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PubMed1987

[Determination of human resources needs from task analysis].

This study describes the problem in the health field of integrating teaching and services, since there is no clear definition of the functions and tasks of manpower required in services nor a specification of how the manpower must be trained in the educational system. As an example of a systematic analysis of the problem, the study cites a research project carried out in Mexico, whose objectives were: to develop a technique to determine the kind and number of health personnel that must be trained; to provide a link between the training units and health service institutions and to try to integrate the curricula of each of the categories of health personnel. The subsequent stages give a detailed description of the task analysis process. At the educational level, the information obtained leads to the development of curricula more relevant to national needs; at the institutional level, it leads to the introduction of standards of evaluation for a better analysis of services and to the establishment of services with more extensive coverage. Another advantage is that the system can be used at the regional level without duplicating the model for each locality. In addition, the information produced is conducive to the development of curricula that provide for the lateral and vertical mobility of manpower.

Curriculum↗

PubMed2003

Coronary artery, aortic wall, and valvular calcification in nondialyzed individuals with type 2 diabetes and renal disease.

BACKGROUND: Individuals with end-stage renal disease (ESRD) have highly prevalent and severe vascular and valvular calcification. We undertook this study to test the hypothesis that vascular and valvular calcification begins and is often severe long before diabetic renal disease progresses to ESRD. METHODS: A total of 32 nondialyzed individuals with type 2 diabetes mellitus and diabetic renal disease (albumin excretion rate>30 microg/min) [mean glomerular filtration rate (GFR), 49.8 +/- 6.1 mL/min/1.73 m2] were identified and compared with a group of 18 normoalbuminuric diabetics. We used 3:1 matching to identify 95 nondiabetic controls without renal disease, matched for age, gender, ethnicity, and the presence/absence of dyslipidemia, hypertension, and known coronary artery disease (CAD). RESULTS: Using electron beam computed tomography (CT), the prevalence of coronary artery calcification was significantly greater among diabetic renal disease individuals (prevalence, 94% vs. 59%, P < 0.001; median score, 238 vs. 10, P < 0.001) than the nondiabetic controls. The coronary artery calcification scores were significantly more severe among diabetic renal disease individuals than either the diabetic or nondiabetic controls. Among individuals with diabetic renal disease, the coronary artery calcification and aortic wall calcification scores were several-fold greater among those with known CAD than among those without. There was also a significantly greater prevalence of aortic and mitral valve calcification among diabetic renal disease individuals than nondiabetic controls (aortic, 23% vs. 6%, P = 0.03; mitral, 25% vs. 2%, P < 0.001). Multivariate analysis using all three groups reproduced these findings and also consistently identified age and diabetic renal disease as additional predictors for the presence or severity of coronary artery and aortic wall calcification. CONCLUSION: In this first, systematic analysis among nondialyzed individuals with diabetic renal disease, these data demonstrate that vascular and valvular calcification is present and often severe long before the disease progresses to ESRD. The data also suggest that the coronary artery and aortic wall calcification may represent atherosclerosis.

Aortic Diseases↗

PubMed2000

Geometric analysis and comparison of protein-DNA interfaces: why is there no simple code for recognition?

Structural studies of protein-DNA complexes have shown that there are many distinct families of DNA-binding proteins, and have shown that there is no simple "code" describing side-chain/base interactions. However, systematic analysis and comparison of protein-DNA complexes has been complicated by the diversity of observed contacts, the sheer number of complexes currently available and the absence of any consistent method of comparison that retains detailed structural information about the protein-DNA interface. To address these problems, we have developed geometric methods for characterizing the local structural environment in which particular side-chain/base interactions are observed. In particular, we develop methods for analyzing and comparing spatial relationships at the protein-DNA interface. Our method involves attaching local coordinate systems to the DNA bases and to the C(alpha) atoms of the peptide backbone (these are relatively rigid structural units). We use these tools to consider how the position and orientation of the polypeptide backbone (with respect to the DNA) helps to determine what contacts are possible at any given position in a protein-DNA complex. Here, we focus on base contacts that are made in the major groove, and we use spatial relationships in analyzing: (i) the observed patterns of side-chain/base interactions; (ii) observed helix docking orientations; (iii) family/subfamily relationships among DNA-binding proteins; and (iv) broader questions about evolution, altered specificity mutants and the limits for the design of new DNA-binding proteins. Our analysis, which highlights differences in spatial relationships in different complexes and at different positions in a complex, helps explain why there is no simple, general code for protein-DNA recognition.

Computer Simulation↗

PubMed2003

Analysis of microsatellite instability in sporadic parathyroid adenomas.

Microsatellite instability (MSI) is the form of genomic instability associated with defective DNA mismatch repair (MMR) in human tumorigenesis. Recent reports have suggested a role for MSI in the pathogenesis of sporadic parathyroid adenomas. However, because of their small sample sizes and/or lack of systematic analysis of genome-wide MSI, these studies have not provided conclusive evidence that MMR defects are a common occurrence in parathyroid neoplasia. To further investigate whether MSI plays an important role in parathyroid tumorigenesis, we analyzed 49 sporadic parathyroid adenomas for MSI using a panel of 5 microsatellite DNA markers that has been recommended for sensitive detection of MSI by the NCI Workshop and validated in other tumor types. These microsatellite loci were amplified by PCR using fluorescent-labeled primers from the 49 samples of template tumor DNA and matching normal DNA isolated from the same patients' peripheral blood leukocytes. None of the 49 tumors showed evidence of MSI at any of the analyzed loci of the NCI marker panel. These observations strongly suggest that defective DNA MMR plays a minor role, if any, in the pathogenesis of sporadic parathyroid adenomas.

Adenoma↗

PubMed2004

[Use of information on nosocomial outbreaks for infection control].

Outbreaks of nosocomial infections can be associated with significant morbidity in the patients involved and require time, effort, and resources. In addition, they may lead to panic reactions among health care workers and patients as well as the community. However, their systematic analysis can contribute to knowledge about the sources and transmission of nosocomial infections and the best methods for prevention. Furthermore, the results of outbreak investigations may serve as a valuable tool for education. That is why a systematic register of nosocomial outbreaks would be a very useful instrument for people working in the field of nosocomial infection control. This article describes the need for a systematic collection of outbreaks published in the literature and an available possibility for filling this gap.

Adult↗

PubMed1997

A model for analysis of the nurse-patient interactive process (MAIP).

A model for analysis of the nurse-patient interactive process (MAIP), based on the analysis of the content of that interaction, is proposed as a method for determining appropriate psychosocial nursing diagnoses for the patient. The model focuses on the qualitative aspects of the phenomenon of interaction. The MAIP permits a systematic analysis of the nurse-patient interaction, and in turn will provide guidance for the professional in their actions in the interactive process.

Communication↗

PubMed2000

Prevention of venous thromboembolism after injury: an evidence-based report--part I: analysis of risk factors and evaluation of the role of vena caval filters.

BACKGROUND: Trauma surgeons use a variety of methods to prevent venous thromboembolism (VT). The rationale for their use frequently is based on conclusions from research on nontrauma populations. Existing recommendations are based on expert opinion and consensus statements rather than systematic analysis of the existing literature and synthesis of available data. The objective is to produce an evidence-based report on the methods of prevention of VT after injury. METHODS: A panel of 17 national authorities from the academic, private, and managed care sectors helped design and review the project. We searched three electronic databases (MEDLINE, EM-BASE, and Cochrane Controlled Trial Register) to identify articles relevant to four key questions: methods of prophylaxis, methods of screening, risk factors for VT, and the role of vena caval filters. The initial 4,093 titles yielded 73 articles for meta-analysis. A random-effects model was used for all pooled results. Study quality was evaluated by previously published quality scores. In this article (part I), we report on the question ranked by the experts as the most important, i.e., Which is the best method to prevent VT?, and also on the incidence of deep venous thrombosis and pulmonary embolism in trauma patients. RESULTS: The incidence of deep venous thrombosis and pulmonary embolism reported in different studies varies widely. The pooled rates are 11.8% for deep venous thrombosis and 1.5% for pulmonary embolism. Only a few randomized controlled trials have evaluated the methods of VT prophylaxis among trauma patients, and combining their data is difficult because of different designs and preventive methods used. The quality of most studies is low. Meta-analysis shows no evidence that low-dose heparin, mechanical prophylaxis, or low-molecular-weight heparin are more effective than no prophylaxis or each other. However, the 95% confidence intervals of many of the comparisons are wide; therefore, a clinically important difference may exist. CONCLUSION: The trauma literature on VT prophylaxis provides inconsistent data. There is no evidence that any existing method of VT prophylaxis is clearly superior to the other methods or even to no prophylaxis. Our results cast serious doubt on the existing policies on VT prophylaxis, and we call for a large, high-quality, multicenter trial that can provide definitive answers.

Evidence-Based Medicine↗

PubMed1999

Extradural temporal lobe retraction in the middle fossa approach to the internal auditory canal: biomechanical analysis.

HYPOTHESIS: The middle fossa (MF) approach is undergoing a marked resurgence in vestibular schwannoma surgery as a hearing conservation technique. It is widely recognized that the extradural temporal lobe retractors used in this procedure, despite their cleverness of design, could be improved. METHODS: To identify the characteristics of an ideal MF retractor, a systematic analysis of the safety and functionality of four commonly used retractors (House-Urban, Fisch, Garcia-Ibanez, and UCSF) in a human anatomical model was conducted. Intensity of temporal lobe compression, width of exposure, angle of visualization, obstruction to instrument access, ergonomic convenience of use, and adaptability to other subtemporal procedures (e.g. lesions of Meckel's cave and cavernous sinus) were quantified. RESULTS: Because the intracranial portions of the retractors are similar, the force transmitted to the brain differed little among the four retractors. Numerous differences were noted in the ergonomics of use and versatility of the various designs. CONCLUSIONS: The optimal MF retractor would incorporate the best features of each of the existing systems: the integral suction of the Garcia-Ibanez, the bone contour-following design of the Fisch retractor base, the unobtrusiveness and adaptability of the UCSF, and the three-plane adjustability of the vintage House-Urban. Evolution of an "ideal" MF retractor requires further technical refinements and the development of an experimental model of extradural brain retraction to assess the optimal strategy for obtaining exposure while minimizing the risk for temporal lobe injury.

Craniotomy↗

PubMed2026

DORSSAA: Drug-Target interactOmics Resource Based on Stability/Solubility Alteration Assay.

Advancements in high-throughput techniques such as Thermal Proteome Profiling and the high-throughput Proteome Integral Solubility Alteration assay have revolutionized our understanding of drug-protein interactions. Despite these innovations, the absence of an integrative platform for cross-study analysis of stability and solubility alteration data represents a significant bottleneck. To address this gap, we introduce Drug-target interactOmics Resource based on Stability/Solubility Alteration Assay (DORSSAA), an interactive and expandable web-based platform for the systematic analysis and visualization of proteome stability and solubility alteration assay datasets. Currently, DORSSAA features 1,135,985 records spanning 38 cell lines and organisms, 135 compounds, and 40,742 protein targets. Through its user-friendly interface, the resource supports comparative drug-protein interaction analysis and facilitates the discovery of actionable therapeutic targets. Through two case studies, methotrexate target profiling in A549 cells and combinatorial-therapy drug-target interactions in leukemia cell lines, we demonstrate DORSSAA's utility for identifying protein-drug interactions across diverse experimental contexts. This resource empowers researchers to accelerate drug discovery and enhance our understanding of protein behavior. Compared with data repositories and interaction databases, DORSSAA provides direct protein-level evidence of mechanisms of action with strict statistical control for each study. This enables more reliable identification of drug targets, off-target effects, and potential drug combinations.

Humans↗

PubMed2000

Systematic health, environment and safety activities: do they influence occupational environment, behaviour and health?

This study investigated the relationships between systematic health, environment and safety (HES) activities (as defined by Norway's Internal Control Regulation), the working environment, and workers' health-related behaviour and health. A questionnaire on systematic HES activities was answered by 237 managers of motor vehicle repair garages. A further questionnaire, on the working environment, health-related behaviour and health, was answered by workers (n = 2174) from the same garages. Using regression analysis, systematic HES activities were positively and significantly correlated with the following separate outcome variables, measured at an individual level: satisfaction with HES activities, physical working environment, social support, HES-related management support, health-related support, and control and workers' participation in activities related to occupational health. Workers at garages with systematic HES activities reported fewer musculoskeletal symptoms. Firm conclusions on the direction of causality are difficult to draw because of the cross-sectional design.

Accidents, Occupational↗

PubMed2005

Using Healthcare Failure Mode and Effect Analysis tool to review the process of ordering and administrating potassium chloride and potassium phosphate.

During the spring of 2004, in the Calgary Health Region (CHR) two critical incidents occurred involving patients receiving continuous renal replacement therapy (CRRT) in the intensive care unit (ICU). The outcome of these events resulted in the sudden death of both patients. The Department of Critical Care Medicine's Patient Safety and Adverse Events Team (PSAT), utilized the Healthcare Failure Mode and Effect Analysis (HFMEA) tool to review the process and conditions surrounding the ordering and administration of potassium chloride (KCI) and potassium phosphate (KPO4) in our ICUs. The HFMEA tool and the multidisciplinary team structure provided a solid framework for systematic analysis and prioritization of areas for improvement regarding the use of intravenous, high-concentration KCL and KPO4 in the ICU.

Aged, 80 and over↗

PubMed2001

Dopamine receptors in the brains of schizophrenia patients: a meta-analysis of the findings.

Controversy surrounds the question of whether there are dopamine (DA) receptor abnormalities in the brains of schizophrenia patients; in particular, whether DA receptors of the D2 family are elevated in density. Methodological factors and sample characteristics have been postulated to account for differences in study outcome, but there has been no systematic analysis of the contribution of these factors to study effect sizes. This meta-analysis of the research findings sought to determine the influence of methodologic factors and sample characteristics on the magnitude of diagnostic group differences in DA D2 density (Bmax) and affinity (Kd). The analysis suggests at least moderate effects, such that schizophrenia patients show an elevation in both values when compared to controls. These effects are amplified in medicated patients, but not solely attributable to antipsychotics. The group differences in DA D2 receptor density and affinity increase with age among nonmedicated patients. The use of a butyrophenone ligand also yields larger effects. It is concluded that a subgroup of schizophrenia patients manifests increased DA D2 receptor density and decreased receptor affinity. In the absence of medication, these changes may become more pronounced with age. Differences in study outcome are also partially due to methodologic factors, including the ligand.

Antipsychotic Agents↗

PubMed2003

Genome-wide analysis of microsatellite repeats in humans: their abundance and density in specific genomic regions.

BACKGROUND: Simple sequence repeats (SSRs) are found in most organisms, and occupy about 3% of the human genome. Although it is becoming clear that such repeats are important in genomic organization and function and may be associated with disease conditions, their systematic analysis has not been reported. This is the first report examining the distribution and density of simple sequence repeats (1-6 base-pairs (bp)) in the entire human genome. RESULTS: The densities of SSRs across the human chromosomes were found to be relatively uniform. However, the overall density of SSR was found to be high in chromosome 19. Triplets and hexamers were more predominant in exonic regions compared to intronic and intergenic regions, except for chromosome Y. Comparison of densities of various SSRs revealed that whereas trimers and pentamers showed a similar pattern (500-1,000 bp/Mb) across the chromosomes, di- tetra- and hexa-nucleotide repeats showed patterns of higher (2,000-3,000 bp/Mb) density. Repeats of the same nucleotide were found to be higher than other repeat types. Repeats of A, AT, AC, AAT, AAC, AAG, AGC, AAAC, AAAT, AAAG, AAGG, AGAT predominate, whereas repeats of C, CG, ACT, ACG, AACC, AACG, AACT, AAGC, AAGT, ACCC, ACCG, ACCT, CCCG and CCGG are rare. CONCLUSIONS: The overall SSR density was comparable in all chromosomes. The density of different repeats, however, showed significant variation. Tri- and hexa-nucleotide repeats are more abundant in exons, whereas other repeats are more abundant in non-coding regions.

Dinucleotide Repeats↗

PubMed1999

Bone metastasis: review and critical analysis of random allocation trials of local field treatment.

PURPOSE: Compare and contrast reports of random allocation clinical trials of local field radiation therapy of metastases to bone to determine the techniques producing the best results (frequency, magnitude, and duration of benefit), and relate these to the goals of complete relief of pain and prevention of disability for the remaining life of the patient. METHODS AND MATERIALS: Review all published reports of random allocation clinical trials, and perform a systematic analysis of the processes and outcomes of the several trial reports. RESULTS: All trials were performed on selected populations of patients with symptomatic metastases and most studies included widely diverse groups with regard to: (a) site of primary tumor, (b) location, extent, size, and nature of metastases, (c) duration of survival after treatment All trial reports lack sufficient detail for full and complete analysis. Much collected information is not now available for reanalysis and many important data sets were apparently never collected. Several of the variations in patient and tumor characteristics were found to be much more important than treatment dose in the outcome results. Treatment planning and delivery techniques were unsophisticated and probably resulted in a systematic delivery of less than the assigned dose to some metastases. In general the use and benefit of retreatment was greater in those patients who initially received lower doses but the basis and dose of retreatment was not documented. Follow-up of patients was varied with a large proportion of surviving patients lost to follow-up in several studies. The greatest difference in the reports is the method of calculation of results. The applicability of Kaplan-Meier actuarial analysis, censoring the lost and dead patients, as used in studies with loss to follow-up of a large number of patients is questionable. The censoring involved is "informative" (the processes of loss relate to the outcome) and not acceptable since it results in artificial elevation of the frequency of response. Overall, higher dose fractionated treatment regimens produced a better frequency, magnitude, and duration of response than lower dose single-fraction regimens. Relapse after initial response was frequent. The "median duration of relief" was much shorter than the "median duration of survival" post-treatment. Thus the "net pain relief" is far less than the goal of pain relief for the total duration of life after treatment. CONCLUSIONS: The pain relief obtained in all studies is poor and our care practices need to be improved. Many patients never achieved complete relief and for most who did, the duration of relief was much less than their period of survival after treatment. Higher dose, fractionated treatments produced a greater frequency, magnitude, and duration of response with an improved "net pain relief." Additional trials with selection of comparable cases, good definition of extent of disease, exemplary treatment, and complete follow-up are required.

Analgesics↗

PubMed2000

Systematic management and analysis of yeast gene expression data.

We report steps toward the systematic management, standardization, and analysis of functional genomics data. We developed the ExpressDB database for yeast RNA expression data and loaded it with approximately 17.5 million pieces of data reported by 11 studies with three different kinds of high-throughput RNA assays. A web-based tool supports queries across the data from these studies. We examined comparability of data by converting data from 9 studies (217 conditions) into mRNA relative abundance estimates (ERAs) and by clustering of conditions by ERAs. We report on generation of ERAs and condition clustering for non-microarray data (5 studies, 63 conditions) and describe initial attempts to generate microarray-based ERAs (4 studies, 154 conditions), which exhibit increased error, on our web site http://arep.med.harvard. edu/ExpressDB. We recommend standards for data reporting, suggest research into improving comparability of microarray data through quantifying and standardizing control condition RNA populations, and also suggest research into the calibration of different RNA assays. We introduce a model for a database that integrates different kinds of functional genomics data, Biomolecule Interaction, Growth and Expression Database (BIGED).

Computational Biology↗

PubMed2002

Predicting membrane protein types using residue-pair models based on reduced similarity dataset.

An algorithm to predict the membrane protein types based on the multi-residue-pair effect in the Markov model is proposed. For a newly constructed dataset of 835 membrane proteins with very low sequence similarity, the overall prediction accuracy has been achieved as high as 81.1% and 71.7% in the resubstitution and jackknife test, respectively, for a prediction of type I single-pass, type II single-pass, multi-pass membrane proteins, lipid chain-anchored and GPI-anchored membrane proteins. The improvement of about 11% in the jackknife test can be achieved compared with the component-coupled algorithm merely based on the amino acid composition (AAC approach). The improvement is also confirmed on a high similarity dataset and the other extrapolating test. The result implies that designing more incisive analysis tools, one should develop algorithms based on the representative dataset with lower sequence similarity. The present algorithm is useful to expedite the determination of the types and functions of new membrane proteins and may be useful for the systematic analysis of functional genome data in a large scale. The computer program is available on request.

Algorithms↗

PubMed1979

Measurement of regional cerebral blood flow by intravenous injection of Xe133.

Clearance of Xenon 133 following intravenous injection has been used to perform atraumatic measurements of regional cerebral blood flow (rCBF). rCBF was computed by a two-compartmental analysis of the clearance curves associated with a correction for Xenon recirculation based on the end-tidal tracer concentration. Direct comparison was made between the results of this method and those obtained from the reference intracarotid method. A systematic analysis has shown that the results of the non-invasive method depend on the part of the clearance curves chosen for computation of rCBF. The best concordance with the intra-carotid method was found when the analysed part of the curve was situated between 3 and 11 min. after the beginning of the injection. Under these conditions, the differences between the results from the two methods did not exceed 10% of the flow values even for low flows. Such precision makes the atraumatic measurements of rCBF by intravenous injection of Xenon valuable for clinical applications.

Cerebrovascular Circulation↗

PubMed1991

Phylogenetic analysis of Alloglossidium Simer, 1929 (Digenea: Plagiorchiiformes: Macroderoididae) with discussion of the origin of truncated life cycle patterns in the genus.

Alloglossidium comprises 9 species of North American plagiorchiiform digeneans using ictalurid catfish, freshwater crustacea, and hirudinid leeches as definitive hosts. Two hypotheses about the evolution of this array of definitive hosts were examined using phylogenetic systematic analysis. Two most parsimonious trees, based on 15 homologous series derived from morphological data, each indicated the 2 species utilizing ictalurid catfish definitive hosts are basal members of the group, whereas the 2 species using freshwater crayfish definitive hosts and the 5 utilizing leech definitive hosts each comprise relatively derived monophyletic sister groups. The results suggest that species using crustaceans as definitive hosts are derived by life cycle truncation, whereas those using leeches as definitive hosts appear to be derived through a switch from crustaceans to leeches.

Animals↗