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PubMed2006

Computing the size and location of myocardial ischemia using measurements of ST-segment shift.

It is well known that the presence of myocardial ischemia can be observed as a shift in the ST segment of an electrocardiogram (ECG) recording. The question we address in this paper is whether or not ST shift can be used to compute approximations of the size and location of the ischemic region. We begin by investigating a cost functional (measuring the difference between synthetic recorded data and simulated values of ST shift) for a parameter identification problem to locate the ischemic region. We then formulate a more flexible representation of the ischemia using a level set framework and solve the associated minimization problem for the size and position of the ischemia. We apply this framework to a set of ECG data generated by the Bidomain model using the cell model of Winslow et al. Based on this data, we show that values of ST shift recorded at the body surface are capable of identifying the position and (roughly) the size of the ischemia.

Animals↗
PubMed2004

Therapeutic drug monitoring of cyclosporine.

Therapeutic drug monitoring of cyclosporine has been established as part of the routine clinical treatment for patients after organ transplantation. The inability to define optimal dose (maximize efficacy/minimize toxicity) has been a problem related to drug monitoring of cyclosporine. The original cyclosporine formula showed high intra-patient and inter-patient variability and low bioavailability. The microemulsion formulation of cyclosporine (Neoral) was introduced to address the absorption problems related to the original cyclosporine formulation. With the introduction of Neoral, renewed interest in methods of therapeutic drug monitoring brought us from trough monitoring (C0) to levels measured 2 hours after dosing (C2). The pharmacokinetic rationale for using C2 to monitor patients receiving Neoral has demonstrated a reduced incidence of rejection in de novo patients and improvements in safety profile in both renal and hepatic transplant recipients. Monitoring C2 levels is a more precise method for optimizing cyclosporine dosing and a better way to individualize therapy. Further data are required from prospective trials to evaluate the clinical benefits of adopting C2 monitoring in cardiac and lung transplant recipients as well as in long-term maintenance patients.

Area Under Curve↗
PubMed1999

Comparison of family history measures used to identify high risk of coronary heart disease.

We examined 15 published continuous family history measures (scores) as well as two new formulations in terms of several desirable properties. We applied the scores to sample pedigrees and found that some systematically increase with family size. In contrast to aggregate scores, non-aggregate scores are sensitive to the age, sex, and covariate status of individual relatives but are unstable when the families are small. We also applied these scores to our own population case-control data, characterised by a high proportion of missing and false-negative responses. In these small families, all scores provided significant discrimination between CHD cases and controls beyond the usual categorical definition of positive family history, but appeared no better than detailed categorical definitions or even simple counts. Our new formulations offer no solution to the problems of few data; most scores apply asymptotic approximations to differences between observed and expected number of affected relatives and are not suited to small families. All scores would be improved by ruling out families with only one affected relative, as is being done in the NHLBI Family Heart Study. We recommend that researchers, when using a family history measure, consider the number of informative families and other characteristics of their data prior to choosing any particular formulation.

Age Factors↗
PubMed1998

An efficient motion estimator with application to medical image registration.

Image registration is a very important problem in computer vision and medical image processing. Numerous algorithms for registering single and multi-modal image data have been reported in these areas. Robustness as well as computational efficiency are prime factors of importance in image data registration. In this paper, a robust/reliable and efficient algorithm for estimating the transformation between two image data sets of a patient taken from the same modality over time is presented. Estimating the registration between two image data sets is formulated as a motion-estimation problem. We use a hierarchical optical flow motion model which allows for both global as well as local motion between the data sets. In this hierarchical motion model, we represent the flow field with a B-spline basis which implicitly incorporates smoothness constraints on the field. In computing the motion, we minimize the expectation of the squared differences energy function numerically via a modified Newton iteration scheme. The main idea in the modified Newton method is that we precompute the Hessian of the energy function at the optimum without explicitly knowing the optimum. This idea is used for both global and local motion estimation in the hierarchical motion model. We present examples of motion estimation on synthetic and real data (from a patient acquired during pre- and post-operative stages) and compare the performance of our algorithm with that of competing ones.

Algorithms↗
PubMed2004

Psychiatric conditions in an evolutionary context.

Psychiatric conditions and the institutions and practices that modern society has evolved to handle them originated during the nineteenth century in Anglo European societies. They are products of a historically contingent and culture specific formulation of a class of social problems of behavior that came to the fore in relation to intellectual and political economic changes of those societies. However, such problems have a long ancestry. They are intrinsic to human species and the social and cultural systems that its members have evolved since their emergence. This article reviews intellectual quandaries raised by evolutionary study of psychiatric conditions, those of crossing the human/animal divide and crossing historically contingent cultures; and of framing history of psychiatry in terms of social and cultural evolution. The biological architecture underlying psychiatric conditions and the breakthroughs that indigenous psychiatry of different types of societies underwent in formulating signs and symptoms are discussed.

Cultural Characteristics↗
PubMed1994

On optimal velocity during cycling.

This paper focuses on the solution of two problems related to cycling. One is to determine the velocity as a function of distance which minimizes the cyclist's energy expenditure in covering a given distance in a set time. The other is to determine the velocity as a function of the distance which minimizes time for fixed energy expenditure. To solve these problems, an equation of motion for the cyclist riding over arbitrary terrain is written using Newton's second law. This equation is used to evaluate either energy expenditure or time, and the minimization problems are solved using an optimal control formulation in conjunction with the method of Miele [Optimization Techniques with Applications to Aerospace Systems, pp. 69-98 (1962) Academic Press, New York]. Solutions to both optimal control problems are the same. The solutions are illustrated through two examples. In one example where the relative wind velocity is zero, the optimal cruising velocity is constant regardless of terrain. In the second, where the relative wind velocity fluctuates, the optimal cruising velocity varies.

Acceleration↗
PubMed2005

Benefits of a new testosterone gel formulation for hypogonadal men.

Hypogonadism is a common problem in men. It affects 2% to 30% of men aged 40 to 59 years, 20% to 45% aged 60 to 69 years, 34% to 70% aged 70 to 79 years, and most men aged >80 years. Hypogonadism is also highly prevalent in men with chronic illnesses, such as HIV infection. The low testosterone (T) levels associated with hypogonadism impair sexual function and many other aspects of health and well-being. In aging men and in those who are chronically ill, impaired gonadal function is characterized by subtle changes at many stages of T regulation. T therapy reverses the effects of hypogonadism, improving sexual function, body composition, mood, and well-being. Although many forms of T therapy are available, some therapies have limitations that render them ineffective or inconvenient. A new type of T gel has improved pharmacokinetic and clinical profiles compared with other forms of T therapy. This T gel has been shown to be effective in older men and in men with HIV infection, despite unsatisfactory response to earlier T-gel therapy.

Androgens↗
PubMed1999

Archaeobacterial ether lipid liposomes (archaeosomes) as novel vaccine and drug delivery systems.

Liposomes are artificial, spherical, closed vesicles consisting of one or more lipid bilayer(s). Liposomes made from ester phospholipids have been studied extensively over the last 3 decades as artificial membrane models. Considerable interest has been generated for applications of liposomes in medicine, including their use as diagnostic reagents, as carrier vehicles in vaccine formulations, or as delivery systems for drugs, genes, or cancer imaging agents. The objective of this article is to review the properties and potential applications of novel liposomes made from the membrane lipids of Archaeobacteria (Archaea). These lipids are unique and distinct from those encountered in Eukarya and Bacteria. Polar glycerolipids make up the bulk of the membrane lipids, with the remaining neutral lipids being primarily squalenes and other hydrocarbons. The polar lipids consist of regularly branched, and usually fully saturated, phytanyl chains of 20, 25, or 40 carbon length, with the 20 and 40 being most common. The phytanyl chains are attached via ether bonds to the sn-2,3 carbons of the glycerol backbone(s). It has been shown only recently that total polar lipids of archaeobacteria, and purified lipid fractions therefrom, can form liposomes. We refer to liposomes made with any lipid composition that includes ether lipids characteristic of Archaeobacteria as archaeosomes to distinguish them from vesicles made from the conventional lipids obtained from eukaryotic or eubacterial sources or their synthetic analogs. In general, archaeosomes demonstrate relatively higher stabilities to oxidative stress, high temperature, alkaline pH, action of phospholipases, bile salts, and serum proteins. Some archaeosome formulations can be sterilized by autoclaving, without problems such as fusion or aggregation of the vesicles. The uptake of archaeosomes by phagocytic cells can be up to 50-fold greater than that of conventional liposome formulations. Studies in mice have indicated that systemic administration of several test antigens entrapped within certain archaeosome compositions give humoral immune responses that are comparable to those obtained with the potent but toxic Freund's adjuvant. Archaeosome compositions can be selected to give a prolonged, sustained immune response, and the generation of a memory response. Tissue distribution studies of archaeosomes administered via various systemic and peroral routes indicate potential for targeting to specific organs. All in vitro and in vivo studies performed to date indicate that archaeosomes are safe and do not invoke any noticeable toxicity in mice. The stability, tissue distribution profiles, and adjuvant activity of archaeosome formulations indicate that they may offer a superior alternative to the use of conventional liposomes, at least for some biotechnology applications.

Adjuvants, Immunologic↗
PubMed1993

Coping modeling problem solving versus mastery modeling: effects on adherence, in-session process, and skill acquisition in a residential parent-training program.

This trial compared two approaches used to introduce parenting skills in a residential staff training program. Fifty staff were randomly assigned to: mastery modelling in which videotaped models demonstrated new skills, coping modelling problem solving (CMPS) in which participants formulated their own solutions to the errors depicted by videotaped models, or a waiting-list control group. In both, leaders used modelling, role playing, and homework projects to promote mastery and transfer of new skills. The skills of all groups improved, but CMPS participants attended more sessions, were late to fewer sessions, completed more homework, engaged in more cooperative in-session interaction, rated the program more positively, and reported higher job accomplishment scores. These data suggest that CMPS allowing participants to formulate their own solutions may enhance adherence and reduce the resistance observed in more didactic programs.

Adaptation, Psychological↗
PubMed2005

SNP selection for association studies: maximizing power across SNP choice and study size.

Selection of single nucleotide polymorphisms (SNPs) is a problem of primary importance in association studies and several approaches have been proposed. However, none provides a satisfying answer to the problem of how many SNPs should be selected, and how this should depend on the pattern of linkage disequilibrium (LD) in the region under consideration. Moreover, SNP selection is usually considered as independent from deciding the sample size of the study. However, when resources are limited there is a tradeoff between the study size and the number of SNPs to genotype. We show that tuning the SNP density to the LD pattern can be achieved by looking for the best solution to this tradeoff. Our approach consists of formulating SNP selection as an optimization problem: the objective is to maximize the power of the final association study, whilst keeping the total costs below a given budget. We also propose two alternative algorithms for the solution of this optimization problem: a genetic algorithm and a hill climbing search. These standard techniques efficiently find good solutions, even when the number of possible SNPs to choose from is large. We compare the performance of these two algorithms on different chromosomal regions and show that, as expected, the selected SNPs reflect the LD pattern: the optimal SNP density varies dramatically between chromosomal regions.

Gene Frequency↗
PubMed2005

Statistical analysis of network traffic for adaptive faults detection.

This paper addresses the problem of normal operation baselining for automatic detection of network anomalies. A model of network traffic is presented in which studied variables are viewed as sampled from a finite mixture model. Based on the stochastic approximation of the maximum likelihood function, we propose baselining network normal operation, using the asymptotic distribution of the difference between successive estimates of model parameters. The baseline random variable is shown to be stationary, with mean zero under normal operation. Anomalous events are shown to induce an abrupt jump in the mean. Detection is formulated as an online change point problem, where the task is to process the baseline random variable realizations, sequentially, and raise alarms as soon as anomalies occur. An analytical expression of false alarm rate allows us to choose the design threshold, automatically. Extensive experimental results on a real network showed that our monitoring agent is able to detect unusual changes in the characteristics of network traffic, adapt to diurnal traffic patterns, while maintaining a low alarm rate. Despite large fluctuations in network traffic, this work proves that tailoring traffic modeling to specific goals can be efficiently achieved.

Algorithms↗
PubMed1991

You can get there from here: guide to problem definition in policy development.

1. Nurses can enhance their abilities to formulate and implement health policy through the use of the assessment part of the nursing process. 2. Problem definition, the first step in policy development, includes identifying the issues, discussing and framing the issues, analyzing data and resources, and deciding on a problem definition. 3. Problem definition develops as an interaction between an instrumental, or cognitive, component and an expressive component, which represents the contextual setting of the problem. 4. Problem definitions change over a course of events. Current solutions may lead to new concerns and issues that then require new problem definitions.

Data Interpretation, Statistical↗
PubMed2002

[The multidisciplinary guidelines on nutrition for patients indicated for nursing home care, 2001].

This article describes the most important aspects of these guidelines. The guidelines are composed of two complementary lines of care. The first line focusses on the basic nutritional care in nursing homes and the second specifically on the patient with nutritional problems. The purpose is to help nursing homes in formulating a sensible and patient-centred nutritional policy; and to realize alertness on nutritional problems in patients, so that necessary interventions can be undertaken in time. Attention is also paid to the importance of an adequate implementation of the guidelines.

Aged↗
PubMed1991

Least bad solutions to the 'drugs problem'.

This paper examines the current difficulties being faced in Australia by policy-makers attempting to regulate the non-medical use of illegal drugs, and it is suggested that the difficulties centre upon two aspects. First, existing prohibitions are unsuccessful, with use levels rising and, in some arenas (e.g. cocaine use in the USA), quite out of control. On the other hand, a move towards decriminalization or legalization is difficult because past propaganda has been so vehement that a change now apparently risks sending the wrong messages to young people. This dilemma means that there is no solution, including inertia, which is risk-free, nor is there one free of difficulties. It is thus relevant to think in terms of 'least bad' rather than 'best' when formulating a system to face these problems. The exploration of what this least bad solution might be begins with the examination of the prominent myths (such as 'the drug-free society', 'the evil pusher', 'the user as victim' and 'the young person as cultural dope') that hinder our reasoning. Secondly, by suggesting that, in a climate of increasing crime related to drugs, inability of prohibitions to control that use and escalating health risks attendant on use (including the AIDS problem), the central policy thrust must be harm reduction and damage minimization rather than illusory goals such as widespread abstinence. The paper concludes with a discussion of some relevant evidence on alternative options.

Journal Article↗
PubMed2004

How can a work rehabilitation process be improved?--a qualitative study from the perspective of social insurance officers.

PURPOSE: The aim of this study is to describe social insurance officers' experiences of a work rehabilitation process at a rehabilitation centre in the northern parts of Sweden. In Sweden the social insurance company has a key role to coordinate all efforts concerning work rehabilitation planning between all rehabilitation actors. METHOD: Ten social insurance officers at the social insurance company in a city in northern Sweden were interviewed using a narrative approach about their experiences of work rehabilitation processes in general. The interviews were analysed by qualitative content analysis with a focus on their experiences of goals, content and results of a work rehabilitation process. RESULTS: The social insurance officers' experiences of how a work rehabilitation process could be improved were described in six categories; (1) Early identification of problems, needs and interventions (2) clear goal formulations, (3) a focus on psychosocial factors (4) a greater variety of possible interventions, (5) activating employers to a higher extent in work rehabilitation and (6) a closer cooperation and information exchange with other rehabilitation actors. CONCLUSIONS: It is possible to improve a work rehabilitation process by focusing on early identification of problems, needs and interventions, with a variety of interventions to choose between and with clear goal formulations and recognizing psychosocial factors in the process. To activate employers to a higher extent in work rehabilitation and to make the information exchange between rehabilitation actors more frequent may also improve work rehabilitation processes.

Adult↗
PubMed2004

Triple nucleoside reverse transcriptase inhibitor therapy in children.

Much of the success attributed to HIV therapy in the last few years has resulted from improved ways of using existing drugs in combination therapy regimens. The availability of new, more potent drugs such as protease inhibitors and more accurate viral load tests to aid decisions to start or change treatment has also contributed to the success. Published recommendations for pediatric HIV therapy, generated by a panel of experts and specialists, are readily available and regularly updated. Preferred regimens of 'potent' therapy (referred to as highly active antiretroviral therapy, or HAART) currently consist of two nucleoside reverse transcriptase inhibitors (NRTIs) combined with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor. More intense four-drug regimens using an NNRTI or a second protease inhibitor as a fourth drug are being evaluated. Problems with HAART include: unpalatable drug formulations and adverse effects, coupled with lack of data on the pharmacokinetics, efficacy, and safety of various drug combinations. Adherence is a major factor influencing the efficacy and outcome of antiretroviral therapy. Many children cannot adhere to complex multidrug regimens, which cause virologic failure, despite excellent CD4+ cell count responses. This means a rapid progression through the limited number of treatment regimens available. Simpler regimens such as those containing three NRTIs have been proposed as a method of treatment that will allow suppression of the virus, yet circumvent many of the problems previously mentioned. An additional benefit would be the preservation of antiretroviral drugs from other classes for future treatment options if required. The major advantages of triple NRTI regimens are the simplicity of the regimen, good tolerability, few drug-drug interactions, and infrequent adverse effects coupled with a low pill burden. However, abacavir hypersensitivity remains a major problem. Up to 3% of patients may develop an early idiosyncratic hypersensitivity reaction - fever, malaise, and mucositis with or without rash, which can progress to more advanced stages of shock and death. A major concern is the apparently inferior virologic control of triple NRTI therapy as demonstrated in the AIDS Clinical Trials Group A5095 study with zidovudine/lamivudine/abacavir (Trizivir) combination in adults. Such a combination should only be considered in special situations. Examples cited include informed patient choice based on anticipated poor adherence on other treatment regimens, or if concomitant drugs such as tuberculosis medication are prescribed. The low pill burden of triple NRTI regimens (especially if combined in a single pill such as Trizivir), offers hope that regimen simplification may still be possible in the future.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Methodology for estimation of time-dependent surface heat flux due to cryogen spray cooling.

Cryogen spray cooling (CSC) is an effective technique to protect the epidermis during cutaneous laser therapies. Spraying a cryogen onto the skin surface creates a time-varying heat flux, effectively cooling the skin during and following the cryogen spurt. In previous studies mathematical models were developed to predict the human skin temperature profiles during the cryogen spraying time. However, no studies have accounted for the additional cooling due to residual cryogen left on the skin surface following the spurt termination. We formulate and solve an inverse heat conduction (IHC) problem to predict the time-varying surface heat flux both during and following a cryogen spurt. The IHC formulation uses measured temperature profiles from within a medium to estimate the surface heat flux. We implement a one-dimensional sequential function specification method (SFSM) to estimate the surface heat flux from internal temperatures measured within an in vitro model in response to a cryogen spurt. Solution accuracy and experimental errors are examined using simulated temperature data. Heat flux following spurt termination appears substantial; however, it is less than that during the spraying time. The estimated time-varying heat flux can subsequently be used in forward heat conduction models to estimate temperature profiles in skin during and following a cryogen spurt and predict appropriate timing for onset of the laser pulse.

Administration, Cutaneous↗