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.

The TREAT-NMD DMD Global Database: Analysis of More than 7,000 Duchenne Muscular Dystrophy Mutations.

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

In search for better pharmacological prophylaxis for acute mountain sickness: looking in other directions.

Despite decades of research, the exact pathogenic mechanisms underlying acute mountain sickness (AMS) are still poorly understood. This fact frustrates the search for novel pharmacological prophylaxis for AMS. The prevailing view is that AMS results from an insufficient physiological response to hypoxia and that prophylaxis should aim at stimulating the response. Starting off from the opposite hypothesis that AMS may be caused by an initial excessive response to hypoxia, we suggest that directly or indirectly blunting-specific parts of the response might provide promising research alternatives. This reasoning is based on the observations that (i) humans, once acclimatized, can climb Mt Everest experiencing arterial partial oxygen pressures (PaO2 ) as low as 25 mmHg without AMS symptoms; (ii) paradoxically, AMS usually develops at much higher PaO2 levels; and (iii) several biomarkers, suggesting initial activation of specific pathways at such PaO2 , are correlated with AMS. Apart from looking for substances that stimulate certain hypoxia triggered effects, such as the ventilatory response to hypoxia, we suggest to also investigate pharmacological means aiming at blunting certain other specific hypoxia-activated pathways, or stimulating their agonists, in the quest for better pharmacological prophylaxis for AMS.

Angiotensin converting enzyme inhibitory peptides in Finnish cereals : a database survey

Selostus: Angiotensiini I -muuntavaa entsyymiä estävien peptidien aminohapposekvenssien esiintyminen viljan varastoproteiinien rakenteessa

Clinical effectiveness of direct anterior restorations-A meta-analysis.

OBJECTIVES: This is the first meta-analysis on the efficacy of composite resin restorations in anterior teeth. The objective of the present meta-analysis was to verify whether specific material classes, tooth conditioning methods and operational procedures influence the result for Class III and Class IV restorations. MATERIAL AND METHODS: The database SCOPUS and PubMed were searched for clinical trials on anterior resin composites without restricting the search to the year of publication. The inclusion criteria were: (1) prospective clinical trial with at least 2 years of observation; (2) minimal number of restorations at last recall=20; (3) report on drop-out rate; (4) report of operative technique and materials used in the trial, and (5) utilization of Ryge or modified Ryge evaluation criteria. For the statistical analysis, a linear mixed model was used with random effects to account for the heterogeneity between the studies. p-Values smaller than 0.05 were considered to be significant. RESULTS: Of the 84 clinical trials, 21 studies met the inclusion criteria, 14 of them for Class III restorations, 6 for Class IV restorations and 1 for closure of diastemata; the latter was included in the Class IV group. Twelve of the 21 studies started before 1991 and 18 before 2001. The estimated median overall success rate (without replacement) after 10 years for Class III composite resin restorations was 95% and for Class IV restorations 90%. The main reason for the replacement of Class IV restorations was bulk fractures, which occurred significantly more frequently with microfilled composites than with hybrid and macrofilled composites. Caries adjacent to restorations was infrequent in most studies and accounted only for about 2.5% of all replaced restorations after 10 years irrespective of the cavity class. Class III restorations with glass ionomer derivates suffered significantly more loss of anatomical form than did fillings with other types of material. When the enamel was acid-etched and no bonding agent was applied, significantly more restorations showed marginal staining and detectable margins compared to enamel etching with enamel bonding or the total etch technique; fillings with self-etching systems were in between of these two outcome variables. Bevelling of the enamel was associated with a significantly reduced deterioration of the anatomical form compared to no bevelling but not with less marginal staining or less detectable margins. The type of isolation (absolute/relative) had a statistically significant influence on marginal caries which, however, might be a random finding.

Anther culture properties of oat x wild red oat progenies and a search for RAPD markers associated with anther culture ability

Selostus: Ponsiviljeltävyys ja siihen liittyvät geenimerkit peltokauran ja susikauran risteytysjälkeläisissä

A Database of >20 keV Electron Green's Functions of Interplanetary Transport at 1 AU

We use interplanetary transport simulations to compute a database of electron Green's functions, i.e., differential intensities resulting at the spacecraft position from an impulsive injection of energetic (>20 keV) electrons close to the Sun, for a large number of values of two standard interplanetary transport parameters: the scattering mean free path and the solar wind speed. The nominal energy channels of the ACE, STEREO, and Wind spacecraft have been used in the interplanetary transport simulations to conceive a unique tool for the study of near-relativistic electron events observed at 1 AU. In this paper, we quantify the characteristic times of the Green's functions (onset and peak time, rise and decay phase duration) as a function of the interplanetary transport conditions. We use the database to calculate the FWHM of the pitch-angle distributions at different times of the event and under different scattering conditions. This allows us to provide a first quantitative result that can be compared with observations, and to assess the validity of the frequently used term beam-like pitch-angle distribution.

All-sky search algorithms for monochromatic signals in bar gravitational wave detector data

In this paper we design and develop several filtering strategies for the analysis of data generated by a resonant bar gravitational wave (GW) antenna, with the goal of assessing the presence (or absence) therein of long-duration monochromatic GW signals, as well as the eventual amplitude and frequency of the signals, within the sensitivity band of the detector. Such signals are most likely generated in the fast rotation of slightly asymmetric spinning stars. We develop practical procedures, together with a study of their statistical properties, which will provide us with useful information on the performance of each technique. The selection of candidate events will then be established according to threshold-crossing probabilities, based on the Neyman-Pearson criterion. In particular, it will be shown that our approach, based on phase estimation, presents a better signal-to-noise ratio than does pure spectral analysis, the most common approach.

Design and Testing of Database Libraries

Nokia Push To Talk järjestelmä tarjoaa uuden kommunikointimetodin tavallisen puhelun oheen. Yksi tärkeimmistä uuden järjestelmän ominaisuuksista on puhelunmuodostuksen nopeus. Lisäksi järjestelmän tulee olla telekommunikaatiojärjestelmien yleisten periaatteiden mukainen, mahdollisimman stabiili ja skaalautuva, jotta järjestelmä olisi mahdollisimman vikasietoinen ja laajennettavissa. Diplomityön päätavoite on esitellä "C++"-tietokantakirjastojen suunnittelua ja testausta. Aluksi tutkitaan tietokantajärjestelmien problematiikkaa alkaen tietokantajärjestelmän valinnasta ja huomioiden erityisesti nopeuskriteerit. Sitten esitellään kaksi teknistä toteutusta kahta "C++"-tietokantakirjastoa varten ja pohditaan joitakin vaihtoehtoisia toteutustapoja.

Evolutionary computing in search-based software engineering

This master’s thesis aims to study and represent from literature how evolutionary algorithms are used to solve different search and optimisation problems in the area of software engineering. Evolutionary algorithms are methods, which imitate the natural evolution process. An artificial evolution process evaluates fitness of each individual, which are solution candidates. The next population of candidate solutions is formed by using the good properties of the current population by applying different mutation and crossover operations. Different kinds of evolutionary algorithm applications related to software engineering were searched in the literature. Applications were classified and represented. Also the necessary basics about evolutionary algorithms were presented. It was concluded, that majority of evolutionary algorithm applications related to software engineering were about software design or testing. For example, there were applications about classifying software production data, project scheduling, static task scheduling related to parallel computing, allocating modules to subsystems, N-version programming, test data generation and generating an integration test order. Many applications were experimental testing rather than ready for real production use. There were also some Computer Aided Software Engineering tools based on evolutionary algorithms.

Standardized evaluation methodology and reference database for evaluating IVUS image segmentation

This paper describes an evaluation framework that allows a standardized and quantitative comparison of IVUS lumen and media segmentation algorithms. This framework has been introduced at the MICCAI 2011 Computing and Visualization for (Intra)Vascular Imaging (CVII) workshop, comparing the results of eight teams that participated. We describe the available data-base comprising of multi-center, multi-vendor and multi-frequency IVUS datasets, their acquisition, the creation of the reference standard and the evaluation measures. The approaches address segmentation of the lumen, the media, or both borders; semi- or fully-automatic operation; and 2-D vs. 3-D methodology. Three performance measures for quantitative analysis have been proposed. The results of the evaluation indicate that segmentation of the vessel lumen and media is possible with an accuracy that is comparable to manual annotation when semi-automatic methods are used, as well as encouraging results can be obtained also in case of fully-automatic segmentation. The analysis performed in this paper also highlights the challenges in IVUS segmentation that remains to be solved.

A systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression.

BACKGROUND: Lithium augmentation of antidepressants for treatment of unipolar major depression was one of the first adjunctive strategies based on a neuropharmacologic rationale. Randomized controlled trials supported its efficacy but most trials added lithium to tricyclic antidepressants (TCAs). Despite its efficacy, use of lithium augmentation remains infrequent. The current systematic review and meta-analysis examines the efficacy of lithium augmentation as an adjunct to second generation antidepressants as well as to TCAs and considers reasons for its infrequent use. METHOD: A systematic search of Medline and the Cochrane Clinical Trials database was performed. Randomized, placebo-controlled trials of lithium augmentation were selected. A fixed-effects meta-analysis was performed. Odds ratios for response were calculated for each treatment-control contrast, for the trials grouped by type of initial antidepressant (TCA or second generation antidepressant), and as a meta-analytic summary for all treatments combined. RESULTS: Nine trials that included 237 patients were selected. The odds ratio for response to lithium vs. placebo in all contrasts combined was 2.89 (95% CI 1.65, 5.05, z=3.72, p=0.0002). Heterogeneity was very low, I(2)=0%. Adjunctive lithium was effective with TCAs (7 contrasts) and with second generation agents (3 contrasts). Discontinuation due to adverse events was infrequent and did not differ between lithium and placebo. LIMITATIONS: The meta-analysis is limited by the small size and number of trials and limited data for treatment resistant patients. CONCLUSIONS: Adjunctive lithium appears to be as effective for second generation antidepressants as it was for the tricyclics.

Database Marketing from the Customer Relationship ManagementPerspective

Tietokantamarkkinointi voi olla vain apuväline markkinointitoimenpiteiden suorittamisessa, mutta se voidaan toisaalta nähdä myös olennaisena osana asiakassuhdehallintaa. Tietokantamarkkinointi asiakassuhdehallinnan näkökulmasta tähtää asiakastyytyväisyyteen ja asiakasuskollisuuteen, sekä asiakassuhteen tuottavuuteen ja kannattavuuteen, mikä voidaan saavuttaa tehokkaan tiedonhallinnan avulla. Tämä mahdollistaa räätälöityjen toimenpiteiden suorittamisen ja tehostaa kohdentamista ja segmentointia, myös asiakkaiden tuottavuuden perusteella. Normatiivinen case-tutkimus, joka tehtiin Alankomaissa Eurooppalaisessa tietotekniikan lisäarvoa tuottavassa jälleenmyyntikanavassa osoittaa, että tietokantamarkkinointi etenkin asiakas- suhdehallinnan näkökulmasta olisi sopiva keino lisätä asiakastyytyväisyyttä ja –tuottavuutta. Se myös tehostaisi sisäisiä tietovirtoja ja markkinointitoimenpiteitä, kuten esimerkiksi markkinointiviestintää, kampanjanhallintaa ja myyntiprosesseja yritysten välisessä kaupankäynnissä.

Trust region versus line search for computing the optical flow

We consider the numerical treatment of the optical flow problem by evaluating the performance of the trust region method versus the line search method. To the best of our knowledge, the trust region method is studied here for the first time for variational optical flow computation. Four different optical flow models are used to test the performance of the proposed algorithm combining linear and nonlinear data terms with quadratic and TV regularization. We show that trust region often performs better than line search; especially in the presence of non-linearity and non-convexity in the model.