Optimizing Pavement Base, Subbase, and Subgrade Layers for Cost and Performance of Local Roads, TR-640

This report is one of two products for this project with the other being a design guide. This report describes test results and comparative analysis from 16 different portland cement concrete (PCC) pavement sites on local city and county roads in Iowa. At each site the surface conditions of the pavement (i.e., crack survey) and foundation layer strength, stiffness, and hydraulic conductivity properties were documented. The field test results were used to calculate in situ parameters used in pavement design per SUDAS and AASHTO (1993) design methodologies. Overall, the results of this study demonstrate how in situ and lab testing can be used to assess the support conditions and design values for pavement foundation layers and how the measurements compare to the assumed design values. The measurements show that in Iowa, a wide range of pavement conditions and foundation layer support values exist. The calculated design input values for the test sites (modulus of subgrade reaction, coefficient of drainage, and loss of support) were found to be different than typically assumed. This finding was true for the full range of materials tested. The findings of this study support the recommendation to incorporate field testing as part of the process to field verify pavement design values and to consider the foundation as a design element in the pavement system. Recommendations are provided in the form of a simple matrix for alternative foundation treatment options if the existing foundation materials do not meet the design intent. The PCI prediction model developed from multi-variate analysis in this study demonstrated a link between pavement foundation conditions and PCI. The model analysis shows that by measuring properties of the pavement foundation, the engineer will be able to predict long term performance with higher reliability than by considering age alone. This prediction can be used as motivation to then control the engineering properties of the pavement foundation for new or re-constructed PCC pavements to achieve some desired level of performance (i.e., PCI) with time.

Candidat à l'échec scolaire incompris et ignoré : l'enfant de migrants = Misunderstood and ignored candidate to the school failure: The child of migrants

Immigration, intégration, précarité, échec scolaire, ignorance du français, délinquance sont des thèmes qui animent régulièrement les débats publics, médiatiques et politiques. Bien que les migrations ont toujours fait partie de l'histoire humaine, elles sont souvent décrites comme un trouble aux identités nationales, elles-mêmes mises à mal par la mondialisation. Cependant, les mécanismes sous-tendant les difficultés rencontrées par certains enfants de migrants demeurent bien moins débattus et considérés que leurs conséquences bruyantes et visibles. Après une réflexion sur l'impact de la migration elle-même sur le sujet et un bref aperçu de l'ethnopsychiatrie, nous allons décrire les difficultés que peut rencontrer l'enfant de migrants, leurs origines et leurs conséquences. Nous nous intéresserons ensuite à la manière dont notre société, nos institutions en tiennent compte ou pas. Nous terminerons notre propos par la mise en relief des besoins thérapeutiques et éducatifs spéciaux de ces enfants et la manière dont ceux-ci sont comblés (ou non). Immigration, social integration, precariousness, language barrier, delinquency are constantly stimulating public, political and media debate. Migrations always were part of the human history but they are often described like a disorder of the national identities, themselves put at evil by globalization. However, the origin of the difficulties that certain children of migrants encounter is often overlooked. Only their disturbing implications are frequently studied. After a brief comment on the impact of the migration and the ethnopsychiatry, we will outline the difficulties sometimes faced by the children of migrants, their origins and consequences. Then we will describe how the society and the institutions take them in account (or not). We finally will delineate the specific needs of those children and how they are meeting (or not).

Influence of Assisted Reproductive Techniques in the occurrence of weight discordance in twin gestations

Background:There is no actual evidence that the ART are directly related to the occurrence of weight discordance. In some studies, ART-­‐conceived twin pregnancies are at greater risk than non-­‐ART-­‐conceived ones for pregnancy complications and adverse perinatal outcome: the incidences of pregnancy-­‐induced hypertension, uterine bleeding, premature contractions, IUGR, fetal death, discordance, and cesarean section were significantly higher. Discordance rate was elevated (25.3% vs.17.0%) among ART twins, which can increase perinatal risk (increased incidence of SGA and NICU admission). Other studies say that perinatal and neonatal morbidity, gestational age at delivery, and birth weight are not affected by ART. Regarding the first trimester ultrasound, some studies didn’t notice significant differences in CRL disparity or birth weight discordance between spontaneous and ART-­‐ conceived dichorionic twin pregnancies. In ART-­‐conceived dichorionic twin pregnancies, CRL disparity may be associated with birth weight discordance. In some studies, CRL discordance in twin pregnancies in the first trimester was a frequent finding. Objectives: To analyze the association of the ART in the occurrence of weight discordance in the pregnancies between 2010 and 2013 in the Hospital Universitari de Girona Doctor Josep Trueta, and to describe the proportion of diagnosis of growth discordance in the first trimester by the ultrasonography technology. Methods: A retrospective cohort study will be performed in those patients with twin pregnancies between 2010 and 2013, within the Hospital Universitari de Girona Doctor Josep Trueta (HUJT). A retrospective and descriptive study will be done in those cases with discordance weight in the moment of the birth, in which the CRL will be studied in the first trimester ultrasound, describing the percentage of discordance detected in that moment. The general characteristics of the sample are going to be analyzed by Logistic RegressionInfluenceof

Influence of Assisted Reproductive Techniques in the occurrence of weight discordance in twin gestations

Background:There is no actual evidence that the ART are directly related to the occurrence of weight discordance. In some studies, ART-­‐conceived twin pregnancies are at greater risk than non-­‐ART-­‐conceived ones for pregnancy complications and adverse perinatal outcome: the incidences of pregnancy-­‐induced hypertension, uterine bleeding, premature contractions, IUGR, fetal death, discordance, and cesarean section were significantly higher. Discordance rate was elevated (25.3% vs.17.0%) among ART twins, which can increase perinatal risk (increased incidence of SGA and NICU admission). Other studies say that perinatal and neonatal morbidity, gestational age at delivery, and birth weight are not affected by ART. Regarding the first trimester ultrasound, some studies didn’t notice significant differences in CRL disparity or birth weight discordance between spontaneous and ART-­‐ conceived dichorionic twin pregnancies. In ART-­‐conceived dichorionic twin pregnancies, CRL disparity may be associated with birth weight discordance. In some studies, CRL discordance in twin pregnancies in the first trimester was a frequent finding. Objectives: To analyze the association of the ART in the occurrence of weight discordance in the pregnancies between 2010 and 2013 in the Hospital Universitari de Girona Doctor Josep Trueta, and to describe the proportion of diagnosis of growth discordance in the first trimester by the ultrasonography technology. Methods: A retrospective cohort study will be performed in those patients with twin pregnancies between 2010 and 2013, within the Hospital Universitari de Girona Doctor Josep Trueta (HUJT). A retrospective and descriptive study will be done in those cases with discordance weight in the moment of the birth, in which the CRL will be studied in the first trimester ultrasound, describing the percentage of discordance detected in that moment. The general characteristics of the sample are going to be analyzed by Logistic RegressionInfluenceof

Incidence and risk factors for chronic elevation of alanine aminotransferase levels in HIV-infected persons without hepatitis b or c virus co-infection.

BACKGROUND: Chronic liver disease in human immunodeficiency virus (HIV)-infected patients is mostly caused by hepatitis virus co-infection. Other reasons for chronic alanine aminotransferase (ALT) elevation are more difficult to diagnose. METHODS: We studied the incidence of and risk factors for chronic elevation of ALT levels (greater than the upper limit of normal at 2 consecutive semi-annual visits) in participants of the Swiss HIV Cohort Study without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection who were seen during the period 2002-2008. Poisson regression analysis was used. RESULTS: A total of 2365 participants were followed up for 9972 person-years (median age, 38 years; male sex, 66%; median CD4+ cell count, 426/microL; receipt of antiretroviral therapy [ART], 56%). A total of 385 participants (16%) developed chronic elevated ALT levels, with an incidence of 3.9 cases per 100 person-years (95% confidence interval [CI], 3.5-4.3 cases per 100 person-years). In multivariable analysis, chronic elevated ALT levels were associated with HIV RNA level >100,000 copies/mL (incidence rate ratio [IRR], 2.23; 95% CI, 1.45-3.43), increased body mass index (BMI, defined as weight in kilograms divided by the square of height in meters) (BMI of 25-29.9 was associated with an IRR of 1.56 [95% CI, 1.24-1.96]; a BMI 30 was associated with an IRR of 1.70 [95% CI, 1.16-2.51]), severe alcohol use (1.83 [1.19-2.80]), exposure to stavudine (IRR per year exposure, 1.12 [95% CI, 1.07-1.17]) and zidovudine (IRR per years of exposure, 1.04 [95% CI, 1.00-1.08]). Associations with cumulative exposure to combination ART, nucleoside reverse-transcriptase inhibitors, and unboosted protease inhibitors did not remain statistically significant after adjustment for exposure to stavudine. Black ethnicity was inversely correlated (IRR, 0.52 [95% CI, 0.33-0.82]). Treatment outcome and mortality did not differ between groups with and groups without elevated ALT levels. CONCLUSIONS: Among patients without hepatitis virus co-infection, the incidence of chronic elevated ALT levels was 3.9 cases per 100 person-years, which was associated with high HIV RNA levels, increased BMI, severe alcohol use, and prolonged stavudine and zidovudine exposure. Long-term follow-up is needed to assess whether chronic elevation of ALT levels will result in increased morbidity or mortality.

Influence of Assisted Reproductive Techniques in the occurrence of weight discordance in twin gestations

Background:There is no actual evidence that the ART are directly related to the occurrence of weight discordance. In some studies, ART-­‐conceived twin pregnancies are at greater risk than non-­‐ART-­‐conceived ones for pregnancy complications and adverse perinatal outcome: the incidences of pregnancy-­‐induced hypertension, uterine bleeding, premature contractions, IUGR, fetal death, discordance, and cesarean section were significantly higher. Discordance rate was elevated (25.3% vs.17.0%) among ART twins, which can increase perinatal risk (increased incidence of SGA and NICU admission). Other studies say that perinatal and neonatal morbidity, gestational age at delivery, and birth weight are not affected by ART. Regarding the first trimester ultrasound, some studies didn’t notice significant differences in CRL disparity or birth weight discordance between spontaneous and ART-­‐ conceived dichorionic twin pregnancies. In ART-­‐conceived dichorionic twin pregnancies, CRL disparity may be associated with birth weight discordance. In some studies, CRL discordance in twin pregnancies in the first trimester was a frequent finding. Objectives: To analyze the association of the ART in the occurrence of weight discordance in the pregnancies between 2010 and 2013 in the Hospital Universitari de Girona Doctor Josep Trueta, and to describe the proportion of diagnosis of growth discordance in the first trimester by the ultrasonography technology. Methods: A retrospective cohort study will be performed in those patients with twin pregnancies between 2010 and 2013, within the Hospital Universitari de Girona Doctor Josep Trueta (HUJT). A retrospective and descriptive study will be done in those cases with discordance weight in the moment of the birth, in which the CRL will be studied in the first trimester ultrasound, describing the percentage of discordance detected in that moment. The general characteristics of the sample are going to be analyzed by Logistic RegressionInfluenceof

Prevalence of hypertension in schoolchildren based on repeated measurements and association with overweight.

OBJECTIVE: Most studies assess the prevalence of hypertension in pediatric populations based on blood pressure (BP) readings taken on a single visit. We determined the prevalence of hypertension measured on up to three visits in a Swiss pediatric population and examined the association between hypertension and overweight and selected other factors. METHODS: Anthropometric data and BP were measured in all children of the sixth school grade of the Vaud canton (Switzerland) in 2005-2006. 'Elevated BP' was defined according to sex-specific, age-specific and height-specific US reference data. BP was measured on up to two additional visits in children with elevated BP. 'Hypertension' was defined as 'elevated BP' on all three visits. RESULTS: Out of 6873 children, 5207 (76%) participated [2621 boys, 2586 girls; mean (SD) age, 12.3 (0.5) years]. The prevalence of elevated BP was 11.4, 3.8 and 2.2% on first, second and thirds visits, respectively; hence 2.2% had hypertension. Among hypertensive children, 81% had isolated systolic hypertension. Hypertension was associated with excess body weight, elevated heart rate and parents' history of hypertension. Of the children, 16.1% of boys and 12.4% of girls were overweight or obese (CDC criteria, body mass index >or= 85th percentile). Thirty-seven percent of cases of hypertension could be attributed to overweight or obesity. CONCLUSIONS: The proportion of children with elevated BP based on one visit was five times higher than based on three measurements taken at few-week intervals. Our data re-emphasize the need for prevention and control of overweight in children to curb the global hypertension burden.

Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span.

Children conceived by assisted reproductive technologies (ART) display a level of vascular dysfunction similar to that seen in children of mothers with preeclamspia. The long-term consequences of ART-associated vascular disorders are unknown and difficult to investigate in healthy children. Here, we found that vasculature from mice generated by ART display endothelial dysfunction and increased stiffness, which translated into arterial hypertension in vivo. Progeny of male ART mice also exhibited vascular dysfunction, suggesting underlying epigenetic modifications. ART mice had altered methylation at the promoter of the gene encoding eNOS in the aorta, which correlated with decreased vascular eNOS expression and NO synthesis. Administration of a deacetylase inhibitor to ART mice normalized vascular gene methylation and function and resulted in progeny without vascular dysfunction. The induction of ART-associated vascular and epigenetic alterations appeared to be related to the embryo environment; these alterations were possibly facilitated by the hormonally stimulated ovulation accompanying ART. Finally, ART mice challenged with a high-fat diet had roughly a 25% shorter life span compared with control animals. This study highlights the potential of ART to induce vascular dysfunction and shorten life span and suggests that epigenetic alterations contribute to these problems.

Prevalence of overweight and underweight in public and private schools in the Seychelles.

Abstract Objective. We compared the prevalence of body weight categories between public and private schools in the Seychelles, a rapidly developing small island state in the African region. Methods. In 2004-2006, weight and height were measured and self-reported information on physical activity collected in children of three selected grades in all schools in the country. Overweight, obesity and thinness were defined according to standard criteria. Results. Based on 8 462 students (377 in private schools), the prevalence of overweight (including obesity) was markedly higher in private than public schools (boys: 37% [95% CI: 31-44] vs. 15% [14-16]; girls: 33% [26-41] vs. 20% [19-22]). The prevalence of thinness grade 1 was lower in private than public schools (boys: 9% [5-13] vs. 20% [19-21]; girls: 13% [8-18] vs. 19% [18-20]). Students in private schools reported more physical activity at leisure time while students in public schools reported larger weekly walking time. Conclusions. Our findings suggest that school type may be a useful indicator for assessing the association between socio-economic status and overweight in children, and that overweight affects wealthy children more often than others in developing countries.

Overweight in Swiss children and associations with children's and parents' characteristics et Worldwide trends in childhood obesity

(1) Surpoids chez les enfants suisses et associations avec certaines caractéristiques chez les enfants et leurs parents Le but de cette étude était de mesurer la prévalence du surpoids et de l?obésité chez les enfants de sixième année du canton de Vaud (âge moyen de 12 ans) et les facteurs associés au surpoids. Les données ont été récoltées lors d?une étude menée par l?Institut universitaire de médecine sociale et préventive. Tous les enfants scolarisés en 6ème année à l?école publique du canton de Vaud entre septembre 2005 et mai 2006 étaient éligibles à participer à cette étude. Le taux de participation a atteint 76% (soit 5207 enfants de 12,3 ans en moyenne). Le poids et la taille des enfants ont été mesurés à l?école par des assistants de recherche et les enfants ont rempli, en classe, un questionnaire structuré sur leur mode de vie (notamment : temps quotidien passé à regarder la télévision, à jouer à des jeux sur écran; fréquence de la pratique de diverses activités physiques; fréquence de la consommation de fruits ou de légumes). Des informations sur les parents (niveau d?éducation, nationalité, poids et taille) ont été récoltées au moyen d?un questionnaire structuré envoyé par courrier à ceux-ci. Nous avons utilisé les critères de l?International Obesity Task Force, qui définit les valeurs-seuils de l'indice de masse corporelle pour le surpoids et pour l?obésité, par age et par sexe. La prévalence du surpoids (obésité incluse) dans la population était de 15% chez les garçons et de 12% chez les filles, et la prévalence de l?obésité était de 2% dans les deux sexes. Nous avons trouvé que le surpoids était associé de façon indépendante avec le temps passé à regarder la télévision, ainsi qu?avec certaines caractéristiques des parents, comme le surpoids, un bas niveau d?éducation et une nationalité étrangère. En conclusion, un enfant sur sept est en surpoids ou obèse dans le canton de Vaud. Ces chiffres indiquent un important défi de santé publique, même si cette prévalence dans le canton de Vaud est, actuellement, moindre que dans beaucoup d?autres pays d?Europe, et bien moindre qu?en Amérique du Nord. Les associations entre le surpoids infantile et le temps passé à regarder la télévision, ainsi que les associations avec des variables liées au milieu socio-culturel des parents indiquent plusieurs pistes d?intervention pour prévenir le surpoids chez les enfants. Il est probable que les mesures de prévention ne devraient pas se limiter aux approches individuelles, mais devraient aussi inclure des mesures structurelles sur l?environnement social, physique et économique visant à réduire les facteurs obésogènes dans la société.<br/><br/>Objective: The objective was to assess the prevalence of overweight and obesity in children in a canton of Switzerland and the association with various characteristics of the parents and the children. Research Methods and Procedures: A cross-sectional survey was conducted in all children of the sixth school grade of the canton of Vaud, Switzerland. Weight and height were measured, and selected lifestyle variables were assessed with a self-administered semiquantitative questionnaire. Information on children?s parents was gathered through a mailed structured questionnaire. Overweight and obesity were based on the International Obesity Task Force criteria. Results: Of 6873 eligible children, 5207 (76%) participated (2621 boys, 2586 girls; mean age, 12.3 years; standard deviation, 0.5 year). The prevalence of overweight (including obesity) was 15.0% (95% confidence interval, 13.7% to 16.4%) in boys and 12.4% (11.1% to 13.7%) in girls, and the prevalence of obesity was 1.8% (1.3% to 2.3%) and 1.7% (1.2% to 2.2%), respectively. In both univariate and multivariate analyses, overweight was strongly associated with high television viewing time and selected characteristics of the parents (overweight, low educational level, and foreign nationality). Discussion: The prevalence of pediatric overweight and obesity was lower in this region of Switzerland than in several European countries. The correlates of overweight found in this region suggest areas for potential interventions.

Exploring transparent approaches to the authentication of signatures on artwork

This thesis is composed of three main parts. The first consists of a state of the art of the different notions that are significant to understand the elements surrounding art authentication in general, and of signatures in particular, and that the author deemed them necessary to fully grasp the microcosm that makes up this particular market. Individuals with a solid knowledge of the art and expertise area, and that are particularly interested in the present study are advised to advance directly to the fourth Chapter. The expertise of the signature, it's reliability, and the factors impacting the expert's conclusions are brought forward. The final aim of the state of the art is to offer a general list of recommendations based on an exhaustive review of the current literature and given in light of all of the exposed issues. These guidelines are specifically formulated for the expertise of signatures on paintings, but can also be applied to wider themes in the area of signature examination. The second part of this thesis covers the experimental stages of the research. It consists of the method developed to authenticate painted signatures on works of art. This method is articulated around several main objectives: defining measurable features on painted signatures and defining their relevance in order to establish the separation capacities between groups of authentic and simulated signatures. For the first time, numerical analyses of painted signatures have been obtained and are used to attribute their authorship to given artists. An in-depth discussion of the developed method constitutes the third and final part of this study. It evaluates the opportunities and constraints when applied by signature and handwriting experts in forensic science. A brief summary covering each chapter allows a rapid overview of the study and summarizes the aims and main themes of each chapter. These outlines presented below summarize the aims and main themes addressed in each chapter. Part I - Theory Chapter 1 exposes legal aspects surrounding the authentication of works of art by art experts. The definition of what is legally authentic, the quality and types of the experts that can express an opinion concerning the authorship of a specific painting, and standard deontological rules are addressed. The practices applied in Switzerland will be specifically dealt with. Chapter 2 presents an overview of the different scientific analyses that can be carried out on paintings (from the canvas to the top coat). Scientific examinations of works of art have become more common, as more and more museums equip themselves with laboratories, thus an understanding of their role in the art authentication process is vital. The added value that a signature expertise can have in comparison to other scientific techniques is also addressed. Chapter 3 provides a historical overview of the signature on paintings throughout the ages, in order to offer the reader an understanding of the origin of the signature on works of art and its evolution through time. An explanation is given on the transitions that the signature went through from the 15th century on and how it progressively took on its widely known modern form. Both this chapter and chapter 2 are presented to show the reader the rich sources of information that can be provided to describe a painting, and how the signature is one of these sources. Chapter 4 focuses on the different hypotheses the FHE must keep in mind when examining a painted signature, since a number of scenarios can be encountered when dealing with signatures on works of art. The different forms of signatures, as well as the variables that may have an influence on the painted signatures, are also presented. Finally, the current state of knowledge of the examination procedure of signatures in forensic science in general, and in particular for painted signatures, is exposed. The state of the art of the assessment of the authorship of signatures on paintings is established and discussed in light of the theoretical facets mentioned previously. Chapter 5 considers key elements that can have an impact on the FHE during his or her2 examinations. This includes a discussion on elements such as the skill, confidence and competence of an expert, as well as the potential bias effects he might encounter. A better understanding of elements surrounding handwriting examinations, to, in turn, better communicate results and conclusions to an audience, is also undertaken. Chapter 6 reviews the judicial acceptance of signature analysis in Courts and closes the state of the art section of this thesis. This chapter brings forward the current issues pertaining to the appreciation of this expertise by the non- forensic community, and will discuss the increasing number of claims of the unscientific nature of signature authentication. The necessity to aim for more scientific, comprehensive and transparent authentication methods will be discussed. The theoretical part of this thesis is concluded by a series of general recommendations for forensic handwriting examiners in forensic science, specifically for the expertise of signatures on paintings. These recommendations stem from the exhaustive review of the literature and the issues exposed from this review and can also be applied to the traditional examination of signatures (on paper). Part II - Experimental part Chapter 7 describes and defines the sampling, extraction and analysis phases of the research. The sampling stage of artists' signatures and their respective simulations are presented, followed by the steps that were undertaken to extract and determine sets of characteristics, specific to each artist, that describe their signatures. The method is based on a study of five artists and a group of individuals acting as forgers for the sake of this study. Finally, the analysis procedure of these characteristics to assess of the strength of evidence, and based on a Bayesian reasoning process, is presented. Chapter 8 outlines the results concerning both the artist and simulation corpuses after their optical observation, followed by the results of the analysis phase of the research. The feature selection process and the likelihood ratio evaluation are the main themes that are addressed. The discrimination power between both corpuses is illustrated through multivariate analysis. Part III - Discussion Chapter 9 discusses the materials, the methods, and the obtained results of the research. The opportunities, but also constraints and limits, of the developed method are exposed. Future works that can be carried out subsequent to the results of the study are also presented. Chapter 10, the last chapter of this thesis, proposes a strategy to incorporate the model developed in the last chapters into the traditional signature expertise procedures. Thus, the strength of this expertise is discussed in conjunction with the traditional conclusions reached by forensic handwriting examiners in forensic science. Finally, this chapter summarizes and advocates a list of formal recommendations for good practices for handwriting examiners. In conclusion, the research highlights the interdisciplinary aspect of signature examination of signatures on paintings. The current state of knowledge of the judicial quality of art experts, along with the scientific and historical analysis of paintings and signatures, are overviewed to give the reader a feel of the different factors that have an impact on this particular subject. The temperamental acceptance of forensic signature analysis in court, also presented in the state of the art, explicitly demonstrates the necessity of a better recognition of signature expertise by courts of law. This general acceptance, however, can only be achieved by producing high quality results through a well-defined examination process. This research offers an original approach to attribute a painted signature to a certain artist: for the first time, a probabilistic model used to measure the discriminative potential between authentic and simulated painted signatures is studied. The opportunities and limits that lie within this method of scientifically establishing the authorship of signatures on works of art are thus presented. In addition, the second key contribution of this work proposes a procedure to combine the developed method into that used traditionally signature experts in forensic science. Such an implementation into the holistic traditional signature examination casework is a large step providing the forensic, judicial and art communities with a solid-based reasoning framework for the examination of signatures on paintings. The framework and preliminary results associated with this research have been published (Montani, 2009a) and presented at international forensic science conferences (Montani, 2009b; Montani, 2012).

Approximate Bayesian Computation Reveals the Crucial Role of Oceanic Islands for the Assembly of Continental Biodiversity.

The perceived low levels of genetic diversity, poor interspecific competitive and defensive ability, and loss of dispersal capacities of insular lineages have driven the view that oceanic islands are evolutionary dead ends. Focusing on the Atlantic bryophyte flora distributed across the archipelagos of the Azores, Madeira, the Canary Islands, Western Europe, and northwestern Africa, we used an integrative approach with species distribution modeling and population genetic analyses based on approximate Bayesian computation to determine whether this view applies to organisms with inherent high dispersal capacities. Genetic diversity was found to be higher in island than in continental populations, contributing to mounting evidence that, contrary to theoretical expectations, island populations are not necessarily genetically depauperate. Patterns of genetic variation among island and continental populations consistently fitted those simulated under a scenario of de novo foundation of continental populations from insular ancestors better than those expected if islands would represent a sink or a refugium of continental biodiversity. We, suggest that the northeastern Atlantic archipelagos have played a key role as a stepping stone for transoceanic migrants. Our results challenge the traditional notion that oceanic islands are the end of the colonization road and illustrate the significant role of oceanic islands as reservoirs of novel biodiversity for the assembly of continental floras.

Self-reported nonadherence to antiretroviral therapy as a predictor of viral failure and mortality

OBJECTIVE: To determine the effect of nonadherence to antiretroviral therapy (ART) on virologic failure and mortality in naive individuals starting ART. DESIGN: Prospective observational cohort study. METHODS: Eligible individuals enrolled in the Swiss HIV Cohort Study, started ART between 2003 and 2012, and provided adherence data on at least one biannual clinical visit. Adherence was defined as missed doses (none, one, two, or more than two) and percentage adherence (>95, 90-95, and <90) in the previous 4 weeks. Inverse probability weighting of marginal structural models was used to estimate the effect of nonadherence on viral failure (HIV-1 viral load >500 copies/ml) and mortality. RESULTS: Of 3150 individuals followed for a median 4.7 years, 480 (15.2%) experienced viral failure and 104 (3.3%) died, 1155 (36.6%) reported missing one dose, 414 (13.1%) two doses and, 333 (10.6%) more than two doses of ART. The risk of viral failure increased with each missed dose (one dose: hazard ratio [HR] 1.15, 95% confidence interval 0.79-1.67; two doses: 2.15, 1.31-3.53; more than two doses: 5.21, 2.96-9.18). The risk of death increased with more than two missed doses (HR 4.87, 2.21-10.73). Missing one to two doses of ART increased the risk of viral failure in those starting once-daily (HR 1.67, 1.11-2.50) compared with those starting twice-daily regimens (HR 0.99, 0.64-1.54, interaction P = 0.09). Consistent results were found for percentage adherence. CONCLUSION: Self-report of two or more missed doses of ART is associated with an increased risk of both viral failure and death. A simple adherence question helps identify patients at risk for negative clinical outcomes and offers opportunities for intervention.

Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 ± 11.1 vs. 29.5 ± 8.0 μM) (P < 0.001 ART vs. control). Addition of melatonin (10(-6) M) to culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 ± 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans.