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Scabies outbreak in an extended care unit--a positive outcome.

A recent outbreak of scabies occurred in an extended care unit attached to an acute care hospital. Seventy-eight residents and over 100 staff and family members were treated at a cost of more than $20,000. The protocol in use at that time was found to be inadequate for an outbreak situation because it was based on the assumption that all staff would have previous experience of this type of problem. Close liaison with the head nurse of the affected unit, the occupational health and safety department, the medical microbiologist and the infection control department has resulted in the development of a procedure that reflects all of the concerns that were raised during the outbreak. In addition, a policy was formulated to cover problems associated with contacting medical personnel in a timely manner. This outbreak has resulted in positive changes in procedures as well as improved communication in a wide variety of departments within the hospital.

Cross Infection↗

Toward simplifying and accurately formulating fragment assembly.

The fragment assembly problem is that of reconstructing a DNA sequence from a collection of randomly sampled fragments. Traditionally, the objective of this problem has been to produce the shortest string that contains all the fragments as substrings, but in the case of repetitive target sequences this objective produces answers that are overcompressed. In this paper, the problem is reformulated as one of finding a maximum-likelihood reconstruction with respect to the two-sided Kolmogorov-Smirnov statistic, and it is argued that this is a better formulation of the problem. Next the fragment assembly problem is recast in graph-theoretic terms as one of finding a noncyclic subgraph with certain properties and the objectives of being shortest or maximally likely are also recast in this framework. Finally, a series of graph reduction transformations are given that dramatically reduce the size of the graph to be explored in practical instances of the problem. This reduction is very important as the underlying problems are NP-hard. In practice, the transformed problems are so small that simple branch-and-bound algorithms successfully solve them, thus permitting auxiliary experimental information to be taken into account in the form of overlap, orientation, and distance constraints.

Base Sequence↗

The framing of decisions and the psychology of choice.

The psychological principles that govern the perception of decision problems and the evaluation of probabilities and outcomes produce predictable shifts of preference when the same problem is framed in different ways. Reversals of preference are demonstrated in choices regarding monetary outcomes, both hypothetical and real, and in questions pertaining to the loss of human lives. The effects of frames on preferences are compared to the effects of perspectives on perceptual appearance. The dependence of preferences on the formulation of decision problems is a significant concern for the theory of rational choice.

Choice Behavior↗

Hidden Markov model approach to skill learning and its application to telerobotics.

In this paper, we discuss the problem of how human skill can be represented as a parametric model using a hidden Markov model (HMM), and how an HMM-based skill model can be used to learn human skill. HMM is feasible to characterize a doubly stochastic process--measurable action and immeasurable mental states--that is involved in the skill learning. We formulated the learning problem as a multidimensional HMM and developed a testbed for a variety of skill learning applications. Based on "the most likely performance" criterion, the best action sequence can be selected from all previously measured action data by modeling the skill as an HMM. The proposed method has been implemented in the teleoperation control of space station robot system, and some important implementation issues have been discussed. The method allows a robot to learn human skill in certain tasks and to improve motion performance.

Algorithms↗

Biometry has to improve the quality of decision making both in biomedical research and in clinical practice.

The leading principles of biometrical design, evaluation and decision making in biomedicine can be summarized as follows: (1) formulation of the problem to be solved and of the specific question(s) to be answered; (2) definition of the population in study, ways of sampling and manoeuvres (treatments); (3) determining the kind and number of variables (time intervals of measurement, investigated biomedical parameters); (4) performing the pilot study if necessary (to arrange randomized blocks, to form hypotheses); (5) formulation of zero (alternative) hypothesis, setting the values of alpha(beta) risk; (6) ordering the sample sizes; (7) testing the type of statistical distribution and the homoscedasticity of the obtained data; (8) calculation of the point and interval (confidence, tolerance) estimates; (9) performing the chosen tests, e.g. on the significance of differences or correlations; and (10) the conclusions for science and practice, with eventual return to point (1) on a higher level of knowledge.

Biometry↗

Subcellular trafficking of the cytoplasmic expression system.

Cationic liposomes have provided many advantages over viral vector formulations; however, the problem of inefficient gene expression remains. This is due in part to the nuclear membrane, which limits DNA entry into the nucleus. Cytoplasmic expression systems using T7 RNA polymerase have been developed to express genes in the cytoplasm and avoid the need for nuclear import of DNA. Although these systems show improved transgene expression, little is known about how they function in transfected cells. Direct comparisons between a cytoplasmic and nuclear expression system were carried out with a 293 cell line stably expressing T7 RNA polymerase. A formulation for optimal reporter gene expression was developed and used in conjunction with a variety of subcellular trafficking inhibitors to study the process of DNA endocytosis. Transfected cells were also studied at different stages of the cell cycle to determine the dependence of each system on mitosis. These results showed that cytoplasmic and nuclear expression systems utilize similar endocytosis pathways to the point of endosomal release. Once DNA is released into the cytoplasm, the cytoplasmic expression system shows immediate expression that is proportional to the amount of DNA released. In contrast, DNA targeted for nuclear expression requires additional time for nuclear entry. The level of nuclear expression is also restricted by the limited amount of DNA that is imported into the nucleus. Finally, mitosis is required for effective nuclear expression but not for cytoplasmic expression. Therefore, the cytoplasmic expression system has considerable advantages over traditional nuclear expression systems and may be an effective method for transfecting nondividing cells. Efficient expression of genes delivered by nonviral vectors is hindered owing to poor nuclear transport of plasmid DNA. A potential solution to this problem would be to use a cytoplasmic expression system. Previous studies have shown that this method produces enhanced gene expression when compared with traditional nuclear expression systems; however, the actual mechanisms by which the cytoplasmic expression system works remains unknown. This article focuses on a direct comparison between cytoplasmic and nuclear expression in terms of optimal DNA delivery formulations, intracellular trafficking of DNA, and cell cycle dependence. These results indicate that the cytoplasmic expression system has two primary advantages over nuclear expression in that it does not rely on nuclear DNA transport or mitosis for efficient expression.

Anti-Bacterial Agents↗

A linear programming approach for identifying a consensus sequence on DNA sequences.

MOTIVATION: Maximum-likelihood methods for solving the consensus sequence identification (CSI) problem on DNA sequences may only find a local optimum rather than the global optimum. Additionally, such methods do not allow logical constraints to be imposed on their models. This study develops a linear programming technique to solve CSI problems by finding an optimum consensus sequence. This method is computationally more efficient and is guaranteed to reach the global optimum. The developed method can also be extended to treat more complicated CSI problems with ambiguous conserved patterns. RESULTS: A CSI problem is first formulated as a non-linear mixed 0-1 optimization program, which is then converted into a linear mixed 0-1 program. The proposed method provides the following advantages over maximum-likelihood methods: (1) It is guaranteed to find the global optimum. (2) It can embed various logical constraints into the corresponding model. (3) It is applicable to problems with many long sequences. (4) It can find the second and the third best solutions. An extension of the proposed linear mixed 0-1 program is also designed to solve CSI problems with an unknown spacer length between conserved regions. Two examples of searching for CRP-binding sites and for FNR-binding sites in the Escherichia coli genome are used to illustrate and test the proposed method. AVAILABILITY: A software package, Global Site Seer for the Microsoft Windows operating system is available by http://www.iim.nctu.edu.tw/~cjfu/gss.htm

Algorithms↗

Optimal sample size for a series of pilot trials of new agents.

A new approach is presented for determining the appropriate sample sizes for a series of screening trials to identify promising new therapeutic agents. The formulation of the problem is motivated by recognition of the fact that screening of new agents is a continuing process. Consequently, it does not seem ideal to fix the overall total sample size, as previous authors have done. Instead we fix the error rates and optimize the individual sample sizes to minimize the time to identify a promising agent, using an empirical Bayes formulation. When applied to data from the large historical experience of exploratory vaccination trials at Memorial Sloan-Kettering Cancer Center, the method demonstrates that relatively small individual screening trials are optimal in this setting. The reliability of the results is evaluated using bootstrapping techniques.

Bayes Theorem↗

Women's preferences for vaginal antimicrobial contraceptives. I. Methodology.

Sexually transmitted diseases, including AIDS, and unplanned pregnancies continue to be a serious worldwide problem. A number of organizations are developing woman-controlled vaginal formulations to prevent these problems. However, little information is available regarding the types of products women prefer even though such knowledge is essential to obtain widespread use. This is the first of several articles that describe the results of a consumer preference study for such vaginal formulations performed in Campinas, São Paulo State, Brazil. Because no published methodology was available, the instruments and interview techniques were developed first and procedures established for the identification and participation of research subjects. After preparation of a questionnaire, a pilot study was performed to evaluate it, to establish the interview technique, and to determine the optimal method for subject recruitment. Based on the results, the approach was selected and applied to 635 subjects from different age and socioeconomic groups. The developed methodology and questionnaire, the advantages and the problems encountered, are presented.

Acquired Immunodeficiency Syndrome↗

Resin polymerization problems--are they caused by resin curing lights, resin formulations, or both?

Negative effects of rapid, high-intensity resin curing have been predicted for both argon lasers and plasma-arc curing lights. To address these questions, six different resin restorative materials were cured with 14 different resin curing lights representing differences in intensities ranging from 400 mW/cm2 to 1,900 mW/cm2; delivery modes using constant, ramped, and stepped methods; cure times ranging from 1 second to 40 seconds; and spot sizes of 6.7 mm to 10.9 mm. Two lasers, five plasma-arc lights, and seven halogen lights were used. Shrinkage, modulus, heat generation, strain, and physical changes on the teeth and resins during strain testing were documented. Results showed effects associated with lights were not statistically significant, but resin formulation was highly significant. Microfill resins had the least shrinkage and the lowest modulus. An autocure resin had shrinkage and modulus as high as or higher than the light-cured hybrid resins. Lasers and plasma-arc lights produced the highest heat increases on the surface (up to 21 degrees C) and within the resin restorations (up to 14 degrees C), and the halogen lights produced the most heat within the pulp chamber (up to 2 degrees C). Strain within the tooth was least with Heliomolar and greatest with Z100 Restorative and BISFIL II autocure resin. Clinical effects of strain relief were evident as white lines at the tooth-resin interface and cracks in enamel adjacent to the margins. This work implicates resin formulation, rather than light type or curing mode, as the important factor in polymerization problems. Lower light intensity and use of ramped and stepped curing modes did not provide significant lowering of shrinkage, modulus, or strain, and did not prevent enamel cracking adjacent to margins and formation of "white line" defects at the margins. Until materials with lower shrinkage and modulus are available, use of low-viscosity surface sealants as a final step in resin placement is suggested to seal defects.

Acrylic Resins↗

Approximate Bayesian multibody tracking.

Visual tracking of multiple targets is a challenging problem, especially when efficiency is an issue. Occlusions, if not properly handled, are a major source of failure. Solutions supporting principled occlusion reasoning have been proposed but are yet unpractical for online applications. This paper presents a new solution which effectively manages the trade-off between reliable modeling and computational efficiency. The Hybrid Joint-Separable (HJS) filter is derived from a joint Bayesian formulation of the problem, and shown to be efficient while optimal in terms of compact belief representation. Computational efficiency is achieved by employing a Markov random field approximation to joint dynamics and an incremental algorithm for posterior update with an appearance likelihood that implements a physically-based model of the occlusion process. A particle filter implementation is proposed which achieves accurate tracking during partial occlusions, while in cases of complete occlusion, tracking hypotheses are bound to estimated occlusion volumes. Experiments show that the proposed algorithm is efficient, robust, and able to resolve long-term occlusions between targets with identical appearance.

Algorithms↗

Prospects of formulating proteins/peptides as aerosols for pulmonary drug delivery.

Formulation of proteins/peptides for therapeutic uses has often posed some challenges to drug formulators. The main problem is the relatively weak forces involved in the native conformation of these proteins and so making them quite labile. Furthermore, their susceptibility to proteolytic enzymes in the gut makes oral administration quite challenging. While various routes like, ocular, transdermal, nasal and buccal have been tried, none of these routes has proved to be a potential alternative to the invasive injection. However, various studies have been performed on the formulation of these proteins as aerosols for pulmonary delivery and promising results have been obtained. This article looks at the prospects of inhaled proteins as a delivery route for systemic activity.

Administration, Inhalation↗

The role of theory in the psychophysiology of personality: from Ivan Pavlov to Jeffrey Gray.

Psychophysiological approaches to personality have made significant progress in recent years, partly as a spin-off of technological innovation (e.g., functional neuroimaging) and partly as a result of an emerging theoretical consensus regarding the structure and biology of basic processes. In this field, Jeffrey Gray's influential psychophysiological theory of personality - now widely known as Reinforcement Sensitivity Theory (RST) - owes much to Pavlov, who devoted a large proportion of his later life to personality differences and their implications for psychiatry. In this article, we trace the influence of Pavlov on Hans Eysenck's and Jeffrey Gray's work, and then provide a brief description of RST in order to highlight some of the central problems - as well as some tentative solutions - in the psychophysiology of personality. Specifically, the importance of theory in personality research is stressed by the contrast of Gray's theoretically driven model with less fertile atheoretical (i.e., exploratory-inductive) approaches. The fecundity of RST, which has been in continual development over a period of thirty years, is discussed in the light of Karl Popper's views on the nature of science, especially the formulation of the 'problem situation', which sets up the theoretical and operational conditions under which hypotheses may be challenged and tested to destruction. In this respect, we see the truth of Lewin's [Lewin, K., 1951. Field theory in social science: selected theoretical papers. In: Cartwright, D., (Ed.). Harper & Row, New York] famous phrase, "There is nothing so practical as a good theory".

Animals↗

Intelligent control of a planning system for astronaut training.

This work intends to design, analyze and solve, from the systems control perspective, a complex, dynamic, and multiconstrained planning system for generating training plans for crew members of the NASA-led International Space Station. Various intelligent planning systems have been developed within the framework of artificial intelligence. These planning systems generally lack a rigorous mathematical formalism to allow a reliable and flexible methodology for their design, modeling, and performance analysis in a dynamical, time-critical, and multiconstrained environment. Formulating the planning problem in the domain of discrete-event systems under a unified framework such that it can be modeled, designed, and analyzed as a control system will provide a self-contained theory for such planning systems. This will also provide a means to certify various planning systems for operations in the dynamical and complex environments in space. The work presented here completes the design, development, and analysis of an intricate, large-scale, and representative mathematical formulation for intelligent control of a real planning system for Space Station crew training. This planning system has been tested and used at NASA-Johnson Space Center.

Algorithms↗

Formulation and stability testing of photolabile drugs.

Exposure of a drug to irradiation can influence the stability of the formulation, leading to changes in the physicochemical properties of the product. The influence of excipients of frequently used stabilizers is often difficult to predict and, therefore, stability testing of the final preparation is important. The selection of a protective packaging must be based on knowledge about the wavelength causing the instability. Details on drug photoreactivity will also be helpful in order to minimize side-effects and/or optimize drug targeting by developing photoresponsive drug delivery systems. This review focuses on practical problems related to formulation and stability testing of photolabile drugs.

Chemistry, Pharmaceutical↗

On the stability of double bubbles and double drops.

The stability problems for equilibrium standard "double bubble" and "double drop" configurations are considered. Recent work has shown that a double bubble is stable to volume-preserving perturbations. In this paper, the stability to perturbations that do not conserve the volumes of the individual bubbles is examined. It is shown that a double bubble shape is also stable to these perturbations and, thus, is stable to arbitrary perturbations. The analysis is based on the principle of minimum total energy. A variational principle is used to formulate the stability problem for an equilibrium double drop configuration formed under zero gravity by two drops of immiscible incompressible liquids.

Journal Article↗

The influence of the flow of the reacting gas on the conditions for a thermal explosion.

The classical problem of thermal explosion is modified so that the chemically active gas is not at rest but is flowing in a long cylindrical pipe. Up to a certain section the heat-conducting walls of the pipe are held at low temperature so that the reaction rate is small and there is no heat release; at that section the ambient temperature is increased and an exothermic reaction begins. The question is whether a slow reaction regime will be established or a thermal explosion will occur. The mathematical formulation of the problem is presented. It is shown that when the pipe radius is larger than a critical value, the solution of the new problem exists only up to a certain distance along the axis. The critical radius is determined by conditions in a problem with a uniform axial temperature. The loss of existence is interpreted as a thermal explosion; the critical distance is the safe reactor's length. Both laminar and developed turbulent flow regimes are considered. In a computational experiment the loss of the existence appears as a divergence of a numerical procedure; numerical calculations reveal asymptotic scaling laws with simple powers for the critical distance.

Journal Article↗

[Attempt at a psychoanalytic approach to "concept art"].

In a short review the development of psychoanalytic explorations in art from "pathography to psychobiography" is given. Chasseguet-Smirgel's critique on a limitation to looking for connections between the biography of the artist and his work is discussed as well as Eissler's proposal of an "endopoetic approach". The characteristic of most of the psychoanalytic publications is their orientation on the psychoanalytic conflict-model. New impulses to psychoanalytic interpretations of art were given by ego-psychology. The author tries to understand the artistic creations of "Concept Art" which appeared in the late Sixties, by the psychoanalytic model. It can be shown that especially in these productions which made their theme the "idea" and which are characterised by a degree of abstractness which had not been known before the ego-psychological approach seems to be the most adequate one. Ego performances manifest themselves in these works of concept art at an extreme intensity while the conflictual material of the id is reduced to a minimum or is totally eliminated. The concept artist is not only showing us a mirror of the pathology of our time, but is also giving us ways to overcome these problems. The hypothesis is formulated that concept art is giving us responses to three main problems of our time which is makes it's theme and by doing so tries to solve: it is dealing with the fear of a common psychic disintegration, especially with the danger of outbreaks of aggressive impulses. Moreover single central ego-functions are demonstrated by the concepts to the recipient and he has (actively) to discover them. Lastly the communicative function of art is formulated in concept art in such a radical way as has not been known before. In some of the artistic concepts the recipient is not only meant to reflect upon them, but is also forced to communicative actions.

Art↗