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PubMed2002

Treatment of multifunctional enzymes in metabolic pathway analysis.

In metabolic pathway analysis, it should be considered that many enzymes operate with low specificity (e.g. nucleoside diphosphokinase, uridine kinase, transketolase, aldolase), so that various substrates and products can be converted. Here, we analyze the effect of enzymes with low substrate specificity on the elementary flux modes (pathways). We also study the benefits of two different approaches to describing multifunctional enzymes. The usual description is in terms of (overall) enzymatic reactions. At a more detailed level, the reaction steps (half-reactions, hemi-reactions) of the formation and conversion of enzyme-substrate complexes are considered. Multifunctional enzymes operate according to various mechanisms. This is illustrated here by the reaction schemes for the different enzyme mechanisms of bifunctional enzymes. For enzymes with two or more functions, it is important to consider only linearly independent functions, because otherwise cyclic elementary modes would occur which do not perform any net transformation. However, the choice of linearly independent functions is not a priori unique. We give a method for making this choice unique by considering the extreme pathways of the hemi-reactions system. A formal application of the algorithm for computing elementary flux modes (pathways) yields the result that the number of such modes sometimes depend on the level of description if some reactions are reversible and the products of the multifunctional enzymes are external metabolites or some multifunctional enzymes partly share the same metabolites. However, this problem can be solved by appropriate interpretation of the definition of elementary modes and the correct choice of independent functions of multifunctional enzymes. The analysis is illustrated by a biochemical example taken from nucleotide metabolism, comparing the two ways of description for nucleoside diphosphokinase and adenylate kinase, and by several smaller examples.

Adenylate Kinase↗

PubMedDate not supplied

Can't miss: conquer any number task by making important statistics simple. Part 6. Tests of statistical significance (z test statistic, rejecting the null hypothesis, p value), t test, z test for proportions, statistical significance versus meaningful difference.

Healthcare quality professionals need to understand and use inferential statistics to interpret sample data from their organizations. Since in quality improvement and healthcare research studies all the data from a population often are not available, investigators take samples and make inferences about that population using inferential statistics. This series of six articles will give readers an understanding of the concepts of inferential statistics as well as the specific tools for calculating confidence intervals and tests of statistical significance for samples of data. This article, Part 6, merges the four concepts of the (1) standard error of the difference between sample means, (2) the z test statistic, (3) rejecting the null hypothesis, and (4) the p value to provide a comprehensive view of tests of statistical significance. This is followed by a description of t tests, statistical tests for comparing two sample proportions, and Type I and Type II errors. The series of articles concludes with a description of statistical significance versus meaningful difference.

Confidence Intervals↗

PubMed2003

Reliability of radionuclide gastroesophageal reflux studies using visual and time-activity curve analysis: inter-observer and intra-observer variation and description of minimum detectable reflux.

Radionuclide studies have gained wide acceptance in the evaluation of infants and children with gastroesophageal reflux (GER). For correct interpretation of scan results, knowledge of inter-observer and intra-observer variability and minimum detectable reflux volume is essential. In this study, we evaluated the methodological issues underlying the visual assessment of GER and time activity curve analysis. An in vitro model of stomach and oesophagus was established to determine the minimum detectable reflux by placing various volumes and concentrations representing the diluted activity in the stomach. In the clinical part 99 patients were imaged for 1 h after oral administration of 99mTc sulfur colloid. Eleven patients were excluded from the study either due to incomplete clinical data or suboptimal image quality. Frames of 16 s each, and time-activity curves which were generated after drawing regions of interest from the oesophagus, were read three times by an experienced nuclear medicine physician and a resident in training. On the phantom study, the concentration, volume and duration were the determining factor for the visualization of reflux. In the clinical part, the overall incidence of GER in 88 patients was 69%. The mean intra- and inter-observer reproducibility (kappa values) was 0.76 and 0.7065, respectively. Agreement was slightly higher in the analysis of time-activity curves (0.767 and 0.731). Our results indicate that GER may be reproducibly analysed on scintigraphy by the same and different observers with varying levels of training. Its visualization is associated with reflux duration, volume and dilution factor of radioactivity.

Child↗

PubMed1998

Experimental approaches towards interpreting dolphin-stimulated bioluminescence.

Flow-induced bioluminescence provides a unique opportunity for visualizing the flow field around a swimming dolphin. Unfortunately, previous descriptions of dolphin-stimulated bioluminescence have been largely anecdotal and often conflicting. Most references in the scientific literature report an absence of bioluminescence on the dolphin body, which has been invariably assumed to be indicative of laminar flow. However, hydrodynamicists have yet to find compelling evidence that the flow remains laminar over most of the body. The present study integrates laboratory, computational and field approaches to begin to assess the utility of using bioluminescence as a method for flow visualization by relating fundamental characteristics of the flow to the stimulation of naturally occurring luminescent plankton. Laboratory experiments using fully developed pipe flow revealed that the bioluminescent organisms identified in the field studies can be stimulated in both laminar and turbulent flow when shear stress values exceed approximately 0.1 N m-2. Computational studies of an idealized hydrodynamic representation of a dolphin (modeled as a 6:1 ellipsoid), gliding at a speed of 2 m s-1, predicted suprathreshold surface shear stress values everywhere on the model, regardless of whether the boundary layer flow was laminar or turbulent. Laboratory flow visualization of a sphere demonstrated that the intensity of bioluminescence decreased with increasing flow speed due to the thinning of the boundary layer, while flow separation caused a dramatic increase in intensity due to the significantly greater volume of stimulating flow in the wake. Intensified video recordings of dolphins gliding at speeds of approximately 2 m s-1 confirmed that brilliant displays of bioluminescence occurred on the body of the dolphin. The distribution and intensity of bioluminescence suggest that the flow remained attached over most of the body. A conspicuous lack of bioluminescence was often observed on the dolphin rostrum and melon and on the leading edge of the dorsal and pectoral fins, where the boundary layer is thought to be thinnest. To differentiate between effects related to the thickness of the stimulatory boundary layer and those due to the latency of the bioluminescence response and the upstream depletion of bioluminescence, laboratory and dolphin studies of forced separation and laminar-to-turbulent transition were conducted. The observed pattern of stimulated bioluminescence is consistent with the hypothesis that bioluminescent intensity is directly related to the thickness of the boundary layer.

Animals↗

PubMed1985

Studies on the release of drugs from O/W-emulsion ointments using the mathematical interpretations. Part 1: Influence of the thickness of the ointment layer.

The hyperbolic function Q = t/(A + Bt) has been applied to the quantitative description of the release process from the emulsion ointment as influenced by the thickness of the layer. Results have been compared with the analogous ones obtained by the use of Higuchi's "exponential" equations. This comparison leads to the conclusion that the proposed empirical function is especially usefull for thin ointment layers.

Chemical Phenomena↗

PubMed2004

Using models of the myocyte for functional interpretation of cardiac proteomic data.

There has been significant progress towards the development of highly integrative computational models of the cardiac myocyte over the past decade. Models now incorporate descriptions of voltage-gated ionic currents and membrane transporters, mechanisms of calcium-induced calcium release and intracellular calcium cycling, mitochondrial ATP production and its coupling to energy-requiring membrane transport processes and mechanisms of force generation. There is an extensive literature documenting both the reconstructive and predictive abilities of these models and there is no question that an interplay between quantitative modelling and experimental investigation has become a central component of modern cardiovascular research. As data regarding the cardiovascular proteome in both health and disease emerge, integrative models of the myocyte are becoming useful tools for interpreting the functional significance of changes in protein expression and post-translational modifications (PTMs). Data of particular importance include information on: (a) changes of expressed protein level, (b) changes of protein PTMs, (c) protein localization, and (d) protein-protein interactions, as it is often possible to incorporate and interpret the functional significance of such findings using computational models. We provide two examples of how models may be used in this fashion. In the first example, we show how information on altered expression of the sarcoplasmic reticulum Ca2+-ATPase, when interpreted through the use of a computational model, has provided key insights into fundamental mechanisms regulating cardiac action potential duration. In the second example, we show how information on the effects of phosphorylation of L-type Ca2+ channels, when interpreted through the use of a model, provides insights on how this post-translational modification alters the properties of excitation-contraction coupling and risk for arrhythmia.

Animals↗

PubMed1996

Clinical value of radiologists' interpretations of perioperative radiographs of orthopedic patients.

The content and accuracy of radiographic interpretations by radiologists was assessed to determine the reports' ability to provide sufficient information necessary to make clinical treatment decisions. A retrospective review was performed of 371 radiographic studies (211 consecutive patients) and their reports which had been generated by three Board-certified radiologists. Data were collected regarding fracture assessment and description as well as the description and assessment of orthopedic implants. These descriptions were categorized by their ability to be used clinically (precise) or not (general). Fracture descriptions were considered complete for 85% of reports, while their assessment of alignment and displacement (necessary to determine fracture care) was complete on only 9%. Orthopedic implants were described precisely on 12% of reports with 7% of the descriptions in error. The effect and position of orthopedic implants were described precisely for only 27% and 25% of cases, respectively, while implant stability was assessed precisely in only 4% of cases. For 61% of preoperative studies, the radiologist's report was not available until after the surgical procedure had already been performed. For all variables considered, an average of 3% of descriptions contained an error. Radiologists' reports of radiographs of these patients undergoing orthopedic procedures did not contain sufficient descriptive information to be used clinically, were not promptly available, and contained an error for 3% of variables studied. The attending orthopedic surgeon has traditionally interpreted such radiographs and should continue to do so to provide patients with more immediate and complete clinical evaluation and management.

Fractures, Bone↗

PubMed2006

Interpretation of ambiguous idiomatic statements in schizophrenic and depressive patients. Evidence for common and differential cognitive patterns.

BACKGROUND: This study is concerned with the comprehension of ambiguous idiomatic statements in schizophrenic and depressive patients. AIMS: Using a multiple-choice procedure, we simultaneously tested the presence of concrete and literal elements in the understanding of idiomatic statements. METHOD: Fourteen schizophrenic and 10 patients undergoing a major depressive episode as well as 14 control subjects completed a questionnaire with 10 idiomatic expressions with two possible interpretations (figurative and literal) of equivalent prominence. The participants had to choose one word linked with the different interpretations of these idioms (figurative, literal, concrete or inappropriate meaning). RESULTS: The main results show that, in all the subjects, the contextual characteristics of the task induced a bias in favor of figurative interpretations despite the equivalent prominence of the literal interpretations of the idioms. The selection of responses relating to the concrete meaning of a single word in the idiom constituted a response mode common to both the schizophrenic and depressed patients. Despite the contextual constraints of the task, the schizophrenics opted for the literal responses more often than the other participants. The descriptive analysis argues in favor of a cognitive and clinical heterogeneity of schizophrenic patients. CONCLUSION: Results support the idea that literality and concreteness in idiomatic interpretation are possibly due to distinct cognitive impairments, though only some are specific to schizophrenic patients.

Adult↗

PubMed1999

Genetically structured modeling of protein production in filamentous fungi.

A general framework for a genetically structured model is presented. The framework allows description of the interactions in a system of regulatory and structural genes. The model assumes equilibrium kinetics for the binding of regulatory proteins to the promoter regions of the genes and includes the possible activation of proteins following their synthesis. The model is evaluated by simulating the alcA-expression (alcohol dehydrogenase I) in Aspergillus nidulans which is an inducible system subject to glucose repression. The intracellular enzyme levels in strains with different regulatory mutations are simulated during various growth conditions. The model gives a good description of the experimental data with changes in only a few parameter values which have a mechanistic interpretation.

Alcohol Dehydrogenase↗

PubMed2004

Anatomy of and patterns of water currents through the mantle cavities of pleurotomariid gastropods.

The paired pallial organs of pleurotomariids (slit shells) are generally interpreted as representing the primitive gastropod condition. Relatively few individual pleurotomariids have been observed alive; most anatomical descriptions have been based on retracted, preserved material. In this study, live animals were observed in still and moving water, videotaped, photographed, and relaxed prior to anatomical description. The pleurotomariid Perotrochus maureri formed a siphon with its mantle at the posterior end of the slit in the shell. As expected, water was expelled from the mantle cavity through this siphon. Dye released along the aperture, the area traditionally considered to be the incurrent window, was never observed to enter the mantle cavity. Instead, water entered through the slit just anterior to the siphon. A similar pattern was observed in the deep-slit pleurotomariid Entemnotrochus adansonianus. Thus the "anal" slit provided the sites for the incurrent as well as the excurrent windows. This surprising flow pattern is inconsistent with the traditional scenario of early gastropod evolution.

Animals↗

PubMed1990

Interpretive bioethics: the way of discernment.

This paper critically appraises the applied action-guide approach to bioethics and finds it wanting in two ways: it is tethered to a social contract view of the doctor-patient relationship that is largely incompatible with experiences of illness and care; and, as a formalist doctrine, it lacks critical edge and tends toward accommodationism. An alternative approach is recommended that involves interpreting moral experience by means once associated with the rhetorical arts--practical reasoning, hermeneutics, casuistry, and thick description.

Bioethics↗

PubMed2003

Temporal variability of local abundance, sex ratio and activity in the Sardinian chalk hill blue butterfly.

When capturing and marking of individuals is possible, the application of newly developed capture-recapture models can remove several sources of bias in the estimation of population parameters such as local abundance and sex ratio. For example, observation of distorted sex ratios in counts or captures can reflect either different abundances of the sexes or different sex-specific capture probabilities, and capture-recapture models can help distinguish between these two possibilities. Robust design models and a model selection procedure based on information-theoretic methods were applied to study the local population structure of the endemic Sardinian chalk hill blue butterfly, Polyommatus coridon gennargenti. Seasonal variations of abundance, plus daily and weather-related variations of active populations of males and females were investigated. Evidence was found of protandry and male pioneering of the breeding space. Temporary emigration probability, which describes the proportion of the population not exposed to capture (e.g., absent from the study area) during the sampling process, was estimated, differed between sexes, and was related to temperature, a factor known to influence animal activity. The correlation between temporary emigration and average daily temperature suggested interpreting temporary emigration as inactivity of animals. Robust design models were used successfully to provide a detailed description of the population structure and activity in this butterfly and are recommended for studies of local abundance and animal activity in the field.

Animals↗

PubMed1986

An approach to quantification of biaxial tissue stress-strain data.

Delineation of the mechanical properties of biologic tissues is one of the cornerstones of biomechanics. Abundant data from uniaxial tests exist but these cannot be extrapolated to describe three-dimensional properties of tissue. Biaxial stress-strain studies have been performed using skin, blood vessels and pericardium. Quantitative description of tissue properties in these studies has employed either polynomial or exponential strain-energy functions. Interpretation of these data, however, is difficult because of wide variability of the estimated coefficients of these functions. This variability has been attributed to experimental noise, numerical instabilities in the algorithms, or to strain-history dependence. No systematic method has been proposed to evaluate the variability. This paper describes a statistically based approach to assessing the sources of and accounting for variability of coefficients in describing biaxial stress-strain data. Our data are from canine pericardium subjected to various combinations of simultaneous biaxial stretching. We first determine a suitable strain-energy function with the least number of free parameters that will fit the data reasonably. We then perform residual analysis to see if standard statistical methods can be used to assess the variability. If not, we use a nonparametric method called bootstrapping that is suitable for assessing the uncertainty in the coefficients. Using a five-parameter exponential strain-energy function, pericardial tissue is found to be strain-history dependent and anisotropic. These findings cannot be attributed to either experimental noise or instability in the numerical algorithms.

Animals↗

PubMed2005

Haemangiomas and vascular malformations of the maxillofacial region--a review.

Congenital vascular anomalies have been and remain poorly understood. Since 1982 haemangiomas and vascular malformations have been recognised as distinct entities that exhibit unique characteristics and demand appropriately tailored treatment plans. However, "haemangioma" still continues to be used as a clinical and pathological description of many different types of vascular anomalies, which complicates both the care of patients and the interpretation of reports in journals. In this review we summarise the current classification, terminology, and the pathological basis of these lesions and discuss their management. The various therapeutic options available and their outcome will be discussed in addition to the recent advances in the psychosocial aspects of care, interventional radiology, laser and pharmacological therapy.

Angiography, Digital Subtraction↗

PubMed2006

Linguistic complexity and information structure in Korean: evidence from eye-tracking during reading.

The nature of the memory processes that support language comprehension and the manner in which information packaging influences online sentence processing were investigated in three experiments that used eye-tracking during reading to measure the ease of understanding complex sentences in Korean. All three experiments examined reading of embedded complement sentences; the third experiment additionally examined reading of sentences with object-modifying, object-extracted relative clauses. In Korean, both of these structures place two NPs with nominative case marking early in the sentence, with the embedded and matrix verbs following later. The type (pronoun, name or description) of these two critical NPs was varied in the experiments. When the initial NPs were of the same type, comprehension was slowed after participants had read the sentence-final verbs, a finding that supports the view that working memory in language comprehension is constrained by similarity-based interference during the retrieval of information necessary to determine the syntactic or semantic relations between noun phrases and verb phrases. Ease of comprehension was also influenced by the association between type of NP and syntactic position, with the best performance being observed when more definite NPs (pronouns and names) were in a prominent syntactic position (e.g., matrix subject) and less definite NPs (descriptions) were in a non-prominent syntactic position (embedded subject). This pattern provides evidence that the interpretation of sentences is facilitated by consistent packaging of information in different linguistic elements.

Asian People↗

PubMed2006

Fit for practice? An exploration of the development of newly qualified nurses using focus groups.

UNLABELLED: Previous research in the newly qualified has primarily focused upon their levels of competence at the time of registration rather than upon the way that this continues to develop over time. Though newly qualified nurses are expected to be competent and able to practice independently without direct supervision the reality is that, for most, their training has not equipped them with the knowledge, skills or confidence necessary for independent practice. This belief provided the foundations for this study designed to gain an understanding of the way that competence develops amongst nurses themselves and how this is seen by their managers and those working with them. It focused neither on what competencies nurses possessed nor on the level of overall competence but rather on the factors influencing the development of competence over time. RESEARCH DESIGN: This qualitative exploratory study relied upon a combination of focus groups and individual interviews to access information and perceptions not readily accessible through more quantitative means. DATA COLLECTION: Data was collected using focus groups involving newly qualified staff, including both those on a development programme and those in substantive posts, experienced qualified nurses (preceptors) and practice development nurses. A total of twelve focus groups were conducted yielding a purposive sample of 105 volunteer participants; groups were continued until no new data emerged and saturation was achieved. Ward managers (5) were interviewed individually and their data was added to that obtained from the focus groups. ANALYSIS: Content analysis of the transcripts enabled the material to be explored systematically to identify relevant themes and categories within the data thus helping to clarify descriptions of the major issues identified; these were returned to the participants to ensure validity in data interpretation. FINDINGS: Ward managers appear to have low expectations of the newly qualified while 'new' nurses themselves believe that they are expected to be able to fulfil tasks that they feel ill-equipped to undertake. This emphasises the need for appropriate support to enable them to develop their knowledge, skills and confidence and enable independent practice. While staff development programmes benefit some, others gain equal value from supportive preceptorship in helping them to develop the clinical and managerial skills necessary in today's healthcare climate.

Attitude of Health Personnel↗

PubMed2004

Virologic therapy response significantly correlates with the number of active drugs as evaluated using a LiPA HIV-1 resistance scoring system.

BACKGROUND: Resistance testing is increasingly accepted as a tool in guiding the selection of human immunodeficiency virus type 1 (HIV-1) antiretroviral therapy in HIV-1 infected individuals who fail their current regimen. OBJECTIVES: To descriptively compare the correlation between virologic treatment response and results using three genotypic HIV-1 drug resistance interpretation systems: the VERSANT HIV-1 Resistance Assay (LiPA) system and two sequence-based interpretation systems. STUDY DESIGN: Specimens from 213 HIV-1-infected subjects, either starting (n=104) or switching to (n=109) a regimen of three or four antiretroviral drugs, were collected retrospectively at baseline and after 3 months of uninterrupted therapy. The correlation between viral load change and the number of predicted active drugs in the treatment regimen was assessed. An interpretation algorithm was recently developed to process VERSANT HIV-1 Resistance Assay (LiPA) data. The number of active drugs predicted using this algorithm was rank correlated with the viral load change over a 3-month treatment period. For comparison, a similar calculation was made using two sequence-based algorithms (REGA version 5.5 and VGI GuideLines Rules 4.0), both applied on the same sequences. RESULTS: Statistically significant (p<0.05) correlation coefficients for each of the three HIV-1 drug resistance interpretation systems were observed in the treatment-experienced subjects on a 3-drug regimen (-0.39, -0.38, and -0.42, respectively) as well as on a 4-drug regimen (-0.33, -0.31, and -0.37, respectively). However, no significant correlation was observed in treatment-naive subjects, probably due to the very low frequency of drug resistance in these subjects. CONCLUSION: All three genotypic drug resistance interpretation systems (LiPA version 1, REGA version 5.5, and VGI GuideLines Rules 4.0) were statistically significantly correlated with virologic therapy response as measured by viral load testing.

Adult↗

PubMed2006

Critical parameter of burst pressure measurement in development of bypass grafts is highly dependent on methodology used.

BACKGROUND: Because of the low patency rate of currently available vascular bypass grafts, researchers are working towards the development of alternative bypass grafts, ranging from synthetic prostheses to wholly biologic living grafts. The philosophy of measurement required by regulatory agencies such as the United States Food and Drug Administration (FDA) as well as to gain the Conformité Européene (CE) mark is to test above and beyond the limits that would be expected physiologically. The critical parameter of burst pressure is needed for Conformité Européene (CE) mark or United States Food and Drug Administration (FDA) approval before clinical trials can proceed. An accurate measurement of burst pressure in potential porous vascular bypass grafts is, therefore, of utmost importance to ensure adequate strength on implantation in animals and subsequent clinical use. A wide range of methods to measure burst pressure have been used. We tested the burst pressure of a new polyurethane-based nanocomposite vascular prosthesis by using different methods to assess whether the method used affected the results. METHODS: Water was infused at flow rates of 0.2, 50, and 100 mL/min through a syringe pump into latex sleeve-lined porous prostheses manufactured from a poly(carbonate-urea)urethane nanocomposite incorporating silsesquioxane. At the lowest infusion rate, the inflation was done with and without a nonporous inner lining sleeve. A pressure transducer was used to record the peak pressure achieved. RESULTS: Using a nonporous sleeve resulted in a higher burst pressure (428 mm Hg vs 341 mm Hg) at a flow rate of 0.2 mL/min. A lower infusion rate (0.2 mL/min) produced a lower burst pressure than 50 mL/min (428 mm Hg vs 451 mm Hg). No significant difference was found in burst pressure using infusion rates of 50 mL/min and 100 mL/min. CONCLUSIONS: The use of a nonporous sleeve removes the potential weakness presented by the pores themselves. A continuous high infusion rate consistently overestimates burst pressure. These methods may not reflect the physiologic state. Care needs to be taken in interpretation of methodology for burst pressure measurement, and the rate of infusion should be stated in any description of the method. CLINICAL RELEVANCE: The poor patency of small-caliber vascular bypass prostheses has stimulated a large body of research into alternative graft materials. This includes synthetic and, more recently, tissue-engineered hybrid products. Acceptance for international standards requires demonstration of a rigorous mechanical testing regimen, including graft strength, which has on the whole involved burst strength measurement. However, the methods used to measure burst strength have varied with respect to apparatus used and rate of graft inflation. We show that these variables lead to markedly different results. In particular, fast infusion rates may overestimate the actual burst pressure, leading to a false sense of security.

Biocompatible Materials↗