Skin sensitization potency of methyl methacrylate in the local lymph node assay: comparisons with guinea-pig data and human experience.

PubMed

Betts, Catherine J; Dearman, Rebecca J; Heylings, Jon R; Kimber, Ian; Basketter, David A

2006-09-01

There is compelling evidence that contact allergens differ substantially (by 4 or 5 orders of magnitude) with respect to their inherent skin-sensitizing potency. Relative potency can now be measured effectively using the mouse local lymph node assay (LLNA) and such data form the basis of risk assessment and risk management strategies. Such determinations also facilitate distinctions being drawn between the prevalence of skin sensitization to a particular contact allergen and inherent potency. The distinction is important because chemicals that are implicated as common causes of contact allergy are not necessarily potent sensitizers. One example is provided by nickel that is undoubtedly a common cause of allergic contact dermatitis, but is a comparatively weak sensitizer in predictive tests. In an attempt to explore other examples of contact allergens where there may exist a discrepancy between prevalence and potency, we describe here analyses conducted with methyl methacrylate (MMA). Results of LLNA studies have been interpreted in the context of historical clinical data on occupational allergic contact dermatitis associated with exposure to MMA.

Evapotranspiration-dominated biogeophysical warming effect of urbanization in the Beijing-Tianjin-Hebei region, China

NASA Astrophysics Data System (ADS)

Zhao, Guosong; Dong, Jinwei; Cui, Yaoping; Liu, Jiyuan; Zhai, Jun; He, Tian; Zhou, Yuyu; Xiao, Xiangming

2018-03-01

Given the considerable influences of urbanization on near-surface air temperature (T a ) and surface skin temperature (T s ) at local and regional scales, we investigated the biogeophysical effects of urbanization on T a and T s in the Beijing-Tianjin-Hebei (BTH) region of China, a typical rapidly urbanizing area, using the weather research and forecasting model (WRF). Two experiments were conducted using satellite-derived realistic areal fraction land cover data in 2010 and 1990 as well as localized parameters (e.g. albedo and leaf area index). Without considering anthropogenic heat, experimental differences indicated a regional biogeophysical warming of 0.15 °C (0.16 °C) in summer T a (T s ), but a negligible warming in winter T a (T s ). Sensitivity analyses also showed a stronger magnitude of local warming in summer than in winter. Along with an increase of 10% in the urban fraction, local T a (T s ) increases of 0.185 °C (0.335 °C), 0.212 °C (0.464 °C), and 0.140 °C (0.220 °C) were found at annual, summer, and winter scales, respectively, according to a space-for-time substitution method. The sensitivity analyses will be beneficial to get a rough biogeophysical warming estimation of future urbanization projections. Furthermore, a decomposed temperature metric (DTM) method was applied for the attribution analyses of the change in T s induced by urbanization. Our results showed that the decrease in evapotranspiration-induced latent heat played a dominate role in biogeophysical warming due to urbanization in BTH, indicating that increasing green space could alleviate warming effects, especially in summer.

Demographic origins of skewed operational and adult sex ratios: perturbation analyses of two-sex models.

PubMed

Veran, Sophie; Beissinger, Steven R

2009-02-01

Skewed sex ratios - operational (OSR) and Adult (ASR) - arise from sexual differences in reproductive behaviours and adult survival rates due to the cost of reproduction. However, skewed sex-ratio at birth, sex-biased dispersal and immigration, and sexual differences in juvenile mortality may also contribute. We present a framework to decompose the roles of demographic traits on sex ratios using perturbation analyses of two-sex matrix population models. Metrics of sensitivity are derived from analyses of sensitivity, elasticity, life-table response experiments and life stage simulation analyses, and applied to the stable stage distribution instead of lambda. We use these approaches to examine causes of male-biased sex ratios in two populations of green-rumped parrotlets (Forpus passerinus) in Venezuela. Female local juvenile survival contributed the most to the unbalanced OSR and ASR due to a female-biased dispersal rate, suggesting sexual differences in philopatry can influence sex ratios more strongly than the cost of reproduction.

Comparative analysis of skin sensitization potency of acrylates (methyl acrylate, ethyl acrylate, butyl acrylate, and ethylhexyl acrylate) using the local lymph node assay.

PubMed

Dearman, Rebecca J; Betts, Catherine J; Farr, Craig; McLaughlin, James; Berdasco, Nancy; Wiench, Karin; Kimber, Ian

2007-10-01

There are currently available no systematic experimental data on the skin sensitizing properties of acrylates that are of relevance in occupational settings. Limited information from previous guinea-pig tests or from the local lymph node assay (LLNA) is available; however, these data are incomplete and somewhat contradictory. For those reasons, we have examined in the LLNA 4 acrylates: butyl acrylate (BA), ethyl acrylate (EA), methyl acrylate (MA), and ethylhexyl acrylate (EHA). The LLNA data indicated that all 4 compounds have some potential to cause skin sensitization. In addition, the relative potencies of these acrylates were measured by derivation from LLNA dose-response analyses of EC3 values (the effective concentration of chemical required to induce a threefold increase in proliferation of draining lymph node cells compared with control values). On the basis of 1 scheme for the categorization of skin sensitization potency, BA, EA, and MA were each classified as weak sensitizers. Using the same scheme, EHA was considered a moderate sensitizer. However, it must be emphasized that the EC3 value for this chemical of 9.7% is on the borderline between moderate (<10%) and weak (>10%) categories. Thus, the judicious view is that all 4 chemicals possess relatively weak skin sensitizing potential.

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

The local lymph node assay and skin sensitization: a cut-down screen to reduce animal requirements?

PubMed

Kimber, Ian; Dearman, Rebecca J; Betts, Catherine J; Gerberick, G Frank; Ryan, Cindy A; Kern, Petra S; Patlewicz, Grace Y; Basketter, David A

2006-04-01

The local lymph node assay (LLNA), an alternative approach to skin-sensitizing testing, has made a significant contribution to animal welfare by permitting a reduction and refinement of animal use. Although there is clearly an aspiration to eliminate the use of animals in such tests, it is appropriate also to consider other opportunities for refinement and reduction of animal use. We have therefore explored the use of a modified version of the LLNA for screening purposes when there is a need to evaluate the sensitizing activity of a large number of chemicals, as will be the case under the auspices of registration, evaluation and authorization of chemicals (REACH). Using an existing LLNA database of 211 chemicals, we have examined whether a cut-down assay comprising a single high-dose group and a concurrent vehicle control would provide a realistic approach for screening chemicals for sensitizing potential. The analyses reported here suggest this is the case. We speculate that the animal welfare benefits may be enhanced further by reducing the number of animals per experimental group. However, a detailed evaluation will be necessary to provide reassurance that a reduction in group size would provide adequate sensitivity across a range of skin sensitization potencies.

Economic outcomes of maintenance gefitinib for locally advanced/metastatic non-small-cell lung cancer with unknown EGFR mutations: a semi-Markov model analysis.

PubMed

Zeng, Xiaohui; Li, Jianhe; Peng, Liubao; Wang, Yunhua; Tan, Chongqing; Chen, Gannong; Wan, Xiaomin; Lu, Qiong; Yi, Lidan

2014-01-01

Maintenance gefitinib significantly prolonged progression-free survival (PFS) compared with placebo in patients from eastern Asian with locally advanced/metastatic non-small-cell lung cancer (NSCLC) after four chemotherapeutic cycles (21 days per cycle) of first-line platinum-based combination chemotherapy without disease progression. The objective of the current study was to evaluate the cost-effectiveness of maintenance gefitinib therapy after four chemotherapeutic cycle's stand first-line platinum-based chemotherapy for patients with locally advanced or metastatic NSCLC with unknown EGFR mutations, from a Chinese health care system perspective. A semi-Markov model was designed to evaluate cost-effectiveness of the maintenance gefitinib treatment. Two-parametric Weibull and Log-logistic distribution were fitted to PFS and overall survival curves independently. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the model designed. The model base-case analysis suggested that maintenance gefitinib would increase benefits in a 1, 3, 6 or 10-year time horizon, with incremental $184,829, $19,214, $19,328, and $21,308 per quality-adjusted life-year (QALY) gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was utility of PFS plus rash, followed by utility of PFS plus diarrhoea, utility of progressed disease, price of gefitinib, cost of follow-up treatment in progressed survival state, and utility of PFS on oral therapy. The price of gefitinib is the most significant parameter that could reduce the incremental cost per QALY. Probabilistic sensitivity analysis indicated that the cost-effective probability of maintenance gefitinib was zero under the willingness-to-pay (WTP) threshold of $16,349 (3 × per-capita gross domestic product of China). The sensitivity analyses all suggested that the model was robust. Maintenance gefitinib following first-line platinum-based chemotherapy for patients with locally advanced/metastatic NSCLC with unknown EGFR mutations is not cost-effective. Decreasing the price of gefitinib may be a preferential choice for meeting widely treatment demands in China.

Economic impact of Tegaderm chlorhexidine gluconate (CHG) dressing in critically ill patients.

PubMed

Thokala, Praveen; Arrowsmith, Martin; Poku, Edith; Martyn-St James, Marissa; Anderson, Jeff; Foster, Steve; Elliott, Tom; Whitehouse, Tony

2016-09-01

To estimate the economic impact of a Tegaderm TM chlorhexidine gluconate (CHG) gel dressing compared with a standard intravenous (i.v.) dressing (defined as non-antimicrobial transparent film dressing), used for insertion site care of short-term central venous and arterial catheters (intravascular catheters) in adult critical care patients using a cost-consequence model populated with data from published sources. A decision analytical cost-consequence model was developed which assigned each patient with an indwelling intravascular catheter and a standard dressing, a baseline risk of associated dermatitis, local infection at the catheter insertion site and catheter-related bloodstream infections (CRBSI), estimated from published secondary sources. The risks of these events for patients with a Tegaderm CHG were estimated by applying the effectiveness parameters from the clinical review to the baseline risks. Costs were accrued through costs of intervention (i.e. Tegaderm CHG or standard intravenous dressing) and hospital treatment costs depended on whether the patients had local dermatitis, local infection or CRBSI. Total costs were estimated as mean values of 10,000 probabilistic sensitivity analysis (PSA) runs. Tegaderm CHG resulted in an average cost-saving of £77 per patient in an intensive care unit. Tegaderm CHG also has a 98.5% probability of being cost-saving compared to standard i.v. dressings. The analyses suggest that Tegaderm CHG is a cost-saving strategy to reduce CRBSI and the results were robust to sensitivity analyses.

Observations of Local Positive Low Cloud Feedback Patterns and Their Role in Internal Variability and Climate Sensitivity

NASA Astrophysics Data System (ADS)

Yuan, Tianle; Oreopoulos, Lazaros; Platnick, Steven E.; Meyer, Kerry

2018-05-01

Modeling studies have shown that cloud feedbacks are sensitive to the spatial pattern of sea surface temperature (SST) anomalies, while cloud feedbacks themselves strongly influence the magnitude of SST anomalies. Observational counterparts to such patterned interactions are still needed. Here we show that distinct large-scale patterns of SST and low-cloud cover (LCC) emerge naturally from objective analyses of observations and demonstrate their close coupling in a positive local SST-LCC feedback loop that may be important for both internal variability and climate change. The two patterns that explain the maximum amount of covariance between SST and LCC correspond to the Interdecadal Pacific Oscillation and the Atlantic Multidecadal Oscillation, leading modes of multidecadal internal variability. Spatial patterns and time series of SST and LCC anomalies associated with both modes point to a strong positive local SST-LCC feedback. In many current climate models, our analyses suggest that SST-LCC feedback strength is too weak compared to observations. Modeled local SST-LCC feedback strength affects simulated internal variability so that stronger feedback produces more intense and more realistic patterns of internal variability. To the extent that the physics of the local positive SST-LCC feedback inferred from observed climate variability applies to future greenhouse warming, we anticipate significant amount of delayed warming because of SST-LCC feedback when anthropogenic SST warming eventually overwhelm the effects of internal variability that may mute anthropogenic warming over parts of the ocean. We postulate that many climate models may be underestimating both future warming and the magnitude of modeled internal variability because of their weak SST-LCC feedback.

Local birefringence of the anterior segment of the human eye in a single capture with a full range polarisation-sensitive optical coherence tomography

NASA Astrophysics Data System (ADS)

Li, Qingyun; Karnowski, Karol; Villiger, Martin; Sampson, David D.

2017-04-01

A fibre-based full-range polarisation-sensitive optical coherence tomography system is developed to enable complete capture of the structural and birefringence properties of the anterior segment of the human eye in a single acquisition. The system uses a wavelength swept source centered at 1.3 μm, passively depth-encoded, orthogonal polarisation states in the illumination path and polarisation-diversity detection. Off-pivot galvanometer scanning is used to extend the imaging range and compensate for sensitivity drop-off. A Mueller matrix-based method is used to analyse data. We demonstrate the performance of the system and discuss issues relating to its optimisation.

The local lymph node assay and the assessment of relative potency: status of validation.

PubMed

Basketter, David A; Gerberick, Frank; Kimber, Ian

2007-08-01

For the prediction of skin sensitization potential, the local lymph node assay (LLNA) is a fully validated alternative to guinea-pig tests. More recently, information from LLNA dose-response analyses has been used to assess the relative potency of skin sensitizing chemicals. These data are then deployed for risk assessment and risk management. In this commentary, the utility and validity of these relative potency measurements are reviewed. It is concluded that the LLNA does provide a valuable assessment of relative sensitizing potency in the form of the estimated concentration of a chemical required to produce a threefold stimulation of draining lymph node cell proliferation compared with concurrent controls (EC3 value) and that all reasonable validation requirements have been addressed successfully. EC3 measurements are reproducible in both intra- and interlaboratory evaluations and are stable over time. It has been shown also, by several independent groups, that EC3 values correlate closely with data on relative human skin sensitization potency. Consequently, the recommendation made here is that LLNA EC3 measurements should now be regarded as a validated method for the determination of the relative potency of skin sensitizing chemicals, a conclusion that has already been reached by a number of independent expert groups.

The reduced local lymph node assay: the impact of group size.

PubMed

Ryan, Cindy A; Chaney, Joel G; Kern, Petra S; Patlewicz, Grace Y; Basketter, David A; Betts, Catherine J; Dearman, Rebecca J; Kimber, Ian; Gerberick, G Frank

2008-05-01

The local lymph node assay (LLNA) is a skin sensitization test that provides animal welfare benefits. To reduce animal usage further, a modified version (rLLNA) was proposed. Conducting the rLLNA as a screening test with a single high dose group and vehicle control differentiated accurately between skin sensitizers and non-sensitizers. This study examined whether a reduction in animal number/group is feasible. Historical data were utilized to examine the impact of conducting the rLLNA with two mice/group. To assess the effect on the stimulation index (SI) 41 datasets with individual animal data derived using five mice/group were analysed. SIs were calculated on all possible combinations of two control and two high dose group disintegrations per minute (dpm) values. For 25 of 33 sensitizer datasets, > 96% of possible dpm combinations resulted in a calculated SI > 3. The lowest percentages of positive SIs were observed with weak allergens when, in the standard LLNA, the mean SIs would have been nearer to the threshold value of 3. The results indicate that moderate, strong and extreme allergens are more likely than weak allergens to be identified as sensitizers when group sizes of two mice are used within the rLLNA. It is concluded that a rLLNA with two mice/group would display decreased sensitivity and is inappropriate for use in hazard identification. Copyright (c) 2007 John Wiley & Sons, Ltd.

Cognitive and Neural Bases of Skilled Performance.

DTIC Science & Technology

1987-10-04

advantage is that this method is not computationally demanding, and model -specific analyses such as high -precision source localization with realistic...and a two- < " high -threshold model satisfy theoretical and pragmatic independence. Discrimination and bias measures from these two models comparing...recognition memory of patients with dementing diseases, amnesics, and normal controls. We found the two- high -threshold model to be more sensitive Lloyd

The problem and promise of scale dependency in community phylogenetics.

PubMed

Swenson, Nathan G; Enquist, Brian J; Pither, Jason; Thompson, Jill; Zimmerman, Jess K

2006-10-01

The problem of scale dependency is widespread in investigations of ecological communities. Null model investigations of community assembly exemplify the challenges involved because they typically include subjectively defined "regional species pools." The burgeoning field of community phylogenetics appears poised to face similar challenges. Our objective is to quantify the scope of the problem of scale dependency by comparing the phylogenetic structure of assemblages across contrasting geographic and taxonomic scales. We conduct phylogenetic analyses on communities within three tropical forests, and perform a sensitivity analysis with respect to two scaleable inputs: taxonomy and species pool size. We show that (1) estimates of phylogenetic overdispersion within local assemblages depend strongly on the taxonomic makeup of the local assemblage and (2) comparing the phylogenetic structure of a local assemblage to a species pool drawn from increasingly larger geographic scales results in an increased signal of phylogenetic clustering. We argue that, rather than posing a problem, "scale sensitivities" are likely to reveal general patterns of diversity that could help identify critical scales at which local or regional influences gain primacy for the structuring of communities. In this way, community phylogenetics promises to fill an important gap in community ecology and biogeography research.

Theoretical analyses of localized surface plasmon resonance spectrum with nanoparticles imprinted polymers

NASA Astrophysics Data System (ADS)

Li, Hong; Peng, Wei; Wang, Yanjie; Hu, Lingling; Liang, Yuzhang; Zhang, Xinpu; Yao, Wenjuan; Yu, Qi; Zhou, Xinlei

2011-12-01

Optical sensors based on nanoparticles induced Localized Surface Plasmon Resonance are more sensitive to real-time chemical and biological sensing, which have attracted intensive attentions in many fields. In this paper, we establish a simulation model based on nanoparticles imprinted polymer to increase sensitivity of the LSPR sensor by detecting the changes of Surface Plasmon Resonance signals. Theoretical analysis and numerical simulation of parameters effects to absorption peak and light field distribution are highlighted. Two-dimensional simulated color maps show that LSPR lead to centralization of the light energy around the gold nanoparticles, Transverse Magnetic wave and total reflection become the important factors to enhance the light field in our simulated structure. Fast Fourier Transfer analysis shows that the absorption peak of the surface plasmon resonance signal resulted from gold nanoparticles is sharper while its wavelength is bigger by comparing with silver nanoparticles; a double chain structure make the amplitude of the signals smaller, and make absorption wavelength longer; the absorption peak of enhancement resulted from nanopore arrays has smaller wavelength and weaker amplitude in contrast with nanoparticles. These simulation results of the Localized Surface Plasmon Resonance can be used as an enhanced transduction mechanism for enhancement of sensitivity in recognition and sensing of target analytes in accordance with different requirements.

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.

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

PubMed

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

2010-10-24

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

Use of social network analysis and global sensitivity and uncertainty analyses to better understand an influenza outbreak.

PubMed

Liu, Jianhua; Jiang, Hongbo; Zhang, Hao; Guo, Chun; Wang, Lei; Yang, Jing; Nie, Shaofa

2017-06-27

In the summer of 2014, an influenza A(H3N2) outbreak occurred in Yichang city, Hubei province, China. A retrospective study was conducted to collect and interpret hospital and epidemiological data on it using social network analysis and global sensitivity and uncertainty analyses. Results for degree (χ2=17.6619, P<0.0001) and betweenness(χ2=21.4186, P<0.0001) centrality suggested that the selection of sampling objects were different between traditional epidemiological methods and newer statistical approaches. Clique and network diagrams demonstrated that the outbreak actually consisted of two independent transmission networks. Sensitivity analysis showed that the contact coefficient (k) was the most important factor in the dynamic model. Using uncertainty analysis, we were able to better understand the properties and variations over space and time on the outbreak. We concluded that use of newer approaches were significantly more efficient for managing and controlling infectious diseases outbreaks, as well as saving time and public health resources, and could be widely applied on similar local outbreaks.

Actors and networks in resource conflict resolution under climate change in rural Kenya

NASA Astrophysics Data System (ADS)

Ngaruiya, Grace W.; Scheffran, Jürgen

2016-05-01

The change from consensual decision-making arrangements into centralized hierarchical chieftaincy schemes through colonization disrupted many rural conflict resolution mechanisms in Africa. In addition, climate change impacts on land use have introduced additional socio-ecological factors that complicate rural conflict dynamics. Despite the current urgent need for conflict-sensitive adaptation, resolution efficiency of these fused rural institutions has hardly been documented. In this context, we analyse the Loitoktok network for implemented resource conflict resolution structures and identify potential actors to guide conflict-sensitive adaptation. This is based on social network data and processes that are collected using the saturation sampling technique to analyse mechanisms of brokerage. We find that there are three different forms of fused conflict resolution arrangements that integrate traditional institutions and private investors in the community. To effectively implement conflict-sensitive adaptation, we recommend the extension officers, the council of elders, local chiefs and private investors as potential conduits of knowledge in rural areas. In conclusion, efficiency of these fused conflict resolution institutions is aided by the presence of holistic resource management policies and diversification in conflict resolution actors and networks.

Model tests and numerical analyses on horizontal impedance functions of inclined single piles embedded in cohesionless soil

NASA Astrophysics Data System (ADS)

Goit, Chandra Shekhar; Saitoh, Masato

2013-03-01

Horizontal impedance functions of inclined single piles are measured experimentally for model soil-pile systems with both the effects of local soil nonlinearity and resonant characteristics. Two practical pile inclinations of 5° and 10° in addition to a vertical pile embedded in cohesionless soil and subjected to lateral harmonic pile head loadings for a wide range of frequencies are considered. Results obtained with low-to-high amplitude of lateral loadings on model soil-pile systems encased in a laminar shear box show that the local nonlinearities have a profound impact on the horizontal impedance functions of piles. Horizontal impedance functions of inclined piles are found to be smaller than the vertical pile and the values decrease as the angle of pile inclination increases. Distinct values of horizontal impedance functions are obtained for the `positive' and `negative' cycles of harmonic loadings, leading to asymmetric force-displacement relationships for the inclined piles. Validation of these experimental results is carried out through three-dimensional nonlinear finite element analyses, and the results from the numerical models are in good agreement with the experimental data. Sensitivity analyses conducted on the numerical models suggest that the consideration of local nonlinearity at the vicinity of the soil-pile interface influence the response of the soil-pile systems.

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)

Distributed Evaluation of Local Sensitivity Analysis (DELSA), with application to hydrologic models

USGS Publications Warehouse

Rakovec, O.; Hill, Mary C.; Clark, M.P.; Weerts, A. H.; Teuling, A. J.; Uijlenhoet, R.

2014-01-01

This paper presents a hybrid local-global sensitivity analysis method termed the Distributed Evaluation of Local Sensitivity Analysis (DELSA), which is used here to identify important and unimportant parameters and evaluate how model parameter importance changes as parameter values change. DELSA uses derivative-based “local” methods to obtain the distribution of parameter sensitivity across the parameter space, which promotes consideration of sensitivity analysis results in the context of simulated dynamics. This work presents DELSA, discusses how it relates to existing methods, and uses two hydrologic test cases to compare its performance with the popular global, variance-based Sobol' method. The first test case is a simple nonlinear reservoir model with two parameters. The second test case involves five alternative “bucket-style” hydrologic models with up to 14 parameters applied to a medium-sized catchment (200 km2) in the Belgian Ardennes. Results show that in both examples, Sobol' and DELSA identify similar important and unimportant parameters, with DELSA enabling more detailed insight at much lower computational cost. For example, in the real-world problem the time delay in runoff is the most important parameter in all models, but DELSA shows that for about 20% of parameter sets it is not important at all and alternative mechanisms and parameters dominate. Moreover, the time delay was identified as important in regions producing poor model fits, whereas other parameters were identified as more important in regions of the parameter space producing better model fits. The ability to understand how parameter importance varies through parameter space is critical to inform decisions about, for example, additional data collection and model development. The ability to perform such analyses with modest computational requirements provides exciting opportunities to evaluate complicated models as well as many alternative models.

Early differential sensitivity of evoked-potentials to local and global shape during the perception of three-dimensional objects.

PubMed

Leek, E Charles; Roberts, Mark; Oliver, Zoe J; Cristino, Filipe; Pegna, Alan J

2016-08-01

Here we investigated the time course underlying differential processing of local and global shape information during the perception of complex three-dimensional (3D) objects. Observers made shape matching judgments about pairs of sequentially presented multi-part novel objects. Event-related potentials (ERPs) were used to measure perceptual sensitivity to 3D shape differences in terms of local part structure and global shape configuration - based on predictions derived from hierarchical structural description models of object recognition. There were three types of different object trials in which stimulus pairs (1) shared local parts but differed in global shape configuration; (2) contained different local parts but shared global configuration or (3) shared neither local parts nor global configuration. Analyses of the ERP data showed differential amplitude modulation as a function of shape similarity as early as the N1 component between 146-215ms post-stimulus onset. These negative amplitude deflections were more similar between objects sharing global shape configuration than local part structure. Differentiation among all stimulus types was reflected in N2 amplitude modulations between 276-330ms. sLORETA inverse solutions showed stronger involvement of left occipitotemporal areas during the N1 for object discrimination weighted towards local part structure. The results suggest that the perception of 3D object shape involves parallel processing of information at local and global scales. This processing is characterised by relatively slow derivation of 'fine-grained' local shape structure, and fast derivation of 'coarse-grained' global shape configuration. We propose that the rapid early derivation of global shape attributes underlies the observed patterns of N1 amplitude modulations. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Stable genetic structure and connectivity in pollution-adapted and nearby pollution-sensitive populations of Fundulus heteroclitus

PubMed Central

Biancani, Leann M.; Flight, Patrick A.; Nacci, Diane E.; Rand, David M.; Crawford, Douglas L.; Oleksiak, Marjorie F.

2018-01-01

Populations of the non-migratory estuarine fish Fundulus heteroclitus inhabiting the heavily polluted New Bedford Harbour (NBH) estuary have shown inherited tolerance to local pollutants introduced to their habitats in the past 100 years. Here we examine two questions: (i) Is there pollution-driven selection on the mitochondrial genome across a fine geographical scale? and (ii) What is the pattern of migration among sites spanning a strong pollution gradient? Whole mitochondrial genomes were analysed for 133 F. heteroclitus from seven nearby collection sites: four sites along the NBH pollution cline (approx. 5 km distance), which had pollution-adapted fish, as well as one site adjacent to the pollution cline and two relatively unpolluted sites about 30 km away, which had pollution-sensitive fish. Additionally, we used microsatellite analyses to quantify genetic variation over three F. heteroclitus generations in both pollution-adapted and sensitive individuals collected from two sites at two different time points (1999/2000 and 2007/2008). Our results show no evidence for a selective sweep of mtDNA in the polluted sites. Moreover, mtDNA analyses revealed that both pollution-adapted and sensitive populations harbour similar levels of genetic diversity. We observed a high level of non-synonymous mutations in the most polluted site. This is probably associated with a reduction in Ne and concomitant weakening of purifying selection, a demographic expansion following a pollution-related bottleneck or increased mutation rates. Our demographic analyses suggest that isolation by distance influences the distribution of mtDNA genetic variation between the pollution cline and the clean populations at broad spatial scales. At finer scales, population structure is patchy, and neither spatial distance, pollution concentration or pollution tolerance is a good predictor of mtDNA variation. Lastly, microsatellite analyses revealed stable population structure over the last decade. PMID:29892357

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.

Mass spectrometry imaging: Towards a lipid microscope?

PubMed

Touboul, David; Brunelle, Alain; Laprévote, Olivier

2011-01-01

Biological imaging techniques are the most efficient way to locally measure the variation of different parameters on tissue sections. These analyses are gaining increasing interest since 20 years and allow observing extremely complex biological phenomena at lower and lower time and resolution scale. Nevertheless, most of them only target very few compounds of interest, which are chosen a priori, due to their low resolution power and sensitivity. New chemical imaging technique has to be introduced in order to overcome these limitations, leading to more informative and sensitive analyses for biologists and physicians. Two major mass spectrometry methods can be efficiently used to generate the distribution of biological compounds over a tissue section. Matrix-Assisted Laser Desorption/Ionisation-Mass Spectrometry (MALDI-MS) needs the co-crystallization of the sample with a matrix before to be irradiated by a laser, whereas the analyte is directly desorbed by a primary ion bombardment for Secondary Ion Mass Spectrometry (SIMS) experiments. In both cases, energy used for desorption/ionization is locally deposited -some tens of microns for the laser and some hundreds of nanometers for the ion beam- meaning that small areas over the surface sample can be separately analyzed. Step by step analysis allows spectrum acquisitions over the tissue sections and the data are treated by modern informatics software in order to create ion density maps, i.e., the intensity plot of one specific ion versus the (x,y) position. Main advantages of SIMS and MALDI compared to other chemical imaging techniques lie in the simultaneous acquisition of a large number of biological compounds in mixture with an excellent sensitivity obtained by Time-of-Flight (ToF) mass analyzer. Moreover, data treatment is done a posteriori, due to the fact that no compound is selectively marked, and let us access to the localization of different lipid classes in only one complete acquisition. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Climate fails to predict wood decomposition at regional scales

NASA Astrophysics Data System (ADS)

Bradford, Mark A.; Warren, Robert J., II; Baldrian, Petr; Crowther, Thomas W.; Maynard, Daniel S.; Oldfield, Emily E.; Wieder, William R.; Wood, Stephen A.; King, Joshua R.

2014-07-01

Decomposition of organic matter strongly influences ecosystem carbon storage. In Earth-system models, climate is a predominant control on the decomposition rates of organic matter. This assumption is based on the mean response of decomposition to climate, yet there is a growing appreciation in other areas of global change science that projections based on mean responses can be irrelevant and misleading. We test whether climate controls on the decomposition rate of dead wood--a carbon stock estimated to represent 73 +/- 6 Pg carbon globally--are sensitive to the spatial scale from which they are inferred. We show that the common assumption that climate is a predominant control on decomposition is supported only when local-scale variation is aggregated into mean values. Disaggregated data instead reveal that local-scale factors explain 73% of the variation in wood decomposition, and climate only 28%. Further, the temperature sensitivity of decomposition estimated from local versus mean analyses is 1.3-times greater. Fundamental issues with mean correlations were highlighted decades ago, yet mean climate-decomposition relationships are used to generate simulations that inform management and adaptation under environmental change. Our results suggest that to predict accurately how decomposition will respond to climate change, models must account for local-scale factors that control regional dynamics.

MEG biomarker of Alzheimer's disease: Absence of a prefrontal generator during auditory sensory gating.

PubMed

Josef Golubic, Sanja; Aine, Cheryl J; Stephen, Julia M; Adair, John C; Knoefel, Janice E; Supek, Selma

2017-10-01

Magnetoencephalography (MEG), a direct measure of neuronal activity, is an underexplored tool in the search for biomarkers of Alzheimer's disease (AD). In this study, we used MEG source estimates of auditory gating generators, nonlinear correlations with neuropsychological results, and multivariate analyses to examine the sensitivity and specificity of gating topology modulation to detect AD. Our results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete (binary) detector of AD at the individual level and resulted in recategorizing the participant categories in: (1) controls with mPFC generator localized in response to both the standard and deviant tones; (2) a possible preclinical stage of AD participants (a lower functioning group of controls) in which mPFC activation was localized to the deviant tone only; and (3) symptomatic AD in which mPFC activation was not localized to either the deviant or standard tones. This approach showed a large effect size (0.9) and high accuracy, sensitivity, and specificity (100%) in identifying symptomatic AD patients within a limited research sample. The present results demonstrate high potential of mPFC activation as a noninvasive biomarker of AD pathology during putative preclinical and clinical stages. Hum Brain Mapp 38:5180-5194, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Dimensional stability of curved panels with cocured stiffeners and cobonded frames

NASA Technical Reports Server (NTRS)

Mabson, G. E.; Flynn, B. W.; Swanson, G. D.; Lundquist, R. C.; Rupp, P. L.

1993-01-01

Closed form and finite element analyses are presented for axial direction and transverse direction dimensional stability of skin/stringer panels. Several sensitivity studies are presented to illustrate the influence of various design parameters on the dimensional stability of these panels. Panel geometry, material properties (stiffness and coefficient of thermal expansion), restraint conditions and local details, such as resin fillets, all combine to influence dimensional stability, residual and assembly forces.

Automatic enhancement of skin fluorescence localization due to refractive index matching

NASA Astrophysics Data System (ADS)

Churmakov, Dmitry Y.; Meglinski, Igor V.; Piletsky, Sergey A.; Greenhalgh, Douglas A.

2004-07-01

Fluorescence diagnostic techniques are notable amongst many other optical methods, as they offer high sensitivity and non-invasive measurements of tissue properties. However, a combination of multiple scattering and physical heterogeneity of biological tissues hampers the interpretation of the fluorescence measurements. The analyses of the spatial distribution of endogenous and exogenous fluorophores excitations within tissues and their contribution to the detected signal localization are essential for many applications. We have developed a novel Monte Carlo technique that gives a graphical perception of how the excitation and fluorescence detected signal are localized in tissues. Our model takes into account spatial distribution of fluorophores and their quantum yields. We demonstrate that matching of the refractive indices of ambient medium and topical skin layer improves spatial localization of the detected fluorescence signal within the tissue. This result is consistent with the recent conclusion that administering biocompatible agents results in higher image contrast.

Forest fragmentation and bird community dynamics: inference at regional scales

USGS Publications Warehouse

Boulinier, T.; Nichols, J.D.; Hines, J.E.; Sauer, J.R.; Flather, C.H.; Pollock, K.H.

2001-01-01

With increasing fragmentation of natural areas and a dramatic reduction of forest cover in several parts of the world, quantifying the impact of such changes on species richness and community dynamics has been a subject of much concern. Here, we tested whether in more fragmented landscapes there was a lower number of area-sensitive species and higher local extinction and turnover rates, which could explain higher temporal variability in species richness. To investigate such potential landscape effects at a regional scale, we merged two independent, large-scale monitoring efforts: the North American Breeding Bird Survey (BBS) and the Land Use and Land Cover Classification data from the U.S. Geological Survey. We used methods that accounted for heterogeneity in the probability of detecting species to estimate species richness and temporal changes in the bird communities for BBS routes in three mid-Atlantic U.S. states. Forest breeding bird species were grouped prior to the analyses into area-sensitive and non-area-sensitive species according to previous studies. We tested predictions relating measures of forest structure at one point in time (1974) to species richness at that time and to parameters of forest bird community change over the following 22-yr-period (1975-1996). We used the mean size of forest patches to characterize landscape structure, as high correlations among landscape variables did not allow us to disentangle the relative roles of habitat fragmentation per se and habitat loss. As predicted, together with lower species richness for area-sensitive species on routes surrounded by landscapes with lower mean forest-patch size, we found higher mean year-to-year rates of local extinction. Moreover, the mean year-to-year rates of local turnover (proportion of locally new species) for area-sensitive species were also higher in landscapes with lower mean forest-patch size. These associations were not observed for the non-area-sensitive species group. These results suggest that landscape structure may influence forest bird communities at regional scales through its effects on the total number of species but also on the temporal rates of change in community composition. Evidence for higher rates of local extinction and turnover in more fragmented landscapes suggests that bird communities function as metapopulations at a regional scale, and points out the importance of colonizations and recolonizations from surrounding landscapes to local community dynamics. Further, our results illustrate that the methods used to estimate the community parameters can be a powerful statistical tool in addressing questions relative to the dynamics of communities.

Adaptation to Climatic Hazards in the Savannah Ecosystem: Improving Adaptation Policy and Action

NASA Astrophysics Data System (ADS)

Yiran, Gerald A. B.; Stringer, Lindsay C.

2017-10-01

People in Ghana's savannah ecosystem have historically experienced a range of climatic hazards that have affected their livelihoods. In view of current climate variability and change, and projected increases in extreme events, adaptation to climate risks is vital. Policies have been put in place to enhance adaptation across sub-Saharan Africa in accordance with international agreements. At the same time, local people, through experience, have learned to adapt. This paper examines current policy actions and their implementation alongside an assessment of barriers to local adaptation. In doing so it links adaptation policy and practice. Policy documents were analysed that covered key livelihood sectors, which were identified as climate sensitive. These included agriculture, water, housing and health policies, as well as the National Climate Change Policy. In-depth interviews and focus group discussions were also held with key stakeholders in the Upper East Region of Ghana. Analyses were carried using thematic content analysis. Although policies and actions complement each other, their integration is weak. Financial, institutional, social, and technological barriers hinder successful local implementation of some policy actions, while lack of local involvement in policy formulation also hinders adaptation practice. Integration of local perspectives into policy needs to be strengthened in order to enhance adaptation. Coupled with this is a need to consider adaptation to climate change in development policies and to pursue efforts to reduce or remove the key barriers to implementation at the local level.

Microfluidics, Chromatography, and Atomic-Force Microscopy

NASA Technical Reports Server (NTRS)

Anderson, Mark

2008-01-01

A Raman-and-atomic-force microscope (RAFM) has been shown to be capable of performing several liquid-transfer and sensory functions essential for the operation of a microfluidic laboratory on a chip that would be used to perform rapid, sensitive chromatographic and spectro-chemical analyses of unprecedentedly small quantities of liquids. The most novel aspect of this development lies in the exploitation of capillary and shear effects at the atomic-force-microscope (AFM) tip to produce shear-driven flow of liquids along open microchannels of a microfluidic device. The RAFM can also be used to perform such functions as imaging liquids in microchannels; removing liquid samples from channels for very sensitive, tip-localized spectrochemical analyses; measuring a quantity of liquid adhering to the tip; and dip-pen deposition from a chromatographic device. A commercial Raman-spectroscopy system and a commercial AFM were integrated to make the RAFM so as to be able to perform simultaneous topographical AFM imaging and surface-enhanced Raman spectroscopy (SERS) at the AFM tip. The Raman-spectroscopy system includes a Raman microprobe attached to an optical microscope, the translation stage of which is modified to accommodate the AFM head. The Raman laser excitation beam, which is aimed at the AFM tip, has a wavelength of 785 nm and a diameter of about 5 m, and its power is adjustable up to 10 mW. The AFM is coated with gold to enable tip-localized SERS.

An observationally centred method to quantify local climate change as a distribution

NASA Astrophysics Data System (ADS)

Stainforth, David; Chapman, Sandra; Watkins, Nicholas

2013-04-01

For planning and adaptation, guidance on trends in local climate is needed at the specific thresholds relevant to particular impact or policy endeavours. This requires quantifying trends at specific quantiles in distributions of variables such as daily temperature or precipitation. These non-normal distributions vary both geographically and in time. The trends in the relevant quantiles may not simply follow the trend in the distribution mean. We present a method[1] for analysing local climatic timeseries data to assess which quantiles of the local climatic distribution show the greatest and most robust trends. We demonstrate this approach using E-OBS gridded data[2] timeseries of local daily temperature from specific locations across Europe over the last 60 years. Our method extracts the changing cumulative distribution function over time and uses a simple mathematical deconstruction of how the difference between two observations from two different time periods can be assigned to the combination of natural statistical variability and/or the consequences of secular climate change. This deconstruction facilitates an assessment of the sensitivity of different quantiles of the distributions to changing climate. Geographical location and temperature are treated as independent variables, we thus obtain as outputs how the trend or sensitivity varies with temperature (or occurrence likelihood), and with geographical location. These sensitivities are found to be geographically varying across Europe; as one would expect given the different influences on local climate between, say, Western Scotland and central Italy. We find as an output many regionally consistent patterns of response of potential value in adaptation planning. We discuss methods to quantify the robustness of these observed sensitivities and their statistical likelihood. This also quantifies the level of detail needed from climate models if they are to be used as tools to assess climate change impact. [1] S C Chapman, D A Stainforth, N W Watkins, 2013, On Estimating Local Long Term Climate Trends, Phil. Trans. R. Soc. A, in press [2] Haylock, M.R., N. Hofstra, A.M.G. Klein Tank, E.J. Klok, P.D. Jones and M. New. 2008: A European daily high-resolution gridded dataset of surface temperature and precipitation. J. Geophys. Res (Atmospheres), 113, D20119, doi:10.1029/2008JD10201

Probabilistic assessment of the impact of coal seam gas development on groundwater: Surat Basin, Australia

NASA Astrophysics Data System (ADS)

Cui, Tao; Moore, Catherine; Raiber, Matthias

2018-05-01

Modelling cumulative impacts of basin-scale coal seam gas (CSG) extraction is challenging due to the long time frames and spatial extent over which impacts occur combined with the need to consider local-scale processes. The computational burden of such models limits the ability to undertake calibration and sensitivity and uncertainty analyses. A framework is presented that integrates recently developed methods and tools to address the computational burdens of an assessment of drawdown impacts associated with rapid CSG development in the Surat Basin, Australia. The null space Monte Carlo method combined with singular value decomposition (SVD)-assisted regularisation was used to analyse the uncertainty of simulated drawdown impacts. The study also describes how the computational burden of assessing local-scale impacts was mitigated by adopting a novel combination of a nested modelling framework which incorporated a model emulator of drawdown in dual-phase flow conditions, and a methodology for representing local faulting. This combination provides a mechanism to support more reliable estimates of regional CSG-related drawdown predictions. The study indicates that uncertainties associated with boundary conditions are reduced significantly when expressing differences between scenarios. The results are analysed and distilled to enable the easy identification of areas where the simulated maximum drawdown impacts could exceed trigger points associated with legislative `make good' requirements; trigger points require that either an adjustment in the development scheme or other measures are implemented to remediate the impact. This report contributes to the currently small body of work that describes modelling and uncertainty analyses of CSG extraction impacts on groundwater.

Lumbar Facet Joint Compressive Injury Induces Lasting Changes in Local Structure, Nociceptive Scores, and Inflammatory Mediators in a Novel Rat Model

PubMed Central

Henry, James L.; Yashpal, Kiran; Vernon, Howard; Kim, Jaesung; Im, Hee-Jeong

2012-01-01

Objective. To develop a novel animal model of persisting lumbar facet joint pain. Methods. Sprague Dawley rats were anaesthetized and the right lumbar (L5/L6) facet joint was exposed and compressed to ~1 mm with modified clamps applied for three minutes; sham-operated and naïve animals were used as control groups. After five days, animals were tested for hind-paw sensitivity using von Frey filaments and axial deep tissue sensitivity by algometer on assigned days up to 28 days. Animals were sacrificed at selected times for histological and biochemical analysis. Results. Histological sections revealed site-specific loss of cartilage in model animals only. Tactile hypersensitivity was observed for the ipsi- and contralateral paws lasting 28 days. The threshold at which deep tissue pressure just elicited vocalization was obtained at three lumbar levels; sensitivity at L1 > L3/4 > L6. Biochemical analyses revealed increases in proinflammatory cytokines, especially TNF-α, IL-1α, and IL-1β. Conclusions. These data suggest that compression of a facet joint induces a novel model of local cartilage loss accompanied by increased sensitivity to mechanical stimuli and by increases in inflammatory mediators. This new model may be useful for studies on mechanisms and treatment of lumbar facet joint pain and osteoarthritis. PMID:22966427

An experimental study to evaluate the technological limitations in the understanding of the haemodynamic change in pre-eclampsia.

PubMed

Sengupta

1998-08-01

BACKGROUND: Conventional indices could not define the pathogenesis of pre-eclampsia and its predictability. It has also not been possible to record these indices from the local uteroplacental system where the pathology lies. OBJECTIVE: To investigate the limitations of the currently available blood pressure-flow measuring indices and techniques commonly used in pregnancy.METHOD: Blood pressure and velocity profiles were obtained under various pathophysiological conditions for pregnant and non-pregnant animals and human subjects. The data were analysed using both conventional and computer-based spectral methods. RESULTS: Continuous monitoring of blood pressure and velocity together with their spectral analysis appeared to be a useful sensitive indicator in pregnancy beyond the commonly available conventional analytical method. In high-resistance flow such as in hypertension and in pre-eclampsia, the power amplitude was relatively low at low frequency. Power amplitude remained high at low frequency in normal low-resistance state of pregnancy. CONCLUSION: The results suggest the need to develop a highly sensitive instrumentation whereby any minute variation in mean arterial pressure that is of clinical significance can be measured. Alternatively, analytical advancement, such as use of power spectrum analysers, might prove to be useful and sensitive. Variability of heart rate is an important determinant of the underlying pathophysiology in pregnancy. It is concluded that the heart rate of pre-eclamptics and hypertensives has to increase in order to maintain a constant organic blood flow whereas in normal pregnancy bloow flow can rise even without an incrase in heart rate. Future research should be directed towards blood flow mapping, power spectral analysis and image processing of the blood pressure-flow profile obtained from local and systemic compartments under different pathophysiological conditions of pregnancy.

Age-related differences in BOLD modulation to cognitive control costs in a multitasking paradigm: Global switch, local switch, and compatibility-switch costs.

PubMed

Nashiro, Kaoru; Qin, Shuo; O'Connell, Margaret A; Basak, Chandramallika

2018-05-15

It is well documented that older adults recruit additional brain regions compared to those recruited by younger adults while performing a wide variety of cognitive tasks. However, it is unclear how such age-related over-recruitment interacts with different types of cognitive control, and whether this over-recruitment is compensatory. To test this, we used a multitasking paradigm, which allowed us to examine age-related over-activation associated with three types of cognitive costs (i.e., global switch, local switch, compatibility-switch costs). We found age-related impairments in global switch cost (GSC), evidenced by slower response times for maintaining and coordinating two tasks vs. performing only one task. However, no age-related declines were observed in either local switch cost (LSC), a cognitive cost associated with switching between the two tasks while maintaining two task loads, or compatibility-switch cost (CSC), a cognitive cost associated with incompatible vs. compatible stimulus-response mappings across the two tasks. The fMRI analyses allowed for identification of distinct cognitive cost-sensitive brain regions associated with GSC and LSC. In fronto-parietal GSC and LSC regions, older adults' increased activations were associated with poorer performance (greater costs), whereas a reverse relationship was observed in younger adults. Older adults also recruited additional fronto-parietal brain regions outside the cognitive cost-sensitive areas, which was associated with poorer performance or no behavioral benefits. Our results suggest that older adults exhibit a combination of inefficient activation within cognitive cost-sensitive regions, specifically the GSC and LSC regions, and non-compensatory over-recruitment in age-sensitive regions. Age-related declines in global switching, compared to local switching, was observed earlier in old age at both neural and behavioral levels. Copyright © 2018 Elsevier Inc. All rights reserved.

iTOUGH2: A multiphysics simulation-optimization framework for analyzing subsurface systems

NASA Astrophysics Data System (ADS)

Finsterle, S.; Commer, M.; Edmiston, J. K.; Jung, Y.; Kowalsky, M. B.; Pau, G. S. H.; Wainwright, H. M.; Zhang, Y.

2017-11-01

iTOUGH2 is a simulation-optimization framework for the TOUGH suite of nonisothermal multiphase flow models and related simulators of geophysical, geochemical, and geomechanical processes. After appropriate parameterization of subsurface structures and their properties, iTOUGH2 runs simulations for multiple parameter sets and analyzes the resulting output for parameter estimation through automatic model calibration, local and global sensitivity analyses, data-worth analyses, and uncertainty propagation analyses. Development of iTOUGH2 is driven by scientific challenges and user needs, with new capabilities continually added to both the forward simulator and the optimization framework. This review article provides a summary description of methods and features implemented in iTOUGH2, and discusses the usefulness and limitations of an integrated simulation-optimization workflow in support of the characterization and analysis of complex multiphysics subsurface systems.

Parameterization and Sensitivity Analysis of a Complex Simulation Model for Mosquito Population Dynamics, Dengue Transmission, and Their Control

PubMed Central

Ellis, Alicia M.; Garcia, Andres J.; Focks, Dana A.; Morrison, Amy C.; Scott, Thomas W.

2011-01-01

Models can be useful tools for understanding the dynamics and control of mosquito-borne disease. More detailed models may be more realistic and better suited for understanding local disease dynamics; however, evaluating model suitability, accuracy, and performance becomes increasingly difficult with greater model complexity. Sensitivity analysis is a technique that permits exploration of complex models by evaluating the sensitivity of the model to changes in parameters. Here, we present results of sensitivity analyses of two interrelated complex simulation models of mosquito population dynamics and dengue transmission. We found that dengue transmission may be influenced most by survival in each life stage of the mosquito, mosquito biting behavior, and duration of the infectious period in humans. The importance of these biological processes for vector-borne disease models and the overwhelming lack of knowledge about them make acquisition of relevant field data on these biological processes a top research priority. PMID:21813844

MEG-based detection and localization of perilesional dysfunction in chronic stroke.

PubMed

Chu, Ron K O; Braun, Allen R; Meltzer, Jed A

2015-01-01

Post-stroke impairment is associated not only with structural lesions, but also with dysfunction in surviving perilesional tissue. Previous studies using equivalent current dipole source localization of MEG/EEG signals have demonstrated a preponderance of slow-wave activity localized to perilesional areas. Recent studies have also demonstrated the utility of nonlinear analyses such as multiscale entropy (MSE) for quantifying neuronal dysfunction in a wide range of pathologies. The current study utilized beamformer-based reconstruction of signals in source space to compare spectral and nonlinear measures of electrical activity in perilesional and healthy cortices. Data were collected from chronic stroke patients and healthy controls, both young and elderly. We assessed relative power in the delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz) and beta (15-30 Hz) frequency bands, and also measured the nonlinear complexity of electrical activity using MSE. Perilesional tissue exhibited a general slowing of the power spectrum (increased delta/theta, decreased beta) as well as a reduction in MSE. All measures tested were similarly sensitive to changes in the posterior perilesional regions, but anterior perilesional dysfunction was detected better by MSE and beta power. The findings also suggest that MSE is specifically sensitive to electrophysiological dysfunction in perilesional tissue, while spectral measures were additionally affected by an increase in rolandic beta power with advanced age. Furthermore, perilesional electrophysiological abnormalities in the left hemisphere were correlated with the degree of language task-induced activation in the right hemisphere. Finally, we demonstrate that single subject spectral and nonlinear analyses can identify dysfunctional perilesional regions within individual patients that may be ideal targets for interventions with noninvasive brain stimulation.

Determining the sensitivity of transrectal ultrasonography on a consecutive series of prostate cancers in a clinical and screening setting.

PubMed

Ciatto, Stefano; Bonardi, Rita; Lombardi, Claudio; Zappa, Marco; Gervasi, Ginetta

2002-01-01

To evaluate the sensitivity at transrectal ultrasonography (TRUS) for prostate cancer. A consecutive series of 170 prostate cancers identified by matching local cancer registry and TRUS archives at the Centro per lo Studio e la Prevenzione Oncologica of Florence. TRUS sensitivity was determined as the ratio of TRUS positive to total prostate cancers occurring at different intervals from TRUS date. Univariate and multivariate analyses of sensitivity determinants were performed. Sensitivity at 6 months, 1, 2 and 3 years after the test was 94.1% (95% CI, 90-98), 89.8% (95% CI, 85-95), 80.4% (95% CI, 74-87) and 74.1% (95% CI, 68-81%), respectively. A higher sensitivity (statistically significant) of TRUS was observed only if digital rectal examination was suspicious, whereas no association to sensitivity was observed for age, prostate-specific antigen or prostate-specific antigen density. The study provided a reliable estimate of TRUS sensitivity, particularly reliable being checked against a cancer registry: observed sensitivity was high, at least of the same magnitude of other cancer screening tests. TRUS, which is known to allow for considerable diagnostic anticipation and is more specific than prostate-specific antigen, might still be considered for its contribution to a screening approach.

Variability of temperature sensitivity of extreme precipitation from a regional-to-local impact scale perspective

NASA Astrophysics Data System (ADS)

Schroeer, K.; Kirchengast, G.

2016-12-01

Relating precipitation intensity to temperature is a popular approach to assess potential changes of extreme events in a warming climate. Potential increases in extreme rainfall induced hazards, such as flash flooding, serve as motivation. It has not been addressed whether the temperature-precipitation scaling approach is meaningful on a regional to local level, where the risk of climate and weather impact is dealt with. Substantial variability of temperature sensitivity of extreme precipitation has been found that results from differing methodological assumptions as well as from varying climatological settings of the study domains. Two aspects are consistently found: First, temperature sensitivities beyond the expected consistency with the Clausius-Clapeyron (CC) equation are a feature of short-duration, convective, sub-daily to sub-hourly high-percentile rainfall intensities at mid-latitudes. Second, exponential growth ceases or reverts at threshold temperatures that vary from region to region, as moisture supply becomes limited. Analyses of pooled data, or of single or dispersed stations over large areas make it difficult to estimate the consequences in terms of local climate risk. In this study we test the meaningfulness of the scaling approach from an impact scale perspective. Temperature sensitivities are assessed using quantile regression on hourly and sub-hourly precipitation data from 189 stations in the Austrian south-eastern Alpine region. The observed scaling rates vary substantially, but distinct regional and seasonal patterns emerge. High sensitivity exceeding CC-scaling is seen on the 10-minute scale more than on the hourly scale, in storms shorter than 2 hours duration, and in shoulder seasons, but it is not necessarily a significant feature of the extremes. To be impact relevant, change rates need to be linked to absolute rainfall amounts. We show that high scaling rates occur in lower temperature conditions and thus have smaller effect on absolute precipitation intensities. While reporting of mere percentage numbers can be misleading, scaling studies can add value to process understanding on the local scale, if the factors that influence scaling rates are considered from both a methodological and a physical perspective.

Procedures for adjusting regional regression models of urban-runoff quality using local data

USGS Publications Warehouse

Hoos, A.B.; Sisolak, J.K.

1993-01-01

Statistical operations termed model-adjustment procedures (MAP?s) can be used to incorporate local data into existing regression models to improve the prediction of urban-runoff quality. Each MAP is a form of regression analysis in which the local data base is used as a calibration data set. Regression coefficients are determined from the local data base, and the resulting `adjusted? regression models can then be used to predict storm-runoff quality at unmonitored sites. The response variable in the regression analyses is the observed load or mean concentration of a constituent in storm runoff for a single storm. The set of explanatory variables used in the regression analyses is different for each MAP, but always includes the predicted value of load or mean concentration from a regional regression model. The four MAP?s examined in this study were: single-factor regression against the regional model prediction, P, (termed MAP-lF-P), regression against P,, (termed MAP-R-P), regression against P, and additional local variables (termed MAP-R-P+nV), and a weighted combination of P, and a local-regression prediction (termed MAP-W). The procedures were tested by means of split-sample analysis, using data from three cities included in the Nationwide Urban Runoff Program: Denver, Colorado; Bellevue, Washington; and Knoxville, Tennessee. The MAP that provided the greatest predictive accuracy for the verification data set differed among the three test data bases and among model types (MAP-W for Denver and Knoxville, MAP-lF-P and MAP-R-P for Bellevue load models, and MAP-R-P+nV for Bellevue concentration models) and, in many cases, was not clearly indicated by the values of standard error of estimate for the calibration data set. A scheme to guide MAP selection, based on exploratory data analysis of the calibration data set, is presented and tested. The MAP?s were tested for sensitivity to the size of a calibration data set. As expected, predictive accuracy of all MAP?s for the verification data set decreased as the calibration data-set size decreased, but predictive accuracy was not as sensitive for the MAP?s as it was for the local regression models.

Electron-beam-induced topographical, chemical, and structural patterning of amorphous titanium oxide films.

PubMed

Kern, P; Müller, Y; Patscheider, J; Michler, J

2006-11-30

Electrolytically deposited amorphous TiO2 films on steel are remarkably sensitive to electron beam (e-beam) irradiation at moderate energies at 20 keV, resulting in controlled local oxide reduction and crystallization, opening the possibility for local topographical, chemical, and structural modifications within a biocompatible, amorphous, and semiconducting matrix. The sensitivity is shown to vary significantly with the annealing temperature of as-deposited films. Well-defined irradiation conditions in terms of probe current IP (5 microA) and beam size were achieved with an electron probe microanalyzer. As shown by atomic force and optical microscopy, micro-Raman spectroscopy, wavelength-dispersive X-ray (WDX), and Auger analyses, e-beam exposure below 1 Acm-2 immediately leads to electron-stimulated oxygen desorption, resulting in a well-defined volume loss primarily limited to the irradiated zone under the electron probe and in a blue color shift in this zone because of the presence of Ti2O3. Irradiation at 5 Acm(-2) (IP = 5 microA) results in local crystallization into anatase phase within 1 s of exposure and in reduction to TiO after an extended exposure of 60 s. Further reduction to the metallic state could be observed after 60 s of exposure at approximately 160 Acm(-2). The local reduction could be qualitatively sensed with WDX analysis and Auger line scans. An estimation of the film temperature in the beam center indicates that crystallization occurs at less than 150 degrees C, well below the atmospheric crystallization temperature of the present films. The high e-beam sensitivity in combination with the well-defined volume loss from oxygen desorption allows for precise electron lithographic topographical patterning of the present oxides. Irradiation effects leading to the observed reduction and crystallization phenomena under moderate electron energies are discussed.

How often do sensitivity analyses for economic parameters change cost-utility analysis conclusions?

PubMed

Schackman, Bruce R; Gold, Heather Taffet; Stone, Patricia W; Neumann, Peter J

2004-01-01

There is limited evidence about the extent to which sensitivity analysis has been used in the cost-effectiveness literature. Sensitivity analyses for health-related QOL (HR-QOL), cost and discount rate economic parameters are of particular interest because they measure the effects of methodological and estimation uncertainties. To investigate the use of sensitivity analyses in the pharmaceutical cost-utility literature in order to test whether a change in economic parameters could result in a different conclusion regarding the cost effectiveness of the intervention analysed. Cost-utility analyses of pharmaceuticals identified in a prior comprehensive audit (70 articles) were reviewed and further audited. For each base case for which sensitivity analyses were reported (n = 122), up to two sensitivity analyses for HR-QOL (n = 133), cost (n = 99), and discount rate (n = 128) were examined. Article mentions of thresholds for acceptable cost-utility ratios were recorded (total 36). Cost-utility ratios were denominated in US dollars for the year reported in each of the original articles in order to determine whether a different conclusion would have been indicated at the time the article was published. Quality ratings from the original audit for articles where sensitivity analysis results crossed the cost-utility ratio threshold above the base-case result were compared with those that did not. The most frequently mentioned cost-utility thresholds were $US20,000/QALY, $US50,000/QALY, and $US100,000/QALY. The proportions of sensitivity analyses reporting quantitative results that crossed the threshold above the base-case results (or where the sensitivity analysis result was dominated) were 31% for HR-QOL sensitivity analyses, 20% for cost-sensitivity analyses, and 15% for discount-rate sensitivity analyses. Almost half of the discount-rate sensitivity analyses did not report quantitative results. Articles that reported sensitivity analyses where results crossed the cost-utility threshold above the base-case results (n = 25) were of somewhat higher quality, and were more likely to justify their sensitivity analysis parameters, than those that did not (n = 45), but the overall quality rating was only moderate. Sensitivity analyses for economic parameters are widely reported and often identify whether choosing different assumptions leads to a different conclusion regarding cost effectiveness. Changes in HR-QOL and cost parameters should be used to test alternative guideline recommendations when there is uncertainty regarding these parameters. Changes in discount rates less frequently produce results that would change the conclusion about cost effectiveness. Improving the overall quality of published studies and describing the justifications for parameter ranges would allow more meaningful conclusions to be drawn from sensitivity analyses.

Cost effectiveness of imatinib compared with interferon-alpha or hydroxycarbamide for first-line treatment of chronic myeloid leukaemia.

PubMed

Dalziel, Kim; Round, Ali; Garside, Ruth; Stein, Ken

2005-01-01

To evaluate the cost utility of imatinib compared with interferon (IFN)-alpha or hydroxycarbamide (hydroxyurea) for first-line treatment of chronic myeloid leukaemia. A cost-utility (Markov) model within the setting of the UK NHS and viewed from a health system perspective was adopted. Transition probabilities and relative risks were estimated from published literature. Costs of drug treatment, outpatient care, bone marrow biopsies, radiography, blood transfusions and inpatient care were obtained from the British National Formulary and local hospital databases. Costs (pound, year 2001-03 values) were discounted at 6%. Quality-of-life (QOL) data were obtained from the published literature and discounted at 1.5%. The main outcome measure was cost per QALY gained. Extensive one-way sensitivity analyses were performed along with probabilistic (stochastic) analysis. The incremental cost-effectiveness ratio (ICER) of imatinib, compared with IFNalpha, was pound26,180 per QALY gained (one-way sensitivity analyses ranged from pound19,449 to pound51,870) and compared with hydroxycarbamide was pound86,934 per QALY (one-way sensitivity analyses ranged from pound69,701 to pound147,095) [ pound1=$US1.691=euro1.535 as at 31 December 2002].Based on the probabilistic sensitivity analysis, 50% of the ICERs for imatinib, compared with IFNalpha, fell below a threshold of approximately pound31,000 per QALY gained. Fifty percent of ICERs for imatinib, compared with hydroxycarbamide, fell below approximately pound95,000 per QALY gained. This model suggests, given its underlying data and assumptions, that imatinib may be moderately cost effective when compared with IFNalpha but considerably less cost effective when compared with hydroxycarbamide. There are, however, many uncertainties due to the lack of long-term data.

Sensitivity of the central visual field in 70- to 81-year-old male athletes and in a population sample.

PubMed

Era, P; Pärssinen, O; Pykälä, P; Jokela, J; Suominen, H

1994-10-01

The sensitivity of the central visual field (0 degree-30 degrees) was studied using an automatic Octopus 500E perimeter in elderly male athletes and in a population sample of men of corresponding age. The athletes (N = 96) were endurance and power athletes, who were still active in competitive sports with training histories spanning tens of years. The athletes' results were compared with those of a sample of men of the same age (70-81 years, N = 41) randomly selected from the local population register. The sensitivity values of the athletes, and the endurance athletes in particular, were significantly better than those of the controls, with differences varying from 1 to 2.5 dB in the different areas of the central visual field. Multivariate analyses of the background factors of visual field sensitivity showed that the most important were age, amount of annual training, number of chronic diseases, HDL-cholesterol level, and vital capacity. The results suggest that a long training history, especially of the aerobic type, may be beneficial with respect to the sensitivity of the visual system.

Turbulent transport model of wind shear in thunderstorm gust fronts and warm fronts

NASA Technical Reports Server (NTRS)

Lewellen, W. S.; Teske, M. E.; Segur, H. C. O.

1978-01-01

A model of turbulent flow in the atmospheric boundary layer was used to simulate the low-level wind and turbulence profiles associated with both local thunderstorm gust fronts and synoptic-scale warm fronts. Dimensional analyses of both type fronts provided the physical scaling necessary to permit normalized simulations to represent fronts for any temperature jump. The sensitivity of the thunderstorm gust front to five different dimensionless parameters as well as a change from axisymmetric to planar geometry was examined. The sensitivity of the warm front to variations in the Rossby number was examined. Results of the simulations are discussed in terms of the conditions which lead to wind shears which are likely to be most hazardous for aircraft operations.

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.

Simulation of a Real-Time Local Data Integration System over East-Central Florida

NASA Technical Reports Server (NTRS)

Case, Jonathan

1999-01-01

The Applied Meteorology Unit (AMU) simulated a real-time configuration of a Local Data Integration System (LDIS) using data from 15-28 February 1999. The objectives were to assess the utility of a simulated real-time LDIS, evaluate and extrapolate system performance to identify the hardware necessary to run a real-time LDIS, and determine the sensitivities of LDIS. The ultimate goal for running LDIS is to generate analysis products that enhance short-range (less than 6 h) weather forecasts issued in support of the 45th Weather Squadron, Spaceflight Meteorology Group, and Melbourne National Weather Service operational requirements. The simulation used the Advanced Regional Prediction System (ARPS) Data Analysis System (ADAS) software on an IBM RS/6000 workstation with a 67-MHz processor. This configuration ran in real-time, but not sufficiently fast for operational requirements. Thus, the AMU recommends a workstation with a 200-MHz processor and 512 megabytes of memory to run the AMU's configuration of LDIS in real-time. This report presents results from two case studies and several data sensitivity experiments. ADAS demonstrates utility through its ability to depict high-resolution cloud and wind features in a variety of weather situations. The sensitivity experiments illustrate the influence of disparate data on the resulting ADAS analyses.

In situ temperature monitoring in single-molecule FRET experiments

NASA Astrophysics Data System (ADS)

Hartmann, Andreas; Berndt, Frederic; Ollmann, Simon; Krainer, Georg; Schlierf, Michael

2018-03-01

Thermodynamic properties of single molecules including enthalpic and entropic contributions are often determined from experiments by a direct control and precise measurement of the local temperature. However, common temperature monitoring techniques using, for example, ultrafine temperature probes can lead to uncertainties as the probe cannot be placed in the vicinity of the molecule of interest. Here, we devised an approach to measure the local temperature in freely diffusing confocal single-molecule Förster Resonance Energy Transfer (smFRET) experiments in situ by directly adding the temperature-sensitive fluorescent dye Rhodamine B, whose fluorescence lifetime serves as a probe of the local temperature in the confocal volume. We demonstrate that the temperature and FRET efficiencies of static and dynamic molecules can be extracted within one measurement simultaneously, without the need of a reference chamber. We anticipate this technique to be particularly useful in the physicochemical analyses of temperature-dependent biomolecular processes from single-molecule measurements.

The role of the geophysical template and environmental regimes in controlling stream-living trout populations

USGS Publications Warehouse

Penaluna, Brooke E.; Railsback, Steve F.; Dunham, Jason B.; Johnson, S.; Bilby, Richard E.; Skaugset, Arne E.

2015-01-01

The importance of multiple processes and instream factors to aquatic biota has been explored extensively, but questions remain about how local spatiotemporal variability of aquatic biota is tied to environmental regimes and the geophysical template of streams. We used an individual-based trout model to explore the relative role of the geophysical template versus environmental regimes on biomass of trout (Oncorhynchus clarkii clarkii). We parameterized the model with observed data from each of the four headwater streams (their local geophysical template and environmental regime) and then ran 12 simulations where we replaced environmental regimes (stream temperature, flow, turbidity) of a given stream with values from each neighboring stream while keeping the geophysical template fixed. We also performed single-parameter sensitivity analyses on the model results from each of the four streams. Although our modeled findings show that trout biomass is most responsive to changes in the geophysical template of streams, they also reveal that biomass is restricted by available habitat during seasonal low flow, which is a product of both the stream’s geophysical template and flow regime. Our modeled results suggest that differences in the geophysical template among streams render trout more or less sensitive to environmental change, emphasizing the importance of local fish–habitat relationships in streams.

Systematic identification and prioritization of communities impacted by residential woodsmoke in British Columbia, Canada.

PubMed

Hong, Kris Y; Weichenthal, Scott; Saraswat, Arvind; King, Gavin H; Henderson, Sarah B; Brauer, Michael

2017-01-01

Residential woodsmoke is an under-regulated source of fine particulate matter (PM 2.5 ), often surpassing mobile and industrial emissions in rural communities in North America and elsewhere. In the province of British Columbia (BC), Canada, many municipalities are hesitant to adopt stricter regulations for residential wood burning without empirical evidence that smoke is affecting local air quality. The objective of this study was to develop a retrospective algorithm that uses 1-h PM 2.5 concentrations and daily temperature data to identify smoky days in order to prioritise communities by smoke impacts. Levoglucosan measurements from one of the smokiest communities were used to establish the most informative values for three algorithmic parameters: the daily standard deviation of 1-h PM 2.5 measurements; the daily mean temperature; and the daytime-to-nighttime ratio of PM 2.5 concentrations. Alternate parameterizations were tested in 45 sensitivity analyses. Using the most informative parameter values on the most recent two years of data for each community, the number of smoky days ranged from 5 to 277. Heat maps visualizing seasonal and diurnal variation in PM 2.5 concentrations showed clear differences between the higher- and lower-ranked communities. Some communities were sensitive to one or more of the parameters, but the overall rankings were consistent across the 45 analyses. This information will allow stakeholder agencies to work with local governments on implementing appropriate intervention strategies for the most smoke-impacted communities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dual-band plasmonic resonator based on Jerusalem cross-shaped nanoapertures

NASA Astrophysics Data System (ADS)

Cetin, Arif E.; Kaya, Sabri; Mertiri, Alket; Aslan, Ekin; Erramilli, Shyamsunder; Altug, Hatice; Turkmen, Mustafa

2015-06-01

In this paper, we both experimentally and numerically introduce a dual-resonant metamaterial based on subwavelength Jerusalem cross-shaped apertures. We numerically investigate the physical origin of the dual-resonant behavior, originating from the constituting aperture elements, through finite difference time domain calculations. Our numerical calculations show that at the dual-resonances, the aperture system supports large and easily accessible local electromagnetic fields. In order to experimentally realize the aperture system, we utilize a high-precision and lift-off free fabrication method based on electron-beam lithography. We also introduce a fine-tuning mechanism for controlling the dual-resonant spectral response through geometrical device parameters. Finally, we show the aperture system's highly advantageous far- and near-field characteristics through numerical calculations on refractive index sensitivity. The quantitative analyses on the availability of the local fields supported by the aperture system are employed to explain the grounds behind the sensitivity of each spectral feature within the dual-resonant behavior. Possessing dual-resonances with large and accessible electromagnetic fields, Jerusalem cross-shaped apertures can be highly advantageous for wide range of applications demanding multiple spectral features with strong nearfield characteristics.

STFT or CWT for the detection of Doppler ultrasound embolic signals.

PubMed

Gonçalves, Ivo B; Leiria, Ana; Moura, M M M

2013-09-01

Aiming reliable detection and localization of cerebral blood flow and emboli, embolic signals were added to simulated middle cerebral artery Doppler signals and analysed. Short-time Fourier transform (STFT) and continuous wavelet transform (CWT) were used in the evaluation. The following parameters were used in this study: the powers of the embolic signals added were 5, 6, 6.5, 7, 7.5, 8 and 9 dB; the mother wavelets for CWT analysis were Morlet, Mexican hat, Meyer, Gaussian (order 4) and Daubechies (orders 4 and 8); and the thresholds for detection (equated in terms of false positive, false negative and sensitivity) were 2 and 3.5 dB for the CWT and STFT, respectively. The results indicate that although the STFT allows accurately detecting emboli, better time localization can be achieved with the CWT. Among the CWT, the current best overall results were obtained with Mexican Hat mother wavelet, with optimal results for sensitivity (100% detection rate) for nearly all emboli power values studied. Copyright © 2013 John Wiley & Sons, Ltd.

Cell size and wall dimensions drive distinct variability of earlywood and latewood density in Northern Hemisphere conifers.

PubMed

Björklund, Jesper; Seftigen, Kristina; Schweingruber, Fritz; Fonti, Patrick; von Arx, Georg; Bryukhanova, Marina V; Cuny, Henri E; Carrer, Marco; Castagneri, Daniele; Frank, David C

2017-11-01

Interannual variability of wood density - an important plant functional trait and environmental proxy - in conifers is poorly understood. We therefore explored the anatomical basis of density. We hypothesized that earlywood density is determined by tracheid size and latewood density by wall dimensions, reflecting their different functional tasks. To determine general patterns of variability, density parameters from 27 species and 349 sites across the Northern Hemisphere were correlated to tree-ring width parameters and local climate. We performed the same analyses with density and width derived from anatomical data comprising two species and eight sites. The contributions of tracheid size and wall dimensions to density were disentangled with sensitivity analyses. Notably, correlations between density and width shifted from negative to positive moving from earlywood to latewood. Temperature responses of density varied intraseasonally in strength and sign. The sensitivity analyses revealed tracheid size as the main determinant of earlywood density, while wall dimensions become more influential for latewood density. Our novel approach of integrating detailed anatomical data with large-scale tree-ring data allowed us to contribute to an improved understanding of interannual variations of conifer growth and to illustrate how conifers balance investments in the competing xylem functions of hydraulics and mechanical support. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Factors dominating 3-dimensional ozone distribution during high tropospheric ozone period.

PubMed

Chen, Xiaoyang; Liu, Yiming; Lai, Anqi; Han, Shuangshuang; Fan, Qi; Wang, Xuemei; Ling, Zhenhao; Huang, Fuxiang; Fan, Shaojia

2018-01-01

Data from an in situ monitoring network and five ozone sondes are analysed during August of 2012, and a high tropospheric ozone episode is observed around the 8th of AUG. The Community Multi-scale Air Quality (CMAQ) model and its process analysis tool were used to study factors and mechanisms for high ozone mixing ratio at different levels of ozone vertical profiles. A sensitive scenario without chemical initial and boundary conditions (ICBCs) from MOZART4-GEOS5 was applied to study the impact of stratosphere-troposphere exchange (STE) on vertical ozone. The simulation results indicated that the first high ozone peak near the tropopause was dominated by STE. Results from process analysis showed that: in the urban area, the second peak at approximately 2 km above ground height was mainly caused by local photochemical production. The third peak (near surface) was mainly caused by the upwind transportation from the suburban/rural areas; in the suburban/rural areas, local photochemical production of ozone dominated the high ozone mixing ratio from the surface to approximately 3 km height. Furthermore, the capability of indicators to distinguish O 3 -precursor sensitivity along the vertical O 3 profiles was investigated. Two sensitive scenarios, which had cut 30% anthropogenic NO X or VOC emissions, showed that O 3 -precursor indicators, specifically the ratios of O 3 /NOy, H 2 O 2 /HNO 3 or H 2 O 2 /NO Z , could partly distinguish the O 3 -precursor sensitivity between VOCs-sensitive and NOx-sensitive along the vertical profiles. In urban area, the O 3 -precursor relationship transferred from VOCs-sensitive within the boundary layer to NOx-sensitive at approximately 1-3 km above ground height, further confirming the dominant roles of transportation and photochemical production in high O 3 peaks at the near-ground layer and 2 km above ground height, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

WITHDRAWN. Combined chemotherapy and radiotherapy (without surgery) compared with radiotherapy alone in localized carcinoma of the esophagus.

PubMed

Wong, Rebecca Ks; Malthaner, Richard

2010-01-20

Esophageal carcinoma can be managed primarily with either a surgical or non-surgical radiotherapeutic approach. Combination chemotherapy (CT) and radiotherapy (RT) has been incorporated into clinical practice and applied increasingly, especially in North America. To evaluate combined CT and RT (CTRT) versus RT alone in patients with localized esophageal carcinoma. Outcomes included overall survival, cause-specific survival, local recurrence, dysphagia relief, quality of life, acute and chronic toxicities. The Cochrane strategy for identifying randomized trials was combined with relevant MeSH headings. The Cochrane Library, MEDLINE, CancerLIT and EMBASE were last searched in April 2005. References from relevant articles and personal files were included. Randomized controlled trials in patients with localized esophageal cancer comparing RT alone with combined CTRT were included. Studies comparing non-chemotherapy agents such as pure radiotherapy sensitisers, immunostimulants, planned esophagectomy, were excluded. Two reviewers extracted data independently. Trial quality was assessed using the Jadad scale and Detsky checklist. Sensitivity analyses were planned to examine the effect of concomitant versus sequential treatment, study quality, radiotherapy dose, and whether the drug regimen contained cisplatin or 5-fluorouracil were performed. Nineteen randomized trials were included, with eleven concomitant and eight sequential RTCT studies. Concomitant RTCT provided significant reduction in mortality with a harms ratio (HR) of 0.73 (95% confidence interval (CI) 0.64 to 0.84). Using an estimated mortality rate for the control group of 62% at year one and 83% at year two, the absolute survival benefit for RTCT was 9% (95% CI 5 to 12%) and 4% (95% CI 3 to 6%]) respectively. There was an absolute reduction of local recurrence rate of 12% (95% CI 3 to 22%), number needed to treat (NNT) of 9, when the local recurrence rate for the RT alone arm was 68%. This was associated with a significant risk of severe and life-threatening toxicities (number needed to harm (NNH)of 6). Sensitivity analyses did not identify any factors that interacted with the results. The results from sequential RTCT studies showed no significant benefit in survival or local control but significant toxicities. Based on the available data, when a non-operative approach is selected then concomitant RTCT is superior to RT alone for patients with localized esophageal cancer but with significant toxicities. In patients who are in good general condition, and the risk benefit has been thoroughly discussed with the patient, concomitant RTCT should be considered for the management of esophageal cancer compared with radiotherapy alone.

The Diagnostic Role of Magnetic Resonance Enterography as a Complementary Test to Colonoscopy in Active Crohn's Disease.

PubMed

Aryan, Arvin; Azizi, Zahra; Teimouri, Azam; Ebrahimi Daryani, Nasser; Aletaha, Najme; Jahanbakhsh, Ali; Nouritaromlou, Mohammad Kazem; Alborzi, Forough; Mami, Masoud; Basirat, Vahid; Javid Anbardan, Sanam

2016-04-01

BACKGROUND According to recent studies comparing magnetic resonance enterography (MRE) with ileocolonoscopy for assessing inflammation of small bowel and colonic segments in adults with active Crohn's disease (CD), we aimed to compare the accuracy of these two diagnostic methods in Iranian population. METHODS During 2013-2014 a follow-up study was done on 30 patients with active CD in a gastroenterology clinic affiliated to Tehran University of Medical Sciences. MRE and ileocolonoscopy were performed for all the patients. All statistical analyses were performed using SPSS (version 18) and p-value<0.05 was considered as statistically significant. RESULTS Of the 30 patients with active CD, 11(36.7%) were men and 19 (63.3%) were women with mean age of 37.30±13.66 years (range: 19-67 years). MRE had sensitivity and specificity of 50% and 90% with positive predictive value (PPV) and negative predictive value (NPV) of 71.43 and 78.26, respectively for localizing sigmoid lesions and ileum had sensitivity and specificity of 84.21 and 45.45 with PPV and NPV of 72.73 and 62.50, respectively. CONCLUSION While moderate sensitivity and high specificity of MRE in localizing colonic lesions makes it an appropriate confirmatory test after colonoscopy, the reported high sensitivity and moderate specificity of MRE versus colonoscopy in detecting ileal lesions makes it a suitable screening test for ileal lesions. Finally we can conclude that MRE can be an important complementary test to colonoscopy in detecting active disease.

Cortical processing of speech in individuals with auditory neuropathy spectrum disorder.

PubMed

Apeksha, Kumari; Kumar, U Ajith

2018-06-01

Auditory neuropathy spectrum disorder (ANSD) is a condition where cochlear amplification function (involving outer hair cells) is normal but neural conduction in the auditory pathway is disordered. This study was done to investigate the cortical representation of speech in individuals with ANSD and to compare it with the individuals with normal hearing. Forty-five participants including 21 individuals with ANSD and 24 individuals with normal hearing were considered for the study. Individuals with ANSD had hearing thresholds ranging from normal hearing to moderate hearing loss. Auditory cortical evoked potentials-through odd ball paradigm-were recorded using 64 electrodes placed on the scalp for /ba/-/da/ stimulus. Onset cortical responses were also recorded in repetitive paradigm using /da/ stimuli. Sensitivity and reaction time required to identify the oddball stimuli were also obtained. Behavioural results indicated that individuals in ANSD group had significantly lower sensitivity and longer reaction times compared to individuals with normal hearing sensitivity. Reliable P300 could be elicited in both the groups. However, a significant difference in scalp topographies was observed between the two groups in both repetitive and oddball paradigms. Source localization using local auto regressive analyses revealed that activations were more diffuses in individuals with ANSD when compared to individuals with normal hearing sensitivity. Results indicated that the brain networks and regions activated in individuals with ANSD during detection and discrimination of speech sounds are different from normal hearing individuals. In general, normal hearing individuals showed more focused activations while in individuals with ANSD activations were diffused.

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.

Global sensitivity analysis in stochastic simulators of uncertain reaction networks.

PubMed

Navarro Jimenez, M; Le Maître, O P; Knio, O M

2016-12-28

Stochastic models of chemical systems are often subjected to uncertainties in kinetic parameters in addition to the inherent random nature of their dynamics. Uncertainty quantification in such systems is generally achieved by means of sensitivity analyses in which one characterizes the variability with the uncertain kinetic parameters of the first statistical moments of model predictions. In this work, we propose an original global sensitivity analysis method where the parametric and inherent variability sources are both treated through Sobol's decomposition of the variance into contributions from arbitrary subset of uncertain parameters and stochastic reaction channels. The conceptual development only assumes that the inherent and parametric sources are independent, and considers the Poisson processes in the random-time-change representation of the state dynamics as the fundamental objects governing the inherent stochasticity. A sampling algorithm is proposed to perform the global sensitivity analysis, and to estimate the partial variances and sensitivity indices characterizing the importance of the various sources of variability and their interactions. The birth-death and Schlögl models are used to illustrate both the implementation of the algorithm and the richness of the proposed analysis method. The output of the proposed sensitivity analysis is also contrasted with a local derivative-based sensitivity analysis method classically used for this type of systems.

Global sensitivity analysis in stochastic simulators of uncertain reaction networks

DOE PAGES

Navarro Jimenez, M.; Le Maître, O. P.; Knio, O. M.

2016-12-23

Stochastic models of chemical systems are often subjected to uncertainties in kinetic parameters in addition to the inherent random nature of their dynamics. Uncertainty quantification in such systems is generally achieved by means of sensitivity analyses in which one characterizes the variability with the uncertain kinetic parameters of the first statistical moments of model predictions. In this work, we propose an original global sensitivity analysis method where the parametric and inherent variability sources are both treated through Sobol’s decomposition of the variance into contributions from arbitrary subset of uncertain parameters and stochastic reaction channels. The conceptual development only assumes thatmore » the inherent and parametric sources are independent, and considers the Poisson processes in the random-time-change representation of the state dynamics as the fundamental objects governing the inherent stochasticity. Here, a sampling algorithm is proposed to perform the global sensitivity analysis, and to estimate the partial variances and sensitivity indices characterizing the importance of the various sources of variability and their interactions. The birth-death and Schlögl models are used to illustrate both the implementation of the algorithm and the richness of the proposed analysis method. The output of the proposed sensitivity analysis is also contrasted with a local derivative-based sensitivity analysis method classically used for this type of systems.« less

Global sensitivity analysis in stochastic simulators of uncertain reaction networks

NASA Astrophysics Data System (ADS)

Navarro Jimenez, M.; Le Maître, O. P.; Knio, O. M.

2016-12-01

Stochastic models of chemical systems are often subjected to uncertainties in kinetic parameters in addition to the inherent random nature of their dynamics. Uncertainty quantification in such systems is generally achieved by means of sensitivity analyses in which one characterizes the variability with the uncertain kinetic parameters of the first statistical moments of model predictions. In this work, we propose an original global sensitivity analysis method where the parametric and inherent variability sources are both treated through Sobol's decomposition of the variance into contributions from arbitrary subset of uncertain parameters and stochastic reaction channels. The conceptual development only assumes that the inherent and parametric sources are independent, and considers the Poisson processes in the random-time-change representation of the state dynamics as the fundamental objects governing the inherent stochasticity. A sampling algorithm is proposed to perform the global sensitivity analysis, and to estimate the partial variances and sensitivity indices characterizing the importance of the various sources of variability and their interactions. The birth-death and Schlögl models are used to illustrate both the implementation of the algorithm and the richness of the proposed analysis method. The output of the proposed sensitivity analysis is also contrasted with a local derivative-based sensitivity analysis method classically used for this type of systems.

Modelling the cost-effectiveness of pharmacist-managed anticoagulation service for older adults with atrial fibrillation in Singapore.

PubMed

Chua, Wen Bing Brandon; Cheen, Hua Heng McVin; Kong, Ming Chai; Chen, Li Li; Wee, Hwee Lin

2016-10-01

Background Oral anticoagulation with warfarin is the cornerstone therapy in atrial fibrillation (AF) for stroke prevention. Multi-disciplinary anticoagulation management services have been shown to be cost-effective in the United States, Hong Kong and Thailand, but the findings are not readily generalizable to Singapore's healthcare system. Objective This study aimed to evaluate the cost-effectiveness of pharmacist-managed anticoagulation clinic (ACC) compared with usual care (UC) for the management of older adults with AF receiving oral anticoagulation with warfarin. Setting Pharmacist-managed ACC in an academic medical centre. Method A Markov model with 3-month cycle length and 30-year time horizon compared costs and quality-adjusted life-years (QALYs) of ACC and UC from the patient's and healthcare provider's perspectives. Four pathways based on time in therapeutic range (TTR) were: ACC TTR < 70 %, ACC TTR ≥ 70 %, UC TTR < 70 % and UC TTR ≥ 70 %. A hypothetical cohort of 70-year-old Singaporean AF patients receiving warfarin was utilised. Local data from national disease registries, patient surveys and hospital databases were used. When local data was not available, published studies on Asian populations were utilized when available. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to account for uncertainties. Costs and QALYs were discounted annually by 3 %. Main outcome measure Costs and QALYs of ACC and UC. Results Pharmacist-managed ACC was found to dominate UC in all comparisons. It improved effectiveness by 0.19 and 0.13 QALYs at TTR < 70 % and TTR ≥ 70 % respectively compared with UC. From the patient's perspective, ACC reduced costs by SG$1222.67 (€1110.24) for TTR < 70 % and SG$1008.16 (€915.46) for TTR ≥ 70 %. Similar trends were observed from the healthcare provider's perspective, with ACC reducing costs by SG$1444.79 (€1311.94) for TTR < 70 % and SG$1269.17 (€1152.46) for TTR ≥ 70 % compared with UC. The results were robust to variations of the parameters over their plausible ranges in one-way sensitivity analyses. Probabilistic sensitivity analyses demonstrated that ACC was cost-effective more than 79 % of the time from both perspectives at a willingness-to-pay threshold of SG$69,050 (€62,701) per QALY. Conclusion Pharmacist-managed ACC is more effective and less costly compared with UC regardless of the quality of anticoagulation therapy. The findings support the current body of evidence demonstrating the cost-effectiveness of ACC.

Salt stress-induced changes in antioxidative defense system and proteome profiles of salt-tolerant and sensitive Frankia strains.

PubMed

Srivastava, Amrita; Singh, Anumeha; Singh, Satya S; Mishra, Arun K

2017-04-16

An appreciation of comparative microbial survival is most easily done while evaluating their adaptive strategies during stress. In the present experiment, antioxidative and whole cell proteome variations based on spectrophotometric analysis and SDS-PAGE and 2-dimensional gel electrophoresis have been analysed among salt-tolerant and salt-sensitive Frankia strains. This is the first report of proteomic basis underlying salt tolerance in these newly isolated Frankia strains from Hippophae salicifolia D. Don. Salt-tolerant strain HsIi10 shows higher increment in the contents of superoxide dismutase, catalase and ascorbate peroxidase as compared to salt-sensitive strain HsIi8. Differential 2-DGE profile has revealed differential profiles for salt-tolerant and salt-sensitive strains. Proteomic confirmation of salt tolerance in the strains with inbuilt efficiency of thriving in nitrogen-deficient locales is a definite advantage for these microbes. This would be equally beneficial for improvement of soil nitrogen status. Efficient protein regulation in HsIi10 suggests further exploration for its potential use as biofertilizer in saline soils.

Mixed kernel function support vector regression for global sensitivity analysis

NASA Astrophysics Data System (ADS)

Cheng, Kai; Lu, Zhenzhou; Wei, Yuhao; Shi, Yan; Zhou, Yicheng

2017-11-01

Global sensitivity analysis (GSA) plays an important role in exploring the respective effects of input variables on an assigned output response. Amongst the wide sensitivity analyses in literature, the Sobol indices have attracted much attention since they can provide accurate information for most models. In this paper, a mixed kernel function (MKF) based support vector regression (SVR) model is employed to evaluate the Sobol indices at low computational cost. By the proposed derivation, the estimation of the Sobol indices can be obtained by post-processing the coefficients of the SVR meta-model. The MKF is constituted by the orthogonal polynomials kernel function and Gaussian radial basis kernel function, thus the MKF possesses both the global characteristic advantage of the polynomials kernel function and the local characteristic advantage of the Gaussian radial basis kernel function. The proposed approach is suitable for high-dimensional and non-linear problems. Performance of the proposed approach is validated by various analytical functions and compared with the popular polynomial chaos expansion (PCE). Results demonstrate that the proposed approach is an efficient method for global sensitivity analysis.

The local lymph node assay: current position in the regulatory classification of skin sensitizing chemicals.

PubMed

Basketter, David A; Gerberick, G Frank; Kimber, Ian

2007-01-01

The local lymph node assay (LLNA) is being used increasingly in the identification of skin sensitizing chemicals for regulatory purposes. In the context of new chemicals legislation (REACH) in Europe, it is the preferred assay. The rationale for this is that the LLNA quantitative and objective approach to skin sensitization testing allied with the important animal welfare benefits that the method offers. However, as with certain guinea pig sensitization tests before it, this increasing use also brings experience with an increasingly wide range of industrial and other chemicals where the outcome of the assay does not always necessarily meet with the expectations of those conducting it. Sometimes, the result appears to be a false negative, but rather more commonly, the complaint is that the chemical represents a false positive. Against this background we have here reviewed a number of instances where false positive and false negative results have been described and have sought to reconcile science with expectation. Based on these analyses, it is our conclusion that false positives and false negatives do occur in the LLNA, as they do with any other skin sensitization assay (and indeed with all tests used for hazard identification), and that this occurs for a number of reasons. We further conclude, however, that false positive results in the LLNA, as with the guinea pig maximization test, arise most commonly via failure to distinguish what is scientifically correct from that which is unpalatable. The consequences of this confusion are discussed in the article, particularly in relation to the need to integrate both potency measurement and risk assessments into classification and labelling schemes that aim to manage potential risks to human health.

Cross-correlation focus method with an electrostatic sensor array for local particle velocity measurement in dilute gas-solid two-phase flow

NASA Astrophysics Data System (ADS)

Wang, Chao; Zhang, Jingyu; Gao, Wenbin; Ding, Hongbing; Wu, Weiping

2015-11-01

The gas-solid two-phase flow has been widely applied in the power, chemical and metallurgical industries. It is of great significance in the research of gas-solid two-phase flow to measure particle velocity at different locations in the pipeline. Thus, an electrostatic sensor array comprising eight arc-shaped electrodes was designed. The relationship between the cross-correlation (CC) velocity and the distribution of particle velocity, charge density and electrode spatial sensitivity was analysed. Then the CC sensitivity and its calculation method were proposed. According to the distribution of CC sensitivity, it was found that, between different electrode pairs, it had different focus areas. The CC focus method was proposed for particle velocity measurement at different locations and validated by a belt-style electrostatic induction experiment facility. Finally, the particle velocities at different locations with different flow conditions were measured to research the particle velocity distribution in a dilute horizontal pneumatic conveying pipeline.

Four-year analysis of microbial aetiology and antimicrobial sensitivity patterns of peritoneal-dialysis related peritonitis in a tertiary care facility.

PubMed

Persy, B; Ieven, M

2013-01-01

Peritonitis related to peritoneal dialysis increases morbidity and mortality and is the main reason for switching to haemodialysis. In this study, we analysed the dialysate of 164 peritoneal dialysis patients that was sent to our laboratory between January 2005 and August 2009. There were 196 peritonitis episodes identified in 78 patients. For all episodes, microbial aetiologies and in-vitro antimicrobial sensitivities were determined in addition to parameters such as the leukocyte count (WBC) and the result of the Gram stain. Results in children were analysed separately because of previously described differences in aetiology. In both groups, Gram positives were most commonly isolated, followed by Gram negatives and fungi or yeasts. In children, the proportion of coagulase-negative staphylococci compared to S. aureus is smaller than in adults. Gram stain showed predominant morphotypes concordant with culture results in 28% of episodes. A significant difference in WBC count was found between culture-positive (mean=3117 x 10(9)/L) and culture-negative (mean=981 x 10(9)/L) episodes in adults (p=0.001). The WBC count in episodes caused exclusively by CNS (mean=1502x10(9)/L) was also on average significantly lower (p=0.001) compared to all culture positive episodes. Resistance to methicillin was registered in 33% of cultures, positive for staphylococci. All Gram-positives were sensitive to vancomycin. Coverage of Gram-negatives by ceftazidim and quinolones was excellent (89%). Based on local sensitivity data and known characteristics of antimicrobials, a first-line empirical combination of intraperitoneal vancomycin with orally administered ciprofloxacin seems indicated in our population. Pathogens of positive aerobic cultures were sensitive in-vitro to their combined antimicrobial effect in 90% of cases.

Possible roles of vacuolar H+-ATPase and mitochondrial function in tolerance to air-drying stress revealed by genome-wide screening of Saccharomyces cerevisiae deletion strains.

PubMed

Shima, Jun; Ando, Akira; Takagi, Hiroshi

2008-03-01

Yeasts used in bread making are exposed to air-drying stress during dried yeast production processes. To clarify the genes required for air-drying tolerance, we performed genome-wide screening using the complete deletion strain collection of diploid Saccharomyces cerevisiae. The screening identified 278 gene deletions responsible for air-drying sensitivity. These genes were classified based on their cellular function and on the localization of their gene products. The results showed that the genes required for air-drying tolerance were frequently involved in mitochondrial functions and in connection with vacuolar H(+)-ATPase, which plays a role in vacuolar acidification. To determine the role of vacuolar acidification in air-drying stress tolerance, we monitored intracellular pH. The results showed that intracellular acidification was induced during air-drying and that this acidification was amplified in a deletion mutant of the VMA2 gene encoding a component of vacuolar H(+)-ATPase, suggesting that vacuolar H(+)-ATPase helps maintain intracellular pH homeostasis, which is affected by air-drying stress. To determine the effects of air-drying stress on mitochondria, we analysed the mitochondrial membrane potential under air-drying stress conditions using MitoTracker. The results showed that mitochondria were extremely sensitive to air-drying stress, suggesting that a mitochondrial function is required for tolerance to air-drying stress. We also analysed the correlation between oxidative-stress sensitivity and air-drying-stress sensitivity. The results suggested that oxidative stress is a critical determinant of sensitivity to air-drying stress, although ROS-scavenging systems are not necessary for air-drying stress tolerance. (c) 2008 John Wiley & Sons, Ltd.

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

Rapid allergen-induced interleukin-17 and interferon-γ secretion by skin-resident memory CD8+ T cells.

PubMed

Schmidt, Jonas D; Ahlström, Malin G; Johansen, Jeanne D; Dyring-Andersen, Beatrice; Agerbeck, Christina; Nielsen, Morten M; Poulsen, Steen S; Woetmann, Anders; Ødum, Niels; Thomsen, Allan R; Geisler, Carsten; Bonefeld, Charlotte M

2017-04-01

Skin-resident memory T (T RM ) cells are associated with immunological memory in the skin. Whether immunological memory responses to allergens in the skin are solely localized to previously allergen-exposed sites or are present globally in the skin is not clear. Furthermore, the mechanisms whereby T RM cells induce rapid recall responses need further investigation. To study whether contact allergens induce local and/or global memory, and to determine the mechanisms involved in memory responses in the skin. To address these questions, we analysed responses to contact allergens in mice and humans sensitized to 2,4-dinitrofluorobenzene and nickel, respectively. Challenge responses in both mice and humans were dramatically increased at sites previously exposed to allergens as compared with previously unexposed sites. Importantly, the magnitude of the challenge response correlated with the epidermal accumulation of interleukin (IL)-17A-producing and interferon (IFN)-γ-producing T RM cells. Moreover, IL-17A and IFN-γ enhanced allergen-induced IL-1β production in keratinocytes. We show that sensitization with contact allergens induces a strong, long-lasting local memory and a weaker, temporary global immunological memory response to the allergen that is mediated by IL-17A-producing and IFN-γ-producing CD8 + T RM cells. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An in vivo imaging-based assay for detecting protein interactions over a wide range of binding affinities

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

Fowlkes, Jason Davidson; Owens, Elizabeth T; Standaert, Robert F

2009-01-01

Identifying and characterizing protein interactions are fundamental steps towards understanding and modeling biological networks. Methods that detect protein interactions in intact cells rather than buffered solutions are likely more relevant to natural systems since molecular crowding events in the cytosol can influence the diffusion and reactivity of individual proteins. One in vivo, imaging-based method relies on the co-localization of two proteins of interest fused to DivIVA, a cell division protein from Bacillus subtilis, and green fluorescent protein (GFP). We have modified this imaging-based assay to facilitate rapid cloning by constructing new vectors encoding N- and C-terminal DivIVA or GFP molecularmore » tag fusions based on site-specific recombination technology. The sensitivity of the assay was defined using a well-characterized protein interaction system involving the eukaryotic nuclear import receptor subunit, Importin (Imp ) and variant nuclear localization signals (NLS) representing a range of binding affinities. These data demonstrate that the modified co-localization assay is sensitive enough to detect protein interactions with Kd values that span over four orders of magnitude (1nM to 15 M). Lastly, this assay was used to confirm numerous protein interactions identified from mass spectrometry-based analyses of affinity isolates as part of an interactome mapping project in Rhodopseudomonas palustris« less

The management of patients with T1 adenocarcinoma of the low rectum: a decision analysis.

PubMed

Johnston, Calvin F; Tomlinson, George; Temple, Larissa K; Baxter, Nancy N

2013-04-01

Decision making for patients with T1 adenocarcinoma of the low rectum, when treatment options are limited to a transanal local excision or abdominoperineal resection, is challenging. The aim of this study was to develop a contemporary decision analysis to assist patients and clinicians in balancing the goals of maximizing life expectancy and quality of life in this situation. We constructed a Markov-type microsimulation in open-source software. Recurrence rates and quality-of-life parameters were elicited by systematic literature reviews. Sensitivity analyses were performed on key model parameters. Our base case for analysis was a 65-year-old man with low-lying T1N0 rectal cancer. We determined the sensitivity of our model for sex, age up to 80, and T stage. The main outcome measured was quality-adjusted life-years. In the base case, selecting transanal local excision over abdominoperineal resection resulted in a loss of 0.53 years of life expectancy but a gain of 0.97 quality-adjusted life-years. One-way sensitivity analysis demonstrated a health state utility value threshold for permanent colostomy of 0.93. This value ranged from 0.88 to 1.0 based on tumor recurrence risk. There were no other model sensitivities. Some model parameter estimates were based on weak data. In our model, transanal local excision was found to be the preferable approach for most patients. An abdominoperineal resection has a 3.5% longer life expectancy, but this advantage is lost when the quality-of-life reduction reported by stoma patients is weighed in. The minority group in whom abdominoperineal resection is preferred are those who are unwilling to sacrifice 7% of their life expectancy to avoid a permanent stoma. This is estimated to be approximately 25% of all patients. The threshold increases to 12% of life expectancy in high-risk tumors. No other factors are found to be relevant to the decision.

Development of a microbial contamination susceptibility model for private domestic groundwater sources

NASA Astrophysics Data System (ADS)

Hynds, Paul D.; Misstear, Bruce D.; Gill, Laurence W.

2012-12-01

Groundwater quality analyses were carried out on samples from 262 private sources in the Republic of Ireland during the period from April 2008 to November 2010, with microbial quality assessed by thermotolerant coliform (TTC) presence. Assessment of potential microbial contamination risk factors was undertaken at all sources, and local meteorological data were also acquired. Overall, 28.9% of wells tested positive for TTC, with risk analysis indicating that source type (i.e., borehole or hand-dug well), local bedrock type, local subsoil type, groundwater vulnerability, septic tank setback distance, and 48 h antecedent precipitation were all significantly associated with TTC presence (p < 0.05). A number of source-specific design parameters were also significantly associated with bacterial presence. Hierarchical logistic regression with stepwise parameter entry was used to develop a private well susceptibility model, with the final model exhibiting a mean predictive accuracy of >80% (TTC present or absent) when compared to an independent validation data set. Model hierarchies of primary significance are source design (20%), septic tank location (11%), hydrogeological setting (10%), and antecedent 120 h precipitation (2%). Sensitivity analysis shows that the probability of contamination is highly sensitive to septic tank setback distance, with probability increasing linearly with decreases in setback distance. Likewise, contamination probability was shown to increase with increasing antecedent precipitation. Results show that while groundwater vulnerability category is a useful indicator of aquifer susceptibility to contamination, its suitability with regard to source contamination is less clear. The final model illustrates that both localized (well-specific) and generalized (aquifer-specific) contamination mechanisms are involved in contamination events, with localized bypass mechanisms dominant. The susceptibility model developed here could be employed in the appropriate location, design, construction, and operation of private groundwater wells, thereby decreasing the contamination risk, and hence health risk, associated with these sources.

Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Preoperative Treatment of Extremity Soft Tissue Sarcomas

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

Richard, Patrick, E-mail: patrjr@uw.edu; Phillips, Mark; Smith, Wade

Purpose: Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. Methods and Materials: Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with themore » largest impact on the ICER. Results: Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) than for 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68 years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. Conclusions: Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.« less

An Innovative Technique to Assess Spontaneous Baroreflex Sensitivity with Short Data Segments: Multiple Trigonometric Regressive Spectral Analysis.

PubMed

Li, Kai; Rüdiger, Heinz; Haase, Rocco; Ziemssen, Tjalf

2018-01-01

Objective: As the multiple trigonometric regressive spectral (MTRS) analysis is extraordinary in its ability to analyze short local data segments down to 12 s, we wanted to evaluate the impact of the data segment settings by applying the technique of MTRS analysis for baroreflex sensitivity (BRS) estimation using a standardized data pool. Methods: Spectral and baroreflex analyses were performed on the EuroBaVar dataset (42 recordings, including lying and standing positions). For this analysis, the technique of MTRS was used. We used different global and local data segment lengths, and chose the global data segments from different positions. Three global data segments of 1 and 2 min and three local data segments of 12, 20, and 30 s were used in MTRS analysis for BRS. Results: All the BRS-values calculated on the three global data segments were highly correlated, both in the supine and standing positions; the different global data segments provided similar BRS estimations. When using different local data segments, all the BRS-values were also highly correlated. However, in the supine position, using short local data segments of 12 s overestimated BRS compared with those using 20 and 30 s. In the standing position, the BRS estimations using different local data segments were comparable. There was no proportional bias for the comparisons between different BRS estimations. Conclusion: We demonstrate that BRS estimation by the MTRS technique is stable when using different global data segments, and MTRS is extraordinary in its ability to evaluate BRS in even short local data segments (20 and 30 s). Because of the non-stationary character of most biosignals, the MTRS technique would be preferable for BRS analysis especially in conditions when only short stationary data segments are available or when dynamic changes of BRS should be monitored.

Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients.

PubMed

Skiöld, Sara; Azimzadeh, Omid; Merl-Pham, Juliane; Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet; Tapio, Soile; Harms-Ringdahl, Mats; Haghdoost, Siamak

2015-06-01

Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37°C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

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.

Sensitivity of ground motion parameters to local site effects for areas characterised by a thick buried low-velocity layer.

NASA Astrophysics Data System (ADS)

Farrugia, Daniela; Galea, Pauline; D'Amico, Sebastiano; Paolucci, Enrico

2016-04-01

It is well known that earthquake damage at a particular site depends on the source, the path that the waves travel through and the local geology. The latter is capable of amplifying and changing the frequency content of the incoming seismic waves. In regions of sparse or no strong ground motion records, like Malta (Central Mediterranean), ground motion simulations are used to obtain parameters for purposes of seismic design and analysis. As an input to ground motion simulations, amplification functions related to the shallow subsurface are required. Shear-wave velocity profiles of several sites on the Maltese islands were obtained using the Horizontal-to-Vertical Spectral Ratio (H/V), the Extended Spatial Auto-Correlation (ESAC) technique and the Genetic Algorithm. The sites chosen were all characterised by a layer of Blue Clay, which can be up to 75 m thick, underlying the Upper Coralline Limestone, a fossiliferous coarse grained limestone. This situation gives rise to a velocity inversion. Available borehole data generally extends down till the top of the Blue Clay layer therefore the only way to check the validity of the modelled shear-wave velocity profile is through the thickness of the topmost layer. Surface wave methods are characterised by uncertainties related to the measurements and the model used for interpretation. Moreover the inversion procedure is also highly non-unique. Such uncertainties are not commonly included in site response analysis. Yet, the propagation of uncertainties from the extracted dispersion curves to inversion solutions can lead to significant differences in the simulations (Boaga et al., 2011). In this study, a series of sensitivity analyses will be presented with the aim of better identifying those stratigraphic properties which can perturb the ground motion simulation results. The stochastic one-dimensional site response analysis algorithm, Extended Source Simulation (EXSIM; Motazedian and Atkinson, 2005), was used to perform these analyses. The amplification functions were extracted using the programme SITE_AMP (Boore, 2003), which computes amplifications based on the square root of the effective seismic impedance. Sensitivity indices were obtained by changing two parameters (thickness and shear-wave velocity) of the different layers while keeping the others constant. Additional analyses were carried out by producing various profiles within specified boundaries which are able to fit the experimental data. The analyses also show the important role that the shear-wave velocity profiles play in ground motion simulations. The results obtained highlight the importance of the correct knowledge of both the properties of the Upper Coralline Limestone and the Blue Clay, especially the Blue Clay thickness.

A single-index threshold Cox proportional hazard model for identifying a treatment-sensitive subset based on multiple biomarkers.

PubMed

He, Ye; Lin, Huazhen; Tu, Dongsheng

2018-06-04

In this paper, we introduce a single-index threshold Cox proportional hazard model to select and combine biomarkers to identify patients who may be sensitive to a specific treatment. A penalized smoothed partial likelihood is proposed to estimate the parameters in the model. A simple, efficient, and unified algorithm is presented to maximize this likelihood function. The estimators based on this likelihood function are shown to be consistent and asymptotically normal. Under mild conditions, the proposed estimators also achieve the oracle property. The proposed approach is evaluated through simulation analyses and application to the analysis of data from two clinical trials, one involving patients with locally advanced or metastatic pancreatic cancer and one involving patients with resectable lung cancer. Copyright © 2018 John Wiley & Sons, Ltd.

The novel gene tank, a tumor suppressor homolog, regulates ethanol sensitivity in Drosophila.

PubMed

Devineni, Anita V; Eddison, Mark; Heberlein, Ulrike

2013-05-08

In both mammalian and insect models of ethanol intoxication, high doses of ethanol induce motor impairment and eventually sedation. Sensitivity to the sedative effects of ethanol is inversely correlated with risk for alcoholism. However, the genes regulating ethanol sensitivity are largely unknown. Based on a previous genetic screen in Drosophila for ethanol sedation mutants, we identified a novel gene, tank (CG15626), the homolog of the mammalian tumor suppressor EI24/PIG8, which has a strong role in regulating ethanol sedation sensitivity. Genetic and behavioral analyses revealed that tank acts in the adult nervous system to promote ethanol sensitivity. We localized the function of tank in regulating ethanol sensitivity to neurons within the pars intercerebralis that have not been implicated previously in ethanol responses. We show that acutely manipulating the activity of all tank-expressing neurons, or of pars intercerebralis neurons in particular, alters ethanol sensitivity in a sexually dimorphic manner, since neuronal activation enhanced ethanol sedation in males, but not females. Finally, we provide anatomical evidence that tank-expressing neurons form likely synaptic connections with neurons expressing the neural sex determination factor fruitless (fru), which have been implicated recently in the regulation of ethanol sensitivity. We suggest that a functional interaction with fru neurons, many of which are sexually dimorphic, may account for the sex-specific effect induced by activating tank neurons. Overall, we have characterized a novel gene and corresponding set of neurons that regulate ethanol sensitivity in Drosophila.

The Novel Gene tank, a Tumor Suppressor Homolog, Regulates Ethanol Sensitivity in Drosophila

PubMed Central

Eddison, Mark; Heberlein, Ulrike

2013-01-01

In both mammalian and insect models of ethanol intoxication, high doses of ethanol induce motor impairment and eventually sedation. Sensitivity to the sedative effects of ethanol is inversely correlated with risk for alcoholism. However, the genes regulating ethanol sensitivity are largely unknown. Based on a previous genetic screen in Drosophila for ethanol sedation mutants, we identified a novel gene, tank (CG15626), the homolog of the mammalian tumor suppressor EI24/PIG8, which has a strong role in regulating ethanol sedation sensitivity. Genetic and behavioral analyses revealed that tank acts in the adult nervous system to promote ethanol sensitivity. We localized the function of tank in regulating ethanol sensitivity to neurons within the pars intercerebralis that have not been implicated previously in ethanol responses. We show that acutely manipulating the activity of all tank-expressing neurons, or of pars intercerebralis neurons in particular, alters ethanol sensitivity in a sexually dimorphic manner, since neuronal activation enhanced ethanol sedation in males, but not females. Finally, we provide anatomical evidence that tank-expressing neurons form likely synaptic connections with neurons expressing the neural sex determination factor fruitless (fru), which have been implicated recently in the regulation of ethanol sensitivity. We suggest that a functional interaction with fru neurons, many of which are sexually dimorphic, may account for the sex-specific effect induced by activating tank neurons. Overall, we have characterized a novel gene and corresponding set of neurons that regulate ethanol sensitivity in Drosophila. PMID:23658154

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.

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

Lithium in drinking water and suicide mortality.

PubMed

Kapusta, Nestor D; Mossaheb, Nilufar; Etzersdorfer, Elmar; Hlavin, Gerald; Thau, Kenneth; Willeit, Matthäus; Praschak-Rieder, Nicole; Sonneck, Gernot; Leithner-Dziubas, Katharina

2011-05-01

There is some evidence that natural levels of lithium in drinking water may have a protective effect on suicide mortality. To evaluate the association between local lithium levels in drinking water and suicide mortality at district level in Austria. A nationwide sample of 6460 lithium measurements was examined for association with suicide rates per 100,000 population and suicide standardised mortality ratios across all 99 Austrian districts. Multivariate regression models were adjusted for well-known socioeconomic factors known to influence suicide mortality in Austria (population density, per capita income, proportion of Roman Catholics, as well as the availability of mental health service providers). Sensitivity analyses and weighted least squares regression were used to challenge the robustness of the results. The overall suicide rate (R(2) = 0.15, β = -0.39, t = -4.14, P = 0.000073) as well as the suicide mortality ratio (R(2) = 0.17, β = -0.41, t = -4.38, P = 0.000030) were inversely associated with lithium levels in drinking water and remained significant after sensitivity analyses and adjustment for socioeconomic factors. In replicating and extending previous results, this study provides strong evidence that geographic regions with higher natural lithium concentrations in drinking water are associated with lower suicide mortality rates.

A systematic analysis of commonly used antibodies in cancer diagnostics.

PubMed

Gremel, Gabriela; Bergman, Julia; Djureinovic, Dijana; Edqvist, Per-Henrik; Maindad, Vikas; Bharambe, Bhavana M; Khan, Wasif Ali Z A; Navani, Sanjay; Elebro, Jacob; Jirström, Karin; Hellberg, Dan; Uhlén, Mathias; Micke, Patrick; Pontén, Fredrik

2014-01-01

Immunohistochemistry plays a pivotal role in cancer differential diagnostics. To identify the primary tumour from a metastasis specimen remains a significant challenge, despite the availability of an increasing number of antibodies. The aim of the present study was to provide evidence-based data on the diagnostic power of antibodies used frequently for clinical differential diagnostics. A tissue microarray cohort comprising 940 tumour samples, of which 502 were metastatic lesions, representing tumours from 18 different organs and four non-localized cancer types, was analysed using immunohistochemistry with 27 well-established antibodies used in clinical differential diagnostics. Few antibodies, e.g. prostate-specific antigen and thyroglobulin, showed a cancer type-related sensitivity and specificity of more than 95%. A majority of the antibodies showed a low degree of sensitivity and specificity for defined cancer types. Combinations of antibodies provided limited added value for differential diagnostics of cancer types. The results from analysing 27 diagnostic antibodies on consecutive sections of 940 defined tumours provide a unique repository of data that can empower a more optimal use of clinical immunohistochemistry. Our results highlight the benefit of immunohistochemistry and the unmet need for novel markers to improve differential diagnostics of cancer. © 2013 John Wiley & Sons Ltd.

Innovative Tools and Technology for Analysis of Single Cells and Cell-Cell Interaction.

PubMed

Konry, Tania; Sarkar, Saheli; Sabhachandani, Pooja; Cohen, Noa

2016-07-11

Heterogeneity in single-cell responses and intercellular interactions results from complex regulation of cell-intrinsic and environmental factors. Single-cell analysis allows not only detection of individual cellular characteristics but also correlation of genetic content with phenotypic traits in the same cell. Technological advances in micro- and nanofabrication have benefited single-cell analysis by allowing precise control of the localized microenvironment, cell manipulation, and sensitive detection capabilities. Additionally, microscale techniques permit rapid, high-throughput, multiparametric screening that has become essential for -omics research. This review highlights innovative applications of microscale platforms in genetic, proteomic, and metabolic detection in single cells; cell sorting strategies; and heterotypic cell-cell interaction. We discuss key design aspects of single-cell localization and isolation in microfluidic systems, dynamic and endpoint analyses, and approaches that integrate highly multiplexed detection of various intracellular species.

Detection of Functional Change Using Cluster Trend Analysis in Glaucoma.

PubMed

Gardiner, Stuart K; Mansberger, Steven L; Demirel, Shaban

2017-05-01

Global analyses using mean deviation (MD) assess visual field progression, but can miss localized changes. Pointwise analyses are more sensitive to localized progression, but more variable so require confirmation. This study assessed whether cluster trend analysis, averaging information across subsets of locations, could improve progression detection. A total of 133 test-retest eyes were tested 7 to 10 times. Rates of change and P values were calculated for possible re-orderings of these series to generate global analysis ("MD worsening faster than x dB/y with P < y"), pointwise and cluster analyses ("n locations [or clusters] worsening faster than x dB/y with P < y") with specificity exactly 95%. These criteria were applied to 505 eyes tested over a mean of 10.5 years, to find how soon each detected "deterioration," and compared using survival models. This was repeated including two subsequent visual fields to determine whether "deterioration" was confirmed. The best global criterion detected deterioration in 25% of eyes in 5.0 years (95% confidence interval [CI], 4.7-5.3 years), compared with 4.8 years (95% CI, 4.2-5.1) for the best cluster analysis criterion, and 4.1 years (95% CI, 4.0-4.5) for the best pointwise criterion. However, for pointwise analysis, only 38% of these changes were confirmed, compared with 61% for clusters and 76% for MD. The time until 25% of eyes showed subsequently confirmed deterioration was 6.3 years (95% CI, 6.0-7.2) for global, 6.3 years (95% CI, 6.0-7.0) for pointwise, and 6.0 years (95% CI, 5.3-6.6) for cluster analyses. Although the specificity is still suboptimal, cluster trend analysis detects subsequently confirmed deterioration sooner than either global or pointwise analyses.

High-sensitivity visualization of localized electric fields using low-energy electron beam deflection

NASA Astrophysics Data System (ADS)

Jeong, Samuel; Ito, Yoshikazu; Edwards, Gary; Fujita, Jun-ichi

2018-06-01

The visualization of localized electronic charges on nanocatalysts is expected to yield fundamental information about catalytic reaction mechanisms. We have developed a high-sensitivity detection technique for the visualization of localized charges on a catalyst and their corresponding electric field distribution, using a low-energy beam of 1 to 5 keV electrons and a high-sensitivity scanning transmission electron microscope (STEM) detector. The highest sensitivity for visualizing a localized electric field was ∼0.08 V/µm at a distance of ∼17 µm from a localized charge at 1 keV of the primary electron energy, and a weak local electric field produced by 200 electrons accumulated on the carbon nanotube (CNT) apex can be visualized. We also observed that Au nanoparticles distributed on a CNT forest tended to accumulate a certain amount of charges, about 150 electrons, at a ‑2 V bias.

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.

Linkage disequilibrium network analysis (LDna) gives a global view of chromosomal inversions, local adaptation and geographic structure.

PubMed

Kemppainen, Petri; Knight, Christopher G; Sarma, Devojit K; Hlaing, Thaung; Prakash, Anil; Maung Maung, Yan Naung; Somboon, Pradya; Mahanta, Jagadish; Walton, Catherine

2015-09-01

Recent advances in sequencing allow population-genomic data to be generated for virtually any species. However, approaches to analyse such data lag behind the ability to generate it, particularly in nonmodel species. Linkage disequilibrium (LD, the nonrandom association of alleles from different loci) is a highly sensitive indicator of many evolutionary phenomena including chromosomal inversions, local adaptation and geographical structure. Here, we present linkage disequilibrium network analysis (LDna), which accesses information on LD shared between multiple loci genomewide. In LD networks, vertices represent loci, and connections between vertices represent the LD between them. We analysed such networks in two test cases: a new restriction-site-associated DNA sequence (RAD-seq) data set for Anopheles baimaii, a Southeast Asian malaria vector; and a well-characterized single nucleotide polymorphism (SNP) data set from 21 three-spined stickleback individuals. In each case, we readily identified five distinct LD network clusters (single-outlier clusters, SOCs), each comprising many loci connected by high LD. In A. baimaii, further population-genetic analyses supported the inference that each SOC corresponds to a large inversion, consistent with previous cytological studies. For sticklebacks, we inferred that each SOC was associated with a distinct evolutionary phenomenon: two chromosomal inversions, local adaptation, population-demographic history and geographic structure. LDna is thus a useful exploratory tool, able to give a global overview of LD associated with diverse evolutionary phenomena and identify loci potentially involved. LDna does not require a linkage map or reference genome, so it is applicable to any population-genomic data set, making it especially valuable for nonmodel species. © 2015 The Authors. Molecular Ecology Resources Published by John Wiley & Sons Ltd.

The influence of local spring temperature variance on temperature sensitivity of spring phenology.

PubMed

Wang, Tao; Ottlé, Catherine; Peng, Shushi; Janssens, Ivan A; Lin, Xin; Poulter, Benjamin; Yue, Chao; Ciais, Philippe

2014-05-01

The impact of climate warming on the advancement of plant spring phenology has been heavily investigated over the last decade and there exists great variability among plants in their phenological sensitivity to temperature. However, few studies have explicitly linked phenological sensitivity to local climate variance. Here, we set out to test the hypothesis that the strength of phenological sensitivity declines with increased local spring temperature variance, by synthesizing results across ground observations. We assemble ground-based long-term (20-50 years) spring phenology database (PEP725 database) and the corresponding climate dataset. We find a prevalent decline in the strength of phenological sensitivity with increasing local spring temperature variance at the species level from ground observations. It suggests that plants might be less likely to track climatic warming at locations with larger local spring temperature variance. This might be related to the possibility that the frost risk could be higher in a larger local spring temperature variance and plants adapt to avoid this risk by relying more on other cues (e.g., high chill requirements, photoperiod) for spring phenology, thus suppressing phenological responses to spring warming. This study illuminates that local spring temperature variance is an understudied source in the study of phenological sensitivity and highlight the necessity of incorporating this factor to improve the predictability of plant responses to anthropogenic climate change in future studies. © 2013 John Wiley & Sons Ltd.

Prostate cancer localization with multispectral MRI using cost-sensitive support vector machines and conditional random fields.

PubMed

Artan, Yusuf; Haider, Masoom A; Langer, Deanna L; van der Kwast, Theodorus H; Evans, Andrew J; Yang, Yongyi; Wernick, Miles N; Trachtenberg, John; Yetik, Imam Samil

2010-09-01

Prostate cancer is a leading cause of cancer death for men in the United States. Fortunately, the survival rate for early diagnosed patients is relatively high. Therefore, in vivo imaging plays an important role for the detection and treatment of the disease. Accurate prostate cancer localization with noninvasive imaging can be used to guide biopsy, radiotherapy, and surgery as well as to monitor disease progression. Magnetic resonance imaging (MRI) performed with an endorectal coil provides higher prostate cancer localization accuracy, when compared to transrectal ultrasound (TRUS). However, in general, a single type of MRI is not sufficient for reliable tumor localization. As an alternative, multispectral MRI, i.e., the use of multiple MRI-derived datasets, has emerged as a promising noninvasive imaging technique for the localization of prostate cancer; however almost all studies are with human readers. There is a significant inter and intraobserver variability for human readers, and it is substantially difficult for humans to analyze the large dataset of multispectral MRI. To solve these problems, this study presents an automated localization method using cost-sensitive support vector machines (SVMs) and shows that this method results in improved localization accuracy than classical SVM. Additionally, we develop a new segmentation method by combining conditional random fields (CRF) with a cost-sensitive framework and show that our method further improves cost-sensitive SVM results by incorporating spatial information. We test SVM, cost-sensitive SVM, and the proposed cost-sensitive CRF on multispectral MRI datasets acquired from 21 biopsy-confirmed cancer patients. Our results show that multispectral MRI helps to increase the accuracy of prostate cancer localization when compared to single MR images; and that using advanced methods such as cost-sensitive SVM as well as the proposed cost-sensitive CRF can boost the performance significantly when compared to SVM.

Gravitational wave hotspots: Ranking potential locations of single-source gravitational wave emission

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

Simon, Joseph; Polin, Abigail; Lommen, Andrea

2014-03-20

The steadily improving sensitivity of pulsar timing arrays (PTAs) suggests that gravitational waves (GWs) from supermassive black hole binary (SMBHB) systems in the nearby universe will be detectable sometime during the next decade. Currently, PTAs assume an equal probability of detection from every sky position, but as evidence grows for a non-isotropic distribution of sources, is there a most likely sky position for a detectable single source of GWs? In this paper, a collection of Galactic catalogs is used to calculate various metrics related to the detectability of a single GW source resolvable above a GW background, assuming that everymore » galaxy has the same probability of containing an SMBHB. Our analyses of these data reveal small probabilities that one of these sources is currently in the PTA band, but as sensitivity is improved regions of consistent probability density are found in predictable locations, specifically around local galaxy clusters.« less

Chemodetection and Destruction of Host Urea Allows Helicobacter pylori to Locate the Epithelium

PubMed Central

Huang, Julie Y.; Sweeney, Emily Goers; Sigal, Michael; Zhang, Hai C.; Remington, S. James; Cantrell, Michael A.; Kuo, Calvin J.; Guillemin, Karen; Amieva, Manuel R.

2015-01-01

SUMMARY The gastric pathogen Helicobacter pylori interacts intimately with the gastric mucosa to avoid the microbicidal acid in the stomach lumen. The cues H. pylori senses to locate and colonize the gastric epithelium have not been well defined. We show that metabolites emanating from human gastric organoids rapidly attract H. pylori. This response is largely controlled by the bacterial chemoreceptor TlpB, and the main attractant emanating from epithelia is urea. Our previous structural analyses show that TlpB binds urea with high affinity. Here we demonstrate that this tight binding controls highly sensitive responses, allowing detection of urea concentrations as low as 50 nanomolar. Attraction to urea requires that H. pylori urease simultaneously destroys the signal. We propose that H. pylori has evolved a sensitive urea chemodetection and destruction system that allows the bacterium to dynamically and locally modify the host environment to locate the epithelium. PMID:26269952

Structural health monitoring based on sensitivity vector fields and attractor morphing.

PubMed

Yin, Shih-Hsun; Epureanu, Bogdan I

2006-09-15

The dynamic responses of a thermo-shielding panel forced by unsteady aerodynamic loads and a classical Duffing oscillator are investigated to detect structural damage. A nonlinear aeroelastic model is obtained for the panel by using third-order piston theory to model the unsteady supersonic flow, which interacts with the panel. To identify damage, we analyse the morphology (deformation and movement) of the attractor of the dynamics of the aeroelastic system and the Duffing oscillator. Damages of various locations, extents and levels are shown to be revealed by the attractor-based analysis. For the panel, the type of damage considered is a local reduction in the bending stiffness. For the Duffing oscillator, variations in the linear and nonlinear stiffnesses and damping are considered as damage. Present studies of such problems are based on linear theories. In contrast, the presented approach using nonlinear dynamics has the potential of enhancing accuracy and sensitivity of detection.

Good research practices for measuring drug costs in cost-effectiveness analyses: an international perspective: the ISPOR Drug Cost Task Force report--Part VI.

PubMed

Shi, Lizheng; Hodges, Meredith; Drummond, Michael; Ahn, Jeonghoon; Li, Shu Chuen; Hu, Shanlian; Augustovski, Federico; Hay, Joel W; Smeeding, Jim

2010-01-01

The pharmacoeconomic guidelines available in the literature or promulgated in many countries are either vague or silent about how drug costs should be established or measured so an international comparison of cost-effectiveness analysis (CEA) results can be made. The objective of this report is to provide guidance and recommendations on how drug costs should be measured for CEAs done from an internationally comparative perspective. Members of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (Drug Cost Task Force [DCTF]) subgroup from several countries were experienced developers or users of CEA models, and worked in academia, industry, and as advisors to governments. They solicited comments on drafts from a core group of 174 external reviewers and more broadly, from the members of the ISPOR at the ISPOR 12th Annual International meeting and via the ISPOR Web site. Drug units should be standardized in terms of volume of active ingredient, regardless of packaging and dosing strength variations across countries. Drug costs should be measured in local currency per unit of active ingredient and should be converted to other currencies using sensitivity analyses of purchasing power parities (PPP) and exchange rates, whichever is more appropriate. When using drug prices from different years, the consumer price index for the local currency should be applied before the PPP and/or exchange rate conversion. CEA researchers conducting international pharmacoeconomic analysis should tailor the appropriate measure of drug costs to the international perspective, to maintain clarity and transparency on drug cost measurement in the context of international drug comparison and report the sensitivity of CEA results to reasonable cost conversions.

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.

Molecular Scanning and Morpho-Physiological Dissection of Component Mechanism in Lens Species in Response to Aluminium Stress

PubMed Central

Singh, Dharmendra; Pal, Madan; Singh, Chandan Kumar; Taunk, Jyoti; Jain, Priyanka; Chaturvedi, Ashish Kumar; Maurya, Sadhana; Karwa, Sourabh; Singh, Rajendra; Tomar, Ram Sewak Singh; Nongthombam, Rita; Chongtham, Nandini; Singh, Moirangthem Premjit

2016-01-01

Aluminium (Al) stress was imposed on 285 lentil genotypes at seedling stage under hydroponics to study its effects on morpho-physiological traits where resistant cultigens and wilds showed minimum reduction in root and shoot length and maximum root re-growth (RRG) after staining. Molecular assortment based on 46 simple sequence repeat (SSR) markers clustered the genotypes into 11 groups, where wilds were separated from the cultigens. Genetic diversity and polymorphism information content (PIC) varied between 0.148–0.775 and 0.140–0.739, respectively. Breeding lines which were found to be most resistant (L-7903, L-4602); sensitive cultivars (BM-4, L-4147) and wilds ILWL-185 (resistant), ILWL-436 (sensitive) were grouped into different clusters. These genotypes were also separated on the basis of population structure and Jaccard’s similarity index and analysed to study Al resistance mechanism through determination of different attributes like localization of Al and callose, lipid peroxidation, secretion of organic acids and production of antioxidant enzymes. In contrast to sensitive genotypes, in resistant ones most of the Al was localized in the epidermal cells, where its movement to apoplastic region was restricted due to release of citrate and malate. Under acidic field conditions, resistant genotypes produced maximum seed yield/plant as compared to sensitive genotypes at two different locations i.e. Imphal, Manipur, India and Basar, Arunanchal Pradesh, India during 2012–13, 2013–14 and 2014–15. These findings suggest that Al stress adaptation in lentil is through exclusion mechanism and hybridization between the contrasting genotypes from distinct clusters can help in development of resistant varieties. PMID:27467074

FDG-PET, CT, MRI for diagnosis of local residual or recurrent nasopharyngeal carcinoma, which one is the best? A systematic review.

PubMed

Liu, Tao; Xu, Wen; Yan, Wei-Li; Ye, Ming; Bai, Yong-Rui; Huang, Gang

2007-12-01

To perform a systematic review to compare FDG-PET, CT, and MRI imaging for diagnosis of local residual or recurrent nasopharyngeal carcinoma. MEDLINE, EMBASE, the CBMdisc databases and some other databases were searched for relevant original articles published from January 1990 to June 2007. Inclusion criteria were as follows: Articles were reported in English or Chinese; FDG-PET, CT, or MRI was used to detect local residual or recurrent nasopharyngeal carcinoma; histopathologic analysis and/or close clinical and imaging follow-up for at least 6 months were the reference standard. Two reviewers independently extracted data. A software called "Meta-DiSc" was used to obtain pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curves, and the Q* index. Twenty-one articles fulfilled all inclusion criteria. The pooled sensitivity estimates for PET (95%) were significantly higher than CT (76%) (P<0.001) and MRI (78%) (P<0.001). The pooled specificity estimates for PET (90%) were significantly higher than CT (59%) (P<0.001) and MRI (76%) (P<0.001). The pooled DOR estimates for PET (96.51) were significantly higher than CT (7.01) (P<0.001) and MRI (8.68) (P<0.001). SROC curve for FDG-PET showed better diagnostic accuracy than CT and MRI. The Q* index for PET (0.92) was significantly higher than CT (0.72) (P<0.001) and MRI (0.76) (P<0.01). For PET, the sensitivity and diagnostic OR for using qualitative analysis were significantly higher than using both qualitative and quantitative analyses (P<0.01). For CT, the sensitivity, specificity, diagnostic OR, and the Q* index for dual-section helical and multi-section helical were all significantly higher than nonhelical and single-section helical (P<0.01). And the sensitivity for 'section thickness <5 mm' was significantly lower than ' =5 mm' (P<0.01), while the specificity was significantly higher (P<0.01). For MRI, there were no significant differences found between magnetic field strength <1.5 and > or =1.5 T (P>0.05). FDG-PET was the best modality for diagnosis of local residual or recurrent nasopharyngeal carcinoma. The type of analysis for PET imaging and the section thickness for CT would affect the diagnostic results. Dual-section helical and multi-section helical CT were better than nonhelical and single-section helical CT.

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

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

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

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

Experimental evaluation of the sensitivity to fuel utilization and air management on a 100 kW SOFC system

NASA Astrophysics Data System (ADS)

Santarelli, M.; Leone, P.; Calì, M.; Orsello, G.

The tubular SOFC generator CHP-100, built by Siemens Power Generation (SPG) Stationary Fuel Cells (SFC), is running at the Gas Turbine Technologies (GTT) in Torino (Italy), in the framework of the EOS Project. The nominal load of the generator ensures a produced electric power of around 105 kW e ac and around 60 kW t of thermal power at 250 °C to be used for the custom tailored HVAC system. Several experimental sessions have been scheduled on the generator; the aim is to characterize the operation through the analysis of some global performance index and the detailed control of the operation of the different bundles of the whole stack. All the scheduled tests have been performed by applying the methodology of design of experiment; the main obtained results show the effect of the change of the analysed operating factors in terms of distribution of voltage and temperature over the stack. Fuel consumption tests give information about the sensitivity of the voltage and temperature distribution along the single bundles. On the other hand, since the generator is an air cooled system, the results of the tests on the air stoichs have been used to analyze the generator thermal management (temperature distribution and profiles) and its effect on the polarization. The sensitivity analysis of the local voltage to the overall fuel consumption modifications can be used as a powerful procedure to deduce the local distribution of fuel utilization (FU) along the single bundles: in fact, through a model obtained by deriving the polarization curve respect to FU, it is possible to link the distribution of voltage sensitivities to FC to the distribution of the local FU. The FU distribution will be shown as non-uniform, and this affects the local voltage and temperatures, causing a high warming effect in some rows of the generator. Therefore, a discussion around the effectiveness of the thermal regulation made by the air stoichs, in order to reduce the non-uniform distribution of temperature and the overheating (increasing therefore the voltage behavior along the generator) has been performed. It is demonstrated that the utilization of one air plenum is not effective in the thermal regulation of the whole generator, in particular in the reduction of the temperature gradients linked to the non-uniform fuel distribution.

Tumor-suppressive effects of natural-type interferon-β through CXCL10 in melanoma

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

Kobayashi, Hikaru; Nobeyama, Yoshimasa, E-mail: nobederm@jikei.ac.jp; Nakagawa, Hidemi

2015-08-21

Introduction: Type 1 interferon is in widespread use as adjuvant therapy to inhibit melanoma progression. Considering the tumor-suppressive effects of local administration of interferon-β (IFN-β) on lymphatic metastasis, the present study was conducted to identify melanoma-suppressive molecules that are up-regulated by IFN-β treatment of lymphatic endothelial cells. Materials and methods: Lymphatic endothelial cells, fibroblasts, and melanoma cells were treated with natural-type IFN-β, and melanoma cells were treated with CXCL10. Genome-wide oligonucleotide microarray analysis was performed using lymphatic endothelial cells with or without IFN-β treatment. Quantitative real-time reverse transcription-PCR and an enzyme-linked immunosorbent assay were performed to examine CXCL10 expression. Amore » proliferation assay was performed to examine the effects of IFN-β and CXCL10 in melanoma cells. Results: Genome-wide microarray analyses detected CXCL10 as a gene encoding a secretory protein that was up-regulated by IFN-β in lymphatic endothelial cells. IFN-β treatment significantly induced CXCL10 in dermal lymphatic endothelial cells and melanoma cells that are highly sensitive to IFN-β. CXCL10 reduced melanoma cell proliferation in IFN-β-sensitive cells as well as resistant cells. Melanoma cells in which CXCL10 was knocked down were sensitive to IFN-β. CXCR3-B, which encodes the CXCL10 receptor, was up-regulated in melanoma cells with high sensitivity to IFN-β and down-regulated in melanoma cells with medium to low sensitivity. Conclusions: Our data suggest that IFN-β suppresses proliferation and metastasis from the local lymphatic system and melanoma cells via CXCL10. Down-regulation of CXCR3-B by IFN-β may be associated with resistance to IFN-β. - Highlights: • We search melanoma-suppressive molecules induced by IFN-β. • IFN-β induces a high amount of CXCL10 from lymphatic endothelial cells. • CXCL10 induction level in melanoma cells is correlated with the sensitivity to IFN-β. • CXCL10 reduces proliferation in IFN-β-sensitive cells as well as resistant cells. • CXCR3-B is down-regulated by IFN-β exclusively in IFN-β-resistant cells.« less

Gravitational astrophysics

NASA Astrophysics Data System (ADS)

Hendry, Martin; Woan, Graham

2007-02-01

Like the surface of a busy swimming pool, spacetime is awash with waves generated by the local and distant motions of mass and, in principle, much of this activity can be reconstructed by analysing the waveforms. However, instrumentation with a reasonable chance of directly detecting these gravitational waves has only become available within the past year, with the LIGO detectors now running at design sensitivity. Here we review the burgeoning field of observational gravitational astrophysics: using gravitational wave detectors as telescopes to help answer a wide range of astrophysical questions from neutron-star physics to cosmology. The next generation of ground-based telescopes should be able to make extensive gravitational observations of some of the more energetic events in our local universe. Looking only slightly further ahead, the space-based LISA observatory will reveal the gravitational universe in phenomenal detail, supplying high-quality data on perhaps thousands of sources, and tackling some of the most fascinating questions in contemporary astronomy.

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

Local perceptions of climate change validated by scientific evidence in the Himalayas.

PubMed

Chaudhary, Pashupati; Bawa, Kamaljit S

2011-10-23

The Himalayas are assumed to be undergoing rapid climate change, with serious environmental, social and economic consequences for more than two billion people. However, data on the extent of climate change or its impact on the region are meagre. Based on local knowledge, we report perceived changes in climate and consequences of such changes for biodiversity and agriculture. Our analyses are based on 250 household interviews administered in 18 villages, and focused group discussions conducted in 10 additional villages in Darjeeling Hills, West Bengal, India and Ilam district of Nepal. There is a widespread feeling that weather is getting warmer, the water sources are drying up, the onset of summer and monsoon has advanced during last 10 years and there is less snow on mountains than before. Local perceptions of the impact of climate change on biodiversity included early budburst and flowering, new agricultural pests and weeds and appearance of mosquitoes. People at high altitudes appear more sensitive to climate change than those at low altitudes. Most local perceptions conform to scientific data. Local knowledge can be rapidly and efficiently gathered using systematic tools. Such knowledge can allow scientists to test specific hypotheses, and policy makers to design mitigation and adaptation strategies for climate change, especially in an extraordinarily important part of our world that is experiencing considerable change.

The effect of pre-tectonic reaction and annealing extent on behaviour during subsequent deformation: Insights from paired shear zones in the lower crust of Fiordland, New Zealand

NASA Astrophysics Data System (ADS)

Piazolo, Sandra; Daczko, Nathan R.; Smith, James R.; Evans, Lynn

2015-04-01

The effect of pre-tectonic reaction and annealing extent on the rheology of lower crustal rocks during a subsequent deformation event was studied using field and detailed microstructural analyses combined with numerical simulations to examine. In the studied rocks (Pembroke granulite, South Island, New Zealand) granulite facies two-pyroxene-pargasite orthogneiss partially to completely reacted to garnet bearing granulite either side of felsic dykes. The metamorphic reaction not only changed the abundance of phases but also their shape and grain size distribution. The reaction is most advanced close to the dykes, whereas further away the reaction is incomplete. As a consequence, grain size and the abundance of the rheologically hard phase garnet decreases away from the felsic dykes. Aspect ratios of mafic clusters which may include garnet decrease from high in the host, to near equidimensional close to the dyke. Post-reaction deformation localized in those areas that experienced minor to moderate reaction extent producing two spaced "paired" shear zones within the garnet-bearing reaction zone at either side of the felsic dykes. Our study shows how rock flow properties are governed by the pre-deformation history of a rock in terms of reaction and coupled annealing extent. If the grain size is sufficiently reduced by metamorphic reaction, deformation localizes in the partially finer grained rock domains, where deformation dominantly occurs by grain size sensitive deformation flow. Even if the reaction produces a nominally stronger phase (e.g. garnet) than the reactants, a local switch in dominant deformation behaviour from a grain size insensitive to a grain size sensitive in reaction induced fine-grained portions of the rock may occur and result in significant strain localization.

Linear regression metamodeling as a tool to summarize and present simulation model results.

PubMed

Jalal, Hawre; Dowd, Bryan; Sainfort, François; Kuntz, Karen M

2013-10-01

Modelers lack a tool to systematically and clearly present complex model results, including those from sensitivity analyses. The objective was to propose linear regression metamodeling as a tool to increase transparency of decision analytic models and better communicate their results. We used a simplified cancer cure model to demonstrate our approach. The model computed the lifetime cost and benefit of 3 treatment options for cancer patients. We simulated 10,000 cohorts in a probabilistic sensitivity analysis (PSA) and regressed the model outcomes on the standardized input parameter values in a set of regression analyses. We used the regression coefficients to describe measures of sensitivity analyses, including threshold and parameter sensitivity analyses. We also compared the results of the PSA to deterministic full-factorial and one-factor-at-a-time designs. The regression intercept represented the estimated base-case outcome, and the other coefficients described the relative parameter uncertainty in the model. We defined simple relationships that compute the average and incremental net benefit of each intervention. Metamodeling produced outputs similar to traditional deterministic 1-way or 2-way sensitivity analyses but was more reliable since it used all parameter values. Linear regression metamodeling is a simple, yet powerful, tool that can assist modelers in communicating model characteristics and sensitivity analyses.

Energy dispersive X-ray analyses of organelles of NaCI-treated maize root cells

NASA Astrophysics Data System (ADS)

Stelzer, Ralf

1984-04-01

NaCl sensitive plants of Zea mays cv. ADOUR were grown in nutrient solutions with or without NaCl. Frozen, hydrated root-tip tissues were investigated by means of an ETEC scanning electron microscope fitted with a KEVEX energy dispersive X-ray analyser. Morphological details of the gently etched but non-coated surface of the cross fractured specimen were easy to identify and to analyse using an electron beam with a low intensity at 10 kV. X-ray data obtained from cell compartments and organelles as nuclei, nucleoli and mitochondria within individual cells establish typical X-ray spectra. Comparisons of these spectra support the hypothesis that Na + ions are predominantly localized in vacuoles and also to a lesser extent in the cytoplasm, e.g. in small vesicles, but not in other cell organelles. Furthermore the analysed cell compartments show differences in the distribution of Mg, P, S, Cl, K and Ca effected by the addition of NaCl to the growth medium. The X-ray data are discussed in relation to the physiological meaning of a NaCl induced redistribution of elements within individual maize root cells.

A mathematical model of the mevalonate cholesterol biosynthesis pathway.

PubMed

Pool, Frances; Currie, Richard; Sweby, Peter K; Salazar, José Domingo; Tindall, Marcus J

2018-04-14

We formulate, parameterise and analyse a mathematical model of the mevalonate pathway, a key pathway in the synthesis of cholesterol. Of high clinical importance, the pathway incorporates rate limiting enzymatic reactions with multiple negative feedbacks. In this work we investigate the pathway dynamics and demonstrate that rate limiting steps and negative feedbacks within it act in concert to tightly regulate intracellular cholesterol levels. Formulated using the theory of nonlinear ordinary differential equations and parameterised in the context of a hepatocyte, the governing equations are analysed numerically and analytically. Sensitivity and mathematical analysis demonstrate the importance of the two rate limiting enzymes 3-hydroxy-3-methylglutaryl-CoA reductase and squalene synthase in controlling the concentration of substrates within the pathway as well as that of cholesterol. The role of individual feedbacks, both global (between that of cholesterol and sterol regulatory element-binding protein 2; SREBP-2) and local internal (between substrates in the pathway) are investigated. We find that whilst the cholesterol SREBP-2 feedback regulates the overall system dynamics, local feedbacks activate within the pathway to tightly regulate the overall cellular cholesterol concentration. The network stability is analysed by constructing a reduced model of the full pathway and is shown to exhibit one real, stable steady-state. We close by addressing the biological question as to how farnesyl-PP levels are affected by CYP51 inhibition, and demonstrate that the regulatory mechanisms within the network work in unison to ensure they remain bounded. Copyright © 2018 Elsevier Ltd. All rights reserved.

Differential heat sensitivity index in barley cultivars (Hordeum vulgare L.) monitored by chlorophyll a fluorescence OKJIP.

PubMed

Oukarroum, Abdallah; El Madidi, Saïd; Strasser, Reto J

2016-08-01

The objective of this study was to differentiate the heat tolerance in ten varieties of barley (Hordeum vulgare L.) originating from Morocco. Five modern varieties and five landraces (local varieties) collected at five different geographical localities in the south of Morocco were investigated in the present study. After two weeks of growth, detached leaves were short term exposure to various temperatures (25, 30, 35, 40, and 45 °C) for 10 min in the dark. Two chlorophyll a fluorescence parameters derived from chlorophyll a fluorescence transient (OKJIP) (performance index (PIABS) and relative variable fluorescence at the K-step (VK)) were analysed. Heat treatment had a significant effect on the PIABS and VK at 45 °C treatment and the analysis of variance for PIABS and VK is highly significant between all varieties. The slope of the relationship between logPIABS and VK named heat sensitivity index (HSI) was used to evaluate the thermotolerance of photosystem II (PSII) between the studied barley varieties. According to this approach, barley varieties were screened and ranked for improving heat tolerance. HSI was found to be a new indicator with regard to distinguishing heat tolerance of different barley cultivars. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chemical applicability domain of the Local Lymph Node Assay (LLNA) for skin sensitisation potency. Part 3. Apparent discrepancies between LLNA and GPMT sensitisation potential: False positives or differences in sensitivity?

PubMed

Roberts, David W; Schultz, Terry W; Api, Anne Marie

2016-10-01

The Local Lymph Node Assay (LLNA) is the gold standard regulatory toxicology test for skin sensitisation along with the guinea pig maximisation test (GPMT). Compared with the GPMT, LLNA uses fewer animals, it is quantitative, and it gives a numerical prediction of potency. However several concerns have been raised with this assay, mainly related to false positives and false negatives. Over the years, many authors, including the developers of the assay, have presented cases where there have been discrepancies between the GMPT and LLNA results. Several theories have been put forward for these discrepancies, the main one being the "over-sensitivity" of the GPMT. This paper analyses the data from a systematic study, published in three papers from 2008 to 2011, covering several classes of chemicals, in particular unsaturated fatty acids, sugar surfactants and ethoxylated alcohols, with many cases of chemicals testing positive in the LLNA being negative in the GPMT. Based on consideration of reaction chemistry and structural alerts, it is concluded that these discrepancies are not LLNA false positives, but can be rationalised in terms of the different protocols of the assays. Copyright © 2016 Elsevier Inc. All rights reserved.

Re-evaluating the Localization of Sperm-Retained Histones Revealed the Modification-Dependent Accumulation in Specific Genome Regions.

PubMed

Yamaguchi, Kosuke; Hada, Masashi; Fukuda, Yuko; Inoue, Erina; Makino, Yoshinori; Katou, Yuki; Shirahige, Katsuhiko; Okada, Yuki

2018-06-26

The question of whether retained histones in the sperm genome localize to gene-coding regions or gene deserts has been debated for years. Previous contradictory observations are likely caused by the non-uniform sensitivity of sperm chromatin to micrococcal nuclease (MNase) digestion. Sperm chromatin has a highly condensed but heterogeneous structure and is composed of 90%∼99% protamines and 1%∼10% histones. In this study, we utilized nucleoplasmin (NPM) to improve the solubility of sperm chromatin by removing protamines in vitro. NPM treatment efficiently solubilized histones while maintaining quality and quantity. Chromatin immunoprecipitation sequencing (ChIP-seq) analyses using NPM-treated sperm demonstrated the predominant localization of H4 to distal intergenic regions, whereas modified histones exhibited a modification-dependent preferential enrichment in specific genomic elements, such as H3K4me3 at CpG-rich promoters and H3K9me3 in satellite repeats, respectively, implying the existence of machinery protecting modified histones from eviction. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Polarization sensitive localization based super-resolution microscopy with a birefringent wedge

NASA Astrophysics Data System (ADS)

Sinkó, József; Gajdos, Tamás; Czvik, Elvira; Szabó, Gábor; Erdélyi, Miklós

2017-03-01

A practical method has been presented for polarization sensitive localization based super-resolution microscopy using a birefringent dual wedge. The measurement of the polarization degree at the single molecule level can reveal the chemical and physical properties of the local environment of the fluorescent dye molecule and can hence provide information about the sub-diffraction sized structure of biological samples. Polarization sensitive STORM imaging of the F-Actins proved correlation between the orientation of fluorescent dipoles and the axis of the fibril.

Southern African continental climate since the late Pleistocene: Insights from biomarker analyses of Kalahari salt pan sediments

NASA Astrophysics Data System (ADS)

Belz, Lukas; Schüller, Irka; Wehrmann, Achim; Wilkes, Heinz

2016-04-01

The climate system of sub-tropical southern Africa is mainly controlled by large scale atmospheric and marine circulation processes and, therefore, very sensitive to global climate change. This underlines the importance of paleoenvironmental reconstructions in order to estimate regional implications of current global changes. However, the majority of studies on southern African paleoclimate are based on the investigation of marine sedimentary archives and past climate development especially in continental areas is still poorly understood. This emphasizes the necessity of continental proxy-data from this area. Proxy datasets from local geoarchives especially of the southwestern Kalahari region are still scarce. A main problem is the absence of conventional continental climatic archives, due to the lack of lacustrine systems. In this study we are exploring the utility of sediments from western Kalahari salt pans, i.e. local depressions which are flooded temporarily during rainfall events. An age model based on 14C dating of total organic carbon (TOC) shows evidence that sedimentation predominates over erosional processes with respect to pan formation. Besides the analyses of basic geochemical bulk parameters including TOC, δ13CTOC, total inorganic carbon, δ13CTIC, δ18OTIC, total nitrogen and δ15N, our paleo-climatic approach focuses on reconstruction of local vegetation assemblages to identify changes in the ecosystem. This is pursued using plant biomarkers, particularly leaf wax n-alkanes and n-alcohols and their stable carbon and hydrogen isotopic signatures. Results show prominent shifts in n-alkane and n-alkanol distributions and compound specific carbon isotope values, pointing to changes to a more grass dominated environment during Heinrich Stadial 1 (18.5-14.6 ka BP), while hydrogen isotope values suggest wetter phases during Holocene and LGM. This high variability indicates the local vulnerability to global change.

Technological advances in cosmogenic neutron detectors for measuring soil water content

NASA Astrophysics Data System (ADS)

Zreda, M. G.; Schrön, M.; Köhli, M.

2017-12-01

The cosmic-ray neutron probe is used for measuring area-average soil water content at the hectometer scale. Early work showed a simple exponential decrease with distance of the instrument's sensitivity and a footprint 300 m in radius. Recent research suggested a much higher sensitivity to local neutrons and reduced footprint. We show results confirming the high sensitivity to local neutrons, describe two ways to reduce local and increase far-field effects, and propose ways of measuring neutrons at different spatial scales. Measurements with moderated detectors across a 10-m-wide creek and a 2-m-wide water tank show a decrease by 30% and 20%, respectively, of neutron intensity over water compared to that over land nearby. These results mean that the detector is sensitive to meter-scale heterogeneities of water content. This sensitivity can be reduced by rising the detector or by shielding it from local neutrons. The effect of local water distributions on the measured neutron intensity decreases with height. In the water tank experiment it disappeared almost completely at the height of 2 m, leading to the conjecture that the height roughly equal to the horizontal scale of heterogeneity would eliminate the sensitivity. This may or may not be practical. Shielding the detector below by a hydrogenous material removes a substantial fraction of the local neutrons. The shielded detector has a reduced count rate, reduced sensitivity to local neutrons and increased sensitivity to neutrons farther afield, and a larger footprint. Such a detector could be preferable to the current cosmogenic-neutron probe under heterogeneous soil water conditions. The shielding experiments also inspired the development of a local-area neutron detector. It has hydrogenous neutron shields on all sides except the bottom, substantially blocking the neutrons coming from afar, while allowing the neutrons coming directly from below. Its footprint is equal to its physical dimension when the detector is placed on the surface. Once this detector is calibrated, it can be useful in calibrating the wide-area detector, for example over stony soils that are difficult to sample physically for water content determination, and in high-resolution mapping of neutron intensity and soil moisture.

Non-localization and localization ROC analyses using clinically based scoring

NASA Astrophysics Data System (ADS)

Paquerault, Sophie; Samuelson, Frank W.; Myers, Kyle J.; Smith, Robert C.

2009-02-01

We are investigating the potential for differences in study conclusions when assessing the estimated impact of a computer-aided detection (CAD) system on readers' performance. The data utilized in this investigation were derived from a multi-reader multi-case observer study involving one hundred mammographic background images to which fixed-size and fixed-intensity Gaussian signals were added, generating a low- and high-intensity signal sets. The study setting allowed CAD assessment in two situations: when CAD sensitivity was 1) superior or 2) lower than the average reader. Seven readers were asked to review each set in the unaided and CAD-aided reading modes, mark and rate their findings. Using this data, we studied the effect on study conclusion of three clinically-based receiver operating characteristic (ROC) scoring definitions. These scoring definitions included both location-specific and non-location-specific rules. The results showed agreement in the estimated impact of CAD on the overall reader performance. In the study setting where CAD sensitivity is superior to the average reader, the mean difference in AUC between the CAD-aided read and unaided read was 0.049 (95%CIs: -0.027; 0.130) for the image scoring definition that is based on non-location-specific rules, and 0.104 (95%CIs: 0.036; 0.174) and 0.090 (95%CIs: 0.031; 0.155) for image scoring definitions that are based on location-specific rules. The increases in AUC were statistically significant for the location-specific scoring definitions. It was further observed that the variance on these estimates was reduced when using the location-specific scoring definitions compared to that using a non-location-specific scoring definition. In the study setting where CAD sensitivity is equivalent or lower than the average reader, the mean differences in AUC are slightly above 0.01 for all image scoring definitions. These increases in AUC were not statistical significant for any of the image scoring definitions. The results on the variance analysis differed from those observed in the other study setting. This investigation furthers our understanding of the relationships between non-localization-specific and localization-specific ROC assessment methodologies and their relevance to clinical practice.

The population genomics of archaeological transition in west Iberia: Investigation of ancient substructure using imputation and haplotype-based methods

PubMed Central

Martiniano, Rui; McLaughlin, Russell; Silva, Nuno M.; Manco, Licinio; Pereira, Tania; Coelho, Maria J.; Serra, Miguel; Burger, Joachim; Parreira, Rui; Moran, Elena; Valera, Antonio C.; Silva, Ana M.

2017-01-01

We analyse new genomic data (0.05–2.95x) from 14 ancient individuals from Portugal distributed from the Middle Neolithic (4200–3500 BC) to the Middle Bronze Age (1740–1430 BC) and impute genomewide diploid genotypes in these together with published ancient Eurasians. While discontinuity is evident in the transition to agriculture across the region, sensitive haplotype-based analyses suggest a significant degree of local hunter-gatherer contribution to later Iberian Neolithic populations. A more subtle genetic influx is also apparent in the Bronze Age, detectable from analyses including haplotype sharing with both ancient and modern genomes, D-statistics and Y-chromosome lineages. However, the limited nature of this introgression contrasts with the major Steppe migration turnovers within third Millennium northern Europe and echoes the survival of non-Indo-European language in Iberia. Changes in genomic estimates of individual height across Europe are also associated with these major cultural transitions, and ancestral components continue to correlate with modern differences in stature. PMID:28749934

Hair Zinc: an Index for Zinc Status in Under-Five Children from Low-Income Communities in Kanam Area of North-Central Nigeria.

PubMed

Jaryum, Kiri H; Okoye, Zebulon Sunday C; Stoecker, Barbara

2018-06-01

Nutritional deficiencies of trace elements are among the top ten causes of death in Sub Saharan Africa. In Kanam Local Government Area of Nigeria, the problem is compounded by high levels of poverty and illiteracy. Abnormally low hair zinc levels are important, sensitive diagnostic biochemical indices of Zinc deficiency. The purpose of this study is to assess the zinc status of children less than 5 years in Kanam local government area, north-central Nigeria, by measuring the zinc level in hair samples collected from 44 under-5 children across the area. A household survey was made to assess the pattern and frequency of consumption of zinc-rich foods which was done by means of questionnaire. Hair samples were analysed for zinc content by the inductively coupled plasma-mass spectrophotometry (ICP-MS). The data were analysed statistically using the Student's t test, z test, and Pearson correlation, while questionnaire-captured data were analysed by simple arithmetic. The results of the analyses showed that the average hair zinc level was 74.35 ± 48.05 μg/g. This was below the normal range of 130-140 μg/g, for children less than 5 years. Based on the results, 86.36% have hair zinc level below the lower limit of the normal range of 130 μg/g. Between the gender, boys have higher hair zinc content than girls. Data from the questionnaire showed that 53.45% of the population studied have poor/inadequate intake of zinc-rich foods of animal origin, a dietary behaviour reported to predispose to micronutrient deficiency, including zinc.

Cost-Effectiveness of Screening for Intermediate Age-Related Macular Degeneration during Diabetic Retinopathy Screening.

PubMed

Chan, Christina K W; Gangwani, Rita A; McGhee, Sarah M; Lian, JinXiao; Wong, David S H

2015-11-01

To determine whether screening for age-related macular degeneration (AMD) during a diabetic retinopathy (DR) screening program would be cost effective in Hong Kong. We compared and evaluated the impacts of screening, grading, and vitamin treatment for intermediate AMD compared with no screening using a Markov model. It was based on the natural history of AMD in a cohort with a mean age of 62 years, followed up until 100 years of age or death. Subjects attending a DR screening program were recruited. A cost-effectiveness analysis was undertaken from a public provider perspective. It included grading for AMD using the photographs obtained for DR screening and treatment with vitamin therapy for those with intermediate AMD. The measures of effectiveness were obtained largely from a local study, but the transition probabilities and utility values were from overseas data. Costs were all from local sources. The main assumptions and estimates were tested in sensitivity analyses. The outcome was cost per quality-adjusted life year (QALY) gained. Both costs and benefits were discounted at 3%. All costs are reported in United States dollars ($). The cost per QALY gained through screening for AMD and vitamin treatment for appropriate cases was $12,712 after discounting. This would be considered highly cost effective based on the World Health Organization's threshold of willingness to pay (WTP) for a QALY, that is, less than the annual per capita gross domestic product of $29,889. Because of uncertainty regarding the utility value for those with advanced AMD, we also tested an extreme, conservative value for utility under which screening remained cost effective. One-way sensitivity analyses revealed that, besides utility values, the cost per QALY was most sensitive to the progression rate from intermediate to advanced AMD. The cost-effectiveness acceptability curve showed a WTP for a QALY of $29,000 or more has a more than 86% probability of being cost effective compared with no screening. Our analysis demonstrated that AMD screening carried out simultaneously with DR screening for patients with diabetes would be cost effective in a Hong Kong public healthcare setting. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.

PubMed

Nurmatov, U; Dhami, S; Arasi, S; Pajno, G B; Fernandez-Rivas, M; Muraro, A; Roberts, G; Akdis, C; Alvaro-Lozano, M; Beyer, K; Bindslev-Jensen, C; Burks, W; du Toit, G; Ebisawa, M; Eigenmann, P; Knol, E; Makela, M; Nadeau, K C; O'Mahony, L; Papadopoulos, N; Poulsen, L K; Sackesen, C; Sampson, H; Santos, A F; van Ree, R; Timmermans, F; Sheikh, A

2017-08-01

The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT. © 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.

Perception of biomechanical motions by infants: implementation of various processing constraints.

PubMed

Bertenthal, B I; Proffitt, D R; Kramer, S J

1987-11-01

Geometry informs us that there exist a large number of possible connectivity patterns consistent with a point-light display of a person walking. Yet there is only one pattern consistent with a "stick figure" representation of the human form, and that pattern is uniquely specified by those pairwise connections that remain locally rigid. In this study, sensitivity to local rigidity in biomechanical displays was investigated in 3- and 5-month-old infants. The results of Experiment 1 revealed that by 5 months of age, infants discriminate a locally rigid point-light walker display from one in which local rigidity is perturbed. In Experiment 2 we tested infants' sensitivity to the same stimuli when those stimuli were inverted. Contrary to the preceding experiment, the results revealed no evidence of discrimination. Taken together, these findings suggest that infants are sensitive to local rigidity in biomechanical displays but that this sensitivity is orientation specific. Possible mechanisms for this specificity are discussed in the context of additional constraints on the processing of biomechanical displays.

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.

Assessment of cardiac fibrosis: a morphometric method comparison for collagen quantification.

PubMed

Schipke, Julia; Brandenberger, Christina; Rajces, Alexandra; Manninger, Martin; Alogna, Alessio; Post, Heiner; Mühlfeld, Christian

2017-04-01

Fibrotic remodeling of the heart is a frequent condition linked to various diseases and cardiac dysfunction. Collagen quantification is an important objective in cardiac fibrosis research; however, a variety of different histological methods are currently used that may differ in accuracy. Here, frequently applied collagen quantification techniques were compared. A porcine model of early stage heart failure with preserved ejection fraction was used as an example. Semiautomated threshold analyses were imprecise, mainly due to inclusion of noncollagen structures or failure to detect certain collagen deposits. In contrast, collagen assessment by automated image analysis and light microscopy (LM)-stereology was more sensitive. Depending on the quantification method, the amount of estimated collagen varied and influenced intergroup comparisons. PicroSirius Red, Masson's trichrome, and Azan staining protocols yielded similar results, whereas the measured collagen area increased with increasing section thickness. Whereas none of the LM-based methods showed significant differences between the groups, electron microscopy (EM)-stereology revealed a significant collagen increase between cardiomyocytes in the experimental group, but not at other localizations. In conclusion, in contrast to the staining protocol, section thickness and the quantification method being used directly influence the estimated collagen content and thus, possibly, intergroup comparisons. EM in combination with stereology is a precise and sensitive method for collagen quantification if certain prerequisites are considered. For subtle fibrotic alterations, consideration of collagen localization may be necessary. Among LM methods, LM-stereology and automated image analysis are appropriate to quantify fibrotic changes, the latter depending on careful control of algorithm and comparable section staining. NEW & NOTEWORTHY Direct comparison of frequently applied histological fibrosis assessment techniques revealed a distinct relation of measured collagen and utilized quantification method as well as section thickness. Besides electron microscopy-stereology, which was precise and sensitive, light microscopy-stereology and automated image analysis proved to be appropriate for collagen quantification. Moreover, consideration of collagen localization might be important in revealing minor fibrotic changes. Copyright © 2017 the American Physiological Society.

Local cost structures and the economics of robot assisted radical prostatectomy.

PubMed

Scales, Charles D; Jones, Peter J; Eisenstein, Eric L; Preminger, Glenn M; Albala, David M

2005-12-01

Robot assisted prostatectomy (RAP) is more costly than traditional radical retropubic prostatectomy (RRP) under the cost structures at certain hospitals. However, this finding may not be the case in all care settings. We investigated the sensitivity of RAP and RRP inpatient costs to variations in length of stay (LOS), local hospitalization costs and robotic case volume in the specialist and generalist settings. We developed a model of RAP vs RRP costs in the specialist and generalist settings using published data on operative time and LOS, and cost data from our academic medical center. All inpatient cost centers were included, namely surgery costs, professional fees, postoperative care, robotic equipment and service. Extensive 1 and 2-way sensitivity analyses were performed. Our base case model demonstrated a cost premium for RAP vs RRP of USD $783 and $195 in the specialist and generalist settings, respectively. Sensitivity analysis of our model assumptions demonstrated that RAP could achieve cost equivalence with RRP at a surgical volume of 10 cases weekly. If case volume increased to 14 cases weekly, RAP would be less expensive than RRP in some practice settings in which RAP LOS was less than 1.5 days. The inpatient costs of robotic assisted prostatectomy are volume dependent and cost equivalence with generalist radical retropubic prostatectomy is possible at higher volume RAP specialty centers. While RAP may be cost competitive with RRP at high cost hospitals or high volume RAP specialist centers, this procedure would exist at a cost premium to RRP in other practice settings.

Vulnerability assessment including tangible and intangible components in the index composition: An Amazon case study of flooding and flash flooding.

PubMed

Andrade, Milena Marília Nogueira de; Szlafsztein, Claudio Fabian

2018-07-15

The vulnerability of cities and communities in the Amazon to flooding and flash flooding is increasing. The effects of extreme events on populations vary across landscapes, causing vulnerability to differ spatially. Traditional vulnerability studies in Brazil and across the world have used the vulnerability index for the country and, more recently, municipality scales. The vulnerability dimensions are exposure, sensitivity, and adaptive capacity. For each of these dimensions, there is a group of indicators that constitutes a vulnerability index using quantitative data. Several vulnerability assessments have used sensitivity and exposure analyses and, recently, adaptive capacity has been considered. The Geographical Information Systems (GIS) analysis allows spatial regional modeling using quantitative vulnerability indicators. This paper presents a local-scale vulnerability assessment in an urban Amazonian area, Santarém City, using interdisciplinary methods. Data for exposure and sensitivity were gathered by remote sensing and census data, respectively. However, adaptive capacity refers to local capacities, whether infrastructural or not, and the latter were gathered by qualitative participatory methods. For the mixed data used to study adaptive capacity, we consider tangible components for countable infrastructure that can cope with hazards, and intangible components that reflect social activities based on risk perceptions and collective action. The results indicate that over 80% of the area is highly or moderately vulnerable to flooding and flash flooding. Exposure and adaptive capacity were determinants of the results. Lower values of adaptive capacity play a significant role in vulnerability enhancement. Copyright © 2018 Elsevier B.V. All rights reserved.

Locally refined block-centred finite-difference groundwater models: Evaluation of parameter sensitivity and the consequences for inverse modelling

USGS Publications Warehouse

Mehl, S.; Hill, M.C.

2002-01-01

Models with local grid refinement, as often required in groundwater models, pose special problems for model calibration. This work investigates the calculation of sensitivities and the performance of regression methods using two existing and one new method of grid refinement. The existing local grid refinement methods considered are: (a) a variably spaced grid in which the grid spacing becomes smaller near the area of interest and larger where such detail is not needed, and (b) telescopic mesh refinement (TMR), which uses the hydraulic heads or fluxes of a regional model to provide the boundary conditions for a locally refined model. The new method has a feedback between the regional and local grids using shared nodes, and thereby, unlike the TMR methods, balances heads and fluxes at the interfacing boundary. Results for sensitivities are compared for the three methods and the effect of the accuracy of sensitivity calculations are evaluated by comparing inverse modelling results. For the cases tested, results indicate that the inaccuracies of the sensitivities calculated using the TMR approach can cause the inverse model to converge to an incorrect solution.

Locally refined block-centered finite-difference groundwater models: Evaluation of parameter sensitivity and the consequences for inverse modelling and predictions

USGS Publications Warehouse

Mehl, S.; Hill, M.C.

2002-01-01

Models with local grid refinement, as often required in groundwater models, pose special problems for model calibration. This work investigates the calculation of sensitivities and performance of regression methods using two existing and one new method of grid refinement. The existing local grid refinement methods considered are (1) a variably spaced grid in which the grid spacing becomes smaller near the area of interest and larger where such detail is not needed and (2) telescopic mesh refinement (TMR), which uses the hydraulic heads or fluxes of a regional model to provide the boundary conditions for a locally refined model. The new method has a feedback between the regional and local grids using shared nodes, and thereby, unlike the TMR methods, balances heads and fluxes at the interfacing boundary. Results for sensitivities are compared for the three methods and the effect of the accuracy of sensitivity calculations are evaluated by comparing inverse modelling results. For the cases tested, results indicate that the inaccuracies of the sensitivities calculated using the TMR approach can cause the inverse model to converge to an incorrect solution.

Modelling responses of the inert-gas washout and MRI to bronchoconstriction.

PubMed

Foy, Brody H; Kay, David; Bordas, Rafel

2017-01-01

Many lung diseases lead to an increase in ventilation heterogeneity (VH). Two clinical practices for the measurement of patient VH are in vivo imaging, and the inert gas multiple breath washout (MBW). In this study computational modelling was used to compare the responses of MBW indices LCI and s cond and MRI measured global and local ventilation indices, σ r and σ local , to constriction of airways in the conducting zone of the lungs. The simulations show that s cond , LCI and σ r behave quite similarly to each other, all being sensitive to increases in the severity of constriction, while exhibiting little sensitivity to the depth at which constriction occurs. In contrast, the local MRI index σ local shows strong sensitivity to depth of constriction, but lowered sensitivity to constriction severity. We finish with an analysis of the sensitivity of MRI indices to grid sizes, showing that results should be interpreted with reference to the image resolution. Overall we conclude that the application of both local and global VH measures may help to classify different types of bronchoconstriction. Copyright © 2016 Elsevier B.V. All rights reserved.

Sensitivity enhancement of traveling wave MRI using free local resonators: an experimental demonstration.

PubMed

Zhang, Xiaoliang

2017-04-01

Traveling wave MR uses the far fields in signal excitation and reception, therefore its acquisition efficiency is low in contrast to the conventional near field magnetic resonance (MR). Here we show a simple and efficient method based on the local resonator to improving sensitivity of traveling wave MR technique. The proposed method utilizes a standalone or free local resonator to amplify the radio frequency magnetic fields in the interested target. The resonators have no wire connections to the MR system and thus can be conveniently placed to any place around imaging simples. A rectangular loop L/C resonator to be used as the free local resonator was tuned to the proton Larmor frequency at 7T. Traveling wave MR experiments with and without the wireless free local resonator were performed on a living rat using a 7T whole body MR scanner. The signal-to-noise ratio (SNR) or sensitivity of the images acquired was compared and evaluated. In vivo 7T imaging results show that traveling wave MR with a wireless free local resonator placed near the head of a living rat achieves at least 10-fold SNR gain over the images acquired on the same rat using conventional traveling wave MR method, i.e. imaging with no free local resonators. The proposed free local resonator technique is able to enhance the MR sensitivity and acquisition efficiency of traveling wave MR at ultrahigh fields in vivo . This method can be a simple solution to alleviating low sensitivity problem of traveling wave MRI.

Development and Utilization of an Ex Vivo Bromodeoxyuridine Local Lymph Node Assay (LLNA) Protocol for Assessing Potential Chemical Sensitizers

EPA Science Inventory

The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [3H]m...

Multiplex PCR detection of Cryptosporidium sp, Giardia lamblia and Entamoeba histolytica directly from dried stool samples from Guinea-Bissauan children with diarrhoea.

PubMed

Mero, Sointu; Kirveskari, Juha; Antikainen, Jenni; Ursing, Johan; Rombo, Lars; Kofoed, Poul-Erik; Kantele, Anu

2017-09-01

In developing countries, diarrhoea is the most common cause of death for children under five years of age, with Giardia lamblia, Cryptosporidium and Entamoeba histolytica as the most frequent pathogenic parasites. Traditional microscopy for stool parasites has poor sensitivity and specificity, while new molecular methods may provide more accurate diagnostics. In poor regions with sample storage hampered by uncertain electricity supply, research would benefit from a method capable of analysing dried stools. A real-time multiplex PCR method with internal inhibition control was developed for detecting Giardia lamblia, Cryptosporidium hominis/parvum and Entamoeba histolytica directly from stool specimens. Applicability to dried samples was checked by comparing with fresh ones in a small test material. Finally, the assay was applied to dried specimens collected from Guinea-Bissauan children with diarrhoea. The PCR's analytical sensitivity limit was 0.1 ng/ml for G. lamblia DNA, 0.01 ng/ml for E. histolytica DNA and 0.1 ng/ml for Cryptosporidium sp. In the test material, the assay performed similarly with fresh and dried stools. Of the 52 Guinea-Bissauan samples, local microscopy revealed a parasite in 15%, while PCR detected 62% positive for at least one parasite: 44% of the dried samples had Giardia, 23% Cryptosporidium and 0% E. histolytica. Our new multiplex real-time PCR for protozoa presents a sensitive method applicable to dried samples. As proof of concept, it worked well on stools collected from Guinea-Bissauan children with diarrhoea. It provides an epidemiological tool for analysing dried specimens from regions poor in resources.

Cost-effectiveness Analysis of Stereotactic Radiosurgery Alone Versus Stereotactic Radiosurgery with Upfront Whole Brain Radiation Therapy for Brain Metastases.

PubMed

Kim, H; Rajagopalan, M S; Beriwal, S; Smith, K J

2017-10-01

Stereotactic radiosurgery (SRS) alone or upfront whole brain radiation therapy (WBRT) plus SRS are the most commonly used treatment options for one to three brain oligometastases. The most recent randomised clinical trial result comparing SRS alone with upfront WBRT plus SRS (NCCTG N0574) has favoured SRS alone for neurocognitive function, whereas treatment options remain controversial in terms of cognitive decline and local control. The aim of this study was to conduct a cost-effectiveness analysis of these two competing treatments. A Markov model was constructed for patients treated with SRS alone or SRS plus upfront WBRT based on largely randomised clinical trials. Costs were based on 2016 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER) and effectiveness was measured in quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were carried out. Strategies were evaluated from the healthcare payer's perspective with a willingness-to-pay threshold of $100 000 per QALY gained. In the base case analysis, the median survival was 9 months for both arms. SRS alone resulted in an ICER of $9917 per QALY gained. In one-way sensitivity analyses, results were most sensitive to variation in cognitive decline rates for both groups and median survival rates, but the SRS alone remained cost-effective for most parameter ranges. Based on the current available evidence, SRS alone was found to be cost-effective for patients with one to three brain metastases compared with upfront WBRT plus SRS. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Localized periorbital edema as a clinical manifestation of sulfite sensitivity.

PubMed

Park, H S; Nahm, D

1996-08-01

Sulfite is commonly used in pharmaceuticals as a preservative. We report a unique clinical presentation of localized periorbital edema on the left eye after administration of sulfite-containing dexamethasone. The patient's sulfite sensitivity was confirmed by sulfite oral provocation test: periorbital edema on the same site developed after ingestion of 200 mg sodium bisulfite. She was non-atopic and did not complain of any respiratory symptoms. Allergy skin prick test with 100 mg/ml sodium bisulfite showed a negative result. She also has aspirin-sensitive urticaria which was confirmed by oral provocation test. In conclusion, sulfite can induce a localized periorbital edema, an uncommon manifestation in sensitive patients. Further investigations are needed to clarify the pathogenetic mechanisms.

Sensitivity analysis of a wing aeroelastic response

NASA Technical Reports Server (NTRS)

Kapania, Rakesh K.; Eldred, Lloyd B.; Barthelemy, Jean-Francois M.

1991-01-01

A variation of Sobieski's Global Sensitivity Equations (GSE) approach is implemented to obtain the sensitivity of the static aeroelastic response of a three-dimensional wing model. The formulation is quite general and accepts any aerodynamics and structural analysis capability. An interface code is written to convert one analysis's output to the other's input, and visa versa. Local sensitivity derivatives are calculated by either analytic methods or finite difference techniques. A program to combine the local sensitivities, such as the sensitivity of the stiffness matrix or the aerodynamic kernel matrix, into global sensitivity derivatives is developed. The aerodynamic analysis package FAST, using a lifting surface theory, and a structural package, ELAPS, implementing Giles' equivalent plate model are used.

Innovative Ge Quantum Dot Functional Sensing/Metrology Devices

DTIC Science & Technology

2015-05-20

sensitive to charge number and local temperature with unprecedented precision. Accordingly we have made progresses in the innovative functionalities...sensors feature excellent sensitivity on charge number, local temperature, and photoresponsivity in the visible to near IR wavelength.  “Designer” Ge...Detailed knowledge and understanding of how the QDs are created, and especially their interactions with their local environments are therefore crucial to

Cost-Sensitive Local Binary Feature Learning for Facial Age Estimation.

PubMed

Lu, Jiwen; Liong, Venice Erin; Zhou, Jie

2015-12-01

In this paper, we propose a cost-sensitive local binary feature learning (CS-LBFL) method for facial age estimation. Unlike the conventional facial age estimation methods that employ hand-crafted descriptors or holistically learned descriptors for feature representation, our CS-LBFL method learns discriminative local features directly from raw pixels for face representation. Motivated by the fact that facial age estimation is a cost-sensitive computer vision problem and local binary features are more robust to illumination and expression variations than holistic features, we learn a series of hashing functions to project raw pixel values extracted from face patches into low-dimensional binary codes, where binary codes with similar chronological ages are projected as close as possible, and those with dissimilar chronological ages are projected as far as possible. Then, we pool and encode these local binary codes within each face image as a real-valued histogram feature for face representation. Moreover, we propose a cost-sensitive local binary multi-feature learning method to jointly learn multiple sets of hashing functions using face patches extracted from different scales to exploit complementary information. Our methods achieve competitive performance on four widely used face aging data sets.

Localized movement and morphology of UBF1-positive nucleolar regions are changed by γ-irradiation in G2 phase of the cell cycle

PubMed Central

Sorokin, Dmitry V; Stixová, Lenka; Sehnalová, Petra; Legartová, Soňa; Suchánková, Jana; Šimara, Pavel; Kozubek, Stanislav; Matula, Pavel; Skalníková, Magdalena; Raška, Ivan; Bártová, Eva

2015-01-01

The nucleolus is a well-organized site of ribosomal gene transcription. Moreover, many DNA repair pathway proteins, including ATM, ATR kinases, MRE11, PARP1 and Ku70/80, localize to the nucleolus (Moore et al., 2011). We analyzed the consequences of DNA damage in nucleoli following ultraviolet A (UVA), C (UVC), or γ-irradiation in order to test whether and how radiation-mediated genome injury affects local motion and morphology of nucleoli. Because exposure to radiation sources can induce changes in the pattern of UBF1-positive nucleolar regions, we visualized nucleoli in living cells by GFP-UBF1 expression for subsequent morphological analyses and local motion studies. UVA radiation, but not 5 Gy of γ-rays, induced apoptosis as analyzed by an advanced computational method. In non-apoptotic cells, we observed that γ-radiation caused nucleolar re-positioning over time and changed several morphological parameters, including the size of the nucleolus and the area of individual UBF1-positive foci. Radiation-induced nucleoli re-arrangement was observed particularly in G2 phase of the cell cycle, indicating repair of ribosomal genes in G2 phase and implying that nucleoli are less stable, thus sensitive to radiation, in G2 phase. PMID:26208041

Associations between malaria and local and global climate variability in five regions in Papua New Guinea.

PubMed

Imai, Chisato; Cheong, Hae-Kwan; Kim, Ho; Honda, Yasushi; Eum, Jin-Hee; Kim, Clara T; Kim, Jin Seob; Kim, Yoonhee; Behera, Swadhin K; Hassan, Mohd Nasir; Nealon, Joshua; Chung, Hyenmi; Hashizume, Masahiro

2016-01-01

Malaria is a significant public health issue in Papua New Guinea (PNG) as the burden is among the highest in Asia and the Pacific region. Though PNG's vulnerability to climate change and sensitivity of malaria mosquitoes to weather are well-documented, there are few in-depth epidemiological studies conducted on the potential impacts of climate on malaria incidence in the country. This study explored what and how local weather and global climate variability impact on malaria incidence in five regions of PNG. Time series methods were applied to evaluate the associations of malaria incidence with weather and climate factors, respectively. Local weather factors including precipitation and temperature and global climate phenomena such as El Niño-Southern Oscillation (ENSO), the ENSO Modoki, the Southern Annular Mode, and the Indian Ocean Dipole were considered in analyses. The results showed that malaria incidence was associated with local weather factors in most regions but at the different lag times and in directions. Meanwhile, there were trends in associations with global climate factors by geographical locations of study sites. Overall heterogeneous associations suggest the importance of location-specific approaches in PNG not only for further investigations but also public health interventions in repose to the potential impacts arising from climate change.

'McDonalds and KFC, it's never going to happen': the challenges of working with food outlets to tackle the obesogenic environment.

PubMed

Hanratty, Barbara; Milton, Beth; Ashton, Matthew; Whitehead, Margaret

2012-12-01

Food outlets may make an important contribution to an obesogenic environment. This study investigated barriers and facilitators to public health work with food outlets in disadvantaged areas. In-depth qualitative interviews with 36 directors, managers and public health service delivery staff in a coterminous primary care trust and local authority in northwest England. Data were analysed using the constant comparative method. Three interventions were available to engage with businesses; awards for premises that welcomed breastfeeding mothers or offered healthy menu options and local authority planning powers. Sensitivity to the potential conflict between activities that generate profit and those that promote health, led to compromises, such as awards for cafés that offer only one healthy option on an otherwise unhealthy menu. An absence of existing relationships with businesses and limited time were powerful disincentives to action, leading to greater engagement with public rather than private sector organizations. Hiring staff with commercial experience and incentives for businesses were identified as useful strategies, but seldom used. Encouraging food outlets to contribute to tackling the obesogenic environment is a major challenge for local public health teams that requires supportive national policies. Commitment to engage with the local public health service should be part of any national voluntary agreements with industry.

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.

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.

An Enhanced Platform to Analyse Low-Affinity Amyloid β Protein by Integration of Electrical Detection and Preconcentrator.

PubMed

Yoo, Yong Kyoung; Yoon, Dae Sung; Kim, Gangeun; Kim, Jinsik; Han, Sung Il; Lee, Junwoo; Chae, Myung-Sic; Lee, Sang-Myung; Lee, Kyu Hyoung; Hwang, Kyo Seon; Lee, Jeong Hoon

2017-10-30

Sensitivity and limit of detection (LOD) enhancement are essential criteria for the development of ultrasensitive molecular sensors. Although various sensor types have been investigated to enhance sensitivity and LOD, analyte detection and its quantification are still challenging, particularly for protein-protein interactions with low association constants. To solve this problem, here, we used ion concentration polarization (ICP)-based preconcentration to increase the local concentration of analytes in a microfluidic platform for LOD improvement. This was the first demonstration of a microfluidic device with an integrated ICP preconcentrator and interdigitated microelectrode (IME) sensor to detect small changes in surface binding between antigens and antibodies. We detected the amyloid beta (Aβ) protein, an Alzheimer's disease marker, with low binding affinity to its antibodies by adopting ICP preconcentration phenomena. We demonstrated that a combination of ICP preconcentrator and IME sensor increased the LOD by 13.8-fold to femtomolar level (8.15 fM), which corresponds to a significant advance for clinical applications.

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

NASA Technical Reports Server (NTRS)

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

1984-01-01

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

Nosocomial pneumonia: Search for an empiric and effective antibiotic regimen in high burden tertiary care centre.

PubMed

Gupta, Nitin; Soneja, Manish; Ray, Yogiraj; Sahu, Monalisa; Vinod, Kutty Sharada; Kapil, Arti; Biswas, Ashutosh; Wig, Naveet; Sood, Rita

2018-05-13

The clinical practice guidelines on nosocomial pneumonia recommends an empirical regimen that would work in 95% of the patients based on the local antibiogram. The aim of the study was development of an antibiogram for guiding empiric therapy in settings with high prevalence of multi-drug resistant organisms. A retrospective review of electronic health records (e-hospital portal) was done to analyze all respiratory isolates from patients admitted in medical wards and intensive care unit between May 2016 and May 2017. The samples included brocho-alveolar lavage (BAL), mini broncho-alveolar lavage (mini-BAL) and endotracheal aspirate. The sensitivity pattern (combined and individual) of all bacterial isolates were analysed for commonly used antibiotics and their combinations. Out of the 269 isolates, the most common organisms were Pseudomonas aeruginosa (125, 46%), Acinetobacter baumanni (74, 27%) and Klebsiella pneumoniae (50, 19%). Cefoperazone-sulbactam (43%) had the best sensitivity pattern overall. Cefoperazone-sulbactam plus amikacin (56%) was the combination with the best combined sensitivity overall. There is a high prevalence of resistance in the commonly implicated organisms to the available antibiotics. There is an urgent need for implementation of effective anti-microbial stewardship programmes and development of newer antimicrobials.

Localized periorbital edema as a clinical manifestation of sulfite sensitivity.

PubMed Central

Park, H. S.; Nahm, D.

1996-01-01

Sulfite is commonly used in pharmaceuticals as a preservative. We report a unique clinical presentation of localized periorbital edema on the left eye after administration of sulfite-containing dexamethasone. The patient's sulfite sensitivity was confirmed by sulfite oral provocation test: periorbital edema on the same site developed after ingestion of 200 mg sodium bisulfite. She was non-atopic and did not complain of any respiratory symptoms. Allergy skin prick test with 100 mg/ml sodium bisulfite showed a negative result. She also has aspirin-sensitive urticaria which was confirmed by oral provocation test. In conclusion, sulfite can induce a localized periorbital edema, an uncommon manifestation in sensitive patients. Further investigations are needed to clarify the pathogenetic mechanisms. PMID:8878807

Does media coverage influence the spread of drug addiction?

NASA Astrophysics Data System (ADS)

Ma, Mingju; Liu, Sanyang; Li, Jun

2017-09-01

In this paper, a three dimensional drug model is constructed to investigate the impact of media coverage on the spread and control of drug addiction. The dynamical behavior of the model is studied by using the basic reproduction number R0. The drug-free equilibrium is globally asymptotically stable if R0 < 1 and the drug addiction equilibrium is locally stable if R0 > 1. The results demonstrate that the media effect in human population cannot change the stabilities of equilibria but can affect the number of drug addicts. Sensitivity analyses are performed to seek for effective control measures for drug treatment. Numerical simulations are given to support the theoretical results.

Subcellular localization patterns and their relationship to photodynamic activity of pyropheophorbide-a derivatives.

PubMed

MacDonald, I J; Morgan, J; Bellnier, D A; Paszkiewicz, G M; Whitaker, J E; Litchfield, D J; Dougherty, T J

1999-11-01

To determine if subcellular localization is important to photodynamic therapy (PDT) efficacy, an in vitro fluorescence microscopy study was conducted with a congeneric series of pyropheophorbide-a derivatives in human pharyngeal squamous cell carcinoma (FaDu) cells and murine radiation-induced fibrosarcoma (RIF) mutant cells. In the FaDu cells the octyl, decyl and dodecyl ether derivatives localized to the lysosomes at extracellular concentrations less than needed to produce a 50% cell kill (LD50). At extracellular concentrations equal or greater than the LD50 the compounds localized mainly to mitochondria. The propyl, pentyl, hexyl and heptyl ether derivatives localized mainly to the mitochondria at all concentrations studied. This suggested that mitochondria are a sensitive PDT target for these derivatives. Similar experiments were performed with two Photofrin-PDT resistant RIF cell lines, one of which was found to be resistant to hexyl ether derivative (C6) mediated-PDT and the other sensitive to C6-PDT relative to the parent line. At extracellular concentrations of C6 below the LD50 of each cell line, the mutants exhibited lysosomal localization. At concentrations above these values the patterns shifted to a mainly mitochondrial pattern. In these cell lines mitochondrial localization also correlated with PDT sensitivity. Localization to mitochondria or lysosomes appeared to be affected by the aggregation state of the congeners, all of which are highly aggregated in aqueous medium. Monomers apparently were the active fraction of these compounds because equalizing the extracellular monomer concentrations produced equivalent intracellular concentrations, photoxicity and localization patterns. Compounds that were mainly aggregates localized to the lysosomes where they were rendered less active. Mitochondria appear to be a sensitive target for pyropheophorbide-a-mediated photodamage, and the degree of aggregation seems to be a determinant of the localization site.

Cryptochrome 1 in Retinal Cone Photoreceptors Suggests a Novel Functional Role in Mammals

PubMed Central

Nießner, Christine; Denzau, Susanne; Malkemper, Erich Pascal; Gross, Julia Christina; Burda, Hynek; Winklhofer, Michael; Peichl, Leo

2016-01-01

Cryptochromes are a ubiquitous group of blue-light absorbing flavoproteins that in the mammalian retina have an important role in the circadian clock. In birds, cryptochrome 1a (Cry1a), localized in the UV/violet-sensitive S1 cone photoreceptors, is proposed to be the retinal receptor molecule of the light-dependent magnetic compass. The retinal localization of mammalian Cry1, homologue to avian Cry1a, is unknown, and it is open whether mammalian Cry1 is also involved in magnetic field sensing. To constrain the possible role of retinal Cry1, we immunohistochemically analysed 90 mammalian species across 48 families in 16 orders, using an antiserum against the Cry1 C-terminus that in birds labels only the photo-activated conformation. In the Carnivora families Canidae, Mustelidae and Ursidae, and in some Primates, Cry1 was consistently labeled in the outer segment of the shortwave-sensitive S1 cones. This finding would be compatible with a magnetoreceptive function of Cry1 in these taxa. In all other taxa, Cry1 was not detected by the antiserum that likely also in mammals labels the photo-activated conformation, although Western blots showed Cry1 in mouse retinal cell nuclei. We speculate that in the mouse and the other negative-tested mammals Cry1 is involved in circadian functions as a non-light-responsive protein. PMID:26898837

Cryptochrome 1 in Retinal Cone Photoreceptors Suggests a Novel Functional Role in Mammals.

PubMed

Nießner, Christine; Denzau, Susanne; Malkemper, Erich Pascal; Gross, Julia Christina; Burda, Hynek; Winklhofer, Michael; Peichl, Leo

2016-02-22

Cryptochromes are a ubiquitous group of blue-light absorbing flavoproteins that in the mammalian retina have an important role in the circadian clock. In birds, cryptochrome 1a (Cry1a), localized in the UV/violet-sensitive S1 cone photoreceptors, is proposed to be the retinal receptor molecule of the light-dependent magnetic compass. The retinal localization of mammalian Cry1, homologue to avian Cry1a, is unknown, and it is open whether mammalian Cry1 is also involved in magnetic field sensing. To constrain the possible role of retinal Cry1, we immunohistochemically analysed 90 mammalian species across 48 families in 16 orders, using an antiserum against the Cry1 C-terminus that in birds labels only the photo-activated conformation. In the Carnivora families Canidae, Mustelidae and Ursidae, and in some Primates, Cry1 was consistently labeled in the outer segment of the shortwave-sensitive S1 cones. This finding would be compatible with a magnetoreceptive function of Cry1 in these taxa. In all other taxa, Cry1 was not detected by the antiserum that likely also in mammals labels the photo-activated conformation, although Western blots showed Cry1 in mouse retinal cell nuclei. We speculate that in the mouse and the other negative-tested mammals Cry1 is involved in circadian functions as a non-light-responsive protein.

Simplified Models for the Study of Postbuckled Hat-Stiffened Composite Panels

NASA Technical Reports Server (NTRS)

Vescovini, Riccardo; Davila, Carlos G.; Bisagni, Chiara

2012-01-01

The postbuckling response and failure of multistringer stiffened panels is analyzed using models with three levels of approximation. The first model uses a relatively coarse mesh to capture the global postbuckling response of a five-stringer panel. The second model can predict the nonlinear response as well as the debonding and crippling failure mechanisms in a single stringer compression specimen (SSCS). The third model consists of a simplified version of the SSCS that is designed to minimize the computational effort. The simplified model is well-suited to perform sensitivity analyses for studying the phenomena that lead to structural collapse. In particular, the simplified model is used to obtain a deeper understanding of the role played by geometric and material modeling parameters such as mesh size, inter-laminar strength, fracture toughness, and fracture mode mixity. Finally, a global/local damage analysis method is proposed in which a detailed local model is used to scan the global model to identify the locations that are most critical for damage tolerance.

Recovering from the ShakeOut earthquake

USGS Publications Warehouse

Wein, Anne; Johnson, Laurie; Bernknopf, Richard

2011-01-01

Recovery from an earthquake like the M7.8 ShakeOut Scenario will be a major endeavor taking many years to complete. Hundreds of Southern California municipalities will be affected; most lack recovery plans or previous disaster experience. To support recovery planning this paper 1) extends the regional ShakeOut Scenario analysis into the recovery period using a recovery model, 2) localizes analyses to identify longer-term impacts and issues in two communities, and 3) considers the regional context of local recovery.Key community insights about preparing for post-disaster recovery include the need to: geographically diversify city procurement; set earthquake mitigation priorities for critical infrastructure (e.g., airport), plan to replace mobile homes with earthquake safety measures, consider post-earthquake redevelopment opportunities ahead of time, and develop post-disaster recovery management and governance structures. This work also showed that communities with minor damages are still sensitive to regional infrastructure damages and their potential long-term impacts on community recovery. This highlights the importance of community and infrastructure resilience strategies as well.

[Comparison of simple pooling and bivariate model used in meta-analyses of diagnostic test accuracy published in Chinese journals].

PubMed

Huang, Yuan-sheng; Yang, Zhi-rong; Zhan, Si-yan

2015-06-18

To investigate the use of simple pooling and bivariate model in meta-analyses of diagnostic test accuracy (DTA) published in Chinese journals (January to November, 2014), compare the differences of results from these two models, and explore the impact of between-study variability of sensitivity and specificity on the differences. DTA meta-analyses were searched through Chinese Biomedical Literature Database (January to November, 2014). Details in models and data for fourfold table were extracted. Descriptive analysis was conducted to investigate the prevalence of the use of simple pooling method and bivariate model in the included literature. Data were re-analyzed with the two models respectively. Differences in the results were examined by Wilcoxon signed rank test. How the results differences were affected by between-study variability of sensitivity and specificity, expressed by I2, was explored. The 55 systematic reviews, containing 58 DTA meta-analyses, were included and 25 DTA meta-analyses were eligible for re-analysis. Simple pooling was used in 50 (90.9%) systematic reviews and bivariate model in 1 (1.8%). The remaining 4 (7.3%) articles used other models pooling sensitivity and specificity or pooled neither of them. Of the reviews simply pooling sensitivity and specificity, 41(82.0%) were at the risk of wrongly using Meta-disc software. The differences in medians of sensitivity and specificity between two models were both 0.011 (P<0.001, P=0.031 respectively). Greater differences could be found as I2 of sensitivity or specificity became larger, especially when I2>75%. Most DTA meta-analyses published in Chinese journals(January to November, 2014) combine the sensitivity and specificity by simple pooling. Meta-disc software can pool the sensitivity and specificity only through fixed-effect model, but a high proportion of authors think it can implement random-effect model. Simple pooling tends to underestimate the results compared with bivariate model. The greater the between-study variance is, the more likely the simple pooling has larger deviation. It is necessary to increase the knowledge level of statistical methods and software for meta-analyses of DTA data.

Not rare. But, endangered Elemental profiles of three corticolous lichen species on red spruce in Maine. [Usnea subfloridana; Platismatia glauca; Hypogymnia physodes

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

Stubbs, C.S.; Homola, R.H.

1990-01-01

Usnea subfloridana Stirton, Platismatia glauca (L.) Club. and Club., and Hypogymnia physodes (L.) Nyl. are lichen species moderately to highly sensitive to air pollutants, including acid deposition and ozone. Some researchers have attributed depauperate populations and local extinctions of these species to poor air quality. Since 1985, areas of Maine annually experienced mean summer rain and fog events of pH 4.5 or lower and ozone levels above national standards. Given this possible threat to these and other pollution sensitive species, baseline elemental analyses for Ca, K, P, Mg, Al, B, Fe, Cu, Mn, Zn, N, S, Na, and Pb weremore » performed in 1986 on coastal and inland populations on Picea rubens L. Elemental analyses were again performed on nontransplanted and transplanted lichens from the same populations in 1988. There were statistically significant differences in elemental profiles between nontransplanted 1986 and 1988 samples for all three species, such as significant decreases in Ca and Mg concentrations, and increases in Al, Cu, Fe, and Zn for U. subfloridana. Elemental concentrations between nontransplanted and transplanted material differed significantly, but no consistent pattern emerged. These results, coupled with other evidence (such as luxuriance and density ratings), suggest that both inland and coastal populations of U. subfloridana on red spruce are experiencing ecophysiological stress.« less

Law enforcement tools available at the Savannah River Site

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

Hofstetter, K.J.

A number of nuclear technologies developed and applied at the Savannah River Site in support of nuclear weapons material production and environmental remediation can be applied to problems in law enforcement. Techniques and equipment for high-sensitivity analyses of samples are available to identify and quantify trace elements and establish origins and histories of forensic evidence removed from crime scenes. While some of theses capabilities are available at local crime laboratories, state-of-the-art equipment and breakthroughs in analytical techniques are continually being developed at DOE laboratories. Extensive experience with the handling of radioactive samples at the DOE labs minimizes the chances ofmore » cross-contamination of evidence received from law enforcement. In addition to high-sensitivity analyses, many of the field techniques developed for use in a nuclear facility can assist law enforcement personnel in detecting illicit materials and operations, in retrieving of pertinent evidence and in surveying crime scenes. Some of these tools include chemical sniffers, hand-held detectors, thermal imaging, etc. In addition, mobile laboratories can be deployed to a crime scene to provide field screening of potential evidence. A variety of portable sensors can be deployed on vehicle, aerial, surface or submersible platforms to assist in the location of pertinent evidence or illicit operations. Several specific nuclear technologies available to law enforcement and their potential uses are discussed.« less

Detection of titanium in human tissues after craniofacial surgery.

PubMed

Jorgenson, D S; Mayer, M H; Ellenbogen, R G; Centeno, J A; Johnson, F B; Mullick, F G; Manson, P N

1997-04-01

Generally, titanium fixation plates are not removed after osteosynthesis, because they have high biocompatability and high corrosion resistance characteristics. Experiments with laboratory animals, and limited studies of analyses of human tissues, have reported evidence of titanium release into local and distant tissues. This study summarizes our results of the analysis of soft tissues for titanium in four patients with titanium microfixation plates. Energy dispersive x-ray analysis, scanning electron microscopy, and electrothermal atomic absorption spectrophotometry were used to detect trace amounts of titanium in surrounding soft tissues. A single metal inclusion was detected by scanning electron microscopy and energy dispersive x-ray analysis in one patient, whereas, electrothermal atomic absorption spectrophotometry analyses revealed titanium present in three of four specimens in levels ranging from 7.92 to 31.8 micrograms/gm of dry tissue. Results from this study revealed trace amounts of titanium in tissues surrounding craniofacial plates. At the atomic level, electrothermal atomic absorption spectrophotometry appears to be a sensitive tool to quantitatively detect ultra-trace amounts of metal in human tissue.

Impact Mechanics

NASA Astrophysics Data System (ADS)

Stronge, W. J.

2004-03-01

Impact mechanics is concerned with the reaction forces that develop during a collision and the dynamic response of structures to these reaction forces. The subject has a wide range of engineering applications, from designing sports equipment to improving the crashworthiness of automobiles. This book develops several different methodologies for analysing collisions between structures. These range from rigid body theory for structures that are stiff and compact, to vibration and wave analyses for flexible structures. The emphasis is on low-speed impact where damage is local to the small region of contact between the colliding bodies. The analytical methods presented give results that are more robust or less sensitive to initial conditions than have been achieved hitherto. As a text, Impact Mechanics builds upon foundation courses in dynamics and strength of materials. It includes numerous industrially relevant examples and end-of-chapter homework problems drawn from industry and sports. Practising engineers will also find the methods presented in this book useful in calculating the response of a mechanical system to impact.

Alpha, Beta and Gamma Diversity Differ in Response to Precipitation in the Inner Mongolia Grassland

PubMed Central

Zhang, Qing; Hou, Xiangyang; Li, Frank Yonghong; Niu, Jianming; Zhou, Yanlin; Ding, Yong; Zhao, Liqing; Li, Xin; Ma, Wenjing; Kang, Sarula

2014-01-01

Understanding the distribution pattern and maintenance mechanism of species diversity along environmental gradients is essential for developing biodiversity conservation strategies under environmental change. We have surveyed the species diversity at 192 vegetation sites across different steppe zones in Inner Mongolia, China. We analysed the total species diversity (γ diversity) and its composition (α diversity and β diversity) of different steppe types, and their changes along a precipitation gradient. Our results showed that (i) β diversity contributed more than α diversity to the total (γ) diversity in the Inner Mongolia grassland; the contribution of β diversity increased with precipitation, thus the species-rich (meadow steppe) grassland had greater contribution of β diversity than species-poor (desert steppe) grassland. (ii) All α, β and γ species diversity increased significantly (P<0.05) with precipitation, but their sensitivity to precipitation (diversity change per mm precipitation increase) was different between the steppe types. The sensitivity of α diversity of different steppe community types was negatively (P<0.05) correlated with mean annual precipitation, whereas the sensitivity of β and γ diversity showed no trend along the precipitation gradient (P>0.10). (iii) The α diversity increased logarithmically, while β diversity increased exponentially, with γ diversity. Our results suggest that for local species diversity patterns, the site species pool is more important in lower precipitation areas, while local ecological processes are more important in high precipitation areas. In addition, for β diversity maintenance niche processes and diffusion processes are more important in low and high precipitation areas, respectively. Our results imply that a policy of “multiple small reserves” is better than one of a “single large reserve” for conserving species diversity of a steppe ecosystem, and indicate an urgent need to develop management strategies for climate-sensitive desert steppe ecosystem. PMID:24675900

A modeling tool to evaluate regional coral reef responses to changes in climate and ocean chemistry

USGS Publications Warehouse

Buddemeier, R.W.; Jokiel, P.L.; Zimmerman, K.M.; Lane, D.R.; Carey, J.M.; Bohling, Geoffrey C.; Martinich, J.A.

2008-01-01

We developed a spreadsheet-based model for the use of managers, conservationists, and biologists for projecting the effects of climate change on coral reefs at local-to-regional scales. The COMBO (Coral Mortality and Bleaching Output) model calculates the impacts to coral reefs from changes in average SST and CO2 concentrations, and from high temperature mortality (bleaching) events. The model uses a probabilistic assessment of the frequency of high temperature events under a future climate to address scientific uncertainties about potential adverse effects. COMBO offers data libraries and default factors for three selected regions (Hawai'i, Great Barrier Reef, and Caribbean), but it is structured with user-selectable parameter values and data input options, making possible modifications to reflect local conditions or to incorporate local expertise. Preliminary results from sensitivity analyses and simulation examples for Hawai'i demonstrate the relative importance of high temperature events, increased average temperature, and increased CO2 concentration on the future status of coral reefs; Illustrate significant interactions among variables; and allow comparisons of past environmental history with future predictions. ?? 2008, by the American Society of Limnology and Oceanugraphy, Inc.

An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: first round.

PubMed

Ehling, G; Hecht, M; Heusener, A; Huesler, J; Gamer, A O; van Loveren, H; Maurer, Th; Riecke, K; Ullmann, L; Ulrich, P; Vandebriel, R; Vohr, H-W

2005-08-15

The new OECD guideline 429 (skin sensitization: local lymph node assay) is based upon a protocol, which utilises the incorporation of radioactivity into DNA as a measure for cell proliferation in vivo. The guideline also enables the use of alternative endpoints in order to assess draining lymph node (LN) cell proliferation. Here we describe the first round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in seven laboratories. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products, Swissmedic. Statistical analyses of all data were performed by an independent centre at the University of Bern, Department of Statistics. Ear-draining, LN weight and cell count were used to assess proliferation instead of radioactive labeling of lymph node cells. In addition, the acute inflammatory skin reaction was measured by ear swelling and weight of circular biopsies of the ears to identify skin irritating properties of the test items. Hexylcinnamaldehyde (HCA) and three blinded test items were applied to female, 8--10 weeks old NMRI and BALB/c mice. Results were sent via the independent study coordinator to the statistician. The results of this first round showed that the alternative endpoints of the LLNA are sensitive and robust parameters. The use of ear weights added an important parameter assessing the skin irritation potential, which supports the differentiation of pure irritative from contact allergenic potential. There were absolute no discrepancies between the categorisation of the three test substances A--C determined by each single participating laboratories. The results highlighted also that many parameters do have an impact on the strength of the responses. Therefore, such parameters have to be taken into consideration for the categorisation of compounds due to their relative sensitizing potencies.

Sensitivity of physical parameterizations on prediction of tropical cyclone Nargis over the Bay of Bengal using WRF model

NASA Astrophysics Data System (ADS)

Raju, P. V. S.; Potty, Jayaraman; Mohanty, U. C.

2011-09-01

Comprehensive sensitivity analyses on physical parameterization schemes of Weather Research Forecast (WRF-ARW core) model have been carried out for the prediction of track and intensity of tropical cyclones by taking the example of cyclone Nargis, which formed over the Bay of Bengal and hit Myanmar on 02 May 2008, causing widespread damages in terms of human and economic losses. The model performances are also evaluated with different initial conditions of 12 h intervals starting from the cyclogenesis to the near landfall time. The initial and boundary conditions for all the model simulations are drawn from the global operational analysis and forecast products of National Center for Environmental Prediction (NCEP-GFS) available for the public at 1° lon/lat resolution. The results of the sensitivity analyses indicate that a combination of non-local parabolic type exchange coefficient PBL scheme of Yonsei University (YSU), deep and shallow convection scheme with mass flux approach for cumulus parameterization (Kain-Fritsch), and NCEP operational cloud microphysics scheme with diagnostic mixed phase processes (Ferrier), predicts better track and intensity as compared against the Joint Typhoon Warning Center (JTWC) estimates. Further, the final choice of the physical parameterization schemes selected from the above sensitivity experiments is used for model integration with different initial conditions. The results reveal that the cyclone track, intensity and time of landfall are well simulated by the model with an average intensity error of about 8 hPa, maximum wind error of 12 m s-1and track error of 77 km. The simulations also show that the landfall time error and intensity error are decreasing with delayed initial condition, suggesting that the model forecast is more dependable when the cyclone approaches the coast. The distribution and intensity of rainfall are also well simulated by the model and comparable with the TRMM estimates.

Sensitivity of forces to wall transpiration in flow past an aerofoil

PubMed Central

Mao, X.

2015-01-01

The adjoint-based sensitivity analyses well explored in hydrodynamic stability studies are extended to calculate the sensitivity of forces acting on an aerofoil with respect to wall transpiration. The magnitude of the sensitivity quantifies the controllability of the force, and the distribution of the sensitivity represents a most effective control when the control magnitude is small enough. Since the sensitivity to streamwise control is one order smaller than that to the surface-normal one, the work is concentrated on the normal control. In direct numerical simulations of flow around a NACA0024 aerofoil, the unsteady controls are far less effective than the steady control owing to the lock-in effect. At a momentum coefficient of 0.0008 and a maximum control velocity of 3.6% of the free-stream velocity, the steady surface-normal control reduces drag by 20% or enhances lift by up to 140% at Re=1000. A suction around the low-pressure region on the upper surface upstream of the separation point is found to reduce drag and enhance lift. At higher Reynolds numbers, the uncontrolled flow becomes three dimensional and the sensitivity diverges owing to the chaotic dynamics of the flow. Then the mechanism identified at lower Reynolds numbers is exploited to obtain the control, which is localized and can be generated by a limited number of actuators. The control to reduce drag or enhance lift is found to suppress unsteadiness, e.g. vortex shedding and three-dimensional developments. For example, at Re=2000 and α=10°, the control with a momentum coefficient of 0.0001 reduces drag by 20%, enhances lift by up to 200% and leads to a steady controlled flow. PMID:26807041

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

A study of the Ljubljansko polje aquifer system behaviour and its simulations using multi-tools

NASA Astrophysics Data System (ADS)

Vrzel, J.; Ludwig, R.; Vižintin, G.; Ogrinc, N.

2017-12-01

Our study of comprehensive hydrological system behaviour, where understanding of the interfaces between groundwater and surface water is crucial, includes geochemical analyses for identification of groundwater sources (δ18O and δ2H) and estimation of groundwater mean residence time (3H, 3H/3He). The results of the geochemical analyses were compared with long-term data on precipitation, river discharge, hydraulic head, and groundwater pumping rate. The study is representative for the Ljubljansko polje in Slovenia, which belongs to the Sava River basin. The results show that the Sava River water and local precipitation are the main groundwater sources in this alluvial aquifer with high system sensitivity to both sources, which ranged from a day to a month. For a simulation of such a sensitive system different tools describing water cycle were coupled: simulation of the percolation of the local precipitation was done with the WaSiM-ETH, while the river and groundwater dynamics were performed with the MIKE 11 and FEFLOW, respectively. The WaSiM-ETH and MIKE 11 results were later employed as the upper boundary conditions in the FEFLOW model. The models have high spatial and daily temporal resolutions. A good agreement between geochemical data and modeling results was observed with two main highlights: (1) groundwater sources are in accordance with hydraulic heads and the Sava River water level/precipitation; (2) responsiveness of the aquifer on the high water level in the Sava River and on precipitation events is also synchronic with the mean groundwater residence time. The study shows that links between MIKE 11-FEFLOW-WaSiM-ETH tools is a great solution for a precise groundwater flow simulation, since all the tools are compatible and at the moment there is no routine approach for a precise parallel simulation of groundwater and surface water dynamics. The Project was financially supported by the the EU 7th Research Project - GLOBAQUA.

Cost-Effectiveness of Apixaban versus Warfarin in Chinese Patients with Non-Valvular Atrial Fibrillation: A Real-Life and Modelling Analyses

PubMed Central

Li, Xue; Tse, Vicki C.; Lau, Wallis C. Y.; Cheung, Bernard M. Y.; Lip, Gregory Y. H.; Wong, Ian C. K.; Chan, Esther W.

2016-01-01

Objectives Many of the cost-effectiveness analyses of apixaban against warfarin focused on Western populations but Asian evidence remains less clear. The present study aims to evaluate the cost-effectiveness of apixaban against warfarin in Chinese patients with non-valvular atrial fibrillation (NVAF) from a public institutional perspective in Hong Kong. Methods We used a Markov model incorporating 12 health state transitions, and simulated the disease progression of NVAF in 1,000 hypothetical patients treated with apixaban/warfarin. Risks of clinical events were based on the ARISTOTLE trial and were adjusted with local International Normalized Ratio control, defined as the time in therapeutic range. Real-life input for the model, including patients’ demographics and clinical profiles, post-event treatment patterns, and healthcare costs, were determined by a retrospective cohort of 40,569 incident patients retrieved from a Hong Kong-wide electronic medical database. Main outcome measurements included numbers of thromboembolic and bleeding events, life years, quality-adjusted life years (QALYs) and direct healthcare cost. When comparing apixaban and warfarin, treatment with incremental cost-effectiveness ratio (ICER) less than one local GDP per capita (USD 33,534 in 2014) was defined to be cost-effective. Results In the lifetime simulation, fewer numbers of events were estimated for the apixaban group, resulting in reduced event-related direct medical costs. The estimated ICER of apixaban was USD 7,057 per QALY at base-case analysis and ranged from USD 1,061 to 14,867 per QALY under the 116 tested scenarios in deterministic sensitivity analysis. While in probabilistic sensitivity analysis, the probability of apixaban being the cost-effective alternative to warfarin was 96% and 98% at a willingness to pay threshold of USD 33,534 and 100,602 per QALY, respectively. Conclusions Apixaban is likely to be a cost-effective alternative to warfarin for stroke prophylaxis in Chinese patients with NVAF in Hong Kong. PMID:27362421

Cost-Effectiveness of Apixaban versus Warfarin in Chinese Patients with Non-Valvular Atrial Fibrillation: A Real-Life and Modelling Analyses.

PubMed

Li, Xue; Tse, Vicki C; Lau, Wallis C Y; Cheung, Bernard M Y; Lip, Gregory Y H; Wong, Ian C K; Chan, Esther W

2016-01-01

Many of the cost-effectiveness analyses of apixaban against warfarin focused on Western populations but Asian evidence remains less clear. The present study aims to evaluate the cost-effectiveness of apixaban against warfarin in Chinese patients with non-valvular atrial fibrillation (NVAF) from a public institutional perspective in Hong Kong. We used a Markov model incorporating 12 health state transitions, and simulated the disease progression of NVAF in 1,000 hypothetical patients treated with apixaban/warfarin. Risks of clinical events were based on the ARISTOTLE trial and were adjusted with local International Normalized Ratio control, defined as the time in therapeutic range. Real-life input for the model, including patients' demographics and clinical profiles, post-event treatment patterns, and healthcare costs, were determined by a retrospective cohort of 40,569 incident patients retrieved from a Hong Kong-wide electronic medical database. Main outcome measurements included numbers of thromboembolic and bleeding events, life years, quality-adjusted life years (QALYs) and direct healthcare cost. When comparing apixaban and warfarin, treatment with incremental cost-effectiveness ratio (ICER) less than one local GDP per capita (USD 33,534 in 2014) was defined to be cost-effective. In the lifetime simulation, fewer numbers of events were estimated for the apixaban group, resulting in reduced event-related direct medical costs. The estimated ICER of apixaban was USD 7,057 per QALY at base-case analysis and ranged from USD 1,061 to 14,867 per QALY under the 116 tested scenarios in deterministic sensitivity analysis. While in probabilistic sensitivity analysis, the probability of apixaban being the cost-effective alternative to warfarin was 96% and 98% at a willingness to pay threshold of USD 33,534 and 100,602 per QALY, respectively. Apixaban is likely to be a cost-effective alternative to warfarin for stroke prophylaxis in Chinese patients with NVAF in Hong Kong.

Hospital admissions for severe mental illness in England: changes in equity of utilisation at the small area level between 2006 and 2010.

PubMed

White, Jonathan; Gutacker, Nils; Jacobs, Rowena; Mason, Anne

2014-11-01

Severe Mental Illness (SMI) encompasses a range of chronic conditions including schizophrenia, bipolar disorder and psychoses. Patients with SMI often require inpatient psychiatric care. Despite equity being a key objective in the English National Health Service (NHS) and in many other health care systems worldwide, little is known about the socio-economic equity of hospital care utilisation for patients with SMI and how it has changed over time. This analysis seeks to address that gap in the evidence base. We exploit a five-year (2006-2010) panel dataset of admission rates at small area level (n=162,410). The choice of control variables was informed by a systematic literature search. To assess changes in socio-economic equity of utilisation, OLS-based standardisation was first used to conduct analysis of discrete deprivation groups. Geographical inequity was then illustrated by plotting standardised and crude admission rates at local purchaser level. Lastly, formal statistical tests for changes in socio-economic equity of utilisation were applied to a continuous measure of deprivation using pooled negative binomial regression analysis, adjusting for a range of risk factors. Our results suggest that one additional percentage point of area income deprivation is associated with a 1.5% (p<0.001) increase in admissions for SMI after controlling for population size, age, sex, prevalence of SMI in the local population, as well as other need and supply factors. This finding is robust to sensitivity analyses, suggesting that a pro-poor inequality in utilisation exists for SMI-related inpatient services. One possible explanation is that the supply or quality of primary, community or social care for people with mental health problems is suboptimal in deprived areas. Although there is some evidence that inequity has reduced over time, the changes are small and not always robust to sensitivity analyses. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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…

Subcortical volumetric changes across the adult lifespan: subregional thalamic atrophy accounts for age-related sensorimotor performance declines.

PubMed

Serbruyns, Leen; Leunissen, Inge; Huysmans, Toon; Cuypers, Koen; Meesen, Raf L; van Ruitenbeek, Peter; Sijbers, Jan; Swinnen, Stephan P

2015-04-01

Even though declines in sensorimotor performance during healthy aging have been documented extensively, its underlying neural mechanisms remain unclear. Here, we explored whether age-related subcortical atrophy plays a role in sensorimotor performance declines, and particularly during bimanual manipulative performance (Purdue Pegboard Test). The thalamus, putamen, caudate and pallidum of 91 participants across the adult lifespan (ages 20-79 years) were automatically segmented. In addition to studying age-related changes in the global volume of each subcortical structure, local deformations within these structures, indicative of subregional volume changes, were assessed by means of recently developed shape analyses. Results showed widespread age-related global and subregional atrophy, as well as some notable subregional expansion. Even though global atrophy failed to explain the observed performance declines with aging, shape analyses indicated that atrophy in left and right thalamic subregions, specifically subserving connectivity with the premotor, primary motor and somatosensory cortical areas, mediated the relation between aging and performance decline. It is concluded that subregional volume assessment by means of shape analyses offers a sensitive tool with high anatomical resolution in the search for specific age-related associations between brain structure and behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Observationally-Centred Method to Quantify the Changing Shape of Local Temperature Distributions

NASA Astrophysics Data System (ADS)

Chapman, S. C.; Stainforth, D. A.; Watkins, N. W.

2014-12-01

For climate sensitive decisions and adaptation planning, guidance on how local climate is changing is needed at the specific thresholds relevant to particular impacts or policy endeavours. This requires the quantification of how the distributions of variables, such as daily temperature, are changing at specific quantiles. These temperature distributions are non-normal and vary both geographically and in time. We present a method[1,2] for analysing local climatic time series data to assess which quantiles of the local climatic distribution show the greatest and most robust changes. We have demonstrated this approach using the E-OBS gridded dataset[3] which consists of time series of local daily temperature across Europe over the last 60 years. Our method extracts the changing cumulative distribution function over time and uses a simple mathematical deconstruction of how the difference between two observations from two different time periods can be assigned to the combination of natural statistical variability and/or the consequences of secular climate change. The change in temperature can be tracked at a temperature threshold, at a likelihood, or at a given return time, independently for each geographical location. Geographical correlations are thus an output of our method and reflect both climatic properties (local and synoptic), and spatial correlations inherent in the observation methodology. We find as an output many regionally consistent patterns of response of potential value in adaptation planning. For instance, in a band from Northern France to Denmark the hottest days in the summer temperature distribution have seen changes of at least 2°C over a 43 year period; over four times the global mean change over the same period. We discuss methods to quantify the robustness of these observed sensitivities and their statistical likelihood. This approach also quantifies the level of detail at which one might wish to see agreement between climate models and observations if such models are to be used directly as tools to assess climate change impacts at local scales. [1] S C Chapman, D A Stainforth, N W Watkins, 2013, Phil. Trans. R. Soc. A, 371 20120287. [2] D A Stainforth, S C Chapman, N W Watkins, 2013, Environ. Res. Lett. 8, 034031 [3] Haylock, M.R. et al., 2008, J. Geophys. Res (Atmospheres), 113, D20119

Effects of Lewis number on the statistics of the invariants of the velocity gradient tensor and local flow topologies in turbulent premixed flames

NASA Astrophysics Data System (ADS)

Wacks, Daniel; Konstantinou, Ilias; Chakraborty, Nilanjan

2018-04-01

The behaviours of the three invariants of the velocity gradient tensor and the resultant local flow topologies in turbulent premixed flames have been analysed using three-dimensional direct numerical simulation data for different values of the characteristic Lewis number ranging from 0.34 to 1.2. The results have been analysed to reveal the statistical behaviours of the invariants and the flow topologies conditional upon the reaction progress variable. The behaviours of the invariants have been explained in terms of the relative strengths of the thermal and mass diffusions, embodied by the influence of the Lewis number on turbulent premixed combustion. Similarly, the behaviours of the flow topologies have been explained in terms not only of the Lewis number but also of the likelihood of the occurrence of individual flow topologies in the different flame regions. Furthermore, the sensitivity of the joint probability density function of the second and third invariants and the joint probability density functions of the mean and Gaussian curvatures to the variation in Lewis number have similarly been examined. Finally, the dependences of the scalar-turbulence interaction term on augmented heat release and of the vortex-stretching term on flame-induced turbulence have been explained in terms of the Lewis number, flow topology and reaction progress variable.

Effects of Lewis number on the statistics of the invariants of the velocity gradient tensor and local flow topologies in turbulent premixed flames

PubMed Central

Konstantinou, Ilias; Chakraborty, Nilanjan

2018-01-01

The behaviours of the three invariants of the velocity gradient tensor and the resultant local flow topologies in turbulent premixed flames have been analysed using three-dimensional direct numerical simulation data for different values of the characteristic Lewis number ranging from 0.34 to 1.2. The results have been analysed to reveal the statistical behaviours of the invariants and the flow topologies conditional upon the reaction progress variable. The behaviours of the invariants have been explained in terms of the relative strengths of the thermal and mass diffusions, embodied by the influence of the Lewis number on turbulent premixed combustion. Similarly, the behaviours of the flow topologies have been explained in terms not only of the Lewis number but also of the likelihood of the occurrence of individual flow topologies in the different flame regions. Furthermore, the sensitivity of the joint probability density function of the second and third invariants and the joint probability density functions of the mean and Gaussian curvatures to the variation in Lewis number have similarly been examined. Finally, the dependences of the scalar--turbulence interaction term on augmented heat release and of the vortex-stretching term on flame-induced turbulence have been explained in terms of the Lewis number, flow topology and reaction progress variable. PMID:29740257

Pinhole Micro-SPECT/CT for Noninvasive Monitoring and Quantitation of Oncolytic Virus Dispersion and Percent Infection in Solid Tumors

PubMed Central

Penheiter, Alan R.; Griesmann, Guy E.; Federspiel, Mark J.; Dingli, David; Russell, Stephen J.; Carlson, Stephanie K.

2011-01-01

The purpose of our study was to validate the ability of pinhole micro-single-photon emission computed tomography/computed tomography (SPECT/CT) to 1) accurately resolve the intratumoral dispersion pattern and 2) quantify the infection percentage in solid tumors of an oncolytic measles virus encoding the human sodium iodide symporter (MV-NIS). NIS RNA level and dispersion pattern were determined in control and MV-NIS infected BxPC-3 pancreatic tumor cells and mouse xenografts using quantitative, real-time, reverse transcriptase, polymerase chain reaction, autoradiography, and immunohistochemistry (IHC). Mice with BxPC-3 xenografts were imaged with 123I or 99TcO4 micro-SPECT/CT. Tumor dimensions and radionuclide localization were determined with imaging software. Linear regression and correlation analyses were performed to determine the relationship between tumor infection percentage and radionuclide uptake (% injected dose per gram) above background and a highly significant correlation was observed (r2 = 0.947). A detection threshold of 1.5-fold above the control tumor uptake (background) yielded a sensitivity of 2.7% MV-NIS infected tumor cells. We reliably resolved multiple distinct intratumoral zones of infection from noninfected regions. Pinhole micro-SPECT/CT imaging using the NIS reporter demonstrated precise localization and quantitation of oncolytic MV-NIS infection and can replace more time-consuming and expensive analyses (eg, autoradiography and IHC) that require animal sacrifice. PMID:21753796

[Cost-minimization analysis of subcutaneous abatacept in the treatment of rheumatoid arthritis in Spain].

PubMed

Ariza, R; Van Walsem, A; Canal, C; Roldán, C; Betegón, L; Oyagüez, I; Janssen, K

2014-07-01

To compare the cost of treating rheumatoid arthritis patients that have failed an initial treatment with methotrexate, with subcutaneous abatacept versus other first-line biologic disease-modifying antirheumatic drugs. Subcutaneous abatacept was considered comparable to intravenous abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab and tocilizumab, based on indirect comparison using mixed treatment analysis. A cost-minimization analysis was therefore considered appropriate. The Spanish Health System perspective and a 3 year time horizon were selected. Pharmaceutical and administration costs (Euros 2013) of all available first-line biological disease-modifying antirheumatic drugs were considered. Administration costs were obtained from a local costs database. Patients were considered to have a weight of 70 kg. A 3% annual discount rate was applied. Deterministic and probabilistic sensitivity analyses were performed. Subcutaneous abatacept proved in the base case to be less costly than all other biologic antirrheumatic drugs (ranging from Euros -831.42 to Euros -9,741.69 versus infliximab and tocilizumab, respectively). Subcutaneous abatacept was associated with a cost of Euros 10,760.41 per patient during the first year of treatment and Euros 10,261.29 in subsequent years. The total 3-year cost of subcutaneous abatacept was Euros 29,953.89 per patient. Sensitivity analyses proved the model to be robust. Subcutaneous abatacept remained cost-saving in 100% of probabilistic sensitivity analysis simulations versus adalimumab, certolizumab, etanercept and golimumab, in more than 99.6% versus intravenous abatacept and tocilizumab and in 62.3% versus infliximab. Treatment with subcutaneous abatacept is cost-saving versus intravenous abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab and tocilizumab in the management of rheumatoid arthritis patients initiating treatment with biological antirheumatic drugs. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

The maize WRKY transcription factor ZmWRKY17 negatively regulates salt stress tolerance in transgenic Arabidopsis plants.

PubMed

Cai, Ronghao; Dai, Wei; Zhang, Congsheng; Wang, Yan; Wu, Min; Zhao, Yang; Ma, Qing; Xiang, Yan; Cheng, Beijiu

2017-12-01

We cloned and characterized the ZmWRKY17 gene from maize. Overexpression of ZmWRKY17 in Arabidopsis led to increased sensitivity to salt stress and decreased ABA sensitivity through regulating the expression of some ABA- and stress-responsive genes. The WRKY transcription factors have been reported to function as positive or negative regulators in many different biological processes including plant development, defense regulation and stress response. This study isolated a maize WRKY gene, ZmWRKY17, and characterized its role in tolerance to salt stress by generating transgenic Arabidopsis plants. Expression of the ZmWRKY17 was up-regulated by drought, salt and abscisic acid (ABA) treatments. ZmWRKY17 was localized in the nucleus with no transcriptional activation in yeast. Yeast one-hybrid assay showed that ZmWRKY17 can specifically bind to W-box, and it can activate W-box-dependent transcription in planta. Heterologous overexpression of ZmWRKY17 in Arabidopsis remarkably reduced plant tolerance to salt stress, as determined through physiological analyses of the cotyledons greening rate, root growth, relative electrical leakage and malondialdehyde content. Additionally, ZmWRKY17 transgenic plants showed decreased sensitivity to ABA during seed germination and early seedling growth. Transgenic plants accumulated higher content of ABA than wild-type (WT) plants under NaCl condition. Transcriptome and quantitative real-time PCR analyses revealed that some stress-related genes in transgenic seedlings showed lower expression level than that in the WT when treated with NaCl. Taken together, these results suggest that ZmWRKY17 may act as a negative regulator involved in the salt stress responses through ABA signalling.

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

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

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

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

Three-dimensional synaptic analyses of mitral cell and external tufted cell dendrites in rat olfactory bulb glomeruli.

PubMed

Bourne, Jennifer N; Schoppa, Nathan E

2017-02-15

Recent studies have suggested that the two excitatory cell classes of the mammalian olfactory bulb, the mitral cells (MCs) and tufted cells (TCs), differ markedly in physiological responses. For example, TCs are more sensitive and broadly tuned to odors than MCs and also are much more sensitive to stimulation of olfactory sensory neurons (OSNs) in bulb slices. To examine the morphological bases for these differences, we performed quantitative ultrastructural analyses of glomeruli in rat olfactory bulb under conditions in which specific cells were labeled with biocytin and 3,3'-diaminobenzidine. Comparisons were made between MCs and external TCs (eTCs), which are a TC subtype in the glomerular layer with large, direct OSN signals and capable of mediating feedforward excitation of MCs. Three-dimensional analysis of labeled apical dendrites under an electron microscope revealed that MCs and eTCs in fact have similar densities of several chemical synapse types, including OSN inputs. OSN synapses also were distributed similarly, favoring a distal localization on both cells. Analysis of unlabeled putative MC dendrites further revealed gap junctions distributed uniformly along the apical dendrite and, on average, proximally with respect to OSN synapses. Our results suggest that the greater sensitivity of eTCs vs. MCs is due not to OSN synapse number or absolute location but rather to a conductance in the MC dendrite that is well positioned to attenuate excitatory signals passing to the cell soma. Functionally, such a mechanism could allow rapid and dynamic control of OSN-driven action potential firing in MCs through changes in gap junction properties. J. Comp. Neurol. 525:592-609, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Research protocol for the Picture Talk Project: a qualitative study on research and consent with remote Australian Aboriginal communities

PubMed Central

Fitzpatrick, Emily F M; Carter, Maureen; Oscar, June; Lawford, Tom; Martiniuk, Alexandra L C; D’Antoine, Heather A; Elliott, Elizabeth J

2017-01-01

Introduction Research with Indigenous populations is not always designed with cultural sensitivity. Few publications evaluate or describe in detail seeking consent for research with Indigenous participants. When potential participants are not engaged in a culturally respectful manner, participation rates and research quality can be adversely affected. It is unethical to proceed with research without truly informed consent. Methods and analysis We describe a culturally appropriate research protocol that is invited by Aboriginal communities of the Fitzroy Valley in Western Australia. The Picture Talk Project is a research partnership with local Aboriginal leaders who are also chief investigators. We will interview Aboriginal leaders about research, community engagement and the consent process and hold focus groups with Aboriginal community members about individual consent. Cultural protocols will be applied to recruit and conduct research with participants. Transcripts will be analysed using NVivo10 qualitative software and themes synthesised to highlight the key issues raised by the community about the research process. This protocol will guide future research with the Aboriginal communities of the Fitzroy Valley and may inform the approach to research with other Indigenous communities of Australia or the world. It must be noted that no community is the same and all research requires local consultation and input. To conduct culturally sensitive research, respected local people from the community who have knowledge of cultural protocol and language are engaged to guide each step of the research process from the project design to the delivery of results. Ethics and dissemination Ethics approval was granted by the University of Sydney Human Research Ethics Committee (No. 2012/348, reference:14760), the Western Australia Country Health Service Ethics Committee (No. 2012:15), the Western Australian Aboriginal Health Ethics Committee and reviewed by the Kimberley Aboriginal Health Planning Forum Research Sub-Committee (No. 2012–008). Results will be disseminated through peer review articles, a local Fitzroy Valley report and conference presentations. PMID:29288181

An Arabidopsis mitochondria-localized RRL protein mediates abscisic acid signal transduction through mitochondrial retrograde regulation involving ABI4.

PubMed

Yao, Xuan; Li, Juanjuan; Liu, Jianping; Liu, Kede

2015-10-01

The molecular mechanisms of abscisic acid (ABA) signalling have been studied for many years; however, how mitochondria-localized proteins play roles in ABA signalling remains unclear. Here an Arabidopsis mitochondria-localized protein RRL (RETARDED ROOT GROWTH-LIKE) was shown to function in ABA signalling. A previous study had revealed that the Arabidopsis mitochondria-localized protein RRG (RETARDED ROOT GROWTH) is required for cell division in the root meristem. RRL shares 54% and 57% identity at the nucleotide and amino acid sequences, respectively, with RRG; nevertheless, RRL shows a different function in Arabidopsis. In this study, disruption of RRL decreased ABA sensitivity whereas overexpression of RRL increased ABA sensitivity during seed germination and seedling growth. High expression levels of RRL were found in germinating seeds and developing seedlings, as revealed by β-glucuronidase (GUS) staining of ProRRL-GUS transgenic lines. The analyses of the structure and function of mitochondria in the knockout rrl mutant showed that the disruption of RRL causes extensively internally vacuolated mitochondria and reduced ABA-stimulated reactive oxygen species (ROS) production. Previous studies have revealed that the expression of alternative oxidase (AOX) in the alternative respiratory pathway is increased by mitochondrial retrograde regulation to regain ROS levels when the mitochondrial electron transport chain is impaired. The APETALA2 (AP2)-type transcription factor ABI4 is a regulator of ALTERNATIVE OXIDASE1a (AOX1a) in mitochondrial retrograde signalling. This study showed that ABA-induced AOX1a and ABI4 expression was inhibited in the rrl mutant, suggesting that RRL is probably involved in ABI4-mediated mitochondrial retrograde signalling. Furthermore, the results revealed that ABI4 is a downstream regulatory factor in RRL-mediated ABA signalling in seed germination and seedling growth. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Transient Mild Hyperthermia Induces E-selectin Mediated Localization of Mesoporous Silicon Vectors in Solid Tumors

PubMed Central

Kirui, Dickson K.; Mai, Juahua; Palange, Anna-Lisa; Qin, Guoting; van de Ven, Anne L.; Liu, Xuewu; Shen, Haifa; Ferrari, Mauro

2014-01-01

Background Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT) to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs). We also determined the optimal time window at which maximal accumulation occur. Results In this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm2) amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm) adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion. Conclusions Our findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy. PMID:24558362

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.

Can (18)F-FDG PET/CT scan change treatment planning and be prognostic in recurrent colorectal carcinoma? A prospective and follow-up study.

PubMed

Artiko, Vera; Odalovic, Strahinja; Sobic-Saranovic, Dragana; Petrovic, Milorad; Stojiljkovic, Milica; Petrovic, Nebojsa; Kozarevic, Nebojsa; Grozdic-Milojevic, Isidora; Obradovic, Vladimir

2015-01-01

To prospectively study whether in patients with resected primary colorectal cancer fluorine- 18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) examination could diagnose the stage, specify treatment procedure and be prognostic. This prospective study included 75 patients with resected primary colorectal adenocarcinoma referred for (18)F-FDG PET/CT to the National PET Center, at the Clinical Center of Serbia, Belgrade, from January 2010 to May 2013. Findings of (18)F-FDG PET/CT were compared to findings of subsequent histopathological examinations or with results of clinical and imaging follow-up. Patients were followed after PET/CT examination for a mean follow-up time of 16.7±5.9 months. In the detection of recurrent disease (18)F-FDG PET/CT showed overall sensitivity, specificity, PPV, NPV and accuracy of 96.6%, 82.4%, 94.9%, 87.5% and 93.3%, respectively. In the detection of stages I and II sensitivity, specificity and accuracy of (18)F-FDG PET/CT were: 88%, 96.6% and 94.7%, respectively, and in the detection of stages III and IV sensitivity, specificity and accuracy were 94.9%, 87.5% and 93.3%, respectively. These findings prevented or changed intended surgical treatment in 12/32 cases. Univariate and multivariate Cox proportional regression analyses revealed that metastatic recurrence (stages III and IV) was the only and independent prognostic factor of disease progression during follow-up (P=0.012 and P=0.023, respectively). Although, survival seemed better in patients with local recurrence compared to metastatic recurrent disease, this difference did not reach significance (Log-rank test; P=0.324). In addition, progression-free survival time was significantly longer in patients in whom (18)F-FDG PET/CT scan led to treatment changes (Log-rank test; P=0.037). (18)F-FDG PET/CT was sensitive and accurate for the detection and staging of local and metastatic recurrent colorectal carcinoma, with higher specificity in the detection of local recurrences. The (18)F-FDG PET/CT scan induced treatment changes in 30/75 patients, including 12/32 patients in which surgical treatment was previously planned, and progression free survival time was significantly longer in these patients.

A Tree Locality-Sensitive Hash for Secure Software Testing

DTIC Science & Technology

2017-09-14

errors, or to look for vulnerabilities that could allow a nefarious actor to use our software against us. Ultimately, all testing is designed to find...and an equivalent number of feasible paths discovered by Klee. 1.5 Summary This document the Tree Locality-Sensitive Hash (TLSH), a locality-senstive...performing two groups of tests that verify the accuracy and usefulness of TLSH. Chapter 5 summarizes the contents of the dissertation and lists avenues

DIETARY VITAMIN A ENHANCES SENSITIVITY OF THE LOCAL LYMPH NODE ASSAY

EPA Science Inventory

Murine assays such as the mouse ear swelling test (MEST) and the local lymph node assay (LLNA) are popular alternatives to guinea pig models for the identification of contact sensitizers, yet there has been concern over the effectiveness of these assays to detect weak and moderat...

Detection of bladder metabolic artifacts in (18)F-FDG PET imaging.

PubMed

Roman-Jimenez, Geoffrey; Crevoisier, Renaud De; Leseur, Julie; Devillers, Anne; Ospina, Juan David; Simon, Antoine; Terve, Pierre; Acosta, Oscar

2016-04-01

Positron emission tomography using (18)F-fluorodeoxyglucose ((18)F-FDG-PET) is a widely used imaging modality in oncology. It enables significant functional information to be included in analyses of anatomical data provided by other image modalities. Although PET offers high sensitivity in detecting suspected malignant metabolism, (18)F-FDG uptake is not tumor-specific and can also be fixed in surrounding healthy tissue, which may consequently be mistaken as cancerous. PET analyses may be particularly hampered in pelvic-located cancers by the bladder׳s physiological uptake potentially obliterating the tumor uptake. In this paper, we propose a novel method for detecting (18)F-FDG bladder artifacts based on a multi-feature double-step classification approach. Using two manually defined seeds (tumor and bladder), the method consists of a semi-automated double-step clustering strategy that simultaneously takes into consideration standard uptake values (SUV) on PET, Hounsfield values on computed tomography (CT), and the distance to the seeds. This method was performed on 52 PET/CT images from patients treated for locally advanced cervical cancer. Manual delineations of the bladder on CT images were used in order to evaluate bladder uptake detection capability. Tumor preservation was evaluated using a manual segmentation of the tumor, with a threshold of 42% of the maximal uptake within the tumor. Robustness was assessed by randomly selecting different initial seeds. The classification averages were 0.94±0.09 for sensitivity, 0.98±0.01 specificity, and 0.98±0.01 accuracy. These results suggest that this method is able to detect most (18)F-FDG bladder metabolism artifacts while preserving tumor uptake, and could thus be used as a pre-processing step for further non-parasitized PET analyses. Copyright © 2016. Published by Elsevier Ltd.

Projected climate impacts for the amphibians of the western hemisphere

USGS Publications Warehouse

Lawler, Joshua J.; Shafer, Sarah L.; Bancroft, Betsy A.; Blaustein, Andrew R.

2010-01-01

Given their physiological requirements, limited dispersal abilities, and hydrologically sensitive habitats, amphibians are likely to be highly sensitive to future climatic changes. We used three approaches to map areas in the western hemisphere where amphibians are particularly likely to be affected by climate change. First, we used bioclimatic models to project potential climate-driven shifts in the distribution of 413 amphibian species based on 20 climate simulations for 2071–2100. We summarized these projections to produce estimates of species turnover. Second, we mapped the distribution of 1099 species with restricted geographic ranges. Finally, using the 20 future climate-change simulations, we mapped areas that were consistently projected to receive less seasonal precipitation in the coming century and thus were likely to have altered microclimates and local hydrologies. Species turnover was projected to be highest in the Andes Mountains and parts of Central America and Mexico, where, on average, turnover rates exceeded 60% under the lower of two emissions scenarios. Many of the restricted-range species not included in our range-shift analyses were concentrated in parts of the Andes and Central America and in Brazil's Atlantic Forest. Much of Central America, southwestern North America, and parts of South America were consistently projected to experience decreased precipitation by the end of the century. Combining the results of the three analyses highlighted several areas in which amphibians are likely to be significantly affected by climate change for multiple reasons. Portions of southern Central America were simultaneously projected to experience high species turnover, have many additional restricted-range species, and were consistently projected to receive less precipitation. Together, our three analyses form one potential assessment of the geographic vulnerability of amphibians to climate change and as such provide broad-scale guidance for directing conservation efforts.

Projected climate impacts for the amphibians of the Western hemisphere.

PubMed

Lawler, Joshua J; Shafer, Sarah L; Bancroft, Betsy A; Blaustein, Andrew R

2010-02-01

Given their physiological requirements, limited dispersal abilities, and hydrologically sensitive habitats, amphibians are likely to be highly sensitive to future climatic changes. We used three approaches to map areas in the western hemisphere where amphibians are particularly likely to be affected by climate change. First, we used bioclimatic models to project potential climate-driven shifts in the distribution of 413 amphibian species based on 20 climate simulations for 2071-2100. We summarized these projections to produce estimates of species turnover. Second, we mapped the distribution of 1099 species with restricted geographic ranges. Finally, using the 20 future climate-change simulations, we mapped areas that were consistently projected to receive less seasonal precipitation in the coming century and thus were likely to have altered microclimates and local hydrologies. Species turnover was projected to be highest in the Andes Mountains and parts of Central America and Mexico, where, on average, turnover rates exceeded 60% under the lower of two emissions scenarios. Many of the restricted-range species not included in our range-shift analyses were concentrated in parts of the Andes and Central America and in Brazil's Atlantic Forest. Much of Central America, southwestern North America, and parts of South America were consistently projected to experience decreased precipitation by the end of the century. Combining the results of the three analyses highlighted several areas in which amphibians are likely to be significantly affected by climate change for multiple reasons. Portions of southern Central America were simultaneously projected to experience high species turnover, have many additional restricted-range species, and were consistently projected to receive less precipitation. Together, our three analyses form one potential assessment of the geographic vulnerability of amphibians to climate change and as such provide broad-scale guidance for directing conservation efforts.

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.

Space shuttle SRM plume expansion sensitivity analysis. [flow characteristics of exhaust gases from solid propellant rocket engines

NASA Technical Reports Server (NTRS)

Smith, S. D.; Tevepaugh, J. A.; Penny, M. M.

1975-01-01

The exhaust plumes of the space shuttle solid rocket motors can have a significant effect on the base pressure and base drag of the shuttle vehicle. A parametric analysis was conducted to assess the sensitivity of the initial plume expansion angle of analytical solid rocket motor flow fields to various analytical input parameters and operating conditions. The results of the analysis are presented and conclusions reached regarding the sensitivity of the initial plume expansion angle to each parameter investigated. Operating conditions parametrically varied were chamber pressure, nozzle inlet angle, nozzle throat radius of curvature ratio and propellant particle loading. Empirical particle parameters investigated were mean size, local drag coefficient and local heat transfer coefficient. Sensitivity of the initial plume expansion angle to gas thermochemistry model and local drag coefficient model assumptions were determined.

Stochastic techno-economic analysis of alcohol-to-jet fuel production.

PubMed

Yao, Guolin; Staples, Mark D; Malina, Robert; Tyner, Wallace E

2017-01-01

Alcohol-to-jet (ATJ) is one of the technical feasible biofuel technologies. It produces jet fuel from sugary, starchy, and lignocellulosic biomass, such as sugarcane, corn grain, and switchgrass, via fermentation of sugars to ethanol or other alcohols. This study assesses the ATJ biofuel production pathway for these three biomass feedstocks, and advances existing techno-economic analyses of biofuels in three ways. First, we incorporate technical uncertainty for all by-products and co-products though statistical linkages between conversion efficiencies and input and output levels. Second, future price uncertainty is based on case-by-case time-series estimation, and a local sensitivity analysis is conducted with respect to each uncertain variable. Third, breakeven price distributions are developed to communicate the inherent uncertainty in breakeven price. This research also considers uncertainties in utility input requirements, fuel and by-product outputs, as well as price uncertainties for all major inputs, products, and co-products. All analyses are done from the perspective of a private firm. The stochastic dominance results of net present values (NPV) and breakeven price distributions show that sugarcane is the lowest cost feedstock over the entire range of uncertainty with the least risks, followed by corn grain and switchgrass, with the mean breakeven jet fuel prices being $0.96/L ($3.65/gal), $1.01/L ($3.84/gal), and $1.38/L ($5.21/gal), respectively. The variation of revenues from by-products in corn grain pathway can significantly impact its profitability. Sensitivity analyses show that technical uncertainty significantly impacts breakeven price and NPV distributions. Technical uncertainty is critical in determining the economic performance of the ATJ fuel pathway. Technical uncertainty needs to be considered in future economic analyses. The variation of revenues from by-products plays a significant role in profitability. With the distribution of breakeven prices, potential investors can apply whatever risk preferences they like to determine an appropriate bid or breakeven price that matches their risk profile.

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

PubMed

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

2017-05-01

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

Local Atopy in Childhood Adenotonsillar Hypertrophy.

PubMed

Cho, Kyu-Sup; Kim, Seong Heon; Hong, Sung-Lyong; Lee, Jaeyoung; Mun, Sue Jean; Roh, Young Eun; Kim, Young Mi; Kim, Hye-Young

2018-05-01

Background Although the cause of adenotonsillar hypertrophy remains unknown, some studies have shown that allergy may be a risk factor. Purpose This study determined the levels of allergen-specific immunoglobulin E (sIgE) in the adenotonsillar tissues of children with adenotonsillar hypertrophy and evaluated the clinical significance of local atopy in adenotonsillar tissues. Methods We measured 21 types of specific immunoglobulin E in the serum and adenotonsillar tissues of 102 children with adenotonsillar hypertrophy and compared the sensitization patterns of the serum and local tissues. The patients were divided into three groups-atopy, local atopy, and nonatopy-according to the sensitization of serum and adenotonsillar tissues, and the clinical symptoms among the groups were analyzed. Results Seventy-two (70.6%) children with adenotonsillar hypertrophy were sensitized to more than one allergen in the serum and/or adenotonsillar tissue. Thirty (29.4%) children had no IgE positivity to any allergen in both serum and adenotonsillar tissues. Fifty-five (53.9%) were sensitized to at least one allergen in the serum. Seventy (68.6%) were sensitized to at least one allergen in the adenotonsillar tissue. Seventeen (36.2%) of 47 children with specific immunoglobulin E-negative serum had specific immunoglobulin E-positive adenotonsillar tissues. The rate of specific immunoglobulin E was significantly higher in local tissues than in serum. The rate of inhalant allergen specific immunoglobulin E was significantly higher in the adenoids than in the tonsils. However, the rate of food allergen specific immunoglobulin E was significantly higher in the tonsils than adenoids. The lifetime prevalence of asthma and allergic rhinitis, recent symptoms or treatment of allergic rhinitis, and severity of nasal symptoms (rhinorrhea, sneezing, and nasal itching) were significantly higher in children with local atopy than with nonatopy. Conclusions These results confirm that allergic response may be a risk factor for adenotonsillar hypertrophy. Local allergic inflammation may play an important role in childhood adenotonsillar hypertrophy, and local atopy in adenotonsillar tissues can cause respiratory allergic symptoms in children.

A generalizable energetics-based model of avian migration to facilitate continental-scale waterbird conservation

USGS Publications Warehouse

Lonsdorf, Eric V.; Thogmartin, Wayne E.; Jacobi, Sarah; Coppen, Jorge; Davis, Amélie Y.; Fox, Timothy J.; Heglund, Patricia J.; Johnson, Rex; Jones, Tim; Kenow, Kevin P.; Lyons, James E.; Luke, Kirsten E.; Still, Shannon; Tavernia, Brian G.

2016-01-01

Conserving migratory birds is made especially difficult because of movement among spatially disparate locations across the annual cycle. In light of challenges presented by the scale and ecology of migratory birds, successful conservation requires integrating objectives, management, and monitoring across scales, from local management units to ecoregional and flyway administrative boundaries. We present an integrated approach using a spatially explicit energetic-based mechanistic bird migration model useful to conservation decision-making across disparate scales and locations. This model moves a mallard-like bird (Anas platyrhynchos), through spring and fall migration as a function of caloric gains and losses across a continental scale energy landscape. We predicted with this model that fall migration, where birds moved from breeding to wintering habitat, took a mean of 27.5 days of flight with a mean seasonal survivorship of 90.5% (95% CI = 89.2%, 91.9%) whereas spring migration took a mean of 23.5 days of flight with mean seasonal survivorship of 93.6% (95% CI = 92.5%, 94.7%). Sensitivity analyses suggested that survival during migration was sensitive to flight speed, flight cost, the amount of energy the animal could carry and the spatial pattern of energy availability, but generally insensitive to total energy availability per se. Nevertheless, continental patterns in the bird-use days occurred principally in relation to wetland cover and agricultural habitat in the fall. Bird-use days were highest in both spring and fall in the Mississippi Alluvial Valley and along the coast and near-shore environments of South Carolina. Spatial sensitivity analyses suggested that locations nearer to migratory endpoints were less important to survivorship; for instance, removing energy from a 1,036 km2 stopover site at a time from the Atlantic Flyway suggested coastal areas between New Jersey and North Carolina, including Chesapeake Bay and the North Carolina piedmont, are essential locations for efficient migration and increasing survivorship during spring migration but not locations in Ontario and Massachusetts. This sort of spatially explicit information may allow decision-makers to prioritize their conservation actions toward locations most influential to migratory success. Thus, this mechanistic model of avian migration provides a decision-analytic medium integrating the potential consequences of local actions to flyway-scale phenomena.

Feasibility and effectiveness of a low cost campaign on antibiotic prescribing in Italy: community level, controlled, non-randomised trial.

PubMed

Formoso, Giulio; Paltrinieri, Barbara; Marata, Anna Maria; Gagliotti, Carlo; Pan, Angelo; Moro, Maria Luisa; Capelli, Oreste; Magrini, Nicola

2013-09-12

To test the hypothesis that a multifaceted, local public campaign could be feasible and influence antibiotic prescribing for outpatients. Community level, controlled, non-randomised trial. Provinces of Modena and Parma in Emilia-Romagna, northern Italy, November 2011 to February 2012. 1,150,000 residents of Modena and Parma (intervention group) and 3,250,000 residents in provinces in the same region but where no campaign had been implemented (control group). Campaign materials (mainly posters, brochures, and advertisements on local media, plus a newsletter on local antibiotic resistance targeted at doctors and pharmacists). General practitioners and paediatricians in the intervention area participated in designing the campaign messages. Primary outcome was the average change in prescribing rates of antibiotics for outpatient in five months, measured as defined daily doses per 1000 inhabitants/day, using health districts as the unit of analysis. Antibiotic prescribing was reduced in the intervention area compared with control area (-4.3%, 95% confidence interval -7.1% to -1.5%). This result was robust to "sensitivity analysis" modifying the baseline period from two months (main analysis) to one month. A higher decrease was observed for penicillins resistant to β lactamase and a lower decrease for penicillins susceptible to β lactamase, consistent with the content of the newsletter on antibiotic resistance directed at health professionals. The decrease in expenditure on antibiotics was not statistically significant in a district level analysis with a two month baseline period (main analysis), but was statistically significant in sensitivity analyses using either a one month baseline period or a more powered doctor level analysis. Knowledge and attitudes of the target population about the correct use of antibiotics did not differ between the intervention and control areas. A local low cost information campaign targeted at citizens, combined with a newsletter on local antibiotic resistance targeted at doctors and pharmacists, was associated with significantly decreased total rates of antibiotic prescribing but did not affect the population's knowledge and attitudes about antibiotic resistance. ClinicalTrials.gov NCT01604096.

Monitoring local heating around an interventional MRI antenna with RF radiometry

PubMed Central

Ertürk, M. Arcan; El-Sharkawy, AbdEl-Monem M.; Bottomley, Paul A.

2015-01-01

Purpose: Radiofrequency (RF) radiometry uses thermal noise detected by an antenna to measure the temperature of objects independent of medical imaging technologies such as magnetic resonance imaging (MRI). Here, an active interventional MRI antenna can be deployed as a RF radiometer to measure local heating, as a possible new method of monitoring device safety and thermal therapy. Methods: A 128 MHz radiometer receiver was fabricated to measure the RF noise voltage from an interventional 3 T MRI loopless antenna and calibrated for temperature in a uniformly heated bioanalogous gel phantom. Local heating (ΔT) was induced using the antenna for RF transmission and measured by RF radiometry, fiber-optic thermal sensors, and MRI thermometry. The spatial thermal sensitivity of the antenna radiometer was numerically computed using a method-of-moment electric field analyses. The gel’s thermal conductivity was measured by MRI thermometry, and the localized time-dependent ΔT distribution computed from the bioheat transfer equation and compared with radiometry measurements. A “H-factor” relating the 1 g-averaged ΔT to the radiometric temperature was introduced to estimate peak temperature rise in the antenna’s sensitive region. Results: The loopless antenna radiometer linearly tracked temperature inside a thermally equilibrated phantom up to 73 °C to within ±0.3 °C at a 2 Hz sample rate. Computed and MRI thermometric measures of peak ΔT agreed within 13%. The peak 1 g-average temperature was H = 1.36 ± 0.02 times higher than the radiometric temperature for any media with a thermal conductivity of 0.15–0.50 (W/m)/K, indicating that the radiometer can measure peak 1 g-averaged ΔT in physiologically relevant tissue within ±0.4 °C. Conclusions: Active internal MRI detectors can serve as RF radiometers at the MRI frequency to provide accurate independent measures of local and peak temperature without the artifacts that can accompany MRI thermometry or the extra space needed to accommodate alternative thermal transducers. A RF radiometer could be integrated in a MRI scanner to permit “self-monitoring” for assuring device safety and/or monitoring delivery of thermal therapy. PMID:25735295

Observation of Anderson localization in disordered nanophotonic structures

NASA Astrophysics Data System (ADS)

Sheinfux, Hanan Herzig; Lumer, Yaakov; Ankonina, Guy; Genack, Azriel Z.; Bartal, Guy; Segev, Mordechai

2017-06-01

Anderson localization is an interference effect crucial to the understanding of waves in disordered media. However, localization is expected to become negligible when the features of the disordered structure are much smaller than the wavelength. Here we experimentally demonstrate the localization of light in a disordered dielectric multilayer with an average layer thickness of 15 nanometers, deep into the subwavelength regime. We observe strong disorder-induced reflections that show that the interplay of localization and evanescence can lead to a substantial decrease in transmission, or the opposite feature of enhanced transmission. This deep-subwavelength Anderson localization exhibits extreme sensitivity: Varying the thickness of a single layer by 2 nanometers changes the reflection appreciably. This sensitivity, approaching the atomic scale, holds the promise of extreme subwavelength sensing.

[Role of desensitization in the treatment of respiratory allergies].

PubMed

Vervloet, D; Romanet, S; Magnan, A

2000-02-01

Most authors consider immunotherapy as an efficient and safe treatment for pollen and mite allergic rhinitis. Recent meta-analyses showed that immunotherapy brings a significant benefit to some asthmatic patients depending on the type of allergen used, the severity of the disease, the number of allergenic sensitivities. Nevertheless everybody agrees that pharmacological treatment of asthma and immunotherapy must be complementary when indications of desensitization are given. All precautions to avoid adverse systemic effects or to cure them immediately must be taken. More work is needed as concerning the duration of the treatment, the efficacy of some local allergen administrations, the indications in the young child. The future is based on the use of antigenic peptides and of recombinant allergens.

New approach to estimating variability in visual field data using an image processing technique.

PubMed Central

Crabb, D P; Edgar, D F; Fitzke, F W; McNaught, A I; Wynn, H P

1995-01-01

AIMS--A new framework for evaluating pointwise sensitivity variation in computerised visual field data is demonstrated. METHODS--A measure of local spatial variability (LSV) is generated using an image processing technique. Fifty five eyes from a sample of normal and glaucomatous subjects, examined on the Humphrey field analyser (HFA), were used to illustrate the method. RESULTS--Significant correlation between LSV and conventional estimates--namely, HFA pattern standard deviation and short term fluctuation, were found. CONCLUSION--LSV is not dependent on normals' reference data or repeated threshold determinations, thus potentially reducing test time. Also, the illustrated pointwise maps of LSV could provide a method for identifying areas of fluctuation commonly found in early glaucomatous field loss. PMID:7703196

Postoperative pain treatment after total knee arthroplasty: A systematic review

PubMed Central

Wetterslev, Mik; Hansen, Signe Elisa; Hansen, Morten Sejer; Mathiesen, Ole; Dahl, Jørgen B.

2017-01-01

Introduction The aim of this systematic review was to document efficacy, safety and quality of evidence of analgesic interventions after total knee arthroplasty (TKA). Methods This PRISMA-compliant and PROSPERO-registered review includes all-language randomized controlled trials of medication-based analgesic interventions after TKA. Bias was evaluated according to Cochrane methodology. Outcomes were opioid consumption (primary), pain scores at rest and during mobilization, adverse events, and length of stay. Interventions investigated in three or more trials were meta-analysed. Outcomes were evaluated using forest plots, Grading of Recommendations Assessment, Development and Evaluation (GRADE), L’Abbe Plots and trial sequential analysis. Results The included 113 trials, investigating 37 different analgesic interventions, were characterized by unclear/high risk of bias, low assay sensitivity and considerable differences in pain assessment tools, basic analgesic regimens, and reporting of adverse events. In meta-analyses single and continuous femoral nerve block (FNB), intrathecal morphine, local infiltration analgesia, intraarticular injection of local anaesthetics, non-steroidal anti-inflammatory drugs, and gabapentinoids demonstrated significant analgesic effects. The 24-hour morphine-sparing effects ranged from 4.2 mg (CI: 1.3, 7.2; intraarticular local anaesthetics), to 16.6 mg (CI: 11.2, 22; single FNB). Pain relieving effects at rest at 6 hours ranged from 4 mm (CI: -10, 2; gabapentinoids), to 19 mm (CI: 8, 31; single FNB), and at 24 hours from 3 mm (CI: -2, 8; gabapentinoids), to 16 mm (CI: 8, 23; continuous FNB). GRADE-rated quality of evidence was generally low. Conclusion A low quality of evidence, small sample sizes and heterogeneity of trial designs prohibit designation of an optimal procedure-specific analgesic regimen after TKA. PMID:28273133

Anastomotic Leaks After Restorative Resections for Rectal Cancer Compromise Cancer Outcomes and Survival.

PubMed

Lu, Zheqin R; Rajendran, Nirooshun; Lynch, A Craig; Heriot, Alexander G; Warrier, Satish K

2016-03-01

Anastomotic leaks after restorative resections for rectal cancer may lead to worse long-term outcomes. The purpose of this study was to evaluate the best current evidence assessing anastomotic leaks in rectal cancer resections with curative intent and their impact on survival and cancer recurrence. A meta-analysis was performed using MEDLINE, EMBASE, and Cochrane search engines for relevant studies published between January 1982 and January 2015. Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology was used to screen and select relevant studies for the review using key words "colorectal surgery; colorectal neoplasm; rectal neoplasm" and "anastomotic leak." Anastomotic leak groups were compared with nonanastomotic leak groups. ORs were calculated from binary data for local recurrence, distant recurrence, and cancer-specific mortality. A random-effects model was then used to calculate pooled ORs with 95% CIs. Eleven studies with 13,655 patients met the inclusion criteria. This included 5 prospective cohort and 6 retrospective cohort studies. Median follow-up was 60 months. Higher cancer-specific mortality was noted in the leak group with an OR of 1.30 (95% CI, 1.04-1.62; p < 0.05). Local recurrences were more likely in rectal cancer resections complicated by anastomotic leaks (OR = 1.61 (95% CI, 1.25-2.09); p < 0.001). Distant recurrence was not more likely in the anastomotic leak group (OR = 1.07 (95% CI, 0.87-1.33); p = 0.52). All 11 studies are level 3 evidence cohort studies. Additional sensitivity analyses were performed to minimize cross-study heterogeneity. Anastomotic leaks after restorative resections for rectal cancer adversely impact cancer-specific mortality and local recurrence.

'Silent' and 'noisy' areas: acute flaccid paralysis surveillance at subnational level, Australia, 2001-2015.

PubMed

Butler, Michelle; Paterson, Beverley J; Martin, Nicolee; Hobday, Linda; Thorley, Bruce; Durrheim, David N

2017-05-01

Acute flaccid paralysis (AFP) surveillance rates are used as an indicator of surveillance sensitivity to detect poliomyelitis with an expected rate of ≥1 case per 100 000 population in children under 15 years of age. The Australian AFP detection rates at sub-national (statistical local area) level were analysed using χ2 goodness of fit tests and exact Poisson probabilities for the combined years 2001-2015 to detect 'silent areas', which may require improved AFP detection efforts, and areas with greater than expected rates, which may indicate unexplained clusters such as those due to enterovirus infection. Eight (n=8/87, 9%) local areas had AFP surveillance detection rates that were less than expected, and eighteen local areas (n=18/87, 21%) had rates that were greater than expected. However, based on available evidence, it is unlikely that these indicated previously unidentified, enterovirus clusters. While Australia has regularly met the national AFP surveillance performance indicators, at the subnational level nine per cent of local areas demonstrated statistically significant lower AFP detection rates. All countries, even those with relatively small populations, should actively identify silent AFP areas to prompt surveillance improvements. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

CO{sub 2} Sequestration Capacity and Associated Aspects of the Most Promising Geologic Formations in the Rocky Mountain Region: Local-Scale Analyses

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

Laes, Denise; Eisinger, Chris; Morgan, Craig

2013-07-30

The purpose of this report is to provide a summary of individual local-­scale CCS site characterization studies conducted in Colorado, New Mexico and Utah. These site-­ specific characterization analyses were performed as part of the “Characterization of Most Promising Sequestration Formations in the Rocky Mountain Region” (RMCCS) project. The primary objective of these local-­scale analyses is to provide a basis for regional-­scale characterization efforts within each state. Specifically, limits on time and funding will typically inhibit CCS projects from conducting high-­ resolution characterization of a state-­sized region, but smaller (< 10,000 km{sup 2}) site analyses are usually possible, and suchmore » can provide insight regarding limiting factors for the regional-­scale geology. For the RMCCS project, the outcomes of these local-­scale studies provide a starting point for future local-­scale site characterization efforts in the Rocky Mountain region.« less

N-Glycomic and Microscopic Subcellular Localization Analyses of NPP1, 2 and 6 Strongly Indicate that trans-Golgi Compartments Participate in the Golgi to Plastid Traffic of Nucleotide Pyrophosphatase/Phosphodiesterases in Rice

PubMed Central

Kaneko, Kentaro; Takamatsu, Takeshi; Inomata, Takuya; Oikawa, Kazusato; Itoh, Kimiko; Hirose, Kazuko; Amano, Maho; Nishimura, Shin-Ichiro; Toyooka, Kiminori; Matsuoka, Ken; Pozueta-Romero, Javier; Mitsui, Toshiaki

2016-01-01

Nucleotide pyrophosphatase/phosphodiesterases (NPPs) are widely distributed N-glycosylated enzymes that catalyze the hydrolytic breakdown of numerous nucleotides and nucleotide sugars. In many plant species, NPPs are encoded by a small multigene family, which in rice are referred to NPP1–NPP6. Although recent investigations showed that N-glycosylated NPP1 is transported from the endoplasmic reticulum (ER)–Golgi system to the chloroplast through the secretory pathway in rice cells, information on N-glycan composition and subcellular localization of other NPPs is still lacking. Computer-assisted analyses of the amino acid sequences deduced from different Oryza sativa NPP-encoding cDNAs predicted all NPPs to be secretory glycoproteins. Confocal fluorescence microscopy observation of cells expressing NPP2 and NPP6 fused with green fluorescent protein (GFP) revealed that NPP2 and NPP6 are plastidial proteins. Plastid targeting of NPP2–GFP and NPP6–GFP was prevented by brefeldin A and by the expression of ARF1(Q71L), a dominant negative mutant of ADP-ribosylation factor 1 that arrests the ER to Golgi traffic, indicating that NPP2 and NPP6 are transported from the ER–Golgi to the plastidial compartment. Confocal laser scanning microscopy and high-pressure frozen/freeze-substituted electron microscopy analyses of transgenic rice cells ectopically expressing the trans-Golgi marker sialyltransferase fused with GFP showed the occurrence of contact of Golgi-derived membrane vesicles with cargo and subsequent absorption into plastids. Sensitive and high-throughput glycoblotting/mass spectrometric analyses showed that complex-type and paucimannosidic-type glycans with fucose and xylose residues occupy approximately 80% of total glycans of NPP1, NPP2 and NPP6. The overall data strongly indicate that the trans-Golgi compartments participate in the Golgi to plastid trafficking and targeting mechanism of NPPs. PMID:27335351

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...

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.

Comparison of different spatial transformations applied to EEG data: A case study of error processing.

PubMed

Cohen, Michael X

2015-09-01

The purpose of this paper is to compare the effects of different spatial transformations applied to the same scalp-recorded EEG data. The spatial transformations applied are two referencing schemes (average and linked earlobes), the surface Laplacian, and beamforming (a distributed source localization procedure). EEG data were collected during a speeded reaction time task that provided a comparison of activity between error vs. correct responses. Analyses focused on time-frequency power, frequency band-specific inter-electrode connectivity, and within-subject cross-trial correlations between EEG activity and reaction time. Time-frequency power analyses showed similar patterns of midfrontal delta-theta power for errors compared to correct responses across all spatial transformations. Beamforming additionally revealed error-related anterior and lateral prefrontal beta-band activity. Within-subject brain-behavior correlations showed similar patterns of results across the spatial transformations, with the correlations being the weakest after beamforming. The most striking difference among the spatial transformations was seen in connectivity analyses: linked earlobe reference produced weak inter-site connectivity that was attributable to volume conduction (zero phase lag), while the average reference and Laplacian produced more interpretable connectivity results. Beamforming did not reveal any significant condition modulations of connectivity. Overall, these analyses show that some findings are robust to spatial transformations, while other findings, particularly those involving cross-trial analyses or connectivity, are more sensitive and may depend on the use of appropriate spatial transformations. Copyright © 2014 Elsevier B.V. All rights reserved.

Closed-Loop Estimation of Retinal Network Sensitivity by Local Empirical Linearization

PubMed Central

2018-01-01

Abstract Understanding how sensory systems process information depends crucially on identifying which features of the stimulus drive the response of sensory neurons, and which ones leave their response invariant. This task is made difficult by the many nonlinearities that shape sensory processing. Here, we present a novel perturbative approach to understand information processing by sensory neurons, where we linearize their collective response locally in stimulus space. We added small perturbations to reference stimuli and tested if they triggered visible changes in the responses, adapting their amplitude according to the previous responses with closed-loop experiments. We developed a local linear model that accurately predicts the sensitivity of the neural responses to these perturbations. Applying this approach to the rat retina, we estimated the optimal performance of a neural decoder and showed that the nonlinear sensitivity of the retina is consistent with an efficient encoding of stimulus information. Our approach can be used to characterize experimentally the sensitivity of neural systems to external stimuli locally, quantify experimentally the capacity of neural networks to encode sensory information, and relate their activity to behavior. PMID:29379871

Cost-effectiveness analysis of a universal mass vaccination program with a PHiD-CV 2+1 schedule in Malaysia.

PubMed

Wang, Xiao Jun; Saha, Ashwini; Zhang, Xu-Hao

2017-01-01

Currently, two pediatric pneumococcal conjugate vaccines are available in the private market of Malaysia-13-valent pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide and non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). This study aimed to evaluate the cost-effectiveness of a universal mass vaccination program with a PHiD-CV 2+1 schedule versus no vaccination or with a PCV13 2+1 schedule in Malaysia. A published Markov cohort model was adapted to evaluate the epidemiological and economic consequences of programs with no vaccination, a PHiD-CV 2+1 schedule or a PCV13 2+1 schedule over a 10-year time horizon. Disease cases, deaths, direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated. Locally published epidemiology and cost data were used whenever possible. Vaccine effectiveness and disutility data were based on the best available published data. All data inputs and assumptions were validated by local clinical and health economics experts. Analyses were conducted from the perspective of the Malaysian government for a birth cohort of 508,774. Costs and QALYs were discounted at 3% per annum. One-way and probabilistic sensitivity analyses were performed. Compared with no vaccination, a PHiD-CV 2+1 program was projected to prevent 1109 invasive pneumococcal disease (IPD), 24,679 pneumonia and 72,940 acute otitis media (AOM) cases and 103 IPD/pneumonia deaths over 10 years, with additional costs and QALYs of United States dollars (USD) 30.9 million and 1084 QALYs, respectively, at an ICER of USD 28,497/QALY. Compared with a PCV13 2+1 program, PHiD-CV 2+1 was projected to result in similar reductions in IPD cases (40 cases more) but significantly fewer AOM cases (30,001 cases less), with cost savings and additional QALYs gained of USD 5.2 million and 116 QALYs, respectively, demonstrating dominance over PCV13. Results were robust to variations in one-way and probabilistic sensitivity analyses. A PHiD-CV 2+1 universal mass vaccination program could substantially reduce pneumococcal disease burden versus no vaccination, and was expected to be cost-effective in Malaysia. A PHiD-CV 2+1 program was also expected to be a dominant choice over a PCV13 2+1 program in Malaysia.

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 perceptual space of local image statistics.

PubMed

Victor, Jonathan D; Thengone, Daniel J; Rizvi, Syed M; Conte, Mary M

2015-12-01

Local image statistics are important for visual analysis of textures, surfaces, and form. There are many kinds of local statistics, including those that capture luminance distributions, spatial contrast, oriented segments, and corners. While sensitivity to each of these kinds of statistics have been well-studied, much less is known about visual processing when multiple kinds of statistics are relevant, in large part because the dimensionality of the problem is high and different kinds of statistics interact. To approach this problem, we focused on binary images on a square lattice - a reduced set of stimuli which nevertheless taps many kinds of local statistics. In this 10-parameter space, we determined psychophysical thresholds to each kind of statistic (16 observers) and all of their pairwise combinations (4 observers). Sensitivities and isodiscrimination contours were consistent across observers. Isodiscrimination contours were elliptical, implying a quadratic interaction rule, which in turn determined ellipsoidal isodiscrimination surfaces in the full 10-dimensional space, and made predictions for sensitivities to complex combinations of statistics. These predictions, including the prediction of a combination of statistics that was metameric to random, were verified experimentally. Finally, check size had only a mild effect on sensitivities over the range from 2.8 to 14min, but sensitivities to second- and higher-order statistics was substantially lower at 1.4min. In sum, local image statistics form a perceptual space that is highly stereotyped across observers, in which different kinds of statistics interact according to simple rules. Copyright © 2015 Elsevier Ltd. All rights reserved.

A perceptual space of local image statistics

PubMed Central

Victor, Jonathan D.; Thengone, Daniel J.; Rizvi, Syed M.; Conte, Mary M.

2015-01-01

Local image statistics are important for visual analysis of textures, surfaces, and form. There are many kinds of local statistics, including those that capture luminance distributions, spatial contrast, oriented segments, and corners. While sensitivity to each of these kinds of statistics have been well-studied, much less is known about visual processing when multiple kinds of statistics are relevant, in large part because the dimensionality of the problem is high and different kinds of statistics interact. To approach this problem, we focused on binary images on a square lattice – a reduced set of stimuli which nevertheless taps many kinds of local statistics. In this 10-parameter space, we determined psychophysical thresholds to each kind of statistic (16 observers) and all of their pairwise combinations (4 observers). Sensitivities and isodiscrimination contours were consistent across observers. Isodiscrimination contours were elliptical, implying a quadratic interaction rule, which in turn determined ellipsoidal isodiscrimination surfaces in the full 10-dimensional space, and made predictions for sensitivities to complex combinations of statistics. These predictions, including the prediction of a combination of statistics that was metameric to random, were verified experimentally. Finally, check size had only a mild effect on sensitivities over the range from 2.8 to 14 min, but sensitivities to second- and higher-order statistics was substantially lower at 1.4 min. In sum, local image statistics forms a perceptual space that is highly stereotyped across observers, in which different kinds of statistics interact according to simple rules. PMID:26130606

Critical Loads of Atmospheric Nitrogen Deposition for Aquatic Ecosystems in Yosemite and Sequoia and Kings Canyon National Parks

NASA Astrophysics Data System (ADS)

Nanus, L.; Clow, D. W.; Sickman, J. O.

2016-12-01

High-elevation aquatic ecosystems in Yosemite (YOSE) and Sequoia and Kings Canyon (SEKI) National Parks are impacted by atmospheric nitrogen (N) deposition associated with local and regional air pollution. Documented effects include elevated surface water nitrate concentrations, increased algal productivity, and changes in diatom species assemblages. Annual wet inorganic N deposition maps, developed at 1-km resolution for YOSE and SEKI to quantify N deposition to sensitive high-elevation ecosystems, range from 1.0 to over 5.0 kg N ha-1 yr-1. Critical loads of N deposition for nutrient enrichment of aquatic ecosystems were quantified and mapped using a geostatistical approach, with N deposition, topography, vegetation, geology, and climate as potential explanatory variables. Multiple predictive models were created using various combinations of explanatory variables; this approach allowed us to better quantify uncertainty and more accurately identify the areas most sensitive to atmospherically deposited N. The lowest critical loads estimates and highest exceedances identified within YOSE and SEKI occurred in high-elevation basins with steep slopes, sparse vegetation, and areas of neoglacial till and talus. These results are consistent with previous analyses in the Rocky Mountains, and highlight the sensitivity of alpine ecosystems to atmospheric N deposition.

Allergenicity evaluation of fragrance mix and its ingredients by using ex vivo local lymph node assay-BrdU endpoints.

PubMed

Ulker, Ozge Cemiloglu; Kaymak, Yesim; Karakaya, Asuman

2014-03-01

The present studies were performed to compare the differences between sensitization potency of fragrance mix and its ingredients (oak moss absolute, isoeugenol, eugenol, cinnamal, hydroxycitronellal, geraniol, cinnamic alcohol, alpha amyl cinnamal), by using ex vivo LLNA-BrdU ELISA. The SI and EC3 values were calculated and potency classification was found for the mixture and for each ingredients. TH1 cytokines (IL-2, IFN-γ) and TH2 cytokines (IL-4, IL-5) releases from lymph node cell culture were also investigated as contact sensitization endpoints. The EC3 values were calculated and the potency of contact sensitization were classified for fragrance mix, oak moss absolute, isoeugenol, eugenol, cinnamal, hydroxycitronellal, geraniol, cinnamic alcohol, alpha amyl cinnamal respectively: 4.4% (moderate), 3.4% (moderate), 0.88% (strong), 16.6% (weak), 1.91% (moderate), 9.77% (moderate), 13.1% (weak), 17.93% (weak), 7.74% (moderate). According to our results it should be concluded that exposure to fragrance mix does not constitute an evidently increased hazard compared to exposure to each of the eight fragrance ingredients separately. Cytokine analyses results indicate that both TH1 and TH2 cytokines are involved in the regulation of murine contact allergy and can be considered as useful endpoints. Copyright © 2014 Elsevier Ltd. All rights reserved.

Detecting asymptomatic Trichomonas vaginalis in females using the BD ProbeTec™ Trichomonas vaginalis Qx nucleic acid amplification test.

PubMed

Lord, Emily; Newnham, Tana; Dorrell, Lucy; Jesuthasan, Gerald; Clarke, Lorraine; Jeffery, Katie; Sherrard, Jackie

2017-03-01

Trichomonas vaginalis (TV) rates in women are increasing and many are asymptomatic. Nucleic acid amplification tests (NAATs) are becoming the 'gold standard' for diagnosis. We aimed to establish our asymptomatic TV rates by testing all women attending Oxfordshire's Sexual Health service, regardless of symptoms, using the BD ProbeTec™ TV Q x NAATs (BDQ x ). During BDQ x 's verification process, the sensitivity and specificity were calculated using results of 220 endocervical samples from symptomatic women, compared with culture. BDQ x was subsequently implemented and prospectively evaluated over 6 months in female attendees. Wet mount microscopy was also performed in symptomatics. Demographic and clinical characteristics of those diagnosed were analysed. From 220 samples tested by BDQ x and culture: 5 were positive on both and one solely using BDQ x , giving a sensitivity and specificity of 100% and 99.53%, respectively. In the prospective cohort, of 5775 BDQ x tests, 33 (0.57%) were positive. 11/33 (33%) patients were asymptomatic. All patients diagnosed had risk factors: age >25 years (85%), residence in a deprived area (79%) and black ethnicity (21%). Despite BDQ x being highly sensitive and specific, with our low TV prevalence universal screening may not be justified. Targeted screening using local demographic data merits further investigation.

Coastal and river flood risk analyses for guiding economically optimal flood adaptation policies: a country-scale study for Mexico

NASA Astrophysics Data System (ADS)

Haer, Toon; Botzen, W. J. Wouter; van Roomen, Vincent; Connor, Harry; Zavala-Hidalgo, Jorge; Eilander, Dirk M.; Ward, Philip J.

2018-06-01

Many countries around the world face increasing impacts from flooding due to socio-economic development in flood-prone areas, which may be enhanced in intensity and frequency as a result of climate change. With increasing flood risk, it is becoming more important to be able to assess the costs and benefits of adaptation strategies. To guide the design of such strategies, policy makers need tools to prioritize where adaptation is needed and how much adaptation funds are required. In this country-scale study, we show how flood risk analyses can be used in cost-benefit analyses to prioritize investments in flood adaptation strategies in Mexico under future climate scenarios. Moreover, given the often limited availability of detailed local data for such analyses, we show how state-of-the-art global data and flood risk assessment models can be applied for a detailed assessment of optimal flood-protection strategies. Our results show that especially states along the Gulf of Mexico have considerable economic benefits from investments in adaptation that limit risks from both river and coastal floods, and that increased flood-protection standards are economically beneficial for many Mexican states. We discuss the sensitivity of our results to modelling uncertainties, the transferability of our modelling approach and policy implications. This article is part of the theme issue `Advances in risk assessment for climate change adaptation policy'.

Nonlinear Analysis of the Space Shuttle Superlightweight LO2 Tank. Part 2; Behavior Under 3g End-of-Flight Loads

NASA Technical Reports Server (NTRS)

Nemeth, Michael P.; Young, Richard D.; Collins, Timothy J.; Starnes, James H.,Jr.

1998-01-01

Results of linear bifurcation and nonlinear analyses of the Space Shuttle super lightweight (SLWT) external liquid-oxygen (LO2) tank are presented for an important end-of-flight loading condition. These results illustrate an important type of response mode for thin-walled shells, that are subjected to combined mechanical and thermal loads, that may be encountered in the design of other liquid-fuel launch vehicles. Linear bifurcation analyses are presented that predict several nearly equal eigenvalues that correspond to local buckling modes in the aft dome of the LO2 tank. In contrast, the nonlinear response phenomenon is shown to consist of a short-wavelength bending deformation in the aft elliptical dome of the LO2 tank that grows in amplitude in a stable manner with increasing load. Imperfection sensitivity analyses are presented that show that the presence of several nearly equal eigenvalues does not lead to a premature general instability mode for the aft dome. For the linear bifurcation and nonlinear analyses, the results show that accurate predictions of the response of the shell generally require a large-scale, high fidelity finite-element model. Results are also presented that show that the SLWT LO2 tank can support loads in excess of approximately 1.9 times the values of the operational loads considered.

Sensitization of TRPV1 by protein kinase C in rats with mono-iodoacetate-induced joint pain.

PubMed

Koda, K; Hyakkoku, K; Ogawa, K; Takasu, K; Imai, S; Sakurai, Y; Fujita, M; Ono, H; Yamamoto, M; Fukuda, I; Yamane, S; Morita, A; Asaki, T; Kanemasa, T; Sakaguchi, G; Morioka, Y

2016-07-01

To assess the functional changes of Transient receptor potential vanilloid 1 (TRPV1) receptor and to clarify its mechanism in a rat mono-iodoacetate (MIA)-induced joint pain model (MIA rats), which has joint degeneration with cartilage loss similar to osteoarthritis. Sensitization of TRPV1 in MIA rats was assessed by transient spontaneous pain behavior induced by capsaicin injection in knee joints and electrophysiological changes of dorsal root ganglion (DRG) neurons innervating knee joints in response to capsaicin. Mechanisms of TRPV1 sensitization were analyzed by a newly developed sandwich enzyme-linked immunosorbent assay that detects phosphorylated TRPV1, followed by functional and expression analyses of protein kinase C (PKC) in vivo and in vitro, which involves TRPV1 phosphorylation. Pain-related behavior induced by intra-articular injection of capsaicin was significantly increased in MIA rats compared with sham rats. In addition, capsaicin sensitivity, evaluated by capsaicin-induced inward currents, was significantly increased in DRG neurons of MIA rats. Protein levels of TRPV1 remained unchanged, but phosphorylated TRPV1 at Ser800 increased in DRG neurons of MIA rats. Phosphorylated-PKCɛ (p-PKCɛ) increased and co-localized with TRPV1 in DRG neurons of MIA rats. Capsaicin-induced pain-related behavior in MIA rats was inhibited by intra-articular pretreatment of the PKC inhibitor bisindolylmaleimide I. In addition, intra-articular injection of the PKC activator phorbol 12-myristate 13-acetate increased capsaicin-induced pain-related behavior in normal rats. TRPV1 was sensitized at the knee joint and at DRG neurons of MIA rats through PKC activation. Thus, TRPV1 sensitization might be involved in chronic pain caused by osteoarthritis. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Accurate Sound Localization in Reverberant Environments is Mediated by Robust Encoding of Spatial Cues in the Auditory Midbrain

PubMed Central

Devore, Sasha; Ihlefeld, Antje; Hancock, Kenneth; Shinn-Cunningham, Barbara; Delgutte, Bertrand

2009-01-01

In reverberant environments, acoustic reflections interfere with the direct sound arriving at a listener’s ears, distorting the spatial cues for sound localization. Yet, human listeners have little difficulty localizing sounds in most settings. Because reverberant energy builds up over time, the source location is represented relatively faithfully during the early portion of a sound, but this representation becomes increasingly degraded later in the stimulus. We show that the directional sensitivity of single neurons in the auditory midbrain of anesthetized cats follows a similar time course, although onset dominance in temporal response patterns results in more robust directional sensitivity than expected, suggesting a simple mechanism for improving directional sensitivity in reverberation. In parallel behavioral experiments, we demonstrate that human lateralization judgments are consistent with predictions from a population rate model decoding the observed midbrain responses, suggesting a subcortical origin for robust sound localization in reverberant environments. PMID:19376072

Allergic contact dermatitis from ethyl chloride and benzocaine.

PubMed

Carazo, Juan Luis Anguita; Morera, Blanca Sáenz de San Pedro; Colom, Luis Palacios; Gálvez Lozano, José Manuel

2009-01-01

Ethyl chloride (EC) or chloroethane (C2H5Cl) is a volatile halogenated hydrocarbon. Reports of contact sensitivity to this gas are infrequent considering its widespread use as a local anesthetic, and it may have a relatively low sensitization potential. Benzocaine is another local anesthetic derivative of the ethyl ester of para-aminobenzoic acid, previously reported as a causative agent of delayed hypersensitivity reactions. We present a patient who developed a generalized itching dermatitis after the application of a medical aerosol containing EC, as well as facial angioedema and tongue swelling after the local application of benzocaine. Patch-test results were positive for EC "as is" (++), benzocaine 5% in petrolatum (++), and caine mix (+++) at 96 hours (day 4). The possibility of cross-sensitization between both drugs would not have been chemically plausible. We report the first published clinical case of contact allergic dermatitis from two chemically unrelated local anesthetics (EC and benzocaine) in the same patient.

A transfer matrix approach to vibration localization in mistuned blade assemblies

NASA Technical Reports Server (NTRS)

Ottarson, Gisli; Pierre, Chritophe

1993-01-01

A study of mode localization in mistuned bladed disks is performed using transfer matrices. The transfer matrix approach yields the free response of a general, mono-coupled, perfectly cyclic assembly in closed form. A mistuned structure is represented by random transfer matrices, and the expansion of these matrices in terms of the small mistuning parameter leads to the definition of a measure of sensitivity to mistuning. An approximation of the localization factor, the spatially averaged rate of exponential attenuation per blade-disk sector, is obtained through perturbation techniques in the limits of high and low sensitivity. The methodology is applied to a common model of a bladed disk and the results verified by Monte Carlo simulations. The easily calculated sensitivity measure may prove to be a valuable design tool due to its system-independent quantification of mistuning effects such as mode localization.

Three-dimensional sensitivity distribution and sample volume of low-induction-number electromagnetic-induction instruments

USGS Publications Warehouse

Callegary, J.B.; Ferré, T.P.A.; Groom, R.W.

2012-01-01

There is an ongoing effort to improve the understanding of the correlation of soil properties with apparent soil electrical conductivity as measured by low-induction-number electromagnetic-induction (LIN FEM) instruments. At a minimum, the dimensions of LIN FEM instruments' sample volume, the spatial distribution of sensitivity within that volume, and implications for surveying and analyses must be clearly defined and discussed. Therefore, a series of numerical simulations was done in which a conductive perturbation was moved systematically through homogeneous soil to elucidate the three-dimensional sample volume of LIN FEM instruments. For a small perturbation with electrical conductivity similar to that of the soil, instrument response is a measure of local sensitivity (LS). Our results indicate that LS depends strongly on the orientation of the instrument's transmitter and receiver coils and includes regions of both positive and negative LS. Integration of the absolute value of LS from highest to lowest was used to contour cumulative sensitivity (CS). The 90% CS contour was used to define the sample volume. For both horizontal and vertical coplanar coil orientations, the longest dimension of the sample volume was at the surface along the main instrument axis with a length of about four times the intercoil spacing (s) with maximum thicknesses of about 1 and 0.3 s, respectively. The imaged distribution of spatial sensitivity within the sample volume is highly complex and should be considered in conjunction with the expected scale of heterogeneity before the use and interpretation of LIN FEM for mapping and profiling. ?? Soil Science Society of America.

Effectiveness of an Evidence-Based Quality Improvement Approach to Cultural Competence Training: The Veterans Affairs' "Caring for Women Veterans" Program.

PubMed

Fox, Annie B; Hamilton, Alison B; Frayne, Susan M; Wiltsey-Stirman, Shannon; Bean-Mayberry, Bevanne; Carney, Diane; Di Leone, Brooke A L; Gierisch, Jennifer M; Goldstein, Karen M; Romodan, Yasmin; Sadler, Anne G; Yano, Elizabeth M; Yee, Ellen F; Vogt, Dawne

2016-01-01

Although providing culturally sensitive health care is vitally important, there is little consensus regarding the most effective strategy for implementing cultural competence trainings in the health care setting. Evidence-based quality improvement (EBQI), which involves adapting evidence-based practices to meet local needs, may improve uptake and effectiveness of a variety of health care innovations. Yet, to our knowledge, EBQI has not yet been applied to cultural competence training. To evaluate whether EBQI could enhance the impact of an evidence-based training intended to improve veterans affairs health care staff gender sensitivity and knowledge (Caring for Women Veterans; CWV), we compared the reach and effectiveness of EBQI delivery versus standard web-based implementation strategies of CWV and assessed barriers and facilitators to EBQI implementation. Workgroups at four diverse veterans affairs health care sites were randomized to either an EBQI or standard web-based implementation condition (SI). All EBQI sites selected a group-based implementation strategy. Employees (N = 84) completed pretraining and posttraining assessments of gender sensitivity and knowledge, and focus groups/interviews were conducted with leadership and staff before and after implementation. Reach of CWV was greater in the EBQI condition versus the SI condition. Whereas both gender sensitivity and knowledge improved in the EBQI condition, only gender sensitivity improved in the SI condition. Qualitative analyses revealed that the EBQI approach was well received, although a number of barriers were identified. Findings suggest that EBQI can enhance the uptake and effectiveness of employee trainings. However, the decision to pursue EBQI must be informed by a consideration of available resources.

Geometrical optimization of a local ballistic magnetic sensor

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

Kanda, Yuhsuke; Hara, Masahiro; Nomura, Tatsuya

2014-04-07

We have developed a highly sensitive local magnetic sensor by using a ballistic transport property in a two-dimensional conductor. A semiclassical simulation reveals that the sensitivity increases when the geometry of the sensor and the spatial distribution of the local field are optimized. We have also experimentally demonstrated a clear observation of a magnetization process in a permalloy dot whose size is much smaller than the size of an optimized ballistic magnetic sensor fabricated from a GaAs/AlGaAs two-dimensional electron gas.

Tolerability of Crisaborole Ointment for Application on Sensitive Skin Areas: A Randomized, Double-Blind, Vehicle-Controlled Study in Healthy Volunteers.

PubMed

Zane, Lee T; Hughes, Matilda H; Shakib, Sepehr

2016-10-01

Inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis often present in sensitive and thin-skinned areas that are at higher risk for topical treatment-related skin irritation (e.g., burning, stinging). Our objective was to address the need for topical treatments that can be safely applied to these areas. We assessed the local tolerability of crisaborole topical ointment when applied to sensitive and thin-skinned areas of healthy volunteers. In this phase I, randomized, double-blind, vehicle-controlled, single-center study, 32 subjects were randomized 3:1 to twice-daily application of crisaborole topical ointment, 2 %, (n = 24) or vehicle ointment (n = 8) for 21 days to 13 anatomic skin areas, including the face/hairline, genitals, extensor, and intertriginous areas. The primary endpoint was assessment of the frequency and severity of local tolerability symptoms (burning/stinging, erythema, and pruritus) using the Local Tolerability Scale. Overall, 98.8 % of all tolerability assessments had a grade of 0 (no signs/symptoms of irritation) and 0.1 % had a grade >1 (mild); no differences were observed in the frequency of local tolerability scores between treatment groups. The total frequency of local tolerability assessments graded >0 (none) was lower across all application sites with crisaborole ointment (0.0-2.2 %) than with vehicle ointment (2.4-7.1 %). Local tolerability did not change over time, and was comparable between sensitive and nonsensitive skin areas. Crisaborole ointment application to sensitive skin areas was well tolerated in healthy volunteers, supporting its potential role as a topical treatment alternative for patients with AD or psoriasis.

Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia in Ukraine.

PubMed

Mandrik, Olena; Corro Ramos, Isaac; Knies, Saskia; Al, Maiwenn; Severens, Johan L

2015-01-01

The aim of this study was to assess the cost-effectiveness, from a health care perspective, of adding rituximab to fludarabine and cyclophosphamide scheme (FCR versus FC) for treatment-naïve and refractory/relapsed Ukrainian patients with chronic lymphocytic leukemia. A decision-analytic Markov cohort model with three health states and 1-month cycle time was developed and run within a life time horizon. Data from two multinational, prospective, open-label Phase 3 studies were used to assess patients' survival. While utilities were generalized from UK data, local resource utilization and disease-associated treatment, hospitalization, and side effect costs were applied. The alternative scenario was performed to assess the impact of lower life expectancy of the general population in Ukraine on the incremental cost-effectiveness ratio (ICER) for treatment-naïve patients. One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the robustness of the results. The ICER (in US dollars) of treating chronic lymphocytic leukemia patients with FCR versus FC is US$8,704 per quality-adjusted life year gained for treatment-naïve patients and US$11,056 for refractory/relapsed patients. When survival data were modified to the lower life expectancy of the general population in Ukraine, the ICER for treatment-naïve patients was higher than US$13,000. This value is higher than three times the current gross domestic product per capita in Ukraine. Sensitivity analyses have shown a high impact of rituximab costs and a moderate impact of differences in utilities on the ICER. Furthermore, probabilistic sensitivity analyses have shown that for refractory/relapsed patients the probability of FCR being cost-effective is higher than for treatment-naïve patients and is close to one if the threshold is higher than US$15,000. State coverage of rituximab treatment may be considered a cost-effective treatment for the Ukrainian population under conditions of economic stability, cost-effectiveness threshold growth, or rituximab price negotiations.

Insulin-like growth factor-binding protein 7 alters the sensitivity to interferon-based anticancer therapy in hepatocellular carcinoma cells.

PubMed

Tomimaru, Y; Eguchi, H; Wada, H; Noda, T; Murakami, M; Kobayashi, S; Marubashi, S; Takeda, Y; Tanemura, M; Umeshita, K; Doki, Y; Mori, M; Nagano, H

2010-05-11

A striking efficiency of interferon (IFN)-based anticancer therapy for advanced hepatocellular carcinoma (HCC) has been reported. Because its clinical efficiency greatly depends on each patient's local response, prediction of local response is crucial. Continuous exposure of IFN-alpha to parental PLC/PRF/5 cells (PLC-P) and a limiting dilution method resulted in the establishment of IFN-resistant cell clones (PLC-Rs). Microarray analyses of PLC-P and PLC-Rs identified insulin-like growth factor-binding protein 7 (IGFBP7) as one of the most significantly downregulated genes in PLC-Rs. Changes in anticancer effects of IFN-alpha were examined in HCC cells after genetic manipulation of IGFBP7 expression. The correlation between immunohistochemically determined IGFBP7 expression and the response to IFN-alpha/5-fluorouracil (5-FU) therapy was investigated in surgically resected HCC specimens. PLC-R cells showed a remarkable downregulation of IGFBP7 and resistance to IFN-alpha, compared with PLC-P. Parental PLC/PRF/5 cells transfected with short hairpin RNA against IGFBP7 showed a significant resistance to IFN-alpha relative to control cells (IC(50) fold increase=14.38 times). Insulin-like growth factor-binding protein 7 transfection into PLC-R restored sensitivity to IFN-alpha. In resected specimens, IGFBP7 expression significantly correlated with the response to IFN-alpha/5-FU therapy. IGFBP7 could be a useful predictor of the response to IFN-based therapy in advanced HCC.

Spectrophotometric and cytochemical analyses of phosphatase activity in Beta vulgaris L.

PubMed

Pesacreta, T C; Bennett, A B; Lucas, W J

1986-03-01

Spectrophotometric and cytochemical methods were used to investigate the localization and/or the sensitivity of phosphatase activities in aldehyde-fixed beet leaves and membrane fractions. The nonspecific acid phosphatase substrates, p-nitrophenyl phosphate and beta-glycerol phosphate, each exhibited unique spectrophotometric patterns of hydrolysis as a function of pH. Additionally, beta-glycerol phosphatase activity was primarily present on the tonoplast, whereas p-nitrophenyl phosphatase was present on the plasma membrane. Because of the unique pH response of each enzyme and their different localization, we conclude that they cannot be entirely "nonspecific." The spectrophotometric pattern of ATP hydrolysis differed from that of p-nitrophenol phosphate in that it decreased at pH 5.0-5.5 and was greatly inhibited by 10 mM sodium fluoride; however, both activities were on the plasma membrane. Therefore, we conclude that these activities represent either two enzymes or only one enzyme that differs in its ability to hydrolyze these two substrates. Generally, enzymatically produced lead deposits on the plasma membrane of non-vascular cells were as frequent and large as those on phloem cells; frequently, deposits on sieve element plasma membranes were relatively small. We therefore conclude that there is no evidence for the presence of relatively intense ATPase activity on the plasma membrane of phloem cells in beet leaf, in contrast to other species. Studies with membrane fractions indicated that formaldehyde could completely inhibit the inhibitor-sensitive phosphatase activities in mitochondrial and vacuolar fractions while preserving significant activity in the plasma membrane fraction.

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.

Identifying and counting point defects in carbon nanotubes.

PubMed

Fan, Yuwei; Goldsmith, Brett R; Collins, Philip G

2005-12-01

The prevailing conception of carbon nanotubes and particularly single-walled carbon nanotubes (SWNTs) continues to be one of perfectly crystalline wires. Here, we demonstrate a selective electrochemical method that labels point defects and makes them easily visible for quantitative analysis. High-quality SWNTs are confirmed to contain one defect per 4 microm on average, with a distribution weighted towards areas of SWNT curvature. Although this defect density compares favourably to high-quality, silicon single-crystals, the presence of a single defect can have tremendous electronic effects in one-dimensional conductors such as SWNTs. We demonstrate a one-to-one correspondence between chemically active point defects and sites of local electronic sensitivity in SWNT circuits, confirming the expectation that individual defects may be critical to understanding and controlling variability, noise and chemical sensitivity in SWNT electronic devices. By varying the SWNT synthesis technique, we further show that the defect spacing can be varied over orders of magnitude. The ability to detect and analyse point defects, especially at very low concentrations, indicates the promise of this technique for quantitative process analysis, especially in nanoelectronics development.

Measurement Equivalence of the Patient Reported Outcomes Measurement Information System® (PROMIS®) Pain Interference Short Form Items: Application to Ethnically Diverse Cancer and Palliative Care Populations.

PubMed

Teresi, Jeanne A; Ocepek-Welikson, Katja; Cook, Karon F; Kleinman, Marjorie; Ramirez, Mildred; Reid, M Carrington; Siu, Albert

2016-01-01

Reducing the response burden of standardized pain measures is desirable, particularly for individuals who are frail or live with chronic illness, e.g., those suffering from cancer and those in palliative care. The Patient Reported Outcome Measurement Information System ® (PROMIS ® ) project addressed this issue with the provision of computerized adaptive tests (CAT) and short form measures that can be used clinically and in research. Although there has been substantial evaluation of PROMIS item banks, little is known about the performance of PROMIS short forms, particularly in ethnically diverse groups. Reviewed in this article are findings related to the differential item functioning (DIF) and reliability of the PROMIS pain interference short forms across diverse sociodemographic groups. DIF hypotheses were generated for the PROMIS short form pain interference items. Initial analyses tested item response theory (IRT) model assumptions of unidimensionality and local independence. Dimensionality was evaluated using factor analytic methods; local dependence (LD) was tested using IRT-based LD indices. Wald tests were used to examine group differences in IRT parameters, and to test DIF hypotheses. A second DIF-detection method used in sensitivity analyses was based on ordinal logistic regression with a latent IRT-derived conditioning variable. Magnitude and impact of DIF were investigated, and reliability and item and scale information statistics were estimated. The reliability of the short form item set was excellent. However, there were a few items with high local dependency, which affected the estimation of the final discrimination parameters. As a result, the item, "How much did pain interfere with enjoyment of social activities?" was excluded in the DIF analyses for all subgroup comparisons. No items were hypothesized to show DIF for race and ethnicity; however, five items showed DIF after adjustment for multiple comparisons in both primary and sensitivity analyses: ability to concentrate, enjoyment of recreational activities, tasks away from home, participation in social activities, and socializing with others. The magnitude of DIF was small and the impact negligible. Three items were consistently identified with DIF for education: enjoyment of life, ability to concentrate, and enjoyment of recreational activities. No item showed DIF above the magnitude threshold and the impact of DIF on the overall measure was minimal. No item showed gender DIF after correction for multiple comparisons in the primary analyses. Four items showed consistent age DIF: enjoyment of life, ability to concentrate, day to day activities, and enjoyment of recreational activities, none with primary magnitude values above threshold. Conditional on the pain state, Spanish speakers were hypothesized to report less pain interference on one item, enjoyment of life. The DIF findings confirmed the hypothesis; however, the magnitude was small. Using an arbitrary cutoff point of theta ( θ ) ≥ 1.0 to classify respondents with acute pain interference, the highest number of changes were for the education groups analyses. There were 231 respondents (4% of the total sample) who changed from the designation of no acute pain interference to acute interference after the DIF adjustment. There was no change in the designations for race/ethnic subgroups, and a small number of changes for respondents aged 65 to 84. Although significant DIF was observed after correction for multiple comparisons, all DIF was of low magnitude and impact. However, some individual-level impact was observed for low education groups. Reliability estimates were high. Thus, the PROMIS short form pain items examined in this ethnically diverse sample performed relatively well; although one item was problematic and removed from the analyses. It is concluded that the majority of the PROMIS pain interference short form items can be recommended for use among ethnically diverse groups, including those in palliative care and with cancer and chronic illness.

Measurement Equivalence of the Patient Reported Outcomes Measurement Information System® (PROMIS®) Pain Interference Short Form Items: Application to Ethnically Diverse Cancer and Palliative Care Populations

PubMed Central

Teresi, Jeanne A.; Ocepek-Welikson, Katja; Cook, Karon F.; Kleinman, Marjorie; Ramirez, Mildred; Reid, M. Carrington; Siu, Albert

2017-01-01

Reducing the response burden of standardized pain measures is desirable, particularly for individuals who are frail or live with chronic illness, e.g., those suffering from cancer and those in palliative care. The Patient Reported Outcome Measurement Information System® (PROMIS®) project addressed this issue with the provision of computerized adaptive tests (CAT) and short form measures that can be used clinically and in research. Although there has been substantial evaluation of PROMIS item banks, little is known about the performance of PROMIS short forms, particularly in ethnically diverse groups. Reviewed in this article are findings related to the differential item functioning (DIF) and reliability of the PROMIS pain interference short forms across diverse sociodemographic groups. Methods DIF hypotheses were generated for the PROMIS short form pain interference items. Initial analyses tested item response theory (IRT) model assumptions of unidimensionality and local independence. Dimensionality was evaluated using factor analytic methods; local dependence (LD) was tested using IRT-based LD indices. Wald tests were used to examine group differences in IRT parameters, and to test DIF hypotheses. A second DIF-detection method used in sensitivity analyses was based on ordinal logistic regression with a latent IRT-derived conditioning variable. Magnitude and impact of DIF were investigated, and reliability and item and scale information statistics were estimated. Results The reliability of the short form item set was excellent. However, there were a few items with high local dependency, which affected the estimation of the final discrimination parameters. As a result, the item, “How much did pain interfere with enjoyment of social activities?” was excluded in the DIF analyses for all subgroup comparisons. No items were hypothesized to show DIF for race and ethnicity; however, five items showed DIF after adjustment for multiple comparisons in both primary and sensitivity analyses: ability to concentrate, enjoyment of recreational activities, tasks away from home, participation in social activities, and socializing with others. The magnitude of DIF was small and the impact negligible. Three items were consistently identified with DIF for education: enjoyment of life, ability to concentrate, and enjoyment of recreational activities. No item showed DIF above the magnitude threshold and the impact of DIF on the overall measure was minimal. No item showed gender DIF after correction for multiple comparisons in the primary analyses. Four items showed consistent age DIF: enjoyment of life, ability to concentrate, day to day activities, and enjoyment of recreational activities, none with primary magnitude values above threshold. Conditional on the pain state, Spanish speakers were hypothesized to report less pain interference on one item, enjoyment of life. The DIF findings confirmed the hypothesis; however, the magnitude was small. Using an arbitrary cutoff point of theta (θ) ≥ 1.0 to classify respondents with acute pain interference, the highest number of changes were for the education groups analyses. There were 231 respondents (4% of the total sample) who changed from the designation of no acute pain interference to acute interference after the DIF adjustment. There was no change in the designations for race/ethnic subgroups, and a small number of changes for respondents aged 65 to 84. Conclusions Although significant DIF was observed after correction for multiple comparisons, all DIF was of low magnitude and impact. However, some individual-level impact was observed for low education groups. Reliability estimates were high. Thus, the PROMIS short form pain items examined in this ethnically diverse sample performed relatively well; although one item was problematic and removed from the analyses. It is concluded that the majority of the PROMIS pain interference short form items can be recommended for use among ethnically diverse groups, including those in palliative care and with cancer and chronic illness. PMID:28983449

A suite of microplate reader-based colorimetric methods to quantify ammonium, nitrate, orthophosphate and silicate concentrations for aquatic nutrient monitoring.

PubMed

Ringuet, Stephanie; Sassano, Lara; Johnson, Zackary I

2011-02-01

A sensitive, accurate and rapid analysis of major nutrients in aquatic systems is essential for monitoring and maintaining healthy aquatic environments. In particular, monitoring ammonium (NH(4)(+)) concentrations is necessary for maintenance of many fish stocks, while accurate monitoring and regulation of ammonium, orthophosphate (PO(4)(3-)), silicate (Si(OH)(4)) and nitrate (NO(3)(-)) concentrations are required for regulating algae production. Monitoring of wastewater streams is also required for many aquaculture, municipal and industrial wastewater facilities to comply with local, state or federal water quality effluent regulations. Traditional methods for quantifying these nutrient concentrations often require laborious techniques or expensive specialized equipment making these analyses difficult. Here we present four alternative microcolorimetric assays that are based on a standard 96-well microplate format and microplate reader that simplify the quantification of each of these nutrients. Each method uses small sample volumes (200 µL), has a detection limit ≤ 1 µM in freshwater and ≤ 2 µM in saltwater, precision of at least 8% and compares favorably with standard analytical procedures. Routine use of these techniques in the laboratory and at an aquaculture facility to monitor nutrient concentrations associated with microalgae growth demonstrates that they are rapid, accurate and highly reproducible among different users. These techniques offer an alternative to standard nutrient analyses and because they are based on the standard 96-well format, they significantly decrease the cost and time of processing while maintaining high precision and sensitivity.

Economic Evaluation of Lipid-Lowering Therapy in the Secondary Prevention Setting in the Philippines.

PubMed

Tumanan-Mendoza, Bernadette A; Mendoza, Victor L

2013-05-01

To determine the cost-effectiveness of lipid-lowering therapy in the secondary prevention of cardiovascular events in the Philippines. A cost-utility analysis was performed by using Markov modeling in the secondary prevention setting. The models incorporated efficacy of lipid-lowering therapy demonstrated in randomized controlled trials and mortality rates obtained from local life tables. Average and incremental cost-effectiveness ratios were obtained for simvastatin, atorvastatin, pravastatin, and gemfibrozil. The costs of the following were included: medications, laboratory examinations, consultation and related expenses, and production losses. The costs were expressed in current or nominal prices as of the first quarter of 2010 (Philippine peso). Utility was expressed in quality-adjusted life-years gained. Sensitivity analyses were performed by using variations in the cost centers, discount rates, starting age, and differences in utility weights for stroke. In the analysis using the lower-priced generic counterparts, therapy using 40 mg simvastatin daily was the most cost-effective option compared with the other therapies, while pravastatin 40 mg daily was the most cost-effective alternative if the higher-priced innovator drugs were used. In all sensitivity analyses, gemfibrozil was strongly dominated by the statins. In secondary prevention, simvastatin or pravastatin were the most cost-effective options compared with atorvastatin and gemfibrozil in the Philippines. Gemfibrozil was strongly dominated by the statins. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

SNAP-23 regulates phagosome formation and maturation in macrophages

PubMed Central

Sakurai, Chiye; Hashimoto, Hitoshi; Nakanishi, Hideki; Arai, Seisuke; Wada, Yoh; Sun-Wada, Ge-Hong; Wada, Ikuo; Hatsuzawa, Kiyotaka

2012-01-01

Synaptosomal associated protein of 23 kDa (SNAP-23), a plasma membrane–localized soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE), has been implicated in phagocytosis by macrophages. For elucidation of its precise role in this process, a macrophage line overexpressing monomeric Venus–tagged SNAP-23 was established. These cells showed enhanced Fc receptor–mediated phagocytosis. Detailed analyses of each process of phagocytosis revealed a marked increase in the production of reactive oxygen species within phagosomes. Also, enhanced accumulation of a lysotropic dye, as well as augmented quenching of a pH-sensitive fluorophore were observed. Analyses of isolated phagosomes indicated the critical role of SNAP-23 in the functional recruitment of the NADPH oxidase complex and vacuolar-type H+-ATPase to phagosomes. The data from the overexpression experiments were confirmed by SNAP-23 knockdown, which demonstrated a significant delay in phagosome maturation and a reduction in uptake activity. Finally, for analyzing whether phagosomal SNAP-23 entails a structural change in the protein, an intramolecular Förster resonance energy transfer (FRET) probe was constructed, in which the distance within a TagGFP2-TagRFP was altered upon close approximation of the N-termini of its two SNARE motifs. FRET efficiency on phagosomes was markedly enhanced only when VAMP7, a lysosomal SNARE, was coexpressed. Taken together, our results strongly suggest the involvement of SNAP-23 in both phagosome formation and maturation in macrophages, presumably by mediating SNARE-based membrane traffic. PMID:23087210

Optimizing EFL Learners' Sensitizing Reading Skill: Development of Local Content-Based Textbook

ERIC Educational Resources Information Center

Arifani, Yudhi

2016-01-01

The development of local wisdom based sensitizing reading material is aimed at penetrating one of the imperishable gaps between authentic and non-authentic reading materials dispute in an EFL teaching context. Promoting EFL learners' needs for the first semester students of English department at university level, who rarely or even never have a…

The Global/Local Nexus in Comparative Policy Studies: Analysing the Triple Bonus System in Mongolia over Time

ERIC Educational Resources Information Center

Steiner-Khamsi, Gita

2012-01-01

The article analyses a phenomenon that has accompanied teacher salary reform in Mongolia: the import of two global education policies that were nearly identical to the already existing local bonus system ("olympiads"). To make sense of an import that appears superfluous, the author analyses the reception and translation of the triple…

Analysis of the localization of Michelson interferometer fringes using Fourier optics and temporal coherence

NASA Astrophysics Data System (ADS)

Narayanamurthy, C. S.

2009-01-01

Fringes formed in a Michelson interferometer never localize in any plane, in the detector plane and in the localization plane. Instead, the fringes are assumed to localize at infinity. Except for some explanation in Principles of Optics by Born and Wolf (1964 (New York: Macmillan)), the fringe localization phenomena of Michelson's interferometer have never been analysed seriously in any book. Because Michelson's interferometer is one of the important and fundamental optical experiments taught at both undergraduate and graduate levels, it would be appropriate to explain the localization of these fringes. In this paper, we analyse the localization of Michelson interferometer fringes using Fourier optics and temporal coherence, and show that they never localize at any plane even at infinity.

Quantitative estimation of localization errors of 3d transition metal pseudopotentials in diffusion Monte Carlo

DOE PAGES

Dzubak, Allison L.; Krogel, Jaron T.; Reboredo, Fernando A.

2017-07-10

The necessarily approximate evaluation of non-local pseudopotentials in diffusion Monte Carlo (DMC) introduces localization errors. In this paper, we estimate these errors for two families of non-local pseudopotentials for the first-row transition metal atoms Sc–Zn using an extrapolation scheme and multideterminant wavefunctions. Sensitivities of the error in the DMC energies to the Jastrow factor are used to estimate the quality of two sets of pseudopotentials with respect to locality error reduction. The locality approximation and T-moves scheme are also compared for accuracy of total energies. After estimating the removal of the locality and T-moves errors, we present the range ofmore » fixed-node energies between a single determinant description and a full valence multideterminant complete active space expansion. The results for these pseudopotentials agree with previous findings that the locality approximation is less sensitive to changes in the Jastrow than T-moves yielding more accurate total energies, however not necessarily more accurate energy differences. For both the locality approximation and T-moves, we find decreasing Jastrow sensitivity moving left to right across the series Sc–Zn. The recently generated pseudopotentials of Krogel et al. reduce the magnitude of the locality error compared with the pseudopotentials of Burkatzki et al. by an average estimated 40% using the locality approximation. The estimated locality error is equivalent for both sets of pseudopotentials when T-moves is used. Finally, for the Sc–Zn atomic series with these pseudopotentials, and using up to three-body Jastrow factors, our results suggest that the fixed-node error is dominant over the locality error when a single determinant is used.« less

Influences of Cutting Speed and Material Mechanical Properties on Chip Deformation and Fracture during High-Speed Cutting of Inconel 718.

PubMed

Wang, Bing; Liu, Zhanqiang; Hou, Xin; Zhao, Jinfu

2018-03-21

The paper aims to investigate the influences of material constitutive and fracture parameters in addition to cutting speed on chip formation during high-speed cutting of Inconel 718. Finite element analyses for chip formation are conducted with Johnson-Cook constitutive and fracture models. Meanwhile, experiments of high-speed orthogonal cutting are performed to verify the simulation results with cutting speeds ranging from 50 m/min to 7000 m/min. The research indicates that the chip morphology transforms from serrated to fragmented at the cutting speed of 7000 m/min due to embrittlement of the workpiece material under ultra-high cutting speeds. The parameter of shear localization sensitivity is put forward to describe the influences of material mechanical properties on serrated chip formation. The results demonstrate that the effects of initial yield stress and thermal softening coefficient on chip shear localization are much more remarkable than the other constitutive parameters. For the material fracture parameters, the effects of initial fracture strain and exponential factor of stress state on chip shear localization are more much prominent. This paper provides guidance for controlling chip formation through the adjustment of material mechanical properties and the selection of appropriate cutting parameters.

Influences of Cutting Speed and Material Mechanical Properties on Chip Deformation and Fracture during High-Speed Cutting of Inconel 718

PubMed Central

Hou, Xin; Zhao, Jinfu

2018-01-01

The paper aims to investigate the influences of material constitutive and fracture parameters in addition to cutting speed on chip formation during high-speed cutting of Inconel 718. Finite element analyses for chip formation are conducted with Johnson–Cook constitutive and fracture models. Meanwhile, experiments of high-speed orthogonal cutting are performed to verify the simulation results with cutting speeds ranging from 50 m/min to 7000 m/min. The research indicates that the chip morphology transforms from serrated to fragmented at the cutting speed of 7000 m/min due to embrittlement of the workpiece material under ultra-high cutting speeds. The parameter of shear localization sensitivity is put forward to describe the influences of material mechanical properties on serrated chip formation. The results demonstrate that the effects of initial yield stress and thermal softening coefficient on chip shear localization are much more remarkable than the other constitutive parameters. For the material fracture parameters, the effects of initial fracture strain and exponential factor of stress state on chip shear localization are more much prominent. This paper provides guidance for controlling chip formation through the adjustment of material mechanical properties and the selection of appropriate cutting parameters. PMID:29561770

Pollution-Induced Community Tolerance To Diagnose Hazardous Chemicals in Multiple Contaminated Aquatic Systems.

PubMed

Rotter, Stefanie; Gunold, Roman; Mothes, Sibylle; Paschke, Albrecht; Brack, Werner; Altenburger, Rolf; Schmitt-Jansen, Mechthild

2015-08-18

Aquatic ecosystems are often contaminated with large numbers of chemicals, which cannot be sufficiently addressed by chemical target analyses. Effect-directed analysis (EDA) enables the identification of toxicants in complex contaminated environmental samples. This study suggests pollution-induced community tolerance (PICT) as a confirmation tool for EDA to identify contaminants which actually impact on local communities. The effects of three phytotoxic compounds local periphyton communities, cultivated at a reference (R-site) and a polluted site (P-site), were assessed to confirm the findings of a former EDA study on sediments. The sensitivities of R- and P-communities to prometryn, tributyltin (TBT) and N-phenyl-2-naphthylamine (PNA) were quantified in short-term toxicity tests and exposure concentrations were determined. Prometryn and PNA concentrations were significantly higher at the P-site, whereas TBT concentrations were in the same range at both sites. Periphyton communities differed in biomass, but algal class composition and diatom diversity were similar. Community tolerance of P-communities was significantly enhanced for prometryn, but not for PNA and TBT, confirming site-specific effects on local periphyton for prometryn only. Thus, PICT enables in situ effect confirmation of phytotoxic compounds at the community level and seems to be suitable to support confirmation and enhance ecological realism of EDA.

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.

Decadal-scale sensitivity of Northeast Greenland ice flow to errors in surface mass balance using ISSM

NASA Astrophysics Data System (ADS)

Schlegel, N.-J.; Larour, E.; Seroussi, H.; Morlighem, M.; Box, J. E.

2013-06-01

The behavior of the Greenland Ice Sheet, which is considered a major contributor to sea level changes, is best understood on century and longer time scales. However, on decadal time scales, its response is less predictable due to the difficulty of modeling surface climate, as well as incomplete understanding of the dynamic processes responsible for ice flow. Therefore, it is imperative to understand how modeling advancements, such as increased spatial resolution or more comprehensive ice flow equations, might improve projections of ice sheet response to climatic trends. Here we examine how a finely resolved climate forcing influences a high-resolution ice stream model that considers longitudinal stresses. We simulate ice flow using a two-dimensional Shelfy-Stream Approximation implemented within the Ice Sheet System Model (ISSM) and use uncertainty quantification tools embedded within the model to calculate the sensitivity of ice flow within the Northeast Greenland Ice Stream to errors in surface mass balance (SMB) forcing. Our results suggest that the model tends to smooth ice velocities even when forced with extreme errors in SMB. Indeed, errors propagate linearly through the model, resulting in discharge uncertainty of 16% or 1.9 Gt/yr. We find that mass flux is most sensitive to local errors but is also affected by errors hundreds of kilometers away; thus, an accurate SMB map of the entire basin is critical for realistic simulation. Furthermore, sensitivity analyses indicate that SMB forcing needs to be provided at a resolution of at least 40 km.

Evaluation of non-radioactive endpoints of ex vivo local lymph node assay-BrdU to investigate select contact sensitizers.

PubMed

Ulker, Ozge Cemiloglu; Ates, Ilker; Atak, Aysegul; Karakaya, Asuman

2013-01-01

The present study sought to verify the utility of the non-radioactive endpoints LLNA BrdU (5-bromo-2'-deoxyuridine) ex vivo incorporation and cytokine release using auricular lymph node cells isolated from BALB/c mice topically treated with a strong (formaldehyde or p-phenylene-diamine [PPD]), moderate sensitizer (cinnamal), or weak sensitizer (eugenol). Stimulation index (SI) and EC₃ values were calculated for each agent. Based on the results of ex vivo LLNA-BrdU assays, EC₃ values were calculated to be 0.29, 0.09, 1.91, and 16.60% for formaldehyde, PPD, cinnamal, and eugenol, respectively. These results were in good agreement with data from previous standard radioactive LLNA. Cytokine analyses indicated T(H)1 and T(H)2 cytokine involvement in the regulation of murine contact allergy and these could be utilized as endpoints in assessments of contact allergy in mice. In conclusion, the current study provided evidence that the non-radioactive endpoint LLNA BrdU ex vivo incorporation could be of use as a viable alternative approach to assess the skin sensitization potential of test compound with respect to improving animal welfare. This is of particular importance in the case of any laboratory where it might be difficult to handle and/or readily employ radioisotopes. Further studies will be required to confirm--across test agents--the reproducibility as well as the limits of utility of this new ex vivo BrdU method.

Sensitivity Analysis of PM2.5 in Seoul to Emissions and Reaction Rates Using the GEOS-Chem and its Adjoint Model

NASA Astrophysics Data System (ADS)

Lee, H. M.; Park, R.; Henze, D. K.; Shim, C.; Shin, H. J.; Song, I. H.; Park, J. S.; Park, S. M.; Moon, K. J.

2015-12-01

The sources of PM2.5 are poorly quantified in Seoul, Korea, where tens of millions of populations are daily exposed to the exceedance of PM2.5 concentrations to the air quality criteria. We used a global 3-D chemical transport model (GEOS-Chem) and its adjoint to investigate the sensitivities of PM2.5 concentrations in Seoul to emission sources, sectors, and chemical reaction rates. We first conduct forward model simulations using a nested version of GEOS-Chem with 0.25°x0.3125° spatial resolutions in East Asia for July 2012 - July 2013. We evaluated the model by comparing it with PM2.5 mass and chemical composition observations at National Institute of Environmental Research sites in Korea. The model reasonably reproduces the observed seasonal variability of PM2.5 concentrations (R=0.3-0.6), but tends to overestimate the observations in summer and underestimate them in winter. Our sensitivity analyses show the dominant contributions from local emission sources to PM2.5 concentrations in Seoul compared to the trans-boundary transport influences from the outside, which are important for long-lived tracers in spring. Other results including the model sensitivity to input parameters and the updated emissions are used to improve the model performance and to provide strategic information for the KORUS-AQ flight measurement campaign in May-June, 2016.

Automatic diagnosis of imbalanced ophthalmic images using a cost-sensitive deep convolutional neural network.

PubMed

Jiang, Jiewei; Liu, Xiyang; Zhang, Kai; Long, Erping; Wang, Liming; Li, Wangting; Liu, Lin; Wang, Shuai; Zhu, Mingmin; Cui, Jiangtao; Liu, Zhenzhen; Lin, Zhuoling; Li, Xiaoyan; Chen, Jingjing; Cao, Qianzhong; Li, Jing; Wu, Xiaohang; Wang, Dongni; Wang, Jinghui; Lin, Haotian

2017-11-21

Ocular images play an essential role in ophthalmological diagnoses. Having an imbalanced dataset is an inevitable issue in automated ocular diseases diagnosis; the scarcity of positive samples always tends to result in the misdiagnosis of severe patients during the classification task. Exploring an effective computer-aided diagnostic method to deal with imbalanced ophthalmological dataset is crucial. In this paper, we develop an effective cost-sensitive deep residual convolutional neural network (CS-ResCNN) classifier to diagnose ophthalmic diseases using retro-illumination images. First, the regions of interest (crystalline lens) are automatically identified via twice-applied Canny detection and Hough transformation. Then, the localized zones are fed into the CS-ResCNN to extract high-level features for subsequent use in automatic diagnosis. Second, the impacts of cost factors on the CS-ResCNN are further analyzed using a grid-search procedure to verify that our proposed system is robust and efficient. Qualitative analyses and quantitative experimental results demonstrate that our proposed method outperforms other conventional approaches and offers exceptional mean accuracy (92.24%), specificity (93.19%), sensitivity (89.66%) and AUC (97.11%) results. Moreover, the sensitivity of the CS-ResCNN is enhanced by over 13.6% compared to the native CNN method. Our study provides a practical strategy for addressing imbalanced ophthalmological datasets and has the potential to be applied to other medical images. The developed and deployed CS-ResCNN could serve as computer-aided diagnosis software for ophthalmologists in clinical application.

Local effects of redundant terrestrial and GPS-based tie vectors in ITRF-like combinations

NASA Astrophysics Data System (ADS)

Abbondanza, Claudio; Altamimi, Zuheir; Sarti, Pierguido; Negusini, Monia; Vittuari, Luca

2009-11-01

Tie vectors (TVs) between co-located space geodetic instruments are essential for combining terrestrial reference frames (TRFs) realised using different techniques. They provide relative positioning between instrumental reference points (RPs) which are part of a global geodetic network such as the international terrestrial reference frame (ITRF). This paper gathers the set of very long baseline interferometry (VLBI)-global positioning system (GPS) local ties performed at the observatory of Medicina (Northern Italy) during the years 2001-2006 and discusses some important aspects related to the usage of co-location ties in the combinations of TRFs. Two measurement approaches of local survey are considered here: a GPS-based approach and a classical approach based on terrestrial observations (i.e. angles, distances and height differences). The behaviour of terrestrial local ties, which routinely join combinations of space geodetic solutions, is compared to that of GPS-based local ties. In particular, we have performed and analysed different combinations of satellite laser ranging (SLR), VLBI and GPS long term solutions in order to (i) evaluate the local effects of the insertion of the series of TVs computed at Medicina, (ii) investigate the consistency of GPS-based TVs with respect to space geodetic solutions, (iii) discuss the effects of an imprecise alignment of TVs from a local to a global reference frame. Results of ITRF-like combinations show that terrestrial TVs originate the smallest residuals in all the three components. In most cases, GPS-based TVs fit space geodetic solutions very well, especially in the horizontal components (N, E). On the contrary, the estimation of the VLBI RP Up component through GPS technique appears to be awkward, since the corresponding post fit residuals are considerably larger. Besides, combination tests including multi-temporal TVs display local effects of residual redistribution, when compared to those solutions where Medicina TVs are added one at a time. Finally, the combination of TRFs turns out to be sensitive to the orientation of the local tie into the global frame.

Examination of ductile spall failure through direct numerical simulation

NASA Astrophysics Data System (ADS)

Becker, Richard

2017-06-01

Direct numerical simulation is used to examine the growth and coalescence of a random population of voids leading to spall failure. Void nucleating particles are explicitly represented in the initial geometry, and the arbitrary Lagrange-Eulerian finite element code tracks the void evolution to create the spall surface. The flow fields capture strain localization associated with void interaction at low porosities and ligament necking at final coalescence. Simulations are run to assess the influence of material strain hardening and strain rate sensitivity on void growth and coalescence. These analyses also provide the evolution of longitudinal stress and the energy dissipated, and they reveal a length scale associated with the spall. Additional calculations are performed to examine the influence of loading pulse shape on spall behavior for triangular shaped pressure loading. A dependence of spall scab thickness on pulse shape is determined. These results show localization delayed until porosities reach a few percent and they demonstrate a consistent stress versus porosity relation. The simulations also provide a direct correlation between the spall stress history and the free surface velocity, which can aid in understanding stress corrections applied to experimental data.

BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire

PubMed Central

Najafova, Zeynab; Tirado-Magallanes, Roberto; Subramaniam, Malayannan; Hossan, Tareq; Schmidt, Geske; Nagarajan, Sankari; Baumgart, Simon J.; Mishra, Vivek Kumar; Bedi, Upasana; Hesse, Eric; Knapp, Stefan; Hawse, John R.; Johnsen, Steven A.

2017-01-01

Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4. PMID:27651452

BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire.

PubMed

Najafova, Zeynab; Tirado-Magallanes, Roberto; Subramaniam, Malayannan; Hossan, Tareq; Schmidt, Geske; Nagarajan, Sankari; Baumgart, Simon J; Mishra, Vivek Kumar; Bedi, Upasana; Hesse, Eric; Knapp, Stefan; Hawse, John R; Johnsen, Steven A

2017-01-09

Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

SEM probe of IC radiation sensitivity

NASA Technical Reports Server (NTRS)

Gauthier, M. K.; Stanley, A. G.

1979-01-01

Scanning Electron Microscope (SEM) used to irradiate single integrated circuit (IC) subcomponent to test for radiation sensitivity can localize area of IC less than .03 by .03 mm for determination of exact location of radiation sensitive section.

A multi-emitter fitting algorithm for potential live cell super-resolution imaging over a wide range of molecular densities.

PubMed

Takeshima, T; Takahashi, T; Yamashita, J; Okada, Y; Watanabe, S

2018-05-25

Multi-emitter fitting algorithms have been developed to improve the temporal resolution of single-molecule switching nanoscopy, but the molecular density range they can analyse is narrow and the computation required is intensive, significantly limiting their practical application. Here, we propose a computationally fast method, wedged template matching (WTM), an algorithm that uses a template matching technique to localise molecules at any overlapping molecular density from sparse to ultrahigh density with subdiffraction resolution. WTM achieves the localization of overlapping molecules at densities up to 600 molecules μm -2 with a high detection sensitivity and fast computational speed. WTM also shows localization precision comparable with that of DAOSTORM (an algorithm for high-density super-resolution microscopy), at densities up to 20 molecules μm -2 , and better than DAOSTORM at higher molecular densities. The application of WTM to a high-density biological sample image demonstrated that it resolved protein dynamics from live cell images with subdiffraction resolution and a temporal resolution of several hundred milliseconds or less through a significant reduction in the number of camera images required for a high-density reconstruction. WTM algorithm is a computationally fast, multi-emitter fitting algorithm that can analyse over a wide range of molecular densities. The algorithm is available through the website. https://doi.org/10.17632/bf3z6xpn5j.1. © 2018 The Authors. Journal of Microscopy published by JohnWiley & Sons Ltd on behalf of Royal Microscopical Society.

Oxygen and strontium isotope tracing of human migration at the Bell Beaker site Le Tumulus des Sables, France.

NASA Astrophysics Data System (ADS)

Willmes, Malte; James, Hannah; Boel, Ceridwen; Courtaud, Patrice; Chancerel, Antoine; McMorrow, Linda; Armstrong, Richard; Kinsley, Les; Aubert, Maxime; Eggins, Stephen; Moffat, Ian; Grün, Rainer

2014-05-01

Oxygen (δ18O) and strontium (87Sr/86Sr) isotopes were used as tools to investigate human migration at the early Bell Beaker site (2500-2000 BC) Le Tumulus des Sables, Saint-Laurent-Médoc, south-west France. The O and Sr isotope ratios measured in tooth enamel record the average dietary isotope signature ingested by that individual during their childhood. When this data is compared to the isotope signature of the burial site it can be used to indicate if the individual migrated into this area during their lifetime. The O isotopic composition of meteoric water changes depending on climate, temperature and quantity of precipitation. O isotope ratios in skeletal and dental remains are related to body water, which in turn is influenced by diet, physiology and climate. Most of the water consumed by large mammals comes from drinking water, typically sourced locally. Sr isotope ratios on the other hand vary between different geologic regions, depending on their age and composition. Sr is released through weathering and transported into the soil, ground and surface water, where it becomes available for uptake by plants, enters the food cycle and eventually ends up in skeletal and dental tissue where it substitutes for calcium. We analysed the teeth of 18 adult and 8 juvenile disarticulated skeletons from Le Tumulus des Sables. O isotopes were analysed in-situ by Sensitive High Resolution Ion Micro Probe (SHRIMP).The Sr isotope analysis involved drilling a 0.2-0.5 mg sample of enamel from the tooth. The Sr was then chemically separated and analysed by Thermal Ionization Mass Spectrometry (TIMS). These results were then compared to the O isoscape of Europe and bioavailable Sr isotope data (fauna, plants, soils) from the IRHUM database. We found that most of the individuals at Le Tumulus des Sables show O and Sr isotope ratios corresponding to the local environmental signal and we interpret these as part of the local population. 3 adults however show slightly higher 87Sr/86Sr ratios, which correspond to a clay and limestone unit in close proximity (

Autoradiographic localization of voltage-dependent sodium channels on the mouse neuromuscular junction using /sup 125/I-alpha scorpion toxin. I. Preferential labeling of glial cells on the presynaptic side

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

Boudier, J.L.; Jover, E.; Cau, P.

1988-05-01

Alpha-scorpion toxins bind specifically to the voltage-sensitive sodium channel in excitable membranes, and binding is potential-dependent. The radioiodinated toxin II from the scorpion Androctonus australis Hector (alpha ScTx) was used to localize voltage-sensitive sodium channels on the presynaptic side of mouse neuromuscular junctions (NMJ) by autoradiography using both light and electron microscopy. Silver grain localization was analyzed by the cross-fire method. At the light-microscopic level, grain density over NMJ appeared 6-8x higher than over nonjunctional muscle membrane. The specificity of labeling was verified by competition/displacement with an excess of native alpha ScTx. Labeling was also inhibited by incubation in depolarizingmore » conditions, showing its potential-dependence. At the electron-microscopic level, analysis showed that voltage-sensitive sodium channels labeled with alpha ScTx were almost exclusively localized on membranes, as expected. Due to washout after incubation, appreciable numbers of binding sites were not found on the postsynaptic membranes. However, on the presynaptic side, alpha ScTx-labeled voltage-sensitive sodium channels were localized on the membrane of non-myelin-forming Schwann cells covering NMJ. The axonal presynaptic membrane was not labeled. These results show that voltage-sensitive sodium channels are present on glial cells in vivo, as already demonstrated in vitro. It is proposed that these glial channels could be indirectly involved in the ionic homeostasis of the axonal environment.« less

Behavioural sensitivity to binaural spatial cues in ferrets: evidence for plasticity in the duplex theory of sound localization

PubMed Central

Keating, Peter; Nodal, Fernando R; King, Andrew J

2014-01-01

For over a century, the duplex theory has guided our understanding of human sound localization in the horizontal plane. According to this theory, the auditory system uses interaural time differences (ITDs) and interaural level differences (ILDs) to localize low-frequency and high-frequency sounds, respectively. Whilst this theory successfully accounts for the localization of tones by humans, some species show very different behaviour. Ferrets are widely used for studying both clinical and fundamental aspects of spatial hearing, but it is not known whether the duplex theory applies to this species or, if so, to what extent the frequency range over which each binaural cue is used depends on acoustical or neurophysiological factors. To address these issues, we trained ferrets to lateralize tones presented over earphones and found that the frequency dependence of ITD and ILD sensitivity broadly paralleled that observed in humans. Compared with humans, however, the transition between ITD and ILD sensitivity was shifted toward higher frequencies. We found that the frequency dependence of ITD sensitivity in ferrets can partially be accounted for by acoustical factors, although neurophysiological mechanisms are also likely to be involved. Moreover, we show that binaural cue sensitivity can be shaped by experience, as training ferrets on a 1-kHz ILD task resulted in significant improvements in thresholds that were specific to the trained cue and frequency. Our results provide new insights into the factors limiting the use of different sound localization cues and highlight the importance of sensory experience in shaping the underlying neural mechanisms. PMID:24256073

Overview of Sensitivity Analysis and Shape Optimization for Complex Aerodynamic Configurations

NASA Technical Reports Server (NTRS)

Newman, Perry A.; Newman, James C., III; Barnwell, Richard W.; Taylor, Arthur C., III; Hou, Gene J.-W.

1998-01-01

This paper presents a brief overview of some of the more recent advances in steady aerodynamic shape-design sensitivity analysis and optimization, based on advanced computational fluid dynamics. The focus here is on those methods particularly well- suited to the study of geometrically complex configurations and their potentially complex associated flow physics. When nonlinear state equations are considered in the optimization process, difficulties are found in the application of sensitivity analysis. Some techniques for circumventing such difficulties are currently being explored and are included here. Attention is directed to methods that utilize automatic differentiation to obtain aerodynamic sensitivity derivatives for both complex configurations and complex flow physics. Various examples of shape-design sensitivity analysis for unstructured-grid computational fluid dynamics algorithms are demonstrated for different formulations of the sensitivity equations. Finally, the use of advanced, unstructured-grid computational fluid dynamics in multidisciplinary analyses and multidisciplinary sensitivity analyses within future optimization processes is recommended and encouraged.

Host Resistance, Population Structure and the Long-Term Persistence of Bubonic Plague: Contributions of a Modelling Approach in the Malagasy Focus

PubMed Central

Gascuel, Fanny; Choisy, Marc; Duplantier, Jean-Marc; Débarre, Florence; Brouat, Carine

2013-01-01

Although bubonic plague is an endemic zoonosis in many countries around the world, the factors responsible for the persistence of this highly virulent disease remain poorly known. Classically, the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible rodents in natural foci, and/or to a metapopulation structure of reservoirs. Here, we test separately the effect of each of these factors on the long-term persistence of plague. We analyse the dynamics and equilibria of a model of plague propagation, consistent with plague ecology in Madagascar, a major focus where this disease is endemic since the 1920s in central highlands. By combining deterministic and stochastic analyses of this model, and including sensitivity analyses, we show that (i) endemicity is favoured by intermediate host population sizes, (ii) in large host populations, the presence of resistant rats is sufficient to explain long-term persistence of plague, and (iii) the metapopulation structure of susceptible host populations alone can also account for plague endemicity, thanks to both subdivision and the subsequent reduction in the size of subpopulations, and extinction-recolonization dynamics of the disease. In the light of these results, we suggest scenarios to explain the localized presence of plague in Madagascar. PMID:23675291

Host resistance, population structure and the long-term persistence of bubonic plague: contributions of a modelling approach in the Malagasy focus.

PubMed

Gascuel, Fanny; Choisy, Marc; Duplantier, Jean-Marc; Débarre, Florence; Brouat, Carine

2013-01-01

Although bubonic plague is an endemic zoonosis in many countries around the world, the factors responsible for the persistence of this highly virulent disease remain poorly known. Classically, the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible rodents in natural foci, and/or to a metapopulation structure of reservoirs. Here, we test separately the effect of each of these factors on the long-term persistence of plague. We analyse the dynamics and equilibria of a model of plague propagation, consistent with plague ecology in Madagascar, a major focus where this disease is endemic since the 1920s in central highlands. By combining deterministic and stochastic analyses of this model, and including sensitivity analyses, we show that (i) endemicity is favoured by intermediate host population sizes, (ii) in large host populations, the presence of resistant rats is sufficient to explain long-term persistence of plague, and (iii) the metapopulation structure of susceptible host populations alone can also account for plague endemicity, thanks to both subdivision and the subsequent reduction in the size of subpopulations, and extinction-recolonization dynamics of the disease. In the light of these results, we suggest scenarios to explain the localized presence of plague in Madagascar.

Screening for circulating RAS/RAF mutations by multiplex digital PCR.

PubMed

Andersen, Rikke Fredslund; Jakobsen, Anders

2016-07-01

Recent years have shown a large interest in the application of liquid biopsies in cancer management. Circulating tumor DNA (ctDNA) has been investigated for potential use in treatment selection, monitoring of treatment response, and early detection of recurrence. Advances have been hampered by technical challenges primarily due to the low levels of ctDNA in patients with localized disease and in patients responding to therapy. The approach presented here is a multiplex digital PCR method of screening for 31 mutations in the KRAS, NRAS, BRAF, and PIK3CA genes in the plasma. The upper level of the limit of blank, which defines the specificity of the multiplexes, was 0.006%-0.06%. Mutations found by multiplex analyses were identified and quantified by duplex analyses. The method was tested on samples from cholangiocarcinoma patients with known tumor mutational status. Mutations found in the tumor were also found in plasma samples in all cases with analyses for all other mutations being negative. There was a perfect agreement as to wild type status in tumor and plasma. The method combines a high sensitivity with the ability to analyze for several mutations at a time and could be a step towards routine clinical application of liquid biopsies. Copyright © 2016 Elsevier B.V. All rights reserved.

Testing the reliability of δ13C of tree rings as climate tool in Pistacia khinjuk of Syrian desert

NASA Astrophysics Data System (ADS)

Caracuta, Valentina; Fiorentino, Girolamo

2010-05-01

High-resolution measures of past climate variations have been found to be of a critical importance for understanding anthropic resilience in drought-sensitive areas. The hills (Jebels) Abu-Rujmain and Abd al Aziz, with their 350 millimetre of rain and their steppe-forest spreading in the middle of the flat syrian desert, represent an unicum where analysing the effect of short term climate changes on pastoral communities. Thanks to a cooperation project in Syrian Arab republic with CIHEAM-Mediterranean Agronomic Institute of Bari -Italy (Rationalization of Ras El Ain Irrigation systems), we were allowed to carry out dendroclimate and carbon isotope analyses on tree-rings of local Pistacia khinjuk, a long-lived wood taxon, in order to test their reliability as tool for determining annual and seasonal rainfall/temperature variations. Comparison between the last 25 year rainfall and temperature values of the nearby meteorological stations and dendro-isotopes values have been carried out to point out which factor mostly affect the growth pattern of the trees in that particular area.

Stochastic modeling of wetland-groundwater systems

NASA Astrophysics Data System (ADS)

Bertassello, Leonardo Enrico; Rao, P. Suresh C.; Park, Jeryang; Jawitz, James W.; Botter, Gianluca

2018-02-01

Modeling and data analyses were used in this study to examine the temporal hydrological variability in geographically isolated wetlands (GIWs), as influenced by hydrologic connectivity to shallow groundwater, wetland bathymetry, and subject to stochastic hydro-climatic forcing. We examined the general case of GIWs coupled to shallow groundwater through exfiltration or infiltration across wetland bottom. We also examined limiting case with the wetland stage as the local expression of the shallow groundwater. We derive analytical expressions for the steady-state probability density functions (pdfs) for wetland water storage and stage using few, scaled, physically-based parameters. In addition, we analyze the hydrologic crossing time properties of wetland stage, and the dependence of the mean hydroperiod on climatic and wetland morphologic attributes. Our analyses show that it is crucial to account for shallow groundwater connectivity to fully understand the hydrologic dynamics in wetlands. The application of the model to two different case studies in Florida, jointly with a detailed sensitivity analysis, allowed us to identify the main drivers of hydrologic dynamics in GIWs under different climate and morphologic conditions.

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

A high figure of merit localized surface plasmon sensor based on a gold nanograting on the top of a gold planar film

NASA Astrophysics Data System (ADS)

Zhang, Zu-Yin; Wang, Li-Na; Hu, Hai-Feng; Li, Kang-Wen; Ma, Xun-Peng; Song, Guo-Feng

2013-10-01

We investigate the sensitivity and figure of merit (FOM) of a localized surface plasmon (LSP) sensor with gold nanograting on the top of planar metallic film. The sensitivity of the localized surface plasmon sensor is 317 nm/RIU, and the FOM is predicted to be above 8, which is very high for a localized surface plasmon sensor. By employing the rigorous coupled-wave analysis (RCWA) method, we analyze the distribution of the magnetic field and find that the sensing property of our proposed system is attributed to the interactions between the localized surface plasmon around the gold nanostrips and the surface plasmon polarition on the surface of the gold planar metallic film. These findings are important for developing high FOM localized surface plasmon sensors.

An ATP sensitive light addressable biosensor for extracellular monitoring of single taste receptor cell.

PubMed

Wu, Chunsheng; Du, Liping; Zou, Ling; Zhao, Luhang; Wang, Ping

2012-12-01

Adenosine triphosphate (ATP) is considered as the key neurotransmitter in taste buds for taste signal transmission and processing. Measurements of ATP secreted from single taste receptor cell (TRC) with high sensitivity and specificity are essential for investigating mechanisms underlying taste cell-to-cell communications. In this study, we presented an aptamer-based biosensor for the detection of ATP locally secreted from single TRC. ATP sensitive DNA aptamer was used as recognition element and its DNA competitor was served as signal transduction element that was covalently immobilized on the surface of light addressable potentiometric sensor (LAPS). Due to the light addressable capability of LAPS, local ATP secretion from single TRC can be detected by monitoring the working potential shifts of LAPS. The results show this biosensor can detect ATP with high sensitivity and specificity. It is demonstrated this biosensor can effectively detect the local ATP secretion from single TRC responding to tastant mixture. This biosensor could provide a promising new tool for the research of taste cell-to-cell communications as well as for the detection of local ATP secretion from other types of ATP secreting individual cells.

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.

Balancing data sharing requirements for analyses with data sensitivity

USGS Publications Warehouse

Jarnevich, C.S.; Graham, J.J.; Newman, G.J.; Crall, A.W.; Stohlgren, T.J.

2007-01-01

Data sensitivity can pose a formidable barrier to data sharing. Knowledge of species current distributions from data sharing is critical for the creation of watch lists and an early warning/rapid response system and for model generation for the spread of invasive species. We have created an on-line system to synthesize disparate datasets of non-native species locations that includes a mechanism to account for data sensitivity. Data contributors are able to mark their data as sensitive. This data is then 'fuzzed' in mapping applications and downloaded files to quarter-quadrangle grid cells, but the actual locations are available for analyses. We propose that this system overcomes the hurdles to data sharing posed by sensitive data. ?? 2006 Springer Science+Business Media B.V.

The effect of brain lesions on sound localization in complex acoustic environments.

PubMed

Zündorf, Ida C; Karnath, Hans-Otto; Lewald, Jörg

2014-05-01

Localizing sound sources of interest in cluttered acoustic environments--as in the 'cocktail-party' situation--is one of the most demanding challenges to the human auditory system in everyday life. In this study, stroke patients' ability to localize acoustic targets in a single-source and in a multi-source setup in the free sound field were directly compared. Subsequent voxel-based lesion-behaviour mapping analyses were computed to uncover the brain areas associated with a deficit in localization in the presence of multiple distracter sound sources rather than localization of individually presented sound sources. Analyses revealed a fundamental role of the right planum temporale in this task. The results from the left hemisphere were less straightforward, but suggested an involvement of inferior frontal and pre- and postcentral areas. These areas appear to be particularly involved in the spectrotemporal analyses crucial for effective segregation of multiple sound streams from various locations, beyond the currently known network for localization of isolated sound sources in otherwise silent surroundings.

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

In situ fluorescence imaging of localized corrosion with a pH-sensitive imaging fiber

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

Panova, A.A.; Pantano, P.; Walt, D.R.

1997-12-01

A fiber optic pH-sensor capable of both visualizing corrosion sites and measuring local chemical concentrations is applied to real-time corrosion monitoring. The imaging fiber`s distal face containing an immobilized pH-sensitive fluorescent dye is brought into contact with metal surfaces submerged in aqueous buffers and fluorescence images are acquired as a function of time. The observed changes in fluorescence due to increases in pH at cathodic sites and decreases in pH at anodic sites are indicative of localized corrosion rates.

Cost-effectiveness of a disease-specific oral nutritional support for pressure ulcer healing.

PubMed

Cereda, Emanuele; Klersy, Catherine; Andreola, Manuela; Pisati, Roberto; Schols, Jos M G A; Caccialanza, Riccardo; D'Andrea, Federico

2017-02-01

The Oligo Element Sore Trial has shown that supplementation with a disease-specific nutritional formula enriched with arginine, zinc, and antioxidants improves pressure ulcer (PU) healing in malnourished patients compared to an isocaloric-isonitrogenous support. However, the use of such a nutritional formula needs to be supported also by a cost-effectiveness evaluation. This economic evaluation - from a local healthcare system perspective - was conducted alongside a multicenter, randomized, controlled trial following a piggy-back approach. The primary efficacy endpoint was the percentage of change in PU area at 8 weeks. The cost analysis focused on: the difference in direct medical costs of local PU care between groups and incremental cost-effectiveness ratio (ICER) of nutritional therapy related to significant study endpoints (percentage of change in PU area and ≥40% reduction in PU area at 8 weeks). Although the experimental formula was more expensive (mean difference: 39.4 Euros; P < 0.001), its use resulted in money saving with respect to both non-nutritional PU care activities (difference, -113.7 Euros; P = 0.001) and costs of local PU care (difference, -74.3 Euros; P = 0.013). Therefore, given its efficacy it proved to be a cost-effective intervention. The robustness of these results was confirmed by the sensitivity analyses. The use of a disease-specific oral nutritional formula not only results in better healing of PUs, but also reduces the costs of local PU care from a local healthcare system perspective. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Analysis of parameter estimation and optimization application of ant colony algorithm in vehicle routing problem

NASA Astrophysics Data System (ADS)

Xu, Quan-Li; Cao, Yu-Wei; Yang, Kun

2018-03-01

Ant Colony Optimization (ACO) is the most widely used artificial intelligence algorithm at present. This study introduced the principle and mathematical model of ACO algorithm in solving Vehicle Routing Problem (VRP), and designed a vehicle routing optimization model based on ACO, then the vehicle routing optimization simulation system was developed by using c ++ programming language, and the sensitivity analyses, estimations and improvements of the three key parameters of ACO were carried out. The results indicated that the ACO algorithm designed in this paper can efficiently solve rational planning and optimization of VRP, and the different values of the key parameters have significant influence on the performance and optimization effects of the algorithm, and the improved algorithm is not easy to locally converge prematurely and has good robustness.

Univariate and bivariate likelihood-based meta-analysis methods performed comparably when marginal sensitivity and specificity were the targets of inference.

PubMed

Dahabreh, Issa J; Trikalinos, Thomas A; Lau, Joseph; Schmid, Christopher H

2017-03-01

To compare statistical methods for meta-analysis of sensitivity and specificity of medical tests (e.g., diagnostic or screening tests). We constructed a database of PubMed-indexed meta-analyses of test performance from which 2 × 2 tables for each included study could be extracted. We reanalyzed the data using univariate and bivariate random effects models fit with inverse variance and maximum likelihood methods. Analyses were performed using both normal and binomial likelihoods to describe within-study variability. The bivariate model using the binomial likelihood was also fit using a fully Bayesian approach. We use two worked examples-thoracic computerized tomography to detect aortic injury and rapid prescreening of Papanicolaou smears to detect cytological abnormalities-to highlight that different meta-analysis approaches can produce different results. We also present results from reanalysis of 308 meta-analyses of sensitivity and specificity. Models using the normal approximation produced sensitivity and specificity estimates closer to 50% and smaller standard errors compared to models using the binomial likelihood; absolute differences of 5% or greater were observed in 12% and 5% of meta-analyses for sensitivity and specificity, respectively. Results from univariate and bivariate random effects models were similar, regardless of estimation method. Maximum likelihood and Bayesian methods produced almost identical summary estimates under the bivariate model; however, Bayesian analyses indicated greater uncertainty around those estimates. Bivariate models produced imprecise estimates of the between-study correlation of sensitivity and specificity. Differences between methods were larger with increasing proportion of studies that were small or required a continuity correction. The binomial likelihood should be used to model within-study variability. Univariate and bivariate models give similar estimates of the marginal distributions for sensitivity and specificity. Bayesian methods fully quantify uncertainty and their ability to incorporate external evidence may be useful for imprecisely estimated parameters. Copyright © 2017 Elsevier Inc. All rights reserved.

Surface-enhanced localized surface plasmon resonance biosensing of avian influenza DNA hybridization using subwavelength metallic nanoarrays

NASA Astrophysics Data System (ADS)

Kim, Shin Ae; Byun, Kyung Min; Kim, Kyujung; Jang, Sung Min; Ma, Kyungjae; Oh, Youngjin; Kim, Donghyun; Kim, Sung Guk; Shuler, Michael L.; Kim, Sung June

2010-09-01

We demonstrated enhanced localized surface plasmon resonance (SPR) biosensing based on subwavelength gold nanoarrays built on a thin gold film. Arrays of nanogratings (1D) and nanoholes (2D) with a period of 200 nm were fabricated by electron-beam lithography and used for the detection of avian influenza DNA hybridization. Experimental results showed that both nanoarrays provided significant sensitivity improvement and, especially, 1D nanogratings exhibited higher SPR signal amplification compared with 2D nanohole arrays. The sensitivity enhancement is associated with changes in surface-limited reaction area and strong interactions between bound molecules and localized plasmon fields. Our approach is expected to improve both the sensitivity and sensing resolution and can be applicable to label-free detection of DNA without amplification by polymerase chain reaction.

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

NASA Technical Reports Server (NTRS)

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

1977-01-01

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

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

Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirin-like drugs in the dog knee joint.

PubMed

Moncada, S; Ferreira, S H; Vane, J R

1975-04-01

A method has been developed to measure the analgesic action of aspirin-like drugs in knee joints of anaesthetized dogs. Bradykinin, injected into the joint cavity, induced a reflex rise in blood pressure which was dose-dependent; this was used as a measure of nociceptive activity. The joint cavity became more sensitive to bradykinin as the experiment proceeded, or when a low concentration of prostaglandin E1 or E2 was infused locally. The increase in sensitivity with time was prevented by local injection of aspirin or indomethacin, but that induced by exogenous prostaglandin infusion was not. Injections of carrageenin into dog knee joints increased the prostaglandin E2 content of synovial fluid by up to 160 ng per joint; indomethacin prevented this increase. These experiments support our previous conclusion that local biosynthesis of a prostaglandin (induced by mild trauma) sensitizes pain receptors to mechanical or chemical stimuli. Aspirin-like drugs are analgesic because they prevent prostaglandin biosynthesis, thereby preventing this sensitization.

Sensitivity Analysis of the Static Aeroelastic Response of a Wing

NASA Technical Reports Server (NTRS)

Eldred, Lloyd B.

1993-01-01

A technique to obtain the sensitivity of the static aeroelastic response of a three dimensional wing model is designed and implemented. The formulation is quite general and accepts any aerodynamic and structural analysis capability. A program to combine the discipline level, or local, sensitivities into global sensitivity derivatives is developed. A variety of representations of the wing pressure field are developed and tested to determine the most accurate and efficient scheme for representing the field outside of the aerodynamic code. Chebyshev polynomials are used to globally fit the pressure field. This approach had some difficulties in representing local variations in the field, so a variety of local interpolation polynomial pressure representations are also implemented. These panel based representations use a constant pressure value, a bilinearly interpolated value. or a biquadraticallv interpolated value. The interpolation polynomial approaches do an excellent job of reducing the numerical problems of the global approach for comparable computational effort. Regardless of the pressure representation used. sensitivity and response results with excellent accuracy have been produced for large integrated quantities such as wing tip deflection and trim angle of attack. The sensitivities of such things as individual generalized displacements have been found with fair accuracy. In general, accuracy is found to be proportional to the relative size of the derivatives to the quantity itself.

A novel versatile microbiosensor for local hydrogen detection by means of scanning photoelectrochemical microscopy.

PubMed

Zhao, Fangyuan; Conzuelo, Felipe; Hartmann, Volker; Li, Huaiguang; Stapf, Stefanie; Nowaczyk, Marc M; Rögner, Matthias; Plumeré, Nicolas; Lubitz, Wolfgang; Schuhmann, Wolfgang

2017-08-15

The development of a versatile microbiosensor for hydrogen detection is reported. Carbon-based microelectrodes were modified with a [NiFe]-hydrogenase embedded in a viologen-modified redox hydrogel for the fabrication of a sensitive hydrogen biosensor By integrating the microbiosensor in a scanning photoelectrochemical microscope, it was capable of serving simultaneously as local light source to initiate photo(bio)electrochemical reactions while acting as sensitive biosensor for the detection of hydrogen. A hydrogen evolution biocatalyst based on photosystem 1-platinum nanoparticle biocomplexes embedded into a specifically designed redox polymer was used as a model for proving the capability of the developed hydrogen biosensor for the detection of hydrogen upon localized illumination. The versatility and sensitivity of the proposed microbiosensor as probe tip allows simplification of the set-up used for the evaluation of complex electrochemical processes and the rapid investigation of local photoelectrocatalytic activity of biocatalysts towards light-induced hydrogen evolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Local Populations of Arabidopsis thaliana Show Clear Relationship between Photoperiodic Sensitivity of Flowering Time and Altitude

PubMed Central

Lewandowska-Sabat, Anna M.; Fjellheim, Siri; Olsen, Jorunn E.; Rognli, Odd A.

2017-01-01

Adaptation of plants to local conditions that vary substantially within their geographic range is essential for seasonal timing of flowering, a major determinant of plant reproductive success. This study investigates photoperiodic responses in natural populations of Arabidopsis thaliana from high northern latitudes and their significance for local adaptation. Thirty lineages from ten local A. thaliana populations, representing different locations across an altitudinal gradient (2–850 m a.s.l.) in Norway, were grown under uniform controlled conditions, and used to screen for responses to five different photoperiods. We studied relationships between variation in photoperiodic sensitivity of flowering time, altitude, and climatic factors associated with the sites of origin. We found that variation in response to photoperiod is significantly correlated with altitude and climatic variables associated with the sites of origin of the populations. Populations originating from lower altitudes showed stronger photoperiodic sensitivity than populations from higher altitudes. Our results indicate that the altitudinal climatic gradient generates clinal variation in adaptive traits in A. thaliana. PMID:28659966

Plasticity in variation of xylem and phloem cell characteristics of Norway spruce under different local conditions

PubMed Central

Gričar, Jožica; Prislan, Peter; de Luis, Martin; Gryc, Vladimír; Hacurová, Jana; Vavrčík, Hanuš; Čufar, Katarina

2015-01-01

There is limited information on intra-annual plasticity of secondary tissues of tree species growing under different environmental conditions. To increase the knowledge about the plasticity of secondary growth, which allows trees to adapt to specific local climatic regimes, we examined climate–radial growth relationships of Norway spruce [Picea abies (L.) H. Karst.] from three contrasting locations in the temperate climatic zone by analyzing tree-ring widths for the period 1932–2010, and cell characteristics in xylem and phloem increments formed in the years 2009–2011. Variation in the structure of xylem and phloem increments clearly shows that plasticity in seasonal dynamics of cambial cell production and cell differentiation exists on xylem and phloem sides. Anatomical characteristics of xylem and phloem cells are predominantly site-specific characteristics, because they varied among sites but were fairly uniform among years in trees from the same site. Xylem and phloem tissues formed in the first part of the growing season seemed to be more stable in structure, indicating their priority over latewood and late phloem for tree performance. Long-term climate and radial growth analyses revealed that growth was in general less dependent on precipitation than on temperature; however, growth sensitivity to local conditions differed among the sites. Only partial dependence of radial growth of spruce on climatic factors on the selected sites confirms its strategy to adapt the structure of wood and phloem increments to function optimally in local conditions. PMID:26442044

Meta-epidemiologic study showed frequent time trends in summary estimates from meta-analyses of diagnostic accuracy studies.

PubMed

Cohen, Jérémie F; Korevaar, Daniël A; Wang, Junfeng; Leeflang, Mariska M; Bossuyt, Patrick M

2016-09-01

To evaluate changes over time in summary estimates from meta-analyses of diagnostic accuracy studies. We included 48 meta-analyses from 35 MEDLINE-indexed systematic reviews published between September 2011 and January 2012 (743 diagnostic accuracy studies; 344,015 participants). Within each meta-analysis, we ranked studies by publication date. We applied random-effects cumulative meta-analysis to follow how summary estimates of sensitivity and specificity evolved over time. Time trends were assessed by fitting a weighted linear regression model of the summary accuracy estimate against rank of publication. The median of the 48 slopes was -0.02 (-0.08 to 0.03) for sensitivity and -0.01 (-0.03 to 0.03) for specificity. Twelve of 96 (12.5%) time trends in sensitivity or specificity were statistically significant. We found a significant time trend in at least one accuracy measure for 11 of the 48 (23%) meta-analyses. Time trends in summary estimates are relatively frequent in meta-analyses of diagnostic accuracy studies. Results from early meta-analyses of diagnostic accuracy studies should be considered with caution. Copyright © 2016 Elsevier Inc. All rights reserved.

Optical Fibers Would Sense Local Strains

NASA Technical Reports Server (NTRS)

Egalon, Claudio O.; Rogowski, Robert S.

1994-01-01

Proposed fiber-optic transducers measure local strains. Includes lead-in and lead-out lengths producing no changes in phase shifts, plus short sensing length in which phase shift is sensitive to strain. Phase shifts in single-mode fibers vary with strains. In alternative version, multiple portions of optical fiber sensitive to strains characteristic of specific vibrational mode of object. Same principle also used with two-mode fiber.

Diagnostic value of CT-localizer and axial low-dose computed tomography for the detection of drug body packing.

PubMed

Aissa, Joel; Kohlmeier, Antonia; Rubbert, Christian; Hohn, Ulrich; Blondin, Dirk; Schleich, Christoph; Kröpil, Patric; Boos, Johannes; Antoch, Gerald; Miese, Falk

2016-01-01

The purpose of this study was to assess the diagnostic performance of CT-localizers in the detection of intracorporal containers. This study was approved by the research ethics committee of our clinic. From March 2012 to March 2013, 108 subjects were referred to our institute with suspected body packing. The CT-localizer and the axial CT-images were compared by two blinded observers retrospectively. Presence of body packs was assessed in consensus. Sensitivity and specificity, PPV and NPV of the CT-localizer were calculated. Packets were detected in the CT-localizer of 19 suspects. In 28 of 108 cases packs were detected in axial CT-images. Sensitivity of CT-localizer for detection of packs was 0.68, and specificity was 1.00. There were no cases rated as false positive. The PPV was 1.0 and the NPV was 0.89. The omission of the axial CT-images would have led to a mean radiation dose reduction of 1.94 ± 0.5 mSv. The value of CT-localizers lies in their high PPV. Localizers are limited by low sensitivity, compared to axial CT-images in screening of potential body packers. However, in positive cases their high PPV may possibly allow to omit the complete axial abdominal CT to achieve even lower radiation exposure. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

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.

The diagnostic accuracy of neck ultrasound, 4D-Computed tomographyand sestamibi imaging in parathyroid carcinoma.

PubMed

Christakis, Ioannis; Vu, Thinh; Chuang, Hubert H; Fellman, Bryan; Figueroa, Angelica M Silva; Williams, Michelle D; Busaidy, Naifa L; Perrier, Nancy D

2017-10-01

Our aim was to investigate the accuracy of available imaging modalities for parathyroid carcinoma (PC) in our institution and to identify which imaging modality, or combination thereof, is optimal in preoperative determination of precise tumor location. All operated PC patients in our institution between 2000 and 2015 that had at least one of the following in-house preoperative scans: neck ultrasonography (US), neck 4D-Computed Tomography (4DCT) and 99mTc Sestamibi SPECT/CT (MIBI). Sensitivity, specificity and accuracy of PC tumor localization were assessed individually and in combination. 20 patients fulfilled the inclusion criteria and were analysed. There were 18 US, 18 CT and 9 MIBI scans. The sensitivity and accuracy for tumor localisation of US was 80% (CI 56-94%) and 73% respectively, of 4DCT was 79% (CI 58-93%) and 82%, and of MIBI was 81% (CI 54-96%) and 78%. The sensitivity and accuracy of the combination of CT and MIBI was 94% (CI 73-100%) and 95% and for the combination of US, CT and MIBI was 100% (CI 72-100%) and 100% respectively. The wash-out of the PC lesions, expressed as a percentage change in Hounsfield Units from the arterial phase to early delayed phase was -9.29% and to the late delayed phase was -16.88% (n=11). The sensitivity of solitary preoperative imaging of PC patients, whether by US, CT or MIBI, is approximately 80%. Combinations of CT with MIBI and US increase the sensitivity to 95% or better. Combined preoperative imaging of patients with clinical possibility of PC is therefore recommended. Copyright © 2017 Elsevier B.V. All rights reserved.

Parallel magnetic resonance imaging using coils with localized sensitivities.

PubMed

Goldfarb, James W; Holland, Agnes E

2004-09-01

The purpose of this study was to present clinical examples and illustrate the inefficiencies of a conventional reconstruction using a commercially available phased array coil with localized sensitivities. Five patients were imaged at 1.5 T using a cardiac-synchronized gadolinium-enhanced acquisition and a commercially available four-element phased array coil. Four unique sets of images were reconstructed from the acquired k-space data: (a) sum-of-squares image using four elements of the coil; localized sum-of-squares images from the (b) anterior coils and (c) posterior coils and a (c) local reconstruction. Images were analyzed for artifacts and usable field-of-view. Conventional image reconstruction produced images with fold-over artifacts in all cases spanning a portion of the image (mean 90 mm; range 36-126 mm). The local reconstruction removed fold-over artifacts and resulted in an effective increase in the field-of-view (mean 50%; range 20-70%). Commercially available phased array coils do not always have overlapping sensitivities. Fold-over artifacts can be removed using an alternate reconstruction method. When assessing the advantages of parallel imaging techniques, gains achieved using techniques such as SENSE and SMASH should be gauged against the acquisition time of the localized method rather than the conventional sum-of-squares method.

Sensitivity Analysis for Steady State Groundwater Flow Using Adjoint Operators

NASA Astrophysics Data System (ADS)

Sykes, J. F.; Wilson, J. L.; Andrews, R. W.

1985-03-01

Adjoint sensitivity theory is currently being considered as a potential method for calculating the sensitivity of nuclear waste repository performance measures to the parameters of the system. For groundwater flow systems, performance measures of interest include piezometric heads in the vicinity of a waste site, velocities or travel time in aquifers, and mass discharge to biosphere points. The parameters include recharge-discharge rates, prescribed boundary heads or fluxes, formation thicknesses, and hydraulic conductivities. The derivative of a performance measure with respect to the system parameters is usually taken as a measure of sensitivity. To calculate sensitivities, adjoint sensitivity equations are formulated from the equations describing the primary problem. The solution of the primary problem and the adjoint sensitivity problem enables the determination of all of the required derivatives and hence related sensitivity coefficients. In this study, adjoint sensitivity theory is developed for equations of two-dimensional steady state flow in a confined aquifer. Both the primary flow equation and the adjoint sensitivity equation are solved using the Galerkin finite element method. The developed computer code is used to investigate the regional flow parameters of the Leadville Formation of the Paradox Basin in Utah. The results illustrate the sensitivity of calculated local heads to the boundary conditions. Alternatively, local velocity related performance measures are more sensitive to hydraulic conductivities.

Evaluation of a National Call Center and a Local Alerts System for Detection of New Cases of Ebola Virus Disease - Guinea, 2014-2015.

PubMed

Lee, Christopher T; Bulterys, Marc; Martel, Lise D; Dahl, Benjamin A

2016-03-11

The epidemic of Ebola virus disease (Ebola) in West Africa began in Guinea in late 2013 (1), and on August 8, 2014, the World Health Organization (WHO) declared the epidemic a Public Health Emergency of International Concern (2). Guinea was declared Ebola-free on December 29, 2015, and is under a 90 day period of enhanced surveillance, following 3,351 confirmed and 453 probable cases of Ebola and 2,536 deaths (3). Passive surveillance for Ebola in Guinea has been conducted principally through the use of a telephone alert system. Community members and health facilities report deaths and suspected Ebola cases to local alert numbers operated by prefecture health departments or to a national toll-free call center. The national call center additionally functions as a source of public health information by responding to questions from the public about Ebola. To evaluate the sensitivity of the two systems and compare the sensitivity of the national call center with the local alerts system, the CDC country team performed probabilistic record linkage of the combined prefecture alerts database, as well as the national call center database, with the national viral hemorrhagic fever (VHF) database; the VHF database contains records of all known confirmed Ebola cases. Among 17,309 alert calls analyzed from the national call center, 71 were linked to 1,838 confirmed Ebola cases in the VHF database, yielding a sensitivity of 3.9%. The sensitivity of the national call center was highest in the capital city of Conakry (11.4%) and lower in other prefectures. In comparison, the local alerts system had a sensitivity of 51.1%. Local public health infrastructure plays an important role in surveillance in an epidemic setting.

Delta of the local ventriculo-atrial intervals at the septal location to differentiate tachycardia using septal accessory pathways from atypical atrioventricular nodal re-entry.

PubMed

Calvo, David; Pérez, Diego; Rubín, José; García, Daniel; Ávila, Pablo; Javier García-Fernández, F; Pachón, Marta; Bravo, Loreto; Hernández, Jesús; Miracle, Ángel L; Valverde, Irene; Gozalez-Vasserot, Mar; Árias, Miguel Ángel; Jimenez-Candíl, Javier; Morís, César

2018-01-02

Tachycardia mediated by septal accessory pathways (AP) and atypical atrioventricular nodal re-entry (AVNRT) require careful electrophysiologic evaluation for differential diagnosis. We aim to describe the differential behaviour of local ventriculo-atrial (VA) intervals which predicts the tachycardia mechanism. The local VA intervals at the para-Hisian septum were measured under three different situations: (i) tachycardia; (ii) sustained entrainment from the right ventricular apex (RVA); and (iii) continuous pacing from the RVA during sinus rhythm. Differences were computed as follows: Δ-VAentr = VA during entrainment - VA during tachycardia; and Δ-VApac = VA while pacing during sinus rhythm - VA during tachycardia. In contrast to AVNRT, we hypothesized that an invariable retrograde conduction through the septal AP will keep the result of the subtractions close to 0 ms in cases of ortodromic atrioventricular re-entrant tachycardia (AVRT). We analysed 55 atypical AVNRT (45% posterior type) and 82 AVRT (10 anteroseptal, 18 para-Hisian, 12 mid-septal, and 42 posteroseptal). Δ-VAentr was longer for AVNRT (98.5 ± 40.3 ms) compared with septal AP (-5.7 ± 19.3 ms; P < 0.001). A value of 50 ms showed 98.7% sensitivity and 92% specificity (AUC 0.99; 95% CI 0.98-1). According to physiological criteria, a negative Δ-VAentr remains unobserved in the case of AVNRT (positive predictive value 100% for septal AP). Δ-VApac was also longer for AVNRT (66.5 ± 14.6 ms) compared with septal AP (-9.7 ± 3.3 ms; P < 0.001). A value of 50 ms showed 100% sensitivity and 74% specificity (AUC 0.86; 95% CI 0.76-0.93). Delta of the local VA intervals enables distinction between atypical AVNRT and AVRT mediated by septal AP. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

Coastal and river flood risk analyses for guiding economically optimal flood adaptation policies: a country-scale study for Mexico.

PubMed

Haer, Toon; Botzen, W J Wouter; van Roomen, Vincent; Connor, Harry; Zavala-Hidalgo, Jorge; Eilander, Dirk M; Ward, Philip J

2018-06-13

Many countries around the world face increasing impacts from flooding due to socio-economic development in flood-prone areas, which may be enhanced in intensity and frequency as a result of climate change. With increasing flood risk, it is becoming more important to be able to assess the costs and benefits of adaptation strategies. To guide the design of such strategies, policy makers need tools to prioritize where adaptation is needed and how much adaptation funds are required. In this country-scale study, we show how flood risk analyses can be used in cost-benefit analyses to prioritize investments in flood adaptation strategies in Mexico under future climate scenarios. Moreover, given the often limited availability of detailed local data for such analyses, we show how state-of-the-art global data and flood risk assessment models can be applied for a detailed assessment of optimal flood-protection strategies. Our results show that especially states along the Gulf of Mexico have considerable economic benefits from investments in adaptation that limit risks from both river and coastal floods, and that increased flood-protection standards are economically beneficial for many Mexican states. We discuss the sensitivity of our results to modelling uncertainties, the transferability of our modelling approach and policy implications.This article is part of the theme issue 'Advances in risk assessment for climate change adaptation policy'. © 2018 The Author(s).

Characterization of emission microscopy and liquid crystal thermography in IC fault localization

NASA Astrophysics Data System (ADS)

Lau, C. K.; Sim, K. S.

2013-05-01

This paper characterizes two fault localization techniques - Emission Microscopy (EMMI) and Liquid Crystal Thermography (LCT) by using integrated circuit (IC) leakage failures. The majority of today's semiconductor failures do not reveal a clear visual defect on the die surface and therefore require fault localization tools to identify the fault location. Among the various fault localization tools, liquid crystal thermography and frontside emission microscopy are commonly used in most semiconductor failure analysis laboratories. Many people misunderstand that both techniques are the same and both are detecting hot spot in chip failing with short or leakage. As a result, analysts tend to use only LCT since this technique involves very simple test setup compared to EMMI. The omission of EMMI as the alternative technique in fault localization always leads to incomplete analysis when LCT fails to localize any hot spot on a failing chip. Therefore, this research was established to characterize and compare both the techniques in terms of their sensitivity in detecting the fault location in common semiconductor failures. A new method was also proposed as an alternative technique i.e. the backside LCT technique. The research observed that both techniques have successfully detected the defect locations resulted from the leakage failures. LCT wass observed more sensitive than EMMI in the frontside analysis approach. On the other hand, EMMI performed better in the backside analysis approach. LCT was more sensitive in localizing ESD defect location and EMMI was more sensitive in detecting non ESD defect location. Backside LCT was proven to work as effectively as the frontside LCT and was ready to serve as an alternative technique to the backside EMMI. The research confirmed that LCT detects heat generation and EMMI detects photon emission (recombination radiation). The analysis results also suggested that both techniques complementing each other in the IC fault localization. It is necessary for a failure analyst to use both techniques when one of the techniques produces no result.

Analysis of non locality proofs in Quantum Mechanics

NASA Astrophysics Data System (ADS)

Nisticò, Giuseppe

2012-02-01

Two kinds of non-locality theorems in Quantum Mechanics are taken into account: the theorems based on the criterion of reality and the quite different theorem proposed by Stapp. In the present work the analyses of the theorem due to Greenberger, Horne, Shimony and Zeilinger, based on the criterion of reality, and of Stapp's argument are shown. The results of these analyses show that the alleged violations of locality cannot be considered definitive.

Drivers of Change in Managed Water Resources: Modeling the Impacts of Climate and Socioeconomic Changes Using the US Midwest as a Case Study

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

Voisin, Nathalie; Leung, Lai-Yung R.; Hejazi, Mohamad I.

A global integrated assessment model including a water-demand model driven by socio-economics, is coupled in a one-way fashion with a land surface hydrology – routing – water resources management model. The integrated modeling framework is applied to the U.S. Upper Midwest (Missouri, Upper Mississippi, and Ohio) to advance understanding of the regional impacts of climate and socio-economic changes on integrated water resources. Implications for future flow regulation, water supply, and supply deficit are investigated using climate change projections with the B1 and A2 emission scenarios, which affect both natural flow and water demand. Changes in water demand are driven bymore » socio-economic factors, energy and food demands, global markets and prices. The framework identifies the multiple spatial scales of interactions between the drivers of changes (natural flow and water demand) and the managed water resources (regulated flow, supply and supply deficit). The contribution of the different drivers of change are quantified regionally, and also evaluated locally, using covariances. The integrated framework shows that water supply deficit is more predictable over the Missouri than the other regions in the Midwest. The predictability of the supply deficit mostly comes from long term changes in water demand although changes in runoff has a greater contribution, comparable to the contribution of changes in demand, over shorter time periods. The integrated framework also shows that spatially, water demand drives local supply deficit. Using elasticity, the sensitivity of supply deficit to drivers of change is established. The supply deficit is found to be more sensitive to changes in runoff than to changes in demand regionally. It contrasts with the covariance analysis that shows that water demand is the dominant driver of supply deficit over the analysed periods. The elasticity indicates the level of mitigation needed to control the demand in order to reduce the vulnerability of the integrated system in future periods. The elasticity analyses also emphasize the need to address uncertainty with respect to changes in natural flow in integrated assessment.« less

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

PubMed

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

2016-04-01

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

Seasonal hydrologic responses to climate change in the Pacific Northwest

NASA Astrophysics Data System (ADS)

Vano, Julie A.; Nijssen, Bart; Lettenmaier, Dennis P.

2015-04-01

Increased temperatures and changes in precipitation will result in fundamental changes in the seasonal distribution of streamflow in the Pacific Northwest and will have serious implications for water resources management. To better understand local impacts of regional climate change, we conducted model experiments to determine hydrologic sensitivities of annual, seasonal, and monthly runoff to imposed annual and seasonal changes in precipitation and temperature. We used the Variable Infiltration Capacity (VIC) land-surface hydrology model applied at 1/16° latitude-longitude spatial resolution over the Pacific Northwest (PNW), a scale sufficient to support analyses at the hydrologic unit code eight (HUC-8) basin level. These experiments resolve the spatial character of the sensitivity of future water supply to precipitation and temperature changes by identifying the seasons and locations where climate change will have the biggest impact on runoff. The PNW exhibited a diversity of responses, where transitional (intermediate elevation) watersheds experience the greatest seasonal shifts in runoff in response to cool season warming. We also developed a methodology that uses these hydrologic sensitivities as basin-specific transfer functions to estimate future changes in long-term mean monthly hydrographs directly from climate model output of precipitation and temperature. When principles of linearity and superposition apply, these transfer functions can provide feasible first-order estimates of the likely nature of future seasonal streamflow change without performing downscaling and detailed model simulations.

Determination of subthalamic nucleus location by quantitative analysis of despiked background neural activity from microelectrode recordings obtained during deep brain stimulation surgery.

PubMed

Danish, Shabbar F; Baltuch, Gordon H; Jaggi, Jurg L; Wong, Stephen

2008-04-01

Microelectrode recording during deep brain stimulation surgery is a useful adjunct for subthalamic nucleus (STN) localization. We hypothesize that information in the nonspike background activity can help identify STN boundaries. We present results from a novel quantitative analysis that accomplishes this goal. Thirteen consecutive microelectrode recordings were retrospectively analyzed. Spikes were removed from the recordings with an automated algorithm. The remaining "despiked" signals were converted via root mean square amplitude and curve length calculations into "feature profile" time series. Subthalamic nucleus boundaries determined by inspection, based on sustained deviations from baseline for each feature profile, were compared against those determined intraoperatively by the clinical neurophysiologist. Feature profile activity within STN exhibited a sustained rise in 10 of 13 tracks (77%). The sensitivity of STN entry was 60% and 90% for curve length and root mean square amplitude, respectively, when agreement within 0.5 mm of the neurophysiologist's prediction was used. Sensitivities were 70% and 100% for 1 mm accuracy. Exit point sensitivities were 80% and 90% for both features within 0.5 mm and 1.0 mm, respectively. Reproducible activity patterns in deep brain stimulation microelectrode recordings can allow accurate identification of STN boundaries. Quantitative analyses of this type may provide useful adjunctive information for electrode placement in deep brain stimulation surgery.

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

PubMed Central

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

2014-01-01

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

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

Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity.

PubMed

Vogl, Thomas; Eisenblätter, Michel; Völler, Tom; Zenker, Stefanie; Hermann, Sven; van Lent, Peter; Faust, Andreas; Geyer, Christiane; Petersen, Beatrix; Roebrock, Kirsten; Schäfers, Michael; Bremer, Christoph; Roth, Johannes

2014-08-06

Inflammation has a key role in the pathogenesis of various human diseases. The early detection, localization and monitoring of inflammation are crucial for tailoring individual therapies. However, reliable biomarkers to detect local inflammatory activities and to predict disease outcome are still missing. Alarmins, which are locally released during cellular stress, are early amplifiers of inflammation. Here, using optical molecular imaging, we demonstrate that the alarmin S100A8/S100A9 serves as a sensitive local and systemic marker for the detection of even sub-clinical disease activity in inflammatory and immunological processes like irritative and allergic contact dermatitis. In a model of collagen-induced arthritis, we use S100A8/S100A9 imaging to predict the development of disease activity. Furthermore, S100A8/S100A9 can act as a very early and sensitive biomarker in experimental leishmaniasis for phagocyte activation linked to an effective Th1-response. In conclusion, the alarmin S100A8/S100A9 is a valuable and sensitive molecular target for novel imaging approaches to monitor clinically relevant inflammatory disorders on a molecular level.

Automated Detection, Localization, and Classification of Traumatic Vertebral Body Fractures in the Thoracic and Lumbar Spine at CT

PubMed Central

Burns, Joseph E.; Yao, Jianhua; Muñoz, Hector

2016-01-01

Purpose To design and validate a fully automated computer system for the detection and anatomic localization of traumatic thoracic and lumbar vertebral body fractures at computed tomography (CT). Materials and Methods This retrospective study was HIPAA compliant. Institutional review board approval was obtained, and informed consent was waived. CT examinations in 104 patients (mean age, 34.4 years; range, 14–88 years; 32 women, 72 men), consisting of 94 examinations with positive findings for fractures (59 with vertebral body fractures) and 10 control examinations (without vertebral fractures), were performed. There were 141 thoracic and lumbar vertebral body fractures in the case set. The locations of fractures were marked and classified by a radiologist according to Denis column involvement. The CT data set was divided into training and testing subsets (37 and 67 subsets, respectively) for analysis by means of prototype software for fully automated spinal segmentation and fracture detection. Free-response receiver operating characteristic analysis was performed. Results Training set sensitivity for detection and localization of fractures within each vertebra was 0.82 (28 of 34 findings; 95% confidence interval [CI]: 0.68, 0.90), with a false-positive rate of 2.5 findings per patient. The sensitivity for fracture localization to the correct vertebra was 0.88 (23 of 26 findings; 95% CI: 0.72, 0.96), with a false-positive rate of 1.3. Testing set sensitivity for the detection and localization of fractures within each vertebra was 0.81 (87 of 107 findings; 95% CI: 0.75, 0.87), with a false-positive rate of 2.7. The sensitivity for fracture localization to the correct vertebra was 0.92 (55 of 60 findings; 95% CI: 0.79, 0.94), with a false-positive rate of 1.6. The most common cause of false-positive findings was nutrient foramina (106 of 272 findings [39%]). Conclusion The fully automated computer system detects and anatomically localizes vertebral body fractures in the thoracic and lumbar spine on CT images with a high sensitivity and a low false-positive rate. © RSNA, 2015 Online supplemental material is available for this article. PMID:26172532

Quantitative method to determine the regional drinking water odorant regulation goals based on odor sensitivity distribution: illustrated using 2-MIB.

PubMed

Yu, Jianwei; An, Wei; Cao, Nan; Yang, Min; Gu, Junong; Zhang, Dong; Lu, Ning

2014-07-01

Taste and odor (T/O) in drinking water often cause consumer complaints and are thus regulated in many countries. However, people in different regions may exhibit different sensitivities toward T/O. This study proposed a method to determine the regional drinking water odorant regulation goals (ORGs) based on the odor sensitivity distribution of the local population. The distribution of odor sensitivity to 2-methylisoborneol (2-MIB) by the local population in Beijing, China was revealed by using a normal distribution function/model to describe the odor complaint response to a 2-MIB episode in 2005, and a 2-MIB concentration of 12.9 ng/L and FPA (flavor profile analysis) intensity of 2.5 was found to be the critical point to cause odor complaints. Thus the Beijing ORG for 2-MIB was determined to be 12.9 ng/L. Based on the assumption that the local FPA panel can represent the local population in terms of sensitivity to odor, and that the critical FPA intensity causing odor complaints was 2.5, this study tried to determine the ORGs for seven other cities of China by performing FPA tests using an FPA panel from the corresponding city. ORG values between 12.9 and 31.6 ng/L were determined, showing that a unified ORG may not be suitable for drinking water odor regulations. This study presents a novel approach for setting drinking water odor regulations. Copyright © 2014. Published by Elsevier B.V.

Nuclear-localized AtHSPR links abscisic acid-dependent salt tolerance and antioxidant defense in Arabidopsis.

PubMed

Yang, Tao; Zhang, Liang; Hao, Hongyan; Zhang, Peng; Zhu, Haowei; Cheng, Wei; Wang, Yongli; Wang, Xinyu; Wang, Chongying

2015-12-01

Salt stress from soil or irrigation water limits plant growth. A T-DNA insertion mutant in C24, named athspr (Arabidopsis thaliana heat shock protein-related), showed several phenotypes, including reduced organ size and enhanced sensitivity to environmental cues. The athspr mutant is severely impaired under salinity levels at which wild-type (WT) plants grow normally. AtHSPR encodes a nuclear-localized protein with ATPase activity, and its expression was enhanced by high salinity and abscisic acid (ABA). Overexpression (OE) of AtHSPR significantly enhanced tolerance to salt stress by increasing the activities of the antioxidant system and by maintaining K(+) /Na(+) homeostasis. Quantitative RT-PCR analyses showed that OE of AtHSPR increased the expression of ABA/stress-responsive, salt overly sensitive (SOS)-related and antioxidant-related genes. In addition, ABA content was reduced in athspr plants with or without salt stress, and exogenous ABA restored WT-like salt tolerance to athspr plants. athspr exhibited increased leaf stomatal density and stomatal index, slower ABA-induced stomatal closure and reduced drought tolerance relative to the WT. AtHSPR OE enhanced drought tolerance by reducing leaf water loss and stomatal aperture. Transcript profiling in athspr showed a differential salt-stress response for genes involved in accumulation of reactive oxygen species (ROS), ABA signaling, cell death, stress response and photosynthesis. Taken together, our results suggested that AtHSPR is involved in salt tolerance in Arabidopsis through modulation of ROS levels, ABA-dependent stomatal closure, photosynthesis and K(+) /Na(+) homeostasis. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Types of drinkers and drinking settings: an application of a mathematical model.

PubMed

Mubayi, Anuj; Greenwood, Priscilla; Wang, Xiaohong; Castillo-Chávez, Carlos; Gorman, Dennis M; Gruenewald, Paul; Saltz, Robert F

2011-04-01

US college drinking data and a simple population model of alcohol consumption are used to explore the impact of social and contextual parameters on the distribution of light, moderate and heavy drinkers. Light drinkers become moderate drinkers under social influence, moderate drinkers may change environments and become heavy drinkers. We estimate the drinking reproduction number, R(d) , the average number of individual transitions from light to moderate drinking that result from the introduction of a moderate drinker in a population of light drinkers. Ways of assessing and ranking progression of drinking risks and data-driven definitions of high- and low-risk drinking environments are introduced. Uncertainty and sensitivity analyses, via a novel statistical approach, are conducted to assess R(d) variability and to analyze the role of context on drinking dynamics. Our estimates show R(d) well above the critical value of 1. R(d) estimates correlate positively with the proportion of time spent by moderate drinkers in high-risk drinking environments. R(d) is most sensitive to variations in local social mixing contact rates within low-risk environments. The parameterized model with college data suggests that high residence times of moderate drinkers in low-risk environments maintain heavy drinking. With regard to alcohol consumption in US college students, drinking places, the connectivity (traffic) between drinking venues and the strength of socialization in local environments are important determinants in transitions between light, moderate and heavy drinking as well as in long-term prediction of the drinking dynamics. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

Adaptive population divergence and directional gene flow across steep elevational gradients in a climate-sensitive mammal.

PubMed

Waterhouse, Matthew D; Erb, Liesl P; Beever, Erik A; Russello, Michael A

2018-06-01

The ecological effects of climate change have been shown in most major taxonomic groups; however, the evolutionary consequences are less well-documented. Adaptation to new climatic conditions offers a potential long-term mechanism for species to maintain viability in rapidly changing environments, but mammalian examples remain scarce. The American pika (Ochotona princeps) has been impacted by recent climate-associated extirpations and range-wide reductions in population sizes, establishing it as a sentinel mammalian species for climate change. To investigate evidence for local adaptation and reconstruct patterns of genomic diversity and gene flow across rapidly changing environments, we used a space-for-time design and restriction site-associated DNA sequencing to genotype American pikas along two steep elevational gradients at 30,966 SNPs and employed independent outlier detection methods that scanned for genotype-environment associations. We identified 338 outlier SNPs detected by two separate analyses and/or replicated in both transects, several of which were annotated to genes involved in metabolic function and oxygen transport. Additionally, we found evidence of directional gene flow primarily downslope from high-elevation populations, along with reduced gene flow at outlier loci. If this trend continues, elevational range contractions in American pikas will likely be from local extirpation rather than upward movement of low-elevation individuals; this, in turn, could limit the potential for adaptation within this landscape. These findings are of particular relevance for future conservation and management of American pikas and other elevationally restricted, thermally sensitive species. © 2018 John Wiley & Sons Ltd.

Monitoring local heating around an interventional MRI antenna with RF radiometry

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

Ertürk, M. Arcan; El-Sharkawy, AbdEl-Monem M.; Bottomley, Paul A., E-mail: bottoml@mri.jhu.edu

Purpose: Radiofrequency (RF) radiometry uses thermal noise detected by an antenna to measure the temperature of objects independent of medical imaging technologies such as magnetic resonance imaging (MRI). Here, an active interventional MRI antenna can be deployed as a RF radiometer to measure local heating, as a possible new method of monitoring device safety and thermal therapy. Methods: A 128 MHz radiometer receiver was fabricated to measure the RF noise voltage from an interventional 3 T MRI loopless antenna and calibrated for temperature in a uniformly heated bioanalogous gel phantom. Local heating (ΔT) was induced using the antenna for RFmore » transmission and measured by RF radiometry, fiber-optic thermal sensors, and MRI thermometry. The spatial thermal sensitivity of the antenna radiometer was numerically computed using a method-of-moment electric field analyses. The gel’s thermal conductivity was measured by MRI thermometry, and the localized time-dependent ΔT distribution computed from the bioheat transfer equation and compared with radiometry measurements. A “H-factor” relating the 1 g-averaged ΔT to the radiometric temperature was introduced to estimate peak temperature rise in the antenna’s sensitive region. Results: The loopless antenna radiometer linearly tracked temperature inside a thermally equilibrated phantom up to 73 °C to within ±0.3 °C at a 2 Hz sample rate. Computed and MRI thermometric measures of peak ΔT agreed within 13%. The peak 1 g-average temperature was H = 1.36 ± 0.02 times higher than the radiometric temperature for any media with a thermal conductivity of 0.15–0.50 (W/m)/K, indicating that the radiometer can measure peak 1 g-averaged ΔT in physiologically relevant tissue within ±0.4 °C. Conclusions: Active internal MRI detectors can serve as RF radiometers at the MRI frequency to provide accurate independent measures of local and peak temperature without the artifacts that can accompany MRI thermometry or the extra space needed to accommodate alternative thermal transducers. A RF radiometer could be integrated in a MRI scanner to permit “self-monitoring” for assuring device safety and/or monitoring delivery of thermal therapy.« less

Edge crack sensitivity of lightweight materials under different load conditions

NASA Astrophysics Data System (ADS)

Tsoupis, I.; Merklein, M.

2016-11-01

This study addresses the analysis of edge crack sensitivity of DP800 steel and AA5182 aluminum alloy in dependency of punching and machining operation as well as load case of subsequent forming. The inserting of a round hole by punching with defined punch-to- die-clearance, milling and drilling is compared. Subsequent forming is performed by standardized hole expansion test and by Nakajima-tests with three different specimen geometries. Local strain distribution at the surface for Nakajima-tests is measured by optical strain measurement technique and investigated in order to evaluate local deformation before failure. Additionally, resulting hole expansion ratio λ is determined. Significant higher X as well as local strain values ε max are achieved by machined holes. This is directly coupled to higher local formability and stretchability for both materials. Furthermore, the load condition has a strong impact on the edge crack sensitivity of the material. Prior failure is observed with changing stress conditions using different specimen geometries also influencing the reachable maximum failure strain. Higher edge crack sensitivity is observed for DP800, which is in good accordance to the material properties in terms of ductility and strength. These data in dependency of the process parameter can be used for the design of automotive components.

Local symmetric distortion boosted photon up-conversion and thermometric sensitivity in lanthanum oxide nanospheres.

PubMed

Suo, Hao; Zhao, Xiaoqi; Zhang, Zhiyu; Shi, Rui; Wu, Yanfang; Xiang, Jinmeng; Guo, Chongfeng

2018-05-17

It is essential to simultaneously boost the luminescence intensity and thermometric sensitivity of up-converted optical thermometers towards potential biomedical sensing applications. Herein, the effects of local site symmetry on the up-conversion (UC) emission and thermal sensing ability in trigonal-phased La2O3:Er3+/Yb3+ nanospheres were qualitatively explored using cubic-phased Lu2O3 and Y2O3 with a similar shape and phonon energy as contrasts. Under 980 nm light excitation, much stronger UC emissions were detected in La2O3 samples than that in cubic Lu2O3 and Y2O3 samples, and the possible mechanisms were elaborately proposed using Eu3+ as a luminescent probe. Thermo-responsive emission intensity from 2H11/2/4S3/2 levels was monitored to evaluate the absolute sensitivity of three samples, which strongly depends on the dopant-induced local site symmetric distortions according to the Judd-Ofelt theory. The potentiality of La2O3:Er3+/Yb3+ for sub-tissue thermometry was also validated by ex vivo experiments. Results open a promising avenue for realizing highly sensitive thermometry with a large signal-to-noise ratio in sub-tissues via finely tailoring the local site symmetry.

Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice.

PubMed

Jung, Dae Young; Ko, Hwi Jin; Lichtman, Eben I; Lee, Eunjung; Lawton, Elizabeth; Ong, Helena; Yu, Kristine; Azuma, Yoshihiro; Friedline, Randall H; Lee, Ki Won; Kim, Jason K

2013-05-01

Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.

Cost-effectiveness of possible future smoking cessation strategies in Hungary: results from the EQUIPTMOD.

PubMed

Németh, Bertalan; Józwiak-Hagymásy, Judit; Kovács, Gábor; Kovács, Attila; Demjén, Tibor; Huber, Manuel B; Cheung, Kei-Long; Coyle, Kathryn; Lester-George, Adam; Pokhrel, Subhash; Vokó, Zoltán

2018-01-25

To evaluate potential health and economic returns from implementing smoking cessation interventions in Hungary. The EQUIPTMOD, a Markov-based economic model, was used to assess the cost-effectiveness of three implementation scenarios: (a) introducing a social marketing campaign; (b) doubling the reach of existing group-based behavioural support therapies and proactive telephone support; and (c) a combination of the two scenarios. All three scenarios were compared with current practice. The scenarios were chosen as feasible options available for Hungary based on the outcome of interviews with local stakeholders. Life-time costs and quality-adjusted life years (QALYs) were calculated from a health-care perspective. The analyses used various return on investment (ROI) estimates, including incremental cost-effectiveness ratios (ICERs), to compare the scenarios. Probabilistic sensitivity analyses assessed the extent to which the estimated mean ICERs were sensitive to the model input values. Introducing a social marketing campaign resulted in an increase of 0.3014 additional quitters per 1 000 smokers, translating to health-care cost-savings of €0.6495 per smoker compared with current practice. When the value of QALY gains was considered, cost-savings increased to €14.1598 per smoker. Doubling the reach of existing group-based behavioural support therapies and proactive telephone support resulted in health-care savings of €0.2539 per smoker (€3.9620 with the value of QALY gains), compared with current practice. The respective figures for the combined scenario were €0.8960 and €18.0062. Results were sensitive to model input values. According to the EQUIPTMOD modelling tool, it would be cost-effective for the Hungarian authorities introduce a social marketing campaign and double the reach of existing group-based behavioural support therapies and proactive telephone support. Such policies would more than pay for themselves in the long term. © 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

The Micronesia Challenge: Assessing the Relative Contribution of Stressors on Coral Reefs to Facilitate Science-to-Management Feedback

PubMed Central

Houk, Peter; Camacho, Rodney; Johnson, Steven; McLean, Matthew; Maxin, Selino; Anson, Jorg; Joseph, Eugene; Nedlic, Osamu; Luckymis, Marston; Adams, Katrina; Hess, Don; Kabua, Emma; Yalon, Anthony; Buthung, Eva; Graham, Curtis; Leberer, Trina; Taylor, Brett; van Woesik, Robert

2015-01-01

Fishing and pollution are chronic stressors that can prolong recovery of coral reefs and contribute to ecosystem decline. While this premise is generally accepted, management interventions are complicated because the contributions from individual stressors are difficult to distinguish. The present study examined the extent to which fishing pressure and pollution predicted progress towards the Micronesia Challenge, an international conservation strategy initiated by the political leaders of 6 nations to conserve at least 30% of marine resources by 2020. The analyses were rooted in a defined measure of coral-reef-ecosystem condition, comprised of biological metrics that described functional processes on coral reefs. We report that only 42% of the major reef habitats exceeded the ecosystem-condition threshold established by the Micronesia Challenge. Fishing pressure acting alone on outer reefs, or in combination with pollution in some lagoons, best predicted both the decline and variance in ecosystem condition. High variances among ecosystem-condition scores reflected the large gaps between the best and worst reefs, and suggested that the current scores were unlikely to remain stable through time because of low redundancy. Accounting for the presence of marine protected area (MPA) networks in statistical models did little to improve the models’ predictive capabilities, suggesting limited efficacy of MPAs when grouped together across the region. Yet, localized benefits of MPAs existed and are expected to increase over time. Sensitivity analyses suggested that (i) grazing by large herbivores, (ii) high functional diversity of herbivores, and (iii) high predator biomass were most sensitive to fishing pressure, and were required for high ecosystem-condition scores. Linking comprehensive fisheries management policies with these sensitive metrics, and targeting the management of pollution, will strengthen the Micronesia Challenge and preserve ecosystem services that coral reefs provide to societies in the face of climate change. PMID:26087252

The Micronesia Challenge: Assessing the Relative Contribution of Stressors on Coral Reefs to Facilitate Science-to-Management Feedback.

PubMed

Houk, Peter; Camacho, Rodney; Johnson, Steven; McLean, Matthew; Maxin, Selino; Anson, Jorg; Joseph, Eugene; Nedlic, Osamu; Luckymis, Marston; Adams, Katrina; Hess, Don; Kabua, Emma; Yalon, Anthony; Buthung, Eva; Graham, Curtis; Leberer, Trina; Taylor, Brett; van Woesik, Robert

2015-01-01

Fishing and pollution are chronic stressors that can prolong recovery of coral reefs and contribute to ecosystem decline. While this premise is generally accepted, management interventions are complicated because the contributions from individual stressors are difficult to distinguish. The present study examined the extent to which fishing pressure and pollution predicted progress towards the Micronesia Challenge, an international conservation strategy initiated by the political leaders of 6 nations to conserve at least 30% of marine resources by 2020. The analyses were rooted in a defined measure of coral-reef-ecosystem condition, comprised of biological metrics that described functional processes on coral reefs. We report that only 42% of the major reef habitats exceeded the ecosystem-condition threshold established by the Micronesia Challenge. Fishing pressure acting alone on outer reefs, or in combination with pollution in some lagoons, best predicted both the decline and variance in ecosystem condition. High variances among ecosystem-condition scores reflected the large gaps between the best and worst reefs, and suggested that the current scores were unlikely to remain stable through time because of low redundancy. Accounting for the presence of marine protected area (MPA) networks in statistical models did little to improve the models' predictive capabilities, suggesting limited efficacy of MPAs when grouped together across the region. Yet, localized benefits of MPAs existed and are expected to increase over time. Sensitivity analyses suggested that (i) grazing by large herbivores, (ii) high functional diversity of herbivores, and (iii) high predator biomass were most sensitive to fishing pressure, and were required for high ecosystem-condition scores. Linking comprehensive fisheries management policies with these sensitive metrics, and targeting the management of pollution, will strengthen the Micronesia Challenge and preserve ecosystem services that coral reefs provide to societies in the face of climate change.

Field-Deployable Reverse Transcription-Insulated Isothermal PCR (RT-iiPCR) Assay for Rapid and Sensitive Detection of Foot-and-Mouth Disease Virus.

PubMed

Ambagala, A; Fisher, M; Goolia, M; Nfon, C; Furukawa-Stoffer, T; Ortega Polo, R; Lung, O

2017-10-01

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which can decimate the livestock industry and economy of countries previously free of this disease. Rapid detection of foot-and-mouth disease virus (FMDV) is critical to containing an FMD outbreak. Availability of a rapid, highly sensitive and specific, yet simple and field-deployable assay would support local decision-making during an FMDV outbreak. Here we report validation of a novel reverse transcription-insulated isothermal PCR (RT-iiPCR) assay that can be performed on a commercially available, compact and portable POCKIT ™ analyser that automatically analyses data and displays '+' or '-' results. The FMDV RT-iiPCR assay targets the 3D region of the FMDV genome and was capable of detecting 9 copies of in vitro-transcribed RNA standard with 95% confidence. It accurately identified 63 FMDV strains belonging to all seven serotypes and showed no cross-reactivity with viruses causing similar clinical diseases in cloven-hoofed animals. The assay was able to identify FMDV RNA in multiple sample types including oral, nasal and lesion swabs, epithelial tissue suspensions, vesicular and oral fluid samples, even before the appearance of clinical signs. Clinical sensitivity of the assay was comparable or slightly higher than the laboratory-based real-time RT-PCR assay in use. The assay was able to detect FMDV RNA in vesicular fluid samples without nucleic acid extraction. For RNA extraction from more complex sample types, a commercially available taco ™ mini transportable magnetic bead-based, automated extraction system was used. This assay provides a potentially useful field-deployable diagnostic tool for rapid detection of FMDV in an outbreak in FMD-free countries or for routine diagnostics in endemic countries with less structured laboratory systems. © 2016 Her Majesty the Queen in Right of Canada.

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.

The conduct of Australian Indigenous primary health care research focusing on social and emotional wellbeing: a systematic review.

PubMed

Farnbach, Sara; Eades, Anne-Maree; Gwynn, Josephine D; Glozier, Nick; Hackett, Maree L

2018-06-14

Objectives and importance of study: Values and ethics: guidelines for ethical conduct in Aboriginal and Torres Strait Islander health research (Values and ethics) describes key values that should underpin Aboriginal and Torres Strait Islander (Indigenous)-focused health research. It is unclear how research teams address this document in primary health care research. We systematically review the primary health care literature focusing on Indigenous social and emotional wellbeing (SEWB) to identify how Values and ethics and community preferences for standards of behaviour (local protocols) are addressed during research. Systematic review in accordance with PRISMA Guidelines and MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies. We searched four databases and one Indigenous-specific website for qualitative, quantitative and mixed-method studies published since Values and ethics was implemented (2003). Included studies were conducted in primary health care services, focused on Indigenous SEWB and were conducted by research teams. Using standard data extraction forms, we identified actions taken (reported by authors or identified by us) relating to Values and ethics and local protocols. A total of 25 studies were included. Authors of two studies explicitly mentioned the Values and ethics document, but neither reported how their actions related to the document's values. In more than half the studies, we identified at least three actions relating to the values. Some actions related to multiple values, including use of culturally sensitive research processes and involving Indigenous representatives in the research team. Local protocols were rarely reported. Addressing Values and ethics appears to improve research projects. The academic community should focus on culturally sensitive research processes, relationship building and developing the Indigenous research workforce, to facilitate acceptable research that affects health outcomes. For Values and ethics to achieve its full impact and to improve learning between research teams, authors should be encouraged to report how the principles are addressed during research, including barriers and enablers that are encountered.

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.

An evaluation of independent component analyses with an application to resting-state fMRI

PubMed Central

Matteson, David S.; Ruppert, David; Eloyan, Ani; Caffo, Brian S.

2013-01-01

Summary We examine differences between independent component analyses (ICAs) arising from different as-sumptions, measures of dependence, and starting points of the algorithms. ICA is a popular method with diverse applications including artifact removal in electrophysiology data, feature extraction in microarray data, and identifying brain networks in functional magnetic resonance imaging (fMRI). ICA can be viewed as a generalization of principal component analysis (PCA) that takes into account higher-order cross-correlations. Whereas the PCA solution is unique, there are many ICA methods–whose solutions may differ. Infomax, FastICA, and JADE are commonly applied to fMRI studies, with FastICA being arguably the most popular. Hastie and Tibshirani (2003) demonstrated that ProDenICA outperformed FastICA in simulations with two components. We introduce the application of ProDenICA to simulations with more components and to fMRI data. ProDenICA was more accurate in simulations, and we identified differences between biologically meaningful ICs from ProDenICA versus other methods in the fMRI analysis. ICA methods require nonconvex optimization, yet current practices do not recognize the importance of, nor adequately address sensitivity to, initial values. We found that local optima led to dramatically different estimates in both simulations and group ICA of fMRI, and we provide evidence that the global optimum from ProDenICA is the best estimate. We applied a modification of the Hungarian (Kuhn-Munkres) algorithm to match ICs from multiple estimates, thereby gaining novel insights into how brain networks vary in their sensitivity to initial values and ICA method. PMID:24350655

Utilization of Large Scale Surface Models for Detailed Visibility Analyses

NASA Astrophysics Data System (ADS)

Caha, J.; Kačmařík, M.

2017-11-01

This article demonstrates utilization of large scale surface models with small spatial resolution and high accuracy, acquired from Unmanned Aerial Vehicle scanning, for visibility analyses. The importance of large scale data for visibility analyses on the local scale, where the detail of the surface model is the most defining factor, is described. The focus is not only the classic Boolean visibility, that is usually determined within GIS, but also on so called extended viewsheds that aims to provide more information about visibility. The case study with examples of visibility analyses was performed on river Opava, near the Ostrava city (Czech Republic). The multiple Boolean viewshed analysis and global horizon viewshed were calculated to determine most prominent features and visibility barriers of the surface. Besides that, the extended viewshed showing angle difference above the local horizon, which describes angular height of the target area above the barrier, is shown. The case study proved that large scale models are appropriate data source for visibility analyses on local level. The discussion summarizes possible future applications and further development directions of visibility analyses.

Local sensitivity of per-recruit fishing mortality reference points.

PubMed

Cadigan, N G; Wang, S

2016-12-01

We study the sensitivity of fishery management per-recruit harvest rates which may be part of a quantitative harvest strategy designed to achieve some objective for catch or population size. We use a local influence sensitivity analysis to derive equations that describe how these reference harvest rates are affected by perturbations to productivity processes. These equations give a basic theoretical understanding of sensitivity that can be used to predict what the likely impacts of future changes in productivity will be. Our results indicate that per-recruit reference harvest rates are more sensitive to perturbations when the equilibrium catch or population size per recruit, as functions of the harvest rate, have less curvature near the reference point. Overall our results suggest that per recruit reference points will, with some exceptions, usually increase if (1) growth rates increase, (2) natural mortality rates increase, or (3) fishery selectivity increases to an older age.

A dual pH/thermal responsive nanocarrier for combined chemo-thermotherapy based on a copper-doxorubicin complex and gold nanorods

NASA Astrophysics Data System (ADS)

Lei, Mingzhu; Ma, Man; Pang, Xiaojuan; Tan, Fengping; Li, Nan

2015-09-01

The development of treatment protocols that results in a complete response to chemotherapy has been hampered by low efficacy and systemic toxicity. Here, we created a pH sensitive copper-doxorubicin complex within the core of temperature-sensitive liposomes to maintain the stability during blood circulation and trigger Dox release in the tumor site. Synergistically, we also rationally applied gold nanorods (AuNRs) coupled with near-infrared (NIR) field strength to produce a precise and localized temperature, which not only remotely controlled the drug release but also directly destroyed the tumor, to enhance the therapeutic efficacy. As expected, the in vitro release studies showed that the drug release from CuDox-TSLs (Copper ion mediated Doxorubicin loading-Temperature Sensitive Liposomes) was both pH-dependent and temperature-dependent. Furthermore, MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assays showed that CuDox-TSLs combined with AuNRs exhibited a closer antiproliferative activity to free Dox in MCF-7 cells. The efficient intracellular Dox release from CuDox-TSLs toward the tumor cells further confirmed the anti-tumor effect. Moreover, the in vivo imaging and biodistribution studies revealed that CuDox-TSLs combined with AuNRs could actively target the tumor site. In addition, the therapeutic studies in MCF-7 nude mice exhibited CuDox-TSLs plus AuNRs in combination with NIR irradiation inhibited tumor growth to a great extent and possessed much lower side effects, which were further confirmed by systemic histological analyses. All detailed evidence suggested a considerable potential of CuDox-TSLs combined with AuNRs for treatment of metastatic cancer.The development of treatment protocols that results in a complete response to chemotherapy has been hampered by low efficacy and systemic toxicity. Here, we created a pH sensitive copper-doxorubicin complex within the core of temperature-sensitive liposomes to maintain the stability during blood circulation and trigger Dox release in the tumor site. Synergistically, we also rationally applied gold nanorods (AuNRs) coupled with near-infrared (NIR) field strength to produce a precise and localized temperature, which not only remotely controlled the drug release but also directly destroyed the tumor, to enhance the therapeutic efficacy. As expected, the in vitro release studies showed that the drug release from CuDox-TSLs (Copper ion mediated Doxorubicin loading-Temperature Sensitive Liposomes) was both pH-dependent and temperature-dependent. Furthermore, MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assays showed that CuDox-TSLs combined with AuNRs exhibited a closer antiproliferative activity to free Dox in MCF-7 cells. The efficient intracellular Dox release from CuDox-TSLs toward the tumor cells further confirmed the anti-tumor effect. Moreover, the in vivo imaging and biodistribution studies revealed that CuDox-TSLs combined with AuNRs could actively target the tumor site. In addition, the therapeutic studies in MCF-7 nude mice exhibited CuDox-TSLs plus AuNRs in combination with NIR irradiation inhibited tumor growth to a great extent and possessed much lower side effects, which were further confirmed by systemic histological analyses. All detailed evidence suggested a considerable potential of CuDox-TSLs combined with AuNRs for treatment of metastatic cancer. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04353k

Imaging of tumor hypermetabolism with near-infrared fluorescence contrast agents

NASA Astrophysics Data System (ADS)

Chen, Yu; Zheng, Gang; Zhang, Zhihong; Blessington, Dana; Intes, Xavier; Achilefu, Samuel I.; Chance, Britton

2004-08-01

We have developed a high sensitivity near-infrared (NIR) optical imaging system for non-invasive cancer detection through molecular labeled fluorescent contrast agents. Near-infrared (NIR) imaging can probe tissue deeply thus possess the potential for non-invasively detection of breast or lymph node cancer. Recent developments in molecular beacons can selectively label various pre-cancer/cancer signatures and provide high tumor to background contrast. To increase the sensitivity in detecting fluorescent photons and the accuracy of localization, phase cancellation (in- and anti-phase) device is employed. This frequency-domain system utilizes the interference-like pattern of diffuse photon density wave to achieve high detection sensitivity and localization accuracy for the fluorescent heterogeneity embedded inside the scattering media. The opto-electronic system consists of the laser sources, fiber optics, interference filter to select the fluorescent photons and the high sensitivity photon detector (photomultiplier tube). The source-detector pair scans the tissue surface in multiple directions and the two-dimensional localization image can be obtained using goniometric reconstruction. In vivo measurements with tumor-bearing mouse model using the novel Cypate-mono-2-deoxy-glucose (Cypate-2-D-Glucosamide) fluorescent contrast agent, which targets the enhanced tumor glycolysis, demonstrated the feasibility on detection of 2 cm deep subsurface tumor in the tissue-like medium, with a localization accuracy within 2 ~ 3 mm. This instrument has the potential for tumor diagnosis and imaging, and the accuracy of the localization suggests that this system could help to guide the clinical fine-needle biopsy. This portable device would be complementary to X-ray mammogram and provide add-on information on early diagnosis and localization of early breast tumor.

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…

Improved Overall Survival with Aggressive Primary Tumor Radiotherapy for Patients with Metastatic Esophageal Cancer.

PubMed

Guttmann, David M; Mitra, Nandita; Bekelman, Justin; Metz, James M; Plastaras, John; Feng, Weiwei; Swisher-McClure, Samuel

2017-07-01

The aim of this study was to characterize utilization and survival outcomes associated with primary tumor-directed radiotherapy (PTDRT) in patients with newly diagnosed metastatic esophageal cancer. We conducted an observational cohort study using the National Cancer Data Base to evaluate patients with newly diagnosed metastatic esophageal cancer between 2004 and 2012. Overall survival outcomes after treatment with chemotherapy plus conventional palliative dose radiotherapy (<5040 cGy), chemotherapy plus definitive dose radiotherapy (≥5040 cGy), or chemotherapy alone were compared by using Cox proportional hazards models with inverse probability of treatment weighting using the propensity score. Potential unmeasured confounding was assessed through sensitivity analyses. The final cohort consisted of 12,683 patients: 57% were treated with chemotherapy alone, 24% were treated with chemotherapy plus palliative dose radiotherapy, and 19% were treated with chemotherapy plus definitive dose radiotherapy. Compared with chemotherapy alone, chemotherapy plus definitive dose radiotherapy was associated with improved survival (median overall survival of 8.3 versus 11.3 months [hazard ratio = 0.72, 95% confidence interval: 0.70-0.74, p ≤ 0.001]), whereas chemotherapy plus palliative dose radiotherapy was associated with slightly inferior outcomes (median overall survival of 8.3 months versus 7.5 months (hazard ratio = 1.10, 95% confidence interval 1.07-1.13, p ≤ 0.001). These findings were robust to potential unmeasured confounding in sensitivity analyses. Additionally, landmark analyses confirmed these findings in patients surviving 12 months or longer. Definitive dose, but not conventional palliative dose, PTDRT is associated with improved overall survival in metastatic esophageal cancer, suggesting that local control may be important to prognosis. These findings support integrating PTDRT into future clinical trials aimed at refining personalized treatment for patients with metastatic esophageal cancer. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. 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.

Participation of the nitric oxide-cyclic GMP-ATP-sensitive K(+) channel pathway in the antinociceptive action of ketorolac.

PubMed

Lázaro-Ibáñez, G G; Torres-López, J E; Granados-Soto, V

2001-08-24

The involvement of nitric oxide (NO), cyclic GMP and ATP-sensitive K(+) channels in the antinociceptive effect of ketorolac was assessed using the formalin test in the rat. Local administration of ketorolac in a formalin-injured paw produced a dose-dependent antinociceptive effect due to a local action, as drug administration in the contralateral paw was ineffective. Pretreatment of the injured paw with N(G)-L-nitro-arginine methyl ester (L-NAME, an NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) or glibenclamide (an ATP-sensitive K(+) channel blocker) prevented ketorolac-induced antinociception. However, pretreatment with saline or N(G)-D-nitro-arginine methyl ester (D-NAME) did not block antinociception. Local administration of S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) was inactive by itself, but increased the effect of ketorolac. The present results suggest that the antinociceptive effect of ketorolac involves activation of the NO-cyclic GMP pathway, followed by an opening of ATP-sensitive K(+) channels at the peripheral level.

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

Hydrodynamic Instability and Thermal Coupling in a Dynamic Model of Liquid-Propellant Combustion

NASA Technical Reports Server (NTRS)

Margolis, S. B.

1999-01-01

For liquid-propellant combustion, the Landau/Levich hydrodynamic models have been combined and extended to account for a dynamic dependence of the burning rate on the local pressure and temperature fields. Analysis of these extended models is greatly facilitated by exploiting the realistic smallness of the gas-to-liquid density ratio rho. Neglecting thermal coupling effects, an asymptotic expression was then derived for the cellular stability boundary A(sub p)(k) where A(sub p) is the pressure sensitivity of the burning rate and k is the disturbance wavenumber. The results explicitly indicate the stabilizing effects of gravity on long-wave disturbances, and those of viscosity and surface tension on short-wave perturbations, and the instability associated with intermediate wavenumbers for critical negative values of A(sub p). In the limit of weak gravity, hydrodynamic instability in liquid-propellant combustion becomes a long-wave, instability phenomenon, whereas at normal gravity, this instability is first manifested through O(1) wavenumbers. In addition, surface tension and viscosity (both liquid and gas) each produce comparable effects in the large-wavenumber regime, thereby providing important modifications to the previous analyses in which one or more of these effects was neglected. For A(sub p)= O, the Landau/Levich results are recovered in appropriate limiting cases, although this typically corresponds to a hydrodynamically unstable parameter regime for p << 1. In addition to the classical cellular form of hydrodynamic stability, there exists a pulsating form corresponding to the loss of stability of steady, planar burning to time-dependent perturbations. This occurs for negative values of the parameter A(sub p), and is thus absent from the original Landau/Levich models. In the extended model, however, there exists a stable band of negative pressure sensitivities bounded above by the Landau type of instability, and below by this pulsating form of hydrodynamic instability. Indeed, nonsteady modes of combustion have been observed at low pressures in hydroxylammonium nitrate (HAN)-based liquid propellants, which often exhibit negative pressure sensitivities. While nonsteady combustion may correspond to secondary and higher-order bifurcations above the cellular boundary, it may also be a manifestation of this pulsating type of hydrodynamic instability. In the present work, a nonzero temperature sensitivity is incorporated into our previous asymptotic analyses. This entails a coupling of the energy equation to the previous purely hydrodynamic problem, and leads to a significant modification of the pulsating boundary such that, for sufficiently large values of the temperature-sensitivity parameter, liquid-propellant combustion can become intrinsically unstable to this alternative form of hydrodynamic instability. For simplicity, further attention is confined here to the inviscid version of the problem since, despite the fact that viscous and surface-tension effects are comparable, the qualitative nature of the cellular boundary remains preserved in the zero-viscosity limit, as does the existence of the pulsating boundary. The mathematical model adopts the classical assumption that there is no distributed reaction in either the liquid or gas phases, but now the reaction sheet, representing either a pyrolysis reaction or an exothermic decomposition at the liquid/gas interface, is assumed to depend on local conditions there.

Immunophenotyping does not improve predictivity of the local lymph node assay in mice.

PubMed

Strauss, Volker; Kolle, Susanne N; Honarvar, Naveed; Dammann, Martina; Groeters, Sibylle; Faulhammer, Frank; Landsiedel, Robert; van Ravenzwaay, Bennard

2015-04-01

The local lymph node assay (LLNA) is a regulatory accepted test for the identification of skin sensitizing substances by measuring radioactive thymidine incorporation into the lymph node. However, there is evidence that LLNA is overestimating the sensitization potential of certain substance classes in particular those exerting skin irritation. Some reports describe the additional use of flow cytometry-based immunophenotyping to better discriminate irritants from sensitizing irritants in LLNA. In the present study, the 22 performance standards plus 8 surfactants were assessed using the radioactive LLNA method. In addition, lymph node cells were immunophenotyped to evaluate the specificity of the lymph node response using cell surface markers such as B220 or CD19, CD3, CD4, CD8, I-A(κ) and CD69 with the aim to allow a better discrimination above all between irritants and sensitizers, but also non-irritating sensitizers and non-sensitizers. However, the markers assessed in this study do not sufficiently differentiate between irritants and irritant sensitizers and therefore did not improve the predictive capacity of the LLNA. Copyright © 2014 John Wiley & Sons, Ltd.

Adjoint sensitivity analysis of a tumor growth model and its application to spatiotemporal radiotherapy optimization.

PubMed

Fujarewicz, Krzysztof; Lakomiec, Krzysztof

2016-12-01

We investigate a spatial model of growth of a tumor and its sensitivity to radiotherapy. It is assumed that the radiation dose may vary in time and space, like in intensity modulated radiotherapy (IMRT). The change of the final state of the tumor depends on local differences in the radiation dose and varies with the time and the place of these local changes. This leads to the concept of a tumor's spatiotemporal sensitivity to radiation, which is a function of time and space. We show how adjoint sensitivity analysis may be applied to calculate the spatiotemporal sensitivity of the finite difference scheme resulting from the partial differential equation describing the tumor growth. We demonstrate results of this approach to the tumor proliferation, invasion and response to radiotherapy (PIRT) model and we compare the accuracy and the computational effort of the method to the simple forward finite difference sensitivity analysis. Furthermore, we use the spatiotemporal sensitivity during the gradient-based optimization of the spatiotemporal radiation protocol and present results for different parameters of the model.

Field-sensitivity To Rheological Parameters

NASA Astrophysics Data System (ADS)

Freund, Jonathan; Ewoldt, Randy

2017-11-01

We ask this question: where in a flow is a quantity of interest Q quantitatively sensitive to the model parameters θ-> describing the rheology of the fluid? This field sensitivity is computed via the numerical solution of the adjoint flow equations, as developed to expose the target sensitivity δQ / δθ-> (x) via the constraint of satisfying the flow equations. Our primary example is a sphere settling in Carbopol, for which we have experimental data. For this Carreau-model configuration, we simultaneously calculate how much a local change in the fluid intrinsic time-scale λ, limit-viscosities ηo and η∞, and exponent n would affect the drag D. Such field sensitivities can show where different fluid physics in the model (time scales, elastic versus viscous components, etc.) are important for the target observable and generally guide model refinement based on predictive goals. In this case, the computational cost of solving the local sensitivity problem is negligible relative to the flow. The Carreau-fluid/sphere example is illustrative; the utility of field sensitivity is in the design and analysis of less intuitive flows, for which we provide some additional examples.

Forced Vibration Analysis of a Multidegree Impact Vibrator

NASA Astrophysics Data System (ADS)

Pun, D.; Lau, S. L.; Law, S. S.; Cao, D. Q.

1998-06-01

The dynamics of a multidegree impact vibrator subject to harmonic loading is investigated. The system is represented by a lumped mass model which hits and rebounds from a rigid wall during vibration. The periodic solution to the equations of motion withNforcing cycles andPimpacts is formulated. The variational equations and the resulting transition matrix for investigating local stability of the periodic solutions are derived. A two-degree-of-freedom example is analysed, and a variety of motion types are found. Chaotic windows are present between regions of periodic response, and at these boundariesN-Pmotions are prevalent. Low velocity impacts are evident at exciting frequencies away from the natural frequencies. Two basins of attraction are computed, and the sensitivity to initial conditions is noted. The quality of theN-Pmotion is discussed from an engineering application perspective.

Matrix assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) for direct visualization of plant metabolites in situ

DOE PAGES

Sturtevant, Drew; Lee, Young -Jin; Chapman, Kent D.

2015-11-22

Direct visualization of plant tissues by matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) has revealed key insights into the localization of metabolites in situ. Recent efforts have determined the spatial distribution of primary and secondary metabolites in plant tissues and cells. Strategies have been applied in many areas of metabolism including isotope flux analyses, plant interactions, and transcriptional regulation of metabolite accumulation. Technological advances have pushed achievable spatial resolution to subcellular levels and increased instrument sensitivity by several orders of magnitude. Furthermore, it is anticipated that MALDI-MSI and other MSI approaches will bring a new level of understanding tomore » metabolomics as scientists will be encouraged to consider spatial heterogeneity of metabolites in descriptions of metabolic pathway regulation.« less

Cross-scale analysis of cluster correspondence using different operational neighborhoods

NASA Astrophysics Data System (ADS)

Lu, Yongmei; Thill, Jean-Claude

2008-09-01

Cluster correspondence analysis examines the spatial autocorrelation of multi-location events at the local scale. This paper argues that patterns of cluster correspondence are highly sensitive to the definition of operational neighborhoods that form the spatial units of analysis. A subset of multi-location events is examined for cluster correspondence if they are associated with the same operational neighborhood. This paper discusses the construction of operational neighborhoods for cluster correspondence analysis based on the spatial properties of the underlying zoning system and the scales at which the zones are aggregated into neighborhoods. Impacts of this construction on the degree of cluster correspondence are also analyzed. Empirical analyses of cluster correspondence between paired vehicle theft and recovery locations are conducted on different zoning methods and across a series of geographic scales and the dynamics of cluster correspondence patterns are discussed.

Matrix assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) for direct visualization of plant metabolites in situ

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

Sturtevant, Drew; Lee, Young -Jin; Chapman, Kent D.

Direct visualization of plant tissues by matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) has revealed key insights into the localization of metabolites in situ. Recent efforts have determined the spatial distribution of primary and secondary metabolites in plant tissues and cells. Strategies have been applied in many areas of metabolism including isotope flux analyses, plant interactions, and transcriptional regulation of metabolite accumulation. Technological advances have pushed achievable spatial resolution to subcellular levels and increased instrument sensitivity by several orders of magnitude. Furthermore, it is anticipated that MALDI-MSI and other MSI approaches will bring a new level of understanding tomore » metabolomics as scientists will be encouraged to consider spatial heterogeneity of metabolites in descriptions of metabolic pathway regulation.« less

Comparison of large-scale structures and velocities in the local universe

NASA Technical Reports Server (NTRS)

Yahil, Amos

1994-01-01

Comparison of the large-scale density and velocity fields in the local universe shows detailed agreement, strengthening the standard paradigm of the gravitational origin of these structures. Quantitative analysis can determine the cosmological density parameter, Omega, and biasing factor, b; there is virtually no sensitivity in any local analyses to the cosmologial constant, lambda. Comparison of the dipole anisotropy of the cosmic microwave background with the acceleration due to the Infrared Astronomy Satellite (IRAS) galaxies puts the linear growth factor in the range beta approximately equals Omega (exp 0.6)/b = 0.6(+0.7/-0.3) (95% confidence). A direct comparison of the density and velocity fields of nearby galaxies gives beta = 1.3 (+0.7/-0.6), and from nonlinear analysis the weaker limit (Omega greater than 0.45 for b greater than 0.5 (again 95% confidence). A tighter limit (Omega greater than 0.3 (4-6 sigma)), is obtained by a reconstruction of the probability distribution function of the initial fluctuations from which the structures observed today arose. The last two methods depend critically on the smooth velocity field determined from the observed velocities of nearby galaxies by the POTENT method. A new analysis of these velocities, with more than three times the data used to obtain the above quoted results, is now underway and promises to tighten the uncertainties considerably, as well as reduce systematic bias.

Transmitter-induced glycogenolysis and gluconeogenesis in leech segmental ganglia.

PubMed

Pennington, A J; Pentreath, V W

1987-01-01

1. The utilization and control of glycogen stores were studied in the isolated segmental ganglia of the horse leech, Haemopis sanguisuga. The glycogen in the ganglia was extracted and assayed fluorimetrically and its cellular localization and turnover studied by autoradiography in conjunction with [3H] glucose. 2. The glycogen levels were measured after incubation with different neurotransmitters for 60 min at 28 degrees C. The results for each experimental ganglion were compared to a paired control ganglion, and the results analysed by paired t-tests. 3. Several transmitter substances (5-HT, octopamine, dopamine, noradrenaline, histamine) produced reductions in glycogen (glycogenolysis); other transmitters (glutamate, GABA) produced increases in glycogen (gluconeogenesis); others (adenosine, glycine) produced reductions or increases, depending on concentration. Acetylcholine had no effect on the glycogen levels. 4. Most of the glycogen in the ganglia is localized in the packet glial cells, which surround the neuron perikarya. Autoradiographic analysis demonstrated that the effects of histamine and dopamine were principally on the glycogen in the glial cells. 5. Adenylate cyclase was demonstrated by electron microscope histochemistry to be localized on the plasma membranes of the glial cells, and to a lesser extent on the neuronal membranes. 6. It is concluded that the changes in glycogen in the glial cells may be party controlled by transmitters via adenylate cyclase. This may provide a sensitive mechanism for coupling neuronal activity with energy metabolism.

Practice variation in the Dutch long-term care and the role of supply-sensitive care: Is access to the Dutch long-term care equitable?

PubMed

Duell, Daisy; Koolman, Xander; Portrait, France

2017-12-01

Universal access and generous coverage are important goals of the Dutch long-term care (LTC) system. It is a legal requirement that everyone eligible for LTC should be able to receive it. Institutional care (IC) made up for 90% of Dutch LTC spending. To investigate whether access to IC is as equitable as the Dutch government aspires, we explored practice variation in entitlements to IC across Dutch regions. We used a unique dataset that included all individual applications for Dutch LTC in January 2010-December 2013 (N = 3,373,358). This dataset enabled an accurate identification of the need for care. We examined the local variation in the probability of being granted long-term IC and in the intensity of the care granted given that individuals have applied for LTC. We also investigated whether the variation observed was related to differences in the local availability of care facilities. Although our analyses indicated the presence of some practice variation, its magnitude was very small by national and international standards (up to 3%). Only a minor part of the practice variation could be accounted for by local supply differences in care facilities. Overall, we conclude that, unlike many other developed countries, the Dutch system ensured equitable access to long-term IC. © 2017 The Authors. Health Economics Published by John Wiley & Sons Ltd.

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

Roman bronze artefacts from Thamusida (Morocco): Chemical and phase analyses

NASA Astrophysics Data System (ADS)

Gliozzo, E.; Kockelmann, W.; Bartoli, L.; Tykot, R. H.

2011-02-01

Twenty-six objects (1st to the 3rd century AD) found at the archaeological site of Thamusida (Morocco), which is a military settlement between the 1st and the 3rd century AD, have been investigated by means of portable X-ray fluorescence and time of flight-neutron diffraction. The combination of element-sensitive X-ray fluorescence and structure-sensitive neutron diffraction yields, in a totally non-destructive way, the necessary information to discriminate the copper alloy from corrosion and alteration layers. Results allowed dividing the repertory into five groups: (a) unalloyed copper, (b) binary alloys made of Cu and Sn, frequently leaded; (c) unleaded binary alloys made of Cu and Zn; (d) ternary alloys made of Cu, Sn and Zn, both leaded and unleaded; (e) quaternary alloys made of Cu, Sn, Zn and As. The choice of alloy is heterogeneous, mainly depending on availability and costs of raw and/or scrap materials and on technological constraints. Interestingly, the reconstruction obtained for Thamusida could either anticipate the important change in the Roman use of copper alloys generally referred as 'zinc decline', or more likely, indicate that brass never conspicuously entered the local metal-working activities of this military site.

Stability and sensitivity analysis of hypersonic flow past a blunt cone

NASA Astrophysics Data System (ADS)

Nichols, Joseph W.; Cook, David; Brock, Joseph M.; Candler, Graham V.

2017-11-01

We investigate the effects of nosetip bluntness and low-level distributed roughness on instabilities leading to transition on a 7 degree half-angle blunt cone at Mach 10. To study the sensitivity of boundary layer instabilities to bluntness and roughness, we numerically extract Jacobian matrices directly from the unstructured hypersonic flow solver US3D. These matrices govern the dynamics of small perturbations about otherwise laminar base flows. We consider the frequency response of the resulting linearized dynamical system between different input and output locations along the cone, including close to the nosetip. Using adjoints, our method faithfully captures effects of complex geometry such as strong curvature and roughness that lead to flow acceleration and localized heating in this region. These effects violate the assumption of a slowly-varying base flow that underpins traditional linear stability analyses. We compare our results, which do not rely upon this assumption, to experimental measurements of a Mach 10 blunt cone taken at the AEDC Hypervelocity Ballistic Range G facility. In particular, we assess whether effects of complex geometry can explain discrepancies previously noted between traditional stability analysis and observations. This work is supported by the Office of Naval Research through Grant Number N00014-17-1-2496.

Similarities in butterfly emergence dates among populations suggest local adaptation to climate.

PubMed

Roy, David B; Oliver, Tom H; Botham, Marc S; Beckmann, Bjorn; Brereton, Tom; Dennis, Roger L H; Harrower, Colin; Phillimore, Albert B; Thomas, Jeremy A

2015-09-01

Phenology shifts are the most widely cited examples of the biological impact of climate change, yet there are few assessments of potential effects on the fitness of individual organisms or the persistence of populations. Despite extensive evidence of climate-driven advances in phenological events over recent decades, comparable patterns across species' geographic ranges have seldom been described. Even fewer studies have quantified concurrent spatial gradients and temporal trends between phenology and climate. Here we analyse a large data set (~129 000 phenology measures) over 37 years across the UK to provide the first phylogenetic comparative analysis of the relative roles of plasticity and local adaptation in generating spatial and temporal patterns in butterfly mean flight dates. Although populations of all species exhibit a plastic response to temperature, with adult emergence dates earlier in warmer years by an average of 6.4 days per °C, among-population differences are significantly lower on average, at 4.3 days per °C. Emergence dates of most species are more synchronised over their geographic range than is predicted by their relationship between mean flight date and temperature over time, suggesting local adaptation. Biological traits of species only weakly explained the variation in differences between space-temperature and time-temperature phenological responses, suggesting that multiple mechanisms may operate to maintain local adaptation. As niche models assume constant relationships between occurrence and environmental conditions across a species' entire range, an important implication of the temperature-mediated local adaptation detected here is that populations of insects are much more sensitive to future climate changes than current projections suggest. © 2015 The Authors. Global Change Biology published by John Wiley & Sons Ltd.

Periadolescent exposure to the NMDA antagonist MK-801 impairs the functional maturation of local GABAergic circuits in the adult prefrontal cortex

PubMed Central

Thomases, Daniel R.; Cass, Daryn K.; Tseng, Kuei Y.

2012-01-01

A developmental disruption of prefrontal cortical (PFC) inhibitory circuits is thought to contribute to the adolescent onset of cognitive deficits observed in schizophrenia. However, the developmental mechanisms underlying such a disruption remain elusive. The goal of this study is to examine how repeated exposure to the NMDA receptor antagonist dizocilpine maleate (MK-801) during periadolescence (from postnatal days -PD- 35-40) impacts the normative development of local prefrontal network response in rats. In vivo electrophysiological analyses revealed that MK-801 administration during periadolescence elicits an enduring disinhibited prefrontal local field potential response to ventral hippocampal stimulation at 20Hz (beta) and 40Hz (gamma) in adulthood (PD65-85). Such a disinhibition was not observed when MK-801 was given during adulthood, indicating that the periadolescent transition is indeed a sensitive period for the functional maturation of prefrontal inhibitory control. Accordingly, the pattern of prefrontal local field potential disinhibition induced by periadolescent MK-801 treatment resembles that observed in the normal PD30-40 PFC. Further pharmacological manipulations revealed that these developmentally immature prefrontal responses can be mimicked by single microinfusion of the GABA-A receptor antagonist picrotoxin into the normal adult PFC. Importantly, acute administration of the GABA-A positive allosteric modulator Indiplon into the PFC reversed the prefrontal disinhibitory state induced by periadolescent MK-801 to normal levels. Together, these results indicate a critical role of NMDA receptors in regulating the periadolescent maturation of GABAergic networks in the PFC, and that pharmacologically-induced augmentation of local GABA-A receptor-mediated transmission is sufficient to overcome the disinhibitory prefrontal state associated with the periadolescent MK-801 exposure. PMID:23283319

Emergence and localized circulation of a vaccine-derived poliovirus in an isolated mountain community in Guangxi, China.

PubMed

Yan, Dongmei; Li, Li; Zhu, Shuangli; Zhang, Yong; An, Junjing; Wang, Dongyan; Wen, Ning; Jorba, Jaume; Liu, Wei; Zhong, Ge; Huang, Lin; Kew, Olen; Liang, Xiaofeng; Xu, Wenbo

2010-09-01

From March to May 2006, type 1 circulating vaccine-derived poliovirus (cVDPV) was isolated from one case patient with acute flaccid paralysis (AFP) and six unimmunized healthy contacts in isolated mountain villages in Guangxi, China. We conducted epidemiological investigations in the affected communities and nucleotide sequence analyses of the cVDPV isolates. The results of the investigations showed that the AFP patient, an unimmunized 10-year-old boy, and five laboratory-confirmed contacts lived in the same village; one contact lived in a neighboring village. Only approximately 27% of children 5 to 10 years of age in the affected villages had received three or more doses of the trivalent oral poliovirus vaccine (OPV). Nucleotide sequence analyses revealed that the cVDPV isolates differed from the Sabin 1 (S1) isolate at 1.4 to 2.2% of VP1 nucleotide positions and shared 12 nucleotide substitutions within VP1. All isolates were S1/S2/S1/S3 recombinants sharing common recombination junctions. Key determinants of attenuation were replaced. Phylogenetic analysis suggested that the cVDPV circulated locally for approximately 12 months following the initiating OPV dose. No VDPVs were found after mass OPV immunizations, conducted from May to June 2006, that targeted all children <12 years of age. Our findings reinforce the point that VDPVs can emerge and spread in isolated communities with immunity gaps. Maintenance of sensitive AFP and poliovirus surveillance is essential to permit early detection and a rapid response to VDPV circulation.

Advanced materials for improving biosensing performances of propagating and localized plasmonic transducers

NASA Astrophysics Data System (ADS)

Manera, M. G.; Colombelli, A.; Convertino, A.; Rella, S.; De Lorenzis, E.; Taurino, A.; Malitesta, C.; Rella, R.

2015-05-01

Among all transduction methodologies reported in the field of solid state optical chemical sensors, the attention has been focused onto the optical sensing characterization by using propagating and localized surface plasmon resonance (SPR) techniques. The research in this field is always oriented in the improvement of the sensing features in terms of sensitivity and limits of detection. To this purpose different strategies have been proposed to realize advanced materials for high sensitive plasmonic devices. In this work nanostructured silica nanowires decorated by gold nanoparticles and active magneto-plasmonic transductors are considered as new biosensing transductors useful to increase the performance of sensitive devices.

[Sensitivity of meningococci to the antagonistic activity of nasopharyngeal microflora and antibiotics].

PubMed

Bochkov, I A; Larina, L I

1977-12-01

Comparative study of the meningococcus sensitivity of various serological groups with different localization in the human organism to the antagonistic activity of normal microbes of the nasopharynx and the antibiotics it was found that strains isolated from the cerebrospinal fluid of patients suffering from cerebrospinal meningitis, chiefly of serological group A, had the greatest resistance to the antagonists. Taking into consideration the leading epidemiological role of the cultures belonging to the serological group A in the USSR, it can be supposed that meningococcus sensitivity to the nasopharyngeal antagonists was of significance for the manifestation of their pathogenic properties. No association of the antibiotic sensitivity of the same strains with reference to a definite serological group or the site of the microbe localization was revealed.

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

Costs Of Using “Tiny Targets” to Control Glossina fuscipes fuscipes, a Vector of Gambiense Sleeping Sickness in Arua District of Uganda

PubMed Central

Shaw, Alexandra P. M.; Tirados, Inaki; Mangwiro, Clement T. N.; Esterhuizen, Johan; Lehane, Michael J.; Torr, Stephen J.; Kovacic, Vanja

2015-01-01

Introduction To evaluate the relative effectiveness of tsetse control methods, their costs need to be analysed alongside their impact on tsetse populations. Very little has been published on the costs of methods specifically targeting human African trypanosomiasis Methodology/Principal Findings In northern Uganda, a 250 km2 field trial was undertaken using small (0.5 X 0.25 m) insecticide-treated targets (“tiny targets”). Detailed cost recording accompanied every phase of the work. Costs were calculated for this operation as if managed by the Ugandan vector control services: removing purely research components of the work and applying local salaries. This calculation assumed that all resources are fully used, with no spare capacity. The full cost of the operation was assessed at USD 85.4 per km2, of which USD 55.7 or 65.2% were field costs, made up of three component activities (target deployment: 34.5%, trap monitoring: 10.6% and target maintenance: 20.1%). The remaining USD 29.7 or 34.8% of the costs were for preliminary studies and administration (tsetse surveys: 6.0%, sensitisation of local populations: 18.6% and office support: 10.2%). Targets accounted for only 12.9% of the total cost, other important cost components were labour (24.1%) and transport (34.6%). Discussion Comparison with the updated cost of historical HAT vector control projects and recent estimates indicates that this work represents a major reduction in cost levels. This is attributed not just to the low unit cost of tiny targets but also to the organisation of delivery, using local labour with bicycles or motorcycles. Sensitivity analyses were undertaken, investigating key prices and assumptions. It is believed that these costs are generalizable to other HAT foci, although in more remote areas, with denser vegetation and fewer people, costs would increase, as would be the case for other tsetse control techniques. PMID:25811956

Feeding Patterns of Potential West Nile Virus Vectors in South-West Spain

PubMed Central

Muñoz, Joaquín; Ruiz, Santiago; Soriguer, Ramón; Alcaide, Miguel; Viana, Duarte S.; Roiz, David; Vázquez, Ana; Figuerola, Jordi

2012-01-01

Background Mosquito feeding behaviour determines the degree of vector–host contact and may have a serious impact on the risk of West Nile virus (WNV) epidemics. Feeding behaviour also interacts with other biotic and abiotic factors that affect virus amplification and transmission. Methodology/Principal Findings We identified the origin of blood meals in five mosquito species from three different wetlands in SW Spain. All mosquito species analysed fed with different frequencies on birds, mammals and reptiles. Both ‘mosquito species’ and ‘locality’ explained a similar amount of variance in the occurrence of avian blood meals. However, ‘season of year’ was the main factor explaining the presence of human blood meals. The differences in diet resulted in a marked spatial heterogeneity in the estimated WNV transmission risk. Culex perexiguus, Cx. modestus and Cx. pipiens were the main mosquito species involved in WNV enzootic circulation since they feed mainly on birds, were abundant in a number of localities and had high vector competence. Cx. perexiguus may also be important for WNV transmission to horses, as are Cx. pipiens and Cx. theileri in transmission to humans. Estimates of the WNV transmission risk based on mosquito diet, abundance and vector competence matched the results of previous WNV monitoring programs in the area. Our sensitivity analyses suggested that mosquito diet, followed by mosquito abundance and vector competence, are all relevant factors in understanding virus amplification and transmission risk in the studied wild ecosystems. At some of the studied localities, the risk of enzootic circulation of WNV was relatively high, even if the risk of transmission to humans and horses was less. Conclusions/Significance Our results describe for first time the role of five WNV candidate vectors in SW Spain. Interspecific and local differences in mosquito diet composition has an important effect on the potential transmission risk of WNV to birds, horses and humans. PMID:22745781

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).

Evaluation Methodology between Globalization and Localization Features Approaches for Skin Cancer Lesions Classification

NASA Astrophysics Data System (ADS)

Ahmed, H. M.; Al-azawi, R. J.; Abdulhameed, A. A.

2018-05-01

Huge efforts have been put in the developing of diagnostic methods to skin cancer disease. In this paper, two different approaches have been addressed for detection the skin cancer in dermoscopy images. The first approach uses a global method that uses global features for classifying skin lesions, whereas the second approach uses a local method that uses local features for classifying skin lesions. The aim of this paper is selecting the best approach for skin lesion classification. The dataset has been used in this paper consist of 200 dermoscopy images from Pedro Hispano Hospital (PH2). The achieved results are; sensitivity about 96%, specificity about 100%, precision about 100%, and accuracy about 97% for globalization approach while, sensitivity about 100%, specificity about 100%, precision about 100%, and accuracy about 100% for Localization Approach, these results showed that the localization approach achieved acceptable accuracy and better than globalization approach for skin cancer lesions classification.

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.

Preoperative 4D CT Localization of Nonlocalizing Parathyroid Adenomas by Ultrasound and SPECT-CT.

PubMed

Hinson, Andrew M; Lee, David R; Hobbs, Bradley A; Fitzgerald, Ryan T; Bodenner, Donald L; Stack, Brendan C

2015-11-01

To evaluate 4-dimensional (4D) computed tomography (CT) for the localization of parathyroid adenomas previously considered nonlocalizing on ultrasound and single-photon emission CT with CT scanning (SPECT-CT). To measure radiation exposure associated with 4D-CT and compared it with SPECT-CT. Case series with chart review. University tertiary hospital. Nineteen adults with primary hyperparathyroidism who underwent preoperative 4D CT from November 2013 through July 2014 after nonlocalizing preoperative ultrasound and technetium-99m SPECT-CT scans. Sensitivity, specificity, predictive values, and accuracy of 4D CT were evaluated. Nineteen patients (16 women and 3 men) were included with a mean age of 66 years (range, 39-80 years). Mean preoperative parathyroid hormone level was 108.5 pg/mL (range, 59.3-220.9 pg/mL), and mean weight of the excised gland was 350 mg (range, 83-797 mg). 4D CT sensitivity and specificity for localization to the patient's correct side of the neck were 84.2% and 81.8%, respectively; accuracy was 82.9%. The sensitivity for localizing adenomas to the correct quadrant was 76.5% and 91.5%, respectively; accuracy was 88.2%. 4D CT radiation exposure was significantly less than the radiation associated with SPECT-CT (13.8 vs 18.4 mSv, P = 0.04). 4D CT localizes parathyroid adenomas with relatively high sensitivity and specificity and allows for the localization of some adenomas not observed on other sestamibi-based scans. 4D CT was also associated with less radiation exposure when compared with SPECT-CT based on our study protocol. 4D CT may be considered as first- or second-line imaging for localizing parathyroid adenomas in the setting of primary hyperparathyroidism. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Sensitivity of soil moisture initialization for decadal predictions under different regional climatic conditions in Europe

NASA Astrophysics Data System (ADS)

Khodayar, S.; Sehlinger, A.; Feldmann, H.; Kottmeier, C.

2015-12-01

The impact of soil initialization is investigated through perturbation simulations with the regional climate model COSMO-CLM. The focus of the investigation is to assess the sensitivity of simulated extreme periods, dry and wet, to soil moisture initialization in different climatic regions over Europe and to establish the necessary spin up time within the framework of decadal predictions for these regions. Sensitivity experiments consisted of a reference simulation from 1968 to 1999 and 5 simulations from 1972 to 1983. The Effective Drought Index (EDI) is used to select and quantify drought status in the reference run to establish the simulation time period for the sensitivity experiments. Different soil initialization procedures are investigated. The sensitivity of the decadal predictions to soil moisture initial conditions is investigated through the analysis of water cycle components' (WCC) variability. In an episodic time scale the local effects of soil moisture on the boundary-layer and the propagated effects on the large-scale dynamics are analysed. The results show: (a) COSMO-CLM reproduces the observed features of the drought index. (b) Soil moisture initialization exerts a relevant impact on WCC, e.g., precipitation distribution and intensity. (c) Regional characteristics strongly impact the response of the WCC. Precipitation and evapotranspiration deviations are larger for humid regions. (d) The initial soil conditions (wet/dry), the regional characteristics (humid/dry) and the annual period (wet/dry) play a key role in the time that soil needs to restore quasi-equilibrium and the impact on the atmospheric conditions. Humid areas, and for all regions, a humid initialization, exhibit shorter spin up times, also soil reacts more sensitive when initialised during dry periods. (e) The initial soil perturbation may markedly modify atmospheric pressure field, wind circulation systems and atmospheric water vapour distribution affecting atmospheric stability conditions, thus modifying precipitation intensity and distribution even several years after the initialization.

Scanning laser polarimetry using variable corneal compensation in the detection of glaucoma with localized visual field defects.

PubMed

Kook, Michael S; Cho, Hyun-soo; Seong, Mincheol; Choi, Jaewan

2005-11-01

To evaluate the ability of scanning laser polarimetry parameters and a novel deviation map algorithm to discriminate between healthy and early glaucomatous eyes with localized visual field (VF) defects confined to one hemifield. Prospective case-control study. Seventy glaucomatous eyes with localized VF defects and 66 normal controls. A Humphrey field analyzer 24-2 full-threshold test and scanning laser polarimetry with variable corneal compensation were used. We assessed the sensitivity and specificity of scanning laser polarimetry parameters, sensitivity and cutoff values for scanning laser polarimetry deviation map algorithms at different specificity values (80%, 90%, and 95%) in the detection of glaucoma, and correlations between the algorithms of scanning laser polarimetry and of the pattern deviation derived from Humphrey field analyzer testing. There were significant differences between the glaucoma group and normal subjects in the mean parametric values of the temporal, superior, nasal, inferior, temporal (TSNIT) average, superior average, inferior average, and TSNIT standard deviation (SD) (P<0.05). The sensitivity and specificity of each scanning laser polarimetry variable was as follows: TSNIT, 44.3% (95% confidence interval [CI], 39.8%-49.8%) and 100% (95.4%-100%); superior average, 30% (25.5%-34.5%) and 97% (93.5%-100%); inferior average, 45.7% (42.2%-49.2%) and 100% (95.8%-100%); and TSNIT SD, 30% (25.9%-34.1%) and 97% (93.2%-100%), respectively (when abnormal was defined as P<0.05). Based on nerve fiber indicator cutoff values of > or =30 and > or =51 to indicate glaucoma, sensitivities were 54.3% (50.1%-58.5%) and 10% (6.4%-13.6%), and specificities were 97% (93.2%-100%) and 100% (95.8%-100%), respectively. The range of areas under the receiver operating characteristic curves using the scanning laser polarimetry deviation map algorithm was 0.790 to 0.879. Overall sensitivities combining each probability scale and severity score at 80%, 90%, and 95% specificities were 90.0% (95% CI, 86.4%-93.6%), 71.4% (67.4%-75.4%), and 60.0% (56.2%-63.8%), respectively. There was a statistically significant correlation between the scanning laser polarimetry severity score and the VF severity score (R2 = 0.360, P<0.001). Scanning laser polarimetry parameters may not be sufficiently sensitive to detect glaucomatous patients with localized VF damage. Our algorithm using the scanning laser polarimetry deviation map may enhance the understanding of scanning laser polarimetry printouts in terms of the locality, deviation size, and severity of localized retinal nerve fiber layer defects in eyes with localized VF loss.

German experiences in local fatigue monitoring

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

Abib, E.; Bergholz, S.; Rudolph, J.

The ageing management of nuclear power plants (NPP) has gained an increasing importance in the last years. The reasons are mainly due to the international context of extending period of plants operation. Moreover, new scientific discoveries, such as the corrosive influence of the medium on the fatigue process (environmentally assisted fatigue - EAF) play an important role and influence the code development (ASME, EAF code cases). The fatigue damage process takes a central position in ageing mechanisms of components. It must be ensured through appropriate evidence that facilities are being operated under allowable boundary conditions. In the design phase ofmore » NPP, fatigue analyses are still based on theoretical considerations and empirical values, which are summarized in the design transient catalogue, necessary for licensing. These analyses aim at proving the admissibility of the loads in terms of stress and fatigue usage. These analyses will also provide the fatigue-relevant positions in the NPP and give a basis for future design improvements and optimization of operating modes. The design transients are in practice conservatively correlated with the real transients occurring during operation. Uncertainties reveal very conservative assumptions regarding forecast temperatures, temperature gradients and frequencies of events. During operation of the plant, it has to be recurrently proved, that the plant is being operated under designed boundary conditions. Moreover, operating signals are constantly acquired to enable a fatigue evaluation. For example, in Germany fatigue evaluation is based on decades of experience and regulatory requirements. The rule KTA 3201.4 [1] establishes the rules for qualified fatigue monitoring. The rule DIN 25475-3 [2] on fatigue monitoring systems is available in draft version. Experience shows that some significant differences occur between the design transients and the real occurred transients during plant operation. The reasons for it are the various manual control options and also different operating modes. It is clear that showing the covering of real loads by design loads, requires a relatively complex and well-qualified detection process. The difficulty of this task is increased due to the lack of data or incomplete information and the exclusive reliance on existing operation plant data. The strategy of employing local fatigue monitoring is a straightforward solution enabling the direct measurement of loads on the fatigue-sensitive zones. Nowadays a direct derivation of the complete stress tensor at the fatigue-relevant locations is enabled thanks to the recorded local loads and combination with finite element (FE) analyses. So, additionally to the recorded temperature curves, a representation of the time evolution of the six stress components for each monitored component is possible. This allows the application of the simplified elasto-plastic fatigue check according to design codes. The fatigue level can be realistically analyzed with a suitable cycle-counting method. Furthermore, the knowledge of the time evolution of the stresses and strains enables to take into account an environmental factor to include the corrosive fluid influence in the calculations. Without local recording, it is impossible to calculate realistic fatigue usage. AREVA offers the AREVA fatigue concept (AFC) and the new fatigue monitoring system integrated (FAMOSi), necessary tools to monitor local fatigue and to provide realistic assessment. (authors)« less

Particle Dark Matter Searches Outside the Local Group.

PubMed

Regis, Marco; Xia, Jun-Qing; Cuoco, Alessandro; Branchini, Enzo; Fornengo, Nicolao; Viel, Matteo

2015-06-19

If dark matter (DM) is composed by particles which are nongravitationally coupled to ordinary matter, their annihilations or decays in cosmic structures can result in detectable radiation. We show that the most powerful technique to detect a particle DM signal outside the Local Group is to study the angular cross-correlation of nongravitational signals with low-redshift gravitational probes. This method allows us to enhance the signal to noise from the regions of the Universe where the DM-induced emission is preferentially generated. We demonstrate the power of this approach by focusing on GeV-TeV DM and on the recent cross-correlation analysis between the 2MASS galaxy catalogue and the Fermi-LAT γ-ray maps. We show that this technique is more sensitive than other extragalactic γ-ray probes, such as the energy spectrum and angular autocorrelation of the extragalactic background, and emission from clusters of galaxies. Intriguingly, we find that the measured cross-correlation can be well fitted by a DM component, with a thermal annihilation cross section and mass between 10 and 100 GeV, depending on the small-scale DM properties and γ-ray production mechanism. This solicits further data collection and dedicated analyses.

Particle Dark Matter Searches Outside the Local Group

NASA Astrophysics Data System (ADS)

Regis, Marco; Xia, Jun-Qing; Cuoco, Alessandro; Branchini, Enzo; Fornengo, Nicolao; Viel, Matteo

2015-06-01

If dark matter (DM) is composed by particles which are nongravitationally coupled to ordinary matter, their annihilations or decays in cosmic structures can result in detectable radiation. We show that the most powerful technique to detect a particle DM signal outside the Local Group is to study the angular cross-correlation of nongravitational signals with low-redshift gravitational probes. This method allows us to enhance the signal to noise from the regions of the Universe where the DM-induced emission is preferentially generated. We demonstrate the power of this approach by focusing on GeV-TeV DM and on the recent cross-correlation analysis between the 2MASS galaxy catalogue and the Fermi-LAT γ -ray maps. We show that this technique is more sensitive than other extragalactic γ -ray probes, such as the energy spectrum and angular autocorrelation of the extragalactic background, and emission from clusters of galaxies. Intriguingly, we find that the measured cross-correlation can be well fitted by a DM component, with a thermal annihilation cross section and mass between 10 and 100 GeV, depending on the small-scale DM properties and γ -ray production mechanism. This solicits further data collection and dedicated analyses.

Charged Particle Radiation Therapy for Uveal Melanoma: A Systematic Review and Meta-Analysis

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

Wang, Zhen, E-mail: Wang.Zhen@mayo.edu; Nabhan, Mohammed; Schild, Steven E.

2013-05-01

Charged particle therapy (CPT) delivered with either protons, helium ions, or carbon ions, has been used to treat uveal melanoma. The present analysis was performed to systematically evaluate the efficacy and adverse effects of CPT for uveal melanoma. We searched EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus and cross-referenced recent systematic reviews through January 2012. Two independent reviewers identified clinical trials and observational studies of CPT (protons, helium ions, and carbon ions). These reviewers extracted data and assessed study quality. Twenty-seven studies enrolling 8809 uveal melanoma patients met inclusion criteria. Themore » rate of local recurrence was significantly less with CPT than with brachytherapy (odds ratio [OR] = 0.22, 95% confidence interval [CI], 0.21-0.23). There were no significant differences in mortality or enucleation rates. Results were robust in multiple sensitivity analyses. CPT was also associated with lower retinopathy and cataract formation rates. Data suggest better outcomes may be possible with charged particle therapy with respect to local recurrence, retinopathy, and cataract formation rates. The overall quality of the evidence is low, and higher quality comparative effectiveness studies are needed to provide better evidence.« less

Systemic and local gut-specific antibody responses in preruminant calves sensitive to soya.

PubMed

Lallès, J P; Dréau, D; Huet, A; Toullec, R

1995-07-01

The systemic and local (gut) patterns of antibodies against various proteins from soyabean were analysed in preruminant calves fed milk substitutes based on skim milk powder (SMP) or heated soyabean flour (HSF) as the main protein sources. The titres of IgM, IgA, IgG1 and IgG2 antibodies were determined against feed extracts and purified soyabean proteins by dot-blotting in plasma after three months and jejunal mucous secretions after six months of feeding the experimental diets. The calves fed HSF had higher levels of circulating IgA, IgG1 and IgG2 antibodies against raw or heated soya extracts and purified proteins including alpha-conglycinin, beta-conglycinin, Bowman-Birk protease inhibitors and lectins than the calves fed SMP. In contrast, the differences between the IgM titres of the groups were most often not significant. The patterns of specific antibodies present in the jejunum were broadly similar to those observed in the blood, although the differences between the groups of calves more often reached significance for IgG2 and IgM than for IgA and IgG1, when the purified soyabean proteins were considered.

Strontium isotope systematics of mixing groundwater and oil-field brine at Goose Lake in northeastern Montana, USA

USGS Publications Warehouse

Peterman, Zell E.; Thamke, Joanna N.; Futa, Kiyoto; Preston, Todd

2012-01-01

Groundwater, surface water, and soil in the Goose Lake oil field in northeastern Montana have been affected by Cl−-rich oil-field brines during long-term petroleum production. Ongoing multidisciplinary geochemical and geophysical studies have identified the degree and local extent of interaction between brine and groundwater. Fourteen samples representing groundwater, surface water, and brine were collected for Sr isotope analyses to evaluate the usefulness of 87Sr/86Sr in detecting small amounts of brine. Differences in Sr concentrations and 87Sr/86Sr are optimal at this site for the experiment. Strontium concentrations range from 0.13 to 36.9 mg/L, and corresponding 87Sr/86Sr values range from 0.71097 to 0.70828. The local brine has 168 mg/L Sr and a 87Sr/86Sr value of 0.70802. Mixing relationships are evident in the data set and illustrate the sensitivity of Sr in detecting small amounts of brine in groundwater. The location of data points on a Sr isotope-concentration plot is readily explained by an evaporation-mixing model. The model is supported by the variation in concentrations of most of the other solutes.

ASTROCULTURE (TM) root metabolism and cytochemical analysis

NASA Technical Reports Server (NTRS)

Porterfield, D. M.; Barta, D. J.; Ming, D. W.; Morrow, R. C.; Musgrave, M. E.

2000-01-01

Physiology of the root system is dependent upon oxygen availability and tissue respiration. During hypoxia nutrient and water acquisition may be inhibited, thus affecting the overall biochemical and physiological status of the plant. For the Astroculture (TM) plant growth hardware, the availability of oxygen in the root zone was measured by examining the changes in alcohol dehydrogenase (ADH) activity within the root tissue. ADH activity is a sensitive biochemical indicator of hypoxic conditions in plants and was measured in both spaceflight and control roots. In addition to the biochemical enzyme assays, localization of ADH in the root tissue was examined cytochemically. The results of these analyses showed that ADH activity increased significantly as a result of spaceflight exposure. Enzyme activity increased 248% to 304% in dwarf wheat when compared with the ground controls and Brassica showed increases between 334% and 579% when compared with day zero controls. Cytochemical staining revealed no differences in ADH tissue localization in any of the dwarf wheat treatments. These results show the importance of considering root system oxygenation in designing and building nutrient delivery hardware for spaceflight plant cultivation and confirm previous reports of an ADH response associated with spaceflight exposure.

District nursing workforce planning: a review of the methods.

PubMed

Reid, Bernie; Kane, Kay; Curran, Carol

2008-11-01

District nursing services in Northern Ireland face increasing demands and challenges which may be responded to by effective and efficient workforce planning and development. The aim of this paper is to critically analyse district nursing workforce planning and development methods, in an attempt to find a suitable method for Northern Ireland. A systematic analysis of the literature reveals four methods: professional judgement; population-based health needs; caseload analysis and dependency-acuity. Each method has strengths and weaknesses. Professional judgement offers a 'belt and braces' approach but lacks sensitivity to fluctuating patient numbers. Population-based health needs methods develop staffing algorithms that reflect deprivation and geographical spread, but are poorly understood by district nurses. Caseload analysis promotes equitable workloads but poorly performing district nursing localities may continue if benchmarking processes only consider local data. Dependency-acuity methods provide a means of equalizing and prioritizing workload but are prone to district nurses overstating factors in patient dependency or understating carers' capability. In summary a mixed method approach is advocated to evaluate and adjust the size and mix of district nursing teams using empirically determined patient dependency and activity-based variables based on the population's health needs.

Early Detection for Dengue Using Local Indicator of Spatial Association (LISA) Analysis.

PubMed

Parra-Amaya, Mayra Elizabeth; Puerta-Yepes, María Eugenia; Lizarralde-Bejarano, Diana Paola; Arboleda-Sánchez, Sair

2016-03-29

Dengue is a viral disease caused by a flavivirus that is transmitted by mosquitoes of the genus Aedes . There is currently no specific treatment or commercial vaccine for its control and prevention; therefore, mosquito population control is the only alternative for preventing the occurrence of dengue. For this reason, entomological surveillance is recommended by World Health Organization (WHO) to measure dengue risk in endemic areas; however, several works have shown that the current methodology (aedic indices) is not sufficient for predicting dengue. In this work, we modified indices proposed for epidemic periods. The raw value of the epidemiological wave could be useful for detecting risk in epidemic periods; however, risk can only be detected if analyses incorporate the maximum epidemiological wave. Risk classification was performed according to Local Indicators of Spatial Association (LISA) methodology. The modified indices were analyzed using several hypothetical scenarios to evaluate their sensitivity. We found that modified indices could detect spatial and differential risks in epidemic and endemic years, which makes them a useful tool for the early detection of a dengue outbreak. In conclusion, the modified indices could predict risk at the spatio-temporal level in endemic years and could be incorporated in surveillance activities in endemic places.

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.

Development of a local size hierarchy causes regular spacing of trees in an even-aged Abies forest: analyses using spatial autocorrelation and the mark correlation function.

PubMed

Suzuki, Satoshi N; Kachi, Naoki; Suzuki, Jun-Ichirou

2008-09-01

During the development of an even-aged plant population, the spatial distribution of individuals often changes from a clumped pattern to a random or regular one. The development of local size hierarchies in an Abies forest was analysed for a period of 47 years following a large disturbance in 1959. In 1980 all trees in an 8 x 8 m plot were mapped and their height growth after the disturbance was estimated. Their mortality and growth were then recorded at 1- to 4-year intervals between 1980 and 2006. Spatial distribution patterns of trees were analysed by the pair correlation function. Spatial correlations between tree heights were analysed with a spatial autocorrelation function and the mark correlation function. The mark correlation function was able to detect a local size hierarchy that could not be detected by the spatial autocorrelation function alone. The small-scale spatial distribution pattern of trees changed from clumped to slightly regular during the 47 years. Mortality occurred in a density-dependent manner, which resulted in regular spacing between trees after 1980. The spatial autocorrelation and mark correlation functions revealed the existence of tree patches consisting of large trees at the initial stage. Development of a local size hierarchy was detected within the first decade after the disturbance, although the spatial autocorrelation was not negative. Local size hierarchies that developed persisted until 2006, and the spatial autocorrelation became negative at later stages (after about 40 years). This is the first study to detect local size hierarchies as a prelude to regular spacing using the mark correlation function. The results confirm that use of the mark correlation function together with the spatial autocorrelation function is an effective tool to analyse the development of a local size hierarchy of trees in a forest.

Large-scale variation of electron parameters from Quasi-Thermal Noise during WIND perigees in the Earth's magnetosphere

NASA Astrophysics Data System (ADS)

Issautier, Karine; Ongala-Edoumou, Samuel; Moncuquet, Michel

2016-04-01

The quasi-thermal noise (QTN) method consists in measuring the electrostatic fluctuations produced by the thermal motion of the ambient particles. This noise is detected with a sensitive wave receiver and measured at the terminal of a passive electric antenna, which is immersed in a stable plasma. The analysis of the so-called QTN provides in situ measurements, mainly the total electron density, with a good accuracy, and thermal temperature in a large number of space media. We create a preliminary electron database to analyse the anti-correlation between electron density and temperature deduced from WIND perigees in the Earth's plasmasphere. We analyse the radio power spectra measured by the Thermal Noise Receiver (TNR), using the 100-m long dipole antenna, onboard WIND spacecraft. We develop a systematic routine to determine the electron density, core and halo temperature and the magnitude of the magnetic field based on QTN in Bernstein modes. Indeed, the spectra are weakly banded between gyroharmonics below the upper hybrid frequency, from which we derive the local electron density. From the gyrofrequency determination, we obtain an independent measure of the magnetic field magnitude, which is in close agreement with the onboard magnetometer.

[Approximation to the dynamics of meningococcal meningitis through dynamic systems and time series].

PubMed

Canals, M

1996-02-01

Meningococcal meningitis is subjected to epidemiological surveillance due to its severity and the occasional presentation of epidemic outbreaks. This work analyses previous disease models, generate new ones and analyses monthly cases using ARIMA time series models. The results show that disease dynamics for closed populations is epidemic and the epidemic size is related to the proportion of carriers and the transmissiveness of the agent. In open populations, disease dynamics depends on the admission rate of susceptible and the relative admission of infected individuals. Our model considers a logistic populational growth and carrier admission proportional to populational size, generating an endemic dynamics. Considering a non-instantaneous system response, a greater realism is obtained establishing that the endemic situation may present a dynamics highly sensitive to initial conditions, depending on the transmissiveness and proportion of susceptible individuals in the population. Time series model showed an adequate predictive capacity in terms no longer than 10 months. The lack of long term predictability was attributed to local changes in the proportion of carriers or on transmissiveness that lead to chaotic dynamics over a seasonal pattern. Predictions for 1995 and 1996 were obtained.

Paradoxical psychometric functions (“swan functions”) are explained by dilution masking in four stimulus dimensions

PubMed Central

Baker, Daniel H.; Meese, Tim S.; Georgeson, Mark A.

2013-01-01

The visual system dissects the retinal image into millions of local analyses along numerous visual dimensions. However, our perceptions of the world are not fragmentary, so further processes must be involved in stitching it all back together. Simply summing up the responses would not work because this would convey an increase in image contrast with an increase in the number of mechanisms stimulated. Here, we consider a generic model of signal combination and counter-suppression designed to address this problem. The model is derived and tested for simple stimulus pairings (e.g. A + B), but is readily extended over multiple analysers. The model can account for nonlinear contrast transduction, dilution masking, and signal combination at threshold and above. It also predicts nonmonotonic psychometric functions where sensitivity to signal A in the presence of pedestal B first declines with increasing signal strength (paradoxically dropping below 50% correct in two-interval forced choice), but then rises back up again, producing a contour that follows the wings and neck of a swan. We looked for and found these “swan” functions in four different stimulus dimensions (ocularity, space, orientation, and time), providing some support for our proposal. PMID:23799185

Assessment of topsoil contamination near the Stanisław Siedlecki Polish Polar Station in Hornsund, Svalbard, using magnetic methods

NASA Astrophysics Data System (ADS)

Gonet, T.; Górka-Kostrubiec, B.; Łuczak-Wilamowska, B.

2018-03-01

Topsoil contamination near the Stanisław Siedlecki Polish Polar Station (PPS), Hornsund, Svalbard, has been assessed using magnetic methods supplemented by chemical analyses and microscopic observations. Analysis of magnetic parameters has enabled to evaluate the concentration, magnetic mineralogy, and grain-size distribution of anthropogenic magnetic particles. Heavy-metal contamination near the PPS originates primarily from local sources. Anthropogenic spherical, magnetite-like particles were found near the station, whereas uncontaminated topsoil is devoid of such particles. Magnetic studies indicate that magnetite and goethite are the primary magnetic phases, with magnetite levels being higher in polluted area. Magnetic fraction of contaminated topsoil includes a mixture of single-domain and multi-domain grains, while uncontaminated topsoil contains smaller grains. Results show a clear correspondence between Pollution Load Index and magnetic susceptibility anomalies, and that the areal extent of PPS impact on the environment has not expanded significantly since 2004 (although a new contamination source, the scrap yard, is now present). A comparison of magnetic susceptibility measurements with metal analyses indicates that magnetic methods can be used as a rapid, inexpensive, non-invasive, and sensitive tool for the evaluation of topsoil contamination.

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

Texture Profile and Color Determination on Local and Imported Meat Available in Semarang City, Indonesia

NASA Astrophysics Data System (ADS)

Arifin, Mukh; Ni'matullah Al-Baarri, Ahmad; Etza Setiani, Bhakti; Fazriyati Siregar, Risa

2018-02-01

This study was done for analysing the texture profile and colour performance in local and imported meat in Semarang, Indonesia. Two types of available meat were compared in the hardness, cohesiveness, springiness, adhesiveness and the colour L*a*b* performance. Five fresh beef cut of round meats from local and imported meat were used in this experiments. Data were analysed statistically using T-test. The results showed that local beef exhibit higher in the springiness than imported beef resulting in the remarkable differences. The colour analysis showed that imported beef provided remarkable higher in L* value than local beef. Resulting significant differences among two types of beef. As conclusion, these value might provide the notable of differences among local and imported meat and may give preferences status to the user for further application in meat processing.

Coupling 3D groundwater modeling with CFC-based age dating to classify local groundwater circulation in an unconfined crystalline aquifer

NASA Astrophysics Data System (ADS)

Kolbe, Tamara; Marçais, Jean; Thomas, Zahra; Abbott, Benjamin W.; de Dreuzy, Jean-Raynald; Rousseau-Gueutin, Pauline; Aquilina, Luc; Labasque, Thierry; Pinay, Gilles

2016-12-01

Nitrogen pollution of freshwater and estuarine environments is one of the most urgent environmental crises. Shallow aquifers with predominantly local flow circulation are particularly vulnerable to agricultural contaminants. Water transit time and flow path are key controls on catchment nitrogen retention and removal capacity, but the relative importance of hydrogeological and topographical factors in determining these parameters is still uncertain. We used groundwater dating and numerical modeling techniques to assess transit time and flow path in an unconfined aquifer in Brittany, France. The 35.5 km2 study catchment has a crystalline basement underneath a ∼60 m thick weathered and fractured layer, and is separated into a distinct upland and lowland area by an 80 m-high butte. We used groundwater discharge and groundwater ages derived from chlorofluorocarbon (CFC) concentration to calibrate a free-surface flow model simulating groundwater flow circulation. We found that groundwater flow was highly local (mean travel distance = 350 m), substantially smaller than the typical distance between neighboring streams (∼1 km), while CFC-based ages were quite old (mean = 40 years). Sensitivity analysis revealed that groundwater travel distances were not sensitive to geological parameters (i.e. arrangement of geological layers and permeability profile) within the constraints of the CFC age data. However, circulation was sensitive to topography in the lowland area where the water table was near the land surface, and to recharge rate in the upland area where water input modulated the free surface of the aquifer. We quantified these differences with a local groundwater ratio (rGW-LOCAL), defined as the mean groundwater travel distance divided by the mean of the reference surface distances (the distance water would have to travel across the surface of the digital elevation model). Lowland, rGW-LOCAL was near 1, indicating primarily topographical controls. Upland, rGW-LOCAL was 1.6, meaning the groundwater recharge area is almost twice as large as the topographically-defined catchment for any given point. The ratio rGW-LOCAL is sensitive to recharge conditions as well as topography and it could be used to compare controls on groundwater circulation within or between catchments.

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 local lymph node assay and skin sensitization testing.

PubMed

Kimber, Ian; Dearman, Rebecca J

2010-01-01

The mouse local lymph node assay (LLNA) is a method for the identification and characterization of skin sensitization hazards. In this context the method can be used both to identify contact allergens, and also determine the relative skin sensitizing potency as a basis for derivation of effective risk assessments.The assay is based on measurement of proliferative responses by draining lymph node cells induced following topical exposure of mice to test chemicals. Such responses are known to be causally and quantitatively associated with the acquisition of skin sensitization and therefore provide a relevant marker for characterization of contact allergic potential.The LLNA has been the subject of exhaustive evaluation and validation exercises and has been assigned Organization for Economic Cooperation and Development (OECD) test guideline 429. Herein we describe the conduct and interpretation of the LLNA.

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.

Estimating the effects of Cry1F Bt-maize pollen on non-target Lepidoptera using a mathematical model of exposure

PubMed Central

Perry, Joe N; Devos, Yann; Arpaia, Salvatore; Bartsch, Detlef; Ehlert, Christina; Gathmann, Achim; Hails, Rosemary S; Hendriksen, Niels B; Kiss, Jozsef; Messéan, Antoine; Mestdagh, Sylvie; Neemann, Gerd; Nuti, Marco; Sweet, Jeremy B; Tebbe, Christoph C

2012-01-01

In farmland biodiversity, a potential risk to the larvae of non-target Lepidoptera from genetically modified (GM) Bt-maize expressing insecticidal Cry1 proteins is the ingestion of harmful amounts of pollen deposited on their host plants. A previous mathematical model of exposure quantified this risk for Cry1Ab protein. We extend this model to quantify the risk for sensitive species exposed to pollen containing Cry1F protein from maize event 1507 and to provide recommendations for management to mitigate this risk. A 14-parameter mathematical model integrating small- and large-scale exposure was used to estimate the larval mortality of hypothetical species with a range of sensitivities, and under a range of simulated mitigation measures consisting of non-Bt maize strips of different widths placed around the field edge. The greatest source of variability in estimated mortality was species sensitivity. Before allowance for effects of large-scale exposure, with moderate within-crop host-plant density and with no mitigation, estimated mortality locally was <10% for species of average sensitivity. For the worst-case extreme sensitivity considered, estimated mortality locally was 99·6% with no mitigation, although this estimate was reduced to below 40% with mitigation of 24-m-wide strips of non-Bt maize. For highly sensitive species, a 12-m-wide strip reduced estimated local mortality under 1·5%, when within-crop host-plant density was zero. Allowance for large-scale exposure effects would reduce these estimates of local mortality by a highly variable amount, but typically of the order of 50-fold. Mitigation efficacy depended critically on assumed within-crop host-plant density; if this could be assumed negligible, then the estimated effect of mitigation would reduce local mortality below 1% even for very highly sensitive species. Synthesis and applications. Mitigation measures of risks of Bt-maize to sensitive larvae of non-target lepidopteran species can be effective, but depend on host-plant densities which are in turn affected by weed-management regimes. We discuss the relevance for management of maize events where cry1F is combined (stacked) with a herbicide-tolerance trait. This exemplifies how interactions between biota may occur when different traits are stacked irrespective of interactions between the proteins themselves and highlights the importance of accounting for crop management in the assessment of the ecological impact of GM plants. PMID:22496596

Comparative sensitivities of functional MRI sequences in detection of local recurrence of prostate carcinoma after radical prostatectomy or external-beam radiotherapy.

PubMed

Roy, Catherine; Foudi, Fatah; Charton, Jeanne; Jung, Michel; Lang, Hervé; Saussine, Christian; Jacqmin, Didier

2013-04-01

The aim of this retrospective study was to determine the respective accuracies of three types of functional MRI sequences-diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MRI, and 3D (1)H-MR spectroscopy (MRS)-in the depiction of local prostate cancer recurrence after two different initial therapy options. From a cohort of 83 patients with suspicion of local recurrence based on prostate-specific antigen (PSA) kinetics who were imaged on a 3-T MRI unit using an identical protocol including the three functional sequences with an endorectal coil, we selected 60 patients (group A, 28 patients who underwent radical prostatectomy; group B, 32 patients who underwent external-beam radiation) who had local recurrence ascertained on the basis of a transrectal ultrasound-guided biopsy results and a reduction in PSA level after salvage therapy. All patients presented with a local relapse. Sensitivity with T2-weighted MRI and 3D (1)H-MRS sequences was 57% and 53%, respectively, for group A and 71% and 78%, respectively, for group B. DCE-MRI alone showed a sensitivity of 100% and 96%, respectively, for groups A and B. DWI alone had a higher sensitivity for group B (96%) than for group A (71%). The combination of T2-weighted imaging plus DWI plus DCE-MRI provided a sensitivity as high as 100% in group B. The performance of functional imaging sequences for detecting recurrence is different after radical prostatectomy and external-beam radiotherapy. DCE-MRI is a valid and efficient tool to detect prostate cancer recurrence in radical prostatectomy as well as in external-beam radiotherapy. The combination of DCE-MRI and DWI is highly efficient after radiation therapy. Three-dimensional (1)H-MRS needs to be improved. Even though it is not accurate enough, T2-weighted imaging remains essential for the morphologic analysis of the area.

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.

Influence of local demography on asymptotic and transient dynamics of a yellow-bellied marmot metapopulation.

PubMed

Ozgul, Arpat; Oli, Madan K; Armitage, Kenneth B; Blumstein, Daniel T; Van Vuren, Dirk H

2009-04-01

Despite recent advances in biodemography and metapopulation ecology, we still have limited understanding of how local demographic parameters influence short- and long-term metapopulation dynamics. We used long-term data from 17 local populations, along with the recently developed methods of matrix metapopulation modeling and transient sensitivity analysis, to investigate the influence of local demography on long-term (asymptotic) versus short-term (transient) dynamics of a yellow-bellied marmot metapopulation in Colorado. Both long- and short-term dynamics depended primarily on a few colony sites and were highly sensitive to changes in demography at these sites, particularly in survival of reproductive adult females. Interestingly, the relative importance of sites differed between long- and short-term dynamics; the spatial structure and local population sizes, while insignificant for asymptotic dynamics, were influential on transient dynamics. However, considering the spatial structure was uninformative about the relative influence of local demography on metapopulation dynamics. The vital rates that were the most influential on local dynamics were also the most influential on both long- and short-term metapopulation dynamics. Our results show that an explicit consideration of local demography is essential for a complete understanding of the dynamics and persistence of spatially structured populations.

Statistical analysis of iron geochemical data suggests limited late Proterozoic oxygenation

NASA Astrophysics Data System (ADS)

Sperling, Erik A.; Wolock, Charles J.; Morgan, Alex S.; Gill, Benjamin C.; Kunzmann, Marcus; Halverson, Galen P.; MacDonald, Francis A.; Knoll, Andrew H.; Johnston, David T.

2015-07-01

Sedimentary rocks deposited across the Proterozoic-Phanerozoic transition record extreme climate fluctuations, a potential rise in atmospheric oxygen or re-organization of the seafloor redox landscape, and the initial diversification of animals. It is widely assumed that the inferred redox change facilitated the observed trends in biodiversity. Establishing this palaeoenvironmental context, however, requires that changes in marine redox structure be tracked by means of geochemical proxies and translated into estimates of atmospheric oxygen. Iron-based proxies are among the most effective tools for tracking the redox chemistry of ancient oceans. These proxies are inherently local, but have global implications when analysed collectively and statistically. Here we analyse about 4,700 iron-speciation measurements from shales 2,300 to 360 million years old. Our statistical analyses suggest that subsurface water masses in mid-Proterozoic oceans were predominantly anoxic and ferruginous (depleted in dissolved oxygen and iron-bearing), but with a tendency towards euxinia (sulfide-bearing) that is not observed in the Neoproterozoic era. Analyses further indicate that early animals did not experience appreciable benthic sulfide stress. Finally, unlike proxies based on redox-sensitive trace-metal abundances, iron geochemical data do not show a statistically significant change in oxygen content through the Ediacaran and Cambrian periods, sharply constraining the magnitude of the end-Proterozoic oxygen increase. Indeed, this re-analysis of trace-metal data is consistent with oxygenation continuing well into the Palaeozoic era. Therefore, if changing redox conditions facilitated animal diversification, it did so through a limited rise in oxygen past critical functional and ecological thresholds, as is seen in modern oxygen minimum zone benthic animal communities.

Attribution of floods in the Okavango basin, Southern Africa

NASA Astrophysics Data System (ADS)

Wolski, Piotr; Stone, Dáithí; Tadross, Mark; Wehner, Michael; Hewitson, Bruce

2014-04-01

In the charismatic wetlands of the Okavango Delta, Botswana, the annual floods of 2009-2011 reached magnitudes last seen 20-30 years ago, considerably affecting life of local populations and the economically important tourism industry. In this study, we analyse results from an attribution modelling system designed to examine how anthropogenic greenhouse gas emissions have contributed to weather and flood risk in our current climate. The system is based on comparison of real world climate and hydrological simulations with parallel counterfactual simulations of the climate and hydrological responses under conditions that might have been had human activities not emitted greenhouse gases. The analyses allow us to address the question of whether anthropogenic climate change contributed to increasing the risk of these high flood events in the Okavango system. Results show that the probability of occurrence of high floods during 2009-2011 in the current climate is likely lower than it would have been in a climate without anthropogenic greenhouse gases. This result is robust across the two climate models and various data processing procedures, although the exact figures for the associated decrease in risk differ. Results also differ between the three years examined, indicating that the “time-slice” method used here needs to be applied to multiple years in order to accurately estimate the contribution of emissions to current risk. Simple sensitivity analyses indicate that the reduction in flood risk is attributed to higher temperatures (and thus evaporation) in the current world, with little difference in the analysed domain's rainfall simulated in the two scenarios.

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 ).

FEAST: sensitive local alignment with multiple rates of evolution.

PubMed

Hudek, Alexander K; Brown, Daniel G

2011-01-01

We present a pairwise local aligner, FEAST, which uses two new techniques: a sensitive extension algorithm for identifying homologous subsequences, and a descriptive probabilistic alignment model. We also present a new procedure for training alignment parameters and apply it to the human and mouse genomes, producing a better parameter set for these sequences. Our extension algorithm identifies homologous subsequences by considering all evolutionary histories. It has higher maximum sensitivity than Viterbi extensions, and better balances specificity. We model alignments with several submodels, each with unique statistical properties, describing strongly similar and weakly similar regions of homologous DNA. Training parameters using two submodels produces superior alignments, even when we align with only the parameters from the weaker submodel. Our extension algorithm combined with our new parameter set achieves sensitivity 0.59 on synthetic tests. In contrast, LASTZ with default settings achieves sensitivity 0.35 with the same false positive rate. Using the weak submodel as parameters for LASTZ increases its sensitivity to 0.59 with high error. FEAST is available at http://monod.uwaterloo.ca/feast/.

The local lymph node assay in 2014.

PubMed

Basketter, David A; Gerberick, G Frank; Kimber, Ian

2014-01-01

Toxicology endeavors to predict the potential of materials to cause adverse health (and environmental) effects and to assess the risk(s) associated with exposure. For skin sensitizers, the local lymph node assay was the first method to be fully and independently validated, as well as the first to offer an objective end point with a quantitative measure of sensitizing potency (in addition to hazard identification). Fifteen years later, it serves as the primary standard for the development of in vitro/in chemico/in silico alternatives.

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 ...

Decentralisation and Language Policy: Local Municipalities' Role in Language Education Policies. Insights from Denmark and Estonia

ERIC Educational Resources Information Center

Siiner, Maarja

2014-01-01

The present article contributes to attempts to re-conceptualise the top-down perspective on language policy, by analysing the role of local and city governments' agency in language education policy making. Only few studies analyse the role of lower administrative levels in language policy, other than in implementation of governmental policies, why…

Global and Local Stress Analyses of McDonnell Douglas Stitched/RFI Composite Wing Stub Box

NASA Technical Reports Server (NTRS)

Wang, John T.

1996-01-01

This report contains results of structural analyses performed in support of the NASA structural testing of an all-composite stitched/RFI (resin film infusion) wing stub box. McDonnell Douglas Aerospace Company designed and fabricated the wing stub box. The analyses used a global/local approach. The global model contains the entire test article. It includes the all-composite stub box, a metallic load-transition box and a metallic wing-tip extension box. The two metallic boxes are connected to the inboard and outboard ends of the composite wing stub box, respectively. The load-transition box was attached to a steel and concrete vertical reaction structure and a load was applied at the tip of the extension box to bend the wing stub box upward. The local model contains an upper cover region surrounding three stringer runouts. In that region, a large nonlinear deformation was identified by the global analyses. A more detailed mesh was used for the local model to obtain more accurate analysis results near stringer runouts. Numerous analysis results such as deformed shapes, displacements at selected locations, and strains at critical locations are included in this report.

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.

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.

[Local GABA-ergic modulation of serotonergic neuron activity in the nucleus raphe magnus].

PubMed

Iniushkin, A N; Merkulova, N A; Orlova, A O; Iniushkina, E M

2009-07-01

In voltage-clamp experimental on slices of the rat brainstem the effects of 5-HT and GABA on serotonergic neurons of nucleus raphe magnus were investigated. Local applications of 5-HT induced an increase in IPCSs frequency and amplitude in 45% of serotonergic cells. The effect suppressed by the blocker of fast sodium channels tetradotoxin. Antagonist of GABA receptor gabazine blocked IPSCs in neurons both sensitive and non-sensitive to 5-HT action. Applications of GABA induced a membrane current (I(GABA)), which was completely blocked by gabazine. The data suggest self-control of the activity of serotonergic neurons in nucleus raphe magnus by negative feedback loop via local GABAergic interneurons.

Peptide Functionalized Gold Nanorods for the Sensitive Detection of a Cardiac Biomarker Using Plasmonic Paper Devices.

PubMed

Tadepalli, Sirimuvva; Kuang, Zhifeng; Jiang, Qisheng; Liu, Keng-Ku; Fisher, Marilee A; Morrissey, Jeremiah J; Kharasch, Evan D; Slocik, Joseph M; Naik, Rajesh R; Singamaneni, Srikanth

2015-11-10

The sensitivity of localized surface plasmon resonance (LSPR) of metal nanostructures to adsorbates lends itself to a powerful class of label-free biosensors. Optical properties of plasmonic nanostructures are dependent on the geometrical features and the local dielectric environment. The exponential decay of the sensitivity from the surface of the plasmonic nanotransducer calls for the careful consideration in its design with particular attention to the size of the recognition and analyte layers. In this study, we demonstrate that short peptides as biorecognition elements (BRE) compared to larger antibodies as target capture agents offer several advantages. Using a bioplasmonic paper device (BPD), we demonstrate the selective and sensitive detection of the cardiac biomarker troponin I (cTnI). The smaller sized peptide provides higher sensitivity and a lower detection limit using a BPD. Furthermore, the excellent shelf-life and thermal stability of peptide-based LSPR sensors, which precludes the need for special storage conditions, makes it ideal for use in resource-limited settings.

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

Opportunistic data locality for end user data analysis

NASA Astrophysics Data System (ADS)

Fischer, M.; Heidecker, C.; Kuehn, E.; Quast, G.; Giffels, M.; Schnepf, M.; Heiss, A.; Petzold, A.

2017-10-01

With the increasing data volume of LHC Run2, user analyses are evolving towards increasing data throughput. This evolution translates to higher requirements for efficiency and scalability of the underlying analysis infrastructure. We approach this issue with a new middleware to optimise data access: a layer of coordinated caches transparently provides data locality for high-throughput analyses. We demonstrated the feasibility of this approach with a prototype used for analyses of the CMS working groups at KIT. In this paper, we present our experience both with the approach in general, and our prototype in specific.

Passive-quadrature demodulated localized-Michelson fiber-optic strain sensor embedded in composite materials

NASA Astrophysics Data System (ADS)

Valis, Tomas; Tapanes, Edward; Liu, Kexing; Measures, Raymond M.

1991-04-01

A strain sensor embedded in composite materials that is intrinsic, all fiber, local, and phase demodulated is described. It is the combination of these necessary elements that represents an advance in the state of the art. Sensor localization is achieved by using a pair of mirror-ended optical fibers of different lengths that are mechanically coupled up until the desired gauge length for common-mode suppression has been reached. This fiber-optic sensor has been embedded in both thermoset (Kevlar/epoxy and graphite/epoxy) and thermoplastic (graphite/PEEK) composite materials in order to make local strain measurements at the lamina level. The all-fiber system uses a 3 x 3 coupler for phase demodulation. Parameters such as strain sensitivity, transverse strain sensitivity, failure strain, and frequency response are discussed, along with applications.

Effect of local void morphology on the reaction initiation mechanism in the case of pressed HMX

NASA Astrophysics Data System (ADS)

Roy, Sidhartha; Rai, Nirmal; Udaykumar, H. S.

2017-06-01

The microstructural characteristics of pressed HMX has a significant effect on its sensitivity under shock loading. The microstructure of pressed HMX contains voids of various orientation and aspect ratio. Subject to shock loading, these voids can collapse forming hotspots and initiate chemical reaction. This work shows how the ignition and growth of chemical reaction is dependent on the local microstructural features of the voids. Morphological quantities like size, aspect ratio and orientations are extracted from the real microstructural images of Class III and Class V pressed HMX. These morphological quantities are correlated with the ignition and growth rates of the chemical reaction. The dependency of the sensitivity of a given HMX sample on the local morphological features shows that these local features can create a mocroscale physical response.

Comparison of pelvic phased-array versus endorectal coil magnetic resonance imaging at 3 Tesla for local staging of prostate cancer.

PubMed

Kim, Bum Soo; Kim, Tae-Hwan; Kwon, Tae Gyun; Yoo, Eun Sang

2012-05-01

Several studies have demonstrated the superiority of endorectal coil magnetic resonance imaging (MRI) over pelvic phased-array coil MRI at 1.5 Tesla for local staging of prostate cancer. However, few have studied which evaluation is more accurate at 3 Tesla MRI. In this study, we compared the accuracy of local staging of prostate cancer using pelvic phased-array coil or endorectal coil MRI at 3 Tesla. Between January 2005 and May 2010, 151 patients underwent radical prostatectomy. All patients were evaluated with either pelvic phased-array coil or endorectal coil prostate MRI prior to surgery (63 endorectal coils and 88 pelvic phased-array coils). Tumor stage based on MRI was compared with pathologic stage. We calculated the specificity, sensitivity and accuracy of each group in the evaluation of extracapsular extension and seminal vesicle invasion. Both endorectal coil and pelvic phased-array coil MRI achieved high specificity, low sensitivity and moderate accuracy for the detection of extracapsular extension and seminal vesicle invasion. There were statistically no differences in specificity, sensitivity and accuracy between the two groups. Overall staging accuracy, sensitivity and specificity were not significantly different between endorectal coil and pelvic phased-array coil MRI.

ALS3 encodes a phloem-localized ABC transporter-like protein that is required for aluminum tolerance in Arabidopsis.

PubMed

Larsen, Paul B; Geisler, Matt J B; Jones, Carol A; Williams, Kelly M; Cancel, Jesse D

2005-02-01

Aluminum (Al) toxicity in acid soils is a worldwide agricultural problem that severely limits crop productivity through inhibition of root growth. Previously, Arabidopsis mutants with increased Al sensitivity were isolated in order to identify genes important for Al tolerance in plants. One mutant, als3, exhibited extreme root growth inhibition in the presence of Al, suggesting that this mutation negatively impacts a gene required for Al tolerance. Map-based cloning of the als3-1 mutation resulted in the isolation of a novel gene that encodes a previously undescribed ABC transporter-like protein, which is highly homologous to a putative bacterial metal resistance protein, ybbM. Northern analysis for ALS3 expression revealed that it is found in all organs examined, which is consistent with the global nature of Al sensitivity displayed by als3, and that expression increases in roots following Al treatment. Based on GUS fusion and in situ hybridization analyses, ALS3 is primarily expressed in leaf hydathodes and the phloem throughout the plant, along with the root cortex following Al treatment. Immunolocalization indicates that ALS3 predominantly accumulates in the plasma membrane of cells that express ALS3. From our results, it appears that ALS3 encodes an ABC transporter-like protein that is required for Al resistance/tolerance and may function to redistribute accumulated Al away from sensitive tissues in order to protect the growing root from the toxic effects of Al.

Mapping feature-sensitivity and attentional modulation in human auditory cortex with functional magnetic resonance imaging

PubMed Central

Paltoglou, Aspasia E; Sumner, Christian J; Hall, Deborah A

2011-01-01

Feature-specific enhancement refers to the process by which selectively attending to a particular stimulus feature specifically increases the response in the same region of the brain that codes that stimulus property. Whereas there are many demonstrations of this mechanism in the visual system, the evidence is less clear in the auditory system. The present functional magnetic resonance imaging (fMRI) study examined this process for two complex sound features, namely frequency modulation (FM) and spatial motion. The experimental design enabled us to investigate whether selectively attending to FM and spatial motion enhanced activity in those auditory cortical areas that were sensitive to the two features. To control for attentional effort, the difficulty of the target-detection tasks was matched as closely as possible within listeners. Locations of FM-related and motion-related activation were broadly compatible with previous research. The results also confirmed a general enhancement across the auditory cortex when either feature was being attended to, as compared with passive listening. The feature-specific effects of selective attention revealed the novel finding of enhancement for the nonspatial (FM) feature, but not for the spatial (motion) feature. However, attention to spatial features also recruited several areas outside the auditory cortex. Further analyses led us to conclude that feature-specific effects of selective attention are not statistically robust, and appear to be sensitive to the choice of fMRI experimental design and localizer contrast. PMID:21447093

The meaning of diagnostic test results: a spreadsheet for swift data analysis.

PubMed

Maceneaney, P M; Malone, D E

2000-03-01

To design a spreadsheet program to: (a) analyse rapidly diagnostic test result data produced in local research or reported in the literature; (b) correct reported predictive values for disease prevalence in any population; (c) estimate the post-test probability of disease in individual patients. Microsoft Excel(TM)was used. Section A: a contingency (2 x 2) table was incorporated into the spreadsheet. Formulae for standard calculations [sample size, disease prevalence, sensitivity and specificity with 95% confidence intervals, predictive values and likelihood ratios (LRs)] were linked to this table. The results change automatically when the data in the true or false negative and positive cells are changed. Section B: this estimates predictive values in any population, compensating for altered disease prevalence. Sections C-F: Bayes' theorem was incorporated to generate individual post-test probabilities. The spreadsheet generates 95% confidence intervals, LRs and a table and graph of conditional probabilities once the sensitivity and specificity of the test are entered. The latter shows the expected post-test probability of disease for any pre-test probability when a test of known sensitivity and specificity is positive or negative. This spreadsheet can be used on desktop and palmtop computers. The MS Excel(TM)version can be downloaded via the Internet from the URL ftp://radiography.com/pub/Rad-data99.xls A spreadsheet is useful for contingency table data analysis and assessment of the clinical meaning of diagnostic test results. Copyright 2000 The Royal College of Radiologists.

Defining ADHD symptom persistence in adulthood: optimizing sensitivity and specificity.

PubMed

Sibley, Margaret H; Swanson, James M; Arnold, L Eugene; Hechtman, Lily T; Owens, Elizabeth B; Stehli, Annamarie; Abikoff, Howard; Hinshaw, Stephen P; Molina, Brooke S G; Mitchell, John T; Jensen, Peter S; Howard, Andrea L; Lakes, Kimberley D; Pelham, William E

2017-06-01

Longitudinal studies of children diagnosed with ADHD report widely ranging ADHD persistence rates in adulthood (5-75%). This study documents how information source (parent vs. self-report), method (rating scale vs. interview), and symptom threshold (DSM vs. norm-based) influence reported ADHD persistence rates in adulthood. Five hundred seventy-nine children were diagnosed with DSM-IV ADHD-Combined Type at baseline (ages 7.0-9.9 years) 289 classmates served as a local normative comparison group (LNCG), 476 and 241 of whom respectively were evaluated in adulthood (Mean Age = 24.7). Parent and self-reports of symptoms and impairment on rating scales and structured interviews were used to investigate ADHD persistence in adulthood. Persistence rates were higher when using parent rather than self-reports, structured interviews rather than rating scales (for self-report but not parent report), and a norm-based (NB) threshold of 4 symptoms rather than DSM criteria. Receiver-Operating Characteristics (ROC) analyses revealed that sensitivity and specificity were optimized by combining parent and self-reports on a rating scale and applying a NB threshold. The interview format optimizes young adult self-reporting when parent reports are not available. However, the combination of parent and self-reports from rating scales, using an 'or' rule and a NB threshold optimized the balance between sensitivity and specificity. With this definition, 60% of the ADHD group demonstrated symptom persistence and 41% met both symptom and impairment criteria in adulthood. © 2016 Association for Child and Adolescent Mental Health.

Rural Nevada and climate change: vulnerability, beliefs, and risk perception.

PubMed

Safi, Ahmad Saleh; Smith, William James; Liu, Zhnongwei

2012-06-01

In this article, we present the results of a study investigating the influence of vulnerability to climate change as a function of physical vulnerability, sensitivity, and adaptive capacity on climate change risk perception. In 2008/2009, we surveyed Nevada ranchers and farmers to assess their climate change-related beliefs, and risk perceptions, political orientations, and socioeconomic characteristics. Ranchers' and farmers' sensitivity to climate change was measured through estimating the proportion of their household income originating from highly scarce water-dependent agriculture to the total income. Adaptive capacity was measured as a combination of the Social Status Index and the Poverty Index. Utilizing water availability and use, and population distribution GIS databases; we assessed water resource vulnerability in Nevada by zip code as an indicator of physical vulnerability to climate change. We performed correlation tests and multiple regression analyses to examine the impact of vulnerability and its three distinct components on risk perception. We find that vulnerability is not a significant determinant of risk perception. Physical vulnerability alone also does not impact risk perception. Both sensitivity and adaptive capacity increase risk perception. While age is not a significant determinant of it, gender plays an important role in shaping risk perception. Yet, general beliefs such as political orientations and climate change-specific beliefs such as believing in the anthropogenic causes of climate change and connecting the locally observed impacts (in this case drought) to climate change are the most prominent determinants of risk perception. © 2012 Society for Risk Analysis.

Cross-cultural difference and validation of the Chinese version of Montreal Cognitive Assessment in older adults residing in Eastern China: preliminary findings.

PubMed

Hu, Jian-bo; Zhou, Wei-hua; Hu, Shao-hua; Huang, Man-li; Wei, Ning; Qi, Hong-li; Huang, Jin-wen; Xu, Yi

2013-01-01

To evaluate the psychometric properties of the Chinese Montreal Cognitive Assessment (MoCA-C) and assess cross-cultural differences in a community-based cohort residing in the Eastern China. The study included 72 patients with Alzheimer's disease (AD), 84 patients with mild cognitive impairment (MCI) and 146 cognitively normal controls. Sensitivities and specificities were calculated using the recommended cut-off scores. Receiver operator characteristic (ROC) curve analyses were performed to determine optimal sensitivity and specificity. Criterion validity, inter-rater, test-retest reliability and internal consistencies of the MoCA-C were examined, and clinical observations made. The influence of age, education level and gender on MoCA score was examined. Using the recommended cut-off score of 26, the area under the ROC (AUC) for predicting MCI groups using the MoCA-C was 0.930 (95%CI: 0.894; 0.965). The MoCA-C demonstrated 92% sensitivity and 85% specificity in screening for MCI. Cultural differences from the original MoCA affected the test response rate. The MoCA-C appears to have utility as a cognitive screen for early detection of AD and for MCI and warrants further investigation regarding its applicability in primary care settings in elderly Chinese people. It will be necessary to revise the contents of the questionnaire to account for by local characteristics. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Efficacy of preoperative ibuprofen and meloxicam on the success rate of inferior alveolar nerve block for teeth with irreversible pulpitis.

PubMed

Shantiaee, Yazdan; Javaheri, Sahar; Movahhedian, Amir; Eslami, Sarah; Dianat, Omid

2017-04-01

The purpose of this study was to determine whether premedication with ibuprofen or meloxicam increases the success rate of anaesthesia in teeth with irreversible pulpitis. In this parallel, double-blind clinical trial, 92 patients diagnosed with irreversible pulpitis were randomly divided into four groups of 23 patients. The first group (the no-premedication group) received no premedication, the second group (the meloxicam group) received 7.5 mg of meloxicam, the third group (the ibuprofen group) received 600 mg of ibuprofen, and the fourth group (the placebo group) received placebo 1 hour before intervention. Before taking the medication, electrical pulp testing (EPT) and the Heft-Parker visual analogue scale (VAS) were used to evaluate sensitivity and pain at baseline. Then, local anaesthesia was injected, and after 15 minutes, EPT was used again to evaluate tooth sensitivity. The pain during access preparation was also recorded using the Heft-Parker VAS. Ninety-two patients were analysed. The success rates of local anaesthesia were 21.7%, 34.8%, 78.3% and 73.9% in the no-premedication, placebo, ibuprofen and meloxicam groups, respectively, according to the EPT values. Considering the Heft-Parker VAS values, no premedication gave a 21.7% success rate, placebo gave a 34.8% success rate, ibuprofen gave an 82.6% success rate and meloxicam gave a 65.2% success rate. The ibuprofen and meloxicam groups showed significantly better results than the placebo and no-premedication groups (P < 0.001). However, the difference between meloxicam and ibuprofen groups was not significant. Premedication with meloxicam and ibuprofen significantly increased the success rates of inferior alveolar nerve block anaesthesia for teeth with irreversible pulpitis; however, neither drug provided profound anaesthesia. © 2016 FDI World Dental Federation.

Primary treatments for clinically localized prostate cancer: a comprehensive lifetime cost-utility analysis

PubMed Central

Cooperberg, Matthew R.; Ramakrishna, Naren R.; Duff, Steven B.; Hughes, Kathleen E.; Sadownik, Sara; Smith, Joseph A.; Tewari, Ashutosh K.

2012-01-01

Objectives To characterize the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (dose-escalated 3-dimensional conformal radiation, intensity-modulated radiation, brachytherapy, or combination), using a comprehensive, lifetime decision analytic model. Patients and Methods A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes following primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. Patients could experience remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the U.S. payer perspective, with incorporation of patient costs in a sensitivity analysis. Results Differences in quality-adjusted life years across modalities were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6 to 10.5 for intermediate-risk patients, and 7.8 to 9.3 for high-risk patients. There were no statistically significant differences among surgical modalities, which tended to be more effective than radiation modalities, with the exception of combination external beam + brachytherapy for high-risk disease. Radiation modalities were consistently more expensive than surgical modalities; costs ranged from $19,901 (robot-assisted prostatectomy for low-risk disease) to $50,276 (combination radiation for high-risk disease). These findings were robust to an extensive set of sensitivity analyses. Conclusions Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives. These findings may inform future policy discussions regarding strategies to improve efficiency of treatment selection for localized prostate cancer. PMID:23279038

An ABA-regulated and Golgi-localized protein phosphatase controls water loss during leaf senescence in Arabidopsis.

PubMed

Zhang, Kewei; Xia, Xiuying; Zhang, Yanyan; Gan, Su-Sheng

2012-02-01

It is known that a senescing leaf loses water faster than a non-senescing leaf and that ABA has an important role in promoting leaf senescence. However, questions such as why water loss is faster, how water loss is regulated, and how ABA functions in leaf senescence are not well understood. Here we report on the identification and functional analysis of a leaf senescence associated gene called SAG113. The RNA blot and GUS reporter analyses all show that SAG113 is expressed in senescing leaves and is induced by ABA in Arabidopsis. The SAG113 expression levels are significantly reduced in aba2 and abi4 mutants. A GFP fusion protein analysis revealed that SAG113 protein is localized in the Golgi apparatus. SAG113 encodes a protein phosphatase that belongs to the PP2C family and is able to functionally complement a yeast PP2C-deficient mutant TM126 (ptc1Δ). Leaf senescence is delayed in the SAG113 knockout mutant compared with that in the wild type, stomatal movement in the senescing leaves of SAG113 knockouts is more sensitive to ABA than that of the wild type, and the rate of water loss in senescing leaves of SAG113 knockouts is significantly reduced. In contrast, inducible over-expression of SAG113 results in a lower sensitivity of stomatal movement to ABA treatment, more rapid water loss, and precocious leaf senescence. No other aspects of growth and development, including seed germination, were observed. These findings suggest that SAG113, a negative regulator of ABA signal transduction, is specifically involved in the control of water loss during leaf senescence. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

Impact of Early and Late Visual Deprivation on the Structure of the Corpus Callosum: A Study Combining Thickness Profile with Surface Tensor-Based Morphometry.

PubMed

Shi, Jie; Collignon, Olivier; Xu, Liang; Wang, Gang; Kang, Yue; Leporé, Franco; Lao, Yi; Joshi, Anand A; Leporé, Natasha; Wang, Yalin

2015-07-01

Blindness represents a unique model to study how visual experience may shape the development of brain organization. Exploring how the structure of the corpus callosum (CC) reorganizes ensuing visual deprivation is of particular interest due to its important functional implication in vision (e.g., via the splenium of the CC). Moreover, comparing early versus late visually deprived individuals has the potential to unravel the existence of a sensitive period for reshaping the CC structure. Here, we develop a novel framework to capture a complete set of shape differences in the CC between congenitally blind (CB), late blind (LB) and sighted control (SC) groups. The CCs were manually segmented from T1-weighted brain MRI and modeled by 3D tetrahedral meshes. We statistically compared the combination of local area and thickness at each point between subject groups. Differences in area are found using surface tensor-based morphometry; thickness is estimated by tracing the streamlines in the volumetric harmonic field. Group differences were assessed on this combined measure using Hotelling's T(2) test. Interestingly, we observed that the total callosal volume did not differ between the groups. However, our fine-grained analysis reveals significant differences mostly localized around the splenium areas between both blind groups and the sighted group (general effects of blindness) and, importantly, specific dissimilarities between the LB and CB groups, illustrating the existence of a sensitive period for reorganization. The new multivariate statistics also gave better effect sizes for detecting morphometric differences, relative to other statistics. They may boost statistical power for CC morphometric analyses.

Detection of hepatocellular carcinoma in transgenic mice by Gd-DTPA- and rhodamine 123-conjugated human serum albumin nanoparticles in T1 magnetic resonance imaging.

PubMed

Watcharin, Waralee; Schmithals, Christian; Pleli, Thomas; Köberle, Verena; Korkusuz, Hüdayi; Hübner, Frank; Waidmann, Oliver; Zeuzem, Stefan; Korf, Horst-Werner; Terfort, Andreas; Gelperina, Svetlana; Vogl, Thomas J; Kreuter, Jörg; Piiper, Albrecht

2015-02-10

Nanoparticle (NP)-based contrast agents that enable high resolution anatomic T1-weighted magnetic resonance imaging (MRI) offer the prospect of improving differential diagnosis of liver tumors such as hepatocellular carcinoma (HCC). In the present study, we investigated the possibility of employing novel non-toxic human serum albumin nanoparticles conjugated with Gd-DTPA and rhodamine 123 (Gd-Rho-HSA-NPs) for the detection of HCC by T1-weighted MRI. In addition, the influence of surface coating of the NPs with poloxamine 908, which alters the absorptive behavior of NPs and changes their distribution between the liver and tumor was examined. MRI of transgenic mice with endogenously formed HCCs following intravenous injection of Gd-Rho-HSA-NPs revealed a strong negative contrast of the tumors. Contrasting of the HCCs by NP-enhanced MRI required less Gd as compared to gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid-enhanced MRI, which currently provides the most sensitive detection of HCC in patients. Immunohistochemical analyses revealed that the Gd-Rho-HSA-NPs were localized to macrophages, which were - similar to HCC in patients - fewer in number in HCC as compared to the liver tissue, which is in agreement with the negative contrasting of HCC in Gd-Rho-HSA-NP-enhanced MRI. Poloxamine-coated NPs showed lower accumulation in the tumor macrophages and caused a longer lasting enhancement of the MRI signal. These data indicate that Gd-Rho-HSA-NPs enable sensitive detection of HCC by T1-weighted MRI in mice with endogenous HCC through their uptake by macrophages. Poloxamine coating of the NPs delayed the tumor localization of the NPs. Copyright © 2014 Elsevier B.V. All rights reserved.

IMPACT OF EARLY AND LATE VISUAL DEPRIVATION ON THE STRUCTURE OF THE CORPUS CALLOSUM: A STUDY COMBINING THICKNESS PROFILE WITH SURFACE TENSOR-BASED MORPHOMETRY

PubMed Central

Shi, Jie; Collignon, Olivier; Xu, Liang; Wang, Gang; Kang, Yue; Leporé, Franco; Lao, Yi; Joshi, Anand A.

2015-01-01

Blindness represents a unique model to study how visual experience may shape the development of brain organization. Exploring how the structure of the corpus callosum (CC) reorganizes ensuing visual deprivation is of particular interest due to its important functional implication in vision (e.g. via the splenium of the CC). Moreover, comparing early versus late visually deprived individuals has the potential to unravel the existence of a sensitive period for reshaping the CC structure. Here, we develop a novel framework to capture a complete set of shape differences in the CC between congenitally blind (CB), late blind (LB) and sighted control (SC) groups. The CCs were manually segmented from T1-weighted brain MRI and modeled by 3D tetrahedral meshes. We statistically compared the combination of local area and thickness at each point between subject groups. Differences in area are found using surface tensor-based morphometry; thickness is estimated by tracing the streamlines in the volumetric harmonic field. Group differences were assessed on this combined measure using Hotelling’s T2 test. Interestingly, we observed that the total callosal volume did not differ between the groups. However, our fine-grained analysis reveals significant differences mostly localized around the splenium areas between both blind groups and the sighted group (general effects of blindness) and, importantly, specific dissimilarities between the LB and CB groups, illustrating the existence of a sensitive period for reorganization. The new multivariate statistics also gave better effect sizes for detecting morphometric differences, relative to other statistics. They may boost statistical power for CC morphometric analyses. PMID:25649876

The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1

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

Kulebyakin, Konstantin; Penkov, Dmitry; IFOM – the FIRC Institute of Molecular Oncology, Via Adamello 16, Milan, 20139

Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to searchmore » new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. - Highlights: • A novel model of liver-specific Prep1 knockout is established. • Ablation of Prep1 in hepatocytes increases insulin sensitivity. • Prep1 controls hepatic insulin sensitivity by regulating localization of FOXO1. • Prep1 regulates localization of FOXO1 via Wnt/β-catenin signaling pathway.« less

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.

Detecting activity-evoked pH changes in human brain

PubMed Central

Magnotta, Vincent A.; Heo, Hye-Young; Dlouhy, Brian J.; Dahdaleh, Nader S.; Follmer, Robin L.; Thedens, Daniel R.; Welsh, Michael J.; Wemmie, John A.

2012-01-01

Localized pH changes have been suggested to occur in the brain during normal function. However, the existence of such pH changes has also been questioned. Lack of methods for noninvasively measuring pH with high spatial and temporal resolution has limited insight into this issue. Here we report that a magnetic resonance imaging (MRI) strategy, T1 relaxation in the rotating frame (T1ρ), is sufficiently sensitive to detect widespread pH changes in the mouse and human brain evoked by systemically manipulating carbon dioxide or bicarbonate. Moreover, T1ρ detected a localized acidosis in the human visual cortex induced by a flashing checkerboard. Lactate measurements and pH-sensitive 31P spectroscopy at the same site also identified a localized acidosis. Consistent with the established role for pH in blood flow recruitment, T1ρ correlated with blood oxygenation level-dependent contrast commonly used in functional MRI. However, T1ρ was not directly sensitive to blood oxygen content. These observations indicate that localized pH fluctuations occur in the human brain during normal function. Furthermore, they suggest a unique functional imaging strategy based on pH that is independent of traditional functional MRI contrast mechanisms. PMID:22566645

Planning for subacute care: predicting demand using acute activity data.

PubMed

Green, Janette P; McNamee, Jennifer P; Kobel, Conrad; Seraji, Md Habibur R; Lawrence, Suanne J

2016-01-01

Objective The aim of the present study was to develop a robust model that uses the concept of 'rehabilitation-sensitive' Diagnosis Related Groups (DRGs) in predicting demand for rehabilitation and geriatric evaluation and management (GEM) care following acute in-patient episodes provided in Australian hospitals. Methods The model was developed using statistical analyses of national datasets, informed by a panel of expert clinicians and jurisdictional advice. Logistic regression analysis was undertaken using acute in-patient data, published national hospital statistics and data from the Australasian Rehabilitation Outcomes Centre. Results The predictive model comprises tables of probabilities that patients will require rehabilitation or GEM care after an acute episode, with columns defined by age group and rows defined by grouped Australian Refined (AR)-DRGs. Conclusions The existing concept of rehabilitation-sensitive DRGs was revised and extended. When applied to national data, the model provided a conservative estimate of 83% of the activity actually provided. An example demonstrates the application of the model for service planning. What is known about the topic? Health service planning is core business for jurisdictions and local areas. With populations ageing and an acknowledgement of the underservicing of subacute care, it is timely to find improved methods of estimating demand for this type of care. Traditionally, age-sex standardised utilisation rates for individual DRGs have been applied to Australian Bureau of Statistics (ABS) population projections to predict the future need for subacute services. Improved predictions became possible when some AR-DRGs were designated 'rehabilitation-sensitive'. This improved methodology has been used in several Australian jurisdictions. What does this paper add? This paper presents a new tool, or model, to predict demand for rehabilitation and GEM services based on in-patient acute activity. In this model, the methodology based on rehabilitation-sensitive AR-DRGs has been extended by updating them to AR-DRG Version 7.0, quantifying the level of 'sensitivity' and incorporating the patient's age to improve the prediction of demand for subacute services. What are the implications for practitioners? The predictive model takes the form of tables of probabilities that patients will require rehabilitation or GEM care after an acute episode and can be applied to acute in-patient administrative datasets in any Australian jurisdiction or local area. The use of patient-level characteristics will enable service planners to improve their forecasting of demand for these services. Clinicians and jurisdictional representatives consulted during the project regarded the model favourably and believed that it was an improvement on currently available methods.

Consequences of acid strength for isomerization and elimination catalysis on solid acids.

PubMed

Macht, Josef; Carr, Robert T; Iglesia, Enrique

2009-05-13

We address here the manner in which acid catalysis senses the strength of solid acids. Acid strengths for Keggin polyoxometalate (POM) clusters and zeolites, chosen because of their accurately known structures, are described rigorously by their deprotonation energies (DPE). Mechanistic interpretations of the measured dynamics of alkane isomerization and alkanol dehydration are used to obtain rate and equilibrium constants and energies for intermediates and transition states and to relate them to acid strength. n-Hexane isomerization rates were limited by isomerization of alkoxide intermediates on bifunctional metal-acid mixtures designed to maintain alkane-alkene equilibrium. Isomerization rate constants were normalized by the number of accessible protons, measured by titration with 2,6-di-tert-butylpyridine during catalysis. Equilibrium constants for alkoxides formed by protonation of n-hexene increased slightly with deprotonation energies (DPE), while isomerization rate constants decreased and activation barriers increased with increasing DPE, as also shown for alkanol dehydration reactions. These trends are consistent with thermochemical analyses of the transition states involved in isomerization and elimination steps. For all reactions, barriers increased by less than the concomitant increase in DPE upon changes in composition, because electrostatic stabilization of ion-pairs at the relevant transition states becomes more effective for weaker acids, as a result of their higher charge density at the anionic conjugate base. Alkoxide isomerization barriers were more sensitive to DPE than for elimination from H-bonded alkanols, the step that limits 2-butanol and 1-butanol dehydration rates; the latter two reactions showed similar DPE sensitivities, despite significant differences in their rates and activation barriers, indicating that slower reactions are not necessarily more sensitive to acid strength, but instead reflect the involvement of more unstable organic cations at their transition states. These compensating effects from electrostatic stabilization depend on how similar the charge density in these organic cations is to that in the proton removed. Cations with more localized charge favor strong electrostatic interactions with anions and form more stable ionic structures than do cations with more diffuse charges. Ion-pairs at elimination transition states contain cations with higher local charge density at the sp(2) carbon than for isomerization transition states; as a result, these ion-pairs recover a larger fraction of the deprotonation energy, and, consequently, their reactions become less sensitive to acid strength. These concepts lead us to conclude that the energetic difficulty of a catalytic reaction, imposed by gas-phase reactant proton affinities in transition state analogues, does not determine its sensitivity to the acid strength of solid catalysts.

Imaging work-up for screening of paraganglioma and pheochromocytoma in SDHx mutation carriers: a multicenter prospective study from the PGL.EVA Investigators.

PubMed

Gimenez-Roqueplo, Anne-Paule; Caumont-Prim, Aurore; Houzard, Claire; Hignette, Chantal; Hernigou, Anne; Halimi, Philippe; Niccoli, Patricia; Leboulleux, Sophie; Amar, Laurence; Borson-Chazot, Françoise; Cardot-Bauters, Catherine; Delemer, Brigitte; Chabolle, Frédéric; Coupier, Isabelle; Libé, Rossella; Peitzsch, Mirko; Peyrard, Séverine; Tenenbaum, Florence; Plouin, Pierre-François; Chatellier, Gilles; Rohmer, Vincent

2013-01-01

Recommendations have not been established concerning imaging to screen SDHx mutation carriers for paraganglioma and pheochromocytoma. Our objective was to compare the performance of gadolinium-enhanced magnetic resonance angiography, contrast-enhanced computed tomography, and [(123)I]metaiodo-benzylguanidine and somatostatin receptor scintigraphies for detecting head and neck and thoracic-abdominal-pelvic paragangliomas in SDHx mutation carriers. We conducted a prospective, multicenter study from June 2005 to December 2009 at 23 French medical centers. A total of 238 index cases or relatives carrying mutations in SDHD, SDHB, or SDHC genes were included. Images obtained by each technique were analyzed blind, without knowledge of results from other tests, first in each local center and then centrally. We evaluated sensitivity, specificity, and likelihood ratios for individual and combinations of tests, the gold standard being the consensus of an expert committee. Two hundred two tumors were diagnosed in 96 subjects. At local assessment, the sensitivity of anatomical imaging for detecting all tumors was higher (85.7%) than that of both scintigraphic techniques (42.7% for [(123)I]metaiodo-benzylguanidine and 69.5% for somatostatin receptor scintigraphy), except for thoracic localizations where somatostatin receptor scintigraphy was more sensitive (61.5 vs. 46.2% for anatomical imaging and 30.8% for [(123)I]metaiodo-benzylguanidine scintigraphy). The best diagnostic performance during local assessment was obtained by combining anatomical imaging tests and somatostatin receptor scintigraphy (sensitivity 91.7%). Central assessment significantly increased the sensitivity (98.6%) of tests in combination. In routine practice, the imaging work-up for screening SDHx mutation carriers should include thoraco-abdomino-pelvic computed tomography, head and neck magnetic angiography, and somatostatin receptor scintigraphy. Expert centralized image assessment is recommended.

Histidine residues in the Na+-coupled ascorbic acid transporter-2 (SVCT2) are central regulators of SVCT2 function, modulating pH sensitivity, transporter kinetics, Na+ cooperativity, conformational stability, and subcellular localization.

PubMed

Ormazabal, Valeska; Zuñiga, Felipe A; Escobar, Elizabeth; Aylwin, Carlos; Salas-Burgos, Alexis; Godoy, Alejandro; Reyes, Alejandro M; Vera, Juan Carlos; Rivas, Coralia I

2010-11-19

Na(+)-coupled ascorbic acid transporter-2 (SVCT2) activity is impaired at acid pH, but little is known about the molecular determinants that define the transporter pH sensitivity. SVCT2 contains six histidine residues in its primary sequence, three of which are exofacial in the transporter secondary structure model. We used site-directed mutagenesis and treatment with diethylpyrocarbonate to identify histidine residues responsible for SVCT2 pH sensitivity. We conclude that five histidine residues, His(109), His(203), His(206), His(269), and His(413), are central regulators of SVCT2 function, participating to different degrees in modulating pH sensitivity, transporter kinetics, Na(+) cooperativity, conformational stability, and subcellular localization. Our results are compatible with a model in which (i) a single exofacial histidine residue, His(413), localized in the exofacial loop IV that connects transmembrane helices VII-VIII defines the pH sensitivity of SVCT2 through a mechanism involving a marked attenuation of the activation by Na(+) and loss of Na(+) cooperativity, which leads to a decreased V(max) without altering the transport K(m); (ii) exofacial histidine residues His(203), His(206), and His(413) may be involved in maintaining a functional interaction between exofacial loops II and IV and influence the general folding of the transporter; (iii) histidines 203, 206, 269, and 413 affect the transporter kinetics by modulating the apparent transport K(m); and (iv) histidine 109, localized at the center of transmembrane helix I, might be fundamental for the interaction of SVCT2 with the transported substrate ascorbic acid. Thus, histidine residues are central regulators of SVCT2 function.

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.

Localized Surface Plasmon Resonance Biosensing: Current Challenges and Approaches

PubMed Central

Unser, Sarah; Bruzas, Ian; He, Jie; Sagle, Laura

2015-01-01

Localized surface plasmon resonance (LSPR) has emerged as a leader among label-free biosensing techniques in that it offers sensitive, robust, and facile detection. Traditional LSPR-based biosensing utilizes the sensitivity of the plasmon frequency to changes in local index of refraction at the nanoparticle surface. Although surface plasmon resonance technologies are now widely used to measure biomolecular interactions, several challenges remain. In this article, we have categorized these challenges into four categories: improving sensitivity and limit of detection, selectivity in complex biological solutions, sensitive detection of membrane-associated species, and the adaptation of sensing elements for point-of-care diagnostic devices. The first section of this article will involve a conceptual discussion of surface plasmon resonance and the factors affecting changes in optical signal detected. The following sections will discuss applications of LSPR biosensing with an emphasis on recent advances and approaches to overcome the four limitations mentioned above. First, improvements in limit of detection through various amplification strategies will be highlighted. The second section will involve advances to improve selectivity in complex media through self-assembled monolayers, “plasmon ruler” devices involving plasmonic coupling, and shape complementarity on the nanoparticle surface. The following section will describe various LSPR platforms designed for the sensitive detection of membrane-associated species. Finally, recent advances towards multiplexed and microfluidic LSPR-based devices for inexpensive, rapid, point-of-care diagnostics will be discussed. PMID:26147727

Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA

NASA Astrophysics Data System (ADS)

Abbott, B. P.; Abbott, R.; Abbott, T. D.; Abernathy, M. R.; Acernese, F.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Aiello, L.; Ain, A.; Ajith, P.; Akutsu, T.; Allen, B.; Allocca, A.; Altin, P. A.; Ananyeva, A.; Anderson, S. B.; Anderson, W. G.; Ando, M.; Appert, S.; Arai, K.; Araya, A.; Araya, M. C.; Areeda, J. S.; Arnaud, N.; Arun, K. G.; Asada, H.; Ascenzi, S.; Ashton, G.; Aso, Y.; Ast, M.; Aston, S. M.; Astone, P.; Atsuta, S.; Aufmuth, P.; Aulbert, C.; Avila-Alvarez, A.; Awai, K.; Babak, S.; Bacon, P.; Bader, M. K. M.; Baiotti, L.; Baker, P. T.; Baldaccini, F.; Ballardin, G.; Ballmer, S. W.; Barayoga, J. C.; Barclay, S. E.; Barish, B. C.; Barker, D.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Barton, M. A.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J. C.; Baune, C.; Bavigadda, V.; Bazzan, M.; Bécsy, B.; Beer, C.; Bejger, M.; Belahcene, I.; Belgin, M.; Bell, A. S.; Berger, B. K.; Bergmann, G.; Berry, C. P. L.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Billman, C. R.; Birch, J.; Birney, R.; Birnholtz, O.; Biscans, S.; Bisht, A.; Bitossi, M.; Biwer, C.; Bizouard, M. A.; Blackburn, J. K.; Blackman, J.; Blair, C. D.; Blair, D. G.; Blair, R. M.; Bloemen, S.; Bock, O.; Boer, M.; Bogaert, G.; Bohe, A.; Bondu, F.; Bonnand, R.; Boom, B. A.; Bork, R.; Boschi, V.; Bose, S.; Bouffanais, Y.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Branchesi, M.; Brau, J. E.; Briant, T.; Brillet, A.; Brinkmann, M.; Brisson, V.; Brockill, P.; Broida, J. E.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brown, N. M.; Brunett, S.; Buchanan, C. C.; Buikema, A.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cabero, M.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Calderón Bustillo, J.; Callister, T. A.; Calloni, E.; Camp, J. B.; Cannon, K. C.; Cao, H.; Cao, J.; Capano, C. D.; Capocasa, E.; Carbognani, F.; Caride, S.; Casanueva Diaz, J.; Casentini, C.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C. B.; Cerboni Baiardi, L.; Cerretani, G.; Cesarini, E.; Chamberlin, S. J.; Chan, M.; Chao, S.; Charlton, P.; Chassande-Mottin, E.; Cheeseboro, B. D.; Chen, H. Y.; Chen, Y.; Cheng, H.-P.; Chincarini, A.; Chiummo, A.; Chmiel, T.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Q.; Chua, A. J. K.; Chua, S.; Chung, S.; Ciani, G.; Clara, F.; Clark, J. A.; Cleva, F.; Cocchieri, C.; Coccia, E.; Cohadon, P.-F.; Colla, A.; Collette, C. G.; Cominsky, L.; Constancio, M.; Conti, L.; Cooper, S. J.; Corbitt, T. R.; Cornish, N.; Corsi, A.; Cortese, S.; Costa, C. A.; Coughlin, M. W.; Coughlin, S. B.; Coulon, J.-P.; Countryman, S. T.; Couvares, P.; Covas, P. B.; Cowan, E. E.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Creighton, J. D. E.; Creighton, T. D.; Cripe, J.; Crowder, S. G.; Cullen, T. J.; Cumming, A.; Cunningham, L.; Cuoco, E.; Canton, T. Dal; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Dasgupta, A.; Da Silva Costa, C. F.; Dattilo, V.; Dave, I.; Davier, M.; Davies, G. S.; Davis, D.; Daw, E. J.; Day, B.; Day, R.; De, S.; DeBra, D.; Debreczeni, G.; Degallaix, J.; De Laurentis, M.; Deléglise, S.; Del Pozzo, W.; Denker, T.; Dent, T.; Dergachev, V.; De Rosa, R.; DeRosa, R. T.; DeSalvo, R.; Devine, R. C.; Dhurandhar, S.; Díaz, M. C.; Fiore, L. Di; Giovanni, M. Di; Girolamo, T. Di; Lieto, A. Di; Pace, S. Di; Palma, I. Di; Virgilio, A. Di; Doctor, Z.; Doi, K.; Dolique, V.; Donovan, F.; Dooley, K. L.; Doravari, S.; Dorrington, I.; Douglas, R.; Dovale Álvarez, M.; Downes, T. P.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Du, Z.; Ducrot, M.; Dwyer, S. E.; Eda, K.; Edo, T. B.; Edwards, M. C.; Effler, A.; Eggenstein, H.-B.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Eisenstein, R. A.; Essick, R. C.; Etienne, Z.; Etzel, T.; Evans, M.; Evans, T. M.; Everett, R.; Factourovich, M.; Fafone, V.; Fair, H.; Fairhurst, S.; Fan, X.; Farinon, S.; Farr, B.; Farr, W. M.; Fauchon-Jones, E. J.; Favata, M.; Fays, M.; Fehrmann, H.; Fejer, M. M.; Fernández Galiana, A.; Ferrante, I.; Ferreira, E. C.; Ferrini, F.; Fidecaro, F.; Fiori, I.; Fiorucci, D.; Fisher, R. P.; Flaminio, R.; Fletcher, M.; Fong, H.; Forsyth, S. S.; Fournier, J.-D.; Frasca, S.; Frasconi, F.; Frei, Z.; Freise, A.; Frey, R.; Frey, V.; Fries, E. M.; Fritschel, P.; Frolov, V. V.; Fujii, Y.; Fujimoto, M.-K.; Fulda, P.; Fyffe, M.; Gabbard, H.; Gadre, B. U.; Gaebel, S. M.; Gair, J. R.; Gammaitoni, L.; Gaonkar, S. G.; Garufi, F.; Gaur, G.; Gayathri, V.; Gehrels, N.; Gemme, G.; Genin, E.; Gennai, A.; George, J.; Gergely, L.; Germain, V.; Ghonge, S.; Ghosh, Abhirup; Ghosh, Archisman; Ghosh, S.; Giaime, J. A.; Giardina, K. D.; Giazotto, A.; Gill, K.; Glaefke, A.; Goetz, E.; Goetz, R.; Gondan, L.; González, G.; Gonzalez Castro, J. M.; Gopakumar, A.; Gorodetsky, M. L.; Gossan, S. E.; Gosselin, M.; Gouaty, R.; Grado, A.; Graef, C.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greco, G.; Green, A. C.; Groot, P.; Grote, H.; Grunewald, S.; Guidi, G. M.; Guo, X.; Gupta, A.; Gupta, M. K.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hacker, J. J.; Hagiwara, A.; Hall, B. R.; Hall, E. D.; Hammond, G.; Haney, M.; Hanke, M. M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hanson, J.; Hardwick, T.; Harms, J.; Harry, G. M.; Harry, I. W.; Hart, M. J.; Hartman, M. T.; Haster, C.-J.; Haughian, K.; Hayama, K.; Healy, J.; Heidmann, A.; Heintze, M. C.; Heitmann, H.; Hello, P.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennig, J.; Henry, J.; Heptonstall, A. W.; Heurs, M.; Hild, S.; Hirose, E.; Hoak, D.; Hofman, D.; Holt, K.; Holz, D. E.; Hopkins, P.; Hough, J.; Houston, E. A.; Howell, E. J.; Hu, Y. M.; Huerta, E. A.; Huet, D.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh-Dinh, T.; Indik, N.; Ingram, D. R.; Inta, R.; Ioka, K.; Isa, H. N.; Isac, J.-M.; Isi, M.; Isogai, T.; Itoh, Y.; Iyer, B. R.; Izumi, K.; Jacqmin, T.; Jani, K.; Jaranowski, P.; Jawahar, S.; Jiménez-Forteza, F.; Johnson, W. W.; Jones, D. I.; Jones, R.; Jonker, R. J. G.; Ju, L.; Junker, J.; Kagawa, T.; Kajita, T.; Kakizaki, M.; Kalaghatgi, C. V.; Kalogera, V.; Kamiizumi, M.; Kanda, N.; Kandhasamy, S.; Kanemura, S.; Kaneyama, M.; Kang, G.; Kanner, J. B.; Karki, S.; Karvinen, K. S.; Kasprzack, M.; Kataoka, Y.; Katsavounidis, E.; Katzman, W.; Kaufer, S.; Kaur, T.; Kawabe, K.; Kawai, N.; Kawamura, S.; Kéfélian, F.; Keitel, D.; Kelley, D. B.; Kennedy, R.; Key, J. S.; Khalili, F. Y.; Khan, I.; Khan, S.; Khan, Z.; Khazanov, E. A.; Kijbunchoo, N.; Kim, C.; Kim, H.; Kim, J. C.; Kim, J.; Kim, W.; Kim, Y.-M.; Kimbrell, S. J.; Kimura, N.; King, E. J.; King, P. J.; Kirchhoff, R.; Kissel, J. S.; Klein, B.; Kleybolte, L.; Klimenko, S.; Koch, P.; Koehlenbeck, S. M.; Kojima, Y.; Kokeyama, K.; Koley, S.; Komori, K.; Kondrashov, V.; Kontos, A.; Korobko, M.; Korth, W. Z.; Kotake, K.; Kowalska, I.; Kozak, D. B.; Krämer, C.; Kringel, V.; Krishnan, B.; Królak, A.; Kuehn, G.; Kumar, P.; Kumar, Rahul; Kumar, Rakesh; Kuo, L.; Kuroda, K.; Kutynia, A.; Kuwahara, Y.; Lackey, B. D.; Landry, M.; Lang, R. N.; Lange, J.; Lantz, B.; Lanza, R. K.; Lartaux-Vollard, A.; Lasky, P. D.; Laxen, M.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lebigot, E. O.; Lee, C. H.; Lee, H. K.; Lee, H. M.; Lee, H. W.; Lee, K.; Lehmann, J.; Lenon, A.; Leonardi, M.; Leong, J. R.; Leroy, N.; Letendre, N.; Levin, Y.; Li, T. G. F.; Libson, A.; Littenberg, T. B.; Liu, J.; Lockerbie, N. A.; Lombardi, A. L.; London, L. T.; Lord, J. E.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J. D.; Lousto, C. O.; Lovelace, G.; Lück, H.; Lundgren, A. P.; Lynch, R.; Ma, Y.; Macfoy, S.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magaña-Sandoval, F.; Majorana, E.; Maksimovic, I.; Malvezzi, V.; Man, N.; Mandic, V.; Mangano, V.; Mano, S.; Mansell, G. L.; Manske, M.; Mantovani, M.; Marchesoni, F.; Marchio, M.; Marion, F.; Márka, S.; Márka, Z.; Markosyan, A. S.; Maros, E.; Martelli, F.; Martellini, L.; Martin, I. W.; Martynov, D. V.; Mason, K.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Mastrogiovanni, S.; Matichard, F.; Matone, L.; Matsumoto, N.; Matsushima, F.; Mavalvala, N.; Mazumder, N.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McGrath, C.; McGuire, S. C.; McIntyre, G.; McIver, J.; McManus, D. J.; McRae, T.; McWilliams, S. T.; Meacher, D.; Meadors, G. D.; Meidam, J.; Melatos, A.; Mendell, G.; Mendoza-Gandara, D.; Mercer, R. A.; Merilh, E. L.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Metzdorff, R.; Meyers, P. M.; Mezzani, F.; Miao, H.; Michel, C.; Michimura, Y.; Middleton, H.; Mikhailov, E. E.; Milano, L.; Miller, A. L.; Miller, A.; Miller, B. B.; Miller, J.; Millhouse, M.; Minenkov, Y.; Ming, J.; Mirshekari, S.; Mishra, C.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Miyakawa, O.; Miyamoto, A.; Miyamoto, T.; Miyoki, S.; Moggi, A.; Mohan, M.; Mohapatra, S. R. P.; Montani, M.; Moore, B. C.; Moore, C. J.; Moraru, D.; Moreno, G.; Morii, W.; Morisaki, S.; Moriwaki, Y.; Morriss, S. R.; Mours, B.; Mow-Lowry, C. M.; Mueller, G.; Muir, A. W.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, S.; Mukund, N.; Mullavey, A.; Munch, J.; Muniz, E. A. M.; Murray, P. G.; Mytidis, A.; Nagano, S.; Nakamura, K.; Nakamura, T.; Nakano, H.; Nakano, Masaya; Nakano, Masayuki; Nakao, K.; Napier, K.; Nardecchia, I.; Narikawa, T.; Naticchioni, L.; Nelemans, G.; Nelson, T. J. N.; Neri, M.; Nery, M.; Neunzert, A.; Newport, J. M.; Newton, G.; Nguyen, T. T.; Ni, W.-T.; Nielsen, A. B.; Nissanke, S.; Nitz, A.; Noack, A.; Nocera, F.; Nolting, D.; Normandin, M. E. N.; Nuttall, L. K.; Oberling, J.; Ochsner, E.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohashi, M.; Ohishi, N.; Ohkawa, M.; Ohme, F.; Okutomi, K.; Oliver, M.; Ono, K.; Ono, Y.; Oohara, K.; Oppermann, P.; Oram, Richard J.; O'Reilly, B.; O'Shaughnessy, R.; Ottaway, D. J.; Overmier, H.; Owen, B. J.; Pace, A. E.; Page, J.; Pai, A.; Pai, S. A.; Palamos, J. R.; Palashov, O.; Palomba, C.; Pal-Singh, A.; Pan, H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Paoletti, F.; Paoli, A.; Papa, M. A.; Paris, H. R.; Parker, W.; Pascucci, D.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patricelli, B.; Pearlstone, B. L.; Pedraza, M.; Pedurand, R.; Pekowsky, L.; Pele, A.; Peña Arellano, F. E.; Penn, S.; Perez, C. J.; Perreca, A.; Perri, L. M.; Pfeiffer, H. P.; Phelps, M.; Piccinni, O. J.; Pichot, M.; Piergiovanni, F.; Pierro, V.; Pillant, G.; Pinard, L.; Pinto, I. M.; Pitkin, M.; Poe, M.; Poggiani, R.; Popolizio, P.; Post, A.; Powell, J.; Prasad, J.; Pratt, J. W. W.; Predoi, V.; Prestegard, T.; Prijatelj, M.; Principe, M.; Privitera, S.; Prodi, G. A.; Prokhorov, L. G.; Puncken, O.; Punturo, M.; Puppo, P.; Pürrer, M.; Qi, H.; Qin, J.; Qiu, S.; Quetschke, V.; Quintero, E. A.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Radkins, H.; Raffai, P.; Raja, S.; Rajan, C.; Rakhmanov, M.; Rapagnani, P.; Raymond, V.; Razzano, M.; Re, V.; Read, J.; Regimbau, T.; Rei, L.; Reid, S.; Reitze, D. H.; Rew, H.; Reyes, S. D.; Rhoades, E.; Ricci, F.; Riles, K.; Rizzo, M.; Robertson, N. A.; Robie, R.; Robinet, F.; Rocchi, A.; Rolland, L.; Rollins, J. G.; Roma, V. J.; Romano, R.; Romie, J. H.; Rosińska, D.; Rowan, S.; Rüdiger, A.; Ruggi, P.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadeghian, L.; Sago, N.; Saijo, M.; Saito, Y.; Sakai, K.; Sakellariadou, M.; Salconi, L.; Saleem, M.; Salemi, F.; Samajdar, A.; Sammut, L.; Sampson, L. M.; Sanchez, E. J.; Sandberg, V.; Sanders, J. R.; Sasaki, Y.; Sassolas, B.; Sathyaprakash, B. S.; Sato, S.; Sato, T.; Saulson, P. R.; Sauter, O.; Savage, R. L.; Sawadsky, A.; Schale, P.; Scheuer, J.; Schmidt, E.; Schmidt, J.; Schmidt, P.; Schnabel, R.; Schofield, R. M. S.; Schönbeck, A.; Schreiber, E.; Schuette, D.; Schutz, B. F.; Schwalbe, S. G.; Scott, J.; Scott, S. M.; Sekiguchi, T.; Sekiguchi, Y.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Sequino, V.; Sergeev, A.; Setyawati, Y.; Shaddock, D. A.; Shaffer, T. J.; Shahriar, M. S.; Shapiro, B.; Shawhan, P.; Sheperd, A.; Shibata, M.; Shikano, Y.; Shimoda, T.; Shoda, A.; Shoemaker, D. H.; Shoemaker, D. M.; Siellez, K.; Siemens, X.; Sieniawska, M.; Sigg, D.; Silva, A. D.; Singer, A.; Singer, L. P.; Singh, A.; Singh, R.; Singhal, A.; Sintes, A. M.; Slagmolen, B. J. J.; Smith, B.; Smith, J. R.; Smith, R. J. E.; Somiya, K.; Son, E. J.; Sorazu, B.; Sorrentino, F.; Souradeep, T.; Spencer, A. P.; Srivastava, A. K.; Staley, A.; Steinke, M.; Steinlechner, J.; Steinlechner, S.; Steinmeyer, D.; Stephens, B. C.; Stevenson, S. P.; Stone, R.; Strain, K. A.; Straniero, N.; Stratta, G.; Strigin, S. E.; Sturani, R.; Stuver, A. L.; Sugimoto, Y.; Summerscales, T. Z.; Sun, L.; Sunil, S.; Sutton, P. J.; Suzuki, T.; Swinkels, B. L.; Szczepańczyk, M. J.; Tacca, M.; Tagoshi, H.; Takada, S.; Takahashi, H.; Takahashi, R.; Takamori, A.; Talukder, D.; Tanaka, H.; Tanaka, K.; Tanaka, T.; Tanner, D. B.; Tápai, M.; Taracchini, A.; Tatsumi, D.; Taylor, R.; Telada, S.; Theeg, T.; Thomas, E. G.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thrane, E.; Tippens, T.; Tiwari, S.; Tiwari, V.; Tokmakov, K. V.; Toland, K.; Tomaru, T.; Tomlinson, C.; Tonelli, M.; Tornasi, Z.; Torrie, C. I.; Töyrä, D.; Travasso, F.; Traylor, G.; Trifirò, D.; Trinastic, J.; Tringali, M. C.; Trozzo, L.; Tse, M.; Tso, R.; Tsubono, K.; Tsuzuki, T.; Turconi, M.; Tuyenbayev, D.; Uchiyama, T.; Uehara, T.; Ueki, S.; Ueno, K.; Ugolini, D.; Unnikrishnan, C. S.; Urban, A. L.; Ushiba, T.; Usman, S. A.; Vahlbruch, H.; Vajente, G.; Valdes, G.; van Bakel, N.; van Beuzekom, M.; van den Brand, J. F. J.; Van Den Broeck, C.; Vander-Hyde, D. C.; van der Schaaf, L.; van Heijningen, J. V.; van Putten, M. H. P. M.; van Veggel, A. A.; Vardaro, M.; Varma, V.; Vass, S.; Vasúth, M.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Venugopalan, G.; Verkindt, D.; Vetrano, F.; Viceré, A.; Viets, A. D.; Vinciguerra, S.; Vine, D. J.; Vinet, J.-Y.; Vitale, S.; Vo, T.; Vocca, H.; Vorvick, C.; Voss, D. V.; Vousden, W. D.; Vyatchanin, S. P.; Wade, A. R.; Wade, L. E.; Wade, M.; Wakamatsu, T.; Walker, M.; Wallace, L.; Walsh, S.; Wang, G.; Wang, H.; Wang, M.; Wang, Y.; Ward, R. L.; Warner, J.; Was, M.; Watchi, J.; Weaver, B.; Wei, L.-W.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Wen, L.; Weßels, P.; Westphal, T.; Wette, K.; Whelan, J. T.; Whiting, B. F.; Whittle, C.; Williams, D.; Williams, R. D.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wimmer, M. H.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Woehler, J.; Worden, J.; Wright, J. L.; Wu, D. S.; Wu, G.; Yam, W.; Yamamoto, H.; Yamamoto, K.; Yamamoto, T.; Yancey, C. C.; Yano, K.; Yap, M. J.; Yokoyama, J.; Yokozawa, T.; Yoon, T. H.; Yu, Hang; Yu, Haocun; Yuzurihara, H.; Yvert, M.; Zadrożny, A.; Zangrando, L.; Zanolin, M.; Zeidler, S.; Zendri, J.-P.; Zevin, M.; Zhang, L.; Zhang, M.; Zhang, T.; Zhang, Y.; Zhao, C.; Zhou, M.; Zhou, Z.; Zhu, S. J.; Zhu, X. J.; Zucker, M. E.; Zweizig, J.

2018-04-01

We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5-20 deg^2 requires at least three detectors of sensitivity within a factor of ˜ 2 of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA.

PubMed

Abbott, B P; Abbott, R; Abbott, T D; Abernathy, M R; Acernese, F; Ackley, K; Adams, C; Adams, T; Addesso, P; Adhikari, R X; Adya, V B; Affeldt, C; Agathos, M; Agatsuma, K; Aggarwal, N; Aguiar, O D; Aiello, L; Ain, A; Ajith, P; Akutsu, T; Allen, B; Allocca, A; Altin, P A; Ananyeva, A; Anderson, S B; Anderson, W G; Ando, M; Appert, S; Arai, K; Araya, A; Araya, M C; Areeda, J S; Arnaud, N; Arun, K G; Asada, H; Ascenzi, S; Ashton, G; Aso, Y; Ast, M; Aston, S M; Astone, P; Atsuta, S; Aufmuth, P; Aulbert, C; Avila-Alvarez, A; Awai, K; Babak, S; Bacon, P; Bader, M K M; Baiotti, L; Baker, P T; Baldaccini, F; Ballardin, G; Ballmer, S W; Barayoga, J C; Barclay, S E; Barish, B C; Barker, D; Barone, F; Barr, B; Barsotti, L; Barsuglia, M; Barta, D; Bartlett, J; Barton, M A; Bartos, I; Bassiri, R; Basti, A; Batch, J C; Baune, C; Bavigadda, V; Bazzan, M; Bécsy, B; Beer, C; Bejger, M; Belahcene, I; Belgin, M; Bell, A S; Berger, B K; Bergmann, G; Berry, C P L; Bersanetti, D; Bertolini, A; Betzwieser, J; Bhagwat, S; Bhandare, R; Bilenko, I A; Billingsley, G; Billman, C R; Birch, J; Birney, R; Birnholtz, O; Biscans, S; Bisht, A; Bitossi, M; Biwer, C; Bizouard, M A; Blackburn, J K; Blackman, J; Blair, C D; Blair, D G; Blair, R M; Bloemen, S; Bock, O; Boer, M; Bogaert, G; Bohe, A; Bondu, F; Bonnand, R; Boom, B A; Bork, R; Boschi, V; Bose, S; Bouffanais, Y; Bozzi, A; Bradaschia, C; Brady, P R; Braginsky, V B; Branchesi, M; Brau, J E; Briant, T; Brillet, A; Brinkmann, M; Brisson, V; Brockill, P; Broida, J E; Brooks, A F; Brown, D A; Brown, D D; Brown, N M; Brunett, S; Buchanan, C C; Buikema, A; Bulik, T; Bulten, H J; Buonanno, A; Buskulic, D; Buy, C; Byer, R L; Cabero, M; Cadonati, L; Cagnoli, G; Cahillane, C; Calderón Bustillo, J; Callister, T A; Calloni, E; Camp, J B; Cannon, K C; Cao, H; Cao, J; Capano, C D; Capocasa, E; Carbognani, F; Caride, S; Casanueva Diaz, J; Casentini, C; Caudill, S; Cavaglià, M; Cavalier, F; Cavalieri, R; Cella, G; Cepeda, C B; Cerboni Baiardi, L; Cerretani, G; Cesarini, E; 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2018-01-01

We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and [Formula: see text] credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5-[Formula: see text] requires at least three detectors of sensitivity within a factor of [Formula: see text] of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

Cost-effectiveness analysis of PET-CT-guided management for locally advanced head and neck cancer.

PubMed

Smith, A F; Hall, P S; Hulme, C T; Dunn, J A; McConkey, C C; Rahman, J K; McCabe, C; Mehanna, H

2017-11-01

A recent large United Kingdom (UK) clinical trial demonstrated that positron-emission tomography-computed tomography (PET-CT)-guided administration of neck dissection (ND) in patients with advanced head and neck cancer after primary chemo-radiotherapy treatment produces similar survival outcomes to planned ND (standard care) and is cost-effective over a short-term horizon. Further assessment of long-term outcomes is required to inform a robust adoption decision. Here we present results of a lifetime cost-effectiveness analysis of PET-CT-guided management from a UK secondary care perspective. Initial 6-month cost and health outcomes were derived from trial data; subsequent incidence of recurrence and mortality was simulated using a de novo Markov model. Health benefit was measured in quality-adjusted life years (QALYs) and costs reported in 2015 British pounds. Model parameters were derived from trial data and published literature. Sensitivity analyses were conducted to assess the impact of uncertainty and broader National Health Service (NHS) and personal social services (PSS) costs on the results. PET-CT management produced an average per-person lifetime cost saving of £1485 and an additional 0.13 QALYs. At a £20,000 willingness-to-pay per additional QALY threshold, there was a 75% probability that PET-CT was cost-effective, and the results remained cost-effective over the majority of sensitivity analyses. When adopting a broader NHS and PSS perspective, PET-CT management produced an average saving of £700 and had an 81% probability of being cost-effective. This analysis indicates that PET-CT-guided management is cost-effective in the long-term and supports the case for wide-scale adoption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Physiological joint line total knee arthroplasty designs are especially sensitive to rotational placement - A finite element analysis.

PubMed

Moewis, Philippe; Checa, Sara; Kutzner, Ines; Hommel, Hagen; Duda, Georg N

2018-01-01

Mechanical and kinematical aligning techniques are the usual positioning methods during total knee arthroplasty. However, alteration of the physiological joint line and unbalanced medio-lateral load distribution are considered disadvantages in the mechanical and kinematical techniques, respectively. The aim of this study was to analyse the influence of the joint line on the strain and stress distributions in an implanted knee and their sensitivity to rotational mal-alignment. Finite element calculations were conducted to analyse the stresses in the PE-Inlay and the mechanical strains at the bone side of the tibia component-tibia bone interface during normal positioning of the components and internal and external mal-rotation of the tibial component. Two designs were included, a horizontal and a physiological implant. The loading conditions are based on internal knee joint loads during walking. A medialization of the stresses on the PE-Inlay was observed in the physiological implant in a normal position, accompanied by higher stresses in the mal-rotated positions. Within the tibia component-tibia bone interface, similar strain distributions were observed in both implant geometries in the normal position. However, a medialization of the strains was observed in the physiological implant in both mal-rotated conditions with greater bone volume affected by higher strains. Although evident changes due to mal-rotation were observed, the stresses do not suggest a local plastic deformation of the PE-Inlay. The strains values within most of the tibia component-tibia bone interface were in the physiological strain zone and no significant bone changes would be expected. The physiological cut on the articular aspect showed no detrimental effect compared to the horizontal implant.

Patient experience and the role of postgraduate GP training: a cross-sectional analysis of national Patient Survey data in England

PubMed Central

Ashworth, Mark; Schofield, Peter; Durbaba, Stevo; Ahluwalia, Sanjiv

2014-01-01

Background Quality indicators for primary care focus predominantly on the public health model and organisational measures. Patient experience is an important dimension of quality. Accreditation for GP training practices requires demonstration of a series of attributes including patient-centred care. Aim The national GP Patient Survey (GPPS) was used to determine the characteristics of general practices scoring highly in responses relating to the professional skills and characteristics of doctors. Specifically, to determine whether active participation in postgraduate GP training was associated with more positive experiences of care. Design and setting Retrospective cross-sectional study in general practices in England. Method Data were obtained from the national QOF dataset for England, 2011/12 (8164 general practices); the GPPS in 2012 (2.7 million questionnaires in England; response rate 36%); general practice and demographic characteristics. Sensitivity analyses included local data validated by practice inspections. Outcome measures: multilevel regression models adjusted for clustering. Results GP training practice status (29% of practices) was a significant predictor of positive GPPS responses to all questions in the ‘doctor care’ (n = 6) and ‘overall satisfaction’ (n = 2) domains but not to any of the ‘nurse care’ or ‘out-of-hours’ domain questions. The findings were supported by the sensitivity analyses. Other positive determinants were: smaller practice and individual GP list sizes, more older patients, lower social deprivation and fewer ethnic minority patients. Conclusion Based on GPPS responses, doctors in GP training practices appeared to offer more patient-centred care with patients reporting more positively on attributes of doctors such as ‘listening’ or ‘care and concern’. PMID:24567656

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

Yoshioka, Yasuo; Ogawa, Kazuhiko, E-mail: kogawa@radonc.med.osaka-u.ac.jp; Oikawa, Hirobumi

Purpose: To determine whether adding intraluminal brachytherapy (ILBT) to definitive radiation therapy (RT) for unresectable biliary tract cancer has a positive impact on survival outcome. Methods and Materials: The original cohort comprised 209 patients, including 153 who underwent external beam RT (EBRT) alone and 56 who received both ILBT and EBRT. By matching propensity scores, 56 pairs (112 patients) consisting of 1 patient with and 1 patient without ILBT were selected. They were well balanced in terms of sex, age, performance status, clinical stage, jaundice, and addition of chemotherapy. The impact of ILBT on overall survival (OS), disease-specific survival (DSS),more » and local control (LC) was investigated. Results: The 2-year OS rates were 31% for the ILBT+ group and 40% for theILBT– group (P=.862). The 2-year DSS rates were 42% for the ILBT+ group and 41% for the ILBT– group (P=.288). The 2-year LC rates were 65% for the ILBT+ group and 35% for the ILBT– group (P=.094). Three of the 4 sensitivity analyses showed a significantly better LC for the ILBT+ group (P=.010, .025, .049), and another showed a marginally better LC (P=.068), and none of the sensitivity analyses showed any statistically significant differences in OS or DSS. Conclusions: In the treatment for unresectable biliary tract cancer, the addition of ILBT to RT has no impact on OS or DSS but is associated with better LC. Therefore, the role of ILBT should be addressed by other measures than survival benefit, for example, by less toxicity, prolonged biliary tract patency decreasing the need for further palliative interventions, or patient quality of life.« less

Small-area distribution of multiple sclerosis incidence in western France: in search of environmental triggers.

PubMed

Hammas, Karima; Yaouanq, Jacqueline; Lannes, Morgane; Edan, Gilles; Viel, Jean-François

2017-09-21

Despite intensive research over several decades, the etiology of multiple sclerosis (MS) remains poorly understood, although environmental factors are supposedly implicated. Our goal was to identify spatial clusters of MS incident cases at the small-area level to provide clues to local environmental risk factors that might cause or trigger the disease. A population-based and multi-stage study was performed in the French Brittany region to accurately ascertain the clinical onset of disease during the 2000-2004 period. The municipality of residence at the time of clinical onset was geocoded. To test for the presence of MS incidence clusters and to identify their approximate locations, we used a spatial scan statistic. We adjusted for socioeconomic deprivation, known to be strongly associated with increased MS incident rates, and scanned simultaneously for areas with either high or low rates. Sensitivity analyses (focusing on relapsing-remitting forms and/or places of residence available within the year following clinical onset) were performed. A total of 848 incident cases of MS were registered in Brittany, corresponding to a crude annual incidence rate of 5.8 per 100,000 inhabitants. The spatial scan statistic did not find a significant cluster of MS incidence in either the primary analysis (p value ≥ 0.56) or in the sensitivity analyses (p value ≥ 0.16). The findings of this study indicate that MS incidence is not markedly affected across space, suggesting that in the years preceding the first clinical expression of the disease, no environmental trigger is operative at the small-area population level in the French Brittany region.

Cost-Effectiveness of Pre-exposure HIV Prophylaxis During Pregnancy and Breastfeeding in Sub-Saharan Africa

PubMed Central

Wheeler, Stephanie B.; Stranix-Chibanda, Lynda; Hosek, Sybil G.; Watts, D. Heather; Siberry, George K.; Spiegel, Hans M. L.; Stringer, Jeffrey S.; Chi, Benjamin H.

2016-01-01

Introduction: Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit. Methods: We developed a decision analytic model to evaluate a strategy of daily oral PrEP during pregnancy and breastfeeding in SSA. We approached the analysis from a health care system perspective across a lifetime time horizon. Model inputs were derived from existing literature and local sources. The incremental cost-effectiveness ratio (ICER) of PrEP versus no PrEP was calculated in 2015 U.S. dollars per disability-adjusted life year (DALY) averted. We evaluated the effect of uncertainty in baseline estimates through one-way and probabilistic sensitivity analyses. Results: PrEP administered to pregnant and breastfeeding women in SSA was cost-effective. In a base case of 10,000 women, the administration of PrEP averted 381 HIV infections but resulted in 779 more preterm births. PrEP was more costly per person ($450 versus $117), but resulted in fewer disability-adjusted life years (DALYs) (3.15 versus 3.49). The incremental cost-effectiveness ratio of $965/DALY averted was below the recommended regional threshold for cost-effectiveness of $6462/DALY. Probabilistic sensitivity analyses demonstrated robustness of the model. Conclusions: Providing PrEP to pregnant and breastfeeding women in SSA is likely cost-effective, although more data are needed about adherence and safety. For populations at high risk of HIV acquisition, PrEP may be considered as part of a broader combination HIV prevention strategy. PMID:27355502

A collaborative characterization of North American grasslands and rangelands: climate, ecohydrology and carbon sink-source dynamics

NASA Astrophysics Data System (ADS)

Petrie, M. D.; Brunsell, N. A.; Vargas, R.; Collins, S. L.

2013-12-01

Grassland and rangeland ecoregions extend across the North American continent and exhibit diversity in climate, ecosystem services, and biophysical processes. In many grasslands and rangelands, the potential for reductions in ecosystem services and for large-scale ecosystem state change may increase under future climate scenarios. Climate change projections for North America vary, however, and the way changing climate will influence specific ecoregions is largely unknown. To better understand the regional effects of climate change on grasslands and rangelands, it is important to better understand the biophysical characteristics of these systems locally, and to identify the sensitivity of these characteristics to observed climate variation. In our study, we propose to use eddy covariance, soil moisture and precipitation data to identify how the grasslands and rangelands of North America differ in their responses to climate variability through time, with specific focus on the active growing season. Our primary goal is to determine the sensitivity of ecosystem Net Primary Productivity [NPP] to variation in temperature and precipitation patterns, and classify North American grasslands and rangelands by these sensitivities in addition to more standard climate and productivity variables. Our preliminary analyses in mesic, semiarid and arid grasslands in Kansas, Colorado and New Mexico show significant (P < 0.05) differences in climate, carbon sink strength and growing season length, and suggest that patterns of seasonal productivity and precipitation sensitivity may elucidate important grassland and rangeland responses to changing climate. Using change in Gross Primary Productivity (GPP) as an indicator of the onset of photosynthesis in spring and of senescense in the fall, grassland and rangeland ecosystems in Kansas (top and bottom left panels) and New Mexico (bottom right panel) display differing patterns of activity throughout the year.

ASPASIA: A toolkit for evaluating the effects of biological interventions on SBML model behaviour.

PubMed

Evans, Stephanie; Alden, Kieran; Cucurull-Sanchez, Lourdes; Larminie, Christopher; Coles, Mark C; Kullberg, Marika C; Timmis, Jon

2017-02-01

A calibrated computational model reflects behaviours that are expected or observed in a complex system, providing a baseline upon which sensitivity analysis techniques can be used to analyse pathways that may impact model responses. However, calibration of a model where a behaviour depends on an intervention introduced after a defined time point is difficult, as model responses may be dependent on the conditions at the time the intervention is applied. We present ASPASIA (Automated Simulation Parameter Alteration and SensItivity Analysis), a cross-platform, open-source Java toolkit that addresses a key deficiency in software tools for understanding the impact an intervention has on system behaviour for models specified in Systems Biology Markup Language (SBML). ASPASIA can generate and modify models using SBML solver output as an initial parameter set, allowing interventions to be applied once a steady state has been reached. Additionally, multiple SBML models can be generated where a subset of parameter values are perturbed using local and global sensitivity analysis techniques, revealing the model's sensitivity to the intervention. To illustrate the capabilities of ASPASIA, we demonstrate how this tool has generated novel hypotheses regarding the mechanisms by which Th17-cell plasticity may be controlled in vivo. By using ASPASIA in conjunction with an SBML model of Th17-cell polarisation, we predict that promotion of the Th1-associated transcription factor T-bet, rather than inhibition of the Th17-associated transcription factor RORγt, is sufficient to drive switching of Th17 cells towards an IFN-γ-producing phenotype. Our approach can be applied to all SBML-encoded models to predict the effect that intervention strategies have on system behaviour. ASPASIA, released under the Artistic License (2.0), can be downloaded from http://www.york.ac.uk/ycil/software.

Local identifiability and sensitivity analysis of neuromuscular blockade and depth of hypnosis models.

PubMed

Silva, M M; Lemos, J M; Coito, A; Costa, B A; Wigren, T; Mendonça, T

2014-01-01

This paper addresses the local identifiability and sensitivity properties of two classes of Wiener models for the neuromuscular blockade and depth of hypnosis, when drug dose profiles like the ones commonly administered in the clinical practice are used as model inputs. The local parameter identifiability was assessed based on the singular value decomposition of the normalized sensitivity matrix. For the given input signal excitation, the results show an over-parameterization of the standard pharmacokinetic/pharmacodynamic models. The same identifiability assessment was performed on recently proposed minimally parameterized parsimonious models for both the neuromuscular blockade and the depth of hypnosis. The results show that the majority of the model parameters are identifiable from the available input-output data. This indicates that any identification strategy based on the minimally parameterized parsimonious Wiener models for the neuromuscular blockade and for the depth of hypnosis is likely to be more successful than if standard models are used. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

PubMed

Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

2016-02-01

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

Geomatics for Maritime Parks and Preserved Areas

NASA Astrophysics Data System (ADS)

Lo Tauro, Agata

2009-11-01

The aim of this research is to use hyperspectral MIVIS data for protection of sensitive cultural, natural resources, Nature Reserves and maritime parks. A knowledge of the distribution of submerged vegetation is useful to monitor the health of ecosystems in coastal areas. The objective of this project was to develop a new methodology within geomatic environment to facilitate the analysis and application of Local Institutions who are not familiar with Spatial Analysis softwares in order to implement new research activities in this field of study. Field controls may be carried out with the support of accurate and novel in situ analysis in order to determine the training sites for the novel tested classification. The methodology applied demonstrates that the combination of hyperspectral sensors and ESA Remote Sensing (RS) data can be used to analyse thematic cartography of submerged vegetation and land use analysis for Sustainable Development. This project will be implemented for Innovative Educational and Research Programmes.

a Voxel-Based Filtering Algorithm for Mobile LIDAR Data

NASA Astrophysics Data System (ADS)

Qin, H.; Guan, G.; Yu, Y.; Zhong, L.

2018-04-01

This paper presents a stepwise voxel-based filtering algorithm for mobile LiDAR data. In the first step, to improve computational efficiency, mobile LiDAR points, in xy-plane, are first partitioned into a set of two-dimensional (2-D) blocks with a given block size, in each of which all laser points are further organized into an octree partition structure with a set of three-dimensional (3-D) voxels. Then, a voxel-based upward growing processing is performed to roughly separate terrain from non-terrain points with global and local terrain thresholds. In the second step, the extracted terrain points are refined by computing voxel curvatures. This voxel-based filtering algorithm is comprehensively discussed in the analyses of parameter sensitivity and overall performance. An experimental study performed on multiple point cloud samples, collected by different commercial mobile LiDAR systems, showed that the proposed algorithm provides a promising solution to terrain point extraction from mobile point clouds.

A shock absorber model for structure-borne noise analyses

NASA Astrophysics Data System (ADS)

Benaziz, Marouane; Nacivet, Samuel; Thouverez, Fabrice

2015-08-01

Shock absorbers are often responsible for undesirable structure-borne noise in cars. The early numerical prediction of this noise in the automobile development process can save time and money and yet remains a challenge for industry. In this paper, a new approach to predicting shock absorber structure-borne noise is proposed; it consists in modelling the shock absorber and including the main nonlinear phenomena responsible for discontinuities in the response. The model set forth herein features: compressible fluid behaviour, nonlinear flow rate-pressure relations, valve mechanical equations and rubber mounts. The piston, base valve and complete shock absorber model are compared with experimental results. Sensitivity of the shock absorber response is evaluated and the most important parameters are classified. The response envelope is also computed. This shock absorber model is able to accurately reproduce local nonlinear phenomena and improves our state of knowledge on potential noise sources within the shock absorber.

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

Stephan Harrison; Ann V. Rowan; Neil F. Glasser

It is widely believed that the last glaciers in the British Isles disappeared at the end of the Younger Dryas stadial (12.9–11.7 cal. kyr BP). Here, we use a glacier–climate model driven by data from local weather stations to show for the first time that glaciers developed during the Little Ice Age (LIA) in the Cairngorm Mountains. Our model is forced from contemporary conditions by a realistic difference in mean annual air temperature of -1.5 degrees C and an increase in annual precipitation of 10%, and confirmed by sensitivity analyses. These results are supported by the presence of small bouldermore » moraines well within Younger Dryas ice limits, and by a dating programme on a moraine in one cirque. As a result, we argue that the last glaciers in the Cairngorm Mountains (and perhaps elsewhere in upland Britain) existed in the LIA within the last few hundred years, rather than during the Younger Dryas.« less

Elastic-Plastic Nonlinear Response of a Space Shuttle External Tank Stringer. Part 1; Stringer-Feet Imperfections and Assembly

NASA Technical Reports Server (NTRS)

Knight, Norman F., Jr.; Song, Kyongchan; Elliott, Kenny B.; Raju, Ivatury S.; Warren, Jerry E.

2012-01-01

Elastic-plastic, large-deflection nonlinear stress analyses are performed for the external hat-shaped stringers (or stiffeners) on the intertank portion of the Space Shuttle s external tank. These stringers are subjected to assembly strains when the stringers are initially installed on an intertank panel. Four different stringer-feet configurations including the baseline flat-feet, the heels-up, the diving-board, and the toes-up configurations are considered. The assembly procedure is analytically simulated for each of these stringer configurations. The location, size, and amplitude of the strain field associated with the stringer assembly are sensitive to the assumed geometry and assembly procedure. The von Mises stress distributions from these simulations indicate that localized plasticity will develop around the first eight fasteners for each stringer-feet configuration examined. However, only the toes-up configuration resulted in high assembly hoop strains.

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.

Local Rural Product as a "Relic" Spatial Strategy in Globalised Rural Spaces: Evidence from County Clare (Ireland)

ERIC Educational Resources Information Center

Wilson, Geoff A.; Whitehead, Ian

2012-01-01

Using a case study from County Clare (Ireland), this study critically analyses notions of "local" rural production. It investigates where rural businesses source the different components of their products and how these interrelate with the locality, how local businesses use the notion of "local" in their product branding, and…

Nanoparticles based fiber optic SPR sensor

NASA Astrophysics Data System (ADS)

Shah, Kruti; Sharma, Navneet K.

2018-05-01

Localized surface plasmon resonance based fiber optic sensor using platinum nanoparticles is proposed and theoretically analyzed. Increase in thickness of nanoparticles layer increases the sensitivity of sensor. 50 nm thick platinum nanoparticles layer based sensor reveals highest sensitivity.

High sensitive detection of copper II ions using D-penicillamine-coated gold nanorods based on localized surface plasmon resonance

NASA Astrophysics Data System (ADS)

Hong, Yoochan; Jo, Seongjae; Park, Joohyung; Park, Jinsung; Yang, Jaemoon

2018-05-01

In this paper, we describe the development of a nanoplasmonic biosensor based on the localized surface plasmon resonance (LSPR) effect that enables a sensitive and selective recognition of copper II ions. First, we fabricated the nanoplasmonics as LSPR substrates using gold nanorods (GNR) and the nano-adsorption method. The LSPR sensitivity of the nanoplasmonics was evaluated using various solvents with different refractive indexes. Subsequently, D-penicillamine (DPA)—a chelating agent of copper II ions—was conjugated to the surface of the GNR. The limit of detection (LOD) for the DPA-conjugated nanoplasmonics was 100 pM. Furthermore, selectivity tests were conducted using various divalent cations, and sensitivity tests were conducted on the nanoplasmonics under blood-like environments. Finally, the developed nanoplasmonic biosensor based on GNR shows great potential for the effective recognition of copper II ions, even in human blood conditions.

Sensitivity of resistive and Hall measurements to local inhomogeneities

NASA Astrophysics Data System (ADS)

Koon, Daniel W.; Wang, Fei; Hjorth Petersen, Dirch; Hansen, Ole

2013-10-01

We derive exact, analytic expressions for the sensitivity of resistive and Hall measurements to local inhomogeneities in a specimen's material properties in the combined linear limit of a weak perturbation over an infinitesimal area in a small magnetic field. We apply these expressions both to four-point probe measurements on an infinite plane and to symmetric, circular van der Pauw discs, obtaining functions consistent with published results. These new expressions speed up calculation of the sensitivity for a specimen of arbitrary shape to little more than the solution of two Laplace equation boundary-value problems of the order of N3 calculations, rather than N2 problems of total order N5, and in a few cases produces an analytic expression for the sensitivity. These functions provide an intuitive, visual explanation of how, for example, measurements can predict the wrong carrier type in n-type ZnO.

High sensitive detection of copper II ions using D-penicillamine-coated gold nanorods based on localized surface plasmon resonance.

PubMed

Hong, Yoochan; Jo, Seongjae; Park, Joohyung; Park, Jinsung; Yang, Jaemoon

2018-05-25

In this paper, we describe the development of a nanoplasmonic biosensor based on the localized surface plasmon resonance (LSPR) effect that enables a sensitive and selective recognition of copper II ions. First, we fabricated the nanoplasmonics as LSPR substrates using gold nanorods (GNR) and the nano-adsorption method. The LSPR sensitivity of the nanoplasmonics was evaluated using various solvents with different refractive indexes. Subsequently, D-penicillamine (DPA)-a chelating agent of copper II ions-was conjugated to the surface of the GNR. The limit of detection (LOD) for the DPA-conjugated nanoplasmonics was 100 pM. Furthermore, selectivity tests were conducted using various divalent cations, and sensitivity tests were conducted on the nanoplasmonics under blood-like environments. Finally, the developed nanoplasmonic biosensor based on GNR shows great potential for the effective recognition of copper II ions, even in human blood conditions.

Prostate lesion detection and localization based on locality alignment discriminant analysis

NASA Astrophysics Data System (ADS)

Lin, Mingquan; Chen, Weifu; Zhao, Mingbo; Gibson, Eli; Bastian-Jordan, Matthew; Cool, Derek W.; Kassam, Zahra; Chow, Tommy W. S.; Ward, Aaron; Chiu, Bernard

2017-03-01

Prostatic adenocarcinoma is one of the most commonly occurring cancers among men in the world, and it also the most curable cancer when it is detected early. Multiparametric MRI (mpMRI) combines anatomic and functional prostate imaging techniques, which have been shown to produce high sensitivity and specificity in cancer localization, which is important in planning biopsies and focal therapies. However, in previous investigations, lesion localization was achieved mainly by manual segmentation, which is time-consuming and prone to observer variability. Here, we developed an algorithm based on locality alignment discriminant analysis (LADA) technique, which can be considered as a version of linear discriminant analysis (LDA) localized to patches in the feature space. Sensitivity, specificity and accuracy generated by the proposed algorithm in five prostates by LADA were 52.2%, 89.1% and 85.1% respectively, compared to 31.3%, 85.3% and 80.9% generated by LDA. The delineation accuracy attainable by this tool has a potential in increasing the cancer detection rate in biopsies and in minimizing collateral damage of surrounding tissues in focal therapies.

Anderson localization of shear waves observed by magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Papazoglou, S.; Klatt, D.; Braun, J.; Sack, I.

2010-07-01

In this letter we present for the first time an experimental investigation of shear wave localization using motion-sensitive magnetic resonance imaging (MRI). Shear wave localization was studied in gel phantoms containing arrays of randomly positioned parallel glass rods. The phantoms were exposed to continuous harmonic vibrations in a frequency range from 25 to 175 Hz, yielding wavelengths on the order of the elastic mean free path, i.e. the Ioffe-Regel criterion of Anderson localization was satisfied. The experimental setup was further chosen such that purely shear horizontal waves were induced to avoid effects due to mode conversion and pressure waves. Analysis of the distribution of shear wave intensity in experiments and simulations revealed a significant deviation from Rayleigh statistics indicating that shear wave energy is localized. This observation is further supported by experiments on weakly scattering samples exhibiting Rayleigh statistics and an analysis of the multifractality of wave functions. Our results suggest that motion-sensitive MRI is a promising tool for studying Anderson localization of time-harmonic shear waves, which are increasingly used in dynamic elastography.

Effects of strain differences and vehicles on results of local lymph node assays.

PubMed

Anzai, Takayuki; Ullmann, Ludwig G; Hayashi, Daisuke; Satoh, Tetsuo; Kumazawa, Takeshi; Sato, Keizo

2010-01-01

The Local Lymph Node Assay (LLNA) is now regarded as the worldwide standard. The analysis of accumulated LLNA data reveals that the animal strains and vehicles employed are likely to affect LLNA results. Here we show that an obvious strain difference in the local lymph node response was observed between DMSO-treated CBA/CaOlaHsd and CBA/CaHsdRcc mice. We also show that a vehicle difference in the response was observed when CBA/CaHsdRcc mice were exposed to 6 vehicles; 4:1 v/v acetone/olive oil (AOO), ethanol/water (70% EtOH), N,N-dimethylformamide (DMF), 2-butanone (BN), propylene glycol (PG), and dimethylsulfoxide (DMSO). The dpm/LN level was lowest in the 70% EtOH group and highest in the DMSO group. When alpha-hexylcinnamaldehyde (HCA) was used as a sensitizer for the LLNA, HCA was a weak sensitizer when AOO or DMSO was used as a vehicle, but a moderate sensitizer when the other 4 vehicles were used. This study showed that there are vehicle differences in the local lymph node response (dpm/LN level) in the LLNA and that the sensitization potency of HCA may be classified in different categories when using different vehicles. This suggests that careful consideration should be exercised in selecting a vehicle for the LLNA. A further comprehensive study will be needed to investigate why vehicle differences are observed in the LLNA.

Spatial covert attention increases contrast sensitivity across the CSF: support for signal enhancement

NASA Technical Reports Server (NTRS)

Carrasco, M.; Penpeci-Talgar, C.; Eckstein, M.

2000-01-01

This study is the first to report the benefits of spatial covert attention on contrast sensitivity in a wide range of spatial frequencies when a target alone was presented in the absence of a local post-mask. We used a peripheral precue (a small circle indicating the target location) to explore the effects of covert spatial attention on contrast sensitivity as assessed by orientation discrimination (Experiments 1-4), detection (Experiments 2 and 3) and localization (Experiment 3) tasks. In all four experiments the target (a Gabor patch ranging in spatial frequency from 0.5 to 10 cpd) was presented alone in one of eight possible locations equidistant from fixation. Contrast sensitivity was consistently higher for peripherally- than for neutrally-cued trials, even though we eliminated variables (distracters, global masks, local masks, and location uncertainty) that are known to contribute to an external noise reduction explanation of attention. When observers were presented with vertical and horizontal Gabor patches an external noise reduction signal detection model accounted for the cueing benefit in a discrimination task (Experiment 1). However, such a model could not account for this benefit when location uncertainty was reduced, either by: (a) Increasing overall performance level (Experiment 2); (b) increasing stimulus contrast to enable fine discriminations of slightly tilted suprathreshold stimuli (Experiment 3); and (c) presenting a local post-mask (Experiment 4). Given that attentional benefits occurred under conditions that exclude all variables predicted by the external noise reduction model, these results support the signal enhancement model of attention.

Identifying optimal threshold statistics for elimination of hookworm using a stochastic simulation model.

PubMed

Truscott, James E; Werkman, Marleen; Wright, James E; Farrell, Sam H; Sarkar, Rajiv; Ásbjörnsdóttir, Kristjana; Anderson, Roy M

2017-06-30

There is an increased focus on whether mass drug administration (MDA) programmes alone can interrupt the transmission of soil-transmitted helminths (STH). Mathematical models can be used to model these interventions and are increasingly being implemented to inform investigators about expected trial outcome and the choice of optimum study design. One key factor is the choice of threshold for detecting elimination. However, there are currently no thresholds defined for STH regarding breaking transmission. We develop a simulation of an elimination study, based on the DeWorm3 project, using an individual-based stochastic disease transmission model in conjunction with models of MDA, sampling, diagnostics and the construction of study clusters. The simulation is then used to analyse the relationship between the study end-point elimination threshold and whether elimination is achieved in the long term within the model. We analyse the quality of a range of statistics in terms of the positive predictive values (PPV) and how they depend on a range of covariates, including threshold values, baseline prevalence, measurement time point and how clusters are constructed. End-point infection prevalence performs well in discriminating between villages that achieve interruption of transmission and those that do not, although the quality of the threshold is sensitive to baseline prevalence and threshold value. Optimal post-treatment prevalence threshold value for determining elimination is in the range 2% or less when the baseline prevalence range is broad. For multiple clusters of communities, both the probability of elimination and the ability of thresholds to detect it are strongly dependent on the size of the cluster and the size distribution of the constituent communities. Number of communities in a cluster is a key indicator of probability of elimination and PPV. Extending the time, post-study endpoint, at which the threshold statistic is measured improves PPV value in discriminating between eliminating clusters and those that bounce back. The probability of elimination and PPV are very sensitive to baseline prevalence for individual communities. However, most studies and programmes are constructed on the basis of clusters. Since elimination occurs within smaller population sub-units, the construction of clusters introduces new sensitivities for elimination threshold values to cluster size and the underlying population structure. Study simulation offers an opportunity to investigate key sources of sensitivity for elimination studies and programme designs in advance and to tailor interventions to prevailing local or national conditions.

Localized Mechanical Properties of Friction Stir Processed Sensitized 5456-H116 Al

DTIC Science & Technology

2013-04-01

5  Tensile Testing and Fractography ...boundaries and sensitization was performed using Barker’s reagent and a 40% phosphoric etch respectively. Post-fracture fractography was performed...Tensile Testing and Fractography As the level of sensitization is reduced or unobserved within the stir zone and up to 12mm from the edges, micro-tensile

Results with OECD recommended positive control sensitizers in the maximization, Buehler and local lymph node assays.

PubMed

Basketter, D A; Selbie, E; Scholes, E W; Lees, D; Kimber, I; Botham, P A

1993-01-01

The guinea pig maximization test and the Buehler occluded patch test are used widely to identify the sensitization potential of new chemicals. This information enables toxicologists and/or regulatory authorities to determine whether a chemical should be classified formally as a skin sensitizer. Both to improve and to harmonize these assessments internationally, the OECD has recommended recently that moderate rather than strong contact sensitizers are used as positive control substances. The purpose is to ensure an adequate level of sensitivity in sensitization assays performed at specific testing establishments. Results from two laboratories reported here show that the minimum acceptable standard laid down by the OECD can be achieved and indeed commonly exceeded by a substantial margin. Furthermore, results with these positive controls in a new method, the local lymph node assay, also appear to satisfy similar criteria, suggesting results from this assay, including negative data, should be acceptable for classification purposes. However, a review of the way in which results with new chemicals will be interpreted for regulatory purposes, in the context of positive control data, reveals that considerable inadequacies still exist. It is recommended that ultimately, sensitization data can only be interpreted meaningfully (i.e. to protect humans from sensitization hazards) by considering the potency of the contact allergen in the context of the sensitivity of the assay performed at the particular testing institution.

Financing intersectoral health promotion programmes: some reasons why collaborators are collaborating as indicated by cost-effectiveness analyses.

PubMed

Johansson, Pia; Tillgren, Per

2011-03-01

Intersectoral collaboration is an important part of many health promotion programmes. The reasons for the local organisations to collaborate, i.e. to finance programmes, are presumably based on benefits they derive from the collaboration. The aim of this study is to discuss whether subsector financial analyses based on data from cost-effectiveness analyses reflect incentives of collaborating organisations in two intersectoral health promotion programmes. Within economics, financial incentives are important reasons for actions. The financial incentives of collaborators are exemplified with two subsector financial analyses containing avoided disease-related costs as estimated in two cost-effectiveness analyses, on an elderly safety promotion programme (Safe Seniors in Sundbyberg) and on a diabetes prevention programme (Stockholm Diabetes Prevention Program, SDPP) from Stockholm, Sweden. The subsector financial analyses indicate that there are financial incentives for the key local community organisation, i.e. the local authority, to collaborate in one of the programmes but not the other. There are no financial benefits for other important community organisations, such as non-governmental organisations. The reasons for collaborating organisations to collaborate within intersectoral health promotion programmes extend beyond financial benefits from averted disease. Thus, the reported subsector financial analyses are only partial reflections of the incentives of collaborators, but they might be used as a starting point for discussions on cost sharing among potential intersectoral collaborators.

Sensitivities of Greenland ice sheet volume inferred from an ice sheet adjoint model

NASA Astrophysics Data System (ADS)

Heimbach, P.; Bugnion, V.

2009-04-01

We present a new and original approach to understanding the sensitivity of the Greenland ice sheet to key model parameters and environmental conditions. At the heart of this approach is the use of an adjoint ice sheet model. Since its introduction by MacAyeal (1992), the adjoint method has become widespread to fit ice stream models to the increasing number and diversity of satellite observations, and to estimate uncertain model parameters such as basal conditions. However, no attempt has been made to extend this method to comprehensive ice sheet models. As a first step toward the use of adjoints of comprehensive three-dimensional ice sheet models we have generated an adjoint of the ice sheet model SICOPOLIS of Greve (1997). The adjoint was generated by means of the automatic differentiation (AD) tool TAF. The AD tool generates exact source code representing the tangent linear and adjoint model of the nonlinear parent model provided. Model sensitivities are given by the partial derivatives of a scalar-valued model diagnostic with respect to the controls, and can be efficiently calculated via the adjoint. By way of example, we determine the sensitivity of the total Greenland ice volume to various control variables, such as spatial fields of basal flow parameters, surface and basal forcings, and initial conditions. Reliability of the adjoint was tested through finite-difference perturbation calculations for various control variables and perturbation regions. Besides confirming qualitative aspects of ice sheet sensitivities, such as expected regional variations, we detect regions where model sensitivities are seemingly unexpected or counter-intuitive, albeit ``real'' in the sense of actual model behavior. An example is inferred regions where sensitivities of ice sheet volume to basal sliding coefficient are positive, i.e. where a local increase in basal sliding parameter increases the ice sheet volume. Similarly, positive ice temperature sensitivities in certain parts of the ice sheet are found (in most regions it is negativ, i.e. an increase in temperature decreases ice sheet volume), the detection of which seems highly unlikely if only conventional perturbation experiments had been used. An effort to generate an efficient adjoint with the newly developed open-source AD tool OpenAD is also under way. Available adjoint code generation tools now open up a variety of novel model applications, notably with regard to sensitivity and uncertainty analyses and ice sheet state estimation or data assimilation.

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

Perceptual interaction of local motion signals

PubMed Central

Nitzany, Eyal I.; Loe, Maren E.; Palmer, Stephanie E.; Victor, Jonathan D.

2016-01-01

Motion signals are a rich source of information used in many everyday tasks, such as segregation of objects from background and navigation. Motion analysis by biological systems is generally considered to consist of two stages: extraction of local motion signals followed by spatial integration. Studies using synthetic stimuli show that there are many kinds and subtypes of local motion signals. When presented in isolation, these stimuli elicit behavioral and neurophysiological responses in a wide range of species, from insects to mammals. However, these mathematically-distinct varieties of local motion signals typically co-exist in natural scenes. This study focuses on interactions between two kinds of local motion signals: Fourier and glider. Fourier signals are typically associated with translation, while glider signals occur when an object approaches or recedes. Here, using a novel class of synthetic stimuli, we ask how distinct kinds of local motion signals interact and whether context influences sensitivity to Fourier motion. We report that local motion signals of different types interact at the perceptual level, and that this interaction can include subthreshold summation and, in some subjects, subtle context-dependent changes in sensitivity. We discuss the implications of these observations, and the factors that may underlie them. PMID:27902829

Perceptual interaction of local motion signals.

PubMed

Nitzany, Eyal I; Loe, Maren E; Palmer, Stephanie E; Victor, Jonathan D

2016-11-01

Motion signals are a rich source of information used in many everyday tasks, such as segregation of objects from background and navigation. Motion analysis by biological systems is generally considered to consist of two stages: extraction of local motion signals followed by spatial integration. Studies using synthetic stimuli show that there are many kinds and subtypes of local motion signals. When presented in isolation, these stimuli elicit behavioral and neurophysiological responses in a wide range of species, from insects to mammals. However, these mathematically-distinct varieties of local motion signals typically co-exist in natural scenes. This study focuses on interactions between two kinds of local motion signals: Fourier and glider. Fourier signals are typically associated with translation, while glider signals occur when an object approaches or recedes. Here, using a novel class of synthetic stimuli, we ask how distinct kinds of local motion signals interact and whether context influences sensitivity to Fourier motion. We report that local motion signals of different types interact at the perceptual level, and that this interaction can include subthreshold summation and, in some subjects, subtle context-dependent changes in sensitivity. We discuss the implications of these observations, and the factors that may underlie them.

Magnitude of pseudopotential localization errors in fixed node diffusion quantum Monte Carlo

DOE PAGES

Kent, Paul R.; Krogel, Jaron T.

2017-06-22

Growth in computational resources has lead to the application of real space diffusion quantum Monte Carlo to increasingly heavy elements. Although generally assumed to be small, we find that when using standard techniques, the pseudopotential localization error can be large, on the order of an electron volt for an isolated cerium atom. We formally show that the localization error can be reduced to zero with improvements to the Jastrow factor alone, and we define a metric of Jastrow sensitivity that may be useful in the design of pseudopotentials. We employ an extrapolation scheme to extract the bare fixed node energymore » and estimate the localization error in both the locality approximation and the T-moves schemes for the Ce atom in charge states 3+/4+. The locality approximation exhibits the lowest Jastrow sensitivity and generally smaller localization errors than T-moves although the locality approximation energy approaches the localization free limit from above/below for the 3+/4+ charge state. We find that energy minimized Jastrow factors including three-body electron-electron-ion terms are the most effective at reducing the localization error for both the locality approximation and T-moves for the case of the Ce atom. Less complex or variance minimized Jastrows are generally less effective. Finally, our results suggest that further improvements to Jastrow factors and trial wavefunction forms may be needed to reduce localization errors to chemical accuracy when medium core pseudopotentials are applied to heavy elements such as Ce.« less

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

A Methodological Review of US Budget-Impact Models for New Drugs.

PubMed

Mauskopf, Josephine; Earnshaw, Stephanie

2016-11-01

A budget-impact analysis is required by many jurisdictions when adding a new drug to the formulary. However, previous reviews have indicated that adherence to methodological guidelines is variable. In this methodological review, we assess the extent to which US budget-impact analyses for new drugs use recommended practices. We describe recommended practice for seven key elements in the design of a budget-impact analysis. Targeted literature searches for US studies reporting estimates of the budget impact of a new drug were performed and we prepared a summary of how each study addressed the seven key elements. The primary finding from this review is that recommended practice is not followed in many budget-impact analyses. For example, we found that growth in the treated population size and/or changes in disease-related costs expected during the model time horizon for more effective treatments was not included in several analyses for chronic conditions. In addition, all drug-related costs were not captured in the majority of the models. Finally, for most studies, one-way sensitivity and scenario analyses were very limited, and the ranges used in one-way sensitivity analyses were frequently arbitrary percentages rather than being data driven. The conclusions from our review are that changes in population size, disease severity mix, and/or disease-related costs should be properly accounted for to avoid over- or underestimating the budget impact. Since each budget holder might have different perspectives and different values for many of the input parameters, it is also critical for published budget-impact analyses to include extensive sensitivity and scenario analyses based on realistic input values.

Detection of Subtle Hydromechanical Medium Changes Caused By a Small-Magnitude Earthquake Swarm in NE Brazil

NASA Astrophysics Data System (ADS)

D'Hour, V.; Schimmel, M.; Do Nascimento, A. F.; Ferreira, J. M.; Lima Neto, H. C.

2016-04-01

Ambient noise correlation analyses are largely used in seismology to map heterogeneities and to monitor the temporal evolution of seismic velocity changes associated mostly with stress field variations and/or fluid movements. Here we analyse a small earthquake swarm related to a main mR 3.7 intraplate earthquake in North-East of Brazil to study the corresponding post-seismic effects on the medium. So far, post-seismic effects have been observed mainly for large magnitude events. In our study, we show that we were able to detect localized structural changes even for a small earthquake swarm in an intraplate setting. Different correlation strategies are presented and their performances are also shown. We compare the classical auto-correlation with and without pre-processing, including 1-bit normalization and spectral whitening, and the phase auto-correlation. The worst results were obtained for the pre-processed data due to the loss of waveform details. The best results were achieved with the phase cross-correlation which is amplitude unbiased and sensitive to small amplitude changes as long as there exist waveform coherence superior to other unrelated signals and noise. The analysis of 6 months of data using phase auto-correlation and cross-correlation resulted in the observation of a progressive medium change after the major recorded event. The progressive medium change is likely related to the swarm activity through opening new path ways for pore fluid diffusion. We further observed for the auto-correlations a lag time frequency-dependent change which likely indicates that the medium change is localized in depth. As expected, the main change is observed along the fault.

Colon and rectal cancer incidence and water trihalomethane concentrations in New South Wales, Australia

PubMed Central

2014-01-01

Background There is evidence, although inconsistent, that long term exposure to disinfection by products (DBPs) increases the risk of bowel cancer. No study has been conducted in Australia to examine this association and due to difference in the methods of disinfection the risk can vary across geographical regions and. This study was conducted to analyse the association of trihalomethanes (THMs) in water with colon and rectal cancer in NSW Australia. Methods Average yearly concentrations of total and individual species of THMs were obtained for 50 local government areas (LGAs). Indirectly-standardized incidence rates of colon and rectal cancers in LGAs for the period 1995 to 2001 were regressed against mean THM concentrations lagged five years, adjusting for socioeconomic status, high risk drinking, smoking status, usual source of water and year of diagnosis, including local and global random effects within a Bayesian framework. The incidence rate ratios (IRRs) for an interquartile range (IQR) increase in THMs were estimated. Results Using five year lag of exposure there was a positive association between bromoform concentration and CRC in men (IRR = 1.025, 95% CI 1.010, 1.040) but not in women (IRR = 1.003, 95% CI 0.987, 1.018). The association in men was mainly found in colon cancer with bromoform (IRR = 1.035, 95% CI 1.017, 1.053). There was no appreciable association of colorectal cancer with other species of THMs. Sensitivity analyses did not materially change the associations observed. Conclusion A positive association was observed between colon cancer and water bromoform concentrations in men. Given the potential population impact of such an association, further research into the relationship between THMs, particularly brominated species, and colorectal cancer is warranted. PMID:24938491

The NURSING-Positive Recruitment Arabic Model (NURS-P.R.A.M.): A Mixed Methods Study.

PubMed

Tawash, Eman; Cowman, Seamus

2018-06-12

To identify factors influencing high school students' choice of nursing and explore strategic interventions to promote nursing as a career in the Arab region. This study forms part of a PhD thesis, conducted in Bahrain, in a healthcare environment with a high dependence on expatriate nurses to maintain nursing services. However, in attracting local candidates to study nursing, the public image of nursing in the Middle East must be improved by implementing strategies that are sensitive to the Arabic culture. A mixed methods approach incorporating quantitative and qualitative dimensions. Data were collected between 2012-2015 using self-administered questionnaires, semi-structured interviews, focus groups and written narratives. The study sample included high school students, parents, career guidance counsellors and nursing students. A one-group pre-test post-test design was used to introduce a nursing recruitment intervention to high school students. SPSS was used to analyse quantitative data. Colaizzi's (1978) and Krueger's (1994) frameworks were applied to analyse the qualitative data. It is proposed that the public perceptions of Arab people about nursing may be grounded in strong cultural influences and any efforts to improve the enrolment and retention of local nurses should consider enhancing the social values of the nursing profession. The NURSING-Positive Recruitment Arabic Model incorporates essential elements which will guide nursing recruitment in the Arabic cultures. The study findings reflect certain issues similar to the core international literature on nursing recruitment, however there are fundamental issues particular to the Arab region, which must be included in the development of a nursing recruitment strategy for Arabic nursing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Health reform and out-of-pocket payments: lessons from China.

PubMed

Zhang, Lufa; Liu, Nan

2014-03-01

China's ongoing new health reform aims to reduce individual out-of-pocket (OOP) payments for healthcare services. The aim of this article is to analyse the impact of this reform and to draw policy implications. Data are retrieved from the relevant government publications. Polynomial regression models are used to predict future health expenditures. An extensive sensitivity analysis is conducted to investigate the ratios of OOP payments to the total health expenditures (THEs) and to the disposable personal income (DPI) for 2009-11 under different scenarios of cost projections and personal income distributions. Both quantitative and qualitative analyses are carried out to draw conclusions. The ratios of OOP payments to THE and DPI vary significantly across scenarios tested. Only if all committed government investments and social health expenditure are realized can China's new health reform reduce both ratios and achieve its target goals. In particular, the ratio of OOP payments to DPI can also be significantly reduced by improving income distribution. Due to the complicated interplay among different cost components in health expenditures, these two ratios may not change in the same direction, indicating that both need to be examined when evaluating the reform. The new health reform in China aims to alleviate the high OOP payments for healthcare services, but it has not yet been able to reduce both OOP-to-THE and OOP-to-DPI ratios simultaneously. Major reasons include (1) inability of local governments to fulfil their responsible investments due to health finance decentralization and uneven economic development in China and (2) a serious cost inflation in health expenditures coupled with a low level of income distribution. It is suggested that the central government should bear more financial responsibility and assist local governments to fully invest, and should improve individual incomes, in particular for the poor.

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.

Multi-scale approach for 3D hydrostratigraphic and groundwater flow modelling of Milan (Northern Italy) urban aquifers.

NASA Astrophysics Data System (ADS)

De Caro, Mattia; Crosta, Giovanni; Frattini, Paolo; Perico, Roberta

2017-04-01

During the last century, urban groundwater was heavily exploited for public and industrial supply. As the water demands of industry have fallen, many cities are now experiencing rising groundwater levels with consequent concerns about localized flooding of basements, reduction of soil bearing capacities under foundations, soil internal erosion and the mobilization of contaminants. The city of Milan (Northern Italy) draws water for domestic and industrial purposes from aquifers beneath the urban area. The rate of abstraction has been varying during the last century, depending upon the number of inhabitants and the development of industrial activities. The groundwater abstraction raised to a maximum of about 350x106 m3/yr in the middle 1970s and has successively decreased to a value of about 230x106 m3/yr at present days. This caused a water table raise at an average rate of about 1 m/yr inducing infiltrations and flooding of deep constructions (e.g. building foundations and basements, underground subway excavations). Starting from a large hydrostratigraphic database (8628 borehole logs), a multi-scale approach for the reconstruction of the aquifers geometry (unconfined and semi-confined) at regional-scale has been used. First, a three-level hierarchical classification of the lithologies (lithofacies, hydrofacies, aquifer groups) has been adopted. Then, the interpretation of several 2D cross-sections was attained with Target for ArcGIS exploration software. The interpretation of cross-sections was based on the characteristics of depositional environments of the analysed aquifers (from meandering plain to proximal outwash deposits), on the position of quaternary deposits, and on the distribution of geochemical parameters (i.e. indicator contaminants and major ions). Finally, the aquifer boundary surfaces were interpolated with standard algorithms. The hydraulic properties of analysed aquifers were estimated through the analyses of available step-drawdown tests (Theis with the superimposition solution) and use of empirical relationships from grain-size distribution data, respectively for semi-confined and unconfined aquifers. Finally, 3D Finite Element groundwater flow models have been developed both at regional and local "metropolitan" scale. The regional model covers an area of 3,135.15 km2, while the local model comprises the Milan metropolitan area with an extension of 457 km2. Both models were discretized into a triangular finite element mesh with local refinement in proximity of pumping wells. The element size ranges from 350 to 30 meters and from 200 to 2 meters, respectively for regional and local model. The calibration was done by the comparison with the available water level data for different years (from 1994 to 2016). The calibrated permeability values are consistent with the estimated ones and the sensitivity analysis on hydraulic parameters suggests a minor influence of the aquiclude layer separating the two aquifers. The challenge is to provide the basis for new types of applied outputs so that they may better inform strategic planning options, ground investigation, and abstraction strategies.

Differential gene expression responses distinguish contact and respiratory sensitizers and nonsensitizing irritants in the local lymph node assay.

PubMed

Adenuga, David; Woolhiser, Michael R; Gollapudi, B Bhaskar; Boverhof, Darrell R

2012-04-01

Genomic approaches have the potential to enhance the specificity and predictive accuracy of existing toxicology endpoints, including those for chemical sensitization. The present study was conducted to determine whether gene expression responses can distinguish contact sensitizers (1-chloro-2,4-dinitrobenzene [DNCB] and hexyl cinnamic aldehyde [HCA]), respiratory sensitizers (ortho-phthalaldehyde and trimellitic anhydride [TMA]), and nonsensitizing irritants (methyl salicylate [MS] and nonanoic acid [NA]) in the local lymph node assay (LLNA). Female Balb/c mice received doses of each chemical as per the standard LLNA dosing regimen on days 1, 2, and 3. Auricular lymph nodes were analyzed for tritiated thymidine ((3)HTdR) incorporation on day 6 and for gene expression responses on days 6 and 10. All chemicals induced dose-dependent increases in stimulation index, which correlated strongly with the number of differentially expressed genes. A majority of genes modulated by the irritants were similarly altered by the sensitizers, consistent with the irritating effects of the sensitizers. However, a select number of responses involved with immune-specific functions, such as dendritic cell activation, were unique to the sensitizers and may offer the ability to distinguish sensitizers from irritants. Genes for the mast cell proteases 1 and 8, Lgals7, Tim2, Aicda, Il4, and Akr1c18 were more strongly regulated by respiratory sensitizers compared with contact sensitizers and may represent potential biomarkers for discriminating between contact and respiratory sensitizers. Collectively, these data suggest that gene expression responses may serve as useful biomarkers to distinguish between respiratory and contact sensitizers and nonsensitizing irritants in the LLNA.