The Impact of Uncertainty in the AIDS Incubation Period on Reconstructions of the HIV Epidemic

Backcalculation is the primary method used to reconstruct past human immunodeficiency virus (HIV) infection rates, to estimate current prevalence of HIV infection, and to project future incidence of acquired immunodeficiency syndrome (AIDS). The method is very sensitive to uncertainty about the incubation period. We estimate incubation distributions from three sets of cohort data and find that the estimates for the cohorts are substantially different. Backcalculations employing the different estimates produce equally good fits to reported AIDS counts but quite different estimates of cumulative infections. These results suggest that the incubation distribution is likely to differ for different populations and that the differences are large enough to have a big impact on the resulting estimates of HIV infection rates. This seriously limits the usefulness of backcalculation for populations (such as intravenous drug users, heterosexuals, and women) that lack precise information on incubation times.

QUANTIFYING UNCERTAINTY IN GENOTYPE CALLS

Genome-wide association studies (GWAS) are used to discover genes underlying complex, heritable disorders for which less powerful study designs have failed in the past. The number of GWAS has skyrocketed recently with findings reported in top journals and the mainstream media. Mircorarrays are the genotype calling technology of choice in GWAS as they permit exploration of more than a million single nucleotide polymorphisms (SNPs)simultaneously. The starting point for the statistical analyses used by GWAS, to determine association between loci and disease, are genotype calls (AA, AB, or BB). However, the raw data, microarray probe intensities, are heavily processed before arriving at these calls. Various sophisticated statistical procedures have been proposed for transforming raw data into genotype calls. We find that variability in microarray output quality across different SNPs, different arrays, and different sample batches has substantial inuence on the accuracy of genotype calls made by existing algorithms. Failure to account for these sources of variability, GWAS run the risk of adversely affecting the quality of reported findings. In this paper we present solutions based on a multi-level mixed model. Software implementation of the method described in this paper is available as free and open source code in the crlmm R/BioConductor.

Quantifying uncertainty in cost effectiveness analyses

This study compared four alternative approaches (Taylor, Fieller, percentile bootstrap, and bias-corrected bootstrap methods) to estimating confidence intervals (CIs) around cost-effectiveness (CE) ratio. The study consisted of two components: (1) Monte Carlo simulation was conducted to identify characteristics of hypothetical cost-effectiveness data sets which might lead one CI estimation technique to outperform another. These results were matched to the characteristics of an (2) extant data set derived from the National AIDS Demonstration Research (NADR) project. The methods were used to calculate (CIs) for data set. These results were then compared. The main performance criterion in the simulation study was the percentage of times the estimated (CIs) contained the “true” CE. A secondary criterion was the average width of the confidence intervals. For the bootstrap methods, bias was estimated. ^ Simulation results for Taylor and Fieller methods indicated that the CIs estimated using the Taylor series method contained the true CE more often than did those obtained using the Fieller method, but the opposite was true when the correlation was positive and the CV of effectiveness was high for each value of CV of costs. Similarly, the CIs obtained by applying the Taylor series method to the NADR data set were wider than those obtained using the Fieller method for positive correlation values and for values for which the CV of effectiveness were not equal to 30% for each value of the CV of costs. ^ The general trend for the bootstrap methods was that the percentage of times the true CE ratio was contained in CIs was higher for the percentile method for higher values of the CV of effectiveness, given the correlation between average costs and effects and the CV of effectiveness. The results for the data set indicated that the bias corrected CIs were wider than the percentile method CIs. This result was in accordance with the prediction derived from the simulation experiment. ^ Generally, the bootstrap methods are more favorable for parameter specifications investigated in this study. However, the Taylor method is preferred for low CV of effect, and the percentile method is more favorable for higher CV of effect. ^

Theory of uncertainty in illness in patients with cancer of unknown primary origin: Structure providers as antecedents of uncertainty in a population of cancer patients with an unknown primary diagnosis

Uncertainty has been found to be a major component of the cancer experience and can dramatically affect psychosocial adaptation and outcomes of a patient's disease state (McCormick, 2002). Patients with a diagnosis of Carcinoma of Unknown Primary (CUP) may experience higher levels of uncertainty due to the unpredictability of current and future symptoms, limited treatment options and an undetermined life expectancy. To date, only one study has touched upon uncertainty and its' effects on those with CUP but no information exists concerning the effects of uncertainty regarding diagnosis and treatment on the distress level and psychosocial adjustment of this population (Parker & Lenzi, 2003). ^ Mishel's Uncertainty in Illness Theory (1984) proposes that uncertainty is preceded by three variables, one of which being Structure Providers. Structure Providers include credible authority, the degree of trust and confidence the patient has with their doctor, education and social support. It was the goal of this study to examine the relationship between uncertainty and Structure Providers to support the following hypotheses: (1) There will be a negative association between credible authority and uncertainty, (2) There will be a negative association between education level and uncertainty, and (3) There will be a negative association between social support and uncertainty. ^ This cross-sectional analysis utilized data from 219 patients following their initial consultation with their oncologist. Data included the Mishel Uncertainty in Illness Scale (MUIS) which was used to determine patients' uncertainty levels, the Medical Outcomes Study-Social Support Scale (MOSS-SSS) to assess patients, levels of social support, the Patient Satisfaction Questionnaire (PSQ-18) and the Cancer Diagnostic Interview Scale (CDIS) to measure credible authority and general demographic information to assess age, education, marital status and ethnicity. ^ In this study we found that uncertainty levels were generally higher in this sample as compared to other types of cancer populations. And while our results seemed to support most of our hypothesis, we were only able to show significant associations between two. The analyses indicated that credible authority measured by both the CDIS and the PSQ was a significant predictor of uncertainty as was social support measured by the MOSS-SS. Education has shown to have an inconsistent pattern of effect in relation to uncertainty and in the current study there was not enough data to significantly support our hypothesis. ^ The results of this study generally support Mishel's Theory of Uncertainty in Illness and highlight the importance of taking into consideration patients, psychosocial factors as well as employing proper communication practices between physicians and their patients.^

Strategic trade policy and non-linear subsidy : in the case of price competition

In a strategic trade policy, it is assumed, in this paper, that a government changes disbursement or levy method so that the reaction function of home firm approaches infinitely close to that of foreign firm. In the framework of Bertrand-Nash equilibrium, Eaton and Grossman[1986] showed that export tax is preferable to export subsidy. In this paper, it is shown that export subsidy is preferable to export tax in some cases in the framework of Bertrand-Nash equilibrium, considering the uncertainty in demand. Historically, many economists mentioned non-linear subsidy or tax. However, optimum solution of it has not yet been shown. The optimum solution is shown in this paper.

A Comparison of different Uncertainty Activation Cross-Section Data Libraries: Application to the Prediction Uncertainty in Tritium Production

T actitivity in LiPb LiPb mock-up material irradiated in Frascati: measurement and MCNP results

Traffic uncertainty in toll motorway concessions in Spain

This study assessed the inaccuracy of the traffic estimates for toll motorway concessions in Spain. It was found that the estimates conducted by both the government and the concessionaire showed a significant bias towards overestimating traffic. The level of overestimation in Spain is even greater than that reported by other studies based on worldwide data. The notorious levels of overestimation entail severe burdens to the economics of the concessionaires that often prompt renegotiations of the contracts, which are often accepted by the government. These renegotiations usually end up with toll changes or extension of the concession terms, which have to be ultimately borne by future motorway users. It is postulated herein that the bias towards overestimating traffic in toll motorways in Spain is mostly caused by strategic issues rather than by modelling errors.

Calculus of the uncertainty in acoustic field measurements: comparative study between the uncertainty propagation method and the distribution propagation method

The new Spanish Regulation in Building Acoustic establishes values and limits for the different acoustic magnitudes whose fulfillment can be verify by means field measurements. In this sense, an essential aspect of a field measurement is to give the measured magnitude and the uncertainty associated to such a magnitude. In the calculus of the uncertainty it is very usual to follow the uncertainty propagation method as described in the Guide to the expression of Uncertainty in Measurements (GUM). Other option is the numerical calculus based on the distribution propagation method by means of Monte Carlo simulation. In fact, at this stage, it is possible to find several publications developing this last method by using different software programs. In the present work, we used Excel for the Monte Carlo simulation for the calculus of the uncertainty associated to the different magnitudes derived from the field measurements following ISO 140-4, 140-5 and 140-7. We compare the results with the ones obtained by the uncertainty propagation method. Although both methods give similar values, some small differences have been observed. Some arguments to explain such differences are the asymmetry of the probability distributions associated to the entry magnitudes,the overestimation of the uncertainty following the GUM

Uncertainty in ellipse fitting using a flatbed scanner: development and experimental verification

In the field of dimensional metrology, the use of optical measuring machines requires the handling of a large number of measurement points, or scanning points, taken from the image of the measurand. The presence of correlation between these measurement points has a significant influence on the uncertainty of the result. The aim of this work is the development of an estimation procedure for the uncertainty of measurement in a geometrically elliptical shape, taking into account the correlation between the scanning points. These points are obtained from an image produced using a commercial flat bed scanner. The characteristic parameters of the ellipse (coordinates of the center, semi-axes and the angle of the semi-major axis with regard to the horizontal) are determined using a least squares fit and orthogonal distance regression. The uncertainty is estimated using the information from the auto-correlation function of the residuals and is propagated through the fitting algorithm according to the rules described in Evaluation of Measurement Data—Supplement 2 to the ‘Guide to the Expression of Uncertainty in Measurement’—Extension to any number of output quantities. By introducing the concept of cut-off length, it can be observed how it is possible to take into account the presence of the correlation in the estimation of uncertainty in a very simple way while avoiding underestimation.

Uncertainty in optical bio-sensors due to the spectral displacement of the interference modes of the transduction signal. Incertidumbre en bio-sensores ópticos asociada al desplazamiento espectral de los modos de interferencia de la señal de transducción

The analysis of the interference modes has an increasing application, especially in the field of optical biosensors. In this type of sensors, the displacement Δν of the interference modes of the transduction signal is observed when a particular biological agent is placed over the biosensor. In order to measure this displacement, the position of a maximum (or a minimum) of the signal must be detected before and after placing the agent over the sensor. A parameter of great importance for this kind of sensors is the period Pν of the signal, which is inversely proportional to the optical thickness h0 of the sensor in the absence of the biological agent. The increase of this period improves the sensitivity of the sensor but it worsens the detection of the maximum. In this paper, authors analyze the propagation of uncertainties in these sensors when using least squares techniques for the detection of the maxima (or minima) of the signal. Techniques described in supplement 2 of the ISO-GUM Guide are used. The result of the analysis allows a metrological educated answer to the question of which is the optimal period Pν of the signal. El análisis del comportamiento de los modos de interferencia tiene una aplicación cada vez más amplia, especialmente en el campo de los biosensores ópticos. En este tipo de sensores se observa el desplazamiento Δν de los modos de interferencia de la señal de transducción al reconocer un de-terminado agente biológico. Para medir ese desplazamiento se debe detectar la posición de un máximo o mínimo de la señal antes y después de dicho desplazamiento. En este tipo de biosensores un parámetro de gran importancia es el periodo Pν de la señal el cual es inversamente proporcional al espesor óptico h0 del sensor en ausencia de agente biológico. El aumento de dicho periodo mejora la sensibilidad del sensor pero parece dificultar la detección del mínimo o máximo. Por tanto, su efecto sobre la incertidumbre del resultado de la medida presenta dos efectos contrapuestos: la mejora de la sensibilidad frente a la dificultad creciente en la detección del mínimo ó máximo. En este trabajo, los autores analizan la propagación de incertidumbres en estos sensores utilizando herramientas de ajuste por MM.CC. para la detección de los mínimos o máximos de la señal y técnicas de propagación de incertidumbres descritas en el suplemento 2 de la Guía ISO-GUM. El resultado del análisis permite dar una respuesta, justificada desde el punto de vista metrológico, de en que condiciones es conveniente o no aumentar el periodo Pν de la señal.