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PubMed1992

A mathematical model for the growth and classification of a solid tumor: a new approach via nonlinear elasticity theory using strain-energy functions.

Medically, tumors are classified into two important classes--benign and malignant. Generally speaking, the two classes display different behaviour with regard to their rate and manner of growth and subsequent possible spread. In this paper, we formulate a new approach to tumor growth using results and techniques from nonlinear elasticity theory. A mathematical model is given for the growth of a solid tumor using membrane and thick-shell theory. A central feature of the model is the characterization of the material composition of the tumor through the use of a strain energy function, thus permitting a mathematical description of the degree of differentiation of the tumor explicitly in the model. Conditions are given in terms of the strain energy function for the processes of invasion and metastasis occurring in a tumor, being interpreted as the bifurcation modes of the spherical shell, which the tumor is essentially modeled as. Our results are compared with actual medical experimental results and with the general behavior shown by benign and malignant tumors. Finally, we use these results in conjunction with aspects of surface morphogenesis of tumors (in particular, the Gaussian and mean curvatures of the surface of a solid tumor) in an attempt to produce a mathematical formulation and description of the important medical processes of staging and grading cancers. We hope that this approach may form the basis of a practical application.

Animals↗

PubMed2006

On the interpretation of quantitative experimental data on nucleation rates using classical nucleation theory.

We consider how experimental data for nucleation rates can be analyzed if it is assumed that classical nucleation theory is a reasonable description of the nucleation. In particular, we consider in detail experimental results for the nucleation of the protein lysozyme. Classical nucleation theory makes predictions for the functional form of the nucleation rate; physically reasonable bounds can be placed on the parameters of this functional form. The experimental data for lysozyme implies values for a parameter (the preexponential factor) that are outside the physically reasonable bounds for homogeneous nucleation but are consistent with heterogeneous nucleation. Also, the functional form of the rate suggests that there is a distribution of barrier heights. Such a distribution is likely for heterogeneous nucleation but not possible for homogeneous nucleation. Modeling experimental data with classical nucleation theory is a generally applicable way of distinguishing between homogeneous and heterogeneous nucleation.

Journal Article↗

PubMed1989

A high density in vitro extracellular electrode array: description and implementation.

The detailed activation sequence in myocardium provides information critical to the understanding of the mechanisms of cardiac arrhythmias and the influence of interventions. Despite the pivotal role of activation mapping, the interpretation of isochronic maps and the correlation to detailed tissue morphology may be limited when the interelectrode distances are large with respect to cell dimensions. Additionally, dynamic beat-to-beat variations in the activation pattern or the effect of interventions such as single extra stimuli cannot be assessed adequately without recording from all sites simultaneously. To surmount these limitations, we have fabricated and tested an extracellular recording array consisting of 224 bipolar tungsten wire electrodes with a 350-microns interelectrode distance (140 microns edge-to-edge distance), and used signal processing equipment to record from all electrodes simultaneously at a 2-kHz sample rate. Stimulation can be performed sequentially from 12 different sites at 30 degree angles around the periphery of the recording array. Transarray bipoles can be recorded from any combination of eight radially oriented sites. Activation maps recorded in normal tissue after programmed stimulation and activation maps from an area of fixed anatomic block in the epicardial border zone of infarcted tissue are presented. The results demonstrate a lack of influence of the recording array on the electrophysiological properties of the tissue as verified with transmembrane action potential recordings and sequential extracellular maps. This electrode permits precise assessment of transient details of the activation sequence with unparalleled anatomic resolution.

Animals↗

PubMedDate not supplied

Issues in developmental neurotoxicology: interpretation and implications of the data.

The potential for environmental contaminants to produce neurological, cognitive, or other behaviour deficits as a result of developmental exposure has received increasing attention. The focus has shifted from description of frank neurotoxicity observed in a relatively few individuals to more subtle impairment in a much greater number of children. With this shift has come the recognition that subtle deficits such as a small decrease in IQ can have important societal impact when large numbers of children are affected. For example, the result of a 1 microgram/dL decrease in blood lead concentration in children in the United States with blood lead concentrations between 10 and 20 micrograms/dL would translate into a savings of 5-7.5 billion U.S. dollars a year in increased earning power alone. In addition, behavioural problems such as increased aggression and poor social adjustment identified early in childhood may escalate to serious antisocial behaviour such as delinquency as the child approaches puberty. Exposure to neurotoxic agents during development or over a significant portion of the lifespan may also result in acceleration of age-related neurodegenerative diseases. Such changes in the functional abilities of a significant proportion of a population have potentially serious consequences for society as well as for affected individuals.

Brain↗

PubMedDate not supplied

[Biomechanical-clinical interpretation of firearm wounds. General problems. IX. Propedeutic ABC of terminal ballistics].

In this chapter, the leading role is played by the mechanical-thermal-ballistic device, issued as a long-barrelled regulation firearm to modern armies. The most accurate description of this type of firearm and its present and possible future development seeks to be in line with the objective comparison between the biological matter and the mechanical material, which constitutes the essential basis for any optimal nosological, aetiological, or pathogenetic classification of bullet wounds. We should not forget that the advent of the M 16 A 1 has aroused great technical interest, particularly--though not only--as regards the hydroshock aspect, and that the technological developments in future can hardly fail to increasingly confirm the singular nature of bullet wounds, which refuse to be encompassed merely within the somewhat limited sphere of their strictly local effects, but carry a broader significance in a critical context open to further verification in the future. There can be no denying that this unique nature of modern bullet wounds makes them ideal candidates bearing witness to a new interpretation of traumatism, which at present is only in its infancy.

Biomechanical Phenomena↗

PubMed1993

Modelling the growth of solid tumours and incorporating a method for their classification using nonlinear elasticity theory.

Medically, tumours are classified into two important classes--benign and malignant. Generally speaking, the two classes display different behaviour with regard to their rate and manner of growth and subsequent possible spread. In this paper, we formulate a new approach to tumour growth using results and techniques from nonlinear elasticity theory. A mathematical model is given for the growth of a solid tumour using membrane and thick-shell theory. A central feature of the model is the characterisation of the material composition of the model through the use of a strain-energy function, thus permitting a mathematical description of the degree of differentiation of the tumour explicitly in the model. Conditions are given in terms of the strain-energy function for the processes of invasion and metastasis occurring in a tumour, being interpreted as the bifurcation modes of the spherical shell which the tumour is essentially modelled as. Our results are compared with actual experimental results and with the general behaviour shown by benign and malignant tumours. Finally, we use these results in conjunction with aspects of surface morphogenesis of tumours (in particular, the Gaussian and mean curvatures of the surface of a solid tumour) in an attempt to produce a mathematical formulation and description of the important medical processes of staging and grading cancers. We hope that this approach may form the basis of a practical application.

Cell Division↗

PubMed1986

Structure and function of specialized cilia in the exocrine pancreas.

Cilia are found in acinar and ductular lumina. Most descriptions of human or dog pancreatic tissue have indicated that these are probably motile structures which move and/or mix pancreatic secretion. A recent study interpreted arrangements of microtubules within cilia which deviated from the classic 9 + 2 pattern as indicating pathological change. There have been suggestions, however, from studies on nonmammalian and human pancreas, that the structure of pancreatic cilia suggests a sensory function. The present paper reports studies on the ultrastructural organization of the specialized cilia in human and canine pancreatic tissue. The pattern of microtubular organization resembles that of cilia modified for chemoreception rather than that of classic kinocilia. It is concluded that pancreatic ductular cilia are sensory rather than motile, providing a mechanism for monitoring general or specific molecular concentrations.

Animals↗

PubMed2005

Application of automated measurement stations for continuous water quality monitoring of the Dender river in Flanders, Belgium.

During the summer of 1999, two automated water quality measurement stations were installed along the Dender river in Belgium. The variables dissolved oxygen, temperature, conductivity, pH, rain-intensity, flow and solar radiation were measured continuously. In this paper these on-line measurement series are presented and interpreted using also additional measurements and ecological expert-knowledge. The purpose was to demonstrate the variability in time and space of the aquatic processes and the consequences of conducting and interpreting discrete measurements for river quality assessment and management. The large fluctuations of the data illustrated the importance of continuous measurements for the complete description and modelling of the biological processes in the river.

Ammonia↗

PubMed1983

Selected organizational features of certain Polish health care institutions.

A special feature of the Polish health care system in the 70s was the process toward organizational centralization. This consisted in integrating independent organizational units into larger, more complex ones, and transferring the processes of decision-making to higher management levels. This transition was introduced in 1975. One of its effects was incorporating into one organization all health care systems in a given area, primary care hospitals, specialist care units, laboratory bases, emergency and social welfare agencies and subsuming all these institutions under one management. The ensuing organization was named the Health Care Complex (HCC). It is interesting that in the HCC area other organizations were founded to cover industrial workers. These were called Occupational Health Care Complexes (OHCC). This paper deals with a description of a variety of OHCC organizational structures, an analysis of the relationships between different parameters of organizational structures (leaving aside, however, their casual interpretation), and an examination of the possibilities for applying empirical data to OHCC organizational structural analysis.

Humans↗

PubMed2005

Refined structure of the nicotinic acetylcholine receptor at 4A resolution.

We present a refined model of the membrane-associated Torpedo acetylcholine (ACh) receptor at 4A resolution. An improved experimental density map was obtained from 342 electron images of helical tubes, and the refined structure was derived to an R-factor of 36.7% (R(free) 37.9%) by standard crystallographic methods, after placing the densities corresponding to a single molecule into an artificial unit cell. The agreement between experimental and calculated phases along the helical layer-lines was used to monitor progress in the refinement and to give an independent measure of the accuracy. The atomic model allowed a detailed description of the whole receptor in the closed-channel form, including the ligand-binding and intracellular domains, which have not previously been interpreted at a chemical level. We confirm that the two ligand-binding alpha subunits have a different extended conformation from the three other subunits in the closed channel, and identify several interactions on both pairs of subunit interfaces, and within the alpha subunits, which may be responsible for their "distorted" structures. The ACh-coordinating amino acid side-chains of the alpha subunits are far apart in the closed channel, indicating that a localised rearrangement, involving closure of loops B and C around the bound ACh molecule, occurs upon activation. A comparison of the structure of the alpha subunit with that of AChBP having ligand present, suggests how the localised rearrangement overcomes the distortions and initiates the rotational movements associated with opening of the channel. Both vestibules of the channel are strongly electronegative, providing a cation-stabilising environment at either entrance of the membrane pore. Access to the pore on the intracellular side is further influenced by narrow lateral windows, which would be expected to screen out electrostatically ions of the wrong charge and size.

Amino Acid Sequence↗

PubMed2005

Ictal dystonic posturing in mesial versus neocortical temporal lobe seizures.

PURPOSE: Ictal contralateral dystonic posturing is a frequently observed clinical feature in temporal lobe seizures. It is generally interpreted as the result of spread of the ictal discharge into basal ganglia structure. In previous reports, analysing ictal behavior, a precise definition and description of the upper limb ictal dystonia is often lacking or contradictory. In our study we aimed to determine whether different subtypes of dystonia and their latency from the clinical onset of seizure might be of value for the differentiation between mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE). METHODS: Eighty seizures (51 MTLE and 29 NTLE) and 30 patients (20 MTLE and 10 NTLE) were analyzed with regard to dystonic posturing of the upper limb. Ictal dystonia was subdivided into different subtypes according to distinct clinical features. Their frequency and latency from the clinical onset of seizure were assessed. RESULTS: Frequencies of all subtypes were similar in MTLE and NTLE. Concerning the latencies contralateral dystonic posturing characterized by sustained muscle contractions with flexion of the wrist and fist closure, a frequently appearing feature, occurred significantly earlier in NTLE than in MTLE seizures. CONCLUSIONS: This difference between the two groups may provide a differentiation between an epileptic focus of mesial from neocortical temporal lobe origin.

Adult↗

PubMed1989

On the quantum physical theory of subjective antedating.

This paper explores the question of mental events causing neural events through the actions of the quantum physical probability field. After showing how quantum mechanical descriptions pertain to the influence that mental events have upon neural events, the question of Libet's "delay-and-antedating" observation is examined in the light of quantum mechanical description, specifically in the action of the probability field. The probability field is the product of two quantum wave functions. According to the transactional interpretation (TI) of quantum physics these wave functions can be pictured as offer and echo waves--the offer wave passing from an initial event to a future event and the echo wave passing from the future event back in time towards the initial event. I propose that two events so correlated are experienced as one and the same event; that is, any two quantum physically correlated events separated in time or space will constitute a single experience--an event in "consciousness." Using the TI then suggests a quantum physical resolution of the "delay-and-antedating" hypothesis/paradox put forward by Libet, B., Wright, E. W., Feinstein, B., & Pearl, D. K. (Brain, 1979, 102, 193). It also offers a first step towards the development of a quantum physical theory of subjective antedating based on the transactional interpretation of quantum mechanics.

Brain↗

PubMed2005

Investigations on the reaction pattern of photosystem II in leaves from Arabidopsis thaliana by time-resolved fluorometric analysis.

The transients of normalized fluorescence yield induced by an actinic laser flash in dark adapted leaves of Arabidopsis thaliana plants were measured with new equipment, that was developed as part of this work and permits the covarage of a wide time domain of 8 decades from 100 ns to 10 s. The raw data obtained were processed and analyzed within the framework of the "3-quencher" model with Q(A) as photochemical and P680(+)(*) and (3)Car as nonphotochemical quenchers. Comparative measurements with hydroxylamine treated PS II membrane fragments from spinach revealed that the widely used "dogma"of virtually identical efficiency of photochemical (Q(A)) and nonphotochemical (P680(+)(*)) quenching has to be revised: the constant of the latter exceeds that of the former by a factor of about 2. As a consequence, the probability of recombination between P680(+)(*) and Q(A)(-) and its kinetics have to be explicitly taken into account for the interpretation of flash induced fluorescence yield transients. The analysis of the experimental data within this extended "3-quencher" model reveals that a fully consistent description is achieved for the data gathered from measurements with intact leaves from wild type plants excited with actinic laser flashes of different energies (number of photons per flash and unit area). On the basis of these results it is shown that, in dark adapted leaves excited with a single laser flash, P680(+)(*) is predominantly (about 80% of the total reaction) reduced by Y(Z) via nanosecond kinetics and Q(A)(-) reoxidation is dominated by a kinetics of about 150 mus that are ascribed to PS II complexes with the Q(B) site occupied by PQ. The excess of excited chlorophyll singlet states decays to a significant extent via the carotenoid "triplet valve"with transient population of (3)Car. The present data provide the basis for analyses of A. thaliana mutants with modified lipid content and composition. The results of these investigations are described in an accompanying report (Steffen, R., Kelly, A. A., Huyer, J., Dormann, P., and Renger, G. (2005) Investigations on the reaction pattern of photosystem II in leaves from Arabidopsis thaliana wild type plants and mutants with genetically modified lipid content, Biochemistry 44, 3134-3142).

Arabidopsis Proteins↗

PubMed2000

[Neuropsychological testing in childhood and adolescence].

Among a number of issues and disorder pictures neuropsychological diagnostics should occupy a solid position, both in the initial assessment, as well as in that of the course. With an eye towards its use in child and adolescent psychiatry, a descriptive definition of this area of psychological diagnostics must be provided. In so doing, several essentially different approaches arise, whose effects on psychometrics and interpretation must be examined. Regardless of the fact that the current availability of standardized neuropsychological diagnostics is satisfactory only in certain areas, the methods used in clinical practice and/or research are presented. In addition to the individual test batteries, individual test methods for the areas of visual and auditory memory functions, attention functions, functions associated with speech, and executive functions are discussed. The current status of neuropsychological diagnostics generates essential tasks towards its further development. This is true with regard to goals attainable in the short term, such as adaptation or standardization of available instruments, as well as for long-term research tasks.

Adolescent↗

PubMed1981

The effect of inattention on form perception.

A state of inattention was achieved by having subjects selectively attend to one of two overlapping novel figures in a series of such overlapping figures. Recognition of form directly afterward was good for figures that had been attended to but was essentially nil for the unattended figures. Recognition failed to occur even if a familiar figure was in the unattended series and even if that figure was presented 1 sec before the test. A further experiment showed that certain general characteristics of the unattended figures other than form were recognized. The results are interpreted as indicating that attention is necessary for form perception, not merely for memory of form. It is suggested that a cognitive process of description constitutes the essence of form perception. Diverting attention eliminates the cognitive operation of describing the spatial relations that characterize a figure.

Attention↗

PubMed1998

Dermatoepidemiology. III. ABC principles for a critical review of the literature.

EPIDEMIOLOGY: Is the study of disease occurrence in human populations. As a science, epidemiology emphasizes descriptive and analytic observation, clinical trial, behavioral intervention, and the practical utility of diagnostic tests. "Epidemiology" is derived from the Greek epi (among), demos (people), and logos (doctrine). CLINICAL EPIDEMIOLOGY: Is the application of epidemiologic principles and methods to problems arising in clinical medicine, dermatology included. For dermatologists, understanding this discipline is as important as mastering other basic sciences, such as immunology, microbiology, and dermatopathology. The recognization of Lyme disease is a classic work of "infectious" disease epidemiology. In 1972, a disease characterized by erythema chronicum migrans and "endemic arthritis" clustered in Lyme, Connecticut. By 1975, an infectious agent was suspected to be the cause of the disease. In 1977, the tick was thought to be the vector; in 1980, the spirochete became the prime suspect and, in 1982, Borrelia burgdorferi was identified as the etiologic agent. The study of hexachlorobenzene exposure, resulting in porphyria turcica, is an example of classic "chronic" disease epidemiology. The illness began in 1955 when sporadic cases of porphyria occurred in eastern Turkey. In 1957, the first case with illness resembling congenital erythropoietic porphyria was described. In subsequent years, over 3000 patients developed "epidemic" porphyria. The cause was due to the ingestion of seed wheat which had been treated with fungicides containing 20% hexachlorobenzene. EPIDEMIOLOGIC METHODS: For research, published elsewhere as Dermatoepidemiology. I., include descriptive observational study, analytic observational study, epidemiologic experimental study and tests for sensitivity, specificity, and positive/negative predictive value. Epidemiologic principles, instead, stress the correct interpretation of data, minimization of bias, and the appreciation of natural variations in collected data.

Bias↗

PubMed2004

Enhancing validity: what counts as an asthma attack?

BACKGROUND: Major epidemiological studies in asthma use the question: "How many attacks of asthma have you had in the last 12 months?" We set out to study what constitutes an asthma attack from the perspective of people with asthma. We also examined concordance between qualitative responses and standard quantitative measures of this question. METHODS: Individuals aged 18 to 70 years who sought care for asthma at Emergency Departments in an Australian central city, a suburban and a regional hospital were recruited. Sixty two (43 women and 19 men) participants were interviewed in depth. All interviews were taped, transcribed and thematically analyzed. Demographic data and responses to respiratory health data were also collected. FINDINGS: Widely varying responses to the question, "How many attacks of asthma have you had in the last 12 months?" were found in the quantitative data set. Comparison of quantitative and qualitative data sets showed good agreement between these two responses (intraclass correlation 0.66). People defined asthma attacks as "major" and "minor," as determined by the degree of personal control they were able to exercise. A strongly unifying description of a severe attack was that it was "out of control." Patient's recognized that upper respiratory tract infections commonly triggered major attacks. INTERPRETATION: A commonly asked question about the number of asthma attacks in the past year needs refinement in order to enhance validity. Asthma action plans should use the words "out of control" when defining a severe attack of asthma.

Adolescent↗

PubMed2002

Values and voices in teaching gerontology and geriatrics: case studies as stories.

Case studies are used extensively in gerontological and geriatric education and practice, especially to present clinically relevant examples and to illustrate abstract concepts, principles, and theories in the study of aging. This article reviews the important pedagogical, clinical, and ethical issues involved in their design and use, and presents an argument that both case study developers and discussants need to become more reflective when they think about the nature of writing and listening to case studies as stories. The major themes from the literature in narrative and clinical ethics on case studies as stories are surveyed, including consideration of both facts and values, the debate on generalization versus specificity, and the need for interpreters and commentators. The implications of these insights for teaching and clinical education are considered, including the importance of addressing the need for rich description, multiple voices, open-endedness, and critical analysis.

Education, Medical↗