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PubMed2002

Problems of contact angle and solid surface free energy determination.

The current general problems of formulation and determination of surface free energy are discussed. So far several theories and approaches have been proposed, but formulation of surface and interfacial free energy, as regards its components, is still a very debatable issue. However, as long as no method for determination of real surface free energy quantities is known, even relative values charged with many simplified assumptions are useful for better understanding of the wetting processes. In this paper special focus is concentrated on powdered solids for which direct measurement of the contact angles is not possible. For such solids the porous layer imbibition techniques are most frequently applied. Then, using the wicking results the contact angle is calculated from Washburn's equation. However, such a procedure leads to overestimated contact angle values in comparison to those measured directly on smooth surfaces of the same solid, if such surface can be obtained at all. As a consequence, the solid surface free energy components calculated via such overestimated contact angles are significantly lower than those obtained from contact angles measured directly. Methodologies to avoid this problem are also described.

Journal Article↗
PubMed1994

The impact of social science research on health policy.

The relationship between research and health policy is discussed from a policy process perspective, describing communication problems in the course of policy formulation, implementation and evaluation. Policy process is often expected by researchers to be rational, having logical sequence of steps and the objective evaluation of alternatives based on scientific knowledge. In fact, policies are often formulated without clear problem identification or based on wrong assumption. The timing of research and policy-making differs. Policy-makers need to respond quickly. Evaluations may be regarded by politicians as embarrassing if they point to a need for significant change. It is not satisfactory to consider only research and policy-making: their relationship is influenced by the media, different interest groups and by the general public. Health policy formulation is embedded in the general policy environment of particular societies. Some countries have a long tradition of consensus-building, while in others health reforms have been formulated and introduced in a centralized way. Traditional bio-medical thinking influences health policy-makers. The importance of social and political acceptability tends to be overlooked. The paper emphasizes that we are experiencing an era of scarcity of resources and growing tension concerning allocation decisions. Existing institutions provide insufficient incentives for policy-makers and researchers to promote public dialogue about such issues. The paper concludes that there is a need for new approaches to policy development and implementation, new structures in policy-making, changes in research financing and co-operation between disciplines and new structures for public participation in policy-making. Research should facilitate more open and democratic dialogue about policy options and the consequences of alternative choices.

Communication↗
PubMed1999

Planning and analysis of repeated measures at key time-points in clinical trials sponsored by pharmaceutical companies.

In this paper we explore the possible reasons why medical papers reporting clinical trials sponsored by the pharmaceutical industry often analyse repeated measures data at certain key time-points instead of employing sophisticated models of repeated measures proposed by many statisticians. A survey indicated that the priority reason in the industry for having repeated measures in clinical trials is to monitor the trial and to utilize the early results for strategic decision making. We discuss what the common statistical methods do and do not offer for analysis of repeated measures in such clinical trials. We advocate the need to improve the understanding of the medical interest in conducting longitudinal trials in the industry, and to plan and analyse the repeated measures accordingly. We address the medical interest by formulating the problem and give illustrative examples for both phases II and III trials.

Alendronate↗
PubMed2001

Compact clinical MRI magnet design using a multi-layer current density approach.

In this work, a new method of optimization is successfully applied to the theoretical design of compact, actively shielded, clinical MRI magnets. The problem is formulated as a two-step process in which the desired current densities on multiple, co-axial surface layers are first calculated by solving Fredholm equations of the first kind. Non-linear optimization methods with inequality constraints are then invoked to fit practical magnet coils to the desired current densities. The current density approach allows rapid prototyping of unusual magnet designs. The emphasis of this work is on the optimal design of short, actively-shielded MRI magnets for whole-body imaging. Details of the hybrid numerical model are presented, and the model is used to investigate compact, symmetric, and asymmetric MRI magnets. Magnet designs are presented for actively-shielded, symmetric magnets of coil length 1.0 m, which is considerably shorter than currently available designs of comparable dsv size. Novel, actively-shielded, asymmetric magnet designs are also presented in which the beginning of a 50-cm dsv is positioned just 11 cm from the end of the coil structure, allowing much improved access to the patient and reduced patient claustrophobia. Magn Reson Med 45:331-340, 2001.

Magnetic Resonance Imaging↗
PubMed1976

Maximization of steady-state bacterial production in a chemostat with pH and substrate control.

This analytical study deals with the steady-state behavior and control of microbial growth in continuous cultures. A second order Haldane-Monod model of continuous cultures is used as a basis for study of the effects of the adjustment of pH by the addition of acidic (or basic) materials. The treatment of a hydrogen ion concentration, in addition to substrate and microbial concentrations as state variables, results in a third order system of equations describing the process. The analysis of the system in equilibrium yields several admissible steady states, that is, steady states which satisfy all constraints. An optimal control problem is formulated and subsequently solved to maximize steady-state microbial production.

Bacteria↗
PubMed1993

The estrogenic activity of synthetic progestins used in oral contraceptives.

BACKGROUND: Oral contraceptives (OC) contain an orally active estrogen in combination with an orally active synthetic progestin derived from 19-nortestosterone. OC have had an enormous positive impact on public health for the past three decades, and in the main, there has been a remarkably low incidence of troublesome side effects. Although estrogens are implicated in an increased incidence of breast and endometrial cancer, epidemiologic studies have not provided convincing evidence to support a direct correlation between OC use and an increase in breast cancer incidence. By contrast, OC do cause a decrease in the incidence of endometrial and ovarian carcinoma. During the past decade, several isolated reports have linked an increased incidence of breast cancer with the use of synthetic progestins. No mechanism for the proliferative potential of progestins has been offered. Therefore, the authors investigated this problem to formulate a hypothesis, based on laboratory data, that might be evaluated in populations at risk. METHODS: The synthetic progestins (19-nortestosterone derivatives) chosen for the study were norethynodrel, norethindrone, norgestrel (levonorgestrel), and gestodene. These were compared with the actions of medroxyprogesterone acetate (MPA). To determine whether the progestins produced their effects via the ER, the cells were transfected with a chloramphenicol acetyl transferase (CAT) reporter gene containing an estrogen response element only activated by ER. RESULTS: The 19-nortestosterone derivatives all stimulated the growth of estrogen receptor (ER)-positive but not ER-negative breast cancer cells in culture. Antiestrogens, but not the antiprogestin mifepristone (also known as RU 486), inhibited progestin-stimulated cell proliferation. MPA did not stimulate cell proliferation. All the synthetic progestins that increased replication also activated CAT. Activation was blocked by antiestrogens but not by mifepristone; the synthetic progestin MPA was inactive. CONCLUSIONS: These studies provided direct evidence that some synthetic progestins exert estrogenic effects through the ER. The results demonstrated that progestins can have a dual effect on estrogen target tissues either to stimulate or differentiate cells. The results suggest that some beneficial estrogen-like effects could be produced by synthetic progestins (e.g., bone preservation), but epidemiologic studies of OC use should focus of the "total estrogen" content to establish whether some formulations place some groups of women at greater risk of having breast cancer.

Breast Neoplasms↗
PubMed1989

The analysis of titration studies in phase III clinical trials.

Clinical trials commonly employ the titration design for certain drugs such as antihypertensives. In a Phase III trial the design has purposes distinct from those of a Phase I or II trial, as well as from those of a trial with a parallel design. In this paper we compare the titration design with the usual parallel design in their respective purposes for Phase III trials, explore the relevant questions addressed, and examine typical data from such trials. We also discuss work which focuses primarily on the Phase I or II titration trials. We formulate the problem in the framework of one-way contingency table augmented with incomplete data and obtain the maximum likelihood estimates of the parameters and their estimated variances/covariances via the EM algorithm. An example of a Phase III study of an antihypertensive agent illustrates the proposed procedure.

Analysis of Variance↗
PubMed1993

A method to test for a recent increase in HIV-1 seroconversion incidence: results from the Multicenter AIDS Cohort Study (MACS).

We have formulated the problem of determining whether there has been an upturn in HIV-1 seroconversion incidence over the first five years of follow-up in the Multicenter AIDS Cohort Study (MACS) as that of locating the minimum of a quadratic regression or examination of two-knot piecewise spline models. Under a quadratic model, we propose a method to obtain a direct estimate and a bootstrap estimate for the location of the temporal turning point (local minimum) for HIV-1 seroconversion incidence and three methods to estimate confidence intervals for the location of the turning point for HIV seroconversion incidence: (1) Wald confidence interval estimate with or without log transformation assuming the asymptotic normality and applying the Delta method; (2) asymmetric confidence intervals using Fieller's Theorem and its modification; and (3) bootstrapping confidence intervals. Inferences for the temporal turning point based on Wald tests for a single regression term in a non-linear regression model were not reliable compared to inferences based on confidence intervals placed on calendar time. We present results using these different methods applied to the MACS data and we obtain power estimates to illustrate the performances of different methods.

Cohort Studies↗
PubMed2001

Steady Vapor Bubbles in Rectangular Microchannels.

We consider vapor bubbles in microchannels in which the vapor is produced by a heater element and condenses in cooler parts of the interface. The free boundary problem is formulated for a long steady-state bubble in a rectangular channel with a heated bottom. Lubrication-type equations are derived for the shape of the liquid-vapor interface in a cross-sectional plane and in the regime for which the vapor phase fills most of the cross section. These equations are then solved numerically over a range of parameter values with given temperature profiles in the walls and subject to a global integral condition requiring evaporation near the heater to balance condensation in colder areas of the interface. Our results show that depending on the temperature, the side walls can be either dry or covered with a liquid film and we identify criteria for these two different regimes. The asymptotic method breaks down in the limit when capillary condensation becomes important near the bubble top and a different approach is used to determine the shape of the bubble in this limit. Solutions here involve localized regions of large mass fluxes, which are asymptotically matched to capillary-statics regions where the heat transfer is negligible. Copyright 2001 Academic Press.

Journal Article↗
PubMed1999

Asymmetric MRI magnet design using a hybrid numerical method.

This paper describes a hybrid numerical method for the design of asymmetric magnetic resonance imaging magnet systems. The problem is formulated as a field synthesis and the desired current density on the surface of a cylinder is first calculated by solving a Fredholm equation of the first kind. Nonlinear optimization methods are then invoked to fit practical magnet coils to the desired current density. The field calculations are performed using a semi-analytical method. A new type of asymmetric magnet is proposed in this work. The asymmetric MRI magnet allows the diameter spherical imaging volume to be positioned close to one end of the magnet. The main advantages of making the magnet asymmetric include the potential to reduce the perception of claustrophobia for the patient, better access to the patient by attending physicians, and the potential for reduced peripheral nerve stimulation due to the gradient coil configuration. The results highlight that the method can be used to obtain an asymmetric MRI magnet structure and a very homogeneous magnetic field over the central imaging volume in clinical systems of approximately 1.2 m in length. Unshielded designs are the focus of this work. This method is flexible and may be applied to magnets of other geometries.

Algorithms↗
PubMed2000

Multidrug resistance genotypes (insertions in the beta3-beta4 finger subdomain and MDR mutations) of HIV-1 reverse transcriptase from extensively treated patients: incidence and association with other resistance mutations.

Multiple nucleoside resistance involves specific mutational patterns of the HIV-1 pol gene that are independent of the classic mutations conferring resistance to individual dideoxynucleosides. These include a cluster of five mutations in the reverse-transcriptase (RT) coding region (A62V, V75I, F77L, F116Y, and Q151M) generally referred to as multidrug resistance (MDR) mutations, and insertions of one or several amino acid residues between codons 67 and 70 of RT, a flexible region joining two antiparrallel beta sheets (beta3-beta4 insertions). The objectives of this study were (i) to determine the prevalence of multidrug resistance genotypes (MDR mutations and beta3-beta4 insertions) in a cohort of 632 patients who were extensively pretreated with anti-HIV drugs and not responding to their current antiretroviral therapy, and (ii) to analyze the association of multidrug resistance genotypes with other resistance mutations in the RT and protease genes. Among viruses sequenced from these patients, 15 (2.4%) of them contained an insertion and 2 (0.3%) contained a deletion in the beta3-beta4 finger subdomain of RT. In 9 cases, the insertion was associated with a D67S, G, or E mutation. In addition, we identified 13 (2.1%) viruses harboring specific MDR mutations (mainly Q151M and/or A62V, V75I, F116Y). Interestingly, the A62V mutation was found in 6 of the 15 strains with an insertion, whereas the other MDR mutations were not observed in insertion mutant strains. Especially high levels of resistance to zidovudine were observed for viruses with a beta3-beta4 insertion in the background of A62V, L210W, and T215Y. Otherwise, MDR mutations and beta3-beta4 insertions were found in association with the classic mutations conferring resistance to zidovudine, lamivudine, nonnucleoside RT inhibitors, and protease inhibitors, according to treatment history. Finally, we observed a genome with a deletion of codon 70 associated with a Q151M MDR mutation. These data suggest that the emergence of HIV-1 multidrug resistance, which may occur in various genetic contexts, poses a challenging problem in formulating treatment strategies.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Synthesis and biological activity of oligosaccharide libraries.

Random glycosylation has proven remarkably effective for the generation of mixtures of oligosaccharides. Clearly, not all of the possible glycosidically-linked isomers are formed in equal quantity in these reactions. In the instances where product structures have been thoroughly investigated, however, all have been shown to be present. So far, only one random glycosylation step has been performed and the challenge will be to see if two tandem steps can generate a useful oligosaccharide library. Whether or not the present formulation of random glycosylation succeeds as a dominant strategy for the synthesis of oligosaccharide libraries, this important challenge is open to many approaches where creativity in both formulating the problem, as well as experimentally addressing it, warrants a major international effort.

Carbohydrate Sequence↗
PubMed1989

[Electronic data processing of the patient record for computer-assisted evaluation of pregnancy and labor].

This article describes an EDP-adequate data collection system which can also be used in the conventional way. The relational data base system used is PROFESSIONAL ORACLE, Revision 5.1.; the requisite hardware consists of 3 IBM-AT-compatible personal computers with a main storage comprising 4 MB, system MS/PC-DOS, and a hard disk of at least 20 MB. The standardized case history compiles the user to collect the data carefully and completely. Besides formulating research problems the system automatically prepares the discharge report. By means of statistical analysis a continuous internal quality assessment was realized.

Electronic Data Processing↗
PubMed1999

[Definition and specification requirements for PAC-systems (picture archiving and communication system). A performance index with reference to the standard "IEEE Recommended Practice for Software Requirement Specifications"].

PROBLEM: The formulation of requirements is necessary to control the goals of a PACS project. Furthermore, in this way, the scope of functionality necessary to support radiological working processes becomes clear. METHOD: Definitions of requirements and specification are formulated independently of systems according to the IEEE standard "Recommended Practice for Software Requirements Specifications". Definitions are given in the Request for Information, specifications in the Request for Proposal. Functional and non-functional requirements are distinguished. The solutions are rated with respect to scope, appropriateness and quality of implementation. RESULTS: A PACS checklist was created according to the methods described above. It is published on the homepage of the "Arbeitsgemeinschaft Informationstechnologie" (AGIT) within the "Deutsche Röntgengesellschaft" (DRG) (http://www.uni-marburg.de/mzr/agit). CONCLUSION: The checklist provides a discussion forum which should contribute to an agreement on accepted basic PACS functionalities.

Humans↗
PubMed2006

Mathematical modelling of engineered tissue growth using a multiphase porous flow mixture theory.

This paper outlines the framework of a porous flow mixture theory for the mathematical modelling of in vitro tissue growth, and gives an application of this theory to an aspect of tissue engineering. The problem is formulated as a set of partial differential equations governing the space and time dependence of the amounts of each component of the tissue (phase), together with the physical stresses in each component. The theory requires constitutive relations to specify the material properties of each phase, and also requires relations to specify the stresses developed due to mechanical interactions, both within each phase and between different phases. An application of the theory is given to the study of the mobility and aggregation of a population of cells seeded into an artificial polymeric scaffold. Stability analysis techniques show that the interplay of the forces between the tissue constituents results in two different regimes: either the cells form aggregates or disperse through the scaffold.

Algorithms↗
PubMed1993

Optimization of structure and movement of the legs of animals.

The legs of animals, and their movements, have presumably been optimized by evolution and/or learning for the functions required of them in life. This paper presents a series of studies in which attempts have been made to formulate optimization problems, to which the legs and their movements may be solutions. These are studies of the ratio of radius to wall thickness in tubular bones; of the strengths of bones; of tendon thickness; of the gaits of turtles and of mammals; and of the technique of human high jumping. They illustrate some serious difficulties that may arise in inverse optimization studies but also show that the approach is helping to improve our understanding of legs and gaits.

Animals↗