Reporting of methodologic information on trial registries for quality assessment: a study of trial records retrieved from the WHO search portal

Background: Although randomized clinical trials (RCTs) are considered the gold standard of evidence, their reporting is often suboptimal. Trial registries have the potential to contribute important methodologic information for critical appraisal of study results. Methods and Findings: The objective of the study was to evaluate the reporting of key methodologic study characteristics in trial registries. We identified a random sample (n = 265) of actively recruiting RCTs using the World Health Organization International Clinical Trials Registry Platform (ICTRP) search portal in 2008. We assessed the reporting of relevant domains from the Cochrane Collaboration’s ‘Risk of bias’ tool and other key methodological aspects. Our primary outcomes were the proportion of registry records with adequate reporting of random sequence generation, allocation concealment, blinding, and trial outcomes. Two reviewers independently assessed each record. Weighted overall proportions in the ICTRP search portal for adequate reporting of sequence generation, allocation concealment, blinding (including and excluding open label RCT) and primary outcomes were 5.7% (95% CI 3.0–8.4%), 1.4% (0–2.8%), 41% (35–47%), 8.4% (4.1–13%), and 66% (60–72%), respectively. The proportion of adequately reported RCTs was higher for registries that used specific methodological fields for describing methods of randomization and allocation concealment compared to registries that did not. Concerning other key methodological aspects, weighted overall proportions of RCTs with adequately reported items were as follows: eligibility criteria (81%), secondary outcomes (46%), harm (5%) follow-up duration (62%), description of the interventions (53%) and sample size calculation (1%). Conclusions: Trial registries currently contain limited methodologic information about registered RCTs. In order to permit adequate critical appraisal of trial results reported in journals and registries, trial registries should consider requesting details on key RCT methods to complement journal publications. Full protocols remain the most comprehensive source of methodologic information and should be made publicly available.

Growth and yield models in Spain: historical overview, contemporary examples and perspectives

En el presente trabajo se presenta una revisión sobre los modelos forestales desarrollados en España durante los últimos años, tanto para la producción maderable como no maderable y, para la dinámica de los bosques (regeneración, mortalidad). Se presentan modelos tanto de rodal completo como de clases diamétricas y de árbol individual. Los modelos desarrollados hasta la fecha se han desarrollado a partir de datos procedentes de parcelas permanentes, ensayos y el Inventario Forestal Nacional. En el trabajo se muestran los diferentes submodelos desarrollados hasta la fecha, así como las plataformas informáticas que permiten utilizar dichos modelos. Se incluyen las principales perspectivas de desarrollo de la modelización forestal en España.

Mitochondrial DNA damage and animal longevity: insights from comparative studies

Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur, even under physiological conditions. Aging, in this chemical context, could be viewed as an entropic process, the result of chemical side reactions that chronically and cumulatively degrade the function of biological systems. Mitochondria are a main source of reactive oxygen species (ROS) and chemical sidereactions in healthy aerobic tissues and are the only known extranuclear cellular organelles in animal cells that contain their own DNA (mtDNA). ROS can modify mtDNA directly at the sugar-phosphate backbone or at the bases, producing many different oxidatively modified purines and pyrimidines, as well as single and double strand breaks and DNA mutations. In this scenario, natural selection tends to decrease the mitochondrial ROS generation, the oxidative damage to mtDNA, and the mitochondrial mutation rate in long-lived species, in agreement with the mitochondrial oxidative stress theory of aging.

Generation and interconnection capacity expansion in cross-border electricity markets : the need for policy coordination

Electricity is a strategic service in modern societies. Thus, it is extremely important for governments to be able to guarantee an affordable and reliable supply, which depends to a great extent on an adequate expansion of the generation and transmission capacities. Cross- border integration of electricity markets creates new challenges for the regulators, since the evolution of the market is now influenced by the characteristics and policies of neighbouring countries. There is still no agreement on why and how regions should integrate their electricity markets. The aim of this thesis is to improve the understanding of integrated electricity markets and how their behaviour depends on the prevailing characteristics of the national markets and the policies implemented in each country. We developed a simulation model to analyse under what circumstances integration is desirable. This model is used to study three cases of interconnection between two countries. Several policies regarding interconnection expansion and operation, combined with different generation capacity adequacy mechanisms, are evaluated. The thesis is composed of three papers. The first paper presents a detailed description of the model and an analysis of the case of Colombia and Ecuador. It shows that market coupling can bring important benefits, but the relative size of the countries can lead to import dependency issues in the smaller country. The second paper compares the case of Colombia and Ecuador with the case of Great Britain and France. These countries are significantly different in terms of electricity sources, hydro- storage capacity, complementarity and demand growth. We show that complementarity is essential in order to obtain benefits from integration, while higher demand growth and hydro- storage capacity can lead to counterintuitive outcomes, thus complicating policy design. In the third paper, an extended version of the model presented in the first paper is used to analyse the case of Finland and its interconnection with Russia. Different trading arrangements are considered. We conclude that unless interconnection capacity is expanded, the current trading arrangement, where a single trader owns the transmission rights and limits the flow during peak hours, is beneficial for Finland. In case of interconnection expansion, market coupling would be preferable. We also show that the costs of maintaining a strategic reserve in Finland are justified in order to limit import dependency, while still reaping the benefits of interconnection. In general, we conclude that electricity market integration can bring benefits if the right policies are implemented. However, a large interconnection capacity is only desirable if the countries exhibit significant complementarity and trust each other. The outcomes of policies aimed at guaranteeing security of supply at a national level can be quite counterintuitive due to the interactions between neighbouring countries and their effects on interconnection and generation investments. Thus, it is important for regulators to understand these interactions and coordinate their decisions in order to take advantage of the interconnection without putting security of supply at risk. But it must be taken into account that even when integration brings benefits to the region, some market participants lose and might try to hinder the integration process. -- Dans les sociétés modernes, l'électricité est un service stratégique. Il est donc extrêmement important pour les gouvernements de pouvoir garantir la sécurité d'approvisionnement à des prix abordables. Ceci dépend en grande mesure d'une expansion adéquate des capacités de génération et de transmission. L'intégration des marchés électriques pose des nouveaux défis pour les régulateurs, puisque l'évolution du marché est maintenant influencée par les caractéristiques et les politiques des pays voisins. Il n'est pas encore claire pourquoi ni comment les marches électriques devraient s'intégrer. L'objectif de cette thèse est d'améliorer la compréhension des marchés intégrés d'électricité et de leur comportement en fonction des caractéristiques et politiques de chaque pays. Un modèle de simulation est proposé pour étudier les conditions dans lesquelles l'intégration est désirable. Ce modèle est utilisé pour étudier trois cas d'interconnexion entre deux pays. Plusieurs politiques concernant l'expansion et l'opération de l'interconnexion, combinées avec différents mécanismes de rémunération de la capacité, sont évalués. Cette thèse est compose de trois articles. Le premier présente une description détaillée du modèle et une analyse du cas de la Colombie et de l'Equateur. Il montre que le couplage de marchés peut amener des bénéfices importants ; cependant, la différence de taille entre pays peut créer des soucis de dépendance aux importations pour le pays le plus petit. Le second papier compare le cas de la Colombie et l'Equateur avec le cas de la Grande Bretagne et de la France. Ces pays sont très différents en termes de ressources, taille des réservoirs d'accumulation pour l'hydro, complémentarité et croissance de la demande. Nos résultats montrent que la complémentarité joue un rôle essentiel dans l'obtention des bénéfices potentiels de l'intégration, alors qu'un taux élevé de croissance de la demande, ainsi qu'une grande capacité de stockage, mènent à des résultats contre-intuitifs, ce qui complique les décisions des régulateurs. Dans le troisième article, une extension du modèle présenté dans le premier article est utilisée pour analyser le cas de la Finlande et de la Russie. Différentes règles pour les échanges internationaux d'électricité sont considérées. Nos résultats indiquent qu'à un faible niveau d'interconnexion, la situation actuelle, où un marchand unique possède les droits de transmission et limite le flux pendant les heures de pointe, est bénéfique pour la Finlande. Cependant, en cas d'expansion de la capacité d'interconnexion, «market coupling» est préférable. préférable. Dans tous les cas, la Finlande a intérêt à garder une réserve stratégique, car même si cette politique entraine des coûts, elle lui permet de profiter des avantages de l'intégration tout en limitant ca dépendance envers les importations. En général, nous concluons que si les politiques adéquates sont implémentées, l'intégration des marchés électriques peut amener des bénéfices. Cependant, une grande capacité d'interconnexion n'est désirable que si les pays ont une complémentarité importante et il existe une confiance mutuelle. Les résultats des politiques qui cherchent à préserver la sécurité d'approvisionnement au niveau national peuvent être très contre-intuitifs, étant données les interactions entre les pays voisins et leurs effets sur les investissements en génération et en interconnexion. Il est donc très important pour les régulateurs de comprendre ces interactions et de coordonner décisions à fin de pouvoir profiter de l'interconnexion sans mettre en danger la sécurité d'approvisionnement. Mais il faut être conscients que même quand l'intégration amène de bénéfices pour la région, certains participants au marché sont perdants et pourraient essayer de bloquer le processus d'intégration.

From room for books to room for users: an old infantry barrack as an answer to the lack of space

At the beginning of the 21st century, some Catalan university libraries detected a need stemming from the lack of space and the reconversion of physical libraries within the new European educational panorama. With the same cooperative spirit that characterized previous CBUC (Consortium of Academic Libraries of Catalonia) programs and services, the Consortium set in motion a project to address this need. An initial study was commissioned in 2002, and in 2003 a suitable building (old infantry barracks) was found in Lleida. The official opening took place in 2008. GEPA (Guaranteed Space for the Preservation of Access) facility is a cooperative repository, whose objectives are to store and preserve low use documents, ensuring their future access when needed, to convert room for books into room for library users, and doing it saving both space and money. The paper presents a brief historical introduction about the physical management of collections in libraries, and a short overview about high density library repositories all over the world, as an answer to the pressing problem of lack of spaces. The main goals of the communication are to comment the architectural project and its librarian issues, and to show how the GEPA facility allowed to change the spaces in university libraries in Catalonia. On the one hand, the paper deals with the selection of an old building to be renovated, the determination of the librarian needs, the compact shelving system chosen to store the documents in the building, the relation between physical space and information management, and the logistics involved in the load of low use documents from the libraries into the facility. On the other hand, we will show some examples of physical changes in Catalan libraries after large loads of documents to GEPA.

ZnO nanorods for efficient third harmonic UV generation.

ZnO nanorods grown by both high temperature vapour phase transport and low temperature chemical bath deposition are very promising sources for UV third harmonic generation. Material grown by both methods show comparable efficiencies, in both cases an order of magnitude higher than surface third harmonic generation at the quartz-air interface of a bare quartz substrate. This result is in stark contrast to the linear optical properties of ZnO nanorods grown by these two methods, which show vastly different PL efficiencies. The third harmonic generated signal is analysed using intensity dependent measurements and interferometric frequency resolved optical gating, allowing extraction of the laser pulse parameters. The comparable levels of efficiency of ZnO grown by these very different methods as sources for third harmonic UV generation provides a broad suite of possible growth methods to suit various substrates, coverage and scalability requirements. Potential application areas range from interferometric frequency resolved optical gating characterization of few cycle fs pulses to single cell UV irradiation for biophysical studies.

Collecting Transaction Data in a Fourth Generation Mobile Network

Tässä diplomityössä on oletettu että neljännen sukupolven mobiiliverkko on saumaton yhdistelmä olemassa olevia toisen ja kolmannen sukupolven langattomia verkkoja sekä lyhyen kantaman WLAN- ja Bluetooth-radiotekniikoita. Näiden tekniikoiden on myös oletettu olevan niin yhteensopivia ettei käyttäjä havaitse saanti verkon muuttumista. Työ esittelee neljännen sukupolven mobiiliverkkoihin liittyvien tärkeimpien langattomien tekniikoiden arkkitehtuurin ja perustoiminta-periaatteet. Työ kuvaa eri tekniikoita ja käytäntöjä tiedon mittaamiseen ja keräämiseen. Saatuja transaktiomittauksia voidaan käyttää tarjottaessa erilaistettuja palvelutasoja sekä verkko- ja palvelukapasiteetin optimoimisessa. Lisäksi työssä esitellään Internet Business Information Manager joka on ohjelmistokehys hajautetun tiedon keräämiseen. Sen keräämää mittaustietoa voidaan käyttää palvelun tason seurannassa j a raportoinnissa sekä laskutuksessa. Työn käytännön osuudessa piti kehittää langattoman verkon liikennettä seuraava agentti joka tarkkailisi palvelun laatua. Agentti sijaitsisi matkapuhelimessa mitaten verkon liikennettä. Agenttia ei kuitenkaan voitu toteuttaa koska ohjelmistoympäristö todettiin vajaaksi. Joka tapauksessa työ osoitti että käyttäjän näkökulmasta tietoa kerääville agenteille on todellinen tarve.

Kolmannen sukupolven matkaviestinverkon puhelunohjaus MSC Server –konseptilla

Tietoliikenneala elää muutosten aikaa. Vanhat piirikytketyt kapeakaistaiset verkot ovat väistymässä seuraavan sukupolven verkkojen tieltä. GPRS-verkot tekevät tuloaan ja 3G-verkkojen kehitystyö on kiivaimmillaan laitetoimittajien ratkoessa verkoille asetettuja haasteita. Jää nähtäväksi, kykenevätkö 3G-verkot vastaamaan näihin haasteisiin. Työssä käsitellään 3G-verkon arkkitehtuuria, toimintaa ja puhelunohjausta MSC Server -konseptissa, sekä käydään läpi muutamia puheluesimerkkejä. 3G-verkon arkkitehtuuri, jossa puhelunohjaus on erotettu mediakerroksesta, esitetään ja uudet verkkoelementit ja niiden toiminta käsitellään. Esitelty teoria perustuu kirjallisuuteen sekä yleisesti hyväksyttyihin 3G- verkon standardeihin. Näitä standardeja julkaisevat muun muassa ITU-T ja 3GPP yhdessä yhteistyöyritystensä kanssa. Standardointityö on monin osin vielä kesken ja se on vaikeuttanut 3G-verkkojen suunnittelutyötä merkittävästi. Työn tarkoituksena on selvittää puhelunohjausta 3G-verkossa ja sen toteuttamista MSC Server –konseptilla. MSC Serverin toteutusvaihtoehtoja arvioidaan ja niistä valitaan yksi 3G-verkon puhelunohjauksen toteutusmalliksi. Työtä jatketaan tämän diplomityön jälkeen tarkemman toteutuksen suunnittelulla, päämääränä rakentaa 3G-verkko.

The Architecture of a Fourth Generation Mobile Network

Neljännen sukupolven mobiiliverkot yhdistävät saumattomasti televerkot, Internetin ja niiden palvelut. Alkuperin Internetiä käytettiin vain paikallaan pysyviltä tietokoneilta perinteisten televerkkojen tarjotessa puhelin- ja datapalveluita. Neljännen sukupolven mobiiliverkkojen käyttäjät voivat käyttää sekä Internetiin perustuvia että perinteisten televerkkojen palveluita liikkuessaankin. Tämä diplomityö esittelee neljännen sukupolven mobiiliverkon yleisen arkkitehtuurin. Arkkitehtuurin perusosat kuvaillaan ja arkkitehtuuria verrataan toisen ja kolmannen sukupolven mobiiliverkkoihin. Aiheeseen liittyvät Internet-standardit esitellään ja niiden soveltuvuutta mobiiliverkkoihin pohditaan. Langattomia, lyhyen kantaman nopeita liitäntäverkkotekniikoita esitellään. Neljännen sukupolven mobiiliverkoissa tarvittavia päätelaitteiden ja käyttäjien liikkuvuuden hallintamenetelmiä esitellään. Esitelty arkkitehtuuri perustuu langattomiin, lyhyen kantaman nopeisiin liitäntäverkkotekniikoihin ja Internet-standardeihin. Arkkitehtuuri mahdollistaa yhteydet toisiin käyttäjiin ilman tietoa heidän senhetkisestä päätelaitteesta tai sijainnista. Internetin palveluitavoidaan käyttää missä tahansa neljännen sukupolven mobiiliverkon alueella. Yleiskäytöistä liikkuvuuden hallintamenetelmää yhden verkon alueelle ehdotetaan. Menetelmää voidaan käyttää yhdessä esitellyn arkkitehtuurin kanssa.

MULTIMEDIATIETOPANKKI VERKOSSA

Työ käsittelee multimediatietopankin tietosisällön hallintaa ja kehittämistä. Multimediatietopankki verkossa –projektissa multimediatietopankilla tarkoitetaan vuorovaikutteista ja sisältörikasta liikkuvan ja staattisen kuvan (video, animaatio, valokuvat, 3D, grafiikka), äänten (musiikki ja muut äänet) ja tietokantojen yhdistelmää. Sisällön eri osa-alueet ja vuorovaikutteisuus tukevat kokonaisuutta, jolla on oma viestinnällinen tarkoituksensa. Tätä kokonaistoteutusta levitetään www:n, digitaalitelevision ja mobiililaitteiden välityksellä loppukäyttäjälle. Multimedia- ja matkaviestinteknologioiden nopea kehitys antaa mahdollisuuden kehittää uusia palveluja. Erilaisiin päätelaitteisiin ja vaihteleviin ympäristöihin tarkoitettujen helppokäyttöisten multimedia- ja mobiilipalvelujen kysyntä on jatkuvassa kasvussa. Multimediatietopankkiprojektissa esitetään kuinka multimediapalveluita voidaan toteuttaa integroidussa ympäristössä. Integroidulla ympäristöllä tässä työssä tarkoitetaan Internetin, mobiilien palvelujen, WAP:in, kämmentietokoneen, digitaalisen television sekä uusien multimediakännyköiden käyttöä multimediatietopankin tarjoamien palvelujen välittämisessä. Projekti on jaettu yksittäisiin lukuihin, joissa tarkoituksena on syventää multimediatietopankin yksityiskohtia sisällön tuottamisessa teknologian näkökannalta. Multimediatietokannan toteutuksessa mallinnetaan palvelun sisältö tietokantaan XHTML-muodossa mediaolioiden sisään sekä tallennetaan tietopankin metatietoa multimediarelaatiotietokantaan, josta on mahdollista hakea tietoa minkä tahansa päätelaitteen kyselyjen avulla.Tässä työssä keskitytään multimediatietokannan hallintajärjestelmän tehtäviin ja rakenteeseen, siihen miten multimediadata tallennetaan tietokantaan sekä siihen miten tietokannassa olevaa metatietoa haetaan käyttäen tietokannassa kehitettyjä hakumenetelmiä.

Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells.

Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy.

Beyond the net generation debate: A comparison of digital learners in face-to-face and virtual universities

In the last decade, an important debate has arisen about the characteristics of today"s students due to their intensive experience as users of ICT. The main belief is that frequent use of technologies in everyday life implies that competent users are able to transfer their digital skills to learning activities. However, empirical studies developed in different countries reveal similar results suggesting that the"digital native" label does not provide evidence of a better use of technology to support learning. The debate has to go beyond the characteristics of the new generation and focus on the implications of being a learner in a digitalised world. This paper is based on the hypothesis that the use of technology to support learning is not related to whether a student belongs to the Net Generation, but that it is mainly influenced by the teaching model. The study compares behaviour and preferences towards ICT use in two groups of university students: face-to-face students and online students. A questionnaire was applied to a sample of students from five universities with different characteristics (one offers online education and four offer face-to-face education with LMS teaching support). Findings suggest that although access to and use of ICT is widespread, the influence of teaching methodology is very decisive. For academic purposes, students seem to respond to the requirements of their courses, programmes, and universities. There is a clear relationship between students" perception of usefulness regarding certain ICT resources and their teachers" suggested uses of technologies. The most highly rated technologies correspond with those proposed by teachers. The study shows that the educational model (face-to-face or online) has a stronger influence on students" perception of usefulness regarding ICT support for learning than the fact of being a digital native.

Coarse-graining and thermodynamics in far-from-equilibrium systems

Lying at the core of statistical physics is the need to reduce the number of degrees of freedom in a system. Coarse-graining is a frequently-used procedure to bridge molecular modeling with experiments. In equilibrium systems, this task can be readily performed; however in systems outside equilibrium, a possible lack of equilibration of the eliminated degrees of freedom may lead to incomplete or even misleading descriptions. Here, we present some examples showing how an improper coarse-graining procedure may result in linear approaches to nonlinear processes, miscalculations of activation rates and violations of the fluctuation-dissipation theorem.

A copula-based method for synthetic microarray data generation

In this work, we propose a copula-based method to generate synthetic gene expression data that account for marginal and joint probability distributions features captured from real data. Our method allows us to implant significant genes in the synthetic dataset in a controlled manner, giving the possibility of testing new detection algorithms under more realistic environments.

Analysis of the mitochondrial DNA of Schizophrenia patients by next generation sequencing

Mitochondrial DNA (mtDNA), a maternally inherited 16.6-Kb molecule crucial for energy production, is implicated in numerous human traits and disorders. It has been hypothesized that the presence of mutations in the mtDNA may contribute to the complex genetic basis of schizophreniadisease, due to the evidence of maternal inheritance and the presence of schizophrenia symptoms in patients affected of a mitochondrial disorder related to a mtDNA mutation. The present project aims to study the association of variants of mitochondrial DNA (mtDNA), and an increased risk of schizophrenia in a cohort of patients and controls from the same population. The entire mtDNA of 55 schizophrenia patients with an apparent maternal transmission of the disease and 38 controls was sequenced by Next Generation Sequencing (Ion Torrent PGM, Life Technologies) and compared to the reference sequence. The current method for establishing mtDNA haplotypes is Sanger sequencing, which is laborious, timeconsuming, and expensive. With the emergence of Next Generation Sequencing technologies, this sequencing process can be much more quickly and cost-efficiently. We have identified 14 variants that have not been previously reported. Two of them were missense variants: MTATP6 p.V113M and MTND5 p.F334L ,and also three variants encoding rRNA and one variant encoding tRNA. Not significant differences have been found in the number of variants between the two groups. We found that the sequence alignment algorithm employed to align NGS reads played a significant role in the analysis of the data and the resulting mtDNA haplotypes. Further development of the bioinformatics analysis and annotation step would be desirable to facilitate the application of NGS in mtDNA analysis.