A national level assessment of metal contamination in bats

Abstract Many populations of bat species across the globe are declining, with chemical contamination one of many potential stressors implicated in these demographic changes. Metals still contaminate a wide range of habitats, but the risks to bats remain poorly understood. This study is the first to present a national scale assessment of toxic metal (Cd, Pb) and essential trace metal (Cu, Zn) concentrations in bats. Metal concentrations in tissues (kidneys, liver, stomach -stomach content, bones and fur) were measured in 193 Pipistrellus sp. in England and Wales using ICP-MS, and compared to critical toxic concentrations for small mammals. The concentrations of metals determined in bat tissues were generally lower than those reported elsewhere. Strong positive associations were found between concentrations in tissues for a given metal (liver and kidneys for Cd, Cu and Pb; stomach and fur and fur and bones for Pb), suggesting recent as well as long term exposure to these contaminants. In addition, positive correlations between concentrations of different metals in the same tissues (Cd and Zn, Cu and Zn, Cd and Pb, Pb and Zn) suggest a co-exposure of metals to bats. Approximately 21% of the bats sampled contained residues of at least one metal at concentrations high enough to elicit toxic effects (associated with kidney damage), or to be above the upper level measured in other mammal species. Pb was found to pose the greatest risk (with 7–11% of the bats containing concentrations of toxicological concern), followed by Cu (4–9%), Zn (0.5–5.2%) and Cd (0%). Our data suggest that leaching of metals into our storage matrix, formaldehyde, may have occurred, especially for Cu. The overall findings suggest that metal contamination is an environmental stressor affecting bat populations, and that further research is needed into the direct links between metal contamination and bat population declines worldwide

Fur : A non-invasive approach to monitor metal exposure in bats

This paper presents a novel assessment of the use of fur as a non-invasive proxy to biomonitor metal contamination in insectivorous bats. Concentrations of metals (cadmium, copper, lead and zinc) were measured using ICP-MS in tissues (kidneys, liver, stomach and stomach content, bones and fur) obtained from 193 Pipistrellus pipistrellus/pygmaeus bats. The bats were collected across a gradient of metal pollution in England and Wales. The utility of small samples of fur as an indicator of metal exposure from the environment was demonstrated with strong relationships obtained between the concentrations of non-essential metals in fur with concentrations in stomach content, kidneys, liver and bones. Stronger relationships were observed for non-essential metals than for essential metals. Fur analyses might therefore be a useful non-invasive proxy for understanding recent, as well as long term and chronic, metal exposure of live animals. The use of fur may provide valuable information on the level of endogenous metal exposure and contamination of bat populations and communities

Consumption of whole grains in French children, adolescents and adults

The consumption of whole grain foods is associated with many nutritional, health and weight control benefits. The present study assessed whole grain intake in France on the basis of a 7d dietary survey in a representative sample of children, adolescents and adults (Comportements et Consommations Alimentaires en France 2010 survey). Special care was taken to identify and assess the intake of all whole grains. All foods consumed were considered, with no lower limit on whole grain content. For the majority of foods, details regarding the whole grain contents were obtained from brand information and quantitative nutrient declarations on food labels. Over half of the respondents reported never consuming any whole grain. In participants who did, consumption levels were very low (about 9·1g/d in children and 14·4g/d in adults). The main food sources of whole grains were breakfast cereals in children and adolescents and bread in adults. Consumers of whole grains had higher daily intakes of fibre and several vitamins and minerals than non-consumers. In adults but not in children, the OR for overweight/obesity decreased significantly as the level of whole grain consumption increased. Although a majority of French consumers comply with the national recommendation to consume a starchy food with each meal, they do so with minimal consumption of whole grain food

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Les échanges industriels entre la France et les pays d'Europe centrale et orientale : premières tendances de la spécialisation

[ger] Der Industriehandel zwischen Frankreich und den mittel- und osteuropaischen Lândern: erste Spezialisierungstendenzen . Der Austausch zwischen Frankreich und den mittel- und sischen Exporte von Investitionsgùtem und High-Tech- osteuropâischen Lândern hat seit dem Zusammenbruch Erzeugnissen (Elektronikgeràte, Prazisionsinstrumente) des Rats fur Gegenseitige Wirtschaftshilfe (COMECON) gefôrdert. im Jahre 1990 stark zugenommen, wenn auch seine Handelstrôme mit diesen Lândern betragsmâBig noch . recht gering sind. 1993 hatten diese Lander komparative Vorteile bei den Produkten, die einen hohen Arbeitskrafte- einsatz mit geringem Qualifikationsgrad (Textil-, . Bekleidungs-, Môbel- und Schuhindustrie) erforderlich machen, sowie in geringerem Ma3e bei manchen sehr kapitalintensiven Produkten (Basischemie, Eisen- und . Stahlindustrie, Metallverarbeitung). Im Gegenzug haben die notwendigen MaBnahmen zur Modernisierung und Umstrukturierung ihres Produktionsapparates die franzô- . Seit Beginn des Ûbergangsprozesses nâhert sich die Spezialisierung dieser Lander immer mehr derjenigen der westlichen Industrielânder an. Die Exporte diversifizieren sich, und neue Industrien entstehen dank den Technologie- transfers der Industrielânder. So nehmen beispielsweise die Automobilindustrie und die Elektronik bei ihren Ausfuhren einen immer grôBeren Platz ein. Der gekreuzte Handel mit àhnlichen Produkten ist innerhalb von zwei Jahren ebenfalls stark angestiegen. [spa] Los intercambios industriaies entre Francia y los pafses de Europa central y oriental : primeras tendencias de la especializaciôn . Los intercambios entre Francia y los pafses de Europa central y oriental crecieron sobremanera desde el derrumbamiento del Consejo de Ayuda Mutua Econômica (CAME) en 1990, aunque no representen los flujos comerciales con dichos pafses sino sumas menores. En 1993, éstos se benefician de ventajas comparativas para los productos de abundante mano de obra y poco cualificada (industrias textil y del vestido, del mueble y del calzado) y, dentro de lo que cabe, para unos productos de fuerte intensidad capitalfstica (industria qufmica bâsica, siderugia, metalurgia). A la inversa, las necesidades de modernizaciôn y de ajuste de su aparato productivo fueron un incentivo para las exportaciones francesas de . bienes de equipo y de productos de alta tecnologfa (materiales electrônicos, instrumentes de precision). . Desde el inicio de la transiciôn, la especializaciôn de estos pafses se va acercando a la de los pafses industriales occidentales. Las exportaciones se diversifican y emergen nuevas industrias gracias a las transferencias de tecnologfa de los pafses industrializados. Asf, los sectores automovilfstico y electrônico representan una cuota cre- ciente en sus exportaciones. Los intercambios cruzados de productos similares también se intensificaron en el espacio de dos anos. [fre] Les échanges industriels entre la France et les pays d'Europe centrale et orientale : premières tendances de la spécialisation . Les échanges entre la France et les pays d'Europe centrale et orientale se sont fortement développés depuis l'effondrement du Conseil d'assistance économique mutuel (CAEM) en 1 990, même si les flux commerciaux avec ces pays restent encore de faibles montants. En 1 993, ils bénéficient d'avantages comparatifs pour les produits à main-d'œuvre abondante et peu qualifiée (textile-habillement, meubles, chaussure) et, dans une moindre mesure, pour certains produits à forte intensité capitalistique (chimie de base, sidérurgie, travail des métaux). À l'inverse, les besoins de modernisation et de restructuration de leur appareil productif ont stimulé les exportations françaises de biens d'équipement et de produits à haute technologie (matériel électronique, instruments de précision). . Depuis le début de la transition, la spécialisation de ces pays tend à se rapprocher de celle des pays industrialisés occidentaux. Les exportations se diversifient et de nouvelles industries émergent grâce aux transferts de technologie des pays industrialisés. Ainsi, l'automobile et l'électronique occupent une place croissante dans leurs exportations. Les échanges croisés de produits similaires se sont aussi fortement intensifiés en l'espace de deux ans. [eng] Industrial Trade Between France and the Central and East European Countries: Emerging Trends Towards Specialization . Trade between France and the Central and East European countries has grown considerably since the collapse of the Council for Mutual Economic Assistance (COMECON) in 1990, even though the volume of commercial flows with these countries remains low. In 1 993, they benef itted from comparative advantages in . products using abundant and relatively unskilled labour (textiles and clothing, furniture, and shoes) and certain highly capital-intensive products to a lesser extent (basic chemicals, iron and steel, and metal working). Conversely, the need to modernize and restructure their productive capacities has stimulated French exports of capital goods and high-tech products (electronic equipment and precision instruments). Since the beginning of the transition, these countries have tended to specialize in the same way as the Western industrialized countries. Exports are diversifying and new industries emerging as a result of technology transfers from industrialized countries. Motor vehicles and electronics are therefore accounting for a growing share of their exports. The two-way trade of similar products has also risen substantially in the space of two years.

High Throughput Methods to Transfer DNA in Cells and Perspectives

Genome sequencing led to thousands of genes to study and their molecular cloning to provide ORF collection plasmids. The main approach to study their function involves analysis of the biological consequences of their expression or knockdown, in a cellular context. Given that, the starting point of such experiments is the delivery of the exogenous material, including plasmid DNA in cells. During the last decades, efforts were made to develop efficient methods and protocols to achieve this goal. The present chapter will first give a rapid overview of the main DNA transfer methods described so far: physical, chemical, and biological. Secondly, it will focus on the different methods having reached high-throughput nowadays. Finally, it will discuss the perspectives of this field in terms of future enhancements

Structure du capital et coûts d'information : le cas des entreprises françaises à la fin des années quatre-vingt

[spa] Estructura del capital y costes de informaciôn : el caso de las empresas francesas a finales de los ochenta . La estructura de financiaciôn de una empresa es el resultado de un arbitraje entre los costes de los diferentes recursos : autofinanciaciôn, deudas o emisiones de acciones. Estes costes son determinados, en su mayor parte, por las asimetrfas de informaciôn y los conflictos de interés entre los agentes que participan a la movilizaciôn de fondos y a la elecciôn de las inversiones (accionistas, dirigentes, bancos y otros acreedores). De esta manera, en el movimiento de desendeudamiento que se manifeste a finales de los ochenta, destacan el efecto de unas reformas institucionales que apuntaban a reducir el coste de acceso a los fondos propios, y el peso de las exigencias en cuanto a informaciôn (abertura del segundo mercado, desarrollo del capital-riesgo...). . El estudio empi'rico de un panel de empresas a finales de los ochenta confirma la pertinencia, en el caso francés, de una red de anâlisis basada en las teorfas de la agencia : los impedimentos al acceso a los recursos, interpretados como impedimentos de carâcter informacional, desem- penan sin duda un papel importante para explicar el endeudamiento mayor de las firmas jôvenes, pequenas o no cotizadas. La presencia de unas entidades financières en el capital de una empresa mejora, por otra parte, la informaciôn de la disponen la totalidad de los acreedores, y les incita a invertir mâs todavfa sus recursos en la empresa. En fin, la capacidad de la firma en combinar sus deudas con garantîas le permite movilizar con mayor facilidad recursos a largo plazo. [ger] Kapitalstruktur und Informationskosten: Unternehmen Ende der achtziger Jahre . Die Finanzierungsstruktur eines Unternehmens ist das Ergebnis einer Arbitration zwischen den Kosten der verschiedenen Ressourcen: Eigenfinanzierung, Verschuldung Oder Ausgabe von Aktien. Diese Kosten sind zum groBen Teil durch die Informationsasymmetrien und die Interessenkonflikte zwischen den Akteuren bestimmt, die sich an der Kapitalmobilisierung und an der Investitionswahl beteiligen (Aktionâre, Unternehmer, Banken und sonstige Glâubiger). Somit kann man die Ende der achtziger Jahre beobachtete Entschuldungs- bewegung als Effekt der institutionellen Reformen betrachten, mit denen einerseits die Kosten fur den Zugang zu den Eigenmitteln und andererseits die Informationserfordernisse (Ôffnung des Sekundâr- marktes, Entwicklung des Risikokapitals) gesenkt werden sollten. . die Situation der franzôsischen . Die empirische Untersuchung, die Ende der achtziger Jahre anhand eines Untemehmenspanels durchgefùhrt wurde, bestâtigt im Falle Frankreichs die Relevanz eines Analyserasters, das auf den Agentur-Theorien beruht: die Zwànge beim Zugang zu den Ressourcen, die als Informationszwànge verstanden werden, spielen zweifelsohne eine wichtige Rolle bei der Erklarung der Grûnde, weshalb die jungen, kleinen oder nicht an der Bôrse notierten Untemehmen eine hôhere Verschuldung aufweisen. Die Beteiligung von Finanzinstituten am Kapital eines Unternehmens trâgt im ùbrigen zu einer besseren Information aller Glâubiger bei und stellt fur sie einen Anreiz dar, ihre Ressourcen verstârkt in das Unternehmen zu investieren. Der Zugang zu den lang- fristigen Ressourcen wird auBerdem erleichtert, wenn ein Unternehmen fur seine Schulden Garantien bieten kann. [eng] The Structure of Capital and Agency Costs: French Companies in the Late 1980s . A company's financing structure results from a choice between the costs of the different resources: self-financing, debt or share issues. These costs are largely determined by information asymmetries and clashes of interest between the parties involved in mobilizing the funds and those who decide on the investments (shareholders, managers, banks and other debt holders). The debt reduction trend observed in the late 1980s therefore shows the effect of institutional reforms to reduce the cost of access to equity capital and the importance of information requirements (launching of the unlisted securities market in France, development of risk capital, etc.). . An empirical study of a sample group of companies at the end of the 1980s confirms the pertinence for France of an analytic grid based on agency theories: constraints on access to resources, which are interpreted as informational constraints, unquestionably play a significant role in explaining the higher indebtedness of small, young, unlisted firms. The presence of financial institutions in a company's capital moreover improves the information available to all the creditors and encourages them to invest more of their resources in the company. Lastly, the firm's ability to mix secured liabilities means that it can mobilize long-term resources more easily. [fre] Structure du capital et coûts d'information : le cas des entreprises françaises à la fin des années quatre-vingt . La structure de financement d'une entreprise résulte d'un arbitrage entre les coûts des différentes ressources : autofinancement, dettes ou émission d'actions. Ces coûts sont, pour une large part, déterminés par les asymétries d'information et les conflits d'intérêt entre les acteurs qui participent à la mobilisation des fonds et au choix des investissements (actionnaires, dirigeants, banques et autres créanciers). Ainsi, on peut voir, dans le mouvement de désendettement observé à la fin des années quatre-vingt, l'effet de réformes institutionnelles visant à réduire le coût d'accès aux fonds propres et le poids des exigences en termes d'information (ouverture du second marché, développement du capital-risque, etc.). . L'étude empirique d'un panel d'entreprises à la fin des années quatre-vingt confirme la pertinence, dans le cas de la France, d'une grille d'analyse fondée sur les théories de l'agence : les contraintes d'accès aux ressources, interprétées comme des contraintes informationnelles, jouent assurément un rôle important pour expliquer l'endettement plus élevé des firmes jeunes, petites ou non cotées. La présence d'institutions financières dans le capital d'une entreprise améliore, par ailleurs, l'information dont disposent l'ensemble des créanciers et les incite à placer davantage leurs ressources dans l'entreprise. Enfin, la capacité de la firme à assortir les dettes de garanties lui permet de mobiliser plus facilement des ressources longues.