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PubMed2003

Express: a Web-based technology to support human and computational experimentation.

Experimental cognitive psychology has been greatly assisted by the development of general computer-based experiment presentation packages. Typically, however, such packages provide little support for running participants on different computers. It is left to the experimenter to ensure that group sizes are balanced between conditions and to merge data gathered on different computers once the experiment is complete. Equivalent issues arise in the evaluation of parameterized computational models, where it is frequently necessary to test a model's behavior over a range of parameter values (which amount to between-subjects factors) and where such testing can be speeded up significantly by the use of multiple processors. This article describes Express, a Web-based technology for coordinating "clients" participants or computational models) and collating client data. The technology provides an experiment design editor, client coordination facilities (e.g., automated randomized assignment of clients to groups so that group sizes are balanced), general data collation and tabulation facilities, a range of basic statistical functions (which are constrained by the specified experimental design), and facilities to export data to standard statistical packages (such as SPSS). We report case studies demonstrating the utility of Express in both human and computational experiments. Express may be freely downloaded from the Express Web site (http://express.psyc.bbk.ac.uk/).

Computers↗
PubMed1994

Navigating the Brookhaven Protein Data Bank.

The Protein Data Bank maintained at Brookhaven National Laboratories has expanded to the point where even experienced users have difficulty understanding, exploring, and exploiting it. This paper describes a text file, an annotation of the Protein Data Bank, which helps users find information on related files and structures. The most recent version of this file includes information on homologous structures, including both sequence homology and structural homology. This file is in ASCII format and is available electronically. It is easy to search locally on any type of computer, using an editor or a pattern-matching program, such as grep.

Base Sequence↗
PubMedDate not supplied

Supporting faculty proposal development and publication.

The Hispanic Health Disparities Research Center, a collaborative venture between the University of Texas at El Paso and the University of Texas at Houston Health Sciences Center, supports the research capabilities of junior faculty through a variety of programs. Novice researchers often need practical help in conducting literature reviews, extracting data, evaluating the evidence, and formulating a research question of significant importance to be funded yet narrow enough to fit within the scope of the proposal. The authors discuss a successful proposal development program that includes mentoring by more senior faculty and structured sessions with a medical writer and editor.

Data Collection↗
PubMed2006

Authors and publication practices.

Although authors are usually considered to be the main perpetrators of research and publication misconduct, any person involved in the process has the potential to offend. Editors may breach ethical standards particularly with respect to conflicts of interest. In the same way that authors are now required to declare competing interests, notably commercial affiliations, financial interests and personal connections, so must editors. Editors can influence the chances of acceptance or rejection of a paper by reviewer selection. Reviewers should also be ready to disclose conflicts of interest. They must ensure that their reviews are evidence based and free from destructive criticism driven by self interest. It seems likely that ultimately we will progressively move towards 'open' peer review in which both the authors and the reviewers are known to each other. There is an urgent need for increased transparency of the relationship between editors and owners. The events of the last few years indicate that unless this interface is fully understood by all parties, conflicts may arise. There is also a need for a radical overhaul in the relationship between journals, journal editors and the biomedical industry. It is now increasingly accepted that all clinical trials should be registered in a centrally held database and that protocols should include the primary and secondary outcome measures and the intended approach to data analysis thereby avoiding opportunistic post hoc analyses. However, the even more radical proposal that journals should cease to publish clinical trials sponsored by industry deserves wider debate.

Authorship↗
PubMed1980

Pathology accessioning and retrieval system with encoding by computer (PARSEC). A microcomputer-based system for anatomic pathology featuring automated SNOP coding and multiple administrative functions.

A pathology accessioning and retrieval system with encoding by computer (PARSEC) has been developed, employing a relatively inexpensive microcomputer. PARSEC performs a variety of administrative functions for anatomic pathology, including accessioning of surgical specimens, storage of patient demographic information, editing, retrieval, and archiving of patient data, as well as CAP (college of American Pathologists) workload units, billing, and inventory functions for histopathology. In addition, appropriate gross and microscopic descriptions and pathologic diagnoses can be entered into the system by a text editor. Automatic assignment of SNOP (Systematized Nomenclature of Pathology) codes, is accomplished via an online SNOP lexicon, allowing the ultimate generation of completed surgical pathology reports. The data base management system employed makes optimum use of disk storage space, while permitting rapid data retrieval. Data file maintenance is automatically accomplished by the system, requiring no user intervention.

Computers↗
PubMed2005

Architectures and tools for innovative Health Information Systems: the Guide Project.

This paper describes the architecture of the Guide Project, a proposal for innovation of Health Information Systems, putting together medical and organizational issues through the Separation of Concerns paradigm. In particular, we focus on one building block of the architecture: the Guideline Management System handling the whole life cycle of computerized Clinical Practice Guidelines. The communication between the Guideline Management System and the other components of the project architecture is message-based, according to specific contracts that allow an easy integration of the components developed by different parties and, in particular, with legacy systems (i.e. existing electronic patient records). In turn, the Guideline Management System components are organized in a distributed architecture: an editor to formalize guidelines, a repository to store and publish them, an enactment system to implement guidelines instances in a multi-user environment and a reporting system able to completely trace any individual physician's guideline-based decision process. The repository is organized in different levels that can be international, national, regional, down to the specific health care organization, according to the healthcare delivery policy of a country. Different organizations can get Clinical Practice Guidelines from the repository, adapt and introduce them in clinical practice.

Computer Systems↗
PubMed1989

Multiple publication of reports of drug trials.

Fourty-four multiple publications of 31 comparative trials of nonsteroidal anti-inflammatory drugs in rheumatoid arthritis were examined for mutual agreement. Thirty-two of the papers were published in the same language as the primary version. Important discrepancies were seen in 14 trials, involving description of the study design in two, exclusion of protocol violators in two, inconsistency in the number of effect variables in five, in the number of side-effects in five, and in the significance level in one. In three articles the conclusion became more favourable for the new drug with time. Only half of the trials had the same first author and number of authors. For six trials, multiple publication was difficult to detect. Adherence to the manuscript guidelines published by the International Committee of Medical Journal Editors should diminish the risk of inflated meta-analyses, reference lists and curricula vitae, and inexplicable discrepancies in articles based on the same data.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2026

Structure and evolution-guided design of minimal RNA-guided nucleases.

The design of RNA-guided nucleases with properties not limited by evolution can expand programmable genome-editing capabilities. However, generating diverse multidomain proteins with robust enzymatic properties remains challenging. Here, we use a protein design strategy that couples a structure-guided inverse-folding model with evolution-informed residue constraints to generate active, divergent variants of TnpB, a minimal CRISPR-Cas12-like nuclease, termed SynTnpBs. High-throughput screening of artificial intelligence-generated variants yielded editors that retained or exceeded wild-type activity in bacterial, plant, and human cells. Cryo-electron microscopy-based structure determination of the most divergent variant revealed stabilizing contacts in the RNA-DNA interfaces across conformations, demonstrating the design potential of this approach. Together, these results establish a strategy for creating non-natural RNA-guided nucleases and conformationally active nucleic acid binders, enlarging the designable protein space.

Humans↗
PubMed2006

Biology of the rabbit.

In recognition of Dr. Nathan Brewer's many years of dedicated service to AALAS and the community of research animal care specialists, the premier issue of JAALAS includes the following compilation of Dr. Brewer's essays on rabbit anatomy and physiology. These essays were originally published in the ASLAP newsletter (formerly called Synapse), and are reprinted here with the permission and endorsement of that organization. I would like to thank Nina Hahn, Jane Lacher, and Nancy Austin for assistance in compiling these essays. Publishing this information in JAALAS allows Dr. Brewer's work to become part of the searchable literature for laboratory animal science and medicine and also assures that the literature references and information he compiled will not be lost to posterity. However, readers should note that this material has undergone only minor editing for style, has not been edited for content, and, most importantly, has not undergone peer review. With the agreement of the associate editors and the AALAS leadership, I elected to forego peer review of this work, in contradiction to standard JAALAS policy, based on the status of this material as pre-published information from an affiliate organization that holds the copyright and on the esteem in which we hold for Dr. Brewer as a founding father of our organization.

Animals↗
PubMed1983

Homology between an endogenous viral LTR and sequences inserted in an activated cellular oncogene.

Recently, some of us reported the detection and molecular cloning of a rearranged cellular oncogene, designated rc-mos, from a non-virally-induced mouse myeloma, XRPC24. Recombinant lambda phage DNA containing the rc-mos gene was active in transforming NIH 3T3 cells in a transfection assay, whereas recombinant DNA containing the unrearranged c-mos gene was not. In rc-mos, coding sequences from the 5' end of c-mos were found to have been displaced by a novel cellular element whose nucleotide sequence was reported. We now document the fact that a 349-base pair (bp) segment of the novel DNA immediately adjacent to the retained c-mos sequences in rc-mos has close homology with the long terminal repeat (LTR) of a known intracisternal A-particle gene. This homology was mentioned in Nature recently after it had been brought to the attention of the editors (N. Hozumi and R. Hawley, personal communication).

Base Sequence↗
PubMed1994

A quantitative comparison of DNA sequence assembly programs.

We have compared 11 sequence assembly programs for the accuracy and reproducibility with which they assemble DNA fragments into a completed sequence. To test the assemblers under controlled conditions, the rat multidrug resistance (RATMDRM) gene sequence was randomly divided into overlapping 200- to 400-base fragments. Various degrees of error, in the form of miss-identified bases, missed bases, and duplicated bases, were randomly added to these fragments. The probability of an error, and the type of error, was modified using an error distribution template that was developed by comparing the original fragments used to sequence RATMDRM with the final, edited sequence stored in GenBank. From 0 to 15% error was then added to independent sets of fragments, and assemblage was attempted. The quality of the assemblages was evaluated by comparing the number of differences between the assembled sequence and the original sequence. Tests were also done to determine if the order in which fragments were added to a project affected the final sequence and if the quality of assemblage was sequence dependent. Similar results were also obtained using other, unrelated sequences. The programs could be roughly divided into three groups based on the accuracy and reproducibility of assembly. Three (GCG, FAB, and AutoAssembler) consistently produced consensus sequences of low error and high reproducibility. Intermediate results were obtained with five other programs (Sequencher, AssemblyLIGN, XBAP, SeqMan, and AutoAssembler in a mode that made use of an external special processor). Less satisfactory results were obtained with the remaining three programs (GeneWorks, GENeration, and PC/Gene). The ability of the programs to edit the assembled sequence was also compared. Five of the programs were able to display and edit automatic sequencer trace files. The Sequencher program had a particularly well-designed sequence editor that allowed rapid examination and correction of assembly errors.

Animals↗
PubMed2006

Extending systematic reviews to include evidence on implementation: methodological work on a review of community-based initiatives to prevent injuries.

Unintentional injury is a leading cause of mortality and disability among young and old. While evidence about the effectiveness of interventions in reducing injuries is accumulating, reviews of this evidence frequently fail to include details of implementation processes. Our research, of which the work reported here formed a part, had two main objectives: (1) to identify evidence about the implementation of interventions aimed at reducing unintentional injuries amongst children and young people; and (2) to explore methods for systematically reviewing evidence on implementation. Existing systematic reviews of the effectiveness of interventions aiming to reduce unintentional injuries in children and young people formed the starting point for the work reported here. In summary, many of the published papers we identified contained little information on implementation processes and, even when these were discussed, the extent to which authors' claims were based on research evidence was unclear. On the basis of the studies we reviewed implementation data were insufficiently strong to provide a sound evidence base for practitioners and policymakers. Notwithstanding this, we identified valuable data about the context in which such initiatives are implemented and the type of factors that might impinge on implementation. This work has implications in three areas: (1) researchers with an interest in evidence-based public health could be encouraged to consider implementation issues in the design of intervention studies; (2) funding bodies could be encouraged to prioritise intervention studies using mixed methods that will enable researchers to consider effectiveness and implementation; (3) journal editors could work towards increasing the quality of reporting on implementation issues through the development of guidelines.

Accident Prevention↗
PubMed1985

Quality of controlled clinical trials. The case of imaging ultrasound in obstetrics: a review.

Randomized controlled trials are increasingly used to assess clinical practices in obstetrics and gynaecology. The strength of these studies is that they usually address the issue of selection bias satisfactorily. Yet, as with any form of scientific investigation, the randomized controlled trial has inherent limitations and is subject to flaws in its conduct. Using basic methodological criteria, this report assesses the quality of the four published controlled trials in which a policy of routine imaging ultrasonography in pregnancy was compared with a more restrictive policy. In addition, a pooled analysis using data from all four trials was conducted to illustrate how increasing the sample size may reveal differences between the two policies which remain undetected in trials using small samples. The researchers in these studies reached different conclusions as to the effectiveness of routine ultrasound screening. Taken together, these four trials provide valuable information about routine ultrasound screening but fail to demonstrate adequately the usefulness of imaging ultrasound as a screening procedure for all pregnant women. The assessment criteria presented here could be used by investigators, editors, referees and other readers as a guideline for assessing the quality of therapeutic studies upon which clinical practice should be based.

Clinical Trials as Topic↗
PubMed1994

[The application of graphic (visual) databases in neurology and neuropathology].

The possibilities and principles of creation in Windows environment of visual databases are described which could be used for elaboration of multimedial encyclopedia of selected nosological entities. Such databases are particularly important in education making possible finding of data and their relative comparison. The method of organization of "files" using standard programmes of Windows packs and the method of application of the technique of image coding for forms of symbolic icons are presented. Examples of graphic bases of neurological and neuropathological data evolved in Windows environment using professional application programmes (framing and retouching of images in graphic editors, coding of icons of macroinstruction of reading of information introduced into the relating visual database of the analysed cases.

Brain Diseases↗
PubMed2000

Guideline-based careflow systems.

This paper describes a methodology for achieving an efficient implementation of clinical practice guidelines. Three main steps are illustrated: knowledge representation, model simulation and implementation within a health care organisation. The resulting system can be classified as a 'guideline-based careflow management system'. It is based on computational formalisms representing both medical and health care organisational knowledge. This aggregation allows the implementation of a guideline, not only as a simple reminder, but also as an 'organiser' that facilitates health care processes. As a matter of fact, the system not only suggests the tasks to be performed, but also the resource allocation. The methodology initially comprehends a graphical editor, that allows an unambiguous representation of the guideline. Then the guideline is translated into a high-level Petri net. The resources, both human and technological necessary for performing guideline-based activities, are also represented by means of an organisational model. This allows the running of the Petri net for simulating the implementation of the guideline in the clinical setting. The purpose of the simulation is to validate the careflow model and to suggest the optimal resource allocation before the careflow system is installed. The final step is the careflow implementation. In this phase, we show that the 'workflow management' technology, widely used in business process automation, may be transferred to the health care setting. This requires augmenting the typical workflow management systems with the flexibility and the uncertainty management, typical of the health care processes. For illustrating the proposed methodology, we consider a guideline for the management of patients with acute ischemic stroke.

Artificial Intelligence↗
PubMed2004

Assessing the probability that a positive report is false: an approach for molecular epidemiology studies.

Too many reports of associations between genetic variants and common cancer sites and other complex diseases are false positives. A major reason for this unfortunate situation is the strategy of declaring statistical significance based on a P value alone, particularly, any P value below.05. The false positive report probability (FPRP), the probability of no true association between a genetic variant and disease given a statistically significant finding, depends not only on the observed P value but also on both the prior probability that the association between the genetic variant and the disease is real and the statistical power of the test. In this commentary, we show how to assess the FPRP and how to use it to decide whether a finding is deserving of attention or "noteworthy." We show how this approach can lead to improvements in the design, analysis, and interpretation of molecular epidemiology studies. Our proposal can help investigators, editors, and readers of research articles to protect themselves from overinterpreting statistically significant findings that are not likely to signify a true association. An FPRP-based criterion for deciding whether to call a finding noteworthy formalizes the process already used informally by investigators--that is, tempering enthusiasm for remarkable study findings with considerations of plausibility.

Analysis of Variance↗