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PubMed1984

The structure of images.

In practice the relevant details of images exist only over a restricted range of scale. Hence it is important to study the dependence of image structure on the level of resolution. It seems clear enough that visual perception treats images on several levels of resolution simultaneously and that this fact must be important for the study of perception. However, no applicable mathematically formulated theory to deal with such problems appears to exist. In this paper it is shown that any image can be embedded in a one-parameter family of derived images (with resolution as the parameter) in essentially only one unique way if the constraint that no spurious detail should be generated when the resolution is diminished, is applied. The structure of this family is governed by the well known diffusion equation (a parabolic, linear, partial differential equation of the second order). As such the structure fits into existing theories that treat the front end of the visual system as a continuous stack of homogeneous layers, characterized by iterated local processing schemes. When resolution is decreased the images becomes less articulated because the extrem ("light and dark blobs") disappear one after the other. This erosion of structure is a simple process that is similar in every case. As a result any image can be described as a juxtaposed and nested set of light and dark blobs, wherein each blob has a limited range of resolution in which it manifests itself. The structure of the family of derived images permits a derivation of the sampling density required to sample the image at multiple scales of resolution.(ABSTRACT TRUNCATED AT 250 WORDS)

Cybernetics↗
PubMed1985

Chemistry and synthetic development of misoprostol.

Misoprostol is a synthetic prostaglandin which is related structurally to naturally occurring prostaglandin E1 (PGE1). PGE1 has long been recognized as an effective inhibitor of gastric acid secretion when administered intravenously. However, three major problems have prevented the use of natural PGE1 as a therapeutic treatment for peptic ulcer disease. Each of these problems, lack of oral activity, side-effects, and short duration of action, has been overcome by the chemical development of misoprostol from PGE1. The major structural alteration of PGE1 was the relocation of the 15-hydroxy group to the adjacent 16-position. This important modification significantly reduced typical prostaglandin side-effects such as diarrhea, yet retained full antisecretory potency and also provided a degree of oral activity. The second modification was the addition of a methyl group to carbon-16 to prevent metabolic oxidation of the hydroxy group. This structural change greatly increased both oral potency and duration of action and completed the synthetic development of misoprostol. Misoprostol is chemically unstable at room temperature, as is PGE1. This problem has been solved by pharmaceutical formulation studies which led to a stable and solid dosage form.

Alprostadil↗
PubMed2002

[Evidence based trauma surgery].

It is wise for surgeons to critically analyze their decision making, to add evidence in addition to the normal approaches, i.e. expert opinion and pathophysiological rationale. What evidence, is how it works, how often it is used in orthopedic surgery are the main topics of this article, as well as problems and limits to evidence-based medicine (EbM). EbM operates in five steps: 1. formulate an answerable question with respect to the patient's problems; 2. search the relevant literature; 3. critically appraise the assembled information through evidence based standards; 4. implement these evidence supported findings in your daily practice; 5. evaluate your evidence-based practice. When one builds decisions upon evidence the following effects become apparent: rational choice of possible, alternative decisions, reduction of diagnostic and therapeutic risks, improvements in medical education and efficient delivery of health care. A literature search reveals few evidence-based investigations published in orthopedic surgery. Lastly, we discuss limitations of EbM, showing that both misunderstanding about EbM and technical problems contribute to mistrust in EbM. These may include problems with population heterogeneity, standardization of surgical procedures, conducting random studies, the lack of statistical power and often "publication bias". Overcoming present problems with EbM by further ("evidence-based") research should lead to better understanding of the evidence paradigm and eventually modify this approach. The literature already demonstrates that EbM attains its goal. A valid judgment of EbM will result if one evaluates one's own evidence-based practices. The implementation of EbM is also a matter of policy.

Decision Support Systems, Clinical↗
PubMed1992

The safety of oral contraceptives: epidemiologic insights from the first 30 years.

Because oral contraceptives are used by tens of millions of healthy women, their safety for short-term and long-term use is an important issue that has been examined in a large number of epidemiologic studies. These studies have become more rigorous and have increased in size and analytic sophistication over the years. Although breast cancer remains the most important safety concern, the bulk of recent data suggests that oral contraceptives have no overall impact on a woman's risk of developing this disease. The results are less clear on the risk of cervical cancer and its precursors because of methodologic problems. However, the newer oral contraceptive formulations no longer appear to be associated with an increased risk of myocardial infarction or stroke.

Cardiovascular Diseases↗
PubMed1985

The urethral catheter--a review of its implication in urinary-tract infection.

The research into acquisition of urinary-tract infection over the last few decades has established three ways in which organisms may gain access to the urinary tract of the catheterized patients: Firstly, during the process of passing the catheter into the bladder should complete asepsis not be observed; secondly by travelling along the urethra in the small, fluid-filled cavity between catheter and mucosa; Thirdly following contamination of the drainage system, along the inside of the catheter directly into the bladder. The relative importance of each route is not clear and is still the subject of much controversy but it would seem that all these routes have a part to play in allowing infection to develop. The risk of catheterized patients acquiring urinary-tract infection is so great that where possible catheterization should be avoided. The most important preventive measure which may be taken is to limit the duration of indwelling catheterization. In addition, a considerable amount of research has attempted to distinguish other factors which might affect the rate at which urinary-tract infection in the catheterized patient becomes established so that high-risk patients may be identified. The evidence indicates that the risk increases with duration of catheterization, age, length of hospital stay, immunosuppressant treatment, that it is greater in female than male patients and that a patient with a serious or fatal underlying disease is also more likely to develop bacteriuria. Finally, properties of the urine and the host defence mechanisms may affect the susceptibility of the individual to urinary-tract infection. Identification of the routes of infection and patients at risk is only part of the problem. The next stage is to formulate criteria for the care of catheterized patients which reduce the risk of infection to the absolute minimum and will hopefully go some way towards diminishing the unsatisfactory high levels of urinary-tract infection that are currently associated with indwelling catheterization.

Age Factors↗
PubMed1980

Preschool language disorders and subsequent language and academic difficulties.

Sixty-three language-disordered children first evaluated in their preschool years were followed four to five years after initial diagnosis. At follow-up approximately 40% of these children continued to present speech and language problems and approximately 40% presented other learning problems. Preschool levels of language comprehension, formulation, semantics, syntax, phonology, and speech production were found to be moderately correlated to subsequent class placement in the elementary grades. Duration of preschool therapy was not related to either the severity of preschool language disorder or to any subsequent speech, language, or academic abilities. Duration of school therapy was related to severity of phonologic deficit as rated during the preschool years and to all follow-up ratings for speech, language, and academic abilities.

Achievement↗
PubMed1994

Protein classification by stochastic modeling and optimal filtering of amino-acid sequences.

The prediction of a protein's tertiary structural class from its amino-acid sequence is formulated as a signal-processing problem. The amino-acid sequence is treated as a "time series" of symbols containing signals that determine the protein's structural class. A methodology is described for building detailed stochastic signal models for recognized structural classes of single-domain proteins. We solve the problem of determining that model, from a set of candidates, which is the most probable generator of a protein's entire amino-acid sequence. The solution employs a nonlinear, optimal filtering algorithm, which is suited for implementation on parallel computer architectures. Previous approaches have only been able to classify correctly 80% of single-domain proteins within three very broad structural types, while our approach achieves this level across twelve much more detailed classes.

Amino Acid Sequence↗
PubMed2004

Formation and stability of nano-emulsions.

This review describes the principles of formation and stability of nano-emulsions. It starts with an introduction highlighting the main advantages of nano-emulsions over macroemulsions for personal care and cosmetic formulations. It also describes the main problems with lack of progress on nano-emulsions. The second section deals with the mechanism of emulsification and the dynamic light scattering technique for measurement of the droplet size of nano-emulsions. This is followed by a section on methods of emulsification and the role of surfactants. Three methods are described for nano-emulsion preparation, namely high energy emulsification (using homogenisers), low energy emulsification whereby water is added to an oil solution of the surfactant and the principle of the phase inversion temperature (PIT). A section is devoted to steric stabilisation and the role of the adsorbed layer thickness. The problem of Ostwald ripening (which is the main instability process of nano-emulsions) is described in some detail. The methods that can be applied to reduce Ostwald ripening are briefly described. This involves the addition of a second less soluble oil phase such as squalene and/or addition of a strongly adsorbed and water insoluble polymeric surfactant. The last part of the review gives some examples of nano-emulsions that are prepared by the PIT method as well as using high pressure homogeniser. A comparison of the two methods is given and the rate of Ostwald ripening is measured in both cases. The effect of changing the alkyl chain length and branching of the oil was investigated using decane, dodecane, tertadecane, hexadecane and isohexadecane. The branched oil isohexadcecane showed higher Ostwald ripening rate when compared with a linear chain oil with the same carbon number.

Journal Article↗
PubMed2006

Experimental verification of a computational technique for determining ground reactions in human bipedal stance.

We have developed a three-dimensional (3D) biomechanical model of human standing that enables us to study the mechanisms of posture and balance simultaneously in various directions in space. Since the two feet are on the ground, the system defines a kinematically closed-chain which has redundancy problems that cannot be resolved using the laws of mechanics alone. We have developed a computational (optimization) technique that avoids the problems with the closed-chain formulation thus giving users of such models the ability to make predictions of joint moments, and potentially, muscle activations using more sophisticated musculoskeletal models. This paper describes the experimental verification of the computational technique that is used to estimate the ground reaction vector acting on an unconstrained foot while the other foot is attached to the ground, thus allowing human bipedal standing to be analyzed as an open-chain system. The computational approach was verified in terms of its ability to predict lower extremity joint moments derived from inverse dynamic simulations performed on data acquired from four able-bodied volunteers standing in various postures on force platforms. Sensitivity analyses performed with model simulations indicated which ground reaction force (GRF) and center of pressure (COP) components were most critical for providing better estimates of the joint moments. Overall, the joint moments predicted by the optimization approach are strongly correlated with the joint moments computed using the experimentally measured GRF and COP (0.78 < or = r(2) < or = 0.99,median,0.96) with a best-fit that was not statistically different from a straight line with unity slope (experimental=computational results) for postures of the four subjects examined. These results indicate that this model-based technique can be relied upon to predict reasonable and consistent estimates of the joint moments using the predicted GRF and COP for most standing postures.

Computer Simulation↗
PubMed2006

A new approach to diabetic control: fuzzy logic and insulin pump technology.

Diabetes is a major health problem. Since the utilisation of insulin in the 1920s there have been myriad problems in developing suitable technologies to formulate and administer correct dosages to temper this metabolic disease. From multiple daily injections, nasal inhalations and enzymatic supplementation these artificial shortcuts still do not have the ability to fully replicate a 'normoglycaemic' state of being. In this paper, we sought to explore the use of insulin pumps and the application of fuzzy logic technology to act as an 'artificial pancreas' in diabetic patients. This paper builds on our previous work [Grant P, Naesh, O. Fuzzy logic and decision-making in anaesthetics. J Roy Soc Med 2005;98(1):7-9 [review]].

Biotechnology↗
PubMed2006

Drug insurance instability and its correlates: results from the 2000 Medical Expenditure Panel Survey.

BACKGROUND: Health insurance instability (ie, temporal gaps in health insurance coverage) is a prevalent phenomenon in the United States. To date, most studies have focused on the factors that affect the intermittent lack of health insurance coverage. However, no studies known to the authors have examined the factors associated with prescription drug insurance instability (ie, temporal gaps in drug insurance coverage) among working-age adults. Developing an accurate profile of persons with unstable drug insurance is essential to formulate rational policy to address this problem. OBJECTIVES: The objectives of this study were to (1) document the prevalence of prescription insurance instability among working-age adults and (2) describe the association between prescription drug insurance instability and demographic, socioeconomic status, and employment characteristics. METHODS: The data source used in this study was the 2000 Medical Expenditure Panel Survey. This study used a cross-sectional design using data provided by respondents at each of the 3 interviews conducted during the year 2000. Chi-square and hierarchical multinomial logistic regression analyses were used to describe the associations among (1) demographics, (2) socioeconomic status, and (3) employment characteristics and drug insurance status (classified as continuous, absent, or unstable). RESULTS: During the year 2000, 12.5% (21.1 million) of the working-age adults in the United States had unstable prescription drug coverage. Persons aged 35-54 years had lower rates of drug insurance instability compared with those aged 18-24 [adjusted odds ratio 0.66 (95% confidence interval 0.54-0.80)]. The least educated (12 or fewer years of education) were more likely than those with more education (13-16 years) to experience at least one period without drug coverage (62% vs 32%, P<0.01). The poorest respondents (those at less than 200% of the federal poverty level) were more likely than the wealthiest respondents (those at more than 400% of the poverty level) to report at least some time without drug coverage (37% vs 28%, P<0.01). Those experiencing a divorce or death of a spouse were more than twice as likely as stably married persons to experience at least one period without drug insurance [adjusted odds ratio 2.23 (95% confidence interval 1.68-2.96)]. Adults who were unstably employed during the year and/or who worked for small firms generally experienced higher rates of drug insurance instability. CONCLUSIONS: Prescription drug insurance instability is a prevalent phenomenon among working-age adults in the United States, with approximately 1 in 8 experiencing this problem during 2000. Our results suggest that demographics, socioeconomic status, and employment characteristics all play important roles in predicting prescription drug insurance status, with the least educated and poorest being particularly vulnerable to interruptions in drug coverage. Premium assistance programs providing subsidies to small firms' low-income employees and permitting small firms to form insurance pools may help to decrease the number of drug coverage uninsurance spells in this population.

Adolescent↗
PubMed2006

Inverse estimation of nonpoint sources of fecal coliform for establishing allowable load for Wye River, Maryland.

An estimation of the nonpoint sources of fecal coliform (FC) has been formulated as an inverse parameter estimation problem, using FC observation data from the receiving waters. An inverse algorithm was integrated into the three-dimensional transport model, HEM-3D. The modified Gauss-Newton method was used for the optimal estimation of the loads. The approach is straightforward and requires less effort in modification of the existing hydrodynamic model. Model experiments were conducted to investigate the feasibility of load estimation in a tidal river. The parameter uncertainty and accuracy associated with load estimation are discussed using data sets with different sampling sizes. The inverse model was applied to the tidal Wye River, Maryland, USA, to estimate FC nonpoint sources and to develop an allowable load for the river to attain water quality standards. The model results suggest that the inverse modeling approach is suitable for estimating FC nonpoint sources. The inverse method not only provides an efficient approach to assess the contribution of nonpoint sources, but has the additional advantage of addressing the problems of the uncertainty and error associated with FC simulation in the estuary using hydrodynamic models.

Feces↗
PubMed1991

A probabilistic view on steady-state enzyme reactions.

A new theoretical description of steady-state enzyme reactions is proposed. The description is based on the concepts of the probability theory instead of the conventional formalism of chemical kinetics. A general steady-state rate equation is obtained using a probabilistic model of the catalytic act. As a result, the classical problems of enzyme kinetics can be formulated and considered in a different aspect. It is shown that the new theory presents a clearer treatment of some commonly obscure questions, such as the steady-state establishment. The theory also gives additional possibilities in the interpretation of the experimental results of traditional methods and proposes certain new ways in experimental investigations of enzymes.

Animals↗
PubMed2003

A note on estimation of dynamics of multiple gene expression based on singular value decomposition.

Recently, data on multiple gene expression at sequential time points were analyzed, using singular value decomposition (SVD) as a means to capture dominant trends, called characteristic modes, followed by fitting of a linear discrete-time dynamical system in which the expression values at a given time point are linear combinations of the values at a previous time point. We attempt to address several aspects of the method. To obtain the model we formulate a non-linear optimization problem and present how to solve it numerically using standard MATLAB procedures. We use publicly available data to test the approach. For reader's convenience, we provide a straightforward, ready-to-use, procedure in MATLAB, which employs its standard features to analyze data of this kind. Then, we investigate the sensitivity of the method to missing measurements and its possibilities to reconstruct missing data. Also, we discuss the possible consequences of data regularization, called sometimes 'polishing', on the outcome of analysis, especially when model is to be used for prediction purposes. Summarizing we point out that approximation of multiple gene expression data preceded by SVD provides some insight into the dynamics but may also lead to unexpected difficulties, like overfitting problems.

Algorithms↗
PubMed1976

Computerization in microbiology.

Computerization of the clinical microbiology laboratory is finally coming of age. Operations and functions easily adapted from other clinical laboratories have already been implemented in the microbiology laboratory, e.g., fiscal, clerical, and other administrative housekeeping chores. Similarly, storage, retrieval, and analysis of banks of data easily collected and filed have also been successfully accomplished in microbiology for several years. The more challenging problems of computerization still deserve and require the attention of microbiologists. These problems lie in the smooth sequential formulation and transmission of clinical microbiological test results from the laboratory to clinical records; the manipulation of relevant data by the computer prospectively for the detection and prediction of nosocomial infections or miniepidemics; and the development of programed lessons and examinations for computerized instruction, retraining, and examination of technologists and other individuals interested in microbiology.

Clinical Laboratory Techniques↗
PubMed2000

Mathematical modeling of diffusion-mediated release from bulk degrading matrices.

The release of active agent from a bulk degrading matrix is formulated as a linear reaction diffusion problem. Two pools of active agent are assumed to contribute to the release: a pool of mobile active agent which readily diffuses out of the matrix upon immersion in an aqueous medium and a pool of immobilized active agent which can diffuse only after matrix degradation. Due to the linearity of our model, the dynamics of the two pools of active agent can be considered separately, for any mode of bulk degradation kinetics. For definiteness, we consider the case of first order degradation kinetics and a rectangular parallelepiped shaped matrix. A closed form solution is obtained for the release under perfect sink conditions which is then used to describe the in vitro release of the PerioChip¿trade mark omitted¿. This solution can explain the bi-phasic release profile characteristic of many hydrolytically degradable matrices. The case of mass transfer boundary conditions is solved numerically using the finite element method (FEM). This analysis indicates that under ordinary mixing conditions the diffusion layer is not rate limiting and the release is very well approximated by the analytical result for perfect sink conditions.

Aerosols↗
PubMed2001

Multicomponent simulation of wastewater-derived nitrogen and carbon in shallow unconfined aquifers. I. Model formulation and performance.

One of the most common methods to dispose of domestic wastewater involves the release of septic effluent from drains located in the unsaturated zone. Nitrogen from such systems is currently of concern because of nitrate contamination of drinking water supplies and eutrophication of coastal waters. The objectives of this study are to develop and assess the performance of a mechanistic flow and reactive transport model which couples the most relevant physical, geochemical and biochemical processes involved in wastewater plume evolution in sandy aquifers. The numerical model solves for variably saturated groundwater flow and reactive transport of multiple carbon- and nitrogen-containing species in a three-dimensional porous medium. The reactive transport equations are solved using the Strang splitting method which is shown to be accurate for Monod and first- and second-order kinetic reactions, and two to four times more efficient than sequential iterative splitting. The reaction system is formulated as a fully kinetic chemistry problem, which allows for the use of several special-purpose ordinary differential equation (ODE) solvers. For reaction systems containing both fast and slow kinetic reactions, such as the combined nitrogen-carbon system, it is found that a specialized stiff explicit solver fails to obtain a solution. An implicit solver is more robust and its computational performance is improved by scaling of the fastest reaction rates. The model is used to simulate wastewater migration in a 1-m-long unsaturated column and the results show significant oxidation of dissolved organic carbon (DOC), the generation of nitrate by nitrification, and a slight decrease in pH.

Fresh Water↗
PubMed1996

Antigens linked to synthetic microspheres induce immune responses in primates in the absence of adjuvant.

Although most strategies of vaccination require immunopotentiation to induce efficient immune responses, the development of new adjuvants for human vaccines is highly limited by safety problems. In order to overcome this problem, we developed a new vaccine formulation based on the covalent linkage of protein or peptide to synthetic microspheres. In previous experiments performed in mice, we demonstrated that these particulate antigens induce strong antigen-specific CD4+ T cell proliferative responses in the absence of adjuvant. In the present study, we analyzed the immunogenicity in primate Saimiri sciureus monkeys of two different proteins linked to synthetic microspheres. Immune responses induced by these particulate proteins administered without adjuvant were compared to those stimulated by the soluble antigens injected with alum. We currently demonstrated that, in monkeys, particulate antigens administered without adjuvant, induced good PBMC proliferative response and antibody production. Furthermore, the analysis of antibody responses using mAbs specific for different Saimiri sciureus immunoglobulins showed that the antibody response profiles were different in monkeys immunized with soluble versus particulate form of antigens. Results of this study demonstrate that particulate form of antigen may stimulate qualitatively different immune responses as compared to alum and therefore suggest that this new antigen formulation could be an attractive candidate for the development of vaccines.

Animals↗