'ai travaillé sur la détection d'altérations somatiques en nombres de copies (SCNA) et de leurs conséquences pour le cancer (chapitre 5). Ce projet fut une collaboration initiée par l'Institut Ludwig de Recherche contre le Cancer et impliquant l'Institut Suisse de Bioinformatique, le CHUV et les Universités de Lausanne et Genève. Je me suis concentré sur l'identification de gènes affectés par des SCNAs et avec une sur- ou sous-expression dans des lignées cellulaires dérivées de mélanomes métastatiques. Les données utilisées ont été générées par des puces ADN (CGH et SNP) et du séquençage à haut débit du transcriptome. Mes recherches ont montrées que peu de gènes sont récurrents entre les mélanomes, ce qui rend difficile l'interprétation des résultats. Pour contourner ces limitations, j'ai utilisé une analyse de réseaux pour définir si des réseaux de signalisations enrichis en gènes amplifiés ou perdus, étaient communs aux différents échantillons. En fait, parmi les 28 réseaux détectés, quatre réseaux sont potentiellement dérégulés chez six mélanomes, et six réseaux supplémentaires sont affectés chez cinq mélanomes. La validation de ces résultats avec deux larges jeux de données publiques, a confirmée tous ces réseaux sauf trois. Ceci démontre l'utilité de cette approche pour l'analyse de petits et de larges jeux de données.Résumé grand publicL'avènement de la biologie moléculaire, en particulier ces dix dernières années, a révolutionné la recherche en génétique médicale. Grâce à la disponibilité du génome humain de référence dès 2001, de nouvelles technologies telles que les puces à ADN sont apparues et ont permis d'étudier le génome dans son ensemble avec une résolution dite sous-microscopique jusque-là impossible par les techniques traditionnelles de cytogénétique. Un des exemples les plus importants est l'étude des variations structurales du génome, en particulier l'étude du nombre de copies des gènes. Il était établi dès 1959 avec l'identification de la trisomie 21 par le professeur Jérôme Lejeune que le gain d'un chromosome supplémentaire était à l'origine de syndrome génétique avec des répercussions graves pour la santé du patient. Ces observations ont également été réalisées en oncologie sur les cellules cancéreuses qui accumulent fréquemment des aberrations en nombre de copies (telles que la perte ou le gain d'un ou plusieurs chromosomes). Dès 2004, plusieurs groupes de recherches ont répertorié des changements en nombre de copies dans des individus provenant de la population générale (c'est-à-dire sans symptômes cliniques visibles). En 2006, le Dr. Richard Redon a établi la première carte de variation en nombre de copies dans la population générale. Ces découvertes ont démontrées que les variations dans le génome était fréquentes et que la plupart d'entre elles étaient bénignes, c'est-à-dire sans conséquence clinique pour la santé de l'individu. Ceci a suscité un très grand intérêt pour comprendre les variations naturelles entre individus mais aussi pour mieux appréhender la prédisposition génétique à certaines maladies.Lors de ma thèse, j'ai développé de nouveaux outils informatiques pour l'analyse de puces à ADN dans le but de cartographier ces variations à l'échelle génomique. J'ai utilisé ces outils pour établir les variations dans la population suisse et je me suis consacré par la suite à l'étude de facteurs pouvant expliquer la prédisposition aux maladies telles que l'obésité. Cette étude en collaboration avec le Centre Hospitalier Universitaire Vaudois a permis l'identification d'une délétion sur le chromosome 16 expliquant 0.7% des cas d'obésité morbide. Cette étude a plusieurs répercussions. Tout d'abord elle permet d'effectuer le diagnostique chez les enfants à naître afin de déterminer leur prédisposition à l'obésité. Ensuite ce locus implique une vingtaine de gènes. Ceci permet de formuler de nouvelles hypothèses de travail et d'orienter la recherche afin d'améliorer notre compréhension de la maladie et l'espoir de découvrir un nouveau traitement Enfin notre étude fournit une alternative aux études d'association génétique qui n'ont eu jusqu'à présent qu'un succès mitigé.Dans la dernière partie de ma thèse, je me suis intéressé à l'analyse des aberrations en nombre de copies dans le cancer. Mon choix s'est porté sur l'étude de mélanomes, impliqués dans le cancer de la peau. Le mélanome est une tumeur très agressive, elle est responsable de 80% des décès des cancers de la peau et est souvent résistante aux traitements utilisés en oncologie (chimiothérapie, radiothérapie). Dans le cadre d'une collaboration entre l'Institut Ludwig de Recherche contre le Cancer, l'Institut Suisse de Bioinformatique, le CHUV et les universités de Lausanne et Genève, nous avons séquencés l'exome (les gènes) et le transcriptome (l'expression des gènes) de sept mélanomes métastatiques, effectués des analyses du nombre de copies par des puces à ADN et des caryotypes. Mes travaux ont permis le développement de nouvelles méthodes d'analyses adaptées au cancer, d'établir la liste des réseaux de signalisation cellulaire affectés de façon récurrente chez le mélanome et d'identifier deux cibles thérapeutiques potentielles jusqu'alors ignorées dans les cancers de la peau.

Genetic and karyotypic structure of a hybrid zone between the chromosomal races Cordon and Valais in the common shrew, Sorex araneus

Hybrid zones between genetically differentiated populations provide material to study evolutionary processes. Since the discovery of chromosomal races in Sorex araneus, contact zones have attracted attention of scientists. So far, studies on genetic markers in Sorex hybrid zones are missing. The acrocentric chromosomal race Cordon and the highly metacentric race Valais meet and hybridize at Les Houches in the Western Alps. On a transect through the hybrid zone, 273 shrews were caught at 15 localities over 4 years. Karyotype as well as the nuclear protein loci Alb and Pg were analyzed. F-st and F-is values were calculated by F-statistics. An analysis on pooled samples revealed the genetical differences between the hybridizing races as the only cause of population structuring. Genetical markers show dines with very strong frequency shifts at a mountain torrent, but behave differently through the zone. The performance of the torrent in maintaining the hybrid zone, selection against hybrids, possible assortative mating and linkage of the Valais Pg allele to a diagnostic chromosome arm, are discussed.

Genetic bottlenecks driven by population disconnection.

Connectivity among populations plays a crucial role in maintaining genetic variation at a local scale, especially in small populations affected strongly by genetic drift. The negative consequences of population disconnection on allelic richness and gene diversity (heterozygosity) are well recognized and empirically established. It is not well recognized, however, that a sudden drop in local effective population size induced by such disconnection produces a temporary disequilibrium in allelic frequency distributions that is akin to the genetic signature of a demographic bottleneck. To document this effect, we used individual-based simulations and empirical data on allelic richness and gene diversity in six pairs of isolated versus well-connected (core) populations of European tree frogs. In our simulations, population disconnection depressed allelic richness more than heterozygosity and thus resulted in a temporary excess in gene diversity relative to mutation drift equilibrium (i.e., signature of a genetic bottleneck). We observed a similar excess in gene diversity in isolated populations of tree frogs. Our results show that population disconnection can create a genetic bottleneck in the absence of demographic collapse.

Profiling of steroid metabolites after transdermal and oral administration of testosterone by ultra-high pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

The screening of testosterone (T) misuse for doping control is based on the urinary steroid profile, including T, its precursors and metabolites. Modifications of individual levels and ratio between those metabolites are indicators of T misuse. In the context of screening analysis, the most discriminant criterion known to date is based on the T glucuronide (TG) to epitestosterone glucuronide (EG) ratio (TG/EG). Following the World Anti-Doping Agency (WADA) recommendations, there is suspicion of T misuse when the ratio reaches 4 or beyond. While this marker remains very sensitive and specific, it suffers from large inter-individual variability, with important influence of enzyme polymorphisms. Moreover, use of low dose or topical administration forms makes the screening of endogenous steroids difficult while the detection window no longer suits the doping habit. As reference limits are estimated on the basis of population studies, which encompass inter-individual and inter-ethnic variability, new strategies including individual threshold monitoring and alternative biomarkers were proposed to detect T misuse. The purpose of this study was to evaluate the potential of ultra-high pressure liquid chromatography (UHPLC) coupled with a new generation high resolution quadrupole time-of-flight mass spectrometer (QTOF-MS) to investigate the steroid metabolism after transdermal and oral T administration. An approach was developed to quantify 12 targeted urinary steroids as direct glucuro- and sulfo-conjugated metabolites, allowing the conservation of the phase II metabolism information, reflecting genetic and environmental influences. The UHPLC-QTOF-MS(E) platform was applied to clinical study samples from 19 healthy male volunteers, having different genotypes for the UGT2B17 enzyme responsible for the glucuroconjugation of T. Based on reference population ranges, none of the traditional markers of T misuse could detect doping after topical administration of T, while the detection window was short after oral TU ingestion. The detection ability of the 12 targeted steroids was thus evaluated by using individual thresholds following both transdermal and oral administration. Other relevant biomarkers and minor metabolites were studied for complementary information to the steroid profile, including sulfoconjugated analytes and hydroxy forms of glucuroconjugated metabolites. While sulfoconjugated steroids may provide helpful screening information for individuals with homozygotous UGT2B17 deletion, hydroxy-glucuroconjugated analytes could enhance the detection window of oral T undecanoate (TU) doping.

A matter of time: delayed mate encounter postpones mating window initiation and reduces the strength of female choosiness

Reproductive success is determined by the presence and timing of encounter of mates. The latter depends on species-specific reproductive characteristics (e.g. initiation/duration of the mating window), season, and reproductive strategies (e.g. intensity of choosiness) that may potentially mitigate constraints imposed by mating windows. Despite their potentially crucial role for fitness and population dynamics, limited evidence exists about mating window initiation, duration and reproductive strategies. Here, we experimentally tested the mechanisms of initiation and the duration of the common lizard's Zootoca vivipara mating window, by manipulating the timing of mate encounter and analyzing its effect on (re-)mating probability. We furthermore tested treatment effects on female reproductive strategies, by measuring female choosiness. The timing of mate encounter and season did not significantly affect mating probability. However, a longer delay until mate encounter reduced female choosiness. Re-mating probability decreased with re-mating delay and was independent of mating delay. This indicates that mating window initiation depends on mate encounter, that its duration is fixed, and that plastic reproductive strategies exist. These findings contrast with previous beliefs and shows that mating windows per se may not necessarily constrain reproductive success, which is congruent with rapid range expansion and absence of positive density-effects on reproductive success (Allee effects). In summary, our results show that predicting the effect of mating windows on reproduction is complex and that experimental evidence is essential for evaluating their effect on reproduction and reproductive strategies, both being important determinants of population dynamics and the colonization of new habitats.

Impact of phenotype definition on genome-wide association signals: empirical evaluation in human immunodeficiency virus type 1 infection.

Discussion on improving the power of genome-wide association studies to identify candidate variants and genes is generally centered on issues of maximizing sample size; less attention is given to the role of phenotype definition and ascertainment. The authors used genome-wide data from patients infected with human immunodeficiency virus type 1 (HIV-1) to assess whether differences in type of population (622 seroconverters vs. 636 seroprevalent subjects) or the number of measurements available for defining the phenotype resulted in differences in the effect sizes of associations between single nucleotide polymorphisms and the phenotype, HIV-1 viral load at set point. The effect estimate for the top 100 single nucleotide polymorphisms was 0.092 (95% confidence interval: 0.074, 0.110) log(10) viral load (log(10) copies of HIV-1 per mL of blood) greater in seroconverters than in seroprevalent subjects. The difference was even larger when the authors focused on chromosome 6 variants (0.153 log(10) viral load) or on variants that achieved genome-wide significance (0.232 log(10) viral load). The estimates of the genetic effects tended to be slightly larger when more viral load measurements were available, particularly among seroconverters and for variants that achieved genome-wide significance. Differences in phenotype definition and ascertainment may affect the estimated magnitude of genetic effects and should be considered in optimizing power for discovering new associations.

Mucoviscidose: illustration de la complexité du dépistage génétique. [The example of cystic fibrosis to highlight the complexity of genetic screening].

Différentes organisations et différents pays aboutissent souvent à des conclusions différentes quant à la pertinence d'introduire un test de dépistage génétique dans la population générale. Cet article décrit la complexité du dépistage basé sur des tests génétiques. Utilisant l'exemple de la mucoviscidose - pour laquelle un groupe de travail national est en train d'évaluer la pertinence d'un dépistage génétique - les auteurs relèvent les situaions où les recommandations de dépistage sont parfois basées sur l'émergence de nouvelles technologies (par exemple, test génétique) et d'opinion publique plutôt que sur la base d'évidences. Ils présentent également les enjeux éthiques et économiques du dépistage génétique de la mucoviscidose. [Abstract] Various institutions and countries often reach different conclusions about the utility of introducing a newborn screening test in the general population. This paper highlights the complexity of population screening including genetic tests. Using the example of cystic fibrosis genetic screening, for which a Swiss Working Group for Cystic Fibrosis is currently evaluating the pertinence, we outline that screening recommendations are often based more on expert opinion and emerging new technologies rather than on evidence. We also present some ethical and economic issues related to cystic fibrosis genetic screening.

Seasonality of cardiovascular risk factors: an analysis including over 230 000 participants in 15 countries.

OBJECTIVE: To assess the seasonality of cardiovascular risk factors (CVRF) in a large set of population-based studies. METHODS: Cross-sectional data from 24 population-based studies from 15 countries, with a total sample size of 237 979 subjects. CVRFs included Body Mass Index (BMI) and waist circumference; systolic (SBP) and diastolic (DBP) blood pressure; total, high (HDL) and low (LDL) density lipoprotein cholesterol; triglycerides and glucose levels. Within each study, all data were adjusted for age, gender and current smoking. For blood pressure, lipids and glucose levels, further adjustments on BMI and drug treatment were performed. RESULTS: In the Northern and Southern Hemispheres, CVRFs levels tended to be higher in winter and lower in summer months. These patterns were observed for most studies. In the Northern Hemisphere, the estimated seasonal variations were 0.26 kg/m(2) for BMI, 0.6 cm for waist circumference, 2.9 mm Hg for SBP, 1.4 mm Hg for DBP, 0.02 mmol/L for triglycerides, 0.10 mmol/L for total cholesterol, 0.01 mmol/L for HDL cholesterol, 0.11 mmol/L for LDL cholesterol, and 0.07 mmol/L for glycaemia. Similar results were obtained when the analysis was restricted to studies collecting fasting blood samples. Similar seasonal variations were found for most CVRFs in the Southern Hemisphere, with the exception of waist circumference, HDL, and LDL cholesterol. CONCLUSIONS: CVRFs show a seasonal pattern characterised by higher levels in winter, and lower levels in summer. This pattern could contribute to the seasonality of CV mortality.

Increasing prehospital emergency medical service interventions for nursing home residents.

QUESTION: In the ageing European population, the proportion of interventions by the emergency medical services (EMS) for elderly patients is increasing, but little is known about the recent trend of EMS interventions in nursing homes. The aim of this analysis was to describe the evolution of the incidence of requests for prehospital EMS interventions for nursing home residents aged 65 years and over between 2004 and 2013. METHODS: A prospective population-based register of routinely collected data for each EMS intervention in the Canton of Vaud. Linear time trends of incidence of requests to the EMS in nursing homes were calculated and stratified by age categories. RESULTS: The number of ambulance interventions in nursing homes for people aged 65 years and over (65+) increased by 68.9% (1124‒1898) between 2004 and 2013. A significant linear increase of the annual incidence of requests to EMS per 1,000 nursing home residents was found for people aged 65-79 (10.2, 95% confidence interval [CI] 6.2-14.2), 80-89 (16.5, 95% CI 14.0-19.0) and over 90 (12.1, 95% CI 5.8-18.4). EMS interventions in nursing home residents who required an emergency physician increased during the same period by 205.6% (from 106 to 324), representing an increase from 2% to 7% of all emergency physician interventions in the Canton. CONCLUSIONS: Our results confirmed an important increase in the incidence of EMS interventions in nursing homes during the last decade, far exceeding the actual increase of the nursing home population during the same period. This evolution represents an important opportunity to reconsider the EMS missions in the context of an ageing society.

Global Diversity Lines-A Five-Continent Reference Panel of Sequenced Drosophila melanogaster Strains.

Reference collections of multiple Drosophila lines with accumulating collections of "omics" data have proven especially valuable for the study of population genetics and complex trait genetics. Here we present a description of a resource collection of 84 strains of Drosophila melanogaster whose genome sequences were obtained after 12 generations of full-sib inbreeding. The initial rationale for this resource was to foster development of a systems biology platform for modeling metabolic regulation by the use of natural polymorphisms as perturbations. As reference lines, they are amenable to repeated phenotypic measurements, and already a large collection of metabolic traits have been assayed. Another key feature of these strains is their widespread geographic origin, coming from Beijing, Ithaca, Netherlands, Tasmania, and Zimbabwe. After obtaining 12.5× coverage of paired-end Illumina sequence reads, SNP and indel calls were made with the GATK platform. Thorough quality control was enabled by deep sequencing one line to >100×, and single-nucleotide polymorphisms and indels were validated using ddRAD-sequencing as an orthogonal platform. In addition, a series of preliminary population genetic tests were performed with these single-nucleotide polymorphism data for assessment of data quality. We found 83 segregating inversions among the lines, and as expected these were especially abundant in the African sample. We anticipate that this will make a useful addition to the set of reference D. melanogaster strains, thanks to its geographic structuring and unusually high level of genetic diversity.

Dispatch centres: what is the right population catchment size?

Literature on medical dispatch is growing, focusing mainly on efficiency (under and overtriage) and dispatch-assisted CPR. But the issue of population catchment size, functional costs and rationalization is rarely addressed. If we can observe a trend toward a decreasing number of dispatch centres in many European countries, there is today no evidence on what is the right catchment size to reach the best balance between quality of services and costs.