SEARCH · Search PubMed

Results for “cost of complexity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources

PubMed2003

A practical approach to fire hazard analysis for offshore structures.

Offshore quantitative risk assessments (QRA) have historically been complex and costly. For large offshore design projects, the level of detail required for a QRA is often not available until well into the detailed design phase of the project. In these cases, the QRA may be unable to provide timely hazard understanding. As a result, the risk reduction measures identified often come too late to allow for cost effective changes to be implemented. This forces project management to make a number of difficult or costly decisions. This paper demonstrates how a scenario-based approached to fire risk assessment can be effectively applied early in a project's development. The scenario or design basis fire approach calculates the consequence of a select number of credible fire scenarios, determines the potential impact on the platform process equipment, structural members, egress routes, safety systems, and determines the effectiveness of potential options for mitigation. The early provision of hazard data allows the project team to select an optimum design that is safe and will meet corporate or regulatory risk criteria later in the project cycle. The focus of this paper is on the application of the scenario-based approach to gas jet fires. This paper draws on recent experience in the Gulf of Mexico (GOM) and other areas to outline an approach to fire hazard analysis and fire hazard management for deep-water structures. The methods presented will include discussions from the recent June 2002 International Workshop for Fire Loading and Response.

Facility Design and Construction↗

PubMed2000

Genetic typing and HIV-1 diagnosis by using 96 capillary array electrophoresis and ultraviolet absorption detection.

Current high-throughput approaches to the analysis of PCR products are based primarily on electrophoretic separation and laser-excited fluorescence detection. We show that capillary array electrophoresis can be applied to HIV-1 diagnosis and D1S80 VNTR genetic typing based simply on UV absorption detection. The additive contribution of each base pair to the total absorption signal provides adequate detection sensitivity for analyzing most PCR products. Not only is the use of specialized and potentially toxic fluorescent labels eliminated, but also the complexity and cost of the instrumentation are greatly reduced.

Electrophoresis, Capillary↗

PubMed1999

Routine analysis of amphetamine class drugs as their naphthaquinone derivatives in human urine by high-performance liquid chromatography.

We describe a simple HPLC method which is suitable for the routine confirmation of immunoassay positive amphetamine urine samples. The precolumn derivisation method employing sodium naphthaquinone-4-sulphonate was found to have adequate sensitivity, selectivity and precision for the measurement of amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxyethylamphetamine (MDEA) at 500 microg/l cutoff level for confirmatory analysis of amphetamines in urine. The specificity of the method is enhanced by detecting the peaks at two different wavelengths. The ratios of the peak heights measured at the two wavelengths were different for each of the 5 amphetamines analysed. There was no interference from other phenylethylamine analogues that are commonly found in "over the counter" preparations. The HPLC method is compared to a commercial TLC system for detecting amphetamines in urine of drug abusers attending drug rehabilitation programmes. The HPLC confirmatory method described is a viable alternative to GC or to the more complex and costly GC-MS techniques for confirming amphetamine, methamphetamine, MDMA, MDA and MDEA in urine of drug abusers especially when used in a clinical care setting.

Amphetamines↗

PubMed2003

A qualitative study of physicians' perceptions of three decision aids.

The study objective was to investigate physicians' perceptions of three patient decision aids (DA). Semi-structured telephone interviews were conducted with 20 family physicians and 12 gynecologists about a DA for women considering long-term hormone replacement therapy; with 16 respirologists about a DA for the use of intubation and mechanical ventilation for patients with severe chronic obstructive pulmonary disease; and with 19 physicians (geriatricians, gastroenterologists, internists) about a DA for long-term placement of feeding tubes in the elderly. Participants were identified by a snowball sampling technique. The interviews were analyzed using standard qualitative methods. Most participants (81%) indicated some willingness to use the DAs. The characteristics of the DA viewed positively included it being: balanced, well organized, a useful tool, evidence-based, improves decision making process and multimedia. Some of the negative characteristics were stated as: too complex, the cost, the availability, only appropriate for certain groups of patients, and time consuming. The DAs were acceptable to most participants. Perceived positive and negative factors were similar for all DAs. Uptake of decision aids may be facilitated if physicians have an opportunity to examine and try them, and if they can have unfettered access to them for distribution purposes.

Attitude of Health Personnel↗

PubMed2000

Knowledge discovery and knowledge validation in intensive care.

Operational protocols are a valuable means for quality control. However, developing operational protocols is a highly complex and costly task. We present an integrated approach involving both intelligent data analysis and knowledge acquisition from experts that support the development of operational protocols. The aim is to ensure high quality standards for the protocol through empirical validation during the development, as well as lower development cost through the use of machine learning and statistical techniques. We demonstrate our approach of integrating expert knowledge with data driven techniques based on our effort to develop an operational protocol for the hemodynamic system.

Artificial Intelligence↗

PubMed2001

Emerging protein delivery methods.

The efficient and safe delivery of therapeutic proteins is the key to commercial success and, in some cases, the demonstration of efficacy in current and future biotechnology products. Numerous delivery technologies and companies have evolved over the past year. To critically evaluate the available options, each method must be assessed in terms of how easily it can be manufactured, impact on protein quality, bioavailability, and toxicity. Recent advances in depot delivery systems have, for the most part, overcome all of these obstacles except for complex and costly manufacturing. On the other hand, pulmonary delivery usually involves efficient manufacturing, but low protein bioavailability resulting in higher doses compared with injections. Although recent advances in transdermal and oral delivery have been significant, both of these delivery routes require logarithmic increases in bioavailability to make them viable candidates for commercialization. In the next few years, protein delivery for commercial products will probably be limited to injection devices, depot systems and pulmonary administration.

Biological Availability↗

PubMed1998

Ability of alternative indices of insulin sensitivity to predict cardiovascular risk: comparison with the "minimal model". Insulin Resistance Atherosclerosis Study (IRAS) Investigators.

INTRODUCTION: Although recognition of insulin sensitivity as a risk factor for cardiovascular disease is growing, a deeper understanding of its role is impeded by the cost and complexity of currently available measures. This report evaluates previously described alternative indices of insulin sensitivity with the goal of identifying a reliable, but logistically simpler, alternative. METHODS: Data from 1460 participants in the Insulin Resistance Atherosclerosis Study (IRAS) were used to assess the proportion of the relationship between a recognized measure of insulin sensitivity (Bergman's SI) and cardiovascular risk factors that is contained in each of nine alternative measures. RESULTS: A number of the alternative indices contained a substantial proportion of the information available in Bergman's SI. The Galvin's index and the homeostasis model were most promising. However, there remained a significant amount of the information in Bergman's SI that was not contained in any of the alternative indices. DISCUSSION: There are simpler alternative indices of insulin sensitivity for use in epidemiological studies, but each alternative is associated with some loss of information. It may be possible that this loss can be overcome with an increased sample size; however, using the alternative indices may also confound the assessment of insulin sensitivity with other underlying factors (i.e., hyperinsulinemia). The alternative indices are not recommended for the clinical assessment of insulin sensitivity for an individual patient or subject.

Cardiovascular Diseases↗

PubMed2001

Directed evolution of new glycosynthases from Agrobacterium beta-glucosidase: a general screen to detect enzymes for oligosaccharide synthesis.

BACKGROUND: Oligosaccharide synthesis is becoming increasingly important to industry as diverse therapeutic roles for these molecules are discovered. The chemical synthesis of oligosaccharides on an industrial scale is often prohibitively complex and costly. An alternative, that of enzymatic synthesis, is limited by the difficulty of obtaining an appropriate enzyme. A general screen for enzymes that catalyze the synthesis of the glycosidic bond would enable the identification and engineering of new or improved enzymes. RESULTS: Glycosynthases are nucleophile mutants of retaining glycosidases that efficiently catalyze the synthesis of the glycosidic linkage by condensing an activated glycosyl fluoride donor with a suitable acceptor sugar. A novel agar plate-based coupled-enzyme screen was developed (using a two-plasmid system) and used to select an improved glycosynthase from a library of mutants. CONCLUSIONS: Plate-based coupled-enzyme screens of this type are extremely valuable for identification of functional synthetic enzymes and can be applied to the evolution of a range of glycosyl transferases.

Directed Molecular Evolution↗

PubMed2001

Exact mass measurements for confirmation of pesticides and herbicides determined by liquid chromatography/time-of-flight mass spectrometry.

The accuracy and precision of exact mass measurements are determined using positive ions formed in the electrospray of 10 nonvolatile or thermally unstable carbamate, urea, and thiourea pesticides and herbicides. Environmentally significant approximately 7-ng quantities of the analytes were separated with microbore liquid chromatography, and the exact mass measurements were made in real time with a benchtop time-of-flight mass spectrometer. The positive ion electrospray mass spectra of the analytes generally consist of one or a few ions which are usually adducts of the molecule with a proton, a sodium ion, or an ammonium ion. Fragment ions and the rich mass spectra typical of electron ionization (EI) are generally not produced in the soft electrospray ionization process. Confirmation of the identity of a nonvolatile pesticide or herbicide depends largely on the masses of the few ions formed and the retention time, which can vary with chromatography conditions. Identifications of these analytes in environmental or other samples are less certain than identifications of volatile pesticides determinated by gas chromatography and EI mass spectrometry. The benchtop time-of-flight mass spectrometer was equipped with an electrostatic mirror, and resolving powers of 3500-5000 were routinely obtained and used for these exact mass measurements. This type of mass spectrometer is significantly less costly and complex than other types of mass spectrometers with exact mass measurement capabilities. The mean errors from three replicate exact mass measurements of the 10 test analytes were in the range of 0-5.4 parts-per-million. Potential interferences from substances with similar exact masses were evaluated.

Calibration↗

PubMed1996

A mechanism for reducing entropic cost of induced fit in protein--RNA recognition.

Induced fit has been postulated to be an important component of ligand interactions with proteins, including protein-DNA interactions. We imagined that the entropic cost of induced fit might be highly dependent on the local protein sequence context around critical contact residues. To investigate this question, we analyzed the basis for active or inactive phenotypes found in a library of combinatorial sequence variants of a surface-located helix-loop peptide which is essential for the anticodon-binding activity of a class I tRNA synthetase. Molecular dynamics simulations of the domain encompassing the helix-loop peptide of the active variants consistently demonstrated fixation of the local motion of five critical (for function) residues which are highly mobile in inactive variants. Additional experiments with other rationally chosen mutants extended the correlation between phenotype and motion of these vital residues. We propose that the need for fixation of local motion is an important constraint on sequences of surface peptides which form parts of RNA-binding sites. The fixation of motion of critical residues in the unbound protein can significantly reduce the entropic cost of complex formation by induced fit.

Amino Acid Sequence↗

PubMed2002

Simulation analysis of pneumatic tube systems.

Pneumatic tube systems play an important material handling role in many hospitals. These systems are costly and complex to design and operate, yet little exists in the way of analytical methodologies for them. We present a decision support framework based on defining relevant system performance metrics, traffic analysis reporting, as well as discrete event simulation modeling. We have used this approach to analyze numerous pneumatic tubes systems in the United States and present a representative case study from a large tertiary care hospital. Our general approach can be generalized to other computer controlled hospital operational systems such as elevators, track vehicles, automatic guided vehicles, workflow enabled processes, and laboratory automation systems.

Computer Simulation↗

PubMed1997

The limitations of decision trees and automatic learning in real world medical decision making.

The decision tree approach is one of the most common approaches in automatic learning and decision making. The automatic learning of decision trees and their use usually show very good results in various "theoretical" environments. But in real life it is often impossible to find the desired number of representative training objects for various reasons. The lack of possibilities to measure attribute values, high cost and complexity of such measurements, and unavailability of all attributes at the same time are the typical representatives. For this reason we decided to use the decision trees not for their primary task--the decision making--but for outlining the most important attributes. This was possible by using a well-known property of the decision trees--their knowledge representation, which can be easily understood by humans. In a delicate field of medical decision making, we cannot allow ourselves to make any inaccurate decisions and the "tips," provided by the decision trees, can be of a great assistance. Our main interest was to discover a predisposition to two forms of acidosis: the metabolic acidosis and respiratory acidosis, which can both have serious effects on child's health. We decided to construct different decision trees from a set of training objects. Instead of using a test set for evaluation of a decision tree, we asked medical experts to take a closer look at the generated trees. They examined and evaluated the decision trees branch by branch. Their comments show that trees generated from the available training set mainly have surprisingly good branches, but on the other hand, for some, no medical explanation could be found.

Acidosis↗

PubMed2001

Cataract surgery and effectiveness. 2. An index approach for the measurement of output and efficiency of cataract surgery at different surgery departments.

PURPOSE: To describe a model for comparing the performance of cataract surgery among ophthalmology departments in terms of economic efficiency. METHODS: An index approach for the measurement of outcome of cataract surgery is modeled. The index approach uses information about activities and difficulties in daily life as well as visual acuity and age. The change in activities and difficulties after surgery is expressed by changes in distances, and an overall index score is calculated as ratios of values to distances. Values to distances are estimated as solutions to linear programming problems. Index scores are calculated for two groups of patients, those with an ocular co-morbidity and those without. Economic efficiency is also estimated by use of an index approach. In the estimation of efficiency we use the calculated index scores of outcome of surgery as a measure of output of the ophthalmology department. Four different departments providing cataract surgery are compared. RESULTS: The studied departments showed differences to a great extent when traditional measures of cataract surgery outcomes were used. These differences changed when the outcomes were compared by use of index scores. When economic efficiency was calculated the difference between the departments was further reduced and only one department was considered inefficient according to the model. CONCLUSION: An index approach was used to study outcomes of cataract surgery and economic efficiency in four departments. This approach takes into account the complexity of cost in relation to feasible outcome. The ranking between the departments described by traditional methods turned out differently using the model.

Cataract Extraction↗

PubMed2002

Cyclosporine microemulsion (Neoral) absorption profiling and sparse-sample predictors during the first 3 months after renal transplantation.

UNLABELLED: Recent data suggest that optimal cyclosporine (CsA) exposure early post-transplant significantly reduces the risk of acute graft rejection. They indicate that trough level monitoring is inadequate for precise concentration-controlled therapy, and suggest that absorption profiling may offer a superior approach for guiding clinical immunosuppression with Neoral. An international, prospective, multicenter study examined the feasibility, accuracy, precision and clinical utility of cyclosporine microemulsion (Neoral) absorption profiling in de novo renal transplant recipients receiving basiliximab immunoprophylaxis and cyclosporine microemulsion maintenance immunosuppression. The nested pharmacokinetic study reported here was conducted in 4 study centers in which full (11-point) pharmacokinetic profiles were performed on days 3, 7, 14 and 84 post-transplant to examine absorption profile and absorption efficiency, and to determine optimal sparse-sampling pharmacokinetic methods to predict Neoral exposure. Twenty-four patients had complete 12-h pharmacokinetic (PK) data on all 4 sampling days. Area under the time-concentration curve (AUC) over the first 4 h of the 12-h dosage interval (AUC[0-4]) and AUC over the entire 12-h dosage interval (AUC[0-12]) reached 3803 +/- 1033 and 7462 +/- 2120 microg.h/L respectively, by day 3, remained stable throughout the first 2 weeks, and declined to 2310 +/- 698 and 4062 +/- 1158 microg.h/L by day 84 (p < 0.001). AUC[0-4], capturing the drug absorption phase, represented 52% of the AUC[0-12] values across the four PK study days (mean R2 > 0.90). Between-patient variability was highest for C0 and C1 (mean coefficient of variation [c.v.] 36-47%), and lower for C2 (mean c.v. 28%) and subsequent time-points during the dosing interval. Mean relative CsA absorption, measured by dose- and weight-adjusted AUC[0-4] and AUC[0-12], increased significantly over time. The dose- and weight-corrected AUC[0-4h] (DWC.AUC[0-4]) rose by over 100% (p < 0.001) from 753 +/- 202 at day 3 to 905 +/- 232 at day 7, 1080 +/- 330 at day 14 and 1521 +/- 316 by day 84, while the dose-and weight-corrected AUC[0-12h] (DWC.AUC[0-12]) rose by over 80% (p < 0.001) from 1477 +/- 390 microg.h/L/ mg/kg on day 3, to 1721 +/- 426 on day 7, 2086 +/- 478 on day 14 and 2690 +/- 602 on day 84 (p < 0.001). Relative CsA absorption varied over 5-fold between patients at day 3, but patients tended to remain within the same quartiles over time. Sparse-sample modeling identified optimum 3-point, 2-point and 1-point predictors for AUC[0-4] and AUC[0-12]. C2 was the most accurate and robust .1-point predictor for AUC[0-4] (mean R2: 0.80), while C3 was superior for AUC[0-12] (mean R2: 0.75). C0 was not a good predictor of either AUC[0-4] or AUC[0-12] (mean R2: 0.13 and 0.24, respectively). CONCLUSION: Absorption profiling defines the heterogeneity in CsA exposure and relative absorption post-transplant. A 2-h post-dose blood sample is the most consistent, accurate and robust single-point predictor of the absorption phase measured by AUC[0-4] and should replace trough level monitoring for accurate concentration-control of Neoral therapy in the clinical setting. The use of additional samples at 1 and 3h is more complex and costly, but increases prediction accuracy and may be valuable in selected patients with erratic absorption.

Area Under Curve↗

PubMed1992

Lessons from 20 years of curative therapy of childhood acute leukaemia.

The past 20 years of curative therapeutics of childhood acute leukaemia has been largely a period of consolidation of gains, refinement of techniques and dissemination of expertise and technology. However, certain lessons have been learned. First, cure can be permanent but the complexity and cost of curative treatment currently restricts its accessibility; prevention or simple curative treatment is needed. Secondly, cure of the child demands that the risk of adverse sequelae of treatments be carefully balanced with known therapeutic benefits. Thirdly, preventive meningeal irradiation is no longer required. Fourth, treatment intensification is self-limiting. Adverse reactions can cancel out or exceed therapeutic benefits, resulting in a lower cure rate or a similar cure rate with lower quality of cure. Finally, morphology, immunophenotype and genotype of acute leukaemia are important criteria for selecting and scheduling drug therapy. Genotype may be the most important since leukaemia is a genetic disorder for which morphology and immunophenotype are mere reflections. However, none of these features, individually or together, are sufficient to explain all the difference in outcome among children on a given treatment plan or to completely fulfill the need of criteria for selection of treatment. Acute leukaemia remains an unsolved problem demanding considerably more basic and clinical research to meet the need for prevention and simple dependable curative treatment.

Acute Disease↗

PubMed1997

Precise quantification of dialysis using continuous sampling of spent dialysate and total dialysate volume measurement.

The "gold standard" method to evaluate the mass balances achieved during dialysis for a given solute remains total dialysate collection (TDC). However, since handling over 100 liter volumes is unfeasible in our current dialysis units, alternative methods have been proposed, including urea kinetic modeling, partial dialysate collection (PDC) and more recently, monitoring of dialysate urea by on-line devices. Concerned by the complexity and costs generated by these devices, we aimed to adapt the simple "gold standard" TDC method to clinical practice by diminishing the total volumes to be handled. We describe a new system based on partial dialysate collection, the continuous spent sampling of dialysate (CSSD), and present its technical validation. Further, and for the first time, we report a long-term assessment of dialysis dosage in a dialysis clinic using both the classical PDC and the new CSSD system in a group of six stable dialysis patients who were followed for a period of three years. For the CSSD technique, spent dialysate was continuously sampled by a reversed automatic infusion pump at a rate of 10 ml/hr. The piston was automatically driven by the dialysis machine: switched on when dialysis started, off when dialysis terminated and held during the by pass periods. At the same time the number of production cycles of dialysate was monitored and the total volume of dialysate was calculated by multiplying the volume of the production chamber by the number of cycles. Urea and creatinine concentrations were measured in the syringe and the masses were obtained by multiplying this concentration by the total volume. CSSD and TDC were simultaneously performed in 20 dialysis sessions. The total mass of urea removed was calculated as 58038 and 60442 mmol/session (CSSD and TDC respectively; 3.1 +/- 1.2% variation; r = 0.99; y = 0.92x -28.9; P < 0.001). The total mass of creatinine removed was 146,941,143 and 150,071,195 mumol/session (2.2 +/- 0.9% variation; r = 0.99; y = 0.99x + 263; P < 0.001). To determine the long-term clinical use of PDC and CSSD, all the dialysis sessions monitored during three consecutive summers with PDC (during 1993 and 1994) and with CSSD (1995) in six stable dialysis patients were included. The clinical study comparing PDC and CSSD showed similar urea removal: 510 +/- 59 during the first year with PDC and 516 +/- 46 mmol/dialysis session during the third year, using CSSD. Protein catabolic rate (PCR) could be calculated from total urea removal and was 1.05 +/- 0.11 and 1.05 +/- 0.09 g/kg/day with PDC and CSSD for the same periods. PCR values were clearly more stable when calculated from the daily dialysate collections than when obtained with urea kinetic modeling performed once monthly. We found that CSSD is a simple and accurate method to monitor mass balances of urea or any other solute of clinical interest. With CSSD, dialysis efficacy can be monitored at every dialysis session without the need for bleeding a patient. As it is external to the dialysis machine, it can be attached to any type of machine with a very low cost. The sample of dialysate is easy to handle, since it is already taken in a syringe that is sent directly to the laboratory. The CSSD system is currently in routine use in our unit and has demonstrated its feasibility, low cost and high clinical interest in monitoring dialysis patients.

Creatinine↗

PubMed2026

Scalable near-real-time Bayesian phylogenetics for outbreaks with Delphy.

Pathogen genomic analysis is central to tracking, understanding and containing outbreaks1-13, but the complexity and cost of state-of-the-art phylogenetic tools limit global access and impact. Here we introduce Delphy, an exact reformulation of Bayesian phylogenetics14-17 designed to transform its speed, scalability and accessibility while retaining Bayesian state-of-the-art accuracy. Delphy's central data structure, an explicit mutation-annotated tree, takes advantage of the high sequence similarity of large-scale epidemic datasets18-20 for efficient tree exploration and convergence. By reproducing key analyses from recent major epidemics, including Ebola1,21, Zika2, SARS-CoV-2 (ref. 22), mpox3,4 and H5N1 (refs. 23,24), we demonstrate state-of-the-art accuracy with up to 2-3 orders of magnitude improvements in speed. Assessing Delphy's scalability, we show that a simulated dataset of 100,000 sequences can be analysed within a day. We distribute Delphy as a client-side web application that enables local, interactive analysis of raw data on the user's machine. Delphy automatically identifies key viral lineages and mutations, as well as their emergence and prevalence through time, with quantified uncertainties grounded in Bayesian theory. Delphy establishes Bayesian phylogenetics as a fast, accessible frontline tool for future outbreak response.

Journal Article↗

PubMed2000

Gastrostomy: an improved technique.

Gastrostomy is a commonly performed procedure. The forceps described in this article help make this procedure easier and safer to carry out, reducing the need for complex and costly equipment. The forceps used have been adapted from standard surgical steel instruments by soldering a guidance device to one jaw. This device enables guided placement of a needle alongside the forceps tip. Any hospital technical service department could adapt standard forceps for this procedure.

Gastrostomy↗