Space Station Freedom electric power system availability study

NASA Technical Reports Server (NTRS)

Turnquist, Scott R.

1990-01-01

The results are detailed of follow-on availability analyses performed on the Space Station Freedom electric power system (EPS). The scope includes analyses of several EPS design variations, these are: the 4-photovoltaic (PV) module baseline EPS design, a 6-PV module EPS design, and a 3-solar dynamic module EPS design which included a 10 kW PV module. The analyses performed included: determining the discrete power levels that the EPS will operate at upon various component failures and the availability of each of these operating states; ranking EPS components by the relative contribution each component type gives to the power availability of the EPS; determining the availability impacts of including structural and long-life EPS components in the availability models used in the analyses; determining optimum sparing strategies, for storing space EPS components on-orbit, to maintain high average-power-capability with low lift-mass requirements; and analyses to determine the sensitivity of EPS-availability to uncertainties in the component reliability and maintainability data used.

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-02-25

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index on 2 October 2014. We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. Based on the combined Cochrane Hepato-Biliary Group score, we classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2017-05-18

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index - Science, and LILACS (May 2017). We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-09-17

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index (August 2015). We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for-profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed-effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random-effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics.

Pharmacoeconomic evaluations of pharmacogenetic and genomic screening programmes: a systematic review on content and adherence to guidelines.

PubMed

Vegter, Stefan; Boersma, Cornelis; Rozenbaum, Mark; Wilffert, Bob; Navis, Gerjan; Postma, Maarten J

2008-01-01

The fields of pharmacogenetics and pharmacogenomics have become important practical tools to progress goals in medical and pharmaceutical research and development. As more screening tests are being developed, with some already used in clinical practice, consideration of cost-effectiveness implications is important. A systematic review was performed on the content of and adherence to pharmacoeconomic guidelines of recent pharmacoeconomic analyses performed in the field of pharmacogenetics and pharmacogenomics. Economic analyses of screening strategies for genetic variations, which were evidence-based and assumed to be associated with drug efficacy or safety, were included in the review. The 20 papers included cover a variety of healthcare issues, including screening tests on several cytochrome P450 (CYP) enzyme genes, thiopurine S-methyltransferase (TMPT) and angiotensin-converting enzyme (ACE) insertion deletion (ACE I/D) polymorphisms. Most economic analyses reported that genetic screening was cost effective and often even clearly dominated existing non-screening strategies. However, we found a lack of standardization regarding aspects such as the perspective of the analysis, factors included in the sensitivity analysis and the applied discount rates. In particular, an important limitation of several studies related to the failure to provide a sufficient evidence-based rationale for an association between genotype and phenotype. Future economic analyses should be conducted utilizing correct methods, with adherence to guidelines and including extensive sensitivity analyses. Most importantly, genetic screening strategies should be based on good evidence-based rationales. For these goals, we provide a list of recommendations for good pharmacoeconomic practice deemed useful in the fields of pharmacogenetics and pharmacogenomics, regardless of country and origin of the economic analysis.

On the Exploitation of Sensitivity Derivatives for Improving Sampling Methods

NASA Technical Reports Server (NTRS)

Cao, Yanzhao; Hussaini, M. Yousuff; Zang, Thomas A.

2003-01-01

Many application codes, such as finite-element structural analyses and computational fluid dynamics codes, are capable of producing many sensitivity derivatives at a small fraction of the cost of the underlying analysis. This paper describes a simple variance reduction method that exploits such inexpensive sensitivity derivatives to increase the accuracy of sampling methods. Three examples, including a finite-element structural analysis of an aircraft wing, are provided that illustrate an order of magnitude improvement in accuracy for both Monte Carlo and stratified sampling schemes.

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

Sampling and sensitivity analyses tools (SaSAT) for computational modelling

PubMed Central

Hoare, Alexander; Regan, David G; Wilson, David P

2008-01-01

SaSAT (Sampling and Sensitivity Analysis Tools) is a user-friendly software package for applying uncertainty and sensitivity analyses to mathematical and computational models of arbitrary complexity and context. The toolbox is built in Matlab®, a numerical mathematical software package, and utilises algorithms contained in the Matlab® Statistics Toolbox. However, Matlab® is not required to use SaSAT as the software package is provided as an executable file with all the necessary supplementary files. The SaSAT package is also designed to work seamlessly with Microsoft Excel but no functionality is forfeited if that software is not available. A comprehensive suite of tools is provided to enable the following tasks to be easily performed: efficient and equitable sampling of parameter space by various methodologies; calculation of correlation coefficients; regression analysis; factor prioritisation; and graphical output of results, including response surfaces, tornado plots, and scatterplots. Use of SaSAT is exemplified by application to a simple epidemic model. To our knowledge, a number of the methods available in SaSAT for performing sensitivity analyses have not previously been used in epidemiological modelling and their usefulness in this context is demonstrated. PMID:18304361

Aerobrake concepts for NTP systems study

NASA Technical Reports Server (NTRS)

Cruz, Manuel I.

1992-01-01

Design concepts are described for landing large spacecraft masses on the Mars surface in support of manned missions with interplanetary transportation using Nuclear Thermal Propulsion (NTP). Included are the mission and systems analyses, trade studies and sensitivity analyses, design analyses, technology assessment, and derived requirements to support this concept. The mission phases include the Mars de-orbit, entry, terminal descent, and terminal touchdown. The study focuses primarily on Mars surface delivery from orbit after Mars orbit insertion using an NTP. The requirements associated with delivery of logistical supplies, habitats, and other equipment on minimum energy Earth to Mars transfers are also addressed in a preliminary fashion.

CO2 Push-Pull Dual (Conjugate) Faults Injection Simulations

DOE Data Explorer

Oldenburg, Curtis (ORCID:0000000201326016); Lee, Kyung Jae; Doughty, Christine; Jung, Yoojin; Borgia, Andrea; Pan, Lehua; Zhang, Rui; Daley, Thomas M.; Altundas, Bilgin; Chugunov, Nikita

2017-07-20

This submission contains datasets and a final manuscript associated with a project simulating carbon dioxide push-pull into a conjugate fault system modeled after Dixie Valley- sensitivity analysis of significant parameters and uncertainty prediction by data-worth analysis. Datasets include: (1) Forward simulation runs of standard cases (push & pull phases), (2) Local sensitivity analyses (push & pull phases), and (3) Data-worth analysis (push & pull phases).

Validity of self-reported stroke in elderly African Americans, Caribbean Hispanics, and Whites.

PubMed

Reitz, Christiane; Schupf, Nicole; Luchsinger, José A; Brickman, Adam M; Manly, Jennifer J; Andrews, Howard; Tang, Ming X; DeCarli, Charles; Brown, Truman R; Mayeux, Richard

2009-07-01

The validity of a self-reported stroke remains inconclusive. To validate the diagnosis of self-reported stroke using stroke identified by magnetic resonance imaging (MRI) as the standard. Community-based cohort study of nondemented, ethnically diverse elderly persons in northern Manhattan. High-resolution quantitative MRIs were acquired for 717 participants without dementia. Sensitivity and specificity of stroke by self-report were examined using cross-sectional analyses and the chi(2) test. Putative relationships between factors potentially influencing the reporting of stroke, including memory performance, cognitive function, and vascular risk factors, were assessed using logistic regression models. Subsequently, all analyses were repeated, stratified by age, sex, ethnic group, and level of education. In analyses of the whole sample, sensitivity of stroke self-report for a diagnosis of stroke on MRI was 32.4%, and specificity was 78.9%. In analyses stratified by median age (80.1 years), the validity between reported stroke and detection of stroke on MRI was significantly better in the younger than the older age group (for all vascular territories: sensitivity and specificity, 36.7% and 81.3% vs 27.6% and 26.2%; P = .02). Impaired memory, cognitive skills, or language ability and the presence of hypertension or myocardial infarction were associated with higher rates of false-negative results. Using brain MRI as the standard, specificity and sensitivity of stroke self-report are low. Accuracy of self-report is influenced by age, presence of vascular disease, and cognitive function. In stroke research, sensitive neuroimaging techniques rather than stroke self-report should be used to determine stroke history.

Sensitivity analysis of FeCrAl cladding and U3Si2 fuel under accident conditions

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

Gamble, Kyle Allan Lawrence; Hales, Jason Dean

2016-08-01

The purpose of this milestone report is to highlight the results of sensitivity analyses performed on two accident tol- erant fuel concepts: U3Si2 fuel and FeCrAl cladding. The BISON fuel performance code under development at Idaho National Laboratory was coupled to Sandia National Laboratories’ DAKOTA software to perform the sensitivity analyses. Both Loss of Coolant (LOCA) and Station blackout (SBO) scenarios were analyzed using main effects studies. The results indicate that for FeCrAl cladding the input parameters with greatest influence on the output metrics of interest (fuel centerline temperature and cladding hoop strain) during the LOCA were the isotropic swellingmore » and fuel enrichment. For U3Si2 the important inputs were found to be the intergranular diffusion coefficient, specific heat, and fuel thermal conductivity. For the SBO scenario, Young’s modulus was found to be influential in FeCrAl in addition to the isotropic swelling and fuel enrichment. Contrarily to the LOCA case, the specific heat of U3Si2 was found to have no effect during the SBO. The intergranular diffusion coefficient and fuel thermal conductivity were still found to be of importance. The results of the sensitivity analyses have identified areas where further research is required including fission gas behavior in U3Si2 and irradiation swelling in FeCrAl. Moreover, the results highlight the need to perform the sensitivity analyses on full length fuel rods for SBO scenarios.« less

Further evaluation of leisure items in the attention condition of functional analyses.

PubMed

Roscoe, Eileen M; Carreau, Abbey; MacDonald, Jackie; Pence, Sacha T

2008-01-01

Research suggests that including leisure items in the attention condition of a functional analysis may produce engagement that masks sensitivity to attention. In this study, 4 individuals' initial functional analyses indicated that behavior was maintained by nonsocial variables (n = 3) or by attention (n = 1). A preference assessment was used to identify items for subsequent functional analyses. Four conditions were compared, attention with and without leisure items and control with and without leisure items. Following this, either high- or low-preference items were included in the attention condition. Problem behavior was more probable during the attention condition when no leisure items or low-preference items were included, and lower levels of problem behavior were observed during the attention condition when high-preference leisure items were included. These findings suggest how preferred items may hinder detection of behavioral function.

Ground water flow modeling with sensitivity analyses to guide field data collection in a mountain watershed

USGS Publications Warehouse

Johnson, Raymond H.

2007-01-01

In mountain watersheds, the increased demand for clean water resources has led to an increased need for an understanding of ground water flow in alpine settings. In Prospect Gulch, located in southwestern Colorado, understanding the ground water flow system is an important first step in addressing metal loads from acid-mine drainage and acid-rock drainage in an area with historical mining. Ground water flow modeling with sensitivity analyses are presented as a general tool to guide future field data collection, which is applicable to any ground water study, including mountain watersheds. For a series of conceptual models, the observation and sensitivity capabilities of MODFLOW-2000 are used to determine composite scaled sensitivities, dimensionless scaled sensitivities, and 1% scaled sensitivity maps of hydraulic head. These sensitivities determine the most important input parameter(s) along with the location of observation data that are most useful for future model calibration. The results are generally independent of the conceptual model and indicate recharge in a high-elevation recharge zone as the most important parameter, followed by the hydraulic conductivities in all layers and recharge in the next lower-elevation zone. The most important observation data in determining these parameters are hydraulic heads at high elevations, with a depth of less than 100 m being adequate. Evaluation of a possible geologic structure with a different hydraulic conductivity than the surrounding bedrock indicates that ground water discharge to individual stream reaches has the potential to identify some of these structures. Results of these sensitivity analyses can be used to prioritize data collection in an effort to reduce time and money spend by collecting the most relevant model calibration data.

Variation of a test's sensitivity and specificity with disease prevalence.

PubMed

Leeflang, Mariska M G; Rutjes, Anne W S; Reitsma, Johannes B; Hooft, Lotty; Bossuyt, Patrick M M

2013-08-06

Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. We used data from 23 meta-analyses, each of which included 10-39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation.

Variation of a test’s sensitivity and specificity with disease prevalence

PubMed Central

Leeflang, Mariska M.G.; Rutjes, Anne W.S.; Reitsma, Johannes B.; Hooft, Lotty; Bossuyt, Patrick M.M.

2013-01-01

Background: Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. Methods: We used data from 23 meta-analyses, each of which included 10–39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. Results: Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. Interpretation: The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation. PMID:23798453

iTOUGH2 v7.1

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

FINSTERLE, STEFAN; JUNG, YOOJIN; KOWALSKY, MICHAEL

2016-09-15

iTOUGH2 (inverse TOUGH2) provides inverse modeling capabilities for TOUGH2, a simulator for multi-dimensional, multi-phase, multi-component, non-isothermal flow and transport in fractured porous media. iTOUGH2 performs sensitivity analyses, data-worth analyses, parameter estimation, and uncertainty propagation analyses in geosciences and reservoir engineering and other application areas. iTOUGH2 supports a number of different combinations of fluids and components (equation-of-state (EOS) modules). In addition, the optimization routines implemented in iTOUGH2 can also be used for sensitivity analysis, automatic model calibration, and uncertainty quantification of any external code that uses text-based input and output files using the PEST protocol. iTOUGH2 solves the inverse problem bymore » minimizing a non-linear objective function of the weighted differences between model output and the corresponding observations. Multiple minimization algorithms (derivative-free, gradient-based, and second-order; local and global) are available. iTOUGH2 also performs Latin Hypercube Monte Carlo simulations for uncertainty propagation analyses. A detailed residual and error analysis is provided. This upgrade includes (a) global sensitivity analysis methods, (b) dynamic memory allocation (c) additional input features and output analyses, (d) increased forward simulation capabilities, (e) parallel execution on multicore PCs and Linux clusters, and (f) bug fixes. More details can be found at http://esd.lbl.gov/iTOUGH2.« less

Report of the LSPI/NASA Workshop on Lunar Base Methodology Development

NASA Technical Reports Server (NTRS)

Nozette, Stewart; Roberts, Barney

1985-01-01

Groundwork was laid for computer models which will assist in the design of a manned lunar base. The models, herein described, will provide the following functions for the successful conclusion of that task: strategic planning; sensitivity analyses; impact analyses; and documentation. Topics addressed include: upper level model description; interrelationship matrix; user community; model features; model descriptions; system implementation; model management; and plans for future action.

Violent video game effects on aggression, empathy, and prosocial behavior in eastern and western countries: a meta-analytic review.

PubMed

Anderson, Craig A; Shibuya, Akiko; Ihori, Nobuko; Swing, Edward L; Bushman, Brad J; Sakamoto, Akira; Rothstein, Hannah R; Saleem, Muniba

2010-03-01

Meta-analytic procedures were used to test the effects of violent video games on aggressive behavior, aggressive cognition, aggressive affect, physiological arousal, empathy/desensitization, and prosocial behavior. Unique features of this meta-analytic review include (a) more restrictive methodological quality inclusion criteria than in past meta-analyses; (b) cross-cultural comparisons; (c) longitudinal studies for all outcomes except physiological arousal; (d) conservative statistical controls; (e) multiple moderator analyses; and (f) sensitivity analyses. Social-cognitive models and cultural differences between Japan and Western countries were used to generate theory-based predictions. Meta-analyses yielded significant effects for all 6 outcome variables. The pattern of results for different outcomes and research designs (experimental, cross-sectional, longitudinal) fit theoretical predictions well. The evidence strongly suggests that exposure to violent video games is a causal risk factor for increased aggressive behavior, aggressive cognition, and aggressive affect and for decreased empathy and prosocial behavior. Moderator analyses revealed significant research design effects, weak evidence of cultural differences in susceptibility and type of measurement effects, and no evidence of sex differences in susceptibility. Results of various sensitivity analyses revealed these effects to be robust, with little evidence of selection (publication) bias.

Preliminary performance assessment for the Waste Isolation Pilot Plant, December 1992. Volume 5, Uncertainty and sensitivity analyses of gas and brine migration for undisturbed performance

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

Not Available

1993-08-01

Before disposing of transuranic radioactive waste in the Waste Isolation Pilot Plant (WIPP), the United States Department of Energy (DOE) must evaluate compliance with applicable long-term regulations of the United States Environmental Protection Agency (EPA). Sandia National Laboratories is conducting iterative performance assessments (PAs) of the WIPP for the DOE to provide interim guidance while preparing for a final compliance evaluation. This volume of the 1992 PA contains results of uncertainty and sensitivity analyses with respect to migration of gas and brine from the undisturbed repository. Additional information about the 1992 PA is provided in other volumes. Volume 1 containsmore » an overview of WIPP PA and results of a preliminary comparison with 40 CFR 191, Subpart B. Volume 2 describes the technical basis for the performance assessment, including descriptions of the linked computational models used in the Monte Carlo analyses. Volume 3 contains the reference data base and values for input parameters used in consequence and probability modeling. Volume 4 contains uncertainty and sensitivity analyses with respect to the EPA`s Environmental Standards for the Management and Disposal of Spent Nuclear Fuel, High-Level and Transuranic Radioactive Wastes (40 CFR 191, Subpart B). Finally, guidance derived from the entire 1992 PA is presented in Volume 6. Results of the 1992 uncertainty and sensitivity analyses indicate that, conditional on the modeling assumptions and the assigned parameter-value distributions, the most important parameters for which uncertainty has the potential to affect gas and brine migration from the undisturbed repository are: initial liquid saturation in the waste, anhydrite permeability, biodegradation-reaction stoichiometry, gas-generation rates for both corrosion and biodegradation under inundated conditions, and the permeability of the long-term shaft seal.« less

SVDS plume impingement modeling development. Sensitivity analysis supporting level B requirements

NASA Technical Reports Server (NTRS)

Chiu, P. B.; Pearson, D. J.; Muhm, P. M.; Schoonmaker, P. B.; Radar, R. J.

1977-01-01

A series of sensitivity analyses (trade studies) performed to select features and capabilities to be implemented in the plume impingement model is described. Sensitivity analyses were performed in study areas pertaining to geometry, flowfield, impingement, and dynamical effects. Recommendations based on these analyses are summarized.

Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis.

PubMed

Mazza, Mario Gennaro; Lucchi, Sara; Tringali, Agnese Grazia Maria; Rossetti, Aurora; Botti, Eugenia Rossana; Clerici, Massimo

2018-06-08

The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p < 0.001; I 2  = 82.4% and SMD = 0.425; p = 0.048; I 2  = 86.53%). Heterogeneity-based sensitivity analyses confirmed these findings. Subgroup analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. Copyright © 2018 Elsevier Inc. All rights reserved.

Search Strategy to Identify Dental Survival Analysis Articles Indexed in MEDLINE.

PubMed

Layton, Danielle M; Clarke, Michael

2016-01-01

Articles reporting survival outcomes (time-to-event outcomes) in patients over time are challenging to identify in the literature. Research shows the words authors use to describe their dental survival analyses vary, and that allocation of medical subject headings by MEDLINE indexers is inconsistent. Together, this undermines accurate article identification. The present study aims to develop and validate a search strategy to identify dental survival analyses indexed in MEDLINE (Ovid). A gold standard cohort of articles was identified to derive the search terms, and an independent gold standard cohort of articles was identified to test and validate the proposed search strategies. The first cohort included all 6,955 articles published in the 50 dental journals with the highest impact factors in 2008, of which 95 articles were dental survival articles. The second cohort included all 6,514 articles published in the 50 dental journals with the highest impact factors for 2012, of which 148 were dental survival articles. Each cohort was identified by a systematic hand search. Performance parameters of sensitivity, precision, and number needed to read (NNR) for the search strategies were calculated. Sensitive, precise, and optimized search strategies were developed and validated. The performances of the search strategy maximizing sensitivity were 92% sensitivity, 14% precision, and 7.11 NNR; the performances of the strategy maximizing precision were 93% precision, 10% sensitivity, and 1.07 NNR; and the performances of the strategy optimizing the balance between sensitivity and precision were 83% sensitivity, 24% precision, and 4.13 NNR. The methods used to identify search terms were objective, not subjective. The search strategies were validated in an independent group of articles that included different journals and different publication years. Across the three search strategies, dental survival articles can be identified with sensitivity up to 92%, precision up to 93%, and NNR of less than two articles to identify relevant records. This research has highlighted the impact that variation in reporting and indexing has on article identification and has improved researchers' ability to identify dental survival articles.

Head-To-Head Comparison Between High- and Standard-b-Value DWI for Detecting Prostate Cancer: A Systematic Review and Meta-Analysis.

PubMed

Woo, Sungmin; Suh, Chong Hyun; Kim, Sang Youn; Cho, Jeong Yeon; Kim, Seung Hyup

2018-01-01

The purpose of this study was to perform a head-to-head comparison between high-b-value (> 1000 s/mm 2 ) and standard-b-value (800-1000 s/mm 2 ) DWI regarding diagnostic performance in the detection of prostate cancer. The MEDLINE and EMBASE databases were searched up to April 1, 2017. The analysis included diagnostic accuracy studies in which high- and standard-b-value DWI were used for prostate cancer detection with histopathologic examination as the reference standard. Methodologic quality was assessed with the revised Quality Assessment of Diagnostic Accuracy Studies tool. Sensitivity and specificity of all studies were calculated and were pooled and plotted in a hierarchic summary ROC plot. Meta-regression and multiple-subgroup analyses were performed to compare the diagnostic performances of high- and standard-b-value DWI. Eleven studies (789 patients) were included. High-b-value DWI had greater pooled sensitivity (0.80 [95% CI, 0.70-0.87]) (p = 0.03) and specificity (0.92 [95% CI, 0.87-0.95]) (p = 0.01) than standard-b-value DWI (sensitivity, 0.78 [95% CI, 0.66-0.86]); specificity, 0.87 [95% CI, 0.77-0.93] (p < 0.01). Multiple-subgroup analyses showed that specificity was consistently higher for high- than for standard-b-value DWI (p ≤ 0.05). Sensitivity was significantly higher for high- than for standard-b-value DWI only in the following subgroups: peripheral zone only, transition zone only, multiparametric protocol (DWI and T2-weighted imaging), visual assessment of DW images, and per-lesion analysis (p ≤ 0.04). In a head-to-head comparison, high-b-value DWI had significantly better sensitivity and specificity for detection of prostate cancer than did standard-b-value DWI. Multiple-subgroup analyses showed that specificity was consistently superior for high-b-value DWI.

Advances in global sensitivity analyses of demographic-based species distribution models to address uncertainties in dynamic landscapes.

PubMed

Naujokaitis-Lewis, Ilona; Curtis, Janelle M R

2016-01-01

Developing a rigorous understanding of multiple global threats to species persistence requires the use of integrated modeling methods that capture processes which influence species distributions. Species distribution models (SDMs) coupled with population dynamics models can incorporate relationships between changing environments and demographics and are increasingly used to quantify relative extinction risks associated with climate and land-use changes. Despite their appeal, uncertainties associated with complex models can undermine their usefulness for advancing predictive ecology and informing conservation management decisions. We developed a computationally-efficient and freely available tool (GRIP 2.0) that implements and automates a global sensitivity analysis of coupled SDM-population dynamics models for comparing the relative influence of demographic parameters and habitat attributes on predicted extinction risk. Advances over previous global sensitivity analyses include the ability to vary habitat suitability across gradients, as well as habitat amount and configuration of spatially-explicit suitability maps of real and simulated landscapes. Using GRIP 2.0, we carried out a multi-model global sensitivity analysis of a coupled SDM-population dynamics model of whitebark pine (Pinus albicaulis) in Mount Rainier National Park as a case study and quantified the relative influence of input parameters and their interactions on model predictions. Our results differed from the one-at-time analyses used in the original study, and we found that the most influential parameters included the total amount of suitable habitat within the landscape, survival rates, and effects of a prevalent disease, white pine blister rust. Strong interactions between habitat amount and survival rates of older trees suggests the importance of habitat in mediating the negative influences of white pine blister rust. Our results underscore the importance of considering habitat attributes along with demographic parameters in sensitivity routines. GRIP 2.0 is an important decision-support tool that can be used to prioritize research, identify habitat-based thresholds and management intervention points to improve probability of species persistence, and evaluate trade-offs of alternative management options.

Advances in global sensitivity analyses of demographic-based species distribution models to address uncertainties in dynamic landscapes

PubMed Central

Curtis, Janelle M.R.

2016-01-01

Developing a rigorous understanding of multiple global threats to species persistence requires the use of integrated modeling methods that capture processes which influence species distributions. Species distribution models (SDMs) coupled with population dynamics models can incorporate relationships between changing environments and demographics and are increasingly used to quantify relative extinction risks associated with climate and land-use changes. Despite their appeal, uncertainties associated with complex models can undermine their usefulness for advancing predictive ecology and informing conservation management decisions. We developed a computationally-efficient and freely available tool (GRIP 2.0) that implements and automates a global sensitivity analysis of coupled SDM-population dynamics models for comparing the relative influence of demographic parameters and habitat attributes on predicted extinction risk. Advances over previous global sensitivity analyses include the ability to vary habitat suitability across gradients, as well as habitat amount and configuration of spatially-explicit suitability maps of real and simulated landscapes. Using GRIP 2.0, we carried out a multi-model global sensitivity analysis of a coupled SDM-population dynamics model of whitebark pine (Pinus albicaulis) in Mount Rainier National Park as a case study and quantified the relative influence of input parameters and their interactions on model predictions. Our results differed from the one-at-time analyses used in the original study, and we found that the most influential parameters included the total amount of suitable habitat within the landscape, survival rates, and effects of a prevalent disease, white pine blister rust. Strong interactions between habitat amount and survival rates of older trees suggests the importance of habitat in mediating the negative influences of white pine blister rust. Our results underscore the importance of considering habitat attributes along with demographic parameters in sensitivity routines. GRIP 2.0 is an important decision-support tool that can be used to prioritize research, identify habitat-based thresholds and management intervention points to improve probability of species persistence, and evaluate trade-offs of alternative management options. PMID:27547529

The Usefulness of Selected Physicochemical Indices, Cell Membrane Integrity and Sperm Chromatin Structure in Assessments of Boar Semen Sensitivity

PubMed Central

Wysokińska, A.; Kondracki, S.; Iwanina, M.

2015-01-01

The present work describes experiments undertaken to evaluate the usefulness of selected physicochemical indices of semen, cell membrane integrity and sperm chromatin structure for the assessment of boar semen sensitivity to processes connected with pre-insemination procedures. The experiments were carried out on 30 boars: including 15 regarded as providers of sensitive semen and 15 regarded as providers of semen that is little sensitive to laboratory processing. The selection of boars for both groups was based on sperm morphology analyses, assuming secondary morphological change incidence in spermatozoa as the criterion. Two ejaculates were manually collected from each boar at an interval of 3 to 4 months. The following analyses were carried out for each ejaculate: sperm motility assessment, sperm pH measurement, sperm morphology assessment, sperm chromatin structure evaluation and cell membrane integrity assessment. The analyses were performed three times. Semen storage did not cause an increase in the incidence of secondary morphological changes in the group of boars considered to provide sperm of low sensitivity. On the other hand, with continued storage there was a marked increase in the incidence of spermatozoa with secondary morphological changes in the group of boars regarded as producing more sensitive semen. Ejaculates of group I boars evaluated directly after collection had an approximately 6% smaller share of spermatozoa with undamaged cell membranes than the ejaculates of boars in group II (p≤0.05). In the process of time the percentage of spermatozoa with undamaged cell membranes decreased. The sperm of group I boars was characterised with a lower sperm motility than the semen of group II boars. After 1 hour of storing diluted semen, the sperm motility of boars producing highly sensitive semen was already 4% lower (p≤0.05), and after 24 hours of storage it was 6.33% lower than that of the boars that produced semen with a low sensitivity. Factors that confirm the accuracy of insemination male selection can include a low rate of sperm motility decrease during the storage of diluted semen, low and contained incidence of secondary morphological changes in spermatozoa during semen storage and a high frequency of spermatozoa with undamaged cell membranes. PMID:26580438

LASER BIOLOGY AND MEDICINE: Application of tunable diode lasers for a highly sensitive analysis of gaseous biomarkers in exhaled air

NASA Astrophysics Data System (ADS)

Stepanov, E. V.; Milyaev, Varerii A.

2002-11-01

The application of tunable diode lasers for a highly sensitive analysis of gaseous biomarkers in exhaled air in biomedical diagnostics is discussed. The principle of operation and the design of a laser analyser for studying the composition of exhaled air are described. The results of detection of gaseous biomarkers in exhaled air, including clinical studies, which demonstrate the diagnostic possibilities of the method, are presented.

An Investigation of the Dynamic Response of a Seismically Stable Platform

DTIC Science & Technology

1982-08-01

PAD. The controls on the -9system are of two types. A low frequency tilt control, with a 10 arc second sensitivity, 2-axis tiltmeter as sensor ...Inertial Sensors Structural Analysis Holloman AFB, NiM. Support to this effort includes structural analyses toward active servo frequency band. This report...controlled to maintain a null position of a sensitive height sensor . The 6-degree-of- freedom high frequency controls are based on seismometers as sensors

Structural optimization: Status and promise

NASA Astrophysics Data System (ADS)

Kamat, Manohar P.

Chapters contained in this book include fundamental concepts of optimum design, mathematical programming methods for constrained optimization, function approximations, approximate reanalysis methods, dual mathematical programming methods for constrained optimization, a generalized optimality criteria method, and a tutorial and survey of multicriteria optimization in engineering. Also included are chapters on the compromise decision support problem and the adaptive linear programming algorithm, sensitivity analyses of discrete and distributed systems, the design sensitivity analysis of nonlinear structures, optimization by decomposition, mixed elements in shape sensitivity analysis of structures based on local criteria, and optimization of stiffened cylindrical shells subjected to destabilizing loads. Other chapters are on applications to fixed-wing aircraft and spacecraft, integrated optimum structural and control design, modeling concurrency in the design of composite structures, and tools for structural optimization. (No individual items are abstracted in this volume)

Financial analysis of cardiovascular wellness program provided to self-insured company from pharmaceutical care provider's perspective.

PubMed

Wilson, Justin B; Osterhaus, Matt C; Farris, Karen B; Doucette, William R; Currie, Jay D; Bullock, Tammy; Kumbera, Patty

2005-01-01

To perform a retrospective financial analysis on the implementation of a self-insured company's wellness program from the pharmaceutical care provider's perspective and conduct sensitivity analyses to estimate costs versus revenues for pharmacies without resident pharmacists, program implementation for a second employer, the second year of the program, and a range of pharmacist wages. Cost-benefit and sensitivity analyses. Self-insured employer with headquarters in Canton, N.C. 36 employees at facility in Clinton, Iowa. Pharmacist-provided cardiovascular wellness program. Costs and revenues collected from pharmacy records, including pharmacy purchasing records, billing records, and pharmacists' time estimates. All costs and revenues were calculated for the development and first year of the intervention program. Costs included initial and follow-up screening supplies, office supplies, screening/group presentation time, service provision time, documentation/preparation time, travel expenses, claims submission time, and administrative fees. Revenues included initial screening revenues, follow-up screening revenues, group session revenues, and Heart Smart program revenues. For the development and first year of Heart Smart, net benefit to the pharmacy (revenues minus costs) amounted to dollars 2,413. All sensitivity analyses showed a net benefit. For pharmacies without a resident pharmacist, the net benefit was dollars 106; for Heart Smart in a second employer, the net benefit was dollars 6,024; for the second year, the projected net benefit was dollars 6,844; factoring in a lower pharmacist salary, the net benefit was dollars 2,905; and for a higher pharmacist salary, the net benefit was dollars 1,265. For the development and first year of Heart Smart, the revenues of the wellness program in a self-insured company outweighed the costs.

Evaluation of a Method for Remote Detection of Fuel Relocation Outside the Original Core Volumes of Fukushima Reactor Units 1-3

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

Douglas W. Akers; Edwin A. Harvego

2012-08-01

This paper presents the results of a study to evaluate the feasibility of remotely detecting and quantifying fuel relocation from the core to the lower head, and to regions outside the reactor vessel primary containment of the Fukushima 1-3 reactors. The goals of this study were to determine measurement conditions and requirements, and to perform initial radiation transport sensitivity analyses for several potential measurement locations inside the reactor building. The radiation transport sensitivity analyses were performed based on reactor design information for boiling water reactors (BWRs) similar to the Fukushima reactors, ORIGEN2 analyses of 3-cycle BWR fuel inventories, and datamore » on previously molten fuel characteristics from TMI- 2. A 100 kg mass of previously molten fuel material located on the lower head of the reactor vessel was chosen as a fuel interrogation sensitivity target. Two measurement locations were chosen for the transport analyses, one inside the drywell and one outside the concrete biological shield surrounding the drywell. Results of these initial radiation transport analyses indicate that the 100 kg of previously molten fuel material may be detectable at the measurement location inside the drywell, but that it is highly unlikely that any amount of fuel material inside the RPV will be detectable from a location outside the concrete biological shield surrounding the drywell. Three additional fuel relocation scenarios were also analyzed to assess detection sensitivity for varying amount of relocated material in the lower head of the reactor vessel, in the control rods perpendicular to the detector system, and on the lower head of the drywell. Results of these analyses along with an assessment of background radiation effects and a discussion of measurement issues, such as the detector/collimator design, are included in the paper.« less

The sensitivity of the ESA DELTA model

NASA Astrophysics Data System (ADS)

Martin, C.; Walker, R.; Klinkrad, H.

Long-term debris environment models play a vital role in furthering our understanding of the future debris environment, and in aiding the determination of a strategy to preserve the Earth orbital environment for future use. By their very nature these models have to make certain assumptions to enable informative future projections to be made. Examples of these assumptions include the projection of future traffic, including launch and explosion rates, and the methodology used to simulate break-up events. To ensure a sound basis for future projections, and consequently for assessing the effectiveness of various mitigation measures, it is essential that the sensitivity of these models to variations in key assumptions is examined. The DELTA (Debris Environment Long Term Analysis) model, developed by QinetiQ for the European Space Agency, allows the future projection of the debris environment throughout Earth orbit. Extensive analyses with this model have been performed under the auspices of the ESA Space Debris Mitigation Handbook and following the recent upgrade of the model to DELTA 3.0. This paper draws on these analyses to present the sensitivity of the DELTA model to changes in key model parameters and assumptions. Specifically the paper will address the variation in future traffic rates, including the deployment of satellite constellations, and the variation in the break-up model and criteria used to simulate future explosion and collision events.

Sensitivity to Change and Responsiveness of Four Balance Measures for Community-Dwelling Older Adults

PubMed Central

Latham, Nancy K.; Jette, Alan M.; Wagenaar, Robert C.; Ni, Pengsheng; Slavin, Mary D.; Bean, Jonathan F.

2012-01-01

Background Impaired balance has a significant negative impact on mobility, functional independence, and fall risk in older adults. Although several, well-respected balance measures are currently in use, there is limited evidence regarding the most appropriate measure to assess change in community-dwelling older adults. Objective The aim of this study was to compare floor and ceiling effects, sensitivity to change, and responsiveness across the following balance measures in community-dwelling elderly people with functional limitations: Berg Balance Scale (BBS), Performance-Oriented Mobility Assessment total scale (POMA-T), POMA balance subscale (POMA-B), and Dynamic Gait Index (DGI). Design Retrospective data from a 16-week exercise trial were used. Secondary analyses were conducted on the total sample and by subgroups of baseline functional limitation or baseline balance scores. Methods Participants were 111 community-dwelling older adults 65 years of age or older, with functional limitations. Sensitivity to change was assessed using effect size, standardized response mean, and paired t tests. Responsiveness was assessed using minimally important difference (MID) estimates. Results No floor effects were noted. Ceiling effects were observed on all measures, including in people with moderate to severe functional limitations. The POMA-T, POMA-B, and DGI showed significantly larger ceiling effects compared with the BBS. All measures had low sensitivity to change in total sample analyses. Subgroup analyses revealed significantly better sensitivity to change in people with lower compared with higher baseline balance scores. Although both the total sample and lower baseline balance subgroups showed statistically significant improvement from baseline to 16 weeks on all measures, only the lower balance subgroup showed change scores that consistently exceeded corresponding MID estimates. Limitations This study was limited to comparing 4 measures of balance, and anchor-based methods for assessing MID could not be reported. Conclusions Important limitations, including ceiling effects and relatively low sensitivity to change and responsiveness, were noted across all balance measures, highlighting their limited utility across the full spectrum of the community-dwelling elderly population. New, more challenging measures are needed for better discrimination of balance ability in community-dwelling elderly people at higher functional levels. PMID:22114200

Racial and ethnic differences in experimental pain sensitivity: systematic review and meta-analysis.

PubMed

Kim, Hee Jun; Yang, Gee Su; Greenspan, Joel D; Downton, Katherine D; Griffith, Kathleen A; Renn, Cynthia L; Johantgen, Meg; Dorsey, Susan G

2017-02-01

Our objective was to describe the racial and ethnic differences in experimental pain sensitivity. Four databases (PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO) were searched for studies examining racial/ethnic differences in experimental pain sensitivity. Thermal-heat, cold-pressor, pressure, ischemic, mechanical cutaneous, electrical, and chemical experimental pain modalities were assessed. Risk of bias was assessed using the Agency for Healthcare Research and Quality guideline. Meta-analysis was used to calculate standardized mean differences (SMDs) by pain sensitivity measures. Studies comparing African Americans (AAs) and non-Hispanic whites (NHWs) were included for meta-analyses because of high heterogeneity in other racial/ethnic group comparisons. Statistical heterogeneity was assessed by subgroup analyses by sex, sample size, sample characteristics, and pain modalities. A total of 41 studies met the review criteria. Overall, AAs, Asians, and Hispanics had higher pain sensitivity compared with NHWs, particularly lower pain tolerance, higher pain ratings, and greater temporal summation of pain. Meta-analyses revealed that AAs had lower pain tolerance (SMD: -0.90, 95% confidence intervals [CIs]: -1.10 to -0.70) and higher pain ratings (SMD: 0.50, 95% CI: 0.30-0.69) but no significant differences in pain threshold (SMD: -0.06, 95% CI: -0.23 to 0.10) compared with NHWs. Estimates did not vary by pain modalities, nor by other demographic factors; however, SMDs were significantly different based on the sample size. Racial/ethnic differences in experimental pain sensitivity were more pronounced with suprathreshold than with threshold stimuli, which is important in clinical pain treatment. Additional studies examining mechanisms to explain such differences in pain tolerance and pain ratings are needed.

Adjoint-Based Sensitivity and Uncertainty Analysis for Density and Composition: A User’s Guide

DOE PAGES

Favorite, Jeffrey A.; Perko, Zoltan; Kiedrowski, Brian C.; ...

2017-03-01

The ability to perform sensitivity analyses using adjoint-based first-order sensitivity theory has existed for decades. This paper provides guidance on how adjoint sensitivity methods can be used to predict the effect of material density and composition uncertainties in critical experiments, including when these uncertain parameters are correlated or constrained. Two widely used Monte Carlo codes, MCNP6 (Ref. 2) and SCALE 6.2 (Ref. 3), are both capable of computing isotopic density sensitivities in continuous energy and angle. Additionally, Perkó et al. have shown how individual isotope density sensitivities, easily computed using adjoint methods, can be combined to compute constrained first-order sensitivitiesmore » that may be used in the uncertainty analysis. This paper provides details on how the codes are used to compute first-order sensitivities and how the sensitivities are used in an uncertainty analysis. Constrained first-order sensitivities are computed in a simple example problem.« less

Autonomous Mars ascent and orbit rendezvous for earth return missions

NASA Technical Reports Server (NTRS)

Edwards, H. C.; Balmanno, W. F.; Cruz, Manuel I.; Ilgen, Marc R.

1991-01-01

The details of tha assessment of autonomous Mars ascent and orbit rendezvous for earth return missions are presented. Analyses addressing navigation system assessments, trajectory planning, targeting approaches, flight control guidance strategies, and performance sensitivities are included. Tradeoffs in the analysis and design process are discussed.

Data to DecisionsTerminate, Tolerate, Transfer, or Treat

DTIC Science & Technology

2016-07-25

and patching, a risk-based cyber - security decision model that enables a pre- dictive capability to respond to impending cyber -attacks is needed...States. This sensitive data includes business proprietary information on key programs of record and infrastructure, including government documents at...leverage nationally. The Institute for Defense Analyses (IDA) assisted the DoD CIO in formalizing a proof of concept for cyber initiatives and

Magnesium Oxide (MgO) pH-sensitive Sensing Membrane in Electrolyte-Insulator-Semiconductor Structures with CF4 Plasma Treatment.

PubMed

Kao, Chyuan-Haur; Chang, Chia Lung; Su, Wei Ming; Chen, Yu Tzu; Lu, Chien Cheng; Lee, Yu Shan; Hong, Chen Hao; Lin, Chan-Yu; Chen, Hsiang

2017-08-03

Magnesium oxide (MgO) sensing membranes in pH-sensitive electrolyte-insulator-semiconductor structures were fabricated on silicon substrate. To optimize the sensing capability of the membrane, CF 4 plasma was incorporated to improve the material quality of MgO films. Multiple material analyses including FESEM, XRD, AFM, and SIMS indicate that plasma treatment might enhance the crystallization and increase the grain size. Therefore, the sensing behaviors in terms of sensitivity, linearity, hysteresis effects, and drift rates might be improved. MgO-based EIS membranes with CF 4 plasma treatment show promise for future industrial biosensing applications.

Quality of clinical and economic evidence in dossier formulary submissions.

PubMed

Colmenero, Fernando; Sullivan, Sean D; Palmer, Jennifer A; Brauer, Carmen A; Bungay, Kathleen; Watkins, John; Neumann, Peter J

2007-07-01

To investigate the quality and completeness of clinical and economic data in dossiers submitted by drug companies to a health plan using Academy of Managed Care Pharmacy guidelines (the Format) for formulary submissions. We reviewed the quality of economic analyses in dossiers submitted to Premera Blue Cross Health Plan (Mountlake Terrace, Washington; enrollment 1.6 million) between January 2002 and September 2005. For dossiers submitted in 2003, we examined the clinical studies included. Dossiers were audited with a data collection form to judge the types of clinical studies used to support labeled and off-label indications, and the quality and transparency of economic analyses. We compared economic analyses for high-cost (30-day treatment cost > $1000) versus low-cost products, and for "innovative" versus "me-too" drugs. Evidence to support off-label indications often was included in 2003 dossiers, but the information was less extensive and of poorer quality than data for labeled indications. Of 115 dossiers submitted between 2002 and 2005, 53 (46%) included economic analyses. The economic analyses had low levels of compliance with standards: only 43% performed sensitivity analysis; 38% stated the study perspective; 37% discussed relevant treatment alternatives; 20% stated assumptions clearly; and 18% mentioned caveats to conclusions. Economic analyses of high-cost products and innovative products had higher compliance with recommended practices. Drug companies are submitting dossiers of evidence to formulary committees. Dossiers often included clinical data to support off-label indications, but concerns persist about their quality. About half of dossiers included economic analyses, but these analyses had relatively low levels of compliance with recommended practices.

Clinical effects of pre-adjusted edgewise orthodontic brackets: a systematic review and meta-analysis.

PubMed

Papageorgiou, Spyridon N; Konstantinidis, Ioannis; Papadopoulou, Konstantina; Jäger, Andreas; Bourauel, Christoph

2014-06-01

Fixed-appliance treatment is a major part of orthodontic treatment, but clinical evidence remains scarce. Objective of this systematic review was to investigate how the therapeutic effects and side-effects of brackets used during the fixed-appliance orthodontic treatment are affected by their characteristics. SEARCH METHODS AND SELECTION CRITERIA: We searched MEDLINE and 18 other databases through April 2012 without restrictions for randomized controlled trials and quasi-randomized controlled trials investigating any bracket characteristic. After duplicate selection and extraction procedures, risk of bias was assessed also in duplicate according to Cochrane guidelines and quality of evidence according to the Grades of Recommendation. Assessment, Development and Evaluation approach. Random-effects meta-analyses, subgroup analyses, and sensitivity analyses were performed with the corresponding 95 per cent confidence intervals (CI) and 95 per cent prediction intervals (PI). We included 25 trials on 1321 patients, with most comparing self-ligated (SL) and conventional brackets. Based on the meta-analyses, the duration of orthodontic treatment was on average 2.01 months longer among patients with SL brackets (95 per cent CI: 0.45 to 3.57). The 95 per cent PIs for a future trial indicated that the difference could be considerable (-1.46 to 5.47 months). Treatment characteristics, outcomes, and side-effects were clinically similar between SL and conventional brackets. For most bracket characteristics, evidence is insufficient. Some meta-analyses included trials with high risk of bias, but sensitivity analyses indicated robustness. Based on existing evidence, no clinical recommendation can be made regarding the bracket material or different ligation modules. For SL brackets, no conclusive benefits could be proven, while their use was associated with longer treatment durations.

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

PubMed

Kepes, Sven; McDaniel, Michael A

2015-01-01

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. 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. 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. 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.

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

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.

Informing the Symptom Profile of Complicated Grief

PubMed Central

Simon, Naomi M.; Wall, Melanie M.; Keshaviah, Aparna; Dryman, M. Taylor; LeBlanc, Nicole J.; Shear, M. Katherine

2010-01-01

Background Complicated Grief (CG) is under consideration as a new diagnosis in DSM5. We sought to add empirical support to the current dialogue by examining the commonly used Inventory of Complicated Grief (ICG) scale completed by 782 bereaved individuals. Methods We employed IRT analyses, factor analyses, and sensitivity and specificity analyses utilizing our full sample (n=782), and also compared confirmed CG cases (n=288) to non-cases (n=377). Confirmed CG cases were defined as individuals bereaved at least 6 months who were seeking care for CG, had an ICG ≥ 30, and received a structured clinical interview for CG by a certified clinician confirming CG as their primary illness. Non-cases were bereaved individuals who did not present with CG as a primary complaint (including those with depression, bipolar disorder, anxiety disorders and controls) and had an ICG<25. Results IRT analyses provided guidance about the most informative individual items and their association with CG severity. Factor analyses demonstrated a single factor solution when the full sample was considered, but within CG cases, six symptom clusters emerged: 1) yearning and preoccupation with the deceased, 2) anger and bitterness, 3) shock and disbelief, 4) estrangement from others, 5) hallucinations of the deceased, and 6) behavior change, including avoidance and proximity seeking. The presence of at least one symptom from three different symptom clusters optimized sensitivity (94.8%) and specificity (98.1%). Conclusions These data, derived from a diverse and predominantly clinical help seeking population, add an important perspective to existing suggestions for DSM5 criteria for CG. PMID:21284064

SIMULATING RADIONUCLIDE FATE AND TRANSPORT IN THE UNSATURATED ZONE: EVALUATION AND SENSITIVITY ANALYSES OF SELECT COMPUTER MODELS

EPA Science Inventory

Numerical, mathematical models of water and chemical movement in soils are used as decision aids for determining soil screening levels (SSLs) of radionuclides in the unsaturated zone. Many models require extensive input parameters which include uncertainty due to soil variabil...

Collapse of elongated voids in porous energetic materials: Effects of void orientation and aspect ratio on initiation

NASA Astrophysics Data System (ADS)

Rai, Nirmal Kumar; Schmidt, Martin J.; Udaykumar, H. S.

2017-04-01

The sensitivity of porous energetic materials depends on mesostructural heterogeneities such as voids, defects, cracks, and grain boundaries. The mesostructure of pressed explosives contains voids of arbitrary shapes including elongated voids of various orientations and aspect ratios. Mesoscale simulations to date have analyzed the effect of void morphology on the sensitivity of energetic materials for idealized shapes such as cylindrical, conical, and elliptical. This work analyzes the sensitivity behavior of elongated voids in an HMX matrix subject to shock loading. Simulations show that sensitivity of elongated voids depends strongly on orientation as well as aspect ratio. Ranges of orientations and aspects ratios are identified that enhance or inhibit initiation. Insights obtained from single elongated void analyses are used to identify sensitive locations in an imaged mesostructure of a pressed explosive sample.

Chromatic and achromatic visual fields in relation to choroidal thickness in patients with high myopia: A pilot study.

PubMed

García-Domene, M C; Luque, M J; Díez-Ajenjo, M A; Desco-Esteban, M C; Artigas, J M

2018-02-01

To analyse the relationship between the choroidal thickness and the visual perception of patients with high myopia but without retinal damage. All patients underwent ophthalmic evaluation including a slit lamp examination and dilated ophthalmoscopy, subjective refraction, best corrected visual acuity, axial length, optical coherence tomography, contrast sensitivity function and sensitivity of the visual pathways. We included eleven eyes of subjects with high myopia. There are statistical correlations between choroidal thickness and almost all the contrast sensitivity values. The sensitivity of magnocellular and koniocellular pathways is the most affected, and the homogeneity of the sensibility of the magnocellular pathway depends on the choroidal thickness; when the thickness decreases, the sensitivity impairment extends from the center to the periphery of the visual field. Patients with high myopia without any fundus changes have visual impairments. We have found that choroidal thickness correlates with perceptual parameters such as contrast sensitivity or mean defect and pattern standard deviation of the visual fields of some visual pathways. Our study shows that the magnocellular and koniocellular pathways are the most affected, so that these patients have impairment in motion perception and blue-yellow contrast perception. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Climate sensitivity of shrub growth across the tundra biome

NASA Astrophysics Data System (ADS)

Myers-Smith, Isla H.; Elmendorf, Sarah C.; Beck, Pieter S. A.; Wilmking, Martin; Hallinger, Martin; Blok, Daan; Tape, Ken D.; Rayback, Shelly A.; Macias-Fauria, Marc; Forbes, Bruce C.; Speed, James D. M.; Boulanger-Lapointe, Noémie; Rixen, Christian; Lévesque, Esther; Schmidt, Niels Martin; Baittinger, Claudia; Trant, Andrew J.; Hermanutz, Luise; Collier, Laura Siegwart; Dawes, Melissa A.; Lantz, Trevor C.; Weijers, Stef; Jørgensen, Rasmus Halfdan; Buchwal, Agata; Buras, Allan; Naito, Adam T.; Ravolainen, Virve; Schaepman-Strub, Gabriela; Wheeler, Julia A.; Wipf, Sonja; Guay, Kevin C.; Hik, David S.; Vellend, Mark

2015-09-01

Rapid climate warming in the tundra biome has been linked to increasing shrub dominance. Shrub expansion can modify climate by altering surface albedo, energy and water balance, and permafrost, yet the drivers of shrub growth remain poorly understood. Dendroecological data consisting of multi-decadal time series of annual shrub growth provide an underused resource to explore climate-growth relationships. Here, we analyse circumpolar data from 37 Arctic and alpine sites in 9 countries, including 25 species, and ~42,000 annual growth records from 1,821 individuals. Our analyses demonstrate that the sensitivity of shrub growth to climate was: (1) heterogeneous, with European sites showing greater summer temperature sensitivity than North American sites, and (2) higher at sites with greater soil moisture and for taller shrubs (for example, alders and willows) growing at their northern or upper elevational range edges. Across latitude, climate sensitivity of growth was greatest at the boundary between the Low and High Arctic, where permafrost is thawing and most of the global permafrost soil carbon pool is stored. The observed variation in climate-shrub growth relationships should be incorporated into Earth system models to improve future projections of climate change impacts across the tundra biome.

Characterizing Uncertainty and Variability in PBPK Models ...

EPA Pesticide Factsheets

Mode-of-action based risk and safety assessments can rely upon tissue dosimetry estimates in animals and humans obtained from physiologically-based pharmacokinetic (PBPK) modeling. However, risk assessment also increasingly requires characterization of uncertainty and variability; such characterization for PBPK model predictions represents a continuing challenge to both modelers and users. Current practices show significant progress in specifying deterministic biological models and the non-deterministic (often statistical) models, estimating their parameters using diverse data sets from multiple sources, and using them to make predictions and characterize uncertainty and variability. The International Workshop on Uncertainty and Variability in PBPK Models, held Oct 31-Nov 2, 2006, sought to identify the state-of-the-science in this area and recommend priorities for research and changes in practice and implementation. For the short term, these include: (1) multidisciplinary teams to integrate deterministic and non-deterministic/statistical models; (2) broader use of sensitivity analyses, including for structural and global (rather than local) parameter changes; and (3) enhanced transparency and reproducibility through more complete documentation of the model structure(s) and parameter values, the results of sensitivity and other analyses, and supporting, discrepant, or excluded data. Longer-term needs include: (1) theoretic and practical methodological impro

Breastfeeding and its relation to maternal sensitivity and infant attachment.

PubMed

Tharner, Anne; Luijk, Maartje P C M; Raat, Hein; Ijzendoorn, Marinus H; Bakermans-Kranenburg, Marian J; Moll, Henriette A; Jaddoe, Vincent W V; Hofman, Albert; Verhulst, Frank C; Tiemeier, Henning

2012-06-01

To examine the association of breastfeeding with maternal sensitive responsiveness and infant-mother attachment security and disorganization. We included 675 participants of a prospective cohort study. Questionnaires about breastfeeding practices were administered at 2 and 6 months postpartum. At 14 months, maternal sensitive responsiveness was assessed in a 13-minute laboratory procedure using Ainsworth's sensitivity scales, and attachment quality was assessed with the Strange Situation Procedure. Mothers were genotyped for oxytocin receptor genes OXTR rs53576 and OXTR rs2254298. Linear regressions and analyses of covariance adjusted for various background variables were conducted. We tested for mediation and moderation by maternal sensitive responsiveness and maternal oxytocin receptor genotype. Continuous analyses showed that longer duration of breastfeeding was associated with more maternal sensitive responsiveness (B = 0.11, 95% confidence interval [CI] 0.02; 0.20, p < .05), more attachment security (B = 0.24, 95% CI = 0.02; 0.46, p < .05), and less attachment disorganization (B = -0.20, 95% CI -0.36; -0.03, p < .05). Duration of breastfeeding was not related to the risk of insecure-avoidant or insecure-resistant versus secure attachment classification, but longer duration of breastfeeding predicted a lower risk of disorganized versus secure attachment classification (n = 151; odds ratio [OR] = 0.81, 95% CI 0.66 to 0.99, p = .04). Maternal sensitive responsiveness did not mediate the associations, and maternal oxytocin receptor genotype was not a significant moderator. Although duration of breastfeeding was not associated with differences in infant-mother attachment classifications, we found subtle positive associations between duration of breastfeeding and sensitive responsiveness, attachment security, and disorganization.

Panic and phobic anxiety: associations among neuroticism, physiological hyperarousal, anxiety sensitivity, and three phobias.

PubMed

Longley, Susan L; Watson, David; Noyes, Russell; Yoder, Kevin

2006-01-01

A dimensional and psychometrically informed taxonomy of anxiety is emerging, but the specific and nonspecific dimensions of panic and phobic anxiety require greater clarification. In this study, confirmatory factor analyses of data from a sample of 438 college students were used to validate a model of panic and phobic anxiety with six content factors; multiple scales from self-report measures were indicators of each model component. The model included a nonspecific component of (1) neuroticism and two specific components of panic attack, (2) physiological hyperarousal, and (3) anxiety sensitivity. The model also included three phobia components of (4) classically defined agoraphobia, (5) social phobia, and (6) blood-injection phobia. In these data, agoraphobia correlated more strongly with both the social phobia and blood phobia components than with either the physiological hyperarousal or the anxiety sensitivity components. These findings suggest that the association between panic attacks and agoraphobia warrants greater attention.

Shared Genetic Control of Brain Activity During Sleep and Insulin Secretion: A Laboratory-Based Family Study.

PubMed

Morselli, Lisa L; Gamazon, Eric R; Tasali, Esra; Cox, Nancy J; Van Cauter, Eve; Davis, Lea K

2018-01-01

Over the past 20 years, a large body of experimental and epidemiologic evidence has linked sleep duration and quality to glucose homeostasis, although the mechanistic pathways remain unclear. The aim of the current study was to determine whether genetic variation influencing both sleep and glucose regulation could underlie their functional relationship. We hypothesized that the genetic regulation of electroencephalographic (EEG) activity during non-rapid eye movement sleep, a highly heritable trait with fingerprint reproducibility, is correlated with the genetic control of metabolic traits including insulin sensitivity and β-cell function. We tested our hypotheses through univariate and bivariate heritability analyses in a three-generation pedigree with in-depth phenotyping of both sleep EEG and metabolic traits in 48 family members. Our analyses accounted for age, sex, adiposity, and the use of psychoactive medications. In univariate analyses, we found significant heritability for measures of fasting insulin sensitivity and β-cell function, for time spent in slow-wave sleep, and for EEG spectral power in the delta, theta, and sigma ranges. Bivariate heritability analyses provided the first evidence for a shared genetic control of brain activity during deep sleep and fasting insulin secretion rate. © 2017 by the American Diabetes Association.

Comprehensive Evaluation of the Contribution of X Chromosome Genes to Platinum Sensitivity

PubMed Central

Gamazon, Eric R.; Im, Hae Kyung; O’Donnell, Peter H.; Ziliak, Dana; Stark, Amy L.; Cox, Nancy J.; Dolan, M. Eileen; Huang, Rong Stephanie

2011-01-01

Utilizing a genome-wide gene expression dataset generated from Affymetrix GeneChip® Human Exon 1.0ST array, we comprehensively surveyed the role of 322 X chromosome gene expression traits on cellular sensitivity to cisplatin and carboplatin. We identified 31 and 17 X chromosome genes whose expression levels are significantly correlated (after multiple testing correction) with sensitivity to carboplatin and cisplatin, respectively, in the combined HapMap CEU and YRI populations (false discovery rate, FDR<0.05). Of those, 14 overlap for both cisplatin and carboplatin. Employing an independent gene expression quantification method, the Illumina Sentrix Human-6 Expression BeadChip, measured on the same HapMap cell lines, we found that 4 and 2 of these genes are significantly associated with carboplatin and cisplatin sensitivity respectively in both analyses. Two genes, CTPS2 and DLG3, were identified by both genome-wide gene expression analyses as correlated with cellular sensitivity to both platinating agents. The expression of DLG3 gene was also found to correlate with cellular sensitivity to platinating agents in NCI60 cancer cell lines. In addition, we evaluated the role of X chromosome gene expression to the observed differences in sensitivity to the platinums between CEU and YRI derived cell lines. Of the 34 distinct genes significantly correlated with either carboplatin or cisplatin sensitivity, 14 are differentially expressed (defined as p<0.05) between CEU and YRI. Thus, sex chromosome genes play a role in cellular sensitivity to platinating agents and differences in the expression level of these genes are an important source of variation that should be included in comprehensive pharmacogenomic studies. PMID:21252287

Sediment delivery modeling in practice: Comparing the effects of watershed characteristics and data resolution across hydroclimatic regions.

PubMed

Hamel, Perrine; Falinski, Kim; Sharp, Richard; Auerbach, Daniel A; Sánchez-Canales, María; Dennedy-Frank, P James

2017-02-15

Geospatial models are commonly used to quantify sediment contributions at the watershed scale. However, the sensitivity of these models to variation in hydrological and geomorphological features, in particular to land use and topography data, remains uncertain. Here, we assessed the performance of one such model, the InVEST sediment delivery model, for six sites comprising a total of 28 watersheds varying in area (6-13,500km 2 ), climate (tropical, subtropical, mediterranean), topography, and land use/land cover. For each site, we compared uncalibrated and calibrated model predictions with observations and alternative models. We then performed correlation analyses between model outputs and watershed characteristics, followed by sensitivity analyses on the digital elevation model (DEM) resolution. Model performance varied across sites (overall r 2 =0.47), but estimates of the magnitude of specific sediment export were as or more accurate than global models. We found significant correlations between metrics of sediment delivery and watershed characteristics, including erosivity, suggesting that empirical relationships may ultimately be developed for ungauged watersheds. Model sensitivity to DEM resolution varied across and within sites, but did not correlate with other observed watershed variables. These results were corroborated by sensitivity analyses performed on synthetic watersheds ranging in mean slope and DEM resolution. Our study provides modelers using InVEST or similar geospatial sediment models with practical insights into model behavior and structural uncertainty: first, comparison of model predictions across regions is possible when environmental conditions differ significantly; second, local knowledge on the sediment budget is needed for calibration; and third, model outputs often show significant sensitivity to DEM resolution. Copyright © 2016 Elsevier B.V. All rights reserved.

Quantitative aspects of inductively coupled plasma mass spectrometry

NASA Astrophysics Data System (ADS)

Bulska, Ewa; Wagner, Barbara

2016-10-01

Accurate determination of elements in various kinds of samples is essential for many areas, including environmental science, medicine, as well as industry. Inductively coupled plasma mass spectrometry (ICP-MS) is a powerful tool enabling multi-elemental analysis of numerous matrices with high sensitivity and good precision. Various calibration approaches can be used to perform accurate quantitative measurements by ICP-MS. They include the use of pure standards, matrix-matched standards, or relevant certified reference materials, assuring traceability of the reported results. This review critically evaluates the advantages and limitations of different calibration approaches, which are used in quantitative analyses by ICP-MS. Examples of such analyses are provided. This article is part of the themed issue 'Quantitative mass spectrometry'.

LOX/GOX sensitivity of fluoroelastomers. [effect of formulation components and addition of fire retardants

NASA Technical Reports Server (NTRS)

Kirshen, N.; Mill, T.

1973-01-01

The effect of formulation components and the addition of fire retardants on the impact sensitivity of Viton B fluoroelastomer in liquid oxygen was studied with the objective of developing a procedure for reliably reducing this sensitivity. Component evaluation, carried out on more than 40 combinations of components and cure cycles, showed that almost all the standard formulation agents, including carbon, MgO, Diak-3, and PbO2, will sensitize the Viton stock either singly or in combinations, some combinations being much more sensitive than others. Cure and postcure treatments usually reduced the sensitivity of a given formulation, often dramatically, but no formulated Viton was as insensitive as the pure Viton B stock. Coating formulated Viton with a thin layer of pure Viton gave some indication of reduced sensitivity, but additional tests are needed. It is concluded that sensitivity in formulated Viton arises from a variety of sources, some physical and some chemical in origin. Elemental analyses for all the formulated Vitons are reported as are the results of a literature search on the subject of LOX impact sensitivity.

Frequency band justifications for passive sensors 10.0 to 385 GHz, chapter 2. [for monitoring earth resources and the environment

NASA Technical Reports Server (NTRS)

1976-01-01

Sensitivity requirements of the various measurements obtained by microwave sensors, and radiometry techniques are described. Analytical techniques applied to detailed sharing analyses are discussed. A bibliography of publications pertinent to the scientific justification of frequency requirements for passive microwave remote sensing is included.

Performance of Stratified and Subgrouped Disproportionality Analyses in Spontaneous Databases.

PubMed

Seabroke, Suzie; Candore, Gianmario; Juhlin, Kristina; Quarcoo, Naashika; Wisniewski, Antoni; Arani, Ramin; Painter, Jeffery; Tregunno, Philip; Norén, G Niklas; Slattery, Jim

2016-04-01

Disproportionality analyses are used in many organisations to identify adverse drug reactions (ADRs) from spontaneous report data. Reporting patterns vary over time, with patient demographics, and between different geographical regions, and therefore subgroup analyses or adjustment by stratification may be beneficial. The objective of this study was to evaluate the performance of subgroup and stratified disproportionality analyses for a number of key covariates within spontaneous report databases of differing sizes and characteristics. Using a reference set of established ADRs, signal detection performance (sensitivity and precision) was compared for stratified, subgroup and crude (unadjusted) analyses within five spontaneous report databases (two company, one national and two international databases). Analyses were repeated for a range of covariates: age, sex, country/region of origin, calendar time period, event seriousness, vaccine/non-vaccine, reporter qualification and report source. Subgroup analyses consistently performed better than stratified analyses in all databases. Subgroup analyses also showed benefits in both sensitivity and precision over crude analyses for the larger international databases, whilst for the smaller databases a gain in precision tended to result in some loss of sensitivity. Additionally, stratified analyses did not increase sensitivity or precision beyond that associated with analytical artefacts of the analysis. The most promising subgroup covariates were age and region/country of origin, although this varied between databases. Subgroup analyses perform better than stratified analyses and should be considered over the latter in routine first-pass signal detection. Subgroup analyses are also clearly beneficial over crude analyses for larger databases, but further validation is required for smaller databases.

GEOS-3 phase B ground truth summary

NASA Technical Reports Server (NTRS)

Parsons, C. L.; Goodman, L. R.

1975-01-01

Ground truth data collected during the experiment systems calibration and evaluation phase of the Geodynamics experimental Ocean Satellite (GEOS-3) experiment are summarized. Both National Weather Service analyses and aircraft sensor data are included. The data are structured to facilitate the use of the various data products in calibrating the GEOS-3 radar altimeter and in assessing the altimeter's sensitivity to geophysical phenomena. Brief statements are made concerning the quality and completeness of the included data.

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

Analyses of microstructural and elastic properties of porous SOFC cathodes based on focused ion beam tomography

NASA Astrophysics Data System (ADS)

Chen, Zhangwei; Wang, Xin; Giuliani, Finn; Atkinson, Alan

2015-01-01

Mechanical properties of porous SOFC electrodes are largely determined by their microstructures. Measurements of the elastic properties and microstructural parameters can be achieved by modelling of the digitally reconstructed 3D volumes based on the real electrode microstructures. However, the reliability of such measurements is greatly dependent on the processing of raw images acquired for reconstruction. In this work, the actual microstructures of La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) cathodes sintered at an elevated temperature were reconstructed based on dual-beam FIB/SEM tomography. Key microstructural and elastic parameters were estimated and correlated. Analyses of their sensitivity to the grayscale threshold value applied in the image segmentation were performed. The important microstructural parameters included porosity, tortuosity, specific surface area, particle and pore size distributions, and inter-particle neck size distribution, which may have varying extent of effect on the elastic properties simulated from the microstructures using FEM. Results showed that different threshold value range would result in different degree of sensitivity for a specific parameter. The estimated porosity and tortuosity were more sensitive than surface area to volume ratio. Pore and neck size were found to be less sensitive than particle size. Results also showed that the modulus was essentially sensitive to the porosity which was largely controlled by the threshold value.

The analysis sensitivity to tropical winds from the Global Weather Experiment

NASA Technical Reports Server (NTRS)

Paegle, J.; Paegle, J. N.; Baker, W. E.

1986-01-01

The global scale divergent and rotational flow components of the Global Weather Experiment (GWE) are diagnosed from three different analyses of the data. The rotational flow shows closer agreement between the analyses than does the divergent flow. Although the major outflow and inflow centers are similarly placed in all analyses, the global kinetic energy of the divergent wind varies by about a factor of 2 between different analyses while the global kinetic energy of the rotational wind varies by only about 10 percent between the analyses. A series of real data assimilation experiments has been performed with the GLA general circulation model using different amounts of tropical wind data during the First Special Observing Period of the Global Weather Experiment. In exeriment 1, all available tropical wind data were used; in the second experiment, tropical wind data were suppressed; while, in the third and fourth experiments, only tropical wind data with westerly and easterly components, respectively, were assimilated. The rotational wind appears to be more sensitive to the presence or absence of tropical wind data than the divergent wind. It appears that the model, given only extratropical observations, generates excessively strong upper tropospheric westerlies. These biases are sufficiently pronounced to amplify the globally integrated rotational flow kinetic energy by about 10 percent and the global divergent flow kinetic energy by about a factor of 2. Including only easterly wind data in the tropics is more effective in controlling the model error than including only westerly wind data. This conclusion is especially noteworthy because approximately twice as many upper tropospheric westerly winds were available in these cases as easterly winds.

How Efficacious is Danshen (Salvia miltiorrhiza) Dripping Pill in Treating Angina Pectoris? Evidence Assessment for Meta-Analysis of Randomized Controlled Trials.

PubMed

Jia, Yongliang; Leung, Siu-Wai

2017-09-01

More than 230 randomized controlled trials (RCTs) of danshen dripping pill (DSP) and isosorbide dinitrate (ISDN) in treating angina pectoris after the first preferred reporting items for systematic reviews and meta-analyses-compliant comprehensive meta-analysis were published in 2010. Other meta-analyses had flaws in study selection, statistical meta-analysis, and evidence assessment. This study completed the meta-analysis with an extensive assessment of the evidence. RCTs published from 1994 to 2016 on DSP and ISDN in treating angina pectoris for at least 4 weeks were included. The risk of bias (RoB) of included RCTs was assessed with the Cochrane's tool for assessing RoB. Meta-analyses based on a random-effects model were performed on two outcome measures: symptomatic (SYM) and electrocardiography (ECG) improvements. Subgroup analysis, sensitivity analysis, metaregression, and publication bias analysis were also conducted. The evidence strength was evaluated with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) method. Among the included 109 RCTs with 11,973 participants, 49 RCTs and 5042 participants were new (after 2010). The RoB of included RCTs was high in randomization and blinding. Overall effect sizes in odds ratios for DSP over ISDN were 2.94 (95% confidence interval [CI]: 2.53-3.41) on SYM (n = 108) and 2.37 (95% CI: 2.08-2.69) by ECG (n = 81) with significant heterogeneities (I 2  = 41%, p < 0.0001 on SYM and I 2  = 44%, p < 0.0001 on ECG). Subgroup, sensitivity, and metaregression analyses showed consistent results without publication bias. However, the evidence strength was low in GRADE. The efficacy of DSP was still better than ISDN in treating angina pectoris, but the confidence decreased due to high RoB and heterogeneities.

Automated Cancer Registry Notifications: Validation of a Medical Text Analytics System for Identifying Patients with Cancer from a State-Wide Pathology Repository

PubMed Central

Nguyen, Anthony N; Moore, Julie; O'Dwyer, John; Philpot, Shoni

2016-01-01

The paper assesses the utility of Medtex on automating Cancer Registry notifications from narrative histology and cytology reports from the Queensland state-wide pathology information system. A corpus of 45.3 million pathology HL7 messages (including 119,581 histology and cytology reports) from a Queensland pathology repository for the year of 2009 was analysed by Medtex for cancer notification. Reports analysed by Medtex were consolidated at a patient level and compared against patients with notifiable cancers from the Queensland Oncology Repository (QOR). A stratified random sample of 1,000 patients was manually reviewed by a cancer clinical coder to analyse agreements and discrepancies. Sensitivity of 96.5% (95% confidence interval: 94.5-97.8%), specificity of 96.5% (95.3-97.4%) and positive predictive value of 83.7% (79.6-86.8%) were achieved for identifying cancer notifiable patients. Medtex achieved high sensitivity and specificity across the breadth of cancers, report types, pathology laboratories and pathologists throughout the State of Queensland. The high sensitivity also resulted in the identification of cancer patients that were not found in the QOR. High sensitivity was at the expense of positive predictive value; however, these cases may be considered as lower priority to Cancer Registries as they can be quickly reviewed. Error analysis revealed that system errors tended to be tumour stream dependent. Medtex is proving to be a promising medical text analytic system. High value cancer information can be generated through intelligent data classification and extraction on large volumes of unstructured pathology reports. PMID:28269893

Automated Cancer Registry Notifications: Validation of a Medical Text Analytics System for Identifying Patients with Cancer from a State-Wide Pathology Repository.

PubMed

Nguyen, Anthony N; Moore, Julie; O'Dwyer, John; Philpot, Shoni

2016-01-01

The paper assesses the utility of Medtex on automating Cancer Registry notifications from narrative histology and cytology reports from the Queensland state-wide pathology information system. A corpus of 45.3 million pathology HL7 messages (including 119,581 histology and cytology reports) from a Queensland pathology repository for the year of 2009 was analysed by Medtex for cancer notification. Reports analysed by Medtex were consolidated at a patient level and compared against patients with notifiable cancers from the Queensland Oncology Repository (QOR). A stratified random sample of 1,000 patients was manually reviewed by a cancer clinical coder to analyse agreements and discrepancies. Sensitivity of 96.5% (95% confidence interval: 94.5-97.8%), specificity of 96.5% (95.3-97.4%) and positive predictive value of 83.7% (79.6-86.8%) were achieved for identifying cancer notifiable patients. Medtex achieved high sensitivity and specificity across the breadth of cancers, report types, pathology laboratories and pathologists throughout the State of Queensland. The high sensitivity also resulted in the identification of cancer patients that were not found in the QOR. High sensitivity was at the expense of positive predictive value; however, these cases may be considered as lower priority to Cancer Registries as they can be quickly reviewed. Error analysis revealed that system errors tended to be tumour stream dependent. Medtex is proving to be a promising medical text analytic system. High value cancer information can be generated through intelligent data classification and extraction on large volumes of unstructured pathology reports.

Compliance and stress sensitivity of spur gear teeth

NASA Technical Reports Server (NTRS)

Cornell, R. W.

1983-01-01

The magnitude and variation of tooth pair compliance with load position affects the dynamics and loading significantly, and the tooth root stressing per load varies significantly with load position. Therefore, the recently developed time history, interactive, closed form solution for the dynamic tooth loads for both low and high contact ratio spur gears was expanded to include improved and simplified methods for calculating the compliance and stress sensitivity for three involute tooth forms as a function of load position. The compliance analysis has an improved fillet/foundation. The stress sensitivity analysis is a modified version of the Heywood method but with an improvement in the magnitude and location of the peak stress in the fillet. These improved compliance and stress sensitivity analyses are presented along with their evaluation using test, finite element, and analytic transformation results, which showed good agreement.

Which Measures of Online Control Are Least Sensitive to Offline Processes?

PubMed

de Grosbois, John; Tremblay, Luc

2018-02-28

A major challenge to the measurement of online control is the contamination by offline, planning-based processes. The current study examined the sensitivity of four measures of online control to offline changes in reaching performance induced by prism adaptation and terminal feedback. These measures included the squared Z scores (Z 2 ) of correlations of limb position at 75% movement time versus movement end, variable error, time after peak velocity, and a frequency-domain analysis (pPower). The results indicated that variable error and time after peak velocity were sensitive to the prism adaptation. Furthermore, only the Z 2 values were biased by the terminal feedback. Ultimately, the current study has demonstrated the sensitivity of limb kinematic measures to offline control processes and that pPower analyses may yield the most suitable measure of online control.

Association between response rates and survival outcomes in patients with newly diagnosed multiple myeloma. A systematic review and meta-regression analysis.

PubMed

Mainou, Maria; Madenidou, Anastasia-Vasiliki; Liakos, Aris; Paschos, Paschalis; Karagiannis, Thomas; Bekiari, Eleni; Vlachaki, Efthymia; Wang, Zhen; Murad, Mohammad Hassan; Kumar, Shaji; Tsapas, Apostolos

2017-06-01

We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM). Response outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression-free survival (PFS). We used random-effect meta-regression models and conducted sensitivity analyses based on definition of CR and study quality. Seventy-two trials were included in the systematic review, 63 of which contributed data in meta-regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] -0.06, 0.10), in patients undergoing ASCT (-.11, 95% CI -0.44, 0.22) and in trials comparing ASCT with non-ASCT patients (.04, 95% CI -0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results. This meta-regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses

PubMed Central

Soares, Marta O.; Palmer, Stephen; Ades, Anthony E.; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M.

2015-01-01

Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. PMID:25712447

Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses.

PubMed

Welton, Nicky J; Soares, Marta O; Palmer, Stephen; Ades, Anthony E; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M

2015-07-01

Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. © The Author(s) 2015.

[Inappropriate analyses of automated external defibrillators used during out-of-hospital cardiac arrests].

PubMed

Ballesteros Peña, Sendoa

2013-04-01

To estimate the frequency of therapeutic errors and to evaluate the diagnostic accuracy in the recognition of shockable rhythms by automated external defibrillators. A retrospective descriptive study. Nine basic life support units from Biscay (Spain). Included 201 patients with cardiac arrest, since 2006 to 2011. The study was made of the suitability of treatment (shock or not) after each analysis and medical errors identified. The sensitivity, specificity and predictive values with 95% confidence intervals were then calculated. A total of 811 electrocardiographic rhythm analyses were obtained, of which 120 (14.1%), from 30 patients, corresponded to shockable rhythms. Sensitivity and specificity for appropriate automated external defibrillators management of a shockable rhythm were 85% (95% CI, 77.5% to 90.3%) and 100% (95% CI, 99.4% to 100%), respectively. Positive and negative predictive values were 100% (95% CI, 96.4% to 100%) and 97.5% (95% CI, 96% to 98.4%), respectively. There were 18 (2.2%; 95% CI, 1.3% to 3.5%) errors associated with defibrillator management, all relating to cases of shockable rhythms that were not shocked. One error was operator dependent, 6 were defibrillator dependent (caused by interaction of pacemakers), and 11 were unclassified. Automated external defibrillators have a very high specificity and moderately high sensitivity. There are few operator dependent errors. Implanted pacemakers interfere with defibrillator analyses. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Examining the potential role of a supervised injection facility in Saskatoon, Saskatchewan, to avert HIV among people who inject drugs

PubMed Central

Jozaghi, Ehsan; Jackson, Asheka

2015-01-01

Background: Research predicting the public health and fiscal impact of Supervised Injection Facilities (SIFs), across different cities in Canada, has reported positive results on the reduction of HIV cases among People Who Inject Drugs (PWID). Most of the existing studies have focused on the outcomes of Insite, located in the Vancouver Downtown Eastside (DTES). Previous attention has not been afforded to other affected areas of Canada. The current study seeks to address this deficiency by assessing the cost-effectiveness of opening a SIF in Saskatoon, Saskatchewan. Methods: We used two different mathematical models commonly used in the literature, including sensitivity analyses, to estimate the number of HIV infections averted due to the establishment of a SIF in the city of Saskatoon, Saskatchewan. Results: Based on cumulative cost-effectiveness results, SIF establishment is cost-effective. The benefit to cost ratio was conservatively estimated to be 1.35 for the first two potential facilities. The study relied on 34% and 14% needle sharing rates for sensitivity analyses. The result for both sensitivity analyses and the base line estimates indicated positive prospects for the establishment of a SIF in Saskatoon. Conclusion: The opening of a SIF in Saskatoon, Saskatchewan is financially prudent in the reduction of tax payers’ expenses and averting HIV infection rates among PWID PMID:26029896

Validation of a portable nitric oxide analyzer for screening in primary ciliary dyskinesias.

PubMed

Harris, Amanda; Bhullar, Esther; Gove, Kerry; Joslin, Rhiannon; Pelling, Jennifer; Evans, Hazel J; Walker, Woolf T; Lucas, Jane S

2014-02-10

Nasal nitric oxide (nNO) levels are very low in primary ciliary dyskinesia (PCD) and it is used as a screening test. We assessed the reliability and usability of a hand-held analyser in comparison to a stationary nitric oxide (NO) analyser in 50 participants (15 healthy, 13 PCD, 22 other respiratory diseases; age 6-79 years). Nasal NO was measured using a stationary NO analyser during a breath-holding maneuver, and using a hand-held analyser during tidal breathing, sampling at 2 ml/sec or 5 ml/sec. The three methods were compared for their specificity and sensitivity as a screen for PCD, their success rate in different age groups, within subject repeatability and acceptability. Correlation between methods was assessed. Valid nNO measurements were obtained in 94% of participants using the stationary analyser, 96% using the hand-held analyser at 5 ml/sec and 76% at 2 ml/sec. The hand-held device at 5 ml/sec had excellent sensitivity and specificity as a screening test for PCD during tidal breathing (cut-off of 30 nL/min,100% sensitivity, >95% specificity). The cut-off using the stationary analyser during breath-hold was 38 nL/min (100% sensitivity, 95% specificity). The stationary and hand-held analyser (5 ml/sec) showed reasonable within-subject repeatability(% coefficient of variation = 15). The hand-held NO analyser provides a promising screening tool for PCD.

SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool

PubMed Central

Zi, Zhike; Zheng, Yanan; Rundell, Ann E; Klipp, Edda

2008-01-01

Background 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. Results 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. Conclusion SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes. PMID:18706080

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.

The geochemical landscape of northwestern Wisconsin and adjacent parts of northern Michigan and Minnesota (geochemical data files)

USGS Publications Warehouse

Cannon, William F.; Woodruff, Laurel G.

2003-01-01

This data set consists of nine files of geochemical information on various types of surficial deposits in northwestern Wisconsin and immediately adjacent parts of Michigan and Minnesota. The files are presented in two formats: as dbase files in dbaseIV form and Microsoft Excel form. The data present multi-element chemical analyses of soils, stream sediments, and lake sediments. Latitude and longitude values are provided in each file so that the dbf files can be readily imported to GIS applications. Metadata files are provided in outline form, question and answer form and text form. The metadata includes information on procedures for sample collection, sample preparation, and chemical analyses including sensitivity and precision.

Quantitative aspects of inductively coupled plasma mass spectrometry

PubMed Central

Wagner, Barbara

2016-01-01

Accurate determination of elements in various kinds of samples is essential for many areas, including environmental science, medicine, as well as industry. Inductively coupled plasma mass spectrometry (ICP-MS) is a powerful tool enabling multi-elemental analysis of numerous matrices with high sensitivity and good precision. Various calibration approaches can be used to perform accurate quantitative measurements by ICP-MS. They include the use of pure standards, matrix-matched standards, or relevant certified reference materials, assuring traceability of the reported results. This review critically evaluates the advantages and limitations of different calibration approaches, which are used in quantitative analyses by ICP-MS. Examples of such analyses are provided. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644971

Neptune Aerocapture Systems Analysis

NASA Technical Reports Server (NTRS)

Lockwood, Mary Kae

2004-01-01

A Neptune Aerocapture Systems Analysis is completed to determine the feasibility, benefit and risk of an aeroshell aerocapture system for Neptune and to identify technology gaps and technology performance goals. The high fidelity systems analysis is completed by a five center NASA team and includes the following disciplines and analyses: science; mission design; aeroshell configuration screening and definition; interplanetary navigation analyses; atmosphere modeling; computational fluid dynamics for aerodynamic performance and database definition; initial stability analyses; guidance development; atmospheric flight simulation; computational fluid dynamics and radiation analyses for aeroheating environment definition; thermal protection system design, concepts and sizing; mass properties; structures; spacecraft design and packaging; and mass sensitivities. Results show that aerocapture can deliver 1.4 times more mass to Neptune orbit than an all-propulsive system for the same launch vehicle. In addition aerocapture results in a 3-4 year reduction in trip time compared to all-propulsive systems. Aerocapture is feasible and performance is adequate for the Neptune aerocapture mission. Monte Carlo simulation results show 100% successful capture for all cases including conservative assumptions on atmosphere and navigation. Enabling technologies for this mission include TPS manufacturing; and aerothermodynamic methods and validation for determining coupled 3-D convection, radiation and ablation aeroheating rates and loads, and the effects on surface recession.

Practicing participatory research in American Indian communities1–3

PubMed Central

Davis, Sally M; Reid, Raymond

2016-01-01

The purpose of this article is to explore the historical issues that affect research in American Indian communities and examine the implications of these issues as they relate to culturally sensitive, respectful, and appropriate research with this population. Methods include review and analysis of the literature and examination of our collective experience and that of our colleagues. Recommendations are given for conducting culturally sensitive, participatory research. We conclude that research efforts must build on the establishment of partnerships between investigators and American Indian communities to ensure accurate findings and analyses and to implement culturally relevant benefits. PMID:10195598

Progress in multidisciplinary design optimization at NASA Langley

NASA Technical Reports Server (NTRS)

Padula, Sharon L.

1993-01-01

Multidisciplinary Design Optimization refers to some combination of disciplinary analyses, sensitivity analysis, and optimization techniques used to design complex engineering systems. The ultimate objective of this research at NASA Langley Research Center is to help the US industry reduce the costs associated with development, manufacturing, and maintenance of aerospace vehicles while improving system performance. This report reviews progress towards this objective and highlights topics for future research. Aerospace design problems selected from the author's research illustrate strengths and weaknesses in existing multidisciplinary optimization techniques. The techniques discussed include multiobjective optimization, global sensitivity equations and sequential linear programming.

Gender-specific Differences in Recurrence of Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis.

PubMed

Uhlig, Annemarie; Strauss, Arne; Seif Amir Hosseini, Ali; Lotz, Joachim; Trojan, Lutz; Schmid, Marianne; Uhlig, Johannes

2017-09-06

The incidence of urothelial carcinoma of the bladder (UCB) is lower in women; however, women tend to present with more advanced disease. To date, there is no quantitative synthesis of studies reporting gender-specific outcomes in non-muscle-invasive UCB. To conduct a meta-analysis evaluating gender-specific differences in recurrence of non-muscle-invasive urinary bladder cancer (NMIBC). An unrestricted systematic literature search of the MEDLINE, EMBASE, and Cochrane libraries was conducted. Studies evaluating the impact of gender on disease recurrence after local treatment of NMIBC using multivariable Cox proportional hazard models were included. Random effect meta-analysis, subgroup analyses, meta-influence, and cumulative meta-analyses were conducted. Publication bias was assessed via a funnel plot and Eggeŕs test. Of 609 studies screened, 27 comprising 23 754 patients were included. Random effect meta-analyses indicated women at increased risk for UCB recurrence compared with men (hazard ratio [HR]=1.11, 95% confidence interval [CI]: 1.01-1.23, p=0.03). Subgroup analyses yielded estimates between HR=0.99 and HR=1.68. Gender-specific differences in UCB recurrence were most pronounced in studies administering exclusively bacillus Calmette-Guerin (BCG; HR=1.64, 95% CI: 1.13-2.39, p=0.01), especially in a long-term treatment regimen (HR=1.68, 95% CI: 1.32-2.15, p<0.001). Sensitivity analyses confirmed female patients at increased risk for UCB recurrence. Women are at increased risk for disease recurrence after local treatment of NMIBC compared with male patients. Reduced effectiveness of BCG treatment might underlie this observation. Gender-specific differences were evident across various subgroups and proved robust upon sensitivity analyses. In this report, we combined several studies on gender-specific differences in relapse of superficial bladder cancer. Women were more likely to experience cancer relapse than men. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Pretest analysis document for Semiscale Test S-LH-1

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

Shaw, R.A.

Results from various pretest calculations which were performed for Test S-LH-1 are included in this report. Test S-LH-1 has been designed to produce primary liquid holdup in the steam generator U-tubes similar to Tests S-UT-8. The analyses included in this report indicate liquid will be held in the tubes, the core liquid level will be appropriately depressed, and a core heater rod temperature excursion should occur. Several sensitivity studies are also included which identify parameters which could affect the response.

The Effect of Regular Exercise on Insulin Sensitivity in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

PubMed Central

Hackett, Daniel A.; Baker, Michael K.

2016-01-01

The purpose of this study was to examine the effect of regular exercise training on insulin sensitivity in adults with type 2 diabetes mellitus (T2DM) using the pooled data available from randomised controlled trials. In addition, we sought to determine whether short-term periods of physical inactivity diminish the exercise-induced improvement in insulin sensitivity. Eligible trials included exercise interventions that involved ≥3 exercise sessions, and reported a dynamic measurement of insulin sensitivity. There was a significant pooled effect size (ES) for the effect of exercise on insulin sensitivity (ES, –0.588; 95% confidence interval [CI], –0.816 to –0.359; P<0.001). Of the 14 studies included for meta-analyses, nine studies reported the time of data collection from the last exercise bout. There was a significant improvement in insulin sensitivity in favour of exercise versus control between 48 and 72 hours after exercise (ES, –0.702; 95% CI, –1.392 to –0.012; P=0.046); and this persisted when insulin sensitivity was measured more than 72 hours after the last exercise session (ES, –0.890; 95% CI, –1.675 to –0.105; P=0.026). Regular exercise has a significant benefit on insulin sensitivity in adults with T2DM and this may persist beyond 72 hours after the last exercise session. PMID:27535644

Methodological issues in assessing changes in costs pre- and post-medication switch: a schizophrenia study example.

PubMed

Faries, Douglas E; Nyhuis, Allen W; Ascher-Svanum, Haya

2009-05-27

Schizophrenia is a severe, chronic, and costly illness that adversely impacts patients' lives and health care payer budgets. Cost comparisons of treatment regimens are, therefore, important to health care payers and researchers. Pre-Post analyses ("mirror-image"), where outcomes prior to a medication switch are compared to outcomes post-switch, are commonly used in such research. However, medication changes often occur during a costly crisis event. Patients may relapse, be hospitalized, have a medication change, and then spend a period of time with intense use of costly resources (post-medication switch). While many advantages and disadvantages of Pre-Post methodology have been discussed, issues regarding the attributability of costs incurred around the time of medication switching have not been fully investigated. Medical resource use data, including medications and acute-care services (hospitalizations, partial hospitalizations, emergency department) were collected for patients with schizophrenia who switched antipsychotics (n = 105) during a 1-year randomized, naturalistic, antipsychotic cost-effectiveness schizophrenia trial. Within-patient changes in total costs per day were computed during the pre- and post-medication change periods. In addition to the standard Pre-Post analysis comparing costs pre- and post-medication change, we investigated the sensitivity of results to varying assumptions regarding the attributability of acute care service costs occurring just after a medication switch that were likely due to initial medication failure. Fifty-six percent of all costs incurred during the first week on the newly initiated antipsychotic were likely due to treatment failure with the previous antipsychotic. Standard analyses suggested an average increase in cost-per-day for each patient of $2.40 after switching medications. However, sensitivity analyses removing costs incurred post-switch that were potentially due to the failure of the initial medication suggested decreases in costs in the range of $4.77 to $9.69 per day post-switch. Pre-Post cost analyses are sensitive to the approach used to handle acute-service costs occurring just after a medication change. Given the importance of quality economic research on the cost of switching treatments, thorough sensitivity analyses should be performed to identify the impact of crisis events around the time of medication change.

Classification of hydrological parameter sensitivity and evaluation of parameter transferability across 431 US MOPEX basins

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

Ren, Huiying; Hou, Zhangshuan; Huang, Maoyi

The Community Land Model (CLM) represents physical, chemical, and biological processes of the terrestrial ecosystems that interact with climate across a range of spatial and temporal scales. As CLM includes numerous sub-models and associated parameters, the high-dimensional parameter space presents a formidable challenge for quantifying uncertainty and improving Earth system predictions needed to assess environmental changes and risks. This study aims to evaluate the potential of transferring hydrologic model parameters in CLM through sensitivity analyses and classification across watersheds from the Model Parameter Estimation Experiment (MOPEX) in the United States. The sensitivity of CLM-simulated water and energy fluxes to hydrologicalmore » parameters across 431 MOPEX basins are first examined using an efficient stochastic sampling-based sensitivity analysis approach. Linear, interaction, and high-order nonlinear impacts are all identified via statistical tests and stepwise backward removal parameter screening. The basins are then classified accordingly to their parameter sensitivity patterns (internal attributes), as well as their hydrologic indices/attributes (external hydrologic factors) separately, using a Principal component analyses (PCA) and expectation-maximization (EM) –based clustering approach. Similarities and differences among the parameter sensitivity-based classification system (S-Class), the hydrologic indices-based classification (H-Class), and the Koppen climate classification systems (K-Class) are discussed. Within each S-class with similar parameter sensitivity characteristics, similar inversion modeling setups can be used for parameter calibration, and the parameters and their contribution or significance to water and energy cycling may also be more transferrable. This classification study provides guidance on identifiable parameters, and on parameterization and inverse model design for CLM but the methodology is applicable to other models. Inverting parameters at representative sites belonging to the same class can significantly reduce parameter calibration efforts.« less

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

Pairing attachment theory and social learning theory in video-feedback intervention to promote positive parenting.

PubMed

Juffer, Femmie; Bakermans-Kranenburg, Marian J; van IJzendoorn, Marinus H

2017-06-01

Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) is a social-learning and attachment-based intervention using video feedback to support sensitive parenting and at the same time setting firm limits. Empirical studies and meta-analyses have shown that sensitive parenting is the key determinant to promote secure child-parent attachment relationships and that adequate parental discipline contributes to fewer behavior problems in children. Building on this evidence, VIPP-SD has been tested in various populations of at-risk parents and vulnerable children (in the age range of zero to six years), as well as in the context of child care. In twelve randomized controlled trials including 1116 parents and caregivers, VIPP-SD proved to be effective in promoting sensitive caregiving, while positive social-emotional child outcomes were also found. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel approach for modelling vegetation distributions and analysing vegetation sensitivity through trait-climate relationships in China

PubMed Central

Yang, Yanzheng; Zhu, Qiuan; Peng, Changhui; Wang, Han; Xue, Wei; Lin, Guanghui; Wen, Zhongming; Chang, Jie; Wang, Meng; Liu, Guobin; Li, Shiqing

2016-01-01

Increasing evidence indicates that current dynamic global vegetation models (DGVMs) have suffered from insufficient realism and are difficult to improve, particularly because they are built on plant functional type (PFT) schemes. Therefore, new approaches, such as plant trait-based methods, are urgently needed to replace PFT schemes when predicting the distribution of vegetation and investigating vegetation sensitivity. As an important direction towards constructing next-generation DGVMs based on plant functional traits, we propose a novel approach for modelling vegetation distributions and analysing vegetation sensitivity through trait-climate relationships in China. The results demonstrated that a Gaussian mixture model (GMM) trained with a LMA-Nmass-LAI data combination yielded an accuracy of 72.82% in simulating vegetation distribution, providing more detailed parameter information regarding community structures and ecosystem functions. The new approach also performed well in analyses of vegetation sensitivity to different climatic scenarios. Although the trait-climate relationship is not the only candidate useful for predicting vegetation distributions and analysing climatic sensitivity, it sheds new light on the development of next-generation trait-based DGVMs. PMID:27052108

Application of an integrated biomarker response index to assess ground water contamination in the vicinity of a rare earth mine tailings site.

PubMed

Si, Wantong; He, Xiaoying; Li, Ailing; Liu, Li; Li, Jisheng; Gong, Donghui; Liu, Juan; Liu, Jumei; Shen, Weishou; Zhang, Xuefeng

2016-09-01

We utilized a multi-biomarker approach (Integrated Biomarker Response version 2, IBRv2) to investigate the scope and dispersion of groundwater contamination surrounding a rare earth mine tailings impoundment. Parameters of SD rat included in our IBRv2 analyses were glutathione levels, superoxide dismutase, catalase, and glutathione peroxidase activities, total anti-oxidative capacity, chromosome aberration, and micronucleus formation. The concentration of 20 pollutants including Cl(-), SO4 (2-), Na(+), K(+), Mg(2+), Ca(2+), TH, CODMn, As, Se, TDS, Be, Mn, Co, Ni, Cu, Zn, Mo, Cd, and Pb in the groundwater were also analyzed. The results of this study indicated that groundwater polluted by tailings impoundment leakage exhibited significant ecotoxicological effects. The selected biomarkers responded sensitively to groundwater pollution. Analyses showed a significant relationship between IBRv2 values and the Nemerow composite index. IBRv2 could serve as a sensitive ecotoxicological diagnosis method for assessing groundwater contamination in the vicinity of rare earth mine tailings. According to the trend of IBRv2 value and Nemerow composite index, the maximum diffusion distance of groundwater pollutants from rare earth mine tailings was approximately 5.7 km.

The Anxiety Sensitivity Index--Revised: Confirmatory Factor Analyses, Structural Invariance in Caucasian and African American Samples, and Score Reliability and Validity

ERIC Educational Resources Information Center

Arnau, Randolph C.; Broman-Fulks, Joshua J.; Green, Bradley A.; Berman, Mitchell E.

2009-01-01

The most commonly used measure of anxiety sensitivity is the 36-item Anxiety Sensitivity Index--Revised (ASI-R). Exploratory factor analyses have produced several different factors structures for the ASI-R, but an acceptable fit using confirmatory factor analytic approaches has only been found for a 21-item version of the instrument. We evaluated…

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

PubMed

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

2014-12-01

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. 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. We apply our general method to data from two smoking cessation trials. A total of 489 and 1758 participants from two smoking cessation trials. The abstinence outcomes were obtained using telephone interviews. 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. 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. © 2014 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Incremental cost of nosocomial bacteremia according to the focus of infection and antibiotic sensitivity of the causative microorganism in a university hospital.

PubMed

Riu, Marta; Chiarello, Pietro; Terradas, Roser; Sala, Maria; Garcia-Alzorriz, Enric; Castells, Xavier; Grau, Santiago; Cots, Francesc

2017-04-01

To estimate the incremental cost of nosocomial bacteremia according to the causative focus and classified by the antibiotic sensitivity of the microorganism.Patients admitted to Hospital del Mar in Barcelona from 2005 to 2012 were included. We analyzed the total hospital costs of patients with nosocomial bacteremia caused by microorganisms with a high prevalence and, often, with multidrug-resistance. A control group was defined by selecting patients without bacteremia in the same diagnosis-related group.Our hospital has a cost accounting system (full-costing) that uses activity-based criteria to estimate per-patient costs. A logistic regression was fitted to estimate the probability of developing bacteremia (propensity score) and was used for propensity-score matching adjustment. This propensity score was included in an econometric model to adjust the incremental cost of patients with bacteremia with differentiation of the causative focus and antibiotic sensitivity.The mean incremental cost was estimated at &OV0556;15,526. The lowest incremental cost corresponded to bacteremia caused by multidrug-sensitive urinary infection (&OV0556;6786) and the highest to primary or unknown sources of bacteremia caused by multidrug-resistant microorganisms (&OV0556;29,186).This is one of the first analyses to include all episodes of bacteremia produced during hospital stays in a single study. The study included accurate information about the focus and antibiotic sensitivity of the causative organism and actual hospital costs. It provides information that could be useful to improve, establish, and prioritize prevention strategies for nosocomial infections.

Pharmacoeconomic analysis of antifungal therapy for primary treatment of invasive candidiasis caused by Candida albicans and non-albicans Candida species.

PubMed

Ou, Huang-Tz; Lee, Tsung-Ying; Chen, Yee-Chun; Charbonneau, Claudie

2017-07-10

Cost-effectiveness studies of echinocandins for the treatment of invasive candidiasis, including candidemia, are rare in Asia. No study has determined whether echinocandins are cost-effective for both Candida albicans and non-albicans Candida species. There have been no economic evaluations that compare non-echinocandins with the three available echinocandins. This study was aimed to assess the cost-effectiveness of individual echinocandins, namely caspofungin, micafungin, and anidulafungin, versus non-echinocandins for C. albicans and non-albicans Candida species, respectively. A decision tree model was constructed to assess the cost-effectiveness of echinocandins and non-echinocandins for invasive candidiasis. The probability of treatment success, mortality rate, and adverse drug events were extracted from published clinical trials. The cost variables (i.e., drug acquisition) were based on Taiwan's healthcare system from the perspective of a medical payer. One-way sensitivity analyses and probability sensitivity analyses were conducted. For treating invasive candidiasis (all species), as compared to fluconazole, micafungin and caspofungin are dominated (less effective, more expensive), whereas anidulafungin is cost-effective (more effective, more expensive), costing US$3666.09 for each life-year gained, which was below the implicit threshold of the incremental cost-effectiveness ratio in Taiwan. For C. albicans, echinocandins are cost-saving as compared to non-echinocandins. For non-albicans Candida species, echinocandins are cost-effective as compared to non-echinocandins, costing US$652 for each life-year gained. The results were robust over a wide range of sensitivity analyses and were most sensitive to the clinical efficacy of antifungal treatment. Echinocandins, especially anidulafungin, appear to be cost-effective for invasive candidiasis caused by C. albicans and non-albicans Candida species in Taiwan.

Dandelions, tulips and orchids: evidence for the existence of low-sensitive, medium-sensitive and high-sensitive individuals.

PubMed

Lionetti, Francesca; Aron, Arthur; Aron, Elaine N; Burns, G Leonard; Jagiellowicz, Jadzia; Pluess, Michael

2018-01-22

According to empirical studies and recent theories, people differ substantially in their reactivity or sensitivity to environmental influences with some being generally more affected than others. More sensitive individuals have been described as orchids and less-sensitive ones as dandelions. Applying a data-driven approach, we explored the existence of sensitivity groups in a sample of 906 adults who completed the highly sensitive person (HSP) scale. According to factor analyses, the HSP scale reflects a bifactor model with a general sensitivity factor. In contrast to prevailing theories, latent class analyses consistently suggested the existence of three rather than two groups. While we were able to identify a highly sensitive (orchids, 31%) and a low-sensitive group (dandelions, 29%), we also detected a third group (40%) characterised by medium sensitivity, which we refer to as tulips in keeping with the flower metaphor. Preliminary cut-off scores for all three groups are provided. In order to characterise the different sensitivity groups, we investigated group differences regarding the Big Five personality traits, as well as experimentally assessed emotional reactivity in an additional independent sample. According to these follow-up analyses, the three groups differed in neuroticism, extraversion and emotional reactivity to positive mood induction with orchids scoring significantly higher in neuroticism and emotional reactivity and lower in extraversion than the other two groups (dandelions also differed significantly from tulips). Findings suggest that environmental sensitivity is a continuous and normally distributed trait but that people fall into three distinct sensitive groups along a sensitivity continuum.

Cost-effectiveness analysis of interferon beta-1b for the treatment of patients with a first clinical event suggestive of multiple sclerosis.

PubMed

Caloyeras, John P; Zhang, Bin; Wang, Cheng; Eriksson, Marianne; Fredrikson, Sten; Beckmann, Karola; Knappertz, Volker; Pohl, Christoph; Hartung, Hans-Peter; Shah, Dhvani; Miller, Jeffrey D; Sandbrink, Rupert; Lanius, Vivian; Gondek, Kathleen; Russell, Mason W

2012-05-01

To assess, from a Swedish societal perspective, the cost effectiveness of interferon β-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment). A Markov model was developed, using patient level data from the BENEFIT trial and published literature, to estimate health outcomes and costs associated with IFNB-1b for hypothetical cohorts of patients after an initial clinical event suggestive of MS. Health states were defined by Kurtzke Expanded Disability Status Scale (EDSS) scores. Model outcomes included quality-adjusted life years (QALYs), total costs (including both direct and indirect costs), and incremental cost-effectiveness ratios. Sensitivity analyses were performed on key model parameters to assess the robustness of model results. In the base case scenario, early IFNB-1b treatment was economically dominant (ie, less costly and more effective) versus delayed IFNB-1b treatment when QALYs were used as the effectiveness metric. Sensitivity analyses showed that the cost-effectiveness results were sensitive to model time horizon. Compared with the delayed treatment strategy, early treatment of MS was also associated with delayed EDSS progressions, prolonged time to CDMS diagnosis, and a reduction in frequency of relapse. Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Sensory sensitivity and symptom severity represent unique dimensions of chronic pain: a MAPP Research Network study.

PubMed

Schrepf, Andrew; Williams, David A; Gallop, Robert; Naliboff, Bruce; Basu, Neil; Kaplan, Chelsea; Harper, Daniel E; Landis, Richard; Clemens, J Quentin; Strachan, Eric; Griffith, James W; Afari, Niloofar; Hassett, Afton; Pontari, Michel A; Clauw, Daniel J; Harte, Steven E

2018-05-28

Chronic Overlapping Pain Conditions (COPCs) are characterized by aberrant central nervous system processing of pain. This 'centralized pain' phenotype has been described using a large and diverse set of symptom domains, including the spatial distribution of pain, pain intensity, fatigue, mood imbalances, cognitive dysfunction, altered somatic sensations, and hypersensitivity to external stimuli. Here we used three cohorts, including patients with Urologic Chronic Pelvic Pain Syndrome (UCPPS), a mixed pain cohort with other COPCs, and healthy individuals (total n = 1039) from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to explore the factor structure of symptoms of centralized pain. Using exploratory and confirmatory factor analysis, we identified two general factors in all three cohorts, one characterized by a broad increased sensitivity to internal somatic sensations and environmental stimuli, and diffuse pain, termed Generalized Sensory Sensitivity (GSS), and one characterized by constitutional symptoms - Sleep, Pain, Affect, Cognition, Energy (SPACE). Longitudinal analyses in the UCPPS cohort found the same two factor structure at month six and one year, suggesting that the two factor structure is reproducible over time. In secondary analyses we found that GSS particularly is associated with the presence of comorbid COPCs, while SPACE shows modest associations with measures of disability and urinary symptoms. These factors may represent important and distinct continuum of symptoms that are indicative of the centralized pain phenotype at high levels. Future research of COPCs should accommodate the measurement of each factor.

The Impact of Rainfall on Soil Moisture Dynamics in a Foggy Desert.

PubMed

Li, Bonan; Wang, Lixin; Kaseke, Kudzai F; Li, Lin; Seely, Mary K

2016-01-01

Soil moisture is a key variable in dryland ecosystems since it determines the occurrence and duration of vegetation water stress and affects the development of weather patterns including rainfall. However, the lack of ground observations of soil moisture and rainfall dynamics in many drylands has long been a major obstacle in understanding ecohydrological processes in these ecosystems. It is also uncertain to what extent rainfall controls soil moisture dynamics in fog dominated dryland systems. To this end, in this study, twelve to nineteen months' continuous daily records of rainfall and soil moisture (from January 2014 to August 2015) obtained from three sites (one sand dune site and two gravel plain sites) in the Namib Desert are reported. A process-based model simulating the stochastic soil moisture dynamics in water-limited systems was used to study the relationships between soil moisture and rainfall dynamics. Model sensitivity in response to different soil and vegetation parameters under diverse soil textures was also investigated. Our field observations showed that surface soil moisture dynamics generally follow rainfall patterns at the two gravel plain sites, whereas soil moisture dynamics in the sand dune site did not show a significant relationship with rainfall pattern. The modeling results suggested that most of the soil moisture dynamics can be simulated except the daily fluctuations, which may require a modification of the model structure to include non-rainfall components. Sensitivity analyses suggested that soil hygroscopic point (sh) and field capacity (sfc) were two main parameters controlling soil moisture output, though permanent wilting point (sw) was also very sensitive under the parameter setting of sand dune (Gobabeb) and gravel plain (Kleinberg). Overall, the modeling results were not sensitive to the parameters in non-bounded group (e.g., soil hydraulic conductivity (Ks) and soil porosity (n)). Field observations, stochastic modeling results as well as sensitivity analyses provide soil moisture baseline information for future monitoring and the prediction of soil moisture patterns in the Namib Desert.

The Impact of Rainfall on Soil Moisture Dynamics in a Foggy Desert

PubMed Central

Li, Bonan; Wang, Lixin; Kaseke, Kudzai F.; Li, Lin; Seely, Mary K.

2016-01-01

Soil moisture is a key variable in dryland ecosystems since it determines the occurrence and duration of vegetation water stress and affects the development of weather patterns including rainfall. However, the lack of ground observations of soil moisture and rainfall dynamics in many drylands has long been a major obstacle in understanding ecohydrological processes in these ecosystems. It is also uncertain to what extent rainfall controls soil moisture dynamics in fog dominated dryland systems. To this end, in this study, twelve to nineteen months’ continuous daily records of rainfall and soil moisture (from January 2014 to August 2015) obtained from three sites (one sand dune site and two gravel plain sites) in the Namib Desert are reported. A process-based model simulating the stochastic soil moisture dynamics in water-limited systems was used to study the relationships between soil moisture and rainfall dynamics. Model sensitivity in response to different soil and vegetation parameters under diverse soil textures was also investigated. Our field observations showed that surface soil moisture dynamics generally follow rainfall patterns at the two gravel plain sites, whereas soil moisture dynamics in the sand dune site did not show a significant relationship with rainfall pattern. The modeling results suggested that most of the soil moisture dynamics can be simulated except the daily fluctuations, which may require a modification of the model structure to include non-rainfall components. Sensitivity analyses suggested that soil hygroscopic point (sh) and field capacity (sfc) were two main parameters controlling soil moisture output, though permanent wilting point (sw) was also very sensitive under the parameter setting of sand dune (Gobabeb) and gravel plain (Kleinberg). Overall, the modeling results were not sensitive to the parameters in non-bounded group (e.g., soil hydraulic conductivity (Ks) and soil porosity (n)). Field observations, stochastic modeling results as well as sensitivity analyses provide soil moisture baseline information for future monitoring and the prediction of soil moisture patterns in the Namib Desert. PMID:27764203

The rise of multiple imputation: a review of the reporting and implementation of the method in medical research.

PubMed

Hayati Rezvan, Panteha; Lee, Katherine J; Simpson, Julie A

2015-04-07

Missing data are common in medical research, which can lead to a loss in statistical power and potentially biased results if not handled appropriately. Multiple imputation (MI) is a statistical method, widely adopted in practice, for dealing with missing data. Many academic journals now emphasise the importance of reporting information regarding missing data and proposed guidelines for documenting the application of MI have been published. This review evaluated the reporting of missing data, the application of MI including the details provided regarding the imputation model, and the frequency of sensitivity analyses within the MI framework in medical research articles. A systematic review of articles published in the Lancet and New England Journal of Medicine between January 2008 and December 2013 in which MI was implemented was carried out. We identified 103 papers that used MI, with the number of papers increasing from 11 in 2008 to 26 in 2013. Nearly half of the papers specified the proportion of complete cases or the proportion with missing data by each variable. In the majority of the articles (86%) the imputed variables were specified. Of the 38 papers (37%) that stated the method of imputation, 20 used chained equations, 8 used multivariate normal imputation, and 10 used alternative methods. Very few articles (9%) detailed how they handled non-normally distributed variables during imputation. Thirty-nine papers (38%) stated the variables included in the imputation model. Less than half of the papers (46%) reported the number of imputations, and only two papers compared the distribution of imputed and observed data. Sixty-six papers presented the results from MI as a secondary analysis. Only three articles carried out a sensitivity analysis following MI to assess departures from the missing at random assumption, with details of the sensitivity analyses only provided by one article. This review outlined deficiencies in the documenting of missing data and the details provided about imputation. Furthermore, only a few articles performed sensitivity analyses following MI even though this is strongly recommended in guidelines. Authors are encouraged to follow the available guidelines and provide information on missing data and the imputation process.

An economic evaluation based on a randomized placebo-controlled trial of varenicline in smokers with cardiovascular disease: results for Belgium, Spain, Portugal, and Italy.

PubMed

Wilson, Koo; Hettle, Robert; Marbaix, Sophie; Diaz Cerezo, Silvia; Ines, Monica; Santoni, Laura; Annemans, Lieven; Prignot, Jacques; Lopez de Sa, Esteban

2012-10-01

An estimated 17.2% of patients continue to smoke following diagnosis of cardiovascular disease (CVD). To reduce the risk of further morbidity or mortality in cardiovascular patients, smoking cessation has been shown to reduce the risk of mortality by 36% and myocardial infarction by 32%. The objective of this study was to evaluate the long-term health and economic consequences of smoking cessation in patients with CVD. Results of a randomized clinical trial comparing varenicline plus counselling vs. placebo plus counselling were extrapolated using a Markov model to simulate the lifetime costs and health consequences of smoking cessation in patients with stable CVD. For the base case, we considered a payer's perspective including direct costs attributed to the healthcare provider, measuring cumulative life years (LY) and quality adjusted life (QALY) years as outcome measures. Secondary analyses were conducted from a societal perspective, evaluating lost productivity due to premature mortality. Sensitivity and subgroup analyses were also undertaken. Results were analysed for Belgium, Spain, Portugal, and Italy. Varenicline plus counselling was associated with a gain in LY and QALY across all countries; relative to placebo plus counselling. From a payer's perspective, incremental cost effectiveness ratios were € 6120 (Belgium), € 5151 (Spain), € 5357 (Portugal), and € 5433 (Italy) per QALY gained. From a societal perspective, varenicline in addition to counselling was less costly than placebo and counselling in all cases. Sensitivity analyses showed little sensitivity in outcomes to model assumptions or uncertainty in model parameters. Varenicline in addition to counselling is cost-effective compared to placebo and counselling in smokers with CVD.

Cost-Effectiveness of Diagnostic Strategies for Suspected Scaphoid Fractures.

PubMed

Yin, Zhong-Gang; Zhang, Jian-Bing; Gong, Ke-Tong

2015-08-01

The aim of this study was to assess the cost effectiveness of multiple competing diagnostic strategies for suspected scaphoid fractures. With published data, the authors created a decision-tree model simulating the diagnosis of suspected scaphoid fractures. Clinical outcomes, costs, and cost effectiveness of immediate computed tomography (CT), day 3 magnetic resonance imaging (MRI), day 3 bone scan, week 2 radiographs alone, week 2 radiographs-CT, week 2 radiographs-MRI, week 2 radiographs-bone scan, and immediate MRI were evaluated. The primary clinical outcome was the detection of scaphoid fractures. The authors adopted societal perspective, including both the costs of healthcare and the cost of lost productivity. The incremental cost-effectiveness ratio (ICER), which expresses the incremental cost per incremental scaphoid fracture detected using a strategy, was calculated to compare these diagnostic strategies. Base case analysis, 1-way sensitivity analyses, and "worst case scenario" and "best case scenario" sensitivity analyses were performed. In the base case, the average cost per scaphoid fracture detected with immediate CT was $2553. The ICER of immediate MRI and day 3 MRI compared with immediate CT was $7483 and $32,000 per scaphoid fracture detected, respectively. The ICER of week 2 radiographs-MRI was around $170,000. Day 3 bone scan, week 2 radiographs alone, week 2 radiographs-CT, and week 2 radiographs-bone scan strategy were dominated or extendedly dominated by MRI strategies. The results were generally robust in multiple sensitivity analyses. Immediate CT and MRI were the most cost-effective strategies for diagnosing suspected scaphoid fractures. Economic and Decision Analyses Level II. See Instructions for Authors for a complete description of levels of evidence.

Economic and clinical comparison of atypical depot antipsychotic drugs for treatment of chronic schizophrenia in the Czech Republic.

PubMed

Einarson, Thomas R; Zilbershtein, Roman; Skoupá, Jana; Veselá, Sárka; Garg, Madhur; Hemels, Michiel E H

2013-09-01

The Czech Republic is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. A pharmacoeconomic analysis was conducted to determine the cost-effectiveness of atypical depots. An existing 1-year decision-analytic framework was adapted to model drug use in this healthcare system. The average direct costs to the General Insurance Company of the Czech Republic of using paliperidone palmitate (Xeplion®), risperidone (Risperdal Consta®), and olanzapine pamoate (Zypadhera®) were determined. Literature-derived clinical rates populated the model, with costs adjusted to 2012 Euros using the consumer price index. Outcomes included quality-adjusted life-years (QALYs), days in remission, and proportions hospitalized or visiting emergency rooms. One-way sensitivity analyses were calculated for all important inputs. A multivariate probability analysis was used to examine the stability of results using 10,000 iterations of simulated input over reasonable ranges of all included variables. Expected average costs/per patient treated were €5377 for PP-LAI, €6118 for RIS-LAI, and €6537 for OLZ-LAI. Respective QALYs were 0.817, 0.809, and 0.811; ER visits were 0.127, 0.134, and 0.141; hospitalizations were 0.252, 0.298, and 0.289. Results were generally robust in sensitivity analyses. PP-LAI dominated RIS-LAI and OLZ-LAI in 90.2% and 92.1% of simulations, respectively. Results were insensitive to drug prices but sensitive to adherence and hospitalization rates. PP-LAI dominated the other two drugs, as it had a lower overall cost and superior clinical outcomes, making it the preferred choice. Using PP-LAI in place of RIS-LAI for chronic relapsing schizophrenia would reduce the overall costs of care for the healthcare system.

Peripheral absolute threshold spectral sensitivity in retinitis pigmentosa.

PubMed Central

Massof, R W; Johnson, M A; Finkelstein, D

1981-01-01

Dark-adapted spectral sensitivities were measured in the peripheral retinas of 38 patients diagnosed as having typical retinitis pigmentosa (RP) and in 3 normal volunteers. The patients included those having autosomal dominant and autosomal recessive inheritance patterns. Results were analysed by comparisons with the CIE standard scotopic spectral visibility function and with Judd's modification of the photopic spectral visibility function, with consideration of contributions from changes in spectral transmission of preretinal media. The data show 3 general patterns. One group of patients had absolute threshold spectral sensitivities that were fit by Judd's photopic visibility curve. Absolute threshold spectral sensitivities for a second group of patients were fit by a normal scotopic spectral visibility curve. The third group of patients had absolute threshold spectral sensitivities that were fit by a combination of scotopic and photopic spectral visibility curves. The autosomal dominant and autosomal recessive modes of inheritance were represented in each group of patients. These data indicate that RP patients have normal rod and/or cone spectral sensitivities, and support the subclassification of patients described previously by Massof and Finkelstein. PMID:7459312

Sleep System Sensitization: Evidence for Changing Roles of Etiological Factors in Insomnia

PubMed Central

Kalmbach, David A.; Pillai, Vivek; Arnedt, J. Todd; Anderson, Jason R.; Drake, Christopher L.

2016-01-01

Objectives To test for sensitization of the sleep system in response to insomnia development and major life stress. In addition, to evaluate the impact on depression and anxiety associated with sleep system sensitization. Methods A longitudinal study with three annual assessments. The community-based sample included 262 adults with no history of insomnia or depression who developed insomnia 1 year after baseline (67.6% female; 44.0±13.4y). Measures included the Ford Insomnia Response to Stress Test to assess sleep reactivity, Quick Inventory of Depressive Symptomatology, and Beck Anxiety Inventory. Insomnia classification was based on DSM-IV criteria. Sleep system sensitization was operationally defined as significant increases in sleep reactivity. Results Sensitization of the sleep system was observed from baseline to insomnia onset at 1-y follow-up among insomniacs with low premorbid vulnerability (p<.001), resulting in 68.3% of these individuals re-classified as highly sleep reactive. Major life stress was associated with greater sleep system sensitization (p=.02). Results showed that sleep reactivity at 2-y follow-up remained elevated among those with low premorbid vulnerability, even after insomnia remission (p<.01). Finally, analyses revealed that increases in sleep reactivity predicted greater depression (p<.001) and anxiety (p<.001) at insomnia onset. The impact of sensitization on depression was stable at 2-y follow-up (p=.01). Conclusions Evidence supports sensitization of the sleep system as consequence of insomnia development and major life stress among individuals with low premorbid sleep reactivity. Sleep system sensitization may serve as a mechanism by which insomnia is perpetuated. Harmful effects of the sensitization process may increase risk for insomnia-related depression and anxiety. PMID:27448474

Sleep system sensitization: evidence for changing roles of etiological factors in insomnia.

PubMed

Kalmbach, David A; Pillai, Vivek; Arnedt, J Todd; Anderson, Jason R; Drake, Christopher L

2016-05-01

To test for sensitization of the sleep system in response to insomnia development and major life stress. In addition, to evaluate the impact on depression and anxiety associated with sleep system sensitization. A longitudinal study with three annual assessments. The community-based sample included 262 adults with no history of insomnia or depression who developed insomnia one year after baseline (67.6% female; 44.0 ± 13.4 yr). Measures included the Ford Insomnia Response to Stress Test to assess sleep reactivity, Quick Inventory of Depressive Symptomatology, and Beck Anxiety Inventory. Insomnia classification was based on DSM-IV criteria. Sleep system sensitization was operationally defined as significant increases in sleep reactivity. Sensitization of the sleep system was observed from baseline to insomnia onset at 1-yr follow-up among insomniacs with low premorbid vulnerability (p < 0.001), resulting in 68.3% of these individuals re-classified as highly sleep reactive. Major life stress was associated with greater sleep system sensitization (p = 0.02). Results showed that sleep reactivity at 2-yr follow-up remained elevated among those with low premorbid vulnerability, even after insomnia remission (p < 0.01). Finally, analyses revealed that increases in sleep reactivity predicted greater depression (p < 0.001) and anxiety (p < 0.001) at insomnia onset. The impact of sensitization on depression was stable at 2-yr follow-up (p = 0.01). Evidence supports sensitization of the sleep system as a consequence of insomnia development and major life stress among individuals with low premorbid sleep reactivity. Sleep system sensitization may serve as a mechanism by which insomnia is perpetuated. Harmful effects of the sensitization process may increase risk for insomnia-related depression and anxiety. Copyright © 2016 Elsevier B.V. All rights reserved.

Resistance profiles to antimicrobial agents in bacteria isolated from acute endodontic infections: systematic review and meta-analysis.

PubMed

Lang, Pauline M; Jacinto, Rogério C; Dal Pizzol, Tatiane S; Ferreira, Maria Beatriz C; Montagner, Francisco

2016-11-01

Infected root canal or acute apical abscess exudates can harbour several species, including Fusobacterium, Porphyromonas, Prevotella, Parvimonas, Streptococcus, Treponema, Olsenella and not-yet cultivable species. A systematic review and meta-analysis was performed to assess resistance rates to antimicrobial agents in clinical studies that isolated bacteria from acute endodontic infections. Electronic databases and the grey literature were searched up to May 2015. Clinical studies in humans evaluating the antimicrobial resistance of primary acute endodontic infection isolates were included. PRISMA guidelines were followed. A random-effect meta-analysis was employed. The outcome was described as the pooled resistance rates for each antimicrobial agent. Heterogeneity and sensitivity analyses were performed. Subgroup analyses were conducted based upon report or not of the use of antibiotics prior to sampling as an exclusion factor (subgroups A and B, respectively). Data from seven studies were extracted. Resistance rates for 15 different antimicrobial agents were evaluated (range, 3.5-40.0%). Lower resistance rates were observed for amoxicillin/clavulanic acid and amoxicillin; higher resistance rates were detected for tetracycline. Resistance rates varied according to previous use of an antimicrobial agent as demonstrated by the subgroup analyses. Heterogeneity was observed for the resistance profiles of penicillin G in subgroup A and for amoxicillin, clindamycin, metronidazole and tetracycline in subgroup B. Sensitivity analyses demonstrated that resistance rates changed for metronidazole, clindamycin, tetracycline and amoxicillin. These findings suggest that clinical isolates had low resistance to β-lactams. Further well-designed studies are needed to clarify whether the differences in susceptibility among the antimicrobial agents may influence clinical responses to treatment. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Alcohol consumption and the intention to engage in unprotected sex: systematic review and meta-analysis of experimental studies.

PubMed

Rehm, Jürgen; Shield, Kevin D; Joharchi, Narges; Shuper, Paul A

2012-01-01

To review and analyse in experimentally controlled studies the impact of alcohol consumption on intentions to engage in unprotected sex. To draw conclusions with respect to the question of whether alcohol has an independent effect on the incidence of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). A systematic review and meta-analysis of randomized controlled studies examined the association between blood alcohol content (BAC) and self-perceived likelihood of using a condom during intercourse. The systematic review and meta-analysis were conducted according to internationally standardized protocols (Preferred Reporting Items for Systematic Reviews and Meta-Analyses: PRISMA). The meta-analysis included an estimate of the dose-response effect, tests for publication bias and sensitivity analyses. Of the 12 studies included in the quantitative synthesis, our pooled analysis indicated that an increase in BAC of 0.1 mg/ml resulted in an increase of 5.0% (95% CI: 2.8-7.1%) in the indicated likelihood (indicated by a Likert scale) of engaging in unprotected sex. After adjusting for potential publication bias, this estimate dropped to 2.9% (95% CI: 2.0-3.9%). Thus, the larger the alcohol intake and the subsequent level of BAC, the higher the intentions to engage in unsafe sex. The main results were homogeneous, persisted in sensitivity analyses and after correction for publication bias. Alcohol use is an independent risk factor for intentions to engage in unprotected sex, and as risky sex intentions have been shown to be linked to actual risk behavior, the role of alcohol consumption in the transmission of HIV and other STIs may be of public health importance. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Results of hair analyses for drugs of abuse and comparison with self-reports and urine tests.

PubMed

Musshoff, F; Driever, F; Lachenmeier, K; Lachenmeier, D W; Banger, M; Madea, B

2006-01-27

Urine as well as head and pubic hair samples from drug abusers were analysed for opiates, cocaine and its metabolites, amphetamines, methadone and cannabinoids. Urine immunoassay results and the results of hair tests by means of gas chromatography-mass spectrometry were compared to the self-reported data of the patients in an interview protocol. With regard to the study group, opiate abuse was claimed from the majority in self-reports (89%), followed by cannabinoids (55%), cocaine (38%), and methadone (32%). Except for opiates the comparison between self-reported drug use and urinalysis at admission showed a low correlation. In contrast to urinalysis, hair tests revealed consumption in more cases. There was also a good agreement between self-reports of patients taking part in an official methadone maintenance program and urine test results concerning methadone. However, hair test results demonstrated that methadone abuse in general was under-reported by people who did not participate in a substitution program. Comparing self-reports and the results of hair analyses drug use was dramatically under-reported, especially cocaine. Cocaine hair tests appeared to be highly sensitive and specific in identifying past cocaine use even in settings of negative urine tests. In contrast to cocaine, hair lacks sensitivity as a detection agent for cannabinoids and a proof of cannabis use by means of hair analysis should include the sensitive detection of the metabolite THC carboxylic acid in the lower picogram range.

Sample preconcentration with chemical derivatization in capillary electrophoresis. Capillary as preconcentrator, microreactor and chiral selector for high-throughput metabolite screening.

PubMed

Ptolemy, Adam S; Britz-McKibbin, Philip

2006-02-17

New strategies for integrating sample pretreatment with chemical analyses under a single format is required for rapid, sensitive and enantioselective analyses of low abundance metabolites in complex biological samples. Capillary electrophoresis (CE) offers a unique environment for controlling analyte/reagent band dispersion and electromigration properties using discontinuous electrolyte systems. Recent work in our laboratory towards developing a high-throughput CE platform for low abundance metabolites via on-line sample preconcentration with chemical derivatization (SPCD) is primarily examined in this review, as there have been surprisingly only a few strategies reported in the literature to date. In-capillary sample preconcentration serves to enhance concentration sensitivity via electrokinetic focusing of long sample injection volumes for lower detection limits, whereas chemical derivatization by zone passing is used to expand detectability and selectivity, notably for enantiomeric resolution of metabolites lacking intrinsic chromophores using nanolitre volumes of reagent. Together, on-line SPCD-CE can provide over a 100-fold improvement in concentration sensitivity, shorter total analysis times, reduced sample handling and improved reliability for a variety of amino acid and amino sugar metabolites, which is also amenable to automated high-throughput screening. This review will highlight basic method development and optimization parameters relevant to SPCD-CE, including applications to bacterial metabolite flux and biomarker analyses. Insight into the mechanism of analyte focusing and labeling by SPCD-CE is also discussed, as well as future directions for continued research.

Trends in mass spectrometry instrumentation for proteomics

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

Smith, Richard D.

2002-12-01

Mass spectrometry has become a primary tool for proteomics due to its capabilities for rapid and sensitive protein identification and quantitation. It is now possible to identify thousands of proteins from microgram sample quantities in a single day and to quantify relative protein abundances. However, the needs for increased capabilities for proteome measurements are immense and are now driving both new strategies and instrument advances. These developments include those based on integration with multi-dimensional liquid separations and high accuracy mass measurements, and promise more than order of magnitude improvements in sensitivity, dynamic range, and throughput for proteomic analyses in themore » near future.« less

Implementation of structural response sensitivity calculations in a large-scale finite-element analysis system

NASA Technical Reports Server (NTRS)

Giles, G. L.; Rogers, J. L., Jr.

1982-01-01

The methodology used to implement structural sensitivity calculations into a major, general-purpose finite-element analysis system (SPAR) is described. This implementation includes a generalized method for specifying element cross-sectional dimensions as design variables that can be used in analytically calculating derivatives of output quantities from static stress, vibration, and buckling analyses for both membrane and bending elements. Limited sample results for static displacements and stresses are presented to indicate the advantages of analytically calculating response derivatives compared to finite difference methods. Continuing developments to implement these procedures into an enhanced version of SPAR are also discussed.

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

Exploring sensitivity of a multistate occupancy model to inform management decisions

USGS Publications Warehouse

Green, A.W.; Bailey, L.L.; Nichols, J.D.

2011-01-01

Dynamic occupancy models are often used to investigate questions regarding the processes that influence patch occupancy and are prominent in the fields of population and community ecology and conservation biology. Recently, multistate occupancy models have been developed to investigate dynamic systems involving more than one occupied state, including reproductive states, relative abundance states and joint habitat-occupancy states. Here we investigate the sensitivities of the equilibrium-state distribution of multistate occupancy models to changes in transition rates. We develop equilibrium occupancy expressions and their associated sensitivity metrics for dynamic multistate occupancy models. To illustrate our approach, we use two examples that represent common multistate occupancy systems. The first example involves a three-state dynamic model involving occupied states with and without successful reproduction (California spotted owl Strix occidentalis occidentalis), and the second involves a novel way of using a multistate occupancy approach to accommodate second-order Markov processes (wood frog Lithobates sylvatica breeding and metamorphosis). In many ways, multistate sensitivity metrics behave in similar ways as standard occupancy sensitivities. When equilibrium occupancy rates are low, sensitivity to parameters related to colonisation is high, while sensitivity to persistence parameters is greater when equilibrium occupancy rates are high. Sensitivities can also provide guidance for managers when estimates of transition probabilities are not available. Synthesis and applications. Multistate models provide practitioners a flexible framework to define multiple, distinct occupied states and the ability to choose which state, or combination of states, is most relevant to questions and decisions about their own systems. In addition to standard multistate occupancy models, we provide an example of how a second-order Markov process can be modified to fit a multistate framework. Assuming the system is near equilibrium, our sensitivity analyses illustrate how to investigate the sensitivity of the system-specific equilibrium state(s) to changes in transition rates. Because management will typically act on these transition rates, sensitivity analyses can provide valuable information about the potential influence of different actions and when it may be prudent to shift the focus of management among the various transition rates. ?? 2011 The Authors. Journal of Applied Ecology ?? 2011 British Ecological Society.

Capturing strain localization behind a geosynthetic-reinforced soil wall

NASA Astrophysics Data System (ADS)

Lai, Timothy Y.; Borja, Ronaldo I.; Duvernay, Blaise G.; Meehan, Richard L.

2003-04-01

This paper presents the results of finite element (FE) analyses of shear strain localization that occurred in cohesionless soils supported by a geosynthetic-reinforced retaining wall. The innovative aspects of the analyses include capturing of the localized deformation and the accompanying collapse mechanism using a recently developed embedded strong discontinuity model. The case study analysed, reported in previous publications, consists of a 3.5-m tall, full-scale reinforced wall model deforming in plane strain and loaded by surcharge at the surface to failure. Results of the analysis suggest strain localization developing from the toe of the wall and propagating upward to the ground surface, forming a curved failure surface. This is in agreement with a well-documented failure mechanism experienced by the physical wall model showing internal failure surfaces developing behind the wall as a result of the surface loading. Important features of the analyses include mesh sensitivity studies and a comparison of the localization properties predicted by different pre-localization constitutive models, including a family of three-invariant elastoplastic constitutive models appropriate for frictional/dilatant materials. Results of the analysis demonstrate the potential of the enhanced FE method for capturing a collapse mechanism characterized by the presence of a failure, or slip, surface through earthen materials.

GetReal in mathematical modelling: a review of studies predicting drug effectiveness in the real world.

PubMed

Panayidou, Klea; Gsteiger, Sandro; Egger, Matthias; Kilcher, Gablu; Carreras, Máximo; Efthimiou, Orestis; Debray, Thomas P A; Trelle, Sven; Hummel, Noemi

2016-09-01

The performance of a drug in a clinical trial setting often does not reflect its effect in daily clinical practice. In this third of three reviews, we examine the applications that have been used in the literature to predict real-world effectiveness from randomized controlled trial efficacy data. We searched MEDLINE, EMBASE from inception to March 2014, the Cochrane Methodology Register, and websites of key journals and organisations and reference lists. We extracted data on the type of model and predictions, data sources, validation and sensitivity analyses, disease area and software. We identified 12 articles in which four approaches were used: multi-state models, discrete event simulation models, physiology-based models and survival and generalized linear models. Studies predicted outcomes over longer time periods in different patient populations, including patients with lower levels of adherence or persistence to treatment or examined doses not tested in trials. Eight studies included individual patient data. Seven examined cardiovascular and metabolic diseases and three neurological conditions. Most studies included sensitivity analyses, but external validation was performed in only three studies. We conclude that mathematical modelling to predict real-world effectiveness of drug interventions is not widely used at present and not well validated. © 2016 The Authors Research Synthesis Methods Published by John Wiley & Sons Ltd. © 2016 The Authors Research Synthesis Methods Published by John Wiley & Sons Ltd.

Uncertainty Analysis of Decomposing Polyurethane Foam

NASA Technical Reports Server (NTRS)

Hobbs, Michael L.; Romero, Vicente J.

2000-01-01

Sensitivity/uncertainty analyses are necessary to determine where to allocate resources for improved predictions in support of our nation's nuclear safety mission. Yet, sensitivity/uncertainty analyses are not commonly performed on complex combustion models because the calculations are time consuming, CPU intensive, nontrivial exercises that can lead to deceptive results. To illustrate these ideas, a variety of sensitivity/uncertainty analyses were used to determine the uncertainty associated with thermal decomposition of polyurethane foam exposed to high radiative flux boundary conditions. The polyurethane used in this study is a rigid closed-cell foam used as an encapsulant. Related polyurethane binders such as Estane are used in many energetic materials of interest to the JANNAF community. The complex, finite element foam decomposition model used in this study has 25 input parameters that include chemistry, polymer structure, and thermophysical properties. The response variable was selected as the steady-state decomposition front velocity calculated as the derivative of the decomposition front location versus time. An analytical mean value sensitivity/uncertainty (MV) analysis was used to determine the standard deviation by taking numerical derivatives of the response variable with respect to each of the 25 input parameters. Since the response variable is also a derivative, the standard deviation was essentially determined from a second derivative that was extremely sensitive to numerical noise. To minimize the numerical noise, 50-micrometer element dimensions and approximately 1-msec time steps were required to obtain stable uncertainty results. As an alternative method to determine the uncertainty and sensitivity in the decomposition front velocity, surrogate response surfaces were generated for use with a constrained Latin Hypercube Sampling (LHS) technique. Two surrogate response surfaces were investigated: 1) a linear surrogate response surface (LIN) and 2) a quadratic response surface (QUAD). The LHS techniques do not require derivatives of the response variable and are subsequently relatively insensitive to numerical noise. To compare the LIN and QUAD methods to the MV method, a direct LHS analysis (DLHS) was performed using the full grid and timestep resolved finite element model. The surrogate response models (LIN and QUAD) are shown to give acceptable values of the mean and standard deviation when compared to the fully converged DLHS model.

Navigation and Dispersion Analysis of the First Orion Exploration Mission

NASA Technical Reports Server (NTRS)

Zanetti, Renato; D'Souza, Christopher

2015-01-01

This paper seeks to present the Orion EM-1 Linear Covariance Analysis for the DRO mission. The delta V statistics for each maneuver are presented. Included in the memo are several sensitivity analyses: variation in the time of OTC-1 (the first outbound correction maneuver), variation in the accuracy of the trans-Lunar injection, and variation in the length of the optical navigation passes.

Identifying the Cognitive Decrements Caused By HIV

DTIC Science & Technology

1994-06-10

critical analyses 46 pointed to further assessment of frontal lobe structures. Most of the 15 different tests yielded more than on* dependent variable...is also one of the tests included in the Multicenter AIDS Cohort Study longitudinal research on the progression of HIV infection. Left frontal lobe ...structures underlie verbal fluency performance and the particular sensitivity of frontal lobe structures to perturbations with HIV infection would

Space Station needs, attributes and architectural options. Volume 2, book 1, part 1: Mission requirements

NASA Technical Reports Server (NTRS)

1983-01-01

The baseline mission model used to develop the space station mission-related requirements is described as well as the 90 civil missions that were evaluated, (including the 62 missions that formed the baseline model). Mission-related requirements for the space station baseline are defined and related to space station architectural development. Mission-related sensitivity analyses are discussed.

Impact of Sensory Sensitivity on Physiological Stress Response and Novel Peer Interaction in Children with and without Autism Spectrum Disorder.

PubMed

Corbett, Blythe A; Muscatello, Rachael A; Blain, Scott D

2016-01-01

For many children with Autism Spectrum Disorder (ASD), social interactions can be stressful. Previous research shows that youth with ASD exhibit greater physiological stress response during peer interaction, compared to typically developing (TD) peers. Heightened sensory sensitivity may contribute to maladaptive patterns of stress and anxiety. The current study investigated between-group differences in stress response to peer interaction, as well as the role of sensory sensitivity. Participants included 80 children (40 ASD) between 8 and 12 years. Children participated in the peer interaction paradigm (PIP), an ecologically valid protocol that simulates real-world social interaction. Salivary cortisol was collected before and after the 20 min PIP. Parents completed questionnaires pertaining to child stress (Stress Survey Schedule) and sensory sensitivity (Short Sensory Profile). Statistical analyses included t-tests and ANCOVA models to examine between-group differences in cortisol and play; Pearson correlations to determine relations between cortisol, play, and questionnaire scores; and moderation analyses to investigate interactions among variables. Controlling for baseline cortisol values, children with ASD showed significantly higher cortisol levels than TD peers, in response to the PIP [F (1, 77) = 5.77, p = 0.02]. Cortisol during play was negatively correlated with scores on the SSP (r = -0.242, p = 0.03), and positively correlated with SSS (r = 0.273, p = 0.02) indicating that higher cortisol was associated with greater sensory sensitivity (lower SSP reflects more impairment) and enhanced stress in various contexts (higher SSS reflects more stress). Furthermore, diagnosis was a significant moderator of the relation between cortisol and SSP, at multiple time points during the PIP (p < 0.05). The current study extends previous findings by showing that higher physiological arousal during play is associated with heightened sensory sensitivity and a pattern of increased stress in various contexts. RESULTS are discussed in a broader context, emphasizing the need to examine relationships between social, behavioral, and physiological profiles in ASD to enhance understanding and improve treatments aimed at ameliorating stress and sensory dysfunction, while enhancing social skills.

Pre-study feasibility and identifying sensitivity analyses for protocol pre-specification in comparative effectiveness research.

PubMed

Girman, Cynthia J; Faries, Douglas; Ryan, Patrick; Rotelli, Matt; Belger, Mark; Binkowitz, Bruce; O'Neill, Robert

2014-05-01

The use of healthcare databases for comparative effectiveness research (CER) is increasing exponentially despite its challenges. Researchers must understand their data source and whether outcomes, exposures and confounding factors are captured sufficiently to address the research question. They must also assess whether bias and confounding can be adequately minimized. Many study design characteristics may impact on the results; however, minimal if any sensitivity analyses are typically conducted, and those performed are post hoc. We propose pre-study steps for CER feasibility assessment and to identify sensitivity analyses that might be most important to pre-specify to help ensure that CER produces valid interpretable results.

Association between alcohol consumption and amyotrophic lateral sclerosis: a meta-analysis of five observational studies.

PubMed

E, Meng; Yu, Sufang; Dou, Jianrui; Jin, Wu; Cai, Xiang; Mao, Yiyang; Zhu, Daojian; Yang, Rumei

2016-08-01

The purpose of this study is to examine the association between alcohol consumption and amyotrophic lateral sclerosis. Published literature on the association between alcohol consumption and amyotrophic lateral sclerosis was retrieved from the PubMed and Embase databases. Two authors independently extracted the data. The quality of the identified studies was evaluated according to the Newcastle-Ottawa scale. Subgroup and sensitivity analyses were performed and publication bias was assessed. Five articles, including one cohort study and seven case-control studies, and a total of 431,943 participants, were identified. The odds ratio for the association between alcohol consumption and amyotrophic lateral sclerosis was 0.57 (95 % confidence interval 0.51-0.64). Subgroup and sensitivity analyses confirmed the result. Evidence for publication bias was detected. Alcohol consumption reduced the risk of developing amyotrophic lateral sclerosis compared with non-drinking. Alcohol, therefore, has a potentially neuroprotective effect on the development of amyotrophic lateral sclerosis.

Solid state SPS microwave generation and transmission study. Volume 2, phase 2: Appendices

NASA Technical Reports Server (NTRS)

Maynard, O. E.

1980-01-01

The solid state sandwich concept for SPS was further defined. The design effort concentrated on the spacetenna, but did include some system analysis for parametric comparison reasons. Basic solid state microwave devices were defined and modeled. An initial conceptual subsystems and system design was performed as well as sidelobe control and system selection. The selected system concept and parametric solid state microwave power transmission system data were assessed relevant to the SPS concept. Although device efficiency was not a goal, the sensitivities to design of this efficiency were parametrically treated. Sidelobe control consisted of various single step tapers, multistep tapers and Gaussian tapers. A hybrid concept using tubes and solid state was evaluated. Thermal analyses are included with emphasis on sensitivities to waste heat radiator form factor, emissivity, absorptivity, amplifier efficiency, material and junction temperature.

Applications of Optical Microcavity Resonators in Analytical Chemistry

PubMed Central

Wade, James H.; Bailey, Ryan C.

2018-01-01

Optical resonator sensors are an emerging class of analytical technologies that use recirculating light confined within a microcavity to sensitively measure the surrounding environment. Bolstered by advances in microfabrication, these devices can be configured for a wide variety of chemical or biomolecular sensing applications. The review begins with a brief description of optical resonator sensor operation followed by discussions regarding sensor design, including different geometries, choices of material systems, methods of sensor interrogation, and new approaches to sensor operation. Throughout, key recent developments are highlighted, including advancements in biosensing and other applications of optical sensors. Alternative sensing mechanisms and hybrid sensing devices are then discussed in terms of their potential for more sensitive and rapid analyses. Brief concluding statements offer our perspective on the future of optical microcavity sensors and their promise as versatile detection elements within analytical chemistry. PMID:27049629

Identification of the need for home visiting nurse: development of a new assessment tool.

PubMed

Taguchi, Atsuko; Nagata, Satoko; Naruse, Takashi; Kuwahara, Yuki; Yamaguchi, Takuhiro; Murashima, Sachiyo

2014-01-01

To develop a Home Visiting Nursing Service Need Assessment Form (HVNS-NAF) to standardize the decision about the need for home visiting nursing service. The sample consisted of older adults who had received coordinated services by care managers. We defined the need for home visiting nursing service by elderly individuals as the decision of the need by a care manager so that the elderly can continue to live independently. Explanatory variables included demographic factors, medical procedure, severity of illness, and caregiver variables. Multiple logistic regression was carried out after univariate analyses to decide the variables to include and the weight of each variable in the HVNS-NAF. We then calculated the sensitivity and specificity of each cutoff value, and defined the score with the highest sensitivity and specificity as the cutoff value. Nineteen items were included in the final HVNS-NAF. When the cutoff value was 2 points, the sensitivity was 77.0%, specificity 68.5%, and positive predictive value 56.8%. HVNS-NAF is the first validated standard based on characteristics of elderly clients who required home visiting nursing service. Using the HVNS-NAF may result in reducing the unmet need for home visiting nursing service and preventing hospitalization.

Using archived ITS data for sensitivity analyses in the estimation of mobile source emissions

DOT National Transportation Integrated Search

2000-12-01

The study described in this paper demonstrates the use of archived ITS data from San Antonio's TransGuide traffic management center (TMC) for sensitivity analyses in the estimation of on-road mobile source emissions. Because of the stark comparison b...

Difficult Decisions Made Easier

NASA Technical Reports Server (NTRS)

2006-01-01

NASA missions are extremely complex and prone to sudden, catastrophic failure if equipment falters or if an unforeseen event occurs. For these reasons, NASA trains to expect the unexpected. It tests its equipment and systems in extreme conditions, and it develops risk-analysis tests to foresee any possible problems. The Space Agency recently worked with an industry partner to develop reliability analysis software capable of modeling complex, highly dynamic systems, taking into account variations in input parameters and the evolution of the system over the course of a mission. The goal of this research was multifold. It included performance and risk analyses of complex, multiphase missions, like the insertion of the Mars Reconnaissance Orbiter; reliability analyses of systems with redundant and/or repairable components; optimization analyses of system configurations with respect to cost and reliability; and sensitivity analyses to identify optimal areas for uncertainty reduction or performance enhancement.

Simulation-based sensitivity analysis for non-ignorably missing data.

PubMed

Yin, Peng; Shi, Jian Q

2017-01-01

Sensitivity analysis is popular in dealing with missing data problems particularly for non-ignorable missingness, where full-likelihood method cannot be adopted. It analyses how sensitively the conclusions (output) may depend on assumptions or parameters (input) about missing data, i.e. missing data mechanism. We call models with the problem of uncertainty sensitivity models. To make conventional sensitivity analysis more useful in practice we need to define some simple and interpretable statistical quantities to assess the sensitivity models and make evidence based analysis. We propose a novel approach in this paper on attempting to investigate the possibility of each missing data mechanism model assumption, by comparing the simulated datasets from various MNAR models with the observed data non-parametrically, using the K-nearest-neighbour distances. Some asymptotic theory has also been provided. A key step of this method is to plug in a plausibility evaluation system towards each sensitivity parameter, to select plausible values and reject unlikely values, instead of considering all proposed values of sensitivity parameters as in the conventional sensitivity analysis method. The method is generic and has been applied successfully to several specific models in this paper including meta-analysis model with publication bias, analysis of incomplete longitudinal data and mean estimation with non-ignorable missing data.

Sensitivity analysis in economic evaluation: an audit of NICE current practice and a review of its use and value in decision-making.

PubMed

Andronis, L; Barton, P; Bryan, S

2009-06-01

To determine how we define good practice in sensitivity analysis in general and probabilistic sensitivity analysis (PSA) in particular, and to what extent it has been adhered to in the independent economic evaluations undertaken for the National Institute for Health and Clinical Excellence (NICE) over recent years; to establish what policy impact sensitivity analysis has in the context of NICE, and policy-makers' views on sensitivity analysis and uncertainty, and what use is made of sensitivity analysis in policy decision-making. Three major electronic databases, MEDLINE, EMBASE and the NHS Economic Evaluation Database, were searched from inception to February 2008. The meaning of 'good practice' in the broad area of sensitivity analysis was explored through a review of the literature. An audit was undertaken of the 15 most recent NICE multiple technology appraisal judgements and their related reports to assess how sensitivity analysis has been undertaken by independent academic teams for NICE. A review of the policy and guidance documents issued by NICE aimed to assess the policy impact of the sensitivity analysis and the PSA in particular. Qualitative interview data from NICE Technology Appraisal Committee members, collected as part of an earlier study, were also analysed to assess the value attached to the sensitivity analysis components of the economic analyses conducted for NICE. All forms of sensitivity analysis, notably both deterministic and probabilistic approaches, have their supporters and their detractors. Practice in relation to univariate sensitivity analysis is highly variable, with considerable lack of clarity in relation to the methods used and the basis of the ranges employed. In relation to PSA, there is a high level of variability in the form of distribution used for similar parameters, and the justification for such choices is rarely given. Virtually all analyses failed to consider correlations within the PSA, and this is an area of concern. Uncertainty is considered explicitly in the process of arriving at a decision by the NICE Technology Appraisal Committee, and a correlation between high levels of uncertainty and negative decisions was indicated. The findings suggest considerable value in deterministic sensitivity analysis. Such analyses serve to highlight which model parameters are critical to driving a decision. Strong support was expressed for PSA, principally because it provides an indication of the parameter uncertainty around the incremental cost-effectiveness ratio. The review and the policy impact assessment focused exclusively on documentary evidence, excluding other sources that might have revealed further insights on this issue. In seeking to address parameter uncertainty, both deterministic and probabilistic sensitivity analyses should be used. It is evident that some cost-effectiveness work, especially around the sensitivity analysis components, represents a challenge in making it accessible to those making decisions. This speaks to the training agenda for those sitting on such decision-making bodies, and to the importance of clear presentation of analyses by the academic community.

Skin sensitizer identification by IL-8 secretion and CD86 expression on THP-1 cells.

PubMed

Parise, Carolina Bellini; Sá-Rocha, Vanessa Moura; Moraes, Jane Zveiter

2015-12-25

Substantial progress has been made in the development of alternative methods for skin sensitization in the last decade in several countries around the world. Brazil is experiencing an increasing concern about using animals for product development, since the publication of the Law 9605/1998, which prohibits the use of animals when an alternative method is available. In this way, an in vitro test to evaluate allergenic potential is a pressing need.This preliminary study started setting the use of myelomonocytic THP-1 cell line, according to the human cell line activation test (h-CLAT), already under validation process. We found that 48-h chemical exposure was necessary to identify 22 out of 23 sensitizers by the analyses of CD86 expression. In addition, the CD54 expression analyses presented a poor efficiency to discriminate sensitizers from non-sensitizers in our conditions. In view of these results, we looked for changes of pro-inflammatory interleukin profile. The IL-8 secretion analyses after 24-h chemical incubation seemed to be an alternative for CD54 expression assessing.Altogether, our findings showed that the combination of the analyses of CD86 expression and IL-8 secretion allowed predicting allergenicity.

Application of global sensitivity analysis methods to Takagi-Sugeno-Kang rainfall-runoff fuzzy models

NASA Astrophysics Data System (ADS)

Jacquin, A. P.; Shamseldin, A. Y.

2009-04-01

This study analyses the sensitivity of the parameters of Takagi-Sugeno-Kang rainfall-runoff fuzzy models previously developed by the authors. These models can be classified in two types, where the first type is intended to account for the effect of changes in catchment wetness and the second type incorporates seasonality as a source of non-linearity in the rainfall-runoff relationship. The sensitivity analysis is performed using two global sensitivity analysis methods, namely Regional Sensitivity Analysis (RSA) and Sobol's Variance Decomposition (SVD). In general, the RSA method has the disadvantage of not being able to detect sensitivities arising from parameter interactions. By contrast, the SVD method is suitable for analysing models where the model response surface is expected to be affected by interactions at a local scale and/or local optima, such as the case of the rainfall-runoff fuzzy models analysed in this study. The data of six catchments from different geographical locations and sizes are used in the sensitivity analysis. The sensitivity of the model parameters is analysed in terms of two measures of goodness of fit, assessing the model performance from different points of view. These measures are the Nash-Sutcliffe criterion and the index of volumetric fit. The results of the study show that the sensitivity of the model parameters depends on both the type of non-linear effects (i.e. changes in catchment wetness or seasonality) that dominates the catchment's rainfall-runoff relationship and the measure used to assess the model performance. Acknowledgements: This research was supported by FONDECYT, Research Grant 11070130. We would also like to express our gratitude to Prof. Kieran M. O'Connor from the National University of Ireland, Galway, for providing the data used in this study.

The link between hypomania risk and creativity: The role of heightened behavioral activation system (BAS) sensitivity.

PubMed

Kim, Bin-Na; Kwon, Seok-Man

2017-06-01

The relationship between bipolar disorder (BD) and creativity is well-known; however, relatively little is known about its potential mechanism. We investigated whether heightened behavioral activation system (BAS) sensitivity may mediate such relationship. Korean young adults (N=543) completed self-report questionnaires that included the Hypomanic Personality Scale (HPS), the Behavioral Activation System(BAS) Scale, the Everyday Creativity Scale (ECS), the Positive Affect and Negative Affect Schedule (PANAS), and the Altman Self-Rating Mania Scale (ASRM). Correlational, hierarchical regression and mediation analyses using bootstrap confidence intervals were conducted. As predicted, BAS sensitivity was associated with self-reported creativity as well as hypomania risk and symptoms. Even when positive affect was controlled, BAS sensitivity predicted incrementally significant variance in explaining creativity. In mediation analysis, BAS sensitivity partially mediated the relation between hypomania risk and creativity. Reliance on self-report measures in assessing creativity and usage of non-clinical sample. BAS sensitivity was related not only to mood pathology but also to creativity. As a basic affective temperament, BAS sensitivity may help explain incompatible sides of adaptation associated with BD. Copyright © 2017 Elsevier B.V. All rights reserved.

Effectiveness of Light Sources on In-Office Dental Bleaching: A Systematic Review and Meta-Analyses.

PubMed

SoutoMaior, J R; de Moraes, Sld; Lemos, Caa; Vasconcelos, Bc do E; Montes, Majr; Pellizzer, E P

2018-06-12

A systematic review and meta-analyses were performed to evaluate the efficacy of tooth color change and sensitivity of teeth following in-office bleaching with and without light gel activation in adult patients. This review was registered at PROSPERO (CRD 42017060574) and is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic systematic searches of PubMed/MEDLINE, Web of Science, and the Cochrane Library were conducted for published articles. Only randomized clinical trials among adults that compared in-office bleaching with and without light activation with the same bleaching gel concentrations were selected. The outcomes were tooth color change and tooth sensitivity prevalence and intensity. Twenty-three articles from 1054 data sources met the eligibility criteria. After title and abstract screening, 39 studies remained. Sixteen studies were further excluded. Twenty-three studies remained for qualitative analyses and 20 for meta-analyses of primary and secondary outcomes. No significant differences in tooth color change or tooth sensitivity incidence were found between the compared groups; however, tooth sensitivity intensity decreased when light sources were applied. The use of light sources for in-office bleaching is not imperative to achieve esthetic clinical results.

A miniaturised laser ablation/ionisation analyser for investigation of elemental/isotopic composition with the sub-ppm detection sensitivity

NASA Astrophysics Data System (ADS)

Tulej, M.; Riedo, A.; Meyer, S.; Iakovleva, M.; Neuland, M.; Wurz, P.

2012-04-01

Detailed knowledge of the elemental and isotopic composition of solar system objects imposes critical constraints on models describing the origin of our solar system and can provide insight to chemical and physical processes taking place during the planetary evolution. So far, the investigation of chemical composition of planetary surfaces could be conducted almost exclusively by remotely controlled spectroscopic instruments from orbiting spacecraft, landers or rovers. With some exceptions, the sensitivity of these techniques is, however, limited and often only abundant elements can be investigated. Nevertheless, the spectroscopic techniques proved to be successful for global chemical mapping of entire planetary objects such as the Moon, Mars and asteroids. A combined afford of the measurements from orbit, landers and rovers can also yield the determination of local mineralogy. New instruments including Laser Induced Breakdown Spectroscopy (LIBS) and Laser Ablation/Ionisation Mass Spectrometer (LIMS), have been recently included for several landed missions. LIBS is thought to improve flexibility of the investigations and offers a well localised chemical probing from distances up to 10-13 m. Since LIMS is a mass spectrometric technique it allows for very sensitive measurements of elements and isotopes. We will demonstrate the results of the current performance tests obtained by application of a miniaturised laser ablation/ionisation mass spectrometer, a LIMS instrument, developed in Bern for the chemical analysis of solids. So far, the only LIMS instrument on a spacecraft is the LAZMA instrument. This spectrometer was a part of the payload for PHOBOS-GRUNT mission and is also currently selected for LUNA-RESURCE and LUNA-GLOB missions to the lunar south poles (Managadze et al., 2011). Our LIMS instrument has the dimensions of 120 x Ø60 mm and with a weight of about 1.5 kg (all electronics included), it is the lightest mass analyser designed for in situ chemical analysis of solid materials on the planetary surfaces (Rohner et al., 2003). Initial laboratory tests that were conducted with an IR laser radiation for the ablation, atomisation and ionisation of the material, indicated a high performance of the instrument in terms of sensitivity, dynamic range and mass resolution (Tulej et al., 2011). After some technical improvements and implementation of a computer-controlled performance optimiser we have achieved further improvements of both, the instrumental sensitivity down to sub-ppm level and reproducibility of the measurements. We will demonstrate the potential of the mass analyser to perform the quantitative elemental analysis of solids with a spatial (vertical, lateral) resolution commensurate with typical grain sizes, and its capabilities for investigation of isotopic patterns with accuracy and precision comparable to that of large analytical laboratory instruments, e.g., TIMS, SIMS, LA-ICP-MS. The results can be of considerable interest for in situ dating or investigation of other fine isotopic fractionation effects including studies of bio-markers.

Exposure to traffic-related air pollution and risk of development of childhood asthma: A systematic review and meta-analysis.

PubMed

Khreis, Haneen; Kelly, Charlotte; Tate, James; Parslow, Roger; Lucas, Karen; Nieuwenhuijsen, Mark

2017-03-01

The question of whether children's exposure to traffic-related air pollution (TRAP) contributes to their development of asthma is unresolved. We conducted a systematic review and performed meta-analyses to analyze the association between TRAP and asthma development in childhood. We systematically reviewed epidemiological studies published until 8 September 2016 and available in the Embase, Ovid MEDLINE (R), and Transport databases. We included studies that examined the association between children's exposure to TRAP metrics and their risk of 'asthma' incidence or lifetime prevalence, from birth to age 18years old. We extracted key characteristics of each included study using a predefined data items template and these were tabulated. We used the Critical Appraisal Skills Programme checklists to assess the validity of each included study. Where four or more independent risk estimates were available for a continuous pollutant exposure, we conducted overall and age-specific meta-analyses, and four sensitivity analyses for each summary meta-analytic exposure-outcome association. Forty-one studies met our eligibility criteria. There was notable variability in asthma definitions, TRAP exposure assessment methods and confounder adjustment. The overall random-effects risk estimates (95% CI) were 1.08 (1.03, 1.14) per 0.5×10 -5 m -1 black carbon (BC), 1.05 (1.02, 1.07) per 4μg/m 3 nitrogen dioxide (NO 2 ), 1.48 (0.89, 2.45) per 30μg/m 3 nitrogen oxides (NO x ), 1.03 (1.01, 1.05) per 1μg/m 3 Particulate Matter <2.5μm in diameter (PM 2.5 ), and 1.05 (1.02, 1.08) per 2μg/m 3 Particulate Matter <10μm in diameter (PM 10 ). Sensitivity analyses supported these findings. Across the main analysis and age-specific analysis, the least heterogeneity was seen for the BC estimates, some heterogeneity for the PM 2.5 and PM 10 estimates and the most heterogeneity for the NO 2 and NO x estimates. The overall risk estimates from the meta-analyses showed statistically significant associations for BC, NO 2 , PM 2.5 , PM 10 exposures and risk of asthma development. Our findings support the hypothesis that childhood exposure to TRAP contributes to their development of asthma. Future meta-analyses would benefit from greater standardization of study methods including exposure assessment harmonization, outcome harmonization, confounders' harmonization and the inclusion of all important confounders in individual studies. PROSPERO 2014: CRD42014015448. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elastic cavitation and fracture via injection.

PubMed

Hutchens, Shelby B; Fakhouri, Sami; Crosby, Alfred J

2016-03-07

The cavitation rheology technique extracts soft materials mechanical properties through pressure-monitored fluid injection. Properties are calculated from the system's response at a critical pressure that is governed by either elasticity or fracture (or both); however previous elementary analysis has not been capable of accurately determining which mechanism is dominant. We combine analyses of both mechanisms in order to determine how the full system thermodynamics, including far-field compliance, dictate whether a bubble in an elastomeric solid will grow through either reversible or irreversible deformations. Applying these analyses to experimental data, we demonstrate the sensitivity of cavitation rheology to microstructural variation via a co-dependence between modulus and fracture energy.

Sensitivity of double centrifugation sugar fecal flotation for detecting intestinal helminths in coyotes (Canis latrans).

PubMed

Liccioli, Stefano; Catalano, Stefano; Kutz, Susan J; Lejeune, Manigandan; Verocai, Guilherme G; Duignan, Padraig J; Fuentealba, Carmen; Ruckstuhl, Kathreen E; Massolo, Alessandro

2012-07-01

Fecal analysis is commonly used to estimate prevalence and intensity of intestinal helminths in wild carnivores, but few studies have assessed the reliability of fecal flotation compared to analysis of intestinal tracts. We investigated sensitivity of the double centrifugation sugar fecal flotation and kappa agreement between fecal flotation and postmortem examination of intestines for helminths of coyotes (Canis latrans). We analyzed 57 coyote carcasses that were collected between October 2010 and March 2011 in the metropolitan area of Calgary and Edmonton, Alberta, Canada. Before analyses, intestines and feces were frozen at -80 C for 72 hr to inactivate Echinococcus eggs, protecting operators from potential exposure. Five species of helminths were found by postmortem examination, including Toxascaris leonina, Uncinaria stenocephala, Ancylostoma caninum, Taenia sp., and Echinococcus multilocularis. Sensitivity of fecal flotation was high (0.84) for detection of T. leonina but low for Taenia sp. (0.27), E. multilocularis (0.46), and U. stenocephala (0.00). Good kappa agreement between techniques was observed only for T. leonina (0.64), for which we detected also a significant correlation between adult female parasite intensity and fecal egg counts (R(s)=0.53, P=0.01). Differences in sensitivity may be related to parasite characteristics that affect recovery of eggs on flotation. Fecal parasitologic analyses are highly applicable to study the disease ecology of urban carnivores, and they often provide important information on environmental contamination and potential of zoonotic risks. However, fecal-based parasitologic surveys should first assess the sensitivity of the techniques to understand their biases and limitations.

Behavioral Training as New Treatment for Adult Amblyopia: A Meta-Analysis and Systematic Review.

PubMed

Tsirlin, Inna; Colpa, Linda; Goltz, Herbert C; Wong, Agnes M F

2015-06-01

New behavioral treatment methods, including dichoptic training, perceptual learning, and video gaming, have been proposed to improve visual function in adult amblyopia. Here, we conducted a meta-analysis of these methods to investigate the factors involved in amblyopia recovery and their clinical significance. Mean and individual participant data meta-analyses were performed on 24 studies using the new behavioral methods in adults. Studies were identified using PubMed, Google Scholar, and published reviews. The new methods yielded a mean improvement in visual acuity of 0.17 logMAR with 32% participants achieving gains ≥ 0.2 logMAR, and a mean improvement in stereo sensitivity of 0.01 arcsec-1 with 42% of participants improving ≥2 octaves. The most significant predictor of treatment outcome was visual acuity at the onset of treatment. Participants with more severe amblyopia improved more on visual acuity and less on stereo sensitivity than those with milder amblyopia. Better initial stereo sensitivity was a predictor of greater gains in stereo sensitivity following treatment. Treatment type, amblyopia type, age, and training duration did not have any significant influence on visual and stereo acuity outcomes. Our analyses showed that some participants may benefit from the new treatments; however, clinical trials are required to confirm these findings. Despite the diverse nature of the new behavioral methods, the lack of significant differences in visual and stereo sensitivity outcomes among them suggests that visual attention-a common element among the varied treatment methods-may play an important role in amblyopia recovery.

Comparison of the abbreviated minimal assessment of cognitive function in multiple sclerosis (aMACFIMS) and the brief international cognitive assessment for multiple sclerosis (BICAMS).

PubMed

Gromisch, Elizabeth S; Portnoy, Jeffrey G; Foley, Frederick W

2018-05-15

Cognitive impairment is a prevalent and often intrusive problem among persons with multiple sclerosis (PwMS). Valid and reliable assessments, including quick screening measures, are crucial. The Brief International Cognitive Assessment for MS (BICAMS) was developed for this reason. While it lends itself to use in locations where formal neuropsychological resources might be limited, it does not include measures of verbal fluency or executive functioning, domains assessed as part of the Minimal Assessment of Cognitive Function in MS (MACFIMS). Given previous evidence that shortened MACFIMS measures have strong criterion validity, this study aimed to determine which of these should be included in the abbreviated MACFIMS (aMACFIMS), and how the aMACFIMS compares to the BICAMS. One hundred forty-seven PwMS were included in the analyses. A stepwise logistic regression was used to determine the measures in the aMACFIMS. Receiver-operating-characteristic (ROC) curves assessed the classification accuracy, sensitivity, and specificity. The batteries' sensitivity, specificity, and predictive values were then compared. Compared to the BICAMS, the final aMACFIMS had higher specificity (87% versus 72%) and positive predictive value (86% versus 77%), but lower sensitivity (71% versus 81%). The aMACFIMS has several benefits, including reduced administration time and the addition of a verbal fluency/executive functioning measure. Copyright © 2018 Elsevier B.V. All rights reserved.

Sensitivity analysis of static resistance of slender beam under bending

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

Valeš, Jan

2016-06-08

The paper deals with statical and sensitivity analyses of resistance of simply supported I-beams under bending. The resistance was solved by geometrically nonlinear finite element method in the programme Ansys. The beams are modelled with initial geometrical imperfections following the first eigenmode of buckling. Imperfections were, together with geometrical characteristics of cross section, and material characteristics of steel, considered as random quantities. The method Latin Hypercube Sampling was applied to evaluate statistical and sensitivity resistance analyses.

Prediction of coefficients of thermal expansion for unidirectional composites

NASA Technical Reports Server (NTRS)

Bowles, David E.; Tompkins, Stephen S.

1989-01-01

Several analyses for predicting the longitudinal, alpha(1), and transverse, alpha(2), coefficients of thermal expansion of unidirectional composites were compared with each other, and with experimental data on different graphite fiber reinforced resin, metal, and ceramic matrix composites. Analytical and numerical analyses that accurately accounted for Poisson restraining effects in the transverse direction were in consistently better agreement with experimental data for alpha(2), than the less rigorous analyses. All of the analyses predicted similar values of alpha(1), and were in good agreement with the experimental data. A sensitivity analysis was conducted to determine the relative influence of constituent properties on the predicted values of alpha(1), and alpha(2). As would be expected, the prediction of alpha(1) was most sensitive to longitudinal fiber properties and the prediction of alpha(2) was most sensitive to matrix properties.

SPS market analysis

NASA Astrophysics Data System (ADS)

Goff, H. C.

1980-05-01

A market analysis task included personal interviews by GE personnel and supplemental mail surveys to acquire statistical data and to identify and measure attitudes, reactions and intentions of prospective small solar thermal power systems (SPS) users. Over 500 firms were contacted, including three ownership classes of electric utilities, industrial firms in the top SIC codes for energy consumption, and design engineering firms. A market demand model was developed which utilizes the data base developed by personal interviews and surveys, and projected energy price and consumption data to perform sensitivity analyses and estimate potential markets for SPS.

Lower sensitivity of serum (1,3)-β-d-glucan for the diagnosis of candidaemia due to Candida parapsilosis.

PubMed

Mikulska, M; Giacobbe, D R; Furfaro, E; Mesini, A; Marchese, A; Del Bono, V; Viscoli, C

2016-07-01

The aim of this study was to evaluate the sensitivity and the levels of 1,3-β-d-glucan (BDG) among patients with candidaemia due to different Candida species. Retrospective study of all patients who had a single-species candidaemia and BDG testing performed within 48 h from the onset of candidaemia during 2009-2015 was performed. Factors influencing the sensitivity of BDG, including the presence of a central venous catheter, antifungal therapy and Candida species, were analysed in univariate and multivariate models. In all, 107 patients with the following Candida distribution were included: 46 (43%) Candida albicans, 37 (35%) Candida parapsilosis, and 24 (22%) other species. BDG sensitivity and levels were the highest in C. albicans candidaemia and lowest for C. parapsilosis (respectively, 72% and 410 pg/mL for C. albicans, 41% and 39 pg/mL for C. parapsilosis, and 63% and 149 pg/mL for other species; p 0.015 and p 0.003). In multivariate analysis, Candida species (parapsilosis versus others) was the only factor influencing the sensitivity of BDG (OR 0.3, 95% CI 0.1-0.7, p 0.006). The sensitivity of BDG in candidaemia seems highly dependent on the fungal species, with the lowest being for C. parapsilosis. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Sensitivities of projected 1980 photovoltaic system costs to major system cost drivers

NASA Technical Reports Server (NTRS)

Zimmerman, L. W.; Smith, J. L.

1984-01-01

The sensitivity of projected 1990 photovoltaic (PV) system costs to major system cost drivers was examined. It includes: (1) module costs and module efficiencies; (2) area related balance of system (BOS) costs; (3) inverter costs and efficiencies; and (4) module marketing and distribution markups and system integration fees. Recent PV system cost experiences and the high costs of electricity from the systems are reviewed. The 1990 system costs are projected for five classes of PV systems, including four ground mounted 5-MWp systems and one residential 5-kWp system. System cost projections are derived by first projecting costs and efficiencies for all subsystems and components. Sensitivity analyses reveal that reductions in module cost and engineering and system integration fees seem to have the greatest potential for contributing to system cost reduction. Although module cost is clearly the prime candidate for fruitful PV research and development activities, engineering and system integration fees seem to be more amenable to reduction through appropriate choice of system size and market strategy. Increases in inverter and module efficiency yield significant benefits, especially for systems with high area related costs.

Methodological issues in assessing changes in costs pre- and post-medication switch: a schizophrenia study example

PubMed Central

Faries, Douglas E; Nyhuis, Allen W; Ascher-Svanum, Haya

2009-01-01

Background Schizophrenia is a severe, chronic, and costly illness that adversely impacts patients' lives and health care payer budgets. Cost comparisons of treatment regimens are, therefore, important to health care payers and researchers. Pre-Post analyses ("mirror-image"), where outcomes prior to a medication switch are compared to outcomes post-switch, are commonly used in such research. However, medication changes often occur during a costly crisis event. Patients may relapse, be hospitalized, have a medication change, and then spend a period of time with intense use of costly resources (post-medication switch). While many advantages and disadvantages of Pre-Post methodology have been discussed, issues regarding the attributability of costs incurred around the time of medication switching have not been fully investigated. Methods Medical resource use data, including medications and acute-care services (hospitalizations, partial hospitalizations, emergency department) were collected for patients with schizophrenia who switched antipsychotics (n = 105) during a 1-year randomized, naturalistic, antipsychotic cost-effectiveness schizophrenia trial. Within-patient changes in total costs per day were computed during the pre- and post-medication change periods. In addition to the standard Pre-Post analysis comparing costs pre- and post-medication change, we investigated the sensitivity of results to varying assumptions regarding the attributability of acute care service costs occurring just after a medication switch that were likely due to initial medication failure. Results Fifty-six percent of all costs incurred during the first week on the newly initiated antipsychotic were likely due to treatment failure with the previous antipsychotic. Standard analyses suggested an average increase in cost-per-day for each patient of $2.40 after switching medications. However, sensitivity analyses removing costs incurred post-switch that were potentially due to the failure of the initial medication suggested decreases in costs in the range of $4.77 to $9.69 per day post-switch. Conclusion Pre-Post cost analyses are sensitive to the approach used to handle acute-service costs occurring just after a medication change. Given the importance of quality economic research on the cost of switching treatments, thorough sensitivity analyses should be performed to identify the impact of crisis events around the time of medication change. PMID:19473545

Subjective global assessment of nutritional status in children.

PubMed

Mahdavi, Aida Malek; Ostadrahimi, Alireza; Safaiyan, Abdolrasool

2010-10-01

This study was aimed to compare the subjective and objective nutritional assessments and to analyse the performance of subjective global assessment (SGA) of nutritional status in diagnosing undernutrition in paediatric patients. One hundred and forty children (aged 2-12 years) hospitalized consecutively in Tabriz Paediatric Hospital from June 2008 to August 2008 underwent subjective assessment using the SGA questionnaire and objective assessment, including anthropometric and biochemical measurements. Agreement between two assessment methods was analysed by the kappa (κ) statistic. Statistical indicators including (sensitivity, specificity, predictive values, error rates, accuracy, powers, likelihood ratios and odds ratio) between SGA and objective assessment method were determined. The overall prevalence of undernutrition according to the SGA (70.7%) was higher than that by objective assessment of nutritional status (48.5%). Agreement between the two evaluation methods was only fair to moderate (κ = 0.336, P < 0.001). The sensitivity, specificity, positive and negative predictive value of the SGA method for screening undernutrition in this population were 88.235%, 45.833%, 60.606% and 80.487%, respectively. Accuracy, positive and negative power of the SGA method were 66.428%, 56.074% and 41.25%, respectively. Likelihood ratio positive, likelihood ratio negative and odds ratio of the SGA method were 1.628, 0.256 and 6.359, respectively. Our findings indicated that in assessing nutritional status of children, there is not a good level of agreement between SGA and objective nutritional assessment. In addition, SGA is a highly sensitive tool for assessing nutritional status and could identify children at risk of developing undernutrition. © 2009 Blackwell Publishing Ltd.

Cost Analyses in the US and Japan: A Cross-Country Comparative Analysis Applied to the PRONOUNCE Trial in Non-Squamous Non-Small Cell Lung Cancer.

PubMed

Hess, Lisa M; Rajan, Narayan; Winfree, Katherine; Davey, Peter; Ball, Mark; Knox, Hediyyih; Graham, Christopher

2015-12-01

Health technology assessment is not required for regulatory submission or approval in either the United States (US) or Japan. This study was designed as a cross-country evaluation of cost analyses conducted in the US and Japan based on the PRONOUNCE phase III lung cancer trial, which compared pemetrexed plus carboplatin followed by pemetrexed (PemC) versus paclitaxel plus carboplatin plus bevacizumab followed by bevacizumab (PCB). Two cost analyses were conducted in accordance with International Society For Pharmacoeconomics and Outcomes Research good research practice standards. Costs were obtained based on local pricing structures; outcomes were considered equivalent based on the PRONOUNCE trial results. Other inputs were included from the trial data (e.g., toxicity rates) or from local practice sources (e.g., toxicity management). The models were compared across key input and transferability factors. Despite differences in local input data, both models demonstrated a similar direction, with the cost of PemC being consistently lower than the cost of PCB. The variation in individual input parameters did affect some of the specific categories, such as toxicity, and impacted sensitivity analyses, with the cost differential between comparators being greater in Japan than in the US. When economic models are based on clinical trial data, many inputs and outcomes are held consistent. The alterable inputs were not in and of themselves large enough to significantly impact the results between countries, which were directionally consistent with greater variation seen in sensitivity analyses. The factors that vary across jurisdictions, even when minor, can have an impact on trial-based economic analyses. Eli Lilly and Company.

Sensitivity of Assimilated Tropical Tropospheric Ozone to the Meteorological Analyses

NASA Technical Reports Server (NTRS)

Hayashi, Hiroo; Stajner, Ivanka; Pawson, Steven; Thompson, Anne M.

2002-01-01

Tropical tropospheric ozone fields from two different experiments performed with an off-line ozone assimilation system developed in NASA's Data Assimilation Office (DAO) are examined. Assimilated ozone fields from the two experiments are compared with the collocated ozone profiles from the Southern Hemispheric Additional Ozonesondes (SHADOZ) network. Results are presented for 1998. The ozone assimilation system includes a chemistry-transport model, which uses analyzed winds from the Goddard Earth Observing System (GEOS) Data Assimilation System (DAS). The two experiments use wind fields from different versions of GEOS DAS: an operational version of the GEOS-2 system and a prototype of the GEOS-4 system. While both versions of the DAS utilize the Physical-space Statistical Analysis System and use comparable observations, they use entirely different general circulation models and data insertion techniques. The shape of the annual-mean vertical profile of the assimilated ozone fields is sensitive to the meteorological analyses, with the GEOS-4-based ozone being closest to the observations. This indicates that the resolved transport in GEOS-4 is more realistic than in GEOS-2. Remaining uncertainties include quantification of the representation of sub-grid-scale processes in the transport calculations, which plays an important role in the locations and seasons where convection dominates the transport.

MEDICAL DEVICE PRICES IN ECONOMIC EVALUATIONS.

PubMed

Akpinar, Ilke; Jacobs, Philip; Husereau, Don

2015-01-01

Economic evaluations, although not formally used in purchasing decisions for medical devices in Canada, are still being conducted and published. The aim of this study was to examine the way that prices have been included in Canadian economic evaluations of medical devices. We conducted a review of the economic concepts and implications of methods used for economic evaluations of the eleven most implanted medical devices from the Canadian perspective. We found Canadian economic studies for five of the eleven medical devices and identified nineteen Canadian studies. Overall, the device costs were important components of total procedure cost, with an average ratio of 44.1 %. Observational estimates of the device costs were obtained from buyers or sellers in 13 of the 19 studies. Although most of the devices last more than 1 year, standard costing methods for capital equipment was never used. In addition, only eight studies included a sensitivity analysis for the device cost. None of the sensitivity analyses were based on actual price distributions. Economic evaluations are potentially important for policy making, but although they are being conducted, there is no standardized approach for incorporating medical device prices in economic analyses. Our review provides suggestions for improvements in how the prices are incorporated for economic evaluations of medical devices.

Effect of exercise on depression in university students: a meta-analysis of randomized controlled trials.

PubMed

Yan, Shi; Jin, YinZhe; Oh, YongSeok; Choi, YoungJun

2016-06-01

The aim of this study was to assess the effect of exercise on depression in university students. A systematic literature search was conducted in PubMed, EMBASE and the Cochrane library from their inception through December 10, 2014 to identify relevant articles. The heterogeneity across studies was examined by Cochran's Q statistic and the I2 statistic. Standardized mean difference (SMD) and 95% confidence interval (CI) were pooled to evaluate the effect of exercise on depression. Then, sensitivity and subgroup analyses were performed. In addition, publication bias was assessed by drawing a funnel plot. A total of 352 participants (154 cases and 182 controls) from eight included trials were included. Our pooled result showed a significant alleviative depression after exercise (SMD=-0.50, 95% CI: -0.97 to -0.03, P=0.04) with significant heterogeneity (P=0.003, I2=67%). Sensitivity analyses showed that the pooled result may be unstable. Subgroup analysis indicated that sample size may be a source of heterogeneity. Moreover, no publication bias was observed in this study. Exercise may be an effective therapy for treating depression in university students. However, further clinical studies with strict design and large samples focused on this specific population should be warranted in the future.

Optical coherence tomography for the diagnosis of malignant skin tumors: a meta-analysis

NASA Astrophysics Data System (ADS)

Xiong, Yi-Quan; Mo, Yun; Wen, Yu-Qi; Cheng, Ming-Ji; Huo, Shu-Ting; Chen, Xue-Jiao; Chen, Qing

2018-02-01

Optical coherence tomography (OCT) is an emergent imaging tool used for noninvasive diagnosis of skin diseases. The present meta-analysis was carried out to assess the accuracy of OCT for the diagnosis of skin cancer. We conducted a systematic literature search though EMBASE, Medline, PubMed, the Cochrane Library, and Web of Science database for relevant articles published up to June 6, 2017. The quality of the included studies was assessed using the QUADAS-2 tool and the Oxford Levels of Evidence Scale. Statistical analyses were conducted using the software Meta-Disc version 1.4 and STATA version 12.0. A total of 14 studies involving more than 813 patients with a total of 1958 lesions were included in our analyses. The pooled sensitivity and specificity of OCT for skin cancer diagnoses were 91.8% and 86.7%, respectively. Subgroup analysis showed that the pooled sensitivities of OCT for detecting basal cell carcinoma (BCC), squamous cell carcinoma (SCC), actinic keratosis, and malignant melanoma were 92.4%, 92.3%, 73.8%, and 81.0%, respectively. The pooled specificities were 86.9%, 99.5%, 91.5%, and 93.8%, respectively. OCT appears to be useful for the detection of BCC and SCC. It is a valuable diagnostic method when screening for early skin cancers.

Analysis strategies for high-resolution UHF-fMRI data.

PubMed

Polimeni, Jonathan R; Renvall, Ville; Zaretskaya, Natalia; Fischl, Bruce

2018-03-01

Functional MRI (fMRI) benefits from both increased sensitivity and specificity with increasing magnetic field strength, making it a key application for Ultra-High Field (UHF) MRI scanners. Most UHF-fMRI studies utilize the dramatic increases in sensitivity and specificity to acquire high-resolution data reaching sub-millimeter scales, which enable new classes of experiments to probe the functional organization of the human brain. This review article surveys advanced data analysis strategies developed for high-resolution fMRI at UHF. These include strategies designed to mitigate distortion and artifacts associated with higher fields in ways that attempt to preserve spatial resolution of the fMRI data, as well as recently introduced analysis techniques that are enabled by these extremely high-resolution data. Particular focus is placed on anatomically-informed analyses, including cortical surface-based analysis, which are powerful techniques that can guide each step of the analysis from preprocessing to statistical analysis to interpretation and visualization. New intracortical analysis techniques for laminar and columnar fMRI are also reviewed and discussed. Prospects for single-subject individualized analyses are also presented and discussed. Altogether, there are both specific challenges and opportunities presented by UHF-fMRI, and the use of proper analysis strategies can help these valuable data reach their full potential. Copyright © 2017 Elsevier Inc. All rights reserved.

Antibiotic treatment of bacterial vaginosis in pregnancy: multiple meta-analyses and dilemmas in interpretation.

PubMed

Varma, Rajesh; Gupta, Janesh K

2006-01-01

There is considerable evidence to show an association between genital tract infections, such as bacterial vaginosis (BV), and preterm delivery (PTD). Meta-analyses to date have shown screening and treating BV in pregnancy does not prevent PTD. This casts doubt on a cause and effect relationship between BV and PTD. However, the meta-analyses reported significant clinical, methodological and statistical heterogeneity of the included studies. We therefore undertook a repeat meta-analysis, included recently published trials, and applied strict criteria on data extraction. We meta-analysed low and high-risk pregnancies separately. We found that screening and treating BV in low-risk pregnancies produced a statistically significant reduction in spontaneous PTD (RR 0.73; 95% CI 0.55-0.98). This beneficial effect was not observed in high-risk or combined risk groups. The differences in antibiotic sensitivity between high and low risk groups may suggest differing causal contributions of the infectious process to PTD. The evidence, along with prior knowledge of differing predisposing factors and prognosis between these risk groups, supports the hypothesis that PTD in high and low risk pregnant women are different entities and not linear extremes of the same syndrome.

Self-perceived weather sensitivity and joint pain in older people with osteoarthritis in six European countries: results from the European Project on OSteoArthritis (EPOSA)

PubMed Central

2014-01-01

Background People with osteoarthritis (OA) frequently report that their joint pain is influenced by weather conditions. This study aimed to examine whether there are differences in perceived joint pain between older people with OA who reported to be weather-sensitive versus those who did not in six European countries with different climates and to identify characteristics of older persons with OA that are most predictive of perceived weather sensitivity. Methods Baseline data from the European Project on OSteoArthritis (EPOSA) were used. ACR classification criteria were used to determine OA. Participants with OA were asked about their perception of weather as influencing their pain. Using a two-week follow-up pain calendar, average self-reported joint pain was assessed (range: 0 (no pain)-10 (greatest pain intensity)). Linear regression analyses, logistic regression analyses and an independent t-test were used. Analyses were adjusted for several confounders. Results The majority of participants with OA (67.2%) perceived the weather as affecting their pain. Weather-sensitive participants reported more pain than non-weather-sensitive participants (M = 4.1, SD = 2.4 versus M = 3.1, SD = 2.4; p < 0.001). After adjusting for several confounding factors, the association between self-perceived weather sensitivity and joint pain remained present (B = 0.37, p = 0.03). Logistic regression analyses revealed that women and more anxious people were more likely to report weather sensitivity. Older people with OA from Southern Europe were more likely to indicate themselves as weather-sensitive persons than those from Northern Europe. Conclusions Weather (in)stability may have a greater impact on joint structures and pain perception in people from Southern Europe. The results emphasize the importance of considering weather sensitivity in daily life of older people with OA and may help to identify weather-sensitive older people with OA. PMID:24597710

Self-perceived weather sensitivity and joint pain in older people with osteoarthritis in six European countries: results from the European Project on OSteoArthritis (EPOSA).

PubMed

Timmermans, Erik J; van der Pas, Suzan; Schaap, Laura A; Sánchez-Martínez, Mercedes; Zambon, Sabina; Peter, Richard; Pedersen, Nancy L; Dennison, Elaine M; Denkinger, Michael; Castell, Maria Victoria; Siviero, Paola; Herbolsheimer, Florian; Edwards, Mark H; Otero, Angel; Deeg, Dorly J H

2014-03-05

People with osteoarthritis (OA) frequently report that their joint pain is influenced by weather conditions. This study aimed to examine whether there are differences in perceived joint pain between older people with OA who reported to be weather-sensitive versus those who did not in six European countries with different climates and to identify characteristics of older persons with OA that are most predictive of perceived weather sensitivity. Baseline data from the European Project on OSteoArthritis (EPOSA) were used. ACR classification criteria were used to determine OA. Participants with OA were asked about their perception of weather as influencing their pain. Using a two-week follow-up pain calendar, average self-reported joint pain was assessed (range: 0 (no pain)-10 (greatest pain intensity)). Linear regression analyses, logistic regression analyses and an independent t-test were used. Analyses were adjusted for several confounders. The majority of participants with OA (67.2%) perceived the weather as affecting their pain. Weather-sensitive participants reported more pain than non-weather-sensitive participants (M = 4.1, SD = 2.4 versus M = 3.1, SD = 2.4; p < 0.001). After adjusting for several confounding factors, the association between self-perceived weather sensitivity and joint pain remained present (B = 0.37, p = 0.03). Logistic regression analyses revealed that women and more anxious people were more likely to report weather sensitivity. Older people with OA from Southern Europe were more likely to indicate themselves as weather-sensitive persons than those from Northern Europe. Weather (in)stability may have a greater impact on joint structures and pain perception in people from Southern Europe. The results emphasize the importance of considering weather sensitivity in daily life of older people with OA and may help to identify weather-sensitive older people with OA.

Sensitivity analysis of reactive ecological dynamics.

PubMed

Verdy, Ariane; Caswell, Hal

2008-08-01

Ecological systems with asymptotically stable equilibria may exhibit significant transient dynamics following perturbations. In some cases, these transient dynamics include the possibility of excursions away from the equilibrium before the eventual return; systems that exhibit such amplification of perturbations are called reactive. Reactivity is a common property of ecological systems, and the amplification can be large and long-lasting. The transient response of a reactive ecosystem depends on the parameters of the underlying model. To investigate this dependence, we develop sensitivity analyses for indices of transient dynamics (reactivity, the amplification envelope, and the optimal perturbation) in both continuous- and discrete-time models written in matrix form. The sensitivity calculations require expressions, some of them new, for the derivatives of equilibria, eigenvalues, singular values, and singular vectors, obtained using matrix calculus. Sensitivity analysis provides a quantitative framework for investigating the mechanisms leading to transient growth. We apply the methodology to a predator-prey model and a size-structured food web model. The results suggest predator-driven and prey-driven mechanisms for transient amplification resulting from multispecies interactions.

Prenatal Depressive Symptoms and Toddler Behavior Problems: The Role of Maternal Sensitivity and Child Sex.

PubMed

Edwards, Renee C; Hans, Sydney L

2016-10-01

Increasing evidence suggests that maternal depression during pregnancy is associated with child behavioral outcomes even after accounting for later maternal depression. The purpose of this study was to examine various mechanisms, including maternal sensitivity, neonatal problems, and concurrent maternal depression, that might explain the association between prenatal maternal depressive symptoms and toddler behavior problems. Young, low income, African American mothers (n = 196) were interviewed during pregnancy and at 24-months postpartum, medical records were collected at the birth, and mother-child interactions were video-recorded at 24 months. Path analyses revealed that the association between prenatal depression and toddler behavior problems was mediated by maternal sensitivity and maternal depressive symptoms at 24 months. No evidence was found for a mediating effect of neonatal problems. Path models examining sex differences suggested that different mediating factors may be important for boys and girls, with boys being particularly susceptible to the effects of maternal sensitivity.

hhjj production at the LHC

DOE PAGES

Dolan, Matthew J.; Englert, Christoph; Greiner, Nicolas; ...

2015-08-25

The search for di-Higgs production at the LHC in order to set limits on the Higgs trilinear coupling and constraints on new physics is one of the main motivations for the LHC high-luminosity phase. Recent experimental analyses suggest that such analyses will only be successful if information from a range of channels is included. We therefore investigate di-Higgs production in association with two hadronic jets and give a detailed discussion of both the gluon- and the weak boson-fusion (WBF) contributions, with a particular emphasis on the phenomenology with modified Higgs trilinear and quartic gauge couplings. We perform a detailed investigationmore » of the full hadronic final state and find that hhjj production should add sensitivity to a di-Higgs search combination at the HL-LHC with 3 ab -1. Since the WBF and GF contributions are sensitive to different sources of physics beyond the Standard Model, we devise search strategies to disentangle and isolate these production modes. In addition, while gluon fusion remains non-negligible in WBF-type selections, sizeable new physics contributions to the latter can still be constrained. As an example of the latter point we investigate the sensitivity that can be obtained for a measurement of the quartic Higgs–gauge boson couplings.« less

Meta-analyses including data from observational studies.

PubMed

O'Connor, Annette M; Sargeant, Jan M

2014-02-15

Observational studies represent a wide group of studies where the disease or condition of interest is naturally occurring and the investigator does not control allocation to interventions or exposures. Observational studies are used to test hypotheses about the efficacy of interventions or about exposure-disease relationships, to estimate incidence or prevalence of conditions, and to assess the sensitivity and specificity of diagnostic assays. Experimental-study designs and randomized controlled trials (RCTs) can also contribute to the body of evidence about such questions. Meta-analyses (either with or without systematic reviews) aim to combine information from primary research studies to better describe the entire body of work. The aim of meta-analyses may be to obtain a summary effect size, or to understand factors that affect effect sizes. In this paper, we discuss the role of observational studies in meta-analysis questions and some factors to consider when deciding whether a meta-analysis should include results from such studies. Our suggestion is that one should only include studies that are not at high risk of inherent bias when calculating a summary effect size. Study design however can be a meaningful variable in assessment of outcome heterogeneity. Copyright © 2013 Elsevier B.V. All rights reserved.

Sources of sensitization, cross-reactions, and occupational sensitization to topical anaesthetics among general dermatology patients.

PubMed

Jussi, Liippo; Lammintausta, Kaija

2009-03-01

Contact sensitization to local anaesthetics is often from topical medicaments. Occupational sensitization to topical anaesthetics may occur in certain occupations. The aim of the study was to analyse the occurrence of contact sensitization to topical anaesthetics in general dermatology patients. Patch testing with topical anaesthetics was carried out in 620 patients. Possible sources of sensitization and the clinical histories of the patients are analysed. Positive patch test reactions to one or more topical anaesthetics were seen in 25/620 patients. Dibucaine reactions were most common (20/25), and lidocaine sensitization was seen in two patients. Six patients had reactions to ester-type and/or amide-type anaesthetics concurrently. Local preparations for perianal conditions were the most common sensitizers. One patient had developed occupational sensitization to procaine with multiple cross-reactions and with concurrent penicillin sensitization from procaine penicillin. Dibucaine-containing perianal medicaments are the major source of contact sensitization to topical anaesthetics. Although sensitization to multiple anaesthetics can be seen, cross-reactions are possible. Contact sensitization to lidocaine is not common, and possible cross-reactions should be determined when reactions to lidocaine are seen. Occupational procaine sensitization from veterinary medicaments is a risk among animal workers.

Effectiveness of regional DTI measures in distinguishing Alzheimer's disease, MCI, and normal aging☆

PubMed Central

Nir, Talia M.; Jahanshad, Neda; Villalon-Reina, Julio E.; Toga, Arthur W.; Jack, Clifford R.; Weiner, Michael W.; Thompson, Paul M.

2013-01-01

The Alzheimer's Disease Neuroimaging Initiative (ADNI) recently added diffusion tensor imaging (DTI), among several other new imaging modalities, in an effort to identify sensitive biomarkers of Alzheimer's disease (AD). While anatomical MRI is the main structural neuroimaging method used in most AD studies and clinical trials, DTI is sensitive to microscopic white matter (WM) changes not detectable with standard MRI, offering additional markers of neurodegeneration. Prior DTI studies of AD report lower fractional anisotropy (FA), and increased mean, axial, and radial diffusivity (MD, AxD, RD) throughout WM. Here we assessed which DTI measures may best identify differences among AD, mild cognitive impairment (MCI), and cognitively healthy elderly control (NC) groups, in region of interest (ROI) and voxel-based analyses of 155 ADNI participants (mean age: 73.5 ± 7.4; 90 M/65 F; 44 NC, 88 MCI, 23 AD). Both VBA and ROI analyses revealed widespread group differences in FA and all diffusivity measures. DTI maps were strongly correlated with widely-used clinical ratings (MMSE, CDR-sob, and ADAS-cog). When effect sizes were ranked, FA analyses were least sensitive for picking up group differences. Diffusivity measures could detect more subtle MCI differences, where FA could not. ROIs showing strongest group differentiation (lowest p-values) included tracts that pass through the temporal lobe, and posterior brain regions. The left hippocampal component of the cingulum showed consistently high effect sizes for distinguishing groups, across all diffusivity and anisotropy measures, and in correlations with cognitive scores. PMID:24179862

Sensitivity Analyses of the Change in FVC in a Phase 3 Trial of Pirfenidone for Idiopathic Pulmonary Fibrosis.

PubMed

Lederer, David J; Bradford, Williamson Z; Fagan, Elizabeth A; Glaspole, Ian; Glassberg, Marilyn K; Glasscock, Kenneth F; Kardatzke, David; King, Talmadge E; Lancaster, Lisa H; Nathan, Steven D; Pereira, Carlos A; Sahn, Steven A; Swigris, Jeffrey J; Noble, Paul W

2015-07-01

FVC outcomes in clinical trials on idiopathic pulmonary fibrosis (IPF) can be substantially influenced by the analytic methodology and the handling of missing data. We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF. Source data included all 555 study participants randomized to treatment with pirfenidone or placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) study. Sensitivity analyses were conducted to assess whether alternative statistical tests and methods for handling missing data influenced the observed magnitude of treatment effect on the primary end point of change from baseline to week 52 in FVC. The distribution of FVC change at week 52 was systematically different between the two treatment groups and favored pirfenidone in each analysis. The method used to impute missing data due to death had a marked effect on the magnitude of change in FVC in both treatment groups; however, the magnitude of treatment benefit was generally consistent on a relative basis, with an approximate 50% reduction in FVC decline observed in the pirfenidone group in each analysis. Our results confirm the robustness of the statistical finding on the primary end point of change in FVC in the ASCEND trial and corroborate the estimated magnitude of the pirfenidone treatment effect in patients with IPF. ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov.

PROP taster status not related to reported cruciferous vegetable intake among ethnically diverse children

PubMed Central

Baranowski, Tom; Baranowski, Janice C; Watson, Kathleen B; Jago, Russell; Islam, Noemi; Beltran, Alicia; Martin, Shelby J; Nguyen, Nga; Tepper, Beverly J

2011-01-01

Sensitivity to the taste of 6-n-propylthiouracil (PROP) (a bitter tasting chemical related to the phenylthiocarbamide found in cruciferous vegetables) has been related to dietary intake or preferences of cruciferous vegetables among adults and young children, but not middle aged children or adolescents. We hypothesized that PROP taste sensitivity is related to lower reported dietary intake of cruciferous vegetables, primarily among younger children (i.e. a moderating effect of child age). This study examined the relationship of PROP sensitivity to reported dietary intake across three days in two age groups of youth (9–10 years and 17–18 year), while statistically controlling for physical activity, social desirability and reporting bias. Cross sectional design was employed with a multi-ethnic (White, African American, Hispanic, and Other) sample of 843 males and females. Children were recruited from and data were collected in local elementary and high schools that had at least 30% ethnic minority enrollment. Children providing nonplausible reports of dietary intake were deleted from the analyses. BMI was calculated and expressed in z-scores. Energy intake and physical activity were measured by three telephone conducted 24-hour dietary recalls with the Nutrient Data System for Research (NDSR) and 5 days of Actigraph activity monitor. The primary analyses included 347 students. PROP sensitivity was not related to intake of cruciferous vegetables. Intakes of the cruciferous vegetables were low, which may explain the lack of relationship. PMID:21925344

6-n-propylthiouracil taster status not related to reported cruciferous vegetable intake among ethnically diverse children.

PubMed

Baranowski, Tom; Baranowski, Janice C; Watson, Kathleen B; Jago, Russell; Islam, Noemi; Beltran, Alicia; Martin, Shelby J; Nguyen, Nga; Tepper, Beverly J

2011-08-01

Sensitivity to the taste of 6-n-propylthiouracil (PROP) (a bitter chemical related to the phenylthiocarbamide found in cruciferous vegetables) has been related to dietary intake or preferences of cruciferous vegetables among adults and young children but not middle-aged children or adolescents. We hypothesized that PROP taste sensitivity is related to lower reported dietary intake of cruciferous vegetables, primarily among younger children (ie, a moderating effect of child age). This study examined the relationship of PROP sensitivity to reported dietary intake across 3 days in 2 age groups of youth (9-10 and 17-18 years) while statistically controlling for physical activity, social desirability, and reporting bias. Cross-sectional design was used with a multiethnic (white, African American, Hispanic, etc) sample of 843 men and women. Children were recruited from and data were collected in local elementary and high schools that had at least 30% ethnic minority enrollment. Children providing nonplausible reports of dietary intake were deleted from the analyses. Body mass index was calculated and expressed in z scores. Energy intake and physical activity were measured by 3 telephone-conducted 24-hour dietary recalls with the Nutrient Data System for Research and 5 days of Actigraph (ActiGraph, Shalimar, Florida) activity monitor. The primary analyses included 347 students. 6-n-Propylthiouracil sensitivity was not related to intake of cruciferous vegetables. Intakes of the cruciferous vegetables were low, which may explain the lack of relationship. Copyright © 2011 Elsevier Inc. All rights reserved.

Revenue Potential for Inpatient IR Consultation Services: A Financial Model.

PubMed

Misono, Alexander S; Mueller, Peter R; Hirsch, Joshua A; Sheridan, Robert M; Siddiqi, Assad U; Liu, Raymond W

2016-05-01

Interventional radiology (IR) has historically failed to fully capture the value of evaluation and management services in the inpatient setting. Understanding financial benefits of a formally incorporated billing discipline may yield meaningful insights for interventional practices. A revenue modeling tool was created deploying standard financial modeling techniques, including sensitivity and scenario analyses. Sensitivity analysis calculates revenue fluctuation related to dynamic adjustment of discrete variables. In scenario analysis, possible future scenarios as well as revenue potential of different-size clinical practices are modeled. Assuming a hypothetical inpatient IR consultation service with a daily patient census of 35 patients and two new consults per day, the model estimates annual charges of $2.3 million and collected revenue of $390,000. Revenues are most sensitive to provider billing documentation rates and patient volume. A range of realistic scenarios-from cautious to optimistic-results in a range of annual charges of $1.8 million to $2.7 million and a collected revenue range of $241,000 to $601,000. Even a small practice with a daily patient census of 5 and 0.20 new consults per day may expect annual charges of $320,000 and collected revenue of $55,000. A financial revenue modeling tool is a powerful adjunct in understanding economics of an inpatient IR consultation service. Sensitivity and scenario analyses demonstrate a wide range of revenue potential and uncover levers for financial optimization. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

Aeroelastic optimization methodology for viscous and turbulent flows

NASA Astrophysics Data System (ADS)

Barcelos Junior, Manuel Nascimento Dias

2007-12-01

In recent years, the development of faster computers and parallel processing allowed the application of high-fidelity analysis methods to the aeroelastic design of aircraft. However, these methods are restricted to the final design verification, mainly due to the computational cost involved in iterative design processes. Therefore, this work is concerned with the creation of a robust and efficient aeroelastic optimization methodology for inviscid, viscous and turbulent flows by using high-fidelity analysis and sensitivity analysis techniques. Most of the research in aeroelastic optimization, for practical reasons, treat the aeroelastic system as a quasi-static inviscid problem. In this work, as a first step toward the creation of a more complete aeroelastic optimization methodology for realistic problems, an analytical sensitivity computation technique was developed and tested for quasi-static aeroelastic viscous and turbulent flow configurations. Viscous and turbulent effects are included by using an averaged discretization of the Navier-Stokes equations, coupled with an eddy viscosity turbulence model. For quasi-static aeroelastic problems, the traditional staggered solution strategy has unsatisfactory performance when applied to cases where there is a strong fluid-structure coupling. Consequently, this work also proposes a solution methodology for aeroelastic and sensitivity analyses of quasi-static problems, which is based on the fixed point of an iterative nonlinear block Gauss-Seidel scheme. The methodology can also be interpreted as the solution of the Schur complement of the aeroelastic and sensitivity analyses linearized systems of equations. The methodologies developed in this work are tested and verified by using realistic aeroelastic systems.

Oxidative responsiveness to multiple stressors in the key Antarctic species, Adamussium colbecki: Interactions between temperature, acidification and cadmium exposure.

PubMed

Benedetti, Maura; Lanzoni, Ilaria; Nardi, Alessandro; d'Errico, Giuseppe; Di Carlo, Marta; Fattorini, Daniele; Nigro, Marco; Regoli, Francesco

2016-10-01

High-latitude marine ecosystems are ranked to be among the most sensitive regions to climate change since highly stenothermal and specially adapted organisms might be seriously affected by global warming and ocean acidification. The present investigation was aimed to provide new insights on the sensitivity to such environmental stressors in the key Antarctic species, Adamussium colbecki, focussing also on their synergistic effects with cadmium exposure, naturally abundant in this area for upwelling phenomena. Scallops were exposed for 2 weeks to various combinations of Cd (0 and 40 μgL-1), pH (8.05 and 7.60) and temperature (-1 and +1 °C). Beside Cd bioaccumulation, a wide panel of early warning biomarkers were analysed in digestive glands and gills including levels of metallothioneins, individual antioxidants and total oxyradical scavenging capacity, onset of oxidative cell damage like lipid peroxidation, lysosomal stability, DNA integrity and peroxisomal proliferation. Results indicated reciprocal interactions between multiple stressors and their elaboration by a quantitative hazard model based on the relevance and magnitude of effects, highlighted a different sensitivity of analysed tissues. Due to cellular adaptations to high basal Cd content, digestive gland appeared more tolerant toward other prooxidant stressors, but sensitive to variations of the metal. On the other hand, gills were more affected by various combinations of stressors occurring at higher temperature. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regional body fat distribution and metabolic profile in postmenopausal women.

PubMed

Piché, Marie-Eve; Lapointe, Annie; Weisnagel, S John; Corneau, Louise; Nadeau, André; Bergeron, Jean; Lemieux, Simone

2008-08-01

The aim of the study was to examine how body fat distribution variables were associated with metabolic parameters in a sample of 113 postmenopausal women not receiving hormone therapy (56.9 +/- 4.4 years, 28.4 +/- 5.1 kg/m(2)). Body fat distribution variables (visceral adipose tissue [AT], subcutaneous AT, and total midthigh AT) were measured using computed tomography; body fat mass was assessed by hydrostatic weighing; insulin sensitivity was determined with the euglycemic-hyperinsulinemic clamp; fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) concentrations were measured by a 75-g oral glucose load; and (high-sensitivity) C-reactive protein (hs-CRP) was measured using a highly sensitive assay. After controlling for fat mass, visceral AT was positively associated with plasma triglyceride, hs-CRP, FPG, and 2hPG, and negatively associated with high-density lipoprotein cholesterol (HDL-C) and insulin sensitivity. Total midthigh AT was negatively associated with apolipoprotein B, FPG, and 2hPG, and positively associated with insulin sensitivity. Stepwise multiple regression analyses including abdominal visceral AT, subcutaneous AT and total midthigh AT as independent variables showed that abdominal visceral AT best predicted the variance in plasma triglyceride, HDL-C, low-density lipoprotein peak particle size, hs-CRP, FPG, 2hPG, and insulin sensitivity. Abdominal subcutaneous AT was a significant predictor of only insulin sensitivity, whereas total midthigh AT predicted HDL-C, low-density lipoprotein peak particle size, and apolipoprotein B. These multivariate analyses also indicated that total midthigh AT was favorably related to these outcomes, whereas abdominal visceral AT and subcutaneous AT were unfavorably related. These results confirmed that abdominal visceral fat is a critical correlate of metabolic parameters in postmenopausal women. In addition, a higher proportion of AT located in the total midthigh depot is associated with a favorable metabolic profile.

Racial and ethnic disparities in meeting MTM eligibility criteria among patients with asthma.

PubMed

Lu, Degan; Qiao, Yanru; Johnson, Karen C; Wang, Junling

2017-06-01

Asthma is one of the most frequently targeted chronic diseases in the medication therapy management (MTM) programs of the Medicare prescription drug (Part D) benefits. Although racial and ethnic disparities in meeting eligibility criteria for MTM services have been reported, little is known about whether there would be similar disparities among adults with asthma in the United States. Adult patients with asthma (age ≥ 18) from Medical Expenditure Panel Survey (2011-2012) were analyzed. Bivariate analyses were conducted to compare the proportions of patients who would meet Medicare MTM eligibility criteria between non-Hispanic Blacks (Blacks), Hispanics and non-Hispanic Whites (Whites). Survey-weighted logistic regression was performed to adjust for patient characteristics. Main and sensitivity analyses were conducted to cover the entire range of the eligibility thresholds used by Part D plans in 2011-2012. The sample included 4,455 patients with asthma, including 2,294 Whites, 1,218 Blacks, and 943 Hispanics. Blacks and Hispanics had lower proportions of meeting MTM eligibility criteria than did Whites (P < 0.001). According to the main analysis, Blacks and Hispanics had 36% and 32% lower, respectively, likelihood of MTM eligibility than Whites (odds ratio [OR]: 0.64, 95% confidence interval [CI]: 0.45-0.90; OR: 0.68, 95% CI: 0.47-0.98, respectively). Similar results were obtained in sensitivity analyses. There are racial and ethnic disparities in meeting Medicare Part D MTM eligibility criteria among adult patients with asthma. Future studies should examine the implications of such disparities on health outcomes of patients with asthma and explore alternative MTM eligibility criteria.

Additional EIPC Study Analysis: Interim Report on High Priority Topics

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

Hadley, Stanton W

Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations weremore » developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 13 topics was developed for further analysis; this paper discusses the first five.« less

Machine Learning Predictions of a Multiresolution Climate Model Ensemble

NASA Astrophysics Data System (ADS)

Anderson, Gemma J.; Lucas, Donald D.

2018-05-01

Statistical models of high-resolution climate models are useful for many purposes, including sensitivity and uncertainty analyses, but building them can be computationally prohibitive. We generated a unique multiresolution perturbed parameter ensemble of a global climate model. We use a novel application of a machine learning technique known as random forests to train a statistical model on the ensemble to make high-resolution model predictions of two important quantities: global mean top-of-atmosphere energy flux and precipitation. The random forests leverage cheaper low-resolution simulations, greatly reducing the number of high-resolution simulations required to train the statistical model. We demonstrate that high-resolution predictions of these quantities can be obtained by training on an ensemble that includes only a small number of high-resolution simulations. We also find that global annually averaged precipitation is more sensitive to resolution changes than to any of the model parameters considered.

Anaphylaxis to Gelofusine confirmed by in vitro basophil activation test: a case series.

PubMed

Apostolou, E; Deckert, K; Puy, R; Sandrini, A; de Leon, M P; Douglass, J A; Rolland, J M; O'hehir, R E

2006-03-01

The plasma expander Gelofusine (succinylated gelatin) is a recognised cause of peri-operative anaphylaxis. Current diagnosis of Gelofusine sensitivity is by skin testing, a procedure that itself carries a risk of allergic reaction. We evaluated the reliability of the in vitro basophil activation test as a diagnostic assay for Gelofusine sensitivity in subjects with a clinical history highly suggestive of Gelofusine allergy. Six patients with peri-operative anaphylaxis clinically attributed to Gelofusine were skin tested to confirm sensitivity. Control subjects included three healthy subjects and five subjects allergic to a neuromuscular blocking drug, all negative on Gelofusine skin testing. Whole blood basophil activation to Gelofusine was analysed by flow cytometry for CD63 surface expression. All of the Gelofusine sensitive patients and one of the control allergic subjects showed positive basophil activation to Gelofusine. In this series of subjects, the basophil activation test for Gelofusine allergy had a sensitivity of 100% and a specificity of 87.5%. Our findings suggest that basophil activation testing is a safe and reliable in vitro assay for prediction or confirmation of Gelofusine sensitivity in patients with high clinical suspicion of Gelofusine-induced anaphylaxis.

IgE Sensitization Patterns to Commonly Consumed Foods Determined by Skin Prick Test in Korean Adults

PubMed Central

2016-01-01

Offending food allergens can vary with regional preferences in food consumption. In this study, we analysed sensitization rates to commonly consumed foods in Korean adults suspected of having food allergy. One hundred and thirty four subjects underwent a skin prick test (SPT) with 55 food allergens, of which 13 were made by our laboratory and the rest were commercially purchased. Of the 134 patients, 73 (54.5%) were sensitized to one or more food allergens. Sensitization to chrysalis was detected most frequently, at a rate of 25.4%. Sensitization rates to other food allergens were as follows: maize grain (13.4%), shrimp (11.9%), almond (11.1%), wheat flour (8.2%), lobster (8.2%), buckwheat (8.2%), mackerel (5.2%), pollack (5.2%), halibut (4.5%), peanut (4.5%), anchovy (4.4%), squid (3.7%), saury (3.0%), common eel (3.0%), yellow corvina (3.0%), hairtail (2.2%), octopus (2.2%), and others. In addition to well-known food allergens, sensitivity to mackerel, chrysalis, pollack, and halibut, which are popular foods in Korea, was observed at high rates in Korean adults. We suggest that the SPT panel for food allergy in Korea should include these allergens. PMID:27478328

Using global sensitivity analysis to understand higher order interactions in complex models: an application of GSA on the Revised Universal Soil Loss Equation (RUSLE) to quantify model sensitivity and implications for ecosystem services management in Costa Rica

NASA Astrophysics Data System (ADS)

Fremier, A. K.; Estrada Carmona, N.; Harper, E.; DeClerck, F.

2011-12-01

Appropriate application of complex models to estimate system behavior requires understanding the influence of model structure and parameter estimates on model output. To date, most researchers perform local sensitivity analyses, rather than global, because of computational time and quantity of data produced. Local sensitivity analyses are limited in quantifying the higher order interactions among parameters, which could lead to incomplete analysis of model behavior. To address this concern, we performed a GSA on a commonly applied equation for soil loss - the Revised Universal Soil Loss Equation. USLE is an empirical model built on plot-scale data from the USA and the Revised version (RUSLE) includes improved equations for wider conditions, with 25 parameters grouped into six factors to estimate long-term plot and watershed scale soil loss. Despite RUSLE's widespread application, a complete sensitivity analysis has yet to be performed. In this research, we applied a GSA to plot and watershed scale data from the US and Costa Rica to parameterize the RUSLE in an effort to understand the relative importance of model factors and parameters across wide environmental space. We analyzed the GSA results using Random Forest, a statistical approach to evaluate parameter importance accounting for the higher order interactions, and used Classification and Regression Trees to show the dominant trends in complex interactions. In all GSA calculations the management of cover crops (C factor) ranks the highest among factors (compared to rain-runoff erosivity, topography, support practices, and soil erodibility). This is counter to previous sensitivity analyses where the topographic factor was determined to be the most important. The GSA finding is consistent across multiple model runs, including data from the US, Costa Rica, and a synthetic dataset of the widest theoretical space. The three most important parameters were: Mass density of live and dead roots found in the upper inch of soil (C factor), slope angle (L and S factor), and percentage of land area covered by surface cover (C factor). Our findings give further support to the importance of vegetation as a vital ecosystem service provider - soil loss reduction. Concurrent, progress is already been made in Costa Rica, where dam managers are moving forward on a Payment for Ecosystem Services scheme to help keep private lands forested and to improve crop management through targeted investments. Use of complex watershed models, such as RUSLE can help managers quantify the effect of specific land use changes. Moreover, effective land management of vegetation has other important benefits, such as bundled ecosystem services (e.g. pollination, habitat connectivity, etc) and improvements of communities' livelihoods.

Sensitivity analyses of stopping distance for connected vehicles at active highway-rail grade crossings.

PubMed

Hsu, Chung-Jen; Jones, Elizabeth G

2017-02-01

This paper performs sensitivity analyses of stopping distance for connected vehicles (CVs) at active highway-rail grade crossings (HRGCs). Stopping distance is the major safety factor at active HRGCs. A sensitivity analysis is performed for each variable in the function of stopping distance. The formulation of stopping distance treats each variable as a probability density function for implementing Monte Carlo simulations. The result of the sensitivity analysis shows that the initial speed is the most sensitive factor to stopping distances of CVs and non-CVs. The safety of CVs can be further improved by the early provision of onboard train information and warnings to reduce the initial speeds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of Including Higher Actinides in Fast Reactor Transmutation Analyses

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

B. Forget; M. Asgari; R. Ferrer

2007-09-01

Previous fast reactor transmutation studies generally disregarded higher mass minor actinides beyond Cm-246 due to various considerations including deficiencies in nuclear cross-section data. Although omission of these higher mass actinides does not significantly impact the neutronic calculations and fuel cycle performance parameters follow-on neutron dose calculations related to fuel recycling, transportation and handling are significantly impacted. This report shows that including the minor actinides in the equilibrium fast reactor calculations will increase the predicted neutron emission by about 30%. In addition a sensitivity study was initiated by comparing the impact of different cross-section evaluation file for representing these minor actinides.

Accounting for Multiple Births in Neonatal and Perinatal Trials: Systematic Review and Case Study

PubMed Central

Hibbs, Anna Maria; Black, Dennis; Palermo, Lisa; Cnaan, Avital; Luan, Xianqun; Truog, William E; Walsh, Michele C; Ballard, Roberta A

2010-01-01

Objectives To determine the prevalence in the neonatal literature of statistical approaches accounting for the unique clustering patterns of multiple births. To explore the sensitivity of an actual trial to several analytic approaches to multiples. Methods A systematic review of recent perinatal trials assessed the prevalence of studies accounting for clustering of multiples. The NO CLD trial served as a case study of the sensitivity of the outcome to several statistical strategies. We calculated odds ratios using non-clustered (logistic regression) and clustered (generalized estimating equations, multiple outputation) analyses. Results In the systematic review, most studies did not describe the randomization of twins and did not account for clustering. Of those studies that did, exclusion of multiples and generalized estimating equations were the most common strategies. The NO CLD study included 84 infants with a sibling enrolled in the study. Multiples were more likely than singletons to be white and were born to older mothers (p<0.01). Analyses that accounted for clustering were statistically significant; analyses assuming independence were not. Conclusions The statistical approach to multiples can influence the odds ratio and width of confidence intervals, thereby affecting the interpretation of a study outcome. A minority of perinatal studies address this issue. PMID:19969305

Accounting for multiple births in neonatal and perinatal trials: systematic review and case study.

PubMed

Hibbs, Anna Maria; Black, Dennis; Palermo, Lisa; Cnaan, Avital; Luan, Xianqun; Truog, William E; Walsh, Michele C; Ballard, Roberta A

2010-02-01

To determine the prevalence in the neonatal literature of statistical approaches accounting for the unique clustering patterns of multiple births and to explore the sensitivity of an actual trial to several analytic approaches to multiples. A systematic review of recent perinatal trials assessed the prevalence of studies accounting for clustering of multiples. The Nitric Oxide to Prevent Chronic Lung Disease (NO CLD) trial served as a case study of the sensitivity of the outcome to several statistical strategies. We calculated odds ratios using nonclustered (logistic regression) and clustered (generalized estimating equations, multiple outputation) analyses. In the systematic review, most studies did not describe the random assignment of twins and did not account for clustering. Of those studies that did, exclusion of multiples and generalized estimating equations were the most common strategies. The NO CLD study included 84 infants with a sibling enrolled in the study. Multiples were more likely than singletons to be white and were born to older mothers (P < .01). Analyses that accounted for clustering were statistically significant; analyses assuming independence were not. The statistical approach to multiples can influence the odds ratio and width of confidence intervals, thereby affecting the interpretation of a study outcome. A minority of perinatal studies address this issue. Copyright 2010 Mosby, Inc. All rights reserved.

The Sensitivity of Genetic Connectivity Measures to Unsampled and Under-Sampled Sites

PubMed Central

Koen, Erin L.; Bowman, Jeff; Garroway, Colin J.; Wilson, Paul J.

2013-01-01

Landscape genetic analyses assess the influence of landscape structure on genetic differentiation. It is rarely possible to collect genetic samples from all individuals on the landscape and thus it is important to assess the sensitivity of landscape genetic analyses to the effects of unsampled and under-sampled sites. Network-based measures of genetic distance, such as conditional genetic distance (cGD), might be particularly sensitive to sampling intensity because pairwise estimates are relative to the entire network. We addressed this question by subsampling microsatellite data from two empirical datasets. We found that pairwise estimates of cGD were sensitive to both unsampled and under-sampled sites, and FST, Dest, and deucl were more sensitive to under-sampled than unsampled sites. We found that the rank order of cGD was also sensitive to unsampled and under-sampled sites, but not enough to affect the outcome of Mantel tests for isolation by distance. We simulated isolation by resistance and found that although cGD estimates were sensitive to unsampled sites, by increasing the number of sites sampled the accuracy of conclusions drawn from landscape genetic analyses increased, a feature that is not possible with pairwise estimates of genetic differentiation such as FST, Dest, and deucl. We suggest that users of cGD assess the sensitivity of this measure by subsampling within their own network and use caution when making extrapolations beyond their sampled network. PMID:23409155

Theoretical study on the phenylpropanolamine drug interaction with the pristine, Si and Al doped [60] fullerenes

NASA Astrophysics Data System (ADS)

Moradi, Morteza; Nouraliei, Milad; Moradi, Reza

2017-03-01

Phenylpropanolamine (PPA) is a popular drug of abuse and its detection is of great importance for police and drug communities. Herein, we investigated the electronic sensitivity and reactivity of pristine, Al and Si doped C60 fullerenes to the PPA drug, using density functional theory calculations. Two adsorption mechanisms were predicted for PPA on the pristine C60 including cycloaddition and adsorption via -NH2 group. It was found that the pristine C60 has a good sensitivity to this drug but suffers from a weak interaction (adsorption energy -0.1 kcal/mol) because of structural deformation and aromaticity break. The PPA is adsorbed on the Al or Si doped C60 from its -OH or -NH2 groups. The Al-doping significantly improves the reactivity of C60 but decreases its electronic sensitivity. Unlike the Al-doping, the Si-doping increases both the reactivity and electronic sensitivity to the PPA drug. At the presence of PPA drug, the conductivity of the Si-doped C60 considerably increases due to the HOMO-LUMO gap reduction by about 30.3%. Different analyses were used to obtain the results including nucleus independent chemical shift (NICS), density of states (DOS), molecular electrostatic potential (MEP), frontier molecular orbitals (FMO), etc.

Reporting and handling missing outcome data in mental health: a systematic review of Cochrane systematic reviews and meta-analyses.

PubMed

Spineli, Loukia M; Pandis, Nikolaos; Salanti, Georgia

2015-06-01

The purpose of the study was to provide empirical evidence about the reporting of methodology to address missing outcome data and the acknowledgement of their impact in Cochrane systematic reviews in the mental health field. Systematic reviews published in the Cochrane Database of Systematic Reviews after January 1, 2009 by three Cochrane Review Groups relating to mental health were included. One hundred ninety systematic reviews were considered. Missing outcome data were present in at least one included study in 175 systematic reviews. Of these 175 systematic reviews, 147 (84%) accounted for missing outcome data by considering a relevant primary or secondary outcome (e.g., dropout). Missing outcome data implications were reported only in 61 (35%) systematic reviews and primarily in the discussion section by commenting on the amount of the missing outcome data. One hundred forty eligible meta-analyses with missing data were scrutinized. Seventy-nine (56%) of them had studies with total dropout rate between 10 and 30%. One hundred nine (78%) meta-analyses reported to have performed intention-to-treat analysis by including trials with imputed outcome data. Sensitivity analysis for incomplete outcome data was implemented in less than 20% of the meta-analyses. Reporting of the techniques for handling missing outcome data and their implications in the findings of the systematic reviews are suboptimal. Copyright © 2014 John Wiley & Sons, Ltd.

Wide area restoration following biological contamination

NASA Astrophysics Data System (ADS)

Yang, Lynn; Hibbard, Wilthea; Edwards, Donna; Franco, David; Fruetel, Julie; Tucker, Mark; Einfeld, Wayne; Knowlton, Robert; Brown, Gary; Brockmann, John; Greenwalt, Robert; Miles, Robin; Raber, Ellen; Carlsen, Tina; Krauter, Paula; Dillon, Michael; MacQueen, Don; Intrepido, Tony; Hoppes, Bill; Wilson, Wendy; Mancieri, Sav

2008-04-01

Current understanding of how to restore a wide area that has been contaminated following a large biological attack is limited. The Department of Homeland Security and Department of Defense are executing a four-year collaborative program named the Interagency Biological Restoration Demonstration (IBRD) program. This program is aimed at developing technologies, methods, plans and policies necessary to restore a wide area, including military installations and critical infrastructures, in the event of a large outdoor aerosol release of anthrax. The IBRD program partner pilot city is the Seattle Urban Area to include Fort Lewis, WA and McChord Air Force Base. A front-end systems analysis was conducted as part of IBRD, to: 1) assess existing technologies and processes for wide area restoration; from this, 2) develop an "as-is" decision framework for wide area restoration; and 3) identify and prioritize capability gaps. Qualitative assessments and quantitative analyses, including sensitivity, timeline and case study analyses, were conducted to evaluate existing processes and rank capability gaps. This paper describes the approach and results from this front-end systems analysis.

The Negative Affect Hypothesis of Noise Sensitivity

PubMed Central

Shepherd, Daniel; Heinonen-Guzejev, Marja; Heikkilä, Kauko; Dirks, Kim N.; Hautus, Michael J.; Welch, David; McBride, David

2015-01-01

Some studies indicate that noise sensitivity is explained by negative affect, a dispositional tendency to negatively evaluate situations and the self. Individuals high in such traits may report a greater sensitivity to other sensory stimuli, such as smell, bright light and pain. However, research investigating the relationship between noise sensitivity and sensitivity to stimuli associated with other sensory modalities has not always supported the notion of a common underlying trait, such as negative affect, driving them. Additionally, other explanations of noise sensitivity based on cognitive processes have existed in the clinical literature for over 50 years. Here, we report on secondary analyses of pre-existing laboratory (n = 74) and epidemiological (n = 1005) data focusing on the relationship between noise sensitivity to and annoyance with a variety of olfactory-related stimuli. In the first study a correlational design examined the relationships between noise sensitivity, noise annoyance, and perceptual ratings of 16 odors. The second study sought differences between mean noise and air pollution annoyance scores across noise sensitivity categories. Results from both analyses failed to support the notion that, by itself, negative affectivity explains sensitivity to noise. PMID:25993104

Individual differences in personality as a function of degree of handedness: consistent-handers are less sensation seeking, more authoritarian, and more sensitive to disgust.

PubMed

Christman, Stephen

2014-01-01

Prior research indicates that consistent-handedness is associated with decreased access to right hemisphere processing and consequent decreased cognitive flexibility. Handedness differences on three dimensions of personality related to cognitive flexibility were investigated. Experiment 1 found that consistent-handedness was associated with decreased sensation seeking. Experiment 2 found that consistent-handedness was associated with increased Right Wing Authoritarianism. Experiment 3 found that consistent-handedness was associated with increased sensitivity to disgust. Prior research has shown associations between decreased sensation seeking, increased authoritarianism, and increased disgust sensitivity, and consistent-handedness appears to underlie all of these associations. Personality researchers are encouraged to include handedness as a factor in analyses, as failure to do so can lead to systematic mis-estimation of sex differences due to the over-representation of females among consistent-handers.

Measurement of cell respiration and oxygenation in standard multichannel biochips using phosphorescent O2-sensitive probes.

PubMed

Kondrashina, Alina V; Papkovsky, Dmitri B; Dmitriev, Ruslan I

2013-09-07

Measurement of cell oxygenation and oxygen consumption is useful for studies of cell bioenergetics, metabolism, mitochondrial function, drug toxicity and common pathophysiological conditions. Here we present a new platform for such applications which uses commercial multichannel biochips (μ-slides, Ibidi) and phosphorescent O2 sensitive probes. This platform was evaluated with both extracellular and intracellular O2 probes, several different cell types and treatments including mitochondrial uncoupling and inhibition, depletion of extracellular Ca(2+) and inhibition of V-ATPase and histone deacetylases. The results show that compared to the standard microwell plates currently used, the μ-slide platform provides facile O2 measurements with both suspension and adherent cells, higher sensitivity and reproducibility, and faster measurement time. It also allows re-perfusion and multiple treatments of cells and multi-parametric analyses in conjunction with other probes. Optical measurements are conducted on standard fluorescence readers and microscopes.

A comparison of bivariate, multivariate random-effects, and Poisson correlated gamma-frailty models to meta-analyze individual patient data of ordinal scale diagnostic tests.

PubMed

Simoneau, Gabrielle; Levis, Brooke; Cuijpers, Pim; Ioannidis, John P A; Patten, Scott B; Shrier, Ian; Bombardier, Charles H; de Lima Osório, Flavia; Fann, Jesse R; Gjerdingen, Dwenda; Lamers, Femke; Lotrakul, Manote; Löwe, Bernd; Shaaban, Juwita; Stafford, Lesley; van Weert, Henk C P M; Whooley, Mary A; Wittkampf, Karin A; Yeung, Albert S; Thombs, Brett D; Benedetti, Andrea

2017-11-01

Individual patient data (IPD) meta-analyses are increasingly common in the literature. In the context of estimating the diagnostic accuracy of ordinal or semi-continuous scale tests, sensitivity and specificity are often reported for a given threshold or a small set of thresholds, and a meta-analysis is conducted via a bivariate approach to account for their correlation. When IPD are available, sensitivity and specificity can be pooled for every possible threshold. Our objective was to compare the bivariate approach, which can be applied separately at every threshold, to two multivariate methods: the ordinal multivariate random-effects model and the Poisson correlated gamma-frailty model. Our comparison was empirical, using IPD from 13 studies that evaluated the diagnostic accuracy of the 9-item Patient Health Questionnaire depression screening tool, and included simulations. The empirical comparison showed that the implementation of the two multivariate methods is more laborious in terms of computational time and sensitivity to user-supplied values compared to the bivariate approach. Simulations showed that ignoring the within-study correlation of sensitivity and specificity across thresholds did not worsen inferences with the bivariate approach compared to the Poisson model. The ordinal approach was not suitable for simulations because the model was highly sensitive to user-supplied starting values. We tentatively recommend the bivariate approach rather than more complex multivariate methods for IPD diagnostic accuracy meta-analyses of ordinal scale tests, although the limited type of diagnostic data considered in the simulation study restricts the generalization of our findings. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Age-Related Differences in Susceptibility to Carcinogenesis. II. Approaches for Application and Uncertainty Analyses for Individual Genetically Acting Carcinogens

PubMed Central

Hattis, Dale; Goble, Robert; Chu, Margaret

2005-01-01

In an earlier report we developed a quantitative likelihood-based analysis of the differences in sensitivity of rodents to mutagenic carcinogens across three life stages (fetal, birth to weaning, and weaning to 60 days) relative to exposures in adult life. Here we draw implications for assessing human risks for full lifetime exposures, taking into account three types of uncertainties in making projections from the rodent data: uncertainty in the central estimates of the life-stage–specific sensitivity factors estimated earlier, uncertainty from chemical-to-chemical differences in life-stage–specific sensitivities for carcinogenesis, and uncertainty in the mapping of rodent life stages to human ages/exposure periods. Among the uncertainties analyzed, the mapping of rodent life stages to human ages/exposure periods is most important quantitatively (a range of several-fold in estimates of the duration of the human equivalent of the highest sensitivity “birth to weaning” period in rodents). The combined effects of these uncertainties are estimated with Monte Carlo analyses. Overall, the estimated population arithmetic mean risk from lifetime exposures at a constant milligrams per kilogram body weight level to a generic mutagenic carcinogen is about 2.8-fold larger than expected from adult-only exposure with 5–95% confidence limits of 1.5-to 6-fold. The mean estimates for the 0- to 2-year and 2- to 15-year periods are about 35–55% larger than the 10- and 3-fold sensitivity factor adjustments recently proposed by the U.S. Environmental Protection Agency. The present results are based on data for only nine chemicals, including five mutagens. Risk inferences will be altered as data become available for other chemicals. PMID:15811844

Variability in soybean yield in Brazil stemming from the interaction of heterogeneous management and climate variability

NASA Astrophysics Data System (ADS)

Cohn, A.; Bragança, A.; Jeffries, G. R.

2017-12-01

An increasing share of global agricultural production can be found in the humid tropics. Therefore, an improved understanding of the mechanisms governing variability in the output of tropical agricultural systems is of increasing importance for food security including through climate change adaptation. Yet, the long window over which many tropical crops can be sown, the diversity of crop varieties and management practices combine to challenge inference into climate risk to cropping output in analyses of tropical crop-climate sensitivity employing administrative data. In this paper, we leverage a newly developed spatially explicit dataset of soybean yields in Brazil to combat this problem. The dataset was built by training a model of remotely-sensed vegetation index data and land cover classification data using a rich in situ dataset of soybean yield and management variables collected over the period 2006 to 2016. The dataset contains soybean yields by plant date, cropping frequency, and maturity group for each 5km grid cell in Brazil. We model variation in these yields using an approach enabling the estimation of the influence of management factors on the sensitivity of soybean yields to variability in: cumulative solar radiation, extreme degree days, growing degree days, flooding rain in the harvest period, and dry spells in the rainy season. We find strong variation in climate sensitivity by management class. Planting date and maturity group each explained a great deal more variation in yield sensitivity than did cropping frequency. Brazil collects comparatively fine spatial resolution yield data. But, our attempt to replicate our results using administrative soy yield data revealed substantially lesser crop-climate sensitivity; suggesting that previous analyses employing administrative data may have underestimated climate risk to tropical soy production.

Streptococcus A in paediatric accident and emergency: are rapid streptococcal tests and clinical examination of any help?

PubMed

Van Limbergen, J; Kalima, P; Taheri, S; Beattie, T F

2006-01-01

Rapid streptococcal tests (RSTs) for streptococcal pharyngitis have made diagnosis at once simpler and more complicated. The American Academy of Pediatrics recommends that all RSTs be confirmed by a follow up throat culture unless local validation has proved the RST to be equally sensitive. To evaluate (a) RST as a single diagnostic tool, compared with RST with or without throat culture; (b) clinical diagnosis and the relative contribution of different symptoms. The study included 213 patients with clinical signs of pharyngitis. Throat swabs were analysed using Quickvue+ Strep A Test; negative RSTs were backed up by throat culture. Thirteen clinical features commonly associated with strep throat were analysed using backward stepwise logistic regression. Positive results (RST or throat culture) were obtained in 33 patients; RST correctly identified 21. Eleven samples were false negative on RST. At a strep throat prevalence of 15.9%, sensitivity of RST was 65.6% (95% CI 46.8% to 81.4%) and specificity 99.4% (96.7% to 99.9%). Sensitivity of clinical diagnosis alone was 57% (34% to 78%) and specificity 71% (61% to 80%). Clinically, only history of sore throat, rash, and pyrexia contributed to the diagnosis of strep throat (p<0.05). The high specificity of RST facilitates early diagnosis of strep throat. However, the low sensitivity of RST does not support its use as a single diagnostic tool. The sensitivity in the present study is markedly different from that reported by the manufacturer. Clinical examination is of limited value in the diagnosis of strep throat. It is important to audit the performance of new diagnostic tests, previously validated in different settings.

Streptococcus A in paediatric accident and emergency: are rapid streptococcal tests and clinical examination of any help?

PubMed Central

Van Limbergen, J; Kalima, P; Taheri, S; Beattie, T F

2006-01-01

Background Rapid streptococcal tests (RSTs) for streptococcal pharyngitis have made diagnosis at once simpler and more complicated. The American Academy of Pediatrics recommends that all RSTs be confirmed by a follow up throat culture unless local validation has proved the RST to be equally sensitive. Aims To evaluate (a) RST as a single diagnostic tool, compared with RST with or without throat culture; (b) clinical diagnosis and the relative contribution of different symptoms. Methods The study included 213 patients with clinical signs of pharyngitis. Throat swabs were analysed using Quickvue+ Strep A Test; negative RSTs were backed up by throat culture. Thirteen clinical features commonly associated with strep throat were analysed using backward stepwise logistic regression. Results Positive results (RST or throat culture) were obtained in 33 patients; RST correctly identified 21. Eleven samples were false negative on RST. At a strep throat prevalence of 15.9%, sensitivity of RST was 65.6% (95% CI 46.8% to 81.4%) and specificity 99.4% (96.7% to 99.9%). Sensitivity of clinical diagnosis alone was 57% (34% to 78%) and specificity 71% (61% to 80%). Clinically, only history of sore throat, rash, and pyrexia contributed to the diagnosis of strep throat (p<0.05). Conclusion The high specificity of RST facilitates early diagnosis of strep throat. However, the low sensitivity of RST does not support its use as a single diagnostic tool. The sensitivity in the present study is markedly different from that reported by the manufacturer. Clinical examination is of limited value in the diagnosis of strep throat. It is important to audit the performance of new diagnostic tests, previously validated in different settings. PMID:16373800

The Identification and Cloning of the Wnt-1 Receptor

DTIC Science & Technology

1996-10-01

examination of embryos with duplicated axes revealed that Xwnt-5A and hFz5 induced a full array of dorsal tissues, including notochord , neural tube...tube, a notochord and somites in both axes. c). Xwnt-5A plus hfz5 induce ectopic goosecoid (gsc) expression in stage 11 embryos, as visualized by whole...Lai CJ, Olson DJ, Kelly GM: Dissecting Wnt signalling pathways and Wnt-sensitive developmental processes through transient misexpression analyses in

Probing Dynamics in Granular Media of Contrasting Geometries via X-Ray Phase Contrast Imaging and PDV

NASA Astrophysics Data System (ADS)

Crum, Ryan; Pagan, Darren; Lind, Jon; Homel, Michael; Hurley, Ryan; Herbold, Eric; Akin, Minta

Granular systems are ubiquitous in our everyday world and play a central role in many dynamic scientific problems including mine blasting, projectile penetration, astrophysical collisions, explosions, and dynamic compaction. An understanding of granular media's behavior under various loading conditions is an ongoing scientific grand challenge. This is partly due to the intricate interplay between material properties, loading conditions, grain geometry, and grain connectivity. Previous dynamic studies in granular media predominantly utilize the macro-scale analyses VISAR or PDV, diagnostics that are not sensitive to the many degrees of freedom and their interactions, focusing instead on their aggregate effect. Results of a macro-scale analysis leave the principal interactions of these degrees of freedom too entangled to elucidate. To isolate the significance of grain geometry, this study probes various geometries of granular media subjected to gas gun generated waves via in-situ X-ray analysis. Analyses include evaluating displacement fields, grain fracture, inter- and intra-granular densification, and wave front motion. Phase Contrast Imaging (PCI) and PDV analyses feed directly into our concurrent meso-scale granular media modeling efforts to enhance our predictive capabilities.

Cost Effectiveness of Alectinib vs. Crizotinib in First-Line Anaplastic Lymphoma Kinase-Positive Advanced Non-Small-Cell Lung Cancer.

PubMed

Carlson, Josh J; Suh, Kangho; Orfanos, Panos; Wong, William

2018-04-01

The recently completed ALEX trial demonstrated that alectinib improved progression-free survival, and delayed time to central nervous system progression compared with crizotinib in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer. However, the long-term clinical and economic impact of using alectinib vs. crizotinib has not been evaluated. The objective of this study was to determine the potential cost utility of alectinib vs. crizotinib from a US payer perspective. A cost-utility model was developed using partition survival methods and three health states: progression-free, post-progression, and death. ALEX trial data informed the progression-free and overall survival estimates. Costs included drug treatments and supportive care (central nervous system and non-central nervous system). Utility values were obtained from trial data and literature. Sensitivity analyses included one-way and probabilistic sensitivity analyses. Treatment with alectinib vs. crizotinib resulted in a gain of 0.91 life-years, 0.87 quality-adjusted life-years, and incremental costs of US$34,151, resulting in an incremental cost-effectiveness ratio of US$39,312/quality-adjusted life-year. Drug costs and utilities in the progression-free health state were the main drivers of the model in the one-way sensitivity analysis. From the probabilistic sensitivity analysis, alectinib had a 64% probability of being cost effective at a willingness-to-pay threshold of US$100,000/quality adjusted life-year. Alectinib increased time in the progression-free state and quality-adjusted life-years vs. crizotinib. The marginal cost increase was reflective of longer treatment durations in the progression-free state. Central nervous system-related costs were considerably lower with alectinib. Our results suggest that compared with crizotinib, alectinib may be a cost-effective therapy for treatment-naïve patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer.

Identification of the need for home visiting nurse: development of a new assessment tool

PubMed Central

Taguchi, Atsuko; Nagata, Satoko; Naruse, Takashi; Kuwahara, Yuki; Yamaguchi, Takuhiro; Murashima, Sachiyo

2014-01-01

Objective To develop a Home Visiting Nursing Service Need Assessment Form (HVNS-NAF) to standardize the decision about the need for home visiting nursing service. Methods The sample consisted of older adults who had received coordinated services by care managers. We defined the need for home visiting nursing service by elderly individuals as the decision of the need by a care manager so that the elderly can continue to live independently. Explanatory variables included demographic factors, medical procedure, severity of illness, and caregiver variables. Multiple logistic regression was carried out after univariate analyses to decide the variables to include and the weight of each variable in the HVNS-NAF. We then calculated the sensitivity and specificity of each cutoff value, and defined the score with the highest sensitivity and specificity as the cutoff value. Results Nineteen items were included in the final HVNS-NAF. When the cutoff value was 2 points, the sensitivity was 77.0%, specificity 68.5%, and positive predictive value 56.8%. Conclusions HVNS-NAF is the first validated standard based on characteristics of elderly clients who required home visiting nursing service. Using the HVNS-NAF may result in reducing the unmet need for home visiting nursing service and preventing hospitalization. PMID:24665229

MRMer, an interactive open source and cross-platform system for data extraction and visualization of multiple reaction monitoring experiments.

PubMed

Martin, Daniel B; Holzman, Ted; May, Damon; Peterson, Amelia; Eastham, Ashley; Eng, Jimmy; McIntosh, Martin

2008-11-01

Multiple reaction monitoring (MRM) mass spectrometry identifies and quantifies specific peptides in a complex mixture with very high sensitivity and speed and thus has promise for the high throughput screening of clinical samples for candidate biomarkers. We have developed an interactive software platform, called MRMer, for managing highly complex MRM-MS experiments, including quantitative analyses using heavy/light isotopic peptide pairs. MRMer parses and extracts information from MS files encoded in the platform-independent mzXML data format. It extracts and infers precursor-product ion transition pairings, computes integrated ion intensities, and permits rapid visual curation for analyses exceeding 1000 precursor-product pairs. Results can be easily output for quantitative comparison of consecutive runs. Additionally MRMer incorporates features that permit the quantitative analysis experiments including heavy and light isotopic peptide pairs. MRMer is open source and provided under the Apache 2.0 license.

Aerocapture Systems Analysis for a Neptune Mission

NASA Technical Reports Server (NTRS)

Lockwood, Mary Kae; Edquist, Karl T.; Starr, Brett R.; Hollis, Brian R.; Hrinda, Glenn A.; Bailey, Robert W.; Hall, Jeffery L.; Spilker, Thomas R.; Noca, Muriel A.; O'Kongo, N.

2006-01-01

A Systems Analysis was completed to determine the feasibility, benefit and risk of an aeroshell aerocapture system for Neptune and to identify technology gaps and technology performance goals. The systems analysis includes the following disciplines: science; mission design; aeroshell configuration; interplanetary navigation analyses; atmosphere modeling; computational fluid dynamics for aerodynamic performance and aeroheating environment; stability analyses; guidance development; atmospheric flight simulation; thermal protection system design; mass properties; structures; spacecraft design and packaging; and mass sensitivities. Results show that aerocapture is feasible and performance is adequate for the Neptune mission. Aerocapture can deliver 1.4 times more mass to Neptune orbit than an all-propulsive system for the same launch vehicle and results in a 3-4 year reduction in trip time compared to all-propulsive systems. Enabling technologies for this mission include TPS manufacturing; and aerothermodynamic methods for determining coupled 3-D convection, radiation and ablation aeroheating rates and loads.

Detection of Independent Associations of Plasma Lipidomic Parameters with Insulin Sensitivity Indices Using Data Mining Methodology.

PubMed

Kopprasch, Steffi; Dheban, Srirangan; Schuhmann, Kai; Xu, Aimin; Schulte, Klaus-Martin; Simeonovic, Charmaine J; Schwarz, Peter E H; Bornstein, Stefan R; Shevchenko, Andrej; Graessler, Juergen

2016-01-01

Glucolipotoxicity is a major pathophysiological mechanism in the development of insulin resistance and type 2 diabetes mellitus (T2D). We aimed to detect subtle changes in the circulating lipid profile by shotgun lipidomics analyses and to associate them with four different insulin sensitivity indices. The cross-sectional study comprised 90 men with a broad range of insulin sensitivity including normal glucose tolerance (NGT, n = 33), impaired glucose tolerance (IGT, n = 32) and newly detected T2D (n = 25). Prior to oral glucose challenge plasma was obtained and quantitatively analyzed for 198 lipid molecular species from 13 different lipid classes including triacylglycerls (TAGs), phosphatidylcholine plasmalogen/ether (PC O-s), sphingomyelins (SMs), and lysophosphatidylcholines (LPCs). To identify a lipidomic signature of individual insulin sensitivity we applied three data mining approaches, namely least absolute shrinkage and selection operator (LASSO), Support Vector Regression (SVR) and Random Forests (RF) for the following insulin sensitivity indices: homeostasis model of insulin resistance (HOMA-IR), glucose insulin sensitivity index (GSI), insulin sensitivity index (ISI), and disposition index (DI). The LASSO procedure offers a high prediction accuracy and and an easier interpretability than SVR and RF. After LASSO selection, the plasma lipidome explained 3% (DI) to maximal 53% (HOMA-IR) variability of the sensitivity indexes. Among the lipid species with the highest positive LASSO regression coefficient were TAG 54:2 (HOMA-IR), PC O- 32:0 (GSI), and SM 40:3:1 (ISI). The highest negative regression coefficient was obtained for LPC 22:5 (HOMA-IR), TAG 51:1 (GSI), and TAG 58:6 (ISI). Although a substantial part of lipid molecular species showed a significant correlation with insulin sensitivity indices we were able to identify a limited number of lipid metabolites of particular importance based on the LASSO approach. These few selected lipids with the closest connection to sensitivity indices may help to further improve disease risk prediction and disease and therapy monitoring.

Cost-effectiveness analysis in the Spanish setting of the PEAK trial of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer.

PubMed

Rivera, Fernando; Valladares, Manuel; Gea, Salvador; López-Martínez, Noemí

2017-06-01

To assess the cost-effectiveness of panitumumab in combination with mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) vs bevacizumab in combination with mFOLFOX6 as first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC) in Spain. A semi-Markov model was developed including the following health states: Progression free; Progressive disease: Treat with best supportive care; Progressive disease: Treat with subsequent active therapy; Attempted resection of metastases; Disease free after metastases resection; Progressive disease: after resection and relapse; and Death. Parametric survival analyses of patient-level progression free survival and overall survival data from the PEAK Phase II clinical trial were used to estimate health state transitions. Additional data from the PEAK trial were considered for the dose and duration of therapy, the use of subsequent therapy, the occurrence of adverse events, and the incidence and probability of time to metastasis resection. Utility weightings were calculated from patient-level data from panitumumab trials evaluating first-, second-, and third-line treatments. The study was performed from the Spanish National Health System (NHS) perspective including only direct costs. A life-time horizon was applied. Probabilistic sensitivity analyses and scenario sensitivity analyses were performed to assess the robustness of the model. Based on the PEAK trial, which demonstrated greater efficacy of panitumumab vs bevacizumab, both in combination with mFOLFOX6 first-line in wild-type RAS mCRC patients, the estimated incremental cost per life-year gained was €16,567 and the estimated incremental cost per quality-adjusted life year gained was €22,794. The sensitivity analyses showed the model was robust to alternative parameters and assumptions. The analysis was based on a simulation model and, therefore, the results should be interpreted cautiously. Based on the PEAK Phase II clinical trial and taking into account Spanish costs, the results of the analysis showed that first-line treatment of mCRC with panitumumab + mFOLFOX6 could be considered a cost-effective option compared with bevacizumab + mFOLFOX6 for the Spanish NHS.

Evaluation of risk factors for perforated peptic ulcer.

PubMed

Yamamoto, Kazuki; Takahashi, Osamu; Arioka, Hiroko; Kobayashi, Daiki

2018-02-15

The aim of this study was to evaluate the prediction factors for perforated peptic ulcer (PPU). At St. Luke's International Hospital in Tokyo, Japan, a case control study was performed between August 2004 and March 2016. All patients diagnosed with PPU were included. As control subjects, patients with age, sex and date of CT scan corresponding to those of the PPU subjects were included in the study at a proportion of 2 controls for every PPU subject. All data such as past medical histories, physical findings, and laboratory data were collected through chart reviews. Univariate analyses and multivariate analyses with logistic regression were conducted, and receiver operating characteristic curves (ROCs) were calculated to show validity. Sensitivity analyses were performed to confirm results using a stepwise method and conditional logistic regression. A total of 408 patients were included in this study; 136 were a group of patients with PPU, and 272 were a control group. Univariate analysis showed statistical significance in many categories. Four different models of multivariate analyses were conducted, and significant differences were found for muscular defense and a history of peptic ulcer disease (PUD) in all models. The conditional forced-entry analysis of muscular defense showed an odds ratio (OR) of 23.8 (95% confidence interval [CI]: 5.70-100.0), and the analysis of PUD history showed an OR of 6.40 (95% CI: 1.13-36.2). The sensitivity analysis showed consistent results, with an OR of 23.8-366.2 for muscular defense and an OR of 3.67-7.81 for PUD history. The area under the curve (AUC) of all models was high enough to confirm the results. However, anticoagulants, known risk factors for PUD, did not increase the risk for PPU in our study. The conditional forced-entry analysis of anticoagulant use showed an OR of 0.85 (95% CI: 0.03-22.3). The evaluation of prediction factors and development of a prediction rule for PPU may help our decision making in performing a CT scan for patients with acute abdominal pain.

The march from early life food sensitization to allergic disease: a systematic review and meta-analyses of birth cohort studies.

PubMed

Alduraywish, S A; Lodge, C J; Campbell, B; Allen, K J; Erbas, B; Lowe, A J; Dharmage, S C

2016-01-01

There is growing evidence for an increase in food allergies. The question of whether early life food sensitization, a primary step in food allergies, leads to other allergic disease is a controversial but important issue. Birth cohorts are an ideal design to answer this question. We aimed to systematically investigate and meta-analyse the evidence for associations between early food sensitization and allergic disease in birth cohorts. MEDLINE and SCOPUS databases were searched for birth cohorts that have investigated the association between food sensitization in the first 2 years and subsequent wheeze/asthma, eczema and/or allergic rhinitis. We performed meta-analyses using random-effects models to obtain pooled estimates, stratified by age group. The search yielded fifteen original articles representing thirteen cohorts. Early life food sensitization was associated with an increased risk of infantile eczema, childhood wheeze/asthma, eczema and allergic rhinitis and young adult asthma. Meta-analyses demonstrated that early life food sensitization is related to an increased risk of wheeze/asthma (pooled OR 2.9; 95% CI 2.0-4.0), eczema (pooled OR 2.7; 95% CI 1.7-4.4) and allergic rhinitis (pooled OR 3.1; 95% CI 1.9-4.9) from 4 to 8 years. Food sensitization in the first 2 years of life can identify children at high risk of subsequent allergic disease who may benefit from early life preventive strategies. However, due to potential residual confounding in the majority of studies combined with lack of follow-up into adolescence and adulthood, further research is needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anti-Podocalyxin Monoclonal Antibody 47-mG2a Detects Lung Cancers by Immunohistochemistry.

PubMed

Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

2018-04-01

Lung cancer is one of the leading causes of cancer-related deaths in the world. Regardless of the advances in lung cancer treatments, the prognosis is still poor. Podocalyxin (PODXL) is a highly glycosylated type I transmembrane protein that is expressed in normal tissues, including the heart, pancreas, and breast. It is also found and used as a diagnostic marker in many cancers, such as renal, brain, breast, oral, and lung cancers. We previously developed specific and sensitive anti-PODXL monoclonal antibodies, PcMab-47 (mouse IgG 1 , kappa) and its mouse IgG 2a -type (47-mG 2a ), both of which were suitable for immunohistochemical analyses of oral cancers. In this study, we investigated the utility of PcMab-47 and 47-mG 2a for the immunohistochemical analyses of lung cancers. PcMab-47 stained 51/70 (72.9%) cases of lung cancer, whereas 47-mG 2a stained 59/70 (84.3%) cases, indicating that the latter antibody is more sensitive and is useful for detecting PODXL in lung cancers.

[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.

Oncology biomarkers: discovery, validation, and clinical use.

PubMed

Heckman-Stoddard, Brandy M

2012-05-01

To discuss the discovery, validation, and clinical use of multiple types of biomarkers. Medical literature and published guidelines. Formal validation of biomarkers should include both retrospective analyses of well-characterized samples as well as a prospective clinical trial in which the biomarker is tested for its ability to predict the presence of disease or the efficacy of a cancer therapy. Biomarker development is complicated, with very few biomarker discoveries leading to clinically useful tests. Nurses should understand how a biomarker was developed, including the sensitivity and specificity before applying new biomarkers in the clinical setting. Copyright © 2012. Published by Elsevier Inc.

SPS market analysis. [small solar thermal power systems

NASA Technical Reports Server (NTRS)

Goff, H. C.

1980-01-01

A market analysis task included personal interviews by GE personnel and supplemental mail surveys to acquire statistical data and to identify and measure attitudes, reactions and intentions of prospective small solar thermal power systems (SPS) users. Over 500 firms were contacted, including three ownership classes of electric utilities, industrial firms in the top SIC codes for energy consumption, and design engineering firms. A market demand model was developed which utilizes the data base developed by personal interviews and surveys, and projected energy price and consumption data to perform sensitivity analyses and estimate potential markets for SPS.

Enhanced Photoacoustic Gas Analyser Response Time and Impact on Accuracy at Fast Ventilation Rates during Multiple Breath Washout

PubMed Central

Horsley, Alex; Macleod, Kenneth; Gupta, Ruchi; Goddard, Nick; Bell, Nicholas

2014-01-01

Background The Innocor device contains a highly sensitive photoacoustic gas analyser that has been used to perform multiple breath washout (MBW) measurements using very low concentrations of the tracer gas SF6. Use in smaller subjects has been restricted by the requirement for a gas analyser response time of <100 ms, in order to ensure accurate estimation of lung volumes at rapid ventilation rates. Methods A series of previously reported and novel enhancements were made to the gas analyser to produce a clinically practical system with a reduced response time. An enhanced lung model system, capable of delivering highly accurate ventilation rates and volumes, was used to assess in vitro accuracy of functional residual capacity (FRC) volume calculation and the effects of flow and gas signal alignment on this. Results 10–90% rise time was reduced from 154 to 88 ms. In an adult/child lung model, accuracy of volume calculation was −0.9 to 2.9% for all measurements, including those with ventilation rate of 30/min and FRC of 0.5 L; for the un-enhanced system, accuracy deteriorated at higher ventilation rates and smaller FRC. In a separate smaller lung model (ventilation rate 60/min, FRC 250 ml, tidal volume 100 ml), mean accuracy of FRC measurement for the enhanced system was minus 0.95% (range −3.8 to 2.0%). Error sensitivity to flow and gas signal alignment was increased by ventilation rate, smaller FRC and slower analyser response time. Conclusion The Innocor analyser can be enhanced to reliably generate highly accurate FRC measurements down at volumes as low as those simulating infant lung settings. Signal alignment is a critical factor. With these enhancements, the Innocor analyser exceeds key technical component recommendations for MBW apparatus. PMID:24892522

Clinical symptoms, signs and tests for identification of impending and current water-loss dehydration in older people.

PubMed

Hooper, Lee; Abdelhamid, Asmaa; Attreed, Natalie J; Campbell, Wayne W; Channell, Adam M; Chassagne, Philippe; Culp, Kennith R; Fletcher, Stephen J; Fortes, Matthew B; Fuller, Nigel; Gaspar, Phyllis M; Gilbert, Daniel J; Heathcote, Adam C; Kafri, Mohannad W; Kajii, Fumiko; Lindner, Gregor; Mack, Gary W; Mentes, Janet C; Merlani, Paolo; Needham, Rowan A; Olde Rikkert, Marcel G M; Perren, Andreas; Powers, James; Ranson, Sheila C; Ritz, Patrick; Rowat, Anne M; Sjöstrand, Fredrik; Smith, Alexandra C; Stookey, Jodi J D; Stotts, Nancy A; Thomas, David R; Vivanti, Angela; Wakefield, Bonnie J; Waldréus, Nana; Walsh, Neil P; Ward, Sean; Potter, John F; Hunter, Paul

2015-04-30

There is evidence that water-loss dehydration is common in older people and associated with many causes of morbidity and mortality. However, it is unclear what clinical symptoms, signs and tests may be used to identify early dehydration in older people, so that support can be mobilised to improve hydration before health and well-being are compromised. To determine the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs and tests to be used as screening tests for detecting water-loss dehydration in older people by systematically reviewing studies that have measured a reference standard and at least one index test in people aged 65 years and over. Water-loss dehydration was defined primarily as including everyone with either impending or current water-loss dehydration (including all those with serum osmolality ≥ 295 mOsm/kg as being dehydrated). Structured search strategies were developed for MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL, LILACS, DARE and HTA databases (The Cochrane Library), and the International Clinical Trials Registry Platform (ICTRP). Reference lists of included studies and identified relevant reviews were checked. Authors of included studies were contacted for details of further studies. Titles and abstracts were scanned and all potentially relevant studies obtained in full text. Inclusion of full text studies was assessed independently in duplicate, and disagreements resolved by a third author. We wrote to authors of all studies that appeared to have collected data on at least one reference standard and at least one index test, and in at least 10 people aged ≥ 65 years, even where no comparative analysis has been published, requesting original dataset so we could create 2 x 2 tables. Diagnostic accuracy of each test was assessed against the best available reference standard for water-loss dehydration (serum or plasma osmolality cut-off ≥ 295 mOsm/kg, serum osmolarity or weight change) within each study. For each index test study data were presented in forest plots of sensitivity and specificity. The primary target condition was water-loss dehydration (including either impending or current water-loss dehydration). Secondary target conditions were intended as current (> 300 mOsm/kg) and impending (295 to 300 mOsm/kg) water-loss dehydration, but restricted to current dehydration in the final review.We conducted bivariate random-effects meta-analyses (Stata/IC, StataCorp) for index tests where there were at least four studies and study datasets could be pooled to construct sensitivity and specificity summary estimates. We assigned the same approach for index tests with continuous outcome data for each of three pre-specified cut-off points investigated.Pre-set minimum sensitivity of a useful test was 60%, minimum specificity 75%. As pre-specifying three cut-offs for each continuous test may have led to missing a cut-off with useful sensitivity and specificity, we conducted post-hoc exploratory analyses to create receiver operating characteristic (ROC) curves where there appeared some possibility of a useful cut-off missed by the original three. These analyses enabled assessment of which tests may be worth assessing in further research. A further exploratory analysis assessed the value of combining the best two index tests where each had some individual predictive ability. There were few published studies of the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs or tests to be used as screening tests for detecting water-loss dehydration in older people. Therefore, to complete this review we sought, analysed and included raw datasets that included a reference standard and an index test in people aged ≥ 65 years.We included three studies with published diagnostic accuracy data and a further 21 studies provided datasets that we analysed. We assessed 67 tests (at three cut-offs for each continuous outcome) for diagnostic accuracy of water-loss dehydration (primary target condition) and of current dehydration (secondary target condition).Only three tests showed any ability to diagnose water-loss dehydration (including both impending and current water-loss dehydration) as stand-alone tests: expressing fatigue (sensitivity 0.71 (95% CI 0.29 to 0.96), specificity 0.75 (95% CI 0.63 to 0.85), in one study with 71 participants, but two additional studies had lower sensitivity); missing drinks between meals (sensitivity 1.00 (95% CI 0.59 to 1.00), specificity 0.77 (95% CI 0.64 to 0.86), in one study with 71 participants) and BIA resistance at 50 kHz (sensitivities 1.00 (95% CI 0.48 to 1.00) and 0.71 (95% CI 0.44 to 0.90) and specificities of 1.00 (95% CI 0.69 to 1.00) and 0.80 (95% CI 0.28 to 0.99) in 15 and 22 people respectively for two studies, but with sensitivities of 0.54 (95% CI 0.25 to 0.81) and 0.69 (95% CI 0.56 to 0.79) and specificities of 0.50 (95% CI 0.16 to 0.84) and 0.19 (95% CI 0.17 to 0.21) in 21 and 1947 people respectively in two other studies). In post-hoc ROC plots drinks intake, urine osmolality and axillial moisture also showed limited diagnostic accuracy. No test was consistently useful in more than one study.Combining two tests so that an individual both missed some drinks between meals and expressed fatigue was sensitive at 0.71 (95% CI 0.29 to 0.96) and specific at 0.92 (95% CI 0.83 to 0.97).There was sufficient evidence to suggest that several stand-alone tests often used to assess dehydration in older people (including fluid intake, urine specific gravity, urine colour, urine volume, heart rate, dry mouth, feeling thirsty and BIA assessment of intracellular water or extracellular water) are not useful, and should not be relied on individually as ways of assessing presence or absence of dehydration in older people.No tests were found consistently useful in diagnosing current water-loss dehydration. There is limited evidence of the diagnostic utility of any individual clinical symptom, sign or test or combination of tests to indicate water-loss dehydration in older people. Individual tests should not be used in this population to indicate dehydration; they miss a high proportion of people with dehydration, and wrongly label those who are adequately hydrated.Promising tests identified by this review need to be further assessed, as do new methods in development. Combining several tests may improve diagnostic accuracy.

Results of an integrated structure-control law design sensitivity analysis

NASA Technical Reports Server (NTRS)

Gilbert, Michael G.

1988-01-01

Next generation air and space vehicle designs are driven by increased performance requirements, demanding a high level of design integration between traditionally separate design disciplines. Interdisciplinary analysis capabilities have been developed, for aeroservoelastic aircraft and large flexible spacecraft control for instance, but the requisite integrated design methods are only beginning to be developed. One integrated design method which has received attention is based on hierarchal problem decompositions, optimization, and design sensitivity analyses. This paper highlights a design sensitivity analysis method for Linear Quadratic Cost, Gaussian (LQG) optimal control laws, which predicts change in the optimal control law due to changes in fixed problem parameters using analytical sensitivity equations. Numerical results of a design sensitivity analysis for a realistic aeroservoelastic aircraft example are presented. In this example, the sensitivity of the optimally controlled aircraft's response to various problem formulation and physical aircraft parameters is determined. These results are used to predict the aircraft's new optimally controlled response if the parameter was to have some other nominal value during the control law design process. The sensitivity results are validated by recomputing the optimal control law for discrete variations in parameters, computing the new actual aircraft response, and comparing with the predicted response. These results show an improvement in sensitivity accuracy for integrated design purposes over methods which do not include changess in the optimal control law. Use of the analytical LQG sensitivity expressions is also shown to be more efficient that finite difference methods for the computation of the equivalent sensitivity information.

Validation of a patient-centered culturally sensitive health care office staff inventory.

PubMed

Tucker, Carolyn M; Wall, Whitney; Marsiske, Michael; Nghiem, Khanh; Roncoroni, Julia

2015-09-01

Research suggests that patient-perceived culturally sensitive health care encompasses multiple components of the health care delivery system including the cultural sensitivity of front desk office staff. Despite this, research on culturally sensitive health care focuses almost exclusively on provider behaviors, attitudes, and knowledge. This is due in part to the paucity of instruments available to assess the cultural sensitivity of front desk office staff. Thus, the objective of the present study is to determine the psychometric properties of the pilot Tucker-Culturally Sensitive Health Care Office Staff Inventory-Patient Form (T-CSHCOSI-PF), which is an instrument designed to enable patients to evaluate the patient-defined cultural sensitivity of their front desk office staff. A sample of 1648 adult patients was recruited by staff at 67 health care sites across the United States. These patients anonymously completed the T-CSHCOSI-PF, a demographic data questionnaire, and a patient satisfaction questionnaire. Findings Confirmatory factor analyses of the TCSHCOSI-PF revealed that this inventory has two factors with high internal consistency reliability and validity (Cronbach's αs=0.97 and 0.95). It is concluded that the T-CSHCOSI-PF is a psychometrically strong and useful inventory for assessing the cultural sensitivity of front desk office staff. This inventory can be used to support culturally sensitive health care research, evaluate the job performance of front desk office staff, and aid in the development of trainings designed to improve the cultural sensitivity of these office staff.

Comparison of Heidelberg Retina Tomograph-3 glaucoma probability score and Moorfields regression analysis of optic nerve head in glaucoma patients and healthy individuals.

PubMed

Caglar, Çagatay; Gul, Adem; Batur, Muhammed; Yasar, Tekin

2017-01-01

To compare the sensitivity and specificity of Moorfields regression analysis (MRA) and glaucoma probability score (GPS) between healthy and glaucomatous eyes with Heidelberg Retinal Tomograph 3 (HRT-3). The study included 120 eyes of 75 glaucoma patients and 138 eyes of 73 normal subjects, for a total of 258 eyes of 148 individuals. All measurements were performed with the HRT-3. Diagnostic test criteria (sensitivity, specificity, etc.) were used to evaluate how efficiently GPS and MRA algorithms in the HRT-3 discriminated between the glaucoma and control groups. The GPS showed 88 % sensitivity and 66 % specificity, whereas MRA had 71.5 % sensitivity and 82.5 % specificity. There was 71 % agreement between the final results of MRA and GPS in the glaucoma group. Excluding borderline patients from both analyses resulted in 91.6 % agreement. In the control group the level of agreement between MRA and GPS was 64 % including borderline patients and 84.1 % after excluding borderline patients. The accuracy rate is 92 % for MRA and 91 % for GPS in the glaucoma group excluding borderline patients. The difference was nor statistically different. In both cases, agreement was higher between MRA and GPS in the glaucoma group. We found that both sensitivity and specificity increased with disc size for MRA, while the sensitivity increased and specificity decreased with larger disc sizes for GPS. HRT is able to quantify and clearly reveal structural changes in the ONH and RNFL in glaucoma.

Nicotine-induced locomotor sensitization: pharmacological analyses with candidate smoking cessation aids.

PubMed

Goutier, Wouter; Kloeze, Margreet; McCreary, Andrew C

2016-03-01

There are a number of approved therapeutics for the management of alcohol dependence, which might also convey the potential as smoking cessation aids. The present study investigated the effect of a few of these therapeutics and potential candidates (non-peptide vasopressin V1b antagonists) on the expression of nicotine-induced behavioral sensitization in Wistar rats. The following compounds were included in this evaluation: rimonabant, bupropion, topiramate, acamprosate, naltrexone, mecamylamine, nelivaptan (SSR-149415, V1b antagonist) and two novel V1b antagonists. Following the development of nicotine-induced locomotor sensitization and a withdrawal period, the expression of sensitization was assessed in the presence of one of the examined agents given 30 minutes prior to the nicotine challenge injection. Acamprosate, naltrexone, rimonabant, mecamylamine, nelivaptan and V1b antagonist 'compound 2' significantly antagonized the expression of nicotine-induced sensitization. Whereas topiramate showed a trend for effects, the V1b antagonist 'compound 1' did not show any significant effects. Bupropion failed to block sensitization but increased activity alone and was therefore tested in development and cross-sensitization studies. Taken together, these findings provide pre-clinical evidence that these molecules attenuated the expression of nicotine-induced sensitization and should be further investigated as putative treatments for nicotine addiction. Moreover, V1b antagonists should be further investigated as a potential novel smoking cessation aid. © 2014 Society for the Study of Addiction.

A cure for the blues: opsin duplication and subfunctionalization for short-wavelength sensitivity in jewel beetles (Coleoptera: Buprestidae).

PubMed

Lord, Nathan P; Plimpton, Rebecca L; Sharkey, Camilla R; Suvorov, Anton; Lelito, Jonathan P; Willardson, Barry M; Bybee, Seth M

2016-05-18

Arthropods have received much attention as a model for studying opsin evolution in invertebrates. Yet, relatively few studies have investigated the diversity of opsin proteins that underlie spectral sensitivity of the visual pigments within the diverse beetles (Insecta: Coleoptera). Previous work has demonstrated that beetles appear to lack the short-wavelength-sensitive (SWS) opsin class that typically confers sensitivity to the "blue" region of the light spectrum. However, this is contrary to established physiological data in a number of Coleoptera. To explore potential adaptations at the molecular level that may compensate for the loss of the SWS opsin, we carried out an exploration of the opsin proteins within a group of beetles (Buprestidae) where short-wave sensitivity has been demonstrated. RNA-seq data were generated to identify opsin proteins from nine taxa comprising six buprestid species (including three male/female pairs) across four subfamilies. Structural analyses of recovered opsins were conducted and compared to opsin sequences in other insects across the main opsin classes-ultraviolet, short-wavelength, and long-wavelength. All nine buprestids were found to express two opsin copies in each of the ultraviolet and long-wavelength classes, contrary to the single copies recovered in all other molecular studies of adult beetle opsin expression. No SWS opsin class was recovered. Furthermore, the male Agrilus planipennis (emerald ash borer-EAB) expressed a third LWS opsin at low levels that is presumed to be a larval copy. Subsequent homology and structural analyses identified multiple amino acid substitutions in the UVS and LWS copies that could confer short-wavelength sensitivity. This work is the first to compare expressed opsin genes against known electrophysiological data that demonstrate multiple peak sensitivities in Coleoptera. We report the first instance of opsin duplication in adult beetles, which occurs in both the UVS and LWS opsin classes. Through structural comparisons of known insect opsins, we suggest that opsin duplication and amino acid variation within the chromophore binding pocket explains sensitivity in the short-wavelength portion of the visible light spectrum in these species. These findings are the first to reveal molecular complexity of the color vision system within beetles.

Wound infection secondary to snakebite.

PubMed

Wagener, M; Naidoo, M; Aldous, C

2017-03-29

Snakebites can produce severe local and systemic septic complications as well as being associated with significant overall morbidity and even mortality. A prospective audit was undertaken to determine the bacterial causation of wound infection secondary to snakebite, and attempt to quantify the burden of disease. The audit was undertaken at Ngwelezane Hospital, which provides both regional and tertiary services for north-eastern KwaZulu-Natal Province, South Africa, over a 4-month period. Records of patients who required surgical debridement for extensive skin and soft-tissue necrosis were analysed. At the time of debridement, tissue samples of necrotic or infected tissue were sent for bacteriological analysis as standard of care. Microbiology results were analysed. A total of 164 patients were admitted to hospital for management of snakebite, of whom 57 required surgical debridement and 42 were included in the final microbiological analysis. Children were found to be the most frequent victims of snakebite; 57.8% of patients in this study were aged ≤10 years and 73.7% ≤15 years. Culture showed a single organism in 32/42 cases, two organisms in 8 and no growth in 2. Eight different types of organisms were cultured, five of them more than once. Thirty-five specimens (83.3%) grew Gram-negative Enterobacteriaceae, the most frequent being Morganella morganii and Proteus species. Thirteen specimens (31.0%) grew Enterococcus faecalis. Gram-negative Enterobacteriaceae showed 31.4% sensitivity to ampicillin, 40.0% sensitivity to amoxicillin plus clavulanic acid, 34.3% sensitivity to cefuroxime, 97.1% sensitivity to ceftriaxone, and 100% sensitivity to ciprofloxacin, gentamicin and amikacin. E. faecalis was 92.3% sensitive to amoxicillin, 92.3% sensitive to amoxicillin plus clavulanic acid, 100% sensitive to ciprofloxacin, 92.3% resistant to erythromycin and 100% resistant to ceftriaxone. Children are particularly vulnerable to snakebite, and the consequences can be devastating. While the majority of patients in this study were shown to have secondary bacterial infection, debridement and subsequent wound management is considered the mainstay of treatment. Common organisms are Enterobacteriaceae and enterococci. There appears to be a role for antibiotics in the management of these patients. A good antibiotic policy is strongly advocated.

Transport calculations and sensitivity analyses for air-over-ground and air-over-seawater weapons environments

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

Pace, J.V. III; Bartine, D.E.; Mynatt, F.R.

1976-01-01

Two-dimensional neutron and secondary gamma-ray transport calculations and cross-section sensitivity analyses have been performed to determine the effects of varying source heights and cross sections on calculated doses. The air-over-ground calculations demonstrate the existence of an optimal height of burst for a specific ground range and indicate under what conditions they are conservative with respect to infinite air calculations. The air-over-seawater calculations showed the importance of hydrogen and chlorine in gamma production. Additional sensitivity analyses indicated the importance of water in the ground, the amount of reduction in ground thickness for calculational purposes, and the effect of the degree ofmore » Legendre angular expansion of the scattering cross-sections (P/sub l/) on the calculated dose.« less

Diagnostic accuracy of different caries risk assessment methods. A systematic review.

PubMed

Senneby, Anna; Mejàre, Ingegerd; Sahlin, Nils-Eric; Svensäter, Gunnel; Rohlin, Madeleine

2015-12-01

To evaluate the accuracy of different methods used to identify individuals with increased risk of developing dental coronal caries. Studies on following methods were included: previous caries experience, tests using microbiota, buffering capacity, salivary flow rate, oral hygiene, dietary habits and sociodemographic variables. QUADAS-2 was used to assess risk of bias. Sensitivity, specificity, predictive values, and likelihood ratios (LR) were calculated. Quality of evidence based on ≥3 studies of a method was rated according to GRADE. PubMed, Cochrane Library, Web of Science and reference lists of included publications were searched up to January 2015. From 5776 identified articles, 18 were included. Assessment of study quality identified methodological limitations concerning study design, test technology and reporting. No study presented low risk of bias in all domains. Three or more studies were found only for previous caries experience and salivary mutans streptococci and quality of evidence for these methods was low. Evidence regarding other methods was lacking. For previous caries experience, sensitivity ranged between 0.21 and 0.94 and specificity between 0.20 and 1. Tests using salivary mutans streptococci resulted in low sensitivity and high specificity. For children with primary teeth at baseline, pooled LR for a positive test was 3 for previous caries experience and 4 for salivary mutans streptococci, given a threshold ≥10(5) CFU/ml. Evidence on the validity of analysed methods used for caries risk assessment is limited. As methodological quality was low, there is a need to improve study design. Low validity for the analysed methods may lead to patients with increased risk not being identified, whereas some are falsely identified as being at risk. As caries risk assessment guides individualized decisions on interventions and intervals for patient recall, improved performance based on best evidence is greatly needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Methodological quality of diagnostic accuracy studies on non-invasive coronary CT angiography: influence of QUADAS (Quality Assessment of Diagnostic Accuracy Studies included in systematic reviews) items on sensitivity and specificity.

PubMed

Schueler, Sabine; Walther, Stefan; Schuetz, Georg M; Schlattmann, Peter; Dewey, Marc

2013-06-01

To evaluate the methodological quality of diagnostic accuracy studies on coronary computed tomography (CT) angiography using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies included in systematic reviews) tool. Each QUADAS item was individually defined to adapt it to the special requirements of studies on coronary CT angiography. Two independent investigators analysed 118 studies using 12 QUADAS items. Meta-regression and pooled analyses were performed to identify possible effects of methodological quality items on estimates of diagnostic accuracy. The overall methodological quality of coronary CT studies was merely moderate. They fulfilled a median of 7.5 out of 12 items. Only 9 of the 118 studies fulfilled more than 75 % of possible QUADAS items. One QUADAS item ("Uninterpretable Results") showed a significant influence (P = 0.02) on estimates of diagnostic accuracy with "no fulfilment" increasing specificity from 86 to 90 %. Furthermore, pooled analysis revealed that each QUADAS item that is not fulfilled has the potential to change estimates of diagnostic accuracy. The methodological quality of studies investigating the diagnostic accuracy of non-invasive coronary CT is only moderate and was found to affect the sensitivity and specificity. An improvement is highly desirable because good methodology is crucial for adequately assessing imaging technologies. • Good methodological quality is a basic requirement in diagnostic accuracy studies. • Most coronary CT angiography studies have only been of moderate design quality. • Weak methodological quality will affect the sensitivity and specificity. • No improvement in methodological quality was observed over time. • Authors should consider the QUADAS checklist when undertaking accuracy studies.

Bronchial and non-bronchial systemic arteries: value of multidetector CT angiography in diagnosis and angiographic embolisation feasibility analysis.

PubMed

Lin, Yuning; Chen, Ziqian; Yang, Xizhang; Zhong, Qun; Zhang, Hongwen; Yang, Li; Xu, Shangwen; Li, Hui

2013-12-01

The aim of this study is to evaluate the diagnostic performance of multidetector CT angiography (CTA) in depicting bronchial and non-bronchial systemic arteries in patients with haemoptysis and to assess whether this modality helps determine the feasibility of angiographic embolisation. Fifty-two patients with haemoptysis between January 2010 and July 2011 underwent both preoperative multidetector CTA and digital subtraction angiography (DSA) imaging. Diagnostic performance of CTA in depicting arteries causing haemoptysis was assessed on a per-patient and a per-artery basis. The feasibility of the endovascular treatment evaluated by CTA was analysed. Sensitivity, specificity, and positive and negative predictive values for those analyses were determined. Fifty patients were included in the artery-presence-number analysis. In the per-patient analysis, neither CTA (P = 0.25) nor DSA (P = 1.00) showed statistical difference in the detection of arteries causing haemoptysis. The sensitivity, specificity, and positive and negative predictive values were 94%, 100%, 100%, and 40%, respectively, for the presence of pathologic arteries evaluated by CTA, and 98%, 100%, 100%, and 67%, respectively, for DSA. On the per-artery basis, CTA correctly identified 97% (107/110). Fifty-two patients were included in the feasibility analysis. The performance of CTA in predicting the feasibility of angiographic embolisation was not statistically different from the treatment performed (P = 1.00). The sensitivity, specificity, and positive and negative predictive values were 96%, 80%, 98% and 67%, respectively, for CTA. Multidetector CTA is an accurate imaging method in depicting the presence and number of arteries causing haemoptysis. This modality is also useful for determining the feasibility of angiographic embolisation for haemoptysis. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

Comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in older adults: an analysis of Medicare claims data.

PubMed

Singh, Jasvinder A; Cleveland, John D

2017-10-01

To assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in elderly. In a retrospective cohort study using 2006-2012 Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 183 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the HR of incident renal disease with allopurinol use (and dose) versus febuxostat (reference). Sensitivity analyses included multivariable-adjusted regression models. There were 31 465 new allopurinol or febuxostat treatment episodes in 26 443 patients; 8570 ended in incident renal disease. Crude rates of incident renal disease per 1000 person-years were 192 with allopurinol versus 338 with febuxostat. Crude rates of incident renal disease per 1000 person-years were lower with higher daily dose: allopurinol <200, 200-299 and ≥300 mg/day with 238, 176 and 155; and febuxostat 40 and 80 mg/day with 341 and 326, respectively. In propensity-matched analyses, compared with febuxostat, allopurinol use was associated with lower HR of incident renal disease, 0.61 (95% CI 0.49 to 0.77). Compared with febuxostat 40 mg/day, allopurinol doses <200, 200-299 and ≥300 mg/day were associated with lower HR of incident renal disease, 0.75 (95% CI 0.65 to 0.86), 0.61 (95% CI 0.52 to 0.73) and 0.48 (95% CI 0.41 to 0.55), respectively. Sensitivity analyses using multivariable-adjusted regression confirmed these findings. Allopurinol was associated with a lower risk of incident renal disease in elderly patients than febuxostat. Future studies need to examine the mechanism of this potential renal benefit of allopurinol. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sensitivity subgroup analysis based on single-center vs. multi-center trial status when interpreting meta-analyses pooled estimates: the logical way forward.

PubMed

Alexander, Paul E; Bonner, Ashley J; Agarwal, Arnav; Li, Shelly-Anne; Hariharan, Abishek; Izhar, Zain; Bhatnagar, Neera; Alba, Carolina; Akl, Elie A; Fei, Yutong; Guyatt, Gordon H; Beyene, Joseph

2016-06-01

Prior studies regarding whether single-center trial estimates are larger than multi-center are equivocal. We examined the extent to which single-center trials yield systematically larger effects than multi-center trials. We searched the 119 core clinical journals and the Cochrane Database of Systematic Reviews for meta-analyses (MAs) of randomized controlled trials (RCTs) published during 2012. In this meta-epidemiologic study, for binary variables, we computed the pooled ratio of ORs (RORs), and for continuous outcomes mean difference in standardized mean differences (SMDs), we conducted weighted random-effects meta-regression and random-effects MA modeling. Our primary analyses were restricted to MAs that included at least five RCTs and in which at least 25% of the studies used each of single trial center (SC) and more trial center (MC) designs. We identified 81 MAs for the odds ratio (OR) and 43 for the SMD outcome measures. Based on our analytic plan, our primary analysis (core) is based on 25 MAs/241 RCTs (binary outcome) and 18 MAs/173 RCTs (continuous outcome). Based on the core analysis, we found no difference in magnitude of effect between SC and MC for binary outcomes [RORs: 1.02; 95% confidence interval (CI): 0.83, 1.24; I(2) 20.2%]. Effect sizes were systematically larger for SC than MC for the continuous outcome measure (mean difference in SMDs: -0.13; 95% CI: -0.21, -0.05; I(2) 0%). Our results do not support prior findings of larger effects in SC than MC trials addressing binary outcomes but show a very similar small increase in effect in SC than MC trials addressing continuous outcomes. Authors of systematic reviews would be wise to include all trials irrespective of SC vs. MC design and address SC vs. MC status as a possible explanation of heterogeneity (and consider sensitivity analyses). Copyright © 2015 Elsevier Inc. All rights reserved.

Cost-Effectiveness of Haemorrhoidal Artery Ligation versus Rubber Band Ligation for the Treatment of Grade II-III Haemorrhoids: Analysis Using Evidence from the HubBLe Trial.

PubMed

Alshreef, Abualbishr; Wailoo, Allan J; Brown, Steven R; Tiernan, James P; Watson, Angus J M; Biggs, Katie; Bradburn, Mike; Hind, Daniel

2017-09-01

Haemorrhoids are a common condition, with nearly 30,000 procedures carried out in England in 2014/15, and result in a significant quality-of-life burden to patients and a financial burden to the healthcare system. This study examined the cost effectiveness of haemorrhoidal artery ligation (HAL) compared with rubber band ligation (RBL) in the treatment of grade II-III haemorrhoids. This analyses used data from the HubBLe study, a multicentre, open-label, parallel group, randomised controlled trial conducted in 17 acute UK hospitals between September 2012 and August 2015. A full economic evaluation, including long-term cost effectiveness, was conducted from the UK National Health Service (NHS) perspective. Main outcomes included healthcare costs, quality-adjusted life-years (QALYs) and recurrence. Cost-effectiveness results were presented in terms of incremental cost per QALY gained and cost per recurrence avoided. Extrapolation analysis for 3 years beyond the trial follow-up, two subgroup analyses (by grade of haemorrhoids and recurrence following RBL at baseline), and various sensitivity analyses were undertaken. In the primary base-case within-trial analysis, the incremental total mean cost per patient for HAL compared with RBL was £1027 (95% confidence interval [CI] £782-£1272, p < 0.001). The incremental QALYs were 0.01 QALYs (95% CI -0.02 to 0.04, p = 0.49). This generated an incremental cost-effectiveness ratio (ICER) of £104,427 per QALY. In the extrapolation analysis, the estimated probabilistic ICER was £21,798 per QALY. Results from all subgroup and sensitivity analyses did not materially change the base-case result. Under all assessed scenarios, the HAL procedure was not cost effective compared with RBL for the treatment of grade II-III haemorrhoids at a cost-effectiveness threshold of £20,000 per QALY; therefore, economically, its use in the NHS should be questioned.

Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts.

PubMed

Cai, Yutong; Schikowski, Tamara; Adam, Martin; Buschka, Anna; Carsin, Anne-Elie; Jacquemin, Benedicte; Marcon, Alessandro; Sanchez, Margaux; Vierkötter, Andrea; Al-Kanaani, Zaina; Beelen, Rob; Birk, Matthias; Brunekreef, Bert; Cirach, Marta; Clavel-Chapelon, Françoise; Declercq, Christophe; de Hoogh, Kees; de Nazelle, Audrey; Ducret-Stich, Regina E; Valeria Ferretti, Virginia; Forsberg, Bertil; Gerbase, Margaret W; Hardy, Rebecca; Heinrich, Joachim; Hoek, Gerard; Jarvis, Debbie; Keidel, Dirk; Kuh, Diana; Nieuwenhuijsen, Mark J; Ragettli, Martina S; Ranzi, Andrea; Rochat, Thierry; Schindler, Christian; Sugiri, Dorothea; Temam, Sofia; Tsai, Ming-Yi; Varraso, Raphaëlle; Kauffmann, Francine; Krämer, Ursula; Sunyer, Jordi; Künzli, Nino; Probst-Hensch, Nicole; Hansell, Anna L

2014-11-01

This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. Annual average particulate matter (PM(10), PM(2.5), PM(absorbance), PM(coarse)), NO(2), nitrogen oxides (NO(x)) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for ≥3 months of the year for ≥2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis. 15 279 and 10 537 participants respectively were included in the main NO(2) and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO(2) and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PM(coarse) OR 1.31 (1.05 to 1.64) per 5 µg/m(3) increase and PM(10) with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM(2.5abs) (black carbon) exposures. Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease

PubMed Central

Carroll, C. Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A.; Campbell, Claudia M.

2016-01-01

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis), central sensitization, depression, and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. PMID:27320469

Critical factors determining the quantification capability of matrix-assisted laser desorption/ionization– time-of-flight mass spectrometry

PubMed Central

Wang, Chia-Chen; Lai, Yin-Hung; Ou, Yu-Meng; Chang, Huan-Tsung; Wang, Yi-Sheng

2016-01-01

Quantitative analysis with mass spectrometry (MS) is important but challenging. Matrix-assisted laser desorption/ionization (MALDI) coupled with time-of-flight (TOF) MS offers superior sensitivity, resolution and speed, but such techniques have numerous disadvantages that hinder quantitative analyses. This review summarizes essential obstacles to analyte quantification with MALDI-TOF MS, including the complex ionization mechanism of MALDI, sensitive characteristics of the applied electric fields and the mass-dependent detection efficiency of ion detectors. General quantitative ionization and desorption interpretations of ion production are described. Important instrument parameters and available methods of MALDI-TOF MS used for quantitative analysis are also reviewed. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644968

Inhomogeneous Forcing and Transient Climate Sensitivity

NASA Technical Reports Server (NTRS)

Shindell, Drew T.

2014-01-01

Understanding climate sensitivity is critical to projecting climate change in response to a given forcing scenario. Recent analyses have suggested that transient climate sensitivity is at the low end of the present model range taking into account the reduced warming rates during the past 10-15 years during which forcing has increased markedly. In contrast, comparisons of modelled feedback processes with observations indicate that the most realistic models have higher sensitivities. Here I analyse results from recent climate modelling intercomparison projects to demonstrate that transient climate sensitivity to historical aerosols and ozone is substantially greater than the transient climate sensitivity to CO2. This enhanced sensitivity is primarily caused by more of the forcing being located at Northern Hemisphere middle to high latitudes where it triggers more rapid land responses and stronger feedbacks. I find that accounting for this enhancement largely reconciles the two sets of results, and I conclude that the lowest end of the range of transient climate response to CO2 in present models and assessments (less than 1.3 C) is very unlikely.

MAG-EPA resolves lung inflammation in an allergic model of asthma.

PubMed

Morin, C; Fortin, S; Cantin, A M; Rousseau, É

2013-09-01

Asthma is a chronic disease characterized by airways hyperresponsiveness, inflammation and airways remodelling involving reversible bronchial obstruction. Omega-3 fatty acids and their derivatives are known to reduce inflammation in several tissues including lung. The effects of eicosapentaenoic acid monoacylglyceride (MAG-EPA), a newly synthesized EPA derivative, were determined on the resolution of lung inflammation and airway hyperresponsiveness in an in vivo model of allergic asthma. Ovalbumin (OVA)-sensitized guinea-pigs were treated or not with MAG-EPA administered per os. Isometric tension measurements, histological analyses, homogenate preparation for Western blot experiments or total RNA extraction for RT-PCR were performed to assess the effect of MAG-EPA treatments. Mechanical tension measurements revealed that oral MAG-EPA treatments reduced methacholine (MCh)-induced bronchial hyperresponsiveness in OVA-sensitized guinea-pigs. Moreover, MAG-EPA treatments also decreased Ca(2+) hypersensitivity of bronchial smooth muscle. Histological analyses and leucocyte counts in bronchoalveolar lavages revealed that oral MAG-EPA treatments led to less inflammatory cell recruitment in the lung of OVA-sensitized guinea-pigs when compared with lungs from control animals. Results also revealed a reduction in mucin production and MUC5AC expression level in OVA-sensitized animals treated with MAG-EPA. Following MAG-EPA treatments, the transcript levels of pro-inflammatory markers such as IL-5, eotaxin, IL-13 and IL-4 were markedly reduced. Moreover, per os MAG-EPA administrations reduced COX2 over-expression in OVA-sensitized animals. We demonstrate that MAG-EPA reduces airway hyperresponsiveness and lung inflammation in OVA-sensitized animals, a finding consistent with a decrease in IL-4, IL-5, IL-13, COX-2 and MUC5AC expression levels in the lung. The present data suggest that MAG-EPA represents a new potential therapeutic strategy for resolving inflammation in allergic asthma. © 2013 John Wiley & Sons Ltd.

Cost-effectiveness of EOB-MRI for Hepatocellular Carcinoma in Japan.

PubMed

Nishie, Akihiro; Goshima, Satoshi; Haradome, Hiroki; Hatano, Etsuro; Imai, Yasuharu; Kudo, Masatoshi; Matsuda, Masanori; Motosugi, Utaroh; Saitoh, Satoshi; Yoshimitsu, Kengo; Crawford, Bruce; Kruger, Eliza; Ball, Graeme; Honda, Hiroshi

2017-04-01

The objective of the study was to evaluate the cost-effectiveness of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) in the diagnosis and treatment of hepatocellular carcinoma (HCC) in Japan compared with extracellular contrast media-enhanced MRI (ECCM-MRI) and contrast media-enhanced computed tomography (CE-CT) scanning. A 6-stage Markov model was developed to estimate lifetime direct costs and clinical outcomes associated with EOB-MRI. Diagnostic sensitivity and specificity, along with clinical data on HCC survival, recurrence, treatment patterns, costs, and health state utility values, were derived from predominantly Japanese publications. Parameters unavailable from publications were estimated in a Delphi panel of Japanese clinical experts who also confirmed the structure and overall approach of the model. Sensitivity analyses, including one-way, probabilistic, and scenario analyses, were conducted to account for uncertainty in the results. Over a lifetime horizon, EOB-MRI was associated with lower direct costs (¥2,174,869) and generated a greater number of quality-adjusted life years (QALYs) (9.502) than either ECCM-MRI (¥2,365,421, 9.303 QALYs) or CE-CT (¥2,482,608, 9.215 QALYs). EOB-MRI was superior to the other diagnostic strategies considered, and this finding was robust over sensitivity and scenario analyses. A majority of the direct costs associated with HCC in Japan were found to be costs of treatment. The model results revealed the superior cost-effectiveness of the EOB-MRI diagnostic strategy compared with ECCM-MRI and CE-CT. EOB-MRI could be the first-choice imaging modality for medical care of HCC among patients with hepatitis or liver cirrhosis in Japan. Widespread implementation of EOB-MRI could reduce health care expenditures, particularly downstream treatment costs, associated with HCC. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Sensitivity Analyses of the Change in FVC in a Phase 3 Trial of Pirfenidone for Idiopathic Pulmonary Fibrosis

PubMed Central

Bradford, Williamson Z.; Fagan, Elizabeth A.; Glaspole, Ian; Glassberg, Marilyn K.; Glasscock, Kenneth F.; King, Talmadge E.; Lancaster, Lisa H.; Nathan, Steven D.; Pereira, Carlos A.; Sahn, Steven A.; Swigris, Jeffrey J.; Noble, Paul W.

2015-01-01

BACKGROUND: FVC outcomes in clinical trials on idiopathic pulmonary fibrosis (IPF) can be substantially influenced by the analytic methodology and the handling of missing data. We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF. METHODS: Source data included all 555 study participants randomized to treatment with pirfenidone or placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) study. Sensitivity analyses were conducted to assess whether alternative statistical tests and methods for handling missing data influenced the observed magnitude of treatment effect on the primary end point of change from baseline to week 52 in FVC. RESULTS: The distribution of FVC change at week 52 was systematically different between the two treatment groups and favored pirfenidone in each analysis. The method used to impute missing data due to death had a marked effect on the magnitude of change in FVC in both treatment groups; however, the magnitude of treatment benefit was generally consistent on a relative basis, with an approximate 50% reduction in FVC decline observed in the pirfenidone group in each analysis. CONCLUSIONS: Our results confirm the robustness of the statistical finding on the primary end point of change in FVC in the ASCEND trial and corroborate the estimated magnitude of the pirfenidone treatment effect in patients with IPF. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov PMID:25856121

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

Hadgu, Teklu; Appel, Gordon John

Sandia National Laboratories (SNL) continued evaluation of total system performance assessment (TSPA) computing systems for the previously considered Yucca Mountain Project (YMP). This was done to maintain the operational readiness of the computing infrastructure (computer hardware and software) and knowledge capability for total system performance assessment (TSPA) type analysis, as directed by the National Nuclear Security Administration (NNSA), DOE 2010. This work is a continuation of the ongoing readiness evaluation reported in Lee and Hadgu (2014) and Hadgu et al. (2015). The TSPA computing hardware (CL2014) and storage system described in Hadgu et al. (2015) were used for the currentmore » analysis. One floating license of GoldSim with Versions 9.60.300, 10.5 and 11.1.6 was installed on the cluster head node, and its distributed processing capability was mapped on the cluster processors. Other supporting software were tested and installed to support the TSPA-type analysis on the server cluster. The current tasks included verification of the TSPA-LA uncertainty and sensitivity analyses, and preliminary upgrade of the TSPA-LA from Version 9.60.300 to the latest version 11.1. All the TSPA-LA uncertainty and sensitivity analyses modeling cases were successfully tested and verified for the model reproducibility on the upgraded 2014 server cluster (CL2014). The uncertainty and sensitivity analyses used TSPA-LA modeling cases output generated in FY15 based on GoldSim Version 9.60.300 documented in Hadgu et al. (2015). The model upgrade task successfully converted the Nominal Modeling case to GoldSim Version 11.1. Upgrade of the remaining of the modeling cases and distributed processing tasks will continue. The 2014 server cluster and supporting software systems are fully operational to support TSPA-LA type analysis.« less

Sensitivity analyses of factors influencing CMAQ performance for fine particulate nitrate.

PubMed

Shimadera, Hikari; Hayami, Hiroshi; Chatani, Satoru; Morino, Yu; Mori, Yasuaki; Morikawa, Tazuko; Yamaji, Kazuyo; Ohara, Toshimasa

2014-04-01

Improvement of air quality models is required so that they can be utilized to design effective control strategies for fine particulate matter (PM2.5). The Community Multiscale Air Quality modeling system was applied to the Greater Tokyo Area of Japan in winter 2010 and summer 2011. The model results were compared with observed concentrations of PM2.5 sulfate (SO4(2-)), nitrate (NO3(-)) and ammonium, and gaseous nitric acid (HNO3) and ammonia (NH3). The model approximately reproduced PM2.5 SO4(2-) concentration, but clearly overestimated PM2.5 NO3(-) concentration, which was attributed to overestimation of production of ammonium nitrate (NH4NO3). This study conducted sensitivity analyses of factors associated with the model performance for PM2.5 NO3(-) concentration, including temperature and relative humidity, emission of nitrogen oxides, seasonal variation of NH3 emission, HNO3 and NH3 dry deposition velocities, and heterogeneous reaction probability of dinitrogen pentoxide. Change in NH3 emission directly affected NH3 concentration, and substantially affected NH4NO3 concentration. Higher dry deposition velocities of HNO3 and NH3 led to substantial reductions of concentrations of the gaseous species and NH4NO3. Because uncertainties in NH3 emission and dry deposition processes are probably large, these processes may be key factors for improvement of the model performance for PM2.5 NO3(-). The Community Multiscale Air Quality modeling system clearly overestimated the concentration of fine particulate nitrate in the Greater Tokyo Area of Japan, which was attributed to overestimation of production of ammonium nitrate. Sensitivity analyses were conducted for factors associated with the model performance for nitrate. Ammonia emission and dry deposition of nitric acid and ammonia may be key factors for improvement of the model performance.

Cost-effectiveness of pharmacist-participated warfarin therapy management in Thailand.

PubMed

Saokaew, Surasak; Permsuwan, Unchalee; Chaiyakunapruk, Nathorn; Nathisuwan, Surakit; Sukonthasarn, Apichard; Jeanpeerapong, Napawan

2013-10-01

Although pharmacist-participated warfarin therapy management (PWTM) is well established, the economic evaluation of PWTM is still lacking particularly in Asia-Pacific region. The objective of this study was to estimate the cost-effectiveness of PWTM in Thailand using local data where available. A Markov model was used to compare lifetime costs and quality-adjusted life years (QALYs) accrued to patients receiving warfarin therapy through PWTM or usual care (UC). The model was populated with relevant information from both health care system and societal perspectives. Input data were obtained from literatures and database analyses. Incremental cost-effectiveness ratios (ICERs) were presented as year 2012 values. A base-case analysis was performed for patients at age 45 years old. Sensitivity analyses including one-way and probabilistic sensitivity analyses were constructed to determine the robustness of the findings. From societal perspective, PWTM and UC results in 39.5 and 38.7 QALY, respectively. Thus, PWTM increase QALY by 0.79, and increase costs by 92,491 THB (3,083 USD) compared with UC (ICER 116,468 THB [3,882.3 USD] per QALY gained). While, from health care system perspective, PWTM also results in 0.79 QALY, and increase costs by 92,788 THB (3,093 USD) compared with UC (ICER 116,842 THB [3,894.7 USD] per QALY gained). Thus, PWTM was cost-effective compared with usual care, assuming willingness-to-pay (WTP) of 150,000 THB/QALY. Results were sensitive to the discount rate and cost of clinic set-up. Our finding suggests that PWTM is a cost-effective intervention. Policy-makers may consider our finding as part of information in their decision-making for implementing this strategy into healthcare benefit package. Further updates when additional data available are needed. © 2013.

A rural/urban comparison of privacy and confidentiality concerns associated with providing sensitive location information in epidemiologic research involving persons who use drugs.

PubMed

Rudolph, Abby E; Young, April M; Havens, Jennifer R

2017-11-01

Analyses that link contextual factors with individual-level data can improve our understanding of the "risk environment"; however, the accuracy of information provided by participants about locations where illegal/stigmatized behaviors occur may be influenced by privacy/confidentiality concerns that may vary by setting and/or data collection approach. We recruited thirty-five persons who use drugs from a rural Appalachian town and a Mid-Atlantic city to participate in in-depth interviews. Through thematic analyses, we identified and compared privacy/confidentiality concerns associated with two survey methods that (1) collect self-reported addresses/cross-streets and (2) use an interactive web-based map to find/confirm locations in rural and urban settings. Concerns differed more by setting than between methods. For example, (1) rural participants valued interviewer rapport and protections provided by the Certificate of Confidentiality more; (2) locations considered to be sensitive differed in rural (i.e., others' homes) and urban (i.e., where drugs were used) settings; and (3) urban participants were more likely to view providing cross-streets as an acceptable alternative to providing exact addresses for sensitive locations and to prefer the web-based map approach. Rural-urban differences in privacy/confidentiality concerns reflect contextual differences (i.e., where drugs are used/purchased, population density, and prior drug-related arrests). Strategies to alleviate concerns include: (1) obtain a Certificate of Confidentiality, (2) collect geographic data at the scale necessary for proposed analyses, and (3) permit participants to provide intersections/landmarks in close proximity to actual locations rather than exact addresses or to skip questions where providing an intersection/landmark would not obfuscate the actual address. Copyright © 2017 Elsevier Ltd. All rights reserved.

A cost-minimisation analysis comparing photoselective vaporisation (PVP) and transurethral resection of the prostate (TURP) for the management of symptomatic benign prostatic hyperplasia (BPH) in Queensland, Australia.

PubMed

Whitty, Jennifer A; Crosland, Paul; Hewson, Kaye; Narula, Rajan; Nathan, Timothy R; Campbell, Peter A; Keller, Andrew; Scuffham, Paul A

2014-03-01

To compare the costs of photoselective vaporisation (PVP) and transurethral resection of the prostate (TURP) for management of symptomatic benign prostatic hyperplasia (BPH) from the perspective of a Queensland public hospital provider. A decision-analytic model was used to compare the costs of PVP and TURP. Cost inputs were sourced from an audit of patients undergoing PVP or TURP across three hospitals. The probability of re-intervention was obtained from secondary literature sources. Probabilistic and multi-way sensitivity analyses were used to account for uncertainty and test the impact of varying key assumptions. In the base case analysis, which included equipment, training and re-intervention costs, PVP was AU$ 739 (95% credible interval [CrI] -12 187 to 14 516) more costly per patient than TURP. The estimate was most sensitive to changes in procedural costs, fibre costs and the probability of re-intervention. Sensitivity analyses based on data from the most favourable site or excluding equipment and training costs reduced the point estimate to favour PVP (incremental cost AU$ -684, 95% CrI -8319 to 5796 and AU$ -100, 95% CrI -13 026 to 13 678, respectively). However, CrIs were wide for all analyses. In this cost minimisation analysis, there was no significant cost difference between PVP and TURP, after accounting for equipment, training and re-intervention costs. However, PVP was associated with a shorter length of stay and lower procedural costs during audit, indicating PVP potentially provides comparatively good value for money once the technology is established. © 2013 The Authors. BJU International © 2013 BJU International.

Cost Effectiveness of Influenza Vaccine Choices in Children Aged 2–8 Years in the U.S.

PubMed Central

Smith, Kenneth J.; Raviotta, Jonathan M.; DePasse, Jay V.; Brown, Shawn T.; Shim, Eunha; Nowalk, Mary Patricia; Zimmerman, Richard K.

2015-01-01

Introduction Prior evidence found live attenuated influenza vaccine (LAIV) more effective than inactivated influenza vaccine (IIV) in children aged 2–8 years, leading CDC in 2014 to prefer LAIV use in this group. However, since 2013, LAIV has not proven superior, leading CDC in 2015 to rescind their LAIV preference statement. Here, the cost effectiveness of preferred LAIV use compared with IIV in children aged 2–8 years is estimated. Methods A Markov model estimated vaccination strategy cost effectiveness in terms of cost per quality-adjusted life year gained. Base case assumptions were: equal vaccine uptake, IIV use when LAIV was not indicated (in 11.7% of the cohort), and no indirect vaccination effects. Sensitivity analyses included estimates of indirect effects from both equation- and agent-based models. Analyses were performed in 2014–2015. Results Using prior effectiveness data in children aged 2–8 years (LAIV=83%, IIV=64%), preferred LAIV use was less costly and more effective than IIV (dominant), with results sensitive only to LAIV and IIV effectiveness variation. Using 2014–2015 U.S. effectiveness data (LAIV=0%, IIV=15%), IIV was dominant. In two-way sensitivity analyses, LAIV use was cost saving over the entire range of IIV effectiveness (0%–81%) when absolute LAIV effectiveness was >7.1% higher than IIV, but never cost saving when absolute LAIV effectiveness was <3.5% higher than IIV. Conclusions Results support CDC’s decision to no longer prefer LAIV use and provide guidance on effectiveness differences between influenza vaccines that might lead to preferential LAIV recommendation for children aged 2–8 years. PMID:26868283

Comprehensive Design Reliability Activities for Aerospace Propulsion Systems

NASA Technical Reports Server (NTRS)

Christenson, R. L.; Whitley, M. R.; Knight, K. C.

2000-01-01

This technical publication describes the methodology, model, software tool, input data, and analysis result that support aerospace design reliability studies. The focus of these activities is on propulsion systems mechanical design reliability. The goal of these activities is to support design from a reliability perspective. Paralleling performance analyses in schedule and method, this requires the proper use of metrics in a validated reliability model useful for design, sensitivity, and trade studies. Design reliability analysis in this view is one of several critical design functions. A design reliability method is detailed and two example analyses are provided-one qualitative and the other quantitative. The use of aerospace and commercial data sources for quantification is discussed and sources listed. A tool that was developed to support both types of analyses is presented. Finally, special topics discussed include the development of design criteria, issues of reliability quantification, quality control, and reliability verification.

Economic evaluation of ezetimibe treatment in combination with statin therapy in the United States.

PubMed

Davies, Glenn M; Vyas, Ami; Baxter, Carl A

2017-07-01

This study assessed the cost-effectiveness of ezetimibe with statin therapy vs statin monotherapy from a US payer perspective, assuming the impending patent expiration of ezetimibe. A Markov-like economic model consisting of 28 distinct health states was used. Model population data were obtained from US linked claims and electronic medical records, with inclusion criteria based on diagnostic guidelines. Inputs came from recent clinical trials, meta-analyses, and cost-effectiveness analyses. The base-case scenario was used to evaluate the cost-effectiveness of adding ezetimibe 10 mg to statin in patients aged 35-74 years with a history of coronary heart disease (CHD) and/or stroke, and with low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL over a lifetime horizon, assuming a 90% price reduction of ezetimibe after 1 year to take into account the impending patent expiration in the second quarter of 2017. Sub-group analyses included patients with LDL-C levels ≥100 mg/dL and patients with diabetes with LDL-C levels ≥70 mg/dL. The lifetime discounted incremental cost-effectiveness ratio (ICER) for ezetimibe added to statin was $9,149 per quality-adjusted life year (QALY) for the base-case scenario. For patients with LDL-C levels ≥100 mg/dL, the ICER was $839/QALY; for those with diabetes and LDL-C levels ≥70 mg/dL, it was $560/QALY. One-way sensitivity analyses showed that the model was sensitive to changes in cost of ezetimibe, rate reduction of non-fatal CHD, and utility weight for non-fatal CHD in the base-case and sub-group analyses. Indirect costs or treatment discontinuation estimation were not included. Compared with statin monotherapy, ezetimibe with statin therapy was cost-effective for secondary prevention of CHD and stroke and for primary prevention of these conditions in patients whose LDL-C levels are ≥100 mg/dL and in patients with diabetes, taking into account a 90% cost reduction for ezetimibe.

Chronic Use of Aspirin and Total White Matter Lesion Volume: Results from the Women's Health Initiative Memory Study of Magnetic Resonance Imaging Study.

PubMed

Holcombe, Andrea; Ammann, Eric; Espeland, Mark A; Kelley, Brendan J; Manson, JoAnn E; Wallace, Robert; Robinson, Jennifer

2017-10-01

To investigate the relationship between aspirin and subclinical cerebrovascular heath, we evaluated the effect of chronic aspirin use on white matter lesions (WML) volume among women. Chronic aspirin use was assessed in 1365 women who participated in the Women's Health Initiative Memory Study of Magnetic Resonance Imaging. Differences in WML volumes between aspirin users and nonusers were assessed with linear mixed models. A number of secondary analyses were performed, including lobe-specific analyses, subgroup analyses based on participants' overall risk of cerebrovascular disease, and a dose-response relationship analysis. The mean age of the women at magnetic resonance imaging examination was 77.6 years. Sixty-one percent of participants were chronic aspirin users. After adjusting for demographic variables and comorbidities, chronic aspirin use was nonsignificantly associated with 4.8% (95% CI: -6.8%, 17.9%) larger WML volumes. These null findings were confirmed in secondary and sensitivity analyses, including an active comparator evaluation where aspirin users were compared to users of nonaspirin nonsteroidal anti-inflammatory drugs or acetaminophen. There was a nonsignificant difference in WML volumes between aspirin users and nonusers. Further, our results suggest that chronic aspirin use may not have a clinically significant effect on WML volumes in women. Published by Elsevier Inc.

A Systematic Review of the Cost-Effectiveness of Biologics for Ulcerative Colitis.

PubMed

Stawowczyk, Ewa; Kawalec, Paweł

2018-04-01

Ulcerative colitis (UC) is a chronic autoimmune inflammation of the colon. The condition significantly decreases quality of life and generates a substantial economic burden for healthcare payers, patients and the society in which they live. Some patients require chronic pharmacotherapy, and access to novel biologic drugs might be crucial for long-term remission. The analyses of cost-effectiveness for biologic drugs are necessary to assess their efficiency and provide the best available drugs to patients. Our aim was to collect and assess the quality of economic analyses carried out for biologic agents used in the treatment of UC, as well as to summarize evidence on the drivers of cost-effectiveness and evaluate the transferability and generalizability of conclusions. A systematic database review was conducted using MEDLINE (via PubMed), EMBASE, Cost-Effectiveness Analysis Registry and CRD0. Both authors independently reviewed the identified articles to determine their eligibility for final review. Hand searching of references in collected papers was also performed to find any relevant articles. The reporting quality of economic analyses included was evaluated by two reviewers using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement checklist. We reviewed the sensitivity analyses in cost-effectiveness analyses to identify the variables that may have changed the conclusions of the study. Key drivers of cost-effectiveness were selected by identifying uncertain parameters that caused the highest change of the results of the analyses compared with base-case results. Of the 576 identified records, 87 were excluded as duplicates and 16 studies were included in the final review; evaluations for Canada, the UK and Poland were mostly performed. The majority of the evaluations revealed were performed for infliximab (approximately 75% of total volume); however, some assessments were also performed for adalimumab (50%) and golimumab (31%). Only three analyses were conducted for vedolizumab, whereas no relevant studies were found for etrolizumab and tofacitinib. The reporting quality of the included economic analyses was assessed as high, with an average score of 21 points per 24 maximum possible (range 14-23 points according to the ISPOR CHEERS statement checklist). In the case of most analyses, quality-adjusted life-years were used as a clinical outcome, and endpoints such as remission, response and mucosal healing were less common. The higher clinical effectiveness (based on response rates) of biological treatment over non-biological treatments was presented in revealed analyses. The incremental cost-utility ratios for biologics, compared with standard care, varied significantly between the studies and ranged from US$36,309 to US$456,979. The lowest value was obtained for infliximab and the highest for the treatment scheme including infliximab 5 mg/kg and infliximab 10 mg/kg + adalimumab. The change of utility weights and clinical parameters had the most significant influence on the results of the analysis; the variable related to surgery was the least sensitive. Limited data on the cost-effectiveness of UC therapy were identified. In the majority of studies, the lack of cost-effectiveness was revealed for biologics, which was associated with their high costs. Clinical outcomes are transferable to other countries and could be generalized; however, cost inputs are country-specific and therefore limit the transferability and generalizability of conclusions. The key drivers and variables that showed the greatest effect on the analysis results were utility weights and clinical parameters.

Biomarkers in sarcoidosis.

PubMed

Chopra, Amit; Kalkanis, Alexandros; Judson, Marc A

2016-11-01

Numerous biomarkers have been evaluated for the diagnosis, assessment of disease activity, prognosis, and response to treatment in sarcoidosis. In this report, we discuss the clinical and research utility of several biomarkers used to evaluate sarcoidosis. Areas covered: The sarcoidosis biomarkers discussed include serologic tests, imaging studies, identification of inflammatory cells and genetic analyses. Literature was obtained from medical databases including PubMed and Web of Science. Expert commentary: Most of the biomarkers examined in sarcoidosis are not adequately specific or sensitive to be used in isolation to make clinical decisions. However, several sarcoidosis biomarkers have an important role in the clinical management of sarcoidosis when they are coupled with clinical data including the results of other biomarkers.

New Ways to Detect Pediatric Sickle Cell Retinopathy: A Comprehensive Review.

PubMed

Pahl, Daniel A; Green, Nancy S; Bhatia, Monica; Chen, Royce W S

2017-11-01

Sickle retinopathy reflects disease-related vascular injury of the eye, which can potentially result in visual loss from vitreous hemorrhage or retinal detachment. Here we review sickle retinopathy among children with sickle cell disease, describe the epidemiology, pediatric risk factors, pathophysiology, ocular findings, and treatment. Newer, more sensitive ophthalmological imaging modalities are available for retinal imaging, including ultra-widefield fluorescein angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography. Optical coherence tomography angiography provides a noninvasive view of retinal vascular layers that could previously not be imaged and can be quantified for comparative or prospective analyses. Ultra-widefield fluorescein angiography provides a more comprehensive view of the peripheral retina than traditional imaging techniques. Screening for retinopathy by standard fundoscopic imaging modalities detects a prevalence of approximately 10%. In contrast, these more sensitive methods allow for more sensitive examination that includes the retina perimeter where sickle retinopathy is often first detectable. Use of these new imaging modalities may detect a higher prevalence of early sickle pathology among children than has previously been reported. Earlier detection may help in better understanding the pathogenesis of sickle retinopathy and guide future screening and treatment paradigms.

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

Assessing the Optimal Position for Vedolizumab in the Treatment of Ulcerative Colitis: A Simulation Model.

PubMed

Scott, Frank I; Shah, Yash; Lasch, Karen; Luo, Michelle; Lewis, James D

2018-01-18

Vedolizumab, an α4β7 integrin monoclonal antibody inhibiting gut lymphocyte trafficking, is an effective treatment for ulcerative colitis (UC). We evaluated the optimal position of vedolizumab in the UC treatment paradigm. Using Markov modeling, we assessed multiple algorithms for the treatment of UC. The base case was a 35-year-old male with steroid-dependent moderately to severely active UC without previous immunomodulator or biologic use. The model included 4 different algorithms over 1 year, with vedolizumab use prior to: initiating azathioprine (Algorithm 1), combination therapy with infliximab and azathioprine (Algorithm 2), combination therapy with an alternative anti-tumor necrosis factor (anti-TNF) and azathioprine (Algorithm 3), and colectomy (Algorithm 4). Transition probabilities and quality-adjusted life-year (QALY) estimates were derived from the published literature. Primary analyses included simulating 100 trials of 100,000 individuals, assessing clinical outcomes, and QALYs. Sensitivity analyses employed longer time horizons and ranges for all variables. Algorithm 1 (vedolizumab use prior to all other therapies) was the preferred strategy, resulting in 8981 additional individuals in remission, 18 fewer cases of lymphoma, and 1087 fewer serious infections per 100,000 patients compared with last-line use (A4). Algorithm 1 also resulted in 0.0197 to 0.0205 more QALYs compared with other algorithms. This benefit increased with longer time horizons. Algorithm 1 was preferred in all sensitivity analyses. The model suggests that treatment algorithms positioning vedolizumab prior to other therapies should be considered for individuals with moderately to severely active steroid-dependent UC. Further prospective research is needed to confirm these simulated results. © 2018 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Human papillomavirus vaccine and demyelinating diseases-A systematic review and meta-analysis.

PubMed

Mouchet, Julie; Salvo, Francesco; Raschi, Emanuel; Poluzzi, Elisabetta; Antonazzo, Ippazio Cosimo; De Ponti, Fabrizio; Bégaud, Bernard

2018-06-01

Approved in 2006, human papillomavirus (HPV) vaccines were initially targeted for girls aged 9-14 years. Although the safety of these vaccines has been monitored through post-licensure surveillance programmes, cases of neurological events have been reported worldwide. The present study aimed to assess the risk of developing demyelination after HPV immunization by meta-analysing risk estimates from pharmacoepidemiologic studies. A systematic review was conducted in Medline, Embase, ISI Web of Science and the Cochrane Library from inception to 10 May 2017, without language restriction. Only observational studies including a control group were retained. Study selection was performed by two independent reviewers with disagreements solved through discussion. This meta-analysis was performed using a generic inverse variance random-effect model. Outcomes of interest included a broad category of central demyelination, multiple sclerosis (MS), optic neuritis (ON), and Guillain-Barré syndrome (GBS), each being considered independently. Heterogeneity was investigated; sensitivity and subgroup analyses were performed when necessary. In parallel, post-licensure safety studies were considered for a qualitative review. This study followed the PRISMA statement and the MOOSE reporting guideline. Of the 2,863 references identified, 11 articles were selected for meta-analysis. No significant association emerged between HPV vaccination and central demyelination, the pooled odds ratio being 0.96 [95% CI 0.77-1.20], with a moderate but non-significant heterogeneity (I 2  = 29%). Similar results were found for MS and ON. Sensitivity analyses did not alter our conclusions. Findings from qualitative review of 14 safety studies concluded in an absence of a relevant signal. Owing to limited data on GBS, no meta-analysis was performed for this outcome. This study strongly supports the absence of association between HPV vaccines and central demyelination. Copyright © 2018 Elsevier Ltd. All rights reserved.

Experiment Evaluation of Bifurcation in Sands

NASA Technical Reports Server (NTRS)

Alshibi, Khalid A.; Sture, Stein

2000-01-01

The basic principles of bifurcation analysis have been established by several investigators, however several issues remain unresolved, specifically how do stress level, grain size distribution, and boundary conditions affect general bifurcation phenomena in pressure sensitive and dilatant materials. General geometrical and kinematics conditions for moving surfaces of discontinuity was derived and applied to problems of instability of solids. In 1962, the theoretical framework of bifurcation by studying the acceleration waves in elasto-plastic (J2) solids were presented. Bifurcation analysis for more specific forms of constitutive behavior was examined by studying localization in pressure-sensitive, dilatant materials, however, analyses were restricted to plane deformation states only. Bifurcation analyses were presented and applied to predict shear band formations in sand under plane strain condition. The properties of discontinuous bifurcation solutions for elastic-plastic solids under axisymmetric and plane strain loading conditions were studied. The study focused on theory, but also references and comparisons to experiments were made. The current paper includes a presentation of a summary of bifurcation analyses for biaxial and triaxial (axisymmetric) loading conditions. The Coulomb model is implemented using incremental piecewise scheme to predict the constitutive relations and shear band inclination angles. Then, a comprehensive evaluation of bifurcation phenomena is presented based on data from triaxial experiments performed under microgravity conditions aboard the Space Shuttle under very low effective confining pressure (0.05 to 1.30 kPa), in which very high peak friction angles (47 to 75 degrees) and dilatancy angles (30 to 31 degrees) were measured. The evaluation will be extended to include biaxial experiments performed on the same material under low (10 kPa) and moderate (100 kPa) confining pressures. A comparison between the behavior under biaxial and triaxial loading conditions will be presented, and related issues concerning influence of confining pressure will be discussed.

Structure of Preschool Phonological Sensitivity: Overlapping Sensitivity to Rhyme, Words, Syllables, and Phonemes.

ERIC Educational Resources Information Center

Anthony, Jason L.; Lonigan, Christopher J.; Burgess, Stephen R.; Driscoll, Kimberly; Phillips, Beth M.; Cantor, Brenlee G.

2002-01-01

This study examined relations among sensitivity to words, syllables, rhymes, and phonemes in older and younger preschoolers. Confirmatory factor analyses found that a one-factor model best explained the date from both groups of children. Only variance common to all phonological sensitivity skills was related to print knowledge and rudimentary…

Sensitivity analysis of conservative and reactive stream transient storage models applied to field data from multiple-reach experiments

USGS Publications Warehouse

Gooseff, M.N.; Bencala, K.E.; Scott, D.T.; Runkel, R.L.; McKnight, Diane M.

2005-01-01

The transient storage model (TSM) has been widely used in studies of stream solute transport and fate, with an increasing emphasis on reactive solute transport. In this study we perform sensitivity analyses of a conservative TSM and two different reactive solute transport models (RSTM), one that includes first-order decay in the stream and the storage zone, and a second that considers sorption of a reactive solute on streambed sediments. Two previously analyzed data sets are examined with a focus on the reliability of these RSTMs in characterizing stream and storage zone solute reactions. Sensitivities of simulations to parameters within and among reaches, parameter coefficients of variation, and correlation coefficients are computed and analyzed. Our results indicate that (1) simulated values have the greatest sensitivity to parameters within the same reach, (2) simulated values are also sensitive to parameters in reaches immediately upstream and downstream (inter-reach sensitivity), (3) simulated values have decreasing sensitivity to parameters in reaches farther downstream, and (4) in-stream reactive solute data provide adequate data to resolve effective storage zone reaction parameters, given the model formulations. Simulations of reactive solutes are shown to be equally sensitive to transport parameters and effective reaction parameters of the model, evidence of the control of physical transport on reactive solute dynamics. Similar to conservative transport analysis, reactive solute simulations appear to be most sensitive to data collected during the rising and falling limb of the concentration breakthrough curve. ?? 2005 Elsevier Ltd. All rights reserved.

Sensitivity of water resources in the Delaware River basin to climate variability and change

USGS Publications Warehouse

Ayers, Mark A.; Wolock, David M.; McCabe, Gregory J.; Hay, Lauren E.; Tasker, Gary D.

1994-01-01

Because of the greenhouse effect, projected increases in atmospheric carbon dioxide levels might cause global warming, which in turn could result in changes in precipitation patterns and evapotranspiration and in increases in sea level. This report describes the greenhouse effect; discusses the problems and uncertainties associated with the detection, prediction, and effects of climate change; and presents the results of sensitivity analyses of how climate change might affect water resources in the Delaware River basin. Sensitivity analyses suggest that potentially serious shortfalls of certain water resources in the basin could result if some scenarios for climate change come true . The results of model simulations of the basin streamflow demonstrate the difficulty in distinguishing the effects that climate change versus natural climate variability have on streamflow and water supply . The future direction of basin changes in most water resources, furthermore, cannot be precisely determined because of uncertainty in current projections of regional temperature and precipitation . This large uncertainty indicates that, for resource planning, information defining the sensitivities of water resources to a range of climate change is most relevant . The sensitivity analyses could be useful in developing contingency plans for evaluating and responding to changes, should they occur.

Economic evaluation of linaclotide for the treatment of adult patients with irritable bowel syndrome with constipation in the United States.

PubMed

Huang, Huan; Taylor, Douglas C A; Carson, Robyn T; Sarocco, Phil; Friedman, Mark; Munsell, Michael; Blum, Steven I; Menzin, Joseph

2015-04-01

To use techniques of decision-analytic modeling to evaluate the effectiveness and costs of linaclotide vs lubiprostone in the treatment of adult patients with irritable bowel syndrome with constipation (IBS-C). Using model inputs derived from published literature, linaclotide Phase III trial data and a physician survey, a decision-tree model was constructed. Response to therapy was defined as (1) a ≥ 14-point increase from baseline in IBS-Quality-of-Life (IBS-QoL) questionnaire overall score at week 12 or (2) one of the top two responses (moderately/significantly relieved) on a 7-point IBS symptom relief question in ≥ 2 of 3 months. Patients who do not respond to therapy are assumed to fail therapy and accrue costs associated with a treatment failure. Model time horizon is aligned with clinical trial duration of 12 weeks. Model outputs include number of responders, quality-adjusted life-years (QALYs), and total costs (including direct and indirect). Both one-way and probabilistic sensitivity analyses were conducted. Treatment for IBS-C with linaclotide produced more responders than lubiprostone for both response definitions (19.3% vs 13.0% and 61.8% vs 57.2% for IBS-QoL and symptom relief, respectively), lower per-patient costs ($803 vs $911 and $977 vs $1056), and higher QALYs (0.1921 vs 0.1917 and 0.1909 vs 0.1894) over the 12-week time horizon. Results were similar for most one-way sensitivity analyses. In probabilistic sensitivity analyses, the majority of simulations resulted in linaclotide having higher treatment response rates and lower per-patient costs. There are no available head-to-head trials that compare linaclotide with lubiprostone; therefore, placebo-adjusted estimates of relative efficacy were derived for model inputs. The time horizon for this model is relatively short, as it was limited to the duration of available clinical trial data. Linaclotide was found to be a less costly option vs lubiprostone for the treatment of adult patients with IBS-C.

Cost-effectiveness Analysis of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction.

PubMed

Gaziano, Thomas A; Fonarow, Gregg C; Claggett, Brian; Chan, Wing W; Deschaseaux-Voinet, Celine; Turner, Stuart J; Rouleau, Jean L; Zile, Michael R; McMurray, John J V; Solomon, Scott D

2016-09-01

The angiotensin receptor neprilysin inhibitor sacubitril/valsartan was associated with a reduction in cardiovascular mortality, all-cause mortality, and hospitalizations compared with enalapril. Sacubitril/valsartan has been approved for use in heart failure (HF) with reduced ejection fraction in the United States and cost has been suggested as 1 factor that will influence the use of this agent. To estimate the cost-effectiveness of sacubitril/valsartan vs enalapril in the United States. Data from US adults (mean [SD] age, 63.8 [11.5] years) with HF with reduced ejection fraction and characteristics similar to those in the PARADIGM-HF trial were used as inputs for a 2-state Markov model simulated HF. Risks of all-cause mortality and hospitalization from HF or other reasons were estimated with a 30-year time horizon. Quality of life was based on trial EQ-5D scores. Hospital costs combined Medicare and private insurance reimbursement rates; medication costs included the wholesale acquisition cost for sacubitril/valsartan and enalapril. A discount rate of 3% was used. Sensitivity analyses were performed on key inputs including: hospital costs, mortality benefit, hazard ratio for hospitalization reduction, drug costs, and quality-of-life estimates. Hospitalizations, quality-adjusted life-years (QALYs), costs, and incremental costs per QALY gained. The 2-state Markov model of US adult patients (mean age, 63.8 years) calculated that there would be 220 fewer hospital admissions per 1000 patients with HF treated with sacubitril/valsartan vs enalapril over 30 years. The incremental costs and QALYs gained with sacubitril/valsartan treatment were estimated at $35 512 and 0.78, respectively, compared with enalapril, equating to an incremental cost-effectiveness ratio (ICER) of $45 017 per QALY for the base-case. Sensitivity analyses demonstrated ICERs ranging from $35 357 to $75 301 per QALY. For eligible patients with HF with reduced ejection fraction, the Markov model calculated that sacubitril/valsartan would increase life expectancy at an ICER consistent with other high-value accepted cardiovascular interventions. Sensitivity analyses demonstrated sacubitril/valsartan would remain cost-effective vs enalapril.

A Fast, Accurate and Sensitive GC-FID Method for the Analyses of Glycols in Water and Urine

NASA Technical Reports Server (NTRS)

Kuo, C. Mike; Alverson, James T.; Gazda, Daniel B.

2017-01-01

Glycols, specifically ethylene glycol and 1,2-propanediol, are some of the major organic compounds found in the humidity condensate samples collected on the International Space Station. The current analytical method for glycols is a GC/MS method with direct sample injection. This method is simple and fast, but it is not very sensitive. Reporting limits for ethylene glycol and 1,2-propanediol are only 1 ppm. A much more sensitive GC/FID method was developed, in which glycols were derivatized with benzoyl chloride for 10 minutes before being extracted with hexane. Using 1,3-propanediol as an internal standard, the detection limits for the GC/FID method was determined to be 50 ppb and the analysis only takes 7 minutes. Data from the GC/MS and the new GC/FID methods shows excellent agreement with each other. Factors affecting the sensitivity, including sample volume, NaOH concentration and volume, volume of benzoyl chloride, reaction time and temperature, were investigated. Interferences during derivatization and possible method to reduce interferences were also investigated.

Sensitivity analysis of a coupled hydrodynamic-vegetation model using the effectively subsampled quadratures method

USGS Publications Warehouse

Kalra, Tarandeep S.; Aretxabaleta, Alfredo; Seshadri, Pranay; Ganju, Neil K.; Beudin, Alexis

2017-01-01

Coastal hydrodynamics can be greatly affected by the presence of submerged aquatic vegetation. The effect of vegetation has been incorporated into the Coupled-Ocean-Atmosphere-Wave-Sediment Transport (COAWST) Modeling System. The vegetation implementation includes the plant-induced three-dimensional drag, in-canopy wave-induced streaming, and the production of turbulent kinetic energy by the presence of vegetation. In this study, we evaluate the sensitivity of the flow and wave dynamics to vegetation parameters using Sobol' indices and a least squares polynomial approach referred to as Effective Quadratures method. This method reduces the number of simulations needed for evaluating Sobol' indices and provides a robust, practical, and efficient approach for the parameter sensitivity analysis. The evaluation of Sobol' indices shows that kinetic energy, turbulent kinetic energy, and water level changes are affected by plant density, height, and to a certain degree, diameter. Wave dissipation is mostly dependent on the variation in plant density. Performing sensitivity analyses for the vegetation module in COAWST provides guidance for future observational and modeling work to optimize efforts and reduce exploration of parameter space.

Improving the Sensitivity of Mass Spectrometry by Using a New Sheath Flow Electrospray Emitter Array at Subambient Pressures

DOE PAGES

Cox, Jonathan T.; Marginean, Ioan; Kelly, Ryan T.; ...

2014-03-28

Arrays of chemically etched emitters with individualized sheath gas capillaries have been developed to enhance electrospray ionization (ESI) at subambient pressures. By including an emitter array in a subambient pressure ionization with nanoelectrospray (SPIN) source, ionization and transmission efficiency can be maximized allowing for increased sensitivity in mass spectrometric analyses. The SPIN source eliminates the major ion losses at conventional ESI-mass spectrometry (MS) interface by placing the emitter in the first vacuum region of the instrument. To facilitate stable electrospray currents in such conditions we have developed an improved emitter array with individualized sheath gas around each emitter. The utilitymore » of the new emitter arrays for generating stable multi-electrosprays at subambient pressures was probed by coupling the emitter array/SPIN source with a time of flight (TOF) mass spectrometer. The instrument sensitivity was compared between single emitter/SPIN-MS and multi-emitter/SPIN-MS configurations using an equimolar solution of 9 peptides. An increase in sensitivity correlative to the number of emitters in the array was observed.« less

Improving the Sensitivity of Mass Spectrometry by Using a New Sheath Flow Electrospray Emitter Array at Subambient Pressures

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

Cox, Jonathan T.; Marginean, Ioan; Kelly, Ryan T.

Arrays of chemically etched emitters with individualized sheath gas capillaries have been developed to enhance electrospray ionization (ESI) at subambient pressures. By including an emitter array in a subambient pressure ionization with nanoelectrospray (SPIN) source, ionization and transmission efficiency can be maximized allowing for increased sensitivity in mass spectrometric analyses. The SPIN source eliminates the major ion losses at conventional ESI-mass spectrometry (MS) interface by placing the emitter in the first vacuum region of the instrument. To facilitate stable electrospray currents in such conditions we have developed an improved emitter array with individualized sheath gas around each emitter. The utilitymore » of the new emitter arrays for generating stable multi-electrosprays at subambient pressures was probed by coupling the emitter array/SPIN source with a time of flight (TOF) mass spectrometer. The instrument sensitivity was compared between single emitter/SPIN-MS and multi-emitter/SPIN-MS configurations using an equimolar solution of 9 peptides. An increase in sensitivity correlative to the number of emitters in the array was observed.« less

Beware the black box: investigating the sensitivity of FEA simulations to modelling factors in comparative biomechanics.

PubMed

Walmsley, Christopher W; McCurry, Matthew R; Clausen, Phillip D; McHenry, Colin R

2013-01-01

Finite element analysis (FEA) is a computational technique of growing popularity in the field of comparative biomechanics, and is an easily accessible platform for form-function analyses of biological structures. However, its rapid evolution in recent years from a novel approach to common practice demands some scrutiny in regards to the validity of results and the appropriateness of assumptions inherent in setting up simulations. Both validation and sensitivity analyses remain unexplored in many comparative analyses, and assumptions considered to be 'reasonable' are often assumed to have little influence on the results and their interpretation. HERE WE REPORT AN EXTENSIVE SENSITIVITY ANALYSIS WHERE HIGH RESOLUTION FINITE ELEMENT (FE) MODELS OF MANDIBLES FROM SEVEN SPECIES OF CROCODILE WERE ANALYSED UNDER LOADS TYPICAL FOR COMPARATIVE ANALYSIS: biting, shaking, and twisting. Simulations explored the effect on both the absolute response and the interspecies pattern of results to variations in commonly used input parameters. Our sensitivity analysis focuses on assumptions relating to the selection of material properties (heterogeneous or homogeneous), scaling (standardising volume, surface area, or length), tooth position (front, mid, or back tooth engagement), and linear load case (type of loading for each feeding type). Our findings show that in a comparative context, FE models are far less sensitive to the selection of material property values and scaling to either volume or surface area than they are to those assumptions relating to the functional aspects of the simulation, such as tooth position and linear load case. Results show a complex interaction between simulation assumptions, depending on the combination of assumptions and the overall shape of each specimen. Keeping assumptions consistent between models in an analysis does not ensure that results can be generalised beyond the specific set of assumptions used. Logically, different comparative datasets would also be sensitive to identical simulation assumptions; hence, modelling assumptions should undergo rigorous selection. The accuracy of input data is paramount, and simulations should focus on taking biological context into account. Ideally, validation of simulations should be addressed; however, where validation is impossible or unfeasible, sensitivity analyses should be performed to identify which assumptions have the greatest influence upon the results.

Beware the black box: investigating the sensitivity of FEA simulations to modelling factors in comparative biomechanics

PubMed Central

McCurry, Matthew R.; Clausen, Phillip D.; McHenry, Colin R.

2013-01-01

Finite element analysis (FEA) is a computational technique of growing popularity in the field of comparative biomechanics, and is an easily accessible platform for form-function analyses of biological structures. However, its rapid evolution in recent years from a novel approach to common practice demands some scrutiny in regards to the validity of results and the appropriateness of assumptions inherent in setting up simulations. Both validation and sensitivity analyses remain unexplored in many comparative analyses, and assumptions considered to be ‘reasonable’ are often assumed to have little influence on the results and their interpretation. Here we report an extensive sensitivity analysis where high resolution finite element (FE) models of mandibles from seven species of crocodile were analysed under loads typical for comparative analysis: biting, shaking, and twisting. Simulations explored the effect on both the absolute response and the interspecies pattern of results to variations in commonly used input parameters. Our sensitivity analysis focuses on assumptions relating to the selection of material properties (heterogeneous or homogeneous), scaling (standardising volume, surface area, or length), tooth position (front, mid, or back tooth engagement), and linear load case (type of loading for each feeding type). Our findings show that in a comparative context, FE models are far less sensitive to the selection of material property values and scaling to either volume or surface area than they are to those assumptions relating to the functional aspects of the simulation, such as tooth position and linear load case. Results show a complex interaction between simulation assumptions, depending on the combination of assumptions and the overall shape of each specimen. Keeping assumptions consistent between models in an analysis does not ensure that results can be generalised beyond the specific set of assumptions used. Logically, different comparative datasets would also be sensitive to identical simulation assumptions; hence, modelling assumptions should undergo rigorous selection. The accuracy of input data is paramount, and simulations should focus on taking biological context into account. Ideally, validation of simulations should be addressed; however, where validation is impossible or unfeasible, sensitivity analyses should be performed to identify which assumptions have the greatest influence upon the results. PMID:24255817

HYPNOTIC TACTILE ANESTHESIA: Psychophysical and Signal-Detection Analyses

PubMed Central

Tataryn, Douglas J.; Kihlstrom, John F.

2017-01-01

Two experiments that studied the effects of hypnotic suggestions on tactile sensitivity are reported. Experiment 1 found that suggestions for anesthesia, as measured by both traditional psychophysical methods and signal detection procedures, were linearly related to hypnotizability. Experiment 2 employed the same methodologies in an application of the real-simulator paradigm to examine the effects of suggestions for both anesthesia and hyperesthesia. Significant effects of hypnotic suggestion on both sensitivity and bias were found in the anesthesia condition but not for the hyperesthesia condition. A new bias parameter, C′, indicated that much of the bias found in the initial analyses was artifactual, a function of changes in sensitivity across conditions. There were no behavioral differences between reals and simulators in any of the conditions, though analyses of postexperimental interviews suggested the 2 groups had very different phenomenal experiences. PMID:28230465

Automated haematology analysis to diagnose malaria

PubMed Central

2010-01-01

For more than a decade, flow cytometry-based automated haematology analysers have been studied for malaria diagnosis. Although current haematology analysers are not specifically designed to detect malaria-related abnormalities, most studies have found sensitivities that comply with WHO malaria-diagnostic guidelines, i.e. ≥ 95% in samples with > 100 parasites/μl. Establishing a correct and early malaria diagnosis is a prerequisite for an adequate treatment and to minimizing adverse outcomes. Expert light microscopy remains the 'gold standard' for malaria diagnosis in most clinical settings. However, it requires an explicit request from clinicians and has variable accuracy. Malaria diagnosis with flow cytometry-based haematology analysers could become an important adjuvant diagnostic tool in the routine laboratory work-up of febrile patients in or returning from malaria-endemic regions. Haematology analysers so far studied for malaria diagnosis are the Cell-Dyn®, Coulter® GEN·S and LH 750, and the Sysmex XE-2100® analysers. For Cell-Dyn analysers, abnormal depolarization events mainly in the lobularity/granularity and other scatter-plots, and various reticulocyte abnormalities have shown overall sensitivities and specificities of 49% to 97% and 61% to 100%, respectively. For the Coulter analysers, a 'malaria factor' using the monocyte and lymphocyte size standard deviations obtained by impedance detection has shown overall sensitivities and specificities of 82% to 98% and 72% to 94%, respectively. For the XE-2100, abnormal patterns in the DIFF, WBC/BASO, and RET-EXT scatter-plots, and pseudoeosinophilia and other abnormal haematological variables have been described, and multivariate diagnostic models have been designed with overall sensitivities and specificities of 86% to 97% and 81% to 98%, respectively. The accuracy for malaria diagnosis may vary according to species, parasite load, immunity and clinical context where the method is applied. Future developments in new haematology analysers such as considerably simplified, robust and inexpensive devices for malaria detection fitted with an automatically generated alert could improve the detection capacity of these instruments and potentially expand their clinical utility in malaria diagnosis. PMID:21118557

Cost-effectiveness of chronic hepatitis C treatment with thymosin alpha-1.

PubMed

García-Contreras, Fernando; Nevárez-Sida, Armando; Constantino-Casas, Patricia; Abud-Bastida, Fernando; Garduño-Espinosa, Juan

2006-07-01

More than one million individuals in Mexico are infected with hepatitis C virus (HCV), and 80% are at risk for developing a chronic infection that could lead to hepatic cirrhosis and other complications that impact quality of life and institutional costs. The objective of the study was to determine the most cost-effective treatment against HCV among the following: peginterferon, peginterferon plus ribavirin, peginterferon plus ribavirin plus thymosin, and no treatment. We carried out cost-effectiveness analysis using the institutional perspective, including a 45-year time frame and a 3% discount rate for costs and effectiveness. We employed a Bayesian-focused decision tree and a Markov model. One- and two-way sensitivity analyses were performed, as well as threshold-oriented and probabilistic analyses, and we obtained acceptability curves and net health benefits. Triple therapy (peginterferon plus ribavirin plus thymosin alpha-1) was dominant with lower cost and higher utility in relationship with peginterferon + ribavirin option, peginterferon alone and no-treatment option. In triple therapy the cost per unit of success was of 1,908 [USD/quality-adjusted life years (QALY)] compared with peginterferon plus ribavirin 2,277/QALY, peginterferon alone 2,929/QALY, and no treatment 4,204/QALY. Sensitivity analyses confirmed the robustness of the base case. Peginterferon plus ribavirin plus thymosin alpha-1 option was dominant (lowest cost and highest effectiveness). Using no drug was the most expensive and least effective option.

Get even and feel good? Moderating effects of justice sensitivity and counterproductive work behavior on the relationship between illegitimate tasks and self-esteem.

PubMed

Schulte-Braucks, Julia; Baethge, Anja; Dormann, Christian; Vahle-Hinz, Tim

2018-04-23

We proposed that effects of illegitimate tasks, which comprise unreasonable and unnecessary tasks, on self-esteem and counterproductive work behavior (CWB) are enhanced among employees who are highly sensitive to injustice. CWB was further proposed to be a moderating coping strategy, which restores justice and buffers the detrimental effects of illegitimate tasks on self-esteem. In this study, 241 employees participated in a diary study over five workdays and a follow-up questionnaire one week later. Daily effects were determined in multilevel analyses: Unreasonable tasks decreased self-esteem and increased CWB the same day, especially among employees high in trait justice sensitivity. Unnecessary tasks only related to more CWB the same day, regardless of one's justice sensitivity. Weekly effects were determined in cross-lagged panel analyses: Unreasonable and unnecessary tasks increased CWB, and justice sensitivity moderated the effect of unreasonable tasks on CWB and of unnecessary tasks on self-esteem. Moderating effects of CWB were split: In daily analyses, CWB buffered the negative effects of illegitimate tasks. In weekly analyses, CWB enhanced the negative effects of illegitimate tasks. Overall, illegitimate tasks rather affected CWB than self-esteem, with more consistent effects for unreasonable than for unnecessary tasks. Thus, we confirm illegitimate tasks as a relevant work stressor with issues of injustice being central to this concept and personality having an influence on what is perceived as (il)legitimate. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Optimum sensitivity derivatives of objective functions in nonlinear programming

NASA Technical Reports Server (NTRS)

Barthelemy, J.-F. M.; Sobieszczanski-Sobieski, J.

1983-01-01

The feasibility of eliminating second derivatives from the input of optimum sensitivity analyses of optimization problems is demonstrated. This elimination restricts the sensitivity analysis to the first-order sensitivity derivatives of the objective function. It is also shown that when a complete first-order sensitivity analysis is performed, second-order sensitivity derivatives of the objective function are available at little additional cost. An expression is derived whose application to linear programming is presented.

Sensitivity and specificity of subacute computerized neurocognitive testing and symptom evaluation in predicting outcomes after sports-related concussion.

PubMed

Lau, Brian C; Collins, Michael W; Lovell, Mark R

2011-06-01

Concussions affect an estimated 136 000 high school athletes yearly. Computerized neurocognitive testing has been shown to be appropriately sensitive and specific in diagnosing concussions, but no studies have assessed its utility to predict length of recovery. Determining prognosis during subacute recovery after sports concussion will help clinicians more confidently address return-to-play and academic decisions. To quantify the prognostic ability of computerized neurocognitive testing in combination with symptoms during the subacute recovery phase from sports-related concussion. Cohort study (prognosis); Level of evidence, 2. In sum, 108 male high school football athletes completed a computer-based neurocognitive test battery within 2.23 days of injury and were followed until returned to play as set by international guidelines. Athletes were grouped into protracted recovery (>14 days; n = 50) or short-recovery (≤14 days; n = 58). Separate discriminant function analyses were performed using total symptom score on Post-Concussion Symptom Scale, symptom clusters (migraine, cognitive, sleep, neuropsychiatric), and Immediate Postconcussion Assessment and Cognitive Testing neurocognitive scores (verbal memory, visual memory, reaction time, processing speed). Multiple discriminant function analyses revealed that the combination of 4 symptom clusters and 4 neurocognitive composite scores had the highest sensitivity (65.22%), specificity (80.36%), positive predictive value (73.17%), and negative predictive value (73.80%) in predicting protracted recovery. Discriminant function analyses of total symptoms on the Post-Concussion Symptom Scale alone had a sensitivity of 40.81%; specificity, 79.31%; positive predictive value, 62.50%; and negative predictive value, 61.33%. The 4 symptom clusters alone discriminant function analyses had a sensitivity of 46.94%; specificity, 77.20%; positive predictive value, 63.90%; and negative predictive value, 62.86%. Discriminant function analyses of the 4 computerized neurocognitive scores alone had a sensitivity of 53.20%; specificity, 75.44%; positive predictive value, 64.10%; and negative predictive value, 66.15%. The use of computerized neurocognitive testing in conjunction with symptom clusters results improves sensitivity, specificity, positive predictive value, and negative predictive value of predicting protracted recovery compared with each used alone. There is also a net increase in sensitivity of 24.41% when using neurocognitive testing and symptom clusters together compared with using total symptoms on Post-Concussion Symptom Scale alone.

Development and validation of a prediction model for measurement variability of lung nodule volumetry in patients with pulmonary metastases.

PubMed

Hwang, Eui Jin; Goo, Jin Mo; Kim, Jihye; Park, Sang Joon; Ahn, Soyeon; Park, Chang Min; Shin, Yeong-Gil

2017-08-01

To develop a prediction model for the variability range of lung nodule volumetry and validate the model in detecting nodule growth. For model development, 50 patients with metastatic nodules were prospectively included. Two consecutive CT scans were performed to assess volumetry for 1,586 nodules. Nodule volume, surface voxel proportion (SVP), attachment proportion (AP) and absolute percentage error (APE) were calculated for each nodule and quantile regression analyses were performed to model the 95% percentile of APE. For validation, 41 patients who underwent metastasectomy were included. After volumetry of resected nodules, sensitivity and specificity for diagnosis of metastatic nodules were compared between two different thresholds of nodule growth determination: uniform 25% volume change threshold and individualized threshold calculated from the model (estimated 95% percentile APE). SVP and AP were included in the final model: Estimated 95% percentile APE = 37.82 · SVP + 48.60 · AP-10.87. In the validation session, the individualized threshold showed significantly higher sensitivity for diagnosis of metastatic nodules than the uniform 25% threshold (75.0% vs. 66.0%, P = 0.004) CONCLUSION: Estimated 95% percentile APE as an individualized threshold of nodule growth showed greater sensitivity in diagnosing metastatic nodules than a global 25% threshold. • The 95 % percentile APE of a particular nodule can be predicted. • Estimated 95 % percentile APE can be utilized as an individualized threshold. • More sensitive diagnosis of metastasis can be made with an individualized threshold. • Tailored nodule management can be provided during nodule growth follow-up.

Sunflower seeds as eliciting agents of Compositae dermatitis.

PubMed

Paulsen, Evy; El-Houri, Rime B; Andersen, Klaus E; Christensen, Lars P

2015-03-01

Sunflowers may cause dermatitis because of allergenic sesquiterpene lactones (SLs). Contact sensitization to sunflower seeds has also been reported, but the allergens are unknown. To analyse sunflower seeds for the presence of SLs and to assess the prevalence of sunflower sensitization in Compositae-allergic individuals. Sunflower-sensitive patients were identified by aimed patch testing. A dichloromethane extract of whole sunflower seeds was analysed by liquid chromatography-mass spectrometry and high-performance liquid chromatography. The prevalence of sensitivity to sunflower in Compositae-allergic individuals was 56%. A solvent wash of whole sunflower seeds yielded an extract containing SLs, the principal component tentatively being identified as argophyllin A or B, other SLs being present in minute amounts. The concentration of SLs on the sunflower seeds is considered high enough to elicit dermatitis in sensitive persons, and it seems appropriate to warn Compositae-allergic subjects against handling sunflower seeds. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Climate services to improve public health.

PubMed

Jancloes, Michel; Thomson, Madeleine; Costa, María Mánez; Hewitt, Chris; Corvalan, Carlos; Dinku, Tufa; Lowe, Rachel; Hayden, Mary

2014-04-25

A high level expert panel discussed how climate and health services could best collaborate to improve public health. This was on the agenda of the recent Third International Climate Services Conference, held in Montego Bay, Jamaica, 4-6 December 2013. Issues and challenges concerning a demand led approach to serve the health sector needs, were identified and analysed. Important recommendations emerged to ensure that innovative collaboration between climate and health services assist decision-making processes and the management of climate-sensitive health risk. Key recommendations included: a move from risk assessment towards risk management; the engagement of the public health community with both the climate sector and development sectors, whose decisions impact on health, particularly the most vulnerable; to increase operational research on the use of policy-relevant climate information to manage climate- sensitive health risks; and to develop in-country capacities to improve local knowledge (including collection of epidemiological, climate and socio-economic data), along with institutional interaction with policy makers.

Additional EIPC Study Analysis. Final Report

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

Hadley, Stanton W; Gotham, Douglas J.; Luciani, Ralph L.

Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations weremore » developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 14 topics was developed for further analysis. This paper brings together the earlier interim reports of the first 13 topics plus one additional topic into a single final report.« less

Preoperative localization strategies for primary hyperparathyroidism: an economic analysis.

PubMed

Lubitz, Carrie C; Stephen, Antonia E; Hodin, Richard A; Pandharipande, Pari

2012-12-01

Strategies for localizing parathyroid pathology preoperatively vary in cost and accuracy. Our purpose was to compute and compare comprehensive costs associated with common localization strategies. A decision-analytic model was developed to evaluate comprehensive, short-term costs of parathyroid localization strategies for patients with primary hyperparathyroidism. Eight strategies were compared. Probabilities of accurate localization were extracted from the literature, and costs associated with each strategy were based on 2011 Medicare reimbursement schedules. Differential cost considerations included outpatient versus inpatient surgeries, operative time, and costs of imaging. Sensitivity analyses were performed to determine effects of variability in key model parameters upon model results. Ultrasound (US) followed by 4D-CT was the least expensive strategy ($5,901), followed by US alone ($6,028), and 4D-CT alone ($6,110). Strategies including sestamibi (SM) were more expensive, with associated expenditures of up to $6,329 for contemporaneous US and SM. Four-gland, bilateral neck exploration (BNE) was the most expensive strategy ($6,824). Differences in cost were dependent upon differences in the sensitivity of each strategy for detecting single-gland disease, which determined the proportion of patients able to undergo outpatient minimally invasive parathyroidectomy. In sensitivity analysis, US alone was preferred over US followed by 4D-CT only when both the sensitivity of US alone for detecting an adenoma was ≥ 94 %, and the sensitivity of 4D-CT following negative US was ≤ 39 %. 4D-CT alone was the least costly strategy when US sensitivity was ≤ 31 %. Among commonly used strategies for preoperative localization of parathyroid pathology, US followed by selective 4D-CT is the least expensive.

Risk Factors for Hearing Decrement Among U.S. Air Force Aviation-Related Personnel.

PubMed

Greenwell, Brandon M; Tvaryanas, Anthony P; Maupin, Genny M

2018-02-01

The purpose of this study was to analyze historical hearing sensitivity data to determine factors associated with an occupationally significant change in hearing sensitivity in U.S. Air Force aviation-related personnel. This study was a longitudinal, retrospective cohort analysis of audiogram records for Air Force aviation-related personnel on active duty during calendar year 2013 without a diagnosis of non-noise-related hearing loss. The outcomes of interest were raw change in hearing sensitivity from initial baseline to 2013 audiogram and initial occurrence of a significant threshold shift (STS) and non-H1 audiogram profile. Potential predictor variables included age and elapsed time in cohort for each audiogram, gender, and Air Force Specialty Code. Random forest analyses conducted on a learning sample were used to identify relevant predictor variables. Mixed effects models were fitted to a separate validation sample to make statistical inferences. The final dataset included 167,253 nonbaseline audiograms on 10,567 participants. Only the interaction between time since baseline audiogram and age was significantly associated with raw change in hearing sensitivity by STS metric. None of the potential predictors were associated with the likelihood for an STS. Time since baseline audiogram, age, and their interaction were significantly associated with the likelihood for a non-HI hearing profile. In this study population, age and elapsed time since baseline audiogram were modestly associated with decreased hearing sensitivity and increased likelihood for a non-H1 hearing profile. Aircraft type, as determined from Air Force Specialty Code, was not associated with changes in hearing sensitivity by STS metric.Greenwell BM, Tvaryanas AP, Maupin GM. Risk factors for hearing decrement among U.S. Air Force aviation-related personnel. Aerosp Med Hum Perform. 2018; 89(2):80-86.

Longitudinal study of visual function in patients with relapsing-remitting multiple sclerosis with and without a history of optic neuritis.

PubMed

González Gómez, A; García-Ben, A; Soler García, A; García-Basterra, I; Padilla Parrado, F; García-Campos, J M

2017-03-15

The contrast sensitivity test determines the quality of visual function in patients with multiple sclerosis (MS). The purpose of this study is to analyse changes in visual function in patients with relapsing-remitting MS with and without a history of optic neuritis (ON). We conducted a longitudinal study including 61 patients classified into 3 groups as follows: a) disease-free patients (control group); b) patients with MS and no history of ON; and c) patients with MS and a history of unilateral ON. All patients underwent baseline and 6-year follow-up ophthalmologic examinations, which included visual acuity and monocular and binocular Pelli-Robson contrast sensitivity tests. Monocular contrast sensitivity was significantly lower in MS patients with and without a history of ON than in controls both at baseline (P=.00 and P=.01, respectively) and at 6 years (P=.01 and P=.02). Patients with MS and no history of ON remained stable throughout follow-up whereas those with a history of ON displayed a significant loss of contrast sensitivity (P=.01). Visual acuity and binocular contrast sensitivity at baseline and at 6 years was significantly lower in the group of patients with a history of ON than in the control group (P=.003 and P=.002 vs P=.006 and P=.005) and the group with no history of ON (P=.04 and P=.038 vs P=.008 and P=.01). However, no significant differences were found in follow-up results (P=.1 and P=.5). Monocular Pelli-Robson contrast sensitivity test may be used to detect changes in visual function in patients with ON. Copyright © 2017 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.

Metabolomics: beyond biomarkers and towards mechanisms

PubMed Central

Johnson, Caroline H.; Ivanisevic, Julijana; Siuzdak, Gary

2017-01-01

Metabolomics, which is the profiling of metabolites in biofluids, cells and tissues, is routinely applied as a tool for biomarker discovery. Owing to innovative developments in informatics and analytical technologies, and the integration of orthogonal biological approaches, it is now possible to expand metabolomic analyses to understand the systems-level effects of metabolites. Moreover, because of the inherent sensitivity of metabolomics, subtle alterations in biological pathways can be detected to provide insight into the mechanisms that underlie various physiological conditions and aberrant processes, including diseases. PMID:26979502

Preliminary post-emplacement safety analysis of the subseabed disposal of high-level nuclear waste

NASA Astrophysics Data System (ADS)

Kaplan, M. F.; Koplik, C. M.; Klett, R. D.

1984-09-01

The radiological hazard from the disposal of high-level nuclear waste within the deep ocean sediments is evaluated, on a preliminary basis, for locations in the central North Pacific and in the northwestern Atlantic. Radio-nuclide transport in the sediment and water column and by marine organisms is considered. Peak doses to an individual are approximately five orders of magnitude below background levels for both sites. Sensitivity analyses for most aspects of the post-emplacement systems models are included.

Image encryption based on a delayed fractional-order chaotic logistic system

NASA Astrophysics Data System (ADS)

Wang, Zhen; Huang, Xia; Li, Ning; Song, Xiao-Na

2012-05-01

A new image encryption scheme is proposed based on a delayed fractional-order chaotic logistic system. In the process of generating a key stream, the time-varying delay and fractional derivative are embedded in the proposed scheme to improve the security. Such a scheme is described in detail with security analyses including correlation analysis, information entropy analysis, run statistic analysis, mean-variance gray value analysis, and key sensitivity analysis. Experimental results show that the newly proposed image encryption scheme possesses high security.

Implementation of structural response sensitivity calculations in a large-scale finite-element analysis system

NASA Technical Reports Server (NTRS)

Giles, G. L.; Rogers, J. L., Jr.

1982-01-01

The implementation includes a generalized method for specifying element cross-sectional dimensions as design variables that can be used in analytically calculating derivatives of output quantities from static stress, vibration, and buckling analyses for both membrane and bending elements. Limited sample results for static displacements and stresses are presented to indicate the advantages of analytically calclating response derivatives compared to finite difference methods. Continuing developments to implement these procedures into an enhanced version of the system are also discussed.

Analysing uncertainties of supply and demand in the future use of hydrogen as an energy vector

NASA Astrophysics Data System (ADS)

Lenel, U. R.; Davies, D. G. S.; Moore, M. A.

An analytical technique (Analysis with Uncertain Qualities), developed at Fulmer, is being used to examine the sensitivity of the outcome to uncertainties in input quantities in order to highlight which input quantities critically affect the potential role of hydrogen. The work presented here includes an outline of the model and the analysis technique, along with basic considerations of the input quantities to the model (demand, supply and constraints). Some examples are given of probabilistic estimates of input quantities.

Manpower Mix for Health Services

PubMed Central

Shuman, Larry J.; Young, John P.; Naddor, Eliezer

1971-01-01

A model is formulated to determine the mix of manpower and technology needed to provide health services of acceptable quality at a minimum total cost to the community. Total costs include both the direct costs associated with providing the services and with developing additional manpower and the indirect costs (shortage costs) resulting from not providing needed services. The model is applied to a hypothetical neighborhood health center, and its sensitivity to alternative policies is investigated by cost-benefit analyses. Possible extensions of the model to include dynamic elements in health delivery systems are discussed, as is its adaptation for use in hospital planning, with a changed objective function. PMID:5095652

Satellite broadcasting system study

NASA Technical Reports Server (NTRS)

1972-01-01

The study to develop a system model and computer program representative of broadcasting satellite systems employing community-type receiving terminals is reported. The program provides a user-oriented tool for evaluating performance/cost tradeoffs, synthesizing minimum cost systems for a given set of system requirements, and performing sensitivity analyses to identify critical parameters and technology. The performance/ costing philosophy and what is meant by a minimum cost system is shown graphically. Topics discussed include: main line control program, ground segment model, space segment model, cost models and launch vehicle selection. Several examples of minimum cost systems resulting from the computer program are presented. A listing of the computer program is also included.

Sibship size, sibling cognitive sensitivity, and children's receptive vocabulary.

PubMed

Prime, Heather; Pauker, Sharon; Plamondon, André; Perlman, Michal; Jenkins, Jennifer

2014-02-01

The aim of the current study was to examine the relationship between sibship size and children's vocabulary as a function of quality of sibling interactions. It was hypothesized that coming from a larger sibship (ie, 3+ children) would be related to lower receptive vocabulary in children. However, we expected this association to be moderated by the level of cognitive sensitivity shown by children's next-in-age older siblings. Data on 385 children (mean age = 3.15 years) and their next-in-age older siblings (mean age = 5.57 years) were collected and included demographic questionnaires, direct testing of children's receptive vocabulary, and videos of mother-child and sibling interactions. Sibling dyads were taped engaging in a cooperative building task and tapes were coded for the amount of cognitive sensitivity the older sibling exhibited toward the younger sibling. Hierarchical regression analyses were conducted and showed an interaction between sibship size and sibling cognitive sensitivity in the prediction of children's receptive vocabulary; children exposed to large sibships whose next-in-age older sibling exhibited higher levels of cognitive sensitivity were less likely to show low vocabulary skills when compared with those children exposed to large sibships whose siblings showed lower levels of cognitive sensitivity. Children who show sensitivity to the cognitive needs of their younger siblings provide a rich environment for language development. The negative impact of large sibships on language development is moderated by the presence of an older sibling who shows high cognitive sensitivity.

Social Regulation of Leukocyte Homeostasis: The Role of Glucocorticoid Sensitivity

PubMed Central

Cole, Steve W.

2010-01-01

Recent small-scale genomics analyses suggest that physiologic regulation of pro-inflammatory gene expression by endogenous glucocorticoids may be compromised in individuals who experience chronic social isolation. This could potentially contribute to the elevated prevalence of inflammation-related disease previously observed in social isolates. The present study assessed the relationship between leukocyte distributional sensitivity to glucocorticoid regulation and subjective social isolation in a large population-based sample of older adults. Initial analyses confirmed that circulating neutrophil percentages were elevated, and circulating lymphocyte and monocyte percentages were suppressed, in direct proportion to circulating cortisol levels. However, leukocyte distributional sensitivity to endogenous glucocorticoids was abrogated in individuals reporting either occasional or frequent experiences of subjective social isolation. This finding held in both nonparametric univariate analyses and in multivariate linear models controlling for a variety of biological, social, behavioral, and psychological confounders. The present results suggest that social factors may alter immune cell sensitivity to physiologic regulation by the hypothalamic-pituitary-adrenal axis in ways that could ultimately contribute to the increased physical health risks associated with social isolation. PMID:18394861

Parameter sensitivity and identifiability for a biogeochemical model of hypoxia in the northern Gulf of Mexico

EPA Science Inventory

Local sensitivity analyses and identifiable parameter subsets were used to describe numerical constraints of a hypoxia model for bottom waters of the northern Gulf of Mexico. The sensitivity of state variables differed considerably with parameter changes, although most variables ...

MOESHA: A genetic algorithm for automatic calibration and estimation of parameter uncertainty and sensitivity of hydrologic models

EPA Science Inventory

Characterization of uncertainty and sensitivity of model parameters is an essential and often overlooked facet of hydrological modeling. This paper introduces an algorithm called MOESHA that combines input parameter sensitivity analyses with a genetic algorithm calibration routin...

Sensitive and selective determination of methylenedioxylated amphetamines by high-performance liquid chromatography with fluorimetric detection.

PubMed

Sadeghipour, F; Veuthey, J L

1997-11-07

A rapid, sensitive and selective liquid chromatographic method with fluorimetric detection was developed for the separation and quantification of four methylenedioxylated amphetamines without interference of other drugs of abuse and common substances found in illicit tablets. The method was validated by examining linearity, precision and accuracy as well as detection and quantification limits. Methylenedioxylated amphetamines were quantified in eight tablets from illicit drug seizures and results were quantitatively compared to HPLC-UV analyses. To demonstrate the better sensitivity of the fluorimetric detection, methylenedioxylated amphetamines were analyzed in serum after a liquid-liquid extraction procedure and results were also compared to HPLC-UV analyses.

The mode of sensitization and its influence on allograft outcomes in highly sensitized kidney transplant recipients.

PubMed

Redfield, Robert R; Scalea, Joseph R; Zens, Tiffany J; Mandelbrot, Didier A; Leverson, Glen; Kaufman, Dixon B; Djamali, Arjang

2016-10-01

We sought to determine whether the mode of sensitization in highly sensitized patients contributed to kidney allograft survival. An analysis of the United Network for Organ Sharing dataset involving all kidney transplants between 1997 and 2014 was undertaken. Highly sensitized adult kidney transplant recipients [panel reactive antibody (PRA) ≥98%] were compared with adult, primary non-sensitized and re-transplant recipients. Kaplan-Meier survival analyses were used to determine allograft survival rates. Cox proportional hazards regression analyses were conducted to determine the association of graft loss with key predictors. Fifty-three percent of highly sensitized patients transplanted were re-transplants. Pregnancy and transfusion were the only sensitizing event in 20 and 5%, respectively. The 10-year actuarial graft survival for highly sensitized recipients was 43.9% compared with 52.4% for non-sensitized patients, P < 0.001. The combination of being highly sensitized by either pregnancy or blood transfusion increased the risk of graft loss by 23% [hazard ratio (HR) 1.230, confidence interval (CI) 1.150-1.315, P < 0.001], and the combination of being highly sensitized from a prior transplant increased the risk of graft loss by 58.1% (HR 1.581, CI 1.473-1.698, P < 0.001). The mode of sensitization predicts graft survival in highly sensitized kidney transplant recipients (PRA ≥98%). Patients who are highly sensitized from re-transplants have inferior graft survival compared with patients who are highly sensitized from other modes of sensitization. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Technological advances in bovine mastitis diagnosis: an overview.

PubMed

Duarte, Carla M; Freitas, Paulo P; Bexiga, Ricardo

2015-11-01

Bovine mastitis is an economic burden for dairy farmers and preventive control measures are crucial for the sustainability of any dairy business. The identification of etiological agents is necessary in controlling the disease, reducing risk of chronic infections and targeting antimicrobial therapy. The suitability of a detection method for routine diagnosis depends on several factors, including specificity, sensitivity, cost, time in producing results, and suitability for large-scale sampling of milk. This article focuses on current methodologies for identification of mastitis pathogens and for detection of inflammation, as well as the advantages and disadvantages of different methods. Emerging technologies, such as transcriptome and proteome analyses and nano- and microfabrication of portable devices, offer promising, sensitive methods for advanced detection of mastitis pathogens and biomarkers of inflammation. The demand for alternative, fast, and reliable diagnostic procedures is rising as farms become bigger. Several examples of technological and scientific advances are summarized which have given rise to more sensitive, reliable and faster diagnostic results. © 2015 The Author(s).

Comparison of real-time PCR methods for the detection of Naegleria fowleri in surface water and sediment.

PubMed

Streby, Ashleigh; Mull, Bonnie J; Levy, Karen; Hill, Vincent R

2015-05-01

Naegleria fowleri is a thermophilic free-living ameba found in freshwater environments worldwide. It is the cause of a rare but potentially fatal disease in humans known as primary amebic meningoencephalitis. Established N. fowleri detection methods rely on conventional culture techniques and morphological examination followed by molecular testing. Multiple alternative real-time PCR assays have been published for rapid detection of Naegleria spp. and N. fowleri. Foursuch assays were evaluated for the detection of N. fowleri from surface water and sediment. The assays were compared for thermodynamic stability, analytical sensitivity and specificity, detection limits, humic acid inhibition effects, and performance with seeded environmental matrices. Twenty-one ameba isolates were included in the DNA panel used for analytical sensitivity and specificity analyses. N. fowleri genotypes I and III were used for method performance testing. Two of the real-time PCR assays were determined to yield similar performance data for specificity and sensitivity for detecting N. fowleri in environmental matrices.

Comparison of real-time PCR methods for the detection of Naegleria fowleri in surface water and sediment

PubMed Central

Streby, Ashleigh; Mull, Bonnie J.; Levy, Karen

2015-01-01

Naegleria fowleri is a thermophilic free-living ameba found in freshwater environments worldwide. It is the cause of a rare but potentially fatal disease in humans known as primary amebic meningoencephalitis. Established N. fowleri detection methods rely on conventional culture techniques and morphological examination followed by molecular testing. Multiple alternative real-time PCR assays have been published for rapid detection of Naegleria spp. and N. fowleri. Four such assays were evaluated for the detection of N. fowleri from surface water and sediment. The assays were compared for thermodynamic stability, analytical sensitivity and specificity, detection limits, humic acid inhibition effects, and performance with seeded environmental matrices. Twenty-one ameba isolates were included in the DNA panel used for analytical sensitivity and specificity analyses. N. fowleri genotypes I and III were used for method performance testing. Two of the real-time PCR assays were determined to yield similar performance data for specificity and sensitivity for detecting N. fowleri in environmental matrices. PMID:25855343

The cellulose synthase 3 (CesA3) gene of oomycetes: structure, phylogeny and influence on sensitivity to carboxylic acid amide (CAA) fungicides.

PubMed

Blum, Mathias; Gamper, Hannes A; Waldner, Maya; Sierotzki, Helge; Gisi, Ulrich

2012-04-01

Proper disease control is very important to minimize yield losses caused by oomycetes in many crops. Today, oomycete control is partially achieved by breeding for resistance, but mainly by application of single-site mode of action fungicides including the carboxylic acid amides (CAAs). Despite having mostly specific targets, fungicidal activity can differ even in species belonging to the same phylum but the underlying mechanisms are often poorly understood. In an attempt to elucidate the phylogenetic basis and underlying molecular mechanism of sensitivity and tolerance to CAAs, the cellulose synthase 3 (CesA3) gene was isolated and characterized, encoding the target site of this fungicide class. The CesA3 gene was present in all 25 species included in this study representing the orders Albuginales, Leptomitales, Peronosporales, Pythiales, Rhipidiales and Saprolegniales, and based on phylogenetic analyses, enabled good resolution of all the different taxonomic orders. Sensitivity assays using the CAA fungicide mandipropamid (MPD) demonstrated that only species belonging to the Peronosporales were inhibited by the fungicide. Molecular data provided evidence, that the observed difference in sensitivity to CAAs between Peronosporales and CAA tolerant species is most likely caused by an inherent amino acid configuration at position 1109 in CesA3 possibly affecting fungicide binding. The present study not only succeeded in linking CAA sensitivity of various oomycetes to the inherent CesA3 target site configuration, but could also relate it to the broader phylogenetic context. Copyright © 2012 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease.

PubMed

Carroll, C Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A; Campbell, Claudia M

2016-07-01

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared the severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis); central sensitization; and depression and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Effects of matrix shrinkage and swelling on the economics of enhanced-coalbed-methane production and CO{sub 2} sequestration in coal

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

Gorucu, F.B.; Jikich, S.A.; Bromhal, G.S.

2007-08-15

In this work, the Palmer-Mansoori model for coal shrinkage and permeability increases during primary methane production was rewritten to also account for coal swelling caused by CO{sub 2} sorption. The generalized model was added to a compositional, dual porosity coalbed-methane reservoir simulator for primary (CBM) and ECBM production. A standard five-spot of vertical wells and representative coal properties for Appalachian coals was used. Simulations and sensitivity analyses were performed with the modified simulator for nine different parameters, including coal seam and operational parameters and economic criteria. The coal properties and operating parameters that were varied included Young's modulus, Poisson's ratio,more » cleat porosity, and injection pressure. The economic variables included CH{sub 4}, price, Col Cost, CO{sub 2} credit, water disposal cost, and interest rate. Net-present value (NPV) analyses of the simulation results included profits resulting from CH{sub 4}, production and potential incentives for sequestered CO{sub 2}, This work shows that for some coal seams, the combination of compressibility, cleat porosity, and shrinkage/swelling of the coal may have a significant impact on project economics.« less

msgbsR: An R package for analysing methylation-sensitive restriction enzyme sequencing data.

PubMed

Mayne, Benjamin T; Leemaqz, Shalem Y; Buckberry, Sam; Rodriguez Lopez, Carlos M; Roberts, Claire T; Bianco-Miotto, Tina; Breen, James

2018-02-01

Genotyping-by-sequencing (GBS) or restriction-site associated DNA marker sequencing (RAD-seq) is a practical and cost-effective method for analysing large genomes from high diversity species. This method of sequencing, coupled with methylation-sensitive enzymes (often referred to as methylation-sensitive restriction enzyme sequencing or MRE-seq), is an effective tool to study DNA methylation in parts of the genome that are inaccessible in other sequencing techniques or are not annotated in microarray technologies. Current software tools do not fulfil all methylation-sensitive restriction sequencing assays for determining differences in DNA methylation between samples. To fill this computational need, we present msgbsR, an R package that contains tools for the analysis of methylation-sensitive restriction enzyme sequencing experiments. msgbsR can be used to identify and quantify read counts at methylated sites directly from alignment files (BAM files) and enables verification of restriction enzyme cut sites with the correct recognition sequence of the individual enzyme. In addition, msgbsR assesses DNA methylation based on read coverage, similar to RNA sequencing experiments, rather than methylation proportion and is a useful tool in analysing differential methylation on large populations. The package is fully documented and available freely online as a Bioconductor package ( https://bioconductor.org/packages/release/bioc/html/msgbsR.html ).

Trends and advances in food analysis by real-time polymerase chain reaction.

PubMed

Salihah, Nur Thaqifah; Hossain, Mohammad Mosharraf; Lubis, Hamadah; Ahmed, Minhaz Uddin

2016-05-01

Analyses to ensure food safety and quality are more relevant now because of rapid changes in the quantity, diversity and mobility of food. Food-contamination must be determined to maintain health and up-hold laws, as well as for ethical and cultural concerns. Real-time polymerase chain reaction (RT-PCR), a rapid and inexpensive quantitative method to detect the presence of targeted DNA-segments in samples, helps in determining both accidental and intentional adulterations of foods by biological contaminants. This review presents recent developments in theory, techniques, and applications of RT-PCR in food analyses, RT-PCR addresses the limitations of traditional food analyses in terms of sensitivity, range of analytes, multiplexing ability, cost, time, and point-of-care applications. A range of targets, including species of plants or animals which are used as food ingredients, food-borne bacteria or viruses, genetically modified organisms, and allergens, even in highly processed foods can be identified by RT-PCR, even at very low concentrations. Microfluidic RT-PCR eliminates the separate sample-processing step to create opportunities for point-of-care analyses. We also cover the challenges related to using RT-PCR for food analyses, such as the need to further improve sample handling.

Reprint of: Relationship between cataract severity and socioeconomic status.

PubMed

Wesolosky, Jason D; Rudnisky, Christopher J

2015-06-01

To determine the relationship between cataract severity and socioeconomic status (SES). Retrospective, observational case series. A total of 1350 eyes underwent phacoemulsification cataract extraction by a single surgeon using an Alcon Infiniti system. Cataract severity was measured using phaco time in seconds. SES was measured using area-level aggregate census data: median income, education, proportion of common-law couples, and employment rate. Preoperative best corrected visual acuity was obtained and converted to logarithm of the minimum angle of resolution values. For patients undergoing bilateral surgery, the generalized estimating equation was used to account for the correlation between eyes. Univariate analyses were performed using simple regression, and multivariate analyses were performed to account for variables with significant relationships (p < 0.05) on univariate testing. Sensitivity analyses were performed to assess the effect of including patient age in the controlled analyses. Multivariate analyses demonstrated that cataracts were more severe when the median income was lower (p = 0.001) and the proportion of common-law couples living in a patient's community (p = 0.012) and the unemployment rate (p = 0.002) were higher. These associations persisted even when controlling for patient age. Patients of lower SES have more severe cataracts. Copyright © 2015. Published by Elsevier Inc.

Contact allergy to epoxy hardeners.

PubMed

Aalto-Korte, Kristiina; Suuronen, Katri; Kuuliala, Outi; Henriks-Eckerman, Maj-Len; Jolanki, Riitta

2014-09-01

Diglycidylether of bisphenol A resin is the most important sensitizer in epoxy systems, but a minority of patients develop concomitant or solitary contact allergy to epoxy hardeners. At the Finnish Institute of Occupational Health, several in-house test substances of epoxy hardeners have been tested in a special epoxy compound patch test series. To analyse the frequency and clinical relevance of allergic reactions to different epoxy hardeners. Test files (January 1991 to March 2013) were screened for contact allergy to different epoxy hardeners, and the clinical records of patients with allergic reactions were analysed for occupation, concomitant allergic reactions, and exposure. The most commonly positive epoxy hardeners were m-xylylenediamine (n = 24), 2,4,6-tris-(dimethylaminomethyl)phenol (tris-DMP; n = 14), isophorone-diamine (n = 12), and diethylenetriamine (n = 9). Trimethylhexamethylenediamine (n = 7), tetraethylenepentamine (n = 4), and triethylenetetramine (n = 2) elicited some reactions, although most patients were found to have no specific exposure. Allergic reactions to hexamethylenetetramine, dimethylaminopropylamine and ethylenediamine dihydrochloride were not related to epoxy products. Tris-DMP is an important sensitizer in epoxy hardeners, and should be included in the patch test series of epoxy chemicals. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dietary fiber intake reduces risk for Barrett's esophagus and esophageal cancer.

PubMed

Sun, Lingli; Zhang, Zhizhong; Xu, Jian; Xu, Gelin; Liu, Xinfeng

2017-09-02

Observational studies suggest an association between dietary fiber intake and risk of Barrett's esophagus and esophageal cancer. However, the results are inconsistent. To conduct a meta-analysis of observational studies to assess this association. All eligible studies were identified by electronic searches in PubMed and Embase through February 2015. Dose-response, subgroup, sensitivity, and publication bias analyses were performed. A total of 15 studies involving 16,885 subjects were included in the meta-analysis. The pooled odds ratio for the highest compared with the lowest dietary fiber intake was 0.52 (95% CI, 0.43-0.64). Stratified analyses for tumor subtype, study design, geographic location, fiber type, publication year, total sample size, and quality score yielded consistent results. Dose-response analysis indicated that a 10-g/d increment in dietary fiber intake was associated with a 31% reduction in Barrett's esophagus and esophageal cancer risk. Sensitivity analysis restricted to studies with control for conventional risk factors produced similar results, and omission of any single study had little effect on the overall risk estimate. Our findings indicate that dietary fiber intake is inversely associated with risk of Barrett's esophagus and esophageal cancer. Further large prospective studies are warranted.

Disclosure Control using Partially Synthetic Data for Large-Scale Health Surveys, with Applications to CanCORS

PubMed Central

Loong, Bronwyn; Zaslavsky, Alan M.; He, Yulei; Harrington, David P.

2013-01-01

Statistical agencies have begun to partially synthesize public-use data for major surveys to protect the confidentiality of respondents’ identities and sensitive attributes, by replacing high disclosure risk and sensitive variables with multiple imputations. To date, there are few applications of synthetic data techniques to large-scale healthcare survey data. Here, we describe partial synthesis of survey data collected by CanCORS, a comprehensive observational study of the experiences, treatments, and outcomes of patients with lung or colorectal cancer in the United States. We review inferential methods for partially synthetic data, and discuss selection of high disclosure risk variables for synthesis, specification of imputation models, and identification disclosure risk assessment. We evaluate data utility by replicating published analyses and comparing results using original and synthetic data, and discuss practical issues in preserving inferential conclusions. We found that important subgroup relationships must be included in the synthetic data imputation model, to preserve the data utility of the observed data for a given analysis procedure. We conclude that synthetic CanCORS data are suited best for preliminary data analyses purposes. These methods address the requirement to share data in clinical research without compromising confidentiality. PMID:23670983

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry*

PubMed Central

Burnum-Johnson, Kristin E.; Nie, Song; Casey, Cameron P.; Monroe, Matthew E.; Orton, Daniel J.; Ibrahim, Yehia M.; Gritsenko, Marina A.; Clauss, Therese R. W.; Shukla, Anil K.; Moore, Ronald J.; Purvine, Samuel O.; Shi, Tujin; Qian, Weijun; Liu, Tao; Baker, Erin S.; Smith, Richard D.

2016-01-01

Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. PMID:27670688

Emotion-motion interactions in conversion disorder: an FMRI study.

PubMed

Aybek, Selma; Nicholson, Timothy R; O'Daly, Owen; Zelaya, Fernando; Kanaan, Richard A; David, Anthony S

2015-01-01

To evaluate the neural correlates of implicit processing of negative emotions in motor conversion disorder (CD) patients. An event related fMRI task was completed by 12 motor CD patients and 14 matched healthy controls using standardised stimuli of faces with fearful and sad emotional expressions in comparison to faces with neutral expressions. Temporal changes in the sensitivity to stimuli were also modelled and tested in the two groups. We found increased amygdala activation to negative emotions in CD compared to healthy controls in region of interest analyses, which persisted over time consistent with previous findings using emotional paradigms. Furthermore during whole brain analyses we found significantly increased activation in CD patients in areas involved in the 'freeze response' to fear (periaqueductal grey matter), and areas involved in self-awareness and motor control (cingulate gyrus and supplementary motor area). In contrast to healthy controls, CD patients exhibited increased response amplitude to fearful stimuli over time, suggesting abnormal emotional regulation (failure of habituation / sensitization). Patients with CD also activated midbrain and frontal structures that could reflect an abnormal behavioral-motor response to negative including threatening stimuli. This suggests a mechanism linking emotions to motor dysfunction in CD.

A value-based medicine cost-utility analysis of idiopathic epiretinal membrane surgery.

PubMed

Gupta, Omesh P; Brown, Gary C; Brown, Melissa M

2008-05-01

To perform a reference case, cost-utility analysis of epiretinal membrane (ERM) surgery using current literature on outcomes and complications. Computer-based, value-based medicine analysis. Decision analyses were performed under two scenarios: ERM surgery in better-seeing eye and ERM surgery in worse-seeing eye. The models applied long-term published data primarily from the Blue Mountains Eye Study and the Beaver Dam Eye Study. Visual acuity and major complications were derived from 25-gauge pars plana vitrectomy studies. Patient-based, time trade-off utility values, Markov modeling, sensitivity analysis, and net present value adjustments were used in the design and calculation of results. Main outcome measures included the number of discounted quality-adjusted-life-years (QALYs) gained and dollars spent per QALY gained. ERM surgery in the better-seeing eye compared with observation resulted in a mean gain of 0.755 discounted QALYs (3% annual rate) per patient treated. This model resulted in $4,680 per QALY for this procedure. When sensitivity analysis was performed, utility values varied from $6,245 to $3,746/QALY gained, medical costs varied from $3,510 to $5,850/QALY gained, and ERM recurrence rate increased to $5,524/QALY. ERM surgery in the worse-seeing eye compared with observation resulted in a mean gain of 0.27 discounted QALYs per patient treated. The $/QALY was $16,146 with a range of $20,183 to $12,110 based on sensitivity analyses. Utility values ranged from $21,520 to $12,916/QALY and ERM recurrence rate increased to $16,846/QALY based on sensitivity analysis. ERM surgery is a very cost-effective procedure when compared with other interventions across medical subspecialties.

Laser Therapy in the Treatment of Paresthesia: A Retrospective Study of 125 Clinical Cases.

PubMed

de Oliveira, Renata Ferreira; da Silva, Alessandro Costa; Simões, Alyne; Youssef, Michel Nicolau; de Freitas, Patrícia Moreira

2015-08-01

The aim of this retrospective study was to evaluate the effectiveness of laser therapy for acceleration and recovery of nerve sensitivity after orthognathic or minor oral surgeries, by analysis of clinical records of patients treated at the Special Laboratory of Lasers in Dentistry (LELO, School of Dentistry, University of São Paulo), throughout the period 2007-2013. Nerve tissue lesions may occur during various dental and routine surgical procedures, resulting in paresthesia. Laser therapy has been shown to be able to accelerate and enhance the regeneration of the affected nerve tissue; however, there are few studies in the literature that evaluate the effects of treatment with low-power laser on neural changes after orthognathic or minor oral surgeries. A total of 125 clinical records were included, and the data on gender, age, origin of the lesion, nerve, interval between surgery and onset of laser therapy, frequency of laser irradiation (one or two times per week), final evolution, and if there was a need to change the irradiation protocol, were all recorded. These data were related to the recovery of sensitivity in the affected nerve area. Descriptive analyses and modeling for analysis of categorical data (α=5%) were performed. The results from both analyses showed that the recovery of sensitivity was correlated with patient age (p=0.015) and interval between surgery and onset of laser therapy (p=0.002). Within the limits of this retrospective study, it was found that low- power laser therapy with beam emission band in the infrared spectrum (808 nm) can positively affect the recovery of sensitivity after orthognathic or minor oral surgeries.

The Intercultural Sensitivity of Chilean Teachers Serving an Immigrant Population in Schools

ERIC Educational Resources Information Center

Morales Mendoza, Karla; Sanhueza Henríquez, Susan; Friz Carrillo, Miguel; Riquelme Bravo, Paula

2017-01-01

The objective of this article is to evaluate the intercultural sensitivity of teachers working in culturally diverse classrooms, and to analyse differences in intercultural sensitivity based on the gender, age, training (advanced training courses), and intercultural experience of the teachers. A quantitative approach with a comparative descriptive…

Analysis of Sensitivity and Uncertainty in an Individual-Based Model of a Threatened Wildlife Species

EPA Science Inventory

We present a multi-faceted sensitivity analysis of a spatially explicit, individual-based model (IBM) (HexSim) of a threatened species, the Northern Spotted Owl (Strix occidentalis caurina) on a national forest in Washington, USA. Few sensitivity analyses have been conducted on ...

Preparation for implementation of the mechanistic-empirical pavement design guide in Michigan : part 2 - evaluation of rehabilitation fixes (part 2).

DOT National Transportation Integrated Search

2013-08-01

The overall goal of Global Sensitivity Analysis (GSA) is to determine sensitivity of pavement performance prediction models to the variation in the design input values. The main difference between GSA and detailed sensitivity analyses is the way the ...

Economic Impact of Dengue Illness in the Americas

PubMed Central

Shepard, Donald S.; Coudeville, Laurent; Halasa, Yara A.; Zambrano, Betzana; Dayan, Gustavo H.

2011-01-01

The growing burden of dengue in endemic countries and outbreaks in previously unaffected countries stress the need to assess the economic impact of this disease. This paper synthesizes existing studies to calculate the economic burden of dengue illness in the Americas from a societal perspective. Major data sources include national case reporting data from 2000 to 2007, prospective cost of illness studies, and analyses quantifying underreporting in national routine surveillance systems. Dengue illness in the Americas was estimated to cost $2.1 billion per year on average (in 2010 US dollars), with a range of $1–4 billion in sensitivity analyses and substantial year to year variation. The results highlight the substantial economic burden from dengue in the Americas. The burden for dengue exceeds that from other viral illnesses, such as human papillomavirus (HPV) or rotavirus. Because this study does not include some components (e.g., vector control), it may still underestimate total economic consequences of dengue. PMID:21292885

The childhood executive function inventory: confirmatory factor analyses and cross-cultural clinical validity in a sample of 8- to 11-year-old children.

PubMed

Catale, Corinne; Meulemans, Thierry; Thorell, Lisa B

2015-06-01

The aim was to investigate the psychometric characteristics of the French adaptation of the Childhood Executive Functioning Inventory (CHEXI) in children and to explore the cross-cultural validity of the CHEXI in discriminating between children with ADHD and controls in two culturally different samples (Belgian and Swedish). Study I included normally developing children (n = 242), whereas Study II included both children diagnosed with ADHD (n = 87) and controls (n = 87). CHEXI ratings were collected from parents. Confirmatory factor analyses replicated the two-factor solution, referred to as inhibition and working memory, which had been identified previously. Both subscales had good psychometric properties. Furthermore, the CHEXI was found to discriminate, with high sensitivity and specificity, between children with ADHD and controls in both cultural samples. The CHEXI can be considered as a valuable screening measure for ADHD in children, but the cross-cultural clinical implications of ratings have to be considered. © 2013 SAGE Publications.

A spectral power analysis of driving behavior changes during the transition from nondistraction to distraction.

PubMed

Wang, Yuan; Bao, Shan; Du, Wenjun; Ye, Zhirui; Sayer, James R

2017-11-17

This article investigated and compared frequency domain and time domain characteristics of drivers' behaviors before and after the start of distracted driving. Data from an existing naturalistic driving study were used. Fast Fourier transform (FFT) was applied for the frequency domain analysis to explore drivers' behavior pattern changes between nondistracted (prestarting of visual-manual task) and distracted (poststarting of visual-manual task) driving periods. Average relative spectral power in a low frequency range (0-0.5 Hz) and the standard deviation in a 10-s time window of vehicle control variables (i.e., lane offset, yaw rate, and acceleration) were calculated and further compared. Sensitivity analyses were also applied to examine the reliability of the time and frequency domain analyses. Results of the mixed model analyses from the time and frequency domain analyses all showed significant degradation in lateral control performance after engaging in visual-manual tasks while driving. Results of the sensitivity analyses suggested that the frequency domain analysis was less sensitive to the frequency bandwidth, whereas the time domain analysis was more sensitive to the time intervals selected for variation calculations. Different time interval selections can result in significantly different standard deviation values, whereas average spectral power analysis on yaw rate in both low and high frequency bandwidths showed consistent results, that higher variation values were observed during distracted driving when compared to nondistracted driving. This study suggests that driver state detection needs to consider the behavior changes during the prestarting periods, instead of only focusing on periods with physical presence of distraction, such as cell phone use. Lateral control measures can be a better indicator of distraction detection than longitudinal controls. In addition, frequency domain analyses proved to be a more robust and consistent method in assessing driving performance compared to time domain analyses.

Phylogenomic analyses reveal novel relationships among snake families.

PubMed

Streicher, Jeffrey W; Wiens, John J

2016-07-01

Snakes are a diverse and important group of vertebrates. However, relationships among the major groups of snakes have remained highly uncertain, with recent studies hypothesizing very different (and typically weakly supported) relationships. Here, we address family-level snake relationships with new phylogenomic data from 3776 nuclear loci from ultraconserved elements (1.40million aligned base pairs, 52% missing data overall) sampled from 29 snake species that together represent almost all families, a dataset ∼100 times larger than used in previous studies. We found relatively strong support from species-tree analyses (NJst) for most relationships, including three largely novel clades: (1) a clade uniting the boas, pythons and their relatives, (2) a clade placing cylindrophiids and uropeltids with this clade, and (3) a clade uniting bolyeriids (Round Island boas) with pythonids and their relatives (xenopeltids and loxocemids). Relationships among families of advanced snakes (caenophidians) were also strongly supported. The results show the potential for phylogenomic analyses to resolve difficult groups, but also show a surprising sensitivity of the analyses to the inclusion or exclusion of outgroups. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation and recommendation of sensitivity analysis methods for application to Stochastic Human Exposure and Dose Simulation models.

PubMed

Mokhtari, Amirhossein; Christopher Frey, H; Zheng, Junyu

2006-11-01

Sensitivity analyses of exposure or risk models can help identify the most significant factors to aid in risk management or to prioritize additional research to reduce uncertainty in the estimates. However, sensitivity analysis is challenged by non-linearity, interactions between inputs, and multiple days or time scales. Selected sensitivity analysis methods are evaluated with respect to their applicability to human exposure models with such features using a testbed. The testbed is a simplified version of a US Environmental Protection Agency's Stochastic Human Exposure and Dose Simulation (SHEDS) model. The methods evaluated include the Pearson and Spearman correlation, sample and rank regression, analysis of variance, Fourier amplitude sensitivity test (FAST), and Sobol's method. The first five methods are known as "sampling-based" techniques, wheras the latter two methods are known as "variance-based" techniques. The main objective of the test cases was to identify the main and total contributions of individual inputs to the output variance. Sobol's method and FAST directly quantified these measures of sensitivity. Results show that sensitivity of an input typically changed when evaluated under different time scales (e.g., daily versus monthly). All methods provided similar insights regarding less important inputs; however, Sobol's method and FAST provided more robust insights with respect to sensitivity of important inputs compared to the sampling-based techniques. Thus, the sampling-based methods can be used in a screening step to identify unimportant inputs, followed by application of more computationally intensive refined methods to a smaller set of inputs. The implications of time variation in sensitivity results for risk management are briefly discussed.

Should cell-free DNA testing be used to target antenatal rhesus immune globulin administration?

PubMed

Ma, Kimberly K; Rodriguez, Maria I; Cheng, Yvonne W; Norton, Mary E; Caughey, Aaron B

2016-01-01

To compare the rates of alloimmunization with the use of cell-free DNA (cfDNA) screening to target antenatal rhesus immune globulin (RhIG) prenatally, versus routine administration of RhIG in rhesus D (RhD)-negative pregnant women in a theoretic cohort using a decision-analytic model. A decision-analytic model compared cfDNA testing to routine antenatal RhIG administration. The primary outcome was maternal sensitization to RhD antigen. Sensitivity and specificity of cfDNA testing were assumed to be 99.8% and 95.3%, respectively. Univariate and bivariate sensitivity analyses, Monte Carlo simulation, and threshold analyses were performed. In a cohort of 10,000 RhD-negative women, 22.6 sensitizations would occur with utilization of cfDNA, while 20 sensitizations would occur with routine RhIG. Only when the sensitivity of the cfDNA test reached 100%, the rate of sensitization was equal for both cfDNA and RhIG. Otherwise, routine RhIG minimized the rate of sensitization, especially given RhIG is readily available in the United States. Adoption of cfDNA testing would result in a 13.0% increase in sensitization among RhD-negative women in a theoretical cohort taking into account the ethnic diversity of the United States' population.

Protein molecular data from ancient (>1 million years old) fossil material: pitfalls, possibilities and grand challenges.

PubMed

Schweitzer, Mary Higby; Schroeter, Elena R; Goshe, Michael B

2014-07-15

Advances in resolution and sensitivity of analytical techniques have provided novel applications, including the analyses of fossil material. However, the recovery of original proteinaceous components from very old fossil samples (defined as >1 million years (1 Ma) from previously named limits in the literature) is far from trivial. Here, we discuss the challenges to recovery of proteinaceous components from fossils, and the need for new sample preparation techniques, analytical methods, and bioinformatics to optimize and fully utilize the great potential of information locked in the fossil record. We present evidence for survival of original components across geological time, and discuss the potential benefits of recovery, analyses, and interpretation of fossil materials older than 1 Ma, both within and outside of the fields of evolutionary biology.

Design, analysis, and test verification of advanced encapsulation systems

NASA Technical Reports Server (NTRS)

Mardesich, N.; Minning, C.

1982-01-01

Design sensitivities are established for the development of photovoltaic module criteria and the definition of needed research tasks. The program consists of three phases. In Phase I, analytical models were developed to perform optical, thermal, electrical, and structural analyses on candidate encapsulation systems. From these analyses several candidate systems will be selected for qualification testing during Phase II. Additionally, during Phase II, test specimens of various types will be constructed and tested to determine the validity of the analysis methodology developed in Phase I. In Phse III, a finalized optimum design based on knowledge gained in Phase I and II will be developed. All verification testing was completed during this period. Preliminary results and observations are discussed. Descriptions of the thermal, thermal structural, and structural deflection test setups are included.

Cost effectiveness analysis of immunotherapy in patients with grass pollen allergic rhinoconjunctivitis in Germany.

PubMed

Westerhout, K Y; Verheggen, B G; Schreder, C H; Augustin, M

2012-01-01

An economic evaluation was conducted to assess the outcomes and costs as well as cost-effectiveness of the following grass-pollen immunotherapies: OA (Oralair; Stallergenes S.A., Antony, France) vs GRZ (Grazax; ALK-Abelló, Hørsholm, Denmark), and ALD (Alk Depot SQ; ALK-Abelló) (immunotherapy agents alongside symptomatic medication) and symptomatic treatment alone for grass pollen allergic rhinoconjunctivitis. The costs and outcomes of 3-year treatment were assessed for a period of 9 years using a Markov model. Treatment efficacy was estimated using an indirect comparison of available clinical trials with placebo as a common comparator. Estimates for immunotherapy discontinuation, occurrence of asthma, health state utilities, drug costs, resource use, and healthcare costs were derived from published sources. The analysis was conducted from the insurant's perspective including public and private health insurance payments and co-payments by insurants. Outcomes were reported as quality-adjusted life years (QALYs) and symptom-free days. The uncertainty around incremental model results was tested by means of extensive deterministic univariate and probabilistic multivariate sensitivity analyses. In the base case analysis the model predicted a cost-utility ratio of OA vs symptomatic treatment of €14,728 per QALY; incremental costs were €1356 (95%CI: €1230; €1484) and incremental QALYs 0.092 (95%CI: 0.052; 0.140). OA was the dominant strategy compared to GRZ and ALD, with estimated incremental costs of -€1142 (95%CI: -€1255; -€1038) and -€54 (95%CI: -€188; €85) and incremental QALYs of 0.015 (95%CI: -0.025; 0.056) and 0.027 (95%CI: -0.022; 0.075), respectively. At a willingness-to-pay threshold of €20,000, the probability of OA being the most cost-effective treatment was predicted to be 79%. Univariate sensitivity analyses show that incremental outcomes were moderately sensitive to changes in efficacy estimates. The main study limitation was the requirement of an indirect comparison involving several steps to assess relative treatment effects. The analysis suggests OA to be cost-effective compared to GRZ and ALD, and a symptomatic treatment. Sensitivity analyses showed that uncertainty surrounding treatment efficacy estimates affected the model outcomes.

msap: a tool for the statistical analysis of methylation-sensitive amplified polymorphism data.

PubMed

Pérez-Figueroa, A

2013-05-01

In this study msap, an R package which analyses methylation-sensitive amplified polymorphism (MSAP or MS-AFLP) data is presented. The program provides a deep analysis of epigenetic variation starting from a binary data matrix indicating the banding pattern between the isoesquizomeric endonucleases HpaII and MspI, with differential sensitivity to cytosine methylation. After comparing the restriction fragments, the program determines if each fragment is susceptible to methylation (representative of epigenetic variation) or if there is no evidence of methylation (representative of genetic variation). The package provides, in a user-friendly command line interface, a pipeline of different analyses of the variation (genetic and epigenetic) among user-defined groups of samples, as well as the classification of the methylation occurrences in those groups. Statistical testing provides support to the analyses. A comprehensive report of the analyses and several useful plots could help researchers to assess the epigenetic and genetic variation in their MSAP experiments. msap is downloadable from CRAN (http://cran.r-project.org/) and its own webpage (http://msap.r-forge.R-project.org/). The package is intended to be easy to use even for those people unfamiliar with the R command line environment. Advanced users may take advantage of the available source code to adapt msap to more complex analyses. © 2013 Blackwell Publishing Ltd.

Anaphylaxis to foods in a population of adolescents: incidence, characteristics and associated risks.

PubMed

Vetander, M; Protudjer, J L P; Lilja, G; Kull, I; Hedlin, G; van Hage, M; Östblom, E; Bergström, A; Wickman, M

2016-12-01

Information about severe reactions to foods in adolescence is limited. To describe reactions to foods, including anaphylaxis, with regard to incidence, characteristics and associated risks, among 16-year-olds (adolescents) in a large, population-based birth cohort. Parent-reported questionnaire data from ages 2-3 months, and 1, 2 and 16 years were used (N = 3153). Anaphylaxis at age 16 years was defined per NIAID/FAAN criteria. Immunoglobulin E (IgE) antibodies to 14 common food and inhalant allergens were analysed at ages 4 (n = 2283) and 16 years (n = 2510). Among adolescents with food-related symptoms (FRS) and for whom blood was available (n = 221), 25 additional food allergen extracts or allergen components were analysed. Associations between reactions to foods, and sensitization and allergic multimorbidity were investigated. In the 12 months prior to the 16-year assessment, 8.5% of adolescents had FRS. This included 0.8% (n = 24) adolescents who were classified as having anaphylaxis, yielding an incidence rate of 761/100 000 person-years. One-third of adolescents accessed health care during anaphylaxis. Allergic multimorbidity in infancy, as well as sensitization to foods and airborne allergens at age 4 years, was associated with an increased risk for FRS in adolescence. Peanuts and tree nuts were the most common culprit foods for anaphylaxis, and fruits and vegetables for non-anaphylactic reactions. Adolescents with anaphylaxis were significantly more likely to be sensitized to storage proteins (Ara h 2, Cor a 9, Cor a 14) and to be polysensitized to foods (P < 0.001 vs. non-anaphylactic reactions). The incidence of food-induced anaphylaxis during adolescence in our population-based birth cohort is higher than previously reported. Adolescents with anaphylaxis differ from adolescents with non-anaphylactic FRS with regard to culprit foods and sensitization. Adolescents with previous anaphylaxis are likely to be polysensitized to foods, particularly tree nut and peanut storage proteins, and which warrants consideration at follow-up. © 2016 John Wiley & Sons Ltd.

Psychological traits and the cortisol awakening response: results from the Netherlands Study of Depression and Anxiety.

PubMed

van Santen, Aafke; Vreeburg, Sophie A; Van der Does, A J Willem; Spinhoven, Philip; Zitman, Frans G; Penninx, Brenda W J H

2011-02-01

Hypothalamus-Pituitary-Adrenal (HPA) axis dysregulation is often seen in major depression, and is thought to represent a trait vulnerability - rather than merely an illness marker - for depressive disorder and possibly anxiety disorder. Vulnerability traits associated with stress-related disorders might reflect increased sensitivity for the development of psychopathology through an association with HPA axis activity. Few studies have examined the association between psychological trait factors and the cortisol awakening response, with inconsistent results. The present study examined the relationship between multiple psychological trait factors and the cortisol awakening curve, including both the dynamic of the CAR and overall cortisol awakening levels, in a sample of persons without psychopathology, hypothesizing that persons scoring high on vulnerability traits demonstrate an elevated cortisol awakening curve. From 2981 participants of the Netherlands Study of Depression and Anxiety (NESDA), baseline data from 381 controls (aged 18-65) without previous, current and parental depression and anxiety disorders were analyzed. Psychological measures included the Big Five personality traits (neuroticism, extraversion, openness to experience, conscientiousness, and agreeableness) measured using the NEO-FFI, anxiety sensitivity assessed by the Anxiety Sensitivity Index, cognitive reactivity to sadness (hopelessness, acceptance/coping, aggression, control/perfectionism, risk aversion, and rumination) as measured by the LEIDS-R questionnaire, and mastery, assessed using the Pearlin and Schooler Mastery scale. Salivary cortisol levels were measured at awakening, and 30, 45, and 60 min afterwards. In adjusted analyses, high scores of hopelessness reactivity (β=.13, p=.02) were consistently associated with a higher cortisol awakening response. In addition, although inconsistent across analyses, persons scoring higher on extraversion, control/perfectionism reactivity, and mastery tended to show a slightly flatter CAR. No significant associations were found for neuroticism, openness to experience, agreeableness, conscientiousness, anxiety sensitivity, and acceptance/coping, aggression, or risk aversion reactivity. Of various psychological traits, only hopelessness reactivity, a trait that has been associated with depression and suicidality, is consistently associated with HPA axis dysregulation. Hopelessness reactivity may represent a predisposing vulnerability for the development of a depressive or anxiety disorder, possibly in part mediated by HPA axis activity. Copyright © 2010 Elsevier Ltd. All rights reserved.

Developing graduate student competency in providing culturally sensitive end of life care in critical care environments - a pilot study of a teaching innovation.

PubMed

Northam, Holly L; Hercelinskyj, Gylo; Grealish, Laurie; Mak, Anita S

2015-11-01

Australia's immigration policy has generated a rich diverse cultural community of staff and patients in critical care environments. Many different cultural perspectives inform individual actions in the context of critical care, including the highly sensitive area of end of life care, with nurses feeling poorly prepared to provide culturally sensitive end of life care. This article describes and evaluates the effectiveness of an educational innovation designed to develop graduate-level critical care nurses' capacity for effective interpersonal communication, as members of a multi-disciplinary team in providing culturally sensitive end-of-life care. A mixed method pilot study was conducted using a curriculum innovation intervention informed by The Excellence in Cultural Experiential Learning and Leadership Program (EXCELL),(1) which is a higher education intervention which was applied to develop the nurses' intercultural communication skills. 12 graduate nursing students studying critical care nursing participated in the study. 42% (n=5) of the participants were from an international background. Information about students' cultural learning was recorded before and after the intervention, using a cultural learning development scale. Student discussions of end of life care were recorded at Week 2 and 14 of the curriculum. The quantitative data was analysed using descriptive statistical analysis and qualitative data was thematically analysed. Students demonstrated an increase in cultural learning in a range of areas in the pre-post surveys including understandings of cultural diversity, interpersonal skills, cross cultural interactions and participating in multicultural groups. Thematic analysis of the end of life discussions revealed an increase in the levels of nurse confidence in approaching end of life care in critical care environments. The EXCELL program provides an effective and supportive educational framework to increase graduate nurses' cultural learning development and competence to manage culturally complex clinical issues such as end of life care, and is recommended as a framework for health care students to learn the skills required to provide culturally competent care in a range of culturally complex health care settings. Copyright © 2015 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

Cost-Effectiveness Analysis of Probiotic Use to Prevent Clostridium difficile Infection in Hospitalized Adults Receiving Antibiotics.

PubMed

Shen, Nicole T; Leff, Jared A; Schneider, Yecheskel; Crawford, Carl V; Maw, Anna; Bosworth, Brian; Simon, Matthew S

2017-01-01

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. 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. 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. 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%.

Economic evaluation in chronic pain: a systematic review and de novo flexible economic model.

PubMed

Sullivan, W; Hirst, M; Beard, S; Gladwell, D; Fagnani, F; López Bastida, J; Phillips, C; Dunlop, W C N

2016-07-01

There is unmet need in patients suffering from chronic pain, yet innovation may be impeded by the difficulty of justifying economic value in a field beset by data limitations and methodological variability. A systematic review was conducted to identify and summarise the key areas of variability and limitations in modelling approaches in the economic evaluation of treatments for chronic pain. The results of the literature review were then used to support the development of a fully flexible open-source economic model structure, designed to test structural and data assumptions and act as a reference for future modelling practice. The key model design themes identified from the systematic review included: time horizon; titration and stabilisation; number of treatment lines; choice/ordering of treatment; and the impact of parameter uncertainty (given reliance on expert opinion). Exploratory analyses using the model to compare a hypothetical novel therapy versus morphine as first-line treatments showed cost-effectiveness results to be sensitive to structural and data assumptions. Assumptions about the treatment pathway and choice of time horizon were key model drivers. Our results suggest structural model design and data assumptions may have driven previous cost-effectiveness results and ultimately decisions based on economic value. We therefore conclude that it is vital that future economic models in chronic pain are designed to be fully transparent and hope our open-source code is useful in order to aspire to a common approach to modelling pain that includes robust sensitivity analyses to test structural and parameter uncertainty.

Symmetric encryption algorithms using chaotic and non-chaotic generators: A review

PubMed Central

Radwan, Ahmed G.; AbdElHaleem, Sherif H.; Abd-El-Hafiz, Salwa K.

2015-01-01

This paper summarizes the symmetric image encryption results of 27 different algorithms, which include substitution-only, permutation-only or both phases. The cores of these algorithms are based on several discrete chaotic maps (Arnold’s cat map and a combination of three generalized maps), one continuous chaotic system (Lorenz) and two non-chaotic generators (fractals and chess-based algorithms). Each algorithm has been analyzed by the correlation coefficients between pixels (horizontal, vertical and diagonal), differential attack measures, Mean Square Error (MSE), entropy, sensitivity analyses and the 15 standard tests of the National Institute of Standards and Technology (NIST) SP-800-22 statistical suite. The analyzed algorithms include a set of new image encryption algorithms based on non-chaotic generators, either using substitution only (using fractals) and permutation only (chess-based) or both. Moreover, two different permutation scenarios are presented where the permutation-phase has or does not have a relationship with the input image through an ON/OFF switch. Different encryption-key lengths and complexities are provided from short to long key to persist brute-force attacks. In addition, sensitivities of those different techniques to a one bit change in the input parameters of the substitution key as well as the permutation key are assessed. Finally, a comparative discussion of this work versus many recent research with respect to the used generators, type of encryption, and analyses is presented to highlight the strengths and added contribution of this paper. PMID:26966561

Economic evaluation of the 70-gene prognosis-signature (MammaPrint®) in hormone receptor-positive, lymph node-negative, human epidermal growth factor receptor type 2-negative early stage breast cancer in Japan.

PubMed

Kondo, Masahide; Hoshi, Shu-Ling; Ishiguro, Hiroshi; Toi, Masakazu

2012-06-01

The 70-gene prognosis-signature is validated as a good predictor of recurrence for hormone receptor-positive (ER+), lymph node-negative (LN-), human epidermal growth factor receptor type 2-negative (HER2-) early stage breast cancer (ESBC) in Japanese patient population. Its high cost and potential in avoiding unnecessary adjuvant chemotherapy arouse interest in its economic impact. This study evaluates the cost-effectiveness of including the assay into Japan's social health insurance benefit package. An economic decision tree and Markov model under Japan's health system from the societal perspective is constructed with clinical evidence from the pool analysis of validation studies. One-way sensitivity analyses are also performed. Incremental cost-effectiveness ratio is estimated as ¥3,873,922/quality adjusted life year (QALY) (US$43,044/QALY), which is not more than the suggested social willingness-to-pay for one QALY gain from an innovative medical intervention in Japan, ¥5,000,000/QALY (US$55,556/QALY). However, sensitivity analyses show the instability of this estimation. The introduction of the assay into Japanese practice of ER+, LN-, HER2- ESBC treatment by including it to Japan's social health insurance benefit package has a reasonable chance to be judged as cost-effective and may be justified as an efficient deployment of finite health care resources.

Recommendations for Methicillin-Resistant Staphylococcus aureus Prevention in Adult ICUs: A Cost-Effectiveness Analysis.

PubMed

Whittington, Melanie D; Atherly, Adam J; Curtis, Donna J; Lindrooth, Richard C; Bradley, Cathy J; Campbell, Jonathan D

2017-08-01

Patients in the ICU are at the greatest risk of contracting healthcare-associated infections like methicillin-resistant Staphylococcus aureus. This study calculates the cost-effectiveness of methicillin-resistant S aureus prevention strategies and recommends specific strategies based on screening test implementation. A cost-effectiveness analysis using a Markov model from the hospital perspective was conducted to determine if the implementation costs of methicillin-resistant S aureus prevention strategies are justified by associated reductions in methicillin-resistant S aureus infections and improvements in quality-adjusted life years. Univariate and probabilistic sensitivity analyses determined the influence of input variation on the cost-effectiveness. ICU. Hypothetical cohort of adults admitted to the ICU. Three prevention strategies were evaluated, including universal decolonization, targeted decolonization, and screening and isolation. Because prevention strategies have a screening component, the screening test in the model was varied to reflect commonly used screening test categories, including conventional culture, chromogenic agar, and polymerase chain reaction. Universal and targeted decolonization are less costly and more effective than screening and isolation. This is consistent for all screening tests. When compared with targeted decolonization, universal decolonization is cost-saving to cost-effective, with maximum cost savings occurring when a hospital uses more expensive screening tests like polymerase chain reaction. Results were robust to sensitivity analyses. As compared with screening and isolation, the current standard practice in ICUs, targeted decolonization, and universal decolonization are less costly and more effective. This supports updating the standard practice to a decolonization approach.

VIIRS-J1 Polarization Narrative

NASA Technical Reports Server (NTRS)

Waluschka, Eugene; McCorkel, Joel; McIntire, Jeff; Moyer, David; McAndrew, Brendan; Brown, Steven W.; Lykke, Keith; Butler, James; Meister, Gerhard; Thome, Kurtis J.

2015-01-01

The VIS/NIR bands polarization sensitivity of Joint Polar Satellite Sensor 1 (JPSS1) Visible/Infrared Imaging Radiometer Suite (VIIRS) instrument was measured using a broadband source. While polarization sensitivity for bands M5-M7, I1, and I2 was less than 2.5%, the maximum polarization sensitivity for bands M1, M2, M3, and M4 was measured to be 6.4%, 4.4%, 3.1%, and 4.3%, respectively with a polarization characterization uncertainty of less than 0.3%. A detailed polarization model indicated that the large polarization sensitivity observed in the M1 to M4 bands was mainly due to the large polarization sensitivity introduced at the leading and trailing edges of the newly manufactured VISNIR bandpass focal plane filters installed in front of the VISNIR detectors. This was confirmed by polarization measurements of bands M1 and M4 bands using monochromatic light. Discussed are the activities leading up to and including the instruments two polarization tests, some discussion of the polarization model and the model results, the role of the focal plane filters, the polarization testing of the Aft-Optics-Assembly, the testing of the polarizers at Goddard and NIST and the use of NIST's T-SIRCUS for polarization testing and associated analyses and results.

Psychobiological Influences on Maternal Sensitivity in the Context of Adversity

PubMed Central

Finegood, Eric D.; Blair, Clancy; Granger, Douglas A.; Hibel, Leah C.; Mills-Koonce, Roger

2016-01-01

This study evaluated prospective longitudinal relations among an index of poverty-related cumulative risk, maternal salivary cortisol, child negative affect, and maternal sensitivity across the first two postpartum years. Participants included 1,180 biological mothers residing in rural and predominantly low-income communities in the US. Multilevel growth curve analyses indicated that an index of cumulative risk was positively associated with maternal cortisol across the postpartum (study visits occurring at approximately 7, 15, and 24 months postpartum) over and above effects for African American ethnicity, time of day of saliva collection, age, parity status, having given birth to another child, contraceptive use, tobacco smoking, body mass index, and breastfeeding. Consistent with a psychobiological theory of mothering, maternal salivary cortisol was negatively associated with maternal sensitivity observed during parent-child interactions across the first two postpartum years over and above effects for poverty-related cumulative risk, child negative affect, as well as a large number of covariates associated with cortisol and maternal sensitivity. Child negative affect expressed during parent-child interactions was negatively associated with observed maternal sensitivity at late (24 months) but not early time points of observation (7 months) and cumulative risk was negatively associated with maternal sensitivity across the postpartum and this effect strengthened over time. Results advance our understanding of the dynamic, transactional, and psychobiological influences on parental caregiving behaviors across the first two postpartum years. PMID:27337514

Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes.

PubMed

Xie, Weijia; Wood, Andrew R; Lyssenko, Valeriya; Weedon, Michael N; Knowles, Joshua W; Alkayyali, Sami; Assimes, Themistocles L; Quertermous, Thomas; Abbasi, Fahim; Paananen, Jussi; Häring, Hans; Hansen, Torben; Pedersen, Oluf; Smith, Ulf; Laakso, Markku; Dekker, Jacqueline M; Nolan, John J; Groop, Leif; Ferrannini, Ele; Adam, Klaus-Peter; Gall, Walter E; Frayling, Timothy M; Walker, Mark

2013-06-01

Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we performed a genome-wide association study (GWAS) of 14 insulin sensitivity-related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2, and Stanford], MAGIC, and DIAGRAM). We identified four associations with three metabolites-glycine (rs715 at CPS1), serine (rs478093 at PHGDH), and betaine (rs499368 at SLC6A12; rs17823642 at BHMT)-and one association signal with glycine-to-serine ratio (rs1107366 at ALDH1L1). There was no robust evidence for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits.

[Comparison of the antibiotic sensitivity of lipophilic Corynebacterium sp. isolated from patients on the day of admission and during hospitalization].

PubMed

Ciok-Pater, Emilia; Mikucka, Agnieszka; Gospodarek, Eugenia

2005-01-01

Lipophilic species of Corynebacterium are increasing problem in hospital infections. The aim of this study was to evaluate occurrence of these microorganisms in the materials taken from patients in the day of admission and during the hospitalization as well as comparison of their antibiotic sensitivity. The investigation included 65 strains isolated from hospitalized patients and 48 strains isolated from unchanged skin. Using Api Coryne test 5 species were identified. C. urealyticum dominated, the other were C. subsp. lipophilum and C. jeikeium. Among strains isolated from unchanged diseased skin the most C. jeikeium and C. accolens occurred. All strains were sensitive to glycopeptide, quinupristin/dalphopristin. The strains isolated from hospitalized patients were usually sensitive to fuside acid, doxycycline as well as tetracycline. Strains isolated from unchanged skin were sensitive to almost all tested antibiotics. In the group of 65 strains isolated from hospitalized patients 99.0% were multiresistant. In the group of strains isolated from unchanged skin only two strains were multiresistant. Differences in antibiotic sensitivity among analysed Corynebacterium sp. were confirmed. Majority of the "hospital strains" were characterized by multiresistance. Basing on these results it is possible to suppose, that multiresistance is main factor that favours lipophilic Corynebacterium species in the process of colonization of mucous membranes, skins as well as developing infections.

Negotiating policy in practice: child and family health nurses' approach to the process of postnatal psychosocial assessment.

PubMed

Rollans, Mellanie; Schmied, Virginia; Kemp, Lynn; Meade, Tanya

2013-04-08

There is growing recognition internationally of the need to identify women with risk factors for poor perinatal mental health in pregnancy and following birth. In the state of New South Wales, Australia the Supporting Families Early policy provides a framework of assessment and support for women and families and includes routine psychosocial assessment and depression screening. This study investigated the approach taken by Child and Family Health Nurses (CFHNs) following birth to assessment and screening as recommended by state policy. This was a qualitative ethnographic study that included 83 CFHN and 20 women. Observations occurred with thirteen nurses; with 20 women, in the home or the clinic environment. An additional 70 nurses participated in discussion groups. An observational tool (4D&4R) and field notes were used to record observations and analysed descriptively using frequencies. Field notes, interview data and discussion group transcripts were analysed thematically. This was a qualitative ethnographic study that included 83 CFHN and 20 women. Observations occurred with thirteen nurses; with 20 women, in the home or the clinic environment. An additional 70 nurses participated in discussion groups. An observational tool (4D&4R) and field notes were used to record observations and analysed descriptively using frequencies. Field notes, interview data and discussion group transcripts were analysed thematically. CFHNs demonstrated a range of approaches to assessment and screening. Psychosocial assessment was conducted in 50% (10 out of the 20) of the interactions observed; however, all the women were screened using the Edinburgh Depression Scale. Four major themes that represent the approach taken to the assessment process were identified: 'Engagement: getting that first bit right', 'Doing some paperwork', 'Creating comfort' and 'Psychosocial assessment: doing it another way'. Nurses utilised other skills such as observing the women interacting with their baby, taking note of non verbal communication and using intuition to develop a clinical decision. Overall, nurses' took a sensitive and caring approach to assessment and screening, however, there were differences in interpretations of the policy recommendations across the two sites. Nurses adopt a flexible, relationship-based approach to the assessment process; however, they experience tension when required to incorporate structured psychosocial assessment processes. To undertake assessment and screening effectively, CFHNs require ongoing support, training and supervision to maintain this sensitive and emotionally challenging work.

CADDIS Volume 4. Data Analysis: Advanced Analyses - Controlling for Natural Variability

EPA Pesticide Factsheets

Methods for controlling natural variability, predicting environmental conditions from biological observations method, biological trait data, species sensitivity distributions, propensity scores, Advanced Analyses of Data Analysis references.

A method for high-throughput, sensitive analysis of IgG Fc and Fab glycosylation by capillary electrophoresis.

PubMed

Mahan, Alison E; Tedesco, Jacquelynne; Dionne, Kendall; Baruah, Kavitha; Cheng, Hao D; De Jager, Philip L; Barouch, Dan H; Suscovich, Todd; Ackerman, Margaret; Crispin, Max; Alter, Galit

2015-02-01

The N-glycan of the IgG constant region (Fc) plays a central role in tuning and directing multiple antibody functions in vivo, including antibody-dependent cellular cytotoxicity, complement deposition, and the regulation of inflammation, among others. However, traditional methods of N-glycan analysis, including HPLC and mass spectrometry, are technically challenging and ill suited to handle the large numbers of low concentration samples analyzed in clinical or animal studies of the N-glycosylation of polyclonal IgG. Here we describe a capillary electrophoresis-based technique to analyze plasma-derived polyclonal IgG-glycosylation quickly and accurately in a cost-effective, sensitive manner that is well suited for high-throughput analyses. Additionally, because a significant fraction of polyclonal IgG is glycosylated on both Fc and Fab domains, we developed an approach to separate and analyze domain-specific glycosylation in polyclonal human, rhesus and mouse IgGs. Overall, this protocol allows for the rapid, accurate, and sensitive analysis of Fc-specific IgG glycosylation, which is critical for population-level studies of how antibody glycosylation may vary in response to vaccination or infection, and across disease states ranging from autoimmunity to cancer in both clinical and animal studies. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Prophylactic plasma transfusion for surgical patients with abnormal preoperative coagulation tests: a single-institution propensity-adjusted cohort study.

PubMed

Jia, Qing; Brown, Michael J; Clifford, Leanne; Wilson, Gregory A; Truty, Mark J; Stubbs, James R; Schroeder, Darrell R; Hanson, Andrew C; Gajic, Ognjen; Kor, Daryl J

2016-03-01

Perioperative haemorrhage negatively affects patient outcomes and results in substantial consumption of health-care resources. Plasma transfusions are often administered to address abnormal preoperative coagulation tests, with the hope to mitigate bleeding complications. We aimed to assess the associations between preoperative plasma transfusion and bleeding complications in patients with elevated international normalised ratio (INR) undergoing non-cardiac surgery. We did an observational study in a consecutive sample of adult patients undergoing non-cardiac surgery with preoperative INR greater than or equal to 1·5. The exposure of interest was transfusion of preoperative plasma for elevated INR. The primary outcome was WHO grade 3 bleeding in the early perioperative period (from entry into the operating room until 24 h following exit from operating room). Hypotheses were tested with univariate and propensity-matched analyses. We did multiple sensitivity analyses to further evaluate the robustness of study findings. Between Jan 1, 2008, and Dec 31, 2011, we identified 1234 (8·4%) of 14 743 patients who had an INR of 1·5 or above and were included in this investigation. Of 1234 study participants, 139 (11%) received a preoperative plasma transfusion. WHO grade 3 bleeding occurred in 73 (53%) of 139 patients who received preoperative plasma compared with 350 (32%) of 1095 patients who did not (odds ratio [OR] 2·35, 95% CI 1·65-3·36; p<0·0001). Among the propensity-matched cohort, 65 (52%) of 125 plasma recipients had WHO grade 3 bleeding compared with 97 (40%) of 242 of those who did not receive preoperative plasma (OR 1·75, 95% CI 1·09-2·81; p=0·021). Results from multiple sensitivity analyses were qualitatively similar. Preoperative plasma transfusion for elevated international normalised ratios was associated with an increased frequency of perioperative bleeding complications. Findings were robust in the sensitivity analyses, suggestive that more conservative management of abnormal preoperative international normalised ratios is warranted. Mayo Clinic, National Institutes of Health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Age-related changes in perception of movement in driving scenes.

PubMed

Lacherez, Philippe; Turner, Laura; Lester, Robert; Burns, Zoe; Wood, Joanne M

2014-07-01

Age-related changes in motion sensitivity have been found to relate to reductions in various indices of driving performance and safety. The aim of this study was to investigate the basis of this relationship in terms of determining which aspects of motion perception are most relevant to driving. Participants included 61 regular drivers (age range 22-87 years). Visual performance was measured binocularly. Measures included visual acuity, contrast sensitivity and motion sensitivity assessed using four different approaches: (1) threshold minimum drift rate for a drifting Gabor patch, (2) Dmin from a random dot display, (3) threshold coherence from a random dot display, and (4) threshold drift rate for a second-order (contrast modulated) sinusoidal grating. Participants then completed the Hazard Perception Test (HPT) in which they were required to identify moving hazards in videos of real driving scenes, and also a Direction of Heading task (DOH) in which they identified deviations from normal lane keeping in brief videos of driving filmed from the interior of a vehicle. In bivariate correlation analyses, all motion sensitivity measures significantly declined with age. Motion coherence thresholds, and minimum drift rate threshold for the first-order stimulus (Gabor patch) both significantly predicted HPT performance even after controlling for age, visual acuity and contrast sensitivity. Bootstrap mediation analysis showed that individual differences in DOH accuracy partly explained these relationships, where those individuals with poorer motion sensitivity on the coherence and Gabor tests showed decreased ability to perceive deviations in motion in the driving videos, which related in turn to their ability to detect the moving hazards. The ability to detect subtle movements in the driving environment (as determined by the DOH task) may be an important contributor to effective hazard perception, and is associated with age, and an individuals' performance on tests of motion sensitivity. The locus of the processing deficits appears to lie in first-order, rather than second-order motion pathways. © 2014 The Authors Ophthalmic & Physiological Optics © 2014 The College of Optometrists.

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 Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis).

PubMed

Galor, Anat; Small, Leslie; Feuer, William; Levitt, Roy C; Sarantopoulos, Konstantinos D; Yosipovitch, Gil

2017-08-01

To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Analyses were performed to examine for differences between those with and without subjective complaints of ocular itch. The mean age was 62 years with 92% being male. Symptoms of DE and NOP were more frequent in patients with moderate-severe ocular itch compared to those with no or mild ocular itch symptoms. With the exception of ocular surface inflammation (abnormal matrix metalloproteinase 9 testing) which was less common in those with moderate-severe ocular itch symptoms, DE signs were not related to ocular itch. Individuals with moderate-severe ocular itch also demonstrated greater sensitivity to evoked pain on the forearm and had higher non-ocular pain, depression, and post-traumatic stress disorders scores, compared to those with no or mild itch symptoms. Subjects with moderate-severe ocular itch symptoms have more severe symptoms of DE, NOP, non-ocular pain and demonstrate abnormal somatosensory testing in the form of increased sensitivity to evoked pain at a site remote from the eye, consistent with generalized hypersensitivity.

The Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis)

PubMed Central

Galor, Anat; Small, Leslie; Feuer, William; Levitt, Roy C.; Sarantopoulos, Konstantinos D.; Yosipovitch, Gil

2017-01-01

Purpose To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. Methods A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Analyses were performed to examine for differences between those with and without subjective complaints of ocular itch. Results The mean age was 62 years with 92% being male. Symptoms of DE and NOP were more frequent in patients with moderate-severe ocular itch compared to those with no or mild ocular itch symptoms. With the exception of ocular surface inflammation (abnormal matrix metalloproteinase 9 testing) which was less common in those with moderate-severe ocular itch symptoms, DE signs were not related to ocular itch. Individuals with moderate-severe ocular itch also demonstrated greater sensitivity to evoked pain on the forearm and had higher non-ocular pain, depression, and post-traumatic stress disorders scores, compared to those with no or mild itch symptoms. Conclusions Subjects with moderate-severe ocular itch symptoms have more severe symptoms of DE, NOP, non-ocular pain and demonstrate abnormal somatosensory testing in the form of increased sensitivity to evoked pain at a site remote from the eye, consistent with generalized hypersensitivity. PMID:29391860

Accuracy of combined dynamic contrast-enhanced magnetic resonance imaging and diffusion-weighted imaging for breast cancer detection: a meta-analysis.

PubMed

Zhang, Li; Tang, Min; Min, Zhiqian; Lu, Jun; Lei, Xiaoyan; Zhang, Xiaoling

2016-06-01

Magnetic resonance imaging (MRI) is increasingly being used to examine patients with suspected breast cancer. To determine the diagnostic performance of combined dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) for breast cancer detection. A comprehensive search of the PUBMED, EMBASE, Web of Science, and Cochrane Library databases was performed up to September 2014. Statistical analysis included pooling of sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and diagnostic accuracy using the summary receiver operating characteristic (SROC). All analyses were conducted using STATA (version 12.0), RevMan (version 5.2), and Meta-Disc 1.4 software programs. Fourteen studies were analyzed, which included a total of 1140 patients with 1276 breast lesions. The pooled sensitivity and specificity of combined DCE-MRI and DWI were 91.6% and 85.5%, respectively. The pooled sensitivity and specificity of DWI-MRI were 86.0% and 75.6%, respectively. The pooled sensitivity and specificity of DCE-MRI were 93.2% and 71.1%. The area under the SROC curve (AUC-SROC) of combined DCE-MRI and DWI was 0.94, the DCE-MRI of 0.85. Deeks testing confirmed no significant publication bias in all studies. Combined DCE-MRI and DWI had superior diagnostic accuracy than either DCE-MRI or DWI alone for the diagnosis of breast cancer. © The Foundation Acta Radiologica 2015.

Association between ambient air pollution and diabetes mellitus in Europe and North America: systematic review and meta-analysis.

PubMed

Eze, Ikenna C; Hemkens, Lars G; Bucher, Heiner C; Hoffmann, Barbara; Schindler, Christian; Künzli, Nino; Schikowski, Tamara; Probst-Hensch, Nicole M

2015-05-01

Air pollution is hypothesized to be a risk factor for diabetes. Epidemiological evidence is inconsistent and has not been systematically evaluated. We systematically reviewed epidemiological evidence on the association between air pollution and diabetes, and synthesized results of studies on type 2 diabetes mellitus (T2DM). We systematically searched electronic literature databases (last search, 29 April 2014) for studies reporting the association between air pollution (particle concentration or traffic exposure) and diabetes (type 1, type 2, or gestational). We systematically evaluated risk of bias and role of potential confounders in all studies. We synthesized reported associations with T2DM in meta-analyses using random-effects models and conducted various sensitivity analyses. We included 13 studies (8 on T2DM, 2 on type 1, 3 on gestational diabetes), all conducted in Europe or North America. Five studies were longitudinal, 5 cross-sectional, 2 case-control, and 1 ecologic. Risk of bias, air pollution assessment, and confounder control varied across studies. Dose-response effects were not reported. Meta-analyses of 3 studies on PM2.5 (particulate matter ≤ 2.5 μm in diameter) and 4 studies on NO2 (nitrogen dioxide) showed increased risk of T2DM by 8-10% per 10-μg/m3 increase in exposure [PM2.5: 1.10 (95% CI: 1.02, 1.18); NO2: 1.08 (95% CI: 1.00, 1.17)]. Associations were stronger in females. Sensitivity analyses showed similar results. Existing evidence indicates a positive association of air pollution and T2DM risk, albeit there is high risk of bias. High-quality studies assessing dose-response effects are needed. Research should be expanded to developing countries where outdoor and indoor air pollution are high.

Comparing short forms of the Social Interaction Anxiety Scale and the Social Phobia Scale.

PubMed

Carleton, R Nicholas; Thibodeau, Michel A; Weeks, Justin W; Teale Sapach, Michelle J N; McEvoy, Peter M; Horswill, Samantha C; Heimberg, Richard G

2014-12-01

The Social Interaction Anxiety Scale (SIAS) and the Social Phobia Scale (SPS; Mattick & Clarke, 1998) are companion scales developed to measure anxiety in social interaction and performance situations, respectively. The measures have strong discriminant and convergent validity; however, their factor structures remain debated, and furthermore, the combined administration length (i.e., 39 items) can be prohibitive for some settings. There have been 4 attempts to assess the factor structures of the scales and reduce the item content: the 14-item Social Interaction Phobia Scale (SIPS; Carleton et al., 2009), the 12-item SIAS-6/SPS-6 (Peters, Sunderland, Andrews, Rapee, & Mattick, 2012), the 21-item abbreviated SIAS/SPS (ASIAS/ASPS; Kupper & Denollet, 2012), and the 12-item Readability SIAS and SPS (RSIAS/RSPS; Fergus, Valentiner, McGrath, Gier-Lonsway, & Kim, 2012). The current study compared the short forms on (a) factor structure, (b) ability to distinguish between clinical and non-clinical populations, (c) sensitivity to change following therapy, and (d) convergent validity with related measures. Participants included 3,607 undergraduate students (55% women) and 283 patients with social anxiety disorder (43% women). Results of confirmatory factor analyses, sensitivity analyses, and correlation analyses support the robust utility of items in the SIPS and the SPS-6 and SIAS-6 relative to the other short forms; furthermore, the SIPS and the SPS-6 and SIAS-6 were also supported by convergent validity analyses within the undergraduate sample. The RSIAS/RSPS and the ASIAS/ASPS were least supported, based on the current results and the principle of parsimony. Accordingly, researchers and clinicians should consider carefully which of the short forms will best suit their needs. (c) 2014 APA, all rights reserved.

Nurse staffing and patient outcomes in Belgian acute hospitals: cross-sectional analysis of administrative data.

PubMed

Van den Heede, Koen; Sermeus, Walter; Diya, Luwis; Clarke, Sean P; Lesaffre, Emmanuel; Vleugels, Arthur; Aiken, Linda H

2009-07-01

Studies have linked nurse staffing levels (number and skill mix) to several nurse-sensitive patient outcomes. However, evidence from European countries has been limited. This study examines the association between nurse staffing levels (i.e. acuity-adjusted Nursing Hours per Patient Day, the proportion of registered nurses with a Bachelor's degree) and 10 different patient outcomes potentially sensitive to nursing care. DESIGN-SETTING-PARTICIPANTS: Cross-sectional analyses of linked data from the Belgian Nursing Minimum Dataset (general acute care and intensive care nursing units: n=1403) and Belgian Hospital Discharge Dataset (general, orthopedic and vascular surgery patients: n=260,923) of the year 2003 from all acute hospitals (n=115). Logistic regression analyses, estimated by using a Generalized Estimation Equation Model, were used to study the association between nurse staffing and patient outcomes. The mean acuity-adjusted Nursing Hours per Patient Day in Belgian hospitals was 2.62 (S.D.=0.29). The variability in patient outcome rates between hospitals is considerable. The inter-quartile ranges for the 10 patient outcomes go from 0.35 for Deep Venous Thrombosis to 3.77 for failure-to-rescue. No significant association was found between the acuity-adjusted Nursing Hours per Patient Day, proportion of registered nurses with a Bachelor's degree and the selected patient outcomes. The absence of associations between hospital-level nurse staffing measures and patient outcomes should not be inferred as implying that nurse staffing does not have an impact on patient outcomes in Belgian hospitals. To better understand the dynamics of the nurse staffing and patient outcomes relationship in acute hospitals, further analyses (i.e. nursing unit level analyses) of these and other outcomes are recommended, in addition to inclusion of other study variables, including data about nursing practice environments in hospitals.

Microarray-Based Comparative Genomic Hybridization Using Sex-Matched Reference DNA Provides Greater Sensitivity for Detection of Sex Chromosome Imbalances than Array-Comparative Genomic Hybridization with Sex-Mismatched Reference DNA

PubMed Central

Yatsenko, Svetlana A.; Shaw, Chad A.; Ou, Zhishuo; Pursley, Amber N.; Patel, Ankita; Bi, Weimin; Cheung, Sau Wai; Lupski, James R.; Chinault, A. Craig; Beaudet, Arthur L.

2009-01-01

In array-comparative genomic hybridization (array-CGH) experiments, the measurement of DNA copy number of sex chromosomal regions depends on the sex of the patient and the reference DNAs used. We evaluated the ability of bacterial artificial chromosomes/P1-derived artificial and oligonucleotide array-CGH analyses to detect constitutional sex chromosome imbalances using sex-mismatched reference DNAs. Twenty-two samples with imbalances involving either the X or Y chromosome, including deletions, duplications, triplications, derivative or isodicentric chromosomes, and aneuploidy, were analyzed. Although concordant results were obtained for approximately one-half of the samples when using sex-mismatched and sex-matched reference DNAs, array-CGH analyses with sex-mismatched reference DNAs did not detect genomic imbalances that were detected using sex-matched reference DNAs in 6 of 22 patients. Small duplications and deletions of the X chromosome were most difficult to detect in female and male patients, respectively, when sex-mismatched reference DNAs were used. Sex-matched reference DNAs in array-CGH analyses provides optimal sensitivity and enables an automated statistical evaluation for the detection of sex chromosome imbalances when compared with an experimental design using sex-mismatched reference DNAs. Using sex-mismatched reference DNAs in array-CGH analyses may generate false-negative, false-positive, and ambiguous results for sex chromosome-specific probes, thus masking potential pathogenic genomic imbalances. Therefore, to optimize both detection of clinically relevant sex chromosome imbalances and ensure proper experimental performance, we suggest that alternative internal controls be developed and used instead of using sex-mismatched reference DNAs. PMID:19324990

The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding.

PubMed

Laursen, S B; Leontiadis, G I; Stanley, A J; Hallas, J; Schaffalitzky de Muckadell, O B

2017-08-01

Observational studies have consistently shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs), probably explained by their inhibition of platelet aggregation. Therefore, treatment with SSRIs is often temporarily withheld in patients with peptic ulcer bleeding. However, abrupt discontinuation of SSRIs is associated with development of withdrawal symptoms in one-third of patients. Further data are needed to clarify whether treatment with SSRIs is associated with poor outcomes, which would support temporary discontinuation of treatment. To identify if treatment with SSRIs is associated with increased risk of: (1) endoscopy-refractory bleeding, (2) rebleeding or (3) 30-day mortality due to peptic ulcer bleeding. A nationwide cohort study. Analyses were performed on prospectively collected data on consecutive patients admitted to hospital with peptic ulcer bleeding in Denmark in the period 2006-2014. Logistic regression analyses were used to investigate the association between treatment with SSRIs and outcome following adjustment for pre-defined confounders. Sensitivity and subgroup analyses were performed to evaluate the validity of the findings. A total of 14 343 patients were included. Following adjustment, treatment with SSRIs was not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] [95% Confidence Interval (CI)]: 1.03 [0.79-1.33]), rebleeding (OR [95% CI]: 0.96 [0.83-1.11]) or 30-day mortality (OR [95% CI]: 1.01 [0.85-1.19]. These findings were supported by sensitivity and subgroup analyses. According to our data, treatment with SSRIs does not influence the risk of endoscopy-refractory bleeding, rebleeding or 30-day mortality in peptic ulcer bleeding. © 2017 John Wiley & Sons Ltd.

Cost-effectiveness of drug-eluting stents versus bare-metal stents in patients undergoing percutaneous coronary intervention.

PubMed

Baschet, Louise; Bourguignon, Sandrine; Marque, Sébastien; Durand-Zaleski, Isabelle; Teiger, Emmanuel; Wilquin, Fanny; Levesque, Karine

2016-01-01

To determine the cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients requiring a percutaneous coronary intervention in France, using a recent meta-analysis including second-generation DES. A cost-effectiveness analysis was performed in the French National Health Insurance setting. Effectiveness settings were taken from a meta-analysis of 117 762 patient-years with 76 randomised trials. The main effectiveness criterion was major cardiac event-free survival. Effectiveness and costs were modelled over a 5-year horizon using a three-state Markov model. Incremental cost-effectiveness ratios and a cost-effectiveness acceptability curve were calculated for a range of thresholds for willingness to pay per year without major cardiac event gain. Deterministic and probabilistic sensitivity analyses were performed. Base case results demonstrated that DES are dominant over BMS, with an increase in event-free survival and a cost-reduction of €184, primarily due to a diminution of second revascularisations, and an absence of myocardial infarction and stent thrombosis. These results are robust for uncertainty on one-way deterministic and probabilistic sensitivity analyses. Using a cost-effectiveness threshold of €7000 per major cardiac event-free year gained, DES has a >95% probability of being cost-effective versus BMS. Following DES price decrease, new-generation DES development and taking into account recent meta-analyses results, the DES can now be considered cost-effective regardless of selective indication in France, according to European recommendations.

How rapidly does the excess risk of lung cancer decline following quitting smoking? A quantitative review using the negative exponential model.

PubMed

Fry, John S; Lee, Peter N; Forey, Barbara A; Coombs, Katharine J

2013-10-01

The excess lung cancer risk from smoking declines with time quit, but the shape of the decline has never been precisely modelled, or meta-analyzed. From a database of studies of at least 100 cases, we extracted 106 blocks of RRs (from 85 studies) comparing current smokers, former smokers (by time quit) and never smokers. Corresponding pseudo-numbers of cases and controls (or at-risk) formed the data for fitting the negative exponential model. We estimated the half-life (H, time in years when the excess risk becomes half that for a continuing smoker) for each block, investigated model fit, and studied heterogeneity in H. We also conducted sensitivity analyses allowing for reverse causation, either ignoring short-term quitters (S1) or considering them smokers (S2). Model fit was poor ignoring reverse causation, but much improved for both sensitivity analyses. Estimates of H were similar for all three analyses. For the best-fitting analysis (S1), H was 9.93 (95% CI 9.31-10.60), but varied by sex (females 7.92, males 10.71), and age (<50years 6.98, 70+years 12.99). Given that reverse causation is taken account of, the model adequately describes the decline in excess risk. However, estimates of H may be biased by factors including misclassification of smoking status. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Interrater reliability of schizoaffective disorder compared with schizophrenia, bipolar disorder, and unipolar depression - A systematic review and meta-analysis.

PubMed

Santelmann, Hanno; Franklin, Jeremy; Bußhoff, Jana; Baethge, Christopher

2016-10-01

Schizoaffective disorder is a common diagnosis in clinical practice but its nosological status has been subject to debate ever since it was conceptualized. Although it is key that diagnostic reliability is sufficient, schizoaffective disorder has been reported to have low interrater reliability. Evidence based on systematic review and meta-analysis methods, however, is lacking. Using a highly sensitive literature search in Medline, Embase, and PsycInfo we identified studies measuring the interrater reliability of schizoaffective disorder in comparison to schizophrenia, bipolar disorder, and unipolar disorder. Out of 4126 records screened we included 25 studies reporting on 7912 patients diagnosed by different raters. The interrater reliability of schizoaffective disorder was moderate (meta-analytic estimate of Cohen's kappa 0.57 [95% CI: 0.41-0.73]), and substantially lower than that of its main differential diagnoses (difference in kappa between 0.22 and 0.19). Although there was considerable heterogeneity, analyses revealed that the interrater reliability of schizoaffective disorder was consistently lower in the overwhelming majority of studies. The results remained robust in subgroup and sensitivity analyses (e.g., diagnostic manual used) as well as in meta-regressions (e.g., publication year) and analyses of publication bias. Clinically, the results highlight the particular importance of diagnostic re-evaluation in patients diagnosed with schizoaffective disorder. They also quantify a widely held clinical impression of lower interrater reliability and agree with earlier meta-analysis reporting low test-retest reliability. Copyright © 2016. Published by Elsevier B.V.

The Child Adolescent Bullying Scale (CABS): Psychometric evaluation of a new measure.

PubMed

Strout, Tania D; Vessey, Judith A; DiFazio, Rachel L; Ludlow, Larry H

2018-06-01

While youth bullying is a significant public health problem, healthcare providers have been limited in their ability to identify bullied youths due to the lack of a reliable, and valid instrument appropriate for use in clinical settings. We conducted a multisite study to evaluate the psychometric properties of a new 22-item instrument for assessing youths' experiences of being bullied, the Child Adolescent Bullying Scale (CABS). The 20 items summed to produce the measure's score were evaluated here. Diagnostic performance was assessed through evaluation of sensitivity, specificity, predictive values, and area under receiver operating characteristic (AUROC) curve. A sample of 352 youths from diverse racial, ethnic, and geographic backgrounds (188 female, 159 male, 5 transgender, sample mean age 13.5 years) were recruited from two clinical sites. Participants completed the CABS and existing youth bullying measures. Analyses grounded in classical test theory, including assessments of reliability and validity, item analyses, and principal components analysis, were conducted. The diagnostic performance and test characteristics of the CABS were also evaluated. The CABS is comprised of one component, accounting for 67% of observed variance. Analyses established evidence of internal consistency reliability (Cronbach's α = 0.97), construct and convergent validity. Sensitivity was 84%, specificity was 65%, and the AUROC curve was 0.74 (95% CI: 0.69-0.80). Findings suggest that the CABS holds promise as a reliable, valid tool for healthcare provider use in screening for bullying exposure in the clinical setting. © 2018 Wiley Periodicals, Inc.

Development of the multiple sclerosis (MS) early mobility impairment questionnaire (EMIQ).

PubMed

Ziemssen, Tjalf; Phillips, Glenn; Shah, Ruchit; Mathias, Adam; Foley, Catherine; Coon, Cheryl; Sen, Rohini; Lee, Andrew; Agarwal, Sonalee

2016-10-01

The Early Mobility Impairment Questionnaire (EMIQ) was developed to facilitate early identification of mobility impairments in multiple sclerosis (MS) patients. We describe the initial development of the EMIQ with a focus on the psychometric evaluation of the questionnaire using classical and item response theory methods. The initial 20-item EMIQ was constructed by clinical specialists and qualitatively tested among people with MS and physicians via cognitive interviews. Data from an observational study was used to make additional updates to the instrument based on exploratory factor analysis (EFA) and item response theory (IRT) analysis, and psychometric analyses were performed to evaluate the reliability and validity of the final instrument's scores and screening properties (i.e., sensitivity and specificity). Based on qualitative interview analyses, a revised 15-item EMIQ was included in the observational study. EFA, IRT and item-to-item correlation analyses revealed redundant items which were removed leading to the final nine-item EMIQ. The nine-item EMIQ performed well with respect to: test-retest reliability (ICC = 0.858); internal consistency (α = 0.893); convergent validity; and known-groups methods for construct validity. A cut-point of 41 on the 0-to-100 scale resulted in sufficient sensitivity and specificity statistics for viably identifying patients with mobility impairment. The EMIQ is a content valid and psychometrically sound instrument for capturing MS patients' experience with mobility impairments in a clinical practice setting. Additional research is suggested to further confirm the EMIQ's screening properties over time.

Variation of facial features among three African populations: Body height match analyses.

PubMed

Taura, M G; Adamu, L H; Gudaji, A

2017-01-01

Body height is one of the variables that show a correlation with facial craniometry. Here we seek to discriminate the three populations (Nigerians, Ugandans and Kenyans) using facial craniometry based on different categories of body height of adult males. A total of 513 individuals comprising 234 Nigerians, 169 Ugandans and 110 Kenyans with mean age of 25.27, s=5.13 (18-40 years) participated. Paired and unpaired facial features were measured using direct craniometry. Multivariate and stepwise discriminate function analyses were used for differentiation of the three populations. The result showed significant overall facial differences among the three populations in all the body height categories. Skull height, total facial height, outer canthal distance, exophthalmometry, right ear width and nasal length were significantly different among the three different populations irrespective of body height categories. Other variables were sensitive to body height. Stepwise discriminant function analyses included maximum of six variables for better discrimination between the three populations. The single best discriminator of the groups was total facial height, however, for body height >1.70m the single best discriminator was nasal length. Most of the variables were better used with function 1, hence, better discrimination than function 2. In conclusion, adult body height in addition to other factors such as age, sex, and ethnicity should be considered in making decision on facial craniometry. However, not all the facial linear dimensions were sensitive to body height. Copyright © 2016 Elsevier GmbH. All rights reserved.

Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis

PubMed Central

Akioyamen, Leo E; Genest, Jacques; Shan, Shubham D; Reel, Rachel L; Albaum, Jordan M; Chu, Anna; Tu, Jack V

2017-01-01

Objectives Heterozygous familial hypercholesterolaemia (FH) confers a significant risk for premature cardiovascular disease (CVD). However, the estimated prevalence of FH varies substantially among studies. We aimed to provide a summary estimate of FH prevalence in the general population and assess variations in frequency across different sociodemographic characteristics. Setting, participants and outcome measures We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO and PubMed for peer-reviewed literature using validated strategies. Results were limited to studies published in English between January 1990 and January 2017. Studies were eligible if they determined FH prevalence using clinical criteria or DNA-based analyses. We determined a pooled point prevalence of FH in adults and children and assessed the variation of the pooled frequency by age, sex, geographical location, diagnostic method, study quality and year of publication. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were investigated through subgroups, meta-regression and sensitivity analyses. Results The pooled prevalence of FH from 19 studies including 2 458 456 unique individuals was 0.40% (95% CI 0.29% to 0.52%) which corresponds to a frequency of 1 in 250 individuals. FH prevalence was found to vary by age and geographical location but not by any other covariates. Results were consistent in sensitivity analyses. Conclusions Our systematic review suggests that FH is a common disorder, affecting 1 in 250 individuals. These findings underscore the need for early detection and management to decrease CVD risk. PMID:28864697

Lifetime cost of everolimus vs axitinib in patients with advanced renal cell carcinoma who failed prior sunitinib therapy in the US.

PubMed

Perrin, Allison; Sherman, Steven; Pal, Sumanta; Chua, Andrew; Gorritz, Magdaliz; Liu, Zhimei; Wang, Xufang; Culver, Kenneth; Casciano, Roman; Garrison, Louis P

2015-03-01

Everolimus and axitinib are approved in the US to treat patients with advanced renal cell carcinoma (RCC) after failure on sunitinib or sorafenib, and one prior systemic therapy (e.g., sunitinib), respectively. Two indirect comparisons performed to evaluate progression-free survival in patients treated with everolimus vs axitinib suggested similar efficacy between the two treatments. Therefore, this analysis compares the lifetime costs of these two therapies among sunitinib-refractory advanced RCC patients from a US payer perspective. A Markov model was developed to simulate a cohort of sunitinib-refractory advanced RCC patients and estimate the cost of treating patients with everolimus vs axitinib. The following health states were included: stable disease without adverse events (AEs), stable disease with AEs, disease progression (PD), and death. The model included the following resources: active treatments, post-progression treatments, adverse events, physician and nurse visits, scans and tests, and palliative care. Resource utilization inputs were derived from a US claims database analysis. Additionally, a 3% annual discount rate was applied to costs, and the robustness of the model results was tested by conducting sensitivity analyses, including those on dosing scheme and post-progression treatment costs. Base case results demonstrated that patients treated with everolimus cost an average of $12,985 (11%) less over their lifetimes than patients treated with axitinib. The primary difference in costs was related to active treatment, which was largely driven by axitinib's higher dose intensity. RESULTS remained consistent across sensitivity analyses for AE and PD treatment costs, as well as dose intensity and discount rates. The results suggest that everolimus likely leads to lower lifetime costs than axitinib for sunitinib-refractory advanced RCC patients in the US.

Cerebrospinal Fluid B-lymphocyte Chemoattractant CXCL13 in the Diagnosis of Acute Lyme Neuroborreliosis in Children.

PubMed

Barstad, Bjørn; Tveitnes, Dag; Noraas, Sølvi; Selvik Ask, Ingvild; Saeed, Maryam; Bosse, Franziskus; Vigemyr, Grete; Huber, Ilka; Øymar, Knut

2017-12-01

Current markers of Lyme neuroborreliosis (LNB) in children have insufficient sensitivity in the early stage of disease. The B-lymphocyte chemoattractant CXCL13 in the cerebrospinal fluid (CSF) may be useful in diagnosing LNB, but its specificity has not been evaluated in studies including children with clinically relevant differential diagnoses. The aim of this study was to elucidate the diagnostic value of CSF CXCL13 in children with symptoms suggestive of LNB. Children with symptoms suggestive of LNB were included prospectively into predefined groups with a high or low likelihood of LNB based on CSF pleocytosis and the detection of Borrelia antibodies or other causative agents. CSF CXCL13 levels were compared between the groups, and receiver-operating characteristic analyses were performed to indicate optimal cutoff levels to discriminate LNB from non-LNB conditions. Two hundred and ten children were included. Children with confirmed LNB (n=59) and probable LNB (n=18) had higher CSF CXCL13 levels than children with possible LNB (n=7), possible peripheral LNB (n=7), non-Lyme aseptic meningitis (n=12), non-meningitis (n=91) and negative controls (n=16). Using 18 pg/mL as a cutoff level, both the sensitivity and specificity of CSF CXCL13 for LNB (confirmed and probable) were 97%. Comparing only children with LNB and non-Lyme aseptic meningitis, the sensitivity and specificity with the same cutoff level were 97% and 83%, respectively. CSF CXCL13 is a sensitive marker of LNB in children. The specificity to discriminate LNB from non-Lyme aseptic meningitis may be more moderate, suggesting that CSF CXCL13 should be used together with other variables in diagnosing LNB in children.

Local and Systemic Changes in Pain Sensitivity After 4 Weeks of Calf Muscle Stretching in a Nonpainful Population: A Randomized Trial.

PubMed

Bartholdy, Cecilie; Zangger, Graziella; Hansen, Lisbeth; Ginnerup-Nielsen, Elisabeth; Bliddal, Henning; Henriksen, Marius

2016-07-01

Stretching is often used in clinical practice for a variety of purposes, including pain therapy. The possible mechanism behind the effect of stretching remains to be clarified. To investigate whether 4 weeks of unilateral stretching of the calf muscles would affect local and central pain sensitivity. This study was a randomized assessor-blinded clinical study. Healthy participants (age 18 to 40) were included and randomized. Participants in the intervention group were instructed to perform 2 stretching exercises targeting the calf muscles; 3 times 30 seconds, 7 days a week for 4 weeks on the dominant leg. Participants in the control group were instructed not to do any stretching for 4 weeks. Pressure pain threshold (PPT) and temporal summation (TS) of pressure pain were measured on the stretched calf, the contra-lateral calf, and contra-lateral lower arm using a computerized cuff algometer. Analyses of variance on the per-protocol population (defined as participants that adhered to the protocol) were used to assess group differences in the changes from baseline. Forty healthy volunteers were included, of which 34 participants adhered to the protocol (15 intervention group/19 control group). No statistically significant group differences in the changes from baseline were found regarding PPT and TS measurements for the stretched calf, the contra-lateral calf, and the arm. Four weeks of regular stretching of the calf muscles does not affect pressure pain sensitivity, suggesting that pressure pain sensitivity is unaffected by stretching in a healthy population. The mechanisms underlying any benefits of regular stretching remain to be explained. © 2015 World Institute of Pain.

Acrylamide levels in Finnish foodstuffs analysed with liquid chromatography tandem mass spectrometry.

PubMed

Eerola, Susanna; Hollebekkers, Koen; Hallikainen, Anja; Peltonen, Kimmo

2007-02-01

Sample clean-up and HPLC with tandem mass spectrometric detection (LC-MS/MS) was validated for the routine analysis of acrylamide in various foodstuffs. The method used proved to be reliable and the detection limit for routine monitoring was sensitive enough for foods and drinks (38 microg/kg for foods and 5 microg/L for drinks). The RSDs for repeatability and day-to-day variation were below 15% in all food matrices. Two hundred and one samples which included more than 30 different types of food and foods manufactured and prepared in various ways were analysed. The main types of food analysed were potato and cereal-based foods, processed foods (pizza, minced beef meat, meat balls, chicken nuggets, potato-ham casserole and fried bacon) and coffee. Acrylamide was detected at levels, ranging from nondetectable to 1480 microg/kg level in solid food, with crisp bread exhibiting the highest levels. In drinks, the highest value (29 microg/L) was found in regular coffee drinks.

Development of a standardized battery of performance tests for the assessment of noise stress effects

NASA Technical Reports Server (NTRS)

Theologus, G. C.; Wheaton, G. R.; Mirabella, A.; Brahlek, R. E.

1973-01-01

A set of 36 relatively independent categories of human performance were identified. These categories encompass human performance in the cognitive, perceptual, and psychomotor areas, and include diagnostic measures and sensitive performance metrics. Then a prototype standardized test battery was constructed, and research was conducted to obtain information on the sensitivity of the tests to stress, the sensitivity of selected categories of performance degradation, the time course of stress effects on each of the selected tests, and the learning curves associated with each test. A research project utilizing a three factor partially repeated analysis of covariance design was conducted in which 60 male subjects were exposed to variations in noise level and quality during performance testing. Effects of randomly intermittent noise on performance of the reaction time tests were observed, but most of the other performance tests showed consistent stability. The results of 14 analyses of covariance of the data taken from the performance of the 60 subjects on the prototype standardized test battery provided information which will enable the final development and test of a standardized test battery and the associated development of differential sensitivity metrics and diagnostic classificatory system.

Sensitivity analysis of a coupled hydrodynamic-vegetation model using the effectively subsampled quadratures method (ESQM v5.2)

NASA Astrophysics Data System (ADS)

Kalra, Tarandeep S.; Aretxabaleta, Alfredo; Seshadri, Pranay; Ganju, Neil K.; Beudin, Alexis

2017-12-01

Coastal hydrodynamics can be greatly affected by the presence of submerged aquatic vegetation. The effect of vegetation has been incorporated into the Coupled Ocean-Atmosphere-Wave-Sediment Transport (COAWST) modeling system. The vegetation implementation includes the plant-induced three-dimensional drag, in-canopy wave-induced streaming, and the production of turbulent kinetic energy by the presence of vegetation. In this study, we evaluate the sensitivity of the flow and wave dynamics to vegetation parameters using Sobol' indices and a least squares polynomial approach referred to as the Effective Quadratures method. This method reduces the number of simulations needed for evaluating Sobol' indices and provides a robust, practical, and efficient approach for the parameter sensitivity analysis. The evaluation of Sobol' indices shows that kinetic energy, turbulent kinetic energy, and water level changes are affected by plant stem density, height, and, to a lesser degree, diameter. Wave dissipation is mostly dependent on the variation in plant stem density. Performing sensitivity analyses for the vegetation module in COAWST provides guidance to optimize efforts and reduce exploration of parameter space for future observational and modeling work.

Sensitive skin is highly frequent in extrinsic atopic dermatitis and correlates with disease severity markers but not necessarily with skin barrier impairment.

PubMed

Yatagai, Tsuyoshi; Shimauchi, Takatoshi; Yamaguchi, Hayato; Sakabe, Jun-Ichi; Aoshima, Masahiro; Ikeya, Shigeki; Tatsuno, Kazuki; Fujiyama, Toshiharu; Ito, Taisuke; Ojima, Toshiyuki; Tokura, Yoshiki

2018-01-01

Sensitive skin is a condition of cutaneous hypersensitivity to environmental factors. Lactic acid stinging test (LAST) is commonly used to assess sensitive skin and composed of four distinct sensations (pain, burning sensation, itch, and crawly feeling). A link between sensitive skin and barrier dysfunction has been proposed in atopic dermatitis (AD) patients. However, clinical and laboratory factors that are associated with sensitive skin remain unelucidated. To investigate relationship between sensitive skin and AD-associated markers. Forty-two Japanese AD patients and 10 healthy subjects (HS) were enrolled. AD patients were divided into extrinsic (EAD; high IgE levels) and intrinsic (IAD; normal IgE levels) types. We conducted 1% LAST by assessing the four distinct sensations and calculated the frequencies of sensitive skin in EAD, IAD, and HS. We also performed clinical AD-related tests, including transepidermal water loss (TEWL), visual analogue scale (VAS) of pruritus, and quality of life, and measured laboratory markers, including blood levels of IgE, CCL17/TARC, lactate dehydrogenase (LDH) and eosinophil counts, and concentration levels of serum Th1/Th2 cytokines. Filaggrin (FLG) mutations were examined in 21 patients. These values were subjected to correlation analyses with each of the four sensation elements. According to the standard criteria for LAST positivity, the frequencies of LAST-positive subjects were 54.8% and 10.0% in AD and HS, respectively (P=0.014). EAD patients showed a significantly (P=0.026) higher frequency of positive LAST (65.6%) than did IAD patients (20.0%). Among the four LAST sensation elements, the crawly feeling and pain scores positively correlated with VAS of pruritus, total serum IgE, mite-specific IgE, CCL17/TARC, and/or LDH. There was no association of the LAST scores with serum Th1/Th2 cytokine levels. Notably, neither TEWL nor FLG mutations correlated with LAST positivity or any sensation scores. The frequency of sensitive skin is higher in EAD than in IAD. Sensitive skin is associated with AD severity, but not necessarily with barrier condition. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Is the Prediction of Adolescent Outcomes From Early Child Care Moderated by Later Maternal Sensitivity? Results From the NICHD Study of Early Child Care and Youth Development

PubMed Central

Burchinal, Margaret R.; Vandell, Deborah Lowe; Belsky, Jay

2016-01-01

Longitudinal data are used to examine whether effects of early child care are amplified and/or attenuated by later parenting. Analyses tested these interactions using parenting as both a categorical and continuous variable to balance power and flexibility in testing moderation. The most consistent finding was that maternal sensitivity during adolescence accentuated the association between child care quality and adolescent academic-cognitive skills at age 15 years when maternal sensitivity during adolescence was high. This interaction was obtained in analyses with maternal sensitivity as both a categorical and continuous variable. Relations between early child care hours and adolescent behavioral outcomes also were moderated by maternal sensitivity, with longer child care hours predicting more impulsivity and externalizing at age 15 when maternal sensitivity during middle childhood, scored as a categorical variable, was low to moderate and when maternal sensitivity during adolescence, scored as a continuous variable, was lower. These findings suggest that some child care effects are moderated by subsequent parenting and that this moderation may take both linear and nonlinear forms. PMID:23937381

Cost–effectiveness analysis of quadrivalent influenza vaccine in Spain

PubMed Central

García, Amos; Ortiz de Lejarazu, Raúl; Reina, Jordi; Callejo, Daniel; Cuervo, Jesús; Morano Larragueta, Raúl

2016-01-01

ABSTRACT Influenza has a major impact on healthcare systems and society, but can be prevented using vaccination. The World Health Organization (WHO) currently recommends that influenza vaccines should include at least two virus A and one virus B lineage (trivalent vaccine; TIV). A new quadrivalent vaccine (QIV), which includes an additional B virus strain, received regulatory approval and is now recommended by several countries. The present study estimates the cost-effectiveness of replacing TIVs with QIV for risk groups and elderly population in Spain. A static, lifetime, multi-cohort Markov model with a one-year cycle time was adapted to assess the costs and health outcomes associated with a switch from TIV to QIV. The model followed a cohort vaccinated each year according to health authority recommendations, for the duration of their lives. National epidemiological data allowed the determination of whether the B strain included in TIVs matched the circulating one. Societal perspective was considered, costs and outcomes were discounted at 3% and one-way and probabilistic sensitivity analyses were performed. Compared to TIVs, QIV reduced more influenza cases and influenza-related complications and deaths during periods of B-mismatch strains in the TIV. The incremental cost-effectiveness ratio (ICER) was 8,748€/quality-adjusted life year (QALY). One-way sensitivity analysis showed mismatch with the B lineage included in the TIV was the main driver for ICER. Probabilistic sensitivity analysis shows ICER below 30,000€/QALY in 96% of simulations. Replacing TIVs with QIV in Spain could improve influenza prevention by avoiding B virus mismatch and provide a cost-effective healthcare intervention. PMID:27184622

Cost-effectiveness analysis of quadrivalent influenza vaccine in Spain.

PubMed

García, Amos; Ortiz de Lejarazu, Raúl; Reina, Jordi; Callejo, Daniel; Cuervo, Jesús; Morano Larragueta, Raúl

2016-09-01

Influenza has a major impact on healthcare systems and society, but can be prevented using vaccination. The World Health Organization (WHO) currently recommends that influenza vaccines should include at least two virus A and one virus B lineage (trivalent vaccine; TIV). A new quadrivalent vaccine (QIV), which includes an additional B virus strain, received regulatory approval and is now recommended by several countries. The present study estimates the cost-effectiveness of replacing TIVs with QIV for risk groups and elderly population in Spain. A static, lifetime, multi-cohort Markov model with a one-year cycle time was adapted to assess the costs and health outcomes associated with a switch from TIV to QIV. The model followed a cohort vaccinated each year according to health authority recommendations, for the duration of their lives. National epidemiological data allowed the determination of whether the B strain included in TIVs matched the circulating one. Societal perspective was considered, costs and outcomes were discounted at 3% and one-way and probabilistic sensitivity analyses were performed. Compared to TIVs, QIV reduced more influenza cases and influenza-related complications and deaths during periods of B-mismatch strains in the TIV. The incremental cost-effectiveness ratio (ICER) was 8,748€/quality-adjusted life year (QALY). One-way sensitivity analysis showed mismatch with the B lineage included in the TIV was the main driver for ICER. Probabilistic sensitivity analysis shows ICER below 30,000€/QALY in 96% of simulations. Replacing TIVs with QIV in Spain could improve influenza prevention by avoiding B virus mismatch and provide a cost-effective healthcare intervention.

Computational Aspects of Sensitivity Calculations in Linear Transient Structural Analysis. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Greene, William H.

1989-01-01

A study has been performed focusing on the calculation of sensitivities of displacements, velocities, accelerations, and stresses in linear, structural, transient response problems. One significant goal was to develop and evaluate sensitivity calculation techniques suitable for large-order finite element analyses. Accordingly, approximation vectors such as vibration mode shapes are used to reduce the dimensionality of the finite element model. Much of the research focused on the accuracy of both response quantities and sensitivities as a function of number of vectors used. Two types of sensitivity calculation techniques were developed and evaluated. The first type of technique is an overall finite difference method where the analysis is repeated for perturbed designs. The second type of technique is termed semianalytical because it involves direct, analytical differentiation of the equations of motion with finite difference approximation of the coefficient matrices. To be computationally practical in large-order problems, the overall finite difference methods must use the approximation vectors from the original design in the analyses of the perturbed models.

Sample pooling for real-time PCR detection and virulence determination of the footrot pathogen Dichelobacter nodosus.

PubMed

Frosth, Sara; König, Ulrika; Nyman, Ann-Kristin; Aspán, Anna

2017-09-01

Dichelobacter nodosus is the principal cause of ovine footrot and strain virulence is an important factor in disease severity. Therefore, detection and virulence determination of D. nodosus is important for proper diagnosis of the disease. Today this is possible by real-time PCR analysis. Analysis of large numbers of samples is costly and laborious; therefore, pooling of individual samples is common in surveillance programs. However, pooling can reduce the sensitivity of the method. The aim of this study was to develop a pooling method for real-time PCR analysis that would allow sensitive detection and simultaneous virulence determination of D. nodosus. A total of 225 sheep from 17 flocks were sampled using ESwabs within the Swedish Footrot Control Program in 2014. Samples were first analysed individually and then in pools of five by real-time PCR assays targeting the 16S rRNA and aprV2/B2 genes of D. nodosus. Each pool consisted of four negative and one positive D. nodosus samples with varying amounts of the bacterium. In the individual analysis, 61 (27.1%) samples were positive in the 16S rRNA and the aprV2/B2 PCR assays and 164 (72.9%) samples were negative. All samples positive in the aprV2/B2 PCR-assay were of aprB2 variant. The pooled analysis showed that all 41 pools were also positive for D. nodosus 16S rRNA and the aprB2 variant. The diagnostic sensitivity for pooled and individual samples was therefore similar. Our method includes concentration of the bacteria before DNA-extraction. This may account for the maintenance of diagnostic sensitivity. Diagnostic sensitivity in the real-time PCR assays of the pooled samples were comparable to the sensitivity obtained for individually analysed samples. Even sub-clinical infections were able to be detected in the pooled PCR samples which is important for control of the disease. This method may therefore be implemented in footrot control programs where it can replace analysis of individual samples.

Three-dimensional steady-state simulation of flow in the sand-and-gravel aquifer, southern Escambia County, Florida

USGS Publications Warehouse

Trapp, Henry; Geiger, L.H.

1986-01-01

The sand-and-gravel aquifer is the only freshwater aquifer in southern Escambia County, Florida and is the source of public water supply for the area, including the City of Pensacola. The aquifer was simulated by a two-layer, digital model to provide hydrologic information for water resource planning. The lower layer represents the main-producing zone; the upper layer represents all of the aquifer above the main-producing zone including an unconfined zone and discontinuous perched, confined , and confining zones. The model was designed for steady-state simulation and predicts the response of the aquifer (changes in water levels) to groundwater pumping where steady-state conditions have been reached. Input to the model includes matrices representing constant-head nodes, starting head, transmissivity of layer 1, leakance between layers 1 and 2, lateral hydraulic conductivity of layer 2, and altitude of the base layer 2. The sources of water to the model are from recharge by infiltrated precipitation (estimated from base runoff), inflow across boundaries, and induced recharge from river leakance in periods of prolonged groundwater pumping. Model output includes final head and drawdown for each layer and total values for discharge and recharge in the model area. The model was calibrated for 1972 pumping and tested by simulating pumpages during 1939-40, 1958, and 1977. Sensitivity analyses showed water levels in both layers were most sensitive to changes in the recharge matrix and least sensitive to river leakage. Suggestions for further development of the model include subdivision and expansion of the grid, assignment of storage coefficients for transient simulations, more intensive study of the stream-aquifer relations, and consideration of the effects of infiltration basins on recharge. (Author 's abstract)

Visual Resource Analysis for Solar Energy Zones in the San Luis Valley

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

Sullivan, Robert; Abplanalp, Jennifer M.; Zvolanek, Emily

This report summarizes the results of a study conducted by Argonne National Laboratory’s (Argonne’s) Environmental Science Division for the U.S. Department of the Interior Bureau of Land Management (BLM). The study analyzed the regional effects of potential visual impacts of solar energy development on three BLM-designated solar energy zones (SEZs) in the San Luis Valley (SLV) in Colorado, and, based on the analysis, made recommendations for or against regional compensatory mitigation to compensate residents and other stakeholders for the potential visual impacts to the SEZs. The analysis was conducted as part of the solar regional mitigation strategy (SRMS) task conductedmore » by BLM Colorado with assistance from Argonne. Two separate analyses were performed. The first analysis, referred to as the VSA Analysis, analyzed the potential visual impacts of solar energy development in the SEZs on nearby visually sensitive areas (VSAs), and, based on the impact analyses, made recommendations for or against regional compensatory mitigation. VSAs are locations for which some type of visual sensitivity has been identified, either because the location is an area of high scenic value or because it is a location from which people view the surrounding landscape and attach some level of importance or sensitivity to what is seen from the location. The VSA analysis included both BLM-administered lands in Colorado and in the Taos FO in New Mexico. The second analysis, referred to as the SEZ Analysis, used BLM visual resource inventory (VRI) and other data on visual resources in the former Saguache and La Jara Field Offices (FOs), now contained within the San Luis Valley FO (SLFO), to determine whether the changes in scenic values that would result from the development of utility-scale solar energy facilities in the SEZs would affect the quality and quantity of valued scenic resources in the SLV region as a whole. If the regional effects were judged to be significant, regional compensatory mitigation was recommended. VRI data was not available for the Taos FO and it was not included in the SEZ analysis; the SEZ analysis includes BLM-administered lands in Colorado only.« less

Improved micromethod for mezlocillin quantitation in serum and urine by high-pressure liquid chromatography.

PubMed Central

Fiore, D; Auger, F A; Drusano, G L; Dandu, V R; Lesko, L J

1984-01-01

A rapid, sensitive, and specific method of analysis for mezlocillin in serum and urine by high-pressure liquid chromatography is described. A solid-phase extraction column was used to remove interfering substances from samples before chromatography. Quantitation included the use of an internal standard, nafcillin. Mezlocillin was chromatographed with a phosphate buffer-acetonitrile (73:27) mobile phase and a C-18 reverse-phase column and detected at a wavelength of 220 nm. The assay had a sensitivity of 1.6 micrograms/ml and a linearity of up to 600 micrograms/ml and 16 mg/ml in serum and urine, respectively, with only 0.1 ml of sample. The interday and intraday coefficients of variation for replicate analyses of spiked serum and urine specimens were less than 6.5%. PMID:6517560

A SENSITIVE METHOD FOR THE DETERMINATION OF CARBOXYHAEMOGLOBIN IN A FINGER PRICK SAMPLE OF BLOOD

PubMed Central

Commins, B. T.; Lawther, P. J.

1965-01-01

About 0·01 ml. of blood taken from a finger prick is dissolved in 10 ml. of 0·04% ammonia solution. The solution is divided into two halves, and oxygen is bubbled through one half to convert any carboxyhaemoglobin into oxyhaemoglobin. The spectra of the two halves are then compared in a spectrophotometer, and the difference between them is used to estimate the carboxyhaemoglobin content of the blood either graphically or by calculation from a simple formula. Calibration is simple and need only be done once. A sample of blood can be analysed in about 20 minutes, which includes the time to collect the sample. The method is sensitive enough to be used for the analysis of solutions of blood containing less than 1% carboxyhaemoglobin. PMID:14278801

Purification and characterization of two bacteriocins produced by lactic acid bacteria isolated from Mongolian airag.

PubMed

Batdorj, B; Dalgalarrondo, M; Choiset, Y; Pedroche, J; Métro, F; Prévost, H; Chobert, J-M; Haertlé, T

2006-10-01

The aim of this study was to isolate and identify bacteriocin-producing lactic acid bacteria (LAB) issued from Mongolian airag (traditional fermented mare's milk), and to purify and characterize bacteriocins produced by these LAB. Identification of the bacteria (Enterococcus durans) was carried out on the basis of its morphological, biochemical characteristics and carbohydrate fermentation profile and by API50CH kit and 16S rDNA analyses. The pH-neutral cell-free supernatant of this bacterium inhibited the growth of several Lactobacillus spp. and food-borne pathogens including Escherichia coli, Staphylococcus aureus and Listeria innocua. The antimicrobial agent (enterocin A5-11) was heat stable and was not sensitive to acid and alkaline conditions (pH 2-10), but was sensitive to several proteolytic enzymes. Its inhibitory activity was completely eliminated after treatment with proteinase K and alpha-chymotrypsin. The activity was however not completely inactivated by other proteases including trypsin and pepsin. Three-step purification procedure with high recovery yields was developed to separate two bacteriocins. The applied procedure allowed the recovery of 16% and 64% of enterocins A5-11A and A5-11B, respectively, present in the culture supernatant with purity higher than 99%. SDS-PAGE analyses revealed that enterocin A5-11 has a molecular mass of 5000 Da and mass spectrometry analyses demonstrates molecular masses of 5206 and 5218 Da for fractions A and B, respectively. Amino acid analyses of both enterocins indicated significant quantitative difference in their contents in threonine, alanine, isoleucine and leucine. Their N-termini were blocked hampering straightforward Edman degradation. Bacteriocins A5-11A and B from Ent. durans belong to the class II of bacteriocins. Judging from molecular masses, amino acid composition and spectrum of activities, bacteriocins A5-11A and B from Ent. durans show high degree of similarity with enterocins L50A and L50B isolated from Enterococcus faecium (Cintas et al. 1998, 2000) and with enterocin I produced by Ent. faecium 6T1a, a strain originally isolated from a Spanish-style green olive fermentation (Floriano et al. 1998).

Systematic Review and Cost Analysis Comparing Use of Chlorhexidine with Use of Iodine for Preoperative Skin Antisepsis to Prevent Surgical Site Infection

PubMed Central

Lee, Ingi; Agarwal, Rajender K.; Lee, Bruce Y.; Fishman, Neil O.; Umscheid, Craig A.

2013-01-01

Objective To compare use of chlorhexidine with use of iodine for preoperative skin antisepsis with respect to effectiveness in preventing surgical site infections (SSIs) and cost. Methods We searched the Agency for Healthcare Research and Quality website, the Cochrane Library, Medline, and EMBASE up to January 2010 for eligible studies. Included studies were systematic reviews, meta-analyses, or randomized controlled trials (RCTs) comparing preoperative skin antisepsis with chlorhexidine and with iodine and assessing for the outcomes of SSI or positive skin culture result after application. One reviewer extracted data and assessed individual study quality, quality of evidence for each outcome, and publication bias. Meta-analyses were performed using a fixed-effects model. Using results from the meta-analysis and cost data from the Hospital of the University of Pennsylvania, we developed a decision analytic cost-benefit model to compare the economic value, from the hospital perspective, of antisepsis with iodine versus antisepsis with 2 preparations of chlorhexidine (ie, 4% chlorhexidine bottle and single-use applicators of a 2% chlorhexidine gluconate [CHG] and 70% isopropyl alcohol [IPA] solution), and also performed sensitivity analyses. Results Nine RCTs with a total of 3,614 patients were included in the meta-analysis. Meta-analysis revealed that chlorhexidine antisepsis was associated with significantly fewer SSIs (adjusted risk ratio, 0.64 [95% confidence interval, [0.51–0.80]) and positive skin culture results (adjusted risk ratio, 0.44 [95% confidence interval, 0.35–0.56]) than was iodine antisepsis. In the cost-benefit model baseline scenario, switching from iodine to chlorhexidine resulted in a net cost savings of $16–$26 per surgical case and $349,904–$568,594 per year for the Hospital of the University of Pennsylvania. Sensitivity analyses showed that net cost savings persisted under most circumstances. Conclusions Preoperative skin antisepsis with chlorhexidine is more effective than preoperative skin antisepsis with iodine for preventing SSI and results in cost savings. PMID:20969449

CADDIS Volume 4. Data Analysis: Advanced Analyses - Controlling for Natural Variability: SSD Plot Diagrams

EPA Pesticide Factsheets

Methods for controlling natural variability, predicting environmental conditions from biological observations method, biological trait data, species sensitivity distributions, propensity scores, Advanced Analyses of Data Analysis references.

Cost-effectiveness analyses of hepatitis A vaccine: a systematic review to explore the effect of methodological quality on the economic attractiveness of vaccination strategies.

PubMed

Anonychuk, Andrea M; Tricco, Andrea C; Bauch, Chris T; Pham, Ba'; Gilca, Vladimir; Duval, Bernard; John-Baptiste, Ava; Woo, Gloria; Krahn, Murray

2008-01-01

Hepatitis A vaccines have been available for more than a decade. Because the burden of hepatitis A virus has fallen in developed countries, the appropriate role of vaccination programmes, especially universal vaccination strategies, remains unclear. Cost-effectiveness analysis is a useful method of relating the costs of vaccination to its benefits, and may inform policy. This article systematically reviews the evidence on the cost effectiveness of hepatitis A vaccination in varying populations, and explores the effects of methodological quality and key modelling issues on the cost-effectiveness ratios.Cost-effectiveness/cost-utility studies of hepatitis A vaccine were identified via a series of literature searches (MEDLINE, EMBASE, HSTAR and SSCI). Citations and full-text articles were reviewed independently by two reviewers. Reference searching, author searches and expert consultation ensured literature saturation. Incremental cost-effectiveness ratios (ICERs) were abstracted for base-case analyses, converted to $US, year 2005 values, and categorised to reflect various levels of cost effectiveness. Quality of reporting, methodological issues and key modelling issues were assessed using frameworks published in the literature.Thirty-one cost-effectiveness studies (including 12 cost-utility analyses) were included from full-text article review (n = 58) and citation screening (n = 570). These studies evaluated universal mass vaccination (n = 14), targeted vaccination (n = 17) and vaccination of susceptibles (i.e. individuals initially screened for antibody and, if susceptible, vaccinated) [n = 13]. For universal vaccination, 50% of the ICERs were <$US20 000 per QALY or life-year gained. Analyses evaluating vaccination in children, particularly in high incidence areas, produced the most attractive ICERs. For targeted vaccination, cost effectiveness was highly dependent on the risk of infection.Incidence, vaccine cost and discount rate were the most influential parameters in sensitivity analyses. Overall, analyses that evaluated the combined hepatitis A/hepatitis B vaccine, adjusted incidence for under-reporting, included societal costs and that came from studies of higher methodological quality tended to have more attractive cost-effectiveness ratios. Methodological quality varied across studies. Major methodological flaws included inappropriate model type, comparator, incidence estimate and inclusion/exclusion of costs.

The Active for Life Year 5 (AFLY5) school-based cluster randomised controlled trial protocol: detailed statistical analysis plan.

PubMed

Lawlor, Debbie A; Peters, Tim J; Howe, Laura D; Noble, Sian M; Kipping, Ruth R; Jago, Russell

2013-07-24

The Active For Life Year 5 (AFLY5) randomised controlled trial protocol was published in this journal in 2011. It provided a summary analysis plan. This publication is an update of that protocol and provides a detailed analysis plan. This update provides a detailed analysis plan of the effectiveness and cost-effectiveness of the AFLY5 intervention. The plan includes details of how variables will be quality control checked and the criteria used to define derived variables. Details of four key analyses are provided: (a) effectiveness analysis 1 (the effect of the AFLY5 intervention on primary and secondary outcomes at the end of the school year in which the intervention is delivered); (b) mediation analyses (secondary analyses examining the extent to which any effects of the intervention are mediated via self-efficacy, parental support and knowledge, through which the intervention is theoretically believed to act); (c) effectiveness analysis 2 (the effect of the AFLY5 intervention on primary and secondary outcomes 12 months after the end of the intervention) and (d) cost effectiveness analysis (the cost-effectiveness of the AFLY5 intervention). The details include how the intention to treat and per-protocol analyses were defined and planned sensitivity analyses for dealing with missing data. A set of dummy tables are provided in Additional file 1. This detailed analysis plan was written prior to any analyst having access to any data and was approved by the AFLY5 Trial Steering Committee. Its publication will ensure that analyses are in accordance with an a priori plan related to the trial objectives and not driven by knowledge of the data. ISRCTN50133740.

Systematic review of publications on economic evaluations of caries prevention programs.

PubMed

Mariño, R J; Khan, A R; Morgan, M

2013-01-01

The aim of this study was to perform a systematic review of economic evaluations (EEs) of dental caries prevention programs to objectively retrieve, synthesize and describe available information on the field. Several strategies were combined to search for literature published between January 1975 and April 2012. MEDLINE, EconoLit and ISI formed the basis of the literature search. The study selection was done using predefined inclusion and exclusion criteria. Bibliographic listings of all retrieved articles were hand-searched. The search identified 206 references. An evaluative framework was developed based on the Centre for Reviews and Dissemination's 'Guidance for undertaking reviews in health care' (York University, 2009). Background information included publication vehicle, year of publication, geographic focus, type of preventive program and type of economic analysis. 63 studies were included in the review. The most common preventive strategies evaluated were dental sealants (n = 13), water fluoridation (n = 12) and mixed interventions (n = 12). By type of EE undertaken, 30 were cost-effectiveness analyses, 22 were cost-benefit analyses, and 5 presented both cost-effectiveness and cost-benefit analyses. Few studies were cost-utility analyses (n = 5) or cost minimization analyses (n = 2). By year of publication, most were published after 2003. The review revealed that, although the number of publications reporting EEs has increased significantly in recent years, the quality of the reporting needs to be improved. The main methodological problems identified in the review were the limited information provided on adjustments for discounting in addition to inadequate sensitivity analyses. Attention also needs to be given to the analysis and interpretation of the results of the EEs. Copyright © 2013 S. Karger AG, Basel.

Comparison of Estimates between Cohort and Case-Control Studies in Meta-Analyses of Therapeutic Interventions: A Meta-Epidemiological Study.

PubMed

Lanza, Amy; Ravaud, Philippe; Riveros, Carolina; Dechartres, Agnes

2016-01-01

Observational studies are increasingly being used for assessing therapeutic interventions. Case-control studies are generally considered to have greater risk of bias than cohort studies, but we lack evidence of differences in effect estimates between the 2 study types. We aimed to compare estimates between cohort and case-control studies in meta-analyses of observational studies of therapeutic interventions by using a meta-epidemiological study. We used a random sample of meta-analyses of therapeutic interventions published in 2013 that included both cohort and case-control studies assessing a binary outcome. For each meta-analysis, the ratio of estimates (RE) was calculated by comparing the estimate in case-control studies to that in cohort studies. Then, we used random-effects meta-analysis to estimate a combined RE across meta-analyses. An RE < 1 indicated that case-control studies yielded larger estimates than cohort studies. The final analysis included 23 meta-analyses: 138 cohort and 133 case-control studies. Treatment effect estimates did not significantly differ between case-control and cohort studies (combined RE 0.97 [95% CI 0.86-1.09]). Heterogeneity was low, with between-meta-analysis variance τ2 = 0.0049. Estimates did not differ between case-control and prospective or retrospective cohort studies (RE = 1.05 [95% CI 0.96-1.15] and RE = 0.99 [95% CI, 0.83-1.19], respectively). Sensitivity analysis of studies reporting adjusted estimates also revealed no significant difference (RE = 1.03 [95% CI 0.91-1.16]). Heterogeneity was also low for these analyses. We found no significant difference in treatment effect estimates between case-control and cohort studies assessing therapeutic interventions.

pyres: a Python wrapper for electrical resistivity modeling with R2

NASA Astrophysics Data System (ADS)

Befus, Kevin M.

2018-04-01

A Python package, pyres, was written to handle common as well as specialized input and output tasks for the R2 electrical resistivity (ER) modeling program. Input steps including handling field data, creating quadrilateral or triangular meshes, and data filtering allow repeatable and flexible ER modeling within a programming environment. pyres includes non-trivial routines and functions for locating and constraining specific known or separately-parameterized regions in both quadrilateral and triangular meshes. Three basic examples of how to run forward and inverse models with pyres are provided. The importance of testing mesh convergence and model sensitivity are also addressed with higher-level examples that show how pyres can facilitate future research-grade ER analyses.

Concurrent validity and clinical usefulness of several individually administered tests of children's social-emotional cognition.

PubMed

McKown, Clark

2007-03-01

In this study, the validity of 5 tests of children's social-emotional cognition, defined as their encoding, memory, and interpretation of social information, was tested. Participants were 126 clinic-referred children between the ages of 5 and 17. All 5 tests were evaluated in terms of their (a) concurrent validity, (b) incremental validity, and (c) clinical usefulness in predicting social functioning. Tests included measures of nonverbal sensitivity, social language, and social problem solving. Criterion measures included parent and teacher report of social functioning. Analyses support the concurrent validity of all measures, and the incremental validity and clinical usefulness of tests of pragmatic language and problem solving.

A Systematic Review and Meta-Analyses of the Association Between Anti-Hypertensive Classes and the Risk of Falls Among Older Adults.

PubMed

Ang, Hui Ting; Lim, Ka Keat; Kwan, Yu Heng; Tan, Pui San; Yap, Kai Zhen; Banu, Zafirah; Tan, Chuen Seng; Fong, Warren; Thumboo, Julian; Ostbye, Truls; Low, Lian Leng

2018-06-23

Falls in individuals aged ≥ 60 years may result in injury, hospitalisation or death. The role of anti-hypertensive medications in falls among older adults is unclear. The objective of this study was to assess the association of six anti-hypertensive medication classes, namely α-blockers (AB), angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), β-blockers (BB), calcium channel blockers (CCB) and diuretics, with the risk of falls, injurious falls or recurrent falls in individuals aged ≥ 60 years compared with non-users. We performed systematic searches in PubMed, EMBASE and CINAHL and included cohort, case-control and cross-sectional studies that investigated the associations between the use of anti-hypertensive medication classes and the risk of falls, injurious falls or recurrent falls in older adults (≥ 60 years) reported in English. We assessed study quality using the Newcastle-Ottawa Scale (NOS). Unadjusted and adjusted odds ratios (ORs) were pooled using random effects model. We performed meta-analyses for each anti-hypertensive medication class and each fall outcome. We also performed sensitivity analyses by pooling studies of high quality and subgroup analyses among studies with an average age of ≥ 80 years. Seventy-eight articles (where 74, 34, 27, 18, 13 and 11 of them examined diuretics, BB, CCB, ACEi, AB and ARB, respectively) met our inclusion and exclusion criteria; we pooled estimates from 60 articles. ACEi [OR 0.85, 95% confidence interval (CI) 0.81-0.89], BB (OR 0.84, 95% CI 0.76-0.93) and CCB (OR 0.81, 95% CI 0.74-0.90) use were associated with a lower risk of injurious falls than in non-users. Results in sensitivity and subgroup analyses were largely consistent. The use of ACEi, BB or CCB among older adults may be associated with a lower risk of injurious falls than non-use.

Measurement techniques for trace metals in coal-plant effluents: A brief review

NASA Technical Reports Server (NTRS)

Singh, J. J.

1979-01-01

The strong features and limitations of techniques for determining trace elements in aerosols emitted from coal plants are discussed. Techniques reviewed include atomic absorption spectroscopy, charged particle scattering and activation, instrumental neutron activation analysis, gas/liquid chromatography, gas chromatographic/mass spectrometric methods, X-ray fluorescence, and charged-particle-induced X-ray emission. The latter two methods are emphasized. They provide simultaneous, sensitive multielement analyses and lend themselves readily to depth profiling. It is recommended that whenever feasible, two or more complementary techniques should be used for analyzing environmental samples.

Structural Assessment of Tungsten-Epoxy Bonding in Spacecraft Composite Enclosures with Enhanced Radiation Protection

NASA Astrophysics Data System (ADS)

Kanerva, M.; Koerselman, J. R.; Revitzer, H.; Johansson, L.-S.; Sarlin, E.; Rautiainen, A.; Brander, T.; Saarela, O.

2014-06-01

Spacecraft include sensitive electronics that must be protected against radiation from the space environment. Hybrid laminates consisting of tungsten layers and carbon- fibre-reinforced epoxy composite are a potential solution for lightweight, efficient, and protective enclosure material. Here, we analysed six different surface treatments for tungsten foils in terms of the resulting surface tension components, composition, and bonding strength with epoxy. A hydrofluoric-nitric-sulfuric-acid method and a diamond-like carbon-based DIARC® coating were found the most potential surface treatments for tungsten foils in this study.

Sensitivity of Multiangle, Multispectral Polarimetric Remote Sensing Over Open Oceans to Water-Leaving Radiance: Analyses of RSP Data Acquired During the MILAGRO Campaign

NASA Technical Reports Server (NTRS)

Chowdhary, Jacek; Cairns, Brian; Waquet, Fabien; Knobelspiesse, Kirk; Ottaviani, Matteo; Redemann, Jens; Travis, Larry; Mishchenko, Michael

2012-01-01

For remote sensing of aerosol over the ocean, there is a contribution from light scattered underwater. The brightness and spectrum of this light depends on the biomass content of the ocean, such that variations in the color of the ocean can be observed even from space. Rayleigh scattering by pure sea water, and Rayleigh-Gans type scattering by plankton, causes this light to be polarized with a distinctive angular distribution. To study the contribution of this underwater light polarization to multiangle, multispectral observations of polarized reflectance over ocean, we previously developed a hydrosol model for use in underwater light scattering computations that produces realistic variations of the ocean color and the underwater light polarization signature of pure sea water. In this work we review this hydrosol model, include a correction for the spectrum of the particulate scattering coefficient and backscattering efficiency, and discuss its sensitivity to variations in colored dissolved organic matter (CDOM) and in the scattering function of marine particulates. We then apply this model to measurements of total and polarized reflectance that were acquired over open ocean during the MILAGRO field campaign by the airborne Research Scanning Polarimeter (RSP). Analyses show that our hydrosol model faithfully reproduces the water-leaving contributions to RSP reflectance, and that the sensitivity of these contributions to Chlorophyll a concentration [Chl] in the ocean varies with the azimuth, height, and wavelength of observations. We also show that the impact of variations in CDOM on the polarized reflectance observed by the RSP at low altitude is comparable to or much less than the standard error of this reflectance whereas their effects in total reflectance may be substantial (i.e. up to >30%). Finally, we extend our study of polarized reflectance variations with [Chl] and CDOM to include results for simulated spaceborne observations.

Diagnosis of Fanconi anemia in patients with bone marrow failure

PubMed Central

Pinto, Fernando O.; Leblanc, Thierry; Chamousset, Delphine; Le Roux, Gwenaelle; Brethon, Benoit; Cassinat, Bruno; Larghero, Jérôme; de Villartay, Jean-Pierre; Stoppa-Lyonnet, Dominique; Baruchel, André; Socié, Gérard; Gluckman, Eliane; Soulier, Jean

2009-01-01

Background Patients with bone marrow failure and undiagnosed underlying Fanconi anemia may experience major toxicity if given standard-dose conditioning regimens for hematopoietic stem cell transplant. Due to clinical variability and/or potential emergence of genetic reversion with hematopoietic somatic mosaicism, a straightforward Fanconi anemia diagnosis can be difficult to make, and diagnostic strategies combining different assays in addition to classical breakage tests in blood may be needed. Design and Methods We evaluated Fanconi anemia diagnosis on blood lymphocytes and skin fibroblasts from a cohort of 87 bone marrow failure patients (55 children and 32 adults) with no obvious full clinical picture of Fanconi anemia, by performing a combination of chromosomal breakage tests, FANCD2-monoubiquitination assays, a new flow cytometry-based mitomycin C sensitivity test in fibroblasts, and, when Fanconi anemia was diagnosed, complementation group and mutation analyses. The mitomycin C sensitivity test in fibroblasts was validated on control Fanconi anemia and non-Fanconi anemia samples, including other chromosomal instability disorders. Results When this diagnosis strategy was applied to the cohort of bone marrow failure patients, 7 Fanconi anemia patients were found (3 children and 4 adults). Classical chromosomal breakage tests in blood detected 4, but analyses on fibroblasts were necessary to diagnose 3 more patients with hematopoietic somatic mosaicism. Importantly, Fanconi anemia was excluded in all the other patients who were fully evaluated. Conclusions In this large cohort of patients with bone marrow failure our results confirmed that when any clinical/biological suspicion of Fanconi anemia remains after chromosome breakage tests in blood, based on physical examination, history or inconclusive results, then further evaluation including fibroblast analysis should be made. For that purpose, the flow-based mitomycin C sensitivity test here described proved to be a reliable alternative method to evaluate Fanconi anemia phenotype in fibroblasts. This global strategy allowed early and accurate confirmation or rejection of Fanconi anemia diagnosis with immediate clinical impact for those who underwent hematopoietic stem cell transplant. PMID:19278965

An Analysis of Factors Influencing Quality of Vision After Big-Bubble Deep Anterior Lamellar Keratoplasty in Keratoconus.

PubMed

Feizi, Sepehr; Javadi, Mohammad Ali; Mohammad-Rabei, Hossein

2016-02-01

To identify causes of reduced visual acuity and contrast sensitivity after big-bubble deep anterior lamellar keratoplasty (DALK) in keratoconus. Prospective interventional case series. This study included 36 eyes in 36 patients with keratoconus who underwent DALK using the big-bubble technique. A bare Descemet membrane was achieved in all cases. Univariate analyses and multiple linear regression were used to investigate recipient-, donor-, and postoperative-related variables capable of influencing the postoperative quality of vision, including best spectacle-corrected visual acuity (BSCVA) and contrast sensitivity. The mean patient age was 27.7 ± 6.9 years, and the patients were followed for 24.6 ± 15.1 months postoperatively. The mean postoperative BSCVA was 0.17 ± 0.09 logMAR. Postoperative BSCVA ≥20/25 was achieved in 14 eyes (38.9%), whereas a BSCVA of 20/30, 20/40, or 20/50 was observed in 15 eyes (41.7%), 6 eyes (16.6%), and 1 eye (2.8%), respectively. Preoperative vitreous length was significantly associated with postoperative BSCVA (β = 0.02, P = .03). Donor-recipient interface reflectivity significantly influenced scotopic (β = -0.002, P = .04) and photopic (β = -0.003, P = .02) contrast sensitivity. The root mean square of tetrafoil was significantly negatively associated with scotopic (β = -0.25, P = .01) and photopic (β = -0.23, P = .04) contrast sensitivity. Recipient age, keratoconus severity, donor-related variables, recipient trephination size, and graft and recipient bed thickness were not significantly associated with postoperative visual acuity or contrast sensitivity. Large vitreous length, higher-order aberrations, and surgical interface haze may contribute to poor visual outcomes after big-bubble DALK in keratoconus. Copyright © 2016 Elsevier Inc. All rights reserved.

Preoperative identification of a suspicious adnexal mass: a systematic review and meta-analysis.

PubMed

Dodge, Jason E; Covens, Allan L; Lacchetti, Christina; Elit, Laurie M; Le, Tien; Devries-Aboud, Michaela; Fung-Kee-Fung, Michael

2012-07-01

To systematically review the existing literature in order to determine the optimal strategy for preoperative identification of the adnexal mass suspicious for ovarian cancer. A review of all systematic reviews and guidelines published between 1999 and 2009 was conducted as a first step. After the identification of a 2004 AHRQ systematic review on the topic, searches of MEDLINE for studies published since 2004 was also conducted to update and supplement the evidentiary base. A bivariate, random-effects meta-regression model was used to produce summary estimates of sensitivity and specificity and to plot summary ROC curves with 95% confidence regions. Four meta-analyses and 53 primary studies were included in this review. The diagnostic performance of each technology was compared and contrasted based on the summary data on sensitivity and specificity obtained from the meta-analysis. Results suggest that 3D ultrasonography has both a higher sensitivity and specificity when compared to 2D ultrasound. Established morphological scoring systems also performed with respectable sensitivity and specificity, each with equivalent diagnostic competence. Explicit scoring systems did not perform as well as other diagnostic testing methods. Assessment of an adnexal mass by colour Doppler technology was neither as sensitive nor as specific as simple ultrasonography. Of the three imaging modalities considered, MRI appeared to perform the best, although results were not statistically different from CT. PET did not perform as well as either MRI or CT. The measurement of the CA-125 tumour marker appears to be less reliable than do other available assessment methods. The best available evidence was collected and included in this rigorous systematic review and meta-analysis. The abundant evidentiary base provided the context and direction for the diagnosis of early-staged ovarian cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Genome-wide bisulfite sensitivity profiling of yeast suggests bisulfite inhibits transcription.

PubMed

Segovia, Romulo; Mathew, Veena; Tam, Annie S; Stirling, Peter C

2017-09-01

Bisulfite, in the form of sodium bisulfite or metabisulfite, is used commercially as a food preservative. Bisulfite is used in the laboratory as a single-stranded DNA mutagen in epigenomic analyses of DNA methylation. Recently it has also been used on whole yeast cells to induce mutations in exposed single-stranded regions in vivo. To understand the effects of bisulfite on live cells we conducted a genome-wide screen for bisulfite sensitive mutants in yeast. Screening the deletion mutant array, and collections of essential gene mutants we define a genetic network of bisulfite sensitive mutants. Validation of screen hits revealed hyper-sensitivity of transcription and RNA processing mutants, rather than DNA repair pathways and follow-up analyses support a role in perturbation of RNA transactions. We propose a model in which bisulfite-modified nucleotides may interfere with transcription or RNA metabolism when used in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Taxometric and Factor Analytic Models of Anxiety Sensitivity among Youth: Exploring the Latent Structure of Anxiety Psychopathology Vulnerability

ERIC Educational Resources Information Center

Bernstein, Amit; Zvolensky, Michael J.; Stewart, Sherry; Comeau, Nancy

2007-01-01

This study represents an effort to better understand the latent structure of anxiety sensitivity (AS), a well-established affect-sensitivity individual difference factor, among youth by employing taxometric and factor analytic approaches in an integrative manner. Taxometric analyses indicated that AS, as indexed by the Child Anxiety Sensitivity…

The Role of Reinforcement Sensitivity in the Development of Childhood Personality

ERIC Educational Resources Information Center

Slobodskaya, Helena R.; Kuznetsova, Valeriya B.

2013-01-01

The study examined the contribution of reinforcement sensitivity to childhood personality at three levels of the hierarchical structure, mid-level traits, the Big Five and two higher-order factors, and the moderating role of sex and age in a sample of 3-18-year-olds. The canonical correlation analyses indicated that reinforcement sensitivity and…

Comparing the Cost of Treatment with Octreotide Long-Acting Release versus Lanreotide in Patients with Metastatic Gastrointestinal Neuroendocrine Tumors.

PubMed

Ayyagari, Rajeev; Neary, Maureen; Li, Shang; Rokito, Ariel; Yang, Hongbo; Xie, Jipan; Benson, Al B

2017-11-01

The 2 somatostatin analogs currently recommended by the National Comprehensive Cancer Network for the treatment of gastrointestinal (GI) neuroendocrine tumors (NETs) include octreotide long-acting release (Sandostatin LAR) for injectable suspension and lanreotide (Somatuline Depot) injection for subcutaneous use. To estimate the costs to payers associated with 30-mg octreotide LAR and 120-mg lanreotide treatment among patients with metastatic GI-NETs. The costs to payers associated with the 2 drugs were estimated by including the costs of each drug, drug administration, and adverse events. The unit drug costs for octreotide LAR and for lanreotide were obtained from ReadyPrice Wholesale Acquisition Cost; the doses were obtained from published studies. The adverse event rates were obtained from 2 phase 3 clinical trials, PROMID and CLARINET. Deterministic one-way sensitivity analyses were used to assess the impact of modifying assumptions and inputs on the results, including the 2017 Average Sales Price (ASP). All costs were estimated in 2016 US dollars, with a constant discount of 3%. The costs to payers associated with the treatment of GI-NETs during 1-, 3-, and 5-year horizons were $74,566, $180,082, and $262,344, respectively, for octreotide LAR and $84,856, $205,562, and $299,667, respectively, for lanreotide. Thus, octreotide LAR was associated with lower costs by $10,290 (1 year), $25,480 (3 years), and $37,323 (5 years) compared with lanreotide. Over a 5-year horizon, the costs of adverse events and administration accounted for 0.72% of the total cost for octreotide LAR and 0.51% of the total cost for lanreotide. Sensitivity analyses confirmed that the main factor affecting the cost difference was the price of the drugs; analyses using the ASP yielded similar results. For the management of metastatic GI-NETs, the cost to payers of treatment with 30-mg octreotide LAR is considerably lower than with 120-mg lanreotide over 1-, 3-, and 5-year horizons. In the presence of healthcare resource constraints, these findings may support decision-making when considering the care of patients with metastatic GI-NETs.

Micropatterned comet assay enables high throughput and sensitive DNA damage quantification

PubMed Central

Ge, Jing; Chow, Danielle N.; Fessler, Jessica L.; Weingeist, David M.; Wood, David K.; Engelward, Bevin P.

2015-01-01

The single cell gel electrophoresis assay, also known as the comet assay, is a versatile method for measuring many classes of DNA damage, including base damage, abasic sites, single strand breaks and double strand breaks. However, limited throughput and difficulties with reproducibility have limited its utility, particularly for clinical and epidemiological studies. To address these limitations, we created a microarray comet assay. The use of a micrometer scale array of cells increases the number of analysable comets per square centimetre and enables automated imaging and analysis. In addition, the platform is compatible with standard 24- and 96-well plate formats. Here, we have assessed the consistency and sensitivity of the microarray comet assay. We showed that the linear detection range for H2O2-induced DNA damage in human lymphoblastoid cells is between 30 and 100 μM, and that within this range, inter-sample coefficient of variance was between 5 and 10%. Importantly, only 20 comets were required to detect a statistically significant induction of DNA damage for doses within the linear range. We also evaluated sample-to-sample and experiment-to-experiment variation and found that for both conditions, the coefficient of variation was lower than what has been reported for the traditional comet assay. Finally, we also show that the assay can be performed using a 4× objective (rather than the standard 10× objective for the traditional assay). This adjustment combined with the microarray format makes it possible to capture more than 50 analysable comets in a single image, which can then be automatically analysed using in-house software. Overall, throughput is increased more than 100-fold compared to the traditional assay. Together, the results presented here demonstrate key advances in comet assay technology that improve the throughput, sensitivity, and robustness, thus enabling larger scale clinical and epidemiological studies. PMID:25527723

Micropatterned comet assay enables high throughput and sensitive DNA damage quantification.

PubMed

Ge, Jing; Chow, Danielle N; Fessler, Jessica L; Weingeist, David M; Wood, David K; Engelward, Bevin P

2015-01-01

The single cell gel electrophoresis assay, also known as the comet assay, is a versatile method for measuring many classes of DNA damage, including base damage, abasic sites, single strand breaks and double strand breaks. However, limited throughput and difficulties with reproducibility have limited its utility, particularly for clinical and epidemiological studies. To address these limitations, we created a microarray comet assay. The use of a micrometer scale array of cells increases the number of analysable comets per square centimetre and enables automated imaging and analysis. In addition, the platform is compatible with standard 24- and 96-well plate formats. Here, we have assessed the consistency and sensitivity of the microarray comet assay. We showed that the linear detection range for H2O2-induced DNA damage in human lymphoblastoid cells is between 30 and 100 μM, and that within this range, inter-sample coefficient of variance was between 5 and 10%. Importantly, only 20 comets were required to detect a statistically significant induction of DNA damage for doses within the linear range. We also evaluated sample-to-sample and experiment-to-experiment variation and found that for both conditions, the coefficient of variation was lower than what has been reported for the traditional comet assay. Finally, we also show that the assay can be performed using a 4× objective (rather than the standard 10× objective for the traditional assay). This adjustment combined with the microarray format makes it possible to capture more than 50 analysable comets in a single image, which can then be automatically analysed using in-house software. Overall, throughput is increased more than 100-fold compared to the traditional assay. Together, the results presented here demonstrate key advances in comet assay technology that improve the throughput, sensitivity, and robustness, thus enabling larger scale clinical and epidemiological studies. © The Author 2014. Published by Oxford University Press on behalf of the Mutagenesis Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Characterizing grazing disturbance in semiarid ecosystems across broad scales, using diverse indices

USGS Publications Warehouse

Beever, E.A.; Tausch, R.J.; Brussard, P.F.

2003-01-01

Although management and conservation strategies continue to move toward broader spatial scales and consideration of many taxonomic groups simultaneously, researchers have struggled to characterize responses to disturbance at these scales. Most studies of disturbance by feral grazers investigate effects on only one or two ecosystem elements across small spatial scales, limiting their applicability to ecosystem-level management. To address this inadequacy, in 1997 and 1998 we examined disturbance created by feral horses (Equus caballus) in nine mountain ranges of the western Great Basin, USA, using plants, small mammals, ants, and soil compaction as indicators. Nine horse-occupied and 10 horse-removed sites were stratified into high- and low-elevation groups, and all sites at each elevation had similar vegetation type, aspect, slope gradient, and recent (≥15-yr) fire and livestock-grazing histories. Using reciprocal averaging and TWINSPAN analyses, we compared relationships among sites using five data sets: abiotic variables, percent cover by plant species, an index of abundance by plant species, 10 disturbance-sensitive response variables, and grass and shrub species considered “key” indicators by land managers. Although reciprocal averaging and TWINSPAN analyses of percent cover, abiotic variables, and key species suggested relationships between sites influenced largely by biogeography (i.e., mountain range), disturbance-sensitive variables clearly segregated horse-occupied and horse-removed sites. These analyses suggest that the influence of feral horses on many Great Basin ecosystem attributes is not being detected by monitoring only palatable plant species. We recommend development of an expanded monitoring strategy based not only on established vegetation measurements investigating forage consumption, but also including disturbance-sensitive variables (e.g., soil surface hardness, abundance of ant mounds) that more completely reflect the suite of effects that a large-bodied grazer may impose on mountain ecosystems, independent of vegetation differences. By providing a broader-based mechanism for detection of adverse effects, this strategy would provide management agencies with defensible data in a sociopolitical arena that has been embroiled in conflict for several decades.

Characterizing grazing disturbance in semiarid ecosystems across broad spatial scales using multiple indices.

USGS Publications Warehouse

Beever, Erik A.; Tausch, Robin J.; Brussard, Peter F.

2003-01-01

Although management and conservation strategies continue to move toward broader spatial scales and consideration of many taxonomic groups simultaneously, researchers have struggled to characterize responses to disturbance at these scales. Most studies of disturbance by feral grazers investigate effects on only one or two ecosystem elements across small spatial scales, limiting their applicability to ecosystem-level management. To address this inadequacy, in 1997 and 1998 we examined disturbance created by feral horses (Equus caballus) in nine mountain ranges of the western Great Basin, USA, using plants, small mammals, ants, and soil compaction as indicators. Nine horse-occupied and 10 horse-removed sites were stratified into high- and low-elevation groups, and all sites at each elevation had similar vegetation type, aspect, slope gradient, and recent (≥15-yr) fire and livestock-grazing histories. Using reciprocal averaging and TWINSPAN analyses, we compared relationships among sites using five data sets: abiotic variables, percent cover by plant species, an index of abundance by plant species, 10 disturbance-sensitive response variables, and grass and shrub species considered “key” indicators by land managers. Although reciprocal averaging and TWINSPAN analyses of percent cover, abiotic variables, and key species suggested relationships between sites influenced largely by biogeography (i.e., mountain range), disturbance-sensitive variables clearly segregated horse-occupied and horse-removed sites. These analyses suggest that the influence of feral horses on many Great Basin ecosystem attributes is not being detected by monitoring only palatable plant species. We recommend development of an expanded monitoring strategy based not only on established vegetation measurements investigating forage consumption, but also including disturbance-sensitive variables (e.g., soil surface hardness, abundance of ant mounds) that more completely reflect the suite of effects that a large-bodied grazer may impose on mountain ecosystems, independent of vegetation differences. By providing a broader-based mechanism for detection of adverse effects, this strategy would provide management agencies with defensible data in a sociopolitical arena that has been embroiled in conflict for several decades.

Cost-effectiveness analysis of thiazolidinediones in uncontrolled type 2 diabetic patients receiving sulfonylureas and metformin in Thailand.

PubMed

Chirakup, Suphachai; Chaiyakunapruk, Nathorn; Chaikledkeaw, Usa; Pongcharoensuk, Petcharat; Ongphiphadhanakul, Boonsong; Roze, Stephane; Valentine, William J; Palmer, Andrew J

2008-03-01

The national essential drug committee in Thailand suggested that only one of thiazolidinediones be included in hospital formulary but little was know about their cost-effectiveness values. This study aims to determine an incremental cost-effectiveness ratio of pioglitazone 45 mg compared with rosiglitazone 8 mg in uncontrolled type 2 diabetic patients receiving sulfonylureas and metformin in Thailand. A Markov diabetes model (Center for Outcome Research model) was used in this study. Baseline characteristics of patients were based on Thai diabetes registry project. Costs of diabetes were calculated mainly from Buddhachinaraj hospital. Nonspecific mortality rate and transition probabilities of death from renal replacement therapy were obtained from Thai sources. Clinical effectiveness of thiazolidinediones was retrieved from a meta-analysis. All analyses were based on the government hospital policymaker perspective. Both cost and outcomes were discounted with the rate of 3%. Base-case analyses were analyzed as incremental cost per quality-adjusted life year (QALY) gained. A series of sensitive analyses were performed. In base-case analysis, the pioglitazone group had a better clinical outcomes and higher lifetime costs. The incremental cost per QALY gained was 186,246 baht (US$ 5389). The acceptability curves showed that the probability of pioglitazone being cost-effective was 29% at the willingness to pay of one time of Thai gross domestic product per capita (GDP per capita). The effect of pioglitazone on %HbA1c decrease was the most sensitive to the final outcomes. Our findings showed that in type 2 diabetic patients who cannot control their blood glucose under the combination of sulfonylurea and metformin, the use of pioglitazone 45 mg fell in the cost-effective range recommended by World Health Organization (one to three times of GDP per capita) on average, compared to rosiglitazone 8 mg. Nevertheless, based on sensitivity analysis, its probability of being cost-effective was quite low. Hospital policymakers may consider our findings as part of information for the decision-making process.

Interpersonal sensitivity mediates the effects of child abuse and affective temperaments on depressive symptoms in the general adult population.

PubMed

Otsuka, Ayano; Takaesu, Yoshikazu; Sato, Mitsuhiko; Masuya, Jiro; Ichiki, Masahiko; Kusumi, Ichiro; Inoue, Takeshi

2017-01-01

Recent studies have suggested that multiple factors interact with the onset and prognosis of major depressive disorders. In this study, we investigated how child abuse, affective temperaments, and interpersonal sensitivity are interrelated, and how they affect depressive symptoms in the general adult population. A total of 415 volunteers from the general adult population completed the Patient Health Questionnaire-9, the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire version, the Child Abuse and Trauma Scale, and the Interpersonal Sensitivity Measure, which are all self-administered questionnaires. Data were subjected to structural equation modeling (Mplus), and single and multiple regression analyses. The effect of child abuse on depressive symptoms was mediated by interpersonal sensitivity and 4 affective temperaments, including depressive, cyclothymic, anxious, and irritable temperaments. In addition, the effect of these temperaments on depressive symptoms was mediated by interpersonal sensitivity, indicating the indirect enhancement of depressive symptoms. In contrast to these 4 temperaments, the hyperthymic temperament did not mediate the effect of child abuse on depressive symptoms; its effect was not mediated by interpersonal sensitivity. However, a greater hyperthymic temperament predicted decreased depressive symptoms and interpersonal sensitivity, independent of any mediation effect. Because this is a cross-sectional study, long-term prospective studies are necessary to confirm its findings. Therefore, recall bias should be considered when interpreting the results. As the subjects were adults from the general population, the results may not be generalizable towards all patients with major depression. This study suggests that child abuse and affective temperaments affect depressive symptoms partly through interpersonal sensitivity. Interpersonal sensitivity may have a major role in forming the link between abuse, affective temperament, and depression.

Task-shifting alcohol interventions for HIV+ persons in Kenya: a cost-benefit analysis.

PubMed

Galárraga, Omar; Gao, Burke; Gakinya, Benson N; Klein, Debra A; Wamai, Richard G; Sidle, John E; Papas, Rebecca K

2017-03-28

Among HIV+ patients, alcohol use is a highly prevalent risk factor for both HIV transmission and poor adherence to HIV treatment. The large-scale implementation of effective interventions for treating alcohol problems remains a challenge in low-income countries with generalized HIV epidemics. It is essential to consider an intervention's cost-effectiveness in dollars-per-health-outcome, and the long-term economic impact -or "return on investment" in monetary terms. We conducted a cost-benefit analysis, measuring economic return on investment, of a task-shifted cognitive-behavioral therapy (CBT) intervention delivered by paraprofessionals to reduce alcohol use in a modeled cohort of 13,440 outpatients in Kenya. In our base-case, we estimated the costs and economic benefits from a societal perspective across a six-year time horizon, with a 3% annual discount rate. Costs included all costs associated with training and administering task-shifted CBT therapy. Benefits included the economic impact of lowered HIV incidence as well as the improvements in household and labor-force productivity. We conducted univariate and multivariate probabilistic sensitivity analyses to test the robustness of our results. Under the base case, total costs for CBT rollout was $554,000, the value of benefits were $628,000, and the benefit-to-cost ratio was 1.13. Sensitivity analyses showed that under most assumptions, the benefit-to-cost ratio remained above unity indicating that the intervention was cost-saving (i.e., had positive return on investment). The duration of the treatment effect most effected the results in sensitivity analyses. CBT can be effectively and economically task-shifted to paraprofessionals in Kenya. The intervention can generate not only reductions in morbidity and mortality, but also economic savings for the health system in the medium and long term. The findings have implications for other countries with generalized HIV epidemics, high prevalence of alcohol consumption, and shortages of mental health professionals. This paper uses data derived from "Cognitive Behavioral Treatment to Reduce Alcohol Use Among HIV-Infected Kenyans (KHBS)" with ClinicalTrials.gov registration NCT00792519 on 11/17/2008; and preliminary data from "A Stage 2 Cognitive-behavioral Trial: Reduce Alcohol First in Kenya Intervention" ( NCT01503255 , registered on 12/16/2011).

Sobol method application in dimensional sensitivity analyses of different AFM cantilevers for biological particles

NASA Astrophysics Data System (ADS)

Korayem, M. H.; Taheri, M.; Ghahnaviyeh, S. D.

2015-08-01

Due to the more delicate nature of biological micro/nanoparticles, it is necessary to compute the critical force of manipulation. The modeling and simulation of reactions and nanomanipulator dynamics in a precise manipulation process require an exact modeling of cantilevers stiffness, especially the stiffness of dagger cantilevers because the previous model is not useful for this investigation. The stiffness values for V-shaped cantilevers can be obtained through several methods. One of them is the PBA method. In another approach, the cantilever is divided into two sections: a triangular head section and two slanted rectangular beams. Then, deformations along different directions are computed and used to obtain the stiffness values in different directions. The stiffness formulations of dagger cantilever are needed for this sensitivity analyses so the formulations have been driven first and then sensitivity analyses has been started. In examining the stiffness of the dagger-shaped cantilever, the micro-beam has been divided into two triangular and rectangular sections and by computing the displacements along different directions and using the existing relations, the stiffness values for dagger cantilever have been obtained. In this paper, after investigating the stiffness of common types of cantilevers, Sobol sensitivity analyses of the effects of various geometric parameters on the stiffness of these types of cantilevers have been carried out. Also, the effects of different cantilevers on the dynamic behavior of nanoparticles have been studied and the dagger-shaped cantilever has been deemed more suitable for the manipulation of biological particles.

Diagnostic accuracy of serological diagnosis of hepatitis C and B using dried blood spot samples (DBS): two systematic reviews and meta-analyses.

PubMed

Lange, Berit; Cohn, Jennifer; Roberts, Teri; Camp, Johannes; Chauffour, Jeanne; Gummadi, Nina; Ishizaki, Azumi; Nagarathnam, Anupriya; Tuaillon, Edouard; van de Perre, Philippe; Pichler, Christine; Easterbrook, Philippa; Denkinger, Claudia M

2017-11-01

Dried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV. We conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias. For the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%-99%) and 100% (95%CI:99-100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95-99) and 99% (CI95%:98-100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews. HCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.

Radiolabeled choline PET/CT before salvage lymphadenectomy dissection: a systematic review and meta-analysis.

PubMed

Evangelista, Laura; Zattoni, Fabio; Karnes, Robert J; Novara, Giacomo; Lowe, Val

2016-12-01

To provide a systematic review of recently published reports and carry out a meta-analysis on the use of radiolabeled choline PET/computed tomography (CT) as a guide for salvage lymph node dissection (sLND) in prostate cancer patients with biochemical recurrence after primary treatments. Bibliographic database searches, from 2005 to May 2015, including Pubmed, Web of Science, and TripDatabase, were performed to find studies that included only patients who underwent sLND after radiolabeled choline PET/CT alone or in combination with other imaging modalities. For the qualitative assessment, all studies including the selected population were considered. Conversely, for the quantitative assessment, articles were included only if absolute numbers of true positive, true negative, false positive, and false negative test results were available or derivable from the text for lymph node metastases. Reviews, clinical reports, and editorial articles were excluded from analyses. Eighteen studies fulfilled the inclusion criteria and were assessed qualitatively. A total of 750 patients underwent radiolabeled choline (such as C-choline or F-choline) PET/CT before sLND. A quantitative evaluation was performed in nine studies. A patient-based, a lesion-based, and a site-based analysis was carried out in nine, four, and five studies, respectively. The pooled sensitivities were 85.3% [95% confidence interval (CI): 78.5-90.3%], 56.2% (95% CI: 41.6-69.7%), 75.3% (95% CI: 56.6-87.7%), and 63.7% (95% CI: 41-81.6%), respectively, for patient-based, lesion-based, pelvic site-based, and retroperitoneal site-based analysis. The pooled positive predictive values (PPVs) were 75% (95% CI: 68-80.9%), 85.8% (95% CI: 66.8-94.8%), 81.2% (95% CI: 70.1-88.9%), and 75.2% (95% CI: 58.7-86.7%), respectively, in the same analyses. High heterogeneities among the studies were found for sensitivities and PPVs ranging between 61.7-93.3% and 60.6-94.5%, respectively. Radiolabeled choline PET/CT has only a moderate sensitivity for the detection of metastatic lymph nodes in patients who are candidates for sLND, although the pooled PPVs ranged between 75 and 85.8% for all type of subanalyses. The presence of high heterogeneity among the studies should be considered carefully.

Analysis of health economics assessment reports for pharmaceuticals in France – understanding the underlying philosophy of CEESP assessment

PubMed Central

Toumi, Mondher; Motrunich, Anastasiia; Millier, Aurélie; Rémuzat, Cécile; Chouaid, Christos; Falissard, Bruno; Aballéa, Samuel

2017-01-01

ABSTRACT Background: Despite the guidelines for Economic and Public Health Assessment Committee (CEESP) submission having been available for nearly six years, the dossiers submitted continue to deviate from them, potentially impacting product prices. Objective: to review the reports published by CEESP, analyse deviations from the guidelines, and discuss their implications for the pricing and reimbursement process. Study design: CEESP reports published until January 2017 were reviewed, and deviations from the guidelines were extracted. The frequency of deviations was described by type of methodological concern (minor, important or major). Results: In 19 reports, we identified 243 methodological concerns, most often concerning modelling, measurement and valuation of health states and results presentation and sensitivity analyses; nearly 63% were minor, 33% were important and 4.5% were major. All reports included minor methodological concerns, and 17 (89%) included at least one important and/or major methodological concern. Global major methodological concerns completely invalidated the analysis in seven dossiers (37%). Conclusion: The CEESP submission dossiers fail to adhere to the guidelines, potentially invalidating the health economics analysis and resulting in pricing negotiations. As these negotiations tend to be unfavourable for the manufacturer, the industry should strive to improve the quality of the analyses submitted to CEESP. PMID:28804600

Pain after root canal treatment with different instruments: A systematic review and meta-analysis.

PubMed

Sun, Chengjun; Sun, Jicheng; Tan, Minmin; Hu, Bo; Gao, Xiang; Song, Jinlin

2018-03-07

The aims of this systematic review were to compare the incidence and intensity of postoperative pain after single-visit root canal treatment using manual, rotary and reciprocating instruments. An extensive literature search in PubMed, EMBASE, Cochrane Library, and Web of Science was performed to identify investigations that evaluated the effects of different instruments on post-endodontic pain. Meta-analyses and additional analyses, including subgroup and sensitivity analyses, were conducted. We included seventeen trials in this study. Pooled results showed that patients treated with rotary instruments experienced a significantly lower incidence of postoperative pain (RR, 0.32, P = 0.0005) and reduced pain intensity than did patients treated with manual instruments. In addition, patients treated with multiple rotary-file systems experienced a significantly lower incidence of postoperative pain than did those treated with reciprocating systems (RR, 0.73; P < 0.0001). The use of rotary instruments contributed to a lower incidence and intensity of postoperative pain than did the use of hand files in patients who received single-visit root canal treatment. In addition, the use of multiple rotary-file systems contributed to a lower incidence of postoperative pain than did the use of reciprocating systems. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Resilience-based performance metrics for water resources management under uncertainty

NASA Astrophysics Data System (ADS)

Roach, Tom; Kapelan, Zoran; Ledbetter, Ralph

2018-06-01

This paper aims to develop new, resilience type metrics for long-term water resources management under uncertain climate change and population growth. Resilience is defined here as the ability of a water resources management system to 'bounce back', i.e. absorb and then recover from a water deficit event, restoring the normal system operation. Ten alternative metrics are proposed and analysed addressing a range of different resilience aspects including duration, magnitude, frequency and volume of related water deficit events. The metrics were analysed on a real-world case study of the Bristol Water supply system in the UK and compared with current practice. The analyses included an examination of metrics' sensitivity and correlation, as well as a detailed examination into the behaviour of metrics during water deficit periods. The results obtained suggest that multiple metrics which cover different aspects of resilience should be used simultaneously when assessing the resilience of a water resources management system, leading to a more complete understanding of resilience compared with current practice approaches. It was also observed that calculating the total duration of a water deficit period provided a clearer and more consistent indication of system performance compared to splitting the deficit periods into the time to reach and time to recover from the worst deficit events.

Evaluation of the divided attention condition during functional analyses.

PubMed

Fahmie, Tara A; Iwata, Brian A; Harper, Jill M; Querim, Angie C

2013-01-01

A common condition included in most functional analyses (FAs) is the attention condition, in which the therapist ignores the client by engaging in a solitary activity (antecedent event) but delivers attention to the client contingent on problem behavior (consequent event). The divided attention condition is similar, except that the antecedent event consists of the therapist conversing with an adult confederate. We compared the typical and divided attention conditions to determine whether behavior in general (Study 1) and problem behavior in particular (Study 2) were more sensitive to one of the test conditions. Results showed that the divided attention condition resulted in faster acquisition or more efficient FA results for 2 of 9 subjects, suggesting that the divided attention condition could be considered a preferred condition when resources are available. © Society for the Experimental Analysis of Behavior.

Application of the High Resolution Melting analysis for genetic mapping of Sequence Tagged Site markers in narrow-leafed lupin (Lupinus angustifolius L.).

PubMed

Kamel, Katarzyna A; Kroc, Magdalena; Święcicki, Wojciech

2015-01-01

Sequence tagged site (STS) markers are valuable tools for genetic and physical mapping that can be successfully used in comparative analyses among related species. Current challenges for molecular markers genotyping in plants include the lack of fast, sensitive and inexpensive methods suitable for sequence variant detection. In contrast, high resolution melting (HRM) is a simple and high-throughput assay, which has been widely applied in sequence polymorphism identification as well as in the studies of genetic variability and genotyping. The present study is the first attempt to use the HRM analysis to genotype STS markers in narrow-leafed lupin (Lupinus angustifolius L.). The sensitivity and utility of this method was confirmed by the sequence polymorphism detection based on melting curve profiles in the parental genotypes and progeny of the narrow-leafed lupin mapping population. Application of different approaches, including amplicon size and a simulated heterozygote analysis, has allowed for successful genetic mapping of 16 new STS markers in the narrow-leafed lupin genome.

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

PubMed

O'Day, Ken; Meyer, Kellie; Stafkey-Mailey, Dana; Watson, Crystal

2015-04-01

To assess the cost-effectiveness of natalizumab vs fingolimod over 2 years in relapsing-remitting multiple sclerosis (RRMS) patients and patients with rapidly evolving severe disease in Sweden. A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from the perspective of the Swedish healthcare system. Modeled 2-year costs in Swedish kronor of treating RRMS patients included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided using data from the AFFIRM and FREEDOMS trials for all patients with RRMS and from post-hoc sub-group analyses for patients with rapidly evolving severe disease. Probabilistic sensitivity analyses were conducted to assess uncertainty. The analysis showed that, in all patients with MS, treatment with fingolimod costs less (440,463 Kr vs 444,324 Kr), but treatment with natalizumab results in more relapses avoided (0.74 vs 0.59), resulting in an incremental cost-effectiveness ratio (ICER) of 25,448 Kr per relapse avoided. In patients with rapidly evolving severe disease, natalizumab dominated fingolimod. Results of the sensitivity analysis demonstrate the robustness of the model results. At a willingness-to-pay (WTP) threshold of 500,000 Kr per relapse avoided, natalizumab is cost-effective in >80% of simulations in both patient populations. Limitations include absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as the primary model outcome, assumption of 100% adherence to MS treatment, and exclusion of adverse event costs in the model. Natalizumab remains a cost-effective treatment option for patients with MS in Sweden. In the RRMS patient population, the incremental cost per relapse avoided is well below a 500,000 Kr WTP threshold per relapse avoided. In the rapidly evolving severe disease patient population, natalizumab dominates fingolimod.

Association between Use of Exogenous Testosterone Therapy and Risk of Venous Thrombotic Events among Exogenous Testosterone Treated and Untreated Men with Hypogonadism.

PubMed

Li, Hu; Benoit, Karin; Wang, Wei; Motsko, Stephen

2016-04-01

Limited information exists about whether exogenous testosterone therapy is associated with a risk of venous thrombotic events. We investigated via cohort and nested case-control analyses whether exogenous testosterone therapy is associated with the risk of venous thrombotic events in men with hypogonadism. Databases were reviewed to identify men prescribed exogenous testosterone therapy and/or men with a hypogonadism diagnosis. Propensity score 1:1 matching was used to select patients for cohort analysis. Cases (men with venous thrombotic events) were matched 1:4 with controls (men without venous thrombotic events) for the nested case-control analysis. Primary outcome was defined as incident idiopathic venous thrombotic events. Cox regression and conditional logistic regression were used to assess HRs and ORs, respectively. Sensitivity analyses were also performed. A total of 102,650 exogenous testosterone treated and 102,650 untreated patients were included in cohort analysis after matching, and 2,785 cases and 11,119 controls were included in case-control analysis. Cohort analysis revealed a HR of 1.08 for all testosterone treated patients (95% CI 0.91, 1.27, p = 0.378). Case-control analysis resulted in an OR of 1.02 (95% CI 0.92, 1.13, p = 0.702) for current exogenous testosterone therapy exposure and an OR of 0.92 (95% CI 0.82, 1.03, p = 0.145) for past exogenous testosterone therapy exposure. These results remained nonstatistically significant after stratifying by exogenous testosterone therapy administration route and age category. Most sensitivity analyses yielded consistent results. No significant association was found between exogenous testosterone therapy and incidents of idiopathic or overall venous thrombotic events in men with hypogonadism. However, some discrepant findings exist for the association between injectable formulations and the risk of overall venous thrombotic events. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Spatiotemporal sensitivity analysis of vertical transport of pesticides in soil

EPA Science Inventory

Environmental fate and transport processes are influenced by many factors. Simulation models that mimic these processes often have complex implementations, which can lead to over-parameterization. Sensitivity analyses are subsequently used to identify critical parameters whose un...

Childhood Leukemia and 50 Hz Magnetic Fields: Findings from the Italian SETIL Case-Control Study

PubMed Central

Salvan, Alberto; Ranucci, Alessandra; Lagorio, Susanna; Magnani, Corrado

2015-01-01

We report on an Italian case-control study on childhood leukemia and exposure to extremely low frequency magnetic fields (ELF-MF). Eligible for inclusion were 745 leukemia cases, aged 0–10 years at diagnosis in 1998–2001, and 1475 sex- and age-matched population controls. Parents of 683 cases and 1044 controls (92% vs. 71%) were interviewed. ELF-MF measurements (24–48 h), in the child’s bedroom of the dwelling inhabited one year before diagnosis, were available for 412 cases and 587 controls included in the main conditional regression analyses. The magnetic field induction was 0.04 μT on average (geometric mean), with 0.6% of cases and 1.6% of controls exposed to >0.3 μT. The impact of changes in the statistical model, exposure metric, and data-set restriction criteria was explored via sensitivity analyses. No exposure-disease association was observed in analyses based on continuous exposure, while analyses based on categorical variables were characterized by incoherent exposure-outcome relationships. In conclusion, our results may be affected by several sources of bias and they are noninformative at exposure levels >0.3 μT. Nonetheless, the study may contribute to future meta- or pooled analyses. Furthermore, exposure levels among population controls are useful to estimate attributable risk. PMID:25689995

Long-term health experience of jet engine manufacturing workers: V. Issues with the analysis of non-malignant central nervous system neoplasms.

PubMed

Buchanich, Jeanine M; Youk, Ada O; Marsh, Gary M; Kennedy, Kathleen J; Lacey, Steven E; Hancock, Roger P; Esmen, Nurtan A; Cunningham, Michael A; Leiberman, Frank S; Fleissner, Mary Lou

2011-01-01

We attempted to examine non-malignant central nervous system (CNS) neoplasms incidence rates for workers at 8 jet engine manufacturing facilities in Connecticut. The objective of this manuscript is to describe difficulties encountered regarding these analyses to aid future studies. We traced the cohort for incident cases of CNS neoplasms in states where 95% of deaths in the total cohort occurred. We used external and internal analyses in an attempt to obtain the true risk of non-malignant CNS in the cohort. Because these analyses were limited by data constraints, we conducted sensitivity analyses, including using state driver's license data to adjust person-year stop dates to help minimize underascertainment and more accurately determine cohort risk estimates. We identified 3 unanticipated challenges: case identification, determination of population-based cancer incidence rates, and handling of case underascertainment. These factors precluded an accurate assessment of non-malignant CNS neoplasm incidence risks in this occupational epidemiology study. The relatively recent (2004) mandate of capturing non-malignant CNS tumor data at the state level means that, in time, it may be possible to conduct external analyses of these data. Meanwhile, similar occupational epidemiology studies may be limited to descriptive analysis of the non-malignant CNS case characteristics.

Relationship between cataract severity and socioeconomic status.

PubMed

Wesolosky, Jason D; Rudnisky, Christopher J

2013-12-01

To determine the relationship between cataract severity and socioeconomic status (SES). Retrospective, observational case series. A total of 1350 eyes underwent phacoemulsification cataract extraction by a single surgeon using an Alcon Infiniti system. Cataract severity was measured using phaco time in seconds. SES was measured using area-level aggregate census data: median income, education, proportion of common-law couples, and employment rate. Preoperative best corrected visual acuity was obtained and converted to logarithm of the minimum angle of resolution values. For patients undergoing bilateral surgery, the generalized estimating equation was used to account for the correlation between eyes. Univariate analyses were performed using simple regression, and multivariate analyses were performed to account for variables with significant relationships (p < 0.05) on univariate testing. Sensitivity analyses were performed to assess the effect of including patient age in the controlled analyses. Multivariate analyses demonstrated that cataracts were more severe when the median income was lower (p = 0.001) and the proportion of common-law couples living in a patient's community (p = 0.012) and the unemployment rate (p = 0.002) were higher. These associations persisted even when controlling for patient age. Patients of lower SES have more severe cataracts. Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Preterm Birth and Childhood Wheezing Disorders: A Systematic Review and Meta-Analysis

PubMed Central

Been, Jasper V.; Lugtenberg, Marlies J.; Smets, Eline; van Schayck, Constant P.; Kramer, Boris W.; Mommers, Monique; Sheikh, Aziz

2014-01-01

Background Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth. Methods and Findings Two reviewers independently searched seven online databases for contemporaneous (1 January 1995–23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated “dose–response” associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations. We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57–1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29–1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61–3.44; adjusted: OR 2.81, 95% CI 2.55–3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ≥3.1%. Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual confounding. Conclusions There is compelling evidence that preterm birth—particularly very preterm birth—increases the risk of asthma. Given the projected global increases in children surviving preterm births, research now needs to focus on understanding underlying mechanisms, and then to translate these insights into the development of preventive interventions. Review Registration PROSPERO CRD42013004965 Please see later in the article for the Editors' Summary PMID:24492409

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.

Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

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

Dong, Lihua; Cui, Jingkun; Tang, Fengjiao

Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATMmore » polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was dependent on the incidence of the injury. These support the evidence of an association between the rs1801516 polymorphism and acute radiation injuries, encouraging further research of this topic.« less

Validity of injecting drug users' self report of hepatitis A, B, and C.

PubMed

Schlicting, Erin G; Johnson, Mark E; Brems, Christiane; Wells, Rebecca S; Fisher, Dennis G; Reynolds, Grace

2003-01-01

To test the validity of drug users self-reports of diseases associated with drug use, in this case hepatitis A, B, and C. Injecting drug users (n = 653) were recruited and asked whether they had been diagnosed previously with hepatitis A, B, and/or C. These self-report data were compared to total hepatitis A antibody, hepatitis B core antibody, and hepatitis C antibody seromarkers as a means of determining the validity of the self-reported information. Anchorage, Alaska. Criteria for inclusion included being at least 18-years old; testing positive on urinalysis for cocaine metabolites, amphetamine, or morphine; having visible signs of injection (track marks). Serological testing for hepatitis A, B, and C. Findings indicate high specificity, low sensitivity, and low kappa coefficients for all three self-report measures. Subgroup analyses revealed significant differences in sensitivity associated with previous substance abuse treatment experience for hepatitis B self-report and with gender for hepatitis C self-report. Given the low sensitivity, the validity of drug users, self-reported information on hepatitis should be considered with caution.

NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience.

PubMed

Singh-Taylor, A; Molet, J; Jiang, S; Korosi, A; Bolton, J L; Noam, Y; Simeone, K; Cope, J; Chen, Y; Mortazavi, A; Baram, T Z

2018-03-01

Resilience to stress-related emotional disorders is governed in part by early-life experiences. Here we demonstrate experience-dependent re-programming of stress-sensitive hypothalamic neurons, which takes place through modification of neuronal gene expression via epigenetic mechanisms. Specifically, we found that augmented maternal care reduced glutamatergic synapses onto stress-sensitive hypothalamic neurons and repressed expression of the stress-responsive gene, Crh. In hypothalamus in vitro, reduced glutamatergic neurotransmission recapitulated the repressive effects of augmented maternal care on Crh, and this required recruitment of the transcriptional repressor repressor element-1 silencing transcription factor/neuron restrictive silencing factor (NRSF). Increased NRSF binding to chromatin was accompanied by sequential repressive epigenetic changes which outlasted NRSF binding. chromatin immunoprecipitation-seq analyses of NRSF targets identified gene networks that, in addition to Crh, likely contributed to the augmented care-induced phenotype, including diminished depression-like and anxiety-like behaviors. Together, we believe these findings provide the first causal link between enriched neonatal experience, synaptic refinement and induction of epigenetic processes within specific neurons. They uncover a novel mechanistic pathway from neonatal environment to emotional resilience.

High order statistical signatures from source-driven measurements of subcritical fissile systems

NASA Astrophysics Data System (ADS)

Mattingly, John Kelly

1998-11-01

This research focuses on the development and application of high order statistical analyses applied to measurements performed with subcritical fissile systems driven by an introduced neutron source. The signatures presented are derived from counting statistics of the introduced source and radiation detectors that observe the response of the fissile system. It is demonstrated that successively higher order counting statistics possess progressively higher sensitivity to reactivity. Consequently, these signatures are more sensitive to changes in the composition, fissile mass, and configuration of the fissile assembly. Furthermore, it is shown that these techniques are capable of distinguishing the response of the fissile system to the introduced source from its response to any internal or inherent sources. This ability combined with the enhanced sensitivity of higher order signatures indicates that these techniques will be of significant utility in a variety of applications. Potential applications include enhanced radiation signature identification of weapons components for nuclear disarmament and safeguards applications and augmented nondestructive analysis of spent nuclear fuel. In general, these techniques expand present capabilities in the analysis of subcritical measurements.

A comparison of maternal sensitivity and verbal stimulation as unique predictors of infant social-emotional and cognitive development.

PubMed

Page, Melissa; Wilhelm, Mari S; Gamble, Wendy C; Card, Noel A

2010-02-01

Although maternal sensitivity has been shown to influence social-emotional development, the role of verbal stimulation on infant developmental outcomes has received less exploration. Recent research has focused on intentional behaviors within the context of a mother-infant interaction as a critical influence and as distinct from sensitivity. In this investigation 6377 mother-infant dyads participated in a teaching task as part of the sample from the Early Childhood Longitudinal Study Birth Cohort (ECLS-B). Analyses focused in deciphering the role of maternal sensitivity and verbal stimulation as contributors to the infant's social-emotional (S-E) and cognitive (Cog) development. We further hypothesized that inclusion of infant age as a moderator of maternal behaviors would illuminate any differences between younger and older infants. For the infant's S-E development, our hypothesis that maternal sensitivity would be a stronger predictor than verbal stimulation was not supported; nor did we find support for our hypothesis that the association would be moderated by age. For Cog development, only verbal stimulation had a direct positive effect on the infant's cognitive ability; our findings for moderation showed that mothers spoke more to older infants than younger infants. Identification of specific maternal behaviors associated with infant outcomes informs the child development field, and also provides strategies for early intervention to assist mothers with developing or maintaining a consistent relationship that includes sensitivity and verbal stimulation. Published by Elsevier Inc.

Psychobiological influences on maternal sensitivity in the context of adversity.

PubMed

Finegood, Eric D; Blair, Clancy; Granger, Douglas A; Hibel, Leah C; Mills-Koonce, Roger

2016-07-01

This study evaluated prospective longitudinal relations among an index of poverty-related cumulative risk, maternal salivary cortisol, child negative affect, and maternal sensitivity across the first 2 postpartum years. Participants included 1,180 biological mothers residing in rural and predominantly low-income communities in the United States. Multilevel growth curve analyses indicated that an index of cumulative risk was positively associated with maternal cortisol across the postpartum (study visits occurring at approximately 7, 15, and 24 months postpartum) over and above effects for African American ethnicity, time of day of saliva collection, age, parity status, having given birth to another child, contraceptive use, tobacco smoking, body mass index, and breastfeeding. Consistent with a psychobiological theory of mothering, maternal salivary cortisol was negatively associated with maternal sensitivity observed during parent-child interactions across the first 2 postpartum years over and above effects for poverty-related cumulative risk, child negative affect, as well as a large number of covariates associated with cortisol and maternal sensitivity. Child negative affect expressed during parent-child interactions was negatively associated with observed maternal sensitivity at late (24 months) but not early time points of observation (7 months) and cumulative risk was negatively associated with maternal sensitivity across the postpartum and this effect strengthened over time. Results advance our understanding of the dynamic, transactional, and psychobiological influences on parental caregiving behaviors across the first 2 postpartum years. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Taxometric and Factor Analytic Models of Anxiety Sensitivity: Integrating Approaches to Latent Structural Research

ERIC Educational Resources Information Center

Bernstein, Amit; Zvolensky, Michael J.; Norton, Peter J.; Schmidt, Norman B.; Taylor, Steven; Forsyth, John P.; Lewis, Sarah F.; Feldner, Matthew T.; Leen-Feldner, Ellen W.; Stewart, Sherry H.; Cox, Brian

2007-01-01

This study represents an effort to better understand the latent structure of anxiety sensitivity (AS), as indexed by the 16-item Anxiety Sensitivity Index (ASI; S. Reiss, R. A. Peterson, M. Gursky, & R. J. McNally, 1986), by using taxometric and factor-analytic approaches in an integrative manner. Taxometric analyses indicated that AS has a…

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

Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection.

PubMed

Varier, Raghu U; Biltaji, Eman; Smith, Kenneth J; Roberts, Mark S; Kyle Jensen, M; LaFleur, Joanne; Nelson, Richard E

2015-04-01

Clostridium difficile infection (CDI) places a high burden on the US healthcare system. Recurrent CDI (RCDI) occurs frequently. Recently proposed guidelines from the American College of Gastroenterology (ACG) and the American Gastroenterology Association (AGA) include fecal microbiota transplantation (FMT) as a therapeutic option for RCDI. The purpose of this study was to estimate the cost-effectiveness of FMT compared with vancomycin for the treatment of RCDI in adults, specifically following guidelines proposed by the ACG and AGA. We constructed a decision-analytic computer simulation using inputs from the published literature to compare the standard approach using tapered vancomycin to FMT for RCDI from the third-party payer perspective. Our effectiveness measure was quality-adjusted life years (QALYs). Because simulated patients were followed for 90 days, discounting was not necessary. One-way and probabilistic sensitivity analyses were performed. Base-case analysis showed that FMT was less costly ($1,669 vs $3,788) and more effective (0.242 QALYs vs 0.235 QALYs) than vancomycin for RCDI. One-way sensitivity analyses showed that FMT was the dominant strategy (both less expensive and more effective) if cure rates for FMT and vancomycin were ≥70% and <91%, respectively, and if the cost of FMT was <$3,206. Probabilistic sensitivity analysis, varying all parameters simultaneously, showed that FMT was the dominant strategy over 10, 000 second-order Monte Carlo simulations. Our results suggest that FMT may be a cost-saving intervention in managing RCDI. Implementation of FMT for RCDI may help decrease the economic burden to the healthcare system.

Comparing five alternative methods of breast reconstruction surgery: a cost-effectiveness analysis.

PubMed

Grover, Ritwik; Padula, William V; Van Vliet, Michael; Ridgway, Emily B

2013-11-01

The purpose of this study was to assess the cost-effectiveness of five standardized procedures for breast reconstruction to delineate the best reconstructive approach in postmastectomy patients in the settings of nonirradiated and irradiated chest walls. A decision tree was used to model five breast reconstruction procedures from the provider perspective to evaluate cost-effectiveness. Procedures included autologous flaps with pedicled tissue, autologous flaps with free tissue, latissimus dorsi flaps with breast implants, expanders with implant exchange, and immediate implant placement. All methods were compared with a "do-nothing" alternative. Data for model parameters were collected through a systematic review, and patient health utilities were calculated from an ad hoc survey of reconstructive surgeons. Results were measured in cost (2011 U.S. dollars) per quality-adjusted life-year. Univariate sensitivity analyses and Bayesian multivariate probabilistic sensitivity analysis were conducted. Pedicled autologous tissue and free autologous tissue reconstruction were cost-effective compared with the do-nothing alternative. Pedicled autologous tissue was the slightly more cost-effective of the two. The other procedures were not found to be cost-effective. The results were robust to a number of sensitivity analyses, although the margin between pedicled and free autologous tissue reconstruction is small and affected by some parameter values. Autologous pedicled tissue was slightly more cost-effective than free tissue reconstruction in irradiated and nonirradiated patients. Implant-based techniques were not cost-effective. This is in agreement with the growing trend at academic institutions to encourage autologous tissue reconstruction because of its natural recreation of the breast contour, suppleness, and resiliency in the setting of irradiated recipient beds.

Cost-effectiveness analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial.

PubMed

Zhan, Mei; Zheng, Hanrui; Xu, Ting; Yang, Yu; Li, Qiu

2017-08-01

Malignant pleural mesothelioma (MPM) is a rare malignancy, and pemetrexed/cisplatin (PC) is the gold standard first-line regime. This study evaluated the cost-effectiveness of the addition of bevacizumab to PC (with maintenance bevacizumab) for unresectable MPM based on a phase III trial that showed a survival benefit compared with chemotherapy alone. To estimate the incremental cost-effectiveness ratio (ICER) of the incorporation of bevacizumab, a Markov model based on the MAPS trial, including the disease states of progression-free survival, progressive disease and death, was used. Total costs were calculated from a Chinese payer perspective, and health outcomes were converted into quality-adjusted life year (QALY). Model robustness was explored in sensitivity analyses. The addition of bevacizumab to PC was estimated to increase the cost by $81446.69, with a gain of 0.112 QALYs, resulting in an ICER of $727202.589 per QALY. In both one-way sensitivity and probabilistic sensitivity analyses, the ICER exceeded the commonly accepted willingness-to-pay threshold of 3 times the gross domestic product per capita of China ($23970.00 per QALY). The cost of bevacizumab had the most important impact on the ICER. The combination of bevacizumab with PC chemotherapy is not a cost-effective treatment option for MPM in China. Given its positive clinical value and extremely low incidence of MPM, an appropriate price discount, assistance programs and medical insurance should be considered to make bevacizumab more affordable for this rare patient population. Copyright © 2017 Elsevier B.V. All rights reserved.

Siemens Immulite Aspergillus-specific IgG assay for chronic pulmonary aspergillosis diagnosis.

PubMed

Page, Iain D; Richardson, Malcolm D; Denning, David W

2018-05-14

Chronic pulmonary aspergillosis (CPA) complicates underlying lung disease, including treated tuberculosis. Measurement of Aspergillus-specific immunoglobulin G (IgG) is a key diagnostic step. Cutoffs have been proposed based on receiver operating characteristic (ROC) curve analyses comparing CPA cases to healthy controls, but performance in at-risk populations with underlying lung disease is unclear. We evaluated optimal cutoffs for the Siemens Immulite Aspergillus-specific IgG assay for CPA diagnosis in relation to large groups of healthy and diseased controls with treated pulmonary tuberculosis. Sera from 241 patients with CPA attending the UK National Aspergillosis Centre, 299 Ugandan blood donors (healthy controls), and 398 Ugandans with treated pulmonary tuberculosis (diseased controls) were tested. Radiological screening removed potential CPA cases from diseased controls (234 screened diseased controls). ROC curve analyses were performed and optimal cutoffs identified by Youden J statistic. CPA versus control ROC area under curve (AUC) results were: healthy controls 0.984 (95% confidence interval 0.972-0.997), diseased controls 0.972 (0.959-0.985), screened diseased controls 0.979 (0.967-0.992). Optimal cutoffs were: healthy controls 15 mg/l (94.6% sensitivity, 98% specificity), unscreened diseased controls 15 mg/l (94.6% sensitivity, 94.5% specificity), screened diseased controls 25 mg/l (92.9% sensitivity, 98.7% specificity). Results were similar in healthy and diseased controls. We advocate a cutoff of 20 mg/l as this is the midpoint of the range of optimal cutoffs. Cutoffs calculated in relation to healthy controls for other assays are likely to remain valid for use in a treated tuberculosis population.

Economic Evaluation of Frequent Home Nocturnal Hemodialysis Based on a Randomized Controlled Trial

PubMed Central

Tonelli, Marcello; Pauly, Robert; Walsh, Michael; Culleton, Bruce; So, Helen; Hemmelgarn, Brenda; Manns, Braden

2014-01-01

Provider and patient enthusiasm for frequent home nocturnal hemodialysis (FHNHD) has been renewed; however, the cost-effectiveness of this technique is unknown. We performed a cost-utility analysis of FHNHD compared with conventional hemodialysis (CvHD; 4 hours three times per week) from a health payer perspective over a lifetime horizon using patient information from the Alberta NHD randomized controlled trial. Costs, including training costs, were obtained using microcosting and administrative data (CAN$2012). We determined the incremental cost per quality-adjusted life year (QALY) gained. Robustness was assessed using scenario, sensitivity, and probabilistic sensitivity analyses. Compared with CvHD (61% in-center, 14% satellite, and 25% home dialysis), FHNHD led to incremental cost savings (−$6700) and an additional 0.38 QALYs. In sensitivity analyses, when the annual probability of technique failure with FHNHD increased from 7.6% (reference case) to ≥19%, FHNHD became unattractive (>$75,000/QALY). The cost/QALY gained became $13,000 if average training time for FHNHD increased from 3.7 to 6 weeks. In scenarios with alternate comparator modalities, FHNHD remained dominant compared with in-center CvHD; cost/QALYs gained were $18,500, $198,000, and $423,000 compared with satellite CvHD, home CvHD, and peritoneal dialysis, respectively. In summary, FHNHD is attractive compared with in-center CvHD in this cohort. However, the attractiveness of FHNHD varies by technique failure rate, training time, and dialysis modalities from which patients are drawn, and these variables should be considered when establishing FHNHD programs. PMID:24231665

The clinical and economic impact of point-of-care CD4 testing in mozambique and other resource-limited settings: a cost-effectiveness analysis.

PubMed

Hyle, Emily P; Jani, Ilesh V; Lehe, Jonathan; Su, Amanda E; Wood, Robin; Quevedo, Jorge; Losina, Elena; Bassett, Ingrid V; Pei, Pamela P; Paltiel, A David; Resch, Stephen; Freedberg, Kenneth A; Peter, Trevor; Walensky, Rochelle P

2014-09-01

Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique. We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9% (95% CI, 60.9%-61.0%), increasing to 65.0% (95% CI, 64.9%-65.1%) with POC-CD4. Discounted life expectancy and per person lifetime costs with LAB-CD4 are 9.6 y (95% CI, 9.6-9.6 y) and US$2,440 (95% CI, US$2,440-US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3-10.3 y) and US$2,800 (95% CI, US$2,790-US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480-US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4. POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited. Please see later in the article for the Editors' Summary.

Bias from historical control groups used in orthodontic research: a meta-epidemiological study.

PubMed

Papageorgiou, Spyridon N; Koretsi, Vasiliki; Jäger, Andreas

2017-02-01

The validity of meta-analysis is dependent upon the quality of included studies. Here, we investigated whether the design of untreated control groups (i.e. source and timing of data collection) influences the results of clinical trials in orthodontic research. This meta-epidemiological study used unrestricted literature searching for meta-analyses in orthodontics including clinical trials with untreated control groups. Differences in standardized mean differences (ΔSMD) and their 95% confidence intervals (CIs) were calculated according to the untreated control group through multivariable random-effects meta-regression controlling for nature of the interventional group and study sample size. Effects were pooled with random-effects synthesis, followed by mixed-effect subgroup and sensitivity analyses. Studies with historical control groups reported deflated treatment effects compared to studies with concurrent control groups (13 meta-analyses; ΔSMD = -0.31; 95% CI = -0.53, -0.10; P = 0.004). Significant differences were found according to the type of historical control group (based either on growth study or clinical archive; 11 meta-analyses; ΔSMD = 0.40; 95% CI = 0.21, 0.59; P < 0.001). The use of historical control groups in orthodontic clinical research was associated with deflation of treatment effects, which was independent from whether the interventional group was prospective or retrospective and from the study's sample size. Caution is warranted when interpreting clinical studies with historical untreated control groups or when interpreting systematic reviews that include such studies. PROSPERO (CRD42015024179). None. © The Author 2016. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Transportation systems analyses. Volume 2: Technical/programmatics

NASA Astrophysics Data System (ADS)

1993-05-01

The principal objective of this study is to accomplish a systems engineering assessment of the nation's space transportation infrastructure. This analysis addresses the necessary elements to perform man delivery and return, cargo transfer, cargo delivery, payload servicing, and the exploration of the Moon and Mars. Specific elements analyzed, but not limited to, include the Space Exploration Initiative (SEI), the National Launch System (NLS), the current expendable launch vehicle (ELV) fleet, ground facilities, the Space Station Freedom (SSF), and other civil, military and commercial payloads. The performance of this study entails maintaining a broad perspective on the large number of transportation elements that could potentially comprise the U.S. space infrastructure over the next several decades. To perform this systems evaluation, top-level trade studies are conducted to enhance our understanding of the relationships between elements of the infrastructure. This broad 'infrastructure-level perspective' permits the identification of preferred infrastructures. Sensitivity analyses are performed to assure the credibility and usefulness of study results. This report documents the three principal transportation systems analyses (TSA) efforts during the period 7 November 92 - 6 May 93. The analyses are as follows: Mixed-Fleet (STS/ELV) strategies for SSF resupply; Transportation Systems Data Book - overview; and Operations Cost Model - overview/introduction.

Disclosure control using partially synthetic data for large-scale health surveys, with applications to CanCORS.

PubMed

Loong, Bronwyn; Zaslavsky, Alan M; He, Yulei; Harrington, David P

2013-10-30

Statistical agencies have begun to partially synthesize public-use data for major surveys to protect the confidentiality of respondents' identities and sensitive attributes by replacing high disclosure risk and sensitive variables with multiple imputations. To date, there are few applications of synthetic data techniques to large-scale healthcare survey data. Here, we describe partial synthesis of survey data collected by the Cancer Care Outcomes Research and Surveillance (CanCORS) project, a comprehensive observational study of the experiences, treatments, and outcomes of patients with lung or colorectal cancer in the USA. We review inferential methods for partially synthetic data and discuss selection of high disclosure risk variables for synthesis, specification of imputation models, and identification disclosure risk assessment. We evaluate data utility by replicating published analyses and comparing results using original and synthetic data and discuss practical issues in preserving inferential conclusions. We found that important subgroup relationships must be included in the synthetic data imputation model, to preserve the data utility of the observed data for a given analysis procedure. We conclude that synthetic CanCORS data are suited best for preliminary data analyses purposes. These methods address the requirement to share data in clinical research without compromising confidentiality. Copyright © 2013 John Wiley & Sons, Ltd.

Optimizing a multi-product closed-loop supply chain using NSGA-II, MOSA, and MOPSO meta-heuristic algorithms

NASA Astrophysics Data System (ADS)

Babaveisi, Vahid; Paydar, Mohammad Mahdi; Safaei, Abdul Sattar

2018-07-01

This study aims to discuss the solution methodology for a closed-loop supply chain (CLSC) network that includes the collection of used products as well as distribution of the new products. This supply chain is presented on behalf of the problems that can be solved by the proposed meta-heuristic algorithms. A mathematical model is designed for a CLSC that involves three objective functions of maximizing the profit, minimizing the total risk and shortages of products. Since three objective functions are considered, a multi-objective solution methodology can be advantageous. Therefore, several approaches have been studied and an NSGA-II algorithm is first utilized, and then the results are validated using an MOSA and MOPSO algorithms. Priority-based encoding, which is used in all the algorithms, is the core of the solution computations. To compare the performance of the meta-heuristics, random numerical instances are evaluated by four criteria involving mean ideal distance, spread of non-dominance solution, the number of Pareto solutions, and CPU time. In order to enhance the performance of the algorithms, Taguchi method is used for parameter tuning. Finally, sensitivity analyses are performed and the computational results are presented based on the sensitivity analyses in parameter tuning.

Optimizing a multi-product closed-loop supply chain using NSGA-II, MOSA, and MOPSO meta-heuristic algorithms

NASA Astrophysics Data System (ADS)

Babaveisi, Vahid; Paydar, Mohammad Mahdi; Safaei, Abdul Sattar

2017-07-01

This study aims to discuss the solution methodology for a closed-loop supply chain (CLSC) network that includes the collection of used products as well as distribution of the new products. This supply chain is presented on behalf of the problems that can be solved by the proposed meta-heuristic algorithms. A mathematical model is designed for a CLSC that involves three objective functions of maximizing the profit, minimizing the total risk and shortages of products. Since three objective functions are considered, a multi-objective solution methodology can be advantageous. Therefore, several approaches have been studied and an NSGA-II algorithm is first utilized, and then the results are validated using an MOSA and MOPSO algorithms. Priority-based encoding, which is used in all the algorithms, is the core of the solution computations. To compare the performance of the meta-heuristics, random numerical instances are evaluated by four criteria involving mean ideal distance, spread of non-dominance solution, the number of Pareto solutions, and CPU time. In order to enhance the performance of the algorithms, Taguchi method is used for parameter tuning. Finally, sensitivity analyses are performed and the computational results are presented based on the sensitivity analyses in parameter tuning.

A human fecal contamination index for ranking impaired ...

EPA Pesticide Factsheets

Human fecal pollution of surface water remains a public health concern worldwide. As a result, there is a growing interest in the application of human-associated fecal source identification quantitative real-time PCR (qPCR) technologies for recreational water quality risk management. The transition from a research subject to a management tool requires the integration of standardized water sampling, laboratory, and data analysis procedures. In this study, a standardized HF183/BacR287 qPCR method was combined with a water sampling strategy and Bayesian data algorithm to establish a human fecal contamination index that can be used to rank impaired recreational water sites polluted with human waste. Stability and bias of index predictions were investigated under various parameters including siteswith different pollution levels, sampling period time range (1-15 weeks), and number of qPCR replicates per sample (2-14 replicates). Sensitivity analyses were conducted with simulated data sets (100 iterations) seeded with HF183/BacR287 qPCR laboratory measurements from water samples collected from three Southern California sites (588 qPCR measurements). Findings suggest that site ranking is feasible and that all parameters tested influence stability and bias in human fecal contamination indexscoring. Trends identified by sensitivity analyses will provide managers with the information needed to design and conduct field studies to rank impaired recreational water sites based

Establishment of Anti-Human ATRX Monoclonal Antibody AMab-6

PubMed Central

Ogasawara, Satoshi; Fujii, Yuki; Kaneko, Mika K.; Oki, Hiroharu; Sabit, Hemragul; Nakada, Mitsutoshi; Suzuki, Hiroyoshi; Ichimura, Koichi; Komori, Takashi

2016-01-01

Gliomas are the most frequently occurring brain tumors with a heterogeneous molecular background. The molecular subgrouping of gliomas more prognostically stratifies patients into distinct groups compared with conventional histological classification. The most important molecules for the subtype diagnosis of diffuse gliomas are mutations of isocitrate dehydrogenase (IDH), TERT promoter, and α-thalassemia/mental-retardation-syndrome-X-linked (ATRX) and the codeletion of 1p/19q. Among them, IDH and ATRX mutations can be diagnosed using specific monoclonal antibodies (mAbs). We have developed many mAbs against IDH mutants, including HMab-1/HMab-2 against IDH1-R132H and multispecific mAbs MsMab-1/MsMab-2 against IDH1/2 mutations. In contrast, highly sensitive mAbs against ATRX remain to be established. In this study, we immunized mice with recombinant human ATRX and developed a novel mAb, AMab-6. The dissociation constant of AMab-6 was determined to be 9.7 × 10−10 M, indicating that the binding affinity of AMab-6 is very high. Furthermore, AMab-6 sensitively detects ATRX in Western blot and immunohistochemical analyses, indicating that AMab-6 could become the standard marker to determine the ATRX mutation status of gliomas in immunohistochemical analyses. PMID:27788029

Establishment of Anti-Human ATRX Monoclonal Antibody AMab-6.

PubMed

Ogasawara, Satoshi; Fujii, Yuki; Kaneko, Mika K; Oki, Hiroharu; Sabit, Hemragul; Nakada, Mitsutoshi; Suzuki, Hiroyoshi; Ichimura, Koichi; Komori, Takashi; Kato, Yukinari

2016-10-01

Gliomas are the most frequently occurring brain tumors with a heterogeneous molecular background. The molecular subgrouping of gliomas more prognostically stratifies patients into distinct groups compared with conventional histological classification. The most important molecules for the subtype diagnosis of diffuse gliomas are mutations of isocitrate dehydrogenase (IDH), TERT promoter, and α-thalassemia/mental-retardation-syndrome-X-linked (ATRX) and the codeletion of 1p/19q. Among them, IDH and ATRX mutations can be diagnosed using specific monoclonal antibodies (mAbs). We have developed many mAbs against IDH mutants, including HMab-1/HMab-2 against IDH1-R132H and multispecific mAbs MsMab-1/MsMab-2 against IDH1/2 mutations. In contrast, highly sensitive mAbs against ATRX remain to be established. In this study, we immunized mice with recombinant human ATRX and developed a novel mAb, AMab-6. The dissociation constant of AMab-6 was determined to be 9.7 × 10 -10 M, indicating that the binding affinity of AMab-6 is very high. Furthermore, AMab-6 sensitively detects ATRX in Western blot and immunohistochemical analyses, indicating that AMab-6 could become the standard marker to determine the ATRX mutation status of gliomas in immunohistochemical analyses.

Ion Beam Analyses Of Bark And Wood In Environmental Studies

NASA Astrophysics Data System (ADS)

Lill, J.-O.; Saarela, K.-E.; Harju, L.; Rajander, J.; Lindroos, A.; Heselius, S.-J.

2011-06-01

A large number of wood and bark samples have been analysed utilizing particle-induced X-ray emission (PIXE) and particle-induced gamma-ray emission (PIGE) techniques. Samples of common tree species like Scots Pine, Norway Spruce and birch were collected from a large number of sites in Southern and Southwestern Finland. Some of the samples were from a heavily polluted area in the vicinity of a copper-nickel smelter. The samples were dry ashed at 550 °C for the removal of the organic matrix in order to increase the analytical sensitivity of the method. The sensitivity was enhanced by a factor of 50 for wood and slightly less for bark. The ashed samples were pressed into pellets and irradiated as thick targets with a millimetre-sized proton beam. By including the ashing procedure in the method, the statistical dispersion due to elemental heterogeneities in wood material could be reduced. As a by-product, information about the elemental composition of ashes was obtained. By comparing the concentration of an element in bark ash to the concentration in wood ash of the same tree useful information from environmental point of view was obtained. The obtained ratio of the ashes was used to distinguish between elemental contributions from anthropogenic atmospheric sources and natural geochemical sources, like soil and bedrock.

A generalised individual-based algorithm for modelling the evolution of quantitative herbicide resistance in arable weed populations.

PubMed

Liu, Chun; Bridges, Melissa E; Kaundun, Shiv S; Glasgow, Les; Owen, Micheal Dk; Neve, Paul

2017-02-01

Simulation models are useful tools for predicting and comparing the risk of herbicide resistance in weed populations under different management strategies. Most existing models assume a monogenic mechanism governing herbicide resistance evolution. However, growing evidence suggests that herbicide resistance is often inherited in a polygenic or quantitative fashion. Therefore, we constructed a generalised modelling framework to simulate the evolution of quantitative herbicide resistance in summer annual weeds. Real-field management parameters based on Amaranthus tuberculatus (Moq.) Sauer (syn. rudis) control with glyphosate and mesotrione in Midwestern US maize-soybean agroecosystems demonstrated that the model can represent evolved herbicide resistance in realistic timescales. Sensitivity analyses showed that genetic and management parameters were impactful on the rate of quantitative herbicide resistance evolution, whilst biological parameters such as emergence and seed bank mortality were less important. The simulation model provides a robust and widely applicable framework for predicting the evolution of quantitative herbicide resistance in summer annual weed populations. The sensitivity analyses identified weed characteristics that would favour herbicide resistance evolution, including high annual fecundity, large resistance phenotypic variance and pre-existing herbicide resistance. Implications for herbicide resistance management and potential use of the model are discussed. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Analysing use of the Chinese HHIE-S for hearing screening of elderly in a northeastern industrial area of China.

PubMed

Wang, Yue; Mo, Lingyan; Li, Yagang; Zheng, Zhongwei; Qi, Yu

2017-04-01

The aim of the present study was to investigate the use of Chinese version of HHIE-S as a hearing screening tool for the elderly in an industrial area in northeast China. Prevalence, sensitivity and specificity of Chinese version of HHIE-S were calculated. Factors that had impact on HHIE-S were analysed. Five hundred and seventy Mandarin speaking participants, aged from 50 to 85 years were included. They were tested with pure tone audiometry and Chinese version of HHIE-S. The prevalence of hearing handicap was 55.3%. The sensitivity and specificity of HHIE-S were 84.5% and 58.3% respectively when the pass/fail criteria were set at PTA 0.5-4kHz >40 dBHL. In general, HHIE-S total and subscale scores were significantly associated with severity of hearing impairment. After stratified by severity of hearing impairment, both the prevalence of reported handicap and the scores of HHIE-S were not significantly associated with age. Male participants had significantly higher HHIE-S scores than female participants did. The Chinese version of HHIE-S contributes useful information to identifying hearing handicap and addressing the rehabilitative needs in the elderly in an industrial city in Mainland China.

Diffusivities of Redox-Sensitive Elements in Basalt vs. Oxygen Fugacity Determined by LA-ICP-MS

NASA Technical Reports Server (NTRS)

Szumila, Ian; Danielson, Lisa; Trail, Dustin

2017-01-01

Several diffusion experiments were conducted in a piston cylinder device across a range of oxygen fugacities (FMQ-3 FMQ-1.2, FMQ+6) at 1 GPa and 1300 C. This was done to explore the effects of oxygen fugacity (fO2) on diffusivity of redox sensitive trace elements. This allows investigation of how these elements diffuse across the fO2 range encountered in different reservoirs on planets and moons in our solar system. The University of Rochester LA-ICP-MS system was used for analysis of samples. Analyses were conducted using an Agilent 7900 quadrupole mass spectrometer connected to a Photon Machines 193 nm G2 laser ablation (LA) system equipped with a HelEx 2-volume sample chamber. Spots used were 35 micrometers circles spaced at 65 micrometers intervals. Laser fluence was 7.81 J/cm^2 with a rep rate of 10 Hz. The iolite software package was used to reduce data collected from laser ablation analysis of experiments with Si-29 used as the internal standard isotope. Iolite's global fit module was used to simultaneously fit elements' diffusivities in each experiment while keeping the Matano interface constant. Elements analysed include V, Nb, W, Mo, La, Ce, Pr, Sm, Eu, Gd, Ta, and W. Figures

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry.

PubMed

Burnum-Johnson, Kristin E; Nie, Song; Casey, Cameron P; Monroe, Matthew E; Orton, Daniel J; Ibrahim, Yehia M; Gritsenko, Marina A; Clauss, Therese R W; Shukla, Anil K; Moore, Ronald J; Purvine, Samuel O; Shi, Tujin; Qian, Weijun; Liu, Tao; Baker, Erin S; Smith, Richard D

2016-12-01

Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Evaluation of two imaging techniques: near-infrared transillumination and dental radiographs for the detection of early approximal enamel caries.

PubMed

Maia, A M A; Karlsson, L; Margulis, W; Gomes, A S L

2011-10-01

The aim of this paper was to evaluate a transillumination (TI) system using near-infrared (NIR) light and bitewing radiographs for the detection of early approximal enamel caries lesions. Mesiodistal sections of teeth (n = 14) were cut with various thicknesses from 1.5 mm to 4.75 mm. Both sides of each section were included, 17 approximal surfaces with natural enamel caries and 11 surfaces considered intact. The approximal surfaces were illuminated by NIR light and X-ray. Captured images were analysed by two calibrated specialists in radiology, and re-analysed after 6 months using stereomicroscope images as a gold standard. The interexaminer reliability (Kappa test statistic) for the NIR TI technique showed moderate agreement on first (0.55) and second (0.48) evaluation, and low agreement for bitewing radiographs on first (0.26) and second (0.32) evaluation. In terms of accuracy, the sensitivity for the NIR TI system was 0.88 and the specificity was 0.72. For the bitewing radiographs the sensitivity ranged from 0.35 to 0.53 and the specificity ranged from 0.50 to 0.72. In the same samples and conditions tested, NIR TI images showed reliability and the enamel caries surfaces were better identified than on dental radiographs.

Evaluation of two imaging techniques: near-infrared transillumination and dental radiographs for the detection of early approximal enamel caries

PubMed Central

Maia, A M A; Karlsson, L; Margulis, W; Gomes, A S L

2011-01-01

Objectives The aim of this paper was to evaluate a transillumination (TI) system using near-infrared (NIR) light and bitewing radiographs for the detection of early approximal enamel caries lesions. Methods Mesiodistal sections of teeth (n = 14) were cut with various thicknesses from 1.5 mm to 4.75 mm. Both sides of each section were included, 17 approximal surfaces with natural enamel caries and 11 surfaces considered intact. The approximal surfaces were illuminated by NIR light and X-ray. Captured images were analysed by two calibrated specialists in radiology, and re-analysed after 6 months using stereomicroscope images as a gold standard. Results The interexaminer reliability (Kappa test statistic) for the NIR TI technique showed moderate agreement on first (0.55) and second (0.48) evaluation, and low agreement for bitewing radiographs on first (0.26) and second (0.32) evaluation. In terms of accuracy, the sensitivity for the NIR TI system was 0.88 and the specificity was 0.72. For the bitewing radiographs the sensitivity ranged from 0.35 to 0.53 and the specificity ranged from 0.50 to 0.72. Conclusion In the same samples and conditions tested, NIR TI images showed reliability and the enamel caries surfaces were better identified than on dental radiographs. PMID:21960400

Heart-type fatty acid binding protein is a sensitive biomarker for early AMI detection in troponin negative patients: a pilot study.

PubMed

Agnello, Luisa; Bivona, Giulia; Novo, Giuseppina; Scazzone, Concetta; Muratore, Roberto; Levantino, Piero; Bellia, Chiara; Lo Sasso, Bruna; Ciaccio, Marcello

2017-10-01

Early detecting AMI in individuals presenting to the ED with chest pain continues to be a challenge. cTn is the gold standard for AMI diagnosis but early presenters (<1 hours from symptom onset) maybe cTn negative on admission. We analysed the diagnostic value of h-FABP and hs-TnI in patients presenting to ED with chest pain and no cTnI elevations. 28 AMI and 28 no-AMI individuals both presented to ED within one hour from pain onset were included. Blood donors were analysed for h-FABP cut-off identification. Among AMI patients, 55% were positive for h-FABP and 34.6% were positive for hs-TnI (p = .015), thus 21% were positive only for h-FABP. The diagnostic accuracy was assessed by ROC curve. h-FABP showed a higher sensitivity but lower specificity than hs-TnI. In our study, the frequency of h-FABP positivity among AMI patients was higher than that of hs-TnI, which would have missed six of them; however, hs-TnI AUC was superior to that of h-FABP. These preliminary findings might confirm that h-FABP may be a good candidate for AMI rule-in/rule-out within the ED context.

Developmental programming: insulin sensitizer treatment improves reproductive function in prenatal testosterone-treated female sheep.

PubMed

Veiga-Lopez, Almudena; Lee, James S; Padmanabhan, Vasantha

2010-08-01

Prenatal testosterone (T) excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested the hypothesis that insulin resistance contributes toward severity of reproductive disruptions in prenatally T-treated females. Pregnant sheep were injected im with 100 mg of T-propionate semiweekly from d 30-90 of gestation. Immediately after the first breeding season, a subset of controls and prenatal T-treated (TR) sheep were administered an insulin sensitizer (rosiglitazone; 8 mg/d) orally for 8 months. Untreated control and prenatal T-treated females (T group) were studied in parallel. Biochemical analyses revealed rosiglitazone to be safe for use in sheep. Glucose tolerance tests performed before and after the insulin sensitizer treatment found that insulin sensitizer decreased cumulative insulin, cumulative insulin/glucose ratio, and insulin area under the curve by about 50% and increased the insulin sensitivity index by about 70% in the TR compared with the T group. Twenty percent of TR females showed a reduced number of cycles in the second relative to first breeding season as opposed to 80% of T group females showing such deterioration. Insulin sensitizer treatment also decreased the number of aberrant cycles (>/=18 d) during the second breeding season in the TR group relative to the first as opposed to the T group females showing an increase in the second breeding season relative to the first. These findings provide evidence that insulin sensitizer treatment prevents further deterioration of the reproductive axis in prenatal T-treated sheep, a finding of translational relevance to women with polycystic ovary syndrome.

Reflex Cough and Disease Duration as Predictors of Swallowing Dysfunction in Parkinson's Disease.

PubMed

Troche, Michelle S; Schumann, Beate; Brandimore, Alexandra E; Okun, Michael S; Hegland, Karen W

2016-12-01

Patients with Parkinson's disease (PD) have progressive and pervasive disorders of airway protection. Recent work has highlighted the relationship between reflex and voluntary cough and swallowing safety. The goal of this study was to test the sensitivity and specificity of several airway protective and disease-specific factors for predicting swallowing safety outcomes in PD. Sixty-four participants (44 males) completed measures of voluntary and reflex cough, and swallowing safety. Clinical predictors included disease severity and duration, and cough airflow and sensitivity measures. ROC and Chi-square analyses identified predictors of swallowing safety (penetration-aspiration score) in PD. Disease duration significantly discriminated between patients with normal and abnormal swallowing safety (p = 0.027, sensitivity: 71 %, specificity: 55.4 %). Cough reflex sensitivity significantly discriminated between patients who penetrated above the level of the vocal folds and those with more severe penetration/aspiration (p = 0.021, sensitivity: 71.0 %, specificity 57.6 %). Urge-to-cough sensitivity (log-log linear slope) was the only variable which significantly discriminated between patients with penetration versus aspiration (p = 0.017, sensitivity: 85.7 %, specificity 73.2 %). It is important to identify the factors which influence airway protective outcomes in PD especially given that aspiration pneumonia is a leading cause of death. Results from this study highlight the ecological validity of reflex cough in the study of airway protection and this study further identifies important factors to consider in the screening of airway protective deficits in PD.

Identification of mission sensitivities for high-power electric propulsion systems

NASA Technical Reports Server (NTRS)

Frisbee, Robert H.; Moeller, Robert C.

2005-01-01

This paper presents the results of mission analyses that expose various mission performance sensitivities and system advantages of the ALFA technology for a small but representative subset of nuclear electric propulsion (NEP) missions considered under NASA's Project Prometheus.

Gender differences in emotion perception and self-reported emotional intelligence: A test of the emotion sensitivity hypothesis

PubMed Central

Kret, Mariska E.; Broekens, Joost

2018-01-01

Previous meta-analyses and reviews on gender differences in emotion recognition have shown a small to moderate female advantage. However, inconsistent evidence from recent studies has raised questions regarding the implications of different methodologies, stimuli, and samples. In the present research based on a community sample of more than 5000 participants, we tested the emotional sensitivity hypothesis, stating that women are more sensitive to perceive subtle, i.e. low intense or ambiguous, emotion cues. In addition, we included a self-report emotional intelligence test in order to examine any discrepancy between self-perceptions and actual performance for both men and women. We used a wide range of stimuli and models, displaying six different emotions at two different intensity levels. In order to better tap sensitivity for subtle emotion cues, we did not use a forced choice format, but rather intensity measures of different emotions. We found no support for the emotional sensitivity account, as both genders rated the target emotions as similarly intense at both levels of stimulus intensity. Men, however, more strongly perceived non-target emotions to be present than women. In addition, we also found that the lower scores of men in self-reported EI was not related to their actual perception of target emotions, but it was to the perception of non-target emotions. PMID:29370198

Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes

PubMed Central

Xie, Weijia; Wood, Andrew R.; Lyssenko, Valeriya; Weedon, Michael N.; Knowles, Joshua W.; Alkayyali, Sami; Assimes, Themistocles L.; Quertermous, Thomas; Abbasi, Fahim; Paananen, Jussi; Häring, Hans; Hansen, Torben; Pedersen, Oluf; Smith, Ulf; Laakso, Markku; Dekker, Jacqueline M.; Nolan, John J.; Groop, Leif; Ferrannini, Ele; Adam, Klaus-Peter; Gall, Walter E.; Frayling, Timothy M.; Walker, Mark

2013-01-01

Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we performed a genome-wide association study (GWAS) of 14 insulin sensitivity–related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2, and Stanford], MAGIC, and DIAGRAM). We identified four associations with three metabolites—glycine (rs715 at CPS1), serine (rs478093 at PHGDH), and betaine (rs499368 at SLC6A12; rs17823642 at BHMT)—and one association signal with glycine-to-serine ratio (rs1107366 at ALDH1L1). There was no robust evidence for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits. PMID:23378610

Phytotoxicity of floodplain soils contaminated with trace metals along the clark fork river, Grant-Kohrs Ranch National Historic Site, Deer Lodge, Montana, United States

USGS Publications Warehouse

Rader, B.R.; Nimmo, D.W.R.; Chapman, P.L.

1997-01-01

Concentrations of metals in sediments and soils deposited along the floodplain of the Clark Fork River, within the Grant-Kohrs Ranch National Historic Site, Deer Lodge, Montana, USA, have exceeded maximum background concentrations in the United States for most metals tested. As a result of mining and smelting activities, portions of the Deer Lodge Valley, including the Grant-Kohrs Ranch, have received National Priority List Designation under the Comprehensive Environmental Response, Compensation and Liability Act. Using a series of plant germination tests, pH measurements, and metal analyses, this study investigated the toxicity of soils from floodplain 'slicken' areas, bare spots devoid of vegetation, along the Clark Fork River. The slicken soils collected from the Grant-Kohrs Ranch were toxic to all four plant species tested. The most sensitive endpoint in the germination tests was root length and the least sensitive was emergence. Considering emergence, the most sensitive species was the resident grass species Agrostis gigantea. The sensitivities were reversed when root lengths were examined, with Echinochloa crusgalli showing the greatest sensitivity. Both elevated concentrations of metals and low pH were necessary to produce an acutely phytotoxic response in laboratory seed germination tests using slicken soils. Moreover, pH values on the Grant-Kohrs Ranch appear to be a better predictor of acutely phytotoxic conditions than total metal levels.

Gender differences in emotion perception and self-reported emotional intelligence: A test of the emotion sensitivity hypothesis.

PubMed

Fischer, Agneta H; Kret, Mariska E; Broekens, Joost

2018-01-01

Previous meta-analyses and reviews on gender differences in emotion recognition have shown a small to moderate female advantage. However, inconsistent evidence from recent studies has raised questions regarding the implications of different methodologies, stimuli, and samples. In the present research based on a community sample of more than 5000 participants, we tested the emotional sensitivity hypothesis, stating that women are more sensitive to perceive subtle, i.e. low intense or ambiguous, emotion cues. In addition, we included a self-report emotional intelligence test in order to examine any discrepancy between self-perceptions and actual performance for both men and women. We used a wide range of stimuli and models, displaying six different emotions at two different intensity levels. In order to better tap sensitivity for subtle emotion cues, we did not use a forced choice format, but rather intensity measures of different emotions. We found no support for the emotional sensitivity account, as both genders rated the target emotions as similarly intense at both levels of stimulus intensity. Men, however, more strongly perceived non-target emotions to be present than women. In addition, we also found that the lower scores of men in self-reported EI was not related to their actual perception of target emotions, but it was to the perception of non-target emotions.

Influential factors on thermoacoustic efficiency of multilayered graphene film loudspeakers for optimal design

NASA Astrophysics Data System (ADS)

Xing, Qianhe; Li, Shuang; Fan, Xueliang; Bian, Anhua; Cao, Shi-Jie; Li, Cheng

2017-09-01

Graphene thermoacoustic loudspeakers, composed of a graphene film on a substrate, generate sound with heat. Improving thermoacoustic efficiency of graphene speakers is a goal for optimal design. In this work, we first modified the existing TA model with respect to small thermal wavelengths, and then built an acoustic platform for model validation. Additionally, sensitivity analyses for influential factors on thermoacoustic efficiency were performed, including the thickness of multilayered graphene films, the thermal effusivity of substrates, and the characteristics of inserted gases. The higher sensitivity coefficients result in the stronger effects on thermoacoustic efficiency. We find that the thickness (5 nm-15 nm) of graphene films plays a trivial role in efficiency, resulting in the sensitivity coefficient less than 0.02. The substrate thermal effusivity, however, has significant effects on efficiency, with the sensitivity coefficient around 1.7. Moreover, substrates with a lower thermal effusivity show better acoustic performances. For influences of ambient gases, the sensitivity coefficients of density ρg, thermal conductivity κg, and specific heat cp,g are 2.7, 0.98, and 0.8, respectively. Furthermore, large magnitudes of both ρg and κg lead to a higher efficiency and the sound pressure level generated by graphene films is approximately proportional to the inverse of cp,g. These findings can refer to the optimal design for graphene thermoacoustic speakers.

Improving inhaler adherence in patients with chronic obstructive pulmonary disease: a cost-effectiveness analysis.

PubMed

van Boven, Job Fm; Tommelein, Eline; Boussery, Koen; Mehuys, Els; Vegter, Stefan; Brusselle, Guy Go; Rutten-van Mölken, Maureen Pmh; Postma, Maarten J

2014-06-14

The PHARMACOP-intervention significantly improved medication adherence and inhalation technique for patients with COPD compared with usual care. This study aimed to evaluate its cost-effectiveness. An economic analysis was performed from the Belgian healthcare payer's perspective. A Markov model was constructed in which a representative group of patients with COPD (mean age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume in 1 second of % predicted of 50), was followed for either receiving the 3-month PHARMACOP-intervention or usual care. Three types of costs were calculated: intervention costs, medication costs and exacerbation costs. Outcome measures included the number of hospital-treated exacerbations, cost per prevented hospital-treated exacerbation and cost per Quality Adjusted Life-Year. Follow-up was 1 year in the basecase analysis. Sensitivity and scenario analyses (including long-term follow-up) were performed to assess uncertainty. In the basecase analysis, the average overall costs per patient for the PHARMACOP-intervention and usual care were €2,221 and €2,448, respectively within the 1-year time horizon. This reflects cost savings of €227 for the PHARMACOP-intervention. The PHARMACOP-intervention resulted in the prevention of 0.07 hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for usual care). Results showed robust cost-savings in various sensitivity analyses. Optimization of current pharmacotherapy (e.g. close monitoring of inhalation technique and medication adherence) has been shown to be cost-saving and should be considered before adding new therapies.

Comparing surgical trays with redundant instruments with trays with reduced instruments: a cost analysis

PubMed Central

John-Baptiste, A.; Sowerby, L.J.; Chin, C.J.; Martin, J.; Rotenberg, B.W.

2016-01-01

Background: When prearranged standard surgical trays contain instruments that are repeatedly unused, the redundancy can result in unnecessary health care costs. Our objective was to estimate potential savings by performing an economic evaluation comparing the cost of surgical trays with redundant instruments with surgical trays with reduced instruments ("reduced trays"). Methods: We performed a cost-analysis from the hospital perspective over a 1-year period. Using a mathematical model, we compared the direct costs of trays containing redundant instruments to reduced trays for 5 otolaryngology procedures. We incorporated data from several sources including local hospital data on surgical volume, the number of instruments on redundant and reduced trays, wages of personnel and time required to pack instruments. From the literature, we incorporated instrument depreciation costs and the time required to decontaminate an instrument. We performed 1-way sensitivity analyses on all variables, including surgical volume. Costs were estimated in 2013 Canadian dollars. Results: The cost of redundant trays was $21 806 and the cost of reduced trays was $8803, for a 1-year cost saving of $13 003. In sensitivity analyses, cost savings ranged from $3262 to $21 395, based on the surgical volume at the institution. Variation in surgical volume resulted in a wider range of estimates, with a minimum of $3253 for low-volume to a maximum of $52 012 for high-volume institutions. Interpretation: Our study suggests moderate savings may be achieved by reducing surgical tray redundancy and, if applied to other surgical specialties, may result in savings to Canadian health care systems. PMID:27975045

Comparing surgical trays with redundant instruments with trays with reduced instruments: a cost analysis.

PubMed

John-Baptiste, A; Sowerby, L J; Chin, C J; Martin, J; Rotenberg, B W

2016-01-01

When prearranged standard surgical trays contain instruments that are repeatedly unused, the redundancy can result in unnecessary health care costs. Our objective was to estimate potential savings by performing an economic evaluation comparing the cost of surgical trays with redundant instruments with surgical trays with reduced instruments ("reduced trays"). We performed a cost-analysis from the hospital perspective over a 1-year period. Using a mathematical model, we compared the direct costs of trays containing redundant instruments to reduced trays for 5 otolaryngology procedures. We incorporated data from several sources including local hospital data on surgical volume, the number of instruments on redundant and reduced trays, wages of personnel and time required to pack instruments. From the literature, we incorporated instrument depreciation costs and the time required to decontaminate an instrument. We performed 1-way sensitivity analyses on all variables, including surgical volume. Costs were estimated in 2013 Canadian dollars. The cost of redundant trays was $21 806 and the cost of reduced trays was $8803, for a 1-year cost saving of $13 003. In sensitivity analyses, cost savings ranged from $3262 to $21 395, based on the surgical volume at the institution. Variation in surgical volume resulted in a wider range of estimates, with a minimum of $3253 for low-volume to a maximum of $52 012 for high-volume institutions. Our study suggests moderate savings may be achieved by reducing surgical tray redundancy and, if applied to other surgical specialties, may result in savings to Canadian health care systems.

Cost-effectiveness analysis of implementing an antimicrobial stewardship program in critical care units.

PubMed

Ruiz-Ramos, Jesus; Frasquet, Juan; Romá, Eva; Poveda-Andres, Jose Luis; Salavert-Leti, Miguel; Castellanos, Alvaro; Ramirez, Paula

2017-06-01

To evaluate the cost-effectiveness of antimicrobial stewardship (AS) program implementation focused on critical care units based on assumptions for the Spanish setting. A decision model comparing costs and outcomes of sepsis, community-acquired pneumonia, and nosocomial infections (including catheter-related bacteremia, urinary tract infection, and ventilator-associated pneumonia) in critical care units with or without an AS was designed. Model variables and costs, along with their distributions, were obtained from the literature. The study was performed from the Spanish National Health System (NHS) perspective, including only direct costs. The Incremental Cost-Effectiveness Ratio (ICER) was analysed regarding the ability of the program to reduce multi-drug resistant bacteria. Uncertainty in ICERs was evaluated with probabilistic sensitivity analyses. In the short-term, implementing an AS reduces the consumption of antimicrobials with a net benefit of €71,738. In the long-term, the maintenance of the program involves an additional cost to the system of €107,569. Cost per avoided resistance was €7,342, and cost-per-life-years gained (LYG) was €9,788. Results from the probabilistic sensitivity analysis showed that there was a more than 90% likelihood that an AS would be cost-effective at a level of €8,000 per LYG. Wide variability of economic results obtained from the implementation of this type of AS program and short information on their impact on patient evolution and any resistance avoided. Implementing an AS focusing on critical care patients is a long-term cost-effective tool. Implementation costs are amortized by reducing antimicrobial consumption to prevent infection by multidrug-resistant pathogens.

Evaluation of cell count and classification capabilities in body fluids using a fully automated Sysmex XN equipped with high-sensitive Analysis (hsA) mode and DI-60 hematology analyzer system.

PubMed

Takemura, Hiroyuki; Ai, Tomohiko; Kimura, Konobu; Nagasaka, Kaori; Takahashi, Toshihiro; Tsuchiya, Koji; Yang, Haeun; Konishi, Aya; Uchihashi, Kinya; Horii, Takashi; Tabe, Yoko; Ohsaka, Akimichi

2018-01-01

The XN series automated hematology analyzer has been equipped with a body fluid (BF) mode to count and differentiate leukocytes in BF samples including cerebrospinal fluid (CSF). However, its diagnostic accuracy is not reliable for CSF samples with low cell concentration at the border between normal and pathologic level. To overcome this limitation, a new flow cytometry-based technology, termed "high sensitive analysis (hsA) mode," has been developed. In addition, the XN series analyzer has been equipped with the automated digital cell imaging analyzer DI-60 to classify cell morphology including normal leukocytes differential and abnormal malignant cells detection. Using various BF samples, we evaluated the performance of the XN-hsA mode and DI-60 compared to manual microscopic examination. The reproducibility of the XN-hsA mode showed good results in samples with low cell densities (coefficient of variation; % CV: 7.8% for 6 cells/μL). The linearity of the XN-hsA mode was established up to 938 cells/μL. The cell number obtained using the XN-hsA mode correlated highly with the corresponding microscopic examination. Good correlation was also observed between the DI-60 analyses and manual microscopic classification for all leukocyte types, except monocytes. In conclusion, the combined use of cell counting with the XN-hsA mode and automated morphological analyses using the DI-60 mode is potentially useful for the automated analysis of BF cells.

Cost-effectiveness of rivaroxaban for stroke prevention in atrial fibrillation in the Portuguese setting.

PubMed

Morais, João; Aguiar, Carlos; McLeod, Euan; Chatzitheofilou, Ismini; Fonseca Santos, Isabel; Pereira, Sónia

2014-09-01

To project the long-term cost-effectiveness of treating non-valvular atrial fibrillation (AF) patients for stroke prevention with rivaroxaban compared to warfarin in Portugal. A Markov model was used that included health and treatment states describing the management and consequences of AF and its treatment. The model's time horizon was set at a patient's lifetime and each cycle at three months. The analysis was conducted from a societal perspective and a 5% discount rate was applied to both costs and outcomes. Treatment effect data were obtained from the pivotal phase III ROCKET AF trial. The model was also populated with utility values obtained from the literature and with cost data derived from official Portuguese sources. The outcomes of the model included life-years, quality-adjusted life-years (QALYs), incremental costs, and associated incremental cost-effectiveness ratios (ICERs). Extensive sensitivity analyses were undertaken to further assess the findings of the model. As there is evidence indicating underuse and underprescription of warfarin in Portugal, an additional analysis was performed using a mixed comparator composed of no treatment, aspirin, and warfarin, which better reflects real-world prescribing in Portugal. This cost-effectiveness analysis produced an ICER of €3895/QALY for the base-case analysis (vs. warfarin) and of €6697/QALY for the real-world prescribing analysis (vs. mixed comparator). The findings were robust when tested in sensitivity analyses. The results showed that rivaroxaban may be a cost-effective alternative compared with warfarin or real-world prescribing in Portugal. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

A health economic model for evaluating a vaccine for the prevention of herpes zoster and post-herpetic neuralgia in the UK.

PubMed

Moore, Lee; Remy, Vanessa; Martin, Monique; Beillat, Maud; McGuire, Alistair

2010-04-30

A live-attenuated vaccine aimed at preventing herpes zoster (HZ) and its main complication, post-herpetic neuralgia (PHN) is available in Europe for immunocompetent adults aged 50 years and more. The study objective is to assess the cost effectiveness of a vaccination program for this population in the UK. A state-transition Markov model has been developed to simulate the natural history of HZ and PHN and to estimate the lifetime effects of vaccination in the UK. Several health states are defined including good health, HZ, PHN, and death. HZ and PHN health states are further divided to reflect pain severity. The model predicts that a vaccination strategy for those aged over 50 years would lead to an incremental cost-effectiveness ratio of pound13,077 per QALY gained from the NHS perspective, when compared to the current strategy of no vaccination. Age-group analyses show that the lowest ICERs ( pound10,984 and pound10,275 for NHS) are observed when vaccinating people between 60-64 and 65-69 years of age. Sensitivity analyses showed that results are sensitive to the duration of vaccine protection, discount rate, utility decrements and pain severity split used. Using the commonly accepted threshold of pound30,000 per QALY gained in the UK, most scenarios of vaccination programmes preventing HZ and PHN, including the potential use of a repeat dose, may be considered cost-effective by the NHS, especially within the 60 to 69 age-groups.

Improving inhaler adherence in patients with Chronic Obstructive Pulmonary Disease: a cost-effectiveness analysis

PubMed Central

2014-01-01

Background The PHARMACOP-intervention significantly improved medication adherence and inhalation technique for patients with COPD compared with usual care. This study aimed to evaluate its cost-effectiveness. Methods An economic analysis was performed from the Belgian healthcare payer’s perspective. A Markov model was constructed in which a representative group of patients with COPD (mean age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume in 1 second of % predicted of 50), was followed for either receiving the 3-month PHARMACOP-intervention or usual care. Three types of costs were calculated: intervention costs, medication costs and exacerbation costs. Outcome measures included the number of hospital-treated exacerbations, cost per prevented hospital-treated exacerbation and cost per Quality Adjusted Life-Year. Follow-up was 1 year in the basecase analysis. Sensitivity and scenario analyses (including long-term follow-up) were performed to assess uncertainty. Results In the basecase analysis, the average overall costs per patient for the PHARMACOP-intervention and usual care were €2,221 and €2,448, respectively within the 1-year time horizon. This reflects cost savings of €227 for the PHARMACOP-intervention. The PHARMACOP-intervention resulted in the prevention of 0.07 hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for usual care). Results showed robust cost-savings in various sensitivity analyses. Conclusions Optimization of current pharmacotherapy (e.g. close monitoring of inhalation technique and medication adherence) has been shown to be cost-saving and should be considered before adding new therapies. PMID:24929799

Methods for detecting, quantifying, and adjusting for dissemination bias in meta-analysis are described.

PubMed

Mueller, Katharina Felicitas; Meerpohl, Joerg J; Briel, Matthias; Antes, Gerd; von Elm, Erik; Lang, Britta; Motschall, Edith; Schwarzer, Guido; Bassler, Dirk

2016-12-01

To systematically review methodological articles which focus on nonpublication of studies and to describe methods of detecting and/or quantifying and/or adjusting for dissemination in meta-analyses. To evaluate whether the methods have been applied to an empirical data set for which one can be reasonably confident that all studies conducted have been included. We systematically searched Medline, the Cochrane Library, and Web of Science, for methodological articles that describe at least one method of detecting and/or quantifying and/or adjusting for dissemination bias in meta-analyses. The literature search retrieved 2,224 records, of which we finally included 150 full-text articles. A great variety of methods to detect, quantify, or adjust for dissemination bias were described. Methods included graphical methods mainly based on funnel plot approaches, statistical methods, such as regression tests, selection models, sensitivity analyses, and a great number of more recent statistical approaches. Only few methods have been validated in empirical evaluations using unpublished studies obtained from regulators (Food and Drug Administration, European Medicines Agency). We present an overview of existing methods to detect, quantify, or adjust for dissemination bias. It remains difficult to advise which method should be used as they are all limited and their validity has rarely been assessed. Therefore, a thorough literature search remains crucial in systematic reviews, and further steps to increase the availability of all research results need to be taken. Copyright © 2016 Elsevier Inc. All rights reserved.

CHD7 Expression Predicts Survival Outcomes in Patients with Resected Pancreatic Cancer

PubMed Central

Colbert, Lauren E.; Petrova, Aleksandra V.; Fisher, Sarah B.; Pantazides, Brooke G.; Madden, Matthew Z.; Hardy, Claire W.; Warren, Matthew D.; Pan, Yunfeng; Nagaraju, Ganji P.; Liu, Elaine A.; Saka, Burcu; Hall, William A.; Shelton, Joseph W.; Gandhi, Khanjan; Pauly, Rini; Kowalski, Jeanne; Kooby, David A.; El-Rayes, Bassel F.; Staley, Charles A.; Adsay, N. Volkan; Curran, Walter J.; Landry, Jerome C.; Maithel, Shishir K.; Yu, David S.

2014-01-01

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor outcomes with current therapies. Gemcitabine is the primary adjuvant drug used clinically, but its effectiveness is limited. In this study, our objective was to utilize a rationale-driven approach to identify novel biomarkers for outcome in patients with early-stage resected PDAC treated with adjuvant gemcitabine. Using a synthetic lethal screen in human PDAC cells, we identified 93 genes including 55 genes linked to DNA damage responses (DDR) that demonstrated gemcitabine sensitization when silenced, including CHD7 which functions in chromatin remodeling. CHD7 depletion sensitized PDAC cells to gemcitabine and delayed their growth in tumor xenografts. Moreover, CHD7 silencing impaired ATR-dependent phosphorylation of CHK1 and increased DNA damage induced by gemcitabine. CHD7 was dysregulated, ranking above the 90th percentile in differential expression in a panel of PDAC clinical specimens, highlighting its potential as a biomarker. Immunohistochemical analysis of specimens from 59 resected PDAC patients receiving adjuvant gemcitabine revealed that low CHD7 expression was associated with increased recurrence-free survival (RFS) and overall survival (OS), in univariate and multivariate analyses. Notably, CHD7 expression was not associated with RFS or OS for patients not receiving gemcitabine. Thus, low CHD7 expression was correlated selectively with gemcitabine sensitivity in this patient population. These results supported our rationale-driven strategy to exploit dysregulated DDR pathways in PDAC to identify genetic determinants of gemcitabine sensitivity, identifying CHD7 as a novel biomarker candidate to evaluate further for individualizing PDAC treatment. PMID:24626090

CSF soluble amyloid precursor proteins in the diagnosis of incipient Alzheimer disease.

PubMed

Perneczky, R; Tsolakidou, A; Arnold, A; Diehl-Schmid, J; Grimmer, T; Förstl, H; Kurz, A; Alexopoulos, P

2011-07-05

To explore if soluble amyloid precursor proteins (sAPP) in CSF improve the identification of patients with incipient Alzheimer disease (AD) in a group of patients with mild cognitive impairment (MCI). A cohort study with follow-up assessments of 58 patients with MCI with baseline CSF sampling was conducted: 21 patients had progressed to probable AD (MCI-AD), 27 still had MCI, 8 had reverted to normal (MCI-NAD), and 2 patients with frontotemporal dementia (FTD) were excluded. Sixteen additional patients with FTD were included to explore the specificity of the CSF markers. CSF concentrations of sAPPα, sAPPβ, tau, and Aβ(1-42) were measured with sensitive and specific ELISAs. Associations between diagnostic status, CSF protein concentrations, and other patient characteristics were explored using multiple logistic regression analyses with stepwise variable selection. The optimal sensitivity and specificity of the best models were derived from receiver operating characteristic curves. The MCI-AD group had significantly higher sAPPβ concentrations than the MCI-NAD and the FTD groups. A combination of sAPPβ, tau, and age differentiated the MCI-AD and the MCI-NAD groups with a sensitivity of 80.00% and a specificity of 81.00%. The best model for the differentiation of the MCI-AD and the FTD groups included sAPPβ and tau, and showed a sensitivity of 95.20% and a specificity of 81.20%. Aβ(1-42) and sAPPα did not significantly contribute to the models. These findings suggest that sAPPβ may be clinically useful, and superior to Aβ(1-42), in the early and differential diagnosis of incipient AD.

Prevalence of cold sensitivity in patients with hand pathology.

PubMed

Novak, Christine B; McCabe, Steven J

2015-06-01

The purpose of this study was to evaluate the prevalence of cold sensitivity in patients with hand- and wrist-related diagnoses. We included English-speaking adults who were more than 1 month following hand injury or onset of symptoms. Patients were asked if exposure to cold air or water provoked cold-related symptoms and to rank symptom severity (scale 0-10). Statistical analyses evaluated the relationships between the cold sensitivity and independent variables (age, gender, history of trauma, and time from injury/symptoms). There were 197 patients (mean age 49 ± 16 years): 98 trauma and 99 non-trauma cases. Cold-induced symptoms were reported by 34 %, with 10 % reporting severe symptoms. Exposure to cold air is the most common catalyst; mean severity score was 6.7 ± 2.2. Those with traumatic injuries compared to non-trauma diagnoses reported significantly more cold-induced symptoms (p = .04). Using backward linear regression, the significant predictors of cold symptom severity were trauma (p = .004) and time since onset (p = .003). Including only the trauma patients in the regression model, the significant predictor was time since injury (p = .005). Cold-induced symptoms are reported by more than 30 % of hand-related diagnoses, and exposure to cold air was the most commonly reported trigger. The significant predictors of cold-induced symptoms are traumatic injuries and longer time from injury. This study provides evidence of the common problem of cold sensitivity in patients with hand pathology. Prognostic Level II.

Targeted Quantitation of Proteins by Mass Spectrometry

PubMed Central

2013-01-01

Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement. PMID:23517332

Test and Analysis of a Buckling-Critical Large-Scale Sandwich Composite Cylinder

NASA Technical Reports Server (NTRS)

Schultz, Marc R.; Sleight, David W.; Gardner, Nathaniel W.; Rudd, Michelle T.; Hilburger, Mark W.; Palm, Tod E.; Oldfield, Nathan J.

2018-01-01

Structural stability is an important design consideration for launch-vehicle shell structures and it is well known that the buckling response of such shell structures can be very sensitive to small geometric imperfections. As part of an effort to develop new buckling design guidelines for sandwich composite cylindrical shells, an 8-ft-diameter honeycomb-core sandwich composite cylinder was tested under pure axial compression to failure. The results from this test are compared with finite-element-analysis predictions and overall agreement was very good. In particular, the predicted buckling load was within 1% of the test and the character of the response matched well. However, it was found that the agreement could be improved by including composite material nonlinearity in the analysis, and that the predicted buckling initiation site was sensitive to the addition of small bending loads to the primary axial load in analyses.

Targeted quantitation of proteins by mass spectrometry.

PubMed

Liebler, Daniel C; Zimmerman, Lisa J

2013-06-04

Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement.

Sensitivity Analysis of earth and environmental models: a systematic review to guide scientific advancement

NASA Astrophysics Data System (ADS)

Wagener, Thorsten; Pianosi, Francesca

2016-04-01

Sensitivity Analysis (SA) investigates how the variation in the output of a numerical model can be attributed to variations of its input factors. SA is increasingly being used in earth and environmental modelling for a variety of purposes, including uncertainty assessment, model calibration and diagnostic evaluation, dominant control analysis and robust decision-making. Here we provide some practical advice regarding best practice in SA and discuss important open questions based on a detailed recent review of the existing body of work in SA. Open questions relate to the consideration of input factor interactions, methods for factor mapping and the formal inclusion of discrete factors in SA (for example for model structure comparison). We will analyse these questions using relevant examples and discuss possible ways forward. We aim at stimulating the discussion within the community of SA developers and users regarding the setting of good practices and on defining priorities for future research.

Total organic carbon analyzer

NASA Technical Reports Server (NTRS)

Godec, Richard G.; Kosenka, Paul P.; Smith, Brian D.; Hutte, Richard S.; Webb, Johanna V.; Sauer, Richard L.

1991-01-01

The development and testing of a breadboard version of a highly sensitive total-organic-carbon (TOC) analyzer are reported. Attention is given to the system components including the CO2 sensor, oxidation reactor, acidification module, and the sample-inlet system. Research is reported for an experimental reagentless oxidation reactor, and good results are reported for linearity, sensitivity, and selectivity in the CO2 sensor. The TOC analyzer is developed with gravity-independent components and is designed for minimal additions of chemical reagents. The reagentless oxidation reactor is based on electrolysis and UV photolysis and is shown to be potentially useful. The stability of the breadboard instrument is shown to be good on a day-to-day basis, and the analyzer is capable of 5 sample analyses per day for a period of about 80 days. The instrument can provide accurate TOC and TIC measurements over a concentration range of 20 ppb to 50 ppm C.

The HEROES Balloon-Borne Hard X-Ray Telescope

NASA Technical Reports Server (NTRS)

Wilson-Hodge, C.; Gaskin, J.; Christe, S.; Shih, A. Y.; Swartz, D. A.; Tennant, A. F.; Ramsey, B.; Kilaru, K.

2014-01-01

The High Energy Replicated Optics to Explore the Sun (HEROES) payload flew on a balloon from Ft. Sumner, NM, September 21-22, 2013. HEROES is sensitive from about 20-75 keV and comprises 8 optics modules (HPD approximately 33" as flown), each consisting of 13-14 nickel replicated optics shells and 8 matching Xenon-filled position-sensitive proportional counter detectors (dE/E=0.05 @ 60 keV). Our targets included the Sun, the Crab Nebula and pulsar and the black hole binary GRS 1915+105. HEROES was pointed using a day/night star camera system for astrophysical observations and a newly developed Solar Aspect System for solar observations (with a shutter protecting the star camera.) We have successfully detected the Crab Nebula. Analyses for GRS 1915+105 and the Sun are ongoing. In this presentation, I will describe the HEROES mission, the data analysis pipeline and calibrations, preliminary results, and plans for follow-on missions.

The HEROES Balloon-borne Hard X-ray Telescope

NASA Astrophysics Data System (ADS)

Wilson-Hodge, Colleen; Gaskin, Jessica; Christe, Steven; Shih, Albert Y.; Swartz, Douglas A.; Tennant, Allyn F.; Ramsey, Brian; Kilaru, Kiranmayee

2014-08-01

The High Energy Replicated Optics to Explore the Sun (HEROES) payload flew on a balloon from Ft. Sumner, NM, September 21-22, 2013. HEROES is sensitive from about 20-75 keV and comprises 8 optics modules (HP 33"), each consisting of 13-14 nickel replicated optics shells and 8 matching Xenon-filled position-sensitive proportional counter detectors (dE/E=0.05 @ 60 keV). Our targets included the Sun, the Crab Nebula and pulsar and the black hole binary GRS 1915+105. HEROES was pointed using a day/night star camera system for astrophysical observations and a newly developed Solar Aspect System for solar observations (with a shutter protecting the star camera.) We have successfully imaged the Crab Nebula. Analyses for GRS 1915+105 and the Sun are ongoing. In this presentation, I will describe the HEROES mission, the data analysis pipeline and calibrations, preliminary results, and plans for follow-on missions.

Technology Assessment in Support of the Presidential Vision for Space Exploration

NASA Technical Reports Server (NTRS)

Weisbin, Charles R.; Lincoln, William; Mrozinski, Joe; Hua, Hook; Merida, Sofia; Shelton, Kacie; Adumitroaie, Virgil; Derleth, Jason; Silberg, Robert

2006-01-01

This paper discusses the process and results of technology assessment in support of the United States Vision for Space Exploration of the Moon, Mars and Beyond. The paper begins by reviewing the Presidential Vision: a major endeavor in building systems of systems. It discusses why we wish to return to the Moon, and the exploration architecture for getting there safely, sustaining a presence, and safely returning. Next, a methodology for optimal technology investment is proposed with discussion of inputs including a capability hierarchy, mission importance weightings, available resource profiles as a function of time, likelihoods of development success, and an objective function. A temporal optimization formulation is offered, and the investment recommendations presented along with sensitivity analyses. Key questions addressed are sensitivity of budget allocations to cost uncertainties, reduction in available budget levels, and shifting funding within constraints imposed by mission timeline.

Modern Perspectives on Numerical Modeling of Cardiac Pacemaker Cell

PubMed Central

Maltsev, Victor A.; Yaniv, Yael; Maltsev, Anna V.; Stern, Michael D.; Lakatta, Edward G.

2015-01-01

Cardiac pacemaking is a complex phenomenon that is still not completely understood. Together with experimental studies, numerical modeling has been traditionally used to acquire mechanistic insights in this research area. This review summarizes the present state of numerical modeling of the cardiac pacemaker, including approaches to resolve present paradoxes and controversies. Specifically we discuss the requirement for realistic modeling to consider symmetrical importance of both intracellular and cell membrane processes (within a recent “coupled-clock” theory). Promising future developments of the complex pacemaker system models include the introduction of local calcium control, mitochondria function, and biochemical regulation of protein phosphorylation and cAMP production. Modern numerical and theoretical methods such as multi-parameter sensitivity analyses within extended populations of models and bifurcation analyses are also important for the definition of the most realistic parameters that describe a robust, yet simultaneously flexible operation of the coupled-clock pacemaker cell system. The systems approach to exploring cardiac pacemaker function will guide development of new therapies, such as biological pacemakers for treating insufficient cardiac pacemaker function that becomes especially prevalent with advancing age. PMID:24748434

Extraction and derivatization of polar herbicides for GC-MS analyses.

PubMed

Ranz, Andreas; Maier, Eveline; Motter, Herbert; Lankmayr, Ernst

2008-09-01

A sample preparation procedure including a simultaneous microwave-assisted (MA) extraction and derivatization for the determination of chlorophenoxy acids in soil samples is presented. For a selective and sensitive measurement, an analytical technique such as GC coupled with MS needs to be adopted. For GC analyses, chlorophenoxy acids have to be converted into more volatile and thermally stable derivatives. Derivatization by means of microwave radiation offers new alternatives in terms of shorter derivatization time and reduces susceptibility for the formation of artefacts. Extraction and derivatization into methyl esters (ME) were performed with sulphuric acid and methanol. Due to the novelty of the simultaneous extraction and derivatization assisted by means of microwave radiation, a careful investigation and optimization of influential reaction parameters was necessary. It could be shown that the combination of sulphuric acid and methanol provides a fast sample preparation including an efficient clean up procedure. The data obtained by the described method are in good agreement with those published for the reference material. Finally, compared to conventional heating and also to the standard procedure of the EPA, the sample preparation time could be considerably shortened.

A Parametric Study on Using Active Debris Removal for LEO Environment Remediation

NASA Technical Reports Server (NTRS)

2010-01-01

Recent analyses on the instability of the orbital debris population in the low Earth orbit (LEO) region and the collision between Iridium 33 and Cosmos 2251 have reignited the interest in using active debris removal (ADR) to remediate the environment. There are; however, monumental technical, resource, operational, legal, and political challenges in making economically viable ADR a reality. Before a consensus on the need for ADR can be reached, a careful analysis of its effectiveness must be conducted. The goal is to demonstrate the need and feasibility of using ADR to better preserve the future environment and to guide its implementation to maximize the benefit-to-cost ratio. This paper describes a new sensitivity study on using ADR to stabilize the future LEO debris environment. The NASA long-term orbital debris evolutionary model, LEGEND, is used to quantify the effects of several key parameters, including target selection criteria/constraints and the starting epoch of ADR implementation. Additional analyses on potential ADR targets among the currently existing satellites and the benefits of collision avoidance maneuvers are also included.

Automated segmentation of lesions including subretinal hyperreflective material in neovascular age-related macular degeneration.

PubMed

Lee, Hyungwoo; Kang, Kyung Eun; Chung, Hyewon; Kim, Hyung Chan

2018-04-12

To evaluate an automated segmentation algorithm with a convolutional neural network (CNN) to quantify and detect intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and subretinal hyperreflective material (SHRM) through analyses of spectral domain optical coherence tomography (SD-OCT) images from patients with neovascular age-related macular degeneration (nAMD). Reliability and validity analysis of a diagnostic tool. We constructed a dataset including 930 B-scans from 93 eyes of 93 patients with nAMD. A CNN-based deep neural network was trained using 11550 augmented images derived from 550 B-scans. The performance of the trained network was evaluated using a validation set including 140 B-scans and a test set of 240 B-scans. The Dice coefficient, positive predictive value (PPV), sensitivity, relative area difference (RAD), and intraclass correlation coefficient (ICC) were used to evaluate segmentation and detection performance. Good agreement was observed for both segmentation and detection of lesions between the trained network and clinicians. The Dice coefficients for segmentation of IRF, SRF, SHRM, and PED were 0.78, 0.82, 0.75, and 0.80, respectively; the PPVs were 0.79, 0.80, 0.75, and 0.80, respectively; and the sensitivities were 0.77, 0.84, 0.73, and 0.81, respectively. The RADs were -4.32%, -10.29%, 4.13%, and 0.34%, respectively, and the ICCs were 0.98, 0.98, 0.97, and 0.98, respectively. All lesions were detected with high PPVs (range 0.94-0.99) and sensitivities (range 0.97-0.99). A CNN-based network provides clinicians with quantitative data regarding nAMD through automatic segmentation and detection of pathological lesions, including IRF, SRF, PED, and SHRM. Copyright © 2018 Elsevier Inc. All rights reserved.

A sensitive multi-residue method for the determination of 35 micropollutants including pharmaceuticals, iodinated contrast media and pesticides in water.

PubMed

Valls-Cantenys, Carme; Scheurer, Marco; Iglesias, Mònica; Sacher, Frank; Brauch, Heinz-Jürgen; Salvadó, Victoria

2016-09-01

A sensitive, multi-residue method using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to determine a representative group of 35 analytes, including corrosion inhibitors, pesticides and pharmaceuticals such as analgesic and anti-inflammatory drugs, five iodinated contrast media, β-blockers and some of their metabolites and transformation products in water samples. Few other methods are capable of determining such a broad range of contrast media together with other analytes. We studied the parameters affecting the extraction of the target analytes, including sorbent selection and extraction conditions, their chromatographic separation (mobile phase composition and column) and detection conditions using two ionisation sources: electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI). In order to correct matrix effects, a total of 20 surrogate/internal standards were used. ESI was found to have better sensitivity than APCI. Recoveries ranging from 79 to 134 % for tap water and 66 to 144 % for surface water were obtained. Intra-day precision, calculated as relative standard deviation, was below 34 % for tap water and below 21 % for surface water, groundwater and effluent wastewater. Method quantification limits (MQL) were in the low ng L(-1) range, except for the contrast agents iomeprol, amidotrizoic acid and iohexol (22, 25.5 and 17.9 ng L(-1), respectively). Finally, the method was applied to the analysis of 56 real water samples as part of the validation procedure. All of the compounds were detected in at least some of the water samples analysed. Graphical Abstract Multi-residue method for the determination of micropollutants including pharmaceuticals, iodinated contrast media and pesticides in waters by LC-MS/MS.

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

Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole-Body Physiology

PubMed Central

Moss, Robert; Grosse, Thibault; Marchant, Ivanny; Lassau, Nathalie; Gueyffier, François; Thomas, S. Randall

2012-01-01

Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a “virtual population” from which “virtual individuals” can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the “virtual individuals” that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models. PMID:22761561

The diagnostic accuracy of magnetic resonance venography in the detection of deep venous thrombosis: a systematic review and meta-analysis.

PubMed

Abdalla, G; Fawzi Matuk, R; Venugopal, V; Verde, F; Magnuson, T H; Schweitzer, M A; Steele, K E

2015-08-01

To search the literature for further evidence for the use of magnetic resonance venography (MRV) in the detection of suspected DVT and to re-evaluate the accuracy of MRV in the detection of suspected deep vein thrombosis (DVT). PubMed, EMBASE, Scopus, Cochrane, and Web of Science were searched. Study quality and the risk of bias were evaluated using the QUADAS 2. A random effects meta-analysis including subgroup and sensitivity analyses were performed. The search resulted in 23 observational studies all from academic centres. Sixteen articles were included in the meta-analysis. The summary estimates for MRV as a diagnostic non-invasive tool revealed a sensitivity of 93% (95% confidence interval [CI]: 89% to 95%) and specificity of 96% (95% CI: 94% to 97%). The heterogeneity of the studies was high. Inconsistency (I2) for sensitivity and specificity was 80.7% and 77.9%, respectively. Further studies investigating the use of MRV in the detection of suspected DVT did not offer further evidence to support the replacement of ultrasound with MRV as the first-line investigation. However, MRV may offer an alternative tool in the detection/diagnosis of DVT for whom ultrasound is inadequate or not feasible (such as in the obese patient). Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The role of large-scale eddies in the climate equilibrium. Part 2: Variable static stability

NASA Technical Reports Server (NTRS)

Zhou, Shuntai; Stone, Peter H.

1993-01-01

Lorenz's two-level model on a sphere is used to investigate how the results of Part 1 are modified when the interaction of the vertical eddy heat flux and static stability is included. In general, the climate state does not depend very much on whether or not this interaction is included, because the poleward eddy heat transport dominates the eddy forcing of mean temperature and wind fields. However, the climatic sensitivity is significantly affected. Compared to two-level model results with fixed static stability, the poleward eddy heat flux is less sensitive to the meridional temperature gradient and the gradient is more sensitive to the forcing. For example, the logarithmic derivative of the eddy flux with respect to the gradient has a slope that is reduced from approximately 15 on a beta-plane with fixed static stability and approximately 6 on a sphere with fixed static stability, to approximately 3 to 4 in the present model. This last result is more in line with analyses from observations. The present model also has a stronger baroclinic adjustment than that in Part 1, more like that in two-level beta-plane models with fixed static stability, that is, the midlatitude isentropic slope is very insensitive to the forcing, the diabatic heating, and the friction, unless the forcing is very weak.

Contact allergy to preservatives: ESSCA* results with the baseline series, 2009-2012.

PubMed

Giménez-Arnau, A M; Deza, G; Bauer, A; Johnston, G A; Mahler, V; Schuttelaar, M-L; Sanchez-Perez, J; Silvestre, J F; Wilkinson, M; Uter, W

2017-04-01

Allergic contact dermatitis caused by biocides is common and causes significant patient morbidity. To describe the current frequency and pattern of patch test reactivity to biocide allergens included in the baseline series of most European countries. Data collected by the European Surveillance System on Contact Allergies (ESSCA) network between 2009 and 2012 from 12 European countries were analysed. Methylisothiazolinone 0.2% aq. produced the highest prevalence of sensitization during the study period, with an overall prevalence of 4.5%. The mixture methylchloroisothiazolinone /methylisothiazolinone tested at 0.02% aq. followed closely, with 4.1% of positive reactions. Other preservatives with lower rates of sensitization, but still over 1%, include methyldibromo glutaronitrile (MDBGN) 0.5% pet. and iodopropynyl butylcarbamate (IPBC) 0.2% pet. Formaldehyde releasers and parabens yielded less than 1% positive reactions during the study period. Some regional differences in the prevalence of contact allergy to biocides among European countries were observed. Contact allergy to biocides is common throughout Europe, and regional differences could be explained by differences in exposure or characteristics of the population tested. Timely regulatory action for isothiazolinones is required. Although MDBGN is banned from cosmetics products since 2005, sensitization prevalence has not appeared to plateau. IPBC is an emerging allergen with an increasing prevalence over the last few years, and its inclusion in the European baseline series may be appropriate. © 2016 European Academy of Dermatology and Venereology.

Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy.

PubMed

Kimer, N; Krag, A; Møller, S; Bendtsen, F; Gluud, L L

2014-07-01

Rifaximin is recommended for prevention of hepatic encephalopathy (HE). The effects of rifaximin on overt and minimal HE are debated. To perform a systematic review and meta-analysis of randomised controlled trials (RCTs) on rifaximin for HE. We performed electronic and manual searches, gathered information from the U.S. Food and Drug Administration Home Page, and obtained unpublished information on trial design and outcome measures from authors and pharmaceutical companies. Meta-analyses were performed and results presented as risk ratios (RR) with 95% confidence intervals (CI) and the number needed to treat. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate the risk of bias and sources of heterogeneity. We included 19 RCTs with 1370 patients. Outcomes were recalculated based on unpublished information of 11 trials. Overall, rifaximin had a beneficial effect on secondary prevention of HE (RR: 1.32; 95% CI 1.06-1.65), but not in a sensitivity analysis on rifaximin after TIPSS (RR: 1.27; 95% CI 1.00-1.53). Rifaximin increased the proportion of patients who recovered from HE (RR: 0.59; 95% CI: 0.46-0.76) and reduced mortality (RR: 0.68, 95% CI 0.48-0.97). The results were robust to adjustments for bias control. No small study effects were identified. The sequential analyses only confirmed the results of the analysis on HE recovery. Rifaximin has a beneficial effect on hepatic encephalopathy and may reduce mortality. The combined evidence suggests that rifaximin may be considered in the evidence-based management of hepatic encephalopathy. © 2014 John Wiley & Sons Ltd.

Cost effectiveness of memantine in Alzheimer's disease: an analysis based on a probabilistic Markov model from a UK perspective.

PubMed

Jones, Roy W; McCrone, Paul; Guilhaume, Chantal

2004-01-01

Clinical trials with memantine, an uncompetitive moderate-affinity NMDA antagonist, have shown improved clinical outcomes, increased independence and a trend towards delayed institutionalisation in patients with moderately severe-to-severe Alzheimer's disease. In a randomised double-blind, placebo-controlled, 28-week study conducted in the US, reductions in resource utilisation and total healthcare costs were noted with memantine relative to placebo. While these findings suggest that, compared with placebo, memantine provides cost savings, further analyses may help to quantify potential economic gains over a longer treatment period. To evaluate the cost effectiveness of memantine therapy compared with no pharmacological treatment in patients with moderately severe-to-severe Alzheimer's disease over a 2-year period. A Markov model was constructed to simulate patient progression through a series of health states related to severity, dependency (determined by patient scores on the Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL] inventory and residential status ('institutionalisation') with a time horizon of 2 years (each 6-month Markov cycle was repeated four times). Transition probabilities from one health state to another 6 months later were mainly derived from a 28-week, randomised, double-blind, placebo-controlled clinical trial. Inputs related to epidemiological and cost data were derived from a UK longitudinal epidemiological study, while data on quality-adjusted life-years (QALYs) were derived from a Danish longitudinal study. To ensure conservative estimates from the model, the base case analysis assumed drug effectiveness was limited to 12 months. Monte Carlo simulations were performed for each state parameter following definition of a priori distributions for the main variables of the model. Sensitivity analyses included worst case scenario in which memantine was effective for 6 months and one-way sensitivity analyses on key parameters. Finally, a subgroup analysis was performed to determine which patients were most likely to benefit from memantine. Informal care was not included in this model as the costs were considered from National Health Service and Personal Social Services perspective. The base case analysis found that, compared with no treatment, memantine was associated with lower costs and greater clinical effectiveness in terms of years of independence, years in the community and QALYs. Sensitivity analyses supported these findings. For each category of Alzheimer's disease patient examined, treatment with memantine was a cost-effective strategy. The greatest economic gain of memantine treatment was in independent patients with a Mini-Mental State Examination score of > or =10. This model suggests that memantine treatment is cost effective and provides cost savings compared with no pharmacological treatment. These benefits appear to result from prolonged patient independence and delayed institutionalisation for moderately severe and severe Alzheimer's disease patients on memantine compared with no pharmacological treatment.

An approach to measure parameter sensitivity in watershed hydrological modelling

EPA Science Inventory

Hydrologic responses vary spatially and temporally according to watershed characteristics. In this study, the hydrologic models that we developed earlier for the Little Miami River (LMR) and Las Vegas Wash (LVW) watersheds were used for detail sensitivity analyses. To compare the...

Sensitivity analyses for simulating pesticide impacts on honey bee colonies

EPA Science Inventory

We employ Monte Carlo simulation and sensitivity analysis techniques to describe the population dynamics of pesticide exposure to a honey bee colony using the VarroaPop + Pesticide model. Simulations are performed of hive population trajectories with and without pesti...

Time to angiographic reperfusion in acute ischemic stroke: decision analysis.

PubMed

Vagal, Achala S; Khatri, Pooja; Broderick, Joseph P; Tomsick, Thomas A; Yeatts, Sharon D; Eckman, Mark H

2014-12-01

Our objective was to use decision analytic modeling to compare 2 treatment strategies of intravenous recombinant tissue-type plasminogen activator (r-tPA) alone versus combined intravenous r-tPA/endovascular therapy in a subgroup of patients with large vessel (internal carotid artery terminus, M1, and M2) occlusion based on varying times to angiographic reperfusion and varying rates of reperfusion. We developed a decision model using Interventional Management of Stroke (IMS) III trial data and comprehensive literature review. We performed 1-way sensitivity analyses for time to reperfusion and 2-way sensitivity for time to reperfusion and rate of reperfusion success. We also performed probabilistic sensitivity analyses to address uncertainty in total time to reperfusion for the endovascular approach. In the base case, endovascular approach yielded a higher expected utility (6.38 quality-adjusted life years) than the intravenous-only arm (5.42 quality-adjusted life years). One-way sensitivity analyses demonstrated superiority of endovascular treatment to intravenous-only arm unless time to reperfusion exceeded 347 minutes. Two-way sensitivity analysis demonstrated that endovascular treatment was preferred when probability of reperfusion is high and time to reperfusion is small. Probabilistic sensitivity results demonstrated an average gain for endovascular therapy of 0.76 quality-adjusted life years (SD 0.82) compared with the intravenous-only approach. In our post hoc model with its underlying limitations, endovascular therapy after intravenous r-tPA is the preferred treatment as compared with intravenous r-tPA alone. However, if time to reperfusion exceeds 347 minutes, intravenous r-tPA alone is the recommended strategy. This warrants validation in a randomized, prospective trial among patients with large vessel occlusions. © 2014 American Heart Association, Inc.

Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults.

PubMed

Shah, Maunank; Hanrahan, Colleen; Wang, Zhuo Yu; Dendukuri, Nandini; Lawn, Stephen D; Denkinger, Claudia M; Steingart, Karen R

2016-05-10

Rapid detection of tuberculosis (TB) among people living with human immunodeficiency virus (HIV) is a global health priority. HIV-associated TB may have different clinical presentations and is challenging to diagnose. Conventional sputum tests have reduced sensitivity in HIV-positive individuals, who have higher rates of extrapulmonary TB compared with HIV-negative individuals. The lateral flow urine lipoarabinomannan assay (LF-LAM) is a new, commercially available point-of-care test that detects lipoarabinomannan (LAM), a lipopolysaccharide present in mycobacterial cell walls, in people with active TB disease. To assess the accuracy of LF-LAM for the diagnosis of active TB disease in HIV-positive adults who have signs and symptoms suggestive of TB (TB diagnosis).To assess the accuracy of LF-LAM as a screening test for active TB disease in HIV-positive adults irrespective of signs and symptoms suggestive of TB (TB screening). We searched the following databases without language restriction on 5 February 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE (PubMed,1966); EMBASE (OVID, from 1980); Science Citation Index Expanded (SCI-EXPANDED, from 1900), Conference Proceedings Citation Index-Science (CPCI-S, from 1900), and BIOSIS Previews (from 1926) (all three using the Web of Science platform; MEDION; LILACS (BIREME, from 1982); SCOPUS (from 1995); the metaRegister of Controlled Trials (mRCT); the search portal of the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP); and ProQuest Dissertations & Theses A&l (from 1861). Eligible study types included randomized controlled trials, cross-sectional studies, and cohort studies that determined LF-LAM accuracy for TB against a microbiological reference standard (culture or nucleic acid amplification test from any body site). A higher quality reference standard was one in which two or more specimen types were evaluated for TB, and a lower quality reference standard was one in which only one specimen type was evaluated for TB. Participants were HIV-positive people aged 15 years and older. Two review authors independently extracted data from each included study using a standardized form. We appraised the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We evaluated the test at two different cut-offs: (grade 1 or 2, based on the reference card scale of five intensity bands). Most analyses used grade 2, the manufacturer's currently recommended cut-off for positivity. We carried out meta-analyses to estimate pooled sensitivity and specificity using a bivariate random-effects model and estimated the models using a Bayesian approach. We determined accuracy of LF-LAM combined with sputum microscopy or Xpert® MTB/RIF. In addition, we explored the influence of CD4 count on the accuracy estimates. We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We included 12 studies: six studies evaluated LF-LAM for TB diagnosis and six studies evaluated the test for TB screening. All studies were cross-sectional or cohort studies. Studies for TB diagnosis were largely conducted among inpatients (median CD4 range 71 to 210 cells per µL) and studies for TB screening were largely conducted among outpatients (median CD4 range 127 to 437 cells per µL). All studies were conducted in low- or middle-income countries. Only two studies for TB diagnosis (33%) and one study for TB screening (17%) used a higher quality reference standard.LF-LAM for TB diagnosis (grade 2 cut-off): meta-analyses showed median pooled sensitivity and specificity (95% credible interval (CrI)) of 45% (29% to 63%) and 92% (80% to 97%), (five studies, 2313 participants, 35% with TB, low quality evidence). The pooled sensitivity of a combination of LF-LAM and sputum microscopy (either test positive) was 59% (47% to 70%), which represented a 19% (4% to 36%) increase over sputum microscopy alone, while the pooled specificity was 92% (73% to 97%), which represented a 6% (1% to 24%) decrease from sputum microscopy alone (four studies, 1876 participants, 38% with TB). The pooled sensitivity of a combination of LF-LAM and sputum Xpert® MTB/RIF (either test positive) was 75% (61% to 87%) and represented a 13% (1% to 37%) increase over Xpert® MTB/RIF alone. The pooled specificity was 93% (81% to 97%) and represented a 4% (1% to 16%) decrease from Xpert® MTB/RIF alone (three studies, 909 participants, 36% with TB). Pooled sensitivity and specificity of LF-LAM were 56% (41% to 70%) and 90% (81% to 95%) in participants with a CD4 count of less than or equal to 100 cells per µL (five studies, 859 participants, 47% with TB) versus 26% (16% to 46%) and 92% (78% to 97%) in participants with a CD4 count greater than 100 cells per µL (five studies, 1410 participants, 30% with TB).LF-LAM for TB screening (grade 2 cut-off): for individual studies, sensitivity estimates (95% CrI) were 44% (30% to 58%), 28% (16% to 42%), and 0% (0% to 71%) and corresponding specificity estimates were 95% (92% to 97%), 94% (90% to 97%), and 95% (92% to 97%) (three studies, 1055 participants, 11% with TB, very low quality evidence). There were limited data for additional analyses.The main limitations of the review were the use of a lower quality reference standard in most included studies, and the small number of studies and participants included in the analyses. The results should, therefore, be interpreted with caution. We found that LF-LAM has low sensitivity to detect TB in adults living with HIV whether the test is used for diagnosis or screening. For TB diagnosis, the combination of LF-LAM with sputum microscopy suggests an increase in sensitivity for TB compared to either test alone, but with a decrease in specificity. In HIV-positive individuals with low CD4 counts who are seriously ill, LF-LAM may help with the diagnosis of TB.

Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset.

PubMed

Seashore-Ludlow, Brinton; Rees, Matthew G; Cheah, Jaime H; Cokol, Murat; Price, Edmund V; Coletti, Matthew E; Jones, Victor; Bodycombe, Nicole E; Soule, Christian K; Gould, Joshua; Alexander, Benjamin; Li, Ava; Montgomery, Philip; Wawer, Mathias J; Kuru, Nurdan; Kotz, Joanne D; Hon, C Suk-Yee; Munoz, Benito; Liefeld, Ted; Dančík, Vlado; Bittker, Joshua A; Palmer, Michelle; Bradner, James E; Shamji, Alykhan F; Clemons, Paul A; Schreiber, Stuart L

2015-11-01

Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset. This analysis reveals insights into small-molecule mechanisms of action, and genomic features that associate with CCL response to small-molecule treatment. We are able to recapitulate known relationships between FDA-approved therapies and cancer dependencies and to uncover new relationships, including for KRAS-mutant cancers and neuroblastoma. To enable the cancer community to explore these data, and to generate novel hypotheses, we created an updated version of the Cancer Therapeutic Response Portal (CTRP v2). We present the largest CCL sensitivity dataset yet available, and an analysis method integrating information from multiple CCLs and multiple small molecules to identify CCL response predictors robustly. We updated the CTRP to enable the cancer research community to leverage these data and analyses. ©2015 American Association for Cancer Research.

Cosmetics and herbal remedies with Compositae plant extracts - are they tolerated by Compositae-allergic patients?

PubMed

Paulsen, Evy; Chistensen, Lars P; Andersen, Klaus E

2008-01-01

Compositae-sensitive patients are routinely warned against topical use of Compositae-containing cosmetics and herbal remedies. However, the risk of elicitation of dermatitis in presensitized persons is unknown. The main aim of this study was to assess the significance of direct plant allergen contact via Compositae-derived cosmetics and herbal remedies in Compositae-allergic patients with special reference to arnica (Arnica montana) and German chamomile (Chamomilla recutita). 8 of 12 chamomile-sensitive patients tested positive to chamomile-containing preparations, including tea, creams, ointments, and oil. 5 of 6 arnica-sensitive persons tested positive to arnica-based products. When the group was patch tested with cosmetic and/or herbal product ingredients, plant allergens elicited positive reactions most frequently, but fragrances, emulsifiers, and preservatives tested positive as well. Plant allergens were mainly derived from Compositae, but avocado oil, and Hamamelis virginiana tincture were unexpectedly detected as sensitizers too. Chemical analyses indicated that the Compositae allergens were both sesquiterpene lactones and other naturally occurring compounds. In conclusion, Compositae-allergic persons should be warned against topical use of Compositae-containing products, not only because of the plant allergens, but also because of allergenic cream constituents that may cause reactions in the group of patients who have multiple contact allergies beside the Compositae allergy.

NARRATIVE AND META-ANALYTIC REVIEW OF INTERVENTIONS AIMING TO IMPROVE MATERNAL-CHILD ATTACHMENT SECURITY.

PubMed

Letourneau, Nicole; Tryphonopoulos, Panagiota; Giesbrecht, Gerald; Dennis, Cindy-Lee; Bhogal, Sanjit; Watson, Barry

2015-01-01

Early secure maternal-child attachment relationships lay the foundation for children's healthy social and mental development. Interventions targeting maternal sensitivity and maternal reflective function during the first year of infant life may be the key to promoting secure attachment. We conducted a narrative systematic review and meta-analysis to examine the effectiveness of interventions aimed at promoting maternal sensitivity and reflective function on maternal-child attachment security, as measured by the gold standard Strange Situation (M. Ainsworth, M. Blehar, B. Waters, & S. Wall, 1978) and Q-set (E. Waters & K. Deane, 1985). Studies were identified from electronic database searches and included randomized or quasi-randomized controlled parallel-group designs. Participants were mothers and their infants who were followed up to 36 months' postpartum. Ten trials, involving 1,628 mother-infant pairs, were included. Examination of the trials that provided sufficient data for combination in meta-analysis revealed that interventions of both types increased the odds of secure maternal-child attachment, as compared with no intervention or standard intervention (n = 7 trials; odds ratio: 2.77; 95% confidence interval: 1.69, 4.53, n = 965). Of the three trials not included in the meta-analyses, two improved the likelihood of secure attachment. We conclude that interventions aimed at improving maternal sensitivity alone or in combination with maternal reflection, implemented in the first year of infants' lives, are effective in promoting secure maternal-child attachments. Intervention aimed at the highest risk families produced the most beneficial effects. © 2015 Michigan Association for Infant Mental Health.