Transpiration stimulée afin d'améliorer l'équilibre hydro-sodé chez les patients hémodialysés : à propos d'un cas [Stimulated sweating in order to improve the water-and-salt balance in hemodialysis patients. A case report].

Obtaining the desired dry weight in dialysis patients is challenging once residual diuresis has disappeared, considering the trend of increasing dietary salt intake and shortening dialysis time over the last 40 years. We describe the case of a 55-year-old patient of Sudanese origin, who presented excessive interdialytic weight gain and hypertension on maintenance hemodialysis. After failure of conservative measures, a therapy of daily hot water baths of 30minutes each on non-dialysis days was introduced. All clinical parameters improved, including potassium profile. In this article, we review the history, pathophysiological mechanisms, efficacy and possible side effects of this interesting, somewhat forgotten technique.

Design of new tools to improve the efficacy of DNA-damaging drugs used in cancer therapy

Résumé Les tumeurs sont diverses et hétérogènes, mais toutes partagent la capacité de proliférer sans contrôle. Une prolifération dérégulée de cellules couplée à une insensibilité à une réponse apoptotique constitue une condition minimale pour que l'évolution d'une tumeur se produise. Un des traitements les plus utilisés pour traité le cancer à l'heure actuelle sont les chimiothérapies, qui sont fréquemment des composés chimiques qui induisent des dommages dans l'ADN. Les agents anticancéreux sont efficaces seulement quand les cellules tumorales sont plus aisément tuées que le tissu normal environnant. L'efficacité de ces agents est en partie déterminée par leur capacité à induire l'apoptose. Nous avons récemment démontré que la protéine RasGAP est un substrat non conventionnel des caspases parce elle peut induire à la fois des signaux anti et pro-apoptotiques, selon l'ampleur de son clivage par les caspases. A un faible niveau d'activité des caspases, RasGAP est clivé, générant deux fragments (le fragment N et le fragment C). Le fragment N semble être un inhibiteur général de l'apoptose en aval de l'activation des caspases. À des niveaux plus élevés d'activité des caspases, la capacité du fragment N de contrecarrer l'apoptose est supprimée quand il est clivé à nouveau par les caspases. Ce dernier clivage produit deux nouveaux fragments, N 1 et N2, qui contrairement au fragment N sensibilisent efficacement des cellules cancéreuses envers des agents chimiothérapeutiques. Dans cette étude nous avons prouvé qu'un peptide, appelé par la suite TAT-RasGAP317-326, qui est dérivé du fragment N2 de RasGAP et est rendu perméable aux cellules, sensibilise spécifiquement des cellules cancéreuses à trois génotoxines différentes utilisées couramment dans des traitements anticancéreux, et cela dans des modèles in vitro et in vivo. Il est important de noté que ce peptide semble ne pas avoir d'effet sur des cellules non cancéreuses. Nous avons également commencé à caractériser les mécanismes moléculaires expliquant les fonctions de sensibilisation de TAT-RasGAP317-326. Nous avons démontré que le facteur de transcription p53 et une protéine sous son activité transcriptionelle, nommée Puma, sont indispensables pour l'activité de TAT-RasGAP317-326. Nous avons également prouvé que TAT-RasGAP317-326 exige la présence d'une protéine appelée G3BP1, une protéine se liant a RasGAP, pour potentialisé les effets d'agents anticancéreux. Les données obtenues dans cette étude montrent qu'il pourrait être possible d'augmenter l'efficacité des chimiothérapies à l'aide d'un composé capable d'augmenter la sensibilité des tumeurs aux génotoxines et ainsi pourrait permettre de traiter de manière plus efficace des patients sous traitement chimiothérapeutiques. Summary Tumors are diverse and heterogeneous, but all share the ability to proliferate without control. Deregulated cell proliferation coupled with suppressed apoptotic sensitivity constitutes a minimal requirement upon which tumor evolution occurs. One of the most commonly used treatments is chemotherapy, which frequently uses chemical compounds that induce DNA damages. Anticancer agents are effective only when tumors cells are more readily killed than the surrounding normal tissue. The efficacy of these agents is partly determined by their ability to induce apoptosis. We have recently demonstrated that the protein RasGAP is an unconventional caspase substrate because it can induce both anti- and pro-apoptotic signals, depending on the extent of its cleavage by caspases. At low levels of caspase activity, RasGAP is cleaved, generating an N-terminal fragment (fragment N) and a C-terminal fragment (fragment C). Fragment N appears to be a general Mocker of apoptosis downstream of caspase activation. At higher levels of caspase activity, the ability of fragment N to counteract apoptosis is suppressed when it is further cleaved. This latter cleavage event generates two fragments, N1 and N2, which in contrast to fragment N potently sensitizes cancer cells toward DNA-damaging agents induced apoptosis. In the present study we show that a cell permeable peptide derived from the N2 fragment of RasGAP, thereafter called TAT-RasGAP317-326, specifically sensitizes cancer cells to three different genotoxins commonly used in chemotherapy in vitro and in vivo models. Importantly this peptide seems not to have any effect on non cancer cells. We have also started to characterize the molecular mechanisms underlying the sensitizing functions of TAT-RasGAP317-326. We have demonstrated that the p53 transcription factor and a protein under its transcriptional activity, called Puma, are required for the activity of TATRasGAP317-326. We have also showed that TAT-RasGAP317-326 requires the presence of a protein called G3BP1, which have been shown to interact with RasGAP, to increase the effect of the DNA-damaging drug cisplatin. The data obtained in this study showed that it is possible to increase the efficacy of current used chemotherapies with a compound able to increase the efficacy of genotoxins which could be beneficial for patients subjected to chemotherapy.

Defining publication bias: protocol for a systematic review of highly cited articles and proposal for a new framework.

BACKGROUND: Selective publication of studies, which is commonly called publication bias, is widely recognized. Over the years a new nomenclature for other types of bias related to non-publication or distortion related to the dissemination of research findings has been developed. However, several of these different biases are often still summarized by the term 'publication bias'. METHODS/DESIGN: As part of the OPEN Project (To Overcome failure to Publish nEgative fiNdings) we will conduct a systematic review with the following objectives:- To systematically review highly cited articles that focus on non-publication of studies and to present the various definitions of biases related to the dissemination of research findings contained in the articles identified.- To develop and discuss a new framework on nomenclature of various aspects of distortion in the dissemination process that leads to public availability of research findings in an international group of experts in the context of the OPEN Project.We will systematically search Web of Knowledge for highly cited articles that provide a definition of biases related to the dissemination of research findings. A specifically designed data extraction form will be developed and pilot-tested. Working in teams of two, we will independently extract relevant information from each eligible article.For the development of a new framework we will construct an initial table listing different levels and different hazards en route to making research findings public. An international group of experts will iteratively review the table and reflect on its content until no new insights emerge and consensus has been reached. DISCUSSION: Results are expected to be publicly available in mid-2013. This systematic review together with the results of other systematic reviews of the OPEN project will serve as a basis for the development of future policies and guidelines regarding the assessment and prevention of publication bias.

Use of a pre-sidedress soil nitrate test (PSNT) to determine nitrogen fertilizer requirements for irrigated corn

In the present study, a 2-year N rate response experiment was conducted in different fields to monitor NO3-N soil profiles, N accumulation by the crop and final crop performance, in order to assess if soil NO3-N at pre-sidedressing (Pre-Sidedress Soil Nitrate Test, PSNT) is a reliable indicator for soil N availability for corn in the irrigated area served by canal d’Urgell (Lleida, Spain), and if the test can be used to separate responsive fields from non-responsive fields to sidedress N fertilizer applications. Preliminary soil N availability (N sidedress fertilizer rate + PSNT) critical levels to identify fields that need supplementary N fertilizer applications were established at ca. 300 and 210 kg NO3-N·ha–1, for PSNTrooting–zone and PSNT0–30 cm, respectively (for a yield goal of 14 t grain·ha–1).

Las condiciones de reproducción de la unidad familiar campesina en la Catalunya Nova: las "Terres de Lleida"

El trabajo intenta evaluar la dimensión mínima de la tierra que debiera poseer la unidad familiar campesina para garantizar su reproducción en el marco histórico de la etapa final de la Edad Moderna. Geográficamente, el trabajo se refiere a las tierras del interior llano catalán, que experimentaron durante el siglo XVIII un notable proceso de colonización agraria para atender los déficits cerealísticos del litoral catalán. Dado que la mayor parte del campesinado no disfruta de explotaciones viables económicamente, se analizan las estrategias campesinas encaminadas a la obtención de ingresos complementarios. Estas, lejos de situarse en actividades no agrarias, tienen una estrecha relación con la agricultura y con el aprovechamiento de los recursos naturales.

A genetic risk score combining 32 SNPs is associated with body mass index and improves obesity prediction in people with major depressive disorder.

BACKGROUND: Obesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD. METHODS: Linear and logistic regression models were conducted to predict BMI and obesity, respectively, in three independent large case-control studies of major depression (Radiant, GSK-Munich, PsyCoLaus). The analyses were first performed in the whole sample and then separately in depressed cases and controls. An unweighted GRS was calculated by summation of the number of risk alleles. A weighted GRS was calculated as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver operating characteristic (ROC) analysis was used to compare the discriminatory ability of predictors of obesity. RESULTS: In the discovery phase, a total of 2,521 participants (1,895 depressed patients and 626 controls) were included from the Radiant study. Both unweighted and weighted GRS were highly associated with BMI (P <0.001) but explained only a modest amount of variance. Adding 'traditional' risk factors to GRS significantly improved the predictive ability with the area under the curve (AUC) in the ROC analysis, increasing from 0.58 to 0.66 (95% CI, 0.62-0.68; χ(2) = 27.68; P <0.0001). Although there was no formal evidence of interaction between depression status and GRS, there was further improvement in AUC in the ROC analysis when depression status was added to the model (AUC = 0.71; 95% CI, 0.68-0.73; χ(2) = 28.64; P <0.0001). We further found that the GRS accounted for more variance of BMI in depressed patients than in healthy controls. Again, GRS discriminated obesity better in depressed patients compared to healthy controls. We later replicated these analyses in two independent samples (GSK-Munich and PsyCoLaus) and found similar results. CONCLUSIONS: A GRS proved to be a highly significant predictor of obesity in people with MDD but accounted for only modest amount of variance. Nevertheless, as more risk loci are identified, combining a GRS approach with information on non-genetic risk factors could become a useful strategy in identifying MDD patients at higher risk of developing obesity.

A melting pot world of species : reply to Speziale et al.

Native plants and animals are a natural heritage threatened by one of the six greatest extinction events in Earth's history. Humans, through habitat transformation, exploitation, and species introductions, are driving this extinction event. To turn this tide, Speziale et al. (2014) suggest reducing human dependence on non-native species by increasing the use, harvest, planting, and raising of native species, thereby increasing their cultural and economic value. The search for new or under-appreciated uses of native species is laudable, especially if it helps protect them and contributes to local cultural diversity. Such efforts are arguably an inherent trait of human curiosity and entrepreneurship and are a central platform of popular movements such as slow foods and native gardening. However, Speziale et al.'s hypothesis - that using native species can protect them - is less simple than they suggest. We refute the idea of nativism that underpins Speziale et al.'s proposal and makes it poorly defensible and considered the unaddressed consequences of the proposal for people and for conservation.

Go-to-market strategy with pharmacies

The purpose of the research is to develop a go-to-market strategy with pharmacies. As it was agreed with the client of the study, Reckitt Benckiser, the focus is solely on non-prescription products. Therefore, prescription medicines are not considered in the study. The main objective of the research is to clarify consumer and pharmacy personnel behavior concerning non-prescription products. These issues are observed with surveys, which are provided to consumers and pharmacy personnel. The go-to-market strategy is based on the survey results and is comprised by utilizing the marketing-mix model. Legislation and the present state & trends are additional minor research problems of the study. The results of the research provide many descriptive insights about consumer and pharmacy personnel behavior. It is concluded that the consumers’ level of involvement with non-prescription products is low and the type of behavior is habitual. It is also demonstrated that several decision-making criteria are very different among different age groups and genders. Concerning pharmacy personnel, the factors that they base their product recommendations are revealed. In addition, the sources of medicine information for both consumers and pharmacy personnel are found out.

Kompostointilaitoksen lopputuotteen käyttömahdollisuudet. Case: Himanka

Työssä selvitetään kompostointilaitoksen lopputuotteen erilaisia käyttömahdollisuuksia. Yleisten käyttökohteiden pohjalta on luotu malli Vapo Oy Biotech:n toimittaman Himangan kompostointilaitoksen kompostin hyödyntämiselle. Laitos sijaitsee Himangan kunnassa Keski- Pohjanmaalla. Laitoksella kompostoidaan pääasiassa Himangan ja ympäröivien kuntien jätevesilietteitä turkiseläinlantaa. Jätehuolto Suomessa ja koko EU:n alueella elää voimakasta muutoskautta. Orgaanisten jätteiden vienti kaatopaikoille pyritään tulevaisuudessa lopettamaan kokonaan, mikä on lisännyt niiden käsittelyä mm. kompostoimalla. Kompostoinnin lopputuotteena saadaan ravinteikasta, humuspitoista ainesta. Kompostoinnin yhtenä tavoitteena on tuottaa hyötykäyttöön soveltuvaa tuotetta, joten käyttökohteen löytäminen kompostille on laitoksen toiminnan kannalta erittäin tärkeää. Kompostin käyttömahdollisuuksiin vaikuttavat lainsäädäntö, kompostin ominaisuudet sekä paikalliset olosuhteet. Käyttökohteet on työssä jaettu ei-energiakäyttöön ja energiakäyttöön. Ei-energiakäyttöön kuuluvat maanparannuskäyttö, lannoitekäyttö, käyttö kasvualustassa, maisemointi ja julkinen rakentaminen sekä joitakin erityissovelluksia. Energiakäytön puolella on tarkasteltu kompostin soveltuvuutta erilaisille polttotekniikoille sekä vertailtu kompostia muihin kiinteisiin polttoaineisiin. Kompostien soveltuvuutta eri kohteisiin on arvioitu kompostin analyysi- ja kasvatuskoetulosten pohjalta. Kompostin ei-energiakaytössa on saatu eri tutkimuksissa lupaavia tuloksia. Kompostin on todettu soveltuvan erittäin hyvin mm. perunanviljelyyn, viljan ja nurmikasvien viljelyyn ja erilaisiin maisemointikohteisiin sekä kotipuutarhakäyttöön. Kompostin käyttöä polttoaineena ei ole vielä kokeiltu missään. Kompostin polton suurimmat ongelmat ovat korkea tuhka-, rikki- ja typpipitoisuus sekä epätasainen laatu.

Under-reporting of dietary energy intake in five populations of the African diaspora.

Studies on the role of diet in the development of chronic diseases often rely on self-report surveys of dietary intake. Unfortunately, many validity studies have demonstrated that self-reported dietary intake is subject to systematic under-reporting, although the vast majority of such studies have been conducted in industrialised countries. The aim of the present study was to investigate whether or not systematic reporting error exists among the individuals of African ancestry (n 324) in five countries distributed across the Human Development Index (HDI) scale, a UN statistic devised to rank countries on non-income factors plus economic indicators. Using two 24 h dietary recalls to assess energy intake and the doubly labelled water method to assess total energy expenditure, we calculated the difference between these two values ((self-report - expenditure/expenditure) × 100) to identify under-reporting of habitual energy intake in selected communities in Ghana, South Africa, Seychelles, Jamaica and the USA. Under-reporting of habitual energy intake was observed in all the five countries. The South African cohort exhibited the highest mean under-reporting ( - 52·1% of energy) compared with the cohorts of Ghana ( - 22·5%), Jamaica ( - 17·9%), Seychelles ( - 25·0%) and the USA ( - 18·5%). BMI was the most consistent predictor of under-reporting compared with other predictors. In conclusion, there is substantial under-reporting of dietary energy intake in populations across the whole range of the HDI, and this systematic reporting error increases according to the BMI of an individual.

Alueellinen verkostoituminen. Case: Kaakkois-Suomen TE-keskus

Tutkimuksen tavoitteena on selvittää Kaakkois-Suomen TE-keskuksen toiminta-ajatuksen ja vision toteutumista alueellisten yhteistyökump-paneiden (ulkoinen näkökulma) ja henkilöstön (sisäinen näkökulma) kannalta, millä lailla he ovat kokeneet voineensa vaikuttaa alueellisten toimijoiden verkostoon, ja minkälaisia rooleja on löydettävissä verkostosta. Tutkimus on kaksiosainen sisältäen kvalitatiivisen teoriaosan, ja empiiriaosan. Teoriaosassa määritellään verkostokäsite ja verkostopiirteitä. Lisäksi pohditaan motiiveja verkostoitumiseen ja tutkitaan erilaisia verkostojaotteluja. Alueellista verkostoitumista käsitellään ei-hyötyä-tavoittelevan organisaation näkökulmasta. Lisäksi käydään läpi organisaation sisäistä näkökulmaa verkostoiduttaessa sekä sitä, voiko verkostoa johtaa. Tutkimuksen empiiriaosassa teemahaastatellaan alueellisia yhteistyökumppaneita sekä henkilöstön edustajia. Tutkimuksen perusteella voidaan todeta, että toiminta-ajatus on sisäistetty verkoston toiminnan lähtökohdaksi. Koetaan, että verkostoon voidaan vaikuttaa, mutta verkoston johtaminen on tilannekohtaista. Verkoston toimivuutta lisäävät siinä toimivien henkilöiden keskinäinen luottamus ja aktiivinen tiedonkulku. Käytännössä roolien erittely ei ole selkeätä, vaan eri roolit sekottuvat tilanteen mukaan. Vapaamuotoiset foorumit koetaan erityisen hedelmällisiksi uusia innovaatioita luotaessa ja hyvä käytäntöjä hyödynnettäessa.

Decades of population genetic research reveal the need for harmonization of molecular markers: the grey wolf Canis lupus as a case study

Following protection measures implemented since the 1970s, large carnivores are currently increasing in number and returning to areas from which they were absent for decades or even centuries. Monitoring programmes for these species rely extensively on non-invasive sampling and genotyping. However, attempts to connect results of such studies at larger spatial or temporal scales often suffer from the incompatibility of genetic markers implemented by researchers in different laboratories. This is particularly critical for long-distance dispersers, revealing the need for harmonized monitoring schemes that would enable the understanding of gene flow and dispersal dynamics. Based on a review of genetic studies on grey wolves Canis lupus from Europe, we provide an overview of the genetic markers currently in use, and identify opportunities and hurdles for studies based on continent-scale datasets. Our results highlight an urgent need for harmonization of methods to enable transnational research based on data that have already been collected, and to allow these data to be linked to material collected in the future. We suggest timely standardization of newly developed genotyping approaches, and propose that action is directed towards the establishment of shared single nucleotide polymorphism panels, next-generation sequencing of microsatellites, a common reference sample collection and an online database for data exchange. Enhanced cooperation among genetic researchers dealing with large carnivores in consortia would facilitate streamlining of methods, their faster and wider adoption, and production of results at the large spatial scales that ultimately matter for the conservation of these charismatic species.

The local configuration of a science and innovation policy : a city into the nanoworld

Local trajectories and arrangements play a significant role because the development of a research field, such as nanoscience and nanotechnology, requires substantial investments in human and instrumental resources. But why are there often concentrated in a limited number of places? What dynamics lead to such concentration? The hypothesis is that there is an assemblage of heterogeneous resources through the action of local actors. The chapter will explore, from an Actor Network Theory (ANT) perspective, how the local emergence of research dynamics from: the revival of local traditions, the local and national action of institutional entrepreneurs, controversial dynamics, and researchers' arrangements to involve other actors. It will examine how they connect up with each other and mutually commit themselves to the development of new technologies. It will focus on the role of narratives in this assembling: how were the local narratives of the past mobilized and to what effect.

Microscopy of Fission Yeast Sexual Lifecycle.

The fission yeast Schizosaccharomyces pombe has been an invaluable model system in studying the regulation of the mitotic cell cycle progression, the mechanics of cell division and cell polarity. Furthermore, classical experiments on its sexual reproduction have yielded results pivotal to current understanding of DNA recombination and meiosis. More recent analysis of fission yeast mating has raised interesting questions on extrinsic stimuli response mechanisms, polarized cell growth and cell-cell fusion. To study these topics in detail we have developed a simple protocol for microscopy of the entire sexual lifecycle. The method described here is easily adjusted to study specific mating stages. Briefly, after being grown to exponential phase in a nitrogen-rich medium, cell cultures are shifted to a nitrogen-deprived medium for periods of time suited to the stage of the sexual lifecycle that will be explored. Cells are then mounted on custom, easily built agarose pad chambers for imaging. This approach allows cells to be monitored from the onset of mating to the final formation of spores.

A broadband leptonic model for gamma-ray emitting microquasars

Observational and theoretical studies point to microquasars (MQs) as possible counterparts of a significant fraction of the unidentified gamma-ray sources detected so far. At present, a proper scenario to explain the emission beyond soft X-rays from these objects is not known, nor what the precise connection is between the radio and the high-energy radiation. We develop a new model where the MQ jet is dynamically dominated by cold protons and radiatively dominated by relativistic leptons. The matter content and power of the jet are both related with the accretion process. The magnetic field is assumed to be close to equipartition, although it is attached to and dominated by the jet matter. For the relativistic particles in the jet, their maximum energy depends on both the acceleration efficiency and the energy losses. The model takes into account the interaction of the relativistic jet particles with the magnetic field and all the photon and matter fields. Such interaction produces significant amounts of radiation from radio to very high energies through synchrotron, relativistic Bremsstrahlung, and inverse Compton (IC) processes. Variability of the emission produced by changes in the accretion process (e.g. via orbital eccentricity) is also expected. The effects of the gamma-ray absorption by the external photon fields on the gamma-ray spectrum have been taken into account, revealing clear spectral features that might be observed. This model is consistent to the accretion scenario, energy conservation laws, and current observational knowledge, and can provide deeper physical information of the source when tested against multiwavelength data.