Genetic variations in drug-induced liver injury (DILI): resolving the puzzle.

Despite stringent requirements for drug development imposed by regulatory agencies, drug-induced liver injury (DILI) is an increasing health problem and a significant cause for failure to approve drugs, market withdrawal of commercialized medications, and adoption of regulatory measures. The pathogenesis is yet undefined, though the rare occurrence of idiosyncratic DILI (1/100,000–1/10,000) and the fact that hepatotoxicity often recurs after re-exposure to the culprit drug under different environmental conditions strongly points toward a major role for genetic variations in the underlying mechanism and susceptibility. Pharmacogenetic studies in DILI have to a large extent focused on genes involved in drug metabolism, as polymorphisms in these genes may generate increased plasma drug concentrations as well as lower clearance rates when treated with standard medication doses. A range of studies have identified a number of genetic variants in drug metabolism Phase I, II, and III genes, including cytochrome P450 (CYP) 2E1, N-acetyltransferase 2, UDP-glucuronosyltransferase 2B7, glutathione S-transferase M1/T1, ABCB11, and ABCC2, that enhance DILI susceptibility (Andrade et al., 2009; Agundez et al., 2011). Several metabolic gene variants, such as CYP2E1c1 and NAT2 slow, have been associated with DILI induced by specific drugs based on individual drug metabolism information. Others, such as GSTM1 and T1 null alleles have been associated with enhanced risk of DILI development induced by a large range of drugs. Hence, these variants appear to have a more general role in DILI susceptibility due to their role in reducing the cell's antioxidative capacity (Lucena et al., 2008). Mitochondrial superoxide dismutase (SOD2) and glutathione peroxidase 1 (GPX1) are two additional enzymes involved in combating oxidative stress, with specific genetic variants shown to enhance the risk of developing DILI

Forecasting changes in population genetic structure of alpine plants in response to global warming.

Species range shifts in response to climate and land use change are commonly forecasted with species distribution models based on species occurrence or abundance data. Although appealing, these models ignore the genetic structure of species, and the fact that different populations might respond in different ways because of adaptation to their environment. Here, we introduced ancestry distribution models, that is, statistical models of the spatial distribution of ancestry proportions, for forecasting intra-specific changes based on genetic admixture instead of species occurrence data. Using multi-locus genotypes and extensive geographic coverage of distribution data across the European Alps, we applied this approach to 20 alpine plant species considering a global increase in temperature from 0.25 to 4 °C. We forecasted the magnitudes of displacement of contact zones between plant populations potentially adapted to warmer environments and other populations. While a global trend of movement in a north-east direction was predicted, the magnitude of displacement was species-specific. For a temperature increase of 2 °C, contact zones were predicted to move by 92 km on average (minimum of 5 km, maximum of 212 km) and by 188 km for an increase of 4 °C (minimum of 11 km, maximum of 393 km). Intra-specific turnover-measuring the extent of change in global population genetic structure-was generally found to be moderate for 2 °C of temperature warming. For 4 °C of warming, however, the models indicated substantial intra-specific turnover for ten species. These results illustrate that, in spite of unavoidable simplifications, ancestry distribution models open new perspectives to forecast population genetic changes within species and complement more traditional distribution-based approaches.

The European Union Perception of Cuba: From Frustation to Irritation

On Friday May 16, the Ministry of Foreign Affairs of Cuba summoned the newly-appointed charged’affairs of the European Commission in Havana and announced the withdrawal of the application procedure for membership in the Cotonou Agreement of the Africa, Caribbean, and Pacific (ACP) countries, and in fact renouncing to benefit from European development aid.1 In a blistering note published in the Granma official newspaper of the Cuban Communist Party, the government blamed the EU Commission for exerting undue pressure, its alleged alignment with the policies of the United States, and censure for the measures taken by Cuba during the previous weeks.2 In reality, Cuba avoided an embarrasin flat rejection for its application. This was the anti-climatic ending for a long process that can be traced back to the end of the Cold War, in a context where Cuba has been testing alternative grounds to substitute for the overwhelming protection of the Soviet Union

Towards a system analysis of the early steps of infectious endocarditis pathogenesis

L'endocardite infectieuse (EI) est une maladie potentiellement mortelle qui doit être prévenue dans toute la mesure du possible. Au cours de ces dernières 50 années, les recommandations Américaines et Européennes pour la prophylaxie de PEI proposaient aux patients à risques de prendre un antibiotique, préventif avant de subir une intervention médico-chirurgicale susceptible d'induire une bactériémie transitoire. Cependant, des études épidémiologiques récentes ont montré que la plupart des EI survenaient en dehors de tous actes médico-chirurgicaux, et indépendamment de la prise ou non de prophylaxie antibiotique . L'EI pourrait donc survenir suite à la cumulation de bactériémies spontanées de faibles intensités, associées à des activités de la vie courante telle que le brossage dentaire pour le streptocoques, ou à partir de tissus colonisés ou de cathéters infectés pour les staphylocoques. En conséquence, les recommandations internationales pour la prophylaxie de PEI ont été revues et proposent une diminution drastique de l'utilisation d'antibiotiques. Cependant, le risque d'EI représenté par le cumul de bactériémies de faibles intensités n'a pas été démontré expérimentalement. Nous avons développé un nouveau modèle d'EI expérimentale induite par une inoculation en continu d'une faible quantité de bactéries, simulant le cumul de bactériémies de faibles intensités chez l'homme, et comparé l'infection de Streptococcus gordonii et de Staphylococcus aureus dans ce modèle avec celle du modèle d'IE induite par une bactériémie brève, mais de forte intensité. Nous avons démontré, après injection d'une quantité égale de bactéries, que le nombre de végétations infectées était similaire dans les deux types d'inoculations. Ces résultats expérimentaux ont confirmé l'hypothèse qu'une exposition cumulée à des bactériémies de faibles intensités, en dehors d'une procédure médico-chirurgicale, représentait un risque pour le développement d'une El, comme le suggéraient les études épidémiologiques. En plus, ces résultats ont validé les nouvelles recommandations pour la prophylaxie de l'El, limitant drastiquement l'utilisation d'antibiotiques. Cependant, ces nouvelles recommandations laissent une grande partie (> 90%) de cas potentiels d'EI sans alternatives de préventions, et des nouvelles stratégies prophylactiques doivent être investiguées. Le nouveau modèle d'EI expérimentale représente un modèle réaliste pour étudier des nouvelles mesures prophylactiques potentielles appliquées à des expositions cumulées de bactériémies de faible nombre. Dans un contexte de bactériémies spontanées répétitives, les antibiotiques ne peuvent pas résoudre le problème de la prévention de l'EI. Nous avons donc étudié la une alternative de prévention par l'utilisation d'agents antiplaquettaires. La logique derrière cette approche était basée sur le fait que les plaquettes sont des composants clés dans la formation des végétations cardiaques, et le fait que les bactéries capables d'interagir avec les plaquettes sont plus enclines à induire une El. Les agents antiplaquettaires utilisés ont été l'aspirine (inhibiteur du COX1), la ticlopidine (inhibiteur du P2Y12, le récepteur de l'ADP), et l'eptifibatide et Pabciximab, deux inhibiteurs du GPIIb/IIIa, le récepteur plaquettaire pour le fibrinogène. Les anticoagulants étaient le dabigatran etexilate, inhibant lathrombine et l'acenocumarol, un antagoniste de la vitamine K. L'aspirine, la ticlopidine ou l'eptifibatide seuls n'ont pas permis de prévenir l'infection valvulaire (> 75% animaux infectés). En revanche, la combinaison d'aspirine et de ticlopidine, aussi bien que l'abciximab, ont protégé 45% - 88% des animaux de l'EI par S. gordonii et par S. aureus. L'antithrombotique dabigatran etexilate à protégé 75% des rats contre l'EI par S. aureus, mais pas (< 30% de protection) par S. gordonii. L'acenocoumarol n'a pas eu d'effet sur aucun des deux organismes. En général, ces résultats suggèrent un possible rôle pour les antiplaquettaires et du dabigatran etexilate dans la prophylaxie de l'EI dans un contexte de bactériémies récurrentes de faibles intensités. Cependant, l'effet bénéfique des antiplaquettaires doit être soupesé avec le risque d'hémorragie inhérent à ces molécules, et le fait que les plaquettes jouent un important rôle dans les défenses de l'hôte contre les infections endovasculaires. En plus, le double effet bénéfique du dabigatran etexilate devrait être revu chez les patients porteurs de valves prothétiques, qui ont besoin d'une anticoagulation à vie, et chez lesquels l'EI à S. aureus est associée avec une mortalité de près de 50%. Comme l'approche avec des antiplaquettaires et des antithrombotiques pourrait avoir des limites, une autre stratégie prophylactique pourrait être la vaccination contre des adhésines de surfaces des pathogènes. Chez S. aureus, la protéine de liaison au fibrinogène, ou dumping factor A (ClfA), et la protéine de liaison à la fibronectine (FnbpA) sont des facteurs de virulence nécessaires à l'initiation et l'évolution de PEI. Elles représentent donc des cibles potentielles pour le développement de vaccins contre cette infection. Récemment, des nombreuses publications ont décrit que la bactérie Lactococcus lactis pouvait être utilisée comme vecteur pour la diffusion d'antigènes bactériens in vivo, et que cette approche pourrait être une stratégie de vaccination contre les infections bactériennes. Nous avons exploré l'effet de l'immunisation par des recombinant de L. lactis exprimant le ClfA, la FnbpA, ou le ClfA ensemble avec et une forme tronquée de la FnbpA (Fnbp, comprenant seulement le domaine de liaison à la fibronectine mais sans le domaine A de liaison au fibrinogène [L. lactis ClfA/Fnbp]), dans la prophylaxie de PIE expérimentale à S. aureus. L. lactis ClfA a été utilisés comme agent d'immunisation contre la souche S. aureus Newman (qui a particularité de n'exprimer que le ClfA, mais pas la FnbpA). L. lactis ClfA, L. lactis FnbpA, et L. lactis ClfA/Fnbp, ont été utilisé comme agents d'immunisation contre une souche isolée d'une IE, S. aureus P8 (exprimant ClfA et FnbpA). L'immunisation avec L. lactis ClfA a généré des anticorps anti-ClfA fonctionnels, capables de bloquer la liaison de S. aureus Newman au fibrinogène in vitro et protéger 13/19 (69%) animaux d'une El due à S. aureus Newman (P < 0.05 comparée aux contrôles). L'immunisation avec L. lactis ClfA, L. lactis FnbpA, ou L. lactis ClfA/Fnbp, a généré des anticorps contre chacun de ces antigènes. Cependant, ils n'ont pas permis de bloquer l'adhésion de S. aureus P8 au fibrinogène et à la fibronectine in vitro. De plus, l'immunisation avec L. lactis ClfA ou L. lactis FnbpA s'est avérée inefficace in vivo (< 10% d'animaux protégés d'une El) et l'immunisation avec L. lactis ClfA/Fnbp a fourni une protection limitée de l'EI (8/23 animaux protégés; P < 0.05 comparée aux contrôles) après inoculation avec S. aureus P8. Dans l'ensemble, ces résultats indiquent que L. lactis est un système efficace pour la présentation d'antigènes in vivo et potentiellement utile pour la prévention de PEI à S. aureus. Cependant, le répertoire de protéines de surface de S. aureus capable d'évoquer une panoplie d'anticorps efficace reste à déterminer.. En résumé, notre étude a démontré expérimentalement, pour la première fois, qu'une bactériémie répétée de faible intensité, simulant la bactériémie ayant lieu, par exemple, lors des activités de la vie quotidienne, est induire un taux d'EI expérimentale similaire à celle induite par une bactériémie de haute intensité suite à une intervention médicale. Dans ce contexte, où l'utilisation d'antibiotiques est pas raisonnable, nous avons aussi montré que d'autres mesures prophylactiques, comme l'utilisation d'agents antiplaquettaires ou antithrombotiques, ou la vaccination utilisant L. lactis comme vecteur d'antigènes bactériens, sont des alternatives prometteuses qui méritent d'être étudiées plus avant. Thesis Summary Infective endocarditis (IE) is a life-threatening disease that should be prevented whenever possible. Over the last 50 years, guidelines for IE prophylaxis proposed the use of antibiotics in patients undergoing dental or medico-surgical procedures that might induce high, but transient bacteremia. However, recent epidemiological studies indicate that IE occurs independently of medico-surgical procedures and the fact that patients had taken antibiotic prophylaxis or not, i.e., by cumulative exposure to random low-grade bacteremia, associated with daily activities (e.g. tooth brushing) in the case of oral streptococci, or with a colonized site or infected device in the case of staphylococci. Accordingly, the most recent American and European guidelines for IE prophylaxis were revisited and updated to drastically restrain antibiotic use. Nevertheless, the relative risk of IE represented by such cumulative low-grade bacteremia had never been demonstrated experimentally. We developed a new model of experimental IE due to continuous inoculation of low-grade bacteremia, mimicking repeated low-grade bacteremia in humans, and compared the infectivity of Streptococcus gordonii and Staphylococcus aureus in this model to that in the model producing brief, high-level bacteremia. We demonstrated that, after injection of identical bacterial numbers, the rate of infected vegetations was similar in both types of challenge. These experimental results support the hypothesis that cumulative exposure to low-grade bacteremia, outside the context of procedure-related bacteremia, represents a genuine risk of IE, as suggested by human epidemiological studies. In addition, they validate the newer guidelines for IE prophylaxis, which drastic limit the procedures in which antibiotic prophylaxis is indicated. Nevertheless, these refreshed guidelines leave the vast majority (> 90%) of potential IE cases without alternative propositions of prevention, and novel strategies must be considered to propose effective alternative and "global" measures to prevent IE initiation. The more realistic experimental model of IE induced by low-grade bacteremia provides an accurate experimental setting to study new preventive measures applying to cumulative exposure to low bacterial numbers. Since in a context of spontaneous low-grade bacteremia antibiotics are unlikely to solve the problem of IE prevention, we addressed the role of antiplatelet and anticoagulant agents for the prophylaxis of experimental IE induced by S. gordonii and S. aureus. The logic of this approach was based on the fact that platelets are key players in vegetation formation and vegetation enlargement, and on the fact that bacteria capable of interacting with platelets are more prone to induce IE. Antiplatelet agents included the COX1 inhibitor aspirin, the inhibitor of the ADP receptor P2Y12 ticlopidine, and two inhibitors of the platelet fibrinogen receptor GPIIb/IIIa, eptifibatide and abciximab. Anticoagulants included the thrombin inhibitor dabigatran etexilate and the vitamin K antagonist acenocoumarol. Aspirin, ticlopidine or eptifibatide alone failed to prevent aortic infection (> 75% infected animals). In contrast, the combination of aspirin with ticlopidine, as well as abciximab, protected 45% to 88% of animals against IE due to S. gordonii and S. aureus. The antithrombin dabigatran etexilate protected 75% of rats against IE due to S. aureus, but failed (< 30% protection) against S. gordonii. Acenocoumarol had no effect against any bacteria. Overall, these results suggest a possible role for antiplatelet agents and dabigatran etexilate in the prophylaxis of IE in humans in a context of recurrent low- grade bacteremia. However, the potential beneficial effect of antiplatelet agents should be balanced against the risk of bleeding and the fact that platelets play an important role in the host defenses against intravascular infections. In addition, the potential dual benefit of dabigatran etexilate might be revisited in patients with prosthetic valves, who require life-long anticoagulation and in whom S. aureus IE is associated with high mortality rate. Because the antiplatelet and anticoagulant approach might be limited in the context of S. aureus bacteremia, other prophylactic strategies for the prevention of S. aureus IE, like vaccination with anti-adhesion proteins was tested. The S. aureus surface proteins fibrinogen-binding protein clumping-factor A (ClfA) and the fibronectin-binding protein A (FnbpA) are critical virulence factors for the initiation and development of IE. Thus, they represent key targets for vaccine development against this disease. Recently, numerous reports have described that the harmless bacteria Lactococcus lactis can be used as a bacterial vector for the efficient delivery of antigens in vivo, and that this approach is a promising vaccination strategy against bacterial infections. We therefore explored the immunization capacity of non- living recombinant L. lactis ClfA, L. lactis FnbpA, or L. lactis expressing ClfA together with Fnbp (a truncated form of FnbpA with only the fibronectin-binding domain but lacking the fibrinogen-binding domain A [L. lactis ClfA/Fnbp]), to protect against S. aureus experimental IE. L. lactis ClfA was used as immunization agent against the laboratory strain S. aureus Newman (expressing ClfA, but lacking FnbpA). L. lactis ClfA, L. lactis FnbpA, as well as L. lactis ClfA/Fnbp, were used as immunization agents against the endocarditis isolate S. aureus P8 (expressing both ClfA and FnbpA). Immunization with L. lactis ClfA produced anti-ClfA functional antibodies, which were able to block the binding of S. aureus Newman to fibrinogen in vitro and protect 13/19 (69%) animals from IE due to S. aureus Newman (P < 0.05 compared to controls). Immunization with L. lactis ClfA, L. lactis FnbpA or L. lactis ClfA/Fnbp, produced antibodies against each antigen. However, they were not sufficient to block S. aureus P8 binding to fibrinogen and fibronectin in vitro. Moreover, immunization with L. lactis ClfA or L. lactis FnbpA was ineffective (< 10% protected animals) and immunization with L. lactis ClfA/Fnbp conferred limited protection from IE (8/23 protected animals; P < 0.05 compared to controls) after challenge with S. aureus P8. Together, these results indicate that L. lactis is an efficient delivering antigen system potentially useful for preventing S. aureus IE. They also demonstrate that expressing multiple antigens in L. lactis, yet to be elucidated, will be necessary to prevent IE due to clinical S. aureus strains fully equipped with virulence determinants. In summary, our study has demonstrated experimentally, for the first time, the hypothesis that low-grade bacteremia, mimicking bacteremia occurring outside of a clinical intervention, is equally prone to induce experimental IE as high-grade bacteremia following medico-surgical procedures. In this context, where the use of antibiotics for the prophylaxis of IE is limited, we showed that other prophylactic measures, like the use of antiplatelets, anticoagulants, or vaccination employing L. lactis as delivery vector of bacterial antigens, are reasonable alternatives that warrant to be further investigated.

Iniciativa emprenedora i immigració: característiques diferenciadores i factors d'èxit

 L’emprenedoria és una de les àrees de recerca que han tingut un major creixement en les dècades recents. En aquest camp, l’anàlisi del comportament dels emprenedors immigrants ha estat reconeguda com un dels temes amb un important increment d’estudis relacionats. En aquests moments, el fenomen de la immigració és un dels processos socials més importants i amb una major repercussió en el continent europeu, i el fet que hi hagi més iniciatives emprenedores liderades per immigrants que per nadius fa que l’anàlisi i l’exploració d’aquest tema tinguin un atractiu especial. Malgrat tot, i encara que en els darrers anys el nombre d’estudis que pretenen donar una explicació a aquest fenomen ha incrementat, la majoria dels estudis l’han analitzat des d’un punt de vista qualitatiu i centrant-se en situacions regionals específiques i grups concrets, sense que se n’hagin pogut extreure conclusions generals sobre el comportament emprenedor immigrant. De manera que uns dels aspectes clau que un estudi en profunditat requereix són ressaltar aquells factors que contribueixen a distingir el comportament emprenedor immigrant del nadiu, així com aquells factors que podrien motivar l’èxit o el fracàs d’aquest tipus d’iniciatives i com aquests factors condicionarien la resta del teixit empresarial. En aquest context, el principal objectiu d’aquest projecte consisteix en l’anàlisi de les característiques distintives del procés emprenedor dels immigrants. Es pretén abordar aquest objectiu desenvolupant diferents metodologies i combinant diferents fonts d’informació que permetin captar la situació i assolir una comprensió més rica del fenomen estudiat. Els principals resultats obtinguts ens han portat a entendre aspectes que afavoreixen l’emprenedoria immigrant, tals com una menor aversió al risc i un major control percebut. A més, s’han posat de manifest algunes barreres legals amb les que s’han d’enfrontar els emprenedors immigrants a Catalunya.

Competències i factors clau per a l’èxit educatiu des de la perspectiva dels estudiants universitaris fills/es dels immigrants

L’estudi realitzat ha abordat quines són les competències i els factors clau que estudiants universitaris d’origen immigrant consideren que han estat claus per arribar a la universitat, assolint així l’èxit educatiu. S’han escollit estudiants que haguessin fet l’escolaritat obligatòria total o parcialment a Catalunya.Per dur a terme la recerca s’ha treballat amb relats de vida (un total de 13 escrits) i narracions audiovisuals (amb un total de 4 produccions), essent finalment 17 les evidències vàlides. Finalment, s’ha elaborat, administrat i processat un qüestionari d’opinió que s’ha remès a 2472 estudiants de la Universitat de Barcelona, dels quals hem aconseguit 128 respostes considerades vàlides. Els relats s’han analitzat amb un procediment inductiu, procedint a una lectura exhaustiva de les paraules dels participants i anant identificant quines són les competències i els factors clau que ells consideraven que els havien ajudat a arribar a la universitat o que, tot i no ser ells conscients, nosaltres identificàvem com a tals. Pel que fa a les narracions audiovisuals, es va dur a terme una anàlisi tant del contingut, tenint com a referència els resultats obtinguts als relats escrits, com d’aspectes més tècnics, centrats en la imatge i el so. Per acabar, els qüestionaris s’han analitzat a partir de processos bàsics d’estadística descriptiva. Pel que fa als resultats obtinguts, respecte a l’eix de competències, la més destacada és la d’autonomia i iniciativa personals, lligada a la responsabilitat i autoexigència. Respecte a l’eix d’èxit educatiu, destaca el paper del professorat, tant pel suport que els ofereixen com per les expectatives que dipositen en ells. I, per acabar, respecte a l’eix d’inclusió social, els aspectes que l’afavoreixen es centren sobretot en el recolzament de la família, en l’entorn més immediat i en el fet d’entendre la possibilitat de viure amb altres cultures com un enriquiment.

Maternal mortality from hemorrhage in the State of Santa Catarina, Brazil

Hemorrhage represents a set of causes that focuses on women during the pregnancy and puerperal period, and that, with improper attention, results in death. The authors aimed to analyze maternal deaths related to hemorrhage that occurred in the state of Santa Catarina, Brazil. The data were obtained from the Mortality Information System and Live Births Information System from the Brazilian Ministry of Health. This was a descriptive study, in which 491 maternal deaths that occurred in the period 1997-2010 were analyzed. Of these, 61 were related to hemorrhage, corresponding to 12.42%; postpartum hemorrhage was the most prevalent cause, with 26 deaths, followed by placental abruption with 15, representing 67.21% of the cases. The maternal mortality from hemorrhage is a public health problem in the state of Santa Catarina, due to its high prevalence and the fact that its underlying causes are preventable.

Contributo das TIC na integração de famílias oriundas do Brasil no concelho de Albufeira

Os fenómenos migratórios tem-se acentuado nas últimas décadas, para este facto muito tem contribuído a era globalizada em que nos encontramos. Com a globalização surgiu o desenvolvimento de redes mundiais, nomeadamente sistemas sociais e económicos, facultando o acesso a meios de transporte mais rápidos e baratos, e as comunicações tornaram-se mais fáceis, promovendo e facilitando as deslocações entre países e continentes, de pessoas e bens. Assim, actualmente com o acesso facilitado nas comunicações e nas deslocações, a migração tornou-se uma constante. Perante a quantidade de indivíduos oriundos das mais diversas partes do globo e com a evolução das tecnologias de informação e comunicação, as barreiras culturais foram reduzidas, permitindo uma rápida difusão de ideias e de meios, possibilitando que indivíduos que se encontram em locais geograficamente longínquos possam comunicar com regularidade. Este estudo teve como objectivo conhecer, por um lado, o impacto da utilização das TIC, por parte dos imigrantes de origem brasileira, como forma de manterem o contacto com o país de origem, por outro, o facto de residirem familiares/amigos em Portugal, aquando da sua vinda, podem contribuir para a sua integração. O estudo foi aplicado no Gabinete da família e no Gabinete do Imigrante, da Divisão de Acção Social Saúde e Juventude, da Câmara Municipal de Albufeira. Teve uma amostragem por conveniência que abrangeu 50 indivíduos oriundos do Brasil, residentes em Albufeira. Foi aplicado um inquérito por questionário que permitiu a caracterização da amostra e recolher informações sobre o impacto da utilização das TIC como forma de manter o contacto com o país de origem e a importância das redes sociais no processo de integração. Constituído por 74 questões fechadas, abertas e semi abertas. Fez-se de seguida uma análise quantitativa e qualitativa dos dados recolhidos. Os resultados obtidos sobre esta problemática permitiram percepcionar que o facto de existir uma rede familiar e de amigos, contribui para a integração da família imigrante na sociedade de acolhimento. Ou seja, todo o suporte familiar e a rede de amigos existente facultam ao imigrante condições para que o mesmo se instale no país de acolhimento e se sinta integrado. O facto de os imigrantes comunicarem, por norma, semanalmente com a família no Brasil, bem como utilizarem as tecnologias de informação e comunicação, contribui em muito para o seu bem estar psicológico e emocional. O contacto regular com a família, ainda que através de uma Web cam, proporciona-lhes tranquilidade e minimiza a distância física, uma vez que os podem ver e ouvir sentindo assim o apoio dos mesmos, ajudando-os a permanecer no nosso país. O uso das novas tecnologias são utilizadas para manter a ligação com a comunidade de origem, fomentando os laços familiares e com amigos. Os imigrantes utilizam a internet para comunicar com os indivíduos da mesma nacionalidade, bem como a família/amigos que se encontram no Brasil. O acesso às TIC e o facto de as utilizarem para comunicar com a família e amigos, no país de origem, pode ser considerada como uma rede social de apoio, proporcionando assim aos imigrantes uma integração no país de acolhimento.

Sistemes logístics de codificació i identificació, i perspectives de futur

Comptar amb sistemes sofisticats de gestió o programes ERP (Enterprise Resource Planning) no és suficient per a les organitzacions. Per a què aquests recursos donin resultats adequats i actualitzats, la informació d’entrada ha de llegir-se de forma automàtica, per aconseguir estalviar en recursos, eliminació d’errors i assegurar el compliment de la qualitat. Per aquest motiu és important comptar amb eines i serveis d’identificació automàtica i col•lecció de dades. Els principals objectius a assolir (a partir de la introducció al lector de la importància dels sistemes logístics d’identificació en un entorn global d’alta competitivitat), són conèixer i comprendre el funcionament de les tres principals tecnologies existents al mercat (codis de barres lineals, codis de barres bidimensionals i sistemes RFID), veure en quin estat d’implantació es troba cadascuna i les seves principals aplicacions. Un cop realitzat aquest primer estudi es pretén comparar les tres tecnologies per o poder obtenir perspectives de futur en l’àmbit de l’autoidentificació. A partir de la situació actual i de les necessitats de les empreses, juntament amb el meravellós món que sembla obrir la tecnologia RFID (Radio Frequency Identification), la principal conclusió a la que s’arribarà és que malgrat les limitacions tècniques dels codis de barres lineals, aquests es troben completament integrats a tota la cadena logística gràcies a l’estandarització i la utilització d’un llenguatge comú, sota el nom de simbologies GTIN (Global Trade Item Number), durant tota la cadena de subministres que garanteixen total traçabilitat dels productes gràcies en part a la gestió de les bases de dades i del flux d’informació. La tecnologia RFUD amb l’EPC (Electronic Product Code) supera aquestes limitacions, convertint-se en el màxim candidat per a substituir els limitats codis de barres. Tot i això, RFID, amb l’EPC, no serà un adequat identificador logístic fins que es superin importants barreres, com són la falta d’estandarització i l’elevat cost d’implantació.

Evidence on the complex link between

Most studies analysing the infrastructure impact on regional growth show a positive relationship between both variables. However, the public capital elasticity estimated in a Cobb-Douglas function, which is the most common specification in these works, is sometimes too big to be credible, so that the results have been partially desestimated. In the present paper, we give some new advances on the real link between public capital and productivity for the Spanish regions in the period 1964-1991. Firstly, we find out that the association for both variables is smaller when controlling for regional effects, being industry the sector which reaps the most benefits from an increase in the infrastructural dotation. Secondly, concerning to the rigidity of the Cobb-Douglas function, it is surpassed by using the variable expansion method. The expanded functional form reveals both the absence of a direct effect of infrastructure and the fact that the link between infrastructure and growth depends on the level of the existing stock (threshold level) and the way infrastructure is articulated in its location relative to other factors. Finally, we analyse the importance of the spatial dimension in infrastructure impact, due to spillover effects. In this sense, the paper provides evidence of the existence of spatial autocorrelation processes that may invalidate previous results.

Evidence on the complex link between

Most studies analysing the infrastructure impact on regional growth show a positive relationship between both variables. However, the public capital elasticity estimated in a Cobb-Douglas function, which is the most common specification in these works, is sometimes too big to be credible, so that the results have been partially desestimated. In the present paper, we give some new advances on the real link between public capital and productivity for the Spanish regions in the period 1964-1991. Firstly, we find out that the association for both variables is smaller when controlling for regional effects, being industry the sector which reaps the most benefits from an increase in the infrastructural dotation. Secondly, concerning to the rigidity of the Cobb-Douglas function, it is surpassed by using the variable expansion method. The expanded functional form reveals both the absence of a direct effect of infrastructure and the fact that the link between infrastructure and growth depends on the level of the existing stock (threshold level) and the way infrastructure is articulated in its location relative to other factors. Finally, we analyse the importance of the spatial dimension in infrastructure impact, due to spillover effects. In this sense, the paper provides evidence of the existence of spatial autocorrelation processes that may invalidate previous results.

An improved method for measuring soil microbial activity by gas phase flow injection analysis

The rate of carbon dioxide production is commonly used as a measure of microbial activity in the soil. The traditional method of CO2 determination involves trapping CO2 in an alkali solution and then determining CO2 concentration indirectly by titration of the remaining alkali in the solution. This method is still commonly employed in laboratories throughout the world due to its relative simplicity and the fact that it does not require expensive, specific equipment. However, there are several drawbacks: the method is time-consuming, requires large amounts of chemicals and the consistency of results depends on the operator's skills. With this in mind, an improved method was developed to analyze CO2 captured in alkali traps, which is cheap and relatively simple, with a substantially shorter sample handling time and reproducibility equivalent to the traditional titration method. A comparison of the concentration values determined by gas phase flow injection analysis (GPFIA) and titration showed no significant difference (p > 0.05), but GPFIA has the advantage that only a tenth of the sample volume of the titration method is required. The GPFIA system does not require the purchase of new, costly equipment but the device was constructed from items commonly found in laboratories, with suggestions for alternative configurations for other detection units. Furthermore, GPFIA for CO2 analysis can be equally applied to samples obtained from either the headspace of microcosms or from a sampling chamber that allows CO2 to be released from alkali trapping solutions. The optimised GPFIA method was applied to analyse CO2 released from degrading hydrocarbons from a site contaminated by diesel spillage.

Evolutionary comparison provides evidence for pathogenicity of RMRP mutations.

Cartilage-hair hypoplasia (CHH) is a pleiotropic disease caused by recessive mutations in the RMRP gene that result in a wide spectrum of manifestations including short stature, sparse hair, metaphyseal dysplasia, anemia, immune deficiency, and increased incidence of cancer. Molecular diagnosis of CHH has implications for management, prognosis, follow-up, and genetic counseling of affected patients and their families. We report 20 novel mutations in 36 patients with CHH and describe the associated phenotypic spectrum. Given the high mutational heterogeneity (62 mutations reported to date), the high frequency of variations in the region (eight single nucleotide polymorphisms in and around RMRP), and the fact that RMRP is not translated into protein, prediction of mutation pathogenicity is difficult. We addressed this issue by a comparative genomic approach and aligned the genomic sequences of RMRP gene in the entire class of mammals. We found that putative pathogenic mutations are located in highly conserved nucleotides, whereas polymorphisms are located in non-conserved positions. We conclude that the abundance of variations in this small gene is remarkable and at odds with its high conservation through species; it is unclear whether these variations are caused by a high local mutation rate, a failure of repair mechanisms, or a relaxed selective pressure. The marked diversity of mutations in RMRP and the low homozygosity rate in our patient population indicate that CHH is more common than previously estimated, but may go unrecognized because of its variable clinical presentation. Thus, RMRP molecular testing may be indicated in individuals with isolated metaphyseal dysplasia, anemia, or immune dysregulation.

Best Practices for Low-Cost Safety Improvements on Iowa’s Local Roads, 2008

Many good maintenance practices are done routinely to ensure safe travel on low-volume local roads. In addition, there are many specific treatments that may go beyond the point of routine maintenance and in fact provide additional safety benefits with a relatively low price tag. The purpose of this publication is to try to assemble many of these treatments that are currently practiced in Iowa by local agencies into one, easy-to-reference handbook that not only provides some clarity to each treatment with photos and narrative, but also features references to agencies currently using that technique. Some strategies that are utilized by Iowa, other states, and are topics of research have also been included to allow the user more information about possible options. Even though some areas overlap, the strategies presented have been grouped together in the following areas: Signing and Delineation, Traffic "Calming," Pavement Marking and Rumble Strips/Stripes, Roadside and Clear Zone, Guardrail and Barriers, Lighting, Pavements and Shoulders, Intersections, Railroad Crossings, Bridges and Culverts, and Miscellaneous. The intention is to make this a “living” document, which will continue to be updated and expanded periodically as other existing practices are recognized or new practices come into being.

Grau de satisfacció d'un col·lectiu de persones grans en relació a l'atenció rebuda dels professionals d'infermeria durant la seva hospitalització

Introducció: La preocupació per la qualitat assistencial, i concretament per la qualitat de les cures infermeres, la satisfacció percebuda pel pacient com element fonamental com a indicador de la qualitat dels serveis sanitaris i clau en la millora de la qualitat assistencial, i el fet que a l’estat espanyol hi ha pocs estudis de satisfacció específics de la població anciana hospitalitzada, ens va portar a plantejar un estudi amb l’objectiu de valorar el grau de satisfacció de les persones grans hospitalitzades en relació a l’atenció rebuda dels professionals d’infermeria. Metodologia: S’ha realitzat un estudi descriptiu i transversal en un col.lectiu de 42 persones hospitalitzades d’edat ≥ 60 anys. El grau de satisfacció es va determinar amb “La Monica Oberst Patient Satisfaction Scale 12” (LOPSS 12), versió reduïda en castellà. La personalització de les cures es va valorar amb un qüestionari que valora la relació infermera-usuari extret de l’Índex de Personalització de les Cures. L'anàlisi estadística es va dur a terme amb el programa informàtic SPSS® vs 21.0. Resultats: Es va evidenciar un elevat grau de satisfacció global amb les cures d’infermeria (8,8  1,5 / 10), però el nivell global de personalització d’aquestes cures no va ser molt satisfactori (3,4  2,1 / 7). Els homes van valorar millor a les infermeres respecte a que consideraven les seves opinions i preferències (p=0,03) i contestaven amb rapidesa les seves trucades (p=0,009). La personalització de les cures millorava conforme incrementava el grau de satisfacció global (r = 0,582; p = 0,000) i amb el temps d’hospitalització (r = 0,344; p = 0,026). Conclusions: El grau de satisfacció global respecte la satisfacció en l’atenció rebuda per part d’infermeria, va ser elevat però amb baix grau de personalització, mostrant major satisfacció els homes respecte les dones. Conèixer l’opinió dels usuaris representa una oportunitat pels professionals de reflexionar sobre la pràctica clínica i ser crítics per avançar en el desenvolupament de la professió, identificant aspectes susceptibles de millora 5 amb la finalitat d’augmentar la qualitat de les cures que es presten, així com la qualitat de vida de les persones.