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PubMed1999

Systematic reviews: a logical methodological extension of evidence-based medicine.

Academic Emergency Medicine is interested in publishing systematic reviews (also known as meta-analyses) containing explicit, quantitative compilations of valid, critically appraised evidence targeted at topics relevant to the science and practice of emergency medicine. This article presents a strategy for the performance and reporting of systematic reviews, based on established recommendations. A well-performed systematic review of the literature may provide clinically relevant information otherwise unobtainable, and has potential to alter patient care. Systematic reviews are logical methodological extensions of evidence-based medicine.

Data Collection↗

PubMed1990

'Lost and found': some logical and methodological limitations of self-report questionnaires as tools to study cognitive ageing.

Laboratory tests show a decline in memory efficiency with age, but may not reflect highly practiced everyday memory skills. Self-rating questionnaires probe memory efficiency in everyday life, but seven logical and methodological problems ambiguate interpretation of the data they yield. To explore these problems, 442 volunteers aged from 50 to 85 years were given the AH 4 IQ tests, Mill Hill Vocabulary Tests, Beck Depression Inventory (BDI), Broadbent Cognitive Failures Questionnaire (CFQ), Sunderland & Harris Memory Failure Questionnaire (MFQ), the 'Lost and Found' Questionnaire (LF, a new domain-specific probe of the variety, frequency and aetiologies of losses of possessions) and two laboratory memory tests. All self-rating questionnaire scores correlated modestly with each other. Counter-intuitively, individuals over 60 years old reported fewer lapses on the LF and on the CFQ. No SRQ scores correlated with performance on laboratory tasks. CFQ scores did not correlate with IQ test scores but high IQ test scorers reported greater recent decline in memory efficiency (MFQ) and greater current frequency of losses of objects (LF). CFQ and LF scores correlated positively with Beck Depression Inventory scores, suggesting some common loading for poor self-regard. The results suggest that subjective self-ratings cannot reflect absolute levels of everyday competence, but only the relative success of individuals' adaptations to idiosyncratic environments which, as they age, may change faster than their abilities. However, besides exposing the limitations of self-report techniques, these analyses also suggest practical ways of adapting and using SRQs which may allow us to gain better insights into changes and individual differences in functional efficiency in everyday life.

Aged↗

PubMedDate not supplied

Modification of the fault logic circuit of a high-energy linear accelerator to accommodate selectively coded, large-field wedges.

A modification to the fault logic circuit that controls the collimator (COLL) fault is described. This modification permits the use of large-field wedges by adding an additional input into the reference voltage that determines the fault condition. The resistor controlling the amount of additional voltage is carried on board each wedge, within the wedge plug. This allows each wedge to determine its own, individual field size limit. Additionally, if no coding resistor is provided, the factory-supplied reference voltage is used, which sets the maximum allowable field size to 15 cm. This permits the use of factory-supplied wedges in conjunction with selected, large-field wedges, allowing proper sensing of the field size maximum in all conditions.

Equipment Safety↗

PubMed2001

Logic gates and computation from assembled nanowire building blocks.

Miniaturization in electronics through improvements in established "top-down" fabrication techniques is approaching the point where fundamental issues are expected to limit the dramatic increases in computing seen over the past several decades. Here we report a "bottom-up" approach in which functional device elements and element arrays have been assembled from solution through the use of electronically well-defined semiconductor nanowire building blocks. We show that crossed nanowire p-n junctions and junction arrays can be assembled in over 95% yield with controllable electrical characteristics, and in addition, that these junctions can be used to create integrated nanoscale field-effect transistor arrays with nanowires as both the conducting channel and gate electrode. Nanowire junction arrays have been configured as key OR, AND, and NOR logic-gate structures with substantial gain and have been used to implement basic computation.

Journal Article↗

PubMed1998

Genomic cis-regulatory logic: experimental and computational analysis of a sea urchin gene.

The genomic regulatory network that controls gene expression ultimately determines form and function in each species. The operational nature of the regulatory programming specified in cis-regulatory DNA sequence was determined from a detailed functional analysis of a sea urchin control element that directs the expression of a gene in the endoderm during development. Spatial expression and repression, and the changing rate of transcription of this gene, are mediated by a complex and extended cis-regulatory system. The system may be typical of developmental cis-regulatory apparatus. All of its activities are integrated in the proximal element, which contains seven target sites for DNA binding proteins. A quantitative computational model of this regulatory element was constructed that explicitly reveals the logical interrelations hard-wired into the DNA.

Animals↗

PubMed1988

ATP-liganded form of aspartate transcarbamoylase, the logical regulatory target for allosteric control in divergent bacterial systems.

In Escherichia coli, the mechanism for regulatory control of aspartate transcarbamoylase is clear; CTP allosterically inhibits catalysis in direct competition with ATP. However, both CTP and ATP may be activators or may have no effect on aspartate transcarbamoylases from other enteric bacteria. A common regulatory logic observed was that the ATP-activated enzymes were rendered less active as the result of competition with CTP, regardless of the independent effects.

Adenosine Triphosphate↗

PubMed1990

Evaluation of the LOGIC system for the rapid identification of members of the family Enterobacteriaceae in the clinical microbiology laboratory.

The LOGIC identification system (J.D. Perry, M. Ford, N. Hjersing, and F.K. Gould, J. Clin. Pathol. 41: 1010-1012, 1988) for gram-negative rods, performed with microdilution plates instead of tubes, was evaluated for strains isolated from all tested specimens except those obtained from stools (for which a different strategy was followed). Systematically extended with the oxidase test and lactose fermentation, it proved to be very reliable and extremely simple and economical.

Bacteriological Techniques↗

PubMed2026

Repurposing anti-phage defenses to differentially arrest the viral lifecycle reveals the regulatory logic of a parasitic satellite.

Mobile genetic elements frequently encode defense mechanisms to protect their bacterial hosts from viral attack. In Vibrio cholerae, these defensive elements include phage-inducible chromosomal island-like elements (PLEs), which are phage satellites that act as highly specialized parasites of the lytic phage ICP1. While PLE transcriptional activation upon ICP1 infection is known to be temporally regulated, the underlying regulatory logic and dependencies on the progression of the phage's developmental program required for activation remain unclear. In this study, we took a novel approach to define these dependencies by introducing independent anti-phage defense systems, BREX and DarTG, as molecular roadblocks to impede the ICP1 lifecycle. We discovered that, for both ICP1 and PLE, late-stage gene expression is fundamentally uncoupled from genome replication, representing a striking departure from the standard paradigm for double-stranded DNA phages. While BREX restricts ICP1 to an immediate-early transcriptional state that stalls PLE activation, DarTG allows the phage to execute its full transcriptional cascade despite the total block in DNA replication. This permissive environment provides the necessary cue(s) for complete PLE induction, revealing that robust PLE activation is profoundly dependent on the transcriptional progression of its helper phage.IMPORTANCEBacteria and their viruses (phages) are locked in perpetual evolutionary conflict. Some bacteria harbor phage satellites, specialized parasites that are activated to hijack the phage's components to spread all the while inhibiting viral production. While some satellites respond to a single viral trigger, the regulation of many satellites, including clinically relevant phage-inducible chromosomal island-like elements (PLEs) in Vibrio cholerae, remains poorly understood. Here, we used bacterial defense systems as molecular roadblocks to probe how PLE activation depends on its helper phage. We found that severe disruptions to viral transcription stall PLE activation. Unexpectedly, both the virus and the satellite can execute their full transcriptional programs even when DNA replication is completely blocked, challenging a fundamental paradigm in virology. These insights reveal a sophisticated level of phage-satellite coordination, illustrating how satellite activation is tightly linked to the transcriptional state of its helper phage, a dependency that ultimately drives the dissemination of mobile genetic elements.

Vibrio cholerae↗

PubMed2000

Development of a logically devised line drawing atlas for grading of knee osteoarthritis.

OBJECTIVES: To (a) develop an atlas of line drawings for the assessment and grading of narrowing and osteophyte (that is, changes of osteoarthritis) on knee radiographs, and (b) compare the performance of this atlas with that of the standard Osteoarthritis Research Society (OARS) photographic atlas of radiographs. METHODS: Normal joint space widths (grade 0) for the medial and lateral tibiofemoral and medial and lateral patellofemoral compartments were obtained from a previous community study. Grades 1-3 narrowing in each compartment was calculated separately for men and women, grade 3 being bone on bone, grades 1 and 2 being two thirds and one third the value of grade 0. Maximum osteophyte size (grade 3) for each of eight sites was determined from 715 bilateral knee x ray films obtained in a knee osteoarthritis (OA) hospital clinic; grades 1-2 were calculated as two thirds and one third reductions in the area of grade 3. Drawings for narrowing and osteophyte were presented separately. 50 sets of bilateral knee x ray radiographs (standing, extended anteroposterior; flexed skyline) showing a spectrum of OA grades were scored by three observers, twice using the OARS atlas and twice using the drawn atlas. RESULTS: Intraobserver and interobserver reproducibility was similar and generally good with both atlases, though varied according to site. All three observers preferred the line drawing atlas for ease and convenience of use. Higher scores for patellofemoral narrowing and lower scores for osteophyte, especially medial femoral osteophyte, were seen using the line drawing atlas, showing that the two atlases are not equivalent instruments. CONCLUSION: A logically derived line drawing atlas for grading of narrowing and osteophyte at the knee has been produced. The atlas showed comparable reproducibility with the OARS atlas, but was discordant in several aspects of grading. Such a system has several theoretical and practical advantages and should be considered for use in knee OA studies.

Adult↗

PubMedDate not supplied

Development of the Logical Observation Identifier Names and Codes (LOINC) vocabulary.

The LOINC (Logical Observation Identifier Names and Codes) vocabulary is a set of more than 10,000 names and codes developed for use as observation identifiers in standardized messages exchanged between clinical computer systems. The goal of the study was to create universal names and codes for clinical observations that could be used by all clinical information systems. The LOINC names are structured to facilitate rapid matching, either automated or manual, between local vocabularies and the universal LOINC codes. If LOINC codes are used in clinical messages, each system participating in data exchange needs to match its local vocabulary to the standard vocabulary only once. This will reduce both the time and cost of implementing standardized interfaces. The history of the development of the LOINC vocabulary and the methodology used in its creation are described.

Classification↗

PubMedDate not supplied

Evaluation of the clinical LOINC (Logical Observation Identifiers, Names, and Codes) semantic structure as a terminology model for standardized assessment measures.

OBJECTIVE: The purpose of this study was to test the adequacy of the Clinical LOINC (Logical Observation Identifiers, Names, and Codes) semantic structure as a terminology model for standardized assessment measures. METHODS: After extension of the definitions, 1, 096 items from 35 standardized assessment instruments were dissected into the elements of the Clinical LOINC semantic structure. An additional coder dissected at least one randomly selected item from each instrument. When multiple scale types occurred in a single instrument, a second coder dissected one randomly selected item representative of each scale type. RESULTS: The results support the adequacy of the Clinical LOINC semantic structure as a terminology model for standardized assessments. Using the revised definitions, the coders were able to dissect into the elements of Clinical LOINC all the standardized assessment items in the sample instruments. Percentage agreement for each element was as follows: component, 100 percent; property, 87.8 percent; timing, 82.9 percent; system/sample, 100 percent; scale, 92.6 percent; and method, 97.6 percent. DISCUSSION: This evaluation was an initial step toward the representation of standardized assessment items in a manner that facilitates data sharing and re-use. Further clarification of the definitions, especially those related to time and property, is required to improve inter-rater reliability and to harmonize the representations with similar items already in LOINC.

Databases, Factual↗

PubMed2002

Surveillance of surgical training by detailed electronic registration of logical components.

OBJECTIVE: To obtain detailed information about the degree of surgical trainee supervision and delegation of procedures in a subspecialised department. DESIGN: Operative procedures and their logical components were recorded in a database constructed in Microsoft Access. Information about operating surgeon and assistants and their grade was registered prospectively over 12 months. SUBJECTS AND METHODS: A total of 1250 intermediate or major procedures were performed by eight consultants, one staff specialist, four senior registrars, three specialist registrars, and five registrars. MAIN MEASURE: Number of components performed by surgeons in each grade and the degree of supervision and delegation. RESULTS: Eight hundred and eighty five of the operations were elective, while 365 were done as emergency procedures. Emergency procedures were far more often done by surgeons in training than by a staff surgeon, while the opposite was true for elective operations. Out of 323 elective operations done by surgeons in training, 189 were done under supervision (58.5%), while 119 out of 276 emergency operations done by surgeons in training were supervised (43.1%; p=0.0002). One hundred and twenty eight of 638 (20%) open abdominal operations were done by the most junior surgeons, and yet they closed 36% of all abdominal wounds. Although the most junior surgeons only served as operating surgeons in 39 of 334 bowel operations (12%), they constructed 24% of all stomas, and 20% of all anastomoses. Registrars and specialist registrars never constructed stomas or anastomoses without supervision. CONCLUSION: Detailed information about individual and general training and supervision was achieved by a simple registration. Significant additional information was obtained about the extent of delegation of components compared with standard registration of operative procedures.

Databases, Factual↗

PubMed2003

Towards discovering structural signatures of protein folds based on logical hidden Markov models.

With the growing number of determined protein structures and the availability of classification schemes, it becomes increasingly important to develop computer methods that automatically extract structural signatures for classes of proteins. In this paper, we introduce and apply a new Machine Learning technique, Logical Hidden Markov Models (LOHMMs), to the task of finding structural signatures of folds according to the classification scheme SCOP. Our results indicate that LOHMMs are applicable to this task and possess several advantages over other approaches.

Algorithms↗

PubMed2003

Towards a broad-coverage biomedical ontology based on description logics.

We describe an ontology engineering methodology by which conceptual knowledge is extracted from an informal medical thesaurus (UMLS) and automatically converted into a formal description logics system (LOOM). Our approach consists of four steps: concept definitions are automatically generated from the UMLS, integrity checking of taxonomic and partonomic hierarchies is performed by LOOM's terminological classifier, cycles and inconsistencies are eliminated, as well as incremental refinement of the evolving knowledge base is performed by a domain expert. We report on experiments with a very large knowledge base composed of 164,000 concepts and 76,000 relations.

Artificial Intelligence↗

PubMed2003

A methodology to migrate the gene ontology to a description logic environment using DAML+OIL.

The Gene Ontology Next Generation Project (GONG) is developing a staged methodology to evolve the current representation of the Gene Ontology into DAML+OIL in order to take advantage of the richer formal expressiveness and the reasoning capabilities of the underlying description logic. Each stage provides a step level increase in formal explicit semantic content with a view to supporting validation, extension and multiple classification of the Gene Ontology. The paper introduces DAML+OIL and demonstrates the activity within each stage of the methodology and the functionality gained.

Classification↗

PubMed1993

The logic and role of meta-analysis in clinical research.

The term meta-analysis refers to the quantitative combination of data from independent trials. Where the result of such combination is a descriptive summary of the weight of the available evidence, the exercise is of undoubted value. Attempts to apply inferential methods, however, are subject to considerable methodological and logical difficulties. The selection and quality of the trials included, population bias, and the specification of the population to which inference may properly be made are problems to which no satisfactory solutions have been proposed. Insightful quantitative description ought not to differ materially from inferential conclusions; where discrepancies exist the inferential techniques should be regarded with extreme caution.

Bias↗

PubMed2005

How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation.

Recognition of temperature is a critical element of sensory perception and allows us to evaluate both our external and internal environments. In vertebrates, the somatosensory system can discriminate discrete changes in ambient temperature, which activate nerve endings of primary afferent fibers. These thermosensitive nerves can be further segregated into those that detect either innocuous or noxious (painful) temperatures; the latter neurons being nociceptors. We now know that thermosensitive afferents express ion channels of the transient receptor potential (TRP) family that respond at distinct temperature thresholds, thus establishing the molecular basis for thermosensation. Much is known of those channels mediating the perception of noxious heat; however, those proposed to be involved in cool to noxious cold sensation, TRPM8 and TRPA1, have only recently been described. The former channel is a receptor for menthol, and links the sensations provided by this and other cooling compounds to temperature perception. While TRPM8 almost certainly performs a critical role in cold signaling, its part in nociception is still at issue. The latter channel, TRPA1, is activated by the pungent ingredients in mustard and cinnamon, but has also been postulated to mediate our perception of noxious cold temperatures. However, a number of conflicting reports have suggested that the role of this channel in cold sensation needs to be confirmed. Thus, the molecular logic for the perception of cold-evoked pain remains enigmatic. This review is intended to summarize our current understanding of these cold thermoreceptors, as well as address the current controversy regarding TRPA1 and cold signaling.

Animals↗

PubMed1980

Causal models and logical inference in epidemiological psychiatry.

The paper examines the nature of causality and how the concept can be interpreted and used in epidemiological psychiatry. The relationship of causality to logical relations is reiterated, and it is emphasized that these relationships in their pure form cannot apply to any one cause of an effect which is the outcome of several causes. In such a case the relation of the cause to the effect is one of weak implication. The fact of weak implication opens the door to the construction of certain causal models, and the possibilities afforded by this situation are illustrated by reference to the work of Brown et al (1975). Weak implication may be an intransitive relationship, and this is shown to invalidate certain ways of testing such models and the conclusions which arise from them.

Female↗