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PubMed1998

Averaging attributable fractions in the multifactorial situation: assumptions and interpretation.

In multifactorial situations, the concept of attributable fraction quantifying the population impact of exposure factors on the disease load needs special methodologic care to take the interrelationship between exposures into account. Recently, new epidemiologic parameters have been introduced to address this issue. These approaches are reconsidered here from a game-theoretical perspective. The derivation of game-theoretical properties of these parameters provides additional motivation for their use in epidemiologic practice and offers new insights into their interpretation in epidemiologic studies. The nontechnical description of the results is illustrated by examples from the Hordaland study on obstructive lung disease.

Causality↗

PubMed1999

Quality of life instruments in oncology.

The objective of this article is to aid clinicians in understanding the current state of the development and application of quality of life (QOL) instruments as outcome measures in cancer clinical research and practice. As a result of the achievements of the past two decades, the concept of QOL has been defined and many reliable and valid measurement tools have been developed. The two main approaches to QOL assessment, psychometric-based and utility-based, are discussed together with a brief description of the strategies for meaningful interpretation of QOL profiles. QOL measures in oncology have the potential to be used to study populations in randomised clinical trials, to aid patient-clinician interactions in routine practice and to support policy decision making and economic evaluation of healthcare provision.

Clinical Trials as Topic↗

PubMed1991

Antiulcer agents. 5. Inhibition of gastric H+/K(+)-ATPase by substituted imidazo[1,2-a]pyridines and related analogues and its implication in modeling the high affinity potassium ion binding site of the gastric proton pump enzyme.

A number of substituted imidazo[1,2-a]pyridines and related analogues were selected for biochemical characterization in vitro against both the purified gastric proton pump enzyme, H+/K(+)-ATPase, and the intact gastric gland. The inhibitory activity in these two in vitro models was then examined for correlation with the gastric antisecretory potency determined for these compounds in vivo by using the histamine-stimulated Heidenhain pouch dog. Analysis of the biological data suggested that the inhibitory activity of the analogues determined in two in vitro models is predictive of their in vivo gastric antisecretory activity following intravenous, but not oral, administration. Furthermore, the good correlation observed between the in vitro and in vivo models suggests that these compounds are gastric proton pump inhibitors in vivo. A molecular modeling study of these compounds using the active analogue approach has defined the molecular volume which is shared by the active analogues, as well as the molecular volume which is common to the inactive analogues. Graphical representation of the difference between these molecular volumes can be interpreted in terms of a hypothetical description of the pharmacophore by means of which 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, Sch 28080 (1) and its analogues interact with the gastric proton pump enzyme, H+/K(+)-ATPase.

Adenosine Triphosphatases↗

PubMed2000

Overview of CARMEM: a new dynamic quantitative cardiac model for ECG monitoring and its adaptation to observed signals.

Different approaches have been proposed in order to achieve knowledge integration for coronary care monitoring applications, usually in the form of expert systems. The clinical impact of these expert systems, which are based only on "shallow" knowledge, has not been remarkable due to the difficulties associated with the construction and maintenance of a complete knowledge base. Model-based systems represent an alternative to these problems because they allow efficient integration of the "deep" knowledge on the underlying physiological phenomena being monitored. In this work, a brief review of existing model-based systems for cardiac rhythm interpretation is presented, followed by the description of a new system for Cardiac Arrhythmia Recognition by Model-Based ECG Matching (CARMEM). Fundamental characteristics of CARMEM are presented; in particular, its ability to provide online parameter adaptation to simulate complex rhythms and to match observed ECG signals. The proposed model can be useful for the explanation of the origin of cardiac arrhythmias and contribute towards their robust characterization in the context of coronary care units.

Artificial Intelligence↗

PubMed1999

Application of the correct information unit analysis to the naturally occurring conversation of a person with aphasia.

The Correct Information Unit (CIU) analysis for measuring the communicative informativeness and efficiency of connected speech (Nicholas & Brookshire, 1993) was applied to the naturally occurring conversation of a person with moderate aphasia. Results indicated that, in this instance, reliable CIU measures could not be obtained. Intrarater reliability for CIU and %CIU was low, reaching only 72%, and interrater reliability was never greater than 63%. However, reliability of word counts was good. Post hoc analysis of rater disagreements in application of the CIU analysis revealed that the majority (72%) resulted from insufficiencies in the scoring rules that were originally designed to measure single speaker connected discourse. Two descriptive categories of disagreements were identified: interpretations of informativeness and absence of rules. The remaining 28% of disagreements were attributable to human error in the application of scoring rules. Comparison of findings with previous research and implications for future research are discussed.

Aphasia↗

PubMed2001

Project normal: defining normal variance in mouse gene expression.

The mouse has become an indispensable and versatile model organism for the study of development, genetics, behavior, and disease. The application of comprehensive gene expression profiling technologies to compare normal and diseased tissues or to assess molecular alterations resulting from various experimental interventions has the potential to provide highly detailed qualitative and quantitative descriptions of these processes. Ideally, to interpret experimental data, the magnitude and diversity of gene expression for the system under study should be well characterized, yet little is known about the normal variation of mouse gene expression in vivo. To assess natural differences in murine gene expression, we used a 5406-clone spotted cDNA microarray to quantitate transcript levels in the kidney, liver, and testis from each of 6 normal male C57BL6 mice. We used ANOVA to compare the variance across the six mice to the variance among four replicate experiments performed for each mouse tissue. For the 6 kidney samples, 102 of 3,088 genes (3.3%) exhibited a statistically significant mouse variance at a level of 0.05. In the testis, 62 of 3,252 genes (1.9%) showed statistically significant variance, and in the liver, there were 21 of 2,514 (0.8%) genes with significantly variable expression. Immune-modulated, stress-induced, and hormonally regulated genes were highly represented among the transcripts that were most variable. The expression levels of several genes varied significantly in more than one tissue. These studies help to define the baseline level of variability in mouse gene expression and emphasize the importance of replicate microarray experiments.

Animals↗

PubMed1991

Mapping mortality and morbidity patterns: an international comparison.

A set of 49 national, intranational and international health atlases was surveyed to characterize their mapping methodology with respect to the populations covered, the diseases represented, the mapping techniques, and statistical methods. Little consistency was found concerning the choice of data function to be mapped, minimum event frequency requirements, method of age standardization, or map colour systems. Many atlases did not include basic epidemiological information; for instance, approximately half the atlases did not quote population denominators. There was a tendency to emphasize statistical significance over rate values, and to focus on high rather than low risk. Very few atlases included supplemental information on environmental factors. Most adopted a descriptive stance, and attempted no aetiological interpretation. We conclude that inter-atlas comparisons are made very difficult by methodological differences, and that even regional comparisons within atlases should be made cautiously. We propose a set of methodological guidelines for consideration in future atlases.

Epidemiology↗

PubMed1991

Diagnostic accuracy and clinical utility of thermography for lumbar radiculopathy. A meta-analysis.

The role of thermography for diagnosing lumbar radiculopathy was evaluated by literature review and meta-analysis. From 81 relevant citations, 28 studies could be analyzed for diagnostic-accuracy data (sensitivity and specificity) and method. Diagnostic-accuracy data varied significantly between studies; therefore meaningful pooled summary statistics could not be reported. Twenty-seven studies had major methodologic flaws including biased test interpretations, faulty cohort assembly, poor clinical descriptions, and small sample size. The only study of reasonably high quality found no discriminant value for liquid-crystal thermography. The role of thermography remains unclear. Rigorous clinical research is required to establish its diagnostic accuracy and clinical utility. Thermography cannot be recommended currently for routine clinical use in evaluating low-back pain.

Back Pain↗

PubMedDate not supplied

Creating a synthesis of intentionality: the role of the bracketing facilitator.

The role of a bracketing facilitator during the analysis phase of phenomenological research is discussed. As a research colleague, a bracketing facilitator plays an important part in a fellow researcher's task of uncovering his or her constitutive relationship with the research phenomenon. The primary task of a bracketing facilitator is providing assistance for a colleague in moving away from the usual cognitive mode of thinking during data analysis and into a state of emotional sensitivity to personal history and experience of the phenomenon. A step-by-step approach to the search for personal connections is presented, including an example of the process of facilitating this search. A table of guidelines that includes specific points for the act of bracketing as well as the content to be bracketed is intended as a tool for the development of phenomenological description.

Data Interpretation, Statistical↗

PubMed2002

On aerodynamic modelling of an insect-like flapping wing in hover for micro air vehicles.

This theoretical paper discusses recent advances in the fluid dynamics of insect and micro air vehicle (MAV) flight and considers theoretical analyses necessary for their future development. The main purpose is to propose a new conceptual framework and, within this framework, two analytic approaches to aerodynamic modelling of an insect-like flapping wing in hover in the context of MAVs. The motion involved is periodic and is composed of two half-cycles (downstroke and upstroke) which, in hover, are mirror images of each other. The downstroke begins with the wing in the uppermost and rearmost position and then sweeps forward while pitching up and plunging down. At the end of the half-cycle, the wing flips, so that the leading edge points backwards and the wing's lower surface becomes its upper side. The upstroke then follows by mirroring the downstroke kinematics and executing them in the opposite direction. Phenomenologically, the interpretation of the flow dynamics involved, and adopted here, is based on recent experimental evidence obtained by biologists from insect flight and related mechanical models. It is assumed that the flow is incompressible, has low Reynolds number and is laminar, and that two factors dominate: (i) forces generated by the bound leading-edge vortex, which models flow separation; and (ii) forces due to the attached part of the flow generated by the periodic pitching, plunging and sweeping. The first of these resembles the analogous phenomenon observed on sharp-edged delta wings and is treated as such. The second contribution is similar to the unsteady aerodynamics of attached flow on helicopter rotor blades and is interpreted accordingly. Theoretically, the fluid dynamic description is based on: (i) the superposition of the unsteady contributions of wing pitching, plunging and sweeping; and (ii) adding corrections due to the bound leading-edge vortex and wake distortion. Viscosity is accounted for indirectly by imposing the Kutta condition on the trailing edge and including the influence of the vortical structure on the leading edge. Mathematically, two analytic approaches are proposed. The first derives all the quantities of interest from the notion of circulation and leads to tractable integral equations. This is an application of the von Kármán-Sears unsteady wing theory and its nonlinear extensions due to McCune and Tavares; the latter can account for the bound leading-edge vortex and wake distortion. The second approach uses the velocity potential as the central concept and leads to relatively simple ordinary differential equations. It is a combination of two techniques: (i) unsteady aerodynamic modelling of attached flow on helicopter rotor blades; and (ii) Polhamus's leading-edge suction analogy. The first of these involves both frequency-domain (Theodorsen style) and time-domain (indicial) methods, including the effects of wing sweeping and returning wake. The second is a nonlinear correction accounting for the bound leading-edge vortex. Connections of the proposed framework with control engineering and aeroelasticity are pointed out.

Animals↗

PubMed2003

Quantal density functional theory of degenerate states.

The treatment of degenerate states within Kohn-Sham density functional theory is a problem of long-standing and current interest. We propose a solution to this mapping from the interacting degenerate system to that of the noninteracting fermion model whereby the equivalent density and energy are obtained via the unifying physical framework of quantal density functional theory. We describe the quantal theory of both ground and excited degenerate states, and for the cases of both pure state and ensemble v-representable densities. The quantal description further provides a rigorous physical interpretation of the corresponding Kohn-Sham energy functionals of the density, ensemble density, bidensity and ensemble bidensity, and of their respective functional derivatives. We conclude with examples of the mappings within the quantal theory.

Journal Article↗

PubMed2004

Discharge planning: "fooling ourselves?"--patient participation in conferences.

BACKGROUND: The aim of discharge planning conferences (DPCs) is to co-ordinate resources and to enhance patient involvement in care in connection with relocation from hospital. DPCs can be characterized as institutional conversations, and are often executed as standard procedures, but the scientific basis for the activity is weak. AIMS AND OBJECTIVES: The aim of this study was to illuminate and describe the communication at DPCs. DESIGN: A purposeful and consecutive sample of eight DPCs was collected in which the future care of eight women, aged 70 years or more, was discussed. METHODS: Transcribed video recordings were analysed in two steps. "The initial analysis" aimed at describing the structure and content of the communication. This description constituted the basis for an interpretation, leading to "the focused analysis" aiming at finding evidence for the assumptions made in the interpretation. RESULTS: The result revealed that the participation of patients was very less the DPCs. The decisions had often already been made, and the women were expected to be pleased with the decision; institutional representatives (IRs) frequently justified their actions by referring to bureaucratic praxis. CONCLUSIONS: The women were both encouraged and excluded from participation by the IRs. This dichotomy occurred because the IRs, as professionals, struggled to simultaneously realize their caring mission and their obligation to enforce the values and rules of the institution, i.e. efficiency and rationality. Thus, IRs and patients were equally imprisoned within the institutional system. RELEVANCE TO CLINICAL RESEARCH: This result illustrates how conflicting paradigms are imbedded and reproduced by healthcare professionals in their communicative praxis. Awareness of this is a prerequisite for improvements in working procedures congruent with a caring paradigm that support patient participation.

Activities of Daily Living↗

PubMed2000

Suffering from care as expressed in the narratives of former patients in somatic wards.

To illuminate patients' experiences of suffering from care, ten former patients in somatic wards narrated a desirable care episode (n = 39) and an undesirable care episode (n = 51). The interviews were analysed using a phenomenological hermeneutic method inspired by Ricoeur's philosophy. Four themes were found: having a good rest, suffering through, searching for autonomy and being cared for by attentive and committed staff. The findings were interpreted in light of Eriksson's description of suffering, which describes three kinds of suffering: 'suffering of life', 'suffering of illness' and 'suffering of caring'. Although not mentioned explicitly, it was evident that cases of suffering from care were indicated in the patients' narratives. The themes were related to the patients' states of health, their experience of the care situation and their descriptions of themselves, and could be understood as related to the acts of the 'drama of suffering' described by Eriksson. The study highlights the need for the patient to find a co-actor in the drama of suffering in order to prevent suffering from care, i.e. prevent hindrance to the patient in her/his struggle against the 'suffering of illness' and the 'suffering of life'. The patients must be seen as the directors of their own dramas of suffering.

Humans↗

PubMed2006

Do intramural virtual electrodes facilitate successful defibrillation? Model-based analysis of experimental evidence.

INTRODUCTION: Recent computer model and experimental studies have suggested that microscopic intramural collagenous planes may facilitate successful defibrillation through the generation of shock-induced virtual electrodes deep within the ventricular wall. Evidence supporting the existence of intramural virtual electrodes has been drawn from several recent studies, which map shock-induced membrane potential (Vm) over the cut transmural surface of dissected segments of porcine left ventricle (LV). The artificially created transmural boundary in these experiments is impermeable to intracellular current. It is not known how this constraint limits the interpretation of these experiments in terms of the shock response of the intact ventricle. METHODS AND RESULTS: This study uses a realistic 3D computer model of LV myocardium to aid experimental interpretation. The model incorporates a microstructural description of intramural cleavage plane discontinuities measured by confocal microscopy of rat LV. Electrical shocks are applied across the model tissue, with and without introduced transmural boundaries. Shocks of varying strength (4-40 V/cm) are also applied to the model and the response analyzed. Results show that shock-induced Vm changes (deltaVm) on a transmural tissue boundary are significantly different to deltaVm of the intact ventricle, and the extent of difference depends on boundary orientation. However, the presence and qualitative behavior of intramural virtual electrodes is preserved irrespective of boundary placement. The model also confirms experimental observations that most rapid transmural activation occurs for shocks of strength 5-10 V/cm. Two distinct mechanisms suppress virtual electrode propagation, and hence slow tissue activation, outside of this optimal shock strength range. CONCLUSIONS: This study supports the hypothesis that distributed microscopic intramural virtual electrodes contribute to rapid activation of the ventricular wall during defibrillation.

Animals↗

PubMedDate not supplied

Doppler echocardiographic evaluation of congenital cardiac disease. An introduction.

M-mode and two-dimensional echocardiography have greatly enhanced the evaluation of animals with congenital cardiac disease. Structural abnormalities can be seen and hemodynamic alterations inferred, e.g., ventricular wall concentric hypertrophy indicating pressure overload to the respective ventricle. Interrogation of the diseased heart by Doppler echocardiography allows acquisition of more direct hemodynamic information without cardiac catheterization, which enables the clinician to give a more precise description of a congenital abnormality. The purpose of this study is to illustrate and describe abnormal blood-flow patterns in selected congenital cardiac defects in animals. Basic background information concerning Doppler echocardiographic principles, flow patterns, and calculations will be briefly discussed. For more detailed descriptions other references should be sought. Interpretation of Doppler echocardiography in animals is based primarily on data derived from human studies since studies involving measurable numbers of veterinary patients have not yet been completed.

Animals↗

PubMed1985

Postextrasystolic potentiation of the isolated canine left ventricle. Relationship to mechanical restitution.

We established, for the isolated, isovolumically beating canine left ventricle, a comprehensive description of postextrasystolic contractile strength (dP/dtmax) as a function of extrasystolic and postextrasystolic stimulus intervals. In contrast to previous studies of postextrasystolic beats in in situ hearts, these isolated ventricles contracted isovolumically so that dP/dtmax was not affected by fluctuations in preload and afterload and was therefore considered to be a reliable index of intrinsic contractility. With the interval preceding extrasystoles constant, postextrasystolic contractile strength increased monoexponentially to a plateau as the interval preceding postextrasystoles lengthened, with a mean time constant (+/- SD) of 182 +/- 44 msec (n = 53). The onset of this increase in postextrasystolic contractile strength coincided with repolarization of the extrasystolic action potential. With the interval preceding postextrasystoles held constant and long (1200 msec), postextrasystolic contractile strength decreased according to a monoexponential function as the interval preceding extrasystoles lengthened [mean time constant (+/- SD) of 176 +/- 18 msec (n = 10)]. These phenomena could be quantitatively summarized by a single equation description of postextrasystolic contractile strength which involved monoexponential functions with one time constant. The mathematical form of this description led us to a simple interpretation of these phenomena in terms of currently proposed excitation-contraction coupling models of the heart.

Animals↗

PubMed1985

Human factor VIII procoagulant protein. Monoclonal antibodies define precursor-product relationships and functional epitopes.

The human Factor VIII procoagulant protein (VIII:C) purified from commercial Factor VIII concentrate consisted of a polypeptide doublet of 80,000 mol wt, a 92,000-mol wt polypeptide, and additional polypeptides of up to 188,000 mol wt. Thrombin digests contained a doublet of 72,000 mol wt, as well as 54,000- and 44,000-mol wt fragments. Proteolysis studies of purified VIII:C using thrombin and activated protein C have suggested that the 92,000- and 80,000 (or 72,000)-mol wt polypeptides comprise activated VIII:C. We have now used seven monoclonal antibodies raised against purified VIII:C to construct a preliminary epitope map of these VIII:C polypeptides. The specific VIII:C polypeptides with which the monoclonal antibodies reacted were determined by immunoblotting of VIII:C onto nitrocellulose sheets after reduced NaDodSO4-polyacrylamide gel electrophoresis. A minimum of five distinct epitopes were defined by these monoclonal anti-VIII:C antibodies. Identification of polypeptides bearing these epitopes allowed localization of distinct thrombin cleavage sites to the 92,000- and 80,000-mol wt chains, helped define polypeptide chain precursor-product relationships, and suggested that both the 92,000- and 80,000-mol wt polypeptides are necessary for VIII:C function. These data and their interpretation are consistent with the published description of the complete primary structure of VIII:C and its thrombin cleavage products. The 92,000- and 80,000-mol wt chains have been located at the amino- and carboxy-terminal ends of the molecule, respectively.

Antibodies, Monoclonal↗

PubMed1999

Discovering a dialectic of care.

Using data from a recent study on the outcomes of child psychiatric hospitalization, the author presents a critique of the intervention-outcome movement that dominates the health care agenda. Employing an exploratory descriptive study design and Denzin's interpretive interactionism method, she presents data that illustrate how interventions can become distorted by contextual factors, conflicting ideologies, agendas, and failure to thoughtfully consider patient needs. She posits that research agendas are heavily tilted toward outcomes research that often discount the nature of structure and process. The marketplace emphasis of health care may result in environments in which a structure and process of caring is replaced by a focus of profits over patients. The value of focusing on interventions and outcomes in research without addressing broader ecosystem variables that influence practice is questioned in view of in-depth data that emerge from practice settings.

Adolescent↗