Uses and misuses of the STROBE statement: bibliographic study

Objectives Appropriate reporting is central to the application of findings from research to clinical practice. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations consist of a checklist of 22 items that provide guidance on the reporting of cohort, case-control and cross-sectional studies, in order to facilitate critical appraisal and interpretation of results. STROBE was published in October 2007 in several journals including The Lancet, BMJ, Annals of Internal Medicine and PLoS Medicine. Within the framework of the revision of the STROBE recommendations, the authors examined the context and circumstances in which the STROBE statement was used in the past. Design The authors searched the Web of Science database in August 2010 for articles which cited STROBE and examined a random sample of 100 articles using a standardised, piloted data extraction form. The use of STROBE in observational studies and systematic reviews (including meta-analyses) was classified as appropriate or inappropriate. The use of STROBE to guide the reporting of observational studies was considered appropriate. Inappropriate uses included the use of STROBE as a tool to assess the methodological quality of studies or as a guideline on how to design and conduct studies. Results The authors identified 640 articles that cited STROBE. In the random sample of 100 articles, about half were observational studies (32%) or systematic reviews (19%). Comments, editorials and letters accounted for 15%, methodological articles for 8%, and recommendations and narrative reviews for 26% of articles. Of the 32 observational studies, 26 (81%) made appropriate use of STROBE, and three uses (10%) were considered inappropriate. Among 19 systematic reviews, 10 (53%) used STROBE inappropriately as a tool to assess study quality. Conclusions The STROBE reporting recommendations are frequently used inappropriately in systematic reviews and meta-analyses as an instrument to assess the methodological quality of observational studies.

Hybridization and Introgression Between Native and Alien Species

Human activities, such intentional and unintentional transplantations, and habitat alterations including the establishment of migration corridors, generate increasing opportunities for formerly allopatric taxa to meet and to hybridize. There is indeed increasing evidence that these introduced plant and animal taxa (including crop plants and domesticated animal taxa) frequently hybridize with native relatives and with other introduced taxa, leading to a growing concern that these hybridizations may compromise the genetic integrity of native taxa to the point of causing extinctions (Abbott 1992; Rhymer and Simberloff 1996; Levin et al. 1996; Ellstrand and Schierenbeck 2000; Vilà et al. 2000). A decade ago, Rhymer and Simberloff (1996) stated in their review on this topic that the known cases are probably just the tip of the iceberg.Using the search term ‘hybridization and introgression’, the Web of Science database yields a total of 1,178 research articles, of which 935 (or 80 %) have been published after 1995 (Fig. 16.1). Indeed, the evidence for natural and man-induced hybridization and introgression appears to have increased exponentially these last few years.

REST-based sensor networks with OData

RESTful services gained a lot of attention recently, even in the enterprise world, which is traditionally more web-service centric. Data centric RESfFul services, as previously mainly known in web environments, established themselves as a second paradigm complementing functional WSDL-based SOA. In the Internet of Things, and in particular when talking about sensor motes, the Constraint Application Protocol (CoAP) is currently in the focus of both research and industry. In the enterprise world a protocol called OData (Open Data Protocol) is becoming the future RESTful data access standard. To integrate sensor motes seamlessly into enterprise networks, an embedded OData implementation on top of CoAP is desirable, not requiring an intermediary gateway device. In this paper we introduce and evaluate an embedded OData implementation. We evaluate the OData protocol in terms of performance and energy consumption, considering different data encodings, and compare it to a pure CoAP implementation. We were able to demonstrate that the additional resources needed for an OData/JSON implementation are reasonable when aiming for enterprise interoperability, where OData is suggested to solve both the semantic and technical interoperability problems we have today when connecting systems

Concepts of Bitemporal Database Theory and the Evolution of Web-Documents

A vast amount of temporal information is provided on the Web. Even though many facts expressed in documents are time-related, the temporal properties of Web presentations have not received much attention. In database research, temporal databases have become a mainstream topic in recent years. In Web documents, temporal data may exist as meta data in the header and as user-directed data in the body of a document. Whereas temporal data can easily be identified in the semi-structured meta data, it is more difficult to determine temporal data and its role in the body. We propose procedures for maintaining temporal integrity of Web pages and outline different approaches of applying bitemporal data concepts for Web documents. In particular, we regard desirable functionalities of Web repositories and other Web-related tools that may support the Webmasters in managing the temporal data of their Web documents. Some properties of a prototype environment are described.

Can a novel web-based computer test predict poor simulated driving performance? A pilot study with healthy and cognitive-impaired participants

BACKGROUND Driving a car is a complex instrumental activity of daily living and driving performance is very sensitive to cognitive impairment. The assessment of driving-relevant cognition in older drivers is challenging and requires reliable and valid tests with good sensitivity and specificity to predict safe driving. Driving simulators can be used to test fitness to drive. Several studies have found strong correlation between driving simulator performance and on-the-road driving. However, access to driving simulators is restricted to specialists and simulators are too expensive, large, and complex to allow easy access to older drivers or physicians advising them. An easily accessible, Web-based, cognitive screening test could offer a solution to this problem. The World Wide Web allows easy dissemination of the test software and implementation of the scoring algorithm on a central server, allowing generation of a dynamically growing database with normative values and ensures that all users have access to the same up-to-date normative values. OBJECTIVE In this pilot study, we present the novel Web-based Bern Cognitive Screening Test (wBCST) and investigate whether it can predict poor simulated driving performance in healthy and cognitive-impaired participants. METHODS The wBCST performance and simulated driving performance have been analyzed in 26 healthy younger and 44 healthy older participants as well as in 10 older participants with cognitive impairment. Correlations between the two tests were calculated. Also, simulated driving performance was used to group the participants into good performers (n=70) and poor performers (n=10). A receiver-operating characteristic analysis was calculated to determine sensitivity and specificity of the wBCST in predicting simulated driving performance. RESULTS The mean wBCST score of the participants with poor simulated driving performance was reduced by 52%, compared to participants with good simulated driving performance (P<.001). The area under the receiver-operating characteristic curve was 0.80 with a 95% confidence interval 0.68-0.92. CONCLUSIONS When selecting a 75% test score as the cutoff, the novel test has 83% sensitivity, 70% specificity, and 81% efficiency, which are good values for a screening test. Overall, in this pilot study, the novel Web-based computer test appears to be a promising tool for supporting clinicians in fitness-to-drive assessments of older drivers. The Web-based distribution and scoring on a central computer will facilitate further evaluation of the novel test setup. We expect that in the near future, Web-based computer tests will become a valid and reliable tool for clinicians, for example, when assessing fitness to drive in older drivers.

Transesophageal echocardiography in cryptogenic stroke and patent foramen ovale: analysis of putative high-risk features from the risk of paradoxical embolism database

BACKGROUND Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS), although the pathogenicity of a discovered PFO in the setting of CS is typically unclear. Transesophageal echocardiography features such as PFO size, associated hypermobile septum, and presence of a right-to-left shunt at rest have all been proposed as markers of risk. The association of these transesophageal echocardiography features with other markers of pathogenicity has not been examined. METHODS AND RESULTS We used a recently derived score based on clinical and neuroimaging features to stratify patients with PFO and CS by the probability that their stroke is PFO-attributable. We examined whether high-risk transesophageal echocardiography features are seen more frequently in patients more likely to have had a PFO-attributable stroke (n=637) compared with those less likely to have a PFO-attributable stroke (n=657). Large physiologic shunt size was not more frequently seen among those with probable PFO-attributable strokes (odds ratio [OR], 0.92; P=0.53). The presence of neither a hypermobile septum nor a right-to-left shunt at rest was detected more often in those with a probable PFO-attributable stroke (OR, 0.80; P=0.45; OR, 1.15; P=0.11, respectively). CONCLUSIONS We found no evidence that the proposed transesophageal echocardiography risk markers of large PFO size, hypermobile septum, and presence of right-to-left shunt at rest are associated with clinical features suggesting that a CS is PFO-attributable. Additional tools to describe PFOs may be useful in helping to determine whether an observed PFO is incidental or pathogenically related to CS.

Towards an Emergent Semantic Web

In his in uential article about the evolution of the Web, Berners-Lee [1] envisions a Semantic Web in which humans and computers alike are capable of understanding and processing information. This vision is yet to materialize. The main obstacle for the Semantic Web vision is that in today's Web meaning is rooted most often not in formal semantics, but in natural language and, in the sense of semiology, emerges not before interpretation and processing. Yet, an automated form of interpretation and processing can be tackled by precisiating raw natural language. To do that, Web agents extract fuzzy grassroots ontologies through induction from existing Web content. Inductive fuzzy grassroots ontologies thus constitute organically evolved knowledge bases that resemble automated gradual thesauri, which allow precisiating natural language [2]. The Web agents' underlying dynamic, self-organizing, and best-effort induction, enable a sub-syntactical bottom up learning of semiotic associations. Thus, knowledge is induced from the users' natural use of language in mutual Web interactions, and stored in a gradual, thesauri-like lexical-world knowledge database as a top-level ontology, eventually allowing a form of computing with words [3]. Since when computing with words the objects of computation are words, phrases and propositions drawn from natural languages, it proves to be a practical notion to yield emergent semantics for the Semantic Web. In the end, an improved understanding by computers on the one hand should upgrade human- computer interaction on the Web, and, on the other hand allow an initial version of human- intelligence amplification through the Web.

PDB-Explorer: a web-based interactive map of the protein data bank in shape space

Background The RCSB Protein Data Bank (PDB) provides public access to experimentally determined 3D-structures of biological macromolecules (proteins, peptides and nucleic acids). While various tools are available to explore the PDB, options to access the global structural diversity of the entire PDB and to perceive relationships between PDB structures remain very limited. Methods A 136-dimensional atom pair 3D-fingerprint for proteins (3DP) counting categorized atom pairs at increasing through-space distances was designed to represent the molecular shape of PDB-entries. Nearest neighbor searches examples were reported exemplifying the ability of 3DP-similarity to identify closely related biomolecules from small peptides to enzyme and large multiprotein complexes such as virus particles. The principle component analysis was used to obtain the visualization of PDB in 3DP-space. Results The 3DP property space groups proteins and protein assemblies according to their 3D-shape similarity, yet shows exquisite ability to distinguish between closely related structures. An interactive website called PDB-Explorer is presented featuring a color-coded interactive map of PDB in 3DP-space. Each pixel of the map contains one or more PDB-entries which are directly visualized as ribbon diagrams when the pixel is selected. The PDB-Explorer website allows performing 3DP-nearest neighbor searches of any PDB-entry or of any structure uploaded as protein-type PDB file. All functionalities on the website are implemented in JavaScript in a platform-independent manner and draw data from a server that is updated daily with the latest PDB additions, ensuring complete and up-to-date coverage. The essentially instantaneous 3DP-similarity search with the PDB-Explorer provides results comparable to those of much slower 3D-alignment algorithms, and automatically clusters proteins from the same superfamilies in tight groups. Conclusion A chemical space classification of PDB based on molecular shape was obtained using a new atom-pair 3D-fingerprint for proteins and implemented in a web-based database exploration tool comprising an interactive color-coded map of the PDB chemical space and a nearest neighbor search tool. The PDB-Explorer website is freely available at www.​cheminfo.​org/​pdbexplorer and represents an unprecedented opportunity to interactively visualize and explore the structural diversity of the PDB.

Stereoselective virtual screening of the ZINC database using atom pair 3D-fingerprints

Background Tools to explore large compound databases in search for analogs of query molecules provide a strategically important support in drug discovery to help identify available analogs of any given reference or hit compound by ligand based virtual screening (LBVS). We recently showed that large databases can be formatted for very fast searching with various 2D-fingerprints using the city-block distance as similarity measure, in particular a 2D-atom pair fingerprint (APfp) and the related category extended atom pair fingerprint (Xfp) which efficiently encode molecular shape and pharmacophores, but do not perceive stereochemistry. Here we investigated related 3D-atom pair fingerprints to enable rapid stereoselective searches in the ZINC database (23.2 million 3D structures). Results Molecular fingerprints counting atom pairs at increasing through-space distance intervals were designed using either all atoms (16-bit 3DAPfp) or different atom categories (80-bit 3DXfp). These 3D-fingerprints retrieved molecular shape and pharmacophore analogs (defined by OpenEye ROCS scoring functions) of 110,000 compounds from the Cambridge Structural Database with equal or better accuracy than the 2D-fingerprints APfp and Xfp, and showed comparable performance in recovering actives from decoys in the DUD database. LBVS by 3DXfp or 3DAPfp similarity was stereoselective and gave very different analogs when starting from different diastereomers of the same chiral drug. Results were also different from LBVS with the parent 2D-fingerprints Xfp or APfp. 3D- and 2D-fingerprints also gave very different results in LBVS of folded molecules where through-space distances between atom pairs are much shorter than topological distances. Conclusions 3DAPfp and 3DXfp are suitable for stereoselective searches for shape and pharmacophore analogs of query molecules in large databases. Web-browsers for searching ZINC by 3DAPfp and 3DXfp similarity are accessible at www.gdb.unibe.ch webcite and should provide useful assistance to drug discovery projects.

A systematic review on the innervation of peri-implant tissues with special emphasis on the influence of implant placement and loading protocols

OBJECTIVES To systematically review the available literature on the influence of dental implant placement and loading protocols on peri-implant innervation. MATERIAL AND METHODS The database MEDLINE, Cochrane, EMBASE, Web of Science, LILACS, OpenGrey and hand searching were used to identify the studies published up to July 2013, with a populations, exposures and outcomes (PEO) search strategy using MeSH keywords, focusing on the question: Is there, and if so, what is the effect of time between tooth extraction and implant placement or implant loading on neural fibre content in the peri-implant hard and soft tissues? RESULTS Of 683 titles retrieved based on the standardized search strategy, only 10 articles fulfilled the inclusion criteria, five evaluating the innervation of peri-implant epithelium, five elucidating the sensory function in peri-implant bone. Three included studies were considered having a methodology of medium quality and the rest were at low quality. All those papers reported a sensory innervation around osseointegrated implants, either in the bone-implant interface or peri-implant epithelium, which expressed a particular innervation pattern. Compared to unloaded implants or extraction sites without implantation, a significant higher density of nerve fibres around loaded dental implants was confirmed. CONCLUSIONS To date, the published literature describes peri-implant innervation with a distinct pattern in hard and soft tissues. Implant loading seems to increase the density of nerve fibres in peri-implant tissues, with insufficient evidence to distinguish between the innervation patterns following immediate and delayed implant placement and loading protocols. Variability in study design and loading protocols across the literature and a high risk of bias in the studies included may contribute to this inconsistency, revealing the need for more uniformity in reporting, randomized controlled trials, longer observation periods and standardization of protocols.

The European Narcolepsy Network (EU-NN) database.

Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease-specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web-based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials.