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Blood pressure and blood flow variation during postural change from sitting to standing: model development and validation.

Short-term cardiovascular responses to postural change from sitting to standing involve complex interactions between the autonomic nervous system, which regulates blood pressure, and cerebral autoregulation, which maintains cerebral perfusion. We present a mathematical model that can predict dynamic changes in beat-to-beat arterial blood pressure and middle cerebral artery blood flow velocity during postural change from sitting to standing. Our cardiovascular model utilizes 11 compartments to describe blood pressure, blood flow, compliance, and resistance in the heart and systemic circulation. To include dynamics due to the pulsatile nature of blood pressure and blood flow, resistances in the large systemic arteries are modeled using nonlinear functions of pressure. A physiologically based submodel is used to describe effects of gravity on venous blood pooling during postural change. Two types of control mechanisms are included: 1) autonomic regulation mediated by sympathetic and parasympathetic responses, which affect heart rate, cardiac contractility, resistance, and compliance, and 2) autoregulation mediated by responses to local changes in myogenic tone, metabolic demand, and CO(2) concentration, which affect cerebrovascular resistance. Finally, we formulate an inverse least-squares problem to estimate parameters and demonstrate that our mathematical model is in agreement with physiological data from a young subject during postural change from sitting to standing.

Autonomic Nervous System↗

Drug formularies--good or evil? A view using prescribing analyses and cost trends data.

In the UK, the drugs bill has almost trebled in the last 10 years and is consuming an increasing proportion of the total National Health Service spend. If the drugs bill can be limited, greater funds will be available for other areas of the health service. Therefore, cost containment measures which include prescribing from a formulary or generic prescribing are now widely encouraged. Prescribing analyses and cost trends data generated from pharmacists sending dispensed general practitioners' prescriptions to a central point for reimbursement are a valuable tool in the assessment of prescribing habits and can be used by general practitioners when preparing a formulary. In the West Midlands, such data have been used to identify areas of growth in cardiovascular drugs and problem areas where prescribing an expensive formulation has led to a dramatic increase in costs.

Cardiovascular Agents↗

Stress, deformation, and atelectasis of the lung.

The lung parenchyma as a tissue has a rather unusual stress-strain relationship. A theoretical derivation of this relationship is presented which connects the surface tension and the tissue elastic stress in the alveolar septa with the alveolar geometry. The mathematical expression contains a few meaningful physical constants which can be determined by in vitro and in vivo experiments. With this stress-strain relationship, the general equations of lung mechanics are formulated, and solutions to some simpler problems are presented. First, the equilibrium of a lung subjected to a uniform inflation pressure (definition: alveolar air pressure - intrapleural pressure - pleural tension X mean curvature of pleura) is analyzed, and the stability of the equilibrium states with respect to small perturbations is examined. Second, an exact solution for a lung in a chest under the influence of gravity is presented; the solution is "exact," of course, for only a particular lung, but it can serve as a standard to check numerical procedures being developed in many laboratories. Finally, three types of possible atelectasis-planar, axial, and focal-are analyzed. The planar type can exist in a normally inflated lung, provided the layers of alveoli are forced to collapse toward a plane by some external agent. But axial atelectasis (alveoli collapse into a cylinder) can occur only if the dimension (at which the elastic tension in the alveolar septa vanishes). Similarly, focal atelectasis can occur only if the entire lung is smaller than the resting volume.

Elasticity↗

Generalized discriminant analysis using a kernel approach.

We present a new method that we call generalized discriminant analysis (GDA) to deal with nonlinear discriminant analysis using kernel function operator. The underlying theory is close to the support vector machines (SVM) insofar as the GDA method provides a mapping of the input vectors into high-dimensional feature space. In the transformed space, linear properties make it easy to extend and generalize the classical linear discriminant analysis (LDA) to nonlinear discriminant analysis. The formulation is expressed as an eigenvalue problem resolution. Using a different kernel, one can cover a wide class of nonlinearities. For both simulated data and alternate kernels, we give classification results, as well as the shape of the decision function. The results are confirmed using real data to perform seed classification.

Algorithms↗

Bayesian assessment of sample size for clinical trials of cost-effectiveness.

The authors present an analysis of the choice of sample sizes for demonstrating cost-effectiveness of a new treatment or procedure, when data on both cost and efficacy will be collected in a clinical trial. The Bayesian approach to statistics is employed, as well as a novel Bayesian criterion that provides insight into the sample size problem and offers a very flexible formulation.

Bayes Theorem↗

Integrating systems theory and attachment theory: the use of radio communication to modify attachments in a patient with psychogenic vomiting.

A case is presented that shows the usefulness of integrating systems theory and attachment theory in the formulation and treatment of a clinical problem. The 5 year old son of East Indian immigrants presented with persistent psychogenic vomiting associated with pathological family attachments. It was evident that the precarious family equilibrium was stabilized by the child's psychogenic vomiting. The therapeutic team suggested to the family that their problems might be more satisfactorily resolved if the mother and child maintained their link by two-way radio. Three weeks later the vomiting had ceased, the child no longer felt that he needed the radio and both parents had established new patterns of relating to their child, whose attendance and peer socialization at school showed marked improvement. To some extent the rapid resolution of the problems was facilitated by the cultural strengths of the family.

Acculturation↗

Prescribing patterns of antibiotics and sensitivity patterns of common microorganisms in the Internal Medicine ward of a teaching hospital in Western Nepal: a prospective study.

BACKGROUND: Information about antibiotic use and resistance patterns of common microorganisms are lacking in hospitals in Western Nepal. Excessive and inappropriate use of antibiotics contributes to the development of bacterial resistance. The parameter: Defined daily dose/100 bed-days, provides an estimate of consumption of drugs among hospital in-patients. This study was carried out to collect relevant demographic information, antibiotic prescribing patterns and the common organisms isolated including their antibiotic sensitivity patterns. METHODS: The study was carried out over a 3-month period (01.04.2002 to 30.06.2002) at the Manipal Teaching Hospital, Western Nepal. The median number of days of hospitalization and mean +/- SD cost of antibiotics prescribed during hospital stay were calculated. The use of antibiotics was classified for prophylaxis, bacteriologically proven infection or non-bacteriologically proven infection. Sensitivity patterns of the common organisms were determined. Defined daily dose/100 bed-days of the ten most commonly prescribed antibiotics were calculated. RESULTS: 203 patients were prescribed antibiotics; 112 were male. Median duration of hospitalization was 5 days. 347 antibiotics were prescribed. The most common were ampicillin, amoxicillin, metronidazole, ciprofloxacin and benzylpenicillin. Mean +/- SD cost of antibiotics was 16.5 +/-13.4 US dollars. Culture and sensitivity testing was carried out in 141 patients. The common organisms isolated were H. influenzae, E. coli, K. pneumoniae and S. aureus. CONCLUSIONS: Antibiotic resistance is becoming a problem in the Internal Medicine ward. Formulation of a policy for hospital antibiotic use and an educational programme especially for junior doctors is required.

Journal Article↗

Hypochondriacal states.

A brief historical introduction traces the evolution of the concept of hypochondriasis. It is suggested that the term should now be used only as a descriptive adjective when there is a morbid preoccupation with health or body. Social and cultural factors are outlined, as well as problems of measurement. The psychopathology, as formulated by Freud and others, is also described. Clinical aspects are discussed under the headings of general symptoms, pain, smell, bodily appearance, sexual, gastro-intestinal, cardio-respiratory, eyes, and ears, nose and throat. Psychiatric syndromes mentioned are: hypochondria as a possible primary state, personality disorders, phobic-anxiety state, neurashthenia, obsessional neurosis, hysteria, depression, paranoid psychosis and organic. In general, hypochondriacal symptoms seem to make the prognosis rather worse. Treatment is to be aimed at the primary condition, which is most commonly depression, anxiety state or conversion reaction.

Anxiety↗

Hamilton-Jacobi modelling of relative motion for formation flying.

A precise analytic model for the relative motion of a group of satellites in slightly elliptic orbits is introduced. With this aim, we describe the relative motion of an object relative to a circular or slightly elliptic reference orbit in the rotating Hill frame via a low-order Hamiltonian, and solve the Hamilton-Jacobi equation. This results in a first-order solution to the relative motion identical to the Clohessy-Wiltshire approach; here, however, rather than using initial conditions as our constants of the motion, we utilize the canonical momenta and coordinates. This allows us to treat perturbations in an identical manner, as in the classical Delaunay formulation of the two-body problem. A precise analytical model for the base orbit is chosen with the included effect of zonal harmonics (J(2), J(3), J(4)). A Hamiltonian describing the real relative motion is formed and by differing this from the nominal Hamiltonian, the perturbing Hamiltonian is obtained. Using the Hamilton equations, the variational equations for the new constants are found. In a manner analogous to the center manifold reduction procedure, the non-periodic part of the motion is canceled through a magnitude analysis leading to simple boundedness conditions that cancel the drift terms due to the higher order perturbations. Using this condition, the variational equations are integrated to give periodic solutions that closely approximate the results from numerical integration (1 mm/per orbit for higher order and eccentricity perturbations and 30 cm/per orbit for zonal perturbations). This procedure provides a compact and insightful analytic description of the resulting relative motion.

Journal Article↗

Mental health services and sexual abuse: the need for staff training.

Identification of child abuse by mental health services is important for formulation of the causes of presenting problems and for development of comprehensive treatment plans. A small but growing number of studies suggest, however, that the majority of child sexual abuse cases are not identified by mental health services. A similarly small literature also suggests that abuse survivors are extremely reluctant to spontaneously tell anyone about the abuse, indicating that professionals have a responsibility to ask rather than wait for spontaneous disclosures. The purpose of this study, therefore, was to add to these two bodies of literature with a New Zealand sample. A postal questionnaire was completed by 191 women who had received counselling for childhood sexual abuse. The average amount of time taken to tell anyone about the abuse was 16 years. Only 22% of those who had been in contact with public mental health services had ever been asked about abuse by those services. It was concluded that New Zealand women are reluctant to disclose abuse and that mental health services are, as is the case elsewhere, failing to assist them with this process. The need for staff training is discussed, and an example described.

Adult↗

Face verification through tracking facial features.

We propose an algorithm for face verification through tracking facial features by using sequential importance sampling. Specifically, we first formulate tracking as a Bayesian inference problem and propose to use Markov chain Monte Carlo techniques for obtaining an empirical solution. A reparameterization is introduced under parametric motion assumption, which facilitates the empirical estimation and also allows verification to be addressed along with tracking. The facial features to be tracked are defined on a grid with Gabor attributes (jets). The motion of facial feature points is modeled as a global two-dimensional (2-D) affine transformation (accounting for head motion) plus a local deformation (accounting for residual motion that is due to inaccuracies in 2-D affine modeling and other factors such as facial expression). Motion of both types is processed simultaneously by the tracker: The global motion is estimated by importance sampling, and the residual motion is handled by incorporating local deformation into the measurement likelihood in computing the weight of a sample. Experiments with a real database of face image sequences are presented.

Journal Article↗

Analytical models of optical refraction in the troposphere.

An extremely accurate but simple asymptotic description (with known error) is obtained for the path of a ray propagating over a curved Earth with radial variations in refractive index. The result is sufficiently simple that analytic solutions for the path can be obtained for linear and quadratic index profiles. As well as rendering the inverse problem trivial for these profiles, this formulation shows that images are uniformly magnified in the vertical direction when viewed through a quadratic refractive-index profile. Nonuniform vertical distortions occur for higher-order refractive-index profiles.

Journal Article↗

Optimal noise filtering in the chemotactic response of Escherichia coli.

Information-carrying signals in the real world are often obscured by noise. A challenge for any system is to filter the signal from the corrupting noise. This task is particularly acute for the signal transduction network that mediates bacterial chemotaxis, because the signals are subtle, the noise arising from stochastic fluctuations is substantial, and the system is effectively acting as a differentiator which amplifies noise. Here, we investigated the filtering properties of this biological system. Through simulation, we first show that the cutoff frequency has a dramatic effect on the chemotactic efficiency of the cell. Then, using a mathematical model to describe the signal, noise, and system, we formulated and solved an optimal filtering problem to determine the cutoff frequency that bests separates the low-frequency signal from the high-frequency noise. There was good agreement between the theory, simulations, and published experimental data. Finally, we propose that an elegant implementation of the optimal filter in combination with a differentiator can be achieved via an integral control system. This paper furnishes a simple quantitative framework for interpreting many of the key notions about bacterial chemotaxis, and, more generally, it highlights the constraints on biological systems imposed by noise.

Chemotaxis↗

Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations.

The approach to paediatric drug dosing needs to be based on the physiological characteristics of the child and the pharmacokinetic parameters of the drug. This review summarises the current knowledge on developmental changes in absorption, distribution, metabolism and excretion and combines this knowledge with in vivo and in vitro pharmacokinetic data that are currently available. In addition, dosage adjustments based on practical problems, such as child-friendly formulations and feeding regimens, disease state, genetic make-up and environmental influences are presented. Modification of a dosage based on absorption, depends on the route of absorption, the physico chemical properties of the drug and the age of the child. For oral drug absorption, a distinction should be made between the very young and children over a few weeks old. In the latter case, it is likely that practical considerations, like appropriate formulations, have much greater relevance to oral drug absorption. The volume of distribution (V(d)) may be altered in children. Hydrophilic drugs with a high V(d) in adults should be normalised to bodyweight in young children (age <2 years), whereas hydrophilic drugs with a low V(d) in adults should be normalised to body surface area (BSA) in these children. For drugs that are metabolised by the liver, the effect of the V(d) becomes apparent in children <2 months of age. In general, only the first dose should be based on the V(d); subsequent doses should be determined by the clearance. Pharmacokinetic studies on renal and liver function clarify that a distinction should be made between maturation and growth of the organs. After the maturation process has finished, the main influences on the clearance of drugs are growth and changes in blood flow of the liver and kidney. Drugs that are primarily metabolised by the liver should be administered with extreme care until the age of 2 months. Modification of dosing should be based on response and on therapeutic drug monitoring. At the age of 2-6 months, a general guideline based on bodyweight may be used. After 6 months of age, BSA is a good marker as a basis for drug dosing. However, even at this age, drugs that are primarily metabolised by cytochrome P450 2D6 and uridine diphosphate glucuronosyltransferase should be normalised to bodyweight. In the first 2 years of life, the renal excretion rate should be determined by markers of renal function, such as serum creatinine and p-aminohippuric acid clearance. A dosage guideline for drugs that are significantly excreted by the kidney should be based on the determination of renal function in first 2 years of life. After maturation, the dose should be normalised to BSA. These guidelines are intended to be used in clinical practice and to form a basis for more research. The integration of these guidelines, and combining them with pharmacodynamic effects, should be considered and could form a basis for further study.

Age Factors↗

Evaluation of cats fed vegetarian diets and attitudes of their caregivers.

OBJECTIVE: To determine motivation and feeding practices of people who feed their cats vegetarian diets as well as taurine and cobalamin status of cats consuming vegetarian diets. DESIGN: Cross-sectional study. ANIMALS: 34 cats that had been exclusively fed a commercial or homemade vegetarian diet and 52 cats that had been fed a conventional diet for > or = 1 year. PROCEDURES: Participants were recruited through a Web site and from attendees of a national animal welfare conference. Caregivers of cats in both groups answered a telephone questionnaire regarding feeding practices for their cats. Blood was obtained from a subset of cats that had been fed vegetarian diets. Blood and plasma taurine and serum cobalamin concentrations were measured. RESULTS: People who fed vegetarian diets to their cats did so largely for ethical considerations and were more likely than people who fed conventional diets to believe that there are health benefits associated with a vegetarian diet and that conventional commercial cat foods are unwholesome. Both groups were aware of the potential health problems that could arise from improperly formulated vegetarian diets. All cats evaluated had serum cobalamin concentrations within reference range, and 14 of 17 had blood taurine concentrations within reference range. CONCLUSIONS AND CLINICAL RELEVANCE: Vegetarian diets are fed to cats primarily for ethical considerations. Results of this study should aid practitioners in communicating with and providing advice to such clients.

Animal Feed↗

Hyperalimentation in cancer.

When response rates to antineoplastic therapy are good and the associated nutritional morbidity is high, TPN is recommended when the gastrointestinal tract is unavailable for use. Patients should not be denied adequate cancer treatment because of the fear of complications secondary to malnutrition. On the other hand, prolongation of pain and suffering for the terminally ill cancer patient is obviously not an indication for TPN. Appropriate clinical judgment is required in proper selection of the TPN candidate. Malnutrition is almost always a prerequisite, as is failure of the gastrointestinal tract. Therapies designed to direct nutritional support to preferentially benefit the host and "starve" the tumor have had only limited short-term success in animal models. The use of diets that are glutamine- and arginine-supplemented are only now being examined in animal experiments. Since TPN allows total and complete control of exogenous nutrients, it should be used to explore alternative therapies in the form of nutrient composition. For example, if tumors are preferential glutamine utilizers, then TPN-enriched solutions might be employed to increase the number of cells in a phase of mitosis that makes them more susceptible to attack by cell-cycle specific chemotherapeutic agents. Stimulation of tumor growth by TPN in patients is not scientifically documented. Only anecdotal reports appear in the literature. Thousands of cancer patients worldwide have received TPN. Were stimulation of tumor growth to be a major problem with TPN solutions as currently formulated, it should be known by now.

Cachexia↗

Capital disadvantage: America's failing capital investment system.

The U.S. system of allocating investment capital is failing, putting American companies at a serious disadvantage and threatening the long-term growth of the nation's economy. The problem, says Michael Porter, goes beyond the usual formulation of the issue: accusations of "short-termism" by U.S. managers, ineffective corporate governance by directors, or a high cost of capital. The problem involves the external capital allocation system by which capital is provided to companies, as well as the system by which companies allocate capital internally. America's system is marked by fluid capital and a financial focus. Other countries--notably Japan and Germany--have systems with dedicated capital and a focus on corporate position. In global competition, where investment increasingly determines a company's capacity to upgrade and innovate, the U.S. system does not measure up. These conclusions come out of a two-year research project sponsored by the Harvard Business School and the Council on Competitiveness. Porter recommends five far-reaching reforms to make the U.S. system superior to Japan's and Germany's: 1. Improve the present macroeconomic environment. 2. Expand true ownership throughout the system so that directors, managers, employees, and even customers and suppliers hold positions as owners. 3. Align the goals of capital providers, corporations, directors, managers, employees, customers, suppliers, and society. 4. Improve the information used in decision making. 5. Foster more productive modes of interaction and influence among capital providers, corporations, and business units.

Capital Expenditures↗

Silicone manufacturing for long-term implants.

The manufacture of silicone materials, particularly silicone elastomers, is described. Chemistry, typical formulations, ingredients, and manufacturing procedures and problems are discussed. Sources and testing for contamination and extractables are reviewed.

Humans↗