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Estimation of annual HIV transmission rates in the United States, 1978-2000.

The HIV/AIDS epidemic in the United States generally has been characterized by AIDS case incidence and AIDS-associated death rates; in a more limited fashion, the epidemic has also been described by AIDS prevalence; population-specific HIV prevalence; and HIV incidence statistics. However, HIV transmission rate information (i.e., the rate of transmission from persons living with HIV to HIV-seronegative persons) has received relatively little attention. The purpose of the present paper is to estimate the annual HIV transmission rate (from HIV-seropositive to HIV-seronegative persons) in the United States for the time period 1978-2000 and to discuss the practical utility of the findings. Using as input annual AIDS-associated deaths and HIV incidence (both variables, especially the latter, contain some element of uncertainty), the model described here finds that HIV transmission rates have dropped dramatically in the United States since the beginning of the epidemic and stayed approximately between 4.00-4.34% during the 1990s. This implies a programmatic success in that for more than roughly 95% of persons living with HIV in any given year, no HIV transmission occurs. Research is urgently needed to fully understand the circumstances that allow the remaining instances of HIV transmission to take place; moreover, serostatus-appropriate HIV-related services are needed to disrupt these remaining instances of transmission.

Acquired Immunodeficiency Syndrome↗

Multiple multipole method for simulating EM problems involving biological bodies.

The three-dimensional implementation of the multiple multipole (MMP) method, based on the generalized multipole technique (GMT), is presented. Its performance in simulating electromagnetic problems involving biological bodies is analyzed. In particular, the step-by-step simulation technique and the built-in procedures to validate the solution on numerical basis are discussed and demonstrated in two examples. A comparison is made with other numerical techniques often applied in this field. The advantages of the MMP method are shown to be in its validation capability, in its efficiency for smoothly shaped bodies and in the achievable accuracy, in particular near boundaries. The method is especially suited to handle high-gradient fields in the vicinity of biological bodies. On the other hand, finite difference (FD) techniques are superior for scatterers with complicated angular shapes or inhomogeneous bodies, for which MMP shows rather strong practical limitations. However, in most cases the inhomogeneities of biological bodies modify the field distribution only locally beyond the uncertainties of models. In these cases, inhomogeneities can be stimulated efficiently and with high accuracy by MMP applying the block iterative technique. Other methods are not general enough to compete with FD or MMP in solving EM problems involving biological tissues.

Animals↗

Simulating nonequilibrium transport of atrazine through saturated soil.

Atrazine, an herbicide widely used for selective control of grassy weeds in the fields where maize is grown, is a potential ground water contaminant in China and, consequently, there is interest in predicting its mobility in agricultural soils. In this study, we determined the nonequilibrium transport characteristics of atrazine in Shahe soil (Beijing sandy loam) using the advection-dispersion equation, and using a sensitivity analysis, we evaluated the contribution of the uncertainty in a given input parameter to the overall uncertainty in model results. The asymmetrical shape and tailing of the atrazine breakthrough curve (BTC) showed that atrazine was subject to nonequilibrium transport. The observed atrazine BTC was best fitted by the chemical nonequilibrium model with a nonlinear least-squares optimization approach. Results from the sensitivity analysis indicated that the retardation factor was the most sensitive parameter. Considering the reliability of the estimated parameters, the best fit to the atrazine BTC was obtained by fixing the retardation factor based on the linear distribution coefficient, and by calculating the dispersion coefficient from the bromide BTC and the average pore water velocity from the measured data; nonequilibrium parameters were the only unknown parameters that were optimized. Model verification procedures were based on best-fit parameters optimized from one soil column experiment and applied to simulate the transport of atrazine in the duplicate experiment. The results showed there was good agreement between measured and simulated concentrations for atrazine leaching in the soil column.

Atrazine↗

Dimensions of subjective uncertainty in social identification and minimal intergroup discrimination.

Social categorization under minimal group conditions reliably produces intergroup discrimination. It is proposed that this might be because the minimal group paradigm engenders high levels of subjective uncertainty among participants, which causes them to use the categorization to define self and thus identify with the minimal group. Uncertainty is generally an aversive state which may be resolved by identification (Hogg, 1996; Hogg & Abrams, 1993). Thus, people may identify with social categories (and express discrimination) when identification resolves uncertainty. To investigate this idea a standard minimal group experiment was conducted, in which the three independent variables of categorizations, task uncertainty and situational uncertainty were manipulated in a 2 x 2 x 2 factorial between-subjects design. Point distribution strategies were measured along with in-group identification, self-esteem, social awareness and, at three occasions, uncertainty about the task and situation. As predicted, under conditions of high task or situational uncertainty, categorized participants identified more with their minimal in-group and exhibited more intergroup discrimination than other participants. There was also some evidence that identification reduced uncertainty. There was only partial support for the mediational role of identification, and similarly, for self-esteem as a derivative motive. These findings are interpreted as supporting an uncertainty reduction model of social identification and group motivation.

Analysis of Variance↗

Remodeling of the rat right and left ventricles in experimental hypertension.

Pathological left ventricular hypertrophy in renovascular hypertension is associated with the accumulation of fibrillar collagen within the extracellular space and around intramyocardial coronary arteries. Even though the angiotensin converting enzyme inhibitor captopril was previously found to attenuate this interstitial and perivascular fibrosis, the relative importance of arterial and ventricular systolic pressures versus circulating angiotensin II (AII) and aldosterone (AL) in promoting hypertrophy and collagen accumulation in renovascular hypertension is uncertain. By drawing on the in-parallel arrangement of the right and left ventricles, with respect to their coronary circulation, and the in-series mechanical alignment of the ventricles, with a pressure-overloaded left and a normotensive right ventricle, this study sought to address this uncertainty. Three models of experimental hypertension, each having a different circulating AII and AL profile, were examined and compared with their controls: renovascular hypertension, where both AII and AL are increased; infrarenal aorta banding, where AII and AL are normal; and a chronic infusion of AL, where AII is suppressed or normal and AL is increased. In renovascular hypertension, as well as with AL, we found a significant rise in the interstitial collagen volume fraction and perivascular collagen area of the pressure-overloaded, hypertrophied left ventricle as well as the normotensive, nonhypertrophied right ventricle. This remodeling was not seen in either ventricle with infrarenal aorta banding despite comparable systemic hypertension and left ventricular hypertrophy. Thus, in experimental arterial hypertension in the rat, myocyte and nonmyocyte compartments of the myocardium are under separate controls: myocyte hypertrophy is most closely related to ventricular loading while circulating AII and AL, acting alone or in concert with other humoral factors, regulate the accumulation of collagen within the right and left ventricles.

Aldosterone↗

Robust mission design through evidence theory and multiagent collaborative search.

In this paper, the preliminary design of a space mission is approached by introducing uncertainties on the design parameters and formulating the resulting reliable design problem as a multiobjective optimization problem. Uncertainties are modelled through evidence theory and the belief, or credibility, that the successful achievement of mission goals is maximized along with the reliability of constraint satisfaction. The multiobjective optimization problem is solved through a novel algorithm based on the collaboration of a population of agents in search for the set of highly reliable solutions. Two typical problems in mission analysis are used to illustrate the proposed methodology.

Journal Article↗

Practical models for the care of HIV and AIDS patients.

Mathematical models for infectious diseases are of limited use in providing practical help to health professionals. In this paper we discuss computer models developed jointly by operational research mathematicians and clinicians to meet this need. We use the term 'operational modelling' to describe this pragmatic approach. The models can aid decision-making at a resource planning level and can also be used by clinicians to monitor and improve patient care. The models incorporate uncertainty and variability and are therefore mathematically complex, but are easy to use and provide a great deal of useful information about morbidity and resource use.

Acquired Immunodeficiency Syndrome↗

Quantitative cancer risk assessment for dioxins using an occupational cohort.

We consider a cohort of 1189 male German factory workers (production period 1952-1984) who produced phenoxy herbicides and were exposed to dioxins. Follow-up until the end of 1992 yielded a significantly increased standardized mortality ratio (SMR) for total cancer (SMR 141; 95% confidence interval 117-168). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) concentrations up to 2252 ng/kg body fat were measured in 275 cohort members. Other higher chlorinated dioxins and furans also occurred in high concentrations. For quantitative analysis, the integrated TCDD concentration over time was used as an exposure variable, which was calculated using results from half-life estimation for TCDD and workplace history data. The other congeners were expressed as toxic equivalency (TEQ) and compared to TCDD using international toxic equivalency factors. Poisson and Cox regressions were used to investigate dose-response relationships. Various covariables (e.g., exposure to beta-hexachlorocyclohexane, employment characteristics) were considered. In all analyses, TCDD and TEQ exposures were related to total cancer mortality. The power model yielded a relative risk (RR) function RR(x) = (1 + 0.17x)0.326 for TCDD (in microgram/kilogram blood fat x years)--only a slightly better fit than a linear RR function--and RR(x) = (1 + 0.023x)0.795 for TEQ. Investigations on latency did not show strong effects. Different methods were applied to investigate the robustness of the results and yielded almost identical results. The results were used for unit risk estimation. Taking into account different sources of variation, an interval of 10(-3) to 10(-2) for the additional lifetime cancer risk under a daily intake of 1 pg TCDD/kg body weight/day was estimated from the dose-response models considered. Uncertainties regarding the dose-response function remain. These data did not indicate the existence of a threshold value; however, such a value cannot be excluded with any certainty.

Adult↗

Toward closure of upwelling radiance in coastal waters.

We present three methods for deriving water-leaving radiance L(w)(lambda) and remote-sensing reflectance using a hyperspectral tethered spectral radiometer buoy (HyperTSRB), profiled spectroradiometers, and Hydrolight simulations. Average agreement for 53 comparisons between HyperTSRB and spectroradiometric determinations of L(w)(lambda) was 26%, 13%, and 17% at blue, green, and red wavelengths, respectively. Comparisons of HyperTSRB (and spectroradiometric) L(w)(lambda) with Hydrolight simulations yielded percent differences of 17% (18%), 17% (18%), and 13% (20%) for blue, green, and red wavelengths, respectively. The differences can be accounted for by uncertainties in model assumptions and model input data (chlorophyll fluorescence quantum efficiency and the spectral chlorophyll-specific absorption coefficient for the red wavelengths, and scattering corrections for input ac-9 absorption data and volume scattering function measurements for blue wavelengths) as well as radiance measurement inaccuracies [largely differences in the depth of the L(u)(lambda, z) sensor on the HyperTSRB].

Journal Article↗

Iterative linear minimum mean-square-error image restoration from partially known blur.

We address the problem of space-invariant image restoration when the blurring operator is not known exactly, a situation that arises regularly in practice. To account for this uncertainty, we model the point-spread function as the sum of a known deterministic component and an unknown random one. Such an approach has been studied before, but the problem of estimating the parameters of the restoration filter to our knowledge has not been addressed systematically. We propose an approach based on a Gaussian statistical assumption and derive an iterative, expectation-maximization algorithm that simultaneously restores the image and estimates the required filter parameters. We obtain two versions of the algorithm based on two different models for the statistics of the image. The computations are performed in the discrete Fourier transform domain; thus they are computationally efficient even for large images. We examine the convergence properties of the resulting estimators and evaluate their performance experimentally.

Algorithms↗

A dynamical approach to evaluate risk in resource management.

With the depletion of many natural resources, we are growing aware of the need to understand the risks that stem from different management decisions. Here, we outline an approach to test the ability of different dynamical signatures to characterize time-series data: how likely is it that a natural population is declining, sustainable, or increasing, and at what rates are these temporal changes likely occurring? These dynamical signatures can serve as a robust foundation on which to formulate alternative scenarios in a decision analysis. They take account of much of the uncertainty in model parameters and have precise mathematical underpinnings with associated risks. We present methods to evaluate the likelihood of these scenarios, and ways that the analysis can be graphically represented. We discuss different ecological factors such as climate variability, life history, ecosystem interactions, and a changing population age structure, all of which impact the dynamics of natural populations. Considering the types of dynamical signatures that emerge from these factors can change our understanding of risk and the decisions that we make.

Decision Making, Organizational↗

Assessment of the spatial distribution of soil properties in a northern Everglades marsh.

Florida Everglades restoration plans are aimed at maintaining and restoring characteristic landscape features such as soil, vegetation, and hydrologic patterns. This study presents the results from an exhaustive spatial sampling of key soil properties in Water Conservation Area 1 (WCA 1), which is part of the northern Everglades. Three soil strata were sampled: floc, upper 0- to 10-cm soil layer, and 10- to 20-cm soil layer. A variety of properties were measured including bulk density (BD), loss on ignition (LOI), total phosphorus (TP), total inorganic phosphorus (TIP), total nitrogen (TN), total carbon (TC), total iron (TFe), total magnesium (TMg), total aluminum (TAl), and total calcium (TCa). Interpolated maps and model prediction uncertainties of properties were generated using geostatistical methods. We found that the uncertainty associated with spatial predictions of floc, particularly floc BD, was highest, whereas spatial predictions of soil chemical properties such as soil Ca were more accurate. The resultant spatial patterns for these soil properties identified three predominant features in WCA 1: (i) a north to south gradient in soil properties associated with the predominant hydrological gradient, (ii) areas of considerable soil nutrient enrichment along the western canal of WCA 1, and (iii) areas of considerable Fe enrichment along the eastern canal. By using geostatistical techniques we were able to describe the spatial dynamics of soil variables and express these predictions with an acceptable level of uncertainty.

Aluminum↗

Novel stimuli are negative stimuli: evidence that negative affect is reduced in the mere exposure effect.

Repeated exposure of a nonreinforced stimulus results in an increased preference for that stimulus, the mere exposure effect. The present study repeatedly presented positive, negative, and neutrally affective faces to 48 participants while they made judgments about the emotional expression. Participants then rated the likeability of novel neutrally expressive faces and some of these previously presented faces, this time in their neutral expression. Faces originally presented as happy were rated as the most likeable, followed by faces originally presented as neutral. Negative and novel faces were not rated significantly differently from each other. These findings support the notion that the increase in preference towards repeatedly presented stimuli is the result of the reduction in negative affect, consistent with the modified two-factor uncertainty-reduction model and classical conditioning model of the mere exposure effect.

Adult↗

Modeling the transmission of schistosomiasis: an introductory view.

The transmission of schistosomiasis can be modeled at various levels of complexity in terms of systems of mathematical equations. This paper shows how such models can be set up, and stresses the importance of incorporating the right basic assumptions from the outset. The use of models for evaluating possible control strategies is illustrated in the context of a simple prevalence model of transmission. Some limitations and uncertainties involved in modeling schistosomiasis are also indicated.

Animals↗

A probabilistic effect assessment model for hazardous substances at the workplace.

A major problem in risk assessment is the quantification of uncertainties. A probabilistic model was developed to consider uncertainties in the effect assessment of hazardous substances at the workplace. Distributions for extrapolation factors (time extrapolation, inter- and intraspecies extrapolation) were determined on the basis of appropriate empirical data. Together with the distribution for the benchmark dose obtained from substance-specific dose-response modelling for the exemplary substances 2,4,4-trimethylpentene (TMP) and aniline, they represent the input distributions for probabilistic modelling. These distributions were combined by Monte Carlo simulation. The resulting target distribution describes the probability that an aspired protection level for workers is achieved at a certain dose and the uncertainty associated with the assessment. In the case of aniline, substance-specific data on differences in susceptibility (between species; among humans due to genetic polymorphisms of N-acetyltransferase) were integrated in the model. Medians of the obtained target distributions of the basic models for TMP and aniline, but not of the specific aniline model are similar to deterministically derived reference values. Differences of more than one order of magnitude between the medians and the 5th percentile of the target distributions indicate substantial uncertainty associated with the effect assessment of these substances. The probabilistic effect assessment model proves to be a practical tool to integrate quantitative information on uncertainty and variability in hazard characterisation.

Alkenes↗

Evaluation of alternative methods for establishing safe levels of occupational exposure to vinyl halides.

The facts that reduction of occupational vinyl chloride exposures to levels within or below the 0.5-5 ppm range has so far been successful in eliminating vinyl chloride-induced liver angiosarcoma and that humans appear to be less sensitive to the carcinogenic effect of vinyl chloride than rats offered an opportunity to verify or dispute risk assessment extrapolation models used, and proposed, by the U.S. EPA. Safe occupational vinyl chloride exposures were defined as levels associated with an incidence of one angiosarcoma in 100,000 exposed workers, determined from rat bioassay data using default no-threshold (linearized multistage model and benchmark dose approach with linear extrapolation) and threshold (NOEL/LOEL and benchmark dose uncertainty factor approaches) models, and then compared against the likely protective range of 0.5-5 ppm. Safe levels derived using either no-threshold model are equivalent and are two to three orders of magnitude below the 0.5-5 ppm range. Safe levels derived using either threshold model, when applying uncertainty factors which reflect equal or less sensitivity in humans compared to rats, fall within the 0.5-5 ppm range. Similar results were obtained for vinyl bromide and vinyl fluoride. These results undermine the U.S. EPA default assumption of no-threshold for vinyl halides as well as for other DNA-reactive carcinogens while simultaneously supporting the notion that a practical threshold exists. They further suggest that when threshold models are appropriate, the default assumption of greater sensitivity in humans compared to rats should be carefully evaluated.

Animals↗

Evaluation of accuracy and uncertainty of ELISA assays for the determination of interleukin-4, interleukin-5, interferon-gamma and tumor necrosis factor-alpha.

The comparison of analytical results calls for validation of the assays used, i.e. for the documentation of accuracy (trueness and precision), linearity and specificity. In addition, there is a growing demand for evaluation and documentation of traceability and uncertainty of analytical results. However, models for establishing the traceability and uncertainty of immunoassay results are lacking. Sandwich enzyme-linked immunosorbent assays (ELISAs) were developed for determination of the human cytokines interleukin-4 (IL-4), interleukin-5 (IL-5), interferon-y (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). The accuracy of each of the assays was evaluated in the ranges of 1-15 microg/l (IL-4), 0.001-1 microg/l (IL-5), 0.5-2.5 microg/l (IFN-T) and 0.14-2.2 microg/l (TNF-alpha). Other evaluated performance characteristics were the limit of detection (LOD), immunological specificity, and robustness. Traceability was ensured by the use of World Health Organization International Standards (WHO IS). An uncertainty budget, which combined the contribution from all known uncertainty components, was established for each cytokine ELISA. The between-run relative analytical standard deviation (RSDA) of the assessed ELISAs was found to be in the range of 11-18%, except for IL-5 where RSDA increased at decreasing concentrations. The LOD was 0.12 microg/l, 0.0077 microg/l, 0.0069 microg/l and 0.0063 microg/l for IL-4, IL-5, IFN-gamma and TNF-alpha, respectively. Traceability to the WHO IS was established for each of the cytokines. The combined relative standard uncertainty (U(result)/C(result)) was 28%, 22-62%, 28% and 24% for the IL-4, IL-5, IFN-gamma and TNF-alpha results, respectively. The major contributions to uncertainty came from the relative analytical standard deviation and from the uncertainty of the mass concentration of the WHO IS. The uncertainty of the WHO IS was not stated in the accompanying certificate and was evaluated by other means. The largest sources of uncertainty were located outside our laboratory. This means that the possibilities to improve the reliability of the results produced by the ELISAs are very limited. The task of evaluating measurement uncertainty would be much easier if producers of international reference standards reported the uncertainty of the value of standards. The model for evaluating uncertainty presented in this paper is applicable to other types of assays and to most analytical methods.

Bias↗