Sensitivity and specificity of indocyanine green near-infrared fluorescence imaging in detection of metastatic lymph nodes in colorectal cancer: Systematic review and meta-analysis.

PubMed

Emile, Sameh H; Elfeki, Hossam; Shalaby, Mostafa; Sakr, Ahmad; Sileri, Pierpaolo; Laurberg, Søren; Wexner, Steven D

2017-11-01

This review aimed to determine the overall sensitivity and specificity of indocyanine green (ICG) near-infrared (NIR) fluorescence in sentinel lymph node (SLN) detection in Colorectal cancer (CRC). A systematic search in electronic databases was conducted. Twelve studies including 248 patients were reviewed. The median sensitivity, specificity, and accuracy rates were 73.7, 100, and 75.7. The pooled sensitivity and specificity rates were 71% and 84.6%. In conclusion, ICG-NIR fluorescence is a promising technique for detecting SLNs in CRC. © 2017 Wiley Periodicals, Inc.

A new u-statistic with superior design sensitivity in matched observational studies.

PubMed

Rosenbaum, Paul R

2011-09-01

In an observational or nonrandomized study of treatment effects, a sensitivity analysis indicates the magnitude of bias from unmeasured covariates that would need to be present to alter the conclusions of a naïve analysis that presumes adjustments for observed covariates suffice to remove all bias. The power of sensitivity analysis is the probability that it will reject a false hypothesis about treatment effects allowing for a departure from random assignment of a specified magnitude; in particular, if this specified magnitude is "no departure" then this is the same as the power of a randomization test in a randomized experiment. A new family of u-statistics is proposed that includes Wilcoxon's signed rank statistic but also includes other statistics with substantially higher power when a sensitivity analysis is performed in an observational study. Wilcoxon's statistic has high power to detect small effects in large randomized experiments-that is, it often has good Pitman efficiency-but small effects are invariably sensitive to small unobserved biases. Members of this family of u-statistics that emphasize medium to large effects can have substantially higher power in a sensitivity analysis. For example, in one situation with 250 pair differences that are Normal with expectation 1/2 and variance 1, the power of a sensitivity analysis that uses Wilcoxon's statistic is 0.08 while the power of another member of the family of u-statistics is 0.66. The topic is examined by performing a sensitivity analysis in three observational studies, using an asymptotic measure called the design sensitivity, and by simulating power in finite samples. The three examples are drawn from epidemiology, clinical medicine, and genetic toxicology. © 2010, The International Biometric Society.

Space shuttle orbiter digital data processing system timing sensitivity analysis OFT ascent phase

NASA Technical Reports Server (NTRS)

Lagas, J. J.; Peterka, J. J.; Becker, D. A.

1977-01-01

Dynamic loads were investigated to provide simulation and analysis of the space shuttle orbiter digital data processing system (DDPS). Segments of the ascent test (OFT) configuration were modeled utilizing the information management system interpretive model (IMSIM) in a computerized simulation modeling of the OFT hardware and software workload. System requirements for simulation of the OFT configuration were defined, and sensitivity analyses determined areas of potential data flow problems in DDPS operation. Based on the defined system requirements and these sensitivity analyses, a test design was developed for adapting, parameterizing, and executing IMSIM, using varying load and stress conditions for model execution. Analyses of the computer simulation runs are documented, including results, conclusions, and recommendations for DDPS improvements.

A new sensitivity analysis for structural optimization of composite rotor blades

NASA Technical Reports Server (NTRS)

Venkatesan, C.; Friedmann, P. P.; Yuan, Kuo-An

1993-01-01

This paper presents a detailed mathematical derivation of the sensitivity derivatives for the structural dynamic, aeroelastic stability and response characteristics of a rotor blade in hover and forward flight. The formulation is denoted by the term semianalytical approach, because certain derivatives have to be evaluated by a finite difference scheme. Using the present formulation, sensitivity derivatives for the structural dynamic and aeroelastic stability characteristics, were evaluated for both isotropic and composite rotor blades. Based on the results, useful conclusions are obtained regarding the relative merits of the semi-analytical approach, for calculating sensitivity derivatives, when compared to a pure finite difference approach.

Sensitivity Analysis of Stability Problems of Steel Structures using Shell Finite Elements and Nonlinear Computation Methods

NASA Astrophysics Data System (ADS)

Kala, Zdeněk; Kala, Jiří

2011-09-01

The main focus of the paper is the analysis of the influence of residual stress on the ultimate limit state of a hot-rolled member in compression. The member was modelled using thin-walled elements of type SHELL 181 and meshed in the programme ANSYS. Geometrical and material non-linear analysis was used. The influence of residual stress was studied using variance-based sensitivity analysis. In order to obtain more general results, the non-dimensional slenderness was selected as a study parameter. Comparison of the influence of the residual stress with the influence of other dominant imperfections is illustrated in the conclusion of the paper. All input random variables were considered according to results of experimental research.

Is High Resolution Melting Analysis (HRMA) Accurate for Detection of Human Disease-Associated Mutations? A Meta Analysis

PubMed Central

Ma, Feng-Li; Jiang, Bo; Song, Xiao-Xiao; Xu, An-Gao

2011-01-01

Background High Resolution Melting Analysis (HRMA) is becoming the preferred method for mutation detection. However, its accuracy in the individual clinical diagnostic setting is variable. To assess the diagnostic accuracy of HRMA for human mutations in comparison to DNA sequencing in different routine clinical settings, we have conducted a meta-analysis of published reports. Methodology/Principal Findings Out of 195 publications obtained from the initial search criteria, thirty-four studies assessing the accuracy of HRMA were included in the meta-analysis. We found that HRMA was a highly sensitive test for detecting disease-associated mutations in humans. Overall, the summary sensitivity was 97.5% (95% confidence interval (CI): 96.8–98.5; I2 = 27.0%). Subgroup analysis showed even higher sensitivity for non-HR-1 instruments (sensitivity 98.7% (95%CI: 97.7–99.3; I2 = 0.0%)) and an eligible sample size subgroup (sensitivity 99.3% (95%CI: 98.1–99.8; I2 = 0.0%)). HRMA specificity showed considerable heterogeneity between studies. Sensitivity of the techniques was influenced by sample size and instrument type but by not sample source or dye type. Conclusions/Significance These findings show that HRMA is a highly sensitive, simple and low-cost test to detect human disease-associated mutations, especially for samples with mutations of low incidence. The burden on DNA sequencing could be significantly reduced by the implementation of HRMA, but it should be recognized that its sensitivity varies according to the number of samples with/without mutations, and positive results require DNA sequencing for confirmation. PMID:22194806

Thermodynamic modeling of transcription: sensitivity analysis differentiates biological mechanism from mathematical model-induced effects.

PubMed

Dresch, Jacqueline M; Liu, Xiaozhou; Arnosti, David N; Ay, Ahmet

2010-10-24

Quantitative models of gene expression generate parameter values that can shed light on biological features such as transcription factor activity, cooperativity, and local effects of repressors. An important element in such investigations is sensitivity analysis, which determines how strongly a model's output reacts to variations in parameter values. Parameters of low sensitivity may not be accurately estimated, leading to unwarranted conclusions. Low sensitivity may reflect the nature of the biological data, or it may be a result of the model structure. Here, we focus on the analysis of thermodynamic models, which have been used extensively to analyze gene transcription. Extracted parameter values have been interpreted biologically, but until now little attention has been given to parameter sensitivity in this context. We apply local and global sensitivity analyses to two recent transcriptional models to determine the sensitivity of individual parameters. We show that in one case, values for repressor efficiencies are very sensitive, while values for protein cooperativities are not, and provide insights on why these differential sensitivities stem from both biological effects and the structure of the applied models. In a second case, we demonstrate that parameters that were thought to prove the system's dependence on activator-activator cooperativity are relatively insensitive. We show that there are numerous parameter sets that do not satisfy the relationships proferred as the optimal solutions, indicating that structural differences between the two types of transcriptional enhancers analyzed may not be as simple as altered activator cooperativity. Our results emphasize the need for sensitivity analysis to examine model construction and forms of biological data used for modeling transcriptional processes, in order to determine the significance of estimated parameter values for thermodynamic models. Knowledge of parameter sensitivities can provide the necessary context to determine how modeling results should be interpreted in biological systems.

Bilingualism delays age at onset of dementia, independent of education and immigration status.

PubMed

Mortimer, James A

2014-05-27

Editors' Note: Mortimer argues that important confounding variables may have biased the conclusion by Alladi et al. on the role of bilingualism in delaying the onset of dementia. Following Mortimer’s comments, Alladi et al. conducted additional analysis of their data to support their conclusion. The attitude of "close enough" is not appropriate when determining brain death. Stadlan comments and supports Frank’s call for action regarding this sensitive issue.

Reinforcement Sensitivity and Social Anxiety in Combat Veterans

PubMed Central

Kimbrel, Nathan A.; Meyer, Eric C.; DeBeer, Bryann B.; Mitchell, John T.; Kimbrel, Azure D.; Nelson-Gray, Rosemery O.; Morissette, Sandra B.

2017-01-01

Objective The present study tested the hypothesis that low behavioral approach system (BAS) sensitivity is associated with social anxiety in combat veterans. Method Self-report measures of reinforcement sensitivity, combat exposure, social interaction anxiety, and social observation anxiety were administered to 197 Iraq/Afghanistan combat veterans. Results As expected, combat exposure, behavioral inhibition system (BIS) sensitivity, and fight-flight-freeze system (FFFS) sensitivity were positively associated with both social interaction anxiety and social observation anxiety. In contrast, BAS sensitivity was negatively associated with social interaction anxiety only. An analysis of the BAS subscales revealed that the Reward Responsiveness subscale was the only BAS subscale associated with social interaction anxiety. BAS-Reward Responsiveness was also associated with social observation anxiety. Conclusion The findings from the present research provide further evidence that low BAS sensitivity may be associated with social anxiety over and above the effects of BIS and FFFS sensitivity. PMID:28966424

Technical advances in flow cytometry-based diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria

PubMed Central

Correia, Rodolfo Patussi; Bento, Laiz Cameirão; Bortolucci, Ana Carolina Apelle; Alexandre, Anderson Marega; Vaz, Andressa da Costa; Schimidell, Daniela; Pedro, Eduardo de Carvalho; Perin, Fabricio Simões; Nozawa, Sonia Tsukasa; Mendes, Cláudio Ernesto Albers; Barroso, Rodrigo de Souza; Bacal, Nydia Strachman

2016-01-01

ABSTRACT Objective: To discuss the implementation of technical advances in laboratory diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria for validation of high-sensitivity flow cytometry protocols. Methods: A retrospective study based on analysis of laboratory data from 745 patient samples submitted to flow cytometry for diagnosis and/or monitoring of paroxysmal nocturnal hemoglobinuria. Results: Implementation of technical advances reduced test costs and improved flow cytometry resolution for paroxysmal nocturnal hemoglobinuria clone detection. Conclusion: High-sensitivity flow cytometry allowed more sensitive determination of paroxysmal nocturnal hemoglobinuria clone type and size, particularly in samples with small clones. PMID:27759825

A preliminary cost-effectiveness analysis of hepatitis E vaccination among pregnant women in epidemic regions.

PubMed

Zhao, Yueyuan; Zhang, Xuefeng; Zhu, Fengcai; Jin, Hui; Wang, Bei

2016-08-02

Objective To estimate the cost-effectiveness of hepatitis E vaccination among pregnant women in epidemic regions. Methods A decision tree model was constructed to evaluate the cost-effectiveness of 3 hepatitis E virus vaccination strategies from societal perspectives. The model parameters were estimated on the basis of published studies and experts' experience. Sensitivity analysis was used to evaluate the uncertainties of the model. Results Vaccination was more economically effective on the basis of the incremental cost-effectiveness ratio (ICER< 3 times China's per capital gross domestic product/quality-adjusted life years); moreover, screening and vaccination had higher QALYs and lower costs compared with universal vaccination. No parameters significantly impacted ICER in one-way sensitivity analysis, and probabilistic sensitivity analysis also showed screening and vaccination to be the dominant strategy. Conclusion Screening and vaccination is the most economical strategy for pregnant women in epidemic regions; however, further studies are necessary to confirm the efficacy and safety of the hepatitis E vaccines.

What Do We Mean By Sensitivity Analysis? The Need For A Comprehensive Characterization Of Sensitivity In Earth System Models

NASA Astrophysics Data System (ADS)

Razavi, S.; Gupta, H. V.

2014-12-01

Sensitivity analysis (SA) is an important paradigm in the context of Earth System model development and application, and provides a powerful tool that serves several essential functions in modelling practice, including 1) Uncertainty Apportionment - attribution of total uncertainty to different uncertainty sources, 2) Assessment of Similarity - diagnostic testing and evaluation of similarities between the functioning of the model and the real system, 3) Factor and Model Reduction - identification of non-influential factors and/or insensitive components of model structure, and 4) Factor Interdependence - investigation of the nature and strength of interactions between the factors, and the degree to which factors intensify, cancel, or compensate for the effects of each other. A variety of sensitivity analysis approaches have been proposed, each of which formally characterizes a different "intuitive" understanding of what is meant by the "sensitivity" of one or more model responses to its dependent factors (such as model parameters or forcings). These approaches are based on different philosophies and theoretical definitions of sensitivity, and range from simple local derivatives and one-factor-at-a-time procedures to rigorous variance-based (Sobol-type) approaches. In general, each approach focuses on, and identifies, different features and properties of the model response and may therefore lead to different (even conflicting) conclusions about the underlying sensitivity. This presentation revisits the theoretical basis for sensitivity analysis, and critically evaluates existing approaches so as to demonstrate their flaws and shortcomings. With this background, we discuss several important properties of response surfaces that are associated with the understanding and interpretation of sensitivity. Finally, a new approach towards global sensitivity assessment is developed that is consistent with important properties of Earth System model response surfaces.

Pain Sensitivity Subgroups in Individuals With Spine Pain: Potential Relevance to Short-Term Clinical Outcome

PubMed Central

Bialosky, Joel E.; Robinson, Michael E.

2014-01-01

Background Cluster analysis can be used to identify individuals similar in profile based on response to multiple pain sensitivity measures. There are limited investigations into how empirically derived pain sensitivity subgroups influence clinical outcomes for individuals with spine pain. Objective The purposes of this study were: (1) to investigate empirically derived subgroups based on pressure and thermal pain sensitivity in individuals with spine pain and (2) to examine subgroup influence on 2-week clinical pain intensity and disability outcomes. Design A secondary analysis of data from 2 randomized trials was conducted. Methods Baseline and 2-week outcome data from 157 participants with low back pain (n=110) and neck pain (n=47) were examined. Participants completed demographic, psychological, and clinical information and were assessed using pain sensitivity protocols, including pressure (suprathreshold pressure pain) and thermal pain sensitivity (thermal heat threshold and tolerance, suprathreshold heat pain, temporal summation). A hierarchical agglomerative cluster analysis was used to create subgroups based on pain sensitivity responses. Differences in data for baseline variables, clinical pain intensity, and disability were examined. Results Three pain sensitivity cluster groups were derived: low pain sensitivity, high thermal static sensitivity, and high pressure and thermal dynamic sensitivity. There were differences in the proportion of individuals meeting a 30% change in pain intensity, where fewer individuals within the high pressure and thermal dynamic sensitivity group (adjusted odds ratio=0.3; 95% confidence interval=0.1, 0.8) achieved successful outcomes. Limitations Only 2-week outcomes are reported. Conclusions Distinct pain sensitivity cluster groups for individuals with spine pain were identified, with the high pressure and thermal dynamic sensitivity group showing worse clinical outcome for pain intensity. Future studies should aim to confirm these findings. PMID:24764070

Effects of aircraft noise on the equilibrium of airport residents: Testing and utilization of a new methodology

NASA Technical Reports Server (NTRS)

Francois, J.

1981-01-01

The focus of the investigation is centered around two main themes: an analysis of the effects of aircraft noise on the psychological and physiological equilibrium of airport residents; and an analysis of the sources of variability of sensitivity to noise. The methodology used is presented. Nine statistical tables are included, along with a set of conclusions.

A three-dimensional cohesive sediment transport model with data assimilation: Model development, sensitivity analysis and parameter estimation

NASA Astrophysics Data System (ADS)

Wang, Daosheng; Cao, Anzhou; Zhang, Jicai; Fan, Daidu; Liu, Yongzhi; Zhang, Yue

2018-06-01

Based on the theory of inverse problems, a three-dimensional sigma-coordinate cohesive sediment transport model with the adjoint data assimilation is developed. In this model, the physical processes of cohesive sediment transport, including deposition, erosion and advection-diffusion, are parameterized by corresponding model parameters. These parameters are usually poorly known and have traditionally been assigned empirically. By assimilating observations into the model, the model parameters can be estimated using the adjoint method; meanwhile, the data misfit between model results and observations can be decreased. The model developed in this work contains numerous parameters; therefore, it is necessary to investigate the parameter sensitivity of the model, which is assessed by calculating a relative sensitivity function and the gradient of the cost function with respect to each parameter. The results of parameter sensitivity analysis indicate that the model is sensitive to the initial conditions, inflow open boundary conditions, suspended sediment settling velocity and resuspension rate, while the model is insensitive to horizontal and vertical diffusivity coefficients. A detailed explanation of the pattern of sensitivity analysis is also given. In ideal twin experiments, constant parameters are estimated by assimilating 'pseudo' observations. The results show that the sensitive parameters are estimated more easily than the insensitive parameters. The conclusions of this work can provide guidance for the practical applications of this model to simulate sediment transport in the study area.

A MATHEMATICAL MODEL OF PHYTOREMEDIATION FOR PETROLEUM CONTAMINATED SOIL: SENSITIVITY ANALYSIS. (R827015C018)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Inaccurate Estimation of Disparities Due to Mischievous Responders: Several Suggestions to Assess Conclusions

ERIC Educational Resources Information Center

Robinson-Cimpian, Joseph P.

2014-01-01

This article introduces novel sensitivity-analysis procedures for investigating and reducing the bias that mischievous responders (i.e., youths who provide extreme, and potentially untruthful, responses to multiple questions) often introduce in adolescent disparity estimates based on data from self-administered questionnaires (SAQs). Mischievous…

Cost effectiveness analysis of screening for sight threatening diabetic eye disease

PubMed Central

James, Marilyn; Turner, David A; Broadbent, Deborah M; Vora, Jiten; Harding, Simon P

2000-01-01

Objective To measure the cost effectiveness of systematic photographic screening for sight threatening diabetic eye disease compared with existing practice. Design Cost effectiveness analysis Setting Liverpool. Subjects A target population of 5000 diabetic patients invited for screening. Main outcome measures Cost effectiveness (cost per true positive) of systematic and opportunistic programmes; incremental cost effectiveness of replacing opportunistic with systematic screening. Results Baseline prevalence of sight threatening eye disease was 14.1%. The cost effectiveness of the systematic programme was £209 (sensitivity 89%, specificity 86%, compliance 80%, annual cost £104 996) and of the opportunistic programme was £289 (combined sensitivity 63%, specificity 92%, compliance 78%, annual cost £99 981). The incremental cost effectiveness of completely replacing the opportunistic programme was £32. Absolute values of cost effectiveness were highly sensitive to varying prevalence, sensitivity and specificity, compliance, and programme size. Conclusion Replacing existing programmes with systematic screening for diabetic eye disease is justified. PMID:10856062

Sensitivity analysis for dose deposition in radiotherapy via a Fokker–Planck model

DOE PAGES

Barnard, Richard C.; Frank, Martin; Krycki, Kai

2016-02-09

In this paper, we study the sensitivities of electron dose calculations with respect to stopping power and transport coefficients. We focus on the application to radiotherapy simulations. We use a Fokker–Planck approximation to the Boltzmann transport equation. Equations for the sensitivities are derived by the adjoint method. The Fokker–Planck equation and its adjoint are solved numerically in slab geometry using the spherical harmonics expansion (P N) and an Harten-Lax-van Leer finite volume method. Our method is verified by comparison to finite difference approximations of the sensitivities. Finally, we present numerical results of the sensitivities for the normalized average dose depositionmore » depth with respect to the stopping power and the transport coefficients, demonstrating the increase in relative sensitivities as beam energy decreases. In conclusion, this in turn gives estimates on the uncertainty in the normalized average deposition depth, which we present.« less

Dynamic sensitivity analysis of biological systems

PubMed Central

Wu, Wu Hsiung; Wang, Feng Sheng; Chang, Maw Shang

2008-01-01

Background A mathematical model to understand, predict, control, or even design a real biological system is a central theme in systems biology. A dynamic biological system is always modeled as a nonlinear ordinary differential equation (ODE) system. How to simulate the dynamic behavior and dynamic parameter sensitivities of systems described by ODEs efficiently and accurately is a critical job. In many practical applications, e.g., the fed-batch fermentation systems, the system admissible input (corresponding to independent variables of the system) can be time-dependent. The main difficulty for investigating the dynamic log gains of these systems is the infinite dimension due to the time-dependent input. The classical dynamic sensitivity analysis does not take into account this case for the dynamic log gains. Results We present an algorithm with an adaptive step size control that can be used for computing the solution and dynamic sensitivities of an autonomous ODE system simultaneously. Although our algorithm is one of the decouple direct methods in computing dynamic sensitivities of an ODE system, the step size determined by model equations can be used on the computations of the time profile and dynamic sensitivities with moderate accuracy even when sensitivity equations are more stiff than model equations. To show this algorithm can perform the dynamic sensitivity analysis on very stiff ODE systems with moderate accuracy, it is implemented and applied to two sets of chemical reactions: pyrolysis of ethane and oxidation of formaldehyde. The accuracy of this algorithm is demonstrated by comparing the dynamic parameter sensitivities obtained from this new algorithm and from the direct method with Rosenbrock stiff integrator based on the indirect method. The same dynamic sensitivity analysis was performed on an ethanol fed-batch fermentation system with a time-varying feed rate to evaluate the applicability of the algorithm to realistic models with time-dependent admissible input. Conclusion By combining the accuracy we show with the efficiency of being a decouple direct method, our algorithm is an excellent method for computing dynamic parameter sensitivities in stiff problems. We extend the scope of classical dynamic sensitivity analysis to the investigation of dynamic log gains of models with time-dependent admissible input. PMID:19091016

Sensitivity to Mental Effort and Test-Retest Reliability of Heart Rate Variability Measures in Healthy Seniors

PubMed Central

Mukherjee, Shalini; Yadav, Rajeev; Yung, Iris; Zajdel, Daniel P.; Oken, Barry S.

2011-01-01

Objectives To determine 1) whether heart rate variability (HRV) was a sensitive and reliable measure in mental effort tasks carried out by healthy seniors and 2) whether non-linear approaches to HRV analysis, in addition to traditional time and frequency domain approaches were useful to study such effects. Methods Forty healthy seniors performed two visual working memory tasks requiring different levels of mental effort, while ECG was recorded. They underwent the same tasks and recordings two weeks later. Traditional and 13 non-linear indices of HRV including Poincaré, entropy and detrended fluctuation analysis (DFA) were determined. Results Time domain (especially mean R-R interval/RRI), frequency domain and, among nonlinear parameters- Poincaré and DFA were the most reliable indices. Mean RRI, time domain and Poincaré were also the most sensitive to different mental effort task loads and had the largest effect size. Conclusions Overall, linear measures were the most sensitive and reliable indices to mental effort. In non-linear measures, Poincaré was the most reliable and sensitive, suggesting possible usefulness as an independent marker in cognitive function tasks in healthy seniors. Significance A large number of HRV parameters was both reliable as well as sensitive indices of mental effort, although the simple linear methods were the most sensitive. PMID:21459665

IMPACTS OF URBANIZATION ON SURFACE HYDROLOGY, LITTLE EAGLE CREEK, INDIANA, AND ANALYSIS OF LTHIA MODEL SENSITIVITY TO DATA RESOLUTION. (R825871)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Resting spontaneous baroreflex sensitivity and cardiac autonomic control in anabolic androgenic steroid users

PubMed Central

dos Santos, Marcelo R.; Sayegh, Ana L.C.; Armani, Rafael; Costa-Hong, Valéria; de Souza, Francis R.; Toschi-Dias, Edgar; Bortolotto, Luiz A.; Yonamine, Mauricio; Negrão, Carlos E.; Alves, Maria-Janieire N.N.

2018-01-01

OBJECTIVES: Misuse of anabolic androgenic steroids in athletes is a strategy used to enhance strength and skeletal muscle hypertrophy. However, its abuse leads to an imbalance in muscle sympathetic nerve activity, increased vascular resistance, and increased blood pressure. However, the mechanisms underlying these alterations are still unknown. Therefore, we tested whether anabolic androgenic steroids could impair resting baroreflex sensitivity and cardiac sympathovagal control. In addition, we evaluate pulse wave velocity to ascertain the arterial stiffness of large vessels. METHODS: Fourteen male anabolic androgenic steroid users and 12 nonusers were studied. Heart rate, blood pressure, and respiratory rate were recorded. Baroreflex sensitivity was estimated by the sequence method, and cardiac autonomic control by analysis of the R-R interval. Pulse wave velocity was measured using a noninvasive automatic device. RESULTS: Mean spontaneous baroreflex sensitivity, baroreflex sensitivity to activation of the baroreceptors, and baroreflex sensitivity to deactivation of the baroreceptors were significantly lower in users than in nonusers. In the spectral analysis of heart rate variability, high frequency activity was lower, while low frequency activity was higher in users than in nonusers. Moreover, the sympathovagal balance was higher in users. Users showed higher pulse wave velocity than nonusers showing arterial stiffness of large vessels. Single linear regression analysis showed significant correlations between mean blood pressure and baroreflex sensitivity and pulse wave velocity. CONCLUSIONS: Our results provide evidence for lower baroreflex sensitivity and sympathovagal imbalance in anabolic androgenic steroid users. Moreover, anabolic androgenic steroid users showed arterial stiffness. Together, these alterations might be the mechanisms triggering the increased blood pressure in this population. PMID:29791601

A novel hypothesis on the sensitivity of the fecal occult blood test: Results of a joint analysis of 3 randomized controlled trials.

PubMed

Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein; Boer, Rob; Zauber, Ann; Habbema, J Dik F

2009-06-01

Estimates of the fecal occult blood test (FOBT) (Hemoccult II) sensitivity differed widely between screening trials and led to divergent conclusions on the effects of FOBT screening. We used microsimulation modeling to estimate a preclinical colorectal cancer (CRC) duration and sensitivity for unrehydrated FOBT from the data of 3 randomized controlled trials of Minnesota, Nottingham, and Funen. In addition to 2 usual hypotheses on the sensitivity of FOBT, we tested a novel hypothesis where sensitivity is linked to the stage of clinical diagnosis in the situation without screening. We used the MISCAN-Colon microsimulation model to estimate sensitivity and duration, accounting for differences between the trials in demography, background incidence, and trial design. We tested 3 hypotheses for FOBT sensitivity: sensitivity is the same for all preclinical CRC stages, sensitivity increases with each stage, and sensitivity is higher for the stage in which the cancer would have been diagnosed in the absence of screening than for earlier stages. Goodness-of-fit was evaluated by comparing expected and observed rates of screen-detected and interval CRC. The hypothesis with a higher sensitivity in the stage of clinical diagnosis gave the best fit. Under this hypothesis, sensitivity of FOBT was 51% in the stage of clinical diagnosis and 19% in earlier stages. The average duration of preclinical CRC was estimated at 6.7 years. Our analysis corroborated a long duration of preclinical CRC, with FOBT most sensitive in the stage of clinical diagnosis. (c) 2009 American Cancer Society.

The Efficacy of Guanxinning Injection in Treating Angina Pectoris: Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Jia, Yongliang; Leung, Siu-wai; Lee, Ming-Yuen; Cui, Guozhen; Huang, Xiaohui; Pan, Fongha

2013-01-01

Objective. The randomized controlled trials (RCTs) on Guanxinning injection (GXN) in treating angina pectoris were published only in Chinese and have not been systematically reviewed. This study aims to provide a PRISMA-compliant and internationally accessible systematic review to evaluate the efficacy of GXN in treating angina pectoris. Methods. The RCTs were included according to prespecified eligibility criteria. Meta-analysis was performed to evaluate the symptomatic (SYMPTOMS) and electrocardiographic (ECG) improvements after treatment. Odds ratios (ORs) were used to measure effect sizes. Subgroup analysis, sensitivity analysis, and metaregression were conducted to evaluate the robustness of the results. Results. Sixty-five RCTs published between 2002 and 2012 with 6064 participants were included. Overall ORs comparing GXN with other drugs were 3.32 (95% CI: [2.72, 4.04]) in SYMPTOMS and 2.59 (95% CI: [2.14, 3.15]) in ECG. Subgroup analysis, sensitivity analysis, and metaregression found no statistically significant dependence of overall ORs upon specific study characteristics. Conclusion. This meta-analysis of eligible RCTs provides evidence that GXN is effective in treating angina pectoris. This evidence warrants further RCTs of higher quality, longer follow-up periods, larger sample sizes, and multicentres/multicountries for more extensive subgroup, sensitivity, and metaregression analyses. PMID:23634167

‎ Anxiety Sensitivity Dimensions and Generalized Anxiety‏ ‏Severity: The ‎Mediating Role of Experiential Avoidance and Repetitive‏ ‏Negative Thinking‎ ‎

PubMed Central

Mohammadkhani, Parvaneh; Pourshahbaz, Abbas; Kami, Maryam; Mazidi, Mahdi; Abasi, Imaneh‏

2016-01-01

Objective: Generalized anxiety disorder is one of the most common anxiety disorders in the general ‎population. Several studies suggest that anxiety sensitivity is a vulnerability factor in generalized ‎anxiety severity. However, some other studies suggest that negative repetitive thinking and ‎experiential avoidance as response factors can explain this relationship. Therefore, this study ‎aimed to investigate the mediating role of experiential avoidance and negative repetitive thinking ‎in the relationship between anxiety sensitivity and generalized anxiety severity.‎ Method: This was a cross-sectional and correlational study. A sample of 475 university students was ‎selected through stratified sampling method. The participants completed Anxiety Sensitivity ‎Inventory-3, Acceptance and Action Questionnaire-II, Perseverative Thinking Questionnaire, and ‎Generalized Anxiety Disorder 7-item Scale. Data were analyzed by Pearson correlation, multiple ‎regression analysis and path analysis.‎ Results: The results revealed a positive relationship between anxiety sensitivity, particularly cognitive ‎anxiety sensitivity, experiential avoidance, repetitive thinking and generalized anxiety severity. In ‎addition, findings showed that repetitive thinking, but not experiential avoidance, fully mediated ‎the relationship between cognitive anxiety sensitivity and generalized anxiety severity. α Level ‎was p<0.005.‎ Conclusion: Consistent with the trans-diagnostic hypothesis, anxiety sensitivity predicts generalized anxiety‏ ‏severity, but its effect is due to the generating repetitive negative thought.‎ PMID:27928245

Longitudinal study of factors affecting taste sense decline in old-old individuals.

PubMed

Ogawa, T; Uota, M; Ikebe, K; Arai, Y; Kamide, K; Gondo, Y; Masui, Y; Ishizaki, T; Inomata, C; Takeshita, H; Mihara, Y; Hatta, K; Maeda, Y

2017-01-01

The sense of taste plays a pivotal role for personal assessment of the nutritional value, safety and quality of foods. Although it is commonly recognised that taste sensitivity decreases with age, alterations in that sensitivity over time in an old-old population have not been previously reported. Furthermore, no known studies utilised comprehensive variables regarding taste changes and related factors for assessments. Here, we report novel findings from a 3-year longitudinal study model aimed to elucidate taste sensitivity decline and its related factors in old-old individuals. We utilised 621 subjects aged 79-81 years who participated in the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians Study for baseline assessments performed in 2011 and 2012, and then conducted follow-up assessments 3 years later in 328 of those. Assessment of general health, an oral examination and determination of taste sensitivity were performed for each. We also evaluated cognitive function using Montreal Cognitive Assessment findings, then excluded from analysis those with a score lower than 20 in order to secure the validity and reliability of the subjects' answers. Contributing variables were selected using univariate analysis, then analysed with multivariate logistic regression analysis. We found that males showed significantly greater declines in taste sensitivity for sweet and sour tastes than females. Additionally, subjects with lower cognitive scores showed a significantly greater taste decrease for salty in multivariate analysis. In conclusion, our longitudinal study revealed that gender and cognitive status are major factors affecting taste sensitivity in geriatric individuals. © 2016 John Wiley & Sons Ltd.

Digital data processing system dynamic loading analysis

NASA Technical Reports Server (NTRS)

Lagas, J. J.; Peterka, J. J.; Tucker, A. E.

1976-01-01

Simulation and analysis of the Space Shuttle Orbiter Digital Data Processing System (DDPS) are reported. The mated flight and postseparation flight phases of the space shuttle's approach and landing test configuration were modeled utilizing the Information Management System Interpretative Model (IMSIM) in a computerized simulation modeling of the ALT hardware, software, and workload. System requirements simulated for the ALT configuration were defined. Sensitivity analyses determined areas of potential data flow problems in DDPS operation. Based on the defined system requirements and the sensitivity analyses, a test design is described for adapting, parameterizing, and executing the IMSIM. Varying load and stress conditions for the model execution are given. The analyses of the computer simulation runs were documented as results, conclusions, and recommendations for DDPS improvements.

Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism

PubMed Central

Vandell, Alexander G; Walker, Joseph; Brown, Karen S; Zhang, George; Lin, Min; Grosso, Michael A; Mercuri, Michele F

2017-01-01

Objective The aim of this study was to investigate whether genetic variants can identify patients with venous thromboembolism (VTE) at an increased risk of bleeding with warfarin. Methods Hokusai-venous thromboembolism (Hokusai VTE), a randomised, multinational, double-blind, non-inferiority trial, evaluated the safety and efficacy of edoxaban versus warfarin in patients with VTE initially treated with heparin. In this subanalysis of Hokusai VTE, patients genotyped for variants in CYP2C9 and VKORC1 genes were divided into three warfarin sensitivity types (normal, sensitive and highly sensitive) based on their genotypes. An exploratory analysis was also conducted comparing normal responders to pooled sensitive responders (ie, sensitive and highly sensitive responders). Results The analysis included 47.7% (3956/8292) of the patients in Hokusai VTE. Among 1978 patients randomised to warfarin, 63.0% (1247) were normal responders, 34.1% (675) were sensitive responders and 2.8% (56) were highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders had heparin therapy discontinued earlier (p<0.001), had a decreased final weekly warfarin dose (p<0.001), spent more time overanticoagulated (p<0.001) and had an increased bleeding risk with warfarin (sensitive responders HR 1.38 [95% CI 1.11 to 1.71], p=0.0035; highly sensitive responders 1.79 [1.09 to 2.99]; p=0.0252). Conclusion In this study, CYP2C9 and VKORC1 genotypes identified patients with VTE at increased bleeding risk with warfarin. Trial registration number NCT00986154. PMID:28689179

The Sensitivity and Specificity of Potassium Hydroxide Smear and Fungal Culture Relative to Clinical Assessment in the Evaluation of Tinea Pedis: A Pooled Analysis

PubMed Central

Levitt, Jacob Oren; Levitt, Barrie H.; Akhavan, Arash; Yanofsky, Howard

2010-01-01

Background. There are relatively few studies published examining the sensitivity and specificity of potassium hydroxide (KOH) smear and fungal culture examination of tinea pedis. Objective. To evaluate the sensitivity and specificity of KOH smear and fungal culture for diagnosing tinea pedis. Methods. A pooled analysis of data from five similarly conducted bioequivalence trials for antifungal drugs was performed. Data from 460 patients enrolled in the vehicle arms of these studies with clinical diagnosis of tinea pedis supported by positive fungal culture were analyzed 6 weeks after initiation of the study to determine the sensitivity and specificity of KOH smear and fungal culture. Results. Using clinical assessment as the gold standard, the sensitivities for KOH smear and culture were 73.3% (95% CI: 66.3 to 79.5%) and 41.7% (34.6 to 49.1%), respectively. The respective specificities for culture and KOH smear were 77.7% (72.2 to 82.5%) and 42.5% (36.6 to 48.6%). Conclusion. KOH smear and fungal culture are complementary diagnostic tests for tinea pedis, with the former being the more sensitive test of the two, and the latter being more specific. PMID:20672004

Basic research for the geodynamics program

NASA Technical Reports Server (NTRS)

1991-01-01

The mathematical models of space very long base interferometry (VLBI) observables suitable for least squares covariance analysis were derived and estimatability problems inherent in the space VLBI system were explored, including a detailed rank defect analysis and sensitivity analysis. An important aim is to carry out a comparative analysis of the mathematical models of the ground-based VLBI and space VLBI observables in order to describe the background in detail. Computer programs were developed in order to check the relations, assess errors, and analyze sensitivity. In order to investigate the estimatability of different geodetic and geodynamic parameters from the space VLBI observables, the mathematical models for time delay and time delay rate observables of space VLBI were analytically derived along with the partial derivatives with respect to the parameters. Rank defect analysis was carried out both by analytical and numerical testing of linear dependencies between the columns of the normal matrix thus formed. Definite conclusions were formed about the rank defects in the system.

Neuromelanin imaging and midbrain volumetry in progressive supranuclear palsy and Parkinson's disease.

PubMed

Taniguchi, Daisuke; Hatano, Taku; Kamagata, Koji; Okuzumi, Ayami; Oji, Yutaka; Mori, Akio; Hori, Masaaki; Aoki, Shigeki; Hattori, Nobutaka

2018-05-14

Background Nigral degeneration patterns differ between PSP and PD. However, the relationship between nigral degeneration and midbrain atrophy in PSP remains unclear. Objective We analyzed differences and relationships between nigral degeneration and midbrain atrophy in PSP and PD. Methods Neuromelanin-sensitive MRI and midbrain volumetry were performed in 11 PSP patients, 24 PD patients, and 10 controls to measure the neuromelanin-sensitive SNpc area and midbrain volume. Results The neuromelanin-sensitive SNpc area and midbrain volume were significantly smaller in PSP patients compared with PD patients and controls. Motor deficits were inversely correlated with neuromelanin-sensitive SNpc area in PD, but not PSP patients. There was no significant correlation between neuromelanin-sensitive SNpc area and midbrain volume in either disease group. Midbrain volumetry discriminated PSP from PD. Diagnostic accuracy was improved when neuromelanin-sensitive MRI analysis was added. Conclusions Neuromelanin-sensitive MRI and midbrain volumetry may reflect the clinical and pathological characteristics of PSP and PD. Combining neuromelanin-sensitive MRI and midbrain volumetry may be useful for differentiating PSP from PD. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Sensitivity analysis of Repast computational ecology models with R/Repast.

PubMed

Prestes García, Antonio; Rodríguez-Patón, Alfonso

2016-12-01

Computational ecology is an emerging interdisciplinary discipline founded mainly on modeling and simulation methods for studying ecological systems. Among the existing modeling formalisms, the individual-based modeling is particularly well suited for capturing the complex temporal and spatial dynamics as well as the nonlinearities arising in ecosystems, communities, or populations due to individual variability. In addition, being a bottom-up approach, it is useful for providing new insights on the local mechanisms which are generating some observed global dynamics. Of course, no conclusions about model results could be taken seriously if they are based on a single model execution and they are not analyzed carefully. Therefore, a sound methodology should always be used for underpinning the interpretation of model results. The sensitivity analysis is a methodology for quantitatively assessing the effect of input uncertainty in the simulation output which should be incorporated compulsorily to every work based on in-silico experimental setup. In this article, we present R/Repast a GNU R package for running and analyzing Repast Simphony models accompanied by two worked examples on how to perform global sensitivity analysis and how to interpret the results.

Pain sensitivity mediates the relationship between stress and headache intensity in chronic tension-type headache

PubMed Central

Cathcart, Stuart; Bhullar, Navjot; Immink, Maarten; Della Vedova, Chris; Hayball, John

2012-01-01

BACKGROUND: A central model for chronic tension-type headache (CTH) posits that stress contributes to headache, in part, by aggravating existing hyperalgesia in CTH sufferers. The prediction from this model that pain sensitivity mediates the relationship between stress and headache activity has not yet been examined. OBJECTIVE: To determine whether pain sensitivity mediates the relationship between stress and prospective headache activity in CTH sufferers. METHOD: Self-reported stress, pain sensitivity and prospective headache activity were measured in 53 CTH sufferers recruited from the general population. Pain sensitivity was modelled as a mediator between stress and headache activity, and tested using a nonparametric bootstrap analysis. RESULTS: Pain sensitivity significantly mediated the relationship between stress and headache intensity. CONCLUSIONS: The results of the present study support the central model for CTH, which posits that stress contributes to headache, in part, by aggravating existing hyperalgesia in CTH sufferers. Implications for the mechanisms and treatment of CTH are discussed. PMID:23248808

Competitive amplification of differentially melting amplicons (CADMA) enables sensitive and direct detection of all mutation types by high-resolution melting analysis.

PubMed

Kristensen, Lasse S; Andersen, Gitte B; Hager, Henrik; Hansen, Lise Lotte

2012-01-01

Sensitive and specific mutation detection is of particular importance in cancer diagnostics, prognostics, and individualized patient treatment. However, the majority of molecular methodologies that have been developed with the aim of increasing the sensitivity of mutation testing have drawbacks in terms of specificity, convenience, or costs. Here, we have established a new method, Competitive Amplification of Differentially Melting Amplicons (CADMA), which allows very sensitive and specific detection of all mutation types. The principle of the method is to amplify wild-type and mutated sequences simultaneously using a three-primer system. A mutation-specific primer is designed to introduce melting temperature decreasing mutations in the resulting mutated amplicon, while a second overlapping primer is designed to amplify both wild-type and mutated sequences. When combined with a third common primer very sensitive mutation detection becomes possible, when using high-resolution melting (HRM) as detection platform. The introduction of melting temperature decreasing mutations in the mutated amplicon also allows for further mutation enrichment by fast coamplification at lower denaturation temperature PCR (COLD-PCR). For proof-of-concept, we have designed CADMA assays for clinically relevant BRAF, EGFR, KRAS, and PIK3CA mutations, which are sensitive to, between 0.025% and 0.25%, mutated alleles in a wild-type background. In conclusion, CADMA enables highly sensitive and specific mutation detection by HRM analysis. © 2011 Wiley Periodicals, Inc.

Nursing-sensitive indicators: a concept analysis

PubMed Central

Heslop, Liza; Lu, Sai

2014-01-01

Aim To report a concept analysis of nursing-sensitive indicators within the applied context of the acute care setting. Background The concept of ‘nursing sensitive indicators’ is valuable to elaborate nursing care performance. The conceptual foundation, theoretical role, meaning, use and interpretation of the concept tend to differ. The elusiveness of the concept and the ambiguity of its attributes may have hindered research efforts to advance its application in practice. Design Concept analysis. Data sources Using ‘clinical indicators’ or ‘quality of nursing care’ as subject headings and incorporating keyword combinations of ‘acute care’ and ‘nurs*’, CINAHL and MEDLINE with full text in EBSCOhost databases were searched for English language journal articles published between 2000–2012. Only primary research articles were selected. Methods A hybrid approach was undertaken, incorporating traditional strategies as per Walker and Avant and a conceptual matrix based on Holzemer's Outcomes Model for Health Care Research. Results The analysis revealed two main attributes of nursing-sensitive indicators. Structural attributes related to health service operation included: hours of nursing care per patient day, nurse staffing. Outcome attributes related to patient care included: the prevalence of pressure ulcer, falls and falls with injury, nosocomial selective infection and patient/family satisfaction with nursing care. Conclusion This concept analysis may be used as a basis to advance understandings of the theoretical structures that underpin both research and practical application of quality dimensions of nursing care performance. PMID:25113388

Algorithm for automatic analysis of electro-oculographic data

PubMed Central

2013-01-01

Background Large amounts of electro-oculographic (EOG) data, recorded during electroencephalographic (EEG) measurements, go underutilized. We present an automatic, auto-calibrating algorithm that allows efficient analysis of such data sets. Methods The auto-calibration is based on automatic threshold value estimation. Amplitude threshold values for saccades and blinks are determined based on features in the recorded signal. The performance of the developed algorithm was tested by analyzing 4854 saccades and 213 blinks recorded in two different conditions: a task where the eye movements were controlled (saccade task) and a task with free viewing (multitask). The results were compared with results from a video-oculography (VOG) device and manually scored blinks. Results The algorithm achieved 93% detection sensitivity for blinks with 4% false positive rate. The detection sensitivity for horizontal saccades was between 98% and 100%, and for oblique saccades between 95% and 100%. The classification sensitivity for horizontal and large oblique saccades (10 deg) was larger than 89%, and for vertical saccades larger than 82%. The duration and peak velocities of the detected horizontal saccades were similar to those in the literature. In the multitask measurement the detection sensitivity for saccades was 97% with a 6% false positive rate. Conclusion The developed algorithm enables reliable analysis of EOG data recorded both during EEG and as a separate metrics. PMID:24160372

Algorithm sensitivity analysis and parameter tuning for tissue image segmentation pipelines

PubMed Central

Kurç, Tahsin M.; Taveira, Luís F. R.; Melo, Alba C. M. A.; Gao, Yi; Kong, Jun; Saltz, Joel H.

2017-01-01

Abstract Motivation: Sensitivity analysis and parameter tuning are important processes in large-scale image analysis. They are very costly because the image analysis workflows are required to be executed several times to systematically correlate output variations with parameter changes or to tune parameters. An integrated solution with minimum user interaction that uses effective methodologies and high performance computing is required to scale these studies to large imaging datasets and expensive analysis workflows. Results: The experiments with two segmentation workflows show that the proposed approach can (i) quickly identify and prune parameters that are non-influential; (ii) search a small fraction (about 100 points) of the parameter search space with billions to trillions of points and improve the quality of segmentation results (Dice and Jaccard metrics) by as much as 1.42× compared to the results from the default parameters; (iii) attain good scalability on a high performance cluster with several effective optimizations. Conclusions: Our work demonstrates the feasibility of performing sensitivity analyses, parameter studies and auto-tuning with large datasets. The proposed framework can enable the quantification of error estimations and output variations in image segmentation pipelines. Availability and Implementation: Source code: https://github.com/SBU-BMI/region-templates/. Contact: teodoro@unb.br Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28062445

Application of neural networks and sensitivity analysis to improved prediction of trauma survival.

PubMed

Hunter, A; Kennedy, L; Henry, J; Ferguson, I

2000-05-01

The performance of trauma departments is widely audited by applying predictive models that assess probability of survival, and examining the rate of unexpected survivals and deaths. Although the TRISS methodology, a logistic regression modelling technique, is still the de facto standard, it is known that neural network models perform better. A key issue when applying neural network models is the selection of input variables. This paper proposes a novel form of sensitivity analysis, which is simpler to apply than existing techniques, and can be used for both numeric and nominal input variables. The technique is applied to the audit survival problem, and used to analyse the TRISS variables. The conclusions discuss the implications for the design of further improved scoring schemes and predictive models.

Sensitivity of the Positive and Negative Syndrome Scale (PANSS) in Detecting Treatment Effects via Network Analysis.

PubMed

Esfahlani, Farnaz Zamani; Sayama, Hiroki; Visser, Katherine Frost; Strauss, Gregory P

2017-12-01

Objective: The Positive and Negative Syndrome Scale is a primary outcome measure in clinical trials examining the efficacy of antipsychotic medications. Although the Positive and Negative Syndrome Scale has demonstrated sensitivity as a measure of treatment change in studies using traditional univariate statistical approaches, its sensitivity to detecting network-level changes in dynamic relationships among symptoms has yet to be demonstrated using more sophisticated multivariate analyses. In the current study, we examined the sensitivity of the Positive and Negative Syndrome Scale to detecting antipsychotic treatment effects as revealed through network analysis. Design: Participants included 1,049 individuals diagnosed with psychotic disorders from the Phase I portion of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. Of these participants, 733 were clinically determined to be treatment-responsive and 316 were found to be treatment-resistant. Item level data from the Positive and Negative Syndrome Scale were submitted to network analysis, and macroscopic, mesoscopic, and microscopic network properties were evaluated for the treatment-responsive and treatment-resistant groups at baseline and post-phase I antipsychotic treatment. Results: Network analysis indicated that treatment-responsive patients had more densely connected symptom networks after antipsychotic treatment than did treatment-responsive patients at baseline, and that symptom centralities increased following treatment. In contrast, symptom networks of treatment-resistant patients behaved more randomly before and after treatment. Conclusions: These results suggest that the Positive and Negative Syndrome Scale is sensitive to detecting treatment effects as revealed through network analysis. Its findings also provide compelling new evidence that strongly interconnected symptom networks confer an overall greater probability of treatment responsiveness in patients with psychosis, suggesting that antipsychotics achieve their effect by enhancing a number of central symptoms, which then facilitate reduction of other highly coupled symptoms in a network-like fashion.

Colonic lesion characterization in inflammatory bowel disease: A systematic review and meta-analysis

PubMed Central

Lord, Richard; Burr, Nicholas E; Mohammed, Noor; Subramanian, Venkataraman

2018-01-01

AIM To perform a systematic review and meta-analysis for the diagnostic accuracy of in vivo lesion characterization in colonic inflammatory bowel disease (IBD), using optical imaging techniques, including virtual chromoendoscopy (VCE), dye-based chromoendoscopy (DBC), magnification endoscopy and confocal laser endomicroscopy (CLE). METHODS We searched Medline, Embase and the Cochrane library. We performed a bivariate meta-analysis to calculate the pooled estimate sensitivities, specificities, positive and negative likelihood ratios (+LHR, -LHR), diagnostic odds ratios (DOR), and area under the SROC curve (AUSROC) for each technology group. A subgroup analysis was performed to investigate differences in real-time non-magnified Kudo pit patterns (with VCE and DBC) and real-time CLE. RESULTS We included 22 studies [1491 patients; 4674 polyps, of which 539 (11.5%) were neoplastic]. Real-time CLE had a pooled sensitivity of 91% (95%CI: 66%-98%), specificity of 97% (95%CI: 94%-98%), and an AUSROC of 0.98 (95%CI: 0.97-0.99). Magnification endoscopy had a pooled sensitivity of 90% (95%CI: 77%-96%) and specificity of 87% (95%CI: 81%-91%). VCE had a pooled sensitivity of 86% (95%CI: 62%-95%) and specificity of 87% (95%CI: 72%-95%). DBC had a pooled sensitivity of 67% (95%CI: 44%-84%) and specificity of 86% (95%CI: 72%-94%). CONCLUSION Real-time CLE is a highly accurate technology for differentiating neoplastic from non-neoplastic lesions in patients with colonic IBD. However, most CLE studies were performed by single expert users within tertiary centres, potentially confounding these results. PMID:29563760

Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis B-related fibrosis: a leading meta-analysis

PubMed Central

2012-01-01

Background The aspartate aminotransferase-to-platelet ratio index (APRI), a tool with limited expense and widespread availability, is a promising noninvasive alternative to liver biopsy for detecting hepatic fibrosis. The objective of this study was to systematically review the performance of the APRI in predicting significant fibrosis and cirrhosis in hepatitis B-related fibrosis. Methods Areas under summary receiver operating characteristic curves (AUROC), sensitivity and specificity were used to examine the accuracy of the APRI for the diagnosis of hepatitis B-related significant fibrosis and cirrhosis. Heterogeneity was explored using meta-regression. Results Nine studies were included in this meta-analysis (n = 1,798). Prevalence of significant fibrosis and cirrhosis were 53.1% and 13.5%, respectively. The summary AUCs of the APRI for significant fibrosis and cirrhosis were 0.79 and 0.75, respectively. For significant fibrosis, an APRI threshold of 0.5 was 84% sensitive and 41% specific. At the cutoff of 1.5, the summary sensitivity and specificity were 49% and 84%, respectively. For cirrhosis, an APRI threshold of 1.0-1.5 was 54% sensitive and 78% specific. At the cutoff of 2.0, the summary sensitivity and specificity were 28% and 87%, respectively. Meta-regression analysis indicated that the APRI accuracy for both significant fibrosis and cirrhosis was affected by histological classification systems, but not influenced by the interval between Biopsy & APRI or blind biopsy. Conclusion Our meta-analysis suggests that APRI show limited value in identifying hepatitis B-related significant fibrosis and cirrhosis. PMID:22333407

Elucidation of high sensitivity of δ-HMX: New insight from first principles simulations

NASA Astrophysics Data System (ADS)

Kuklja, Maija M.; Tsyshevsky, Roman V.; Sharia, Onise

2017-01-01

Understanding of a significant difference in sensitivities of β and δ phases of cyclotetramethylene-tetranitramine (HMX) has been long one of the challenges in the field of high energy density materials. Despite many experimental and theoretical efforts to explain the high sensitivity of the δ phase, convincing reasons behind the HMX behavior remained unclear. We established that the presence of a polar surface in δ-HMX has fundamental implications for stability and overall chemical behavior of the material. A comparative quantum-chemical analysis of decomposition mechanisms in polar δ-HMX and nonpolar β-HMX discovered a considerable difference in dominating dissociation reactions, activation barriers, and reaction rates. The polarization-induced charge transfer offered a logical explanation for different sensitivity of β-HMX and δ-HMX polymorphs to detonation initiation. Our conclusions also removed long-standing contradictions and explained a large range of experimental data on thermal decomposition of HMX.

Physiologically based pharmacokinetic modeling of a homologous series of barbiturates in the rat: a sensitivity analysis.

PubMed

Nestorov, I A; Aarons, L J; Rowland, M

1997-08-01

Sensitivity analysis studies the effects of the inherent variability and uncertainty in model parameters on the model outputs and may be a useful tool at all stages of the pharmacokinetic modeling process. The present study examined the sensitivity of a whole-body physiologically based pharmacokinetic (PBPK) model for the distribution kinetics of nine 5-n-alkyl-5-ethyl barbituric acids in arterial blood and 14 tissues (lung, liver, kidney, stomach, pancreas, spleen, gut, muscle, adipose, skin, bone, heart, brain, testes) after i.v. bolus administration to rats. The aims were to obtain new insights into the model used, to rank the model parameters involved according to their impact on the model outputs and to study the changes in the sensitivity induced by the increase in the lipophilicity of the homologues on ascending the series. Two approaches for sensitivity analysis have been implemented. The first, based on the Matrix Perturbation Theory, uses a sensitivity index defined as the normalized sensitivity of the 2-norm of the model compartmental matrix to perturbations in its entries. The second approach uses the traditional definition of the normalized sensitivity function as the relative change in a model state (a tissue concentration) corresponding to a relative change in a model parameter. Autosensitivity has been defined as sensitivity of a state to any of its parameters; cross-sensitivity as the sensitivity of a state to any other states' parameters. Using the two approaches, the sensitivity of representative tissue concentrations (lung, liver, kidney, stomach, gut, adipose, heart, and brain) to the following model parameters: tissue-to-unbound plasma partition coefficients, tissue blood flows, unbound renal and intrinsic hepatic clearance, permeability surface area product of the brain, have been analyzed. Both the tissues and the parameters were ranked according to their sensitivity and impact. The following general conclusions were drawn: (i) the overall sensitivity of the system to all parameters involved is small due to the weak connectivity of the system structure; (ii) the time course of both the auto- and cross-sensitivity functions for all tissues depends on the dynamics of the tissues themselves, e.g., the higher the perfusion of a tissue, the higher are both its cross-sensitivity to other tissues' parameters and the cross-sensitivities of other tissues to its parameters; and (iii) with a few exceptions, there is not a marked influence of the lipophilicity of the homologues on either the pattern or the values of the sensitivity functions. The estimates of the sensitivity and the subsequent tissue and parameter rankings may be extended to other drugs, sharing the same common structure of the whole body PBPK model, and having similar model parameters. Results show also that the computationally simple Matrix Perturbation Analysis should be used only when an initial idea about the sensitivity of a system is required. If comprehensive information regarding the sensitivity is needed, the numerically expensive Direct Sensitivity Analysis should be used.

Sensitivity Analysis of Mechanical Parameters of Different Rock Layers to the Stability of Coal Roadway in Soft Rock Strata

PubMed Central

Zhao, Zeng-hui; Wang, Wei-ming; Gao, Xin; Yan, Ji-xing

2013-01-01

According to the geological characteristics of Xinjiang Ili mine in western area of China, a physical model of interstratified strata composed of soft rock and hard coal seam was established. Selecting the tunnel position, deformation modulus, and strength parameters of each layer as influencing factors, the sensitivity coefficient of roadway deformation to each parameter was firstly analyzed based on a Mohr-Columb strain softening model and nonlinear elastic-plastic finite element analysis. Then the effect laws of influencing factors which showed high sensitivity were further discussed. Finally, a regression model for the relationship between roadway displacements and multifactors was obtained by equivalent linear regression under multiple factors. The results show that the roadway deformation is highly sensitive to the depth of coal seam under the floor which should be considered in the layout of coal roadway; deformation modulus and strength of coal seam and floor have a great influence on the global stability of tunnel; on the contrary, roadway deformation is not sensitive to the mechanical parameters of soft roof; roadway deformation under random combinations of multi-factors can be deduced by the regression model. These conclusions provide theoretical significance to the arrangement and stability maintenance of coal roadway. PMID:24459447

High frequency QRS ECG predicts ischemic defects during myocardial perfusion imaging

NASA Technical Reports Server (NTRS)

Rahman, Atiar

2006-01-01

Background: Changes in high frequency QRS components of the electrocardiogram (HF QRS ECG) (150-250 Hz) are more sensitive than changes in conventional ST segments for detecting myocardial ischemia. We investigated the accuracy of 12-lead HF QRS ECG in detecting ischemia during adenosine tetrofosmin myocardial perfusion imaging (MPI). Methods and Results: 12-lead HF QRS ECG recordings were obtained from 45 patients before and during adenosine technetium-99 tetrofosmin MPI tests. Before the adenosine infusions, recordings of HF QRS were analyzed according to a morphological score that incorporated the number, type and location of reduced amplitude zones (RAZs) present in the 12 leads. During the adenosine infusions, recordings of HF QRS were analyzed according to the maximum percentage changes (in both the positive and negative directions) that occurred in root mean square (RMS) voltage amplitudes within the 12 leads. The best set of prospective HF QRS criteria had a sensitivity of 94% and a specificity of 83% for correctly identifying the MPI result. The sensitivity of simultaneous ST segment changes (18%) was significantly lower than that of any individual HF QRS criterion (P<0.001). Conclusions: Analysis of 12-lead HF QRS ECG is highly sensitive and specific for detecting ischemic perfusion defects during adenosine MPI stress tests and significantly more sensitive than analysis of conventional ST segments.

Validation of insulin sensitivity and secretion indices derived from the liquid meal tolerance test.

PubMed

Maki, Kevin C; Kelley, Kathleen M; Lawless, Andrea L; Hubacher, Rachel L; Schild, Arianne L; Dicklin, Mary R; Rains, Tia M

2011-06-01

A liquid meal tolerance test (LMTT) has been proposed as a useful alternative to more labor-intensive methods of assessing insulin sensitivity and secretion. This substudy, conducted at the conclusion of a randomized, double-blind crossover trial, compared insulin sensitivity indices from a LMTT (Matsuda insulin sensitivity index [MISI] and LMTT disposition index [LMTT-DI]) with indices derived from minimal model analysis of results from the insulin-modified intravenous glucose tolerance test (IVGTT) (insulin sensitivity index [S(I)] and disposition index [DI]). Participants included men (n = 16) and women (n = 8) without diabetes but with increased abdominal adiposity (waist circumference ≥102 cm and ≥89 cm, respectively) and mean age of 48.9 years. The correlation between S(I) and the MISI was 0.776 (P < 0.0001). The respective associations between S(I) and MISI with waist circumference (r = -0.445 and -0.554, both P < 0.05) and body mass index were similar (r = -0.500 and -0.539, P < 0.05). The correlation between DI and LMTT-DI was 0.604 (P = 0.002). These results indicate that indices of insulin sensitivity and secretion derived from the LMTT correlate well with those from the insulin-modified IVGTT with minimal model analysis, suggesting that they may be useful for application in clinical and population studies of glucose homeostasis.

The Validity of Conscientiousness Is Overestimated in the Prediction of Job Performance

PubMed Central

2015-01-01

Introduction Sensitivity analyses refer to investigations of the degree to which the results of a meta-analysis remain stable when conditions of the data or the analysis change. To the extent that results remain stable, one can refer to them as robust. Sensitivity analyses are rarely conducted in the organizational science literature. Despite conscientiousness being a valued predictor in employment selection, sensitivity analyses have not been conducted with respect to meta-analytic estimates of the correlation (i.e., validity) between conscientiousness and job performance. Methods To address this deficiency, we reanalyzed the largest collection of conscientiousness validity data in the personnel selection literature and conducted a variety of sensitivity analyses. Results Publication bias analyses demonstrated that the validity of conscientiousness is moderately overestimated (by around 30%; a correlation difference of about .06). The misestimation of the validity appears to be due primarily to suppression of small effects sizes in the journal literature. These inflated validity estimates result in an overestimate of the dollar utility of personnel selection by millions of dollars and should be of considerable concern for organizations. Conclusion The fields of management and applied psychology seldom conduct sensitivity analyses. Through the use of sensitivity analyses, this paper documents that the existing literature overestimates the validity of conscientiousness in the prediction of job performance. Our data show that effect sizes from journal articles are largely responsible for this overestimation. PMID:26517553

Cost-Utility Analysis: Sartorius Flap versus Negative Pressure Therapy for Infected Vascular Groin Graft Managment

PubMed Central

Macarios, David; Griffin, Leah; Kosowski, Tomasz; Pyfer, Bryan J.; Offodile, Anaeze C.; Driscoll, Daniel; Maddali, Sirish; Attwood, John

2015-01-01

Background: Sartorius flap coverage and adjunctive negative pressure wound therapy (NPWT) have been described in managing infected vascular groin grafts with varying cost and clinical success. We performed a cost–utility analysis comparing sartorius flap with NPWT in managing an infected vascular groin graft. Methods: A literature review compiling outcomes for sartorius flap and NPWT interventions was conducted from peer-reviewed journals in MEDLINE (PubMed) and EMBASE. Utility scores were derived from expert opinion and used to estimate quality-adjusted life years (QALYs). Medicare current procedure terminology and diagnosis-related groups codes were used to assess the costs for successful graft salvage with the associated complications. Incremental cost-effectiveness was assessed at $50,000/QALY, and both univariate and probabilistic sensitivity analyses were conducted to assess robustness of the conclusions. Results: Thirty-two studies were used pooling 384 patients (234 sartorius flaps and 150 NPWT). NPWT had better clinical outcomes (86.7% success rate, 0.9% minor complication rate, and 13.3% major complication rate) than sartorius flap (81.6% success rate, 8.0% minor complication rate, and 18.4% major complication rate). NPWT was less costly ($12,366 versus $23,516) and slightly more effective (12.06 QALY versus 12.05 QALY) compared with sartorius flap. Sensitivity analyses confirmed the robustness of the base case findings; NPWT was either cost-effective at $50,000/QALY or dominated sartorius flap in 81.6% of all probabilistic sensitivity analyses. Conclusion: In our cost–utility analysis, use of adjunctive NPWT, along with debridement and antibiotic treatment, for managing infected vascular groin graft wounds was found to be a more cost-effective option when compared with sartorius flaps. PMID:26893991

Meta-analysis of diagnostic accuracy studies in mental health

PubMed Central

Takwoingi, Yemisi; Riley, Richard D; Deeks, Jonathan J

2015-01-01

Objectives To explain methods for data synthesis of evidence from diagnostic test accuracy (DTA) studies, and to illustrate different types of analyses that may be performed in a DTA systematic review. Methods We described properties of meta-analytic methods for quantitative synthesis of evidence. We used a DTA review comparing the accuracy of three screening questionnaires for bipolar disorder to illustrate application of the methods for each type of analysis. Results The discriminatory ability of a test is commonly expressed in terms of sensitivity (proportion of those with the condition who test positive) and specificity (proportion of those without the condition who test negative). There is a trade-off between sensitivity and specificity, as an increasing threshold for defining test positivity will decrease sensitivity and increase specificity. Methods recommended for meta-analysis of DTA studies --such as the bivariate or hierarchical summary receiver operating characteristic (HSROC) model --jointly summarise sensitivity and specificity while taking into account this threshold effect, as well as allowing for between study differences in test performance beyond what would be expected by chance. The bivariate model focuses on estimation of a summary sensitivity and specificity at a common threshold while the HSROC model focuses on the estimation of a summary curve from studies that have used different thresholds. Conclusions Meta-analyses of diagnostic accuracy studies can provide answers to important clinical questions. We hope this article will provide clinicians with sufficient understanding of the terminology and methods to aid interpretation of systematic reviews and facilitate better patient care. PMID:26446042

Nonindependence and sensitivity analyses in ecological and evolutionary meta-analyses.

PubMed

Noble, Daniel W A; Lagisz, Malgorzata; O'dea, Rose E; Nakagawa, Shinichi

2017-05-01

Meta-analysis is an important tool for synthesizing research on a variety of topics in ecology and evolution, including molecular ecology, but can be susceptible to nonindependence. Nonindependence can affect two major interrelated components of a meta-analysis: (i) the calculation of effect size statistics and (ii) the estimation of overall meta-analytic estimates and their uncertainty. While some solutions to nonindependence exist at the statistical analysis stages, there is little advice on what to do when complex analyses are not possible, or when studies with nonindependent experimental designs exist in the data. Here we argue that exploring the effects of procedural decisions in a meta-analysis (e.g. inclusion of different quality data, choice of effect size) and statistical assumptions (e.g. assuming no phylogenetic covariance) using sensitivity analyses are extremely important in assessing the impact of nonindependence. Sensitivity analyses can provide greater confidence in results and highlight important limitations of empirical work (e.g. impact of study design on overall effects). Despite their importance, sensitivity analyses are seldom applied to problems of nonindependence. To encourage better practice for dealing with nonindependence in meta-analytic studies, we present accessible examples demonstrating the impact that ignoring nonindependence can have on meta-analytic estimates. We also provide pragmatic solutions for dealing with nonindependent study designs, and for analysing dependent effect sizes. Additionally, we offer reporting guidelines that will facilitate disclosure of the sources of nonindependence in meta-analyses, leading to greater transparency and more robust conclusions. © 2017 John Wiley & Sons Ltd.

Inheritance of Carboxin Resistance in a European Field Isolate of Ustilago nuda.

PubMed

Newcombe, G; Thomas, P L

2000-02-01

ABSTRACT Two carboxin-resistant field isolates of Ustilago nuda from Europe were crossed with a carboxin-sensitive field isolate from North America. Meiotic tetrads isolated from germinating F(1) teliospores of one of the hybrids were tested for carboxin resistance and mating type. Carboxin resistance was shown to be controlled by a single gene (CBX1R), because a 1:1 segregation of carboxin resistance was observed in all 27 tetrads. Tetrad analysis indicated that the loci for carboxin resistance (Cbx1) and mating type (MAT1) segregate independently but may be located on the same chromosome. Tetrad analysis was not possible with the F(1) hybrid of he other field isolate, and its resistance cannot yet be attributed to CBX1R. Carboxin resistance was qualitatively dominant to sensitivity in vitro, as demonstrated by triad analysis of germinating F(1) teliospores. Quantitative in planta infection percents supported the conclusion that CBX1R is dominant, although incompletely, in the F(1) hybrid of one of the field isolates. Also, fewer than expected carboxin-sensitive F(2) individuals were observed in planta. However, inoculations of host plants with U. nuda have resulted in similar, unexpected variation in the past.

Fertility treatment in women with polycystic ovary syndrome: a decision analysis of different oral ovulation induction agents

PubMed Central

Jungheim, Emily S.; Odibo, Anthony O.

2010-01-01

Study objective To compare different oral ovulation induction agents in treating infertile women with polycystic ovary syndrome Design Decision-analytic model comparing three treatment strategies using probability estimates derived from literature review and sensitivity analyses performed on the baseline assumptions Setting Outpatient reproductive medicine and gynecology practices Patients Infertile women with polycystic ovary syndrome Interventions Metformin, clomiphene citrate, or metformin with clomiphene citrate Main Outcome Measures Live birth Results Within the baseline assumptions, combination therapy with metformin and clomiphene citrate was the preferred therapy for achieving live birth in women with polycystic ovary syndrome. Sensitivity analysis revealed the model to be robust over a wide range of probabilities. Conclusions Combination therapy with metformin and clomiphene citrate should be considered as first-line treatment for infertile women with polycystic ovary syndrome PMID:20451181

From web search to healthcare utilization: privacy-sensitive studies from mobile data

PubMed Central

Horvitz, Eric

2013-01-01

Objective We explore relationships between health information seeking activities and engagement with healthcare professionals via a privacy-sensitive analysis of geo-tagged data from mobile devices. Materials and methods We analyze logs of mobile interaction data stripped of individually identifiable information and location data. The data analyzed consist of time-stamped search queries and distances to medical care centers. We examine search activity that precedes the observation of salient evidence of healthcare utilization (EHU) (ie, data suggesting that the searcher is using healthcare resources), in our case taken as queries occurring at or near medical facilities. Results We show that the time between symptom searches and observation of salient evidence of seeking healthcare utilization depends on the acuity of symptoms. We construct statistical models that make predictions of forthcoming EHU based on observations about the current search session, prior medical search activities, and prior EHU. The predictive accuracy of the models varies (65%–90%) depending on the features used and the timeframe of the analysis, which we explore via a sensitivity analysis. Discussion We provide a privacy-sensitive analysis that can be used to generate insights about the pursuit of health information and healthcare. The findings demonstrate how large-scale studies of mobile devices can provide insights on how concerns about symptomatology lead to the pursuit of professional care. Conclusion We present new methods for the analysis of mobile logs and describe a study that provides evidence about how people transition from mobile searches on symptoms and diseases to the pursuit of healthcare in the world. PMID:22661560

Developmental and hormonal regulation of thermosensitive neuron potential activity in rat brain.

PubMed

Belugin, S; Akino, K; Takamura, N; Mine, M; Romanovsky, D; Fedoseev, V; Kubarko, A; Kosaka, M; Yamashita, S

1999-08-01

To understand the involvement of thyroid hormone on the postnatal development of hypothalamic thermosensitive neurons, we focused on the analysis of thermosensitive neuronal activity in the preoptic and anterior hypothalamic (PO/AH) regions of developing rats with and without hypothyroidism. In euthyroid rats, the distribution of thermosensitive neurons in PO/AH showed that in 3-week-old rats (46 neurons tested), 19.5% were warm-sensitive and 80.5% were nonsensitive. In 5- to 12-week-old euthyroid rats (122 neurons), 33.6% were warm-sensitive and 66.4% were nonsensitive. In 5- to 12-week-old hypothyroid rats (108 neurons), however, 18.5% were warm-sensitive and 81.5% were nonsensitive. Temperature thresholds of warm-sensitive neurons were lower in 12-week-old euthyroid rats (36.4+/-0.2 degrees C, n = 15, p<0.01,) than in 3-week-old and in 5-week-old euthyroid rats (38.5+/-0.5 degrees C, n = 9 and 38.0+/-0.3 degrees C, n = 15, respectively). The temperature thresholds of warm-sensitive neurons in 12-week-old hypothyroid rats (39.5+/-0.3 degrees C, n = 8) were similar to that of warm-sensitive neurons of 3-week-old raats (euthyroid and hypothyroid). In contrast, there was no difference in the thresholds of warm-sensitive neurons between hypothyroid and euthyroid rats at the age of 3-5 weeks. In conclusion, monitoring the thermosensitive neuronal tissue activity demonstrated the evidence that thyroid hormone regulates the maturation of warm-sensitive hypothalamic neurons in developing rat brain by electrophysiological analysis.

Rapid Intraoperative Molecular Characterization of Glioma

PubMed Central

Shankar, Ganesh M.; Francis, Joshua M.; Rinne, Mikael L.; Ramkissoon, Shakti H.; Huang, Franklin W.; Venteicher, Andrew S.; Akama-Garren, Elliot H.; Kang, Yun Jee; Lelic, Nina; Kim, James C.; Brown, Loreal E.; Charbonneau, Sarah K.; Golby, Alexandra J.; Pedamallu, Chandra Sekhar; Hoang, Mai P.; Sullivan, Ryan J.; Cherniack, Andrew D.; Garraway, Levi A.; Stemmer-Rachamimov, Anat; Reardon, David A.; Wen, Patrick Y.; Brastianos, Priscilla K.; Curry, William T.; Barker, Fred G.; Hahn, William C.; Nahed, Brian V.; Ligon, Keith L.; Louis, David N.; Cahill, Daniel P.; Meyerson, Matthew

2016-01-01

IMPORTANCE Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low-cellularity infiltrative gliomas. Therefore, we developed a rapid and sensitive genotyping assay to detect somatic single-nucleotide variants in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase 1 (IDH1). OBSERVATIONS This assay was applied to tissue samples from 190 patients with diffuse gliomas, including archived fixed and frozen specimens and tissue obtained intraoperatively. Results demonstrated 96% sensitivity (95% CI, 90%–99%) and 100% specificity (95% CI, 95%–100%) for World Health Organization grades II and III gliomas. In a series of live cases, glioma-defining mutations could be identified within 60 minutes, which could facilitate the diagnosis in an intraoperative timeframe. CONCLUSIONS AND RELEVANCE The genotyping method described herein can establish the diagnosis of low-cellularity tumors like glioma and could be adapted to the point-of-care diagnosis of other lesions that are similarly defined by highly recurrent somatic mutations. PMID:26181761

A methodology to estimate uncertainty for emission projections through sensitivity analysis.

PubMed

Lumbreras, Julio; de Andrés, Juan Manuel; Pérez, Javier; Borge, Rafael; de la Paz, David; Rodríguez, María Encarnación

2015-04-01

Air pollution abatement policies must be based on quantitative information on current and future emissions of pollutants. As emission projections uncertainties are inevitable and traditional statistical treatments of uncertainty are highly time/resources consuming, a simplified methodology for nonstatistical uncertainty estimation based on sensitivity analysis is presented in this work. The methodology was applied to the "with measures" scenario for Spain, concretely over the 12 highest emitting sectors regarding greenhouse gas and air pollutants emissions. Examples of methodology application for two important sectors (power plants, and agriculture and livestock) are shown and explained in depth. Uncertainty bands were obtained up to 2020 by modifying the driving factors of the 12 selected sectors and the methodology was tested against a recomputed emission trend in a low economic-growth perspective and official figures for 2010, showing a very good performance. A solid understanding and quantification of uncertainties related to atmospheric emission inventories and projections provide useful information for policy negotiations. However, as many of those uncertainties are irreducible, there is an interest on how they could be managed in order to derive robust policy conclusions. Taking this into account, a method developed to use sensitivity analysis as a source of information to derive nonstatistical uncertainty bands for emission projections is presented and applied to Spain. This method simplifies uncertainty assessment and allows other countries to take advantage of their sensitivity analyses.

Data mining methods in the prediction of Dementia: A real-data comparison of the accuracy, sensitivity and specificity of linear discriminant analysis, logistic regression, neural networks, support vector machines, classification trees and random forests

PubMed Central

2011-01-01

Background Dementia and cognitive impairment associated with aging are a major medical and social concern. Neuropsychological testing is a key element in the diagnostic procedures of Mild Cognitive Impairment (MCI), but has presently a limited value in the prediction of progression to dementia. We advance the hypothesis that newer statistical classification methods derived from data mining and machine learning methods like Neural Networks, Support Vector Machines and Random Forests can improve accuracy, sensitivity and specificity of predictions obtained from neuropsychological testing. Seven non parametric classifiers derived from data mining methods (Multilayer Perceptrons Neural Networks, Radial Basis Function Neural Networks, Support Vector Machines, CART, CHAID and QUEST Classification Trees and Random Forests) were compared to three traditional classifiers (Linear Discriminant Analysis, Quadratic Discriminant Analysis and Logistic Regression) in terms of overall classification accuracy, specificity, sensitivity, Area under the ROC curve and Press'Q. Model predictors were 10 neuropsychological tests currently used in the diagnosis of dementia. Statistical distributions of classification parameters obtained from a 5-fold cross-validation were compared using the Friedman's nonparametric test. Results Press' Q test showed that all classifiers performed better than chance alone (p < 0.05). Support Vector Machines showed the larger overall classification accuracy (Median (Me) = 0.76) an area under the ROC (Me = 0.90). However this method showed high specificity (Me = 1.0) but low sensitivity (Me = 0.3). Random Forest ranked second in overall accuracy (Me = 0.73) with high area under the ROC (Me = 0.73) specificity (Me = 0.73) and sensitivity (Me = 0.64). Linear Discriminant Analysis also showed acceptable overall accuracy (Me = 0.66), with acceptable area under the ROC (Me = 0.72) specificity (Me = 0.66) and sensitivity (Me = 0.64). The remaining classifiers showed overall classification accuracy above a median value of 0.63, but for most sensitivity was around or even lower than a median value of 0.5. Conclusions When taking into account sensitivity, specificity and overall classification accuracy Random Forests and Linear Discriminant analysis rank first among all the classifiers tested in prediction of dementia using several neuropsychological tests. These methods may be used to improve accuracy, sensitivity and specificity of Dementia predictions from neuropsychological testing. PMID:21849043

Ancient numerical daemons of conceptual hydrological modeling: 2. Impact of time stepping schemes on model analysis and prediction

NASA Astrophysics Data System (ADS)

Kavetski, Dmitri; Clark, Martyn P.

2010-10-01

Despite the widespread use of conceptual hydrological models in environmental research and operations, they remain frequently implemented using numerically unreliable methods. This paper considers the impact of the time stepping scheme on model analysis (sensitivity analysis, parameter optimization, and Markov chain Monte Carlo-based uncertainty estimation) and prediction. It builds on the companion paper (Clark and Kavetski, 2010), which focused on numerical accuracy, fidelity, and computational efficiency. Empirical and theoretical analysis of eight distinct time stepping schemes for six different hydrological models in 13 diverse basins demonstrates several critical conclusions. (1) Unreliable time stepping schemes, in particular, fixed-step explicit methods, suffer from troublesome numerical artifacts that severely deform the objective function of the model. These deformations are not rare isolated instances but can arise in any model structure, in any catchment, and under common hydroclimatic conditions. (2) Sensitivity analysis can be severely contaminated by numerical errors, often to the extent that it becomes dominated by the sensitivity of truncation errors rather than the model equations. (3) Robust time stepping schemes generally produce "better behaved" objective functions, free of spurious local optima, and with sufficient numerical continuity to permit parameter optimization using efficient quasi Newton methods. When implemented within a multistart framework, modern Newton-type optimizers are robust even when started far from the optima and provide valuable diagnostic insights not directly available from evolutionary global optimizers. (4) Unreliable time stepping schemes lead to inconsistent and biased inferences of the model parameters and internal states. (5) Even when interactions between hydrological parameters and numerical errors provide "the right result for the wrong reason" and the calibrated model performance appears adequate, unreliable time stepping schemes make the model unnecessarily fragile in predictive mode, undermining validation assessments and operational use. Erroneous or misleading conclusions of model analysis and prediction arising from numerical artifacts in hydrological models are intolerable, especially given that robust numerics are accepted as mainstream in other areas of science and engineering. We hope that the vivid empirical findings will encourage the conceptual hydrological community to close its Pandora's box of numerical problems, paving the way for more meaningful model application and interpretation.

Sensitivity analysis by approximation formulas - Illustrative examples. [reliability analysis of six-component architectures

NASA Technical Reports Server (NTRS)

White, A. L.

1983-01-01

This paper examines the reliability of three architectures for six components. For each architecture, the probabilities of the failure states are given by algebraic formulas involving the component fault rate, the system recovery rate, and the operating time. The dominant failure modes are identified, and the change in reliability is considered with respect to changes in fault rate, recovery rate, and operating time. The major conclusions concern the influence of system architecture on failure modes and parameter requirements. Without this knowledge, a system designer may pick an inappropriate structure.

Value of high-sensitivity C-reactive protein assays in predicting atrial fibrillation recurrence: a systematic review and meta-analysis

PubMed Central

Yo, Chia-Hung; Lee, Si-Huei; Chang, Shy-Shin; Lee, Matthew Chien-Hung; Lee, Chien-Chang

2014-01-01

Objectives We performed a systematic review and meta-analysis of studies on high-sensitivity C-reactive protein (hs-CRP) assays to see whether these tests are predictive of atrial fibrillation (AF) recurrence after cardioversion. Design Systematic review and meta-analysis. Data sources PubMed, EMBASE and Cochrane databases as well as a hand search of the reference lists in the retrieved articles from inception to December 2013. Study eligibility criteria This review selected observational studies in which the measurements of serum CRP were used to predict AF recurrence. An hs-CRP assay was defined as any CRP test capable of measuring serum CRP to below 0.6 mg/dL. Primary and secondary outcome measures We summarised test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models. Meta-regression analysis was performed to explore the source of heterogeneity. Results We included nine qualifying studies comprising a total of 347 patients with AF recurrence and 335 controls. A CRP level higher than the optimal cut-off point was an independent predictor of AF recurrence after cardioversion (summary adjusted OR: 3.33; 95% CI 2.10 to 5.28). The estimated pooled sensitivity and specificity for hs-CRP was 71.0% (95% CI 63% to 78%) and 72.0% (61% to 81%), respectively. Most studies used a CRP cut-off point of 1.9 mg/L to predict long-term AF recurrence (77% sensitivity, 65% specificity), and 3 mg/L to predict short-term AF recurrence (73% sensitivity, 71% specificity). Conclusions hs-CRP assays are moderately accurate in predicting AF recurrence after successful cardioversion. PMID:24556243

Sensitivity, Specificity, and Posttest Probability of Parotid Fine-Needle Aspiration: A Systematic Review and Meta-analysis

PubMed Central

Liu, C. Carrie; Jethwa, Ashok R.; Khariwala, Samir S.; Johnson, Jonas; Shin, Jennifer J.

2016-01-01

Objectives (1) To analyze the sensitivity and specificity of fine-needle aspiration (FNA) in distinguishing benign from malignant parotid disease. (2) To determine the anticipated posttest probability of malignancy and probability of non-diagnostic and indeterminate cytology with parotid FNA. Data Sources Independently corroborated computerized searches of PubMed, Embase, and Cochrane Central Register were performed. These were supplemented with manual searches and input from content experts. Review Methods Inclusion/exclusion criteria specified diagnosis of parotid mass, intervention with both FNA and surgical excision, and enumeration of both cytologic and surgical histopathologic results. The primary outcomes were sensitivity, specificity, and posttest probability of malignancy. Heterogeneity was evaluated with the I2 statistic. Meta-analysis was performed via a 2-level mixed logistic regression model. Bayesian nomograms were plotted via pooled likelihood ratios. Results The systematic review yielded 70 criterion-meeting studies, 63 of which contained data that allowed for computation of numerical outcomes (n = 5647 patients; level 2a) and consideration of meta-analysis. Subgroup analyses were performed in studies that were prospective, involved consecutive patients, described the FNA technique utilized, and used ultrasound guidance. The I2 point estimate was >70% for all analyses, except within prospectively obtained and ultrasound-guided results. Among the prospective subgroup, the pooled analysis demonstrated a sensitivity of 0.882 (95% confidence interval [95% CI], 0.509–0.982) and a specificity of 0.995 (95% CI, 0.960–0.999). The probabilities of nondiagnostic and indeterminate cytology were 0.053 (95% CI, 0.030–0.075) and 0.147 (95% CI, 0.106–0.188), respectively. Conclusion FNA has moderate sensitivity and high specificity in differentiating malignant from benign parotid lesions. Considerable heterogeneity is present among studies. PMID:26428476

The Clinical Utility and Diagnostic Performance of MRI for Identification of Early and Advanced Knee Osteoarthritis: A Systematic Review

PubMed Central

Quatman, Carmen E.; Hettrich, Carolyn M.; Schmitt, Laura C.; Spindler, Kurt P.

2013-01-01

Background Current diagnostic strategies for detection of structural articular cartilage abnormalities, the earliest structural signs of osteoarthritis, often do not capture the condition until it is too far advanced for the most potential benefit of non-invasive interventions. Purpose Systematically review the literature relative to the following questions: (1) Is MRI a valid, sensitive, specific, accurate and reliable instrument to identify knee articular cartilage abnormalities compared to arthroscopy? (2) Is MRI a sensitive tool that can be utilized to identify early cartilage degeneration? Study Design Systematic Review Methods A systematic search was performed in November 2010 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from 1985), and SCOPUS (from 1996) databases. Results Fourteen level I and 13 level II studies were identified that met inclusion criteria and provided information related to diagnostic performance of MRI compared to arthroscopic evaluation. The diagnostic performance of MRI demonstrated a large range of sensitivities, specificities, and accuracies. The sensitivity for identifying articular cartilage abnormalities in the knee joint was reported between 26–96%. Specificity and accuracy was reported between 50–100% and 49–94%, respectively. The sensitivity, specificity, and accuracy for identifying early osteoarthritis were reported between 0–86%, 48–95%, and 5–94%, respectively. As a result of inconsistencies between imaging techniques and methodological shortcomings of many of the studies, a meta-analysis was not performed and it was difficult to fully synthesize the information to state firm conclusions about the diagnostic performance of MRI. Conclusions There is evidence in some MRI protocols that MRI is a relatively valid, sensitive, specific, accurate, and reliable clinical tool for identifying articular cartilage degeneration. Due to heterogeneity of MRI sequences it is not possible to make definitive conclusions regarding its global clinical utility for guiding diagnosis and treatment strategies. Clinical Relevance Traumatic sports injuries to the knee may be significant precursor events to early onset of posttraumatic osteoarthritis. MRI may aid in early identification of structural injuries to articular cartilage as evidenced by articular cartilage degeneration grading. PMID:21730207

Skin sensitizers differentially regulate signaling pathways in MUTZ-3 cells in relation to their individual potency

PubMed Central

2014-01-01

Background Due to the recent European legislations posing a ban of animal tests for safety assessment within the cosmetic industry, development of in vitro alternatives for assessment of skin sensitization is highly prioritized. To date, proposed in vitro assays are mainly based on single biomarkers, which so far have not been able to classify and stratify chemicals into subgroups, related to risk or potency. Methods Recently, we presented the Genomic Allergen Rapid Detection (GARD) assay for assessment of chemical sensitizers. In this paper, we show how the genome wide readout of GARD can be expanded and used to identify differentially regulated pathways relating to individual chemical sensitizers. In this study, we investigated the mechanisms of action of a range of skin sensitizers through pathway identification, pathway classification and transcription factor analysis and related this to the reactive mechanisms and potency of the sensitizing agents. Results By transcriptional profiling of chemically stimulated MUTZ-3 cells, 33 canonical pathways intimately involved in sensitization to chemical substances were identified. The results showed that metabolic processes, cell cycling and oxidative stress responses are the key events activated during skin sensitization, and that these functions are engaged differently depending on the reactivity mechanisms of the sensitizing agent. Furthermore, the results indicate that the chemical reactivity groups seem to gradually engage more pathways and more molecules in each pathway with increasing sensitizing potency of the chemical used for stimulation. Also, a switch in gene regulation from up to down regulation, with increasing potency, was seen both in genes involved in metabolic functions and cell cycling. These observed pathway patterns were clearly reflected in the regulatory elements identified to drive these processes, where 33 regulatory elements have been proposed for further analysis. Conclusions This study demonstrates that functional analysis of biomarkers identified from our genomics study of human MUTZ-3 cells can be used to assess sensitizing potency of chemicals in vitro, by the identification of key cellular events, such as metabolic and cell cycling pathways. PMID:24517095

Staying theoretically sensitive when conducting grounded theory research.

PubMed

Reay, Gudrun; Bouchal, Shelley Raffin; A Rankin, James

2016-09-01

Background Grounded theory (GT) is founded on the premise that underlying social patterns can be discovered and conceptualised into theories. The method and need for theoretical sensitivity are best understood in the historical context in which GT was developed. Theoretical sensitivity entails entering the field with no preconceptions, so as to remain open to the data and the emerging theory. Investigators also read literature from other fields to understand various ways to construct theories. Aim To explore the concept of theoretical sensitivity from a classical GT perspective, and discuss the ontological and epistemological foundations of GT. Discussion Difficulties in remaining theoretically sensitive throughout research are discussed and illustrated with examples. Emergence - the idea that theory and substance will emerge from the process of comparing data - and staying open to the data are emphasised. Conclusion Understanding theoretical sensitivity as an underlying guiding principle of GT helps the researcher make sense of important concepts, such as delaying the literature review, emergence and the constant comparative method (simultaneous collection, coding and analysis of data). Implications for practice Theoretical sensitivity and adherence to the GT research method allow researchers to discover theories that can bridge the gap between theory and practice.

Landscape sensitivity in a dynamic environment

NASA Astrophysics Data System (ADS)

Lin, Jiun-Chuan; Jen, Chia-Horn

2010-05-01

Landscape sensitivity at different scales and topics is presented in this study. Methodological approach composed most of this paper. According to the environmental records in the south eastern Asia, the environment change is highly related with five factors, such as scale of influence area, background of environment characters, magnitude and frequency of events, thresholds of occurring hazards and influence by time factor. This paper tries to demonstrate above five points from historical and present data. It is found that landscape sensitivity is highly related to the degree of vulnerability of the land and the processes which put on the ground including human activities. The scale of sensitivity and evaluation of sensitivities is demonstrated in this paper by the data around east Asia. The methods of classification are mainly from the analysis of environmental data and the records of hazards. From the trend of rainfall records, rainfall intensity and change of temperature, the magnitude and frequency of earthquake, dust storm, days of draught, number of hazards, there are many coincidence on these factors with landscape sensitivities. In conclusion, the landscape sensitivities could be classified as four groups: physical stable, physical unstable, unstable, extremely unstable. This paper explain the difference.

BAYESIAN ANALYSIS TO EVALUATE TESTS FOR THE DETECTION OF MYCOBACTERIUM BOVIS INFECTION IN FREE-RANGING WILD BISON (BISON BISON ATHABASCAE) IN THE ABSENCE OF A GOLD STANDARD.

PubMed

Chapinal, Núria; Schumaker, Brant A; Joly, Damien O; Elkin, Brett T; Stephen, Craig

2015-07-01

We estimated the sensitivity and specificity of the caudal-fold skin test (CFT), the fluorescent polarization assay (FPA), and the rapid lateral-flow test (RT) for the detection of Mycobacterium bovis in free-ranging wild wood bison (Bison bison athabascae), in the absence of a gold standard, by using Bayesian analysis, and then used those estimates to forecast the performance of a pairwise combination of tests in parallel. In 1998-99, 212 wood bison from Wood Buffalo National Park (Canada) were tested for M. bovis infection using CFT and two serologic tests (FPA and RT). The sensitivity and specificity of each test were estimated using a three-test, one-population, Bayesian model allowing for conditional dependence between FPA and RT. The sensitivity and specificity of the combination of CFT and each serologic test in parallel were calculated assuming conditional independence. The test performance estimates were influenced by the prior values chosen. However, the rank of tests and combinations of tests based on those estimates remained constant. The CFT was the most sensitive test and the FPA was the least sensitive, whereas RT was the most specific test and CFT was the least specific. In conclusion, given the fact that gold standards for the detection of M. bovis are imperfect and difficult to obtain in the field, Bayesian analysis holds promise as a tool to rank tests and combinations of tests based on their performance. Combining a skin test with an animal-side serologic test, such as RT, increases sensitivity in the detection of M. bovis and is a good approach to enhance disease eradication or control in wild bison.

FURTHER ANALYSIS OF SUBTYPES OF AUTOMATICALLY REINFORCED SIB: A REPLICATION AND QUANTITATIVE ANALYSIS OF PUBLISHED DATASETS

PubMed Central

Hagopian, Louis P.; Rooker, Griffin W.; Zarcone, Jennifer R.; Bonner, Andrew C.; Arevalo, Alexander R.

2017-01-01

Hagopian, Rooker, and Zarcone (2015) evaluated a model for subtyping automatically reinforced self-injurious behavior (SIB) based on its sensitivity to changes in functional analysis conditions and the presence of self-restraint. The current study tested the generality of the model by applying it to all datasets of automatically reinforced SIB published from 1982 to 2015. We identified 49 datasets that included sufficient data to permit subtyping. Similar to the original study, Subtype-1 SIB was generally amenable to treatment using reinforcement alone, whereas Subtype-2 SIB was not. Conclusions could not be drawn about Subtype-3 SIB due to the small number of datasets. Nevertheless, the findings support the generality of the model and suggest that sensitivity of SIB to disruption by alternative reinforcement is an important dimension of automatically reinforced SIB. Findings also suggest that automatically reinforced SIB should no longer be considered a single category and that additional research is needed to better understand and treat Subtype-2 SIB. PMID:28032344

Study of effects of fuel properties in turbine-powered business aircraft

NASA Technical Reports Server (NTRS)

Powell, F. D.; Biegen, R. J.; Weitz, P. G., Jr.; Duke, A. M.

1984-01-01

Increased interest in research and technology concerning aviation turbine fuels and their properties was prompted by recent changes in the supply and demand situation of these fuels. The most obvious change is the rapid increase in fuel price. For commercial airplanes, fuel costs now approach 50 percent of the direct operating costs. In addition, there were occasional local supply disruptions and gradual shifts in delivered values of certain fuel properties. Dwindling petroleum reserves and the politically sensitive nature of the major world suppliers make the continuation of these trends likely. A summary of the principal findings, and conclusions are presented. Much of the material, especially the tables and graphs, is considered in greater detail later. The economic analysis and examination of operational considerations are described. Because some of the assumptions on which the economic analysis is founded are not easily verified, the sensitivity of the analysis to alternates for these assumptions is examined. The data base on which the analyses are founded is defined in a set of appendices.

The Relationship Between Serum Endocan Levels With the Presence of Slow Coronary Flow: A Cross-Sectional Study.

PubMed

Kundi, Harun; Gok, Murat; Kiziltunc, Emrullah; Topcuoglu, Canan; Cetin, Mustafa; Cicekcioglu, Hulya; Ugurlu, Burcu; Ulusoy, Feridun Vasfi

2017-07-01

The aim of this study was to investigate the relationship between endocan levels with the presence of slow coronary flow (SCF). In this cross-sectional study, a total of 88 patients, who admitted to our hospital, were included in this study. Of these, 53 patients with SCF and 35 patients with normal coronary flow were included in the final analysis. Coronary flow rates of all patients were determined by the Timi Frame Count (TFC) method. In correlation analysis, endocan levels revealed a significantly positive correlation with high sensitive C-reactive protein and corrected TFC. In multivariate logistic regression analysis, the endocan levels were found as independently associated with the presence of SCF. Finally, using a cutoff level of 2.3, endocan level predicted the presence of SCF with a sensitivity of 77.2% and specificity of 75.2%. In conclusion, our study showed that higher endocan levels were significantly and independently related to the presence of SCF.

Left Ventricular Hypertrophy: An allometric comparative analysis of different ECG markers

NASA Astrophysics Data System (ADS)

Bonomini, M. P.; Ingallina, F.; Barone, V.; Valentinuzzi, M. E.; Arini, P. D.

2011-12-01

Allometry, in general biology, measures the relative growth of a part in relation to the whole living organism. Left ventricular hypertrophy (LVH) is the heart adaptation to excessive load (systolic or diastolic). The increase in left ventricular mass leads to an increase in the electrocardiographic voltages. Based on clinical data, we compared the allometric behavior of three different ECG markers of LVH. To do this, the allometric fit AECG = δ + β (VM) relating left ventricular mass (estimated from ecocardiographic data) and ECG amplitudes (expressed as the Cornell-Voltage, Sokolow and the ECG overall voltage indexes) were compared. Besides, sensitivity and specifity for each index were analyzed. The more sensitive the ECG criteria, the better the allometric fit. In conclusion: The allometric paradigm should be regarded as the way to design new and more sensitive ECG-based LVH markers.

A general method for handling missing binary outcome data in randomized controlled trials

PubMed Central

Jackson, Dan; White, Ian R; Mason, Dan; Sutton, Stephen

2014-01-01

Aims The analysis of randomized controlled trials with incomplete binary outcome data is challenging. We develop a general method for exploring the impact of missing data in such trials, with a focus on abstinence outcomes. Design We propose a sensitivity analysis where standard analyses, which could include ‘missing = smoking’ and ‘last observation carried forward’, are embedded in a wider class of models. Setting We apply our general method to data from two smoking cessation trials. Participants A total of 489 and 1758 participants from two smoking cessation trials. Measurements The abstinence outcomes were obtained using telephone interviews. Findings The estimated intervention effects from both trials depend on the sensitivity parameters used. The findings differ considerably in magnitude and statistical significance under quite extreme assumptions about the missing data, but are reasonably consistent under more moderate assumptions. Conclusions A new method for undertaking sensitivity analyses when handling missing data in trials with binary outcomes allows a wide range of assumptions about the missing data to be assessed. In two smoking cessation trials the results were insensitive to all but extreme assumptions. PMID:25171441

Highly sensitive molecular diagnosis of prostate cancer using surplus material washed off from biopsy needles

PubMed Central

Bermudo, R; Abia, D; Mozos, A; García-Cruz, E; Alcaraz, A; Ortiz, Á R; Thomson, T M; Fernández, P L

2011-01-01

Introduction: Currently, final diagnosis of prostate cancer (PCa) is based on histopathological analysis of needle biopsies, but this process often bears uncertainties due to small sample size, tumour focality and pathologist's subjective assessment. Methods: Prostate cancer diagnostic signatures were generated by applying linear discriminant analysis to microarray and real-time RT–PCR (qRT–PCR) data from normal and tumoural prostate tissue samples. Additionally, after removal of biopsy tissues, material washed off from transrectal biopsy needles was used for molecular profiling and discriminant analysis. Results: Linear discriminant analysis applied to microarray data for a set of 318 genes differentially expressed between non-tumoural and tumoural prostate samples produced 26 gene signatures, which classified the 84 samples used with 100% accuracy. To identify signatures potentially useful for the diagnosis of prostate biopsies, surplus material washed off from routine biopsy needles from 53 patients was used to generate qRT–PCR data for a subset of 11 genes. This analysis identified a six-gene signature that correctly assigned the biopsies as benign or tumoural in 92.6% of the cases, with 88.8% sensitivity and 96.1% specificity. Conclusion: Surplus material from prostate needle biopsies can be used for minimal-size gene signature analysis for sensitive and accurate discrimination between non-tumoural and tumoural prostates, without interference with current diagnostic procedures. This approach could be a useful adjunct to current procedures in PCa diagnosis. PMID:22009027

Non-ignorable missingness in logistic regression.

PubMed

Wang, Joanna J J; Bartlett, Mark; Ryan, Louise

2017-08-30

Nonresponses and missing data are common in observational studies. Ignoring or inadequately handling missing data may lead to biased parameter estimation, incorrect standard errors and, as a consequence, incorrect statistical inference and conclusions. We present a strategy for modelling non-ignorable missingness where the probability of nonresponse depends on the outcome. Using a simple case of logistic regression, we quantify the bias in regression estimates and show the observed likelihood is non-identifiable under non-ignorable missing data mechanism. We then adopt a selection model factorisation of the joint distribution as the basis for a sensitivity analysis to study changes in estimated parameters and the robustness of study conclusions against different assumptions. A Bayesian framework for model estimation is used as it provides a flexible approach for incorporating different missing data assumptions and conducting sensitivity analysis. Using simulated data, we explore the performance of the Bayesian selection model in correcting for bias in a logistic regression. We then implement our strategy using survey data from the 45 and Up Study to investigate factors associated with worsening health from the baseline to follow-up survey. Our findings have practical implications for the use of the 45 and Up Study data to answer important research questions relating to health and quality-of-life. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Analysis of the causes of discrepancies in troponin I concentrations as measured by ARCHITECT High-Sensitive Troponin I ST and STACIA CLEIA cTnI.

PubMed

Kondo, Takashi; Kobayashi, Daisuke; Mochizuki, Maki; Asanuma, Kouichi; Takahashi, Satoshi

2017-01-01

Background Recently developed reagents for the highly sensitive measurement of cardiac troponin I are useful for early diagnosis of acute coronary syndrome. However, differences in measured values between these new reagents and previously used reagents have not been well studied. In this study, we aimed to compare the values between ARCHITECT High-Sensitive Troponin I ST (newly developed reagents), ARCHITECT Troponin I ST and STACIA CLEIA cardiac troponin I (two previously developed reagent kits). Methods Gel filtration high-performance liquid chromatography was used to analyse the causes of differences in measured values. Results The measured values differed between ARCHITECT High-Sensitive Troponin I ST and STACIA CLEIA cardiac troponin I reagents (r = 0.82). Cross-reactivity tests using plasma with added skeletal-muscle troponin I resulted in higher reactivity (2.17-3.03%) for the STACIA CLEIA cardiac troponin I reagents compared with that for the ARCHITECT High-Sensitive Troponin I ST reagents (less than 0.014%). In addition, analysis of three representative samples using gel filtration high-performance liquid chromatography revealed reagent-specific differences in the reactivity against each cardiac troponin I complex; this could explain the differences in values observed for some of the samples. Conclusion The newly developed ARCHITECT High-Sensitive Troponin I ST reagents were not affected by the presence of skeletal-muscle troponin I in the blood and may be useful for routine examinations.

Culturally sensitive substance use treatment for racial/ethnic minority youth: A meta-analytic review.

PubMed

Steinka-Fry, Katarzyna T; Tanner-Smith, Emily E; Dakof, Gayle A; Henderson, Craig

2017-04-01

This systematic review and meta-analysis synthesized findings from studies examining culturally sensitive substance use treatment for racial/ethnic minority youth. An extensive literature search located eight eligible studies using experimental or quasi-experimental designs. The meta-analysis quantitatively synthesized findings comparing seven culturally sensitive treatment conditions to seven alternative conditions on samples composed of at least 90% racial/ethnic minority youth. The results from the meta-analysis indicated that culturally sensitive treatments were associated with significantly larger reductions in post-treatment substance use levels relative to their comparison conditions (g=0.37, 95% CI [0.12, 0.62], k=7, total number participants=723). The average time between pretest and posttest was 21weeks (SD=11.79). There was a statistically significant amount of heterogeneity across the seven studies (Q=26.5, p=0.00, τ 2 =0.08, I 2 =77.4%). Differential effects were not statistically significant when contrasts were active generic counterparts of treatment conditions (direct "bona fide" comparisons; g=-0.08, 95% CI [-0.51, 0.35]) and 'treatment as usual' conditions (g=0.39, 95% CI [-0.14, 0.91]). Strong conclusions from the review were hindered by the small number of available studies for synthesis, variability in comparison conditions across studies, and lack of diversity in the adolescent clients served in the studies. Nonetheless, this review suggests that culturally sensitive treatments offer promise as an effective way to address substance use among racial/ethnic minority youth. Copyright © 2017 Elsevier Inc. All rights reserved.

Cell death, perfusion and electrical parameters are critical in models of hepatic radiofrequency ablation

PubMed Central

Hall, Sheldon K.; Ooi, Ean H.; Payne, Stephen J.

2015-01-01

Abstract Purpose: A sensitivity analysis has been performed on a mathematical model of radiofrequency ablation (RFA) in the liver. The purpose of this is to identify the most important parameters in the model, defined as those that produce the largest changes in the prediction. This is important in understanding the role of uncertainty and when comparing the model predictions to experimental data. Materials and methods: The Morris method was chosen to perform the sensitivity analysis because it is ideal for models with many parameters or that take a significant length of time to obtain solutions. A comprehensive literature review was performed to obtain ranges over which the model parameters are expected to vary, crucial input information. Results: The most important parameters in predicting the ablation zone size in our model of RFA are those representing the blood perfusion, electrical conductivity and the cell death model. The size of the 50 °C isotherm is sensitive to the electrical properties of tissue while the heat source is active, and to the thermal parameters during cooling. Conclusions: The parameter ranges chosen for the sensitivity analysis are believed to represent all that is currently known about their values in combination. The Morris method is able to compute global parameter sensitivities taking into account the interaction of all parameters, something that has not been done before. Research is needed to better understand the uncertainties in the cell death, electrical conductivity and perfusion models, but the other parameters are only of second order, providing a significant simplification. PMID:26000972

Urinary neutrophil gelatinase-associated lipocalin for diagnosis and estimating activity in lupus nephritis: a meta-analysis.

PubMed

Fang, Y G; Chen, N N; Cheng, Y B; Sun, S J; Li, H X; Sun, F; Xiang, Y

2015-12-01

Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is relatively specific in lupus nephritis (LN) patients. However, its diagnostic value has not been evaluated. The aim of this review was to determine the value of uNGAL for diagnosis and estimating activity in LN. A comprehensive search was performed on PubMed, EMBASE, Web of Knowledge, Cochrane electronic databases through December 2014. Meta-analysis of sensitivity and specificity was performed with a random-effects model. Additionally, summary receiver operating characteristic (SROC) curves and area under the curve (AUC) values were calculated. Fourteen studies were selected for this review. With respect to diagnosing LN, the pooled sensitivity and specificity were 73.6% (95% confidence interval (CI), 61.9-83.3) and 78.1% (95% CI, 69.0-85.6), respectively. The SROC-AUC value was 0.8632. Regarding estimating LN activity, the pooled sensitivity and specificity were 66.2% (95% CI, 60.4-71.7) and 62.1% (95% CI, 57.9-66.3), respectively. The SROC-AUC value was 0.7583. In predicting renal flares, the pooled sensitivity and specificity were 77.5% (95% CI, 68.1-85.1) and 65.3% (95% CI, 60.0-70.3), respectively. The SROC-AUC value was 0.7756. In conclusion, this meta-analysis indicates that uNGAL has relatively fair sensitivity and specificity in diagnosing LN, estimating LN activity and predicting renal flares, suggesting that uNGAL is a potential biomarker in diagnosing LN and monitoring LN activity. © The Author(s) 2015.

AKAP150-mediated TRPV1 sensitization is disrupted by calcium/calmodulin

PubMed Central

2011-01-01

Background The transient receptor potential vanilloid type1 (TRPV1) is expressed in nociceptive sensory neurons and is sensitive to phosphorylation. A-Kinase Anchoring Protein 79/150 (AKAP150) mediates phosphorylation of TRPV1 by Protein Kinases A and C, modulating channel activity. However, few studies have focused on the regulatory mechanisms that control AKAP150 association with TRPV1. In the present study, we identify a role for calcium/calmodulin in controlling AKAP150 association with, and sensitization of, TRPV1. Results In trigeminal neurons, intracellular accumulation of calcium reduced AKAP150 association with TRPV1 in a manner sensitive to calmodulin antagonism. This was also observed in transfected Chinese hamster ovary (CHO) cells, providing a model for conducting molecular analysis of the association. In CHO cells, the deletion of the C-terminal calmodulin-binding site of TRPV1 resulted in greater association with AKAP150, and increased channel activity. Furthermore, the co-expression of wild-type calmodulin in CHOs significantly reduced TRPV1 association with AKAP150, as evidenced by total internal reflective fluorescence-fluorescence resonance energy transfer (TIRF-FRET) analysis and electrophysiology. Finally, dominant-negative calmodulin co-expression increased TRPV1 association with AKAP150 and increased basal and PKA-sensitized channel activity. Conclusions the results from these studies indicate that calcium/calmodulin interferes with the association of AKAP150 with TRPV1, potentially extending resensitization of the channel. PMID:21569553

Sensitivity and accuracy of hybrid fluorescence-mediated tomography in deep tissue regions.

PubMed

Rosenhain, Stefanie; Al Rawashdeh, Wa'el; Kiessling, Fabian; Gremse, Felix

2017-09-01

Fluorescence-mediated tomography (FMT) enables noninvasive assessment of the three-dimensional distribution of near-infrared fluorescence in mice. The combination with micro-computed tomography (µCT) provides anatomical data, enabling improved fluorescence reconstruction and image analysis. The aim of our study was to assess sensitivity and accuracy of µCT-FMT under realistic in vivo conditions in deeply-seated regions. Accordingly, we acquired fluorescence reflectance images (FRI) and µCT-FMT scans of mice which were prepared with rectal insertions with different amounts of fluorescent dye. Default and high-sensitivity scans were acquired and background signal was analyzed for three FMT channels (670 nm, 745 nm, and 790 nm). Analysis was performed for the original and an improved FMT reconstruction using the µCT data. While FRI and the original FMT reconstruction could detect 100 pmol, the improved FMT reconstruction could detect 10 pmol and significantly improved signal localization. By using a finer sampling grid and increasing the exposure time, the sensitivity could be further improved to detect 0.5 pmol. Background signal was highest in the 670 nm channel and most prominent in the gastro-intestinal tract and in organs with high relative amounts of blood. In conclusion, we show that µCT-FMT allows sensitive and accurate assessment of fluorescence in deep tissue regions. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Statin Intake Is Associated With Decreased Insulin Sensitivity During Cardiac Surgery

PubMed Central

Sato, Hiroaki; Carvalho, George; Sato, Tamaki; Hatzakorzian, Roupen; Lattermann, Ralph; Codere-Maruyama, Takumi; Matsukawa, Takashi; Schricker, Thomas

2012-01-01

OBJECTIVE Surgical trauma impairs intraoperative insulin sensitivity and is associated with postoperative adverse events. Recently, preprocedural statin therapy is recommended for patients with coronary artery disease. However, statin therapy is reported to increase insulin resistance and the risk of new-onset diabetes. Thus, we investigated the association between preoperative statin therapy and intraoperative insulin sensitivity in nondiabetic, dyslipidemic patients undergoing coronary artery bypass grafting. RESEARCH DESIGN AND METHODS In this prospective, nonrandomized trial, patients taking lipophilic statins were assigned to the statin group and hypercholesterolemic patients not receiving any statins were allocated to the control group. Insulin sensitivity was assessed by the hyperinsulinemic-normoglycemic clamp technique during surgery. The mean, SD of blood glucose, and the coefficient of variation (CV) after surgery were calculated for each patient. The association between statin use and intraoperative insulin sensitivity was tested by multiple regression analysis. RESULTS We studied 120 patients. In both groups, insulin sensitivity gradually decreased during surgery with values being on average ∼20% lower in the statin than in the control group. In the statin group, the mean blood glucose in the intensive care unit was higher than in the control group (153 ± 20 vs. 140 ± 20 mg/dL; P < 0.001). The oscillation of blood glucose was larger in the statin group (SD, P < 0.001; CV, P = 0.001). Multiple regression analysis showed that statin use was independently associated with intraoperative insulin sensitivity (β = −0.16; P = 0.03). CONCLUSIONS Preoperative use of lipophilic statins is associated with increased insulin resistance during cardiac surgery in nondiabetic, dyslipidemic patients. PMID:22829524

Rapid Quantitative Analysis of Multiple Explosive Compound Classes on a Single Instrument via Flow-Injection Analysis Tandem Mass Spectrometry.

PubMed

Ostrinskaya, Alla; Kunz, Roderick R; Clark, Michelle; Kingsborough, Richard P; Ong, Ta-Hsuan; Deneault, Sandra

2018-05-24

A flow-injection analysis tandem mass spectrometry (FIA MSMS) method was developed for rapid quantitative analysis of 10 different inorganic and organic explosives. Performance is optimized by tailoring the ionization method (APCI/ESI), de-clustering potentials, and collision energies for each specific analyte. In doing so, a single instrument can be used to detect urea nitrate, potassium chlorate, 2,4,6-trinitrotoluene, 2,4,6-trinitrophenylmethylnitramine, triacetone triperoxide, hexamethylene triperoxide diamine, pentaerythritol tetranitrate, 1,3,5-trinitroperhydro-1,3,5-triazine, nitroglycerin, and octohy-dro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine with sensitivities all in the picogram per milliliter range. In conclusion, FIA APCI/ESI MSMS is a fast (<1 min/sample), sensitive (~pg/mL LOQ), and precise (intraday RSD < 10%) method for trace explosive detection that can play an important role in criminal and attributional forensics, counterterrorism, and environmental protection areas, and has the potential to augment or replace several of the existing explosive detection methods. © 2018 American Academy of Forensic Sciences.

Timing of prophylactic surgery in prevention of diverticulitis recurrence: a cost-effectiveness analysis.

PubMed

Richards, Robert J; Hammitt, James K

2002-09-01

Although surgery is recommended after two or more attacks of uncomplicated diverticulitis, the optimal timing for surgery in terms of cost-effectiveness is unknown. A Markov model was used to compare the costs and outcomes of performing surgery after one, two, or three uncomplicated attacks in 60-year-old hypothetical cohorts. Transition state probabilities were assigned values using published data and expert opinion. Costs were estimated from Medicare reimbursement rates. Surgery after the third attack is cost saving, yielding more years of life and quality adjusted life years at a lower cost than the other two strategies. The results were not sensitive to many of the variables tested in the model or to changes made in the discount rate (0-5%). In conclusion, performing prophylactic resection after the third attack of diverticulitis is cost saving in comparison to resection performed after the first or second attacks and remains cost-effective during sensitivity analysis.

BPM analysis of all-optical fiber interferometric sensor based on a U-shape microcavity

NASA Astrophysics Data System (ADS)

Wu, Hongbin; Yuan, Lei; Wang, Sumei; Zhao, Longjiang; Cao, Zhitao

2014-02-01

Reflectivity spectrum of beam propagation method (BPM), for the first time to the best of our knowledge, is realized and utilized to model all-optical fiber interferometric sensor formed by a U-shape microcavity embedded in a single mode optical fiber and illustrate the principle of sensor structures varied by the length and the depth of U-shape microcavity. BPM analysis gives a constructive guideline to get a high interferometric fringe visibility which is most important for sensing application. The simulated results are completely in agreement with the interferometric sensor principle of Fabry-Perot interferometer (FPI) theory. With the conclusion of FPI sensor, refractive index (RI) sensitivity and temperature sensitivity are then simulated and obtained as 1049+/-5.2nm/RIU (refractive index unit) within RI range of solutions and 1.04+/-0.03pm/°C respectively.

On the Influence of Material Parameters in a Complex Material Model for Powder Compaction

NASA Astrophysics Data System (ADS)

Staf, Hjalmar; Lindskog, Per; Andersson, Daniel C.; Larsson, Per-Lennart

2016-10-01

Parameters in a complex material model for powder compaction, based on a continuum mechanics approach, are evaluated using real insert geometries. The parameter sensitivity with respect to density and stress after compaction, pertinent to a wide range of geometries, is studied in order to investigate completeness and limitations of the material model. Finite element simulations with varied material parameters are used to build surrogate models for the sensitivity study. The conclusion from this analysis is that a simplification of the material model is relevant, especially for simple insert geometries. Parameters linked to anisotropy and the plastic strain evolution angle have a small impact on the final result.

Development of an automated scanning monochromator for sensitivity calibration of the MUSTANG instrument

NASA Astrophysics Data System (ADS)

Rivers, Thane D.

1992-06-01

An Automated Scanning Monochromator was developed using: an Acton Research Corporation (ARC) Monochromator, Ealing Photomultiplier Tube and a Macintosh PC in conjunction with LabVIEW software. The LabVIEW Virtual Instrument written to operate the ARC Monochromator is a mouse driven user friendly program developed for automated spectral data measurements. Resolution and sensitivity of the Automated Scanning Monochromator System were determined experimentally. The Automated monochromator was then used for spectral measurements of a Platinum Lamp. Additionally, the reflectivity curve for a BaSO4 coated screen has been measured. Reflectivity measurements indicate a large discrepancy with expected results. Further analysis of the reflectivity experiment is required for conclusive results.

Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032

PubMed Central

2010-01-01

Blocking oncogenic signaling induced by the BRAFV600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAFV600E mutation. Seven out of 10 BRAFV600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 μM. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 μM, and three were moderately sensitive with IC50 values between 1 and 10 μM. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity. PMID:20406486

Impact of Missing Data for Body Mass Index in an Epidemiologic Study.

PubMed

Razzaghi, Hilda; Tinker, Sarah C; Herring, Amy H; Howards, Penelope P; Waller, D Kim; Johnson, Candice Y

2016-07-01

Objective To assess the potential impact of missing data on body mass index (BMI) on the association between prepregnancy obesity and specific birth defects. Methods Data from the National Birth Defects Prevention Study (NBDPS) were analyzed. We assessed the factors associated with missing BMI data among mothers of infants without birth defects. Four analytic methods were then used to assess the impact of missing BMI data on the association between maternal prepregnancy obesity and three birth defects; spina bifida, gastroschisis, and cleft lip with/without cleft palate. The analytic methods were: (1) complete case analysis; (2) assignment of missing values to either obese or normal BMI; (3) multiple imputation; and (4) probabilistic sensitivity analysis. Logistic regression was used to estimate crude and adjusted odds ratios (aOR) and 95 % confidence intervals (CI). Results Of NBDPS control mothers 4.6 % were missing BMI data, and most of the missing values were attributable to missing height (~90 %). Missing BMI data was associated with birth outside of the US (aOR 8.6; 95 % CI 5.5, 13.4), interview in Spanish (aOR 2.4; 95 % CI 1.8, 3.2), Hispanic ethnicity (aOR 2.0; 95 % CI 1.2, 3.4), and <12 years education (aOR 2.3; 95 % CI 1.7, 3.1). Overall the results of the multiple imputation and probabilistic sensitivity analysis were similar to the complete case analysis. Conclusions Although in some scenarios missing BMI data can bias the magnitude of association, it does not appear likely to have impacted conclusions from a traditional complete case analysis of these data.

MethylMeter®: bisulfite-free quantitative and sensitive DNA methylation profiling and mutation detection in FFPE samples

PubMed Central

McCarthy, David; Pulverer, Walter; Weinhaeusel, Andreas; Diago, Oscar R; Hogan, Daniel J; Ostertag, Derek; Hanna, Michelle M

2016-01-01

Aim: Development of a sensitive method for DNA methylation profiling and associated mutation detection in clinical samples. Materials & methods: Formalin-fixed and paraffin-embedded tumors received by clinical laboratories often contain insufficient DNA for analysis with bisulfite or methylation sensitive restriction enzymes-based methods. To increase sensitivity, methyl-CpG DNA capture and Coupled Abscription PCR Signaling detection were combined in a new assay, MethylMeter®. Gliomas were analyzed for MGMT methylation, glioma CpG island methylator phenotype and IDH1 R132H. Results: MethylMeter had 100% assay success rate measuring all five biomarkers in formalin-fixed and paraffin-embedded tissue. MGMT methylation results were supported by survival and mRNA expression data. Conclusion: MethylMeter is a sensitive and quantitative method for multitarget DNA methylation profiling and associated mutation detection. The MethylMeter-based GliomaSTRAT assay measures methylation of four targets and one mutation to simultaneously grade gliomas and predict their response to temozolomide. This information is clinically valuable in management of gliomas. PMID:27337298

Value of circulating cell-free DNA analysis as a diagnostic tool for breast cancer: a meta-analysis

PubMed Central

Ma, Xuelei; Zhang, Jing; Hu, Xiuying

2017-01-01

Objectives The aim of this study was to systematically evaluate the diagnostic value of cell free DNA (cfDNA) for breast cancer. Results Among 308 candidate articles, 25 with relevant diagnostic screening qualified for final analysis. The mean sensitivity, specificity and area under the curve (AUC) of SROC plots for 24 studies that distinguished breast cancer patients from healthy controls were 0.70, 0.87, and 0.9314, yielding a DOR of 32.31. When analyzed in subgroups, the 14 quantitative studies produced sensitivity, specificity, AUC, and a DOR of 0.78, 0.83, 0.9116, and 24.40. The 10 qualitative studies produced 0.50, 0.98, 0.9919, and 68.45. For 8 studies that distinguished malignant breast cancer from benign diseases, the specificity, sensitivity, AUC and DOR were 0.75, 0.79, 0.8213, and 9.49. No covariate factors had a significant correlation with relative DOR. Deek's funnel plots indicated an absence of publication bias. Materials and Methods Databases were searched for studies involving the use of cfDNA to diagnose breast cancer. The studies were analyzed to determine sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the summary receiver operating characteristic (SROC). Covariates were evaluated for effect on relative DOR. Deek's Funnel plots were generated to measure publication bias. Conclusions Our analysis suggests a promising diagnostic potential of using cfDNA for breast cancer screening, but this diagnostic method is not yet independently sufficient. Further work refining qualitative cfDNA assays will improve the correct diagnosis of breast cancers. PMID:28460452

"A Bayesian sensitivity analysis to evaluate the impact of unmeasured confounding with external data: a real world comparative effectiveness study in osteoporosis".

PubMed

Zhang, Xiang; Faries, Douglas E; Boytsov, Natalie; Stamey, James D; Seaman, John W

2016-09-01

Observational studies are frequently used to assess the effectiveness of medical interventions in routine clinical practice. However, the use of observational data for comparative effectiveness is challenged by selection bias and the potential of unmeasured confounding. This is especially problematic for analyses using a health care administrative database, in which key clinical measures are often not available. This paper provides an approach to conducting a sensitivity analyses to investigate the impact of unmeasured confounding in observational studies. In a real world osteoporosis comparative effectiveness study, the bone mineral density (BMD) score, an important predictor of fracture risk and a factor in the selection of osteoporosis treatments, is unavailable in the data base and lack of baseline BMD could potentially lead to significant selection bias. We implemented Bayesian twin-regression models, which simultaneously model both the observed outcome and the unobserved unmeasured confounder, using information from external sources. A sensitivity analysis was also conducted to assess the robustness of our conclusions to changes in such external data. The use of Bayesian modeling in this study suggests that the lack of baseline BMD did have a strong impact on the analysis, reversing the direction of the estimated effect (odds ratio of fracture incidence at 24 months: 0.40 vs. 1.36, with/without adjusting for unmeasured baseline BMD). The Bayesian twin-regression models provide a flexible sensitivity analysis tool to quantitatively assess the impact of unmeasured confounding in observational studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Cost-Effectiveness Analysis of Preoperative Versus Postoperative Radiation Therapy in Extremity Soft Tissue Sarcoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, Xuanlu M.; Louie, Alexander V.; Ashman, Jonathan

Purpose: Surgery combined with radiation therapy (RT) is the cornerstone of multidisciplinary management of extremity soft tissue sarcoma (STS). Although RT can be given in either the preoperative or the postoperative setting with similar local recurrence and survival outcomes, the side effect profiles, costs, and long-term functional outcomes are different. The aim of this study was to use decision analysis to determine optimal sequencing of RT with surgery in patients with extremity STS. Methods and Materials: A cost-effectiveness analysis was conducted using a state transition Markov model, with quality-adjusted life years (QALYs) as the primary outcome. A time horizon ofmore » 5 years, a cycle length of 3 months, and a willingness-to-pay threshold of $50,000/QALY was used. One-way deterministic sensitivity analyses were performed to determine the thresholds at which each strategy would be preferred. The robustness of the model was assessed by probabilistic sensitivity analysis. Results: Preoperative RT is a more cost-effective strategy ($26,633/3.00 QALYs) than postoperative RT ($28,028/2.86 QALYs) in our base case scenario. Preoperative RT is the superior strategy with either 3-dimensional conformal RT or intensity-modulated RT. One-way sensitivity analyses identified the relative risk of chronic adverse events as having the greatest influence on the preferred timing of RT. The likelihood of preoperative RT being the preferred strategy was 82% on probabilistic sensitivity analysis. Conclusions: Preoperative RT is more cost effective than postoperative RT in the management of resectable extremity STS, primarily because of the higher incidence of chronic adverse events with RT in the postoperative setting.« less

Modelling ecological and human exposure to POPs in Venice lagoon - Part II: Quantitative uncertainty and sensitivity analysis in coupled exposure models.

PubMed

Radomyski, Artur; Giubilato, Elisa; Ciffroy, Philippe; Critto, Andrea; Brochot, Céline; Marcomini, Antonio

2016-11-01

The study is focused on applying uncertainty and sensitivity analysis to support the application and evaluation of large exposure models where a significant number of parameters and complex exposure scenarios might be involved. The recently developed MERLIN-Expo exposure modelling tool was applied to probabilistically assess the ecological and human exposure to PCB 126 and 2,3,7,8-TCDD in the Venice lagoon (Italy). The 'Phytoplankton', 'Aquatic Invertebrate', 'Fish', 'Human intake' and PBPK models available in MERLIN-Expo library were integrated to create a specific food web to dynamically simulate bioaccumulation in various aquatic species and in the human body over individual lifetimes from 1932 until 1998. MERLIN-Expo is a high tier exposure modelling tool allowing propagation of uncertainty on the model predictions through Monte Carlo simulation. Uncertainty in model output can be further apportioned between parameters by applying built-in sensitivity analysis tools. In this study, uncertainty has been extensively addressed in the distribution functions to describe the data input and the effect on model results by applying sensitivity analysis techniques (screening Morris method, regression analysis, and variance-based method EFAST). In the exposure scenario developed for the Lagoon of Venice, the concentrations of 2,3,7,8-TCDD and PCB 126 in human blood turned out to be mainly influenced by a combination of parameters (half-lives of the chemicals, body weight variability, lipid fraction, food assimilation efficiency), physiological processes (uptake/elimination rates), environmental exposure concentrations (sediment, water, food) and eating behaviours (amount of food eaten). In conclusion, this case study demonstrated feasibility of MERLIN-Expo to be successfully employed in integrated, high tier exposure assessment. Copyright © 2016 Elsevier B.V. All rights reserved.

Automatic burst detection for the EEG of the preterm infant.

PubMed

Jennekens, Ward; Ruijs, Loes S; Lommen, Charlotte M L; Niemarkt, Hendrik J; Pasman, Jaco W; van Kranen-Mastenbroek, Vivianne H J M; Wijn, Pieter F F; van Pul, Carola; Andriessen, Peter

2011-10-01

To aid with prognosis and stratification of clinical treatment for preterm infants, a method for automated detection of bursts, interburst-intervals (IBIs) and continuous patterns in the electroencephalogram (EEG) is developed. Results are evaluated for preterm infants with normal neurological follow-up at 2 years. The detection algorithm (MATLAB®) for burst, IBI and continuous pattern is based on selection by amplitude, time span, number of channels and numbers of active electrodes. Annotations of two neurophysiologists were used to determine threshold values. The training set consisted of EEG recordings of four preterm infants with postmenstrual age (PMA, gestational age + postnatal age) of 29-34 weeks. Optimal threshold values were based on overall highest sensitivity. For evaluation, both observers verified detections in an independent dataset of four EEG recordings with comparable PMA. Algorithm performance was assessed by calculation of sensitivity and positive predictive value. The results of algorithm evaluation are as follows: sensitivity values of 90% ± 6%, 80% ± 9% and 97% ± 5% for burst, IBI and continuous patterns, respectively. Corresponding positive predictive values were 88% ± 8%, 96% ± 3% and 85% ± 15%, respectively. In conclusion, the algorithm showed high sensitivity and positive predictive values for bursts, IBIs and continuous patterns in preterm EEG. Computer-assisted analysis of EEG may allow objective and reproducible analysis for clinical treatment.

Evaluation of microarray data normalization procedures using spike-in experiments

PubMed Central

Rydén, Patrik; Andersson, Henrik; Landfors, Mattias; Näslund, Linda; Hartmanová, Blanka; Noppa, Laila; Sjöstedt, Anders

2006-01-01

Background Recently, a large number of methods for the analysis of microarray data have been proposed but there are few comparisons of their relative performances. By using so-called spike-in experiments, it is possible to characterize the analyzed data and thereby enable comparisons of different analysis methods. Results A spike-in experiment using eight in-house produced arrays was used to evaluate established and novel methods for filtration, background adjustment, scanning, channel adjustment, and censoring. The S-plus package EDMA, a stand-alone tool providing characterization of analyzed cDNA-microarray data obtained from spike-in experiments, was developed and used to evaluate 252 normalization methods. For all analyses, the sensitivities at low false positive rates were observed together with estimates of the overall bias and the standard deviation. In general, there was a trade-off between the ability of the analyses to identify differentially expressed genes (i.e. the analyses' sensitivities) and their ability to provide unbiased estimators of the desired ratios. Virtually all analysis underestimated the magnitude of the regulations; often less than 50% of the true regulations were observed. Moreover, the bias depended on the underlying mRNA-concentration; low concentration resulted in high bias. Many of the analyses had relatively low sensitivities, but analyses that used either the constrained model (i.e. a procedure that combines data from several scans) or partial filtration (a novel method for treating data from so-called not-found spots) had with few exceptions high sensitivities. These methods gave considerable higher sensitivities than some commonly used analysis methods. Conclusion The use of spike-in experiments is a powerful approach for evaluating microarray preprocessing procedures. Analyzed data are characterized by properties of the observed log-ratios and the analysis' ability to detect differentially expressed genes. If bias is not a major problem; we recommend the use of either the CM-procedure or partial filtration. PMID:16774679

The effectiveness of the Herbst appliance for patients with Class II malocclusion: a meta-analysis

PubMed Central

Yang, Xin; Zhu, Yafen; Long, Hu; Zhou, Yang; Jian, Fan; Ye, Niansong; Gao, Meiya

2016-01-01

Summary Objective: To systematically investigate review in literature the effects of the Herbst appliance for patients with Class II malocclusion patients. Method: We performed a comprehensive literature survey on PubMed, Web of Science, Embase, CENTRAL, SIGLE, and ClinicalTrial.gov up to December 2014. The selection criteria: randomized controlled trials or clinical controlled trials; using any kind of Herbst appliances to correct Class II division 1 malocclusions; skeletal and/or dental changes evaluated through lateral cephalograms. And the exclusion criteria: syndromic patients; individual case reports and series of cases; surgical interventions. Article screening, data extraction, assessment of risk of bias, and evaluation of evidence quality through GRADE were conducted independently by two well-trained orthodontic doctors. Consensus was made via group discussion of all authors when there is inconsistent information from the two. After that, sensitivity analysis and subgroup analysis were performed to evaluate the robustness of the meta-analysis. Results: Twelve clinical controlled trials meet the above-mentioned criteria, and were included in this analysis. All included studies have eleven measures taken during both active treatment effect and long term effect periods, including four angular ones (i.e., SNA, SNB, ANB, mandibular plane angle) and seven linear ones (i.e. Co-Go, Co-Gn, overjet, overbite, molar relationship, A point-OLp, Pg-OLp) during active treatment effect period were statistically pooled. Meta-analysis and sensitivity analysis demonstrated that all these measures showed consistent results except for SNA, ANB, and overbite. Subgroup analysis showed significant changes in SNA, overbite, and Pg-OLp. Publication bias was detected in SNB, mandibular plane angle, and A point-OLp. Conclusion: The Herbst appliance is effective for patients with Class II malocclusion in active treatment period. Especially, there are obvious changes on dental discrepancy and skeletal changes on Co-Gn. As to its long-term effects, more evidence is needed to draw conclusions. PMID:26306822

Analysis of the Elodea nuttallii transcriptome in response to mercury and cadmium pollution: development of sensitive tools for rapid ecotoxicological testing.

PubMed

Regier, Nicole; Baerlocher, Loïc; Münsterkötter, Martin; Farinelli, Laurent; Cosio, Claudia

2013-08-06

Toxic metals polluting aquatic ecosystems are taken up by inhabitants and accumulate in the food web, affecting species at all trophic levels. It is therefore important to have good tools to assess the level of risk represented by toxic metals in the environment. Macrophytes are potential organisms for the identification of metal-responsive biomarkers but are still underrepresented in ecotoxicology. In the present study, we used next-generation sequencing to investigate the transcriptomic response of Elodea nuttallii exposed to enhanced concentrations of Hg and Cd. We de novo assembled more than 60 000 contigs, of which we found 170 to be regulated dose-dependently by Hg and 212 by Cd. Functional analysis showed that these genes were notably related to energy and metal homeostasis. Expression analysis using nCounter of a subset of genes showed that the gene expression pattern was able to assess toxic metal exposure in complex environmental samples and was more sensitive than other end points (e.g., bioaccumulation, photosynthesis, etc.). In conclusion, we demonstrate the feasibility of using gene expression signatures for the assessment of environmental contamination, using an organism without previous genetic information. This is of interest to ecotoxicology in a wider sense given the possibility to develop specific and sensitive bioassays.

The treatment of missing data in a large cardiovascular clinical outcomes study.

PubMed

Little, Roderick J; Wang, Julia; Sun, Xiang; Tian, Hong; Suh, Eun-Young; Lee, Michael; Sarich, Troy; Oppenheimer, Leonard; Plotnikov, Alexei; Wittes, Janet; Cook-Bruns, Nancy; Burton, Paul; Gibson, C Michael; Mohanty, Surya

2016-06-01

The potential impact of missing data on the results of clinical trials has received heightened attention recently. A National Research Council study provides recommendations for limiting missing data in clinical trial design and conduct, and principles for analysis, including the need for sensitivity analyses to assess robustness of findings to alternative assumptions about the missing data. A Food and Drug Administration advisory committee raised missing data as a serious concern in their review of results from the ATLAS ACS 2 TIMI 51 study, a large clinical trial that assessed rivaroxaban for its ability to reduce the risk of cardiovascular death, myocardial infarction or stroke in patients with acute coronary syndrome. This case study describes a variety of measures that were taken to address concerns about the missing data. A range of analyses are described to assess the potential impact of missing data on conclusions. In particular, measures of the amount of missing data are discussed, and the fraction of missing information from multiple imputation is proposed as an alternative measure. The sensitivity analysis in the National Research Council study is modified in the context of survival analysis where some individuals are lost to follow-up. The impact of deviations from ignorable censoring is assessed by differentially increasing the hazard of the primary outcome in the treatment groups and multiply imputing events between dropout and the end of the study. Tipping-point analyses are described, where the deviation from ignorable censoring that results in a reversal of significance of the treatment effect is determined. A study to determine the vital status of participants lost to follow-up was also conducted, and the results of including this additional information are assessed. Sensitivity analyses suggest that findings of the ATLAS ACS 2 TIMI 51 study are robust to missing data; this robustness is reinforced by the follow-up study, since inclusion of data from this study had little impact on the study conclusions. Missing data are a serious problem in clinical trials. The methods presented here, namely, the sensitivity analyses, the follow-up study to determine survival of missing cases, and the proposed measurement of missing data via the fraction of missing information, have potential application in other studies involving survival analysis where missing data are a concern. © The Author(s) 2016.

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model

PubMed Central

2010-01-01

Background Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. Methods A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age ≥55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. Results The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). Conclusions This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials. PMID:20433705

Performance of the dipstick screening test as a predictor of negative urine culture

PubMed Central

Marques, Alexandre Gimenes; Doi, André Mario; Pasternak, Jacyr; Damascena, Márcio dos Santos; França, Carolina Nunes; Martino, Marinês Dalla Valle

2017-01-01

ABSTRACT Objective To investigate whether the urine dipstick screening test can be used to predict urine culture results. Methods A retrospective study conducted between January and December 2014 based on data from 8,587 patients with a medical order for urine dipstick test, urine sediment analysis and urine culture. Sensitivity, specificity, positive and negative predictive values were determined and ROC curve analysis was performed. Results The percentage of positive cultures was 17.5%. Nitrite had 28% sensitivity and 99% specificity, with positive and negative predictive values of 89% and 87%, respectively. Leukocyte esterase had 79% sensitivity and 84% specificity, with positive and negative predictive values of 51% and 95%, respectively. The combination of positive nitrite or positive leukocyte esterase tests had 85% sensitivity and 84% specificity, with positive and negative predictive values of 53% and 96%, respectively. Positive urinary sediment (more than ten leukocytes per microliter) had 92% sensitivity and 71% specificity, with positive and negative predictive values of 40% and 98%, respectively. The combination of nitrite positive test and positive urinary sediment had 82% sensitivity and 99% specificity, with positive and negative predictive values of 91% and 98%, respectively. The combination of nitrite or leukocyte esterase positive tests and positive urinary sediment had the highest sensitivity (94%) and specificity (84%), with positive and negative predictive values of 58% and 99%, respectively. Based on ROC curve analysis, the best indicator of positive urine culture was the combination of positives leukocyte esterase or nitrite tests and positive urinary sediment, followed by positives leukocyte and nitrite tests, positive urinary sediment alone, positive leukocyte esterase test alone, positive nitrite test alone and finally association of positives nitrite and urinary sediment (AUC: 0.845, 0.844, 0.817, 0.814, 0.635 and 0.626, respectively). Conclusion A negative urine culture can be predicted by negative dipstick test results. Therefore, this test may be a reliable predictor of negative urine culture. PMID:28444086

Standardized Index of Shape (DCE-MRI) and Standardized Uptake Value (PET/CT): Two quantitative approaches to discriminate chemo-radiotherapy locally advanced rectal cancer responders under a functional profile

PubMed Central

Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Granata, Vincenza; Delrio, Paolo; Bianco, Francesco; Pecori, Biagio; Botti, Gerardo; Tatangelo, Fabiana; Caracò, Corradina; Aloj, Luigi; Avallone, Antonio; Lastoria, Secondo

2017-01-01

Purpose To investigate dynamic contrast enhanced-MRI (DCE-MRI) in the preoperative chemo-radiotherapy (CRT) assessment for locally advanced rectal cancer (LARC) compared to18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Methods 75 consecutive patients with LARC were enrolled in a prospective study. DCE-MRI analysis was performed measuring SIS: linear combination of percentage change (Δ) of maximum signal difference (MSD) and wash-out slope (WOS). 18F-FDG PET/CT analysis was performed using SUV maximum (SUVmax). Tumor regression grade (TRG) were estimated after surgery. Non-parametric tests, receiver operating characteristic were evaluated. Results 55 patients (TRG1-2) were classified as responders while 20 subjects as non responders. ΔSIS reached sensitivity of 93%, specificity of 80% and accuracy of 89% (cut-off 6%) to differentiate responders by non responders, sensitivity of 93%, specificity of 69% and accuracy of 79% (cut-off 30%) to identify pathological complete response (pCR). Therapy assessment via ΔSUVmax reached sensitivity of 67%, specificity of 75% and accuracy of 70% (cut-off 60%) to differentiate responders by non responders and sensitivity of 80%, specificity of 31% and accuracy of 51% (cut-off 44%) to identify pCR. Conclusions CRT response assessment by DCE-MRI analysis shows a higher predictive ability than 18F-FDG PET/CT in LARC patients allowing to better discriminate significant and pCR. PMID:28042958

Comparative Diagnostic Performance of Ultrasonography and 99mTc-Sestamibi Scintigraphy for Parathyroid Adenoma in Primary Hyperparathyroidism; Systematic Review and Meta- Analysis

PubMed

Nafisi Moghadam, Reza; Amlelshahbaz, Amir Pasha; Namiranian, Nasim; Sobhan-Ardekani, Mohammad; Emami-Meybodi, Mahmood; Dehghan, Ali; Rahmanian, Masoud; Razavi-Ratki, Seid Kazem

2017-12-28

Objective: Ultrasonography (US) and parathyroid scintigraphy (PS) with 99mTc-MIBI are common methods for preoperative localization of parathyroid adenomas but there discrepancies exist with regard to diagnostic accuracy. The aim of the study was to compare PS and US for localization of parathyroid adenoma with a systematic review and meta-analysis of the literature. Methods: Pub Med, Scopus (EMbase), Web of Science and the reference lists of all included studies were searched up to 1st January 2016. The search strategy was according PICO characteristics. Heterogeneity between the studies was accounted by P < 0.1. Point estimates were pooled estimate of sensitivity, specificity and positive predictive value of SPECT and ultrasonography with 99% confidence intervals (CIs) by pooling available data. Data analysis was performed using Meta-DiSc software (version 1.4). Results: Among 188 studies and after deletion of duplicated studies (75), a total of 113 titles and abstracts were studied. From these, 12 studies were selected. The meta-analysis determined a pooled sensitivity for scintigraphy of 83% [99% confidence interval (CI) 96.358 -97.412] and for ultra-sonography of 80% [99% confidence interval (CI) 76-83]. Similar results for specificity were also obtained for both approache. Conclusion: According this meta- analysis, there were no significant differences between the two methods in terms of sensitivity and specificity. There were overlaps in 99% confidence intervals. Also features of the two methods are similar. Creative Commons Attribution License

Study of Multimission Modular Spacecraft (MMS) propulsion requirements

NASA Technical Reports Server (NTRS)

Fischer, N. H.; Tischer, A. E.

1977-01-01

The cost effectiveness of various propulsion technologies for shuttle-launched multimission modular spacecraft (MMS) missions was determined with special attention to the potential role of ion propulsion. The primary criterion chosen for comparison for the different types of propulsion technologies was the total propulsion related cost, including the Shuttle charges, propulsion module costs, upper stage costs, and propulsion module development. In addition to the cost comparison, other criteria such as reliability, risk, and STS compatibility are examined. Topics covered include MMS mission models, propulsion technology definition, trajectory/performance analysis, cost assessment, program evaluation, sensitivity analysis, and conclusions and recommendations.

Incremental diagnostic accuracy of hybrid SPECT/CT coronary angiography in a population with an intermediate to high pre-test likelihood of coronary artery disease.

PubMed

Schaap, Jeroen; Kauling, Robert M; Boekholdt, S Matthijs; Nieman, Koen; Meijboom, W Bob; Post, Martijn C; Van der Heyden, Jan A; de Kroon, Thom L; van Es, H Wouter; Rensing, Benno J; Verzijlbergen, J Fred

2013-07-01

Hybrid myocardial perfusion imaging with single photon emission computed tomography (SPECT) and CT coronary angiography (CCTA) has the potential to play a major role in patients with non-conclusive SPECT or CCTA results. We evaluated the performance of hybrid SPECT/CCTA vs. standalone SPECT and CCTA for the diagnosis of significant coronary artery disease (CAD) in patients with an intermediate to high pre-test likelihood of CAD. In total, 98 patients (mean age 62.5 ± 10.1 years, 68.4% male) with stable anginal complaints and a median pre-test likelihood of 87% (range 22-95%) were prospectively included in this study. Hybrid SPECT/CCTA was performed prior to conventional coronary angiography (CA) including fractional flow reserve (FFR) measurements. Hybrid analysis was performed by combined interpretation of SPECT and CCTA images. The sensitivity, specificity, positive (PPV), and negative (NPV) predictive values were calculated for standalone SPECT, CCTA, and hybrid SPECT/CCTA on per patient level, using an FFR <0.80 as a reference for significant CAD. Significant CAD was demonstrated in 56 patients (57.9%). Non-conclusive SPECT or CCTA results were found in 32 (32.7%) patients. SPECT had a sensitivity of 93%, specificity 79%, PPV 85%, and NPV 89%. CCTA had a sensitivity of 98%, specificity 62%, PPV 77%, and NPV 96%. Hybrid analysis of SPECT and CCTA improved the overall performance: sensitivity, specificity, PPV, and NPV for the presence of significant CAD to 96, 95, 96, and 95%, respectively. In > 40% of the patients with a high pre-test likelihood no significant CAD was demonstrated, emphasizing the value of accurate pre-treatment cardiovascular imaging. Hybrid SPECT/CCTA was able to accurately diagnose and exclude significant CAD surpassing standalone myocardial SPECT and CCTA, vs. a reference standard of FFR measurements.

The impact of missing trauma data on predicting massive transfusion

PubMed Central

Trickey, Amber W.; Fox, Erin E.; del Junco, Deborah J.; Ning, Jing; Holcomb, John B.; Brasel, Karen J.; Cohen, Mitchell J.; Schreiber, Martin A.; Bulger, Eileen M.; Phelan, Herb A.; Alarcon, Louis H.; Myers, John G.; Muskat, Peter; Cotton, Bryan A.; Wade, Charles E.; Rahbar, Mohammad H.

2013-01-01

INTRODUCTION Missing data are inherent in clinical research and may be especially problematic for trauma studies. This study describes a sensitivity analysis to evaluate the impact of missing data on clinical risk prediction algorithms. Three blood transfusion prediction models were evaluated utilizing an observational trauma dataset with valid missing data. METHODS The PRospective Observational Multi-center Major Trauma Transfusion (PROMMTT) study included patients requiring ≥ 1 unit of red blood cells (RBC) at 10 participating U.S. Level I trauma centers from July 2009 – October 2010. Physiologic, laboratory, and treatment data were collected prospectively up to 24h after hospital admission. Subjects who received ≥ 10 RBC units within 24h of admission were classified as massive transfusion (MT) patients. Correct classification percentages for three MT prediction models were evaluated using complete case analysis and multiple imputation. A sensitivity analysis for missing data was conducted to determine the upper and lower bounds for correct classification percentages. RESULTS PROMMTT enrolled 1,245 subjects. MT was received by 297 patients (24%). Missing percentage ranged from 2.2% (heart rate) to 45% (respiratory rate). Proportions of complete cases utilized in the MT prediction models ranged from 41% to 88%. All models demonstrated similar correct classification percentages using complete case analysis and multiple imputation. In the sensitivity analysis, correct classification upper-lower bound ranges per model were 4%, 10%, and 12%. Predictive accuracy for all models using PROMMTT data was lower than reported in the original datasets. CONCLUSIONS Evaluating the accuracy clinical prediction models with missing data can be misleading, especially with many predictor variables and moderate levels of missingness per variable. The proposed sensitivity analysis describes the influence of missing data on risk prediction algorithms. Reporting upper/lower bounds for percent correct classification may be more informative than multiple imputation, which provided similar results to complete case analysis in this study. PMID:23778514

Comparison of Ultrasonography and Radiography in Detection of Thoracic Bone Fractures; a Systematic Review and Meta-Analysis

PubMed Central

Yousefifard, Mahmoud; Baikpour, Masoud; Ghelichkhani, Parisa; Asady, Hadi; Darafarin, Abolfazl; Amini Esfahani, Mohammad Reza; Hosseini, Mostafa; Yaseri, Mehdi; Safari, Saeed

2016-01-01

Introduction: The potential benefit of ultrasonography for detection of thoracic bone fractures has been proven in various surveys but no comprehensive conclusion has been drawn yet; therefore, the present study aimed to conduct a thorough meta-analytic systematic review on this subject. Methods: Two reviewers independently carried out a comprehensive systematic search in Medline, EMBASE, ISI Web of Knowledge, Scopus, Cochrane Library, and ProQuest databases. Data were summarized as true positive, false positive, true negative and false negative and were analyzed via STATA 11.0 software using a mixed-effects binary regression model. Sources of heterogeneity were further assessed through subgroup analysis. Results: Data on 1667 patients (807 subjects with and 860 cases without thoracic fractures), whose age ranged from 0 to 92 years, were extracted from 17 surveys. Pooled sensitivity and specificity of ultrasonography in detection of thoracic bone fractures were 0.97 (95% CI: 0.90-0.99; I2= 88.88, p<0.001) and 0.94 (95% CI: 0.86-0.97; I2= 71.97, p<0.001), respectively. The same measures for chest radiography were found to be 0.77 (95% CI: 0.56-0.90; I2= 97.76, p<0.001) and 1.0 (95% CI: 0.91-1.00; I2= 97.24, p<0.001), respectively. The sensitivity of ultrasonography was higher in detection of rib fractures, compared to fractures of sternum or clavicle (97% vs. 91%). Moreover, the sensitivity was found to be higher when the procedure was carried out by a radiologist in comparison to an emergency medicine specialist (96% vs. 90%). Conclusion: Base on the findings of the present meta-analysis, screening performance characteristic of ultrasonography in detection of thoracic bone fractures was found to be higher than radiography. However, these characteristics were more prominent in detection of rib fractures and in cases where was performed by a radiologist. PMID:27274514

Cost effectiveness of universal umbilical cord blood gas and lactate analysis in a tertiary level maternity unit.

PubMed

White, Christopher R H; Doherty, Dorota A; Cannon, Jeffrey W; Kohan, Rolland; Newnham, John P; Pennell, Craig E

2016-07-01

There is an increasing body of literature supporting universal umbilical cord blood gas analysis (UCBGA) into all maternity units. A significant impediment to UCBGA's introduction is the perceived expense of the introduction and associated ongoing costs. Consequently, this study set out to conduct the first cost-effectiveness analysis of introducing universal UCBGA. Analysis was based on 42,100 consecutive deliveries ≥23 weeks of gestation at a single tertiary obstetric unit. Within 4 years of UCBGA's introduction there was a 45% reduction in term special care nursery (SCN) admissions >2499 g. Incurred costs included initial and ongoing costs associated with universal UCBGA. Averted costs were based on local diagnosis-related grouping costs for reduction in term SCN admissions. Incremental cost-effectiveness ratio (ICER) and sensitivity analysis results were reported. Under the base-case scenario, the adoption of universal UCBGA was less costly and more effective than selective UCBGA over 4 years and resulted in saving of AU$641,532 while adverting 376 SCN admissions. Sensitivity analysis showed that UCBGA was cost-effective in 51.8%, 83.3%, 99.6% and 100% of simulations in years 1, 2, 3 and 4. These conclusions were not sensitive to wide, clinically possible variations in parameter values for neonatal intensive care unit and SCN admissions, magnitude of averted SCN admissions, cumulative delivery numbers, and SCN admission costs. Universal UCBGA is associated with significant initial and ongoing costs; however, potential averted costs (due to reduced SCN admissions) exceed incurred costs in most scenarios.

Comparison of the diagnostic ability of Moorfield’s regression analysis and glaucoma probability score using Heidelberg retinal tomograph III in eyes with primary open angle glaucoma

PubMed Central

Jindal, Shveta; Dada, Tanuj; Sreenivas, V; Gupta, Viney; Sihota, Ramanjit; Panda, Anita

2010-01-01

Purpose: To compare the diagnostic performance of the Heidelberg retinal tomograph (HRT) glaucoma probability score (GPS) with that of Moorfield’s regression analysis (MRA). Materials and Methods: The study included 50 eyes of normal subjects and 50 eyes of subjects with early-to-moderate primary open angle glaucoma. Images were obtained by using HRT version 3.0. Results: The agreement coefficient (weighted k) for the overall MRA and GPS classification was 0.216 (95% CI: 0.119 – 0.315). The sensitivity and specificity were evaluated using the most specific (borderline results included as test negatives) and least specific criteria (borderline results included as test positives). The MRA sensitivity and specificity were 30.61 and 98% (most specific) and 57.14 and 98% (least specific). The GPS sensitivity and specificity were 81.63 and 73.47% (most specific) and 95.92 and 34.69% (least specific). The MRA gave a higher positive likelihood ratio (28.57 vs. 3.08) and the GPS gave a higher negative likelihood ratio (0.25 vs. 0.44).The sensitivity increased with increasing disc size for both MRA and GPS. Conclusions: There was a poor agreement between the overall MRA and GPS classifications. GPS tended to have higher sensitivities, lower specificities, and lower likelihood ratios than the MRA. The disc size should be taken into consideration when interpreting the results of HRT, as both the GPS and MRA showed decreased sensitivity for smaller discs and the GPS showed decreased specificity for larger discs. PMID:20952832

Co-morbid pain and opioid addiction: Long term effect of opioid maintenance on acute pain

PubMed Central

Wachholtz, Amy; Gonzalez, Gerardo

2014-01-01

Introduction Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. Method 120 individuals with chronic pain were recruited in 4 groups (n=30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M=121 weeks; SD=23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. Results A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (Log rank=15.50; p<.001) and tolerance (Log rank=20.11; p<.001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p’s<.01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p<.05), with the highest tolerance found among opioid naïve control group participants (p’s<.001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R=.37; p<.05); but duration of abstinence did not alter sensitivity (ns). Conclusion Among individuals with a history of prolonged opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. PMID:25456326

Population and High-Risk Group Screening for Glaucoma: The Los Angeles Latino Eye Study

PubMed Central

Francis, Brian A.; Vigen, Cheryl; Lai, Mei-Ying; Winarko, Jonathan; Nguyen, Betsy; Azen, Stanley

2011-01-01

Purpose. To evaluate the ability of various screening tests, both individually and in combination, to detect glaucoma in the general Latino population and high-risk subgroups. Methods. The Los Angeles Latino Eye Study is a population-based study of eye disease in Latinos 40 years of age and older. Participants (n = 6082) underwent Humphrey visual field testing (HVF), frequency doubling technology (FDT) perimetry, measurement of intraocular pressure (IOP) and central corneal thickness (CCT), and independent assessment of optic nerve vertical cup disc (C/D) ratio. Screening parameters were evaluated for three definitions of glaucoma based on optic disc, visual field, and a combination of both. Analyses were also conducted for high-risk subgroups (family history of glaucoma, diabetes mellitus, and age ≥65 years). Sensitivity, specificity, and receiver operating characteristic curves were calculated for those continuous parameters independently associated with glaucoma. Classification and regression tree (CART) analysis was used to develop a multivariate algorithm for glaucoma screening. Results. Preset cutoffs for screening parameters yielded a generally poor balance of sensitivity and specificity (sensitivity/specificity for IOP ≥21 mm Hg and C/D ≥0.8 was 0.24/0.97 and 0.60/0.98, respectively). Assessment of high-risk subgroups did not improve the sensitivity/specificity of individual screening parameters. A CART analysis using multiple screening parameters—C/D, HVF, and IOP—substantially improved the balance of sensitivity and specificity (sensitivity/specificity 0.92/0.92). Conclusions. No single screening parameter is useful for glaucoma screening. However, a combination of vertical C/D ratio, HVF, and IOP provides the best balance of sensitivity/specificity and is likely to provide the highest yield in glaucoma screening programs. PMID:21245400

Cost-Effectiveness of Double Reading versus Single Reading of Mammograms in a Breast Cancer Screening Programme

PubMed Central

Posso, Margarita; Carles, Misericòrdia; Rué, Montserrat; Puig, Teresa; Bonfill, Xavier

2016-01-01

Objectives The usual practice in breast cancer screening programmes for mammogram interpretation is to perform double reading. However, little is known about its cost-effectiveness in the context of digital mammography. Our purpose was to evaluate the cost-effectiveness of double reading versus single reading of digital mammograms in a population-based breast cancer screening programme. Methods Data from 28,636 screened women was used to establish a decision-tree model and to compare three strategies: 1) double reading; 2) double reading for women in their first participation and single reading for women in their subsequent participations; and 3) single reading. We calculated the incremental cost-effectiveness ratio (ICER), which was defined as the expected cost per one additionally detected cancer. We performed a deterministic sensitivity analysis to test the robustness of the ICER. Results The detection rate of double reading (5.17‰) was similar to that of single reading (4.78‰; P = .768). The mean cost of each detected cancer was €8,912 for double reading and €8,287 for single reading. The ICER of double reading versus single reading was €16,684. The sensitivity analysis showed variations in the ICER according to the sensitivity of reading strategies. The strategy that combines double reading in first participation with single reading in subsequent participations was ruled out due to extended dominance. Conclusions From our results, double reading appears not to be a cost-effective strategy in the context of digital mammography. Double reading would eventually be challenged in screening programmes, as single reading might entail important net savings without significantly changing the cancer detection rate. These results are not conclusive and should be confirmed in prospective studies that investigate long-term outcomes like quality adjusted life years (QALYs). PMID:27459663

Evaluation and construction of diagnostic criteria for inclusion body myositis

PubMed Central

Mammen, Andrew L.; Amato, Anthony A.; Weiss, Michael D.; Needham, Merrilee

2014-01-01

Objective: To use patient data to evaluate and construct diagnostic criteria for inclusion body myositis (IBM), a progressive disease of skeletal muscle. Methods: The literature was reviewed to identify all previously proposed IBM diagnostic criteria. These criteria were applied through medical records review to 200 patients diagnosed as having IBM and 171 patients diagnosed as having a muscle disease other than IBM by neuromuscular specialists at 2 institutions, and to a validating set of 66 additional patients with IBM from 2 other institutions. Machine learning techniques were used for unbiased construction of diagnostic criteria. Results: Twenty-four previously proposed IBM diagnostic categories were identified. Twelve categories all performed with high (≥97%) specificity but varied substantially in their sensitivities (11%–84%). The best performing category was European Neuromuscular Centre 2013 probable (sensitivity of 84%). Specialized pathologic features and newly introduced strength criteria (comparative knee extension/hip flexion strength) performed poorly. Unbiased data-directed analysis of 20 features in 371 patients resulted in construction of higher-performing data-derived diagnostic criteria (90% sensitivity and 96% specificity). Conclusions: Published expert consensus–derived IBM diagnostic categories have uniformly high specificity but wide-ranging sensitivities. High-performing IBM diagnostic category criteria can be developed directly from principled unbiased analysis of patient data. Classification of evidence: This study provides Class II evidence that published expert consensus–derived IBM diagnostic categories accurately distinguish IBM from other muscle disease with high specificity but wide-ranging sensitivities. PMID:24975859

The current practice of handling and reporting missing outcome data in eight widely used PROMs in RCT publications: a review of the current literature.

PubMed

Rombach, Ines; Rivero-Arias, Oliver; Gray, Alastair M; Jenkinson, Crispin; Burke, Órlaith

2016-07-01

Patient-reported outcome measures (PROMs) are designed to assess patients' perceived health states or health-related quality of life. However, PROMs are susceptible to missing data, which can affect the validity of conclusions from randomised controlled trials (RCTs). This review aims to assess current practice in the handling, analysis and reporting of missing PROMs outcome data in RCTs compared to contemporary methodology and guidance. This structured review of the literature includes RCTs with a minimum of 50 participants per arm. Studies using the EQ-5D-3L, EORTC QLQ-C30, SF-12 and SF-36 were included if published in 2013; those using the less commonly implemented HUI, OHS, OKS and PDQ were included if published between 2009 and 2013. The review included 237 records (4-76 per relevant PROM). Complete case analysis and single imputation were commonly used in 33 and 15 % of publications, respectively. Multiple imputation was reported for 9 % of the PROMs reviewed. The majority of publications (93 %) failed to describe the assumed missing data mechanism, while low numbers of papers reported methods to minimise missing data (23 %), performed sensitivity analyses (22 %) or discussed the potential influence of missing data on results (16 %). Considerable discrepancy exists between approved methodology and current practice in handling, analysis and reporting of missing PROMs outcome data in RCTs. Greater awareness is needed for the potential biases introduced by inappropriate handling of missing data, as well as the importance of sensitivity analysis and clear reporting to enable appropriate assessments of treatment effects and conclusions from RCTs.

Application of Dual-Tree Complex Wavelet Transforms to Burst Detection and RF Fingerprint Classification

DTIC Science & Technology

2009-09-01

prior to Traditional VT pro- iv cessing. This proves to be effective and provides more robust burst detection for −3 ≤ SNR ≤ 10 dB. Performance of a...TD and WD Dimensionality . . . . . 74 4.4 Performance Sensitivity Analysis . . . . . . . . . . . . . 77 4.4.1 Effect of Burst Location Error...78 4.4.2 Effect of Dissimilar Signal SNRs . . . . . . . . . 84 4.4.3 Effect of Dissimilar Signal Types . . . . . . . . 86 V. Conclusion

[Comparison of Discriminant Analysis and Decision Trees for the Detection of Subclinical Keratoconus].

PubMed

Kleinhans, Sonja; Herrmann, Eva; Kohnen, Thomas; Bühren, Jens

2017-08-15

Background Iatrogenic keratectasia is one of the most dreaded complications of refractive surgery. In most cases, keratectasia develops after refractive surgery of eyes suffering from subclinical stages of keratoconus with few or no signs. Unfortunately, there has been no reliable procedure for the early detection of keratoconus. In this study, we used binary decision trees (recursive partitioning) to assess their suitability for discrimination between normal eyes and eyes with subclinical keratoconus. Patients and Methods The method of decision tree analysis was compared with discriminant analysis which has shown good results in previous studies. Input data were 32 eyes of 32 patients with newly diagnosed keratoconus in the contralateral eye and preoperative data of 10 eyes of 5 patients with keratectasia after laser in-situ keratomileusis (LASIK). The control group was made up of 245 normal eyes after LASIK and 12-month follow-up without any signs of iatrogenic keratectasia. Results Decision trees gave better accuracy and specificity than did discriminant analysis. The sensitivity of decision trees was lower than the sensitivity of discriminant analysis. Conclusion On the basis of the patient population of this study, decision trees did not prove to be superior to linear discriminant analysis for the detection of subclinical keratoconus. Georg Thieme Verlag KG Stuttgart · New York.

Accuracy of i-Scan for Optical Diagnosis of Colonic Polyps: A Meta-Analysis

PubMed Central

Guo, Chuan-Guo; Ji, Rui; Li, Yan-Qing

2015-01-01

Background i-Scan is a novel virtual chromoendoscopy system designed to enhance surface and vascular patterns to improve optical diagnostic performance. Numerous prospective studies have been done to evaluate the accuracy of i-Scan in differentiating colonic neoplasms from non-neoplasms. i-Scan could be an effective endoscopic technique for optical diagnosis of colonic polyps. Objective Our aim of this study was to perform a meta-analysis of published data to establish the diagnostic accuracy of i-Scan for optical diagnosis of colonic polyps. Methods We searched PubMed, Medline, Elsevier ScienceDirect and Cochrane Library databases. We used a bivariate meta-analysis following a random effects model to summarize the data and plotted hierarchical summary receiver-operating characteristic (HSROC) curves. The area under the HSROC curve (AUC) serves as an indicator of the diagnostic accuracy. Results The meta-analysis included a total of 925 patients and 2312 polyps. For the overall studies, the area under the HSROC curve was 0.96. The summary sensitivity was 90.4% (95%CI 85%-94.1%) and specificity was 90.9% (95%CI 84.3%-94.9%). In 11 studies predicting polyps histology in real-time, the summary sensitivity and specificity was 91.5% (95%CI 85.7%-95.1%) and 92.1% (95%CI 84.5%-96.1%), respectively, with the AUC of 0.97. For three different diagnostic criteria (Kudo, NICE, others), the sensitivity was 86.3%, 93.0%, 85.0%, respectively and specificity was 84.8%, 94.4%, 91.8%, respectively. Conclusions Endoscopic diagnosis with i-Scan has accurate optical diagnostic performance to differentiate neoplastic from non-neoplastic polyps with an area under the HSROC curve exceeding 0.90. Both the sensitivity and specificity for diagnosing colonic polyps are over 90%. PMID:25978459

Potential Impact on Spatial Access to Surgery Under a Low Volume Pledge: A Population-Level Analysis of Patients Undergoing Pancreatectomy

PubMed Central

Fong, Zhi Ven; Loehrer, Andrew P; Castillo, Carlos Fernández-del; Bababekov, Yanik J; Jin, Ginger; Ferrone, Cristina R; Warshaw, Andrew L; Traeger, Lara N; Hutter, Matthew M; Lillemoe, Keith D; Chang, David C

2018-01-01

Background A minimum-volume policy restricting hospitals not meeting the threshold from performing complex surgery may increase travel burden and decrease spatial access to surgery. We aim to identify vulnerable populations that would be sensitive to an added travel burden. Methods We performed a retrospective analysis of the California Office of Statewide Health Planning and Development database for patients undergoing pancreatectomy from 2005 to 2014. Number of hospitals bypassed was used as a metric for travel. Patients bypassing fewer hospitals were deemed to be more sensitive to an added travel burden. Results There were 13,374 patients who underwent a pancreatectomy, of which 2,368 (17.7%) were non-bypassers. On unadjusted analysis, patients >80 year old travelled less than their younger counterparts, bypassing a mean of 10.9 ± 9.5 hospitals compared to 14.2 ± 21.3 hospitals bypassed by the 35–49 year old age group (p<0.001). Racial minorities travelled less when compared to Non-Hispanic Whites (p<0.001). Patients identifying their payer status as self-pay (8.9 ± 15.6 hospitals bypassed) and Medicaid (10.1 ± 17.2 hospitals bypassed) also travelled less when compared to patients with private insurance (13.8 ± 20.4 hospitals bypassed, p<0.001). On multivariate analysis, advanced age, racial minority and patients with self-pay or Medicaid payer status were independently associated with increased sensitivity to an added travel burden. Conclusion In patients undergoing pancreatectomy, the elderly, racial minorities and patients with self-pay or Medicaid payer status were associated with an increased sensitivity to an added travel burden. This vulnerable cohort may be disproportionately affected by a minimum-volume policy. PMID:28504112

Improved computer-aided detection of small polyps in CT colonography using interpolation for curvature estimationa

PubMed Central

Liu, Jiamin; Kabadi, Suraj; Van Uitert, Robert; Petrick, Nicholas; Deriche, Rachid; Summers, Ronald M.

2011-01-01

Purpose: Surface curvatures are important geometric features for the computer-aided analysis and detection of polyps in CT colonography (CTC). However, the general kernel approach for curvature computation can yield erroneous results for small polyps and for polyps that lie on haustral folds. Those erroneous curvatures will reduce the performance of polyp detection. This paper presents an analysis of interpolation’s effect on curvature estimation for thin structures and its application on computer-aided detection of small polyps in CTC. Methods: The authors demonstrated that a simple technique, image interpolation, can improve the accuracy of curvature estimation for thin structures and thus significantly improve the sensitivity of small polyp detection in CTC. Results: Our experiments showed that the merits of interpolating included more accurate curvature values for simulated data, and isolation of polyps near folds for clinical data. After testing on a large clinical data set, it was observed that sensitivities with linear, quadratic B-spline and cubic B-spline interpolations significantly improved the sensitivity for small polyp detection. Conclusions: The image interpolation can improve the accuracy of curvature estimation for thin structures and thus improve the computer-aided detection of small polyps in CTC. PMID:21859029

Novel and Practical Scoring Systems for the Diagnosis of Thyroid Nodules

PubMed Central

Wei, Ying; Zhou, Xinrong; Liu, Siyue; Wang, Hong; Liu, Limin; Liu, Renze; Kang, Jinsong; Hong, Kai; Wang, Daowen; Yuan, Gang

2016-01-01

Objective The clinical management of patients with thyroid nodules that are biopsied by fine-needle aspiration cytology and yield indeterminate results remains unsettled. The BRAF V600E mutation has dubious diagnostic value due to its low sensitivity. Novel strategies are urgently needed to distinguish thyroid malignancies from thyroid nodules. Design This prospective study included 504 thyroid nodules diagnosed by ultrasonography from 468 patients, and fine-needle aspiration cytology was performed under ultrasound guidance. Cytology and molecular analysis, including BRAF V600E, RET/PTC1 and RET/PTC3, were conducted simultaneously. The cytology, ultrasonography results, and mutational status were gathered and analyzed together. Predictive scoring systems were designed using a combination of diagnostic parameters for ultrasonography, cytology and genetic analysis. The utility of the scoring systems was analyzed and compared to detection using the individual methods alone or combined. Result The sensitivity of scoring systema (ultrasonography, cytology, BRAF V600E, RET/PTC) was nearly identical to that of scoring systemb (ultrasonography, cytology, BRAF V600E); these were 91.0% and 90.2%, respectively. These sensitivities were significantly higher than those obtained using FNAC, genetic analysis and US alone or combined; their sensitivities were 63.9%, 70.7% and 87.2%, respectively. Scoring systemc (ultrasonography, cytology) was slightly inferior to the former two scoring systems but still had relatively high sensitivity and specificity (80.5% and 95.1%, respectively), which were significantly superior to those of single cytology, ultrasonography or genetic analysis. In nodules with uncertainty cytology, scoring systema, scoring systemb and scoring systemc could elevate the malignancy detection rates to 69.7%, 69.7% and 63.6%, respectively. Conclusion These three scoring systems were quick for clinicians to master and could provide quantified information to predict the probability of malignant nodules. Scoring systemb is recommended for improving the detection rate among nodules of uncertain cytology. PMID:27654865

Adult vector control, mosquito ecology and malaria transmission

PubMed Central

Brady, Oliver J.; Godfray, H. Charles J.; Tatem, Andrew J.; Gething, Peter W.; Cohen, Justin M.; McKenzie, F. Ellis; Alex Perkins, T.; Reiner, Robert C.; Tusting, Lucy S.; Scott, Thomas W.; Lindsay, Steven W.; Hay, Simon I.; Smith, David L.

2015-01-01

Background Standard advice regarding vector control is to prefer interventions that reduce the lifespan of adult mosquitoes. The basis for this advice is a decades-old sensitivity analysis of ‘vectorial capacity’, a concept relevant for most malaria transmission models and based solely on adult mosquito population dynamics. Recent advances in micro-simulation models offer an opportunity to expand the theory of vectorial capacity to include both adult and juvenile mosquito stages in the model. Methods In this study we revisit arguments about transmission and its sensitivity to mosquito bionomic parameters using an elasticity analysis of developed formulations of vectorial capacity. Results We show that reducing adult survival has effects on both adult and juvenile population size, which are significant for transmission and not accounted for in traditional formulations of vectorial capacity. The elasticity of these effects is dependent on various mosquito population parameters, which we explore. Overall, control is most sensitive to methods that affect adult mosquito mortality rates, followed by blood feeding frequency, human blood feeding habit, and lastly, to adult mosquito population density. Conclusions These results emphasise more strongly than ever the sensitivity of transmission to adult mosquito mortality, but also suggest the high potential of combinations of interventions including larval source management. This must be done with caution, however, as policy requires a more careful consideration of costs, operational difficulties and policy goals in relation to baseline transmission. PMID:25733562

Quantitative Trait Loci for Light Sensitivity, Body Weight, Body Size, and Morphological Eye Parameters in the Bumblebee, Bombus terrestris.

PubMed

Maebe, Kevin; Meeus, Ivan; De Riek, Jan; Smagghe, Guy

2015-01-01

Bumblebees such as Bombus terrestris are essential pollinators in natural and managed ecosystems. In addition, this species is intensively used in agriculture for its pollination services, for instance in tomato and pepper greenhouses. Here we performed a quantitative trait loci (QTL) analysis on B. terrestris using 136 microsatellite DNA markers to identify genes linked with 20 traits including light sensitivity, body size and mass, and eye and hind leg measures. By composite interval mapping (IM), we found 83 and 34 suggestive QTLs for 19 of the 20 traits at the linkage group wide significance levels of p = 0.05 and 0.01, respectively. Furthermore, we also found five significant QTLs at the genome wide significant level of p = 0.05. Individual QTLs accounted for 7.5-53.3% of the phenotypic variation. For 15 traits, at least one QTL was confirmed with multiple QTL model mapping. Multivariate principal components analysis confirmed 11 univariate suggestive QTLs but revealed three suggestive QTLs not identified by the individual traits. We also identified several candidate genes linked with light sensitivity, in particular the Phosrestin-1-like gene is a primary candidate for its phototransduction function. In conclusion, we believe that the suggestive and significant QTLs, and markers identified here, can be of use in marker-assisted breeding to improve selection towards light sensitive bumblebees, and thus also the pollination service of bumblebees.

Low-Temperature Photochemically Activated Amorphous Indium-Gallium-Zinc Oxide for Highly Stable Room-Temperature Gas Sensors.

PubMed

Jaisutti, Rawat; Kim, Jaeyoung; Park, Sung Kyu; Kim, Yong-Hoon

2016-08-10

We report on highly stable amorphous indium-gallium-zinc oxide (IGZO) gas sensors for ultraviolet (UV)-activated room-temperature detection of volatile organic compounds (VOCs). The IGZO sensors fabricated by a low-temperature photochemical activation process and exhibiting two orders higher photocurrent compared to conventional zinc oxide sensors, allowed high gas sensitivity against various VOCs even at room temperature. From a systematic analysis, it was found that by increasing the UV intensity, the gas sensitivity, response time, and recovery behavior of an IGZO sensor were strongly enhanced. In particular, under an UV intensity of 30 mW cm(-2), the IGZO sensor exhibited gas sensitivity, response time and recovery time of 37%, 37 and 53 s, respectively, against 750 ppm concentration of acetone gas. Moreover, the IGZO gas sensor had an excellent long-term stability showing around 6% variation in gas sensitivity over 70 days. These results strongly support a conclusion that a low-temperature solution-processed amorphous IGZO film can serve as a good candidate for room-temperature VOCs sensors for emerging wearable electronics.

Reward and punishment sensitivity in women with gambling disorder or compulsive buying: Implications in treatment outcome

PubMed Central

Mestre-Bach, Gemma; Granero, Roser; Steward, Trevor; Fernández-Aranda, Fernando; Baño, Marta; Aymamí, Neus; Gómez-Peña, Mónica; Agüera, Zaida; Mallorquí-Bagué, Núria; Moragas, Laura; del Pino-Gutiérrez, Amparo; Soriano-Mas, Carles; Navas, Juan Francisco; Perales, José C.; Menchón, José M.; Jiménez-Murcia, Susana

2016-01-01

Background and aims Gray’s Reinforcement Sensitivity Theory has been widely applied to different clinical populations, but few studies have reported empirical evidence based on this theory for treatment outcomes in patients with gambling disorder (GD) and compulsive buying (CB). The aims of this study were to explore the association between clinical variables and personality traits with reward and punishment sensitivity (RPS) levels in women (n = 88) who met diagnostic criteria for GD (n = 61) and CB (n = 27), and to determine the predictive capacity of RPS for primary short-term outcomes in a cognitive-behavioral therapy (CBT) intervention. Methods The CBT intervention consisted of 12 weekly sessions. Data on patients’ personality traits, RPS levels, psychopathology, sociodemographic factors, GD, and CB behavior were used in our analysis. Results High RPS levels were associated with higher psychopathology in both CB and GD, and were a risk factor for dropout in the CB group. In the GD group, higher reward sensitivity scores increased the risk of dropout. Discussion and conclusions Our findings suggest that both sensitivity to reward and sensitivity to punishment independently condition patients’ response to treatment for behavioral addictions. The authors uphold that CBT interventions for such addictions could potentially be enhanced by taking RPS into consideration. PMID:27826998

Reward and punishment sensitivity in women with gambling disorder or compulsive buying: Implications in treatment outcome.

PubMed

Mestre-Bach, Gemma; Granero, Roser; Steward, Trevor; Fernández-Aranda, Fernando; Baño, Marta; Aymamí, Neus; Gómez-Peña, Mónica; Agüera, Zaida; Mallorquí-Bagué, Núria; Moragas, Laura; Del Pino-Gutiérrez, Amparo; Soriano-Mas, Carles; Navas, Juan Francisco; Perales, José C; Menchón, José M; Jiménez-Murcia, Susana

2016-12-01

Background and aims Gray's Reinforcement Sensitivity Theory has been widely applied to different clinical populations, but few studies have reported empirical evidence based on this theory for treatment outcomes in patients with gambling disorder (GD) and compulsive buying (CB). The aims of this study were to explore the association between clinical variables and personality traits with reward and punishment sensitivity (RPS) levels in women (n = 88) who met diagnostic criteria for GD (n = 61) and CB (n = 27), and to determine the predictive capacity of RPS for primary short-term outcomes in a cognitive-behavioral therapy (CBT) intervention. Methods The CBT intervention consisted of 12 weekly sessions. Data on patients' personality traits, RPS levels, psychopathology, sociodemographic factors, GD, and CB behavior were used in our analysis. Results High RPS levels were associated with higher psychopathology in both CB and GD, and were a risk factor for dropout in the CB group. In the GD group, higher reward sensitivity scores increased the risk of dropout. Discussion and conclusions Our findings suggest that both sensitivity to reward and sensitivity to punishment independently condition patients' response to treatment for behavioral addictions. The authors uphold that CBT interventions for such addictions could potentially be enhanced by taking RPS into consideration.

The Impact of Parametric Uncertainties on Biogeochemistry in the E3SM Land Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ricciuto, Daniel; Sargsyan, Khachik; Thornton, Peter

We conduct a global sensitivity analysis (GSA) of the Energy Exascale Earth System Model (E3SM), land model (ELM) to calculate the sensitivity of five key carbon cycle outputs to 68 model parameters. This GSA is conducted by first constructing a Polynomial Chaos (PC) surrogate via new Weighted Iterative Bayesian Compressive Sensing (WIBCS) algorithm for adaptive basis growth leading to a sparse, high-dimensional PC surrogate with 3,000 model evaluations. The PC surrogate allows efficient extraction of GSA information leading to further dimensionality reduction. The GSA is performed at 96 FLUXNET sites covering multiple plant functional types (PFTs) and climate conditions. Aboutmore » 20 of the model parameters are identified as sensitive with the rest being relatively insensitive across all outputs and PFTs. These sensitivities are dependent on PFT, and are relatively consistent among sites within the same PFT. The five model outputs have a majority of their highly sensitive parameters in common. A common subset of sensitive parameters is also shared among PFTs, but some parameters are specific to certain types (e.g., deciduous phenology). In conclusion, the relative importance of these parameters shifts significantly among PFTs and with climatic variables such as mean annual temperature.« less

The Impact of Parametric Uncertainties on Biogeochemistry in the E3SM Land Model

DOE PAGES

Ricciuto, Daniel; Sargsyan, Khachik; Thornton, Peter

2018-02-27

We conduct a global sensitivity analysis (GSA) of the Energy Exascale Earth System Model (E3SM), land model (ELM) to calculate the sensitivity of five key carbon cycle outputs to 68 model parameters. This GSA is conducted by first constructing a Polynomial Chaos (PC) surrogate via new Weighted Iterative Bayesian Compressive Sensing (WIBCS) algorithm for adaptive basis growth leading to a sparse, high-dimensional PC surrogate with 3,000 model evaluations. The PC surrogate allows efficient extraction of GSA information leading to further dimensionality reduction. The GSA is performed at 96 FLUXNET sites covering multiple plant functional types (PFTs) and climate conditions. Aboutmore » 20 of the model parameters are identified as sensitive with the rest being relatively insensitive across all outputs and PFTs. These sensitivities are dependent on PFT, and are relatively consistent among sites within the same PFT. The five model outputs have a majority of their highly sensitive parameters in common. A common subset of sensitive parameters is also shared among PFTs, but some parameters are specific to certain types (e.g., deciduous phenology). In conclusion, the relative importance of these parameters shifts significantly among PFTs and with climatic variables such as mean annual temperature.« less

Comparative Analysis of State Fish Consumption Advisories Targeting Sensitive Populations

PubMed Central

Scherer, Alison C.; Tsuchiya, Ami; Younglove, Lisa R.; Burbacher, Thomas M.; Faustman, Elaine M.

2008-01-01

Objective Fish consumption advisories are issued to warn the public of possible toxicological threats from consuming certain fish species. Although developing fetuses and children are particularly susceptible to toxicants in fish, fish also contain valuable nutrients. Hence, formulating advice for sensitive populations poses challenges. We conducted a comparative analysis of advisory Web sites issued by states to assess health messages that sensitive populations might access. Data sources We evaluated state advisories accessed via the National Listing of Fish Advisories issued by the U.S. Environmental Protection Agency. Data extraction We created criteria to evaluate advisory attributes such as risk and benefit message clarity. Data synthesis All 48 state advisories issued at the time of this analysis targeted children, 90% (43) targeted pregnant women, and 58% (28) targeted women of childbearing age. Only six advisories addressed single contaminants, while the remainder based advice on 2–12 contaminants. Results revealed that advisories associated a dozen contaminants with specific adverse health effects. Beneficial health effects of any kind were specifically associated only with omega-3 fatty acids found in fish. Conclusions These findings highlight the complexity of assessing and communicating information about multiple contaminant exposure from fish consumption. Communication regarding potential health benefits conferred by specific fish nutrients was minimal and focused primarily on omega-3 fatty acids. This overview suggests some lessons learned and highlights a lack of both clarity and consistency in providing the breadth of information that sensitive populations such as pregnant women need to make public health decisions about fish consumption during pregnancy. PMID:19079708

First status report on regional ground-water flow modeling for the Paradox Basin, Utah

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrews, R.W.

1984-05-01

Regional ground-water flow within the principal hydrogeologic units of the Paradox Basin is evaluated by developing a conceptual model of the flow regime in the shallow aquifers and the deep-basin brine aquifers and testing these models using a three-dimensional, finite-difference flow code. Semiquantitative sensitivity analysis (a limited parametric study) is conducted to define the system response to changes in hydrologic properties or boundary conditions. A direct method for sensitivity analysis using an adjoint form of the flow equation is applied to the conceptualized flow regime in the Leadville limestone aquifer. All steps leading to the final results and conclusions aremore » incorporated in this report. The available data utilized in this study is summarized. The specific conceptual models, defining the areal and vertical averaging of litho-logic units, aquifer properties, fluid properties, and hydrologic boundary conditions, are described in detail. Two models were evaluated in this study: a regional model encompassing the hydrogeologic units above and below the Paradox Formation/Hermosa Group and a refined scale model which incorporated only the post Paradox strata. The results are delineated by the simulated potentiometric surfaces and tables summarizing areal and vertical boundary fluxes, Darcy velocities at specific points, and ground-water travel paths. Results from the adjoint sensitivity analysis include importance functions and sensitivity coefficients, using heads or the average Darcy velocities to represent system response. The reported work is the first stage of an ongoing evaluation of the Gibson Dome area within the Paradox Basin as a potential repository for high-level radioactive wastes.« less

VFMA: Topographic Analysis of Sensitivity Data From Full-Field Static Perimetry

PubMed Central

Weleber, Richard G.; Smith, Travis B.; Peters, Dawn; Chegarnov, Elvira N.; Gillespie, Scott P.; Francis, Peter J.; Gardiner, Stuart K.; Paetzold, Jens; Dietzsch, Janko; Schiefer, Ulrich; Johnson, Chris A.

2015-01-01

Purpose: To analyze static visual field sensitivity with topographic models of the hill of vision (HOV), and to characterize several visual function indices derived from the HOV volume. Methods: A software application, Visual Field Modeling and Analysis (VFMA), was developed for static perimetry data visualization and analysis. Three-dimensional HOV models were generated for 16 healthy subjects and 82 retinitis pigmentosa patients. Volumetric visual function indices, which are measures of quantity and comparable regardless of perimeter test pattern, were investigated. Cross-validation, reliability, and cross-sectional analyses were performed to assess this methodology and compare the volumetric indices to conventional mean sensitivity and mean deviation. Floor effects were evaluated by computer simulation. Results: Cross-validation yielded an overall R2 of 0.68 and index of agreement of 0.89, which were consistent among subject groups, indicating good accuracy. Volumetric and conventional indices were comparable in terms of test–retest variability and discriminability among subject groups. Simulated floor effects did not negatively impact the repeatability of any index, but large floor changes altered the discriminability for regional volumetric indices. Conclusions: VFMA is an effective tool for clinical and research analyses of static perimetry data. Topographic models of the HOV aid the visualization of field defects, and topographically derived indices quantify the magnitude and extent of visual field sensitivity. Translational Relevance: VFMA assists with the interpretation of visual field data from any perimetric device and any test location pattern. Topographic models and volumetric indices are suitable for diagnosis, monitoring of field loss, patient counseling, and endpoints in therapeutic trials. PMID:25938002

Diagnostic potential of real-time elastography (RTE) and shear wave elastography (SWE) to differentiate benign and malignant thyroid nodules

PubMed Central

Hu, Xiangdong; Liu, Yujiang; Qian, Linxue

2017-01-01

Abstract Background: Real-time elastography (RTE) and shear wave elastography (SWE) are noninvasive and easily available imaging techniques that measure the tissue strain, and it has been reported that the sensitivity and the specificity of elastography were better in differentiating between benign and malignant thyroid nodules than conventional technologies. Methods: Relevant articles were searched in multiple databases; the comparison of elasticity index (EI) was conducted with the Review Manager 5.0. Forest plots of the sensitivity and specificity and SROC curve of RTE and SWE were performed with STATA 10.0 software. In addition, sensitivity analysis and bias analysis of the studies were conducted to examine the quality of articles; and to estimate possible publication bias, funnel plot was used and the Egger test was conducted. Results: Finally 22 articles which eventually satisfied the inclusion criteria were included in this study. After eliminating the inefficient, benign and malignant nodules were 2106 and 613, respectively. The meta-analysis suggested that the difference of EI between benign and malignant nodules was statistically significant (SMD = 2.11, 95% CI [1.67, 2.55], P < .00001). The overall sensitivities of RTE and SWE were roughly comparable, whereas the difference of specificities between these 2 methods was statistically significant. In addition, statistically significant difference of AUC between RTE and SWE was observed between RTE and SWE (P < .01). Conclusion: The specificity of RTE was statistically higher than that of SWE; which suggests that compared with SWE, RTE may be more accurate on differentiating benign and malignant thyroid nodules. PMID:29068996

Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis

PubMed Central

2013-01-01

Background Depression is characterised partly by blunted reactions to reward. However, tasks probing this deficiency have not distinguished insensitivity to reward from insensitivity to the prediction errors for reward that determine learning and are putatively reported by the phasic activity of dopamine neurons. We attempted to disentangle these factors with respect to anhedonia in the context of stress, Major Depressive Disorder (MDD), Bipolar Disorder (BPD) and a dopaminergic challenge. Methods Six behavioural datasets involving 392 experimental sessions were subjected to a model-based, Bayesian meta-analysis. Participants across all six studies performed a probabilistic reward task that used an asymmetric reinforcement schedule to assess reward learning. Healthy controls were tested under baseline conditions, stress or after receiving the dopamine D2 agonist pramipexole. In addition, participants with current or past MDD or BPD were evaluated. Reinforcement learning models isolated the contributions of variation in reward sensitivity and learning rate. Results MDD and anhedonia reduced reward sensitivity more than they affected the learning rate, while a low dose of the dopamine D2 agonist pramipexole showed the opposite pattern. Stress led to a pattern consistent with a mixed effect on reward sensitivity and learning rate. Conclusion Reward-related learning reflected at least two partially separable contributions. The first related to phasic prediction error signalling, and was preferentially modulated by a low dose of the dopamine agonist pramipexole. The second related directly to reward sensitivity, and was preferentially reduced in MDD and anhedonia. Stress altered both components. Collectively, these findings highlight the contribution of model-based reinforcement learning meta-analysis for dissecting anhedonic behavior. PMID:23782813

Economic evaluation of an implementation strategy for the management of low back pain in general practice.

PubMed

Jensen, Cathrine Elgaard; Riis, Allan; Petersen, Karin Dam; Jensen, Martin Bach; Pedersen, Kjeld Møller

2017-05-01

In connection with the publication of a clinical practice guideline on the management of low back pain (LBP) in general practice in Denmark, a cluster randomised controlled trial was conducted. In this trial, a multifaceted guideline implementation strategy to improve general practitioners' treatment of patients with LBP was compared with a usual implementation strategy. The aim was to determine whether the multifaceted strategy was cost effective, as compared with the usual implementation strategy. The economic evaluation was conducted as a cost-utility analysis where cost collected from a societal perspective and quality-adjusted life years were used as outcome measures. The analysis was conducted as a within-trial analysis with a 12-month time horizon consistent with the follow-up period of the clinical trial. To adjust for a priori selected covariates, generalised linear models with a gamma family were used to estimate incremental costs and quality-adjusted life years. Furthermore, both deterministic and probabilistic sensitivity analyses were conducted. Results showed that costs associated with primary health care were higher, whereas secondary health care costs were lower for the intervention group when compared with the control group. When adjusting for covariates, the intervention was less costly, and there was no significant difference in effect between the 2 groups. Sensitivity analyses showed that results were sensitive to uncertainty. In conclusion, the multifaceted implementation strategy was cost saving when compared with the usual strategy for implementing LBP clinical practice guidelines in general practice. Furthermore, there was no significant difference in effect, and the estimate was sensitive to uncertainty.

Addressing global uncertainty and sensitivity in first-principles based microkinetic models by an adaptive sparse grid approach

NASA Astrophysics Data System (ADS)

Döpking, Sandra; Plaisance, Craig P.; Strobusch, Daniel; Reuter, Karsten; Scheurer, Christoph; Matera, Sebastian

2018-01-01

In the last decade, first-principles-based microkinetic modeling has been developed into an important tool for a mechanistic understanding of heterogeneous catalysis. A commonly known, but hitherto barely analyzed issue in this kind of modeling is the presence of sizable errors from the use of approximate Density Functional Theory (DFT). We here address the propagation of these errors to the catalytic turnover frequency (TOF) by global sensitivity and uncertainty analysis. Both analyses require the numerical quadrature of high-dimensional integrals. To achieve this efficiently, we utilize and extend an adaptive sparse grid approach and exploit the confinement of the strongly non-linear behavior of the TOF to local regions of the parameter space. We demonstrate the methodology on a model of the oxygen evolution reaction at the Co3O4 (110)-A surface, using a maximum entropy error model that imposes nothing but reasonable bounds on the errors. For this setting, the DFT errors lead to an absolute uncertainty of several orders of magnitude in the TOF. We nevertheless find that it is still possible to draw conclusions from such uncertain models about the atomistic aspects controlling the reactivity. A comparison with derivative-based local sensitivity analysis instead reveals that this more established approach provides incomplete information. Since the adaptive sparse grids allow for the evaluation of the integrals with only a modest number of function evaluations, this approach opens the way for a global sensitivity analysis of more complex models, for instance, models based on kinetic Monte Carlo simulations.

Diagnostic value of blood-derived microRNAs for schizophrenia: results of a meta-analysis and validation.

PubMed

Liu, Sha; Zhang, Fuquan; Wang, Xijin; Shugart, Yin Yao; Zhao, Yingying; Li, Xinrong; Liu, Zhifen; Sun, Ning; Yang, Chunxia; Zhang, Kerang; Yue, Weihua; Yu, Xin; Xu, Yong

2017-11-10

There is an increasing interest in searching biomarkers for schizophrenia (SZ) diagnosis, which overcomes the drawbacks inherent with the subjective diagnostic methods. MicroRNA (miRNA) fingerprints have been explored for disease diagnosis. We performed a meta-analysis to examine miRNA diagnostic value for SZ and further validated the meta-analysis results. Using following terms: schizophrenia/SZ, microRNA/miRNA, diagnosis, sensitivity and specificity, we searched databases restricted to English language and reviewed all articles published from January 1990 to October 2016. All extracted data were statistically analyzed and the results were further validated with peripheral blood mononuclear cells (PBMNCs) isolated from patients and healthy controls using RT-qPCR and receiver operating characteristic (ROC) analysis. A total of 6 studies involving 330 patients and 202 healthy controls were included for meta-analysis. The pooled sensitivity, specificity and diagnostic odds ratio were 0.81 (95% CI: 0.75-0.86), 0.81 (95% CI: 0.72-0.88) and 18 (95% CI: 9-34), respectively; the positive and negative likelihood ratio was 4.3 and 0.24 respectively; the area under the curve in summary ROC was 0.87 (95% CI: 0.84-0.90). Validation revealed that miR-181b-5p, miR-21-5p, miR-195-5p, miR-137, miR-346 and miR-34a-5p in PBMNCs had high diagnostic sensitivity and specificity in the context of schizophrenia. In conclusion, blood-derived miRNAs might be promising biomarkers for SZ diagnosis.

Cost analysis of school-based intermittent screening and treatment of malaria in Kenya

PubMed Central

2011-01-01

Background The control of malaria in schools is receiving increasing attention, but there remains currently no consensus as to the optimal intervention strategy. This paper analyses the costs of intermittent screening and treatment (IST) of malaria in schools, implemented as part of a cluster-randomized controlled trial on the Kenyan coast. Methods Financial and economic costs were estimated using an ingredients approach whereby all resources required in the delivery of IST are quantified and valued. Sensitivity analysis was conducted to investigate how programme variation affects costs and to identify potential cost savings in the future implementation of IST. Results The estimated financial cost of IST per child screened is US$ 6.61 (economic cost US$ 6.24). Key contributors to cost were salary costs (36%) and malaria rapid diagnostic tests (RDT) (22%). Almost half (47%) of the intervention cost comprises redeployment of existing resources including health worker time and use of hospital vehicles. Sensitivity analysis identified changes to intervention delivery that can reduce programme costs by 40%, including use of alternative RDTs and removal of supervised treatment. Cost-effectiveness is also likely to be highly sensitive to the proportion of children found to be RDT-positive. Conclusion In the current context, school-based IST is a relatively expensive malaria intervention, but reducing the complexity of delivery can result in considerable savings in the cost of intervention. (Costs are reported in US$ 2010). PMID:21933376

Cost-Effectiveness Analysis of a Capitated Patient Navigation Program for Medicare Beneficiaries with Lung Cancer.

PubMed

Shih, Ya-Chen Tina; Chien, Chun-Ru; Moguel, Rocio; Hernandez, Mike; Hajek, Richard A; Jones, Lovell A

2016-04-01

To assess the cost-effectiveness of implementing a patient navigation (PN) program with capitated payment for Medicare beneficiaries diagnosed with lung cancer. Cost-effectiveness analysis. A Markov model to capture the disease progression of lung cancer and characterize clinical benefits of PN services as timeliness of treatment and care coordination. Taking a payer's perspective, we estimated the lifetime costs, life years (LYs), and quality-adjusted life years (QALYs) and addressed uncertainties in one-way and probabilistic sensitivity analyses. Model inputs were extracted from the literature, supplemented with data from a Centers for Medicare and Medicaid Services demonstration project. Compared to usual care, PN services incurred higher costs but also yielded better outcomes. The incremental cost and effectiveness was $9,145 and 0.47 QALYs, respectively, resulting in an incremental cost-effectiveness ratio of $19,312/QALY. One-way sensitivity analysis indicated that findings were most sensitive to a parameter capturing PN survival benefit for local-stage patients. CE-acceptability curve showed the probability that the PN program was cost-effective was 0.80 and 0.91 at a societal willingness-to-pay of $50,000 and $100,000/QALY, respectively. Instituting a capitated PN program is cost-effective for lung cancer patients in Medicare. Future research should evaluate whether the same conclusion holds in other cancers. © Health Research and Educational Trust.

Optimal management of colorectal liver metastases in older patients: a decision analysis

PubMed Central

Yang, Simon; Alibhai, Shabbir MH; Kennedy, Erin D; El-Sedfy, Abraham; Dixon, Matthew; Coburn, Natalie; Kiss, Alex; Law, Calvin HL

2014-01-01

Background Comparative trials evaluating management strategies for colorectal cancer liver metastases (CLM) are lacking, especially for older patients. This study developed a decision-analytic model to quantify outcomes associated with treatment strategies for CLM in older patients. Methods A Markov-decision model was built to examine the effect on life expectancy (LE) and quality-adjusted life expectancy (QALE) for best supportive care (BSC), systemic chemotherapy (SC), radiofrequency ablation (RFA) and hepatic resection (HR). The baseline patient cohort assumptions included healthy 70-year-old CLM patients after a primary cancer resection. Event and transition probabilities and utilities were derived from a literature review. Deterministic and probabilistic sensitivity analyses were performed on all study parameters. Results In base case analysis, BSC, SC, RFA and HR yielded LEs of 11.9, 23.1, 34.8 and 37.0 months, and QALEs of 7.8, 13.2, 22.0 and 25.0 months, respectively. Model results were sensitive to age, comorbidity, length of model simulation and utility after HR. Probabilistic sensitivity analysis showed increasing preference for RFA over HR with increasing patient age. Conclusions HR may be optimal for healthy 70-year-old patients with CLM. In older patients with comorbidities, RFA may provide better LE and QALE. Treatment decisions in older cancer patients should account for patient age, comorbidities, local expertise and individual values. PMID:24961482

Clinical Evaluation of a Loop-Mediated Amplification Kit for Diagnosis of Imported Malaria

PubMed Central

Polley, Spencer D.; González, Iveth J.; Mohamed, Deqa; Daly, Rosemarie; Bowers, Kathy; Watson, Julie; Mewse, Emma; Armstrong, Margaret; Gray, Christen; Perkins, Mark D.; Bell, David; Kanda, Hidetoshi; Tomita, Norihiro; Kubota, Yutaka; Mori, Yasuyoshi; Chiodini, Peter L.; Sutherland, Colin J.

2013-01-01

Background. Diagnosis of malaria relies on parasite detection by microscopy or antigen detection; both fail to detect low-density infections. New tests providing rapid, sensitive diagnosis with minimal need for training would enhance both malaria diagnosis and malaria control activities. We determined the diagnostic accuracy of a new loop-mediated amplification (LAMP) kit in febrile returned travelers. Methods. The kit was evaluated in sequential blood samples from returned travelers sent for pathogen testing to a specialist parasitology laboratory. Microscopy was performed, and then malaria LAMP was performed using Plasmodium genus and Plasmodium falciparum–specific tests in parallel. Nested polymerase chain reaction (PCR) was performed on all samples as the reference standard. Primary outcome measures for diagnostic accuracy were sensitivity and specificity of LAMP results, compared with those of nested PCR. Results. A total of 705 samples were tested in the primary analysis. Sensitivity and specificity were 98.4% and 98.1%, respectively, for the LAMP P. falciparum primers and 97.0% and 99.2%, respectively, for the Plasmodium genus primers. Post hoc repeat PCR analysis of all 15 tests with discrepant results resolved 4 results in favor of LAMP, suggesting that the primary analysis had underestimated diagnostic accuracy. Conclusions. Malaria LAMP had a diagnostic accuracy similar to that of nested PCR, with a greatly reduced time to result, and was superior to expert microscopy. PMID:23633403

Setting the stage for equity-sensitive monitoring of the maternal and child health Millennium Development Goals.

PubMed Central

Wirth, Meg E.; Balk, Deborah; Delamonica, Enrique; Storeygard, Adam; Sacks, Emma; Minujin, Alberto

2006-01-01

OBJECTIVE: This analysis seeks to set the stage for equity-sensitive monitoring of the health-related Millennium Development Goals (MDGs). METHODS: We use data from international household-level surveys (Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS)) to demonstrate that establishing an equity baseline is necessary and feasible, even in low-income and data-poor countries. We assess data from six countries using 11 health indicators and six social stratifiers. Simple bivariate stratification is complemented by simultaneous stratification to expose the compound effect of multiple forms of vulnerability. FINDINGS: The data reveal that inequities are complex and interactive: inferences cannot be drawn about the nature or extent of inequities in health outcomes from a single stratifier or indicator. CONCLUSION: The MDGs and other development initiatives must become more comprehensive and explicit in their analysis and tracking of inequities. The design of policies to narrow health gaps must take into account country-specific inequities. PMID:16878225

The development and validation of an UHPLC–MS/MS method for the rapid quantification of the antiretroviral agent dapivirine in human plasma

PubMed Central

Seserko, Lauren A; Emory, Joshua F; Hendrix, Craig W; Marzinke, Mark A

2014-01-01

Background Dapivirine is a non-nucleoside reverse transcriptase inhibitor designed to prevent HIV-1 viral replication and subsequent propagation. A sensitive method is required to quantify plasma concentrations to assess drug efficacy. Results Dapivirine-spiked plasma was combined with acetonitrile containing deuterated IS and was processed for analysis. The method has an analytical measuring range from 20 to 10,000 pg/ml. For the LLOQ, low, mid and high QCs, intra- and inter-assay precision (%CV) ranged from 5.58 to 13.89% and 5.23 to 13.36%, respectively, and intra- and inter-day accuracy (% deviation) ranged from -5.61 to 0.75% and -4.30 to 6.24%, respectively. Conclusion A robust and sensitive LC–MS/MS assay for the high-throughput quantification of the antiretroviral drug dapivirine in human plasma was developed and validated following bioanalytical validation guidelines. The assay meets criteria for the analysis of samples from large research trials. PMID:24256358

Performance of Polymerase Chain Reaction Analysis of the Amniotic Fluid of Pregnant Women for Diagnosis of Congenital Toxoplasmosis: A Systematic Review and Meta-Analysis

PubMed Central

2016-01-01

Introduction Congenital infection caused by Toxoplasma gondii can cause serious damage that can be diagnosed in utero or at birth, although most infants are asymptomatic at birth. Prenatal diagnosis of congenital toxoplasmosis considerably improves the prognosis and outcome for infected infants. For this reason, an assay for the quick, sensitive, and safe diagnosis of fetal toxoplasmosis is desirable. Goal To systematically review the performance of polymerase chain reaction (PCR) analysis of the amniotic fluid of pregnant women with recent serological toxoplasmosis diagnoses for the diagnosis of fetal toxoplasmosis. Method A systematic literature review was conducted via a search of electronic databases; the literature included primary studies of the diagnostic accuracy of PCR analysis of amniotic fluid from pregnant women who seroconverted during pregnancy. The PCR test was compared to a gold standard for diagnosis. Results A total of 1.269 summaries were obtained from the electronic database and reviewed, and 20 studies, comprising 4.171 samples, met the established inclusion criteria and were included in the review. The following results were obtained: studies about PCR assays for fetal toxoplasmosis are generally susceptible to bias; reports of the tests’ use lack critical information; the protocols varied among studies; the heterogeneity among studies was concentrated in the tests’ sensitivity; there was evidence that the sensitivity of the tests increases with time, as represented by the trimester; and there was more heterogeneity among studies in which there was more time between maternal diagnosis and fetal testing. The sensitivity of the method, if performed up to five weeks after maternal diagnosis, was 87% and specificity was 99%. Conclusion The global sensitivity heterogeneity of the PCR test in this review was 66.5% (I2). The tests show low evidence of heterogeneity with a sensitivity of 87% and specificity of 99% when performed up to five weeks after maternal diagnosis. The test has a known performance and could be recommended for use up to five weeks after maternal diagnosis, when there is suspicion of fetal toxoplasmosis. PMID:27055272

Influence of various unsteady aerodynamic models on the aeromechanical stability of a helicopter in ground resonance

NASA Technical Reports Server (NTRS)

Friedmann, P. P.; Venkatesan, C.

1985-01-01

The aeromechanical stability of a helicopter in ground resonance was analyzed, by incorporating five different aerodynamic models in the coupled rotor/fuselage analysis. The sensitivity of the results to changes in aerodynamic modelling was carefully examined. The theoretical results were compared with experimental data and useful conclusions are drawn regarding the role of aerodynamic modeling on this aeromechanical stability problem. The aerodynamic model which provided the best all around correlation with the experimental data was identified.

Clinical usefulness of the clock drawing test applying rasch analysis in predicting of cognitive impairment.

PubMed

Yoo, Doo Han; Lee, Jae Shin

2016-07-01

[Purpose] This study examined the clinical usefulness of the clock drawing test applying Rasch analysis for predicting the level of cognitive impairment. [Subjects and Methods] A total of 187 stroke patients with cognitive impairment were enrolled in this study. The 187 patients were evaluated by the clock drawing test developed through Rasch analysis along with the mini-mental state examination of cognitive evaluation tool. An analysis of the variance was performed to examine the significance of the mini-mental state examination and the clock drawing test according to the general characteristics of the subjects. Receiver operating characteristic analysis was performed to determine the cutoff point for cognitive impairment and to calculate the sensitivity and specificity values. [Results] The results of comparison of the clock drawing test with the mini-mental state showed significant differences in according to gender, age, education, and affected side. A total CDT of 10.5, which was selected as the cutoff point to identify cognitive impairement, showed a sensitivity, specificity, Youden index, positive predictive, and negative predicive values of 86.4%, 91.5%, 0.8, 95%, and 88.2%. [Conclusion] The clock drawing test is believed to be useful in assessments and interventions based on its excellent ability to identify cognitive disorders.

Present and future of prophylactic antibiotics for severe acute pancreatitis

PubMed Central

Jiang, Kun; Huang, Wei; Yang, Xiao-Nan; Xia, Qing

2012-01-01

AIM: To investigate the role of prophylactic antibiotics in the reduction of mortality of severe acute pancreatitis (SAP) patients, which is highly questioned by more and more randomized controlled trials (RCTs) and meta-analyses. METHODS: An updated meta-analysis was performed. RCTs comparing prophylactic antibiotics for SAP with control or placebo were included for meta-analysis. The mortality outcomes were pooled for estimation, and re-pooled estimation was performed by the sensitivity analysis of an ideal large-scale RCT. RESULTS: Currently available 11 RCTs were included. Subgroup analysis showed that there was significant reduction of mortality rate in the period before 2000, while no significant reduction in the period from 2000 [Risk Ratio, (RR) = 1.01, P = 0.98]. Funnel plot indicated that there might be apparent publication bias in the period before 2000. Sensitivity analysis showed that the RR of mortality rate ranged from 0.77 to 1.00 with a relatively narrow confidence interval (P < 0.05). However, the number needed to treat having a minor lower limit of the range (7-5096 patients) implied that certain SAP patients could still potentially prevent death by antibiotic prophylaxis. CONCLUSION: Current evidences do not support prophylactic antibiotics as a routine treatment for SAP, but the potentially benefited sub-population requires further investigations. PMID:22294832

Micro-heterogeneity versus clustering in binary mixtures of ethanol with water or alkanes.

PubMed

Požar, Martina; Lovrinčević, Bernarda; Zoranić, Larisa; Primorać, Tomislav; Sokolić, Franjo; Perera, Aurélien

2016-08-24

Ethanol is a hydrogen bonding liquid. When mixed in small concentrations with water or alkanes, it forms aggregate structures reminiscent of, respectively, the direct and inverse micellar aggregates found in emulsions, albeit at much smaller sizes. At higher concentrations, micro-heterogeneous mixing with segregated domains is found. We examine how different statistical methods, namely correlation function analysis, structure factor analysis and cluster distribution analysis, can describe efficiently these morphological changes in these mixtures. In particular, we explain how the neat alcohol pre-peak of the structure factor evolves into the domain pre-peak under mixing conditions, and how this evolution differs whether the co-solvent is water or alkane. This study clearly establishes the heuristic superiority of the correlation function/structure factor analysis to study the micro-heterogeneity, since cluster distribution analysis is insensitive to domain segregation. Correlation functions detect the domains, with a clear structure factor pre-peak signature, while the cluster techniques detect the cluster hierarchy within domains. The main conclusion is that, in micro-segregated mixtures, the domain structure is a more fundamental statistical entity than the underlying cluster structures. These findings could help better understand comparatively the radiation scattering experiments, which are sensitive to domains, versus the spectroscopy-NMR experiments, which are sensitive to clusters.

Meta-analysis of treatment with rabbit and horse antithymocyte globulin for aplastic anemia.

PubMed

Hayakawa, Jin; Kanda, Junya; Akahoshi, Yu; Harada, Naonori; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Yamazaki, Rie; Kako, Shinichi; Kanda, Yoshinobu

2017-05-01

Aplastic anemia patients who received rabbit antithymocyte globulin exhibited response and survival rates inferior to those who received horse antithymocyte globulin in several studies. Therefore, we conducted a meta-analysis to compare rabbit and horse antithymocyte globulin as immunosuppressive therapy for aplastic anemia. We searched online databases for studies that compared antithymocyte globulin regimens as first-line treatment for aplastic anemia, including both randomized and non-randomized controlled trials. The early mortality rate at 3 months and overall response rate at 6 months were evaluated. Thirteen studies were included in the analysis. The risk ratio (RR) of early mortality for rabbit vs. horse antithymocyte globulin was 1.33 [95% confidence interval (CI) 0.69-2.57; P = 0.39], with significant heterogeneity. A sensitivity analysis suggested higher early mortality rate in patients who received rabbit antithymocyte globulin. The overall response rate was significantly higher in patients who received horse antithymocyte globulin (RR 1.27; 95% CI 1.05-1.54; P = 0.015). In conclusion, in aplastic anemia patients treated with ATG, early mortality rate was not significantly different in patients receiving horse or rabbit ATG, although a sensitivity analysis showed higher early mortality in the rabbit ATG group. Horse ATG was associated with significantly higher response rate than rabbit ATG.

Sensitive Multi-Species Emissions Monitoring: Infrared Laser-Based Detection of Trace-Level Contaminants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steill, Jeffrey D.; Huang, Haifeng; Hoops, Alexandra A.

This report summarizes our development of spectroscopic chemical analysis techniques and spectral modeling for trace-gas measurements of highly-regulated low-concentration species present in flue gas emissions from utility coal boilers such as HCl under conditions of high humidity. Detailed spectral modeling of the spectroscopy of HCl and other important combustion and atmospheric species such as H 2 O, CO 2 , N 2 O, NO 2 , SO 2 , and CH 4 demonstrates that IR-laser spectroscopy is a sensitive multi-component analysis strategy. Experimental measurements from techniques based on IR laser spectroscopy are presented that demonstrate sub-ppm sensitivity levels to thesemore » species. Photoacoustic infrared spectroscopy is used to detect and quantify HCl at ppm levels with extremely high signal-to-noise even under conditions of high relative humidity. Additionally, cavity ring-down IR spectroscopy is used to achieve an extremely high sensitivity to combustion trace gases in this spectral region; ppm level CH 4 is one demonstrated example. The importance of spectral resolution in the sensitivity of a trace-gas measurement is examined by spectral modeling in the mid- and near-IR, and efforts to improve measurement resolution through novel instrument development are described. While previous project reports focused on benefits and complexities of the dual-etalon cavity ring-down infrared spectrometer, here details on steps taken to implement this unique and potentially revolutionary instrument are described. This report also illustrates and critiques the general strategy of IR- laser photodetection of trace gases leading to the conclusion that mid-IR laser spectroscopy techniques provide a promising basis for further instrument development and implementation that will enable cost-effective sensitive detection of multiple key contaminant species simultaneously.« less

Circulating TSLP associates with decreased wheezing in non-atopic preschool children: Data from the URECA birth cohort

PubMed Central

Demehri, Shadmehr; Yockey, Laura J.; Visness, Cynthia M.; Jaffee, Katy F.; Turkoz, Ahu; Wood, Robert A.; O'Connor, George T.; Kattan, Meyer; Gern, James E.; Gergen, Peter J.; Holtzman, Michael; Bloomberg, Gordon; Kopan, Raphael

2014-01-01

Background Mouse models of atopic march suggest that systemic, skin-derived Thymic Stromal Lymphopoietin (TSLP) mediates progression from eczema to asthma. Objective We investigated whether circulating TSLP is associated with eczema, allergic sensitization, or recurrent wheezing in young children. Methods A prospective analysis of the relationship between plasma levels of TSLP to allergic sensitization and recurrent wheezing was conducted in the birth cohort from the Urban Environment and Childhood Asthma (URECA) study. Plasma TSLP levels were measured at 1, 2, and 3 years of age and analyzed for correlation with clinical parameters in each of the three years. Only those children with consecutive samples for all three years were included in this analysis. Results We detected TSLP in 33% of 236 children for whom plasma samples were available for all three years. Overall, a consistently significant association was not found between TSLP and eczema or allergic sensitization. With regard to recurrent wheezing, children with detectable TSLP at one year of age were significantly less likely to experience recurrent wheezing by 3 years compared with those children without detectable TSLP, but this was only seen in children without aeroallergen sensitization at 3 years. (p<0.01). Conclusions and Clinical Relevance Contrary to our expectations circulating TSLP was not significantly associated with eczema, allergen sensitization, or recurrent wheezing during the first three years of life. Early presence of circulating TSLP was significantly associated with reduced incidence of recurrent wheeze in those children not sensitized to aeroallergen. These findings suggest a possible underlying distinction between pathogenesis of developing atopic vs. non-atopic recurrent wheeze. PMID:24397611

Economic analysis of waste-to-energy industry in China.

PubMed

Zhao, Xin-Gang; Jiang, Gui-Wu; Li, Ang; Wang, Ling

2016-02-01

The generation of municipal solid waste is further increasing in China with urbanization and improvement of living standards. The "12th five-year plan" period (2011-2015) promotes waste-to-energy technologies for the harmless disposal and recycling of municipal solid waste. Waste-to-energy plant plays an important role for reaching China's energy conservation and emission reduction targets. Industrial policies and market prospect of waste-to-energy industry are described. Technology, cost and benefit of waste-to-energy plant are also discussed. Based on an economic analysis of a waste-to-energy project in China (Return on Investment, Net Present Value, Internal Rate of Return, and Sensitivity Analysis) the paper makes the conclusions. Copyright © 2015 Elsevier Ltd. All rights reserved.

The cost of a case of subclinical ketosis in Canadian dairy herds

PubMed Central

Gohary, Khaled; Overton, Michael W.; Von Massow, Michael; LeBlanc, Stephen J.; Lissemore, Kerry D.; Duffield, Todd F.

2016-01-01

The objective of this study was to develop a model to estimate the cost of a case of subclinical ketosis (SCK) in Canadian dairy herds. Costs were derived from the default inputs, and included increased clinical disease incidence attributable to SCK, $76; longer time to pregnancy, $57; culling and death in early lactation attributable to SCK, $26; milk production loss, $44. Given these figures, the cost of 1 case of SCK was estimated to be $203. Sensitivity analysis showed that the estimated cost of a case of SCK was most sensitive to the herd-level incidence of SCK and the cost of 1 day open. In conclusion, SCK negatively impacts dairy herds and losses are dependent on the herd-level incidence and factors included in the calculation. PMID:27429460

The cost of a case of subclinical ketosis in Canadian dairy herds.

PubMed

Gohary, Khaled; Overton, Michael W; Von Massow, Michael; LeBlanc, Stephen J; Lissemore, Kerry D; Duffield, Todd F

2016-07-01

The objective of this study was to develop a model to estimate the cost of a case of subclinical ketosis (SCK) in Canadian dairy herds. Costs were derived from the default inputs, and included increased clinical disease incidence attributable to SCK, $76; longer time to pregnancy, $57; culling and death in early lactation attributable to SCK, $26; milk production loss, $44. Given these figures, the cost of 1 case of SCK was estimated to be $203. Sensitivity analysis showed that the estimated cost of a case of SCK was most sensitive to the herd-level incidence of SCK and the cost of 1 day open. In conclusion, SCK negatively impacts dairy herds and losses are dependent on the herd-level incidence and factors included in the calculation.

Effect of a single session of muscle-biased therapy on pain sensitivity: a systematic review and meta-analysis of randomized controlled trials

PubMed Central

Gay, Charles W; Alappattu, Meryl J; Coronado, Rogelio A; Horn, Maggie E; Bishop, Mark D

2013-01-01

Background Muscle-biased therapies (MBT) are commonly used to treat pain, yet several reviews suggest evidence for the clinical effectiveness of these therapies is lacking. Inadequate treatment parameters have been suggested to account for inconsistent effects across studies. Pain sensitivity may serve as an intermediate physiologic endpoint helping to establish optimal MBT treatment parameters. The purpose of this review was to summarize the current literature investigating the short-term effect of a single dose of MBT on pain sensitivity in both healthy and clinical populations, with particular attention to specific MBT parameters of intensity and duration. Methods A systematic search for articles meeting our prespecified criteria was conducted using Cumulative Index to Nursing and Allied Health Literature (CINAHL) and MEDLINE from the inception of each database until July 2012, in accordance with guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analysis. Relevant characteristics from studies included type, intensity, and duration of MBT and whether short-term changes in pain sensitivity and clinical pain were noted with MBT application. Study results were pooled using a random-effects model to estimate the overall effect size of a single dose of MBT on pain sensitivity as well as the effect of MBT, dependent on comparison group and population type. Results Reports from 24 randomized controlled trials (23 articles) were included, representing 36 MBT treatment arms and 29 comparative groups, where 10 groups received active agents, 11 received sham/inert treatments, and eight received no treatment. MBT demonstrated a favorable and consistent ability to modulate pain sensitivity. Short-term modulation of pain sensitivity was associated with short-term beneficial effects on clinical pain. Intensity of MBT, but not duration, was linked with change in pain sensitivity. A meta-analysis was conducted on 17 studies that assessed the effect of MBT on pressure pain thresholds. The results suggest that MBT had a favorable effect on pressure pain thresholds when compared with no-treatment and sham/inert groups, and effects comparable with those of other active treatments. Conclusion The evidence supports the use of pain sensitivity measures by future research to help elucidate optimal therapeutic parameters for MBT as an intermediate physiologic marker. PMID:23403507

Renal Mass Biopsy to Guide Treatment Decisions for Small Incidental Renal Tumors: A Cost-effectiveness Analysis1

PubMed Central

Gervais, Debra A.; Hartman, Rebecca I.; Harisinghani, Mukesh G.; Feldman, Adam S.; Mueller, Peter R.; Gazelle, G. Scott

2010-01-01

Purpose: To evaluate the effectiveness, cost, and cost-effectiveness of using renal mass biopsy to guide treatment decisions for small incidentally detected renal tumors. Materials and Methods: A decision-analytic Markov model was developed to estimate life expectancy and lifetime costs for patients with small (≤4-cm) renal tumors. Two strategies were compared: renal mass biopsy to triage patients to surgery or imaging surveillance and empiric nephron-sparing surgery. The model incorporated biopsy performance, the probability of track seeding with malignant cells, the prevalence and growth of benign and malignant tumors, treatment effectiveness and costs, and patient outcomes. An incremental cost-effectiveness analysis was performed to identify strategy preference under a willingness-to-pay threshold of $75 000 per quality-adjusted life-year (QALY). Effects of changes in key parameters on strategy preference were evaluated in sensitivity analysis. Results: Under base-case assumptions, the biopsy strategy yielded a minimally greater quality-adjusted life expectancy (4 days) than did empiric surgery at a lower lifetime cost ($3466), dominating surgery from a cost-effectiveness perspective. Over the majority of parameter ranges tested in one-way sensitivity analysis, the biopsy strategy dominated surgery or was cost-effective relative to surgery based on a $75 000-per-QALY willingness-to-pay threshold. In two-way sensitivity analysis, surgery yielded greater life expectancy when the prevalence of malignancy and propensity for biopsy-negative cancers to metastasize were both higher than expected or when the sensitivity and specificity of biopsy were both lower than expected. Conclusion: The use of biopsy to guide treatment decisions for small incidentally detected renal tumors is cost-effective and can prevent unnecessary surgery in many cases. © RSNA, 2010 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10092013/-/DC1 PMID:20720070

Postoperative complications following colectomy for ulcerative colitis: A validation study

PubMed Central

2012-01-01

Background Ulcerative colitis (UC) patients failing medical management require colectomy. This study compares risk estimates for predictors of postoperative complication derived from administrative data against that of chart review and evaluates the accuracy of administrative coding for this population. Methods Hospital administrative databases were used to identify adults with UC undergoing colectomy from 1996–2007. Medical charts were reviewed and regression analyses comparing chart versus administrative data were performed to assess the effect of age, emergent operation, and Charlson comorbidities on the occurrence of postoperative complications. Sensitivity, specificity, and positive/negative predictive values of administrative coding for identifying the study population, Charlson comorbidities, and postoperative complications were assessed. Results Compared to chart review, administrative data estimated a higher magnitude of effect for emergent admission (OR 2.52 [95% CI: 1.80–3.52] versus 1.49 [1.06–2.09]) and Charlson comorbidities (OR 2.91 [1.86–4.56] versus 1.50 [1.05–2.15]) as predictors of postoperative complications. Administrative data correctly identified UC and colectomy in 85.9% of cases. The administrative database was 37% sensitive in identifying patients with ≥ 1Charlson comorbidity. Restricting analysis to active comorbidities increased the sensitivity to 63%. The sensitivity of identifying patients with at least one postoperative complication was 68%; restricting analysis to more severe complications improved the sensitivity to 84%. Conclusions Administrative data identified the same risk factors for postoperative complications as chart review, but overestimated the magnitude of risk. This discrepancy may be explained by coding inaccuracies that selectively identifying the most serious complications and comorbidities. PMID:22943760

Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density

PubMed Central

Edwards, D. L.; Saleh, A. A.; Greenspan, S. L.

2015-01-01

Summary We performed a systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for DXA-determined osteoporosis or low bone density. Commonly evaluated risk instruments showed high sensitivity approaching or exceeding 90 % at particular thresholds within various populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. Introduction The purpose of the study is to systematically review the performance of clinical risk assessment instruments for screening for dual-energy X-ray absorptiometry (DXA)-determined osteoporosis or low bone density. Methods Systematic review and meta-analysis were performed. Multiple literature sources were searched, and data extracted and analyzed from included references. Results One hundred eight references met inclusion criteria. Studies assessed many instruments in 34 countries, most commonly the Osteoporosis Self-Assessment Tool (OST), the Simple Calculated Osteoporosis Risk Estimation (SCORE) instrument, the Osteoporosis Self-Assessment Tool for Asians (OSTA), the Osteoporosis Risk Assessment Instrument (ORAI), and body weight criteria. Meta-analyses of studies evaluating OST using a cutoff threshold of <1 to identify US postmenopausal women with osteoporosis at the femoral neck provided summary sensitivity and specificity estimates of 89 % (95%CI 82–96 %) and 41 % (95%CI 23–59 %), respectively. Meta-analyses of studies evaluating OST using a cutoff threshold of 3 to identify US men with osteoporosis at the femoral neck, total hip, or lumbar spine provided summary sensitivity and specificity estimates of 88 % (95%CI 79–97 %) and 55 % (95%CI 42–68 %), respectively. Frequently evaluated instruments each had thresholds and populations for which sensitivity for osteoporosis or low bone mass detection approached or exceeded 90 % but always with a trade-off of relatively low specificity. Conclusions Commonly evaluated clinical risk assessment instruments each showed high sensitivity approaching or exceeding 90 % for identifying individuals with DXA-determined osteoporosis or low BMD at certain thresholds in different populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. PMID:25644147

Spectrotemporal Modulation Sensitivity as a Predictor of Speech Intelligibility for Hearing-Impaired Listeners

PubMed Central

Bernstein, Joshua G.W.; Mehraei, Golbarg; Shamma, Shihab; Gallun, Frederick J.; Theodoroff, Sarah M.; Leek, Marjorie R.

2014-01-01

Background A model that can accurately predict speech intelligibility for a given hearing-impaired (HI) listener would be an important tool for hearing-aid fitting or hearing-aid algorithm development. Existing speech-intelligibility models do not incorporate variability in suprathreshold deficits that are not well predicted by classical audiometric measures. One possible approach to the incorporation of such deficits is to base intelligibility predictions on sensitivity to simultaneously spectrally and temporally modulated signals. Purpose The likelihood of success of this approach was evaluated by comparing estimates of spectrotemporal modulation (STM) sensitivity to speech intelligibility and to psychoacoustic estimates of frequency selectivity and temporal fine-structure (TFS) sensitivity across a group of HI listeners. Research Design The minimum modulation depth required to detect STM applied to an 86 dB SPL four-octave noise carrier was measured for combinations of temporal modulation rate (4, 12, or 32 Hz) and spectral modulation density (0.5, 1, 2, or 4 cycles/octave). STM sensitivity estimates for individual HI listeners were compared to estimates of frequency selectivity (measured using the notched-noise method at 500, 1000measured using the notched-noise method at 500, 2000, and 4000 Hz), TFS processing ability (2 Hz frequency-modulation detection thresholds for 500, 10002 Hz frequency-modulation detection thresholds for 500, 2000, and 4000 Hz carriers) and sentence intelligibility in noise (at a 0 dB signal-to-noise ratio) that were measured for the same listeners in a separate study. Study Sample Eight normal-hearing (NH) listeners and 12 listeners with a diagnosis of bilateral sensorineural hearing loss participated. Data Collection and Analysis STM sensitivity was compared between NH and HI listener groups using a repeated-measures analysis of variance. A stepwise regression analysis compared STM sensitivity for individual HI listeners to audiometric thresholds, age, and measures of frequency selectivity and TFS processing ability. A second stepwise regression analysis compared speech intelligibility to STM sensitivity and the audiogram-based Speech Intelligibility Index. Results STM detection thresholds were elevated for the HI listeners, but only for low rates and high densities. STM sensitivity for individual HI listeners was well predicted by a combination of estimates of frequency selectivity at 4000 Hz and TFS sensitivity at 500 Hz but was unrelated to audiometric thresholds. STM sensitivity accounted for an additional 40% of the variance in speech intelligibility beyond the 40% accounted for by the audibility-based Speech Intelligibility Index. Conclusions Impaired STM sensitivity likely results from a combination of a reduced ability to resolve spectral peaks and a reduced ability to use TFS information to follow spectral-peak movements. Combining STM sensitivity estimates with audiometric threshold measures for individual HI listeners provided a more accurate prediction of speech intelligibility than audiometric measures alone. These results suggest a significant likelihood of success for an STM-based model of speech intelligibility for HI listeners. PMID:23636210

System analysis in rotorcraft design: The past decade

NASA Technical Reports Server (NTRS)

Galloway, Thomas L.

1988-01-01

Rapid advances in the technology of electronic digital computers and the need for an integrated synthesis approach in developing future rotorcraft programs has led to increased emphasis on system analysis techniques in rotorcraft design. The task in systems analysis is to deal with complex, interdependent, and conflicting requirements in a structured manner so rational and objective decisions can be made. Whether the results are wisdom or rubbish depends upon the validity and sometimes more importantly, the consistency of the inputs, the correctness of the analysis, and a sensible choice of measures of effectiveness to draw conclusions. In rotorcraft design this means combining design requirements, technology assessment, sensitivity analysis and reviews techniques currently in use by NASA and Army organizations in developing research programs and vehicle specifications for rotorcraft. These procedures span simple graphical approaches to comprehensive analysis on large mainframe computers. Examples of recent applications to military and civil missions are highlighted.

Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid

PubMed Central

Drewes, Asbjorn Mohr; Reddy, Hariprasad; Staahl, Camilla; Pedersen, Jan; Funch-Jensen, Peter; Arendt-Nielsen, Lars; Gregersen, Hans

2005-01-01

AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus. The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization. METHODS: Thirty healthy subjects were included. Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area, volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine. RESULTS: The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change. CONCLUSION: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions. The new model can be used to study abnormal sensory-motor mechanisms in visceral organs. PMID:16038036

Women survivors of child sexual abuse. How can health professionals promote healing?

PubMed Central

Schachter, Candice L.; Radomsky, Nellie A.; Stalker, Carol A.; Teram, Eli

2004-01-01

OBJECTIVE: To explore how health professionals can practise in ways sensitive to adult women survivors of child sexual abuse. DESIGN: Qualitative semistructured in-depth interviews. SETTING: Small and midsize cities in Ontario and Saskatchewan. PARTICIPANTS: Twenty-seven women survivors of childhood sexual abuse. METHODS: Respondents were asked about their experiences with physical therapists and other health professionals and asked how practice could be sensitive to their needs as survivors. A grounded-theory approach was used. After independent analyses, researchers achieved consensus on the main themes. Findings were checked with participants, other survivors, and mental health professionals. MAIN FINDINGS: A crucial theme was the need to feel safe when consulting any health professional. Participants described specific ways for clinicians to facilitate the feeling of safety. Disclosure of abuse history was another key theme; analysis revealed no one "right way" to inquire about it. CONCLUSION: Women survivors of child sexual abuse want safe, accepting environments and sensitive, informed health professionals with whom to work in partnership on all their health concerns. PMID:15318678

HRD1 sensitizes breast cancer cells to Tamoxifen by promoting S100A8 degradation

PubMed Central

Liang, XiuBin; Li, Min; Shi, Ming; Li, Yan; Jenkins, Gareth; Lin, XiaWen; Wei, XueFei; Jia, ZhiJun; Feng, XueFeng; Su, DongMing; Guo, WanHua

2017-01-01

Estrogen receptor alpha positive (ER+) of breast cancer could develop resistance to antiestrogens including Tamoxifen. Our previous study showed that the E3 ubiquitin ligase HRD1 played an important role in anti-breast cancer. However, its role in chemotherapy resistance hasn't been reported. In this study, we found that HRD1 expression was downregulated in Tamoxifen-resistant breast cancer cell line MCF7/Tam compared to the Tamoxifen sensitive cell line MCF7. Moreover, S100A8 is the direct target of HRD1 by proteome analysis. Our data showed that HRD1 decreased the protein level of S100A8 through ubiquitination while HRD1 was regulated by acetylation of histone. More importantly, HRD1 knockdown significantly increased the cell survival of MCF7 cells to the Tamoxifen treatment. HRD1 overexpression sensitized MCF7/Tam cells to the Tamoxifen treatment in vitro and in vivo. In conclusion, the decrease of HRD1 expression contributed to Tamoxifen resistance in breast cancer. PMID:28423597

The Diversity of Cloud Responses to Twentieth Century Sea Surface Temperatures

NASA Astrophysics Data System (ADS)

Silvers, Levi G.; Paynter, David; Zhao, Ming

2018-01-01

Low-level clouds are shown to be the conduit between the observed sea surface temperatures (SST) and large decadal fluctuations of the top of the atmosphere radiative imbalance. The influence of low-level clouds on the climate feedback is shown for global mean time series as well as particular geographic regions. The changes of clouds are found to be important for a midcentury period of high sensitivity and a late century period of low sensitivity. These conclusions are drawn from analysis of amip-piForcing simulations using three atmospheric general circulation models (AM2.1, AM3, and AM4.0). All three models confirm the importance of the relationship between the global climate sensitivity and the eastern Pacific trends of SST and low-level clouds. However, this work argues that the variability of the climate feedback parameter is not driven by stratocumulus-dominated regions in the eastern ocean basins, but rather by the cloudy response in the rest of the tropics.

Effects of tibolone on fibrinogen and antithrombin III: A systematic review and meta-analysis of controlled trials.

PubMed

Bała, Małgorzata; Sahebkar, Amirhossein; Ursoniu, Sorin; Serban, Maria-Corina; Undas, Anetta; Mikhailidis, Dimitri P; Lip, Gregory Y H; Rysz, Jacek; Banach, Maciej

2017-10-01

Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic activity, but the evidence regarding its effects on fibrinogen and antithrombin III (ATIII) has not been conclusive. We assessed the impact of tibolone on fibrinogen and ATIII through a systematic review and meta-analysis of available randomized controlled trials (RCTs). The search included PUBMED, Web of Science, Scopus, and Google Scholar (up to January 31st, 2016) to identify controlled clinical studies investigating the effects of oral tibolone treatment on fibrinogen and ATIII. Overall, the impact of tibolone on plasma fibrinogen concentrations was reported in 10 trials comprising 11 treatment arms. Meta-analysis did not suggest a significant reduction of fibrinogen levels following treatment with tibolone (WMD: -5.38%, 95% CI: -11.92, +1.16, p=0.107). This result was robust in the sensitivity analysis and not influenced after omitting each of the included studies from meta-analysis. When the studies were categorized according to the duration of treatment, there was no effect in the subsets of trials lasting either <12months (WMD: -7.64%, 95% CI: -16.58, +1.29, p=0.094) or ≥12months (WMD: -0.62%, 95% CI: -8.40, +7.17, p=0.876). With regard to ATIII, there was no change following treatment with tibolone (WMD: +0.74%, 95% CI: -1.44, +2.93, p=0.505) and this effect was robust in sensitivity analysis. There was no differential effect of tibolone on plasma ATIII concentrations in trials with either <12months (WMD: +2.26%, 95% CI: -3.14, +7.66, p=0.411) or≥12months (WMD: +0.06%, 95% CI: -1.16, +1.28, p=0.926) duration. Consistent with the results of subgroup analysis, meta-regression did not suggest any significant association between the changes in plasma concentrations of fibrinogen (slope: +0.40; 95% CI: -0.39, +1.19; p=0.317) and ATIII (slope: -0.17; 95% CI: -0.54, +0.20; p=0.374) with duration of treatment. In conclusion, meta-analysis did not suggest a significant reduction of fibrinogen and ATIII levels following treatment with tibolone. Copyright © 2017 Elsevier Ltd. All rights reserved.

Herpesviruses in etiopathogenesis of aggressive periodontitis: A meta-analysis based on case-control studies.

PubMed

Li, Fei; Zhu, Ce; Deng, Feng-Ying; Wong, May Chun Mei; Lu, Hai-Xia; Feng, Xi-Ping

2017-01-01

Previous studies have found that herpesviruses are associated with aggressive periodontitis (AgP). However, these findings are controversial. This meta-analysis was aimed at clarifying the association between herpesviruses and AgP. We identified eligible case-control studies evaluating the association between herpesviruses and AgP from PubMed and Embase databases in October 2015. Original data were extracted and quality assessment was done. Overall odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Random-effects model was determined. The stability was evaluated by sensitivity analysis. Finally, Egger's funnel plot was used to investigate the publication bias. Twelve case-control studies involving 322 patients and 342 controls were included in the present meta-analysis. The included case-control studies were assessed as high quality. The quantitative synthesis results for Epstein-Barr virus (EBV) showed significance (10 studies: p = 0.0008, OR = 6.11, 95% CI = 2.13-17.51); nevertheless, evidence of publication bias for EBV was considerable (EBV: Egger's test, p<0.001). Human cytomegalovirus (HCMV) and Herpes simplex virus type 1 (HSV-1) had significant association with AgP (12 studies for HCMV: p = 0.009, OR = 3.63, 95% CI = 2.15-6.13; 4 studies for HSV-1: p<0.001, OR = 19.19, 95% CI = 4.16-79.06). Sensitivity analyses showed the results yielded consistency, and no significant publication bias was observed for HCMV. The association between Herpes simplex virus type 2 (HSV-2) and AgP was inconclusive (2 studies: p = 0.20, OR = 3.46, 95% CI = 0.51-23.51). This meta-analysis suggests that HCMV and HSV-1 are significantly associated with AgP. However, due to the heterogeneity among studies these conclusions should be cautiously interpreted. There is insufficient evidence to draw any conclusion between EBV, HSV-2 and AgP based on the currently limited data.

Economics in “Global Health 2035”: a sensitivity analysis of the value of a life year estimates

PubMed Central

Chang, Angela Y; Robinson, Lisa A; Hammitt, James K; Resch, Stephen C

2017-01-01

Background In “Global health 2035: a world converging within a generation,” The Lancet Commission on Investing in Health (CIH) adds the value of increased life expectancy to the value of growth in gross domestic product (GDP) when assessing national well–being. To value changes in life expectancy, the CIH relies on several strong assumptions to bridge gaps in the empirical research. It finds that the value of a life year (VLY) averages 2.3 times GDP per capita for low– and middle–income countries (LMICs) assuming the changes in life expectancy they experienced from 2000 to 2011 are permanent. Methods The CIH VLY estimate is based on a specific shift in population life expectancy and includes a 50 percent reduction for children ages 0 through 4. We investigate the sensitivity of this estimate to the underlying assumptions, including the effects of income, age, and life expectancy, and the sequencing of the calculations. Findings We find that reasonable alternative assumptions regarding the effects of income, age, and life expectancy may reduce the VLY estimates to 0.2 to 2.1 times GDP per capita for LMICs. Removing the reduction for young children increases the VLY, while reversing the sequencing of the calculations reduces the VLY. Conclusion Because the VLY is sensitive to the underlying assumptions, analysts interested in applying this approach elsewhere must tailor the estimates to the impacts of the intervention and the characteristics of the affected population. Analysts should test the sensitivity of their conclusions to reasonable alternative assumptions. More work is needed to investigate options for improving the approach. PMID:28400950

Local sensitivity analysis for inverse problems solved by singular value decomposition

USGS Publications Warehouse

Hill, M.C.; Nolan, B.T.

2010-01-01

Local sensitivity analysis provides computationally frugal ways to evaluate models commonly used for resource management, risk assessment, and so on. This includes diagnosing inverse model convergence problems caused by parameter insensitivity and(or) parameter interdependence (correlation), understanding what aspects of the model and data contribute to measures of uncertainty, and identifying new data likely to reduce model uncertainty. Here, we consider sensitivity statistics relevant to models in which the process model parameters are transformed using singular value decomposition (SVD) to create SVD parameters for model calibration. The statistics considered include the PEST identifiability statistic, and combined use of the process-model parameter statistics composite scaled sensitivities and parameter correlation coefficients (CSS and PCC). The statistics are complimentary in that the identifiability statistic integrates the effects of parameter sensitivity and interdependence, while CSS and PCC provide individual measures of sensitivity and interdependence. PCC quantifies correlations between pairs or larger sets of parameters; when a set of parameters is intercorrelated, the absolute value of PCC is close to 1.00 for all pairs in the set. The number of singular vectors to include in the calculation of the identifiability statistic is somewhat subjective and influences the statistic. To demonstrate the statistics, we use the USDA’s Root Zone Water Quality Model to simulate nitrogen fate and transport in the unsaturated zone of the Merced River Basin, CA. There are 16 log-transformed process-model parameters, including water content at field capacity (WFC) and bulk density (BD) for each of five soil layers. Calibration data consisted of 1,670 observations comprising soil moisture, soil water tension, aqueous nitrate and bromide concentrations, soil nitrate concentration, and organic matter content. All 16 of the SVD parameters could be estimated by regression based on the range of singular values. Identifiability statistic results varied based on the number of SVD parameters included. Identifiability statistics calculated for four SVD parameters indicate the same three most important process-model parameters as CSS/PCC (WFC1, WFC2, and BD2), but the order differed. Additionally, the identifiability statistic showed that BD1 was almost as dominant as WFC1. The CSS/PCC analysis showed that this results from its high correlation with WCF1 (-0.94), and not its individual sensitivity. Such distinctions, combined with analysis of how high correlations and(or) sensitivities result from the constructed model, can produce important insights into, for example, the use of sensitivity analysis to design monitoring networks. In conclusion, the statistics considered identified similar important parameters. They differ because (1) with CSS/PCC can be more awkward because sensitivity and interdependence are considered separately and (2) identifiability requires consideration of how many SVD parameters to include. A continuing challenge is to understand how these computationally efficient methods compare with computationally demanding global methods like Markov-Chain Monte Carlo given common nonlinear processes and the often even more nonlinear models.

Co-occurrence of Pain Symptoms and Somatosensory Sensitivity in Burning Mouth Syndrome: A Systematic Review

PubMed Central

Moisset, Xavier; Calbacho, Valentina; Torres, Pilar; Gremeau-Richard, Christelle; Dallel, Radhouane

2016-01-01

Background Burning mouth syndrome (BMS) is a chronic and spontaneous oral pain with burning quality in the tongue or other oral mucosa without any identifiable oral lesion or laboratory finding. Pathogenesis and etiology of BMS are still unknown. However, BMS has been associated with other chronic pain syndromes including other idiopathic orofacial pain, the dynias group and the family of central sensitivity syndromes. This would imply that BMS shares common mechanisms with other cephalic and/or extracephalic chronic pains. The primary aim of this systematic review was to determine whether BMS is actually associated with other pain syndromes, and to analyze cephalic and extracephalic somatosensory sensitivity in these patients. Methods This report followed the PRISMA Statement. An electronic search was performed until January 2015 in PubMed, Cochrane library, Wiley and ScienceDirect. Searched terms included “burning mouth syndrome OR stomatodynia OR glossodynia OR burning tongue OR oral burning”. Studies were selected according to predefined inclusion criteria (report of an association between BMS and other pain(s) symptoms or of cutaneous cephalic and/or extracephalic quantitative sensory testing in BMS patients), and a descriptive analysis conducted. Results The search retrieved 1512 reports. Out of these, twelve articles met criteria for co-occurring pain symptoms and nine studies for quantitative sensory testing (QST) in BMS patients. The analysis reveals that in BMS patients co-occurring pain symptoms are rare, assessed by only 0.8% (12 of 1512) of the retrieved studies. BMS was associated with headaches, TMD, atypical facial pain, trigeminal neuralgia, post-herpetic facial pain, back pain, fibromyalgia, joint pain, abdominal pain, rectal pain or vulvodynia. However, the prevalence of pain symptoms in BMS patients is not different from that in the age-matched general population. QST studies reveal no or inconsistent evidence of abnormal cutaneous cephalic and extracephalic somatosensory sensitivity. Conclusions There is no evidence for a high rate of other pain symptoms or somatosensory impairments co-occurring with BMS. These results thus suggest that BMS rather depends on specific mechanisms, likely at the trigeminal level. Nevertheless, more thoroughly conducted research is required to draw definitive conclusion. PMID:27657531

Targeting Notch1 signaling pathway positively affects the sensitivity of osteosarcoma to cisplatin by regulating the expression and/or activity of Caspase family

PubMed Central

2014-01-01

Background The introduction of cisplatin has improved the long-term survival rate in osteosarcoma patients. However, some patients are intrinsically resistant to cisplatin. This study reported that the activation of Notch1 is positively correlated with cisplatin sensitivity, evidenced by both clinical and in vitro data. Results In this study, a total 8 osteosarcoma specimens were enrolled and divided into two groups according to their cancer chemotherapeutic drugs sensitivity examination results. The relationship between Notch1 expression and cisplatin sensitivity of osteosarcoma patients was detected by immunohistochemistry and semi-quantitative analysis. Subsequently, two typical osteosarcoma cell lines, Saos-2 and MG63, were selected to study the changes of cisplatin sensitivity by up-regulating (NICD1 plasmid transfeciton) or decreasing (gamma-secretase complex inhibitor DAPT) the activation state of Notch1 signaling pathway. Our results showed a significant correlation between the expression of Notch1 and cisplatin sensitivity in patient specimens. In vitro, Saos-2 with higher expression of Notch1 had significantly better cisplatin sensitivity than MG63 whose Notch1 level was relatively lower. By targeting regulation in vitro, the cisplatin sensitivity of Saos-2 and MG63 had significantly increased after the activation of Notch1 signaling pathway, and vice versa. Further mechanism investigation revealed that activation/inhibition of Notch1 sensitized/desensitized cisplatin-induced apoptosis, which probably depended on the changes in the activity of Caspase family, including Caspase 3, Caspase 8 and Caspase 9 in these cells. Conclusions Our data clearly demonstrated that Notch1 is critical for cisplatin sensitivity in osteosarcoma. It can be used as a molecular marker and regulator for cisplatin sensitivity in osteosarcoma patients. PMID:24894297

The performance of the SEPT9 gene methylation assay and a comparison with other CRC screening tests: A meta-analysis.

PubMed

Song, Lele; Jia, Jia; Peng, Xiumei; Xiao, Wenhua; Li, Yuemin

2017-06-08

The SEPT9 gene methylation assay is the first FDA-approved blood assay for colorectal cancer (CRC) screening. Fecal immunochemical test (FIT), FIT-DNA test and CEA assay are also in vitro diagnostic (IVD) tests used in CRC screening. This meta-analysis aims to review the SEPT9 assay performance and compare it with other IVD CRC screening tests. By searching the Ovid MEDLINE, EMBASE, CBMdisc and CJFD database, 25 out of 180 studies were identified to report the SEPT9 assay performance. 2613 CRC cases and 6030 controls were included, and sensitivity and specificity were used to evaluate its performance at various algorithms. 1/3 algorithm exhibited the best sensitivity while 2/3 and 1/1 algorithm exhibited the best balance between sensitivity and specificity. The performance of the blood SEPT9 assay is superior to that of the serum protein markers and the FIT test in symptomatic population, while appeared to be less potent than FIT and FIT-DNA tests in asymptomatic population. In conclusion, 1/3 algorithm is recommended for CRC screening, and 2/3 or 1/1 algorithms are suitable for early detection for diagnostic purpose. The SEPT9 assay exhibited better performance in symptomatic population than in asymptomatic population.

Transvaginal ultrasound versus magnetic resonance imaging for preoperative assessment of myometrial infiltration in patients with endometrial cancer: a systematic review and meta-analysis

PubMed Central

2017-01-01

Objective To compare the diagnostic accuracy of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) for detecting myometrial infiltration (MI) in endometrial carcinoma. Methods An extensive search of papers comparing TVS and MRI in assessing MI in endometrial cancer was performed in MEDLINE (PubMed), Web of Science, and Cochrane Database from January 1989 to January 2017. Quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results Our extended search identified 747 citations but after exclusions we finally included in the meta-analysis 8 articles. The risk of bias for most studies was low for most 4 domains assessed in QUADAS-2. Overall, pooled estimated sensitivity and specificity for diagnosing deep MI were 75% (95% confidence interval [CI]=67%–82%) and 82% (95% CI=75%–93%) for TVS, and 83% (95% CI=76%–89%) and 82% (95% CI=72%–89%) for MRI, respectively. No statistical differences were found when comparing both methods (p=0.314). Heterogeneity was low for sensitivity and high for specificity for TVS and MRI. Conclusion MRI showed a better sensitivity than TVS for detecting deep MI in women with endometrial cancer. However, the difference observed was not statistically significant. PMID:29027404

Specific detection of Mycobacterium sp. genomic DNA using dual labeled gold nanoparticle based electrochemical biosensor.

PubMed

Thiruppathiraja, Chinnasamy; Kamatchiammal, Senthilkumar; Adaikkappan, Periyakaruppan; Santhosh, Devakirubakaran Jayakar; Alagar, Muthukaruppan

2011-10-01

The present study was aimed at the development and evaluation of a DNA electrochemical biosensor for Mycobacterium sp. genomic DNA detection in a clinical specimen using a signal amplifier as dual-labeled AuNPs. The DNA electrochemical biosensors were fabricated using a sandwich detection strategy involving two kinds of DNA probes specific to Mycobacterium sp. genomic DNA. The probes of enzyme ALP and the detector probe both conjugated on the AuNPs and subsequently hybridized with target DNA immobilized in a SAM/ITO electrode followed by characterization with CV, EIS, and DPV analysis using the electroactive species para-nitrophenol generated by ALP through hydrolysis of para-nitrophenol phosphate. The effect of enhanced sensitivity was obtained due to the AuNPs carrying numerous ALPs per hybridization and a detection limit of 1.25 ng/ml genomic DNA was determined under optimized conditions. The dual-labeled AuNP-facilitated electrochemical sensor was also evaluated by clinical sputum samples, showing a higher sensitivity and specificity and the outcome was in agreement with the PCR analysis. In conclusion, the developed electrochemical sensor demonstrated unique sensitivity and specificity for both genomic DNA and sputum samples and can be employed as a regular diagnostics tool for Mycobacterium sp. monitoring in clinical samples. Copyright © 2011 Elsevier Inc. All rights reserved.

Phenotypic and transcriptional response to selection for alcohol sensitivity in Drosophila melanogaster

PubMed Central

Morozova, Tatiana V; Anholt, Robert RH; Mackay, Trudy FC

2007-01-01

Background Alcoholism is a complex disorder determined by interactions between genetic and environmental risk factors. Drosophila represents a powerful model system to dissect the genetic architecture of alcohol sensitivity, as large numbers of flies can readily be reared in defined genetic backgrounds and under controlled environmental conditions. Furthermore, flies exposed to ethanol undergo physiological and behavioral changes that resemble human alcohol intoxication, including loss of postural control, sedation, and development of tolerance. Results We performed artificial selection for alcohol sensitivity for 35 generations and created duplicate selection lines that are either highly sensitive or resistant to ethanol exposure along with unselected control lines. We used whole genome expression analysis to identify 1,678 probe sets with different expression levels between the divergent lines, pooled across replicates, at a false discovery rate of q < 0.001. We assessed to what extent genes with altered transcriptional regulation might be causally associated with ethanol sensitivity by measuring alcohol sensitivity of 37 co-isogenic P-element insertional mutations in 35 candidate genes, and found that 32 of these mutants differed in sensitivity to ethanol exposure from their co-isogenic controls. Furthermore, 23 of these novel genes have human orthologues. Conclusion Combining whole genome expression profiling with selection for genetically divergent lines is an effective approach for identifying candidate genes that affect complex traits, such as alcohol sensitivity. Because of evolutionary conservation of function, it is likely that human orthologues of genes affecting alcohol sensitivity in Drosophila may contribute to alcohol-associated phenotypes in humans. PMID:17973985

Cost-effectiveness analysis of hypertension treatment: controlled release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension--the Nifedipine and Candesartan Combination (NICE-Combi) Study.

PubMed

Fujikawa, Keita; Hasebe, Naoyuki; Kikuchi, Kenjiro

2005-07-01

Societal interest in pharmaco-economic analysis is increasing in Japan. In this study, the cost-effectiveness of low-dose combination therapy with controlled release nifedipine plus candesartan and up-titrated monotherapy with candesartan was estimated, based on the results of the NICE-Combi study. The NICE-Combi study was a double-blind, parallel arm, randomized clinical trial to compare the efficacy of low-dose combination therapy of controlled release nifedipine (20 mg/day) plus candesartan (8 mg/day) vs. up-titrated monotherapy of candesartan (12 mg/day) on blood pressure control in Japanese patients with mild to severe essential hypertension who were not sufficiently controlled by the conventional dose of candesartan (8 mg/ day). The incremental cost effectiveness of each cohort during the 8-week randomization period was compared, from the perspective of a third-party payer (i.e., insurers). The average total cost per patient was 29,943 Japanese yen for the combination therapy group and 33,182 Japanese yen for the candesartan monotherapy group, while the rate of achievement of the target blood pressure was significantly higher in the combination therapy group than in the up-titrated monotherapy group. In the combination therapy group, higher efficacy and lower incremental treatment cost ("Dominance") were observed when compared to the monotherapy group. The sensitivity analyses also supported the results. In conclusion, these results suggest that combination therapy with controlled release nifedipine and low-dose candesartan (8 mg) is "dominant" to up-titrated candesartan monotherapy for the management of essential hypertension. This conclusion was robust to sensitivity analysis.

Electrodermal Activity Is Sensitive to Cognitive Stress under Water.

PubMed

Posada-Quintero, Hugo F; Florian, John P; Orjuela-Cañón, Alvaro D; Chon, Ki H

2017-01-01

When divers are at depth in water, the high pressure and low temperature alone can cause severe stress, challenging the human physiological control systems. The addition of cognitive stress, for example during a military mission, exacerbates the challenge. In these conditions, humans are more susceptible to autonomic imbalance. Reliable tools for the assessment of the autonomic nervous system (ANS) could be used as indicators of the relative degree of stress a diver is experiencing, which could reveal heightened risk during a mission. Electrodermal activity (EDA), a measure of the changes in conductance at the skin surface due to sweat production, is considered a promising alternative for the non-invasive assessment of sympathetic control of the ANS. EDA is sensitive to stress of many kinds. Therefore, as a first step, we tested the sensitivity of EDA, in the time and frequency domains, specifically to cognitive stress during water immersion of the subject (albeit with their measurement finger dry for safety). The data from 14 volunteer subjects were used from the experiment. After a 4-min adjustment and baseline period after being immersed in water, subjects underwent the Stroop task, which is known to induce cognitive stress. The time-domain indices of EDA, skin conductance level (SCL) and non-specific skin conductance responses (NS.SCRs), did not change during cognitive stress, compared to baseline measurements. Frequency-domain indices of EDA, EDASymp (based on power spectral analysis) and TVSymp (based on time-frequency analysis), did significantly change during cognitive stress. This leads to the conclusion that EDA, assessed by spectral analysis, is sensitive to cognitive stress in water-immersed subjects, and can potentially be used to detect cognitive stress in divers.

Evaluating linguistic equivalence of patient-reported outcomes in a cancer clinical trial.

PubMed

Hahn, Elizabeth A; Bode, Rita K; Du, Hongyan; Cella, David

2006-01-01

In order to make meaningful cross-cultural or cross-linguistic comparisons of health-related quality of life (HRQL) or to pool international research data, it is essential to create unbiased measures that can detect clinically important differences. When HRQL scores differ between cultural/linguistic groups, it is important to determine whether this reflects real group differences, or is the result of systematic measurement variability. To investigate the linguistic measurement equivalence of a cancer-specific HRQL questionnaire, and to conduct a sensitivity analysis of treatment differences in HRQL in a clinical trial. Patients with newly diagnosed chronic myelogenous leukemia (n = 1049) completed serial HRQL assessments in an international Phase III trial. Two types of differential item functioning (uniform and non-uniform) were evaluated using item response theory and classical test theory approaches. A sensitivity analysis was conducted to compare HRQL between treatment arms using items without evidence of differential functioning. Among 27 items, nine (33%) did not exhibit any evidence of differential functioning in both linguistic comparisons (English versus French, English versus German). Although 18 items functioned differently, there was no evidence of systematic bias. In a sensitivity analysis, adjustment for differential functioning affected the magnitude, but not the direction or interpretation of clinical trial treatment arm differences. Sufficient sample sizes were available for only three of the eight language groups. Identification of differential functioning in two-thirds of the items suggests that current psychometric methods may be too sensitive. Enhanced methodologies are needed to differentiate trivial from substantive differential item functioning. Systematic variability in HRQL across different groups can be evaluated for its effect upon clinical trial results; a practice recommended when data are pooled across cultural or linguistic groups to make conclusions about treatment effects.

Dose-dependent testosterone sensitivity of the steroidal passport and GC-C-IRMS analysis in relation to the UGT2B17 deletion polymorphism.

PubMed

Strahm, Emmanuel; Mullen, Jenny E; Gårevik, Nina; Ericsson, Magnus; Schulze, Jenny J; Rane, Anders; Ekström, Lena

2015-01-01

The newly implemented Steroid Module of the Athlete Biological Passport has improved doping tests for steroids. A biomarker included in this passport is the urinary testosterone glucuronide to epitestosterone glucuronide (T/E) ratio, a ratio greatly affected by a deletion polymorphism in UGT2B17. Suspect urine doping tests are further analyzed with gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) to determine the origin of the androgen. In this study, we investigated the sensitivity of the steroidal module and the IRMS analysis, in subjects administered with three doses of testosterone enanthate (500, 250, and 125 mg), in relation to the UGT2B17 polymorphism. All subjects carrying the UGT2B17 enzyme reached the traditionally used threshold, a T/E ratio of 4, after all three administered doses, whereas none of the subjects devoid of this enzyme reached a T/E of 4. On the other hand, using the athlete biological passport and IRMS analysis, all three doses could be detected to a high degree of sensitivity. The concentrations of all steroids included in the steroidal module were dose dependently increased, except for epitestosterone which decreased independent of dose. The decrease in epitestosterone was significantly associated with circulatory levels of testosterone post dose (rs =0.60 and p=0.007). In conclusion, these results demonstrate that administration of a single dose of 125-500 mg testosterone enanthate could be detected using the athlete biological passport, together with IRMS. Since IRMS is sensitive to testosterone doping independent of UGT2B17 genotype, also very small changes in the steroidal passport should be investigated with IRMS. Copyright © 2015 John Wiley & Sons, Ltd.

Ignoring correlation in uncertainty and sensitivity analysis in life cycle assessment: what is the risk?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Groen, E.A., E-mail: Evelyne.Groen@gmail.com; Heijungs, R.; Leiden University, Einsteinweg 2, Leiden 2333 CC

Life cycle assessment (LCA) is an established tool to quantify the environmental impact of a product. A good assessment of uncertainty is important for making well-informed decisions in comparative LCA, as well as for correctly prioritising data collection efforts. Under- or overestimation of output uncertainty (e.g. output variance) will lead to incorrect decisions in such matters. The presence of correlations between input parameters during uncertainty propagation, can increase or decrease the the output variance. However, most LCA studies that include uncertainty analysis, ignore correlations between input parameters during uncertainty propagation, which may lead to incorrect conclusions. Two approaches to include correlationsmore » between input parameters during uncertainty propagation and global sensitivity analysis were studied: an analytical approach and a sampling approach. The use of both approaches is illustrated for an artificial case study of electricity production. Results demonstrate that both approaches yield approximately the same output variance and sensitivity indices for this specific case study. Furthermore, we demonstrate that the analytical approach can be used to quantify the risk of ignoring correlations between input parameters during uncertainty propagation in LCA. We demonstrate that: (1) we can predict if including correlations among input parameters in uncertainty propagation will increase or decrease output variance; (2) we can quantify the risk of ignoring correlations on the output variance and the global sensitivity indices. Moreover, this procedure requires only little data. - Highlights: • Ignoring correlation leads to under- or overestimation of the output variance. • We demonstrated that the risk of ignoring correlation can be quantified. • The procedure proposed is generally applicable in life cycle assessment. • In some cases, ignoring correlation has a minimal effect on decision-making tools.« less

Prediction of the severity of acute pancreatitis on admission by urinary trypsinogen activation peptide: A meta-analysis

PubMed Central

Huang, Wei; Altaf, Kiran; Jin, Tao; Xiong, Jun-Jie; Wen, Li; Javed, Muhammad A; Johnstone, Marianne; Xue, Ping; Halloran, Christopher M; Xia, Qing

2013-01-01

AIM: To undertake a meta-analysis on the value of urinary trypsinogen activation peptide (uTAP) in predicting severity of acute pancreatitis on admission. METHODS: Major databases including Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched to identify all relevant studies from January 1990 to January 2013. Pooled sensitivity, specificity and the diagnostic odds ratios (DORs) with 95%CI were calculated for each study and were compared to other systems/biomarkers if mentioned within the same study. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated. RESULTS: In total, six studies of uTAP with a cut-off value of 35 nmol/L were included in this meta-analysis. Overall, the pooled sensitivity and specificity of uTAP for predicting severity of acute pancreatitis, at time of admission, was 71% and 75%, respectively (AUC = 0.83, DOR = 8.67, 95%CI: 3.70-20.33). When uTAP was compared with plasma C-reactive protein, the pooled sensitivity, specificity, AUC and DOR were 0.64 vs 0.67, 0.77 vs 0.75, 0.82 vs 0.79 and 6.27 vs 6.32, respectively. Similarly, the pooled sensitivity, specificity, AUC and DOR of uTAP vs Acute Physiology and Chronic Health Evaluation II within the first 48 h of admission were found to be 0.64 vs 0.69, 0.77 vs 0.61, 0.82 vs 0.73 and 6.27 vs 4.61, respectively. CONCLUSION: uTAP has the potential to act as a stratification marker on admission for differentiating disease severity of acute pancreatitis. PMID:23901239

Automatic Segmentation of Invasive Breast Carcinomas from DCE-MRI using Time Series Analysis

PubMed Central

Jayender, Jagadaeesan; Chikarmane, Sona; Jolesz, Ferenc A.; Gombos, Eva

2013-01-01

Purpose Quantitative segmentation methods based on black-box modeling and pharmacokinetic modeling are highly dependent on imaging pulse sequence, timing of bolus injection, arterial input function, imaging noise and fitting algorithms. To accurately segment invasive ductal carcinomas (IDCs) from dynamic contrast enhanced MRI (DCE-MRI) using time series analysis based on linear dynamic system (LDS) modeling. Methods We modeled the underlying dynamics of the tumor by a LDS and use the system parameters to segment the carcinoma on the DCE-MRI. Twenty-four patients with biopsy-proven IDCs were analyzed. The lesions segmented by the algorithm were compared with an expert radiologist’s segmentation and the output of a commercial software, CADstream. The results are quantified in terms of the accuracy and sensitivity of detecting the lesion and the amount of overlap, measured in terms of the Dice similarity coefficient (DSC). Results The segmentation algorithm detected the tumor with 90% accuracy and 100% sensitivity when compared to the radiologist’s segmentation and 82.1% accuracy and 100% sensitivity when compared to the CADstream output. The overlap of the algorithm output with the radiologist’s segmentation and CADstream output, computed in terms of the DSC was 0.77 and 0.72 respectively. The algorithm also shows robust stability to imaging noise. Simulated imaging noise with zero mean and standard deviation equal to 25% of the base signal intensity was added to the DCE-MRI series. The amount of overlap between the tumor maps generated by the LDS-based algorithm from the noisy and original DCE-MRI was DSC=0.95. Conclusion The time-series analysis based segmentation algorithm provides high accuracy and sensitivity in delineating the regions of enhanced perfusion corresponding to tumor from DCE-MRI. PMID:24115175

Knock-in mice harboring a Ca(2+) desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy.

PubMed

McConnell, Bradley K; Singh, Sonal; Fan, Qiying; Hernandez, Adriana; Portillo, Jesus P; Reiser, Peter J; Tikunova, Svetlana B

2015-01-01

The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca(2+) sensitivity of reconstituted thin filaments by increasing the rate of Ca(2+) dissociation. In addition, the D73N mutation drastically blunted the extent of Ca(2+) desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca(2+) sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca(2+) sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM.

[Assessment of the validity and utility of the Beijing questionnaire as atool to evaluate for obstructive sleep apnea hypopnea syndrome].

PubMed

Wang, X T; Gao, L M; Xu, W; Ding, X

2016-10-20

Objective: To test the Beijing questionnaire as a means of identifying patients with obstructive sleep apnea hypopnea syndrome（OSAHS）. Method: The Beijing questionnaire is designed as an explorative tool consist of 11 questions for patients with obstructive sleep apnea hypopnea, and is targeted toward key symptoms include snoring, apneas, daytime sleepiness, hypertension and overweight. 1 336 female participants living in communities of age≥40 years and 198 male adult subjects visting clinics were given questionnaires. Finally, 59 female and 198 male subjects underwent sleep studies after factor analysis,reliability check,internal consistency study. The correlation analysis was performed between the scores from the Beijing questionnaire and the apnea-hypopnea index from inlaboratory polysomnography.Receiver operating characteristics were constructed to determine optimal sensitivity and specificity. Twenty-four male subjects were recorded in the sleep laberatory again after operative. Result: Factor analysis reduced 11 questions of scale to four common factors as we have designed: snoring,apneas,other symptoms,risk factors. Cronbach's α coefficient of scale reached 0.7.There were an acceptable level of testretest reliability(r=0.619, P <0.01).The apnea hypopnea indices were significantly correlated with their Beijing questionnaire scores( P <0.01).For wemen,an Beijing questionnaire scroe of 19.5 provided a sensitivity of 74.3% and a specificity of 62.5%.For men,an Beijing questionnaire scroe of 22.5 provided a sensitivity of 90.9% and a specificity of 54.5%. And the postoperative Beijing questionnaire scroes changed with the apnea hypopnea indices. Conclusion: This questionnaire has a good validity and reliability and appears to be valid and sensitive to clinical change. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Performance of screening questionnaires for obstructive sleep apnea during pregnancy: A systematic review and meta-analysis.

PubMed

Tantrakul, Visasiri; Numthavaj, Pawin; Guilleminault, Christian; McEvoy, Mark; Panburana, Panyu; Khaing, Win; Attia, John; Thakkinstian, Ammarin

2017-12-01

This review aims to evaluate the performance of obstructive sleep apnea (OSA) screening questionnaires during pregnancy. A systematic review and meta-analysis was performed using MEDLINE Scopus, CINAHL, and the Cochrane library. A bivariate meta-analysis was applied for pooling of diagnostic parameters. Six of the total 4719 articles met the inclusion criteria. The Berlin questionnaire (BQ, N = 604) and Epworth sleepiness scale (ESS, N = 420) were the most frequently used screening tools during pregnancy. The pooled prevalence of OSA during pregnancy was 26.7% (95%CI: 16.9%, 34.4%, I 2  = 83.15%). BQ performance was poor to fair with pooled sensitivity and specificity of 0.66 (95%CI: 0.45, 0.83; I 2  = 78.65%) and 0.62 (95%CI: 0.48, 0.75; I 2  = 81.55%), respectively. BQ performance was heterogeneous depending on type of reference test and pregnancy. Sensitivity increased if diagnosis was based on polysomnography (0.90), and respiratory disturbance index (0.90). However, sensitivity decreased if screening was performed in early pregnancy (≤20 weeks gestation: 0.47), and high-risk pregnancy (0.44). Performance of ESS was poor with pooled sensitivity and specificity of 0.44 (95%CI: 0.33, 0.56; I 2  = 32.8%) and 0.62 (95%CI: 0.48, 0.75; I 2  = 81.55%), respectively. In conclusion, BQ and ESS showed poor performance during pregnancy, hence a new OSA screening questionnaire is needed. Registration: PROSPERO registration CRD42015025848. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

High-Speed Real-Time Resting-State fMRI Using Multi-Slab Echo-Volumar Imaging

PubMed Central

Posse, Stefan; Ackley, Elena; Mutihac, Radu; Zhang, Tongsheng; Hummatov, Ruslan; Akhtari, Massoud; Chohan, Muhammad; Fisch, Bruce; Yonas, Howard

2013-01-01

We recently demonstrated that ultra-high-speed real-time fMRI using multi-slab echo-volumar imaging (MEVI) significantly increases sensitivity for mapping task-related activation and resting-state networks (RSNs) compared to echo-planar imaging (Posse et al., 2012). In the present study we characterize the sensitivity of MEVI for mapping RSN connectivity dynamics, comparing independent component analysis (ICA) and a novel seed-based connectivity analysis (SBCA) that combines sliding-window correlation analysis with meta-statistics. This SBCA approach is shown to minimize the effects of confounds, such as movement, and CSF and white matter signal changes, and enables real-time monitoring of RSN dynamics at time scales of tens of seconds. We demonstrate highly sensitive mapping of eloquent cortex in the vicinity of brain tumors and arterio-venous malformations, and detection of abnormal resting-state connectivity in epilepsy. In patients with motor impairment, resting-state fMRI provided focal localization of sensorimotor cortex compared with more diffuse activation in task-based fMRI. The fast acquisition speed of MEVI enabled segregation of cardiac-related signal pulsation using ICA, which revealed distinct regional differences in pulsation amplitude and waveform, elevated signal pulsation in patients with arterio-venous malformations and a trend toward reduced pulsatility in gray matter of patients compared with healthy controls. Mapping cardiac pulsation in cortical gray matter may carry important functional information that distinguishes healthy from diseased tissue vasculature. This novel fMRI methodology is particularly promising for mapping eloquent cortex in patients with neurological disease, having variable degree of cooperation in task-based fMRI. In conclusion, ultra-high-real-time speed fMRI enhances the sensitivity of mapping the dynamics of resting-state connectivity and cerebro-vascular pulsatility for clinical and neuroscience research applications. PMID:23986677

Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhao, Jianhua; Zeng, Haishan; Kalia, Sunil; Lui, Harvey

2017-02-01

Background: Raman spectroscopy is a non-invasive optical technique which can measure molecular vibrational modes within tissue. A large-scale clinical study (n = 518) has demonstrated that real-time Raman spectroscopy could distinguish malignant from benign skin lesions with good diagnostic accuracy; this was validated by a follow-up independent study (n = 127). Objective: Most of the previous diagnostic algorithms have typically been based on analyzing the full band of the Raman spectra, either in the fingerprint or high wavenumber regions. Our objective in this presentation is to explore wavenumber selection based analysis in Raman spectroscopy for skin cancer diagnosis. Methods: A wavenumber selection algorithm was implemented using variably-sized wavenumber windows, which were determined by the correlation coefficient between wavenumbers. Wavenumber windows were chosen based on accumulated frequency from leave-one-out cross-validated stepwise regression or least and shrinkage selection operator (LASSO). The diagnostic algorithms were then generated from the selected wavenumber windows using multivariate statistical analyses, including principal component and general discriminant analysis (PC-GDA) and partial least squares (PLS). A total cohort of 645 confirmed lesions from 573 patients encompassing skin cancers, precancers and benign skin lesions were included. Lesion measurements were divided into training cohort (n = 518) and testing cohort (n = 127) according to the measurement time. Result: The area under the receiver operating characteristic curve (ROC) improved from 0.861-0.891 to 0.891-0.911 and the diagnostic specificity for sensitivity levels of 0.99-0.90 increased respectively from 0.17-0.65 to 0.20-0.75 by selecting specific wavenumber windows for analysis. Conclusion: Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels.

Acoustic Radiation Force Impulse Imaging for the Differentiation of Benign and Malignant Lymph Nodes: A Systematic Review and Meta-Analysis

PubMed Central

Yu, Cheng; Xie, Mingxing; Lv, Qing

2016-01-01

Objective To evaluate the overall performance of acoustic radiation force impulse imaging (ARFI) in differentiating between benign and malignant lymph nodes (LNs) by conducting a meta-analysis. Methods PubMed, Embase, Web of Science, the Cochrane Library and the China National Knowledge Infrastructure were comprehensively searched for potential studies through August 13th, 2016. Studies that investigated the diagnostic power of ARFI for the differential diagnosis of benign and malignant LNs by using virtual touch tissue quantification (VTQ) or virtual touch tissue imaging quantification (VTIQ) were collected. The included articles were published in English or Chinese. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the methodological quality. The pooled sensitivity, specificity, and the area under the summary receiver operating characteristic (SROC) curve (AUC) were calculated by means of a bivariate mixed-effects regression model. Meta-regression analysis was performed to identify the potential sources of between study heterogeneity. Fagan plot analysis was used to explore the clinical utilities. Publication bias was assessed using Deek’s funnel plot. Results Nine studies involving 1084 LNs from 929 patients were identified to analyze in the meta-analysis. The summary sensitivity and specificity of ARFI in detecting malignant LNs were 0.87 (95% confidence interval [CI], 0.83–0.91) and 0.88 (95% CI, 0.82–0.92), respectively. The AUC was 0.93 (95% CI, 0.90–0.95). The pooled DOR was 49.59 (95% CI, 26.11–94.15). Deek’s funnel plot revealed no significant publication bias. Conclusion ARFI is a promising tool for the differentiation of benign and malignant LNs with high sensitivity and specificity. PMID:27855188

Optical Coherence Tomography Minimum Intensity as an Objective Measure for the Detection of Hydroxychloroquine Toxicity

PubMed Central

Allahdina, Ali M.; Stetson, Paul F.; Vitale, Susan; Wong, Wai T.; Chew, Emily Y.; Ferris, Fredrick L.; Sieving, Paul A.

2018-01-01

Purpose As optical coherence tomography (OCT) minimum intensity (MI) analysis provides a quantitative assessment of changes in the outer nuclear layer (ONL), we evaluated the ability of OCT-MI analysis to detect hydroxychloroquine toxicity. Methods Fifty-seven predominantly female participants (91.2% female; mean age, 55.7 ± 10.4 years; mean time on hydroxychloroquine, 15.0 ± 7.5 years) were enrolled in a case-control study and categorized into affected (i.e., with toxicity, n = 19) and unaffected (n = 38) groups using objective multifocal electroretinographic (mfERG) criteria. Spectral-domain OCT scans of the macula were analyzed and OCT-MI values quantitated for each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. A two-sample U-test and a cross-validation approach were used to assess the sensitivity and specificity of toxicity detection according to OCT-MI criteria. Results The medians of the OCT-MI values in all nine of the ETDRS subfields were significantly elevated in the affected group relative to the unaffected group (P < 0.005 for all comparisons), with the largest difference found for the inner inferior subfield (P < 0.0001). The receiver operating characteristic analysis of median MI values of the inner inferior subfields showed high sensitivity and high specificity in the detection of toxicity with area under the curve = 0.99. Conclusions Retinal changes secondary to hydroxychloroquine toxicity result in increased OCT reflectivity in the ONL that can be detected and quantitated using OCT-MI analysis. Analysis of OCT-MI values demonstrates high sensitivity and specificity for detecting the presence of hydroxychloroquine toxicity in this cohort and may contribute additionally to current screening practices. PMID:29677357

MRI-Guided Focused Ultrasound Surgery for Uterine Fibroid Treatment: A Cost-Effectiveness Analysis

PubMed Central

Kong, Chung Y.; Omer, Zehra B.; Pandharipande, Pari V.; Swan, J. Shannon; Srouji, Serene; Gazelle, G. Scott; Fennessy, Fiona M.

2015-01-01

Objective To evaluate the cost-effectiveness of a treatment strategy for symptomatic uterine fibroids that employs Magnetic Resonance guided Focused Ultrasound (MRgFUS) as a first-line therapy relative to uterine artery embolization (UAE) or abdominal hysterectomy (HYST). Materials and Methods We developed a decision-analytic model to compare the cost-effectiveness of three treatment strategies: MRgFUS, UAE and HYST. Short and long-term utilities specific to each treatment were incorporated, allowing us to account for differences in quality of life across the strategies considered. Lifetime costs and quality-adjusted life-years (QALYs) were calculated for each strategy. An incremental cost-effectiveness analysis was performed, using a societal willingness-to-pay (WTP) threshold of $50,000 per QALY to designate a strategy as cost-effective. Sensitivity analysis was performed on all key model parameters. Results In the base-case analysis, in which treatment for symptomatic fibroids started at age 40, UAE was the most effective and expensive strategy (22.81 QALYs, $22,164), followed by MRgFUS (22.80 QALYs, $19,796) and HYST (22.60 QALYs, $13,291). MRgFUS was cost-effective relative to HYST, with an associated incremental cost-effectiveness ratio (ICER) of $33,110/QALY. MRgFUS was also cost-effective relative to UAE – the ICER of UAE relative to MRgFUS ($270,057) far exceeded the WTP threshold of $50,000/QALY. In sensitivity analysis, results were robust to changes in most parameters, but were sensitive to changes in probabilities of recurrence and symptom relief following certain procedures, and quality of life associated with symptomatic fibroids. Conclusions MRgFUS is cost-effective relative to both UAE and hysterectomy for the treatment of women with symptomatic fibroids. PMID:25055272

Economic Evaluation of First-Line Treatments for Metastatic Renal Cell Carcinoma: A Cost-Effectiveness Analysis in A Health Resource–Limited Setting

PubMed Central

Wu, Bin; Dong, Baijun; Xu, Yuejuan; Zhang, Qiang; Shen, Jinfang; Chen, Huafeng; Xue, Wei

2012-01-01

Background To estimate, from the perspective of the Chinese healthcare system, the economic outcomes of five different first-line strategies among patients with metastatic renal cell carcinoma (mRCC). Methods and Findings A decision-analytic model was developed to simulate the lifetime disease course associated with renal cell carcinoma. The health and economic outcomes of five first-line strategies (interferon-alfa, interleukin-2, interleukin-2 plus interferon-alfa, sunitinib and bevacizumab plus interferon-alfa) were estimated and assessed by indirect comparison. The clinical and utility data were taken from published studies. The cost data were estimated from local charge data and current Chinese practices. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the sunitinib patient assistant program (SPAP) was evaluated via scenario analysis. The base-case analysis showed that the sunitinib strategy yielded the maximum health benefits: 2.71 life years and 1.40 quality-adjusted life-years (QALY). The marginal cost-effectiveness (cost per additional QALY) gained via the sunitinib strategy compared with the conventional strategy was $220,384 (without SPAP, interleukin-2 plus interferon-alfa and bevacizumab plus interferon-alfa were dominated) and $16,993 (with SPAP, interferon-alfa, interleukin-2 plus interferon-alfa and bevacizumab plus interferon-alfa were dominated). In general, the results were sensitive to the hazard ratio of progression-free survival. The probabilistic sensitivity analysis demonstrated that the sunitinib strategy with SPAP was the most cost-effective approach when the willingness-to-pay threshold was over $16,000. Conclusions Our analysis suggests that traditional cytokine therapy is the cost-effective option in the Chinese healthcare setting. In some relatively developed regions, sunitinib with SPAP may be a favorable cost-effective alternative for mRCC. PMID:22412884

Ultrasound for Distal Forearm Fracture: A Systematic Review and Diagnostic Meta-Analysis

PubMed Central

Douma-den Hamer, Djoke; Blanker, Marco H.; Edens, Mireille A.; Buijteweg, Lonneke N.; Boomsma, Martijn F.; van Helden, Sven H.; Mauritz, Gert-Jan

2016-01-01

Study Objective To determine the diagnostic accuracy of ultrasound for detecting distal forearm fractures. Methods A systematic review and diagnostic meta-analysis was performed according to the PRISMA statement. We searched MEDLINE, Web of Science and the Cochrane Library from inception to September 2015. All prospective studies of the diagnostic accuracy of ultrasound versus radiography as the reference standard were included. We excluded studies with a retrospective design and those with evidence of verification bias. We assessed the methodological quality of the included studies with the QUADAS-2 tool. We performed a meta-analysis of studies evaluating ultrasound to calculate the pooled sensitivity and specificity with 95% confidence intervals (CI95%) using a bivariate model with random effects. Subgroup and sensitivity analysis were used to examine the effect of methodological differences and other study characteristics. Results Out of 867 publications we included 16 studies with 1,204 patients and 641 fractures. The pooled test characteristics for ultrasound were: sensitivity 97% (CI95% 93–99%), specificity 95% (CI95% 89–98%), positive likelihood ratio (LR) 20.0 (8.5–47.2) and negative LR 0.03 (0.01–0.08). The corresponding pooled diagnostic odds ratio (DOR) was 667 (142–3,133). Apparent differences were shown for method of viewing, with the 6-view method showing higher specificity, positive LR, and DOR, compared to the 4-view method. Conclusion The present meta-analysis showed that ultrasound has a high accuracy for the diagnosis of distal forearm fractures in children when used by proper viewing method. Based on this, ultrasound should be considered a reliable alternative, which has the advantages of being radiation free. PMID:27196439

Measurement Consistency from Magnetic Resonance Images

PubMed Central

Chung, Dongjun; Chung, Moo K.; Durtschi, Reid B.; Lindell, R. Gentry; Vorperian, Houri K.

2010-01-01

Rationale and Objectives In quantifying medical images, length-based measurements are still obtained manually. Due to possible human error, a measurement protocol is required to guarantee the consistency of measurements. In this paper, we review various statistical techniques that can be used in determining measurement consistency. The focus is on detecting a possible measurement bias and determining the robustness of the procedures to outliers. Materials and Methods We review correlation analysis, linear regression, Bland-Altman method, paired t-test, and analysis of variance (ANOVA). These techniques were applied to measurements, obtained by two raters, of head and neck structures from magnetic resonance images (MRI). Results The correlation analysis and the linear regression were shown to be insufficient for detecting measurement inconsistency. They are also very sensitive to outliers. The widely used Bland-Altman method is a visualization technique so it lacks the numerical quantification. The paired t-test tends to be sensitive to small measurement bias. On the other hand, ANOVA performs well even under small measurement bias. Conclusion In almost all cases, using only one method is insufficient and it is recommended to use several methods simultaneously. In general, ANOVA performs the best. PMID:18790405

Costs and Effects of a Telephonic Diabetes Self-Management Support Intervention Using Health Educators

PubMed Central

Schechter, Clyde B.; Walker, Elizabeth A.; Ortega, Felix M.; Chamany, Shadi; Silver, Lynn D.

2015-01-01

Background Self-management is crucial to successful glycemic control in patients with diabetes, yet it requires patients to initiate and sustain complicated behavioral changes. Support programs can improve glycemic control, but may be expensive to implement. We report here an analysis of the costs of a successful telephone-based self-management support program delivered by lay health educators utilizing a municipal health department A1c registry, and relate them to near-term effectiveness. Methods Costs of implementation were assessed by micro-costing of all resources used. Per-capita costs and cost-effectiveness ratios from the perspective of the service provider are estimated for net A1c reduction, and percentages of patients achieving A1c reductions of 0.5 and 1.0 percentage points. Oneway sensitivity analyses of key cost elements, and a Monte Carlo sensitivity analysis are reported. Results The telephone intervention was provided to 443 people at a net cost of $187.61 each. Each percentage point of net A1c reduction was achieved at a cost of $464.41. Labor costs were the largest component of costs, and cost-effectiveness was most sensitive to the wages paid to the health educators. Conclusions Effective telephone-based self-management support for people in poor diabetes control can be delivered by health educators at moderate cost relative to the gains achieved. The costs of doing so are most sensitive to the prevailing wage for the health educators. PMID:26750743

Altered sensitivity to ellagic acid in neuroblastoma cells undergoing differentiation with 12-O-tetradecanoylphorbol-13-acetate and all-trans retinoic acid.

PubMed

Alfredsson, Christina Fjæraa; Rendel, Filip; Liang, Qui-Li; Sundström, Birgitta E; Nånberg, Eewa

2015-12-01

Ellagic acid has previously been reported to induce reduced proliferation and activation of apoptosis in several tumor cell lines including our own previous data from non-differentiated human neuroblastoma SH-SY5Y cells. The aim of this study was now to investigate if in vitro differentiation with the phorbol ester 12-O- tetradecanoylphorbol-13-acetate or the vitamin A derivative all-trans retinoic acid altered the sensitivity to ellagic acid in SH-SY5Y cells. The methods used were cell counting and LDH-assay for evaluation of cell number and cell death, flow cytometric analysis of SubG1- and TUNEL-analysis for apoptosis and western blot for expression of apoptosis-associated proteins. In vitro differentiation was shown to reduce the sensitivity to ellagic acid with respect to cell detachment, loss of viability and activation of apoptosis. The protective effect was phenotype-specific and most prominent in all-trans retinoic acid-differentiated cultures. Differentiation-dependent up-regulation of Bcl-2 and integrin expression is introduced as possible protective mechanisms. The presented data also point to a positive correlation between proliferative activity and sensitivity to ellagic-acid-induced cell detachment. In conclusion, the presented data emphasize the need to consider degree of neuronal differentiation and phenotype of neuroblastoma cells when discussing a potential pharmaceutical application of ellagic acid in tumor treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Identifying Depressed Older Adults in Primary Care: A Secondary Analysis of a Multisite Randomized Controlled Trial

PubMed Central

Voils, Corrine I.; Olsen, Maren K.; Williams, John W.; for the IMPACT Study Investigators

2008-01-01

Objective: To determine whether a subset of depressive symptoms could be identified to facilitate diagnosis of depression in older adults in primary care. Method: Secondary analysis was conducted on 898 participants aged 60 years or older with major depressive disorder and/or dysthymic disorder (according to DSM-IV criteria) who participated in the Improving Mood–Promoting Access to Collaborative Treatment (IMPACT) study, a multisite, randomized trial of collaborative care for depression (recruitment from July 1999 to August 2001). Linear regression was used to identify a core subset of depressive symptoms associated with decreased social, physical, and mental functioning. The sensitivity and specificity, adjusting for selection bias, were evaluated for these symptoms. The sensitivity and specificity of a second subset of 4 depressive symptoms previously validated in a midlife sample was also evaluated. Results: Psychomotor changes, fatigue, and suicidal ideation were associated with decreased functioning and served as the core set of symptoms. Adjusting for selection bias, the sensitivity of these 3 symptoms was 0.012 and specificity 0.994. The sensitivity of the 4 symptoms previously validated in a midlife sample was 0.019 and specificity was 0.997. Conclusion: We identified 3 depression symptoms that were highly specific for major depressive disorder in older adults. However, these symptoms and a previously identified subset were too insensitive for accurate diagnosis. Therefore, we recommend a full assessment of DSM-IV depression criteria for accurate diagnosis. PMID:18311416

Development of a highly sensitive and specific ELISA method for the determination of l-corydalmine in SD rats with monoclonal antibody.

PubMed

Zhang, Hongwei; Gao, Lan; Shu, Menglin; Liu, Jihua; Yu, Boyang

2018-01-15

l-Corydalmine (l-CDL) is a potent analgesic constituent of the traditional Chinese medicine, Rhizoma Corydalis. However, the pharmacokinetic process and tissue distribution of l-CDL in vivo are still unknown. Therefore, it is necessary to establish a simple and sensitive method to detect l-CDL, which will be helpful to study its distribution and pharmacokinetic process. To determine this compound in biological samples, a monoclonal antibody (mAb) against l-CDL was produced and a fast and highly sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed in this study. The icELISA was applied to determine l-CDL in biological samples. The limit of detection (LOD) of the method was 0.015 ng/mL with a liner range of 1-1000 ng/mL (R 2  = 0.9912). The intra- and inter-day precision were below 15% and the recoveries were within 80-117%. Finally, the developed immunoassay was successfully applied to the analysis of the distribution of l-CDL in SD rats. In conclusion, the icELISA based on the anti-l-CDL mAb could be considered as a highly sensitive and rapid method for the determination of l-CDL in biological samples. The ELISA approach may provide a valuable tool for the analysis of small molecules in biological samples. Copyright © 2017. Published by Elsevier B.V.

Comparison of digital tomosynthesis and chest radiography for the detection of pulmonary nodules: systematic review and meta-analysis

PubMed Central

Kim, Jun H; Lee, Kyung H; Kim, Kyoung-Tae; Ahn, Hyeong S; Kim, Yeo J; Lee, Ha Y; Jeon, Yong S

2016-01-01

Objective: To compare the diagnostic accuracy of digital tomosynthesis (DTS) with that of chest radiography for the detection of pulmonary nodules by meta-analysis. Methods: A systematic literature search was performed to identify relevant original studies from 1 January 1 1976 to 31 August 31 2016. The quality of included studies was assessed by quality assessment of diagnostic accuracy studies-2. Per-patient data were used to calculate the sensitivity and specificity and per-lesion data were used to calculate the detection rate. Summary receiver-operating characteristic curves were drawn for pulmonary nodule detection. Results: 16 studies met the inclusion criteria. 1017 patients on a per-patient basis and 2159 lesions on a per-lesion basis from 16 eligible studies were evaluated. The pooled patient-based sensitivity of DTS was 0.85 [95% confidence interval (CI) 0.83–0.88] and the specificity was 0.95 (0.93–0.96). The pooled sensitivity and specificity of chest radiography were 0.47 (0.44–0.51) and 0.37 (0.34–0.40), respectively. The per-lesion detection rate was 2.90 (95% CI 2.63–3.19). Conclusion: DTS has higher diagnostic accuracy than chest radiography for detection of pulmonary nodules. Chest radiography has low sensitivity but similar specificity, comparable with that of DTS. Advances in knowledge: DTS has higher diagnostic accuracy than chest radiography for the detection of pulmonary nodules. PMID:27759428

Two Cases of Occupational Contact Urticaria Caused by Percutaneous Sensitization to Parvalbumin

PubMed Central

Sano, Akiyo; Yagami, Akiko; Suzuki, Kayoko; Iwata, Yohei; Kobayashi, Tsukane; Arima, Masaru; Kondo, Yasuto; Yoshikawa, Tetsushi; Matsunaga, Kayoko

2015-01-01

Background In recent years, it has been proposed that the primary mechanism for the development of food allergies is percutaneous sensitization. Since 2010, in Japan, the number of immediate-type wheat allergy due to hydrolyzed wheat protein has dramatically increased among those who have been using soap containing hydrolyzed wheat. This incidence supports the hypothesis that food allergens arise through percutaneous sensitization. Clinical Summary A 25-year-old man (case 1) and an 18-year-old girl (case 2) with atopic dermatitis visited our Department because of food allergy and hand eczema. After starting their work with fish, severe itchy eczema appeared on their hands. They subsequently started to experience oral allergic symptoms, intraoral itchiness and dyspnea after eating fish. Specific IgE antibodies were detected for many fishes, and skin prick tests showed positive reactions for a variety of fishes in both cases. Furthermore, the fluorescence intensities of specific IgE antibodies against parvalbumin from various types of fish in microarray immunoassay analysis showed positive reactions. We diagnosed them as contact urticaria caused by percutaneous sensitization to parvalbumin through job-related physical contact with fish. Conclusion The patients' histories and findings indicate the possibility of percutaneous sensitization through occupational exposure to parvalbumin, leading to food allergy. PMID:26464568

An improved method for detecting circulating microRNAs with S-Poly(T) Plus real-time PCR

PubMed Central

Niu, Yanqin; Zhang, Limin; Qiu, Huiling; Wu, Yike; Wang, Zhiwei; Zai, Yujia; Liu, Lin; Qu, Junle; Kang, Kang; Gou, Deming

2015-01-01

We herein describe a simple, sensitive and specific method for analysis of circulating microRNAs (miRNA), termed S-Poly(T) Plus real-time PCR assay. This new method is based on our previously developed S-Poly(T) method, in which a unique S-Poly(T) primer is used during reverse-transcription to increase sensitivity and specificity. Further increased sensitivity and simplicity of S-Poly(T) Plus, in comparison with the S-Poly(T) method, were achieved by a single-step, multiple-stage reaction, where RNAs were polyadenylated and reverse-transcribed at the same time. The sensitivity of circulating miRNA detection was further improved by a modified method of total RNA isolation from serum/plasma, S/P miRsol, in which glycogen was used to increase the RNA yield. We validated our methods by quantifying miRNA expression profiles in the sera of the patients with pulmonary arterial hypertension associated with congenital heart disease. In conclusion, we developed a simple, sensitive, and specific method for detecting circulating miRNAs that allows the measurement of 266 miRNAs from 100 μl of serum or plasma. This method presents a promising tool for basic miRNA research and clinical diagnosis of human diseases based on miRNA biomarkers. PMID:26459910

Inter-laboratory comparison of the in vivo comet assay including three image analysis systems.

PubMed

Plappert-Helbig, Ulla; Guérard, Melanie

2015-12-01

To compare the extent of potential inter-laboratory variability and the influence of different comet image analysis systems, in vivo comet experiments were conducted using the genotoxicants ethyl methanesulfonate and methyl methanesulfonate. Tissue samples from the same animals were processed and analyzed-including independent slide evaluation by image analysis-in two laboratories with extensive experience in performing the comet assay. The analysis revealed low inter-laboratory experimental variability. Neither the use of different image analysis systems, nor the staining procedure of DNA (propidium iodide vs. SYBR® Gold), considerably impacted the results or sensitivity of the assay. In addition, relatively high stability of the staining intensity of propidium iodide-stained slides was found in slides that were refrigerated for over 3 months. In conclusion, following a thoroughly defined protocol and standardized routine procedures ensures that the comet assay is robust and generates comparable results between different laboratories. © 2015 Wiley Periodicals, Inc.

Renal sodium transport in renin-deficient Dahl salt-sensitive rats

PubMed Central

Pavlov, Tengis S; Levchenko, Vladislav; Ilatovskaya, Daria V; Moreno, Carol; Staruschenko, Alexander

2016-01-01

Objective: The Dahl salt-sensitive rat is a well-established model of salt-sensitive hypertension. The goal of this study was to assess the expression and activity of renal sodium channels and transporters in the renin-deficient salt-sensitive rat. Methods: Renin knockout (Ren−/−) rats created on the salt-sensitive rat background were used to investigate the role of renin in the regulation of ion transport in salt-sensitive hypertension. Western blotting and patch-clamp analyses were utilized to assess the expression level and activity of Na+ transporters. Results: It has been described previously that Ren−/− rats exhibit severe kidney underdevelopment, polyuria, and lower body weight and blood pressure compared to their wild-type littermates. Here we found that renin deficiency led to decreased expression of sodium-hydrogen antiporter (NHE3), the Na+/H+ exchanger involved in Na+ absorption in the proximal tubules, but did not affect the expression of Na-K-Cl cotransporter (NKCC2), the main transporter in the loop of Henle. In the distal nephron, the expression of sodium chloride cotransporter (NCC) was lower in Ren−/− rats. Single-channel patch clamp analysis detected decreased ENaC activity in Ren−/− rats which was mediated via changes in the channel open probability. Conclusion: These data illustrate that renin deficiency leads to significant dysregulation of ion transporters. PMID:27443990

Impact of Weight Loss at Presentation on Survival in Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI) Sensitive Mutant Advanced Non-small Cell Lung Cancer (NSCLC) Treated with First-line EGFR-TKI.

PubMed

Lin, Liping; Zhao, Juanjuan; Hu, Jiazhu; Huang, Fuxi; Han, Jianjun; He, Yan; Cao, Xiaolong

2018-01-01

Purpose The aim of this study is to evaluate the impact of weight loss at presentation on treatment outcomes of first-line EGFR-tyrosine kinase inhibitors (EGFR-TKI) in EGFR-TKI sensitive mutant NSCLC patients. Methods We retrospectively analyzed the clinical outcomes of 75 consecutive advanced NSCLC patients with EGFR-TKI sensitive mutations (exon 19 deletion or exon 21 L858R) received first-line gefitinib or erlotinib therapy according to weight loss status at presentation in our single center. Results Of 75 EGFR-TKI sensitive mutant NSCLC patients, 49 (65.3%) patients had no weight loss and 26 (34.7%) had weight loss at presentation, the objective response rate (ORR) to EGFR-TKI treatment were similar between the two groups (79.6% vs. 76.9%, p = 0.533). Patients without weight loss at presentation had significantly longer median progression free survival (PFS) (12.4 months vs. 7.6 months; hazard ratio [HR] 0.356, 95% confidence interval [CI] 0.212-0.596, p < 0.001) and overall survival (OS) (28.5 months vs. 20.7 months; HR 0.408, 95% CI 0.215-0.776, p = 0.006) than those with weight loss at presentation; moreover, the stratified analysis by EGFR-TKI sensitive mutation types also found similar trend between these two groups except for OS in EGFR exon 21 L858R mutation patients. Multivariate analysis identified weight loss at presentation and EGFR-TKI sensitive mutation types were independent predictive factors for PFS and OS. Conclusions Weight loss at presentation had a detrimental impact on PFS and OS in EGFR-TKI sensitive mutant advanced NSCLC patients treated with first-line EGFR-TKI. It should be considered as an important factor in the treatment decision or designing of EGFR-TKI clinical trials.

Diagnostic Accuracy and Cost-Effectiveness of Alternative Methods for Detection of Soil-Transmitted Helminths in a Post-Treatment Setting in Western Kenya

PubMed Central

Kepha, Stella; Kihara, Jimmy H.; Njenga, Sammy M.; Pullan, Rachel L.; Brooker, Simon J.

2014-01-01

Objectives This study evaluates the diagnostic accuracy and cost-effectiveness of the Kato-Katz and Mini-FLOTAC methods for detection of soil-transmitted helminths (STH) in a post-treatment setting in western Kenya. A cost analysis also explores the cost implications of collecting samples during school surveys when compared to household surveys. Methods Stool samples were collected from children (n = 652) attending 18 schools in Bungoma County and diagnosed by the Kato-Katz and Mini-FLOTAC coprological methods. Sensitivity and additional diagnostic performance measures were analyzed using Bayesian latent class modeling. Financial and economic costs were calculated for all survey and diagnostic activities, and cost per child tested, cost per case detected and cost per STH infection correctly classified were estimated. A sensitivity analysis was conducted to assess the impact of various survey parameters on cost estimates. Results Both diagnostic methods exhibited comparable sensitivity for detection of any STH species over single and consecutive day sampling: 52.0% for single day Kato-Katz; 49.1% for single-day Mini-FLOTAC; 76.9% for consecutive day Kato-Katz; and 74.1% for consecutive day Mini-FLOTAC. Diagnostic performance did not differ significantly between methods for the different STH species. Use of Kato-Katz with school-based sampling was the lowest cost scenario for cost per child tested ($10.14) and cost per case correctly classified ($12.84). Cost per case detected was lowest for Kato-Katz used in community-based sampling ($128.24). Sensitivity analysis revealed the cost of case detection for any STH decreased non-linearly as prevalence rates increased and was influenced by the number of samples collected. Conclusions The Kato-Katz method was comparable in diagnostic sensitivity to the Mini-FLOTAC method, but afforded greater cost-effectiveness. Future work is required to evaluate the cost-effectiveness of STH surveillance in different settings. PMID:24810593

Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis

PubMed Central

Beltrame, Anna; Guerriero, Massimo; Angheben, Andrea; Gobbi, Federico; Requena-Mendez, Ana; Zammarchi, Lorenzo; Formenti, Fabio; Perandin, Francesca; Bisoffi, Zeno

2017-01-01

Background Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting. Methodology/Principal findings A retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD) in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA) dipstick test, ELISA, Western blot, immune-chromatographic test (ICT). Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard): ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively), with a high NPV (98%). CCA showed the highest specificity (93%), but low sensitivity (48%). The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests) and Latent Class Analysis (LCA). The latter two models demonstrated excellent agreement (Cohen’s kappa: 0.92) for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96%) and NPV (97%), moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively). ELISA resulted the most specific immunological test (over 99%). The ICT appears to be a suitable screening test, even when used alone. Conclusions The rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants. PMID:28582412

High-sensitivity detection of breast tumors in vivo by use of a pH-sensitive near-infrared fluorescence probe

NASA Astrophysics Data System (ADS)

Mathejczyk, Julia Eva; Pauli, Jutta; Dullin, Christian; Resch-Genger, Ute; Alves, Frauke; Napp, Joanna

2012-07-01

We investigated the potential of the pH-sensitive dye, CypHer5E, conjugated to Herceptin (pH-Her) for the sensitive detection of breast tumors in mice using noninvasive time-domain near-infrared fluorescence imaging and different methods of data analysis. First, the fluorescence properties of pH-Her were analyzed as function of pH and/or dye-to-protein ratio, and binding specificity was confirmed in cell-based assays. Subsequently, the performance of pH-Her in nude mice bearing orthotopic HER2-positive (KPL-4) and HER2-negative (MDA-MB-231) breast carcinoma xenografts was compared to that of an always-on fluorescent conjugate Alexa Fluor 647-Herceptin (Alexa-Her). Subtraction of autofluorescence and lifetime (LT)-gated image analyses were performed for background fluorescence suppression. In mice bearing HER2-positive tumors, autofluorescence subtraction together with the selective fluorescence enhancement of pH-Her solely in the tumor's acidic environment provided high contrast-to-noise ratios (CNRs). This led to an improved sensitivity of tumor detection compared to Alexa-Her. In contrast, LT-gated imaging using LTs determined in model systems did not improve tumor-detection sensitivity in vivo for either probe. In conclusion, pH-Her is suitable for sensitive in vivo monitoring of HER2-expressing breast tumors with imaging in the intensity domain and represents a promising tool for detection of weak fluorescent signals deriving from small tumors or metastases.

Alcohol Sensitivity Moderates the Indirect Associations between Impulsive Traits, Impaired Control over Drinking, and Drinking Outcomes

PubMed Central

Wardell, Jeffrey D.; Quilty, Lena C.; Hendershot, Christian S.

2017-01-01

Objective To examine impaired control over drinking behavior as a mediator of unique pathways from impulsive traits to alcohol outcomes in young adults and to investigate the moderating influence of self-reported sensitivity to alcohol on these pathways. Method Young adult heavy drinkers (N=172; n=82 women) recruited from the community completed self-report measures of impulsive traits (positive urgency, negative urgency, sensation seeking), alcohol sensitivity (Self-Rating of the Effects of Alcohol scale), impaired control over drinking, and alcohol use and problems. Multiple-groups path analysis was used to analyze the data. Results Path coefficients between urgency and impaired control were larger for individuals with lower versus higher self-reported sensitivity to alcohol. The same was true for the association between impaired control and alcohol problems. For participants lower on alcohol sensitivity, significant indirect paths were observed from both positive and negative urgency to all alcohol outcomes (quantity, frequency, and problems) mediated via impaired control. For participants higher on alcohol sensitivity, only the paths from negative urgency (but not positive urgency) to the three alcohol outcomes via impaired control were statistically significant. Sensation seeking was not uniquely associated with impaired control. Conclusions The findings indicate that relatively low sensitivity to the pharmacological effects of alcohol may exacerbate the association of urgency – especially positive urgency – with impaired control, supporting the notion that personality and level of response to alcohol may interact to increase risk for impaired control over drinking. PMID:25785803

Functional-diversity indices can be driven by methodological choices and species richness.

PubMed

Poos, Mark S; Walker, Steven C; Jackson, Donald A

2009-02-01

Functional diversity is an important concept in community ecology because it captures information on functional traits absent in measures of species diversity. One popular method of measuring functional diversity is the dendrogram-based method, FD. To calculate FD, a variety of methodological choices are required, and it has been debated about whether biological conclusions are sensitive to such choices. We studied the probability that conclusions regarding FD were sensitive, and that patterns in sensitivity were related to alpha and beta components of species richness. We developed a randomization procedure that iteratively calculated FD by assigning species into two assemblages and calculating the probability that the community with higher FD varied across methods. We found evidence of sensitivity in all five communities we examined, ranging from a probability of sensitivity of 0 (no sensitivity) to 0.976 (almost completely sensitive). Variations in these probabilities were driven by differences in alpha diversity between assemblages and not by beta diversity. Importantly, FD was most sensitive when it was most useful (i.e., when differences in alpha diversity were low). We demonstrate that trends in functional-diversity analyses can be largely driven by methodological choices or species richness, rather than functional trait information alone.

Illness Absences Among Beryllium Sensitized Workers

PubMed Central

Watkins, Janice P.; Ellis, Elizabeth D.; Girardi, David J.; Cragle, Donna L.

2014-01-01

Objectives. This study examined absence rates among US Department of Energy workers who had beryllium sensitization (BeS) or were diagnosed with chronic beryllium disease (CBD) compared with those of other workers. Methods. We used the lymphocyte proliferation test to determine beryllium sensitivity. In addition, we applied multivariable logistic regression to compare absences from 2002 to 2011 between workers with BeS or CBD to those without, and survival analysis to compare time to first absence by beryllium sensitization status. Finally, we examined beryllium status by occupational group. Results. Fewer than 3% of the 19 305 workers were BeS, and workers with BeS or CBD had more total absences (odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.18, 1.46) and respiratory absences (OR = 1.51; 95% CI = 1.24, 1.84) than did other workers. Time to first absence for all causes and for respiratory conditions occurred earlier for workers with BeS or CBD than for other workers. Line operators and crafts personnel were at increased risk for BeS or CBD. Conclusions. Although not considered “diseased,” workers with BeS have higher absenteeism compared with nonsensitized workers. PMID:25211750

Paris Saponin I Sensitizes Gastric Cancer Cell Lines to Cisplatin via Cell Cycle Arrest and Apoptosis.

PubMed

Song, Shuichuan; Du, Leiwen; Jiang, Hao; Zhu, Xinhai; Li, Jinhui; Xu, Ji

2016-10-18

BACKGROUND Dose-related toxicity is the major restriction of cisplatin and cisplatin-combination chemotherapy, and is a challenge for advanced gastric cancer treatment. We explored the possibility of using Paris saponin I as an agent to sensitize gastric cancer cells to cisplatin, and examined the underlying mechanism. MATERIAL AND METHODS Growth inhibition was detected by MTT assay. The cell cycle and apoptosis were detected using flow cytometry and Annexin V/PI staining. The P21waf1/cip1, Bcl-2, Bax, and caspase-3 protein expression were detected using Western blot analysis. RESULTS The results revealed that PSI sensitized gastric cancer cells to cisplatin, with low toxicity. The IC50 value of cisplatin in SGC-7901 cell lines was decreased when combined with PSI. PSI promoted cisplatin-induced G2/M phase arrest and apoptosis in a cisplatin concentration-dependent manner. Bcl-2 protein expression decreased, but Bax, caspase-3, and P21waf1/cip1 protein expression increased with PSI treatment. CONCLUSIONS The underlying mechanism of Paris saponin I may be related to targeting the apoptosis pathway and cell cycle blocking, which suggests that PSI is a potential therapeutic sensitizer for cisplatin in treating gastric cancer.

Computerized Lung Sound Analysis as diagnostic aid for the detection of abnormal lung sounds: a systematic review and meta-analysis

PubMed Central

Gurung, Arati; Scrafford, Carolyn G; Tielsch, James M; Levine, Orin S; Checkley, William

2011-01-01

Rationale The standardized use of a stethoscope for chest auscultation in clinical research is limited by its inherent inter-listener variability. Electronic auscultation and automated classification of recorded lung sounds may help prevent some these shortcomings. Objective We sought to perform a systematic review and meta-analysis of studies implementing computerized lung sounds analysis (CLSA) to aid in the detection of abnormal lung sounds for specific respiratory disorders. Methods We searched for articles on CLSA in MEDLINE, EMBASE, Cochrane Library and ISI Web of Knowledge through July 31, 2010. Following qualitative review, we conducted a meta-analysis to estimate the sensitivity and specificity of CLSA for the detection of abnormal lung sounds. Measurements and Main Results Of 208 articles identified, we selected eight studies for review. Most studies employed either electret microphones or piezoelectric sensors for auscultation, and Fourier Transform and Neural Network algorithms for analysis and automated classification of lung sounds. Overall sensitivity for the detection of wheezes or crackles using CLSA was 80% (95% CI 72–86%) and specificity was 85% (95% CI 78–91%). Conclusions While quality data on CLSA are relatively limited, analysis of existing information suggests that CLSA can provide a relatively high specificity for detecting abnormal lung sounds such as crackles and wheezes. Further research and product development could promote the value of CLSA in research studies or its diagnostic utility in clinical setting. PMID:21676606

Sensitivity Analysis in Engineering

NASA Technical Reports Server (NTRS)

Adelman, Howard M. (Compiler); Haftka, Raphael T. (Compiler)

1987-01-01

The symposium proceedings presented focused primarily on sensitivity analysis of structural response. However, the first session, entitled, General and Multidisciplinary Sensitivity, focused on areas such as physics, chemistry, controls, and aerodynamics. The other four sessions were concerned with the sensitivity of structural systems modeled by finite elements. Session 2 dealt with Static Sensitivity Analysis and Applications; Session 3 with Eigenproblem Sensitivity Methods; Session 4 with Transient Sensitivity Analysis; and Session 5 with Shape Sensitivity Analysis.

Analysis of a Possible Future Degradation in the DORIS Geodetic Results Related to Changes in the Satellite Constellation

NASA Technical Reports Server (NTRS)

Willis, Pascal

2006-01-01

This viewgraph presentation reviews the consequences of losing one or more of the 4 remaining Doppler & Ranging Information System (DORIS) satellites and any impact such a loss might have on geodesy. The goals of this program are to analyze the sensitivity of the current DORIS geodetic results (station position and polar motion) to the size of the DORIS constellation and to verify if some satellites are most important or less important than others. The conclusions of the study are summarized.

Comparing efficacy of reduced-toxicity allogeneic hematopoietic cell transplantation with conventional chemo-(immuno) therapy in patients with relapsed or refractory CLL: a Markov decision analysis.

PubMed

Kharfan-Dabaja, M A; Pidala, J; Kumar, A; Terasawa, T; Djulbegovic, B

2012-09-01

Despite therapeutic advances, relapsed/refractory CLL, particularly after fludarabine-based regimens, remains a major challenge for which optimal therapy is undefined. No randomized comparative data exist to suggest the superiority of reduced-toxicity allogeneic hematopoietic cell transplantation (RT-allo-HCT) over conventional chemo-(immuno) therapy (CCIT). By using estimates from a systematic review and by meta-analysis of available published evidence, we constructed a Markov decision model to examine these competing modalities. Cohort analysis demonstrated superior outcome for RT-allo-HCT, with a 10-month overall life expectancy (and 6-month quality-adjusted life expectancy (QALE)) advantage over CCIT. Although the model was sensitive to changes in base-case assumptions and transition probabilities, RT-allo-HCT provided superior overall life expectancy through a range of values supported by the meta-analysis. QALE was superior for RT-allo-HCT compared with CCIT. This conclusion was sensitive to change in the anticipated state utility associated with the post-allogeneic HCT state; however, RT-allo-HCT remained the optimal strategy for values supported by existing literature. This analysis provides a quantitative comparison of outcomes between RT-allo-HCT and CCIT for relapsed/refractory CLL in the absence of randomized comparative trials. Confirmation of these findings requires a prospective randomized trial, which compares the most effective RT-allo-HCT and CCIT regimens for relapsed/refractory CLL.

Relationship between C-Reactive Protein Level and Diabetic Retinopathy: A Systematic Review and Meta-Analysis

PubMed Central

Chen, Song; Duan, Hongtao; Kong, Jiahui; Li, Zedong

2015-01-01

Objectives To date, the relationship between C-reactive protein (CRP) level and diabetic retinopathy (DR) remains controversial. Therefore, a systematic review and meta-analysis was used to reveal the potential relationship between CRP level and DR. Methods A systematic search of PubMed, Embase.com, and Web of Science was performed to identify all comparative studies that compared the CRP level of two groups (case group and control group). We defined that diabetic patients without retinopathy and /or matched healthy persons constituted the control group, and patients with DR were the case group. Results Two cross sectional studies and twenty case control studies including a total of 3679 participants were identified. After pooling the data from all 22 studies, obvious heterogeneity existed between the studies, so a subgroup analysis and sensitivity analysis were performed. Removing the sensitivity studies, the blood CRP levels in the case group were observed to be higher than those in the control group [SMD = 0.22, 95% confidence interval (CI), 0.11–0.34], and the blood CRP levels in the proliferative diabetic retinopathy (PDR) group were also higher than those in the non-proliferative diabetic retinopathy (NPDR) group [SMD = 0.50, 95% CI, 0.30–0.70]. Conclusions The results from this current meta-analysis indicate that the CRP level might be used as a biomarker to determine the severity of DR. PMID:26636823

Cost-Effectiveness Analysis of Elective Neck Dissection in Patients With Clinically Node-Negative Oral Cavity Cancer.

PubMed

Acevedo, Joseph R; Fero, Katherine E; Wilson, Bayard; Sacco, Assuntina G; Mell, Loren K; Coffey, Charles S; Murphy, James D

2016-11-10

Purpose Recently, a large randomized trial found a survival advantage among patients who received elective neck dissection in conjunction with primary surgery for clinically node-negative oral cavity cancer compared with those receiving primary surgery alone. However, elective neck dissection comes with greater upfront cost and patient morbidity. We present a cost-effectiveness analysis of elective neck dissection for the initial surgical management of early-stage oral cavity cancer. Methods We constructed a Markov model to simulate primary, adjuvant, and salvage therapy; disease recurrence; and survival in patients with T1/T2 clinically node-negative oral cavity squamous cell carcinoma. Transition probabilities were derived from clinical trial data; costs (in 2015 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollar per quality-adjusted life-year (QALY), were calculated with incremental cost-effectiveness ratios less than $100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty. Results Our base-case model found that over a lifetime the addition of elective neck dissection to primary surgery reduced overall costs by $6,000 and improved effectiveness by 0.42 QALYs compared with primary surgery alone. The decrease in overall cost despite the added neck dissection was a result of less use of salvage therapy. On one-way sensitivity analysis, the model was most sensitive to assumptions about disease recurrence, survival, and the health utility reduction from a neck dissection. Probabilistic sensitivity analysis found that treatment with elective neck dissection was cost effective 76% of the time at a willingness-to-pay threshold of $100,000/QALY. Conclusion Our study found that the addition of elective neck dissection reduces costs and improves health outcomes, making this a cost-effective treatment strategy for patients with early-stage oral cavity cancer.

Early assessment of the likely cost-effectiveness of a new technology: A Markov model with probabilistic sensitivity analysis of computer-assisted total knee replacement.

PubMed

Dong, Hengjin; Buxton, Martin

2006-01-01

The objective of this study is to apply a Markov model to compare cost-effectiveness of total knee replacement (TKR) using computer-assisted surgery (CAS) with that of TKR using a conventional manual method in the absence of formal clinical trial evidence. A structured search was carried out to identify evidence relating to the clinical outcome, cost, and effectiveness of TKR. Nine Markov states were identified based on the progress of the disease after TKR. Effectiveness was expressed by quality-adjusted life years (QALYs). The simulation was carried out initially for 120 cycles of a month each, starting with 1,000 TKRs. A discount rate of 3.5 percent was used for both cost and effectiveness in the incremental cost-effectiveness analysis. Then, a probabilistic sensitivity analysis was carried out using a Monte Carlo approach with 10,000 iterations. Computer-assisted TKR was a long-term cost-effective technology, but the QALYs gained were small. After the first 2 years, the incremental cost per QALY of computer-assisted TKR was dominant because of cheaper and more QALYs. The incremental cost-effectiveness ratio (ICER) was sensitive to the "effect of CAS," to the CAS extra cost, and to the utility of the state "Normal health after primary TKR," but it was not sensitive to utilities of other Markov states. Both probabilistic and deterministic analyses produced similar cumulative serious or minor complication rates and complex or simple revision rates. They also produced similar ICERs. Compared with conventional TKR, computer-assisted TKR is a cost-saving technology in the long-term and may offer small additional QALYs. The "effect of CAS" is to reduce revision rates and complications through more accurate and precise alignment, and although the conclusions from the model, even when allowing for a full probabilistic analysis of uncertainty, are clear, the "effect of CAS" on the rate of revisions awaits long-term clinical evidence.

Accuracy of urinary human papillomavirus testing for presence of cervical HPV: systematic review and meta-analysis

PubMed Central

Pathak, Neha; Dodds, Julie; Khan, Khalid

2014-01-01

Objective To determine the accuracy of testing for human papillomavirus (HPV) DNA in urine in detecting cervical HPV in sexually active women. Design Systematic review and meta-analysis. Data sources Searches of electronic databases from inception until December 2013, checks of reference lists, manual searches of recent issues of relevant journals, and contact with experts. Eligibility criteria Test accuracy studies in sexually active women that compared detection of urine HPV DNA with detection of cervical HPV DNA. Data extraction and synthesis Data relating to patient characteristics, study context, risk of bias, and test accuracy. 2×2 tables were constructed and synthesised by bivariate mixed effects meta-analysis. Results 16 articles reporting on 14 studies (1443 women) were eligible for meta-analysis. Most used commercial polymerase chain reaction methods on first void urine samples. Urine detection of any HPV had a pooled sensitivity of 87% (95% confidence interval 78% to 92%) and specificity of 94% (95% confidence interval 82% to 98%). Urine detection of high risk HPV had a pooled sensitivity of 77% (68% to 84%) and specificity of 88% (58% to 97%). Urine detection of HPV 16 and 18 had a pooled sensitivity of 73% (56% to 86%) and specificity of 98% (91% to 100%). Metaregression revealed an increase in sensitivity when urine samples were collected as first void compared with random or midstream (P=0.004). Limitations The major limitations of this review are the lack of a strictly uniform method for the detection of HPV in urine and the variation in accuracy between individual studies. Conclusions Testing urine for HPV seems to have good accuracy for the detection of cervical HPV, and testing first void urine samples is more accurate than random or midstream sampling. When cervical HPV detection is considered difficult in particular subgroups, urine testing should be regarded as an acceptable alternative. PMID:25232064

Cost effectiveness of OptiMal® rapid diagnostic test for malaria in remote areas of the Amazon Region, Brazil

PubMed Central

2010-01-01

Background In areas with limited structure in place for microscopy diagnosis, rapid diagnostic tests (RDT) have been demonstrated to be effective. Method The cost-effectiveness of the Optimal® and thick smear microscopy was estimated and compared. Data were collected on remote areas of 12 municipalities in the Brazilian Amazon. Data sources included the National Malaria Control Programme of the Ministry of Health, the National Healthcare System reimbursement table, hospitalization records, primary data collected from the municipalities, and scientific literature. The perspective was that of the Brazilian public health system, the analytical horizon was from the start of fever until the diagnostic results provided to patient and the temporal reference was that of year 2006. The results were expressed in costs per adequately diagnosed cases in 2006 U.S. dollars. Sensitivity analysis was performed considering key model parameters. Results In the case base scenario, considering 92% and 95% sensitivity for thick smear microscopy to Plasmodium falciparum and Plasmodium vivax, respectively, and 100% specificity for both species, thick smear microscopy is more costly and more effective, with an incremental cost estimated at US$549.9 per adequately diagnosed case. In sensitivity analysis, when sensitivity and specificity of microscopy for P. vivax were 0.90 and 0.98, respectively, and when its sensitivity for P. falciparum was 0.83, the RDT was more cost-effective than microscopy. Conclusion Microscopy is more cost-effective than OptiMal® in these remote areas if high accuracy of microscopy is maintained in the field. Decision regarding use of rapid tests for diagnosis of malaria in these areas depends on current microscopy accuracy in the field. PMID:20937094

Optimizing Complexity Measures for fMRI Data: Algorithm, Artifact, and Sensitivity

PubMed Central

Rubin, Denis; Fekete, Tomer; Mujica-Parodi, Lilianne R.

2013-01-01

Introduction Complexity in the brain has been well-documented at both neuronal and hemodynamic scales, with increasing evidence supporting its use in sensitively differentiating between mental states and disorders. However, application of complexity measures to fMRI time-series, which are short, sparse, and have low signal/noise, requires careful modality-specific optimization. Methods Here we use both simulated and real data to address two fundamental issues: choice of algorithm and degree/type of signal processing. Methods were evaluated with regard to resilience to acquisition artifacts common to fMRI as well as detection sensitivity. Detection sensitivity was quantified in terms of grey-white matter contrast and overlap with activation. We additionally investigated the variation of complexity with activation and emotional content, optimal task length, and the degree to which results scaled with scanner using the same paradigm with two 3T magnets made by different manufacturers. Methods for evaluating complexity were: power spectrum, structure function, wavelet decomposition, second derivative, rescaled range, Higuchi’s estimate of fractal dimension, aggregated variance, and detrended fluctuation analysis. To permit direct comparison across methods, all results were normalized to Hurst exponents. Results Power-spectrum, Higuchi’s fractal dimension, and generalized Hurst exponent based estimates were most successful by all criteria; the poorest-performing measures were wavelet, detrended fluctuation analysis, aggregated variance, and rescaled range. Conclusions Functional MRI data have artifacts that interact with complexity calculations in nontrivially distinct ways compared to other physiological data (such as EKG, EEG) for which these measures are typically used. Our results clearly demonstrate that decisions regarding choice of algorithm, signal processing, time-series length, and scanner have a significant impact on the reliability and sensitivity of complexity estimates. PMID:23700424

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center.

PubMed

Otoshi, Takehiro; Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

2017-01-01

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung's criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy.

Cost-effectiveness of prucalopride in the treatment of chronic constipation in the Netherlands

PubMed Central

Nuijten, Mark J. C.; Dubois, Dominique J.; Joseph, Alain; Annemans, Lieven

2015-01-01

Objective: To assess the cost-effectiveness of prucalopride vs. continued laxative treatment for chronic constipation in patients in the Netherlands in whom laxatives have failed to provide adequate relief. Methods: A Markov model was developed to estimate the cost-effectiveness of prucalopride in patients with chronic constipation receiving standard laxative treatment from the perspective of Dutch payers in 2011. Data sources included published prucalopride clinical trials, published Dutch price/tariff lists, and national population statistics. The model simulated the clinical and economic outcomes associated with prucalopride vs. standard treatment and had a cycle length of 1 month and a follow-up time of 1 year. Response to treatment was defined as the proportion of patients who achieved “normal bowel function”. One-way and probabilistic sensitivity analyses were conducted to test the robustness of the base case. Results: In the base case analysis, the cost of prucalopride relative to continued laxative treatment was € 9015 per quality-adjusted life-year (QALY). Extensive sensitivity analyses and scenario analyses confirmed that the base case cost-effectiveness estimate was robust. One-way sensitivity analyses showed that the model was most sensitive in response to prucalopride; incremental cost-effectiveness ratios ranged from € 6475 to 15,380 per QALY. Probabilistic sensitivity analyses indicated that there is a greater than 80% probability that prucalopride would be cost-effective compared with continued standard treatment, assuming a willingness-to-pay threshold of € 20,000 per QALY from a Dutch societal perspective. A scenario analysis was performed for women only, which resulted in a cost-effectiveness ratio of € 7773 per QALY. Conclusion: Prucalopride was cost-effective in a Dutch patient population, as well as in a women-only subgroup, who had chronic constipation and who obtained inadequate relief from laxatives. PMID:25926794

[An analysis of spectrum of allergen sensitization among patients with tree pollen allergy in Beijing].

PubMed

Wang, X Y; Ning, H Y; Chu, S M; Jiang, L; Pang, Y J; Jin, W T; Wang, S Q; Wang, X Y

2017-12-05

Objective: To explore the feature of allergic sensitization of tree pollen and the relationship between tree pollen and airborne pollen in Beijing. Method: Two thousand five hundred and twenty-one patients with allergic diseases were enrolled between January to July in 2017 in an allergy department. All patients received SPT of 8 kinds of tree pollen. Result: ①The overall tree pollen positive rate of SPT was 49.3% (1 244/2 521). Male had a higher positive rate than female (56.4% vs 45.0%, P <0.01) while child group had a higher positive rate than adult group (55.9% vs 48.6%, P <0.05). The poly sensitization was observed with a rate of 26.3%, take the percentage of 53.3% of the overall positive subjects. ②The highest sensitization rate was found in March (62.2%), followed by May (52.1%), the lowest was January (27.9%). There was a positive correlation between tree pollen sensitization rate and pollen count of each month ( r =0.929, P <0.01). ③Cypress had the highest positive rate (34.6%), followed by poplar (21.3%), the lowest was sophora (13.3%). The sensitization rate was positively correlated with pollen count among different tree pollen ( r =0.714, P <0.05). Conclusion: The main allergic pollen in Beijing was cypress. The tree pollen sensitization showed a seasonality with the peak in March. The sensitization status was tightly associated with the amount of airborne pollen. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

The clinical utility and diagnostic performance of magnetic resonance imaging for identification of early and advanced knee osteoarthritis: a systematic review.

PubMed

Quatman, Carmen E; Hettrich, Carolyn M; Schmitt, Laura C; Spindler, Kurt P

2011-07-01

Current diagnostic strategies for detection of structural articular cartilage abnormalities, the earliest structural signs of osteoarthritis, often do not capture the condition until it is too far advanced for the most potential benefit of noninvasive interventions. To systematically review the literature relative to the following questions: (1) Is magnetic resonance imaging (MRI) a valid, sensitive, specific, accurate, and reliable instrument to identify knee articular cartilage abnormalities compared with arthroscopy? (2) Is MRI a sensitive tool that can be utilized to identify early cartilage degeneration? Systematic review. A systematic search was performed in November 2010 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from 1985), SCOPUS (from 1996), and EMBASE (from 1974) databases. Fourteen level I and 13 level II studies were identified that met inclusion criteria and provided information related to diagnostic performance of MRI compared with arthroscopic evaluation. The diagnostic performance of MRI demonstrated a large range of sensitivities, specificities, and accuracies. The sensitivity for identifying articular cartilage abnormalities in the knee joint was reported between 26% and 96%. Specificity and accuracy were reported between 50% and 100% and between 49% and 94%, respectively. The sensitivity, specificity, and accuracy for identifying early osteoarthritis were reported between 0% and 86%, 48% and 95%, and 5% and 94%, respectively. As a result of inconsistencies between imaging techniques and methodological shortcomings of many of the studies, a meta-analysis was not performed, and it was difficult to fully synthesize the information to state firm conclusions about the diagnostic performance of MRI. There is evidence in some MRI protocols that MRI is a relatively valid, sensitive, specific, accurate, and reliable clinical tool for identifying articular cartilage degeneration. Because of heterogeneity of MRI sequences, it is not possible to make definitive conclusions regarding its global clinical utility for guiding diagnosis and treatment strategies. Traumatic sports injuries to the knee may be significant precursor events to early onset of posttraumatic osteoarthritis. Magnetic resonance imaging may aid in early identification of structural injuries to articular cartilage as evidenced by articular cartilage degeneration grading.

A rapid and sensitive method for the simultaneous analysis of aliphatic and polar molecules containing free carboxyl groups in plant extracts by LC-MS/MS

PubMed Central

2009-01-01

Background Aliphatic molecules containing free carboxyl groups are important intermediates in many metabolic and signalling reactions, however, they accumulate to low levels in tissues and are not efficiently ionized by electrospray ionization (ESI) compared to more polar substances. Quantification of aliphatic molecules becomes therefore difficult when small amounts of tissue are available for analysis. Traditional methods for analysis of these molecules require purification or enrichment steps, which are onerous when multiple samples need to be analyzed. In contrast to aliphatic molecules, more polar substances containing free carboxyl groups such as some phytohormones are efficiently ionized by ESI and suitable for analysis by LC-MS/MS. Thus, the development of a method with which aliphatic and polar molecules -which their unmodified forms differ dramatically in their efficiencies of ionization by ESI- can be simultaneously detected with similar sensitivities would substantially simplify the analysis of complex biological matrices. Results A simple, rapid, specific and sensitive method for the simultaneous detection and quantification of free aliphatic molecules (e.g., free fatty acids (FFA)) and small polar molecules (e.g., jasmonic acid (JA), salicylic acid (SA)) containing free carboxyl groups by direct derivatization of leaf extracts with Picolinyl reagent followed by LC-MS/MS analysis is presented. The presence of the N atom in the esterified pyridine moiety allowed the efficient ionization of 25 compounds tested irrespective of their chemical structure. The method was validated by comparing the results obtained after analysis of Nicotiana attenuata leaf material with previously described analytical methods. Conclusion The method presented was used to detect 16 compounds in leaf extracts of N. attenuata plants. Importantly, the method can be adapted based on the specific analytes of interest with the only consideration that the molecules must contain at least one free carboxyl group. PMID:19939243

Orthopaedic trauma care in Haiti: a cost-effectiveness analysis of an innovative surgical residency program.

PubMed

Carlson, Lucas C; Slobogean, Gerard P; Pollak, Andrew N

2012-01-01

In an effort to sustainably strengthen orthopaedic trauma care in Haiti, a 2-year Orthopaedic Trauma Care Specialist (OTCS) program for Haitian physicians has been developed. The program will provide focused training in orthopaedic trauma surgery and fracture care utilizing a train-the-trainer approach. The purpose of this analysis was to calculate the cost-effectiveness of the program relative to its potential to decrease disability in the Haitian population. Using established methodology originally outlined in the World Health Organization's Global Burden of Disease project, a cost-effectiveness analysis was performed for the OTCS program in Haiti. Costs and disability-adjusted life-years (DALYs) averted were estimated per fellow trained in the OTCS program by using a 20-year career time horizon. Probabilistic sensitivity analysis was used to simultaneously test the joint uncertainty of the cost and averted DALY estimates. A willingness-to-pay threshold of $1200 per DALY averted, equal to the gross domestic product per capita in Haiti, was selected on the basis of World Health Organization's definition of highly cost-effective health interventions. The OTCS program results in an incremental cost of $1,542,544 ± $109,134 and 12,213 ± 2,983 DALYs averted per fellow trained. The cost-effectiveness ratio of $133.97 ± $34.71 per DALY averted is well below the threshold of $1200 per DALY averted. Furthermore, sensitivity analysis suggests that implementing the OTCS program is the economically preferred strategy with more than 95% probability at a willingness-to-pay threshold of $200 per DALY averted and across the entire range of potential variable inputs. The current economic analysis suggests the OTCS program to be a highly cost-effective intervention. Probabilistic sensitivity analysis demonstrates that the conclusions remain stable even when considering the joint uncertainty of the cost and DALY estimates. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Preterm delivery at low gestational age: risk factors for short latency. A multivariated analysis

PubMed Central

Marzano, Sara; Padula, Francesco; Meloni, Paolo; Anceschi, Maurizio Marco

2008-01-01

Objective The aim of this study is to identify the risk factors for a short latency in preterm delivery at low gestational ages (GA). Study design A retrospective analysis involving, between January 2004 and May 2006, 204 singleton pregnancies with admission diagnosis of preterm labor and, in particular, 91 pregnant women admitted between 24+0 and 31+6 weeks’ gestation. Results In pregnant women with a diagnosis of preterm labor at 24-31+6 weeks’ gestation, at ROC curve, a value of considering WBC and cervical dilatation, combined in the following formula (75.237 - (2.290 * “WBC”) - (10.787 * “cervical dilatation”)) <=33.101 has a 74.2% Sensitivity and a 78.3% Specificity in predicting a latency =< 4 days (+LR 3.42 and -LR 0.33) and a 70% Sensitivity and a 84.3% Specificity in predicting GA at delivery at 24-31 weeks’ gestation (+LR 4.46 and -LR 0.36). Conclusion We suggest a more strictly monitoring and a more aggressive therapy in presence of prognostic parameters of shorter latency. PMID:22439021

Prevalence of allergic sensitization in the U.S.: Results from the National Health and Nutrition Examination Survey (NHANES) 2005–2006

PubMed Central

Salo, Päivi M.; Arbes, Samuel J.; Jaramillo, Renee; Calatroni, Agustin; Weir, Charles H.; Sever, Michelle L.; Hoppin, Jane A.; Rose, Kathryn M.; Liu, Andrew H.; Gergen, Peter J.; Mitchell, Herman E.; Zeldin, Darryl C.

2014-01-01

Background Allergic sensitization is an important risk factor for the development of atopic disease. The National Health and Nutrition Examination Survey (NHANES) 2005–2006 provides the most comprehensive information on IgE-mediated sensitization in the general US population. Objective We investigated clustering, sociodemographic and regional patterns of allergic sensitization and examined risk factors associated with IgE-mediated sensitization. Methods Data for this cross-sectional analysis were obtained from NHANES 2005–2006. Participants aged ≥1 year (N=9440) were tested for sIgEs to inhalant and food allergens; participants ≥6 years were tested for 19 sIgEs, and children aged 1–5 years for 9 sIgEs. Serum samples were analyzed using the ImmunoCAP System. Information on demographics and participant characteristics was collected by questionnaire. Results Of the study population aged 6 and older, 44.6% had detectable sIgEs, while 36.2% of children aged 1–5 years were sensitized to ≥1 allergen. Allergen-specific IgEs clustered into 7 groups that might have largely reflected biological cross-reactivity. Although sensitization to individual allergens and allergen types showed regional variation, the overall prevalence of sensitization did not differ across census regions, except in early childhood. In multivariate modeling, young age, male gender, non-Hispanic black race/ethnicity, geographic location (census region), and reported pet avoidance measures were most consistently associated with IgE-mediated sensitization. Conclusions The overall prevalence of allergic sensitization does not vary across US census regions, except in early life, although allergen-specific sensitization differs by sociodemographic and regional factors. Biological cross-reactivity may be an important, but not a sole, contributor to the clustering of allergen-specific IgEs. Clinical implications IgE-mediated sensitization shows clustering patterns and differs by sociodemographic and regional factors, but the overall prevalence of sensitization may not vary across US census regions. PMID:24522093

Cough and expiration reflexes elicited by inhaled irritant gases are intensified in ovalbumin-sensitized mice.

PubMed

Zhang, Cheng; Lin, Ruei-Lung; Hong, Jeff; Khosravi, Mehdi; Lee, Lu-Yuan

2017-05-01

This study was designed to determine the effect of active sensitization with ovalbumin (Ova) on cough responses to inhaled irritant gases in mice. Conscious mice moved freely in a recording chamber, while the pressure change in the chamber and audio and video signals of the mouse movements were recorded simultaneously to measure the frequencies of cough reflex (CR) and expiration reflex (ER). To further verify the accuracy of cough analysis, the intrapleural pressure was also recorded by a telemetry sensor surgically implanted in the intrapleural space in a subgroup of mice. During the irritant gas inhalation challenge, sulfur dioxide (SO 2 ; 200 and 400 ppm) or ammonia (NH 3 ; 0.1% and 0.2%) was drawn into the chamber at a constant flow rate for 8 min. Ova sensitization and sham sensitization with vehicle (Veh) were performed over a 25-day period in separate groups of mice. Our results showed that 1 ) both SO 2 and NH 3 inhalation challenges increased CR and ER frequencies in a concentration-dependent manner before Ova sensitization; 2 ) the baseline CR frequency was significantly elevated after Ova sensitization, accompanied by pronounced airway inflammation; and 3 ) Ova sensitization also markedly augmented the responses of CR and ER to both SO 2 and NH 3 inhalation challenges; in sharp contrast, the cough responses did not change after sham sensitization in the Veh group. In conclusion, Ova sensitization caused distinct and lingering increases in baseline cough frequency, and also intensified both CR and ER responses to inhaled irritant gases, which probably resulted from an allergic inflammation-induced hypersensitivity of airway sensory nerves. Copyright © 2017 the American Physiological Society.

Sensitivity and specificity of dosing alerts for dosing errors among hospitalized pediatric patients

PubMed Central

Stultz, Jeremy S; Porter, Kyle; Nahata, Milap C

2014-01-01

Objectives To determine the sensitivity and specificity of a dosing alert system for dosing errors and to compare the sensitivity of a proprietary system with and without institutional customization at a pediatric hospital. Methods A retrospective analysis of medication orders, orders causing dosing alerts, reported adverse drug events, and dosing errors during July, 2011 was conducted. Dosing errors with and without alerts were identified and the sensitivity of the system with and without customization was compared. Results There were 47 181 inpatient pediatric orders during the studied period; 257 dosing errors were identified (0.54%). The sensitivity of the system for identifying dosing errors was 54.1% (95% CI 47.8% to 60.3%) if customization had not occurred and increased to 60.3% (CI 54.0% to 66.3%) with customization (p=0.02). The sensitivity of the system for underdoses was 49.6% without customization and 60.3% with customization (p=0.01). Specificity of the customized system for dosing errors was 96.2% (CI 96.0% to 96.3%) with a positive predictive value of 8.0% (CI 6.8% to 9.3). All dosing errors had an alert over-ridden by the prescriber and 40.6% of dosing errors with alerts were administered to the patient. The lack of indication-specific dose ranges was the most common reason why an alert did not occur for a dosing error. Discussion Advances in dosing alert systems should aim to improve the sensitivity and positive predictive value of the system for dosing errors. Conclusions The dosing alert system had a low sensitivity and positive predictive value for dosing errors, but might have prevented dosing errors from reaching patients. Customization increased the sensitivity of the system for dosing errors. PMID:24496386

First results from a combined analysis of CERN computing infrastructure metrics

NASA Astrophysics Data System (ADS)

Duellmann, Dirk; Nieke, Christian

2017-10-01

The IT Analysis Working Group (AWG) has been formed at CERN across individual computing units and the experiments to attempt a cross cutting analysis of computing infrastructure and application metrics. In this presentation we will describe the first results obtained using medium/long term data (1 months — 1 year) correlating box level metrics, job level metrics from LSF and HTCondor, IO metrics from the physics analysis disk pools (EOS) and networking and application level metrics from the experiment dashboards. We will cover in particular the measurement of hardware performance and prediction of job duration, the latency sensitivity of different job types and a search for bottlenecks with the production job mix in the current infrastructure. The presentation will conclude with the proposal of a small set of metrics to simplify drawing conclusions also in the more constrained environment of public cloud deployments.

Profitability analysis of a femtosecond laser system for cataract surgery using a fuzzy logic approach

PubMed Central

Trigueros, José Antonio; Piñero, David P; Ismail, Mahmoud M

2016-01-01

AIM To define the financial and management conditions required to introduce a femtosecond laser system for cataract surgery in a clinic using a fuzzy logic approach. METHODS In the simulation performed in the current study, the costs associated to the acquisition and use of a commercially available femtosecond laser platform for cataract surgery (VICTUS, TECHNOLAS Perfect Vision GmbH, Bausch & Lomb, Munich, Germany) during a period of 5y were considered. A sensitivity analysis was performed considering such costs and the countable amortization of the system during this 5y period. Furthermore, a fuzzy logic analysis was used to obtain an estimation of the money income associated to each femtosecond laser-assisted cataract surgery (G). RESULTS According to the sensitivity analysis, the femtosecond laser system under evaluation can be profitable if 1400 cataract surgeries are performed per year and if each surgery can be invoiced more than $500. In contrast, the fuzzy logic analysis confirmed that the patient had to pay more per surgery, between $661.8 and $667.4 per surgery, without considering the cost of the intraocular lens (IOL). CONCLUSION A profitability of femtosecond laser systems for cataract surgery can be obtained after a detailed financial analysis, especially in those centers with large volumes of patients. The cost of the surgery for patients should be adapted to the real flow of patients with the ability of paying a reasonable range of cost. PMID:27500115

Cost-Effectiveness Analysis of Stereotactic Body Radiation Therapy Compared With Radiofrequency Ablation for Inoperable Colorectal Liver Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Hayeon, E-mail: kimh2@upmc.edu; Gill, Beant; Beriwal, Sushil

Purpose: To conduct a cost-effectiveness analysis to determine whether stereotactic body radiation therapy (SBRT) is a cost-effective therapy compared with radiofrequency ablation (RFA) for patients with unresectable colorectal cancer (CRC) liver metastases. Methods and Materials: A cost-effectiveness analysis was conducted using a Markov model and 1-month cycle over a lifetime horizon. Transition probabilities, quality of life utilities, and costs associated with SBRT and RFA were captured in the model on the basis of a comprehensive literature review and Medicare reimbursements in 2014. Strategies were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs). To account formore » model uncertainty, 1-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Results: In base case analysis, treatment costs for 3 fractions of SBRT and 1 RFA procedure were $13,000 and $4397, respectively. Median survival was assumed the same for both strategies (25 months). The SBRT costs $8202 more than RFA while gaining 0.05 QALYs, resulting in an incremental cost-effectiveness ratio of $164,660 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of median survival from both treatments. Stereotactic body radiation therapy was economically reasonable if better survival was presumed (>1 month gain) or if used for large tumors (>4 cm). Conclusions: If equal survival is assumed, SBRT is not cost-effective compared with RFA for inoperable colorectal liver metastases. However, if better local control leads to small survival gains with SBRT, this strategy becomes cost-effective. Ideally, these results should be confirmed with prospective comparative data.« less

Is the Timed Up and Go test a useful predictor of risk of falls in community dwelling older adults: a systematic review and meta- analysis

PubMed Central

2014-01-01

Background The Timed Up and Go test (TUG) is a commonly used screening tool to assist clinicians to identify patients at risk of falling. The purpose of this systematic review and meta-analysis is to determine the overall predictive value of the TUG in community-dwelling older adults. Methods A literature search was performed to identify all studies that validated the TUG test. The methodological quality of the selected studies was assessed using the QUADAS-2 tool, a validated tool for the quality assessment of diagnostic accuracy studies. A TUG score of ≥13.5 seconds was used to identify individuals at higher risk of falling. All included studies were combined using a bivariate random effects model to generate pooled estimates of sensitivity and specificity at ≥13.5 seconds. Heterogeneity was assessed using the variance of logit transformed sensitivity and specificity. Results Twenty-five studies were included in the systematic review and 10 studies were included in meta-analysis. The TUG test was found to be more useful at ruling in rather than ruling out falls in individuals classified as high risk (>13.5 sec), with a higher pooled specificity (0.74, 95% CI 0.52-0.88) than sensitivity (0.31, 95% CI 0.13-0.57). Logistic regression analysis indicated that the TUG score is not a significant predictor of falls (OR = 1.01, 95% CI 1.00-1.02, p = 0.05). Conclusion The Timed Up and Go test has limited ability to predict falls in community dwelling elderly and should not be used in isolation to identify individuals at high risk of falls in this setting. PMID:24484314

Cost-utility analysis of 10- and 13-valent pneumococcal conjugate vaccines: Protection at what price in the Thai context?

PubMed Central

Kulpeng, Wantanee; Leelahavarong, Pattara; Rattanavipapong, Waranya; Sornsrivichai, Vorasith; Baggett, Henry C.; Meeyai, Aronrag; Punpanich, Warunee; Teerawattananon, Yot

2015-01-01

Objective This study aims to evaluate the costs and outcomes of offering the 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) in Thailand compared to the current situation of no PCV vaccination. Methods Two vaccination schedules were considered: two-dose primary series plus a booster dose (2 + 1) and three-dose primary series plus a booster dose (3 + 1). A cost-utility analysis was conducted using a societal perspective. A Markov simulation model was used to estimate the relevant costs and health outcomes for a lifetime horizon. Costs were collected and values were calculated for the year 2010. The results were reported as incremental cost-effectiveness ratios (ICERs) in Thai Baht (THB) per quality adjusted life year (QALY) gained, with future costs and outcomes being discounted at 3% per annum. One-way sensitivity analysis and probabilistic sensitivity analysis using a Monte Carlo simulation were performed to assess parameter uncertainty. Results Under the base case-scenario of 2 + 1 dose schedule and a five-year protection, without indirect vaccine effects, the ICER for PCV10 and PCV13 were THB 1,368,072 and THB 1,490,305 per QALY gained, respectively. With indirect vaccine effects, the ICER of PCV10 was THB 519,399, and for PCV13 was THB 527,378. The model was sensitive to discount rate, the change in duration of vaccine protection and the incidence of pneumonia for all age groups. Conclusions At current prices, PCV10 and PCV13 are not cost-effective in Thailand. Inclusion of indirect vaccine effects substantially reduced the ICERs for both vaccines, but did not result in cost effectiveness. PMID:23588084

Cost-effectiveness of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction

PubMed Central

McMurray, John J V; Trueman, David; Hancock, Elizabeth; Cowie, Martin R; Briggs, Andrew; Taylor, Matthew; Mumby-Croft, Juliet; Woodcock, Fionn; Lacey, Michael; Haroun, Rola; Deschaseaux, Celine

2018-01-01

Objective Chronic heart failure with reduced ejection fraction (HF-REF) represents a major public health issue and is associated with considerable morbidity and mortality. We evaluated the cost-effectiveness of sacubitril/valsartan (formerly LCZ696) compared with an ACE inhibitor (ACEI) (enalapril) in the treatment of HF-REF from the perspective of healthcare providers in the UK, Denmark and Colombia. Methods A cost-utility analysis was performed based on data from a multinational, Phase III randomised controlled trial. A decision-analytic model was developed based on a series of regression models, which extrapolated health-related quality of life, hospitalisation rates and survival over a lifetime horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER). Results In the UK, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan (using cardiovascular mortality) was £17 100 (€20 400) versus enalapril. In Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (€22 600). In Colombia, the ICER was COP$39.5 million (€11 200) per QALY gained. Deterministic sensitivity analysis showed that results were most sensitive to the extrapolation of mortality, duration of treatment effect and time horizon, but were robust to other structural changes, with most scenarios associated with ICERs below the willingness-to-pay threshold for all three country settings. Probabilistic sensitivity analysis suggested the probability that sacubitril/valsartan was cost-effective at conventional willingness-to-pay thresholds was 68%–94% in the UK, 84% in Denmark and 95% in Colombia. Conclusions Our analysis suggests that, in all three countries, sacubitril/valsartan is likely to be cost-effective compared with an ACEI (the current standard of care) in patients with HF-REF. PMID:29269379

Sensitive determination of thiols in wine samples by a stable isotope-coded derivatization reagent d0/d4-acridone-10-ethyl-N-maleimide coupled with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis.

PubMed

Lv, Zhengxian; You, Jinmao; Lu, Shuaimin; Sun, Weidi; Ji, Zhongyin; Sun, Zhiwei; Song, Cuihua; Chen, Guang; Li, Guoliang; Hu, Na; Zhou, Wu; Suo, Yourui

2017-03-31

As the key aroma compounds, varietal thiols are the crucial odorants responsible for the flavor of wines. Quantitative analysis of thiols can provide crucial information for the aroma profiles of different wine styles. In this study, a rapid and sensitive method for the simultaneous determination of six thiols in wine using d 0 /d 4 -acridone-10-ethyl-N-maleimide (d 0 /d 4 -AENM) as stable isotope-coded derivatization reagent (SICD) by high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) has been developed. Quantification of thiols was performed by using d 4 -AENM labeled thiols as the internal standards (IS), followed by stable isotope dilution HPLC-ESI-MS/MS analysis. The AENM derivatization combined with multiple reactions monitoring (MRM) not only allowed trace analysis of thiols due to the extremely high sensitivity, but also efficiently corrected the matrix effects during HPLC-MS/MS and the fluctuation in MS/MS signal intensity due to instrument. The obtained internal standard calibration curves for six thiols were linear over the range of 25-10,000pmol/L (R 2 ≥0.9961). Detection limits (LODs) for most of analytes were below 6.3pmol/L. The proposed method was successfully applied for the simultaneous determination of six kinds of thiols in wine samples with precisions ≤3.5% and recoveries ≥78.1%. In conclusion, the developed method is expected to be a promising tool for detection of trace thiols in wine and also in other complex matrix. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of l-glutamic acid fermentation by using a dynamic metabolic simulation model of Escherichia coli

PubMed Central

2013-01-01

Background Understanding the process of amino acid fermentation as a comprehensive system is a challenging task. Previously, we developed a literature-based dynamic simulation model, which included transcriptional regulation, transcription, translation, and enzymatic reactions related to glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and the anaplerotic pathway of Escherichia coli. During simulation, cell growth was defined such as to reproduce the experimental cell growth profile of fed-batch cultivation in jar fermenters. However, to confirm the biological appropriateness of our model, sensitivity analysis and experimental validation were required. Results We constructed an l-glutamic acid fermentation simulation model by removing sucAB, a gene encoding α-ketoglutarate dehydrogenase. We then performed systematic sensitivity analysis for l-glutamic acid production; the results of this process corresponded with previous experimental data regarding l-glutamic acid fermentation. Furthermore, it allowed us to predicted the possibility that accumulation of 3-phosphoglycerate in the cell would regulate the carbon flux into the TCA cycle and lead to an increase in the yield of l-glutamic acid via fermentation. We validated this hypothesis through a fermentation experiment involving a model l-glutamic acid-production strain, E. coli MG1655 ΔsucA in which the phosphoglycerate kinase gene had been amplified to cause accumulation of 3-phosphoglycerate. The observed increase in l-glutamic acid production verified the biologically meaningful predictive power of our dynamic metabolic simulation model. Conclusions In this study, dynamic simulation using a literature-based model was shown to be useful for elucidating the precise mechanisms involved in fermentation processes inside the cell. Further exhaustive sensitivity analysis will facilitate identification of novel factors involved in the metabolic regulation of amino acid fermentation. PMID:24053676

Analysis of Bisphenol A, Alkylphenols, and Alkylphenol Ethoxylates in NIST SRM 2585 and Indoor House Dust by Gas Chromatography-Tandem Mass Spectrometry (GC/MS/MS).

PubMed

Fan, Xinghua; Kubwabo, Cariton; Wu, Fang; Rasmussen, Pat E

2018-06-26

Background: Ingestion of house dust has been demonstrated to be an important exposure pathway to several contaminants in young children. These compounds include bisphenol A (BPA), alkylphenols (APs), and alkylphenol ethoxylates (APEOs). Analysis of these compounds in house dust is challenging because of the complex composition of the sample matrix. Objective: The objective was to develop a simple and sensitive method to measure BPA, APs, and APEOs in indoor house dust. Methods: An integrated method that involved solvent extraction using sonication, sample cleanup by solid-phase extraction, derivatization by 2,2,2-trifluoro- N -methyl- N -(trimethylsilyl)acetamide, and analysis by GC coupled with tandem MS was developed for the simultaneous determination of BPA, APs, and APEOs in NIST Standard Reference Material (SRM) 2585 (Organic contaminants in house dust) and in settled house dust samples. Results: Target analytes included BPA, 4- tert -octylphenol (OP), OP monoethoxylate, OP diethoxylate, 4- n -nonylphenol (4 n NP), 4 n NP monoethoxylate (4 n NP 1 EO), branched nonylphenol (NP), NP monoethoxylate, NP diethoxylate, NP triethoxylate, and NP tetraethoxylate. The method was sensitive, with method detection limits ranging from 0.05 to 5.1 μg/g, and average recoveries between 82 and 115%. All target analytes were detected in SRM 2585 and house dust except 4 n NP and 4 n NP 1 EO. Conclusions: The method is simple and fast, with high sensitivity and good reproducibility. It is applicable to the analysis of target analytes in similar matrixes, such as sediments, soil, and biosolids. Highlights: Values measured in SRM 2585 will be useful for future research in method development and method comparison.

Accuracy of Presurgical Functional MR Imaging for Language Mapping of Brain Tumors: A Systematic Review and Meta-Analysis.

PubMed

Weng, Hsu-Huei; Noll, Kyle R; Johnson, Jason M; Prabhu, Sujit S; Tsai, Yuan-Hsiung; Chang, Sheng-Wei; Huang, Yen-Chu; Lee, Jiann-Der; Yang, Jen-Tsung; Yang, Cheng-Ta; Tsai, Ying-Huang; Yang, Chun-Yuh; Hazle, John D; Schomer, Donald F; Liu, Ho-Ling

2018-02-01

Purpose To compare functional magnetic resonance (MR) imaging for language mapping (hereafter, language functional MR imaging) with direct cortical stimulation (DCS) in patients with brain tumors and to assess factors associated with its accuracy. Materials and Methods PubMed/MEDLINE and related databases were searched for research articles published between January 2000 and September 2016. Findings were pooled by using bivariate random-effects and hierarchic summary receiver operating characteristic curve models. Meta-regression and subgroup analyses were performed to evaluate whether publication year, functional MR imaging paradigm, magnetic field strength, statistical threshold, and analysis software affected classification accuracy. Results Ten articles with a total of 214 patients were included in the analysis. On a per-patient basis, the pooled sensitivity and specificity of functional MR imaging was 44% (95% confidence interval [CI]: 14%, 78%) and 80% (95% CI: 54%, 93%), respectively. On a per-tag basis (ie, each DCS stimulation site or "tag" was considered a separate data point across all patients), the pooled sensitivity and specificity were 67% (95% CI: 51%, 80%) and 55% (95% CI: 25%, 82%), respectively. The per-tag analysis showed significantly higher sensitivity for studies with shorter functional MR imaging session times (P = .03) and relaxed statistical threshold (P = .05). Significantly higher specificity was found when expressive language task (P = .02), longer functional MR imaging session times (P < .01), visual presentation of stimuli (P = .04), and stringent statistical threshold (P = .01) were used. Conclusion Results of this study showed moderate accuracy of language functional MR imaging when compared with intraoperative DCS, and the included studies displayed significant methodologic heterogeneity. © RSNA, 2017 Online supplemental material is available for this article.

Developing a testing battery for measuring dogs' stifle functionality: the Finnish Canine Stifle Index (FCSI).

PubMed

Hyytiäinen, Heli K; Mölsä, Sari H; Junnila, Jouni J T; Laitinen-Vapaavuori, Outi M; Hielm-Björkman, Anna K

2018-05-19

This study aimed at developing a quantitative testing battery for dogs' stifle functionality, as, unlike in human medicine, currently none is available in the veterinary field. Forty-three dogs with surgically treated unilateral cranial cruciate ligament rupture and 21 dogs with no known musculoskeletal problems were included. Eight previously studied tests: compensation in sitting and lying positions, symmetry of thrust in hindlimbs when rising from lying and sitting, static weight bearing, stifle flexion and extension and muscle mass symmetry, were summed into the Finnish Canine Stifle Index (FCSI). Sensitivities and specificities of the dichotomised FCSI score were calculated against orthopaedic examination, radiological and force platform analysis and a conclusive assessment (combination of previous). One-way analysis of variance (ANOVA)was used to evaluate FCSI score differences between the groups. Cronbach's alpha for internal consistency was calculated. The range of the index score was 0-263, with a proposed cut-off value of 60 between 'adequate' and 'compromised' functional performance. In comparison to the conclusive assessment, the sensitivity and specificity of the FCSI were 90 per cent and 90.5 per cent, respectively. Cronbach's alpha for internal reliability of the FCSI score was 0.727. An estimate of the surgically treated and control dogs' FCSI scores were 105 (95 per cent CI 93 to 116) and 20 (95 per cent CI 4 to 37), respectively. The difference between the groups was significant (P<0.001). © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Improving Maternal Care through a State-Wide Health Insurance Program: A Cost and Cost-Effectiveness Study in Rural Nigeria

PubMed Central

Gomez, Gabriela B.; Foster, Nicola; Brals, Daniella; Nelissen, Heleen E.; Bolarinwa, Oladimeji A.; Hendriks, Marleen E.; Boers, Alexander C.; van Eck, Diederik; Rosendaal, Nicole; Adenusi, Peju; Agbede, Kayode; Akande, Tanimola M.; Boele van Hensbroek, Michael; Wit, Ferdinand W.; Hankins, Catherine A.; Schultsz, Constance

2015-01-01

Background While the Nigerian government has made progress towards the Millennium Development Goals, further investments are needed to achieve the targets of post-2015 Sustainable Development Goals, including Universal Health Coverage. Economic evaluations of innovative interventions can help inform investment decisions in resource-constrained settings. We aim to assess the cost and cost-effectiveness of maternal care provided within the new Kwara State Health Insurance program (KSHI) in rural Nigeria. Methods and Findings We used a decision analytic model to simulate a cohort of pregnant women. The primary outcome is the incremental cost effectiveness ratio (ICER) of the KSHI scenario compared to the current standard of care. Intervention cost from a healthcare provider perspective included service delivery costs and above-service level costs; these were evaluated in a participating hospital and using financial records from the managing organisations, respectively. Standard of care costs from a provider perspective were derived from the literature using an ingredient approach. We generated 95% credibility intervals around the primary outcome through probabilistic sensitivity analysis (PSA) based on a Monte Carlo simulation. We conducted one-way sensitivity analyses across key model parameters and assessed the sensitivity of our results to the performance of the base case separately through a scenario analysis. Finally, we assessed the sustainability and feasibility of this program’s scale up within the State’s healthcare financing structure through a budget impact analysis. The KSHI scenario results in a health benefit to patients at a higher cost compared to the base case. The mean ICER (US$46.4/disability-adjusted life year averted) is considered very cost-effective compared to a willingness-to-pay threshold of one gross domestic product per capita (Nigeria, US$ 2012, 2,730). Our conclusion was robust to uncertainty in parameters estimates (PSA: median US$49.1, 95% credible interval 21.9–152.3), during one-way sensitivity analyses, and when cost, quality, cost and utilization parameters of the base case scenario were changed. The sustainability of this program’s scale up by the State is dependent on further investments in healthcare. Conclusions This study provides evidence that the investment made by the KSHI program in rural Nigeria is likely to have been cost-effective; however, further healthcare investments are needed for this program to be successfully expanded within Kwara State. Policy makers should consider supporting financial initiatives to reduce maternal mortality tackling both supply and demand issues in the access to care. PMID:26413788

What nursing students reveal about and learn from mentors when using stories of clinical practice.

PubMed

Edwards, Sharon

2017-02-27

Aim This article considers findings from a narrative research analysis that illustrate what nursing students can reveal about being mentored through their stories of clinical practice experience. The aim is to advocate the use of stories as tools to assist mentors in their roles, and to express to them students' concerns, sensitivities and priorities about clinical placement experiences. The findings are extracted from the author's unpublished doctoral thesis Learning from Practice: The Value of Story in Nurse Education ( Edwards 2013 ). Method The data are drawn from nursing students' stories about clinical practice experiences when engaged in the care of patients, and their perceived learning from them. Results Findings suggest stories can help develop understanding of nursing students' concerns, sensitivities and priorities, and can support mentors' important roles in students' learning. Conclusion The article illustrates the value of stories as learning tools in the workplace and, by looking at nursing students' stories about clinical practice, shows that paying attention to their concerns, sensitivities and priorities can improve the already significant role played by mentors in student learning.

A proposal for measuring the degree of public health–sensitivity of patent legislation in the context of the WTO TRIPS Agreement

PubMed Central

Chaves, Gabriela Costa

2007-01-01

Abstract Objective This study aims to propose a framework for measuring the degree of public health-sensitivity of patent legislation reformed after the World Trade Organization’s TRIPS (Trade-Related Aspects of Intellectual Property Rights) Agreement entered into force. Methods The methodology for establishing and testing the proposed framework involved three main steps:(1) a literature review on TRIPS flexibilities related to the protection of public health and provisions considered “TRIPS-plus”; (2) content validation through consensus techniques (an adaptation of Delphi method); and (3) an analysis of patent legislation from nineteen Latin American and Caribbean countries. Findings The results show that the framework detected relevant differences in countries’ patent legislation, allowing for country comparisons. Conclusion The framework’s potential usefulness in monitoring patent legislation changes arises from its clear parameters for measuring patent legislation’s degree of health sensitivity. Nevertheless, it can be improved by including indicators related to government and organized society initiatives that minimize free-trade agreements’ negative effects on access to medicines. PMID:17242758

A Single-Institution Experience in Percutaneous Image-Guided Biopsy of Malignant Pleural Mesothelioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Welch, B. T., E-mail: Welch.brian@mayo.edu; Eiken, P. W.; Atwell, T. D.

PurposeMesothelioma has been considered a difficult pathologic diagnosis to achieve via image-guided core needle biopsy. The purpose of this study was to assess the diagnostic sensitivity of percutaneous image-guided biopsy for diagnosis of pleural mesothelioma.Materials and MethodsRetrospective review was performed to identify patients with a confirmed diagnosis of pleural mesothelioma and who underwent image-guided needle biopsy between January 1, 2002, and January 1, 2016. Thirty-two patients with pleural mesothelioma were identified and included for analysis in 33 image-guided biopsy procedures. Patient, procedural, and pathologic characteristics were recorded. Complications were characterized via standardized nomenclature [Common Terminology for Clinically Adverse Events (CTCAE)].ResultsPercutaneousmore » image-guided biopsy was associated with an overall sensitivity of 81%. No CTCAE clinically significant complications were observed. No image-guided procedures were complicated by pneumothorax or necessitated chest tube placement. No patients had tumor seeding of the biopsy tract.ConclusionPercutaneous image-guided biopsy can achieve high sensitivity for pathologic diagnosis of pleural mesothelioma with a low procedural complication rate, potentially obviating need for surgical biopsy.« less

Detection of living cells in stratospheric samples

NASA Astrophysics Data System (ADS)

Harris, Melanie J.; Wickramasinghe, N. C.; Lloyd, David; Narlikar, J. V.; Rajaratnam, P.; Turner, Michael P.; Al-Mufti, Shirwan; Wallis, Max K.; Ramadurai, S.; Hoyle, Fred

2002-02-01

Air samples collected aseptically over tropical India at various stratospheric altitudes ranging from 20 to 41 km using cryosampler assemblies carried on balloons flown from Hyderabad have shown evidence of living microbial cells. Unambiguous evidence of living cells came from examining micropore filters on which the samples were recovered with the use of voltage sensitive lipophilic dyes that could detect the presents of active cells. Clumps of viable cells were found at all altitudes using this technique, and this conclusion was found to be consistent with images obtained from electron microscopy. Since the 41 km sample was collected well above the local tropopause, a prima facie case for a space incidence of these microorganisms is established. Further work on culturing, PCR analysis and isotopic analysis is in progress.

EBUS-Guided Cautery-Assisted Transbronchial Forceps Biopsies: Safety and Sensitivity Relative to Transbronchial Needle Aspiration

PubMed Central

Bramley, Kyle; Pisani, Margaret A.; Murphy, Terrence E.; Araujo, Katy; Homer, Robert; Puchalski, Jonathan

2016-01-01

Background EBUS-guided transbronchial needle aspiration (TBNA) is important in the evaluation of thoracic lymphadenopathy. Reliably providing excellent diagnostic yield for malignancy, its diagnosis of sarcoidosis is inconsistent. Furthermore, when larger “core” biopsy samples of malignant tissue are required, TBNA may not suffice. The primary objective of this study was to determine if the sequential use of TBNA and a novel technique called cautery-assisted transbronchial forceps biopsies (ca-TBFB) was safe. Secondary outcomes included sensitivity and successful acquisition of tissue. Methods Fifty unselected patients undergoing convex probe EBUS were prospectively enrolled. Under EBUS guidance, all lymph nodes ≥ 1 cm were sequentially biopsied using TBNA and ca-TBFB. Safety and sensitivity were assessed at the nodal level for 111 nodes. Results of each technique were also reported on a per-patient basis. Results There were no significant adverse events. In nodes determined to be malignant, TBNA provided higher sensitivity (100%) than ca-TBFB (78%). However, among nodes with granulomatous inflammation, ca-TBFB exhibited higher sensitivity (90%) than TBNA (33%). For analysis based on patients rather than nodes, 6 of the 31 patients with malignancy would have been missed or understaged if the diagnosis was based on samples obtained by ca-TBFB. On the other hand, 3 of 8 patients with sarcoidosis would have been missed if analysis was based only on TBNA samples. In some cases only ca-TBFB acquired sufficient tissue for the core samples needed in clinical trials of malignancy. Conclusions The sequential use of TBNA and ca-TBFB appears to be safe. The larger samples obtained from ca-TBFB increased its sensitivity to detect granulomatous disease and provided specimens for clinical trials of malignancy when needle biopsies were insufficient. For thoracic surgeons and advanced bronchoscopists, we advocate ca-TBFB as an alternative to TBNA in select clinical scenarios. PMID:26912301

Effects of changes along the risk chain on flood risk

NASA Astrophysics Data System (ADS)

Duha Metin, Ayse; Apel, Heiko; Viet Dung, Nguyen; Guse, Björn; Kreibich, Heidi; Schröter, Kai; Vorogushyn, Sergiy; Merz, Bruno

2017-04-01

Interactions of hydrological and socio-economic factors shape flood disaster risk. For this reason, assessment of flood risk ideally takes into account the whole flood risk chain from atmospheric processes, through the catchment and river system processes to the damage mechanisms in the affected areas. Since very different processes at various scales are interacting along the flood risk, the impact of the single components is rather unclear. However for flood risk management, it is required to know the controlling factor of flood damages. The present study, using the flood-prone Mulde catchment in Germany, discusses the sensitivity of flood risk to disturbances along the risk chain: How do disturbances propagate through the risk chain? How do different disturbances combine or conflict and affect flood risk? In this sensitivity analysis, the five components of the flood risk change are included. These are climate, catchment, river system, exposure and vulnerability. A model framework representing the complete risk chain is combined with observational data to understand how the sensitivities evolve along the risk chain by considering three plausible change scenarios for each of five components. The flood risk is calculated by using the Regional Flood Model (RFM) which is based on a continuous simulation approach, including rainfall-runoff, 1D river network, 2D hinterland inundation and damage estimation models. The sensitivity analysis covers more than 240 scenarios with different combinations of the five components. It is investigated how changes in different components affect risk indicators, such as the risk curve and expected annual damage (EAD). In conclusion, it seems that changes in exposure and vulnerability seem to outweigh changes in hazard.

Systematic Review and Meta-Analysis of CT Features for Differentiating Complicated and Uncomplicated Appendicitis.

PubMed

Kim, Hae Young; Park, Ji Hoon; Lee, Yoon Jin; Lee, Sung Soo; Jeon, Jong-June; Lee, Kyoung Ho

2018-04-01

Purpose To perform a systematic review and meta-analysis to identify computed tomographic (CT) features for differentiating complicated appendicitis in patients suspected of having appendicitis and to summarize their diagnostic accuracy. Materials and Methods Studies on diagnostic accuracy of CT features for differentiating complicated appendicitis (perforated or gangrenous appendicitis) in patients suspected of having appendicitis were searched in Ovid-MEDLINE, EMBASE, and the Cochrane Library. Overlapping descriptors used in different studies to denote the same image finding were subsumed under a single CT feature. Pooled diagnostic accuracy of the CT features was calculated by using a bivariate random effects model. CT features with pooled diagnostic odds ratios with 95% confidence intervals not including 1 were considered as informative. Results Twenty-three studies were included, and 184 overlapping descriptors for various CT findings were subsumed under 14 features. Of these, 10 features were informative for complicated appendicitis. There was a general tendency for these features to show relatively high specificity but low sensitivity. Extraluminal appendicolith, abscess, appendiceal wall enhancement defect, extraluminal air, ileus, periappendiceal fluid collection, ascites, intraluminal air, and intraluminal appendicolith showed pooled specificity greater than 70% (range, 74%-100%), but sensitivity was limited (range, 14%-59%). Periappendiceal fat stranding was the only feature that showed high sensitivity (94%; 95% confidence interval: 86%, 98%) but low specificity (40%; 95% confidence interval, 23%, 60%). Conclusion Ten informative CT features for differentiating complicated appendicitis were identified in this study, nine of which showed high specificity, but low sensitivity. © RSNA, 2017 Online supplemental material is available for this article.

Exploration of Analysis Methods for Diagnostic Imaging Tests: Problems with ROC AUC and Confidence Scores in CT Colonography

PubMed Central

Mallett, Susan; Halligan, Steve; Collins, Gary S.; Altman, Doug G.

2014-01-01

Background Different methods of evaluating diagnostic performance when comparing diagnostic tests may lead to different results. We compared two such approaches, sensitivity and specificity with area under the Receiver Operating Characteristic Curve (ROC AUC) for the evaluation of CT colonography for the detection of polyps, either with or without computer assisted detection. Methods In a multireader multicase study of 10 readers and 107 cases we compared sensitivity and specificity, using radiological reporting of the presence or absence of polyps, to ROC AUC calculated from confidence scores concerning the presence of polyps. Both methods were assessed against a reference standard. Here we focus on five readers, selected to illustrate issues in design and analysis. We compared diagnostic measures within readers, showing that differences in results are due to statistical methods. Results Reader performance varied widely depending on whether sensitivity and specificity or ROC AUC was used. There were problems using confidence scores; in assigning scores to all cases; in use of zero scores when no polyps were identified; the bimodal non-normal distribution of scores; fitting ROC curves due to extrapolation beyond the study data; and the undue influence of a few false positive results. Variation due to use of different ROC methods exceeded differences between test results for ROC AUC. Conclusions The confidence scores recorded in our study violated many assumptions of ROC AUC methods, rendering these methods inappropriate. The problems we identified will apply to other detection studies using confidence scores. We found sensitivity and specificity were a more reliable and clinically appropriate method to compare diagnostic tests. PMID:25353643

Dietary patterns, insulin sensitivity and inflammation in older adults

PubMed Central

Anderson, Amy L.; Harris, Tamara B.; Tylavsky, Frances A.; Perry, Sara E.; Houston, Denise K.; Lee, Jung Sun; Kanaya, Alka M.; Sahyoun, Nadine R.

2011-01-01

Background/Objectives Several studies have linked dietary patterns to insulin sensitivity and systemic inflammation, which affect risk of multiple chronic diseases. The purpose of this study was to investigate the dietary patterns of a cohort of older adults, and examine relationships of dietary patterns with markers of insulin sensitivity and systemic inflammation. Subjects/Methods The Health, Aging and Body Composition (Health ABC) Study is a prospective cohort study of 3075 older adults. In Health ABC, multiple indicators of glucose metabolism and systemic inflammation were assessed. Food intake was estimated with a modified Block food frequency questionnaire (FFQ). In this study, dietary patterns of 1751 participants with complete data were derived by cluster analysis. Results Six clusters were identified, including a ‘Healthy foods’ cluster, characterized by higher intake of lowfat dairy products, fruit, whole grains, poultry, fish and vegetables. In the main analysis, the ‘Healthy foods’ cluster had significantly lower fasting insulin and HOMA-IR than the ‘Breakfast cereal’ and ‘High-fat dairy products’ clusters, and lower fasting glucose than the ‘High-fat dairy products’ cluster (P ≤ 0.05). No differences were found in 2-hour glucose. With respect to inflammation, the ‘Healthy foods’ cluster had lower IL-6 than the ‘Sweets and desserts’ and ‘High-fat dairy products’ clusters, and no differences were seen in CRP or TNF-α. Conclusions A dietary pattern high in lowfat dairy products, fruit, whole grains, poultry, fish and vegetables may be associated with greater insulin sensitivity and lower systemic inflammation in older adults. PMID:21915138

Sensitive and Specific Detection of Early Gastric Cancer Using DNA Methylation Analysis of Gastric Washes

PubMed Central

Watanabe, Yoshiyuki; Kim, Hyun Soo; Castoro, Ryan J.; Chung, Woonbok; Estecio, Marcos R. H.; Kondo, Kimie; Guo, Yi; Ahmed, Saira S.; Toyota, Minoru; Itoh, Fumio; Suk, Ki Tae; Cho, Mee-Yon; Shen, Lanlan; Jelinek, Jaroslav; Issa, Jean-Pierre J.

2009-01-01

Background & Aims Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. Methods We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 non-neoplastic gastric mucosa samples. Results 6 genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer while PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r=0.5 to 0.9, p=0.03 to 0.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the ROC curve (0.961) in terms of tumor detection in gastric washes. Conclusions These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally we have developed a new methodology for gastric cancer detection by DNA methylation in gastric washes. PMID:19375421

Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer

PubMed Central

Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo

2017-01-01

Purpose This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). Materials and Methods We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). Results In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Conclusion Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes. PMID:27669704

ON THE USE OF SHOT NOISE FOR PHOTON COUNTING

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zmuidzinas, Jonas, E-mail: jonas@caltech.edu

Lieu et al. have recently claimed that it is possible to substantially improve the sensitivity of radio-astronomical observations. In essence, their proposal is to make use of the intensity of the photon shot noise as a measure of the photon arrival rate. Lieu et al. provide a detailed quantum-mechanical calculation of a proposed measurement scheme that uses two detectors and conclude that this scheme avoids the sensitivity degradation that is associated with photon bunching. If correct, this result could have a profound impact on radio astronomy. Here I present a detailed analysis of the sensitivity attainable using shot-noise measurement schemesmore » that use either one or two detectors, and demonstrate that neither scheme can avoid the photon bunching penalty. I perform both semiclassical and fully quantum calculations of the sensitivity, obtaining consistent results, and provide a formal proof of the equivalence of these two approaches. These direct calculations are furthermore shown to be consistent with an indirect argument based on a correlation method that establishes an independent limit to the sensitivity of shot-noise measurement schemes. Furthermore, these calculations are directly applicable to the regime of interest identified by Lieu et al. Collectively, these results conclusively demonstrate that the photon-bunching sensitivity penalty applies to shot-noise measurement schemes just as it does to ordinary photon counting, in contradiction to the fundamental claim made by Lieu et al. The source of this contradiction is traced to a logical fallacy in their argument.« less

Seeking a valid gold standard for an innovative, dialect-neutral language test.

PubMed

Pearson, Barbara Zurer; Jackson, Janice E; Wu, Haotian

2014-04-01

PURPOSE In this study, the authors explored alternative gold standards to validate an innovative, dialect-neutral language assessment. METHOD Participants were 78 African American children, ages 5;0 (years;months) to 6;11. Twenty participants had previously been identified as having language impairment. The Diagnostic Evaluation of Language Variation-Norm Referenced (DELV-NR; Seymour, Roeper, & J. de Villiers, 2005) was administered, and concurrent language samples (LSs) were collected. Using LS profiles as the gold standard, sensitivity, specificity, and other measures of diagnostic accuracy were compared for diagnoses made from the DELV-NR and participants' clinical status prior to recruitment. In a second analysis, the authors used results from the first analysis to make evidence-based adjustments in the estimates of DELV-NR diagnostic accuracy. RESULTS Accuracy of the DELV-NR relative to LS profiles was greater than that of prior diagnoses, indicating that the DELV-NR was an improvement over preexisting diagnoses for this group. Specificity met conventional standards, but sensitivity was somewhat low. Reanalysis using the positive and negative predictive power of the preexisting diagnosis in a discrepant-resolution procedure revealed that estimates for sensitivity and specificity for the DELV-NR were .85 and .93, respectively. CONCLUSION The authors found that, even after making allowances for the imperfection of available gold standards, clinical decisions made with the DELV-NR achieved high values on conventional measures of diagnostic accuracy.

Diagnostic Validity of High-Density Barium Sulfate in Gastric Cancer Screening: Follow-up of Screenees by Record Linkage with the Osaka Cancer Registry

PubMed Central

Yamamoto, Kenyu; Yamazaki, Hideo; Kuroda, Chikazumi; Kubo, Tsugio; Oshima, Akira; Katsuda, Toshizo; Kuwano, Tadao; Takeda, Yoshihiro

2010-01-01

Background The use of high-density barium sulfate was recommended by the Japan Society of Gastroenterological Cancer Screening (JSGCS) in 2004. We evaluated the diagnostic validity of gastric cancer screening that used high-density barium sulfate. Methods The study subjects were 171 833 residents of Osaka, Japan who underwent gastric cancer screening tests at the Osaka Cancer Prevention and Detection Center during the period from 1 January 2000 through 31 December 2001. Screening was conducted using either high-density barium sulfate (n = 48 336) or moderate-density barium sulfate (n = 123 497). The subjects were followed up and their medical records were linked to those of the Osaka Cancer Registry through 31 December 2002. The results of follow-up during 1 year were defined as the gold standard, and test performance values were calculated. Results The sensitivity and specificity of the screening test using moderate-density barium sulfate were 92.3% and 91.0%, respectively, while the sensitivity and specificity of the high-density barium test were 91.8% and 91.4%, respectively. The results of area under receiver-operating-characteristic (ROC) curve analysis revealed no significant difference between the 2 screening tests. Conclusions Screening tests using high- and moderate-density barium sulfate had similar validity, as determined by sensitivity, specificity, and ROC curve analysis. PMID:20551581

[Relationship between personality characteristics and turnover intention of medical staff in an infectious disease hospital].

PubMed

Ma, K H; Cui, Z Y; Li, L; Chao, H; Wang, Y

2017-12-20

Objective: To investigate the relationship between personality characteristics and turnover intention of the medical staff in an infectious diseases hospital. Methods: Using the cluster sampling method, a total of 366 members of medical staff were selected from different departments in an infectious disease hospital from May to August, 2013. The general information, such as sex, age, education level, and professional title, were collected and they were subjected to a survey using Cattell's 16 Personality Factor Questionnaire and Turnover Intention Scale. The data were subjected to logistic regression analysis. Results: Compared with the Chinese norm, the medical staff in the infectious disease hospital had significantly higher scores of intelligence, stability, bullying, excitability, perseverance, social boldness, fantasy, privateness, independence, and self-discipline and significantly lower scores of gregariousness, sensitivity, suspicion, anxiety, and tension ( P <0.05). Of the 366 members of medical staff, 22 (6.01%) had a very low turnover intention, low in 152 (41.53%) , high in 61 (16.67%) , and very high in 131 (35.79%). The logistic regression analysis showed that sensitivity, suspicion, fantasy, privateness, anxiety, openness to change, and independence were the risk factors for turnover intention ( P <0.05) . Conclusion: Compared with the Chinese norm, the medical staff in the infectious disease hospital have a better mental quality and a higher turnover intention. The individuals with sensitivity, suspicion, fantasy, and anxiety are prone to having turnover intention.

Comparison of DWI and PET/CT in evaluation of lymph node metastasis in uterine cancer

PubMed Central

Kitajima, Kazuhiro; Yamasaki, Erena; Kaji, Yasushi; Murakami, Koji; Sugimura, Kazuro

2012-01-01

AIM: To investigate diffusion-weighted imaging (DWI) and positron emission tomography and computed tomography (PET/CT) with IV contrast for the preoperative evaluation of pelvic lymph node (LN) metastasis in uterine cancer. METHODS: Twenty-five patients with endometrial or cervical cancer who underwent both DWI and PET/CT before pelvic lymphadenectomy were included in this study. For area specific analysis, LNs were divided into eight regions: both common iliac, external iliac, internal iliac areas, and obturator areas. The classification for malignancy on DWI was a focally abnormal signal intensity in a location that corresponded to the LN chains on the T1WI and T2WI. The criterion for malignancy on PET/CT images was increased tracer uptake by the LN. RESULTS: A total of 36 pathologically positive LN areas were found in 9 patients. With DWI, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for detecting metastatic LNs on an LN area-by-area analysis were 83.3%, 51.2%, 27.3%, 93.3% and 57.0%, respectively, while the corresponding values for PET/CT were 38.9%, 96.3%, 70.0%, 87.8% and 86.0%. Differences in sensitivity, specificity and accuracy were significant (P < 0.0005). CONCLUSION: DWI showed higher sensitivity and lower specificity than PET/CT. Neither DWI nor PET/CT were sufficiently accurate to replace lymphadenectomy. PMID:22761980

Variable Delay Multi-Pulse Train for Fast Chemical Exchange Saturation Transfer and Relayed-Nuclear Overhauser Enhancement MRI

PubMed Central

Xu, Jiadi; Yadav, Nirbhay N.; Bar-Shir, Amnon; Jones, Craig K.; Chan, Kannie W. Y.; Zhang, Jiangyang; Walczak, P.; McMahon, Michael T.; van Zijl, Peter C. M.

2013-01-01

Purpose Chemical exchange saturation transfer (CEST) imaging is a new MRI technology allowing the detection of low concentration endogenous cellular proteins and metabolites indirectly through their exchangeable protons. A new technique, variable delay multi-pulse CEST (VDMP-CEST), is proposed to eliminate the need for recording full Z-spectra and performing asymmetry analysis to obtain CEST contrast. Methods The VDMP-CEST scheme involves acquiring images with two (or more) delays between radiofrequency saturation pulses in pulsed CEST, producing a series of CEST images sensitive to the speed of saturation transfer. Subtracting two images or fitting a time series produces CEST and relayed-nuclear Overhauser enhancement CEST maps without effects of direct water saturation and, when using low radiofrequency power, minimal magnetization transfer contrast interference. Results When applied to several model systems (bovine serum albumin, crosslinked bovine serum albumin, l-glutamic acid) and in vivo on healthy rat brain, VDMP-CEST showed sensitivity to slow to intermediate range magnetization transfer processes (rate < 100–150 Hz), such as amide proton transfer and relayed nuclear Overhauser enhancement-CEST. Images for these contrasts could be acquired in short scan times by using a single radiofrequency frequency. Conclusions VDMP-CEST provides an approach to detect CEST effect by sensitizing saturation experiments to slower exchange processes without interference of direct water saturation and without need to acquire Z-spectra and perform asymmetry analysis. PMID:23813483

Evaluation of dried blood spot samples for screening of hepatitis C and human immunodeficiency virus in a real-world setting.

PubMed

Vázquez-Morón, Sonia; Ryan, Pablo; Ardizone-Jiménez, Beatriz; Martín, Dolores; Troya, Jesus; Cuevas, Guillermo; Valencia, Jorge; Jimenez-Sousa, María A; Avellón, Ana; Resino, Salvador

2018-01-30

Both hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection are underdiagnosed, particularly in low-income countries and in difficult-to-access populations. Our aim was to develop and evaluate a methodology for the detection of HCV and HIV infection based on capillary dry blood spot (DBS) samples taken under real-world conditions. We carried out a cross-sectional study of 139 individuals (31 healthy controls, 68 HCV-monoinfected patients, and 40 HCV/HIV-coinfected patients). ELISA was used for anti-HCV and anti-HIV antibody detection; and SYBR Green RT-PCR was used for HCV-RNA detection. The HIV serological analysis revealed 100% sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The HCV serological analysis revealed a sensitivity of 92.6%, specificity of 100%, PPV of 100%, and NPV of 79.5%. Finally, the HCV-RNA detection test revealed a detection limit of 5 copies/µl with an efficiency of 100% and sensitivity of 99.1%, specificity of 100%, PPV of 100%, and NPV of 96.9%. In conclusion, our methodology was able to detect both HCV infection and HIV infection from the same DBS sample with good diagnostic performance. Screening for HCV and HIV using DBS might be a key strategy in the implementation of national programs for the control of both infections.

Cost effectiveness analysis comparing repetitive transcranial magnetic stimulation to antidepressant medications after a first treatment failure for major depressive disorder in newly diagnosed patients – A lifetime analysis

PubMed Central

2017-01-01

Objective Repetitive Transcranial Magnetic Stimulation (rTMS) commonly is used for the treatment of Major Depressive Disorder (MDD) after patients have failed to benefit from trials of multiple antidepressant medications. No analysis to date has examined the cost-effectiveness of rTMS used earlier in the course of treatment and over a patients’ lifetime. Methods We used lifetime Markov simulation modeling to compare the direct costs and quality adjusted life years (QALYs) of rTMS and medication therapy in patients with newly diagnosed MDD (ages 20–59) who had failed to benefit from one pharmacotherapy trial. Patients’ life expectancies, rates of response and remission, and quality of life outcomes were derived from the literature, and treatment costs were based upon published Medicare reimbursement data. Baseline costs, aggregate per year quality of life assessments (QALYs), Monte Carlo simulation, tornado analysis, assessment of dominance, and one way sensitivity analysis were also performed. The discount rate applied was 3%. Results Lifetime direct treatment costs, and QALYs identified rTMS as the dominant therapy compared to antidepressant medications (i.e., lower costs with better outcomes) in all age ranges, with costs/improved QALYs ranging from $2,952/0.32 (older patients) to $11,140/0.43 (younger patients). One-way sensitivity analysis demonstrated that the model was most sensitive to the input variables of cost per rTMS session, monthly prescription drug cost, and the number of rTMS sessions per year. Conclusion rTMS was identified as the dominant therapy compared to antidepressant medication trials over the life of the patient across the lifespan of adults with MDD, given current costs of treatment. These models support the use of rTMS after a single failed antidepressant medication trial versus further attempts at medication treatment in adults with MDD. PMID:29073256

Digital PCR Improves Mutation Analysis in Pancreas Fine Needle Aspiration Biopsy Specimens.

PubMed

Sho, Shonan; Court, Colin M; Kim, Stephen; Braxton, David R; Hou, Shuang; Muthusamy, V Raman; Watson, Rabindra R; Sedarat, Alireza; Tseng, Hsian-Rong; Tomlinson, James S

2017-01-01

Applications of precision oncology strategies rely on accurate tumor genotyping from clinically available specimens. Fine needle aspirations (FNA) are frequently obtained in cancer management and often represent the only source of tumor tissues for patients with metastatic or locally advanced diseases. However, FNAs obtained from pancreas ductal adenocarcinoma (PDAC) are often limited in cellularity and/or tumor cell purity, precluding accurate tumor genotyping in many cases. Digital PCR (dPCR) is a technology with exceptional sensitivity and low DNA template requirement, characteristics that are necessary for analyzing PDAC FNA samples. In the current study, we sought to evaluate dPCR as a mutation analysis tool for pancreas FNA specimens. To this end, we analyzed alterations in the KRAS gene in pancreas FNAs using dPCR. The sensitivity of dPCR mutation analysis was first determined using serial dilution cell spiking studies. Single-cell laser-microdissection (LMD) was then utilized to identify the minimal number of tumor cells needed for mutation detection. Lastly, dPCR mutation analysis was performed on 44 pancreas FNAs (34 formalin-fixed paraffin-embedded (FFPE) and 10 fresh (non-fixed)), including samples highly limited in cellularity (100 cells) and tumor cell purity (1%). We found dPCR to detect mutations with allele frequencies as low as 0.17%. Additionally, a single tumor cell could be detected within an abundance of normal cells. Using clinical FNA samples, dPCR mutation analysis was successful in all preoperative FNA biopsies tested, and its accuracy was confirmed via comparison with resected tumor specimens. Moreover, dPCR revealed additional KRAS mutations representing minor subclones within a tumor that were not detected by the current clinical gold standard method of Sanger sequencing. In conclusion, dPCR performs sensitive and accurate mutation analysis in pancreas FNAs, detecting not only the dominant mutation subtype, but also the additional rare mutation subtypes representing tumor heterogeneity.

Digital PCR Improves Mutation Analysis in Pancreas Fine Needle Aspiration Biopsy Specimens

PubMed Central

Court, Colin M.; Kim, Stephen; Braxton, David R.; Hou, Shuang; Muthusamy, V. Raman; Watson, Rabindra R.; Sedarat, Alireza; Tseng, Hsian-Rong; Tomlinson, James S.

2017-01-01

Applications of precision oncology strategies rely on accurate tumor genotyping from clinically available specimens. Fine needle aspirations (FNA) are frequently obtained in cancer management and often represent the only source of tumor tissues for patients with metastatic or locally advanced diseases. However, FNAs obtained from pancreas ductal adenocarcinoma (PDAC) are often limited in cellularity and/or tumor cell purity, precluding accurate tumor genotyping in many cases. Digital PCR (dPCR) is a technology with exceptional sensitivity and low DNA template requirement, characteristics that are necessary for analyzing PDAC FNA samples. In the current study, we sought to evaluate dPCR as a mutation analysis tool for pancreas FNA specimens. To this end, we analyzed alterations in the KRAS gene in pancreas FNAs using dPCR. The sensitivity of dPCR mutation analysis was first determined using serial dilution cell spiking studies. Single-cell laser-microdissection (LMD) was then utilized to identify the minimal number of tumor cells needed for mutation detection. Lastly, dPCR mutation analysis was performed on 44 pancreas FNAs (34 formalin-fixed paraffin-embedded (FFPE) and 10 fresh (non-fixed)), including samples highly limited in cellularity (100 cells) and tumor cell purity (1%). We found dPCR to detect mutations with allele frequencies as low as 0.17%. Additionally, a single tumor cell could be detected within an abundance of normal cells. Using clinical FNA samples, dPCR mutation analysis was successful in all preoperative FNA biopsies tested, and its accuracy was confirmed via comparison with resected tumor specimens. Moreover, dPCR revealed additional KRAS mutations representing minor subclones within a tumor that were not detected by the current clinical gold standard method of Sanger sequencing. In conclusion, dPCR performs sensitive and accurate mutation analysis in pancreas FNAs, detecting not only the dominant mutation subtype, but also the additional rare mutation subtypes representing tumor heterogeneity. PMID:28125707

Meta-Analyses of Diagnostic Accuracy in Imaging Journals: Analysis of Pooling Techniques and Their Effect on Summary Estimates of Diagnostic Accuracy.

PubMed

McGrath, Trevor A; McInnes, Matthew D F; Korevaar, Daniël A; Bossuyt, Patrick M M

2016-10-01

Purpose To determine whether authors of systematic reviews of diagnostic accuracy studies published in imaging journals used recommended methods for meta-analysis, and to evaluate the effect of traditional methods on summary estimates of sensitivity and specificity. Materials and Methods Medline was searched for published systematic reviews that included meta-analysis of test accuracy data limited to imaging journals published from January 2005 to May 2015. Two reviewers independently extracted study data and classified methods for meta-analysis as traditional (univariate fixed- or random-effects pooling or summary receiver operating characteristic curve) or recommended (bivariate model or hierarchic summary receiver operating characteristic curve). Use of methods was analyzed for variation with time, geographical location, subspecialty, and journal. Results from reviews in which study authors used traditional univariate pooling methods were recalculated with a bivariate model. Results Three hundred reviews met the inclusion criteria, and in 118 (39%) of those, authors used recommended meta-analysis methods. No change in the method used was observed with time (r = 0.54, P = .09); however, there was geographic (χ(2) = 15.7, P = .001), subspecialty (χ(2) = 46.7, P < .001), and journal (χ(2) = 27.6, P < .001) heterogeneity. Fifty-one univariate random-effects meta-analyses were reanalyzed with the bivariate model; the average change in the summary estimate was -1.4% (P < .001) for sensitivity and -2.5% (P < .001) for specificity. The average change in width of the confidence interval was 7.7% (P < .001) for sensitivity and 9.9% (P ≤ .001) for specificity. Conclusion Recommended methods for meta-analysis of diagnostic accuracy in imaging journals are used in a minority of reviews; this has not changed significantly with time. Traditional (univariate) methods allow overestimation of diagnostic accuracy and provide narrower confidence intervals than do recommended (bivariate) methods. (©) RSNA, 2016 Online supplemental material is available for this article.

Hyperinsulinism–hyperammonaemia syndrome: novel mutations in the GLUD1 gene and genotype–phenotype correlations

PubMed Central

Kapoor, Ritika R; Flanagan, Sarah E; Fulton, Piers; Chakrapani, Anupam; Chadefaux, Bernadette; Ben-Omran, Tawfeg; Banerjee, Indraneel; Shield, Julian P; Ellard, Sian; Hussain, Khalid

2009-01-01

Background Activating mutations in the GLUD1 gene (which encodes for the intra-mitochondrial enzyme glutamate dehydrogenase, GDH) cause the hyperinsulinism–hyperammonaemia (HI/HA) syndrome. Patients present with HA and leucine-sensitive hypoglycaemia. GDH is regulated by another intra-mitochondrial enzyme sirtuin 4 (SIRT4). Sirt4 knockout mice demonstrate activation of GDH with increased amino acid-stimulated insulin secretion. Objectives To study the genotype–phenotype correlations in patients with GLUD1 mutations. To report the phenotype and functional analysis of a novel mutation (P436L) in the GLUD1 gene associated with the absence of HA. Patients and methods Twenty patients with HI from 16 families had mutational analysis of the GLUD1 gene in view of HA (n=19) or leucine sensitivity (n=1). Patients negative for a GLUD1 mutation had sequence analysis of the SIRT4 gene. Functional analysis of the novel P436L GLUD1 mutation was performed. Results Heterozygous missense mutations were detected in 15 patients with HI/HA, 2 of which are novel (N410D and D451V). In addition, a patient with a normal serum ammonia concentration (21 μmol/l) was heterozygous for a novel missense mutation P436L. Functional analysis of this mutation confirms that it is associated with a loss of GTP inhibition. Seizure disorder was common (43%) in our cohort of patients with a GLUD1 mutation. No mutations in the SIRT4 gene were identified. Conclusion Patients with HI due to mutations in the GLUD1 gene may have normal serum ammonia concentrations. Hence, GLUD1 mutational analysis may be indicated in patients with leucine sensitivity; even in the absence of HA. A high frequency of epilepsy (43%) was observed in our patients with GLUD1 mutations. PMID:19690084

Personality moderates the links of social identity with work motivation and job searching.

PubMed

Baay, Pieter E; van Aken, Marcel A G; van der Lippe, Tanja; de Ridder, Denise T D

2014-01-01

Work motivation is critical for successful school-to-work transitions, but little is known about its determinants among labor market entrants. Applying a social identity framework, we examined whether work motivation and job searching are social-contextually determined. We expected that some job seekers are more sensitive to contextual influence, depending on their personality. Mediation analyses on 591 Dutch vocational training students indicate that the perception of more positive work norms in someone's social context was related to higher levels of intrinsic motivation, which in turn predicted higher preparatory job search behavior and job search intentions. Multi-group analysis shows that perceived work norms more strongly predict work motivation among overcontrollers compared to resilients and undercontrollers. In conclusion, work motivation and job searching appear contextually determined: especially among those sensitive to contextual influence, people seem to work when they believe that is what people like them do.

High sensitivity phase retrieval method in grating-based x-ray phase contrast imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Zhao; Gao, Kun; Chen, Jian

2015-02-15

Purpose: Grating-based x-ray phase contrast imaging is considered as one of the most promising techniques for future medical imaging. Many different methods have been developed to retrieve phase signal, among which the phase stepping (PS) method is widely used. However, further practical implementations are hindered, due to its complex scanning mode and high radiation dose. In contrast, the reverse projection (RP) method is a novel fast and low dose extraction approach. In this contribution, the authors present a quantitative analysis of the noise properties of the refraction signals retrieved by the two methods and compare their sensitivities. Methods: Using themore » error propagation formula, the authors analyze theoretically the signal-to-noise ratios (SNRs) of the refraction images retrieved by the two methods. Then, the sensitivities of the two extraction methods are compared under an identical exposure dose. Numerical experiments are performed to validate the theoretical results and provide some quantitative insight. Results: The SNRs of the two methods are both dependent on the system parameters, but in different ways. Comparison between their sensitivities reveals that for the refraction signal, the RP method possesses a higher sensitivity, especially in the case of high visibility and/or at the edge of the object. Conclusions: Compared with the PS method, the RP method has a superior sensitivity and provides refraction images with a higher SNR. Therefore, one can obtain highly sensitive refraction images in grating-based phase contrast imaging. This is very important for future preclinical and clinical implementations.« less

Sensitivity and Specificity of Polysomnographic Criteria for Defining Insomnia

PubMed Central

Edinger, Jack D.; Ulmer, Christi S.; Means, Melanie K.

2013-01-01

Study Objectives: In recent years, polysomnography-based eligibility criteria have been increasingly used to identify candidates for insomnia research, and this has been particularly true of studies evaluating pharmacologic therapy for primary insomnia. However, the sensitivity and specificity of PSG for identifying individuals with insomnia is unknown, and there is no consensus on the criteria sets which should be used for participant selection. In the current study, an archival data set was used to test the sensitivity and specificity of PSG measures for identifying individuals with primary insomnia in both home and lab settings. We then evaluated the sensitivity and specificity of the eligibility criteria employed in a number of recent insomnia trials for identifying primary insomnia sufferers in our sample. Design: Archival data analysis. Settings: Study participants' homes and a clinical sleep laboratory. Participants: Adults: 76 with primary insomnia and 78 non-complaining normal sleepers. Measurements and Results: ROC and cross-tabs analyses were used to evaluate the sensitivity and specificity of PSG-derived total sleep time, latency to persistent sleep, wake after sleep onset, and sleep efficiency for discriminating adults with primary insomnia from normal sleepers. None of the individual criteria accurately discriminated PI from normal sleepers, and none of the criteria sets used in recent trials demonstrated acceptable sensitivity and specificity for identifying primary insomnia. Conclusions: The use of quantitative PSG-based selection criteria in insomnia research may exclude many who meet current diagnostic criteria for an insomnia disorder. Citation: Edinger JD; Ulmer CS; Means MK. Sensitivity and specificity of polysomnographic criteria for defining insomnia. J Clin Sleep Med 2013;9(5):481-491. PMID:23674940

Development of a practical approach to expert elicitation for randomised controlled trials with missing health outcomes: Application to the IMPROVE trial

PubMed Central

Mason, Alexina J; Gomes, Manuel; Grieve, Richard; Ulug, Pinar; Powell, Janet T; Carpenter, James

2017-01-01

Background/aims: The analyses of randomised controlled trials with missing data typically assume that, after conditioning on the observed data, the probability of missing data does not depend on the patient’s outcome, and so the data are ‘missing at random’ . This assumption is usually implausible, for example, because patients in relatively poor health may be more likely to drop out. Methodological guidelines recommend that trials require sensitivity analysis, which is best informed by elicited expert opinion, to assess whether conclusions are robust to alternative assumptions about the missing data. A major barrier to implementing these methods in practice is the lack of relevant practical tools for eliciting expert opinion. We develop a new practical tool for eliciting expert opinion and demonstrate its use for randomised controlled trials with missing data. Methods: We develop and illustrate our approach for eliciting expert opinion with the IMPROVE trial (ISRCTN 48334791), an ongoing multi-centre randomised controlled trial which compares an emergency endovascular strategy versus open repair for patients with ruptured abdominal aortic aneurysm. In the IMPROVE trial at 3 months post-randomisation, 21% of surviving patients did not complete health-related quality of life questionnaires (assessed by EQ-5D-3L). We address this problem by developing a web-based tool that provides a practical approach for eliciting expert opinion about quality of life differences between patients with missing versus complete data. We show how this expert opinion can define informative priors within a fully Bayesian framework to perform sensitivity analyses that allow the missing data to depend upon unobserved patient characteristics. Results: A total of 26 experts, of 46 asked to participate, completed the elicitation exercise. The elicited quality of life scores were lower on average for the patients with missing versus complete data, but there was considerable uncertainty in these elicited values. The missing at random analysis found that patients randomised to the emergency endovascular strategy versus open repair had higher average (95% credible interval) quality of life scores of 0.062 (−0.005 to 0.130). Our sensitivity analysis that used the elicited expert information as pooled priors found that the gain in average quality of life for the emergency endovascular strategy versus open repair was 0.076 (−0.054 to 0.198). Conclusion: We provide and exemplify a practical tool for eliciting the expert opinion required by recommended approaches to the sensitivity analyses of randomised controlled trials. We show how this approach allows the trial analysis to fully recognise the uncertainty that arises from making alternative, plausible assumptions about the reasons for missing data. This tool can be widely used in the design, analysis and interpretation of future trials, and to facilitate this, materials are available for download. PMID:28675302

Semi-Automated Trajectory Analysis of Deep Ballistic Penetrating Brain Injury

PubMed Central

Folio, Les; Solomon, Jeffrey; Biassou, Nadia; Fischer, Tatjana; Dworzak, Jenny; Raymont, Vanessa; Sinaii, Ninet; Wassermann, Eric M.; Grafman, Jordan

2016-01-01

Background Penetrating head injuries (PHIs) are common in combat operations and most have visible wound paths on computed tomography (CT). Objective We assess agreement between an automated trajectory analysis-based assessment of brain injury and manual tracings of encephalomalacia on CT. Methods We analyzed 80 head CTs with ballistic PHI from the Institutional Review Board approved Vietnam head injury registry. Anatomic reports were generated from spatial coordinates of projectile entrance and terminal fragment location. These were compared to manual tracings of the regions of encephalomalacia. Dice’s similarity coefficients, kappa, sensitivities, and specificities were calculated to assess agreement. Times required for case analysis were also compared. Results Results show high specificity of anatomic regions identified on CT with semiautomated anatomical estimates and manual tracings of tissue damage. Radiologist’s and medical students’ anatomic region reports were similar (Kappa 0.8, t-test p < 0.001). Region of probable injury modeling of involved brain structures was sensitive (0.7) and specific (0.9) compared with manually traced structures. Semiautomated analysis was 9-fold faster than manual tracings. Conclusion Our region of probable injury spatial model approximates anatomical regions of encephalomalacia from ballistic PHI with time-saving over manual methods. Results show potential for automated anatomical reporting as an adjunct to current practice of radiologist/neurosurgical review of brain injury by penetrating projectiles. PMID:23707123

Diagnostic accuracy of droplet digital PCR for detection of EGFR T790M mutation in circulating tumor DNA

PubMed Central

Tong, Xiang; Wang, Ye; Wang, Chengdi; Jin, Jing; Tian, Panwen; Li, Weimin

2018-01-01

Objectives Although different methods have been established to detect epidermal growth factor receptor (EGFR) T790M mutation in circulating tumor DNA (ctDNA), a wide range of diagnostic accuracy values were reported in previous studies. The aim of this meta-analysis was to provide pooled diagnostic accuracy measures for droplet digital PCR (ddPCR) in the diagnosis of EGFR T790M mutation based on ctDNA. Materials and methods A systematic review and meta-analysis were carried out based on resources from Pubmed, Web of Science, Embase and Cochrane Library up to October 11, 2017. Data were extracted to assess the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio (NLR), diagnostic OR (DOR), and areas under the summary receiver-operating characteristic curve (SROC). Results Eleven of 311 studies identified have met the including criteria. The sensitivity and specificity of ddPCR for the detection of T790M mutation in ctDNA ranged from 0.0% to 100.0% and 63.2% to 100.0%, respectively. For the pooled analysis, ddPCR had a performance of 70.1% (95% CI, 62.7%–76.7%) sensitivity, 86.9 % (95% CI, 80.6%–91.7%) specificity, 3.67 (95% CI, 2.33–5.79) PLR, 0.41 (95% CI, 0.32–0.55) NLR, and 10.83 (95% CI, 5.86–20.03) DOR, with the area under the SROC curve being 0.82. Conclusion The ddPCR harbored a good performance for detection of EGFR T790M mutation in ctDNA. PMID:29844700

Development and optimization of SPECT gated blood pool cluster analysis for the prediction of CRT outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lalonde, Michel, E-mail: mlalonde15@rogers.com; Wassenaar, Richard; Wells, R. Glenn

2014-07-15

Purpose: Phase analysis of single photon emission computed tomography (SPECT) radionuclide angiography (RNA) has been investigated for its potential to predict the outcome of cardiac resynchronization therapy (CRT). However, phase analysis may be limited in its potential at predicting CRT outcome as valuable information may be lost by assuming that time-activity curves (TAC) follow a simple sinusoidal shape. A new method, cluster analysis, is proposed which directly evaluates the TACs and may lead to a better understanding of dyssynchrony patterns and CRT outcome. Cluster analysis algorithms were developed and optimized to maximize their ability to predict CRT response. Methods: Aboutmore » 49 patients (N = 27 ischemic etiology) received a SPECT RNA scan as well as positron emission tomography (PET) perfusion and viability scans prior to undergoing CRT. A semiautomated algorithm sampled the left ventricle wall to produce 568 TACs from SPECT RNA data. The TACs were then subjected to two different cluster analysis techniques, K-means, and normal average, where several input metrics were also varied to determine the optimal settings for the prediction of CRT outcome. Each TAC was assigned to a cluster group based on the comparison criteria and global and segmental cluster size and scores were used as measures of dyssynchrony and used to predict response to CRT. A repeated random twofold cross-validation technique was used to train and validate the cluster algorithm. Receiver operating characteristic (ROC) analysis was used to calculate the area under the curve (AUC) and compare results to those obtained for SPECT RNA phase analysis and PET scar size analysis methods. Results: Using the normal average cluster analysis approach, the septal wall produced statistically significant results for predicting CRT results in the ischemic population (ROC AUC = 0.73;p < 0.05 vs. equal chance ROC AUC = 0.50) with an optimal operating point of 71% sensitivity and 60% specificity. Cluster analysis results were similar to SPECT RNA phase analysis (ROC AUC = 0.78, p = 0.73 vs cluster AUC; sensitivity/specificity = 59%/89%) and PET scar size analysis (ROC AUC = 0.73, p = 1.0 vs cluster AUC; sensitivity/specificity = 76%/67%). Conclusions: A SPECT RNA cluster analysis algorithm was developed for the prediction of CRT outcome. Cluster analysis results produced results equivalent to those obtained from Fourier and scar analysis.« less

Diffuse reflectance spectroscopy for optical nerve identification. Preliminary ex vivo results for feedback controlled oral and maxillofacial laser surgery

NASA Astrophysics Data System (ADS)

Stelzle, Florian; Zam, Azhar; Adler, Werner; Douplik, Alexandre; Tangermann-Gerk, Katja; Nkenke, Emeka; Neukam, Friedrich Wilhelm; Schmidt, Michael

Objective: Laser surgery has many advantages. However, due to a lack of haptic feedback it is accompanied by the risk of iatrogenic nerve damage. The aim of this study was to evaluate the possibilities of optical nerve identification by diffuse reflectance spectroscopy to set the base for a feedback control system to enhance nerve preservation in oral and maxillofacial laser surgery. Materials and Methods: Diffuse reflectance spectra of nerve tissue, skin, mucosa, fat tissue, muscle, cartilage and bone (15120 spectra) of ex vivo pig heads were acquired in the wavelength range of 350-650 nm. Tissue differentiation was performed by principal components analysis (PCA) followed by linear discriminant analysis (LDA). Specificity and sensitivity were calculated by receiver operating characteristic (ROC) analysis and the area under curve (AUC). Results: Nerve tissue could correctly be identified and differed from skin, mucosa, fat tissue, muscle, cartilage and bone in more than 90% of the cases (AUC results) with a specificity of over 78% and a sensitivity of more than 86%. Conclusion: Nerve tissue can be identified by diffuse reflectance spectroscopy with high precision and reliability. The results may set the base for a feedback system to prevent iatrogenic nerve damage performing oral and maxillofacial laser surgery.

FHR patterns that become significant in connection with ST waveform changes and metabolic acidosis at birth.

PubMed

Rosén, Karl G; Norén, Håkan; Carlsson, Ann

2018-04-18

Recent developments have produced new CTG classification systems and the question is to what extent these may affect the model of FHR + ST interpretation? The two new systems (FIGO2015 and SSOG2017) classify FHR + ST events differently from the current CTG classification system used in the STAN interpretation algorithm (STAN2007). Identify the predominant FHR patterns in connection with ST events in cases of cord artery metabolic acidosis missed by the different CTG classification systems. Indicate to what extent STAN clinical guidelines could be modified enhancing the sensitivity. Provide a pathophysiological rationale. Forty-four cases with umbilical cord artery metabolic acidosis were retrieved from a European multicenter database. Significant FHR + ST events were evaluated post hoc in consensus by an expert panel. Eighteen cases were not identified as in need of intervention and regarded as negative in the sensitivity analysis. In 12 cases, ST changes occurred but the CTG was regarded as reassuring. Visual analysis of the FHR + ST tracings revealed specific FHR patterns: Conclusion: These findings indicate FHR + ST analysis may be undertaken regardless of CTG classification system provided there is a more physiologically oriented approach to FHR assessment in connection with an ST event.

2D-electrophoresis and the urine proteome map: where do we stand?

PubMed

Candiano, Giovanni; Santucci, Laura; Petretto, Andrea; Bruschi, Maurizio; Dimuccio, Veronica; Urbani, Andrea; Bagnasco, Serena; Ghiggeri, Gian Marco

2010-03-10

The discovery of urinary biomarkers is a main topic in clinical medicine. The development of proteomics has rapidly changed the knowledge on urine protein composition and probably will modify it again. Two-dimensional electrophoresis (2D-PAGE) coupled with mass spectrometry has represented for years the technique of choice for the analysis of urine proteins and it is time to draw some conclusions. This review will focus on major methodological aspects related to urine sample collection, storage and analysis by 2D-PAGE and attempt to define an advanced normal urine protein map. Overall, 1118 spots were reproducibly found in normal urine samples but only 275 were characterized as isoforms of 82 proteins. One-hundred height spots belonging to 30 proteins were also detected in plasma and corresponded to typical plasma components. The identity of most of the proteins found in normal urine by 2D-PAGE remains to be determined, the majority being low-molecular weight proteins (<30 kDa). Equalization procedures would also enhance sensitivity of the analysis and allow low abundance proteins to be characterized. Therefore, we are still on the way to define the normal urine composition. Technology advancements in concentrating procedure will improve sensitivity and give the possibility to purify proteins for mass spectrometry. Copyright (c) 2009 Elsevier B.V. All rights reserved.

A Mass Spectrometric Analysis Method Based on PPCA and SVM for Early Detection of Ovarian Cancer.

PubMed

Wu, Jiang; Ji, Yanju; Zhao, Ling; Ji, Mengying; Ye, Zhuang; Li, Suyi

2016-01-01

Background. Surfaced-enhanced laser desorption-ionization-time of flight mass spectrometry (SELDI-TOF-MS) technology plays an important role in the early diagnosis of ovarian cancer. However, the raw MS data is highly dimensional and redundant. Therefore, it is necessary to study rapid and accurate detection methods from the massive MS data. Methods. The clinical data set used in the experiments for early cancer detection consisted of 216 SELDI-TOF-MS samples. An MS analysis method based on probabilistic principal components analysis (PPCA) and support vector machine (SVM) was proposed and applied to the ovarian cancer early classification in the data set. Additionally, by the same data set, we also established a traditional PCA-SVM model. Finally we compared the two models in detection accuracy, specificity, and sensitivity. Results. Using independent training and testing experiments 10 times to evaluate the ovarian cancer detection models, the average prediction accuracy, sensitivity, and specificity of the PCA-SVM model were 83.34%, 82.70%, and 83.88%, respectively. In contrast, those of the PPCA-SVM model were 90.80%, 92.98%, and 88.97%, respectively. Conclusions. The PPCA-SVM model had better detection performance. And the model combined with the SELDI-TOF-MS technology had a prospect in early clinical detection and diagnosis of ovarian cancer.

Does Short-Term Exposure to Mobile Phone Base Station Signals Increase Symptoms in Individuals Who Report Sensitivity to Electromagnetic Fields? A Double-Blind Randomized Provocation Study

PubMed Central

Eltiti, Stacy; Wallace, Denise; Ridgewell, Anna; Zougkou, Konstantina; Russo, Riccardo; Sepulveda, Francisco; Mirshekar-Syahkal, Dariush; Rasor, Paul; Deeble, Roger; Fox, Elaine

2007-01-01

Background Individuals with idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) believe they suffer negative health effects when exposed to electromagnetic fields from everyday objects such as mobile phone base stations. Objectives This study used both open provocation and double-blind tests to determine if sensitive and control individuals experience more negative health effects when exposed to base station-like signals compared with sham. Methods Fifty-six self-reported sensitive and 120 control participants were tested in an open provocation test. Of these, 12 sensitive and 6 controls withdrew after the first session. The remainder completed a series of double-blind tests. Subjective measures of well-being and symptoms as well as physiological measures of blood volume pulse, heart rate, and skin conductance were obtained. Results During the open provocation, sensitive individuals reported lower levels of well-being in both the global system for mobile communication (GSM) and universal mobile telecommunications system (UMTS) compared with sham exposure, whereas controls reported more symptoms during the UMTS exposure. During double-blind tests the GSM signal did not have any effect on either group. Sensitive participants did report elevated levels of arousal during the UMTS condition, whereas the number or severity of symptoms experienced did not increase. Physiological measures did not differ across the three exposure conditions for either group. Conclusions Short-term exposure to a typical GSM base station-like signal did not affect well-being or physiological functions in sensitive or control individuals. Sensitive individuals reported elevated levels of arousal when exposed to a UMTS signal. Further analysis, however, indicated that this difference was likely to be due to the effect of order of exposure rather than the exposure itself. PMID:18007992

Immunohistochemical expression of insulin, glucagon, and somatostatin in pancreatic islets of horses with and without insulin resistance.

PubMed

Newkirk, Kim M; Ehrensing, Gordon; Odoi, Agricola; Boston, Raymond C; Frank, Nicholas

2018-02-01

OBJECTIVE To assess insulin, glucagon, and somatostatin expression within pancreatic islets of horses with and without insulin resistance. ANIMALS 10 insulin-resistant horses and 13 insulin-sensitive horses. PROCEDURES For each horse, food was withheld for at least 10 hours before a blood sample was collected for determination of serum insulin concentration. Horses with a serum insulin concentration < 20 μU/mL were assigned to the insulin-sensitive group, whereas horses with a serum insulin concentration > 20 μU/mL underwent a frequently sampled IV glucose tolerance test to determine sensitivity to insulin by minimal model analysis. Horses with a sensitivity to insulin < 1.0 × 10 -4 L•min -1 •mU -1 were assigned to the insulin-resistant group. All horses were euthanized with a barbiturate overdose, and pancreatic specimens were harvested and immunohistochemically stained for determination of insulin, glucagon, and somatostatin expression in pancreatic islets. Islet hormone expression was compared between insulin-resistant and insulin-sensitive horses. RESULTS Cells expressing insulin, glucagon, and somatostatin made up approximately 62%, 12%, and 7%, respectively, of pancreatic islet cells in insulin-resistant horses and 64%, 18%, and 9%, respectively, of pancreatic islet cells in insulin-sensitive horses. Expression of insulin and somatostatin did not differ between insulin-resistant and insulin-sensitive horses, but the median percentage of glucagon-expressing cells in the islets of insulin-resistant horses was significantly less than that in insulin-sensitive horses. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that, in insulin-resistant horses, insulin secretion was not increased but glucagon production might be downregulated as a compensatory response to hyperinsulinemia.

Heart rate and blood pressure variabilities in salt-sensitive hypertension.

PubMed

Piccirillo, G; Bucca, C; Durante, M; Santagada, E; Munizzi, M R; Cacciafesta, M; Marigliano, V

1996-12-01

In salt-sensitive hypertension, a high sodium intake causes plasma catecholamines to rise and pulmonary baroreceptor plasticity to fall. In salt-sensitive and salt-resistant hypertensive subjects during low and high sodium intakes, we studied autonomic nervous system activity by power spectral analysis of heart rate and arterial pressure variabilities and baroreceptor sensitivity. In all subjects, high sodium intake significantly enhanced the low-frequency power of heart rate and arterial pressures at rest and after sympathetic stress. It also increased heart rate and arterial pressure variabilities. During high sodium intake, salt-sensitive hypertensive subjects had significantly higher low-frequency powers of systolic arterial pressure (7.5 mm Hg2, P < .05) and of heart rate at rest (59.2 +/- 2.4 normalized units [NU], P < .001) than salt-resistant subjects (6.6 +/- 0.3 mm Hg2, 55.0 +/- 3.2 NU) and normotensive control subjects (5.1 +/- 0.5 mm Hg2, 41.6 +/- 2.9 NU). In salt-sensitive subjects, low sodium intake significantly reduced low-frequency normalized units (P < .001) and the ratio of low- to high-power frequency (P < .001). High-sodium intake significantly increased baroreflex sensitivity in control subjects (from 10.0 +/- 0.7 to 17.5 +/- 0.7 ms/mm Hg, P < .001) and salt-resistant subjects (from 6.9 +/- 0.7 to 13.9 +/- 0.9, P < .05) but not in salt-sensitive subjects (7.4 +/- 0.3 to 7.9 +/- 0.4). In conclusion, a high sodium intake markedly enhances cardiac sympathetic activity in salt-sensitive and salt-resistant hypertension. In contrast, although reduced sodium intake lowers arterial pressure and sympathetic activity, it does so only in salt-sensitive subjects. Hence, in salt-resistant subjects, neither arterial pressure nor sympathetic activity depends on salt intake. During a high sodium intake in normotensive subjects and salt-resistant hypertensive subjects, increased sympathetic activity is probably compensated by enhanced baroreflex sensitivity.

An Earthquake Source Sensitivity Analysis for Tsunami Propagation in the Eastern Mediterranean

NASA Astrophysics Data System (ADS)

Necmioglu, Ocal; Meral Ozel, Nurcan

2013-04-01

An earthquake source parameter sensitivity analysis for tsunami propagation in the Eastern Mediterranean has been performed based on 8 August 1303 Crete and Dodecanese Islands earthquake resulting in destructive inundation in the Eastern Mediterranean. The analysis involves 23 cases describing different sets of strike, dip, rake and focal depth, while keeping the fault area and displacement, thus the magnitude, same. The main conclusions of the evaluation are drawn from the investigation of the wave height distributions at Tsunami Forecast Points (TFP). The earthquake vs. initial tsunami source parameters comparison indicated that the maximum initial wave height values correspond in general to the changes in rake angle. No clear depth dependency is observed within the depth range considered and no strike angle dependency is observed in terms of amplitude change. Directivity sensitivity analysis indicated that for the same strike and dip, 180° shift in rake may lead to 20% change in the calculated tsunami wave height. Moreover, an approximately 10 min difference in the arrival time of the initial wave has been observed. These differences are, however, greatly reduced in the far field. The dip sensitivity analysis, performed separately for thrust and normal faulting, has both indicated that an increase in the dip angle results in the decrease of the tsunami wave amplitude in the near field approximately 40%. While a positive phase shift is observed, the period and the shape of the initial wave stays nearly the same for all dip angles at respective TFPs. These affects are, however, not observed at the far field. The resolution of the bathymetry, on the other hand, is a limiting factor for further evaluation. Four different cases were considered for the depth sensitivity indicating that within the depth ranges considered (15-60 km), the increase of the depth has only a smoothing effect on the synthetic tsunami wave height measurements at the selected TFPs. The strike sensitivity analysis showed clear phase shift with respect to the variation of the strike angles, without leading to severe variation of the initial and maximum waves at locations considered. Travel time maps for two cases corresponding to difference in the strike value (60° vs 150°) presented a more complex wave propagation for the case with 60° strike angle due to the fact that the normal of the fault plane is orthogonal to the main bathymetric structure in the region, namely the Eastern section of the Hellenic Arc between Crete and Rhodes Islands. For a given set of strike, dip and focal depth parameters, the effect of the variation in the rake angle has been evaluated in the rake sensitivity analysis. A waveform envelope composed of symmetric synthetic recordings at one TFPs could be clearly observed as a result of rake angle variations in 0-180° range. This could also lead to the conclusion that for a given magnitude (fault size and displacement), the expected maximum and minimum tsunami wave amplitudes could be evaluated as a waveform envelope rather limited to a single point of time or amplitude. The Evaluation of the initial wave arrival times follows an expected pattern controlled by the distance, wheras maximum wave arrival time distribution presents no clear pattern. Nevertheless, the distribution is rather concentrated in time domain for some TFPs. Maximum positive and minimum negative wave amplitude distributions indicates a broader range for a subgroup of TFPs, wheras for the remaining TFPs the distributions are narrow. Any deviation from the expected trend of calculating narrower ranges of amplitude distributions could be interpreted as the result o the bathymetry and focusing effects. As similar studies conducted in the different parts of the globe indicated, the main characteristics of the tsunami propagation are unique for each basin. It should be noted, however, that the synthetic measurements obtained at the TFPs in the absence of high-resolution bathymetric data, should be considered only an overall guidance. The results indicate the importance of the accuracy of earthquake source parameters for reliable tsunami predictions and the need for high-resolution bathymetric data to be able to perform calculations with higher accuracy. On the other hand, this study did not address other parameters, such as heterogeneous slip distribution and rupture duration, which affect the tsunami initiation and propagation process.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bozoki, G.E.; Fitzpatrick, R.G.; Bohn, M.P.

This report details the review of the Diablo Canyon Probabilistic Risk Assessment (DCPRA). The study was performed under contract from the Probabilistic Risk Analysis Branch, Office of Nuclear Reactor Research, USNRC by Brookhaven National Laboratory. The DCPRA is a full scope Level I effort and although the review touched on all aspects of the PRA, the internal events and seismic events received the vast majority of the review effort. The report includes a number of independent systems analyses sensitivity studies, importance analyses as well as conclusions on the adequacy of the DCPRA for use in the Diablo Canyon Long Termmore » Seismic Program.« less

Main propulsion system design recommendations for an advanced Orbit Transfer Vehicle

NASA Technical Reports Server (NTRS)

Redd, L.

1985-01-01

Various main propulsion system configurations of an advanced OTV are evaluated with respect to the probability of nonindependent failures, i.e., engine failures that disable the entire main propulsion system. Analysis of the life-cycle cost (LCC) indicates that LCC is sensitive to the main propulsion system reliability, vehicle dry weight, and propellant cost; it is relatively insensitive to the number of missions/overhaul, failures per mission, and EVA and IVA cost. In conclusion, two or three engines are recommended in view of their highest reliability, minimum life-cycle cost, and fail operational/fail safe capability.

Sensitivity Analysis of Multidisciplinary Rotorcraft Simulations

NASA Technical Reports Server (NTRS)

Wang, Li; Diskin, Boris; Biedron, Robert T.; Nielsen, Eric J.; Bauchau, Olivier A.

2017-01-01

A multidisciplinary sensitivity analysis of rotorcraft simulations involving tightly coupled high-fidelity computational fluid dynamics and comprehensive analysis solvers is presented and evaluated. An unstructured sensitivity-enabled Navier-Stokes solver, FUN3D, and a nonlinear flexible multibody dynamics solver, DYMORE, are coupled to predict the aerodynamic loads and structural responses of helicopter rotor blades. A discretely-consistent adjoint-based sensitivity analysis available in FUN3D provides sensitivities arising from unsteady turbulent flows and unstructured dynamic overset meshes, while a complex-variable approach is used to compute DYMORE structural sensitivities with respect to aerodynamic loads. The multidisciplinary sensitivity analysis is conducted through integrating the sensitivity components from each discipline of the coupled system. Numerical results verify accuracy of the FUN3D/DYMORE system by conducting simulations for a benchmark rotorcraft test model and comparing solutions with established analyses and experimental data. Complex-variable implementation of sensitivity analysis of DYMORE and the coupled FUN3D/DYMORE system is verified by comparing with real-valued analysis and sensitivities. Correctness of adjoint formulations for FUN3D/DYMORE interfaces is verified by comparing adjoint-based and complex-variable sensitivities. Finally, sensitivities of the lift and drag functions obtained by complex-variable FUN3D/DYMORE simulations are compared with sensitivities computed by the multidisciplinary sensitivity analysis, which couples adjoint-based flow and grid sensitivities of FUN3D and FUN3D/DYMORE interfaces with complex-variable sensitivities of DYMORE structural responses.

Genomic profiling of plasma cell disorders in a clinical setting: integration of microarray and FISH, after CD138 selection of bone marrow

PubMed Central

Berry, Nadine Kaye; Bain, Nicole L; Enjeti, Anoop K; Rowlings, Philip

2014-01-01

Aim To evaluate the role of whole genome comparative genomic hybridisation microarray (array-CGH) in detecting genomic imbalances as compared to conventional karyotype (GTG-analysis) or myeloma specific fluorescence in situ hybridisation (FISH) panel in a diagnostic setting for plasma cell dyscrasia (PCD). Methods A myeloma-specific interphase FISH (i-FISH) panel was carried out on CD138 PC-enriched bone marrow (BM) from 20 patients having BM biopsies for evaluation of PCD. Whole genome array-CGH was performed on reference (control) and neoplastic (test patient) genomic DNA extracted from CD138 PC-enriched BM and analysed. Results Comparison of techniques demonstrated a much higher detection rate of genomic imbalances using array-CGH. Genomic imbalances were detected in 1, 19 and 20 patients using GTG-analysis, i-FISH and array-CGH, respectively. Genomic rearrangements were detected in one patient using GTG-analysis and seven patients using i-FISH, while none were detected using array-CGH. I-FISH was the most sensitive method for detecting gene rearrangements and GTG-analysis was the least sensitive method overall. All copy number aberrations observed in GTG-analysis were detected using array-CGH and i-FISH. Conclusions We show that array-CGH performed on CD138-enriched PCs significantly improves the detection of clinically relevant and possibly novel genomic abnormalities in PCD, and thus could be considered as a standard diagnostic technique in combination with IGH rearrangement i-FISH. PMID:23969274

Evaluating the Discriminant Accuracy of a Grammatical Measure With Spanish-Speaking Children

PubMed Central

Gutiérrez-Clellen, Vera F.; Restrepo, M. Adelaida; Simón-Cereijido, Gabriela

2012-01-01

Purpose The purpose of this study was to evaluate the discriminant accuracy of a grammatical measure for the identification of language impairment in Latino Spanish-speaking children. The authors hypothesized that if exposure to and use of English as a second language have an effect on the first language, bilingual children might exhibit lower rates of grammatical accuracy than their peers and be more likely to be misclassified. Method Eighty children with typical language development and 80 with language impairment were sampled from 4 different geographical regions and compared using linear discriminant function analysis. Results Results indicated fair-to-good sensitivity from 4;0 to 5;1 years, good sensitivity from 5;2 to 5;11 years, and poor sensitivity above age 6 years. The discriminant functions derived from the exploratory studies were able to predict group membership in confirmatory analyses with fair-to-excellent sensitivity up to age 6 years. Children who were bilingual did not show lower scores and were not more likely to be misclassified compared with their Spanish-only peers. Conclusions The measure seems to be appropriate for identifying language impairment in either Spanish-dominant or Spanish-only speakers between 4 and 6 years of age. However, for older children, supplemental testing is necessary. PMID:17197491

Combining magnetic nanoparticle with biotinylated nanobodies for rapid and sensitive detection of influenza H3N2

PubMed Central

2014-01-01

Our objective is to develop a rapid and sensitive assay based on magnetic beads to detect the concentration of influenza H3N2. The possibility of using variable domain heavy-chain antibodies (nanobody) as diagnostic tools for influenza H3N2 was investigated. A healthy camel was immunized with inactivated influenza H3N2. A nanobody library of 8 × 108 clones was constructed and phage displayed. After three successive biopanning steps, H3N2-specific nanobodies were successfully isolated, expressed in Escherichia coli, and purified. Sequence analysis of the nanobodies revealed that we possessed four classes of nanobodies against H3N2. Two nanobodies were further used to prepare our rapid diagnostic kit. Biotinylated nanobody was effectively immobilized onto the surface of streptavidin magnetic beads. The modified magnetic beads with nanobody capture specifically influenza H3N2 and can still be recognized by nanobodies conjugated to horseradish peroxidase (HRP) conjugates. Under optimized conditions, the present immunoassay exhibited a relatively high sensitive detection with a limit of 50 ng/mL. In conclusion, by combining magnetic beads with specific nanobodies, this assay provides a promising influenza detection assay to develop a potential rapid, sensitive, and low-cost diagnostic tool to screen for influenza infections. PMID:25328501

State-of-the-Art Fusion-Finder Algorithms Sensitivity and Specificity

PubMed Central

Carrara, Matteo; Beccuti, Marco; Lazzarato, Fulvio; Cavallo, Federica; Cordero, Francesca; Donatelli, Susanna; Calogero, Raffaele A.

2013-01-01

Background. Gene fusions arising from chromosomal translocations have been implicated in cancer. RNA-seq has the potential to discover such rearrangements generating functional proteins (chimera/fusion). Recently, many methods for chimeras detection have been published. However, specificity and sensitivity of those tools were not extensively investigated in a comparative way. Results. We tested eight fusion-detection tools (FusionHunter, FusionMap, FusionFinder, MapSplice, deFuse, Bellerophontes, ChimeraScan, and TopHat-fusion) to detect fusion events using synthetic and real datasets encompassing chimeras. The comparison analysis run only on synthetic data could generate misleading results since we found no counterpart on real dataset. Furthermore, most tools report a very high number of false positive chimeras. In particular, the most sensitive tool, ChimeraScan, reports a large number of false positives that we were able to significantly reduce by devising and applying two filters to remove fusions not supported by fusion junction-spanning reads or encompassing large intronic regions. Conclusions. The discordant results obtained using synthetic and real datasets suggest that synthetic datasets encompassing fusion events may not fully catch the complexity of RNA-seq experiment. Moreover, fusion detection tools are still limited in sensitivity or specificity; thus, there is space for further improvement in the fusion-finder algorithms. PMID:23555082

Children with a history of SLI show reduced sensitivity to audiovisual temporal asynchrony: An ERP Study

PubMed Central

Kaganovich, Natalya; Schumaker, Jennifer; Leonard, Laurence B.; Gustafson, Dana; Macias, Danielle

2014-01-01

Purpose We examined whether school-age children with a history of SLI (H-SLI), their typically developing (TD) peers, and adults differ in sensitivity to audiovisual temporal asynchrony and whether such difference stems from the sensory encoding of audiovisual information. Method 15 H-SLI children, 15 TD children, and 15 adults judged whether a flashed explosion-shaped figure and a 2 kHz pure tone occurred simultaneously. The stimuli were presented at 0, 100, 200, 300, 400, and 500 ms temporal offsets. This task was combined with EEG recordings. Results H-SLI children were profoundly less sensitive to temporal separations between auditory and visual modalities compared to their TD peers. Those H-SLI children who performed better at simultaneity judgment also had higher language aptitude. TD children were less accurate than adults, revealing a remarkably prolonged developmental course of the audiovisual temporal discrimination. Analysis of early ERP components suggested that poor sensory encoding was not a key factor in H-SLI children’s reduced sensitivity to audiovisual asynchrony. Conclusions Audiovisual temporal discrimination is impaired in H-SLI children and is still immature during mid-childhood in TD children. The present findings highlight the need for further evaluation of the role of atypical audiovisual processing in the development of SLI. PMID:24686922

Combining magnetic nanoparticle with biotinylated nanobodies for rapid and sensitive detection of influenza H3N2

NASA Astrophysics Data System (ADS)

Zhu, Min; Hu, Yonghong; Li, Guirong; Ou, Weijun; Mao, Panyong; Xin, Shaojie; Wan, Yakun

2014-09-01

Our objective is to develop a rapid and sensitive assay based on magnetic beads to detect the concentration of influenza H3N2. The possibility of using variable domain heavy-chain antibodies (nanobody) as diagnostic tools for influenza H3N2 was investigated. A healthy camel was immunized with inactivated influenza H3N2. A nanobody library of 8 × 108 clones was constructed and phage displayed. After three successive biopanning steps, H3N2-specific nanobodies were successfully isolated, expressed in Escherichia coli, and purified. Sequence analysis of the nanobodies revealed that we possessed four classes of nanobodies against H3N2. Two nanobodies were further used to prepare our rapid diagnostic kit. Biotinylated nanobody was effectively immobilized onto the surface of streptavidin magnetic beads. The modified magnetic beads with nanobody capture specifically influenza H3N2 and can still be recognized by nanobodies conjugated to horseradish peroxidase (HRP) conjugates. Under optimized conditions, the present immunoassay exhibited a relatively high sensitive detection with a limit of 50 ng/mL. In conclusion, by combining magnetic beads with specific nanobodies, this assay provides a promising influenza detection assay to develop a potential rapid, sensitive, and low-cost diagnostic tool to screen for influenza infections.

Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

PubMed Central

Swellam, Menha; Samy, Nervana; Abdl Wahab, Susan; Ibrahim, Mohamed Saeed

2009-01-01

Objectives: Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE). Authors determine the clinical diagnostic role for thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1) as endothelial markers and C-reactive protein (CRP), and interlukin-6 (IL-6) as inflammatory markers when tested independently or in combinations. Materials and methods: We conducted a retrospective study in a cohort of 185 women grouped as 80 women with PE, 55 normotensive pregnant and 50 healthy non-pregnant. Plasma levels of TM, PAI-1, CRP and IL-6 were examined using enzyme linked immunosorbent assays. Results: Median levels and the positivity rates for the investigated markers were higher in PE as compared to the other groups (P < 0.0001). Using linear regression analysis, the investigated markers were significantly correlated regarding healthy nonpregnant vs PE or normotensive pregnant vs PE. The sensitivity of PAI-1 was the highest (98%) among the tested biomarkers. Combination between the investigated markers revealed absolute sensitivity (100%) and reliable specificity especially when PAI-1 was combined with CRP at 83% specificity. Conclusions: Investigated endothelial and inflammatory markers revealed sensitive diagnostic test for PE. However, coupled combination between PAI-1 with CRP showed superior both sensitivity and specificity which represent a promising new approach for detection of PE. PMID:19597295

Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy

PubMed Central

Ismail, M; Bokaee, S; Davies, J; Harrington, K J; Pandha, H

2009-01-01

Aquaporins (AQPs) are intrinsic membrane proteins that facilitate selective water and small solute movement across the plasma membrane. In this study, we investigate the role of inhibiting AQPs in sensitising prostate cancer cells to cryotherapy. PC-3 and DU145 prostate cancer cells were cooled to 0, −5 and −10°C. The expression of AQP3 in response to freezing was determined using real-time quantitative polymerase chain reaction (RT–qPCR) and western blot analysis. Aquaporins were inhibited using mercuric chloride (HgCl2) and small interfering RNA (siRNA) duplex, and cell survival was assessed using a colorimetric assay. There was a significant increase in AQP3 expression in response to freezing. Cells treated with AQP3 siRNA were more sensitive to cryoinjury compared with control cells (P<0.001). Inhibition of the AQPs by HgCl2 also increased the sensitivity of both cell lines to cryoinjury and there was a complete loss of cell viability at −10°C (P<0.01). In conclusion, we have shown that AQP3 is involved directly in cryoinjury. Inhibition of AQP3 increases the sensitivity of prostate cancer cells to freezing. This strategy may be exploited in the clinic to improve the efficacy of prostate cryotherapy. PMID:19513079

Influence of Neuroblastoma Stage on Serum-Based Detection of MYCN Amplification

PubMed Central

Combaret, Valerie; Hogarty, Michael D; London, Wendy B; McGrady, Patrick; Iacono, Isabelle; Brejon, Stephanie; Swerts, Katrien; Noguera, Rosa; Gross, Nicole; Rousseau, Raphael; Puisieux, Alain

2010-01-01

Background MYCN oncogene amplification has been defined as the most important prognostic factor for neuroblastoma, the most common solid extracranial neoplasm in children. High copy numbers are strongly associated with rapid tumor progression and poor outcome, independently of tumor stage or patient age, and this has become an important factor in treatment stratification. Procedure By Real Time Quantitative PCR analysis, we evaluated the clinical relevance of circulating MYCN DNA of 267 patients with locoregional or metastatic neuroblastoma in children less than 18 months of age. Results For patients in this age group with INSS stage 4 or 4S NB and stage 3 patients, serum-based determination of MYCN DNA sequences had good sensitivity (85%, 83% and 75% respectively) and high specificity (100%) when compared to direct tumor gene determination. In contrast, the approach showed low sensitivity patients with stage 1 and 2 disease. Conclusion Our results show that the sensitivity of the serum-based MYCN DNA sequence determination depends on the stage of the disease. However, this simple, reproducible assay may represent a reasonably sensitive and very specific tool to assess tumor MYCN status in cases with stage 3 and metastatic disease for whom a wait and see strategy is often recommended. PMID:19301388

SUNBURN, SUN EXPOSURE, AND SUN SENSITIVITY IN THE STUDY OF NEVI IN CHILDREN

PubMed Central

Satagopan, Jaya M; Oliveria, Susan A; Arora, Arshi; Marchetti, Michael A; Orlow, Irene; Dusza, Stephen W; Weinstock, Martin A; Scope, Alon; Geller, Alan C; Marghoob, Ashfaq A; Halpern, Allan C

2015-01-01

Purpose To examine the joint effect of sun exposure and sunburn on nevus counts (on the natural logarithm scale; log nevi) and the role of sun sensitivity. Methods We describe an analysis of cross-sectional data from 443 children enrolled in the prospective study of nevi in children. To evaluate the joint effect, we partitioned the sum of squares due to interaction between sunburn and sun exposure into orthogonal components representing: (i) monotonic increase in log nevi with increasing sun exposure (rate of increase of log nevi depends upon sunburn), and (ii) non-monotonic pattern. Results In unadjusted analyses, there was a marginally significant monotonic pattern of interaction (p-value = 0.08). In adjusted analyses, sun exposure was associated with higher log nevi among those without sunburn (p < 0.001), but not among those with sunburn (p = 0.14). Sunburn was independently associated with log nevi (p = 0.02), even though sun sensitivity explained 29% (95% CI: 2%-56%, p = 0.04) of its effect. Children with high sun sensitivity and sunburn had more nevi, regardless of sun exposure. Conclusions A program of increasing sun protection in early childhood as a strategy for reducing nevi, when applied to the general population, may not equally benefit everyone. PMID:26096189

Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia

PubMed Central

Oudejans, Linda; He, Xuan; Niesters, Marieke; Dahan, Albert; Brines, Michael; van Velzen, Monique

2016-01-01

Cornea confocal microscopy (CCM) is a novel non-invasive method to detect small nerve fiber pathology. CCM generally correlates with outcomes of skin biopsies in patients with small fiber pathology. The aim of this study was to quantify the morphology of small nerve fibers of the cornea of patients with fibromyalgia in terms of density, length and branching and further phenotype these patients using standardized quantitative sensory testing (QST). Small fiber pathology was detected in the cornea of 51% of patients: nerve fiber length was significantly decreased in 44% of patients compared to age- and sex-matched reference values; nerve fiber density and branching were significantly decreased in 10% and 28% of patients. The combination of the CCM parameters and sensory tests for central sensitization, (cold pain threshold, mechanical pain threshold, mechanical pain sensitivity, allodynia and/or windup), yielded four phenotypes of fibromyalgia patients in a subgroup analysis: one group with normal cornea morphology without and with signs of central sensitization, and a group with abnormal cornea morphology parameters without and with signs of central sensitization. In conclusion, half of the tested fibromyalgia population demonstrates signs of small fiber pathology as measured by CCM. The four distinct phenotypes suggest possible differences in disease mechanisms and may require different treatment approaches. PMID:27006259

Automated Morphological Analysis of Microglia After Stroke.

PubMed

Heindl, Steffanie; Gesierich, Benno; Benakis, Corinne; Llovera, Gemma; Duering, Marco; Liesz, Arthur

2018-01-01

Microglia are the resident immune cells of the brain and react quickly to changes in their environment with transcriptional regulation and morphological changes. Brain tissue injury such as ischemic stroke induces a local inflammatory response encompassing microglial activation. The change in activation status of a microglia is reflected in its gradual morphological transformation from a highly ramified into a less ramified or amoeboid cell shape. For this reason, the morphological changes of microglia are widely utilized to quantify microglial activation and studying their involvement in virtually all brain diseases. However, the currently available methods, which are mainly based on manual rating of immunofluorescent microscopic images, are often inaccurate, rater biased, and highly time consuming. To address these issues, we created a fully automated image analysis tool, which enables the analysis of microglia morphology from a confocal Z-stack and providing up to 59 morphological features. We developed the algorithm on an exploratory dataset of microglial cells from a stroke mouse model and validated the findings on an independent data set. In both datasets, we could demonstrate the ability of the algorithm to sensitively discriminate between the microglia morphology in the peri-infarct and the contralateral, unaffected cortex. Dimensionality reduction by principal component analysis allowed to generate a highly sensitive compound score for microglial shape analysis. Finally, we tested for concordance of results between the novel automated analysis tool and the conventional manual analysis and found a high degree of correlation. In conclusion, our novel method for the fully automatized analysis of microglia morphology shows excellent accuracy and time efficacy compared to traditional analysis methods. This tool, which we make openly available, could find application to study microglia morphology using fluorescence imaging in a wide range of brain disease models.

Allergic contact dermatitis pattern in Kuwait: nickel leads the pack. In-depth analysis of nickel allergy based on the results from a large prospective patch test series report

PubMed Central

Almutawa, Fahad

2017-01-01

Introduction Contact dermatitis is a relatively common dermatosis reported among several population groups from all around the globe. However, the data from Kuwait is unavailable. Patch tests are essential for the diagnosis of contact sensitization. Aim To determine a relative frequency and pattern of sensitizers to different allergens in patients of suspected contact dermatitis in Kuwait and, also to study the role of the commonest sensitizer in detail. Material and methods Patch tests were performed in 2461 consecutive patients with a clinical diagnosis of contact dermatitis seen at our hospital between September 1, 2014 and August 31, 2015. Out of the total of 1381 (56.1%) patients with positive patch test results to at least one allergen, 546 (22.2%) patients with a single positive reaction to nickel only (single largest sensitizer) were selected as the study population for further detailed analysis. Results At least one positive patch test reaction was found in 1381 (56.12%) patients. Nickel was found to be the most common sensitizer seen in 546 (40%) patients. The mean age was 37.3 ±13.8 years and the mean duration of disease was 27.3 ±13.8 months. Most (387/546) patients sensitized were females. The forearms/hands and wrists were the most prevalent sites (52.56% of the participants). In 58.91% of women, dermatitis was more often confined to other sites, mostly ears and the neck due to earrings and necklaces. Just more than half of the number (51.09%) of nickel allergic patients were found in the age group of 15–25 years. Hairdressers/beauticians were the most affected group followed by house workers (housewives, cleaners, housekeepers). Conclusions Nickel is the single most common sensitizer found in our patients, and female sex, young age, occupation with long hours of contact to nickel are high risk factors. We recommend that a directive, which limits the release of nickel from products with extended skin contact, be approved in Kuwait. PMID:28670248

Clinical evaluation and validation of laboratory methods for the diagnosis of Bordetella pertussis infection: Culture, polymerase chain reaction (PCR) and anti-pertussis toxin IgG serology (IgG-PT)

PubMed Central

Cassiday, Pamela K.; Pawloski, Lucia C.; Tatti, Kathleen M.; Martin, Monte D.; Briere, Elizabeth C.; Tondella, M. Lucia; Martin, Stacey W.

2018-01-01

Introduction The appropriate use of clinically accurate diagnostic tests is essential for the detection of pertussis, a poorly controlled vaccine-preventable disease. The purpose of this study was to estimate the sensitivity and specificity of different diagnostic criteria including culture, multi-target polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and the use of a clinical case definition. An additional objective was to describe the optimal timing of specimen collection for the various tests. Methods Clinical specimens were collected from patients with cough illness at seven locations across the United States between 2007 and 2011. Nasopharyngeal and blood specimens were collected from each patient during the enrollment visit. Patients who had been coughing for ≤ 2 weeks were asked to return in 2–4 weeks for collection of a second, convalescent blood specimen. Sensitivity and specificity of each diagnostic test were estimated using three methods—pertussis culture as the “gold standard,” composite reference standard analysis (CRS), and latent class analysis (LCA). Results Overall, 868 patients were enrolled and 13.6% were B. pertussis positive by at least one diagnostic test. In a sample of 545 participants with non-missing data on all four diagnostic criteria, culture was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA. CRS and LCA methods increased the sensitivity estimates for convalescent serology and the clinical case definition over the culture-based estimates. Culture and PCR were most sensitive when performed during the first two weeks of cough; serology was optimally sensitive after the second week of cough. Conclusions Timing of specimen collection in relation to onset of illness should be considered when ordering diagnostic tests for pertussis. Consideration should be given to including IgG-PT serology as a confirmatory test in the Council of State and Territorial Epidemiologists (CSTE) case definition for pertussis. PMID:29652945

A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: data from the MAINTAIN Nephritis Trial

PubMed Central

Tamirou, Farah; Lauwerys, Bernard R; Dall'Era, Maria; Mackay, Meggan; Rovin, Brad; Cervera, Ricard; Houssiau, Frédéric A

2015-01-01

Background Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT). Methods Long-term (at least 7 years) renal function data were available for 90 patients randomised in the MNT. Receiver operating characteristic curves were built to test the performance of proteinuria measured within the 1st year as short-term predictor of long-term renal outcome. We calculated the positive and negative predictive values (PPV, NPV). Results After 12 months of treatment, achievement of a proteinuria <0.7 g/day best predicted good renal outcome, with a sensitivity and a specificity of 71% and 75%, respectively. The PPV was high (94%) but the NPV low (29%). Addition of the requirement of urine red blood cells ≤5/hpf as response criteria at month 12 reduced sensitivity from 71% to 41%. Conclusions In this cohort of mainly Caucasian patients suffering from a first episode of LN in most cases, achievement of a proteinuria <0.7 g/day at month 12 best predicts good outcome at 7 years and inclusion of haematuria in the set of criteria at month 12 undermines the sensitivity of early proteinuria decrease for the prediction of good outcome. The robustness of these conclusions stems from the very similar results obtained in two distinct LN cohorts. Trial registration number: NCT00204022. PMID:26629352

Ranking of physiotherapeutic evaluation methods as outcome measures of stifle functionality in dogs

PubMed Central

2013-01-01

Background Various physiotherapeutic evaluation methods are used to assess the functionality of dogs with stifle problems. Neither validity nor sensitivity of these methods has been investigated. This study aimed to determine the most valid and sensitive physiotherapeutic evaluation methods for assessing functional capacity in hind limbs of dogs with stifle problems and to serve as a basis for developing an indexed test for these dogs. A group of 43 dogs with unilateral surgically treated cranial cruciate ligament deficiency and osteoarthritic findings was used to test different physiotherapeutic evaluation methods. Twenty-one healthy dogs served as the control group and were used to determine normal variation in static weight bearing and range of motion. The protocol consisted of 14 different evaluation methods: visual evaluation of lameness, visual evaluation of diagonal movement, visual evaluation of functional active range of motion and difference in thrust of hind limbs via functional tests (sit-to-move and lie-to-move), movement in stairs, evaluation of hind limb muscle atrophy, manual evaluation of hind limb static weight bearing, quantitative measurement of static weight bearing of hind limbs with bathroom scales, and passive range of motion of hind limb stifle (flexion and extension) and tarsal (flexion and extension) joints using a universal goniometer. The results were compared with those from an orthopaedic examination, force plate analysis, radiographic evaluation, and a conclusive assessment. Congruity of the methods was assessed with a combination of three statistical approaches (Fisher’s exact test and two differently calculated proportions of agreeing observations), and the components were ranked from best to worst. Sensitivities of all of the physiotherapeutic evaluation methods against each standard were calculated. Results Evaluation of asymmetry in a sitting and lying position, assessment of muscle atrophy, manual and measured static weight bearing, and measurement of stifle passive range of motion were the most valid and sensitive physiotherapeutic evaluation methods. Conclusions Ranking of the various physiotherapeutic evaluation methods was accomplished. Several of these methods can be considered valid and sensitive when examining the functionality of dogs with stifle problems. PMID:23566355

Validity of Heart Failure Diagnoses in Administrative Databases: A Systematic Review and Meta-Analysis

PubMed Central

McCormick, Natalie; Lacaille, Diane; Bhole, Vidula; Avina-Zubieta, J. Antonio

2014-01-01

Objective Heart failure (HF) is an important covariate and outcome in studies of elderly populations and cardiovascular disease cohorts, among others. Administrative data is increasingly being used for long-term clinical research in these populations. We aimed to conduct the first systematic review and meta-analysis of studies reporting on the validity of diagnostic codes for identifying HF in administrative data. Methods MEDLINE and EMBASE were searched (inception to November 2010) for studies: (a) Using administrative data to identify HF; or (b) Evaluating the validity of HF codes in administrative data; and (c) Reporting validation statistics (sensitivity, specificity, positive predictive value [PPV], negative predictive value, or Kappa scores) for HF, or data sufficient for their calculation. Additional articles were located by hand search (up to February 2011) of original papers. Data were extracted by two independent reviewers; article quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Using a random-effects model, pooled sensitivity and specificity values were produced, along with estimates of the positive (LR+) and negative (LR−) likelihood ratios, and diagnostic odds ratios (DOR = LR+/LR−) of HF codes. Results Nineteen studies published from1999–2009 were included in the qualitative review. Specificity was ≥95% in all studies and PPV was ≥87% in the majority, but sensitivity was lower (≥69% in ≥50% of studies). In a meta-analysis of the 11 studies reporting sensitivity and specificity values, the pooled sensitivity was 75.3% (95% CI: 74.7–75.9) and specificity was 96.8% (95% CI: 96.8–96.9). The pooled LR+ was 51.9 (20.5–131.6), the LR− was 0.27 (0.20–0.37), and the DOR was 186.5 (96.8–359.2). Conclusions While most HF diagnoses in administrative databases do correspond to true HF cases, about one-quarter of HF cases are not captured. The use of broader search parameters, along with laboratory and prescription medication data, may help identify more cases. PMID:25126761

Comparative Study of rK39 Leishmania Antigen for Serodiagnosis of Visceral Leishmaniasis: Systematic Review with Meta-Analysis

PubMed Central

Maia, Zuinara; Lírio, Monique; Mistro, Sóstenes; Mendes, Carlos Maurício Cardeal; Mehta, Sanjay R.; Badaro, Roberto

2012-01-01

Background The rK39 recombinant protein is derived from a specific antigen produced by the Leishmania donovani complex, and has been used in the last two decades for the serodiagnosis of visceral leishmaniasis. We present here a systematic review and meta-analysis of studies evaluating serologic assays to diagnose visceral leishmaniasis to determine the accuracy of rK39 antigen in comparison to the use of other antigen preparations. Methodology/Principal Findings A systematic review with meta-analysis of the literature was performed to compare the rK39 strip-test and ELISA formats against serological tests using promastigote antigens derived from whole or soluble parasites for Direct Aglutination Test (DAT), Indirect Immunofluorescence test (IFAT) and ELISA with a promastigote antigen preparation (p-ELISA). Gold standard diagnosis was defined by the demonstration of amastigotes on hematological specimens. A database search was performed on Medline, Lilacs, Scopus, Isi Web of Science, and Cochrane Library. Quality of data was assessed using the QUADAS questionnaire. A search of the electronic databases found 352 papers of which only 14 fulfilled the selection criteria. Three evaluated the rK39 ELISA, while 13 evaluated the rK39 immunochromatographic strip test. The summarized sensitivity for the rK39-ELISA was 92% followed by IFAT 88% and p-ELISA 87%. The summarized specificity for the three diagnostic tests was 81%, 90%, and 77%. Studies comparing the rK39 strip test with DAT found a similar sensitivity of 94%, although the DAT had a slightly higher specificity. The rK39 strip test was more sensitive and specific than the IFAT and p-ELISA. We did not detect any difference in the sensitivity and specificity between strips produced by different manufacturers. Conclusions The rK39 protein used either in a strip test or in an ELISA, and the DAT are the best choices for implementation of rapid, easy and efficient test for serodiagnosis of VL. PMID:22303488

PAX1 and SOX1 methylation as an initial screening method for cervical cancer: a meta-analysis of individual studies in Asians

PubMed Central

Cui, Zhaolei; Xiao, Zhenzhou; Hu, Minhua; Jiang, Chuanhui; Lin, Yingying; Chen, Yansong

2016-01-01

Background Epigenetic alterations of gene or DNA methylation have been highlighted as promising biomarkers for early cervical cancer screening. Herein, we evaluated the diagnostic performance of paired boxed gene 1 (PAX1) and sex determining region Y-box 1 (SOX1) methylation for cervical cancer detection. Methods Eligible studies were retrieved by searching the electronic databases. Study quality was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. The bivariate meta-analysis model was employed to plot the summary receiver operator characteristic (SROC) curve using Stata 12.0 software. Results The pooled sensitivity of PAX1 methylation was estimated to be 0.73 [95% confidence interval (CI): 0.70–0.75] in differentiating patients with HSIL (high-grade squamous intraepithelial lesion) or CIN3+ (cervical intraepithelial neoplasia type III/worse) or cervical cancer from normal individuals, corresponding to a specificity of 0.87 (95% CI: 0.85–0.89) and area under the curve (AUC) of 0.91. The SOX1 methylation test yielded an AUC of 0.82, under which, the pooled sensitivity was 0.71 (95% CI: 0.67–0.74) and specificity was 0.64 (95% CI: 0.61–0.67). Notably, the stratified analysis suggested that combing parallel testing of PAX1 methylation and human papillomavirus (HPV) DNA (AUC, sensitivity, and specificity of 0.89, 0.75, and 0.81, respectively) achieved higher accuracy than single HPV DNA testing (AUC, sensitivity, and specificity of 0.77, 0.81, and 0.70, respectively). Conclusions PAX1 or SOX1 methylation has a prospect to be an auxiliary biomarker for cervical cancer screening, and parallel testing of PAX1 methylation and HPV DNA in cervical swabs confers an improved diagnostic accuracy than single HPV DNA testing. PMID:27826568

Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates

PubMed Central

Yabu, Julie M.; Siebert, Janet C.; Maecker, Holden T.

2016-01-01

Background Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Methods and Findings Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Conclusions Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize medicine to ultimately improve overall outcomes in highly sensitized kidney transplant candidates. PMID:27078882

Prospective evaluation of free-breathing diffusion-weighted imaging for the detection of inflammatory bowel disease with MR enterography in childhood population

PubMed Central

Dubron, Céline; Avni, Freddy; Boutry, Nathalie; Turck, Dominique; Duhamel, Alain

2016-01-01

Objective: To evaluate prospectively the performance of diffusion-weighted imaging (DWI) for the detection of active lesions on MR enterography (MRE) in children with inflammatory bowel disease (IBD). Methods: MRE of 48 children (mean age 13 years) with suspected or known IBD were blindly analysed by 2 independent readers for the presence of active lesions. Two sets of imaging including DWI and gadolinium-enhanced imaging (GEI) were reviewed. A reader consensus was obtained. The gold standard was histopathological findings. In patient-level analysis and segment-level analysis, sensitivity and specificity were calculated for DWI and GEI and compared using McNemar's test or logistic random-effects models. Results: At least 1 active lesion was confirmed in 42 (87.5%) children. Sensitivity and specificity for the detection of at least one lesion were 88.1% (95% CI, 74.3–96.1) and 83.3% (95% CI, 35.9–99.6), respectively, for DWI and 66.7% (95% CI, 50.4–80.4) and 83.3% (95% CI, 35.9–99.6), respectively, for GEI. In segment-level analysis, sensitivity and specificity for the detection of specific segment lesions were 62.5% (95% CI, 48.1–75) and 97.1% (95% CI, 93.5–98.7), respectively, for DWI and 45.7% (95% CI, 30.8–61.3) and 98.2% (95% CI, 95.3–99.4), respectively, for GEI. The sensitivity of DWI was significantly better than that of GEI per patient (p = 0.004) and per segment (p = 0.028). Conclusion: DWI demonstrates better performance than GEI for the detection of active lesions in children with IBD. Advances in knowledge: Examination with no intravenous injection–DWI can replace T1 weighted images when paediatric patients are screened with MRE for IBD. Examination performed in free breathing is better tolerated by children. PMID:26838954

Benchmarking of a treatment planning system for spot scanning proton therapy: Comparison and analysis of robustness to setup errors of photon IMRT and proton SFUD treatment plans of base of skull meningioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harding, R., E-mail: ruth.harding2@wales.nhs.uk; Trnková, P.; Lomax, A. J.

Purpose: Base of skull meningioma can be treated with both intensity modulated radiation therapy (IMRT) and spot scanned proton therapy (PT). One of the main benefits of PT is better sparing of organs at risk, but due to the physical and dosimetric characteristics of protons, spot scanned PT can be more sensitive to the uncertainties encountered in the treatment process compared with photon treatment. Therefore, robustness analysis should be part of a comprehensive comparison between these two treatment methods in order to quantify and understand the sensitivity of the treatment techniques to uncertainties. The aim of this work was tomore » benchmark a spot scanning treatment planning system for planning of base of skull meningioma and to compare the created plans and analyze their robustness to setup errors against the IMRT technique. Methods: Plans were produced for three base of skull meningioma cases: IMRT planned with a commercial TPS [Monaco (Elekta AB, Sweden)]; single field uniform dose (SFUD) spot scanning PT produced with an in-house TPS (PSI-plan); and SFUD spot scanning PT plan created with a commercial TPS [XiO (Elekta AB, Sweden)]. A tool for evaluating robustness to random setup errors was created and, for each plan, both a dosimetric evaluation and a robustness analysis to setup errors were performed. Results: It was possible to create clinically acceptable treatment plans for spot scanning proton therapy of meningioma with a commercially available TPS. However, since each treatment planning system uses different methods, this comparison showed different dosimetric results as well as different sensitivities to setup uncertainties. The results confirmed the necessity of an analysis tool for assessing plan robustness to provide a fair comparison of photon and proton plans. Conclusions: Robustness analysis is a critical part of plan evaluation when comparing IMRT plans with spot scanned proton therapy plans.« less

Quantitative image analysis of immunohistochemical stains using a CMYK color model

PubMed Central

Pham, Nhu-An; Morrison, Andrew; Schwock, Joerg; Aviel-Ronen, Sarit; Iakovlev, Vladimir; Tsao, Ming-Sound; Ho, James; Hedley, David W

2007-01-01

Background Computer image analysis techniques have decreased effects of observer biases, and increased the sensitivity and the throughput of immunohistochemistry (IHC) as a tissue-based procedure for the evaluation of diseases. Methods We adapted a Cyan/Magenta/Yellow/Key (CMYK) model for automated computer image analysis to quantify IHC stains in hematoxylin counterstained histological sections. Results The spectral characteristics of the chromogens AEC, DAB and NovaRed as well as the counterstain hematoxylin were first determined using CMYK, Red/Green/Blue (RGB), normalized RGB and Hue/Saturation/Lightness (HSL) color models. The contrast of chromogen intensities on a 0–255 scale (24-bit image file) as well as compared to the hematoxylin counterstain was greatest using the Yellow channel of a CMYK color model, suggesting an improved sensitivity for IHC evaluation compared to other color models. An increase in activated STAT3 levels due to growth factor stimulation, quantified using the Yellow channel image analysis was associated with an increase detected by Western blotting. Two clinical image data sets were used to compare the Yellow channel automated method with observer-dependent methods. First, a quantification of DAB-labeled carbonic anhydrase IX hypoxia marker in 414 sections obtained from 138 biopsies of cervical carcinoma showed strong association between Yellow channel and positive color selection results. Second, a linear relationship was also demonstrated between Yellow intensity and visual scoring for NovaRed-labeled epidermal growth factor receptor in 256 non-small cell lung cancer biopsies. Conclusion The Yellow channel image analysis method based on a CMYK color model is independent of observer biases for threshold and positive color selection, applicable to different chromogens, tolerant of hematoxylin, sensitive to small changes in IHC intensity and is applicable to simple automation procedures. These characteristics are advantageous for both basic as well as clinical research in an unbiased, reproducible and high throughput evaluation of IHC intensity. PMID:17326824

SU-C-201-04: Quantification of Perfusion Heterogeneity Based On Texture Analysis for Fully Automatic Detection of Ischemic Deficits From Myocardial Perfusion Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Y; Huang, H; Su, T

Purpose: Texture-based quantification of image heterogeneity has been a popular topic for imaging studies in recent years. As previous studies mainly focus on oncological applications, we report our recent efforts of applying such techniques on cardiac perfusion imaging. A fully automated procedure has been developed to perform texture analysis for measuring the image heterogeneity. Clinical data were used to evaluate the preliminary performance of such methods. Methods: Myocardial perfusion images of Thallium-201 scans were collected from 293 patients with suspected coronary artery disease. Each subject underwent a Tl-201 scan and a percutaneous coronary intervention (PCI) within three months. The PCImore » Result was used as the gold standard of coronary ischemia of more than 70% stenosis. Each Tl-201 scan was spatially normalized to an image template for fully automatic segmentation of the LV. The segmented voxel intensities were then carried into the texture analysis with our open-source software Chang Gung Image Texture Analysis toolbox (CGITA). To evaluate the clinical performance of the image heterogeneity for detecting the coronary stenosis, receiver operating characteristic (ROC) analysis was used to compute the overall accuracy, sensitivity and specificity as well as the area under curve (AUC). Those indices were compared to those obtained from the commercially available semi-automatic software QPS. Results: With the fully automatic procedure to quantify heterogeneity from Tl-201 scans, we were able to achieve a good discrimination with good accuracy (74%), sensitivity (73%), specificity (77%) and AUC of 0.82. Such performance is similar to those obtained from the semi-automatic QPS software that gives a sensitivity of 71% and specificity of 77%. Conclusion: Based on fully automatic procedures of data processing, our preliminary data indicate that the image heterogeneity of myocardial perfusion imaging can provide useful information for automatic determination of the myocardial ischemia.« less

The Diagnostic Value of Capillary Refill Time for Detecting Serious Illness in Children: A Systematic Review and Meta-Analysis

PubMed Central

Fleming, Susannah; Gill, Peter; Jones, Caroline; Taylor, James A.; Van den Bruel, Ann; Heneghan, Carl; Roberts, Nia; Thompson, Matthew

2015-01-01

Importance Capillary refill time (CRT) is widely recommended as part of the routine assessment of unwell children. Objective To determine the diagnostic value of capillary refill time for a range of serious outcomes in children. Methods We searched Medline, Embase and CINAHL from inception to June 2014. We included studies that measured both capillary refill time and a relevant clinical outcome such as mortality, dehydration, meningitis, or other serious illnesses in children aged up to 18 years of age. We screened 1,265 references, of which 24 papers were included in this review. Where sufficient studies were available, we conducted meta-analysis and constructed hierarchical summary ROC curves. Results Meta-analysis on the relationship between capillary refill time and mortality resulted in sensitivity of 34.6% (95% CI 23.9 to 47.1%), specificity 92.3% (88.6 to 94.8%), positive likelihood ratio 4.49 (3.06 to 6.57), and negative likelihood ratio 0.71 (0.60 to 0.84). Studies of children attending Emergency Departments with vomiting and diarrhea showed that capillary refill time had specificity of 89 to 94% for identifying 5% dehydration, but sensitivity ranged from 0 to 94%. This level of heterogeneity precluded formal meta-analysis of this outcome. Meta-analysis was not possible for other outcomes due to insufficient data, but we found consistently high specificity for a range of outcomes including meningitis, sepsis, admission to hospital, hypoxia, severity of illness and dengue. Conclusions Our results show that capillary refill time is a specific sign, indicating that it can be used as a “red-flag”: children with prolonged capillary refill time have a four-fold risk of dying compared to children with normal capillary refill time. The low sensitivity means that a normal capillary refill time should not reassure clinicians. PMID:26375953

Robust Optimization and Sensitivity Analysis with Multi-Objective Genetic Algorithms: Single- and Multi-Disciplinary Applications

DTIC Science & Technology

2007-01-01

multi-disciplinary optimization with uncertainty. Robust optimization and sensitivity analysis is usually used when an optimization model has...formulation is introduced in Section 2.3. We briefly discuss several definitions used in the sensitivity analysis in Section 2.4. Following in...2.5. 2.4 SENSITIVITY ANALYSIS In this section, we discuss several definitions used in Chapter 5 for Multi-Objective Sensitivity Analysis . Inner

Serum 25-hydroxyvitamin D and parathyroid hormone are independent determinants of whole-body insulin sensitivity in women and may contribute to lower insulin sensitivity in African Americans123

PubMed Central

Alvarez, Jessica A; Ashraf, Ambika P; Hunter, Gary R; Gower, Barbara A

2010-01-01

Background: Circulating 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) concentrations have been shown to be associated with insulin sensitivity; however, adiposity may confound this relation. Furthermore, African Americans (AAs) have lower insulin sensitivity and 25(OH)D concentrations than do European Americans (EAs); whether these differences are associated in a cause-and-effect manner has not been determined. Objectives: The objectives of this study were to examine the relation of 25(OH)D and PTH concentrations with whole-body insulin sensitivity and to determine whether lower 25(OH)D concentrations in AAs compared with EAs contribute to the lower insulin sensitivity of AAs relative to that of EAs. Design: This was a cross-sectional study of 25 AA and 25 EA women. We determined the whole-body insulin sensitivity index (SI) with an intravenous glucose tolerance test and minimal modeling. Percentage body fat was determined with dual-energy X-ray absorptiometry, and intraabdominal adipose tissue (IAAT) was determined with computed tomography. Results: Multiple linear regression analysis indicated that 25(OH)D and PTH concentrations were independent determinants of SI [standardized β = 0.24 (P = 0.04) and −0.36 (P = 0.002), respectively] after adjustment for age, race, and IAAT. The mean ethnic difference in SI decreased from 2.70 [· 10−4 · min−1/(μIU/mL)] after adjustment for IAAT and percentage body fat to 1.80 [· 10−4 · min−1/(μIU/mL)] after further adjustment for 25(OH)D and PTH concentrations. Conclusions: 25(OH)D and PTH concentrations were independently associated with whole-body insulin sensitivity in a cohort of healthy women, which suggested that these variables may influence insulin sensitivity through independent mechanisms. Furthermore, ethnic differences in 25(OH)D concentrations may contribute to ethnic differences in insulin sensitivity. PMID:20861177

A preliminary result of three-dimensional microarray technology to gene analysis with endoscopic ultrasound-guided fine-needle aspiration specimens and pancreatic juices

PubMed Central

2010-01-01

Background Analysis of gene expression and gene mutation may add information to be different from ordinary pathological tissue diagnosis. Since samples obtained endoscopically are very small, it is desired that more sensitive technology is developed for gene analysis. We investigated whether gene expression and gene mutation analysis by newly developed ultra-sensitive three-dimensional (3D) microarray is possible using small amount samples from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens and pancreatic juices. Methods Small amount samples from 17 EUS-FNA specimens and 16 pancreatic juices were obtained. After nucleic acid extraction, the samples were amplified with labeling and analyzed by the 3D microarray. Results The analyzable rate with the microarray was 46% (6/13) in EUS-FNA specimens of RNAlater® storage, and RNA degradations were observed in all the samples of frozen storage. In pancreatic juices, the analyzable rate was 67% (4/6) in frozen storage samples and 20% (2/10) in RNAlater® storage. EUS-FNA specimens were classified into cancer and non-cancer by gene expression analysis and K-ras codon 12 mutations were also detected using the 3D microarray. Conclusions Gene analysis from small amount samples obtained endoscopically was possible by newly developed 3D microarray technology. High quality RNA from EUS-FNA samples were obtained and remained in good condition only using RNA stabilizer. In contrast, high quality RNA from pancreatic juice samples were obtained only in frozen storage without RNA stabilizer. PMID:20416107

Analyzing small data sets using Bayesian estimation: the case of posttraumatic stress symptoms following mechanical ventilation in burn survivors

PubMed Central

van de Schoot, Rens; Broere, Joris J.; Perryck, Koen H.; Zondervan-Zwijnenburg, Mariëlle; van Loey, Nancy E.

2015-01-01

Background The analysis of small data sets in longitudinal studies can lead to power issues and often suffers from biased parameter values. These issues can be solved by using Bayesian estimation in conjunction with informative prior distributions. By means of a simulation study and an empirical example concerning posttraumatic stress symptoms (PTSS) following mechanical ventilation in burn survivors, we demonstrate the advantages and potential pitfalls of using Bayesian estimation. Methods First, we show how to specify prior distributions and by means of a sensitivity analysis we demonstrate how to check the exact influence of the prior (mis-) specification. Thereafter, we show by means of a simulation the situations in which the Bayesian approach outperforms the default, maximum likelihood and approach. Finally, we re-analyze empirical data on burn survivors which provided preliminary evidence of an aversive influence of a period of mechanical ventilation on the course of PTSS following burns. Results Not suprisingly, maximum likelihood estimation showed insufficient coverage as well as power with very small samples. Only when Bayesian analysis, in conjunction with informative priors, was used power increased to acceptable levels. As expected, we showed that the smaller the sample size the more the results rely on the prior specification. Conclusion We show that two issues often encountered during analysis of small samples, power and biased parameters, can be solved by including prior information into Bayesian analysis. We argue that the use of informative priors should always be reported together with a sensitivity analysis. PMID:25765534

Analyzing small data sets using Bayesian estimation: the case of posttraumatic stress symptoms following mechanical ventilation in burn survivors.

PubMed

van de Schoot, Rens; Broere, Joris J; Perryck, Koen H; Zondervan-Zwijnenburg, Mariëlle; van Loey, Nancy E

2015-01-01

Background : The analysis of small data sets in longitudinal studies can lead to power issues and often suffers from biased parameter values. These issues can be solved by using Bayesian estimation in conjunction with informative prior distributions. By means of a simulation study and an empirical example concerning posttraumatic stress symptoms (PTSS) following mechanical ventilation in burn survivors, we demonstrate the advantages and potential pitfalls of using Bayesian estimation. Methods : First, we show how to specify prior distributions and by means of a sensitivity analysis we demonstrate how to check the exact influence of the prior (mis-) specification. Thereafter, we show by means of a simulation the situations in which the Bayesian approach outperforms the default, maximum likelihood and approach. Finally, we re-analyze empirical data on burn survivors which provided preliminary evidence of an aversive influence of a period of mechanical ventilation on the course of PTSS following burns. Results : Not suprisingly, maximum likelihood estimation showed insufficient coverage as well as power with very small samples. Only when Bayesian analysis, in conjunction with informative priors, was used power increased to acceptable levels. As expected, we showed that the smaller the sample size the more the results rely on the prior specification. Conclusion : We show that two issues often encountered during analysis of small samples, power and biased parameters, can be solved by including prior information into Bayesian analysis. We argue that the use of informative priors should always be reported together with a sensitivity analysis.

Association between diabetes mellitus and gastroesophageal reflux disease: A meta-analysis

PubMed Central

Sun, Xiao-Meng; Tan, Jia-Cheng; Zhu, Ying; Lin, Lin

2015-01-01

AIM: To investigate whether there is a link between diabetes mellitus (DM) and gastroesophageal reflux disease (GERD). METHODS: We conducted a systematic search of PubMed and Web of Science databases, from their respective inceptions until December 31, 2013, for articles evaluating the relationship between DM and GERD. Studies were selected for analysis based on certain inclusion and exclusion criteria. Data were extracted from each study on the basis of predefined items. A meta-analysis was performed to compare the odds ratio (OR) in DM between individuals with and without GERD using a fixed effect or random effect model, depending on the absence or presence of significant heterogeneity. Subgroup analyses were used to identify sources of heterogeneity. Publication bias was assessed by Begg’s test. To evaluate the results, we also performed a sensitivity analysis. RESULTS: When the electronic database and hand searches were combined, a total of nine eligible articles involving 9067 cases and 81 968 controls were included in our meta-analysis. Based on the random-effects model, these studies identified a significant association between DM and the risk of GERD (overall OR = 1.61; 95%CI: 1.36-1.91; P = 0.003). Subgroup analyses indicated that this result persisted in studies on populations from Eastern countries (OR = 1.71; 95%CI: 1.38-2.12; P = 0.003) and in younger patients (mean age < 50 years) (OR = 1.70; 95%CI: 1.22-2.37; P = 0.001). No significant publication bias was observed in this meta-analysis using Begg’s test (P = 0.175). The sensitivity analysis also confirmed the stability of our results. CONCLUSION: This meta-analysis suggests that patients with DM are at greater risk of GERD than those who do not have DM. PMID:25780309

Global sensitivity analysis in wind energy assessment

NASA Astrophysics Data System (ADS)

Tsvetkova, O.; Ouarda, T. B.

2012-12-01

Wind energy is one of the most promising renewable energy sources. Nevertheless, it is not yet a common source of energy, although there is enough wind potential to supply world's energy demand. One of the most prominent obstacles on the way of employing wind energy is the uncertainty associated with wind energy assessment. Global sensitivity analysis (SA) studies how the variation of input parameters in an abstract model effects the variation of the variable of interest or the output variable. It also provides ways to calculate explicit measures of importance of input variables (first order and total effect sensitivity indices) in regard to influence on the variation of the output variable. Two methods of determining the above mentioned indices were applied and compared: the brute force method and the best practice estimation procedure In this study a methodology for conducting global SA of wind energy assessment at a planning stage is proposed. Three sampling strategies which are a part of SA procedure were compared: sampling based on Sobol' sequences (SBSS), Latin hypercube sampling (LHS) and pseudo-random sampling (PRS). A case study of Masdar City, a showcase of sustainable living in the UAE, is used to exemplify application of the proposed methodology. Sources of uncertainty in wind energy assessment are very diverse. In the case study the following were identified as uncertain input parameters: the Weibull shape parameter, the Weibull scale parameter, availability of a wind turbine, lifetime of a turbine, air density, electrical losses, blade losses, ineffective time losses. Ineffective time losses are defined as losses during the time when the actual wind speed is lower than the cut-in speed or higher than the cut-out speed. The output variable in the case study is the lifetime energy production. Most influential factors for lifetime energy production are identified with the ranking of the total effect sensitivity indices. The results of the present research show that the brute force method is best for wind assessment purpose, SBSS outperforms other sampling strategies in the majority of cases. The results indicate that the Weibull scale parameter, turbine lifetime and Weibull shape parameter are the three most influential variables in the case study setting. The following conclusions can be drawn from these results: 1) SBSS should be recommended for use in Monte Carlo experiments, 2) The brute force method should be recommended for conducting sensitivity analysis in wind resource assessment, and 3) Little variation in the Weibull scale causes significant variation in energy production. The presence of the two distribution parameters in the top three influential variables (the Weibull shape and scale) emphasizes the importance of accuracy of (a) choosing the distribution to model wind regime at a site and (b) estimating probability distribution parameters. This can be labeled as the most important conclusion of this research because it opens a field for further research, which the authors see could change the wind energy field tremendously.

Satellite on-board processing for earth resources data

NASA Technical Reports Server (NTRS)

Bodenheimer, R. E.; Gonzalez, R. C.; Gupta, J. N.; Hwang, K.; Rochelle, R. W.; Wilson, J. B.; Wintz, P. A.

1975-01-01

Results of a survey of earth resources user applications and their data requirements, earth resources multispectral scanner sensor technology, and preprocessing algorithms for correcting the sensor outputs and for data bulk reduction are presented along with a candidate data format. Computational requirements required to implement the data analysis algorithms are included along with a review of computer architectures and organizations. Computer architectures capable of handling the algorithm computational requirements are suggested and the environmental effects of an on-board processor discussed. By relating performance parameters to the system requirements of each of the user requirements the feasibility of on-board processing is determined for each user. A tradeoff analysis is performed to determine the sensitivity of results to each of the system parameters. Significant results and conclusions are discussed, and recommendations are presented.

Analytical description of the modern steam automobile

NASA Technical Reports Server (NTRS)

Peoples, J. A.

1974-01-01

The sensitivity of operating conditions upon performance of the modern steam automobile is discussed. The word modern has been used in the title to indicate that emphasis is upon miles per gallon rather than theoretical thermal efficiency. This has been accomplished by combining classical power analysis with the ideal Pressure-Volume diagram. Several parameters are derived which characterize performance capability of the modern steam car. The report illustrates that performance is dictated by the characteristics of the working medium, and the supply temperature. Performance is nearly independent of pressures above 800 psia. Analysis techniques were developed specifically for reciprocating steam engines suitable for automotive application. Specific performance charts have been constructed on the basis of water as a working medium. The conclusions and data interpretation are therefore limited within this scope.

Space station electrical power system availability study

NASA Technical Reports Server (NTRS)

Turnquist, Scott R.; Twombly, Mark A.

1988-01-01

ARINC Research Corporation performed a preliminary reliability, and maintainability (RAM) anlaysis of the NASA space station Electric Power Station (EPS). The analysis was performed using the ARINC Research developed UNIRAM RAM assessment methodology and software program. The analysis was performed in two phases: EPS modeling and EPS RAM assessment. The EPS was modeled in four parts: the insolar power generation system, the eclipse power generation system, the power management and distribution system (both ring and radial power distribution control unit (PDCU) architectures), and the power distribution to the inner keel PDCUs. The EPS RAM assessment was conducted in five steps: the use of UNIRAM to perform baseline EPS model analyses and to determine the orbital replacement unit (ORU) criticalities; the determination of EPS sensitivity to on-orbit spared of ORUs and the provision of an indication of which ORUs may need to be spared on-orbit; the determination of EPS sensitivity to changes in ORU reliability; the determination of the expected annual number of ORU failures; and the integration of the power generator system model results with the distribution system model results to assess the full EPS. Conclusions were drawn and recommendations were made.

Photoresist and stochastic modeling

NASA Astrophysics Data System (ADS)

Hansen, Steven G.

2018-01-01

Analysis of physical modeling results can provide unique insights into extreme ultraviolet stochastic variation, which augment, and sometimes refute, conclusions based on physical intuition and even wafer experiments. Simulations verify the primacy of "imaging critical" counting statistics (photons, electrons, and net acids) and the image/blur-dependent dose sensitivity in describing the local edge or critical dimension variation. But the failure of simple counting when resist thickness is varied highlights a limitation of this exact analytical approach, so a calibratable empirical model offers useful simplicity and convenience. Results presented here show that a wide range of physical simulation results can be well matched by an empirical two-parameter model based on blurred image log-slope (ILS) for lines/spaces and normalized ILS for holes. These results are largely consistent with a wide range of published experimental results; however, there is some disagreement with the recently published dataset of De Bisschop. The present analysis suggests that the origin of this model failure is an unexpected blurred ILS:dose-sensitivity relationship failure in that resist process. It is shown that a photoresist mechanism based on high photodecomposable quencher loading and high quencher diffusivity can give rise to pitch-dependent blur, which may explain the discrepancy.

Global Sensitivity Analysis and Estimation of Model Error, Toward Uncertainty Quantification in Scramjet Computations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huan, Xun; Safta, Cosmin; Sargsyan, Khachik

The development of scramjet engines is an important research area for advancing hypersonic and orbital flights. Progress toward optimal engine designs requires accurate flow simulations together with uncertainty quantification. However, performing uncertainty quantification for scramjet simulations is challenging due to the large number of uncertain parameters involved and the high computational cost of flow simulations. These difficulties are addressed in this paper by developing practical uncertainty quantification algorithms and computational methods, and deploying them in the current study to large-eddy simulations of a jet in crossflow inside a simplified HIFiRE Direct Connect Rig scramjet combustor. First, global sensitivity analysis ismore » conducted to identify influential uncertain input parameters, which can help reduce the system’s stochastic dimension. Second, because models of different fidelity are used in the overall uncertainty quantification assessment, a framework for quantifying and propagating the uncertainty due to model error is presented. In conclusion, these methods are demonstrated on a nonreacting jet-in-crossflow test problem in a simplified scramjet geometry, with parameter space up to 24 dimensions, using static and dynamic treatments of the turbulence subgrid model, and with two-dimensional and three-dimensional geometries.« less

PHYSICAL EXAMINATIONS FOR DIAGNOSING MENISCAL INJURIES: CORRELATION WITH SURGICAL FINDINGS

PubMed Central

Gobbo, Ricardo da Rocha; Rangel, Victor de Oliveira; Karam, Francisco Consoli; Pires, Luiz Antônio Simões

2015-01-01

Objective: A set of five maneuvers for meniscal injuries (McMurray, Apley, Childress and Steinmann 1 and 2) was evaluated and their sensitivity, specificity, accuracy and likelihood were calculated. The same methods were applied to each test individually. Methods: One hundred and fifty-two patients of both sexes who were going to undergo videoarthroscopy on the knee were examined blindly by one of five residents at this hospital, without knowledge of the clinical data and why the patient was going to undergo an operation. This examination was conducted immediately before the videoarthroscopy and its results were recorded in an electronic spreadsheet. The set of maneuvers was considered positive when one was positive. In the individual analysis, it was enough for the test to be positive. Results: The analysis showed that the set of five meniscal tests presented sensitivity of 89%, specificity of 42%, accuracy of 75%, positive likelihood of 1.53 and negative likelihood of 0.26. Individually, the tests presented accuracy of between 48% and 53%. Conclusion: The set of maneuvers for meniscal injuries presented a good accuracy and significant value, especially for ruling out injury. Individually, the tests had less diagnostic value, although the Apley test had better specificity. PMID:27047833

Orthostatic Intolerance and Postural Orthostatic Tachycardia Syndrome in Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome, Hypermobility Type: Neurovegetative Dysregulation or Autonomic Failure?

PubMed

Celletti, Claudia; Camerota, Filippo; Castori, Marco; Censi, Federica; Gioffrè, Laura; Calcagnini, Giovanni; Strano, Stefano

2017-01-01

Background . Joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type (JHS/EDS-HT), is a hereditary connective tissue disorder mainly characterized by generalized joint hypermobility, skin texture abnormalities, and visceral and vascular dysfunctions, also comprising symptoms of autonomic dysfunction. This study aims to further evaluate cardiovascular autonomic involvement in JHS/EDS-HT by a battery of functional tests. Methods . The response to cardiovascular reflex tests comprising deep breathing, Valsalva maneuver, 30/15 ratio, handgrip test, and head-up tilt test was studied in 35 JHS/EDS-HT adults. Heart rate and blood pressure variability was also investigated by spectral analysis in comparison to age and sex healthy matched group. Results . Valsalva ratio was normal in all patients, but 37.2% of them were not able to finish the test. At tilt, 48.6% patients showed postural orthostatic tachycardia, 31.4% orthostatic intolerance, 20% normal results. Only one patient had orthostatic hypotension. Spectral analysis showed significant higher baroreflex sensitivity values at rest compared to controls. Conclusions. This study confirms the abnormal cardiovascular autonomic profile in adults with JHS/EDS-HT and found the higher baroreflex sensitivity as a potential disease marker and clue for future research.

A comprehensive prediction and evaluation method of pilot workload

PubMed Central

Feng, Chuanyan; Wanyan, Xiaoru; Yang, Kun; Zhuang, Damin; Wu, Xu

2018-01-01

BACKGROUND: The prediction and evaluation of pilot workload is a key problem in human factor airworthiness of cockpit. OBJECTIVE: A pilot traffic pattern task was designed in a flight simulation environment in order to carry out the pilot workload prediction and improve the evaluation method. METHODS: The prediction of typical flight subtasks and dynamic workloads (cruise, approach, and landing) were built up based on multiple resource theory, and a favorable validity was achieved by the correlation analysis verification between sensitive physiological data and the predicted value. RESULTS: Statistical analysis indicated that eye movement indices (fixation frequency, mean fixation time, saccade frequency, mean saccade time, and mean pupil diameter), Electrocardiogram indices (mean normal-to-normal interval and the ratio between low frequency and sum of low frequency and high frequency), and Electrodermal Activity indices (mean tonic and mean phasic) were all sensitive to typical workloads of subjects. CONCLUSION: A multinominal logistic regression model based on combination of physiological indices (fixation frequency, mean normal-to-normal interval, the ratio between low frequency and sum of low frequency and high frequency, and mean tonic) was constructed, and the discriminate accuracy was comparatively ideal with a rate of 84.85%. PMID:29710742

Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

NASA Astrophysics Data System (ADS)

Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

2016-05-01

Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63-0.66), 0.73 (95% CI: 0.72-0.74), 2.23 (95% CI: 1.91-2.62), 0.48 (95% CI: 0.44-0.52), 5.31 (95% CI: 4.19-6.73) and 0.75 (95% CI: 0.74-0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.

Measurement of Stigmatization towards Adults with Attention Deficit Hyperactivity Disorder

PubMed Central

Fuermaier, Anselm B. M.; Tucha, Lara; Koerts, Janneke; Mueller, Anna K.; Lange, Klaus W.; Tucha, Oliver

2012-01-01

Objectives In general, assessment tools for stigma in mental disorders such as attention deficit hyperactivity disorder (ADHD) are lacking. Moreover, misbeliefs and misconceptions about ADHD are common, in particular with regard to the adult form of ADHD. The aim of the present study was to develop a questionnaire measuring stigma in adults with ADHD and to demonstrate its sensitivity. Methods A questionnaire initially containing 64 items associated with stigma in adults with ADHD was developed. A total number of 1261 respondents were included in the analyses. The psychometric properties were investigated on a sample of 1033 participants. The sensitivity of the questionnaire was explored on 228 participants consisting of teachers, physicians and control participants. Results Thirty-seven items were extracted due to exploratory factor analysis (EFA) and the internal consistency of items. Confirmatory factor analysis (CFA) revealed good psychometric properties of a 6-factor structure. Teachers and physicians differed significantly in their stigmatizing attitudes from control participants. Conclusions The present data shed light on various dimensions of stigma in adult ADHD. Reliability and Social Functioning, Malingering and Misuse of Medication, Ability to Take Responsibility, Norm-violating and Externalizing Behavior, Consequences of Diagnostic Disclosure and Etiology represent critical aspects associated with stigmatization. PMID:23284760

Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis

PubMed Central

Motta, Caterina; Palermo, Eduardo; Studer, Valeria; Germanotta, Marco; Germani, Giorgio; Centonze, Diego; Cappa, Paolo

2016-01-01

Background The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive. Objective To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis. Methods A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM) for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E) defined as the sum of sROMs was proposed. Results We established two novel observer-independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status. Conclusions Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis. PMID:26863109

Global Sensitivity Analysis and Estimation of Model Error, Toward Uncertainty Quantification in Scramjet Computations

DOE PAGES

Huan, Xun; Safta, Cosmin; Sargsyan, Khachik; ...

2018-02-09

The development of scramjet engines is an important research area for advancing hypersonic and orbital flights. Progress toward optimal engine designs requires accurate flow simulations together with uncertainty quantification. However, performing uncertainty quantification for scramjet simulations is challenging due to the large number of uncertain parameters involved and the high computational cost of flow simulations. These difficulties are addressed in this paper by developing practical uncertainty quantification algorithms and computational methods, and deploying them in the current study to large-eddy simulations of a jet in crossflow inside a simplified HIFiRE Direct Connect Rig scramjet combustor. First, global sensitivity analysis ismore » conducted to identify influential uncertain input parameters, which can help reduce the system’s stochastic dimension. Second, because models of different fidelity are used in the overall uncertainty quantification assessment, a framework for quantifying and propagating the uncertainty due to model error is presented. In conclusion, these methods are demonstrated on a nonreacting jet-in-crossflow test problem in a simplified scramjet geometry, with parameter space up to 24 dimensions, using static and dynamic treatments of the turbulence subgrid model, and with two-dimensional and three-dimensional geometries.« less

Commercial Serological Tests for the Diagnosis of Active Pulmonary and Extrapulmonary Tuberculosis: An Updated Systematic Review and Meta-Analysis

PubMed Central

Steingart, Karen R.; Flores, Laura L.; Dendukuri, Nandini; Schiller, Ian; Laal, Suman; Ramsay, Andrew; Hopewell, Philip C.; Pai, Madhukar

2011-01-01

Background Serological (antibody detection) tests for tuberculosis (TB) are widely used in developing countries. As part of a World Health Organization policy process, we performed an updated systematic review to assess the diagnostic accuracy of commercial serological tests for pulmonary and extrapulmonary TB with a focus on the relevance of these tests in low- and middle-income countries. Methods and Findings We used methods recommended by the Cochrane Collaboration and GRADE approach for rating quality of evidence. In a previous review, we searched multiple databases for papers published from 1 January 1990 to 30 May 2006, and in this update, we add additional papers published from that period until 29 June 2010. We prespecified subgroups to address heterogeneity and summarized test performance using bivariate random effects meta-analysis. For pulmonary TB, we included 67 studies (48% from low- and middle-income countries) with 5,147 participants. For all tests, estimates were variable for sensitivity (0% to 100%) and specificity (31% to 100%). For anda-TB IgG, the only test with enough studies for meta-analysis, pooled sensitivity was 76% (95% CI 63%–87%) in smear-positive (seven studies) and 59% (95% CI 10%–96%) in smear-negative (four studies) patients; pooled specificities were 92% (95% CI 74%–98%) and 91% (95% CI 79%–96%), respectively. Compared with ELISA (pooled sensitivity 60% [95% CI 6%–65%]; pooled specificity 98% [95% CI 96%–99%]), immunochromatographic tests yielded lower pooled sensitivity (53%, 95% CI 42%–64%) and comparable pooled specificity (98%, 95% CI 94%–99%). For extrapulmonary TB, we included 25 studies (40% from low- and middle-income countries) with 1,809 participants. For all tests, estimates were variable for sensitivity (0% to 100%) and specificity (59% to 100%). Overall, quality of evidence was graded very low for studies of pulmonary and extrapulmonary TB. Conclusions Despite expansion of the literature since 2006, commercial serological tests continue to produce inconsistent and imprecise estimates of sensitivity and specificity. Quality of evidence remains very low. These data informed a recently published World Health Organization policy statement against serological tests. Please see later in the article for the Editors' Summary PMID:21857806

Evaluation of Microbial Load in Oropharyngeal Mucosa from Tannery Workers

PubMed Central

Castellanos-Arévalo, Diana C.; Castellanos-Arévalo, Andrea P.; Camarena-Pozos, David A.; Colli-Mull, Juan G.; Maldonado-Vega, María

2014-01-01

Background Animal skin provides an ideal medium for the propagation of microorganisms and it is used like raw material in the tannery and footware industry. The aim of this study was to evaluate and identify the microbial load in oropharyngeal mucosa of tannery employees. Methods The health risk was estimated based on the identification of microorganisms found in the oropharyngeal mucosa samples. The study was conducted in a tanners group and a control group. Samples were taken from oropharyngeal mucosa and inoculated on plates with selective medium. In the samples, bacteria were identified by 16S ribosomal DNA analysis and the yeasts through a presumptive method. In addition, the sensitivity of these microorganisms to antibiotics/antifungals was evaluated. Results The identified bacteria belonged to the families Enterobacteriaceae, Pseudomonadaceae, Neisseriaceae, Alcaligenaceae, Moraxellaceae, and Xanthomonadaceae, of which some species are considered as pathogenic or opportunistic microorganisms; these bacteria were not present in the control group. Forty-two percent of bacteria identified in the tanners group are correlated with respiratory diseases. Yeasts were also identified, including the following species: Candida glabrata, Candida tropicalis, Candida albicans, and Candida krusei. Regarding the sensitivity test of bacteria identified in the tanners group, 90% showed sensitivity to piperacillin/tazobactam, 87% showed sensitivity to ticarcillin/clavulanic acid, 74% showed sensitivity to ampicillin/sulbactam, and 58% showed sensitivity to amoxicillin/clavulanic acid. Conclusion Several of the bacteria and yeast identified in the oropharyngeal mucosa of tanners have been correlated with infections in humans and have already been reported as airborne microorganisms in this working environment, representing a health risk for workers. PMID:25830072

64 slice-coronary computed tomography sensitivity and specificity in the evaluation of coronary artery bypass graft stenosis: A meta-analysis.

PubMed

Barbero, Umberto; Iannaccone, Mario; d'Ascenzo, Fabrizio; Barbero, Cristina; Mohamed, Abdirashid; Annone, Umberto; Benedetto, Sara; Celentani, Dario; Gagliardi, Marco; Moretti, Claudio; Gaita, Fiorenzo

2016-08-01

A non-invasive approach to define grafts patency and stenosis in the follow-up of coronary artery bypass graft (CABG) patients may be an interesting alternative to coronary angiography. 64-slice-coronary computed tomography is nowadays a diffused non-invasive method that permits an accurate evaluation of coronary stenosis, due to a high temporal and spatial resolution. However, its sensitivity and specificity in CABG evaluation has to be clearly defined, since published studies used different protocols and scanners. We collected all studies investigating patients with stable symptoms and previous CABG and reporting the comparison between diagnostic performances of invasive coronary angiography and 64-slice-coronary computed tomography. As a result, sensitivity and specificity of 64-slice-coronary computed tomography for CABG occlusion were 0.99 (95% CI 0.97-1.00) and 0.99 (95% CI: 0.99-1.00) with an area under the curve (AUC) of 0.99. 64-slice-coronary computed tomography sensitivity and specificity for the presence of any CABG stenosis >50% were 0.98 (95% CI: 0.97-0.99) and 0.98 (95% CI: 0.96-0.98), while AUC was 0.99. At meta-regression, neither the age nor the time from graft implantation had effect on sensitivity and specificity of 64-slice-coronary computed tomography detection of significant CABG stenosis or occlusion. In conclusion 64-slice-coronary computed tomography confirmed its high sensitivity and specificity in CABG stenosis or occlusion evaluation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Selling falsehoods? A cross-sectional study of Canadian naturopathy, homeopathy, chiropractic and acupuncture clinic website claims relating to allergy and asthma

PubMed Central

Murdoch, Blake; Carr, Stuart; Caulfield, Timothy

2016-01-01

Objective To identify the frequency and qualitative characteristics of marketing claims made by Canadian chiropractors, naturopaths, homeopaths and acupuncturists relating to the diagnosis and treatment of allergy and asthma. Design Cross-sectional study. Setting Canada. Data set 392 chiropractic, naturopathic, homeopathic and acupuncture clinic websites located in 10 of the largest metropolitan areas in Canada, as identified using 400 Google search results. Duplicates were not excluded from data analysis. Main outcome measures Mention of allergy, sensitivity or asthma, claim of ability to diagnose allergy, sensitivity or asthma, claim of ability to treat allergy, sensitivity or asthma, and claim of allergy, sensitivity or asthma treatment efficacy. Tests and treatments promoted were noted as qualitative examples. Results Naturopath clinic websites have the highest rates of advertising at least one of diagnosis, treatment or efficacy for allergy or sensitivity (85%) and asthma (64%), followed by acupuncturists (68% and 53%, respectively), homeopaths (60% and 54%) and chiropractors (33% and 38%). Search results from Vancouver, British Columbia were most likely to advertise at least one of diagnosis, treatment or efficacy for allergy or sensitivity (72.5%) and asthma (62.5%), and results from London, Ontario were least likely (50% and 40%, respectively). Of the interventions advertised, few are scientifically supported; the majority lack evidence of efficacy, and some are potentially harmful. Conclusions The majority of alternative healthcare clinics studied advertised interventions for allergy and asthma. Many offerings are unproven. A policy response may be warranted in order to safeguard the public interest. PMID:27986744

Statistical analysis of an RNA titration series evaluates microarray precision and sensitivity on a whole-array basis

PubMed Central

Holloway, Andrew J; Oshlack, Alicia; Diyagama, Dileepa S; Bowtell, David DL; Smyth, Gordon K

2006-01-01

Background Concerns are often raised about the accuracy of microarray technologies and the degree of cross-platform agreement, but there are yet no methods which can unambiguously evaluate precision and sensitivity for these technologies on a whole-array basis. Results A methodology is described for evaluating the precision and sensitivity of whole-genome gene expression technologies such as microarrays. The method consists of an easy-to-construct titration series of RNA samples and an associated statistical analysis using non-linear regression. The method evaluates the precision and responsiveness of each microarray platform on a whole-array basis, i.e., using all the probes, without the need to match probes across platforms. An experiment is conducted to assess and compare four widely used microarray platforms. All four platforms are shown to have satisfactory precision but the commercial platforms are superior for resolving differential expression for genes at lower expression levels. The effective precision of the two-color platforms is improved by allowing for probe-specific dye-effects in the statistical model. The methodology is used to compare three data extraction algorithms for the Affymetrix platforms, demonstrating poor performance for the commonly used proprietary algorithm relative to the other algorithms. For probes which can be matched across platforms, the cross-platform variability is decomposed into within-platform and between-platform components, showing that platform disagreement is almost entirely systematic rather than due to measurement variability. Conclusion The results demonstrate good precision and sensitivity for all the platforms, but highlight the need for improved probe annotation. They quantify the extent to which cross-platform measures can be expected to be less accurate than within-platform comparisons for predicting disease progression or outcome. PMID:17118209

Validating the M. D. Anderson Symptom Inventory (MDASI) for use in patients with ovarian cancer

PubMed Central

Sailors, Mary H.; Bodurka, Diane C.; Gning, Ibrahima; Ramondetta, Lois M.; Williams, Loretta A.; Mendoza, Tito R.; Agarwal, Sonika; Sun, Charlotte C.; Cleeland, Charles S.

2013-01-01

Objective The M. D. Anderson Symptom Inventory (MDASI) captures the severity of common cancer symptoms from the patients’ perspective. We describe the validity and sensitivity of a module of the MDASI to be used with patients having ovarian cancer (MDASI-OC). Methods Ovarian cancer–specific module items were developed from 14 qualitative patient interviews. 128 patients with invasive epithelial ovarian, peritoneal, or fallopian-tube cancer treated at MD Anderson Cancer Center were recruited. Patients completed the MDASI-OC, socio-demographic questionnaires, the Functional Assessment of Cancer Therapy-Ovary (FACT-O), and a global quality-of-life (QOL) item. Reliability was assessed using Cronbach α and sensitivity using known group was assessed. Construct validity was tested using exploratory factor analysis. Results The sample was primarily white (85.2%), had a mean age of 57.5 years (±12.7 years), and had previously been treated with chemotherapy (75.0%) and/or surgery (93.8%). Approximately 30% of patients reported disturbed sleep, fatigue, or numbness/tingling of at least moderate severity (≥5 on a 0–10 scale). On the ovarian-cancer-specific symptoms, approximately 20% reported back pain, feeling bloated, or constipation of at least moderate severity. Factor analysis revealed six underlying constructs (pain/sleep; cognitive; disease-related and numbness; treatment-related; affective; gastrointestinal-specific). MDASI-OC symptom and interference items had Cronbach α values of 0.90 and 0.89, respectively. The MDASI-OC was sensitive to symptom severity by performance status (p=0.009), QOL (p=0.002), and FACT-O scores (p<0.001). Conclusions The 27-item MDASI-OC meets common criteria for validation and reliability and is sensitive to expected changes in symptoms related to differences in disease and treatment status. PMID:23685012

Performance of Ultrasound in the Diagnosis of Gout in a Multi-Center Study: Comparison with Monosodium Urate Crystal Analysis as the Gold Standard

PubMed Central

Ogdie, Alexis; Taylor, William J; Neogi, Tuhina; Fransen, Jaap; Jansen, Tim L; Schumacher, H. Ralph; Louthrenoo, Worawit; Vazquez-Mellado, Janitzia; Eliseev, Maxim; McCarthy, Geraldine; Stamp, Lisa K.; Perez-Ruiz, Fernando; Sivera, Francisca; Ea, Hang-Korng; Gerritsen, Martijn; Cagnotto, Giovanni; Cavagna, Lorenzo; Lin, Chingtsai; Chou, Yin-Yi; Tausche, Anne-Kathrin; Ochtrop, Manuella Lima Gomes; Janssen, Matthijs; Chen, Jiunn-Horng; Slot, Ole; Lazovskis, Juris; White, Douglas; Cimmino, Marco A.; Uhlig, Till; Dalbeth, Nicola

2017-01-01

Objectives To examine the performance of ultrasound for the diagnosis of gout using presence of monosodium urate (MSU) crystals as the gold standard. Methods We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multi-center observational cross-sectional study of consecutive subjects with at least one swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with MSU crystal confirmation. Rheumatologists or radiologists, blinded to the results of the MSU crystal analysis, performed ultrasound on one or more clinically affected joints. Ultrasound findings of interest were: double contour sign (DCS), tophus, and ‘snowstorm’ appearance. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive ultrasound results among subjects with gout. Results Ultrasound was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV and NPV for the presence of any one of the features were 76.9%, 84.3%, 83.3% and 78.1% respectively. Sensitivity was higher among subjects with disease ≥2 years duration and among subjects with subcutaneous nodules on exam (suspected tophus). Associations with a positive ultrasound finding included suspected clinical tophus (odds ratio 4.77; 95% CI 2.23–10.21), any abnormal plain film radiograph (4.68; 2.68–8.17) and serum urate (1.31; 1.06–1.62). Conclusions Ultrasound features of MSU crystal deposition had high specificity and high positive predictive value but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi. PMID:27748084

Validation of a Low-Cost Paper-Based Screening Test for Sickle Cell Anemia

PubMed Central

Piety, Nathaniel Z.; Yang, Xiaoxi; Kanter, Julie; Vignes, Seth M.; George, Alex; Shevkoplyas, Sergey S.

2016-01-01

Background The high childhood mortality and life-long complications associated with sickle cell anemia (SCA) in developing countries could be significantly reduced with effective prophylaxis and education if SCA is diagnosed early in life. However, conventional laboratory methods used for diagnosing SCA remain prohibitively expensive and impractical in this setting. This study describes the clinical validation of a low-cost paper-based test for SCA that can accurately identify sickle trait carriers (HbAS) and individuals with SCA (HbSS) among adults and children over 1 year of age. Methods and Findings In a population of healthy volunteers and SCA patients in the United States (n = 55) the test identified individuals whose blood contained any HbS (HbAS and HbSS) with 100% sensitivity and 100% specificity for both visual evaluation and automated analysis, and detected SCA (HbSS) with 93% sensitivity and 94% specificity for visual evaluation and 100% sensitivity and 97% specificity for automated analysis. In a population of post-partum women (with a previously unknown SCA status) at a primary obstetric hospital in Cabinda, Angola (n = 226) the test identified sickle cell trait carriers with 94% sensitivity and 97% specificity using visual evaluation (none of the women had SCA). Notably, our test permits instrument- and electricity-free visual diagnostics, requires minimal training to be performed, can be completed within 30 minutes, and costs about $0.07 in test-specific consumable materials. Conclusions Our results validate the paper-based SCA test as a useful low-cost tool for screening adults and children for sickle trait and disease and demonstrate its practicality in resource-limited clinical settings. PMID:26735691

Screening for phaeochromocytoma and paraganglioma: impact of using supine reference intervals for plasma metanephrines with samples collected from fasted/seated patients.

PubMed

Casey, R; Griffin, T P; Wall, D; Dennedy, M C; Bell, M; O'Shea, P M

2017-01-01

Background The Endocrine Society Clinical Practice Guideline on Phaeochomocytoma and Paraganglioma recommends phlebotomy for plasma-free metanephrines with patients fasted and supine using appropriately defined reference intervals. Studies have shown higher diagnostic sensitivities using these criteria. Further, with seated-sampling protocols, for result interpretation, reference intervals that do not compromise diagnostic sensitivity should be employed. Objective To determine the impact on diagnostic performance and financial cost of using supine reference intervals for result interpretation with our current plasma-free metanephrines fasted/seated-sampling protocol. Methods We conducted a retrospective cohort study of patients who underwent screening for PPGL using plasma-free metanephrines from 2009 to 2014 at Galway University Hospitals. Plasma-free metanephrines were measured using liquid chromatography-tandem mass spectrometry. Supine thresholds for plasma normetanephrine and metanephrine set at 610 pmol/L and 310 pmol/L, respectively, were used. Results A total of 183 patients were evaluated. Mean age of participants was 53.4 (±16.3) years. Five of 183 (2.7%) patients had histologically confirmed PPGL (males, n=4). Using seated reference intervals for plasma-free metanephrines, diagnostic sensitivity and specificity were 100% and 98.9%, respectively, with two false-positive cases. Application of reference intervals established in subjects supine and fasted to this cohort gave diagnostic sensitivity of 100% with specificity of 74.7%. Financial analysis of each pretesting strategy demonstrated cost-equivalence (€147.27/patient). Conclusion Our cost analysis, together with the evidence that fasted/supine-sampling for plasma-free metanephrines, offers more reliable exclusion of PPGL mandates changing our current practice. This study highlights the important advantages of standardized diagnostic protocols for plasma-free metanephrines to ensure the highest diagnostic accuracy for investigation of PPGL.

Quantitative Shear Wave Velocity Measurement on Acoustic Radiation Force Impulse Elastography for Differential Diagnosis between Benign and Malignant Thyroid Nodules: A Meta-analysis.

PubMed

Liu, Bo-Ji; Li, Dan-Dan; Xu, Hui-Xiong; Guo, Le-Hang; Zhang, Yi-Feng; Xu, Jun-Mei; Liu, Chang; Liu, Lin-Na; Li, Xiao-Long; Xu, Xiao-Hong; Qu, Shen; Xing, Mingzhao

2015-12-01

The aim of this study was to evaluate the diagnostic performance of quantitative shear wave velocity (SWV) measurement on acoustic radiation force impulse (ARFI) elastography for differentiation between benign and malignant thyroid nodules using meta-analysis. The databases of PubMed and the Web of Science were searched. Studies published in English on assessment of the sensitivity and specificity of ARFI elastography for the differentiation of thyroid nodules were collected. The quantitative measurement of ARFI elastography was evaluated by SWV (m/s). Meta-Disc Version 1.4 software was used to describe and calculate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and summary receiver operating characteristic curves. We analyzed a total of 13 studies, which included 1,854 thyroid nodules (including 1,339 benign nodules and 515 malignant nodules) from 1,641 patients. The summary sensitivity and specificity for differential diagnosis between benign and malignant thyroid nodules by SWV were 0.81 (95% confidence interval [CI]: 0.77-0.84) and 0.84 (95% CI: 0.81-0.86), respectively. The pooled positive and negative likelihood ratios were 5.21 (95% CI: 3.56-7.62) and 0.23 (95% CI: 0.17-0.32), respectively. The pooled diagnostic odds ratio was 27.53 (95% CI: 14.58-52.01), and the area under the summary receiver operating characteristic curve was 0.91 (Q* = 0.84). In conclusion, SWV measurement on ARFI elastography has high sensitivity and specificity for differential diagnosis between benign and malignant thyroid nodules and can be used in combination with conventional ultrasound. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Apparent diffusion coefficient on magnetic resonance imaging (MRI) in bladder cancer: relations with recurrence/progression risk

PubMed Central

Kikuchi, Ken; Shigihara, Takeshi; Hashimoto, Yuko; Miyajima, Masayuki; Haga, Nobuhiro; Kojima, Yoshiyuki; Shishido, Fumio

2017-01-01

Abstract AIMS: To evaluate the relationship between the apparent diffusion coefficient (ADC) value for bladder cancer and the recurrence/progression risk of post-transurethral resection (TUR). METHODS: Forty-one patients with initial and non-muscle-invasive bladder cancer underwent MRI from 2009 to 2012. Two radiologists measured ADC values. A pathologist calculated the recurrence/progression scores, and risk was classified based on the scores. Pearson’s correlation was used to analyze the correlations of ADC value with each score and with each risk group, and the optimal cut-off value was established based on receiver operating characteristic (ROC) curve analysis. Furthermore, the relationship between actual recurrence / progression of cases and ADC values was examined by Unpaird U test. RESULTS: There were significant correlations between ADC value and the recurrence score as well as the progression score (P<0.01, P<0.01, respectively). There were also significant correlations between ADC value and the recurrence risk group as well as progression risk group (P=0.042, P<0.01, respectively). The ADC cut-off value on ROC analysis was 1.365 (sensitivity 100%; specificity 97.4%) for the low and intermediate recurrence risk groups, 1.024 (sensitivity 47.4%; specificity 100%) for the intermediate and high recurrence risk groups, 1.252 (sensitivity 83.3%; specificity 81.3%) for the low and intermediate progression risk groups, and 0.955 (sensitivity 87.5%; specificity 63.2%) between the intermediate and high progression risk groups. The difference between the ADC values of the recurrence and nonrecurrence group in Unpaired t test was significant (P<0.05). CONCLUSION: ADC on MRI in bladder cancer could potentially be useful, non-invasive measurement for estimating the risks of recurrence and progression. PMID:28680010

Accuracy of early detection of colorectal tumours by stool methylation markers: A meta-analysis

PubMed Central

Zhang, Hu; Qi, Jian; Wu, Ya-Qiong; Zhang, Ping; Jiang, Jun; Wang, Qi-Xian; Zhu, You-Qing

2014-01-01

AIM: To evaluate the accuracy of methylation of genes in stool samples for diagnosing colorectal tumours. METHODS: Electronic databases including PubMed, Web of Science, Chinese Journals Full-Text Database and Wanfang Journals Full-Text Database were searched to find relevant original articles about methylated genes to be used in diagnosing colorectal tumours. A quality assessment of diagnostic accuracy studies tool (QADAS) was used to evaluate the quality of the included articles, and the Meta-disc 1.4 and SPSS 13.0 software programs were used for data analysis. RESULTS: Thirty-seven articles met the inclusion criteria, and 4484 patients were included. The sensitivity and specificity for the detection of colorectal cancer (CRC) were 73% (95%CI: 71%-75%) and 92% (95%CI: 90%-93%), respectively. For adenoma, the sensitivity and specificity were 51% (95%CI: 47%-54%) and 92% (95%CI: 90%-93%), respectively. Pooled diagnostic performance of SFRP2 methylation for CRC provided the following results: the sensitivity was 79% (95%CI: 75%-82%), the specificity was 93% (95%CI: 90%-96%), the diagnostic OR was 47.57 (95%CI: 20.08-112.72), the area under the curve was 0.9565. Additionally, the results of accuracy of SFRP2 methylation for detecting colorectal adenomas were as follows: sensitivity was 43% (95%CI: 38%-49%), specificity was 94% (95%CI: 91%-97%), the diagnostic OR was 11.06 (95%CI: 5.77-21.18), and the area under the curve was 0.9563. CONCLUSION: Stool-based DNA testing may be useful for noninvasively diagnosing colorectal tumours and SFRP2 methylation is a promising marker that has great potential in early CRC diagnosis. PMID:25320544

Prediction error and somatosensory insula activation in women recovered from anorexia nervosa

PubMed Central

Frank, Guido K.W.; Collier, Shaleise; Shott, Megan E.; O’Reilly, Randall C.

2016-01-01

Background Previous research in patients with anorexia nervosa showed heightened brain response during a taste reward conditioning task and heightened sensitivity to rewarding and punishing stimuli. Here we tested the hypothesis that individuals recovered from anorexia nervosa would also experience greater brain activation during this task as well as higher sensitivity to salient stimuli than controls. Methods Women recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm. Results Twenty-four women recovered from anorexia nervosa (mean age 30.3 ± 8.1 yr) and 24 control women (mean age 27.4 ± 6.3 yr) took part in this study. The recovered anorexia nervosa group showed greater left posterior insula activation for the prediction error model analysis than the control group (family-wise error– and small volume–corrected p < 0.05). A group × condition analysis found greater posterior insula response in women recovered from anorexia nervosa than controls for unexpected stimulus omission, but not for unexpected receipt. Sensitivity to punishment was elevated in women recovered from anorexia nervosa. Limitations This was a cross-sectional study, and the sample size was modest. Conclusion Anorexia nervosa after recovery is associated with heightened prediction error–related brain response in the posterior insula as well as greater response to unexpected reward stimulus omission. This finding, together with behaviourally increased sensitivity to punishment, could indicate that individuals recovered from anorexia nervosa are particularly responsive to punishment. The posterior insula processes somatosensory stimuli, including unexpected bodily states, and greater response could indicate altered perception or integration of unexpected or maybe unwanted bodily feelings. Whether those findings develop during the ill state or whether they are biological traits requires further study. PMID:26836623

Sensitizing events as trigger for discursive renewal and institutional change in Flanders’ environmental health approach, 1970s-1990s

PubMed Central

2013-01-01

Background Sensitizing events may trigger and stimulate discursive renewal. From a discursive institutional perspective, changing discourses are the driving force behind the institutional dynamics of policy domains. Theoretically informed by discursive institutionalism, this article assesses the impact of a series of four sensitizing events that triggered serious environmental health concerns in Flanders between the 1970s till the 1990s, and led onto the gradual institutionalization of a Flemish environmental health arrangement. Methods The Policy Arrangement Approach is used as the analytical framework to structure the empirical results of the historical analysis based on document analysis and in-depth interviews. Results Until the 1990s, environmental health was characterized as an ad hoc policy field in Flanders, where agenda setting was based on sensitizing events – also referred to as incident-driven. Each of these events contributed to a gradual rethinking of the epistemological discourses about environmental health risks and uncertainties. These new discourses were the driving forces behind institutional dynamics as they gradually resulted in an increased need for: 1) long-term, policy-oriented, interdisciplinary environmental health research; 2) policy coordination and integration between the environmental and public health policy fields; and 3) new forms of science-policy interactions based on mutual learning. These changes are desirable in order to detect environmental health problems as fast as possible, to react immediately and communicate appropriately. Conclusions The series of four events that triggered serious environmental health concerns in Flanders provided the opportunity to rethink and re-organize the current affairs concerning environmental health and gradually resulted into the institutionalization of a Flemish environmental health arrangement. PMID:23758822

Proteomic Biomarkers Apolipoprotein A1, Truncated Transthyretin and Connective Tissue Activating Protein III Enhance the Sensitivity of CA125 for Detecting Early Stage Epithelial Ovarian Cancer

PubMed Central

Clarke, Charlotte H.; Yip, Christine; Badgwell, Donna; Fung, Eric T.; Coombes, Kevin R.; Zhang, Zhen; Lu, Karen H.; Bast, Robert C.

2011-01-01

Objective The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers. Methods Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls. Results In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P= 0.015, McNemar's test). Conclusion Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer. PMID:21708402

The sensitivity of aquatic insects to divalent metals: a comparative analysis of laboratory and field data.

PubMed

Brix, Kevin V; DeForest, David K; Adams, William J

2011-09-15

Laboratory studies have traditionally indicated that aquatic insects are relatively insensitive to metals while field studies have suggested them to be among the most sensitive aquatic invertebrate taxa. We reviewed and synthesized available studies in the literature to critically assess why this discrepancy exists. Despite the intense effort to study the effects of metals on aquatic biota over the past several decades, we found studies specific to insects to still be relatively limited. In general, the discrepancy between laboratory and field studies continues with few efforts having been made to elucidate the ecological and physiological mechanisms that underlie the relative sensitivity (or insensitivity) of aquatic insects to metals. However, given the limited data available, it appears that aquatic insects are indeed relatively insensitive to acute metal exposures. In contrast, we suggest that some aquatic insect taxa may be quite sensitive to chronic metal exposure and in some cases may not be protected by existing water quality criteria for metals. The discrepancy between laboratory and field studies with respect to chronic sensitivity appears to largely be driven by the relatively short exposure periods in laboratory studies as compared to field studies. It also appears that, in some cases, the sensitivity of aquatic insects in field studies may be the result of direct effects on primary producers, which lead to indirect effects via the food chain on aquatic insects. Finally, available evidence suggests that diet is an important source of metal accumulation in insects, but to date there have been no conclusive studies evaluating whether dietary metal accumulation causes toxicity. There is a clear need for developing a more mechanistic understanding of aquatic insect sensitivity to metals in long-term laboratory and field studies. Copyright © 2011 Elsevier B.V. All rights reserved.

Obesity, Diabetes, and Associated Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union

PubMed Central

Legler, Juliette; Fletcher, Tony; Govarts, Eva; Porta, Miquel; Blumberg, Bruce; Heindel, Jerrold J.

2015-01-01

Context: Obesity and diabetes are epidemic in the European Union (EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity. Objective: The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU. Design: An expert panel evaluated evidence for probability of causation using weight-of-evidence characterization adapted from that applied by the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and burden of disease. Cost estimation as of 2010 utilized published cost estimates for childhood obesity, adult obesity, and adult diabetes. Setting, Patients and Participants, and Intervention: Cost estimation was performed from the societal perspective. Results: The panel identified a 40% to 69% probability of dichlorodiphenyldichloroethylene causing 1555 cases of overweight at age 10 (sensitivity analysis: 1555–5463) in 2010 with associated costs of €24.6 million (sensitivity analysis: €24.6–86.4 million). A 20% to 39% probability was identified for dichlorodiphenyldichloroethylene causing 28 200 cases of adult diabetes (sensitivity analysis: 28 200–56 400) with associated costs of €835 million (sensitivity analysis: €835 million–16.6 billion). The panel also identified a 40% to 69% probability of phthalate exposure causing 53 900 cases of obesity in older women and €15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with €607 million in associated costs. Prenatal bisphenol A exposure was identified to have a 20% to 69% probability of causing 42 400 cases of childhood obesity, with associated lifetime costs of €1.54 billion. Conclusions: EDC exposures in the EU contribute substantially to obesity and diabetes, with a moderate probability of >€18 billion costs per year. This is a conservative estimate; the results emphasize the need to control EDC exposures. PMID:25742518

The cost-effectiveness of smoking cessation support delivered by mobile phone text messaging: Txt2stop.

PubMed

Guerriero, Carla; Cairns, John; Roberts, Ian; Rodgers, Anthony; Whittaker, Robyn; Free, Caroline

2013-10-01

The txt2stop trial has shown that mobile-phone-based smoking cessation support doubles biochemically validated quitting at 6 months. This study examines the cost-effectiveness of smoking cessation support delivered by mobile phone text messaging. The lifetime incremental costs and benefits of adding text-based support to current practice are estimated from a UK NHS perspective using a Markov model. The cost-effectiveness was measured in terms of cost per quitter, cost per life year gained and cost per QALY gained. As in previous studies, smokers are assumed to face a higher risk of experiencing the following five diseases: lung cancer, stroke, myocardial infarction, chronic obstructive pulmonary disease, and coronary heart disease (i.e. the main fatal or disabling, but by no means the only, adverse effects of prolonged smoking). The treatment costs and health state values associated with these diseases were identified from the literature. The analysis was based on the age and gender distribution observed in the txt2stop trial. Effectiveness and cost parameters were varied in deterministic sensitivity analyses, and a probabilistic sensitivity analysis was also performed. The cost of text-based support per 1,000 enrolled smokers is £16,120, which, given an estimated 58 additional quitters at 6 months, equates to £278 per quitter. However, when the future NHS costs saved (as a result of reduced smoking) are included, text-based support would be cost saving. It is estimated that 18 LYs are gained per 1,000 smokers (0.3 LYs per quitter) receiving text-based support, and 29 QALYs are gained (0.5 QALYs per quitter). The deterministic sensitivity analysis indicated that changes in individual model parameters did not alter the conclusion that this is a cost-effective intervention. Similarly, the probabilistic sensitivity analysis indicated a >90 % chance that the intervention will be cost saving. This study shows that under a wide variety of conditions, personalised smoking cessation advice and support by mobile phone message is both beneficial for health and cost saving to a health system.

Situational Discrimination in Repressor-type and Sensitizer-type Approval Seekers and the Birth Order by Subject Sex Interaction

ERIC Educational Resources Information Center

Becker, Gilbert

1970-01-01

Five experiments are reported. One conclusion in that repressor-type high need-for-approval subjects made the discrimination and permitted less favorable self-description, but sensitizer-type high need-for-approval subjects did not. (DB)

Food Sensitivities: Education and Intervention Strategies for the Counselor.

ERIC Educational Resources Information Center

Lawson, David M.

1987-01-01

Discusses the etiology of food sensitivities and their relationship to the counseling profession and presents practical counseling strategies for intervention and remediation. Includes sections on the client predicament, stimulatory and withdrawal symptoms, identifying food addiction, psychosocial factors, a case study, and a conclusion.…

Imaging modalities for characterising focal pancreatic lesions.

PubMed

Best, Lawrence Mj; Rawji, Vishal; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-17

Increasing numbers of incidental pancreatic lesions are being detected each year. Accurate characterisation of pancreatic lesions into benign, precancerous, and cancer masses is crucial in deciding whether to use treatment or surveillance. Distinguishing benign lesions from precancerous and cancerous lesions can prevent patients from undergoing unnecessary major surgery. Despite the importance of accurately classifying pancreatic lesions, there is no clear algorithm for management of focal pancreatic lesions. To determine and compare the diagnostic accuracy of various imaging modalities in detecting cancerous and precancerous lesions in people with focal pancreatic lesions. We searched the CENTRAL, MEDLINE, Embase, and Science Citation Index until 19 July 2016. We searched the references of included studies to identify further studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We planned to include studies reporting cross-sectional information on the index test (CT (computed tomography), MRI (magnetic resonance imaging), PET (positron emission tomography), EUS (endoscopic ultrasound), EUS elastography, and EUS-guided biopsy or FNA (fine-needle aspiration)) and reference standard (confirmation of the nature of the lesion was obtained by histopathological examination of the entire lesion by surgical excision, or histopathological examination for confirmation of precancer or cancer by biopsy and clinical follow-up of at least six months in people with negative index tests) in people with pancreatic lesions irrespective of language or publication status or whether the data were collected prospectively or retrospectively. Two review authors independently searched the references to identify relevant studies and extracted the data. We planned to use the bivariate analysis to calculate the summary sensitivity and specificity with their 95% confidence intervals and the hierarchical summary receiver operating characteristic (HSROC) to compare the tests and assess heterogeneity, but used simpler models (such as univariate random-effects model and univariate fixed-effect model) for combining studies when appropriate because of the sparse data. We were unable to compare the diagnostic performance of the tests using formal statistical methods because of sparse data. We included 54 studies involving a total of 3,196 participants evaluating the diagnostic accuracy of various index tests. In these 54 studies, eight different target conditions were identified with different final diagnoses constituting benign, precancerous, and cancerous lesions. None of the studies was of high methodological quality. None of the comparisons in which single studies were included was of sufficiently high methodological quality to warrant highlighting of the results. For differentiation of cancerous lesions from benign or precancerous lesions, we identified only one study per index test. The second analysis, of studies differentiating cancerous versus benign lesions, provided three tests in which meta-analysis could be performed. The sensitivities and specificities for diagnosing cancer were: EUS-FNA: sensitivity 0.79 (95% confidence interval (CI) 0.07 to 1.00), specificity 1.00 (95% CI 0.91 to 1.00); EUS: sensitivity 0.95 (95% CI 0.84 to 0.99), specificity 0.53 (95% CI 0.31 to 0.74); PET: sensitivity 0.92 (95% CI 0.80 to 0.97), specificity 0.65 (95% CI 0.39 to 0.84). The third analysis, of studies differentiating precancerous or cancerous lesions from benign lesions, only provided one test (EUS-FNA) in which meta-analysis was performed. EUS-FNA had moderate sensitivity for diagnosing precancerous or cancerous lesions (sensitivity 0.73 (95% CI 0.01 to 1.00) and high specificity 0.94 (95% CI 0.15 to 1.00), the extremely wide confidence intervals reflecting the heterogeneity between the studies). The fourth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (dysplasia) provided three tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing invasive carcinoma were: CT: sensitivity 0.72 (95% CI 0.50 to 0.87), specificity 0.92 (95% CI 0.81 to 0.97); EUS: sensitivity 0.78 (95% CI 0.44 to 0.94), specificity 0.91 (95% CI 0.61 to 0.98); EUS-FNA: sensitivity 0.66 (95% CI 0.03 to 0.99), specificity 0.92 (95% CI 0.73 to 0.98). The fifth analysis, of studies differentiating cancerous (high-grade dysplasia or invasive carcinoma) versus precancerous (low- or intermediate-grade dysplasia) provided six tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing cancer (high-grade dysplasia or invasive carcinoma) were: CT: sensitivity 0.87 (95% CI 0.00 to 1.00), specificity 0.96 (95% CI 0.00 to 1.00); EUS: sensitivity 0.86 (95% CI 0.74 to 0.92), specificity 0.91 (95% CI 0.83 to 0.96); EUS-FNA: sensitivity 0.47 (95% CI 0.24 to 0.70), specificity 0.91 (95% CI 0.32 to 1.00); EUS-FNA carcinoembryonic antigen 200 ng/mL: sensitivity 0.58 (95% CI 0.28 to 0.83), specificity 0.51 (95% CI 0.19 to 0.81); MRI: sensitivity 0.69 (95% CI 0.44 to 0.86), specificity 0.93 (95% CI 0.43 to 1.00); PET: sensitivity 0.90 (95% CI 0.79 to 0.96), specificity 0.94 (95% CI 0.81 to 0.99). The sixth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (low-grade dysplasia) provided no tests in which meta-analysis was performed. The seventh analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) provided two tests in which meta-analysis was performed. The sensitivity and specificity for diagnosing cancer were: CT: sensitivity 0.83 (95% CI 0.68 to 0.92), specificity 0.83 (95% CI 0.64 to 0.93) and MRI: sensitivity 0.80 (95% CI 0.58 to 0.92), specificity 0.81 (95% CI 0.53 to 0.95), respectively. The eighth analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) or benign lesions provided no test in which meta-analysis was performed.There were no major alterations in the subgroup analysis of cystic pancreatic focal lesions (42 studies; 2086 participants). None of the included studies evaluated EUS elastography or sequential testing. We were unable to arrive at any firm conclusions because of the differences in the way that study authors classified focal pancreatic lesions into cancerous, precancerous, and benign lesions; the inclusion of few studies with wide confidence intervals for each comparison; poor methodological quality in the studies; and heterogeneity in the estimates within comparisons.

Hypnotic Hypersensitivity to Volatile Anesthetics and Dexmedetomidine in Dopamine β-Hydroxylase Knockout Mice

PubMed Central

Hu, Frances Y.; Hanna, George M.; Han, Wei; Mardini, Feras; Thomas, Steven A.; Wyner, Abraham J.; Kelz, Max B.

2012-01-01

BACKGROUND Multiple lines of evidence suggest that the adrenergic system can modulate sensitivity to anesthetic-induced immobility and anesthetic-induced hypnosis as well. However, several considerations prevent the conclusion that the endogenous adrenergic ligands norepinephrine and epinephrine alter anesthetic sensitivity. METHODS Using dopamine β-hydroxylase (Dbh−/−) mice genetically engineered to lack the adrenergic ligands and their siblings with normal adrenergic levels, we test the contribution of the adrenergic ligands upon volatile anesthetic induction and emergence. Moreover, we investigate the effects of intravenous dexmedetomidine in adrenergic-deficient mice and their siblings using both righting reflex and processed electroencephalographic measures of anesthetic hypnosis. RESULTS We demonstrate that the loss of norepinephrine and epinephrine and not other neuromodulators copackaged in adrenergic neurons is sufficient to cause hypersensitivity to induction of volatile anesthesia. However, the most profound effect of adrenergic deficiency is retarding emergence from anesthesia, which takes two to three times as long in Dbh−/− mice for sevoflurane, isoflurane, and halothane. Having shown that Dbh−/− mice are hypersensitive to volatile anesthetics, we further demonstrate that their hypnotic hypersensitivity persists at multiple doses of dexmedetomidine. Dbh−/− mice exhibit up to 67% shorter latencies to loss of righting reflex and up to 545% longer durations of dexmedetomidine-induced general anesthesia. Central rescue of adrenergic signaling restores control-like dexmedetomidine sensitivity. A novel continuous electroencephalographic analysis illustrates that the longer duration of dexmedetomidine-induced hypnosis is not due to a motor confound, but occurs because of impaired anesthetic emergence. CONCLUSIONS Adrenergic signaling is essential for normal emergence from general anesthesia. Dexmedetomidine-induced general anesthesia does not depend upon inhibition of adrenergic neurotransmission. PMID:23042227

Bayes Factors Unmask Highly Variable Information Content, Bias, and Extreme Influence in Phylogenomic Analyses.

PubMed

Brown, Jeremy M; Thomson, Robert C

2017-07-01

As the application of genomic data in phylogenetics has become routine, a number of cases have arisen where alternative data sets strongly support conflicting conclusions. This sensitivity to analytical decisions has prevented firm resolution of some of the most recalcitrant nodes in the tree of life. To better understand the causes and nature of this sensitivity, we analyzed several phylogenomic data sets using an alternative measure of topological support (the Bayes factor) that both demonstrates and averts several limitations of more frequently employed support measures (such as Markov chain Monte Carlo estimates of posterior probabilities). Bayes factors reveal important, previously hidden, differences across six "phylogenomic" data sets collected to resolve the phylogenetic placement of turtles within Amniota. These data sets vary substantially in their support for well-established amniote relationships, particularly in the proportion of genes that contain extreme amounts of information as well as the proportion that strongly reject these uncontroversial relationships. All six data sets contain little information to resolve the phylogenetic placement of turtles relative to other amniotes. Bayes factors also reveal that a very small number of extremely influential genes (less than 1% of genes in a data set) can fundamentally change significant phylogenetic conclusions. In one example, these genes are shown to contain previously unrecognized paralogs. This study demonstrates both that the resolution of difficult phylogenomic problems remains sensitive to seemingly minor analysis details and that Bayes factors are a valuable tool for identifying and solving these challenges. © The Author(s) 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Using Dynamic Sensitivity Analysis to Assess Testability

NASA Technical Reports Server (NTRS)

Voas, Jeffrey; Morell, Larry; Miller, Keith

1990-01-01

This paper discusses sensitivity analysis and its relationship to random black box testing. Sensitivity analysis estimates the impact that a programming fault at a particular location would have on the program's input/output behavior. Locations that are relatively \\"insensitive" to faults can render random black box testing unlikely to uncover programming faults. Therefore, sensitivity analysis gives new insight when interpreting random black box testing results. Although sensitivity analysis is computationally intensive, it requires no oracle and no human intervention.

Differential sensitivity of polyhydroxyalkanoate producing bacteria to fermentation inhibitors and comparison of polyhydroxybutyrate production from Burkholderia cepacia and Pseudomonas pseudoflava

PubMed Central

2013-01-01

Background The aim of this study is determine the relative sensitivity of a panel of seven polyhydroxyalkanoate producing bacteria to a panel of seven lignocellulosic-derived fermentation inhibitors representing aliphatic acids, furans and phenolics. A further aim was to measure the polyhydroxybutyrate production of select organisms on lignocellulosic-derived monosaccharides arabinose, xylose, glucose and mannose. Findings We examined the sensitivity of seven polyhydroxyalkanoate producing bacteria: Azohydromonas lata, Bacillus megaterium, Bacillus cereus, Burkholderia cepacia, Pseudomonas olevorans, Pseudomonas pseudoflava and Ralstonia eutropha, against seven fermentation inhibitors produced by the saccharification of lignocellulose: acetic acid, levulinic acid, coumaric acid, ferulic acid, syringaldehyde, furfural, and hyroxymethyfurfural. There was significant variation in the sensitivity of these microbes to representative phenolics ranging from 0.25-1.5 g/L coumaric and ferulic acid and between 0.5-6.0 g/L syringaldehyde. Inhibition ranged from 0.37-4 g/L and 0.75-6 g/L with acetic acid and levulinic acid, respectively. B. cepacia and P. pseudoflava were selected for further analysis of polyhydroxyalkanoate production. Conclusions We find significant differences in sensitivity to the fermentation inhibitors tested and find these variations to be over a relevant concentration range given the concentrations of inhibitors typically found in lignocellulosic hydrolysates. Of the seven bacteria tested, B. cepacia demonstrated the greatest inhibitor tolerance. Similarly, of two organisms examined for polyhydroxybutyrate production, B. cepacia was notably more efficient when fermenting pentose substrates. PMID:23734728

Sensitivity and Specificity of Fenyö-Lindberg and Teicher Scores in the Diagnosis of Acute Appendicitis in Women

PubMed

Madžar, Zrinko; Kopljar, Mario; Madžar, Tomislav; Mesić, Marko; Mužina Mišić, Dubravka; Čiček, Slaven; Zovak, Mario

2016-12-01

The aim of the study was to assess diagnostic accuracy (sensitivity and specificity) of Fenyö-Lindberg and Teicher scores for distinguishing patients that need immediate surgical treatment from the others, in a female population from an urban setting. The study prospectively included 130 female patients admitted to the emergency department with abdominal pain indicating acute appendicitis. The scores and parameters of validity were calculated and compared to definitive diagnosis. For Fenyö-Lindberg score of -17 or less, 84.5% sensitivity, 55.6% specificity, 87.9% positive predictive value (PPV) and 48.4% negative predictive value (NPV) were recorded. For cut-off value greater or equal to -2, there was 59.2% sensitivity, 77.8% specificity, 91% PPV and 33.3% NPV. The Receiver Operating Characteristic (ROC) curve analysis of Fenyö-Lindberg score showed that the best single cut-off value for discriminating acute appendicitis in the study population was -15. For Teicher score, values greater than -3 yielded 89.3% sensitivity and 22.2% specificity, 81.4% PPV and 35.3% NPV. In conclusion, Fenyö-Lindberg score could be used as an additional tool to exclude appendicitis and avoid unnecessary appendectomies. Teicher score may help in recognizing patients with appendicitis. None of the two scores can indicate or decline appendectomy in all cases. Scoring systems may be useful for pointing to important clinical signs and symptoms in specific subpopulations.

Three-dimensional texture analysis of contrast enhanced CT images for treatment response assessment in Hodgkin lymphoma: Comparison with F-18-FDG PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knogler, Thomas; El-Rabadi, Karem; Weber, Michael

2014-12-15

Purpose: To determine the diagnostic performance of three-dimensional (3D) texture analysis (TA) of contrast-enhanced computed tomography (CE-CT) images for treatment response assessment in patients with Hodgkin lymphoma (HL), compared with F-18-fludeoxyglucose (FDG) positron emission tomography/CT. Methods: 3D TA of 48 lymph nodes in 29 patients was performed on venous-phase CE-CT images before and after chemotherapy. All lymph nodes showed pathologically elevated FDG uptake at baseline. A stepwise logistic regression with forward selection was performed to identify classic CT parameters and texture features (TF) that enable the separation of complete response (CR) and persistent disease. Results: The TF fraction of imagemore » in runs, calculated for the 45° direction, was able to correctly identify CR with an accuracy of 75%, a sensitivity of 79.3%, and a specificity of 68.4%. Classical CT features achieved an accuracy of 75%, a sensitivity of 86.2%, and a specificity of 57.9%, whereas the combination of TF and CT imaging achieved an accuracy of 83.3%, a sensitivity of 86.2%, and a specificity of 78.9%. Conclusions: 3D TA of CE-CT images is potentially useful to identify nodal residual disease in HL, with a performance comparable to that of classical CT parameters. Best results are achieved when TA and classical CT features are combined.« less

Long Non-Coding RNA (lncRNA) Urothelial Carcinoma-Associated 1 (UCA1) Enhances Tamoxifen Resistance in Breast Cancer Cells via Inhibiting mTOR Signaling Pathway.

PubMed

Wu, Chihua; Luo, Jing

2016-10-21

BACKGROUND Long non-coding RNA (lncRNA) UCA1 is an oncogene in breast cancer. The purpose of this study was to investigate the role of UCA1 in tamoxifen resistance of estrogen receptor positive breast cancer cells. MATERIAL AND METHODS Tamoxifen sensitive MCF-7 cells were transfected for UCA1 overexpression, while tamoxifen resistant LCC2 and LCC9 cells were transfected with UCA siRNA for UCA1 knockdown. qRT-PCR was performed to analyze UCA1 expression. CCK-8 assay, immunofluorescence staining of cleaved caspase-9, and flow cytometric analysis of Annexin V/PI staining were used to assess tamoxifen sensitivity. Western blot analysis was performed to detect p-AKT and p-mTOR expression. RESULTS LncRNA UCA1 was significantly upregulated in tamoxifen resistant breast cancer cells compared to tamoxifen sensitive cells. LCC2 and LCC9 cells transfected with UCA1 siRNA had significantly higher ratio of apoptosis after tamoxifen treatment. UCA1 siRNA significantly decreased the protein levels of p-AKT and p-mTOR in LCC2 and LCC9 cells. Enforced UCA1 expression substantially reduced tamoxifen induced apoptosis in MCF-7 cells, while rapamycin treatment abrogated the protective effect of UCA1. CONCLUSIONS UCA1 upregulation was associated with tamoxifen resistance in breast cancer. Mechanistically, UCA1 confers tamoxifen resistance to breast cancer cells partly via activating the mTOR signaling pathway.

High-resolution Behavioral Economic Analysis of Cigarette Demand to Inform Tax Policy

PubMed Central

MacKillop, James; Few, Lauren R.; Murphy, James G.; Wier, Lauren M.; Acker, John; Murphy, Cara; Stojek, Monika; Carrigan, Maureen; Chaloupka, Frank

2012-01-01

Aims Novel methods in behavioral economics permit the systematic assessment of the relationship between cigarette consumption and price. Toward informing tax policy, the goals of this study were to conduct a high-resolution analysis of cigarette demand in a large sample of adult smokers and to use the data to estimate the effects of tax increases in ten U.S. States. Design In-person descriptive survey assessment. Setting Academic departments at three universities. Participants Adult daily smokers (i.e., 5+ cigarettes/day; 18+ years old; ≥8th grade education); N = 1056. Measurements Estimated cigarette demand, demographics, expired carbon monoxide. Findings The cigarette demand curve exhibited highly variable levels of price sensitivity, especially in the form of ‘left-digit effects’ (i.e., very high price sensitivity as pack prices transitioned from one whole number to the next; e.g., $5.80-$6/pack). A $1 tax increase in the ten states was projected to reduce the economic burden of smoking by an average of $531M (range: $93.6M-$976.5M) and increase gross tax revenue by an average of 162% (range: 114%- 247%). Conclusions Tobacco price sensitivity is nonlinear across the demand curve and in particular for pack-level left-digit price transitions. Tax increases in U.S. states with similar price and tax rates to the sample are projected to result in substantial decreases in smoking-related costs and substantial increases in tax revenues. PMID:22845784

Lithium or Valproate Adjunctive Therapy to Second-generation Antipsychotics and Metabolic Variables in Patients With Schizophrenia or Schizoaffective Disorder

PubMed Central

VINCENZI, BRENDA; GREENE, CLAIRE M.; ULLOA, MELISSA; PARNAROUSKIS, LINDSEY; JACKSON, JOHN W.; HENDERSON, DAVID C.

2017-01-01

Objective People with schizophrenia are at greater risk for cardiovascular disease and their overallmortality rate is elevated compared to the general population. The metabolic side effects of antipsychotic medications have been widely studied; however, the effect of adding conventional mood stabilizers, such as lithium and valproate, to antipsychotic medication has not been assessed in terms of metabolic risk. The primary purpose of this secondary analysis was to examine whether treatment with lithium or valproate in addition to a second-generation antipsychotic is associated with poorer metabolic outcomes than treatment with a second-generation antipsychotic without lithium or depakote. Methods Baseline data from 3 studies, which included measurement of body mass index, waist circumference, fasting glucose, insulin, homeostatic model assessment of insulin resistance, insulin sensitivity index, glucose utilization, and acute insulin response to glucose, were included in the analysis. Results No differences were found between those taking lithium or valproate and those who were not in terms of fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance. Insulin sensitivity was lower among participants taking lithium or valproate. Participants taking lithium or valproate had a higher body mass index than those not taking conventional mood stabilizers, although the difference did not reach statistical significance. Conclusions These cross-sectional findings suggest it may be beneficial to monitor insulin sensitivity and body mass index in patients taking lithium or valproate in combination with a second-generation antipsychotic. PMID:27123797

Effect of soil moisture on the temperature sensitivity of Northern soils

NASA Astrophysics Data System (ADS)

Minions, C.; Natali, S.; Ludwig, S.; Risk, D.; Macintyre, C. M.

2017-12-01

Arctic and boreal ecosystems are vast reservoirs of carbon and are particularly sensitive to climate warming. Changes in the temperature and precipitation regimes of these regions could significantly alter soil respiration rates, impacting atmospheric concentrations and affecting climate change feedbacks. Many incubation studies have shown that both temperature and soil moisture are important environmental drivers of soil respiration; this relationship, however, has rarely been demonstrated with in situ data. Here we present the results of a study at six field sites in Alaska from 2016 to 2017. Low-power automated soil gas systems were used to measure soil surface CO2 flux from three forced diffusion chambers and soil profile concentrations from three soil depth chambers at hourly intervals at each site. HOBO Onset dataloggers were used to monitor soil moisture and temperature profiles. Temperature sensitivity (Q10) was determined at each site using inversion analysis applied over different time periods. With highly resolved data sets, we were able to observe the changes in soil respiration in response to changes in temperature and soil moisture. Through regression analysis we confirmed that temperature is the primary driver in soil respiration, but soil moisture becomes dominant beyond a certain threshold, suppressing CO2 flux in soils with high moisture content. This field study supports the conclusions made from previous soil incubation studies and provides valuable insights into the impact of both temperature and soil moisture changes on soil respiration.

Cost of Behavioral Interventions Utilizing Electronic Drug Monitoring for Antiretroviral Therapy Adherence

PubMed Central

Rasu, Rafia S.; Malewski, David F.; Banderas, Julie W.; Thomson, Domonique Malomo; Goggin, Kathy

2013-01-01

Objective To provide data on the actual costs associated with behavioral ART adherence interventions and electronic drug monitoring used in a clinical trial to inform their implementation in future studies and real-world practice. Methods Direct and time costs were calculated from a multi-site three-arm randomized controlled ART adherence trial. HIV positive participants (n = 204) were randomized to standard care (SC), enhanced counseling (EC), or EC and modified directly observed therapy (mDOT) interventions. Electronic drug monitoring (EDM) was used. Costs were calculated for various components of the 24-week adherence intervention. This economic evaluation was conducted from the perspective of an agency that may wish to implement these strategies. Sensitivity analyses were conducted to examine costs and savings associated with different scenarios. Results Total direct costs were $126,068 ($618/patient). Initial time costs were $53,590 ($262/patient). Base cost of labor was $0.36/minute. EC costs for 134 patients were $18,427 ($137/patient) and mDOT for 64 patients cost $18,638 ($291/patient). Total per patient costs were: SC=$880, EC=$1,018, EC/mDOT=$1,309. Removing driving costs evidenced the most variable impact on savings between the three study arms. The tornado diagram (sensitivity analysis) showed a graphical representation of how each sensitivity assumption reduced costs compared to each other and the resulting comparative costs for each group. Conclusion This novel economic analysis provides valuable cost information to guide treatment implementation and research design decisions. PMID:23337364

Everyday Cognition in Prodromal Huntington Disease

PubMed Central

Williams, Janet K.; Kim, Ji-In; Downing, Nancy; Farias, Sarah; Harrington, Deborah L.; Long, Jeffrey D.; Mills, James A.; Paulsen, Jane S.

2014-01-01

Objective Assessment of daily functions affected by cognitive loss in prodromal Huntington disease (HD) is necessary in practice and clinical trials. We evaluated baseline and longitudinal sensitivity of the Everyday Cognition (ECog) scales in prodromal HD and compared self- and companion-ratings. Method Everyday cognition was self-assessed by 850 participants with prodromal HD and 768 companions. We examined internal structure using confirmatory factor analysis (CFA) on baseline data. For longitudinal analysis, we stratified participants into Low, Medium, and High disease progression groups. We examined ECog scores for group differences and participant-and-companion differences using linear mixed effects regression (LMER). Comparison with the Total Functional Capacity (TFC) scale was made. Results CFA revealed good fit of a 5-factor model having a global factor (total score), and sub factors (subscales) of memory, language, visuospatial perception, and executive function. At study entry, participants and companions in the Medium and High groups reported significantly worsened everyday cognition as well as significant functional decline over time. Losses became more pronounced and participant and companion ratings diverged as individuals progressed. TFC showed significant functional loss over time in the High group but not in the Medium group. Conclusions Disease progression is associated with reduced self- and companion-reported everyday cognition in prodromal HD participants who are less than 13 years to estimated motor onset. Our findings suggest companion ratings are more sensitive than participants’ for detecting longitudinal change in daily cognitive function. ECog appears more sensitive to specific functional changes in the prodrome of HD than the TFC. PMID:25000321

Comparison of linear–stochastic and nonlinear–deterministic algorithms in the analysis of 15-minute clinical ECGs to predict risk of arrhythmic death

PubMed Central

Skinner, James E; Meyer, Michael; Nester, Brian A; Geary, Una; Taggart, Pamela; Mangione, Antoinette; Ramalanjaona, George; Terregino, Carol; Dalsey, William C

2009-01-01

Objective: Comparative algorithmic evaluation of heartbeat series in low-to-high risk cardiac patients for the prospective prediction of risk of arrhythmic death (AD). Background: Heartbeat variation reflects cardiac autonomic function and risk of AD. Indices based on linear stochastic models are independent risk factors for AD in post-myocardial infarction (post-MI) cohorts. Indices based on nonlinear deterministic models have superior predictability in retrospective data. Methods: Patients were enrolled (N = 397) in three emergency departments upon presenting with chest pain and were determined to be at low-to-high risk of acute MI (>7%). Brief ECGs were recorded (15 min) and R-R intervals assessed by three nonlinear algorithms (PD2i, DFA, and ApEn) and four conventional linear-stochastic measures (SDNN, MNN, 1/f-Slope, LF/HF). Out-of-hospital AD was determined by modified Hinkle–Thaler criteria. Results: All-cause mortality at one-year follow-up was 10.3%, with 7.7% adjudicated to be AD. The sensitivity and relative risk for predicting AD was highest at all time-points for the nonlinear PD2i algorithm (p ≤0.001). The sensitivity at 30 days was 100%, specificity 58%, and relative risk >100 (p ≤0.001); sensitivity at 360 days was 95%, specificity 58%, and relative risk >11.4 (p ≤0.001). Conclusions: Heartbeat analysis by the time-dependent nonlinear PD2i algorithm is comparatively the superior test. PMID:19707283

Cost-Utility Analysis: Sartorius Flap versus Negative Pressure Therapy for Infected Vascular Groin Graft Managment.

PubMed

Chatterjee, Abhishek; Macarios, David; Griffin, Leah; Kosowski, Tomasz; Pyfer, Bryan J; Offodile, Anaeze C; Driscoll, Daniel; Maddali, Sirish; Attwood, John

2015-11-01

Sartorius flap coverage and adjunctive negative pressure wound therapy (NPWT) have been described in managing infected vascular groin grafts with varying cost and clinical success. We performed a cost-utility analysis comparing sartorius flap with NPWT in managing an infected vascular groin graft. A literature review compiling outcomes for sartorius flap and NPWT interventions was conducted from peer-reviewed journals in MEDLINE (PubMed) and EMBASE. Utility scores were derived from expert opinion and used to estimate quality-adjusted life years (QALYs). Medicare current procedure terminology and diagnosis-related groups codes were used to assess the costs for successful graft salvage with the associated complications. Incremental cost-effectiveness was assessed at $50,000/QALY, and both univariate and probabilistic sensitivity analyses were conducted to assess robustness of the conclusions. Thirty-two studies were used pooling 384 patients (234 sartorius flaps and 150 NPWT). NPWT had better clinical outcomes (86.7% success rate, 0.9% minor complication rate, and 13.3% major complication rate) than sartorius flap (81.6% success rate, 8.0% minor complication rate, and 18.4% major complication rate). NPWT was less costly ($12,366 versus $23,516) and slightly more effective (12.06 QALY versus 12.05 QALY) compared with sartorius flap. Sensitivity analyses confirmed the robustness of the base case findings; NPWT was either cost-effective at $50,000/QALY or dominated sartorius flap in 81.6% of all probabilistic sensitivity analyses. In our cost-utility analysis, use of adjunctive NPWT, along with debridement and antibiotic treatment, for managing infected vascular groin graft wounds was found to be a more cost-effective option when compared with sartorius flaps.

Diagnostic Performance of Narrow Band Imaging for Laryngeal Cancer: A Systematic Review and Meta-analysis.

PubMed

Sun, Changling; Han, Xue; Li, Xiaoying; Zhang, Yayun; Du, Xiaodong

2017-04-01

Objective To evaluate the performance of narrow band imaging (NBI) for the diagnosis of laryngeal cancer and to compare the diagnostic value of NBI with that of white light endoscopy. Data Sources PubMed, Embase, Cochrane Library, and CNKI databases. Review Methods Data analyses were performed with Meta-DiSc. The updated Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality and potential bias. Publication bias was assessed with the Deeks's asymmetry test. The protocol used in this article has been published on PROSPERO and is in accordance with the PRISMA checklist. The registry number for this study is CRD42015025866. Results Six studies including 716 lesions were included in this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio for the NBI diagnosis of laryngeal cancer were 0.94 (95% confidence interval [95% CI]: 0.91-0.96), 0.89 (95% CI: 0.85-0.92), and 142.12 (95% CI: 46.42-435.15), respectively, and the area under receiver operating characteristics curve was 0.97. Among the 6 studies, 3 evaluated the diagnostic value of white light endoscopy, with a sensitivity of 0.81 (95% CI: 0.76-0.86), a specificity of 0.92 (95% CI: 0.88-0.95), and a diagnostic odds ratio of 33.82 (95% CI: 14.76-77.49). The evaluation of heterogeneity, calculated per the diagnostic odds ratio, gave an I 2 of 66%. No marked publication bias ( P = .84) was detected in this meta-analysis. Conclusion The sensitivity of NBI is superior to white light endoscopy, and the potential value of NBI needs to be validated in future studies.

Serum Mesothelin for Diagnosing Malignant Pleural Mesothelioma: An Individual Patient Data Meta-Analysis

PubMed Central

Hollevoet, Kevin; Reitsma, Johannes B.; Creaney, Jenette; Grigoriu, Bogdan D.; Robinson, Bruce W.; Scherpereel, Arnaud; Cristaudo, Alfonso; Pass, Harvey I.; Nackaerts, Kristiaan; Rodríguez Portal, José A.; Schneider, Joachim; Muley, Thomas; Di Serio, Francesca; Baas, Paul; Tomasetti, Marco; Rai, Alex J.; van Meerbeeck, Jan P.

2012-01-01

Purpose Mesothelin is currently considered the best available serum biomarker of malignant pleural mesothelioma. To examine the diagnostic accuracy and use of serum mesothelin in early diagnosis, we performed an individual patient data (IPD) meta-analysis. Methods The literature search identified 16 diagnostic studies of serum mesothelin, measured with the Mesomark enzyme-linked immunosorbent assay. IPD of 4,491 individuals were collected, including several control groups and 1,026 patients with malignant pleural mesothelioma. Mesothelin levels were standardized for between-study differences and age, after which the diagnostic accuracy and the factors affecting it were examined with receiver operating characteristic (ROC) regression analysis. Results At a common diagnostic threshold of 2.00 nmol/L, the sensitivities and specificities of mesothelin in the different studies ranged widely from 19% to 68% and 88% to 100%, respectively. This heterogeneity can be explained by differences in study population, because type of control group, mesothelioma stage, and histologic subtype significantly affected the diagnostic accuracy. The use of mesothelin in early diagnosis was evaluated by differentiating 217 patients with stage I or II epithelioid and biphasic mesothelioma from 1,612 symptomatic or high-risk controls. The resulting area under the ROC curve was 0.77 (95% CI, 0.73 to 0.81). At 95% specificity, mesothelin displayed a sensitivity of 32% (95% CI, 26% to 40%). Conclusion In patients suspected of having mesothelioma, a positive blood test for mesothelin at a high-specificity threshold is a strong incentive to urge further diagnostic steps. However, the poor sensitivity of mesothelin clearly limits its added value to early diagnosis and emphasizes the need for further biomarker research. PMID:22412141

Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

PubMed Central

Qian, Yushen; Pollom, Erqi L.; King, Martin T.; Dudley, Sara A.; Shaffer, Jenny L.; Chang, Daniel T.; Gibbs, Iris C.; Goldhaber-Fiebert, Jeremy D.; Horst, Kathleen C.

2016-01-01

Purpose The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) –overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab. Patient and Methods We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions. Results Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained. Conclusion THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States. PMID:26351332

Costs and Cost-Effectiveness of Training Traditional Birth Attendants to Reduce Neonatal Mortality in the Lufwanyama Neonatal Survival Study (LUNESP)

PubMed Central

Sabin, Lora L.; Knapp, Anna B.; MacLeod, William B.; Phiri-Mazala, Grace; Kasimba, Joshua; Hamer, Davidson H.; Gill, Christopher J.

2012-01-01

Background The Lufwanyama Neonatal Survival Project (“LUNESP”) was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs) to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness. Methods and Findings We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011–2020). In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs) averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as ‘conservative’ and ‘optimistic’ scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were $118,574 and $127,756, respectively, or $49,469 and $53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were $256,455 and $26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was $1,866, $591, and $3,024, and cost per DALY averted was $74, $24, and $120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation. Conclusions Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was ‘highly cost effective’. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care. PMID:22545117

Patient Perspectives on Gender Identity Data Collection in Electronic Health Records: An Analysis of Disclosure, Privacy, and Access to Care

PubMed Central

Thompson, Hale M.

2016-01-01

Abstract Purpose: In 2015, the Centers for Medicare and Medicaid Services ruled that health organizations comply with additional requirements for electronic health records (EHRs), known as “Meaningful Use,” and develop the capacity to collect gender identity data. Research has established effectiveness of a two-step gender identity question to collect these data. This study examines transgender patient perspectives on the use of a two-step question and experiences with privacy and sensitive disclosures in EHRs and healthcare settings. Methods: Four focus groups (N=30) were conducted in Chicago, Illinois in 2014–2015. Participants were asked to compare two intake forms—one with a two-step question and one with a single question—and discuss experiences with gender identity disclosure, privacy, and access to care. Narratives were transcribed verbatim to identify patterns and themes; the extended case method was used and grounded the data analysis process in the concept of intersectionality. Results: Participants expressed appreciation for improved reliability and competencies that the two-part question may afford. Narratives reveal concerns related to patient privacy, safety, and access because of the contexts in which these data are collected and transmitted. Virtually all participants described situations whereby sensitive gender identity information had been involuntarily disclosed, misinterpreted, or abused, and safety and care were compromised. Conclusion: Participants recognized the potential of the two-part question as a measurement and competency tool, but anticipated new privacy violations and involuntary disclosures. Narratives indicate that effects of sensitive disclosures may vary intersectionally, whereby white participants experienced lesser harms than their immigrant, HIV-positive, and black trans feminine counterparts. Discrimination and privacy violations may occur regardless of a two-part or one-part gender identity question, but increasing these sensitive disclosures within expanding EHR infrastructures may require a range of mechanisms that have flexibility across contexts to safeguard sensitive information and access to care. PMID:28861535

Patient Perspectives on Gender Identity Data Collection in Electronic Health Records: An Analysis of Disclosure, Privacy, and Access to Care.

PubMed

Thompson, Hale M

2016-01-01

Purpose: In 2015, the Centers for Medicare and Medicaid Services ruled that health organizations comply with additional requirements for electronic health records (EHRs), known as "Meaningful Use," and develop the capacity to collect gender identity data. Research has established effectiveness of a two-step gender identity question to collect these data. This study examines transgender patient perspectives on the use of a two-step question and experiences with privacy and sensitive disclosures in EHRs and healthcare settings. Methods: Four focus groups ( N =30) were conducted in Chicago, Illinois in 2014-2015. Participants were asked to compare two intake forms-one with a two-step question and one with a single question-and discuss experiences with gender identity disclosure, privacy, and access to care. Narratives were transcribed verbatim to identify patterns and themes; the extended case method was used and grounded the data analysis process in the concept of intersectionality. Results: Participants expressed appreciation for improved reliability and competencies that the two-part question may afford. Narratives reveal concerns related to patient privacy, safety, and access because of the contexts in which these data are collected and transmitted. Virtually all participants described situations whereby sensitive gender identity information had been involuntarily disclosed, misinterpreted, or abused, and safety and care were compromised. Conclusion: Participants recognized the potential of the two-part question as a measurement and competency tool, but anticipated new privacy violations and involuntary disclosures. Narratives indicate that effects of sensitive disclosures may vary intersectionally, whereby white participants experienced lesser harms than their immigrant, HIV-positive, and black trans feminine counterparts. Discrimination and privacy violations may occur regardless of a two-part or one-part gender identity question, but increasing these sensitive disclosures within expanding EHR infrastructures may require a range of mechanisms that have flexibility across contexts to safeguard sensitive information and access to care.

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center

PubMed Central

Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

2017-01-01

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21–1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung’s criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy. PMID:28968445

Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis

PubMed Central

Taylor-Phillips, Sian; Freeman, Karoline; Geppert, Julia; Agbebiyi, Adeola; Uthman, Olalekan A; Madan, Jason; Clarke, Angus; Quenby, Siobhan; Clarke, Aileen

2016-01-01

Objective To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy. Design Systematic review and meta-analysis of published studies. Data sources PubMed, Ovid Medline, Ovid Embase and the Cochrane Library published from 1997 to 9 February 2015, followed by weekly autoalerts until 1 April 2015. Eligibility criteria for selecting studies English language journal articles describing case–control studies with ≥15 trisomy cases or cohort studies with ≥50 pregnant women who had been given NIPT and a reference standard. Results 41, 37 and 30 studies of 2012 publications retrieved were included in the review for Down, Edwards and Patau syndromes. Quality appraisal identified high risk of bias in included studies, funnel plots showed evidence of publication bias. Pooled sensitivity was 99.3% (95% CI 98.9% to 99.6%) for Down, 97.4% (95.8% to 98.4%) for Edwards, and 97.4% (86.1% to 99.6%) for Patau syndrome. The pooled specificity was 99.9% (99.9% to 100%) for all three trisomies. In 100 000 pregnancies in the general obstetric population we would expect 417, 89 and 40 cases of Downs, Edwards and Patau syndromes to be detected by NIPT, with 94, 154 and 42 false positive results. Sensitivity was lower in twin than singleton pregnancies, reduced by 9% for Down, 28% for Edwards and 22% for Patau syndrome. Pooled sensitivity was also lower in the first trimester of pregnancy, in studies in the general obstetric population, and in cohort studies with consecutive enrolment. Conclusions NIPT using cell-free fetal DNA has very high sensitivity and specificity for Down syndrome, with slightly lower sensitivity for Edwards and Patau syndrome. However, it is not 100% accurate and should not be used as a final diagnosis for positive cases. Trial registration number CRD42014014947. PMID:26781507

SU-E-T-429: Uncertainties of Cell Surviving Fractions Derived From Tumor-Volume Variation Curves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chvetsov, A

2014-06-01

Purpose: To evaluate uncertainties of cell surviving fraction reconstructed from tumor-volume variation curves during radiation therapy using sensitivity analysis based on linear perturbation theory. Methods: The time dependent tumor-volume functions V(t) have been calculated using a twolevel cell population model which is based on the separation of entire tumor cell population in two subpopulations: oxygenated viable and lethally damaged cells. The sensitivity function is defined as S(t)=[δV(t)/V(t)]/[δx/x] where δV(t)/V(t) is the time dependent relative variation of the volume V(t) and δx/x is the relative variation of the radiobiological parameter x. The sensitivity analysis was performed using direct perturbation method wheremore » the radiobiological parameter x was changed by a certain error and the tumor-volume was recalculated to evaluate the corresponding tumor-volume variation. Tumor volume variation curves and sensitivity functions have been computed for different values of cell surviving fractions from the practically important interval S{sub 2}=0.1-0.7 using the two-level cell population model. Results: The sensitivity functions of tumor-volume to cell surviving fractions achieved a relatively large value of 2.7 for S{sub 2}=0.7 and then approached zero as S{sub 2} is approaching zero Assuming a systematic error of 3-4% we obtain that the relative error in S{sub 2} is less that 20% in the range S2=0.4-0.7. This Resultis important because the large values of S{sub 2} are associated with poor treatment outcome should be measured with relatively small uncertainties. For the very small values of S2<0.3, the relative error can be larger than 20%; however, the absolute error does not increase significantly. Conclusion: Tumor-volume curves measured during radiotherapy can be used for evaluation of cell surviving fractions usually observed in radiation therapy with conventional fractionation.« less

Analysis of different device-based intrathoracic impedance vectors for detection of heart failure events (from the Detect Fluid Early from Intrathoracic Impedance Monitoring study).

PubMed

Heist, E Kevin; Herre, John M; Binkley, Philip F; Van Bakel, Adrian B; Porterfield, James G; Porterfield, Linda M; Qu, Fujian; Turkel, Melanie; Pavri, Behzad B

2014-10-15

Detect Fluid Early from Intrathoracic Impedance Monitoring (DEFEAT-PE) is a prospective, multicenter study of multiple intrathoracic impedance vectors to detect pulmonary congestion (PC) events. Changes in intrathoracic impedance between the right ventricular (RV) coil and device can (RVcoil→Can) of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy ICDs (CRT-Ds) are used clinically for the detection of PC events, but other impedance vectors and algorithms have not been studied prospectively. An initial 75-patient study was used to derive optimal impedance vectors to detect PC events, with 2 vector combinations selected for prospective analysis in DEFEAT-PE (ICD vectors: RVring→Can + RVcoil→Can, detection threshold 13 days; CRT-D vectors: left ventricular ring→Can + RVcoil→Can, detection threshold 14 days). Impedance changes were considered true positive if detected <30 days before an adjudicated PC event. One hundred sixty-two patients were enrolled (80 with ICDs and 82 with CRT-Ds), all with ≥1 previous PC event. One hundred forty-four patients provided study data, with 214 patient-years of follow-up and 139 PC events. Sensitivity for PC events of the prespecified algorithms was as follows: ICD: sensitivity 32.3%, false-positive rate 1.28 per patient-year; CRT-D: sensitivity 32.4%, false-positive rate 1.66 per patient-year. An alternative algorithm, ultimately approved by the US Food and Drug Administration (RVring→Can + RVcoil→Can, detection threshold 14 days), resulted in (for all patients) sensitivity of 21.6% and a false-positive rate of 0.9 per patient-year. The CRT-D thoracic impedance vector algorithm selected in the derivation study was not superior to the ICD algorithm RVring→Can + RVcoil→Can when studied prospectively. In conclusion, to achieve an acceptably low false-positive rate, the intrathoracic impedance algorithms studied in DEFEAT-PE resulted in low sensitivity for the prediction of heart failure events. Copyright © 2014 Elsevier Inc. All rights reserved.

Spectrophotometry or visual inspection to most reliably detect xanthochromia in subarachnoid hemorrhage: systematic review.

PubMed

Chu, Kevin; Hann, Angus; Greenslade, Jaimi; Williams, Julian; Brown, Anthony

2014-09-01

We assess the sensitivity and specificity of xanthochromia as adjudicated by visual inspection and spectrophotometry at predicting the presence of cerebral aneurysm in patients with suspected subarachnoid hemorrhage who have a normal computed tomography (CT) head scan result. A systematic review was performed. MEDLINE and EMBASE databases were searched. Relevant studies with clinical data on the diagnostic accuracy of visual inspection or spectrophotometry were considered. Patients who had a normal CT head scan result followed by a lumbar puncture were included in this review. Sensitivities, specificities, and heterogeneity (I(2)) were calculated. Subgroup analyses were performed to explore reasons for the heterogeneity. There were major methodological limitations in the studies found. Twenty-two relevant articles were heterogeneous in regard to time to lumbar puncture, spectrophotometry methods, and follow-up of patients not undergoing cerebral angiography. Twelve of the 22 studies selected patients on the basis of a cerebral aneurysm or subarachnoid hemorrhage on imaging, or a positive lumbar puncture result. These studies were excluded from our initial analysis, which included only patients with clinically suspected subarachnoid hemorrhage. In this initial analysis, pooled estimates of sensitivity and specificity for spectrophotometry were 87% (95% confidence interval [CI] 71% to 96%; I(2)=26%) and 86% (95% CI 84% to 88%; I(2)=96%), respectively. For visual inspection, pooled sensitivity and specificity were 83% (95% CI 59% to 96%; I(2)=52%) and 96% (95% CI 93% to 97%; I(2)=76%), respectively. Sensitivity estimates are difficult to interpret without knowing time to lumbar puncture. The heterogeneity in the underlying studies, combined with significant overlap in pooled confidence limits, makes it impossible to provide a definite conclusion about the diagnostic accuracy of spectrophotometry versus visual inspection. Copyright © 2014 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Quantiferon-TB Gold Plus is a More Sensitive Screening Tool than Quantiferon-TB Gold In-Tube for Latent Tuberculosis Infection among Older Adults in Long-Term Care Facility.

PubMed

Chien, Jung-Yien; Chiang, Hsiu-Tzy; Lu, Min-Chi; Ko, Wen-Chien; Yu, Chong-Jen; Chen, Yen-Hsu; Hsueh, Po-Ren

2018-05-23

We investigated the prevalence of latent tuberculosis infection (LTBI) among the residents in seven long-term care facilities (LTCFs) located in different regions of Taiwan and compared the performance of two interferon-gamma release assays, i.e. QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold plus (QFT-Plus) for screening LTBI. We also assessed the diagnostic performance against a composite reference standard (subjects with persistent-positive, transient-positive, and negative results of QFTs during reproducibility analysis were classified as definite, possible and not LTBI, respectively). Two hundred and forty-four residents were enrolled and 229 subjects were included into analysis. The median age was 80 years (range, 60-102 years old) and 117 (51.1%) were male. Among them, 66 (28.8%) and 74 (32.3%) subjects had positive results of QFT-GIT and QFT-Plus, respectively, and 215 (93.9%) subjects showed agreement results. Using composite reference standard, 66 (28.8%), 11 (4.8%), and 152 (66.4%) were classified as definite, possible and not LTBI, respectively. For definite LTBI, the sensitivity, specificity, positive predictive value, and negative predictive value of QFT-GIT were 89.4%, 95.7%, 89.4%, and 95.7%, respectively, and those for QFT-Plus were 100.0%, 95.1%, 89.2%, and 100.0%. The sensitivity of QFT-GIT decreased gradually with age. Compared to QFT-GIT, QFT-Plus displayed significantly higher sensitivity (100.0% vs. 89.4%, P =0.013) and similar specificity (95.1% vs. 95.7%). In conclusion, a high prevalence of LTBI was found among elders in LTCFs in Taiwan. The new QFT-Plus test demonstrated a higher sensitivity than QFT-GIT in the older adults in LTCFs. Copyright © 2018 American Society for Microbiology.

Probabilistic sensitivity analysis incorporating the bootstrap: an example comparing treatments for the eradication of Helicobacter pylori.

PubMed

Pasta, D J; Taylor, J L; Henning, J M

1999-01-01

Decision-analytic models are frequently used to evaluate the relative costs and benefits of alternative therapeutic strategies for health care. Various types of sensitivity analysis are used to evaluate the uncertainty inherent in the models. Although probabilistic sensitivity analysis is more difficult theoretically and computationally, the results can be much more powerful and useful than deterministic sensitivity analysis. The authors show how a Monte Carlo simulation can be implemented using standard software to perform a probabilistic sensitivity analysis incorporating the bootstrap. The method is applied to a decision-analytic model evaluating the cost-effectiveness of Helicobacter pylori eradication. The necessary steps are straightforward and are described in detail. The use of the bootstrap avoids certain difficulties encountered with theoretical distributions. The probabilistic sensitivity analysis provided insights into the decision-analytic model beyond the traditional base-case and deterministic sensitivity analyses and should become the standard method for assessing sensitivity.

The Sensitivity of Adverse Event Cost Estimates to Diagnostic Coding Error

PubMed Central

Wardle, Gavin; Wodchis, Walter P; Laporte, Audrey; Anderson, Geoffrey M; Baker, Ross G

2012-01-01

Objective To examine the impact of diagnostic coding error on estimates of hospital costs attributable to adverse events. Data Sources Original and reabstracted medical records of 9,670 complex medical and surgical admissions at 11 hospital corporations in Ontario from 2002 to 2004. Patient specific costs, not including physician payments, were retrieved from the Ontario Case Costing Initiative database. Study Design Adverse events were identified among the original and reabstracted records using ICD10-CA (Canadian adaptation of ICD10) codes flagged as postadmission complications. Propensity score matching and multivariate regression analysis were used to estimate the cost of the adverse events and to determine the sensitivity of cost estimates to diagnostic coding error. Principal Findings Estimates of the cost of the adverse events ranged from $16,008 (metabolic derangement) to $30,176 (upper gastrointestinal bleeding). Coding errors caused the total cost attributable to the adverse events to be underestimated by 16 percent. The impact of coding error on adverse event cost estimates was highly variable at the organizational level. Conclusions Estimates of adverse event costs are highly sensitive to coding error. Adverse event costs may be significantly underestimated if the likelihood of error is ignored. PMID:22091908

A model-based analysis of decision making under risk in obsessive-compulsive and hoarding disorders.

PubMed

Aranovich, Gabriel J; Cavagnaro, Daniel R; Pitt, Mark A; Myung, Jay I; Mathews, Carol A

2017-07-01

Attitudes towards risk are highly consequential in clinical disorders thought to be prone to "risky behavior", such as substance dependence, as well as those commonly associated with excessive risk aversion, such as obsessive-compulsive disorder (OCD) and hoarding disorder (HD). Moreover, it has recently been suggested that attitudes towards risk may serve as a behavioral biomarker for OCD. We investigated the risk preferences of participants with OCD and HD using a novel adaptive task and a quantitative model from behavioral economics that decomposes risk preferences into outcome sensitivity and probability sensitivity. Contrary to expectation, compared to healthy controls, participants with OCD and HD exhibited less outcome sensitivity, implying less risk aversion in the standard economic framework. In addition, risk attitudes were strongly correlated with depression, hoarding, and compulsion scores, while compulsion (hoarding) scores were associated with more (less) "rational" risk preferences. These results demonstrate how fundamental attitudes towards risk relate to specific psychopathology and thereby contribute to our understanding of the cognitive manifestations of mental disorders. In addition, our findings indicate that the conclusion made in recent work that decision making under risk is unaltered in OCD is premature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis

PubMed Central

You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

2016-01-01

Background Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. Methods We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Results Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68–0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50–0.92) and flavonols (RR = 0.68, 95% CI = 0.58–0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71–1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger’s test (p = 0.26). Conclusions This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted. PMID:26960146

Cost Effectiveness of Field Trauma Triage among Injured Adults Served by Emergency Medical Services

PubMed Central

Newgard, Craig D; Yang, Zhuo; Nishijima, Daniel; McConnell, K John; Trent, Stacy; Holmes, James F; Daya, Mohamud; Mann, N Clay; Hsia, Renee Y; Rea, Tom; Wang, N Ewen; Staudenmayer, Kristan; Delgado, M Kit

2016-01-01

Background The American College of Surgeons Committee on Trauma sets national targets for the accuracy of field trauma triage at ≥ 95% sensitivity and ≥ 65% specificity, yet the cost-effectiveness of realizing these goals is unknown. We evaluated the cost-effectiveness of current field trauma triage practices compared to triage strategies consistent with the national targets. Study Design This was a cost-effectiveness analysis using data from 79,937 injured adults transported by 48 emergency medical services (EMS) agencies to 105 trauma and non-trauma hospitals in 6 regions of the Western U.S. from 2006 through 2008. Incremental differences in survival, quality adjusted life years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER; costs per QALY gained) were estimated for each triage strategy over a 1-year and lifetime horizon using a decision analytic Markov model. We considered an ICER threshold of less than $100,000 to be cost-effective. Results For these 6 regions, a high sensitivity triage strategy consistent with national trauma policy (sensitivity 98.6%, specificity 17.1%) would cost $1,317,333 per QALY gained, while current triage practices (sensitivity 87.2%, specificity 64.0%) cost $88,000 per QALY gained compared to a moderate sensitivity strategy (sensitivity 71.2%, specificity 66.5%). Refining EMS transport patterns by triage status improved cost-effectiveness. At the trauma system level, a high-sensitivity triage strategy would save 3.7 additional lives per year at a 1-year cost of $8.78 million, while a moderate sensitivity approach would cost 5.2 additional lives and save $781,616 each year. Conclusions A high-sensitivity approach to field triage consistent with national trauma policy is not cost effective. The most cost effective approach to field triage appears closely tied to triage specificity and adherence to triage-based EMS transport practices. PMID:27178369

Dissociation between the Prevalence of Atopy and Allergic Disease in Rural China among Children and Adults

PubMed Central

Kim, Jennifer S; Ouyang, Fengxiu; Pongracic, Jacqueline A; Fang, Yaping; Wang, Binyan; Liu, Xue; Xing, Houxun; Caruso, Deanna; Liu, Xin; Zhang, Shanchun; Xu, Xiping; Wang, Xiaobin

2009-01-01

Background The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend may be associated with lifestyle and urbanization. Objective To describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population. Methods The data was derived from a community-based twin study in Anqing, China. Skin prick testing was performed to foods and aeroallergens. Atopy was defined as sensitization to ≥1 allergen. Allergic disease was ascertained by self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [≥18 years]) and included 1059 same-sex twin pairs. Results Of 2118 subjects, 57.6% were male (n=1220). Ages ranged from 11-71 years; 43.3% were children (n=918). Atopy was observed in 47.2% (n=999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be <1%. Conclusions Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low. Clinical Implications Allergen sensitization was far more common than the rate of self-reported allergic disease in this community. Evidence of sensitization is an inadequate marker of allergic disease and better correlates with clinical disease are needed. Capsule summary Among this large unselected Chinese rural farming community, atopy was observed in nearly half of the study subjects, but the rate of allergic disease was comparatively very low. PMID:18805578

A global analysis of traits predicting species sensitivity to habitat fragmentation

USGS Publications Warehouse

Keinath, Douglas; Doak, Daniel F.; Hodges, Karen E.; Prugh, Laura R.; Fagan, William F.; Sekercioglu, Cagan H.; Buchart, Stuart H. M.; Kauffman, Matthew J.

2017-01-01

AimElucidating patterns in species responses to habitat fragmentation is an important focus of ecology and conservation, but studies are often geographically restricted, taxonomically narrow or use indirect measures of species vulnerability. We investigated predictors of species presence after fragmentation using data from studies around the world that included all four terrestrial vertebrate classes, thus allowing direct inter-taxonomic comparison.LocationWorld-wide.MethodsWe used generalized linear mixed-effect models in an information theoretic framework to assess the factors that explained species presence in remnant habitat patches (3342 patches; 1559 species, mostly birds; and 65,695 records of patch-specific presence–absence). We developed a novel metric of fragmentation sensitivity, defined as the maximum rate of change in probability of presence with changing patch size (‘Peak Change’), to distinguish between general rarity on the landscape and sensitivity to fragmentation per se.ResultsSize of remnant habitat patches was the most important driver of species presence. Across all classes, habitat specialists, carnivores and larger species had a lower probability of presence, and those effects were substantially modified by interactions. Sensitivity to fragmentation (measured by Peak Change) was influenced primarily by habitat type and specialization, but also by fecundity, life span and body mass. Reptiles were more sensitive than other classes. Grassland species had a lower probability of presence, though sample size was relatively small, but forest and shrubland species were more sensitive.Main conclusionsHabitat relationships were more important than life-history characteristics in predicting the effects of fragmentation. Habitat specialization increased sensitivity to fragmentation and interacted with class and habitat type; forest specialists and habitat-specific reptiles were particularly sensitive to fragmentation. Our results suggest that when conservationists are faced with disturbances that could fragment habitat they should pay particular attention to specialists, particularly reptiles. Further, our results highlight that the probability of presence in fragmented landscapes and true sensitivity to fragmentation are predicted by different factors.

Organic Solvents as Risk Factor for Autoimmune Diseases: A Systematic Review and Meta-Analysis

PubMed Central

Barragán-Martínez, Carolina; Speck-Hernández, Cesar A.; Montoya-Ortiz, Gladis; Mantilla, Rubén D.; Anaya, Juan-Manuel; Rojas-Villarraga, Adriana

2012-01-01

Background Genetic and epigenetic factors interacting with the environment over time are the main causes of complex diseases such as autoimmune diseases (ADs). Among the environmental factors are organic solvents (OSs), which are chemical compounds used routinely in commercial industries. Since controversy exists over whether ADs are caused by OSs, a systematic review and meta-analysis were performed to assess the association between OSs and ADs. Methods and Findings The systematic search was done in the PubMed, SCOPUS, SciELO and LILACS databases up to February 2012. Any type of study that used accepted classification criteria for ADs and had information about exposure to OSs was selected. Out of a total of 103 articles retrieved, 33 were finally included in the meta-analysis. The final odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by the random effect model. A sensitivity analysis confirmed results were not sensitive to restrictions on the data included. Publication bias was trivial. Exposure to OSs was associated to systemic sclerosis, primary systemic vasculitis and multiple sclerosis individually and also to all the ADs evaluated and taken together as a single trait (OR: 1.54; 95% CI: 1.25–1.92; p-value<0.001). Conclusion Exposure to OSs is a risk factor for developing ADs. As a corollary, individuals with non-modifiable risk factors (i.e., familial autoimmunity or carrying genetic factors) should avoid any exposure to OSs in order to avoid increasing their risk of ADs. PMID:23284705

Nondestructive Analysis of Tumor-Associated Membrane Protein Integrating Imaging and Amplified Detection in situ Based on Dual-Labeled DNAzyme.

PubMed

Chen, Xiaoxia; Zhao, Jing; Chen, Tianshu; Gao, Tao; Zhu, Xiaoli; Li, Genxi

2018-01-01

Comprehensive analysis of the expression level and location of tumor-associated membrane proteins (TMPs) is of vital importance for the profiling of tumor cells. Currently, two kinds of independent techniques, i.e. ex situ detection and in situ imaging, are usually required for the quantification and localization of TMPs respectively, resulting in some inevitable problems. Methods: Herein, based on a well-designed and fluorophore-labeled DNAzyme, we develop an integrated and facile method, in which imaging and quantification of TMPs in situ are achieved simultaneously in a single system. The labeled DNAzyme not only produces localized fluorescence for the visualization of TMPs but also catalyzes the cleavage of a substrate to produce quantitative fluorescent signals that can be collected from solution for the sensitive detection of TMPs. Results: Results from the DNAzyme-based in situ imaging and quantification of TMPs match well with traditional immunofluorescence and western blotting. In addition to the advantage of two-in-one, the DNAzyme-based method is highly sensitivity, allowing the detection of TMPs in only 100 cells. Moreover, the method is nondestructive. Cells after analysis could retain their physiological activity and could be cultured for other applications. Conclusion: The integrated system provides solid results for both imaging and quantification of TMPs, making it a competitive method over some traditional techniques for the analysis of TMPs, which offers potential application as a toolbox in the future.

PathoScope 2.0: a complete computational framework for strain identification in environmental or clinical sequencing samples

PubMed Central

2014-01-01

Background Recent innovations in sequencing technologies have provided researchers with the ability to rapidly characterize the microbial content of an environmental or clinical sample with unprecedented resolution. These approaches are producing a wealth of information that is providing novel insights into the microbial ecology of the environment and human health. However, these sequencing-based approaches produce large and complex datasets that require efficient and sensitive computational analysis workflows. Many recent tools for analyzing metagenomic-sequencing data have emerged, however, these approaches often suffer from issues of specificity, efficiency, and typically do not include a complete metagenomic analysis framework. Results We present PathoScope 2.0, a complete bioinformatics framework for rapidly and accurately quantifying the proportions of reads from individual microbial strains present in metagenomic sequencing data from environmental or clinical samples. The pipeline performs all necessary computational analysis steps; including reference genome library extraction and indexing, read quality control and alignment, strain identification, and summarization and annotation of results. We rigorously evaluated PathoScope 2.0 using simulated data and data from the 2011 outbreak of Shiga-toxigenic Escherichia coli O104:H4. Conclusions The results show that PathoScope 2.0 is a complete, highly sensitive, and efficient approach for metagenomic analysis that outperforms alternative approaches in scope, speed, and accuracy. The PathoScope 2.0 pipeline software is freely available for download at: http://sourceforge.net/projects/pathoscope/. PMID:25225611

Mercury and gold concentrations of highly polluted environmental samples determined using prompt gamma-ray analysis and instrument neutron activation analysis

NASA Astrophysics Data System (ADS)

Osawa, Takahito; Hatsukawa, Yuichi; Appel, Peter W. U.; Matsue, Hideaki

2011-04-01

The authors have established a method of determining mercury and gold in severely polluted environmental samples using prompt gamma-ray analysis (PGA) and instrumental neutron activation analysis (INAA). Since large amounts of mercury are constantly being released into the environment by small-scale gold mining in many developing countries, the mercury concentration in tailings and water has to be determined to mitigate environmental pollution. Cold-vapor atomic absorption analysis, the most pervasive method of mercury analysis, is not suitable because tailings and water around mining facilities have extremely high mercury concentrations. On the other hand, PGA can determine high mercury concentrations in polluted samples as it has an appropriate level of sensitivity. Moreover, gold concentrations can be determined sequentially by using INAA after PGA. In conclusion, the analytical procedure established in this work using PGA and INAA is the best way to evaluate the degree of pollution and the tailing resource value. This method will significantly contribute to mitigating problems in the global environment.

Ex post facto assessment of diffusion tensor imaging metrics from different MRI protocols: preparing for multicentre studies in ALS.

PubMed

Rosskopf, Johannes; Müller, Hans-Peter; Dreyhaupt, Jens; Gorges, Martin; Ludolph, Albert C; Kassubek, Jan

2015-03-01

Diffusion tensor imaging (DTI) for assessing ALS-associated white matter alterations has still not reached the level of a neuroimaging biomarker. Since large-scale multicentre DTI studies in ALS may be hampered by differences in scanning protocols, an approach for pooling of DTI data acquired with different protocols was investigated. Three hundred and nine datasets from 170 ALS patients and 139 controls were collected ex post facto from a monocentric database reflecting different scanning protocols. A 3D correction algorithm was introduced for a combined analysis of DTI metrics despite different acquisition protocols, with the focus on the CST as the tract correlate of ALS neuropathological stage 1. A homogenous set of data was obtained by application of 3D correction matrices. Results showed that a fractional anisotropy (FA) threshold of 0.41 could be defined to discriminate ALS patients from controls (sensitivity/specificity, 74%/72%). For the remaining test sample, sensitivity/specificity values of 68%/74% were obtained. In conclusion, the objective was to merge data recorded with different DTI protocols with 3D correction matrices for analyses at group level. These post processing tools might facilitate analysis of large study samples in a multicentre setting for DTI analysis at group level to aid in establishing DTI as a non-invasive biomarker for ALS.

Neuraxial blockade for external cephalic version: Cost analysis

PubMed Central

Yamasato, Kelly; Kaneshiro, Bliss; Salcedo, Jennifer

2017-01-01

Aim Neuraxial blockade (epidural or spinal anesthesia/analgesia) with external cephalic version increases the external cephalic version success rate. Hospitals and insurers may affect access to neuraxial blockade for external cephalic version, but the costs to these institutions remain largely unstudied. The objective of this study was to perform a cost analysis of neuraxial blockade use during external cephalic version from hospital and insurance payer perspectives. Secondarily, we estimated the effect of neuraxial blockade on cesarean delivery rates. Methods A decision–analysis model was developed using costs and probabilities occurring prenatally through the delivery hospital admission. Model inputs were derived from the literature, national databases, and local supply costs. Univariate and bivariate sensitivity analyses and Monte Carlo simulations were performed to assess model robustness. Results Neuraxial blockade was cost saving to both hospitals ($30 per delivery) and insurers ($539 per delivery) using baseline estimates. From both perspectives, however, the model was sensitive to multiple variables. Monte Carlo simulation indicated neuraxial blockade to be more costly in approximately 50% of scenarios. The model demonstrated that routine use of neuraxial blockade during external cephalic version, compared to no neuraxial blockade, prevented 17 cesarean deliveries for every 100 external cephalic versions attempted. Conclusions Neuraxial blockade is associated with minimal hospital and insurer cost changes in the setting of external cephalic version, while reducing the cesarean delivery rate. PMID:25771920

Barcoding Melting Curve Analysis for Rapid, Sensitive, and Discriminating Authentication of Saffron (Crocus sativus L.) from Its Adulterants

PubMed Central

Cao, Liang; Yuan, Yuan; Chen, Min; Jin, Yan; Huang, Luqi

2014-01-01

Saffron (Crocus sativus L.) is one of the most important and expensive medicinal spice products in the world. Because of its high market value and premium price, saffron is often adulterated through the incorporation of other materials, such as Carthamus tinctorius L. and Calendula officinalis L. flowers, Hemerocallis L. petals, Daucus carota L. fleshy root, Curcuma longa L. rhizomes, Zea may L., and Nelumbo nucifera Gaertn. stigmas. To develop a straightforward, nonsequencing method for rapid, sensitive, and discriminating detection of these adulterants in traded saffron, we report here the application of a barcoding melting curve analysis method (Bar-MCA) that uses the universal chloroplast plant DNA barcoding region trnH-psbA to identify adulterants. When amplified at DNA concentrations and annealing temperatures optimized for the curve analysis, peaks were formed at specific locations for saffron (81.92°C) and the adulterants: D. carota (81.60°C), C. tinctorius (80.10°C), C. officinalis (79.92°C), Dendranthema morifolium (Ramat.) Tzvel. (79.62°C), N. nucifera (80.58°C), Hemerocallis fulva (L.) L. (84.78°C), and Z. mays (84.33°C). The constructed melting curves for saffron and its adulterants have significantly different peak locations or shapes. In conclusion, Bar-MCA could be a faster and more cost-effective method to authenticate saffron and detect its adulterants. PMID:25548775

Barcoding melting curve analysis for rapid, sensitive, and discriminating authentication of saffron (Crocus sativus L.) from its adulterants.

PubMed

Jiang, Chao; Cao, Liang; Yuan, Yuan; Chen, Min; Jin, Yan; Huang, Luqi

2014-01-01

Saffron (Crocus sativus L.) is one of the most important and expensive medicinal spice products in the world. Because of its high market value and premium price, saffron is often adulterated through the incorporation of other materials, such as Carthamus tinctorius L. and Calendula officinalis L. flowers, Hemerocallis L. petals, Daucus carota L. fleshy root, Curcuma longa L. rhizomes, Zea may L., and Nelumbo nucifera Gaertn. stigmas. To develop a straightforward, nonsequencing method for rapid, sensitive, and discriminating detection of these adulterants in traded saffron, we report here the application of a barcoding melting curve analysis method (Bar-MCA) that uses the universal chloroplast plant DNA barcoding region trnH-psbA to identify adulterants. When amplified at DNA concentrations and annealing temperatures optimized for the curve analysis, peaks were formed at specific locations for saffron (81.92°C) and the adulterants: D. carota (81.60°C), C. tinctorius (80.10°C), C. officinalis (79.92°C), Dendranthema morifolium (Ramat.) Tzvel. (79.62°C), N. nucifera (80.58°C), Hemerocallis fulva (L.) L. (84.78°C), and Z. mays (84.33°C). The constructed melting curves for saffron and its adulterants have significantly different peak locations or shapes. In conclusion, Bar-MCA could be a faster and more cost-effective method to authenticate saffron and detect its adulterants.

Candidate Loci for Insulin Sensitivity and Disposition Index from a Genome Wide Association Analysis of Hispanics in the IRAS Family Study

PubMed Central

Palmer, N. D.; Langefeld, C. D.; Ziegler, J. T.; Hsu, F.; Haffner, S. M.; Fingerlin, T.; Norris, J. M.; Chen, Y. I.; Rich, S. S.; Haritunians, T.; Taylor, K. D.; Bergman, R. N.; Rotter, J. I.; Bowden, D. W.

2009-01-01

Aims/Hypothesis —The majority of type 2 diabetes Genome Wide Association Studies (GWAS) to date have been performed in European-derived populations and have identified few variants that mediate their effect through insulin resistance. The aim of this study was to evaluate two quantitative, directly assessed measures of insulin resistance (SI and DI) in Hispanic Americans using an agnostic, high-density SNP scan and validate these findings in additional samples. Methods —A two-stage GWAS was performed in IRAS-FS Hispanic-American samples. In Stage 1, 317K single nucleotide polymorphisms (SNPs) were assessed 229 DNA samples. SNPs with evidence of association with glucose homeostasis and adiposity traits were then genotyped on the entire set of Hispanic-American samples (n=1190). This report focuses on the glucose homeostasis traits: insulin sensitivity index (SI) and disposition index (DI). Results —Although evidence of association did not reach genome-wide significance (P=5×10−7), in the combined analysis SNPs had admixture-adjusted PADD=0.00010–0.0020 with 8–41% differences in genotypic means for SI and DI. Conclusions/Interpretation —Several candidate loci have been identified which are nominally associated with SI and/or DI in Hispanic Americans. Replication of these findings in independent cohorts and additional focused analysis of these loci is warranted. PMID:19902172

Quantitative x-ray photoelectron spectroscopy: Quadrupole effects, shake-up, Shirley background, and relative sensitivity factors from a database of true x-ray photoelectron spectra

NASA Astrophysics Data System (ADS)

Seah, M. P.; Gilmore, I. S.

2006-05-01

An analysis is provided of the x-ray photoelectron spectroscopy (XPS) intensities measured in the National Physical Laboratory (NPL) XPS database for 46 solid elements. This present analysis does not change our previous conclusions concerning the excellent correlation between experimental intensities, following deconvolving the spectra with angle-averaged reflection electron energy loss data, and the theoretical intensities involving the dipole approximation using Scofield’s cross sections. Here, more recent calculations for cross sections by Trzhaskovskaya involving quadrupole terms are evaluated and it is shown that their cross sections diverge from the experimental database results by up to a factor of 5. The quadrupole angular terms lead to small corrections that are close to our measurement limit but do appear to be supported in the present analysis. Measurements of the extent of shake-up for the 46 elements broadly agree with the calculations of Yarzhemsky but not in detail. The predicted constancy in the shake-up contribution by Yarzhemsky implies that the use of the Shirley background will lead to a peak area that is a constant fraction of the true peak area including the shake-up intensities. However, the measured variability of the shake-up contribution makes the Shirley background invalid for quantification except for situations where the sensitivity factors are from reference samples similar to those being analyzed.

Multiparametric MRI followed by targeted prostate biopsy for men with suspected prostate cancer: a clinical decision analysis

PubMed Central

Willis, Sarah R; Ahmed, Hashim U; Moore, Caroline M; Donaldson, Ian; Emberton, Mark; Miners, Alec H; van der Meulen, Jan

2014-01-01

Objective To compare the diagnostic outcomes of the current approach of transrectal ultrasound (TRUS)-guided biopsy in men with suspected prostate cancer to an alternative approach using multiparametric MRI (mpMRI), followed by MRI-targeted biopsy if positive. Design Clinical decision analysis was used to synthesise data from recently emerging evidence in a format that is relevant for clinical decision making. Population A hypothetical cohort of 1000 men with suspected prostate cancer. Interventions mpMRI and, if positive, MRI-targeted biopsy compared with TRUS-guided biopsy in all men. Outcome measures We report the number of men expected to undergo a biopsy as well as the numbers of correctly identified patients with or without prostate cancer. A probabilistic sensitivity analysis was carried out using Monte Carlo simulation to explore the impact of statistical uncertainty in the diagnostic parameters. Results In 1000 men, mpMRI followed by MRI-targeted biopsy ‘clinically dominates’ TRUS-guided biopsy as it results in fewer expected biopsies (600 vs 1000), more men being correctly identified as having clinically significant cancer (320 vs 250), and fewer men being falsely identified (20 vs 50). The mpMRI-based strategy dominated TRUS-guided biopsy in 86% of the simulations in the probabilistic sensitivity analysis. Conclusions Our analysis suggests that mpMRI followed by MRI-targeted biopsy is likely to result in fewer and better biopsies than TRUS-guided biopsy. Future research in prostate cancer should focus on providing precise estimates of key diagnostic parameters. PMID:24934207

Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials.

PubMed

Sahebkar, Amirhossein; Cicero, Arrigo F G; Simental-Mendía, Luis E; Aggarwal, Bharat B; Gupta, Subash C

2016-05-01

Tumor necrosis factor-α (TNF-α) is a key inflammatory mediator and its reduction is a therapeutic target in several inflammatory diseases. Curcumin, a bioactive polyphenol from turmeric, has been shown in several preclinical studies to block TNF-α effectively. However, clinical evidence has not been fully conclusive. The aim of the present meta-analysis was to evaluate the efficacy of curcumin supplementation on circulating levels of TNF-α in randomized controlled trials (RCTs). The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases by up to September 21, 2015, to identify RCTs investigating the impact of curcumin on circulating TNF-α concentration. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Meta-regression and leave-one-out sensitivity analyses were performed to assess the modifiers of treatment response. Eight RCTs comprising nine treatment arms were finally selected for the meta-analysis. There was a significant reduction of circulating TNF-α concentrations following curcumin supplementation (WMD: -4.69pg/mL, 95% CI: -7.10, -2.28, p<0.001). This effect size was robust in sensitivity analysis. Meta-regression did not suggest any significant association between the circulating TNF-α-lowering effects of curcumin with either dose or duration (slope: 0.197; 95% CI: -1.73, 2.12; p=0.841) of treatment. This meta-analysis of RCTs suggested a significant effect of curcumin in lowering circulating TNF-α concentration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gender role affects experimental pain responses: a systematic review with meta-analysis.

PubMed

Alabas, O A; Tashani, O A; Tabasam, G; Johnson, M I

2012-10-01

Gender role refers to the culturally and socially constructed meanings that describe how women and men should behave in certain situations according to feminine and masculine roles learned throughout life. The aim of this meta-analysis was to evaluate the relationship between gender role and experimental pain responses in healthy human participants. We searched computerized databases for studies published between January 1950 and May 2011 that had measured gender role in healthy human adults and pain response to noxious stimuli. Studies were entered into a meta-analysis if they calculated a correlation coefficient (r) for gender role and experimental pain. Searches yielded 4465 'hits' and 13 studies were eligible for review. Sample sizes were 67-235 participants and the proportion of female participants was 45-67%. Eight types of gender role instrument were used. Meta-analysis of six studies (406 men and 539 women) found a significant positive correlation between masculine and feminine personality traits and pain threshold and tolerance, with a small effect size (r = 0.17, p = 0.01). Meta-analysis of four studies (263 men and 297 women) found a significant negative correlation between gender stereotypes specific to pain and pain threshold and tolerance, with a moderate effect size (r = -0.41, p < 0.001). In conclusion, individuals who considered themselves more masculine and less sensitive to pain than the typical man showed higher pain thresholds and tolerances. Gender stereotypes specific to pain scales showed stronger associations with sex differences in pain sensitivity response than masculine and feminine personality trait scales. © 2012 European Federation of International Association for the Study of Pain Chapters.

A comparative analysis of area navigation systems in general aviation. M.S. Thesis

NASA Technical Reports Server (NTRS)

Dodge, S. M.

1973-01-01

Radio navigation systems which offer the capabilities of area navigation to general aviation operators are discussed. The systems considered are: (1) the VORTAC system, (2) the Loran-C system, and (3) the Differential Omega system. The inital analyses are directed toward a comparison of the systems with respect to their compliance to specified performance parameters and to the cost effectiveness of each system in relation to those specifications. Further analyses lead to the development of system cost sensitivity charts, and the employment of these charts allows conclusions to be drawn relative to the cost-effectiveness of the candidate navigation system.

Prevention of poultry-borne salmonellosis by irradiation: costs and benefits in Scotland

PubMed Central

Yule, B. F.; Sharp, J. C. M.; Forbes, G. I.; Macleod, A. F.

1988-01-01

Poultry-borne salmonellosis is the most common foodborne infection in Scotland for which the vehicle can be identified. The cost of the disease to society in terms of health service use, absence from work, morbidity, and mortality is substantial. The study estimates the total cost of poultry-borne salmonellosis in Scotland and compares it with the cost of a single preventive measure: the irradiation of poultry meat. The results suggest that the public health benefits exceed irradiation costs. This conclusion is, however, sensitive to assumptions made in the analysis, particularly those related to the cost of unreported cases of salmonellosis. PMID:3148375

Using models to manage systems subject to sustainability indicators

USGS Publications Warehouse

Hill, M.C.

2006-01-01

Mathematical and numerical models can provide insight into sustainability indicators using relevant simulated quantities, which are referred to here as predictions. To be useful, many concerns need to be considered. Four are discussed here: (a) mathematical and numerical accuracy of the model; (b) the accuracy of the data used in model development, (c) the information observations provide to aspects of the model important to predictions of interest as measured using sensitivity analysis; and (d) the existence of plausible alternative models for a given system. The four issues are illustrated using examples from conservative and transport modelling, and using conceptual arguments. Results suggest that ignoring these issues can produce misleading conclusions.

Gender-based education during clerkships: a focus group study

PubMed Central

van Leerdam, Lotte; Rietveld, Lianne; Teunissen, Doreth; Lagro-Janssen, Antoine

2014-01-01

Objectives One of the goals of the medical master’s degree is for a student to become a gender-sensitive doctor by applying knowledge of gender differences in practice. This study aims to investigate, from the students’ perspective, whether gender medicine has been taught in daily practice during clerkship. Methods A focus group study was conducted among 29 medical students from Radboud University, Nijmegen, The Netherlands, who had just finished either their internal medicine or surgical clerkships. Data were analyzed in line with the principles of constant comparative analysis. Results Four focus groups were conducted with 29 participating students. Clinical teachers barely discuss gender differences during students’ clerkships. The students mentioned three main explanatory themes: insufficient knowledge; unawareness; and minor impact. As a result, students feel that they have insufficient competencies to become gender-sensitive doctors. Conclusion Medical students at our institution perceive that they have received limited exposure to gender-based education after completing two key clinical clerkships. All students feel that they have insufficient knowledge to become gender-sensitive doctors. They suppose that their clinical teachers have insufficient knowledge regarding gender sensitivity, are unaware of gender differences, and the students had the impression that gender is not regarded as an important issue. We suggest that the medical faculty should encourage clinical teachers to improve their knowledge and awareness of gender issues. PMID:24600301

Bioturbating animals control the mobility of redox-sensitive trace elements in organic-rich mudstone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harazim, Dario; McIlroy, Duncan; Edwards, Nicholas P.

Bioturbating animals modify the original mineralogy, porosity, organic content, and fabric of mud, thus affecting the burial diagenetic pathways of potential hydrocarbon source, seal, and reservoir rocks. High-sensitivity, synchrotron rapid scanning X-ray fluorescence elemental mapping reveals that producers of phycosiphoniform burrows systematically partition redox-sensitive trace elements (i.e., Fe, V, Cr, Mn, Co, Ni, Cu, and As) in fine-grained siliciclastic rocks. Systematic differences in organic carbon content (total organic carbon >1.5 wt%) and quality (Δ 13C org~0.6‰) are measured between the burrow core and host sediment. The relative enrichment of redox-sensitive elements in the burrow core does not correlate with significantmore » neo-formation of early diagenetic pyrite (via trace metal pyritization), but is best explained by physical concentration of clay- and silt-sized components. A measured loss (~–15%) of the large-ionic-radius elements Sr and Ba from both burrow halo and core is most likely associated with the release of Sr and Ba to pore waters during biological ( in vivo) weathering of silt- to clay-sized lithic components and feldspar. In conclusion, this newly documented effect has significant potential to inform the interpretation of geochemical proxy and rock property data, particularly from shales, where elemental analyses are commonly employed to predict reservoir quality and support paleoenvironmental analysis.« less

Contribution of mammography to MRI screening in BRCA mutation carriers by BRCA status and age: individual patient data meta-analysis

PubMed Central

Phi, Xuan-Anh; Saadatmand, Sepideh; De Bock, Geertruida H; Warner, Ellen; Sardanelli, Francesco; Leach, Martin O; Riedl, Christopher C; Trop, Isabelle; Hooning, Maartje J; Mandel, Rodica; Santoro, Filippo; Kwan-Lim, Gek; Helbich, Thomas H; Tilanus-Linthorst, Madeleine MA; van den Heuvel, Edwin R; Houssami, Nehmat

2016-01-01

Background: We investigated the additional contribution of mammography to screening accuracy in BRCA1/2 mutation carriers screened with MRI at different ages using individual patient data from six high-risk screening trials. Methods: Sensitivity and specificity of MRI, mammography and the combination of these tests were compared stratified for BRCA mutation and age using generalised linear mixed models with random effect for studies. Number of screens needed (NSN) for additional mammography-only detected cancer was estimated. Results: In BRCA1/2 mutation carriers of all ages (BRCA1=1219 and BRCA2=732), adding mammography to MRI did not significantly increase screening sensitivity (increased by 3.9% in BRCA1 and 12.6% in BRCA2 mutation carriers, P>0.05). However, in women with BRCA2 mutation younger than 40 years, one-third of breast cancers were detected by mammography only. Number of screens needed for mammography to detect one breast cancer not detected by MRI was much higher for BRCA1 compared with BRCA2 mutation carriers at initial and repeat screening. Conclusions: Additional screening sensitivity from mammography above that from MRI is limited in BRCA1 mutation carriers, whereas mammography contributes to screening sensitivity in BRCA2 mutation carriers, especially those ⩽40 years. The evidence from our work highlights that a differential screening schedule by BRCA status is worth considering. PMID:26908327

Bioturbating animals control the mobility of redox-sensitive trace elements in organic-rich mudstone

DOE PAGES

Harazim, Dario; McIlroy, Duncan; Edwards, Nicholas P.; ...

2015-10-07

Bioturbating animals modify the original mineralogy, porosity, organic content, and fabric of mud, thus affecting the burial diagenetic pathways of potential hydrocarbon source, seal, and reservoir rocks. High-sensitivity, synchrotron rapid scanning X-ray fluorescence elemental mapping reveals that producers of phycosiphoniform burrows systematically partition redox-sensitive trace elements (i.e., Fe, V, Cr, Mn, Co, Ni, Cu, and As) in fine-grained siliciclastic rocks. Systematic differences in organic carbon content (total organic carbon >1.5 wt%) and quality (Δ 13C org~0.6‰) are measured between the burrow core and host sediment. The relative enrichment of redox-sensitive elements in the burrow core does not correlate with significantmore » neo-formation of early diagenetic pyrite (via trace metal pyritization), but is best explained by physical concentration of clay- and silt-sized components. A measured loss (~–15%) of the large-ionic-radius elements Sr and Ba from both burrow halo and core is most likely associated with the release of Sr and Ba to pore waters during biological ( in vivo) weathering of silt- to clay-sized lithic components and feldspar. In conclusion, this newly documented effect has significant potential to inform the interpretation of geochemical proxy and rock property data, particularly from shales, where elemental analyses are commonly employed to predict reservoir quality and support paleoenvironmental analysis.« less

Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity

PubMed Central

Almeida, Jorge R.; Sauce, Delphine; Price, David A.; Papagno, Laura; Shin, So Youn; Moris, Arnaud; Larsen, Martin; Pancino, Gianfranco; Douek, Daniel C.; Autran, Brigitte; Sáez-Cirión, Asier

2009-01-01

CD8+ T cells are major players in the immune response against HIV. However, recent failures in the development of T cell–based vaccines against HIV-1 have emphasized the need to reassess our basic knowledge of T cell–mediated efficacy. CD8+ T cells from HIV-1–infected patients with slow disease progression exhibit potent polyfunctionality and HIV-suppressive activity, yet the factors that unify these properties are incompletely understood. We performed a detailed study of the interplay between T-cell functional attributes using a bank of HIV-specific CD8+ T-cell clones isolated in vitro; this approach enabled us to overcome inherent difficulties related to the in vivo heterogeneity of T-cell populations and address the underlying determinants that synthesize the qualities required for antiviral efficacy. Conclusions were supported by ex vivo analysis of HIV-specific CD8+ T cells from infected donors. We report that attributes of CD8+ T-cell efficacy against HIV are linked at the level of antigen sensitivity. Highly sensitive CD8+ T cells display polyfunctional profiles and potent HIV-suppressive activity. These data provide new insights into the mechanisms underlying CD8+ T-cell efficacy against HIV, and indicate that vaccine strategies should focus on the induction of HIV-specific T cells with high levels of antigen sensitivity to elicit potent antiviral efficacy. PMID:19389882

Repeated high-intensity exercise modulates Ca(2+) sensitivity of human skeletal muscle fibers.

PubMed

Gejl, K D; Hvid, L G; Willis, S J; Andersson, E; Holmberg, H-C; Jensen, R; Frandsen, U; Hansen, J; Plomgaard, P; Ørtenblad, N

2016-05-01

The effects of short-term high-intensity exercise on single fiber contractile function in humans are unknown. Therefore, the purposes of this study were: (a) to access the acute effects of repeated high-intensity exercise on human single muscle fiber contractile function; and (b) to examine whether contractile function was affected by alterations in the redox balance. Eleven elite cross-country skiers performed four maximal bouts of 1300 m treadmill skiing with 45 min recovery. Contractile function of chemically skinned single fibers from triceps brachii was examined before the first and following the fourth sprint with respect to Ca(2+) sensitivity and maximal Ca(2+) -activated force. To investigate the oxidative effects of exercise on single fiber contractile function, a subset of fibers was incubated with dithiothreitol (DTT) before analysis. Ca(2+) sensitivity was enhanced by exercise in both MHC I (17%, P < 0.05) and MHC II (15%, P < 0.05) fibers. This potentiation was not present after incubation of fibers with DTT. Specific force of both MHC I and MHC II fibers was unaffected by exercise. In conclusion, repeated high-intensity exercise increased Ca(2+) sensitivity in both MHC I and MHC II fibers. This effect was not observed in a reducing environment indicative of an exercise-induced oxidation of the human contractile apparatus. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity.

PubMed

Almeida, Jorge R; Sauce, Delphine; Price, David A; Papagno, Laura; Shin, So Youn; Moris, Arnaud; Larsen, Martin; Pancino, Gianfranco; Douek, Daniel C; Autran, Brigitte; Sáez-Cirión, Asier; Appay, Victor

2009-06-18

CD8(+) T cells are major players in the immune response against HIV. However, recent failures in the development of T cell-based vaccines against HIV-1 have emphasized the need to reassess our basic knowledge of T cell-mediated efficacy. CD8(+) T cells from HIV-1-infected patients with slow disease progression exhibit potent polyfunctionality and HIV-suppressive activity, yet the factors that unify these properties are incompletely understood. We performed a detailed study of the interplay between T-cell functional attributes using a bank of HIV-specific CD8(+) T-cell clones isolated in vitro; this approach enabled us to overcome inherent difficulties related to the in vivo heterogeneity of T-cell populations and address the underlying determinants that synthesize the qualities required for antiviral efficacy. Conclusions were supported by ex vivo analysis of HIV-specific CD8(+) T cells from infected donors. We report that attributes of CD8(+) T-cell efficacy against HIV are linked at the level of antigen sensitivity. Highly sensitive CD8(+) T cells display polyfunctional profiles and potent HIV-suppressive activity. These data provide new insights into the mechanisms underlying CD8(+) T-cell efficacy against HIV, and indicate that vaccine strategies should focus on the induction of HIV-specific T cells with high levels of antigen sensitivity to elicit potent antiviral efficacy.

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

PubMed Central

Vrana, Julie A.; Theis, Jason D.; Dasari, Surendra; Mereuta, Oana M.; Dispenzieri, Angela; Zeldenrust, Steven R.; Gertz, Morie A.; Kurtin, Paul J.; Grogg, Karen L.; Dogan, Ahmet

2014-01-01

Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and specific method for the diagnosis of systemic amyloidosis. Here we describe the development and implementation of a clinical assay using mass spectrometry-based proteomics to type amyloidosis in subcutaneous fat aspirates. First, we validated the assay comparing amyloid-positive (n=43) and -negative (n=26) subcutaneous fat aspirates. The assay classified amyloidosis with 88% sensitivity and 96% specificity. We then implemented the assay as a clinical test, and analyzed 366 amyloid-positive subcutaneous fat aspirates in a 4-year period as part of routine clinical care. The assay had a sensitivity of 90%, and diverse amyloid types, including immunoglobulin light chain (74%), transthyretin (13%), serum amyloid A (%1), gelsolin (1%), and lysozyme (1%), were identified. Using bioinformatics, we identified a universal amyloid proteome signature, which has high sensitivity and specificity for amyloidosis similar to that of Congo red staining. We curated proteome databases which included variant proteins associated with systemic amyloidosis, and identified clonotypic immunoglobulin variable gene usage in immunoglobulin light chain amyloidosis, and the variant peptides in hereditary transthyretin amyloidosis. In conclusion, mass spectrometry-based proteomic analysis of subcutaneous fat aspirates offers a powerful tool for the diagnosis and typing of systemic amyloidosis. The assay reveals the underlying pathogenesis by identifying variable gene usage in immunoglobulin light chains and the variant peptides in hereditary amyloidosis. PMID:24747948

Lumbar Facet Joint Compressive Injury Induces Lasting Changes in Local Structure, Nociceptive Scores, and Inflammatory Mediators in a Novel Rat Model

PubMed Central

Henry, James L.; Yashpal, Kiran; Vernon, Howard; Kim, Jaesung; Im, Hee-Jeong

2012-01-01

Objective. To develop a novel animal model of persisting lumbar facet joint pain. Methods. Sprague Dawley rats were anaesthetized and the right lumbar (L5/L6) facet joint was exposed and compressed to ~1 mm with modified clamps applied for three minutes; sham-operated and naïve animals were used as control groups. After five days, animals were tested for hind-paw sensitivity using von Frey filaments and axial deep tissue sensitivity by algometer on assigned days up to 28 days. Animals were sacrificed at selected times for histological and biochemical analysis. Results. Histological sections revealed site-specific loss of cartilage in model animals only. Tactile hypersensitivity was observed for the ipsi- and contralateral paws lasting 28 days. The threshold at which deep tissue pressure just elicited vocalization was obtained at three lumbar levels; sensitivity at L1 > L3/4 > L6. Biochemical analyses revealed increases in proinflammatory cytokines, especially TNF-α, IL-1α, and IL-1β. Conclusions. These data suggest that compression of a facet joint induces a novel model of local cartilage loss accompanied by increased sensitivity to mechanical stimuli and by increases in inflammatory mediators. This new model may be useful for studies on mechanisms and treatment of lumbar facet joint pain and osteoarthritis. PMID:22966427

Ascertainment of Outpatient Visits by Patients with Diabetes: The National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS)

PubMed Central

Asao, Keiko; McEwen, Laura N.; Lee, Joyce M.; Herman, William H.

2015-01-01

Aims To estimate and evaluate the sensitivity and specificity of providers’ diagnosis codes and medication lists to identify outpatient visits by patients with diabetes. Methods We used data from the 2006 to 2010 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey. We assessed the sensitivity and specificity of providers’ diagnoses and medication lists to identify patients with diabetes, using the checkbox for diabetes as the gold standard. We then examined differences in sensitivity by patients’ characteristics using multivariate logistic regression models. Results The checkbox identified 12,647 outpatient visits by adults with diabetes among the 70,352 visits used for this analysis. The sensitivity and specificity of providers’ diagnoses or listed diabetes medications were 72.3% (95% CI: 70.8% to 73.8%) and 99.2% (99.1% to 99.4%), respectively. Diabetic patients ≥75 years pf age, women, non-Hispanics, and those with private insurance or Medicare were more likely to be missed by providers’ diagnoses and medication lists. Diabetic patients who had more diagnosis codes and medications recorded, had glucose or hemoglobin A1c measured, or made office- rather than hospital-outpatient visits were less likely to be missed. Conclusions Providers’ diagnosis codes and medication lists fail to identify approximately one quarter of outpatient visits by patients with diabetes. PMID:25891975

DNA Methylation Analysis of the SHOX2 and RASSF1A Panel in Bronchoalveolar Lavage Fluid for Lung Cancer Diagnosis

PubMed Central

Zhang, Chenzi; Yu, Wenjun; Wang, Lin; Zhao, Mingna; Guo, Qiaomei; Lv, Shaogang; Hu, Xiaomeng; Lou, Jiatao

2017-01-01

Introduction: Currently the majority of lung cancer patients are diagnosed as advanced diseases for no sensitive and specific biomarkers exist, noninvasive biomarkers with high sensitivity and specificity are urgently needed in lung cancer diagnosis. Bronchoscopy is a standard procedure of the diagnostic work-up of patients with suspected lung cancer despite of the limited diagnostic accuracy. Besides, epigenetic changes through DNA methylation play an important role in tumorigenesis. Thus, we examined the aberrant methylation of the SHOX2 and RASSF1A in bronchoalveolar lavage fluid (BALF) in comparing with conventional cytology examination and serum CEA in order to evaluate the new diagnostic method. Patients and Methods: BALF and serum samples were collected from 322 patients at the time of diagnosis, 284 of them were pathologically confirmed lung cancer, 35 were benign lung diseases and 3 were malignancies in other systems. For all of the 322 patients, the methylation status of the SHOX2 and RASSF1A gene were detected by a new RT-PCR platform and then confirmed by sanger sequencing. Serum CEA were detected using electrochemiluminescence immunoassay. Results: Profiling data showed the consistency of RT-PCR and sanger sequencing in detecting the methylation of the SHOX2 and RASSF1A. Besides, the combination of SHOX2 and RASSF1A methylation in BALF yielded a diagnostic sensitivity of 81.0% and specificity of 97.4%. When compared with established cytology examination (sensitivity: 68.3%, specificity: 97.4%) and serum biomarker carcinoembryonic antigen (CEA) (sensitivity: 30.6%, specificity: 100.0%), the SHOX2 and RASSF1A methylation panel showed the highest diagnostic efficiency. Notably, the combination of cytology and the SHOX2 and RASSF1A methylation panel could significantly improve the diagnostic efficacy. Conclusion: The methylation analysis of the SHOX2 and RASSF1A panel in BALF with RT-PCR achieved a satisfactory sensitivity and specificity in lung cancer diagnosis, especially in an early stage. It could be used as a promising noninvasive biomarker for auxiliary diagnosis of lung cancer. PMID:29151944

Sensitive and Specific Target Sequences Selected from Retrotransposons of Schistosoma japonicum for the Diagnosis of Schistosomiasis

PubMed Central

Xu, Jing; Zhu, Xing-Quan; Wang, Sheng-Yue; Xia, Chao-Ming

2012-01-01

Background Schistosomiasis japonica is a serious debilitating and sometimes fatal disease. Accurate diagnostic tests play a key role in patient management and control of the disease. However, currently available diagnostic methods are not ideal, and the detection of the parasite DNA in blood samples has turned out to be one of the most promising tools for the diagnosis of schistosomiasis. In our previous investigations, a 230-bp sequence from the highly repetitive retrotransposon SjR2 was identified and it showed high sensitivity and specificity for detecting Schistosoma japonicum DNA in the sera of rabbit model and patients. Recently, 29 retrotransposons were found in S. japonicum genome by our group. The present study highlighted the key factors for selecting a new perspective sensitive target DNA sequence for the diagnosis of schistosomiasis, which can serve as example for other parasitic pathogens. Methodology/Principal Findings In this study, we demonstrated that the key factors based on the bioinformatic analysis for selecting target sequence are the higher genome proportion, repetitive complete copies and partial copies, and active ESTs than the others in the chromosome genome. New primers based on 25 novel retrotransposons and SjR2 were designed and their sensitivity and specificity for detecting S. japonicum DNA were compared. The results showed that a new 303-bp sequence from non-long terminal repeat (LTR) retrotransposon (SjCHGCS19) had high sensitivity and specificity. The 303-bp target sequence was amplified from the sera of rabbit model at 3 d post-infection by nested-PCR and it became negative at 17 weeks post-treatment. Furthermore, the percentage sensitivity of the nested-PCR was 97.67% in 43 serum samples of S. japonicum-infected patients. Conclusions/Significance Our findings highlighted the key factors based on the bioinformatic analysis for selecting target sequence from S. japonicum genome, which provide basis for establishing powerful molecular diagnostic techniques that can be used for monitoring early infection and therapy efficacy to support schistosomiasis control programs. PMID:22479661

Detection of Echinococcus multilocularis by MC-PCR: evaluation of diagnostic sensitivity and specificity without gold standard

PubMed Central

Wahlström, Helene; Comin, Arianna; Isaksson, Mats; Deplazes, Peter

2016-01-01

Introduction A semi-automated magnetic capture probe-based DNA extraction and real-time PCR method (MC-PCR), allowing for a more efficient large-scale surveillance of Echinococcus multilocularis occurrence, has been developed. The test sensitivity has previously been evaluated using the sedimentation and counting technique (SCT) as a gold standard. However, as the sensitivity of the SCT is not 1, test characteristics of the MC-PCR was also evaluated using latent class analysis, a methodology not requiring a gold standard. Materials and methods Test results, MC-PCR and SCT, from a previous evaluation of the MC-PCR using 177 foxes shot in the spring (n=108) and autumn 2012 (n=69) in high prevalence areas in Switzerland were used. Latent class analysis was used to estimate the test characteristics of the MC-PCR. Although it is not the primary aim of this study, estimates of the test characteristics of the SCT were also obtained. Results and discussion This study showed that the sensitivity of the MC-PCR was 0.88 [95% posterior credible interval (PCI) 0.80–0.93], which was not significantly different than the SCT, 0.83 (95% PCI 0.76–0.88), which is currently considered as the gold standard. The specificity of both tests was high, 0.98 (95% PCI 0.94–0.99) for the MC-PCR and 0.99 (95% PCI 0.99–1) for the SCT. In a previous study, using fox scats from a low prevalence area, the specificity of the MC-PCR was higher, 0.999% (95% PCI 0.997–1). One reason for the lower estimate of the specificity in this study could be that the MC-PCR detects DNA from infected but non-infectious rodents eaten by foxes. When using MC-PCR in low prevalence areas or areas free from the parasite, a positive result in the MC-PCR should be regarded as a true positive. Conclusion The sensitivity of the MC-PCR (0.88) was comparable to the sensitivity of SCT (0.83). PMID:26968153

A Comparison of the Capability of Sensitivity Level 3 and Sensitivity Level 4 Fluorescent Penetrants to Detect Fatigue Cracks in Aluminum

NASA Technical Reports Server (NTRS)

Parker, Bradford, H.

2009-01-01

Historically both sensitivity level 3 and sensitivity level 4 fluorescent penetrants have been used to perform NASA Standard Level inspections of aerospace hardware. In April 2008, NASA-STD-5009 established a requirement that only sensitivity level 4 penetrants were acceptable for inspections of NASA hardware. Having NASA contractors change existing processes or perform demonstration tests to certify sensitivity level 3 penetrants posed a potentially huge cost to the Agency. This study was conducted to directly compare the probability of detection sensitivity level 3 and level 4 penetrants using both Method A and Method D inspection processes. The study results strongly support the conclusion that sensitivity level 3 penetrants are acceptable for NASA Standard Level inspections

Coffee consumption and risk of fractures: a meta-analysis

PubMed Central

Liu, Huifang; Yao, Ke; Zhang, Wenjie; Zhou, Jun; Wu, Taixiang

2012-01-01

Introduction Recent studies have indicated higher risk of fractures among coffee drinkers. To quantitatively assess the association between coffee consumption and the risk of fractures, we conducted this meta-analysis. Material and methods We searched MEDLINE and EMBASE for prospective studies reporting the risk of fractures with coffee consumption. Quality of included studies was assessed with the Newcastle Ottawa scale. We conducted a meta-analysis and a cumulative meta-analysis of relative risk (RR) for an increment of one cup of coffee per day, and explored the potential dose-response relationship. Sensitivity analysis was performed where statistical heterogeneity existed. Results We included 10 prospective studies covering 214,059 participants and 9,597 cases. There was overall 3.5% higher fracture risk for an increment of one cup of coffee per day (RR = 1.035, 95% CI: 1.019-1.052). Pooled RRs were 1.049 (95% CI: 1.022-1.077) for women and 0.910 (95% CI: 0.873-0.949) for men. Among women, RR was 1.055 (95% CI: 0.999-1.114) for younger participants, and 1.047 (95% CI: 1.016-1.080) for older ones. Cumulative meta-analysis indicated that risk estimates reached a stabilization level (RR = 1.035, 95% CI: 1.019-1.052), and it revealed a positive dose-response relationship between coffee consumption and risk of fractures either for men and women combined or women specifically. Conclusions This meta-analysis suggests an overall harm of coffee intake in increasing the risk of fractures, especially for women. But current data are insufficient to reach a convincing conclusion and further research needs to be conducted. PMID:23185185

Detection and classification of human body odor using an electronic nose.

PubMed

Wongchoosuk, Chatchawal; Lutz, Mario; Kerdcharoen, Teerakiat

2009-01-01

An electronic nose (E-nose) has been designed and equipped with software that can detect and classify human armpit body odor. An array of metal oxide sensors was used for detecting volatile organic compounds. The measurement circuit employs a voltage divider resistor to measure the sensitivity of each sensor. This E-nose was controlled by in-house developed software through a portable USB data acquisition card with a principle component analysis (PCA) algorithm implemented for pattern recognition and classification. Because gas sensor sensitivity in the detection of armpit odor samples is affected by humidity, we propose a new method and algorithms combining hardware/software for the correction of the humidity noise. After the humidity correction, the E-nose showed the capability of detecting human body odor and distinguishing the body odors from two persons in a relative manner. The E-nose is still able to recognize people, even after application of deodorant. In conclusion, this is the first report of the application of an E-nose for armpit odor recognition.

Effects of normalization on quantitative traits in association test

PubMed Central

2009-01-01

Background Quantitative trait loci analysis assumes that the trait is normally distributed. In reality, this is often not observed and one strategy is to transform the trait. However, it is not clear how much normality is required and which transformation works best in association studies. Results We performed simulations on four types of common quantitative traits to evaluate the effects of normalization using the logarithm, Box-Cox, and rank-based transformations. The impact of sample size and genetic effects on normalization is also investigated. Our results show that rank-based transformation gives generally the best and consistent performance in identifying the causal polymorphism and ranking it highly in association tests, with a slight increase in false positive rate. Conclusion For small sample size or genetic effects, the improvement in sensitivity for rank transformation outweighs the slight increase in false positive rate. However, for large sample size and genetic effects, normalization may not be necessary since the increase in sensitivity is relatively modest. PMID:20003414

4-Nitroquinoline-1-oxide effects human lung adenocarcinoma A549 cells by regulating the expression of POLD4

PubMed Central

HUANG, QIN-MIAO; ZENG, YI-MING; ZHANG, HUA-PING; LV, LIANG-CHAO; YANG, DONG-YONG; LIN, HUI-HUANG

2016-01-01

The aim of the present study was to explore the expression of POLD4 in human lung adenocarcinoma A549 cells under 4-nitroquinoline-1-oxide (4NQO) stimulation to investigate the role of POLD4 in smoking-induced lung cancer. The lung cancer A549 cell line was treated with 4NQO, with or without MG132 (an inhibitor of proteasome activity), and subsequently the POLD4 level was determined by western blot analysis. Secondly, the cell sensitivity to 4NQO and Taxol was determined when the POLD4 expression level was downregulated by siRNA. The POLD4 protein levels in the A549 cells decreased following treatment with 4NQO; however, MG132 could reverse this phenotype. Downregulation of the POLD4 expression by siRNA enhanced A549 cell sensitivity to 4NQO, but not to Taxol. In conclusion, 4NQO affects human lung adenocarcinoma A549 cells by regulating the expression of POLD4. PMID:26998273

First Trimester Maternal Serum PP13 in the Risk Assessment for Preeclampsia

PubMed Central

ROMERO, Roberto; KUSANOVIC, Juan Pedro; THAN, Nandor Gabor; EREZ, Offer; GOTSCH, Francesca; ESPINOZA, Jimmy; EDWIN, Samuel; CHEFETZ, Ilana; GOMEZ, Ricardo; NIEN, Jyh Kae; SAMMAR, Marei; PINELES, Beth; HASSAN, Sonia S.; MEIRI, Hamutal; TAL, Yossi; KUHNREICH, Ido; PAPP, Zoltan; CUCKLE, Howard S.

2008-01-01

Objective To determine whether first trimester maternal serum Placental Protein 13 (PP13) concentrations can be used in the risk assessment for preeclampsia. Study Design This case-control study included 50 patients with preeclampsia and 250 patients with normal pregnancies. Samples were collected between 8-13 weeks of gestation. Serum PP13 concentrations were measured by ELISA and expressed as medians and multiples of the median (MoM) for gestational age. Sensitivity and specificity were derived from receiver operating characteristic curve analysis. Results 1) Serum PP13 concentration in the first trimester was significantly lower in patients who developed preterm and early-onset preeclampsia than in those with normal pregnancies; and 2) At 80% specificity, a cutoff of 0.39 MoM had a sensitivity of 100% for early-onset preeclampsia and 85% for preterm preeclampsia. Conclusion Maternal serum first trimester PP13 appears to be a reasonable marker for risk assessment, but a weak marker for severe preeclampsia at term, and ineffective for identifying mild preeclampsia at term. PMID:18539259

Detection and Classification of Human Body Odor Using an Electronic Nose

PubMed Central

Wongchoosuk, Chatchawal; Lutz, Mario; Kerdcharoen, Teerakiat

2009-01-01

An electronic nose (E-nose) has been designed and equipped with software that can detect and classify human armpit body odor. An array of metal oxide sensors was used for detecting volatile organic compounds. The measurement circuit employs a voltage divider resistor to measure the sensitivity of each sensor. This E-nose was controlled by in-house developed software through a portable USB data acquisition card with a principle component analysis (PCA) algorithm implemented for pattern recognition and classification. Because gas sensor sensitivity in the detection of armpit odor samples is affected by humidity, we propose a new method and algorithms combining hardware/software for the correction of the humidity noise. After the humidity correction, the E-nose showed the capability of detecting human body odor and distinguishing the body odors from two persons in a relative manner. The E-nose is still able to recognize people, even after application of deodorant. In conclusion, this is the first report of the application of an E-nose for armpit odor recognition. PMID:22399995

High-precision drop shape analysis on inclining flat surfaces: introduction and comparison of this special method with commercial contact angle analysis.

PubMed

Schmitt, Michael; Heib, Florian

2013-10-07

Drop shape analysis is one of the most important and frequently used methods to characterise surfaces in the scientific and industrial communities. An especially large number of studies, which use contact angle measurements to analyse surfaces, are characterised by incorrect or misdirected conclusions such as the determination of surface energies from poorly performed contact angle determinations. In particular, the characterisation of surfaces, which leads to correlations between the contact angle and other effects, must be critically validated for some publications. A large number of works exist concerning the theoretical and thermodynamic aspects of two- and tri-phase boundaries. The linkage between theory and experiment is generally performed by an axisymmetric drop shape analysis, that is, simulations of the theoretical drop profiles by numerical integration onto a number of points of the drop meniscus (approximately 20). These methods work very well for axisymmetric profiles such as those obtained by pendant drop measurements, but in the case of a sessile drop onto real surfaces, additional unknown and misunderstood effects on the dependence of the surface must be considered. We present a special experimental and practical investigation as another way to transition from experiment to theory. This procedure was developed to be especially sensitive to small variations in the dependence of the dynamic contact angle on the surface; as a result, this procedure will allow the properties of the surface to be monitored with a higher precession and sensitivity. In this context, water drops onto a 111 silicon wafer are dynamically measured by video recording and by inclining the surface, which results in a sequence of non-axisymmetric drops. The drop profiles are analysed by commercial software and by the developed and presented high-precision drop shape analysis. In addition to the enhanced sensitivity for contact angle determination, this analysis technique, in combination with innovative fit algorithms and data presentations, can result in enhanced reproducibility and comparability of the contact angle measurements in terms of the material characterisation in a comprehensible way.

High-precision drop shape analysis on inclining flat surfaces: Introduction and comparison of this special method with commercial contact angle analysis

NASA Astrophysics Data System (ADS)

Schmitt, Michael; Heib, Florian

2013-10-01

Drop shape analysis is one of the most important and frequently used methods to characterise surfaces in the scientific and industrial communities. An especially large number of studies, which use contact angle measurements to analyse surfaces, are characterised by incorrect or misdirected conclusions such as the determination of surface energies from poorly performed contact angle determinations. In particular, the characterisation of surfaces, which leads to correlations between the contact angle and other effects, must be critically validated for some publications. A large number of works exist concerning the theoretical and thermodynamic aspects of two- and tri-phase boundaries. The linkage between theory and experiment is generally performed by an axisymmetric drop shape analysis, that is, simulations of the theoretical drop profiles by numerical integration onto a number of points of the drop meniscus (approximately 20). These methods work very well for axisymmetric profiles such as those obtained by pendant drop measurements, but in the case of a sessile drop onto real surfaces, additional unknown and misunderstood effects on the dependence of the surface must be considered. We present a special experimental and practical investigation as another way to transition from experiment to theory. This procedure was developed to be especially sensitive to small variations in the dependence of the dynamic contact angle on the surface; as a result, this procedure will allow the properties of the surface to be monitored with a higher precession and sensitivity. In this context, water drops onto a 111 silicon wafer are dynamically measured by video recording and by inclining the surface, which results in a sequence of non-axisymmetric drops. The drop profiles are analysed by commercial software and by the developed and presented high-precision drop shape analysis. In addition to the enhanced sensitivity for contact angle determination, this analysis technique, in combination with innovative fit algorithms and data presentations, can result in enhanced reproducibility and comparability of the contact angle measurements in terms of the material characterisation in a comprehensible way.

Confronting ‘confounding by health system use’ in Medicare Part D: Comparative effectiveness of propensity score approaches to confounding adjustment

PubMed Central

Polinski, Jennifer M.; Schneeweiss, Sebastian; Glynn, Robert J.; Lii, Joyce; Rassen, Jeremy

2012-01-01

Purpose Under Medicare Part D, patient characteristics influence plan choice, which in turn influences Part D coverage gap entry. We compared pre-defined propensity score (PS) and high-dimensional propensity score (hdPS) approaches to address such ‘confounding by health system use’ in assessing whether coverage gap entry is associated with cardiovascular events or death. Methods We followed 243,079 Medicare patients aged 65+ with linked prescription, medical, and plan-specific data in 2005–2007. Patients reached the coverage gap and were followed until an event or year’s end. Exposed patients were responsible for drug costs in the gap; unexposed patients (patients with non-Part D drug insurance and Part D patients receiving a low-income subsidy (LIS)) received financial assistance. Exposed patients were 1:1 PS- or hdPS-matched to unexposed patients. The PS model included 52 predefined covariates; the hdPS model added 400 empirically identified covariates. Hazard ratios for death and any of five cardiovascular outcomes were compared. In sensitivity analyses, we explored residual confounding using only LIS patients in the unexposed group. Results In unadjusted analyses, exposed patients had no greater hazard of death (HR=1.00; 95% CI, 0.84–1.20) or other outcomes. PS- (HR=1.29;0.99–1.66) and hdPS- (HR=1.11;0.86–1.42) matched analyses showed elevated but non-significant hazards of death. In sensitivity analyses, the PS analysis showed a protective effect (HR=0.78;0.61–0.98), while the hdPS analysis (HR=1.06;0.82–1.37) confirmed the main hdPS findings. Conclusion Although the PS-matched analysis suggested elevated though non-significant hazards of death among patients with no financial assistance during the gap, the hdPS analysis produced lower estimates that were stable across sensitivity analyses. PMID:22552984

[Gender-sensitive epidemiological data analysis: methodological aspects and empirical outcomes. Illustrated by a health reporting example].

PubMed

Jahn, I; Foraita, R

2008-01-01

In Germany gender-sensitive approaches are part of guidelines for good epidemiological practice as well as health reporting. They are increasingly claimed to realize the gender mainstreaming strategy in research funding by the federation and federal states. This paper focuses on methodological aspects of data analysis, as an empirical data example of which serves the health report of Bremen, a population-based cross-sectional study. Health reporting requires analysis and reporting methods that are able to discover sex/gender issues of questions, on the one hand, and consider how results can adequately be communicated, on the other hand. The core question is: Which consequences do a different inclusion of the category sex in different statistical analyses for identification of potential target groups have on the results? As evaluation methods logistic regressions as well as a two-stage procedure were exploratively conducted. This procedure combines graphical models with CHAID decision trees and allows for visualising complex results. Both methods are analysed by stratification as well as adjusted by sex/gender and compared with each other. As a result, only stratified analyses are able to detect differences between the sexes and within the sex/gender groups as long as one cannot resort to previous knowledge. Adjusted analyses can detect sex/gender differences only if interaction terms have been included in the model. Results are discussed from a statistical-epidemiological perspective as well as in the context of health reporting. As a conclusion, the question, if a statistical method is gender-sensitive, can only be answered by having concrete research questions and known conditions. Often, an appropriate statistic procedure can be chosen after conducting a separate analysis for women and men. Future gender studies deserve innovative study designs as well as conceptual distinctiveness with regard to the biological and the sociocultural elements of the category sex/gender.

Association of high sensitivity C-reactive protein and abdominal aortic aneurysm: a meta-analysis and systematic review.

PubMed

Wang, Yunpeng; Shen, Guanghui; Wang, Haiyang; Yao, Ye; Sun, Qingfeng; Jing, Bao; Liu, Gaoyan; Wu, Jia; Yuan, Chao; Liu, Siqi; Liu, Xinyu; Li, Shiyong; Li, Haocheng

2017-12-01

To evaluate the association of high sensitivity C-reactive protein (hsCRP) with the presence of abdominal aortic aneurysm (AAA). Medline, Cochrane, Embase, and Google Scholar databases were searched until 22 June 2016 using the keywords predictive factors, biomarkers, abdominal aortic aneurysm, prediction, high sensitivity C-reactive protein, and hsCRP. Prospective studies, retrospective studies, and cohort studies were included. Twelve case-control studies were included in the meta-analysis with a total of 8345 patients (1977 in the AAA group and 6368 in the control group). The pooled results showed that AAA patients had higher hsCRP value than the control group (difference in means = 1.827, 95% CI = 0.010 to 3.645, p = .049). Subgroup analysis found AAA patients with medium or small aortic diameter (<50 mm) had higher hsCRP plasma levels than the control group (difference in means = 1.301, 95% CI = 0.821 to 1.781, p < .001). In patients with large aortic diameter (≥50 mm), no difference was observed in hsCRP levels between the AAA and control groups (difference in means = 1.769, 95% CI = -1.387 to 4.925, p = .272). Multi-regression analysis found the difference in means of hsCRP plasma levels between AAA and control groups decreased as aortic diameter increased (slope = -0.04, p < .001), suggesting that hsCRP levels may be inversely associated with increasing aneurysm size. Our findings suggest that hsCRP levels may possibly be used as a diagnostic biomarker for AAA patients with medium or small aortic diameter but not for AAA patients with large aortic diameter. The correlation between serum hsCRP level and AAA aneurysm is not conclusive due to the small number of included articles and between-study heterogeneity.

Cost-effectiveness of daclatasvir plus asunaprevir for chronic hepatitis C genotype 1b treatment-naïve patients in China

PubMed Central

Lu, Yun; Jin, Xiuze; Duan, Cheng-a-xin

2018-01-01

Background Hepatitis C is the second fastest growing infectious disease in China. The standard-of-care for chronic hepatitis C in China is Pegylated interferon plus ribavirin (PR), which is associated with tolerability and efficacy issues. An interferon- and ribavirin-free, all-oral regimen comprising daclatasvir (DCV) and asunaprevir (ASV), which displays higher efficacy and tolerability, has recently been approved in China. Objectives This study is to estimate the cost-effectiveness of DCV+ASV (24 weeks) for chronic hepatitis C genotype 1b treatment-naïve patients compared with PR regimen (48 weeks) in China. Methods A cohort-based Markov model was developed from Chinese payer perspective to project the lifetime outcomes of treating 10,000 patients with an average age of 44.5 with two hypothetical regimens, DCV+ASV and PR. Chinese-specific health state costs and efficacy data were used. The annual discount rate was 5%. Base-case analysis and sensitivity analysis were conducted. Results For HCV Genotype 1b treatment-naïve patients, DCV+ASV proved to be dominant over PR, with a cost saving of ¥33,480(5,096 USD) and gains in QALYs and life years of 1.29 and 0.85, respectively. The lifetime risk of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver-related death was greatly reduced with DCV+ASV. Univariate sensitivity analysis demonstrated that key influencers were the discount rate, time horizon, initial disease severity and sustained virological response rate of DCV+ASV, with all scenarios resulting in additional benefit. Probabilistic sensitivity analysis demonstrated that DCV+ASV has a high likelihood (100%) of being cost-effective. Conclusion DCV+ASV is not only an effective and well-tolerated regimen to treat chronic HCV genotype 1b infection treatment-naïve patients, but also is more cost-effective than PR regimen. DCV+ASV can benefit both the public health and reimbursement system in China. PMID:29634736

The art and learning patterns of knowing in nursing.

PubMed

Baixinho, Cristina Lavareda; Ferraz, Isabel Carvalho Beato; Ferreira, Óscar Manuel Ramos; Rafael, Helga Marilia da Silva

2014-12-01

Objective To identify the perception of the students about the use of art as a pedagogical strategy in learning the patterns of knowing in nursing; to identify the dimensions of each pattern valued in the analysis of pieces of art. Method Descriptive mixed study. Data collection used a questionnaire applied to 31 nursing students. Results In the analysis of the students' discourse, it was explicit that empirical knowledge includes scientific knowledge, tradition and nature of care. The aesthetic knowledge implies expressiveness, subjectivity and sensitivity. Self-knowledge, experience, reflective attitude and relationships with others are the subcategories of personal knowledge and the moral and ethics support ethical knowledge. Conclusion It is possible to learn patterns of knowledge through art, especially the aesthetic, ethical and personal. It is necessary to investigate further pedagogical strategies that contribute to the learning patterns of nursing knowledge.

Effective psychological and psychosocial approaches to reduce repetition of self-harm: a systematic review, meta-analysis and meta-regression

PubMed Central

Robinson, Jo; Spittal, Matthew J; Carter, Greg

2016-01-01

Objective To examine the efficacy of psychological and psychosocial interventions for reductions in repeated self-harm. Design We conducted a systematic review, meta-analysis and meta-regression to examine the efficacy of psychological and psychosocial interventions to reduce repeat self-harm in adults. We included a sensitivity analysis of studies with a low risk of bias for the meta-analysis. For the meta-regression, we examined whether the type, intensity (primary analyses) and other components of intervention or methodology (secondary analyses) modified the overall intervention effect. Data sources A comprehensive search of MEDLINE, PsycInfo and EMBASE (from 1999 to June 2016) was performed. Eligibility criteria for selecting studies Randomised controlled trials of psychological and psychosocial interventions for adult self-harm patients. Results Forty-five trials were included with data available from 36 (7354 participants) for the primary analysis. Meta-analysis showed a significant benefit of all psychological and psychosocial interventions combined (risk ratio 0.84; 95% CI 0.74 to 0.96; number needed to treat=33); however, sensitivity analyses showed that this benefit was non-significant when restricted to a limited number of high-quality studies. Meta-regression showed that the type of intervention did not modify the treatment effects. Conclusions Consideration of a psychological or psychosocial intervention over and above treatment as usual is worthwhile; with the public health benefits of ensuring that this practice is widely adopted potentially worth the investment. However, the specific type and nature of the intervention that should be delivered is not yet clear. Cognitive–behavioural therapy or interventions with an interpersonal focus and targeted on the precipitants to self-harm may be the best candidates on the current evidence. Further research is required. PMID:27660314

Long-term effects of low-fat diets either low or high in protein on cardiovascular and metabolic risk factors: a systematic review and meta-analysis

PubMed Central

2013-01-01

Background Meta-analyses of short-term studies indicate favorable effects of higher protein vs. lower protein diets on health outcomes like adiposity or cardiovascular risk factors, but their long-term effects are unknown. Methods Electronic databases (MEDLINE, EMBASE, Cochrane Trial Register) were searched up to August 2012 with no restriction to language or calendar date. A random effect meta-analysis was performed using the Software package by the Cochrane Collaboration Review Manager 5.1. Sensitivity analysis was performed for RCTs with a Jadad Score ≥3, and excluding type 2 diabetic subjects (T2D). Results 15 RCTs met all objectives and were included in the present meta-analysis. No significant differences were observed for weight, waist circumference, fat mass, blood lipids (i.e. total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerols), C-reactive protein, diastolic and systolic blood pressure, fasting glucose and glycosylated hemoglobin. In contrast, improvements of fasting insulin was significantly more pronounced following high protein diets as compared to the low protein counterparts (weighted mean difference: -0.71 μIU/ml, 95% CI -1.36 to -0.05, p = 0.03). Sensitivity analysis of high quality RCTs confirmed the data of the primary analyses, while exclusion of studies with diabetic subjects resulted in an additional benefit of high-protein diets with respect to a more marked increase in HDL-cholesterol. Conclusion According to the present meta-analysis of long-term RCTs, high-protein diets exerted neither specific beneficial nor detrimental effects on outcome markers of obesity, cardiovascular disease or glycemic control. Thus, it seems premature to recommend high-protein diets in the management of overweight and obesity. PMID:23587198

Interpreting the results of chemical stone analysis in the era of modern stone analysis techniques

PubMed Central

Gilad, Ron; Williams, James C.; Usman, Kalba D.; Holland, Ronen; Golan, Shay; Ruth, Tor; Lifshitz, David

2017-01-01

Introduction and Objective Stone analysis should be performed in all first-time stone formers. The preferred analytical procedures are Fourier-transform infrared spectroscopy (FT-IR) or X-ray diffraction (XRD). However, due to limited resources, chemical analysis (CA) is still in use throughout the world. The aim of the study was to compare FT-IR and CA in well matched stone specimens and characterize the pros and cons of CA. Methods In a prospective bi-center study, urinary stones were retrieved from 60 consecutive endoscopic procedures. In order to assure that identical stone samples were sent for analyses, the samples were analyzed initially by micro-computed tomography to assess uniformity of each specimen before submitted for FTIR and CA. Results Overall, the results of CA did not match with the FTIR results in 56% of the cases. In 16% of the cases CA missed the major stone component and in 40% the minor stone component. 37 of the 60 specimens contained CaOx as major component by FTIR, and CA reported major CaOx in 47/60, resulting in high sensitivity, but very poor specificity. CA was relatively accurate for UA and cystine. CA missed struvite and calcium phosphate as a major component in all cases. In mixed stones the sensitivity of CA for the minor component was poor, generally less than 50%. Conclusions Urinary stone analysis using CA provides only limited data that should be interpreted carefully. Urinary stone analysis using CA is likely to result in clinically significant errors in its assessment of stone composition. Although the monetary costs of CA are relatively modest, this method does not provide the level of analytical specificity required for proper management of patients with metabolic stones. PMID:26956131

Rapid identification of apolipoprotein E genotypes by high-resolution melting analysis in Chinese Han and African Fang populations.

PubMed

Zhan, Xiu-Hui; Zha, Guang-Cai; Jiao, Ji-Wei; Yang, Li-Ye; Zhan, Xiao-Fen; Chen, Jiang-Tao; Xie, Dong-DE; Eyi, Urbano Monsuy; Matesa, Rocio Apicante; Obono, Maximo Miko Ondo; Ehapo, Carlos Sala; Wei, Er-Jia; Zheng, Yu-Zhong; Yang, Hui; Lin, Min

2015-02-01

Apolipoprotein E (APOE) gene polymorphism can affect APOE gene transcription, serum lipid levels and repair of tissue damage, which could place individuals at serious risk of cardiovascular disease or certain infectious diseases. Recently, high-resolution melting (HRM) analysis was reported to be a simple, inexpensive, accurate and sensitive method for the genotyping or/and scanning of rare mutations. For this reason, an HRM analysis was used in the present study for APOE genotyping in the Southern Chinese Han and African Fang populations. A total of 100 healthy Southern Chinese Han and 175 healthy African Fang individuals attended the study. Polymerase chain reaction-DNA sequencing was used as a reference method for the genotyping of these samples. The six APOE genotypes could all be rapidly and efficiently identified by HRM analysis, and 100% concordance was found between the HRM analysis and the reference method. The allele frequencies of APOE in the Southern Chinese Han population were 7.0, 87.5 and 5.5% for ɛ2, ɛ3 and ɛ4, respectively. In the African Fang population, the allele frequencies of APOE were 24.3, 65.7 and 10.0% for ɛ2, ɛ3 and ɛ4, respectively. A statistically significant difference was found between the allele frequencies between the populations (P<0.05). In conclusion, the present study revealed the molecular characterization of APOE gene polymorphism in the Han population from the Chaozhou region of Southern China and the Fang population from Equatorial Guinea. The findings of the study indicated that HRM analysis could be used as an accurate and sensitive method for the rapid screening and identification of APOE genotypes in prospective clinical and population genetic analyses.

Effects of coenzyme Q10 supplementation on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Mazidi, Mohsen; Kengne, Andre Pascal; Banach, Maciej

2018-02-01

The aim of this systematic review and meta-analysis of prospective interventional studies was to investigate the effects of coenzyme Q10 (CQ10) on plasma C-reactive protein (CRP) levels. PubMed/Medline, Web of Science (WoS), Cochrane Database and Google Scholar databases were searched (up to December 2016) to identify prospective studies evaluating the impact of CQ10 supplementation on CRP. Random effects models meta-analysis was used for quantitative data synthesis. Sensitivity analysis used the leave-one-out method, and heterogeneity was quantitatively assessed using the I 2 index. Systematic review PROSPERO database registration: CRD42016038155. From a total of 119 entries identified via searches, 7 studies were finally included to the analysis. The results of the meta-analysis indicated a non-significant reduction in CRP concentrations following supplementation with CQ10 with a weighted mean difference [WMD] of -0.25mg/l (95% confidence intervals [CI] -0.56 to 0.06, I 2 =42.0%). The WMD for the effects on interleukin 6 (IL6) was -0.72pg/dl, (95% CI -1.24 to -0.24, I 2 =51.8%). These findings were robust in sensitivity analyses. Random-effects meta-regression revealed that changes in plasma CRP levels were independent of the dosage of CQ10 (slope: -0.0005; 95% CI: -0.005, 0.004; p=0.832) while duration of supplementation was the dependent mediator (slope: slope: -0.111; 95% CI: -0.21, -0.004; p=0.042). In conclusion, CQ10 supplementation has a borderline favourable effect on CRP levels, and a significant effect on IL-6 level. This suggests that CQ10 supplementation likely attenuates subclinical inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mini-implants for orthodontic anchorage.

PubMed

Reynders, Reint Meursinge; Ladu, Luisa

2017-10-27

Data sourcesPubmed, Embase, Cochrane Central Register of Controlled Trials and the Web of Science databases. Hand searches of the journals European Journal of Orthodontics, Journal of Orthodontics, Journal of Clinical Orthodontics, Seminars in Orthodontics, American Journal of Orthodontics & Dentofacial Orthopaedics and Angle Orthodontist.Study selectionTwo reviewers independently selected studies. Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) of orthodontic patients requiring extraction of the maxillary first premolars and closure of the spaces without anchorage loss were considered.Data extraction and synthesisData extraction and risk of bias assessment were carried out independently by two reviewers. Meta-analysis and sensitivity analysis were conducted.ResultsFourteen studies; seven RCTS and seven CCTs were included. In total 303 patients received TISADs with 313 control patients. Overall the quality of the studies was considered to be moderate. Overall the TISAD group had significantly less anchorage loss than the control group. On average, TISADs enabled 1.86mm more anchorage preservation than did conventional methods.ConclusionsThe results of the meta-analysis showed that TISADs are more effective than conventional methods of anchorage reinforcement. The average difference of 2mm seems not only statistically but also clinically significant. However, the results should be interpreted with caution because of the moderate quality of the included studies. More high-quality studies on this issue are necessary to enable drawing more reliable conclusions.

SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool.

PubMed

Zi, Zhike; Zheng, Yanan; Rundell, Ann E; Klipp, Edda

2008-08-15

It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software tools are limited in their ability to perform global sensitivity analyses of these models. This work introduces a freely downloadable, software package, SBML-SAT, which implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL's method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface. SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes.

Sensitivity analysis of a wing aeroelastic response

NASA Technical Reports Server (NTRS)

Kapania, Rakesh K.; Eldred, Lloyd B.; Barthelemy, Jean-Francois M.

1991-01-01

A variation of Sobieski's Global Sensitivity Equations (GSE) approach is implemented to obtain the sensitivity of the static aeroelastic response of a three-dimensional wing model. The formulation is quite general and accepts any aerodynamics and structural analysis capability. An interface code is written to convert one analysis's output to the other's input, and visa versa. Local sensitivity derivatives are calculated by either analytic methods or finite difference techniques. A program to combine the local sensitivities, such as the sensitivity of the stiffness matrix or the aerodynamic kernel matrix, into global sensitivity derivatives is developed. The aerodynamic analysis package FAST, using a lifting surface theory, and a structural package, ELAPS, implementing Giles' equivalent plate model are used.

Effect of dietary fiber on circulating C-reactive protein in overweight and obese adults: a meta-analysis of randomized controlled trials.

PubMed

Jiao, Jun; Xu, Jia-Ying; Zhang, Weiguo; Han, Shufen; Qin, Li-Qiang

2015-02-01

Previous studies suggested that dietary fiber intake may have a lowing effect on circulating C-reactive protein (CRP) level, a sensitive marker of inflammation, in overweight/obese adults with inconsistent results. A literature search was performed in April 2014 for related randomized controlled trials (RCTs) and meta-analysis was conducted. Meta-analysis including 14 RCTs showed that intervention with dietary fiber or fiber-rich food, compared with control, produced a slight, but significant reduction of 0.37 mg/L (95% CI -0.74, 0) in circulating CRP level among this population. Subgroup analyses showed that such a significant reduction was only observed after combining studies where the total fiber intake was 8 g/d higher in the intervention group than in the control group. No obvious heterogeneity and publication bias were found in the meta-analysis. In conclusion, this meta-analysis provides evidence that dietary fiber or food naturally rich in fiber has beneficial effects on circulating CRP level in overweight/obese adults.

Dietary fat intake and ovarian cancer risk: a meta-analysis of epidemiological studies

PubMed Central

Qiu, Wenlong; Lu, Heng; Qi, Yana; Wang, Xiuwen

2016-01-01

Observational studies assessing the association of dietary fat and risk of ovarian cancer yield discrepant results. Pertinent prospective cohort studies were identified by a PubMed search from inception to December 2015. Sixteen independent case-control and nine cohort studies on dietary fat intake were included, with approximately 900,000 subjects in total. Relative risks (RRs) with 95% confidence intervals were pooled using a random effects model. Heterogeneity, sensitivity analysis and publication bias were assessed; subgroup analysis and analysis stratified by EOC histology were conducted. The reported studies showed a significant increase of ovarian cancer risk with high consumption of total-, saturated-, and trans-fats, while serous ovarian cancer was more susceptible to dietary fat consumption than other pathological subtypes. No evidence of positive association between dietary fat intake and ovarian cancer risk was provided by cohort studies. Menopausal status, hormone replacement therapy, body mass index (BMI), and pregnancy times, modified the objective associations. In conclusion, the meta-analysis findings indicate that high consumption of total, saturated and trans-fats increase ovarian cancer risk, and different histological subtypes have different susceptibility to dietary fat. PMID:27119509

Clustering effects on postprandial insulin secretion and sensitivity in response to meals with different fatty acid compositions.

PubMed

Bermudez, Beatriz; Ortega-Gomez, Almudena; Varela, Lourdes M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G; Lopez, Sergio

2014-07-25

Dietary fatty acids play a role in glucose homeostasis. The aim of this study was to assess the individual relationship between dietary saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids with postprandial β-cell function and insulin sensitivity in subjects with normal and high fasting triglycerides. We assessed postprandial β-cell function (by the insulinogenic index and the ratio of the insulin to glucose areas under the time-concentration curve) and insulin sensitivity (by the oral glucose and the minimal model insulin sensitivity indices) over four nonconsecutive, randomly assigned, high-fat meals containing a panel of SFA (palmitic and stearic acids), MUFA (palmitoleic and oleic acids) and PUFA (linoleic and α-linolenic acids) in 14 subjects with normal and in 14 subjects with high fasting triglycerides. The proportions of each fatty acid in the meals and the values for surrogate measures of postprandial β-cell function and insulin sensitivity were subjected to a Pearson correlation and hierarchical cluster analysis, which revealed two classes of dietary fatty acids for regulating postprandial glucose homeostasis. We successfully discriminated the adverse effects of SFA palmitic acid from the beneficial effects of MUFA oleic acid on postprandial β-cell function (r ≥ 0.84 for SFA palmitic acid and r ≥ -0.71 for MUFA oleic acid; P < 0.05) and insulin sensitivity (r ≥ -0.92 for SFA palmitic acid and r ≥ 0.89 for MUFA oleic acid; P < 0.001) both in subjects with normal and high fasting triglycerides. In conclusion, dietary MUFA oleic acid, in contrast to SFA palmitic acid, favours the tuning towards better postprandial glycaemic control in subjects with normal and high fasting triglycerides.

Sensitivity of Hyperdense Basilar Artery Sign on Non-Enhanced Computed Tomography

PubMed Central

Ernst, Marielle; Romero, Javier M.; Buhk, Jan-Hendrik; Cheng, Bastian; Herrmann, Jochen; Fiehler, Jens; Groth, Michael

2015-01-01

Purpose The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO. Materials and Methods 102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio. Results Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54–95%) while specificity was high 91% (95%-CI, 82–96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60–98%) and specificity of 84% (95%-CI, 74–90%). Conclusion In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT. PMID:26479718

Structure-Function Modeling of Optical Coherence Tomography and Standard Automated Perimetry in the Retina of Patients with Autosomal Dominant Retinitis Pigmentosa

PubMed Central

Smith, Travis B.; Parker, Maria; Steinkamp, Peter N.; Weleber, Richard G.; Smith, Ning; Wilson, David J.

2016-01-01

Purpose To assess relationships between structural and functional biomarkers, including new topographic measures of visual field sensitivity, in patients with autosomal dominant retinitis pigmentosa. Methods Spectral domain optical coherence tomography line scans and hill of vision (HOV) sensitivity surfaces from full-field standard automated perimetry were semi-automatically aligned for 60 eyes of 35 patients. Structural biomarkers were extracted from outer retina b-scans along horizontal and vertical midlines. Functional biomarkers were extracted from local sensitivity profiles along the b-scans and from the full visual field. These included topographic measures of functional transition such as the contour of most rapid sensitivity decline around the HOV, herein called HOV slope for convenience. Biomarker relationships were assessed pairwise by coefficients of determination (R2) from mixed-effects analysis with automatic model selection. Results Structure-function relationships were accurately modeled (conditional R2>0.8 in most cases). The best-fit relationship models and correlation patterns for horizontally oriented biomarkers were different than vertically oriented ones. The structural biomarker with the largest number of significant functional correlates was the ellipsoid zone (EZ) width, followed by the total photoreceptor layer thickness. The strongest correlation observed was between EZ width and HOV slope distance (marginal R2 = 0.85, p<10−10). The mean sensitivity defect at the EZ edge was 7.6 dB. Among all functional biomarkers, the HOV slope mean value, HOV slope mean distance, and maximum sensitivity along the b-scan had the largest number of significant structural correlates. Conclusions Topographic slope metrics show promise as functional biomarkers relevant to the transition zone. EZ width is strongly associated with the location of most rapid HOV decline. PMID:26845445

An adjuvant free mouse model of oral allergenic sensitization to rice seeds protein

PubMed Central

2011-01-01

Background Rice is commonly known as a staple crop consumed worldwide, though with several rice proteins being reported for allergic properties in clinical studies. Thus, there is a growing need for the development of an animal model to better understand the allergenicity of rice proteins and the immunological and pathophysiological mechanisms underlying the development of food allergy. Methods Groups of BALB/c mice were sensitized daily with freshly homogenized rice flour (30 mg or 80 mg) without adjuvant by intragastric gavage. In addition, the mice were challenged with extracted rice flour proteins at several time points intragastrically. Hypersensitivity symptoms in mice were evaluated according to a scoring system. Vascular leakage, ELISA of rice protein-specific IgE, histopathology of small intestine, and passive cutaneous anaphylaxis were conducted on challenged mice. Results An adjuvant free mouse model of rice allergy was established with sensitized mice showing increased scratching behaviors and increased vascular permeability. Rice protein-specific IgE was detected after eighteen days of sensitization and from the fifth challenge onwards. Inflammatory damage to the epithelium in the small intestine of mice was observed beyond one month of sensitization. Passive cutaneous anaphylaxis results confirmed the positive rice allergy in the mouse model. Conclusions We introduced a BALB/c mouse model of rice allergy with simple oral sensitization without the use of adjuvant. This model would serve as a useful tool for further analysis on the immunopathogenic mechanisms of the various rice allergens, for the evaluation of the hypersensitivity of rice or other cereal grains, and to serve as a platform for the development of immunotherapies against rice allergens. PMID:21605393

Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers

PubMed Central

Weingartshofer, Sigrid; Rappaport-Fürhauser, Christine; Zeilinger, Robert; Pils, Dietmar; Muhr, Daniela; Braicu, Elena I.; Kastner, Marie-Therese; Tan, Yen Y.; Semmler, Lorenz; Sehouli, Jalid; Singer, Christian F.

2017-01-01

Background Screening for ovarian cancer (OC) in women at high risk consists of a combination of carbohydrate antigen 125 (CA125) and transvaginal ultrasound, despite their low sensitivity and specificity. This could be improved by the combination of several biomarkers, which has been shown in average risk patients but has not been investigated until now in female BRCA mutation carriers. Methods Using a multiplex, bead-based, immunoassay system, we analyzed the concentrations of leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, CA125 and human epididymis antigen 4 in 26 healthy wild type women, 26 healthy BRCA1 mutation carriers, 28 wildtype OC patients and 26 OC patients with BRCA1 mutation. Results Using the ROC analysis, we found a high overall sensitivity of 94.3% in differentiating healthy controls from OC patients with comparable results in the wildtype subgroup (sensitivity 92.8%, AUC = 0.988; p = 5.2e-14) as well as in BRCA1 mutation carriers (sensitivity 95.2%, AUC = 0.978; p = 1.7e-15) at an overall specificity of 92.3%. The used algorithm also allowed to identify healthy BRCA1 mutation carriers when compared to healthy wildtype women (sensitivity 88.4%, specificity 80.7%, AUC = 0.895; p = 6e-08), while this was less pronounced in patients with OC (sensitivity 66.7%, specificity 67.8%, AUC = 0.724; p = 0.00065). Conclusion We have developed an algorithm, which can differentiate between healthy women and OC patients and have for the first time shown, that such an algorithm can also be used in BRCA mutation carriers. To clarify a suggested benefit to the existing early detection program, large prospective trials with mainly early stage OC cases are warranted. PMID:29244844

BAD phosphorylation determines ovarian cancer chemo-sensitivity and patient survival

PubMed Central

Marchion, Douglas C.; Cottrill, Hope M.; Xiong, Yin; Chen, Ning; Bicaku, Elona; Fulp, William J.; Bansal, Nisha; Chon, Hye Sook; Stickles, Xiaomang B.; Kamath, Siddharth G.; Hakam, Ardeshir; Li, Lihua; Su, Dan; Moreno, Carolina; Judson, Patricia L.; Berchuck, Andrew; Wenham, Robert M.; Apte, Sachin M.; Gonzalez-Bosquet, Jesus; Bloom, Gregory C.; Eschrich, Steven A.; Sebti, Said; Chen, Dung-Tsa; Lancaster, Johnathan M.

2011-01-01

Purpose Despite initial sensitivity to chemotherapy, ovarian cancers (OVCA) often develop drug-resistance, which limits patient survival. Using specimens and/or genomic data from 289 patients and a panel of cancer cell lines, we explored genome-wide expression changes that underlie the evolution of OVCA chemo-resistance and characterized the BCL2 antagonist of cell death (BAD) apoptosis pathway as a determinant of chemo-sensitivity and patient survival. Experimental Design Serial OVCA cell cisplatin treatments were performed in parallel with measurements of genome-wide expression changes. Pathway analysis was performed on genes associated with increasing cisplatin-resistance (EC50). BAD-pathway expression and BAD-protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemo-sensitivity and/or clinical outcome and as therapeutic targets. Results Induced in vitro OVCA cisplatin-resistance was associated with BAD-pathway expression (P < 0.001). In OVCA cell lines and primary specimens, BAD-protein phosphorylation was associated with platinum-resistance (n = 147, P < 0.0001) and also with overall patient survival (n = 134, P = 0.0007). Targeted modulation of BAD-phosphorylation levels influenced cisplatin sensitivity. A 47-gene BAD-pathway score was associated with in vitro phosphorylated-BAD levels and with survival in 142 patients with advanced-stage (III/IV) serous OVCA. Integration of BAD-phosphorylation or BAD-pathway score with OVCA surgical cytoreductive status was significantly associated with overall survival by log-rank test (P = 0.004 and <0.0001, respectively). Conclusion The BAD apoptosis pathway influences OVCA chemo-sensitivity and overall survival, likely via modulation of BAD-phosphorylation. The pathway has clinical relevance as a biomarker of therapeutic response, patient survival, and as a promising therapeutic target. PMID:21849418

Structure and Function in Patients with Glaucomatous Defects Near Fixation

PubMed Central

Shafi, Asifa; Swanson, William H.; Dul, Mitchell W.

2010-01-01

Purpose To assess relations between perimetric sensitivity and neuroretinal rim area using high-resolution perimetric mapping in patients with glaucomatous defects within 10 degrees of fixation. Methods One eye was tested in each of 31 patients with open angle glaucoma enrolled in a prospective study of perimetric defects within 10 degrees of fixation. Norms were derived from 110 control subjects free of eye disease ages 21 – 81. Perimetric sensitivity was measured using the 10-2 test pattern with the SITA Standard algorithm (HFAII-i, Carl Zeiss Meditec), stimulus size III. Area of the temporal neuroretinal rim was measured using the Heidelberg Retinal Tomograph (HRT III). Decibel (dB) values were converted into linear units of contrast sensitivity averaged across locations corresponding to the temporal rim sector. Both measures were expressed as percent of mean normal and the Bland-Altman method was used to assess agreement. Perimetric locations corresponding to the temporal sector were determined for six different optic nerve maps. Results Contrast sensitivity was moderately correlated with temporal rim area (r2 > 30%, p < 0.005). For all six optic nerve maps, Bland-Altman analysis found good agreement between perimetric sensitivity and rim area with both measures expressed as fraction of mean normal, and confidence limits for agreement that were consistent with normal between-subject variability in control eyes. Conclusions Using high-resolution perimetric mapping in patients with scotomas within 10° of fixation, we confirmed findings of linear relations between perimetric sensitivity and area of temporal neuroretinal rim, and showed that the confidence limits for agreement in patients with glaucoma were consistent with normal between-subject variability. PMID:20935585

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, M; Finlay, J; Zhu, T

Purpose: Photosensitizer concentration during photodynamic therapy (PDT) is an important parameter for accurate dosimetry. Fluorescence signal can be used as a measure of photosensitizer concentration. Two methods of data acquisition were compared to an ex vivo study both for in vivo and phantom models. Methods: Fluorescence signal of commonly used photosensitizer benzoporphyrin derivative monoacid ring A (BPD) was obtained in phantoms and mouse tumors using an excitation light of 405 nm. Interstitial fluorescence signal was obtained using a side-cut fiber inserted into the tumor tissue of interest. Using a previously developed multi-fiber probe, tumor surface fluorescence measurements were also collected.more » Signals were calibrated according to optical phantoms with known sensitizer fluorescence. Optical properties for each sample were determined and the influence of different absorption and scattering properties on the fluorescence signals was investigated. Using single value decomposition of the spectra, the sensitizer concentration was determined using the two different measurement geometries. An ex vivo analysis was also performed for tumor samples to determine the sensitizer concentration. Results: The two fluorescence signals obtained from the surface multi-fiber probe and the interstitial measurements were compared and were corresponding for both phantoms and mouse models. The values obtained were comparable to the ex vivo measurements as well. Despite the difference in geometry, the surface probe measurements can still be used as a metric for determining the presence of sensitizer in small volume tumors. Conclusion: The multi-fiber contact probe can be used as a tool to measure fluorescence at the surface of the treatment area for PDT and predict sensitizer concentration throughout the tumor. This is advantageous in that the measurement does not damage any tissue. Future work will include investigating the dependence of these results on intratumor sensitizer distribution.« less

Sensitization to Rubber Accelerators in Northeastern Italy: The Triveneto Patch Test Database.

PubMed

Buttazzo, Silvia; Prodi, Andrea; Fortina, Anna Belloni; Corradin, Maria Teresa; Larese Filon, Francesca

2016-01-01

Natural and synthetic rubbers containing rubber accelerators are well-known causes of occupational skin disease. Allergic contact dermatitis caused by rubber gloves is frequent and has almost exclusively been attributed to contact sensitization to accelerators. This study aimed to evaluate the frequency of rubber accelerators sensitization in the population living in northeastern Italy, to find time trend and a correlation with occupations, and to investigate co-sensitization between rubber accelerators. A population of 23,774 subjects was patch tested in 6 cities in northeastern Italy in the years 1996 to 2012 using carba mix 3%, thiuram mix 1%, benzothiazole (MBT) mix 1%, and isopropyl phenyl paraphenylamine diamine (IPPD) mix 0.6%. The overall frequency of carbamates, MBT, thiurams, and IPPD mix sensitization was 3.4%, 0.65%, 1.75%, and 0.83%, respectively. On a logistic regression analysis (control group: white-collar workers), we found a statistically significant association to carbamates (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.03-1.7) and thiurams (OR, 1.6; 95% CI, 1.1-2.3) for health care workers. Thiuram sensitivity was also significantly associated with dermatitis in maids and restaurant workers (OR, 2.2; 95% CI, 1.4-3.6), hairdressers (OR, 3.6; 95% CI, 1.8-7.1), shop assistants (OR, 2.9; 95% CI, 1.2-6.8), construction workers (OR, 2.7; 95% CI, 1.7-4.1), mechanics (OR, 2.1; 95% CI, 1.3-3.4), and professional drivers (OR, 2.6; 95% CI, 1.2-5.9). In conclusion, our results demonstrated that rubber accelerators have an important role in allergic contact dermatitis in the northeast of Italy and their sensitization is associated significantly with occupations that wear gloves or use chemical substances. Between rubber accelerators tested, carbamates sensitization is prevalent and increasing during considered years.

Global Sensitivity Analysis of Environmental Models: Convergence, Robustness and Validation

NASA Astrophysics Data System (ADS)

Sarrazin, Fanny; Pianosi, Francesca; Khorashadi Zadeh, Farkhondeh; Van Griensven, Ann; Wagener, Thorsten

2015-04-01

Global Sensitivity Analysis aims to characterize the impact that variations in model input factors (e.g. the parameters) have on the model output (e.g. simulated streamflow). In sampling-based Global Sensitivity Analysis, the sample size has to be chosen carefully in order to obtain reliable sensitivity estimates while spending computational resources efficiently. Furthermore, insensitive parameters are typically identified through the definition of a screening threshold: the theoretical value of their sensitivity index is zero but in a sampling-base framework they regularly take non-zero values. There is little guidance available for these two steps in environmental modelling though. The objective of the present study is to support modellers in making appropriate choices, regarding both sample size and screening threshold, so that a robust sensitivity analysis can be implemented. We performed sensitivity analysis for the parameters of three hydrological models with increasing level of complexity (Hymod, HBV and SWAT), and tested three widely used sensitivity analysis methods (Elementary Effect Test or method of Morris, Regional Sensitivity Analysis, and Variance-Based Sensitivity Analysis). We defined criteria based on a bootstrap approach to assess three different types of convergence: the convergence of the value of the sensitivity indices, of the ranking (the ordering among the parameters) and of the screening (the identification of the insensitive parameters). We investigated the screening threshold through the definition of a validation procedure. The results showed that full convergence of the value of the sensitivity indices is not necessarily needed to rank or to screen the model input factors. Furthermore, typical values of the sample sizes that are reported in the literature can be well below the sample sizes that actually ensure convergence of ranking and screening.

Emerging Biliteracy and Cross-Cultural Sensitivity in a Language Arts Classroom.

ERIC Educational Resources Information Center

Reyes, Maria de la Luz; And Others

1993-01-01

Presents overall conclusions from research and case studies of four children who showed indicators of emerging biliteracy and cultural sensitivity in a language arts class where the inherent link between culture and language was evident. Illustrates how the language arts instruction in a bilingual classroom affected children's growth in a second…

Clarifying the debate on population-based screening for breast cancer with mammography

PubMed Central

Chen, Tony Hsiu-Hsi; Yen, Amy Ming-Fang; Fann, Jean Ching-Yuan; Gordon, Paula; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Hsu, Chen-Yang; Chang, King-Jen; Lee, Won-Chul; Yeoh, Khay Guan; Saito, Hiroshi; Promthet, Supannee; Hamashima, Chisato; Maidin, Alimin; Robinson, Fredie; Zhao, Li-Zhong

2017-01-01

Abstract Background: The recent controversy about using mammography to screen for breast cancer based on randomized controlled trials over 3 decades in Western countries has not only eclipsed the paradigm of evidence-based medicine, but also puts health decision-makers in countries where breast cancer screening is still being considered in a dilemma to adopt or abandon such a well-established screening modality. Methods: We reanalyzed the empirical data from the Health Insurance Plan trial in 1963 to the UK age trial in 1991 and their follow-up data published until 2015. We first performed Bayesian conjugated meta-analyses on the heterogeneity of attendance rate, sensitivity, and over-detection and their impacts on advanced stage breast cancer and death from breast cancer across trials using Bayesian Poisson fixed- and random-effect regression model. Bayesian meta-analysis of causal model was then developed to assess a cascade of causal relationships regarding the impact of both attendance and sensitivity on 2 main outcomes. Results: The causes of heterogeneity responsible for the disparities across the trials were clearly manifested in 3 components. The attendance rate ranged from 61.3% to 90.4%. The sensitivity estimates show substantial variation from 57.26% to 87.97% but improved with time from 64% in 1963 to 82% in 1980 when Bayesian conjugated meta-analysis was conducted in chronological order. The percentage of over-detection shows a wide range from 0% to 28%, adjusting for long lead-time. The impacts of the attendance rate and sensitivity on the 2 main outcomes were statistically significant. Causal inference made by linking these causal relationships with emphasis on the heterogeneity of the attendance rate and sensitivity accounted for the variation in the reduction of advanced breast cancer (none-30%) and of mortality (none-31%). We estimated a 33% (95% CI: 24–42%) and 13% (95% CI: 6–20%) breast cancer mortality reduction for the best scenario (90% attendance rate and 95% sensitivity) and the poor scenario (30% attendance rate and 55% sensitivity), respectively. Conclusion: Elucidating the scenarios from high to low performance and learning from the experiences of these trials helps screening policy-makers contemplate on how to avoid errors made in ineffective studies and emulate the effective studies to save women lives. PMID:28099330

Sensitivity Analysis of Weather Variables on Offsite Consequence Analysis Tools in South Korea and the United States.

PubMed

Kim, Min-Uk; Moon, Kyong Whan; Sohn, Jong-Ryeul; Byeon, Sang-Hoon

2018-05-18

We studied sensitive weather variables for consequence analysis, in the case of chemical leaks on the user side of offsite consequence analysis (OCA) tools. We used OCA tools Korea Offsite Risk Assessment (KORA) and Areal Location of Hazardous Atmospheres (ALOHA) in South Korea and the United States, respectively. The chemicals used for this analysis were 28% ammonia (NH₃), 35% hydrogen chloride (HCl), 50% hydrofluoric acid (HF), and 69% nitric acid (HNO₃). The accident scenarios were based on leakage accidents in storage tanks. The weather variables were air temperature, wind speed, humidity, and atmospheric stability. Sensitivity analysis was performed using the Statistical Package for the Social Sciences (SPSS) program for dummy regression analysis. Sensitivity analysis showed that impact distance was not sensitive to humidity. Impact distance was most sensitive to atmospheric stability, and was also more sensitive to air temperature than wind speed, according to both the KORA and ALOHA tools. Moreover, the weather variables were more sensitive in rural conditions than in urban conditions, with the ALOHA tool being more influenced by weather variables than the KORA tool. Therefore, if using the ALOHA tool instead of the KORA tool in rural conditions, users should be careful not to cause any differences in impact distance due to input errors of weather variables, with the most sensitive one being atmospheric stability.

A two-step sensitivity analysis for hydrological signatures in Jinhua River Basin, East China

NASA Astrophysics Data System (ADS)

Pan, S.; Fu, G.; Chiang, Y. M.; Xu, Y. P.

2016-12-01

Owing to model complexity and large number of parameters, calibration and sensitivity analysis are difficult processes for distributed hydrological models. In this study, a two-step sensitivity analysis approach is proposed for analyzing the hydrological signatures in Jinhua River Basin, East China, using the Distributed Hydrology-Soil-Vegetation Model (DHSVM). A rough sensitivity analysis is firstly conducted to obtain preliminary influential parameters via Analysis of Variance. The number of parameters was greatly reduced from eighteen-three to sixteen. Afterwards, the sixteen parameters are further analyzed based on a variance-based global sensitivity analysis, i.e., Sobol's sensitivity analysis method, to achieve robust sensitivity rankings and parameter contributions. Parallel-Computing is applied to reduce computational burden in variance-based sensitivity analysis. The results reveal that only a few number of model parameters are significantly sensitive, including rain LAI multiplier, lateral conductivity, porosity, field capacity, wilting point of clay loam, understory monthly LAI, understory minimum resistance and root zone depths of croplands. Finally several hydrological signatures are used for investigating the performance of DHSVM. Results show that high value of efficiency criteria didn't indicate excellent performance of hydrological signatures. For most samples from Sobol's sensitivity analysis, water yield was simulated very well. However, lowest and maximum annual daily runoffs were underestimated. Most of seven-day minimum runoffs were overestimated. Nevertheless, good performances of the three signatures above still exist in a number of samples. Analysis of peak flow shows that small and medium floods are simulated perfectly while slight underestimations happen to large floods. The work in this study helps to further multi-objective calibration of DHSVM model and indicates where to improve the reliability and credibility of model simulation.

(U) Second-Order Sensitivity Analysis of Uncollided Particle Contributions to Radiation Detector Responses Using Ray-Tracing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Favorite, Jeffrey A.

The Second-Level Adjoint Sensitivity System (2nd-LASS) that yields the second-order sensitivities of a response of uncollided particles with respect to isotope densities, cross sections, and source emission rates is derived in Refs. 1 and 2. In Ref. 2, we solved problems for the uncollided leakage from a homogeneous sphere and a multiregion cylinder using the PARTISN multigroup discrete-ordinates code. In this memo, we derive solutions of the 2nd-LASS for the particular case when the response is a flux or partial current density computed at a single point on the boundary, and the inner products are computed using ray-tracing. Both themore » PARTISN approach and the ray-tracing approach are implemented in a computer code, SENSPG. The next section of this report presents the equations of the 1st- and 2nd-LASS for uncollided particles and the first- and second-order sensitivities that use the solutions of the 1st- and 2nd-LASS. Section III presents solutions of the 1st- and 2nd-LASS equations for the case of ray-tracing from a detector point. Section IV presents specific solutions of the 2nd-LASS and derives the ray-trace form of the inner products needed for second-order sensitivities. Numerical results for the total leakage from a homogeneous sphere are presented in Sec. V and for the leakage from one side of a two-region slab in Sec. VI. Section VII is a summary and conclusions.« less

Evaluation of HBsAg and anti-HBc assays in saliva and dried blood spot samples according HIV status.

PubMed

Flores, Geane Lopes; Cruz, Helena Medina; Potsch, Denise Vigo; May, Silvia Beatriz; Brandão-Mello, Carlos Eduardo; Pires, Marcia Maria Amendola; Pilotto, Jose Henrique; Lewis-Ximenez, Lia Laura; Lampe, Elisabeth; Villar, Livia Melo

2017-09-01

Influence of HIV status in HBV markers detection in saliva and dried blood spots (DBS) was not well established. This study aims to evaluate the performance of optimized commercial immunoassay for identifying HBsAg and anti-HBc in saliva and DBS according HIV status. A sum of 535 individuals grouped as HIV + , HBV + , HIV/HBV + and HIV/HBV- were recruited where 347 and 188 were included for HBsAg and anti-HBc evaluation, respectively. Serum, DBS collected in Whatman 903 paper and saliva obtained using salivette device were analyzed using EIA. Increased sample volume and ROC curve analysis for cut off determination were used for DBS and saliva testing. HBsAg detection in saliva and DBS exhibited sensitivities of 80.9% and 85.6% and specificities of 86.8% and 96.3%. Sensitivity of anti-HBc in saliva and DBS were 82.4% and 76.9% and specificities in saliva and DBS were 96.9% and 91.7%. Low sensitivities were observed for HBsAg (62%) and anti-HBc (47%) detection in saliva of HIV/HBV+ individuals. OD values were also lower for HBsAg detection in DBS and saliva of HIV/HBV+ individuals compared to their serum samples. Statistical significance was found for sensitivities in HBsAg detection between saliva and DBS demonstrating high sensitivity for DBS specimens. In conclusion, HIV status or antiretroviral treatment appears to interfere in the performance of HBsAg and anti-HBc detection in DBS and saliva samples using the adapted commercial EIA. Copyright © 2017 Elsevier B.V. All rights reserved.

Penetrating Colorectal Injuries: Diagnostic Performance of Multidetector CT with Trajectography.

PubMed

Dreizin, David; Boscak, Alexis R; Anstadt, Michael J; Tirada, Nikki; Chiu, William C; Munera, Felipe; Bodanapally, Uttam K; Hornick, Michael; Stein, Deborah M

2016-12-01

Purpose To determine the diagnostic performance of multidetector computed tomography (CT) with trajectography for penetrating colorectal injuries. Materials and Methods This institutional review board-approved and HIPAA-compliant study was a 6-year blinded retrospective review by two independent readers of 182 consecutive patients who preoperatively underwent 40- or 64-row multidetector CT for penetrating torso trauma below the diaphragm and had surgically confirmed findings. Colorectal perforation was present in 42 patients. Trajectory analysis with postprocessing software was used for all studies. Additional signs evaluated were rectal contrast agent leak, collections of extruded fecal material, mural defect, wall thickening, abnormal enhancement, free fluid or stranding, and free air. The quality of the colorectal contrast agent administration was recorded. Sensitivity, specificity, predictive values, areas under the receiver operating characteristic curves (AUCs), and Cohen κ were determined. Results In patients with rectal contrast agent administration (n = 151), AUCs were 0.90-0.91, which indicated excellent accuracy. Trajectory was sensitive (88%-91%). For single wounds (n = 104), sensitivity of trajectory was 96% for both readers, but was only 80% for multiple wounds (n = 47). Contrast agent leak was highly specific (96%-98%), but insensitive (42%-46%). Improved diagnostic performance was observed in patients with poor colonic distension or opacification. Accuracy remained high (AUC, 0.86-0.99) in the group without rectal contrast agent administration (n = 31). Conclusion Trajectory had excellent sensitivity, while rectal contrast agent leak was specific but insensitive. Sensitivity of trajectory was lower for multiple wounds. Accuracy remained high in patients without rectal contrast agent administration. © RSNA, 2016.

Microbiological and molecular identification of bacterial species isolated from nasal and oropharyngeal mucosa of fuel workers in Riyadh, Saudi Arabia.

PubMed

AlWakeel, Suaad S

2017-09-01

This study aimed to determine the bacterial species colonizing the nasal and oropharyngeal mucosa of fuel workers in Central Riyadh, Saudi Arabia on a microbiological and molecular level. Throat and nasal swab samples were obtained from 29 fuel station attendants in the period of time extending from March to May 2014 in Riyadh, Saudi Arabia. Microbiological identification techniques were utilized to identify the bacterial species isolated. Antibiotic sensitivity was assessed for each of the bacterial isolates. Molecular identification techniques based on PCR analysis of specific genomic sequences was conducted and was the basis on which phylogeny representation was done for 10 randomly selected samples of the isolates. Blood was drawn and a complete blood count was conducted to note the hematological indices for each of the study participants. Nineteen bacterial species were isolated from both the nasal cavity and the oropharynx including Streptococcus thoraltensis , alpha-hemolytic streptococci, Staphylococcus hominis , coagulase-negative staphylococci, Leuconostoc mesenteroides , Erysipelothrix rhusiopathiae and several others. We found 100% sensitivity of the isolates to ciprofloxacin, cefuroxime and gentamicin. Whereas cefotaxime and azithromycin posted sensitivities of 85.7% and 91.4%, respectively. Low sensitivities (<60% sensitivity) to the antibiotics ampicillin, erythromycin, clarithromycin and norfloxacin were observed. Ninety-seven percent similarity to the microbial bank species was noted when the isolates were compared to it. Most hematological indices recorded were within the normal range. In conclusion, exposure to toxic fumes and compounds within fuel products may be a contributing factor to bacterial colonization of the respiratory tract in fuel workers.

Analysis of the Sensitivity and Specificity of Noninvasive Imaging Tests for the Diagnosis of Renal Artery Stenosis

PubMed Central

Borelli, Flavio Antonio de Oliveira; Pinto, Ibraim M. F.; Amodeo, Celso; Smanio, Paola E. P.; Kambara, Antonio M.; Petisco, Ana Claudia G.; Moreira, Samuel M.; Paiva, Ricardo Calil; Lopes, Hugo Belotti; Sousa, Amanda G. M. R.

2013-01-01

Background Aging and atherosclerosis are related to renovascular hypertension in elderly individuals. Regardless of comorbidities, renal artery stenosis is itself an important cause of cardiovascular morbidity and mortality. Objective To define the sensitivity, specificity, positive predictive value, and negative predictive value of noninvasive imaging tests used in the diagnosis of renal artery stenosis. Methods In a group of 61 patients recruited, 122 arteries were analized, thus permitting the definition of sensitivity, specificity, and the relative contribution of each imaging study performed (Doppler, scintigraphy and computed tomographic angiography in comparison to renal arteriography). Results The mean age was 65.43 years (standard deviation: 8.7). Of the variables related to the study population that were compared to arteriography, two correlated with renal artery stenosis, renal dysfunction and triglycerides. The median glomerular filtration rate was 52.8 mL/min/m2. Doppler showed sensitivity of 82.90%, specificity of 70%, a positive predictive value of 85% and negative predictive value of 66.70%. For tomography, sensitivity was 66.70%, specificity 80%, positive predictive value 87.50% and negative predictive value 55.20%. With these findings, we could identify the imaging tests that best detected stenosis. Conclusion Tomography and Doppler showed good quality and efficacy in the diagnosis of renal artery stenosis, with Doppler having the advantage of not requiring the use of contrast medium for the assessment of a disease that is common in diabetics and is associated with renal dysfunction and severe left ventricular dysfunction. PMID:24061685

Urinary Metabolites Associated with Blood Pressure on a Low- or High-Sodium Diet

PubMed Central

Cheng, Yuan; Song, Haiying; Pan, Xiaoqing; Xue, Hong; Wan, Yifei; Wang, Tao; Tian, Zhongmin; Hou, Entai; Lanza, Ian R.; Liu, Pengyuan; Liu, Yong; Laud, Purushottam W.; Usa, Kristie; He, Yongcheng; Liang, Mingyu

2018-01-01

Dietary salt intake has significant effects on arterial blood pressure and the development of hypertension. Mechanisms underlying salt-dependent changes in blood pressure remain poorly understood, and it is difficult to assess blood pressure salt-sensitivity clinically. Methods: We examined urinary levels of metabolites in 103 participants of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial after nearly 30 days on a defined diet containing high sodium (targeting 150 mmol sodium intake per day) or low sodium (50 mmol per day). Targeted chromatography/mass spectrometry analysis was performed in 24 h urine samples for 47 amino metabolites and 10 metabolites related to the tricarboxylic acid cycle. The effect of an identified metabolite on blood pressure was examined in Dahl salt-sensitive rats. Results: Urinary metabolite levels improved the prediction of classification of blood pressure salt-sensitivity based on race, age and sex. Random forest and generalized linear mixed model analyses identified significant (false discovery rate <0.05) associations of 24 h excretions of β-aminoisobutyric acid, cystine, citrulline, homocysteine and lysine with systolic blood pressure and cystine with diastolic blood pressure. The differences in homocysteine levels between low- and high-sodium intakes were significantly associated with the differences in diastolic blood pressure. These associations were significant with or without considering demographic factors. Treatment with β-aminoisobutyric acid significantly attenuated high-salt-induced hypertension in Dahl salt-sensitive rats. Conclusion: These findings support the presence of new mechanisms of blood pressure regulation involving metabolic intermediaries, which could be developed as markers or therapeutic targets for salt-sensitive hypertension. PMID:29556335

Digital Rectal Examination and Balloon Expulsion Test in the Study of Defecatory Disorders: Are They Suitable as Screening or Excluding Tests?

PubMed

Caetano, Ana C; Santa-Cruz, André; Rolanda, Carla

2016-01-01

Background . Rome III criteria add physiological criteria to symptom-based criteria of chronic constipation (CC) for the diagnosis of defecatory disorders (DD). However, a gold-standard test is still lacking and physiological examination is expensive and time-consuming. Aim . Evaluate the usefulness of two low-cost tests-digital rectal examination (DRE) and balloon expulsion test (BET)-as screening or excluding tests of DD. Methods . We performed a systematic search in PUBMED and MEDLINE. We selected studies where constipated patients were evaluated by DRE or BET. Heterogeneity was assessed and random effect models were used to calculate the sensitivity, specificity, and negative predictive value (NPV) of the DRE and the BET. Results . Thirteen studies evaluating BET and four studies evaluating DRE (2329 patients) were selected. High heterogeneity ( I 2 > 80%) among studies was demonstrated. The studies evaluating the BET showed a sensitivity and specificity of 67% and 80%, respectively. Regarding the DRE, a sensitivity of 80% and specificity of 84% were calculated. NPV of 72% for the BET and NPV of 64% for the DRE were estimated. The sensitivity and specificity were similar when we restrict the analysis to studies using Rome criteria to define CC. The BET seems to perform better when a cut-off time of 2 minutes is used and when it is compared with a combination of physiological tests. Considering the DRE, strict criteria seem to improve the sensitivity but not the specificity of the test. Conclusion . Neither of the low-cost tests seems suitable for screening or excluding DD.

Characterization of Adrenal Adenoma by Gaussian Model-Based Algorithm.

PubMed

Hsu, Larson D; Wang, Carolyn L; Clark, Toshimasa J

2016-01-01

We confirmed that computed tomography (CT) attenuation values of pixels in an adrenal nodule approximate a Gaussian distribution. Building on this and the previously described histogram analysis method, we created an algorithm that uses mean and standard deviation to estimate the percentage of negative attenuation pixels in an adrenal nodule, thereby allowing differentiation of adenomas and nonadenomas. The institutional review board approved both components of this study in which we developed and then validated our criteria. In the first, we retrospectively assessed CT attenuation values of adrenal nodules for normality using a 2-sample Kolmogorov-Smirnov test. In the second, we evaluated a separate cohort of patients with adrenal nodules using both the conventional 10HU unit mean attenuation method and our Gaussian model-based algorithm. We compared the sensitivities of the 2 methods using McNemar's test. A total of 183 of 185 observations (98.9%) demonstrated a Gaussian distribution in adrenal nodule pixel attenuation values. The sensitivity and specificity of our Gaussian model-based algorithm for identifying adrenal adenoma were 86.1% and 83.3%, respectively. The sensitivity and specificity of the mean attenuation method were 53.2% and 94.4%, respectively. The sensitivities of the 2 methods were significantly different (P value < 0.001). In conclusion, the CT attenuation values within an adrenal nodule follow a Gaussian distribution. Our Gaussian model-based algorithm can characterize adrenal adenomas with higher sensitivity than the conventional mean attenuation method. The use of our algorithm, which does not require additional postprocessing, may increase workflow efficiency and reduce unnecessary workup of benign nodules. Copyright © 2016 Elsevier Inc. All rights reserved.

Urinary Metabolites Associated with Blood Pressure on a Low- or High-Sodium Diet.

PubMed

Cheng, Yuan; Song, Haiying; Pan, Xiaoqing; Xue, Hong; Wan, Yifei; Wang, Tao; Tian, Zhongmin; Hou, Entai; Lanza, Ian R; Liu, Pengyuan; Liu, Yong; Laud, Purushottam W; Usa, Kristie; He, Yongcheng; Liang, Mingyu

2018-01-01

Dietary salt intake has significant effects on arterial blood pressure and the development of hypertension. Mechanisms underlying salt-dependent changes in blood pressure remain poorly understood, and it is difficult to assess blood pressure salt-sensitivity clinically. Methods: We examined urinary levels of metabolites in 103 participants of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial after nearly 30 days on a defined diet containing high sodium (targeting 150 mmol sodium intake per day) or low sodium (50 mmol per day). Targeted chromatography/mass spectrometry analysis was performed in 24 h urine samples for 47 amino metabolites and 10 metabolites related to the tricarboxylic acid cycle. The effect of an identified metabolite on blood pressure was examined in Dahl salt-sensitive rats. Results: Urinary metabolite levels improved the prediction of classification of blood pressure salt-sensitivity based on race, age and sex. Random forest and generalized linear mixed model analyses identified significant (false discovery rate <0.05) associations of 24 h excretions of β-aminoisobutyric acid, cystine, citrulline, homocysteine and lysine with systolic blood pressure and cystine with diastolic blood pressure. The differences in homocysteine levels between low- and high-sodium intakes were significantly associated with the differences in diastolic blood pressure. These associations were significant with or without considering demographic factors. Treatment with β-aminoisobutyric acid significantly attenuated high-salt-induced hypertension in Dahl salt-sensitive rats. Conclusion: These findings support the presence of new mechanisms of blood pressure regulation involving metabolic intermediaries, which could be developed as markers or therapeutic targets for salt-sensitive hypertension.

MOVES sensitivity analysis update : Transportation Research Board Summer Meeting 2012 : ADC-20 Air Quality Committee

DOT National Transportation Integrated Search

2012-01-01

OVERVIEW OF PRESENTATION : Evaluation Parameters : EPAs Sensitivity Analysis : Comparison to Baseline Case : MOVES Sensitivity Run Specification : MOVES Sensitivity Input Parameters : Results : Uses of Study

Cost Analysis of the Dutch Obstetric System: low-risk nulliparous women preferring home or short-stay hospital birth - a prospective non-randomised controlled study

PubMed Central

2009-01-01

Background In the Netherlands, pregnant women without medical complications can decide where they want to give birth, at home or in a short-stay hospital setting with a midwife. However, a decrease in the home birth rate during the last decennium may have raised the societal costs of giving birth. The objective of this study is to compare the societal costs of home births with those of births in a short-stay hospital setting. Methods This study is a cost analysis based on the findings of a multicenter prospective non-randomised study comparing two groups of nulliparous women with different preferences for where to give birth, at home or in a short-stay hospital setting. Data were collected using cost diaries, questionnaires and birth registration forms. Analysis of the data is divided into a base case analysis and a sensitivity analysis. Results In the group of home births, the total societal costs associated with giving birth at home were €3,695 (per birth), compared with €3,950 per birth in the group for short-stay hospital births. Statistically significant differences between both groups were found regarding the following cost categories 'Cost of contacts with health care professionals during delivery' (€138.38 vs. €87.94, -50 (2.5-97.5 percentile range (PR)-76;-25), p < 0.05), 'cost of maternity care at home' (€1,551.69 vs. €1,240.69, -311 (PR -485; -150), p < 0.05) and 'cost of hospitalisation mother' (€707.77 vs. 959.06, 251 (PR 69;433), p < 0.05). The highest costs are for hospitalisation (41% of all costs). Because there is a relatively high amount of (partly) missing data, a sensitivity analysis was performed, in which all missing data were included in the analysis by means of general mean substitution. In the sensitivity analysis, the total costs associated with home birth are €4,364 per birth, and €4,541 per birth for short-stay hospital births. Conclusion The total costs associated with pregnancy, delivery, and postpartum care are comparable for home birth and short-stay hospital birth. The most important differences in costs between the home birth group and the short-stay hospital birth group are associated with maternity care assistance, hospitalisation, and travelling costs. PMID:19925673

MOVES regional level sensitivity analysis

DOT National Transportation Integrated Search

2012-01-01

The MOVES Regional Level Sensitivity Analysis was conducted to increase understanding of the operations of the MOVES Model in regional emissions analysis and to highlight the following: : the relative sensitivity of selected MOVES Model input paramet...

MLH1 Promoter Methylation and Prediction/Prognosis of Gastric Cancer: A Systematic Review and Meta and Bioinformatic Analysis.

PubMed

Shen, Shixuan; Chen, Xiaohui; Li, Hao; Sun, Liping; Yuan, Yuan

2018-01-01

Background: The promoter methylation of MLH1 gene and gastric cancer (GC)has been investigated previously. To get a more credible conclusion, we performed a systematic review and meta and bioinformatic analysis to clarify the role of MLH1 methylation in the prediction and prognosis of GC. Methods: Eligible studies were targeted after searching the PubMed, Web of Science, Embase, BIOSIS, CNKI and Wanfang Data to collect the information of MLH1 methylation and GC. The link strength between the two was estimated by odds ratio with its 95% confidence interval. The Newcastle-Ottawa scale was used for quantity assessment . Subgroup and sensitivity analysis were conducted to explore sources of heterogeneity. The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were employed for bioinformatics analysis on the correlation between MLH1 methylation and GC risk, clinicopathological behavior as well as prognosis. Results: 2365 GC and 1563 controls were included in the meta-analysis. The pooled OR of MLH1 methylation in GC was 4.895 (95% CI: 3.149-7.611, P<0.001), which considerably associated with increased GC risk. No significant difference was found in relation to Lauren classification, tumor invasion, lymph node/distant metastasis and tumor stage in GC. Analysis based on GEO and TCGA showed that high MLH1 methylation enhanced GC risk but might not related with GC clinicopathological features and prognosis. Conclusion: MLH1 methylation is an alive biomarker for the prediction of GC and it might not affect GC behavior. Further study could be conducted to verify the impact of MLH1 methylation on GC prognosis.

MLH1 Promoter Methylation and Prediction/Prognosis of Gastric Cancer: A Systematic Review and Meta and Bioinformatic Analysis

PubMed Central

Shen, Shixuan; Chen, Xiaohui; Li, Hao; Sun, Liping; Yuan, Yuan

2018-01-01

Background: The promoter methylation of MLH1 gene and gastric cancer (GC)has been investigated previously. To get a more credible conclusion, we performed a systematic review and meta and bioinformatic analysis to clarify the role of MLH1 methylation in the prediction and prognosis of GC. Methods: Eligible studies were targeted after searching the PubMed, Web of Science, Embase, BIOSIS, CNKI and Wanfang Data to collect the information of MLH1 methylation and GC. The link strength between the two was estimated by odds ratio with its 95% confidence interval. The Newcastle-Ottawa scale was used for quantity assessment. Subgroup and sensitivity analysis were conducted to explore sources of heterogeneity. The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were employed for bioinformatics analysis on the correlation between MLH1 methylation and GC risk, clinicopathological behavior as well as prognosis. Results: 2365 GC and 1563 controls were included in the meta-analysis. The pooled OR of MLH1 methylation in GC was 4.895 (95% CI: 3.149-7.611, P<0.001), which considerably associated with increased GC risk. No significant difference was found in relation to Lauren classification, tumor invasion, lymph node/distant metastasis and tumor stage in GC. Analysis based on GEO and TCGA showed that high MLH1 methylation enhanced GC risk but might not related with GC clinicopathological features and prognosis. Conclusion: MLH1 methylation is an alive biomarker for the prediction of GC and it might not affect GC behavior. Further study could be conducted to verify the impact of MLH1 methylation on GC prognosis. PMID:29896277

Robotic Versus Open Renal Transplantation in Obese Patients: Protocol for a Cost-Benefit Markov Model Analysis

PubMed Central

Puttarajappa, Chethan; Wijkstrom, Martin; Ganoza, Armando; Lopez, Roberto; Tevar, Amit

2018-01-01

Background Recent studies have reported a significant decrease in wound problems and hospital stay in obese patients undergoing renal transplantation by robotic-assisted minimally invasive techniques with no difference in graft function. Objective Due to the lack of cost-benefit studies on the use of robotic-assisted renal transplantation versus open surgical procedure, the primary aim of our study is to develop a Markov model to analyze the cost-benefit of robotic surgery versus open traditional surgery in obese patients in need of a renal transplant. Methods Electronic searches will be conducted to identify studies comparing open renal transplantation versus robotic-assisted renal transplantation. Costs associated with the two surgical techniques will incorporate the expenses of the resources used for the operations. A decision analysis model will be developed to simulate a randomized controlled trial comparing three interventional arms: (1) continuation of renal replacement therapy for patients who are considered non-suitable candidates for renal transplantation due to obesity, (2) transplant recipients undergoing open transplant surgery, and (3) transplant patients undergoing robotic-assisted renal transplantation. TreeAge Pro 2017 R1 TreeAge Software, Williamstown, MA, USA) will be used to create a Markov model and microsimulation will be used to compare costs and benefits for the two competing surgical interventions. Results The model will simulate a randomized controlled trial of adult obese patients affected by end-stage renal disease undergoing renal transplantation. The absorbing state of the model will be patients' death from any cause. By choosing death as the absorbing state, we will be able simulate the population of renal transplant recipients from the day of their randomization to transplant surgery or continuation on renal replacement therapy to their death and perform sensitivity analysis around patients' age at the time of randomization to determine if age is a critical variable for cost-benefit analysis or cost-effectiveness analysis comparing renal replacement therapy, robotic-assisted surgery or open renal transplant surgery. After running the model, one of the three competing strategies will result as the most cost-beneficial or cost-effective under common circumstances. To assess the robustness of the results of the model, a multivariable probabilistic sensitivity analysis will be performed by modifying the mean values and confidence intervals of key parameters with the main intent of assessing if the winning strategy is sensitive to rigorous and plausible variations of those values. Conclusions After running the model, one of the three competing strategies will result as the most cost-beneficial or cost-effective under common circumstances. To assess the robustness of the results of the model, a multivariable probabilistic sensitivity analysis will be performed by modifying the mean values and confidence intervals of key parameters with the main intent of assessing if the winning strategy is sensitive to rigorous and plausible variations of those values. PMID:29519780

Evaluation of digital real-time PCR assay as a molecular diagnostic tool for single-cell analysis.

PubMed

Chang, Chia-Hao; Mau-Hsu, Daxen; Chen, Ke-Cheng; Wei, Cheng-Wey; Chiu, Chiung-Ying; Young, Tai-Horng

2018-02-21

In a single-cell study, isolating and identifying single cells are essential, but these processes often require a large investment of time or money. The aim of this study was to isolate and analyse single cells using a novel platform, the PanelChip™ Analysis System, which includes 2500 microwells chip and a digital real-time polymerase chain reaction (dqPCR) assay, in comparison with a standard PCR (qPCR) assay. Through the serial dilution of a known concentration standard, namely pUC19, the accuracy and sensitivity levels of two methodologies were compared. The two systems were tested on the basis of expression levels of the genetic markers vimentin, E-cadherin, N-cadherin and GAPDH in A549 lung carcinoma cells at two known concentrations. Furthermore, the influence of a known PCR inhibitor commonly found in blood samples, heparin, was evaluated in both methodologies. Finally, mathematical models were proposed and separation method of single cells was verified; moreover, gene expression levels during epithelial-mesenchymal transition in single cells under TGFβ1 treatment were measured. The drawn conclusion is that dqPCR performed using PanelChip™ is superior to the standard qPCR in terms of sensitivity, precision, and heparin tolerance. The dqPCR assay is a potential tool for clinical diagnosis and single-cell applications.

Bias magnification in ecologic studies: a methodological investigation

PubMed Central

Webster, Thomas F

2007-01-01

Background As ecologic studies are often inexpensive to conduct, consideration of the magnitude and direction of ecologic biases may be useful in both study design and sensitivity analysis of results. This paper examines three types of ecologic bias: confounding by group, effect measure modification by group, and non-differential exposure misclassification. Methods Bias of the risk difference on the individual and ecologic levels are compared using two-by-two tables, simple equations, and risk diagrams. Risk diagrams provide a convenient way to simultaneously display information from both levels. Results Confounding by group and effect measure modification by group act in the same direction on the individual and group levels, but have larger impact on the latter. The reduction in exposure variance caused by aggregation magnifies the individual level bias due to ignoring groups. For some studies, the magnification factor can be calculated from the ecologic data alone. Small magnification factors indicate little bias beyond that occurring at the individual level. Aggregation is also responsible for the different impacts of non-differential exposure misclassification on individual and ecologic studies. Conclusion The analytical tools developed here are useful in analyzing ecologic bias. The concept of bias magnification may be helpful in designing ecologic studies and performing sensitivity analysis of their results. PMID:17615079

Cost-effectiveness of methadone maintenance therapy as HIV prevention in an Indonesian high-prevalence setting: a mathematical modeling study.

PubMed

Wammes, Joost J G; Siregar, Adiatma Y; Hidayat, Teddy; Raya, Reynie P; van Crevel, Reinout; van der Ven, André J; Baltussen, Rob

2012-09-01

Indonesia faces an HIV epidemic that is in rapid transition. Injecting drug users (IDUs) are among the most heavily affected risk populations, with estimated prevalence of HIV reaching 50% or more in most parts of the country. Although Indonesia started opening methadone clinics in 2003, coverage remains low. We used the Asian Epidemic Model and Resource Needs Model to evaluate the long-term population-level preventive impact of expanding Methadone Maintenance Therapy (MMT) in West Java (43 million people). We compared intervention costs and the number of incident HIV cases in the intervention scenario with current practice to establish the cost per infection averted by expanding MMT. An extensive sensitivity analysis was performed on costs and epidemiological input, as well as on the cost-effectiveness calculation itself. Our analysis shows that expanding MMT from 5% coverage now to 40% coverage in 2019 would avert approximately 2400 HIV infections, at a cost of approximately US$7000 per HIV infection averted. Sensitivity analyses demonstrate that the use of alternative assumptions does not change the study conclusions. Our analyses suggest that expanding MMT is cost-effective, and support government policies to make MMT widely available as an integrated component of HIV/AIDS control in West Java. Copyright © 2012 Elsevier B.V. All rights reserved.

Mapping the Structure-Function Relationship in Glaucoma and Healthy Patients Measured with Spectralis OCT and Humphrey Perimetry

PubMed Central

Muñoz–Negrete, Francisco J.; Oblanca, Noelia; Rebolleda, Gema

2018-01-01

Purpose To study the structure-function relationship in glaucoma and healthy patients assessed with Spectralis OCT and Humphrey perimetry using new statistical approaches. Materials and Methods Eighty-five eyes were prospectively selected and divided into 2 groups: glaucoma (44) and healthy patients (41). Three different statistical approaches were carried out: (1) factor analysis of the threshold sensitivities (dB) (automated perimetry) and the macular thickness (μm) (Spectralis OCT), subsequently applying Pearson's correlation to the obtained regions, (2) nonparametric regression analysis relating the values in each pair of regions that showed significant correlation, and (3) nonparametric spatial regressions using three models designed for the purpose of this study. Results In the glaucoma group, a map that relates structural and functional damage was drawn. The strongest correlation with visual fields was observed in the peripheral nasal region of both superior and inferior hemigrids (r = 0.602 and r = 0.458, resp.). The estimated functions obtained with the nonparametric regressions provided the mean sensitivity that corresponds to each given macular thickness. These functions allowed for accurate characterization of the structure-function relationship. Conclusions Both maps and point-to-point functions obtained linking structure and function damage contribute to a better understanding of this relationship and may help in the future to improve glaucoma diagnosis. PMID:29850196

A dynamic model of some malaria-transmitting anopheline mosquitoes of the Afrotropical region. I. Model description and sensitivity analysis

PubMed Central

2013-01-01

Background Most of the current biophysical models designed to address the large-scale distribution of malaria assume that transmission of the disease is independent of the vector involved. Another common assumption in these type of model is that the mortality rate of mosquitoes is constant over their life span and that their dispersion is negligible. Mosquito models are important in the prediction of malaria and hence there is a need for a realistic representation of the vectors involved. Results We construct a biophysical model including two competing species, Anopheles gambiae s.s. and Anopheles arabiensis. Sensitivity analysis highlight the importance of relative humidity and mosquito size, the initial conditions and dispersion, and a rarely used parameter, the probability of finding blood. We also show that the assumption of exponential mortality of adult mosquitoes does not match the observed data, and suggest that an age dimension can overcome this problem. Conclusions This study highlights some of the assumptions commonly used when constructing mosquito-malaria models and presents a realistic model of An. gambiae s.s. and An. arabiensis and their interaction. This new mosquito model, OMaWa, can improve our understanding of the dynamics of these vectors, which in turn can be used to understand the dynamics of malaria. PMID:23342980

Quantitative analysis of the thermal requirements for stepwise physical dormancy-break in seeds of the winter annual Geranium carolinianum (Geraniaceae)

PubMed Central

Gama-Arachchige, N. S.; Baskin, J. M.; Geneve, R. L.; Baskin, C. C.

2013-01-01

Background and Aims Physical dormancy (PY)-break in some annual plant species is a two-step process controlled by two different temperature and/or moisture regimes. The thermal time model has been used to quantify PY-break in several species of Fabaceae, but not to describe stepwise PY-break. The primary aims of this study were to quantify the thermal requirement for sensitivity induction by developing a thermal time model and to propose a mechanism for stepwise PY-breaking in the winter annual Geranium carolinianum. Methods Seeds of G. carolinianum were stored under dry conditions at different constant and alternating temperatures to induce sensitivity (step I). Sensitivity induction was analysed based on the thermal time approach using the Gompertz function. The effect of temperature on step II was studied by incubating sensitive seeds at low temperatures. Scanning electron microscopy, penetrometer techniques, and different humidity levels and temperatures were used to explain the mechanism of stepwise PY-break. Key Results The base temperature (Tb) for sensitivity induction was 17·2 °C and constant for all seed fractions of the population. Thermal time for sensitivity induction during step I in the PY-breaking process agreed with the three-parameter Gompertz model. Step II (PY-break) did not agree with the thermal time concept. Q10 values for the rate of sensitivity induction and PY-break were between 2·0 and 3·5 and between 0·02 and 0·1, respectively. The force required to separate the water gap palisade layer from the sub-palisade layer was significantly reduced after sensitivity induction. Conclusions Step I and step II in PY-breaking of G. carolinianum are controlled by chemical and physical processes, respectively. This study indicates the feasibility of applying the developed thermal time model to predict or manipulate sensitivity induction in seeds with two-step PY-breaking processes. The model is the first and most detailed one yet developed for sensitivity induction in PY-break. PMID:23456728

Aspartame Sensitivity? A Double Blind Randomised Crossover Study

PubMed Central

Sathyapalan, Thozhukat; Thatcher, Natalie J.; Hammersley, Richard; Rigby, Alan S.; Pechlivanis, Alexandros; Gooderham, Nigel J.; Holmes, Elaine; le Roux, Carel W.; Atkin, Stephen L.; Courts, Fraser

2015-01-01

Background Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation. Methods This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics. Results Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects. Conclusion Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of aspartame does not have any detectable psychological or metabolic effects in humans. Trial Registration ISRCTN Registry ISRCTN39650237 PMID:25786106

Influence of some design parameters on the thermal performance of domestic refrigerator appliances

NASA Astrophysics Data System (ADS)

Rebora, Alessandro; Senarega, Maurizio; Tagliafico, Luca A.

2006-07-01

This paper presents a thermal study on chest-freezers, the small refrigerators used in domestic and supermarket applications. A thermal and energy model of a particular kind of these refrigerators, the “hot-wall” (or “skin condenser”) refrigerator, is developed and used to perform sensitivity and design optimisation analysis for given working temperatures and useful volume of the refrigerated cell. A finite-element heat transfer model of the refrigerator box is coupled to the complete thermodynamic model of the refrigerating plant, including real working conditions (compressor efficiency, friction pressure losses and so on). A sensitivity study of the main design parameters affecting the global refrigerator performance has been developed (for fixed working temperatures) with reference to the thickness of the metallic plates, to the evaporator and condenser tube diameters and to the evaporator tube pitch (with fixed evaporator-to-condenser tube pitch ratio). The results obtained show that the proposed sensitivity analysis can yield quite reliable results (in comparison with much more complex, albeit more accurate mathematical optimisation algorithms) using small computational resources. The great importance of 2-D heat conduction in the metallic plates is shown, evidencing how the plate thickness and the evaporator and condenser tube diameters affect the global performance of the system according to the well-known “fin efficiency” effect. The influence of the evaporator and condenser tube diameters on the friction pressure losses is also outlined. Some practical suggestions are made in conclusion, regarding the criteria which should be adopted in the thermal design of a hot-wall refrigerator.

Cost-Effectiveness Analysis of Probiotic Use to Prevent Clostridium difficile Infection in Hospitalized Adults Receiving Antibiotics

PubMed Central

Leff, Jared A; Schneider, Yecheskel; Crawford, Carl V; Maw, Anna; Bosworth, Brian; Simon, Matthew S

2017-01-01

Abstract Background Systematic reviews with meta-analyses and meta-regression suggest that timely probiotic use can prevent Clostridium difficile infection (CDI) in hospitalized adults receiving antibiotics, but the cost effectiveness is unknown. We sought to evaluate the cost effectiveness of probiotic use for prevention of CDI versus no probiotic use in the United States. Methods We programmed a decision analytic model using published literature and national databases with a 1-year time horizon. The base case was modeled as a hypothetical cohort of hospitalized adults (mean age 68) receiving antibiotics with and without concurrent probiotic administration. Projected outcomes included quality-adjusted life-years (QALYs), costs (2013 US dollars), incremental cost-effectiveness ratios (ICERs; $/QALY), and cost per infection avoided. One-way, two-way, and probabilistic sensitivity analyses were conducted, and scenarios of different age cohorts were considered. The ICERs less than $100000 per QALY were considered cost effective. Results Probiotic use dominated (more effective and less costly) no probiotic use. Results were sensitive to probiotic efficacy (relative risk <0.73), the baseline risk of CDI (>1.6%), the risk of probiotic-associated bactermia/fungemia (<0.26%), probiotic cost (<$130), and age (>65). In probabilistic sensitivity analysis, at a willingness-to-pay threshold of $100000/QALY, probiotics were the optimal strategy in 69.4% of simulations. Conclusions Our findings suggest that probiotic use may be a cost-effective strategy to prevent CDI in hospitalized adults receiving antibiotics age 65 or older or when the baseline risk of CDI exceeds 1.6%. PMID:29230429

A Methodological Review of US Budget-Impact Models for New Drugs.

PubMed

Mauskopf, Josephine; Earnshaw, Stephanie

2016-11-01

A budget-impact analysis is required by many jurisdictions when adding a new drug to the formulary. However, previous reviews have indicated that adherence to methodological guidelines is variable. In this methodological review, we assess the extent to which US budget-impact analyses for new drugs use recommended practices. We describe recommended practice for seven key elements in the design of a budget-impact analysis. Targeted literature searches for US studies reporting estimates of the budget impact of a new drug were performed and we prepared a summary of how each study addressed the seven key elements. The primary finding from this review is that recommended practice is not followed in many budget-impact analyses. For example, we found that growth in the treated population size and/or changes in disease-related costs expected during the model time horizon for more effective treatments was not included in several analyses for chronic conditions. In addition, all drug-related costs were not captured in the majority of the models. Finally, for most studies, one-way sensitivity and scenario analyses were very limited, and the ranges used in one-way sensitivity analyses were frequently arbitrary percentages rather than being data driven. The conclusions from our review are that changes in population size, disease severity mix, and/or disease-related costs should be properly accounted for to avoid over- or underestimating the budget impact. Since each budget holder might have different perspectives and different values for many of the input parameters, it is also critical for published budget-impact analyses to include extensive sensitivity and scenario analyses based on realistic input values.

Determination of Pain Phenotypes in Knee Osteoarthritis: A Latent Class Analysis using Data from the Osteoarthritis Initiative Study

PubMed Central

Kittelson, Andrew J.; Stevens-Lapsley, Jennifer E.; Schmiege, Sarah J.

2017-01-01

Objective Knee osteoarthritis (OA) is a broadly applied diagnosis that may encompass multiple subtypes of pain. The purpose of this study was to identify phenotypes of knee OA, using measures from the following pain-related domains: 1) knee OA pathology, 2) psychological distress, and 3) altered pain neurophysiology. Methods Data were selected from a total of 3494 participants at Visit #6 of the Osteoarthritis Initiative (OAI) study. Latent Class Analysis was applied to the following variables: radiographic OA severity, quadriceps strength, Body Mass Index (BMI), Charlson Comorbidity Index (CCI), Center for Epidemiologic Studies Depression subscale (CES-D), Coping Strategies Questionnaire-Catastrophizing subscale (CSQ-Cat), number of bodily pain sites, and knee joint tenderness at 4 sites. Resulting classes were compared on the following demographic and clinical factors: age, sex, pain severity, disability, walking speed, and use of arthritis-related healthcare. Results A four-class model was identified. Class 1 (4% of the study population) had higher CCI scores. Class 2 (24%) had higher knee joint sensitivity. Class 3 (10%) had greater psychological distress. Class 4 (62%) had lesser radiographic OA, little psychological involvement, greater strength, and less pain sensitivity. Additionally, Class 1 was the oldest, on average. Class 4 was the youngest, had the lowest disability, and least pain. Class 3 had the worst disability and most pain. Conclusions Four distinct pain phenotypes of knee OA were identified. Psychological factors, comorbidity status, and joint sensitivity appear to be important in defining phenotypes of knee OA-related pain. PMID:26414884

Evaluation of IOTA Simple Ultrasound Rules to Distinguish Benign and Malignant Ovarian Tumours

PubMed Central

Kaur, Amarjit; Mohi, Jaswinder Kaur; Sibia, Preet Kanwal; Kaur, Navkiran

2017-01-01

Introduction IOTA stands for International Ovarian Tumour Analysis group. Ovarian cancer is one of the common cancers in women and is diagnosed at later stage in majority. The limiting factor for early diagnosis is lack of standardized terms and procedures in gynaecological sonography. Introduction of IOTA rules has provided some consistency in defining morphological features of ovarian masses through a standardized examination technique. Aim To evaluate the efficacy of IOTA simple ultrasound rules in distinguishing benign and malignant ovarian tumours and establishing their use as a tool in early diagnosis of ovarian malignancy. Materials and Methods A hospital based case control prospective study was conducted. Patients with suspected ovarian pathology were evaluated using IOTA ultrasound rules and designated as benign or malignant. Findings were correlated with histopathological findings. Collected data was statistically analysed using chi-square test and kappa statistical method. Results Out of initial 55 patients, 50 patients were included in the final analysis who underwent surgery. IOTA simple rules were applicable in 45 out of these 50 patients (90%). The sensitivity for the detection of malignancy in cases where IOTA simple rules were applicable was 91.66% and the specificity was 84.84%. Accuracy was 86.66%. Classifying inconclusive cases as malignant, the sensitivity and specificity was 93% and 80% respectively. High level of agreement was found between USG and histopathological diagnosis with Kappa value as 0.323. Conclusion IOTA simple ultrasound rules were highly sensitive and specific in predicting ovarian malignancy preoperatively yet being reproducible, easy to train and use. PMID:28969237

Diagnostic Performance of Electronic Syndromic Surveillance Systems in Acute Care

PubMed Central

Kashiouris, M.; O’Horo, J.C.; Pickering, B.W.; Herasevich, V.

2013-01-01

Context Healthcare Electronic Syndromic Surveillance (ESS) is the systematic collection, analysis and interpretation of ongoing clinical data with subsequent dissemination of results, which aid clinical decision-making. Objective To evaluate, classify and analyze the diagnostic performance, strengths and limitations of existing acute care ESS systems. Data Sources All available to us studies in Ovid MEDLINE, Ovid EMBASE, CINAHL and Scopus databases, from as early as January 1972 through the first week of September 2012. Study Selection: Prospective and retrospective trials, examining the diagnostic performance of inpatient ESS and providing objective diagnostic data including sensitivity, specificity, positive and negative predictive values. Data Extraction Two independent reviewers extracted diagnostic performance data on ESS systems, including clinical area, number of decision points, sensitivity and specificity. Positive and negative likelihood ratios were calculated for each healthcare ESS system. A likelihood matrix summarizing the various ESS systems performance was created. Results The described search strategy yielded 1639 articles. Of these, 1497 were excluded on abstract information. After full text review, abstraction and arbitration with a third reviewer, 33 studies met inclusion criteria, reporting 102,611 ESS decision points. The yielded I2 was high (98.8%), precluding meta-analysis. Performance was variable, with sensitivities ranging from 21% –100% and specificities ranging from 5%-100%. Conclusions There is significant heterogeneity in the diagnostic performance of the available ESS implements in acute care, stemming from the wide spectrum of different clinical entities and ESS systems. Based on the results, we introduce a conceptual framework using a likelihood ratio matrix for evaluation and meaningful application of future, frontline clinical decision support systems. PMID:23874359

Missing data handling in non-inferiority and equivalence trials: A systematic review.

PubMed

Rabe, Brooke A; Day, Simon; Fiero, Mallorie H; Bell, Melanie L

2018-05-25

Non-inferiority (NI) and equivalence clinical trials test whether a new treatment is therapeutically no worse than, or equivalent to, an existing standard of care. Missing data in clinical trials have been shown to reduce statistical power and potentially bias estimates of effect size; however, in NI and equivalence trials, they present additional issues. For instance, they may decrease sensitivity to differences between treatment groups and bias toward the alternative hypothesis of NI (or equivalence). Our primary aim was to review the extent of and methods for handling missing data (model-based methods, single imputation, multiple imputation, complete case), the analysis sets used (Intention-To-Treat, Per-Protocol, or both), and whether sensitivity analyses were used to explore departures from assumptions about the missing data. We conducted a systematic review of NI and equivalence trials published between May 2015 and April 2016 by searching the PubMed database. Articles were reviewed primarily by 2 reviewers, with 6 articles reviewed by both reviewers to establish consensus. Of 109 selected articles, 93% reported some missing data in the primary outcome. Among those, 50% reported complete case analysis, and 28% reported single imputation approaches for handling missing data. Only 32% reported conducting analyses of both intention-to-treat and per-protocol populations. Only 11% conducted any sensitivity analyses to test assumptions with respect to missing data. Missing data are common in NI and equivalence trials, and they are often handled by methods which may bias estimates and lead to incorrect conclusions. Copyright © 2018 John Wiley & Sons, Ltd.

The effect of icotinib combined with chemotherapy in untreated non-small-cell lung cancer that harbored EGFR-sensitive mutations in a real-life setting: a retrospective analysis

PubMed Central

Wang, Lulu; Li, Yan; Li, Luchun; Wu, Zhijuan; Yang, Dan; Ma, Huiwen; Wang, Donglin

2018-01-01

Purpose This study was conducted to compare the efficacy of a combination of icotinib and chemotherapy with icotinib or chemotherapy alone in untreated non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)-sensitive mutations and to analyze the curative effect of different treatments on different genetic mutations (EGFR 19 exon deletion and L858R mutation) in a real-life setting. Patients and methods One hundred ninety-one patients were studied in this retrospective analysis from January 2013 to December 2015. The baseline characteristics, curative effects and adverse events of patients were analyzed. The primary endpoint was progression free survival (PFS). Results Longer PFS and overall survival (OS), and better objective response rate (ORR) were observed in the combination group compared to icotinib or chemotherapy along. For patients with an EGFR 19 exon deletion, the PFS, OS, and ORR in the combination group were superior to those in the icotinib or chemotherapy group. For the patients with the EGFR L858R mutation, better PFS and ORR were observed in the combination group, but OS was not obviously prolonged. Grade 3 or 4 adverse events were most commonly reported with combination therapy or chemotherapy alone. No possible drug-related interstitial lung disease or of drug related deaths occurred. Conclusion The combination of icotinib and chemotherapy in patients with untreated NSCLC harboring sensitive EGFR mutations resulted in improved PFS and OS, especially in those who harbored the EGFR exon 19 deletion. PMID:29731642

Iowa gambling task performance in euthymic bipolar I disorder: A meta-analysis and empirical study

PubMed Central

Edge, Michael D.; Johnson, Sheri L.; Ng, Tommy; Carver, Charles S.

2013-01-01

Background The Iowa Gambling Task (IGT) has been recommended as an index of reward sensitivity, which is elevated in bipolar disorder. We conducted a meta-analysis of IGT performance in euthymic bipolar I disorder compared with control participants. Findings indicated that people with bipolar disorder make more risky choices than control participants, though the effect is small (g=0.35). It is not clear which of the many processes involved in IGT performance are involved in producing the observed group difference. Methods Fifty-five euthymic people with bipolar disorder and 39 control participants completed the IGT. The Expectancy Valence Model was used to examine differences in IGT. We also examined whether variation in IGT performance within the bipolar group was related to current mood, illness course, impulsivity, or demographics. Results Bipolar and control groups did not differ on the total number of risky choices, rate of learning, or any of the parameters of the Expectancy Valence Model. IGT performance in bipolar disorder was not related to any of the examined individual differences. Limitations It is possible that there are group differences that are too small to detect at our sample size or that are not amenable to study via the Expectancy Valence Model. Conclusions We were unable to identify group differences on the IGT or correlates of IGT performance within bipolar disorder. Though the IGT may serve as a useful model for decision-making, its structure may make it unsuitable for behavioral assessment of reward sensitivity independent of punishment sensitivity. PMID:23219060

Optimization of Parameter Ranges for Composite Tape Winding Process Based on Sensitivity Analysis

NASA Astrophysics Data System (ADS)

Yu, Tao; Shi, Yaoyao; He, Xiaodong; Kang, Chao; Deng, Bo; Song, Shibo

2017-08-01

This study is focus on the parameters sensitivity of winding process for composite prepreg tape. The methods of multi-parameter relative sensitivity analysis and single-parameter sensitivity analysis are proposed. The polynomial empirical model of interlaminar shear strength is established by response surface experimental method. Using this model, the relative sensitivity of key process parameters including temperature, tension, pressure and velocity is calculated, while the single-parameter sensitivity curves are obtained. According to the analysis of sensitivity curves, the stability and instability range of each parameter are recognized. Finally, the optimization method of winding process parameters is developed. The analysis results show that the optimized ranges of the process parameters for interlaminar shear strength are: temperature within [100 °C, 150 °C], tension within [275 N, 387 N], pressure within [800 N, 1500 N], and velocity within [0.2 m/s, 0.4 m/s], respectively.

Point-of-care mobile digital microscopy and deep learning for the detection of soil-transmitted helminths and Schistosoma haematobium

PubMed Central

Holmström, Oscar; Linder, Nina; Ngasala, Billy; Mårtensson, Andreas; Linder, Ewert; Lundin, Mikael; Moilanen, Hannu; Suutala, Antti; Diwan, Vinod; Lundin, Johan

2017-01-01

ABSTRACT Background: Microscopy remains the gold standard in the diagnosis of neglected tropical diseases. As resource limited, rural areas often lack laboratory equipment and trained personnel, new diagnostic techniques are needed. Low-cost, point-of-care imaging devices show potential in the diagnosis of these diseases. Novel, digital image analysis algorithms can be utilized to automate sample analysis. Objective: Evaluation of the imaging performance of a miniature digital microscopy scanner for the diagnosis of soil-transmitted helminths and Schistosoma haematobium, and training of a deep learning-based image analysis algorithm for automated detection of soil-transmitted helminths in the captured images. Methods: A total of 13 iodine-stained stool samples containing Ascaris lumbricoides, Trichuris trichiura and hookworm eggs and 4 urine samples containing Schistosoma haematobium were digitized using a reference whole slide-scanner and the mobile microscopy scanner. Parasites in the images were identified by visual examination and by analysis with a deep learning-based image analysis algorithm in the stool samples. Results were compared between the digital and visual analysis of the images showing helminth eggs. Results: Parasite identification by visual analysis of digital slides captured with the mobile microscope was feasible for all analyzed parasites. Although the spatial resolution of the reference slide-scanner is higher, the resolution of the mobile microscope is sufficient for reliable identification and classification of all parasites studied. Digital image analysis of stool sample images captured with the mobile microscope showed high sensitivity for detection of all helminths studied (range of sensitivity = 83.3–100%) in the test set (n = 217) of manually labeled helminth eggs. Conclusions: In this proof-of-concept study, the imaging performance of a mobile, digital microscope was sufficient for visual detection of soil-transmitted helminths and Schistosoma haematobium. Furthermore, we show that deep learning-based image analysis can be utilized for the automated detection and classification of helminths in the captured images. PMID:28838305

[Bactericidal activity of serum and chemotherapy in sensitive and resistant exciter (author's transl)].

PubMed

Eyer, H; Metz, H; Preac-Mursic, V

1975-11-21

Comparing examinations with Ampicillin sensitive and resistant bacteria-strains show that the bactericidal activity of serum is dependent on the bacteria-strains, on the Ampicillin sensitivity of the particular exciter and on the number of bacteria/ml (germ count). Bactericide effect could always be obtained with sensitive strains as a result of additional chemotherapy. With several resistant strains a bactericide effect could not be obtained in this case the continuous optimal Ampicillin addition was the decisive factor. Because of the extremely complicated process of the bactericide one should not make general conclusions from the individual experimental results.

Coupled Aerodynamic and Structural Sensitivity Analysis of a High-Speed Civil Transport

NASA Technical Reports Server (NTRS)

Mason, B. H.; Walsh, J. L.

2001-01-01

An objective of the High Performance Computing and Communication Program at the NASA Langley Research Center is to demonstrate multidisciplinary shape and sizing optimization of a complete aerospace vehicle configuration by using high-fidelity, finite-element structural analysis and computational fluid dynamics aerodynamic analysis. In a previous study, a multi-disciplinary analysis system for a high-speed civil transport was formulated to integrate a set of existing discipline analysis codes, some of them computationally intensive, This paper is an extension of the previous study, in which the sensitivity analysis for the coupled aerodynamic and structural analysis problem is formulated and implemented. Uncoupled stress sensitivities computed with a constant load vector in a commercial finite element analysis code are compared to coupled aeroelastic sensitivities computed by finite differences. The computational expense of these sensitivity calculation methods is discussed.

High-frequency Electrocardiogram Analysis in the Ability to Predict Reversible Perfusion Defects during Adenosine Myocardial Perfusion Imaging

NASA Technical Reports Server (NTRS)

Tragardh, Elin; Schlegel, Todd T.; Carlsson, Marcus; Pettersson, Jonas; Nilsson, Klas; Pahlm, Olle

2007-01-01

Background: A previous study has shown that analysis of high-frequency QRS components (HF-QRS) is highly sensitive and reasonably specific for detecting reversible perfusion defects on myocardial perfusion imaging (MPI) scans during adenosine. The purpose of the present study was to try to reproduce those findings. Methods: 12-lead high-resolution electrocardiogram recordings were obtained from 100 patients before (baseline) and during adenosine Tc-99m-tetrofosmin MPI tests. HF-QRS were analyzed regarding morphology and changes in root mean square (RMS) voltages from before the adenosine infusion to peak infusion. Results: The best area under the curve (AUC) was found in supine patients (AUC=0.736) in a combination of morphology and RMS changes. None of the measurements, however, were statistically better than tossing a coin (AUC=0.5). Conclusion: Analysis of HF-QRS was not significantly better than tossing a coin for determining reversible perfusion defects on MPI scans.