Image quality, threshold contrast and mean glandular dose in CR mammography

NASA Astrophysics Data System (ADS)

Jakubiak, R. R.; Gamba, H. R.; Neves, E. B.; Peixoto, J. E.

2013-09-01

In many countries, computed radiography (CR) systems represent the majority of equipment used in digital mammography. This study presents a method for optimizing image quality and dose in CR mammography of patients with breast thicknesses between 45 and 75 mm. Initially, clinical images of 67 patients (group 1) were analyzed by three experienced radiologists, reporting about anatomical structures, noise and contrast in low and high pixel value areas, and image sharpness and contrast. Exposure parameters (kV, mAs and target/filter combination) used in the examinations of these patients were reproduced to determine the contrast-to-noise ratio (CNR) and mean glandular dose (MGD). The parameters were also used to radiograph a CDMAM (version 3.4) phantom (Artinis Medical Systems, The Netherlands) for image threshold contrast evaluation. After that, different breast thicknesses were simulated with polymethylmethacrylate layers and various sets of exposure parameters were used in order to determine optimal radiographic parameters. For each simulated breast thickness, optimal beam quality was defined as giving a target CNR to reach the threshold contrast of CDMAM images for acceptable MGD. These results were used for adjustments in the automatic exposure control (AEC) by the maintenance team. Using optimized exposure parameters, clinical images of 63 patients (group 2) were evaluated as described above. Threshold contrast, CNR and MGD for such exposure parameters were also determined. Results showed that the proposed optimization method was effective for all breast thicknesses studied in phantoms. The best result was found for breasts of 75 mm. While in group 1 there was no detection of the 0.1 mm critical diameter detail with threshold contrast below 23%, after the optimization, detection occurred in 47.6% of the images. There was also an average MGD reduction of 7.5%. The clinical image quality criteria were attended in 91.7% for all breast thicknesses evaluated in both

Limitations of on-site dairy farm regulatory debits as milk quality predictors.

PubMed

Borneman, Darand L; Stiegert, Kyle; Ingham, Steve

2015-03-01

In the United States, compliance with grade A raw fluid milk regulatory standards is assessed via laboratory milk quality testing and by on-site inspection of producers (farms). This study evaluated the correlation between on-site survey debits being marked and somatic cell count (SCC) or standard plate count (SPC) laboratory results for 1,301 Wisconsin grade A dairy farms in 2012. Debits recorded on the survey form were tested as predictors of laboratory results utilizing ordinary least squares regression to determine if results of the current method for on-site evaluation of grade A dairy farms accurately predict SCC and SPC test results. Such a correlation may indicate that current methods of on-site inspection serve the primary intended purpose of assuring availability of high-quality milk. A model for predicting SCC was estimated using ordinary least squares regression methods. Step-wise selected regressors of grouped debit items were able to predict SCC levels with some degree of accuracy (adjusted R2=0.1432). Specific debit items, seasonality, and farm size were the best predictors of SCC levels. The SPC data presented an analytical challenge because over 75% of the SPC observations were at or below a 25,000 cfu/mL threshold but were recorded by testing laboratories as at the threshold value. This classic censoring problem necessitated the use of a Tobit regression approach. Even with this approach, prediction of SPC values based on on-site survey criteria was much less successful (adjusted R2=0.034) and provided little support for the on-site survey system as a way to inform farmers about making improvements that would improve SPC. The lower level of correlation with SPC may indicate that factors affecting SPC are more varied and differ from those affecting SCC. Further, unobserved deficiencies in postmilking handling and storage sanitation could enhance bacterial growth and increase SPC, whereas postmilking sanitation will have no effect on SCC because

High-resolution audiometry: an automated method for hearing threshold acquisition with quality control.

PubMed

Bian, Lin

2012-01-01

In clinical practice, hearing thresholds are measured at only five to six frequencies at octave intervals. Thus, the audiometric configuration cannot closely reflect the actual status of the auditory structures. In addition, differential diagnosis requires quantitative comparison of behavioral thresholds with physiological measures, such as otoacoustic emissions (OAEs) that are usually measured in higher resolution. The purpose of this research was to develop a method to improve the frequency resolution of the audiogram. A repeated-measure design was used in the study to evaluate the reliability of the threshold measurements. A total of 16 participants with clinically normal hearing and mild hearing loss were recruited from a population of university students. No intervention was involved in the study. Custom developed system and software were used for threshold acquisition with quality control (QC). With real-ear calibration and monitoring of test signals, the system provided accurate and individualized measure of hearing thresholds that were determined by an analysis based on signal detection theory (SDT). The reliability of the threshold measure was assessed by correlation and differences between the repeated measures. The audiometric configurations were diverse and unique to each individual ear. The accuracy, within-subject reliability, and between-test repeatability are relatively high. With QC, the high-resolution audiograms can be reliably and accurately measured. Hearing thresholds measured as ear canal sound pressures with higher frequency resolution can provide more customized hearing-aid fitting. The test system may be integrated with other physiological measures, such as OAEs, into a comprehensive evaluative tool. American Academy of Audiology.

Groundwater Quality Data for the Tahoe-Martis Study Unit, 2007: Results from the California GAMA Program

USGS Publications Warehouse

Fram, Miranda S.; Munday, Cathy; Belitz, Kenneth

2009-01-01

results obtained from these samples were used to evaluate the quality of the data for the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that data for the groundwater samples were not compromised by possible contamination during sample collection, handling or analysis. Differences between replicate samples were within acceptable ranges. Matrix spike recoveries were within acceptable ranges for most compounds. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, raw water typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw groundwater. However, to provide some context for the results, concentrations of constituents measured in the raw groundwater were compared with regulatory and nonregulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH), and with aesthetic and technical thresholds established by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only and do not indicate of compliance or noncompliance with regulatory thresholds. The concentrations of most constituents detected in groundwater samples from the Tahoe-Martis wells were below drinking-water thresholds. Organic compounds (VOCs and pesticides) were detected in about 40 percent of the samples from grid wells, and most concentrations were less than 1/100th of regulatory and nonregulatory health-based thresholds, although the conentration of perchloroethene in one sample was above the USEPA maximum contaminant level (MCL-US). Concentrations of all trace elements and nutrients in samples from grid wells were below regulatory and nonregulatory health-based thresholds, with five exceptions. Concentra

Development of water quality thresholds during dredging for the protection of benthic primary producer habitats.

PubMed

Sofonia, Jeremy J; Unsworth, Richard K F

2010-01-01

Given the potential for adverse effects of ocean dredging on marine organisms, particularly benthic primary producer communities, the management and monitoring of those activities which cause elevated turbidity and sediment loading is critical. In practice, however, this has proven challenging as the development of water quality threshold values, upon which management responses are based, are subject to a large number of physical and biological parameters that are spatially and temporally specific. As a consequence, monitoring programs to date have taken a wide range of different approaches, most focusing on measures of turbidity reported as nephelometric turbidity units (NTU). This paper presents a potential approach in the determination of water quality thresholds which utilises data gathered through the long-term deployment of in situ water instruments, but suggests a focus on photosynthetic active radiation (PAR) rather than NTU as it is more relevant biologically and inclusive of other site conditions. A simple mathematical approach to data interpretation is also presented which facilitates threshold value development, not individual values of concentrations over specific intervals, but as an equation which may be utilized in numerical modelling.

Just-in-Space: Certified Rural Products, Labor of Quality, and Regulatory Spaces

ERIC Educational Resources Information Center

Mutersbaugh, Tad

2005-01-01

Since the mid-1990s, the number and diversity of "quality-certified" products has increased dramatically. This article examines labor practices and regulatory spaces within 3rd party quality certification and suggests that this distinct configuration be termed "just-in-space" production. A privileging of space derives, on the one hand, from the…

Does GLP enhance the quality of toxicological evidence for regulatory decisions?

PubMed Central

Borgert, Christopher J.; Becker, Richard A.; Carlton, Betsy D.; Hanson, Mark; Kwiatkowski, Patricia L.; Sue Marty, Mary; McCarty, Lynn S.; Quill, Terry F.; Solomon, Keith; Van Der Kraak, Glen; Witorsch, Raphael J.; Don Yi, Kun

2016-01-01

There is debate over whether the requirements of GLP are appropriate standards for evaluating the quality of toxicological data used to formulate regulations. A group promoting the importance of non-monotonic dose responses for endocrine disruptors contend that scoring systems giving primacy to GLP are biased against non-GLP studies from the literature and are merely record-keeping exercises to prevent fraudulent reporting of data from non-published guideline toxicology studies. They argue that guideline studies often employ insensitive species and outdated methods, and ignore the perspectives of subject-matter experts in endocrine disruption, who should be the sole arbiters of data quality. We believe regulatory agencies should use both non-GLP and GLP studies, that GLP requirements assure fundamental tenets of study integrity not typically addressed by journal peer-review, and that use of standardized test guidelines and GLP promotes consistency, reliability, comparability, and harmonization of various types of studies used by regulatory agencies worldwide. This debate suffers two impediments to progress: a conflation of different phases of study interpretation and levels of data validity, and a misleading characterization of many essential components of GLP and regulatory toxicology. Herein we provide clarifications critical for removing those impediments. PMID:27208076

Air Quality Science and Regulatory Efforts Require Geostationary Satellite Measurements

NASA Technical Reports Server (NTRS)

Pickering, Kenneth E.; Allen, D. J.; Stehr, J. W.

2006-01-01

Air quality scientists and regulatory agencies would benefit from the high spatial and temporal resolution trace gas and aerosol data that could be provided by instruments on a geostationary platform. More detailed time-resolved data from a geostationary platform could be used in tracking regional transport and in evaluating mesoscale air quality model performance in terms of photochemical evolution throughout the day. The diurnal cycle of photochemical pollutants is currently missing from the data provided by the current generation of atmospheric chemistry satellites which provide only one measurement per day. Often peak surface ozone mixing ratios are reached much earlier in the day during major regional pollution episodes than during local episodes due to downward mixing of ozone that had been transported above the boundary layer overnight. The regional air quality models often do not simulate this downward mixing well enough and underestimate surface ozone in regional episodes. Having high time-resolution geostationary data will make it possible to determine the magnitude of this lower-and mid-tropospheric transport that contributes to peak eight-hour average ozone and 24-hour average PM2.5 concentrations. We will show ozone and PM(sub 2.5) episodes from the CMAQ model and suggest ways in which geostationary satellite data would improve air quality forecasting. Current regulatory modeling is typically being performed at 12 km horizontal resolution. State and regional air quality regulators in regions with complex topography and/or land-sea breezes are anxious to move to 4-km or finer resolution simulations. Geostationary data at these or finer resolutions will be useful in evaluating such models.

Determination and validation of soil thresholds for cadmium based on food quality standard and health risk assessment.

PubMed

Ding, Changfeng; Ma, Yibing; Li, Xiaogang; Zhang, Taolin; Wang, Xingxiang

2018-04-01

Cadmium (Cd) is an environmental toxicant with high rates of soil-plant transfer. It is essential to establish an accurate soil threshold for the implementation of soil management practices. This study takes root vegetable as an example to derive soil thresholds for Cd based on the food quality standard as well as health risk assessment using species sensitivity distribution (SSD). A soil type-specific bioconcentration factor (BCF, ratio of Cd concentration in plant to that in soil) generated from soil with a proper Cd concentration gradient was calculated and applied in the derivation of soil thresholds instead of a generic BCF value to minimize the uncertainty. The sensitivity variations of twelve root vegetable cultivars for accumulating soil Cd and the empirical soil-plant transfer model were investigated and developed in greenhouse experiments. After normalization, the hazardous concentrations from the fifth percentile of the distribution based on added Cd (HC5 add ) were calculated from the SSD curves fitted by Burr Type III distribution. The derived soil thresholds were presented as continuous or scenario criteria depending on the combination of soil pH and organic carbon content. The soil thresholds based on food quality standard were on average 0.7-fold of those based on health risk assessment, and were further validated to be reliable using independent data from field survey and published articles. The results suggested that deriving soil thresholds for Cd using SSD method is robust and also applicable to other crops as well as other trace elements that have the potential to cause health risk issues. Copyright © 2017 Elsevier B.V. All rights reserved.

Strengthening the regulatory system through the implementation and use of a quality management system.

PubMed

Eisner, Reinhold; Patel, Rakeshkumar

2017-04-20

Quality management systems (QMS), based on ISO 9001 requirements, are applicable to government service organizations such as Health Canada's Biologics and Genetic Therapies Directorate (BGTD). This communication presents the process that the BGTD followed since the early 2000s to implement a quality management system and describes how the regulatory system was improved as a result of this project. BGTD undertook the implementation of a quality management system based on ISO 9001 and containing aspects of ISO 17025 with the goal of strengthening the regulatory system through improvements in the people, processes, and services of the organization. We discuss the strategy used by BGTD to implement the QMS and the benefits that were realized from the various stages of implementation. The eight quality principals upon which the QMS standards of the ISO 9000 series are based were used by senior management as a framework to guide QMS implementation.

Regulatory, policy and quality update for venous thromboembolism and stroke in United States hospitals.

PubMed

Mahan, Charles E

2012-10-01

Stroke and venous thromboembolism (VTE) have a large impact on the United States (US) healthcare system. It is estimated that up to 1.7million new and recurrent stroke and VTE events are occurring in the US on an annual basis with the combined cost approaching over $200billion per year. A significant amount of stroke and VTE are preventable from appropriate antithrombotic use in at-risk patients and the Center for Medicaid and Medicare Services, the Joint Commission, the National Quality Forum and other key quality and regulatory entities have prioritized minimizing the impact of morbidity, mortality and avoidable costs related to these diseases. This review provides a brief history, overview, and update for the development of quality measures, quality systems, and regulatory and policy changes as related to stroke and VTE within the US healthcare system. Copyright © 2012 Elsevier Ltd. All rights reserved.

10 CFR Appendix E to Part 20 - Nationally Tracked Source Thresholds

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Nationally Tracked Source Thresholds E Appendix E to Part 20 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Pt. 20, App. E Appendix E to Part 20— Nationally Tracked Source Thresholds The Terabecquerel (TBq) values are the...

10 CFR Appendix E to Part 20 - Nationally Tracked Source Thresholds

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Nationally Tracked Source Thresholds E Appendix E to Part 20 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Pt. 20, App. E Appendix E to Part 20— Nationally Tracked Source Thresholds The Terabecquerel (TBq) values are the...

10 CFR Appendix E to Part 20 - Nationally Tracked Source Thresholds

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Nationally Tracked Source Thresholds E Appendix E to Part 20 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Pt. 20, App. E Appendix E to Part 20— Nationally Tracked Source Thresholds The Terabecquerel (TBq) values are the...

10 CFR Appendix E to Part 20 - Nationally Tracked Source Thresholds

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Nationally Tracked Source Thresholds E Appendix E to Part 20 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Pt. 20, App. E Appendix E to Part 20— Nationally Tracked Source Thresholds The Terabecquerel (TBq) values are the...

10 CFR Appendix E to Part 20 - Nationally Tracked Source Thresholds

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Nationally Tracked Source Thresholds E Appendix E to Part 20 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Pt. 20, App. E Appendix E to Part 20— Nationally Tracked Source Thresholds The Terabecquerel (TBq) values are the...

Influence of the chemical structure on odor qualities and odor thresholds of halogenated guaiacol-derived odorants

NASA Astrophysics Data System (ADS)

Juhlke, Florian; Lorber, Katja; Wagenstaller, Maria; Buettner, Andrea

2017-12-01

Chlorinated guaiacol derivatives are found in waste water of pulp mills using chlorine in the bleaching process of wood pulp. They can also be detected in fish tissue, possibly causing off-odors. To date, there is no systematic investigation on the odor properties of halogenated guaiacol derivatives. To close this gap, odor thresholds in air and odor qualities of 14 compounds were determined by gas chromatography-olfactometry. Overall, the investigated compounds elicited smells that are characteristic for guaiacol, namely smoky, sweet, vanilla-like, but also medicinal and plaster-like. Their odor thresholds in air were, however, very low, ranging from 0.00072 to 23 ng/Lair. The lowest thresholds were found for 5-chloro- and 5-bromoguaiacol, followed by 4,5-dichloro- and 6-chloroguaiacol. Moreover, some inter-individual differences in odor threshold values could be observed, with the highest variations having been recorded for the individual values of 5-iodo- and 4-bromoguaiacol.

Rethinking the Clinically Based Thresholds of TransCelerate BioPharma for Risk-Based Monitoring.

PubMed

Zink, Richard C; Dmitrienko, Anastasia; Dmitrienko, Alex

2018-01-01

The quality of data from clinical trials has received a great deal of attention in recent years. Of central importance is the need to protect the well-being of study participants and maintain the integrity of final analysis results. However, traditional approaches to assess data quality have come under increased scrutiny as providing little benefit for the substantial cost. Numerous regulatory guidance documents and industry position papers have described risk-based approaches to identify quality and safety issues. In particular, the position paper of TransCelerate BioPharma recommends defining risk thresholds to assess safety and quality risks based on past clinical experience. This exercise can be extremely time-consuming, and the resulting thresholds may only be relevant to a particular therapeutic area, patient or clinical site population. In addition, predefined thresholds cannot account for safety or quality issues where the underlying rate of observing a particular problem may change over the course of a clinical trial, and often do not consider varying patient exposure. In this manuscript, we appropriate rules commonly utilized for funnel plots to define a traffic-light system for risk indicators based on statistical criteria that consider the duration of patient follow-up. Further, we describe how these methods can be adapted to assess changing risk over time. Finally, we illustrate numerous graphical approaches to summarize and communicate risk, and discuss hybrid clinical-statistical approaches to allow for the assessment of risk at sites with low patient enrollment. We illustrate the aforementioned methodologies for a clinical trial in patients with schizophrenia. Funnel plots are a flexible graphical technique that can form the basis for a risk-based strategy to assess data integrity, while considering site sample size, patient exposure, and changing risk across time.

An Approach to Industrial Stormwater Benchmarks: Establishing and Using Site-Specific Threshold Criteria at Lawrence Livermore National Laboratory

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

Campbell, C G; Mathews, S

2006-09-07

Current regulatory schemes use generic or industrial sector specific benchmarks to evaluate the quality of industrial stormwater discharges. While benchmarks can be a useful tool for facility stormwater managers in evaluating the quality stormwater runoff, benchmarks typically do not take into account site-specific conditions, such as: soil chemistry, atmospheric deposition, seasonal changes in water source, and upstream land use. Failing to account for these factors may lead to unnecessary costs to trace a source of natural variation, or potentially missing a significant local water quality problem. Site-specific water quality thresholds, established upon the statistical evaluation of historic data take intomore » account these factors, are a better tool for the direct evaluation of runoff quality, and a more cost-effective trigger to investigate anomalous results. Lawrence Livermore National Laboratory (LLNL), a federal facility, established stormwater monitoring programs to comply with the requirements of the industrial stormwater permit and Department of Energy orders, which require the evaluation of the impact of effluent discharges on the environment. LLNL recognized the need to create a tool to evaluate and manage stormwater quality that would allow analysts to identify trends in stormwater quality and recognize anomalous results so that trace-back and corrective actions could be initiated. LLNL created the site-specific water quality threshold tool to better understand the nature of the stormwater influent and effluent, to establish a technical basis for determining when facility operations might be impacting the quality of stormwater discharges, and to provide ''action levels'' to initiate follow-up to analytical results. The threshold criteria were based on a statistical analysis of the historic stormwater monitoring data and a review of relevant water quality objectives.« less

Groundwater-Quality Data in the Madera-Chowchilla Study Unit, 2008: Results from the California GAMA Program

USGS Publications Warehouse

Shelton, Jennifer L.; Fram, Miranda S.; Belitz, Kenneth

2009-01-01

, oxygen, and carbon, and activities of tritium and carbon-14), and dissolved noble gases also were measured to help identify the sources and ages of the sampled groundwater. In total, approximately 300 constituents and field water-quality indicators were investigated. Three types of quality-control samples (blanks, replicates, and samples for matrix spikes) each were collected at approximately 11 percent of the wells sampled for each analysis, and the results obtained from these samples were used to evaluate the quality of the data for the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that data for the groundwater samples were not compromised by possible contamination during sample collection, handling or analysis. Differences between replicate samples were within acceptable ranges. Matrix spike recoveries were within acceptable ranges for most compounds. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, raw groundwater typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw groundwater. However, to provide some context for the results, concentrations of constituents measured in the raw groundwater were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH), and with aesthetic and technical thresholds established by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only, and are not indicative of compliance or non-compliance with regulatory thresholds. The concentrations of most constituents detected in groundwater samples from MADCHOW wells were below drinking-water thresholds. Organic compounds (VOCs and pesticides

Effects of different regulatory methods on improvement of greenhouse saline soils, tomato quality, and yield.

PubMed

Maomao, Hou; Xiaohou, Shao; Yaming, Zhai

2014-01-01

To identify effective regulatory methods scheduling with the compromise between the soil desalination and the improvement of tomato quality and yield, a 3-year field experiment was conducted to evaluate and compare the effect of straw mulching and soil structure conditioner and water-retaining agent on greenhouse saline soils, tomato quality, and yield. A higher salt removing rate of 80.72% in plough layer with straw mulching was obtained based on the observation of salt mass fraction in 0 ~ 20 cm soil layer before and after the experiment. Salts were also found to move gradually to the deeper soil layer with time. Straw mulching enhanced the content of soil organic matter significantly and was conductive to reserve soil available N, P, and K, while available P and K in soils of plough layer with soil structure conditioner decreased obviously; thus a greater usage of P fertilizer and K fertilizer was needed when applying soil structure conditioner. Considering the evaluation indexes including tomato quality, yield, and desalination effects of different regulatory methods, straw mulching was recommended as the main regulatory method to improve greenhouse saline soils in south China. Soil structure conditioner was the suboptimal method, which could be applied in concert with straw mulching.

Variable-Threshold Threshold Elements,

DTIC Science & Technology

A threshold element is a mathematical model of certain types of logic gates and of a biological neuron. Much work has been done on the subject of... threshold elements with fixed thresholds; this study concerns itself with elements in which the threshold may be varied, variable- threshold threshold ...elements. Physical realizations include resistor-transistor elements, in which the threshold is simply a voltage. Variation of the threshold causes the

Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures

PubMed Central

Wang, Xinchen; Tucker, Nathan R; Rizki, Gizem; Mills, Robert; Krijger, Peter HL; de Wit, Elzo; Subramanian, Vidya; Bartell, Eric; Nguyen, Xinh-Xinh; Ye, Jiangchuan; Leyton-Mange, Jordan; Dolmatova, Elena V; van der Harst, Pim; de Laat, Wouter; Ellinor, Patrick T; Newton-Cheh, Christopher; Milan, David J; Kellis, Manolis; Boyer, Laurie A

2016-01-01

Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability, suggesting that meaningful associations lie 'hidden' below current thresholds. Here, we integrate information from association studies with epigenomic maps to demonstrate that enhancers significantly overlap known loci associated with the cardiac QT interval and QRS duration. We apply functional criteria to identify loci associated with QT interval that do not meet genome-wide significance and are missed by existing studies. We demonstrate that these 'sub-threshold' signals represent novel loci, and that epigenomic maps are effective at discriminating true biological signals from noise. We experimentally validate the molecular, gene-regulatory, cellular and organismal phenotypes of these sub-threshold loci, demonstrating that most sub-threshold loci have regulatory consequences and that genetic perturbation of nearby genes causes cardiac phenotypes in mouse. Our work provides a general approach for improving the detection of novel loci associated with complex human traits. DOI: http://dx.doi.org/10.7554/eLife.10557.001 PMID:27162171

Self-regulatory fatigue in hematologic malignancies: impact on quality of life, coping, and adherence to medical recommendations.

PubMed

Solberg Nes, Lise; Ehlers, Shawna L; Patten, Christi A; Gastineau, Dennis A

2013-03-01

Hematopoietic stem cell transplantation (HSCT) is an intensive cancer therapy entailing numerous physical, emotional, cognitive, and practical challenges. Patients' ability to adjust and cope with such challenges may depend on their ability to exert control over cognitive, emotional, and behavioral processes, that is, ability to self-regulate. Self-regulatory capacity is a limited resource that can be depleted or fatigued (i.e., "self-regulatory fatigue"), particularly in the context of stressful life events such as cancer diagnosis and treatment. This is one of the first studies to examine self-regulatory fatigue in a cancer population. The current study aimed to (1) extract items for a specific scale of self-regulatory capacity and (2) examine the impact of such capacity on adaptation in patients with hematologic malignancies preparing for HSCT. Factor analysis of four existing scales gauging psychological adjustment and well-being in 314 patients preparing for HSCT (63% male and 89% Caucasian) identified 23 items (α = 0.85) related to self-regulatory control or fatigue. This measure was then examined using existing clinical data obtained from 178 patients (57% male and 91% Caucasian) undergoing treatment for hematologic malignancies in relationship to quality of life, coping, and self-reported adherence to physicians' recommendations. Controlling for pain severity, physical fatigue, and depression, self-regulatory fatigue scores were incrementally associated with decreased quality of life, use of avoidance coping strategies, and decreased adherence to physicians' recommendations. These results emphasize the potential role of self-regulatory capacity in coping with and adjusting to hematologic cancers and future research is warranted.

Analytical quality by design: a tool for regulatory flexibility and robust analytics.

PubMed

Peraman, Ramalingam; Bhadraya, Kalva; Padmanabha Reddy, Yiragamreddy

2015-01-01

Very recently, Food and Drug Administration (FDA) has approved a few new drug applications (NDA) with regulatory flexibility for quality by design (QbD) based analytical approach. The concept of QbD applied to analytical method development is known now as AQbD (analytical quality by design). It allows the analytical method for movement within method operable design region (MODR). Unlike current methods, analytical method developed using analytical quality by design (AQbD) approach reduces the number of out-of-trend (OOT) results and out-of-specification (OOS) results due to the robustness of the method within the region. It is a current trend among pharmaceutical industry to implement analytical quality by design (AQbD) in method development process as a part of risk management, pharmaceutical development, and pharmaceutical quality system (ICH Q10). Owing to the lack explanatory reviews, this paper has been communicated to discuss different views of analytical scientists about implementation of AQbD in pharmaceutical quality system and also to correlate with product quality by design and pharmaceutical analytical technology (PAT).

Analytical Quality by Design: A Tool for Regulatory Flexibility and Robust Analytics

PubMed Central

Bhadraya, Kalva; Padmanabha Reddy, Yiragamreddy

2015-01-01

Very recently, Food and Drug Administration (FDA) has approved a few new drug applications (NDA) with regulatory flexibility for quality by design (QbD) based analytical approach. The concept of QbD applied to analytical method development is known now as AQbD (analytical quality by design). It allows the analytical method for movement within method operable design region (MODR). Unlike current methods, analytical method developed using analytical quality by design (AQbD) approach reduces the number of out-of-trend (OOT) results and out-of-specification (OOS) results due to the robustness of the method within the region. It is a current trend among pharmaceutical industry to implement analytical quality by design (AQbD) in method development process as a part of risk management, pharmaceutical development, and pharmaceutical quality system (ICH Q10). Owing to the lack explanatory reviews, this paper has been communicated to discuss different views of analytical scientists about implementation of AQbD in pharmaceutical quality system and also to correlate with product quality by design and pharmaceutical analytical technology (PAT). PMID:25722723

Quality of drug stores: Storage practices & Regulatory compliance in Karachi, Pakistan

PubMed Central

Shah, Syed Shaukat Ali Muttaqi; Naqvi, Baqar Shyum; Fatima, Mashhad; Khaliq, Asif; Sheikh, Abdul Latif; Baqar, Muhammad

2016-01-01

Objective: To assess and evaluate the drug storage quality and regulatory compliance among privately operated drug stores of Karachi Pakistan. Methods: A cross-sectional survey of drug stores located in Karachi was conducted from May to December 2013. A total of 1003 drug stores that were involved in the sales, purchase and dispensing of pharmaceutical products were approached by non-probability purposive sampling technique, and the information was collected using a close ended, structured questionnaire. Results: Out of 1003 drug stores inspected only 4.1%(n=41) were found compliant to regulatory requirements. Most of the stores 74.9%(n=752) were selling general items along with the drugs. Only 12%(n=124) stores were having qualified person working on the store, out of which 33% were pharmacist. 47.4%(n=400) of the stores had drug sales license displayed in the premises and 33.4%(n=282) of the stores had expired drug sales license. 11.4%(n=94) stores were found selling vaccines without proper refrigerator and only 11.7% stores had the power backup for the refrigerator. Only 40.2%(n=403) of stores were protected from direct sunlight and 5.4%(n=54) having air conditioning in the premises. Conclusion: The regulatory compliance of majority of the drug stores operated privately in different areas of Karachi is below standard. Only a few drugs stores have adequate facilities to protect the drugs from extreme temperature, sunlight and provision of refrigeration. Very few of the drug stores carry out drug sales under the supervision of qualified pharmacist. There is a dire need to improve the storage practices in the drug stores by complying with the regulatory standards/laws as specified by the Drug Regulatory Authority of Pakistan. PMID:27881996

Groundwater-Quality Data in the Antelope Valley Study Unit, 2008: Results from the California GAMA Program

USGS Publications Warehouse

Schmitt, Stephen J.; Milby Dawson, Barbara J.; Belitz, Kenneth

2009-01-01

-control samples (blanks, replicates, and samples for matrix spikes) were collected at 12 percent of the wells, and the results for these samples were used to evaluate the quality of the data for the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a noticeable source of bias in the data for the groundwater samples. Differences between replicate samples generally were within acceptable ranges, indicating acceptably low variability. Matrix spike recoveries were within acceptable ranges for most compoundsThis study did not evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw groundwater. However, to provide some context for the results, concentrations of constituents measured in the raw groundwater were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only, and are not indicative of compliance or non-compliance with drinking water standards. Most constituents that were detected in groundwater samples were found at concentrations below drinking-water thresholds. Volatile organic compounds (VOCs) were detected in about one-half of the samples and pesticides detected in about one-third of the samples; all detections of these constituents were below health-based thresholds. Most detections of trace elements and nutrients in samples from ANT wells were below health-based thresholds. Exceptions include: one detection of nitrite plus nitr

Olive oil authentication: A comparative analysis of regulatory frameworks with especial emphasis on quality and authenticity indices, and recent analytical techniques developed for their assessment. A review.

PubMed

Bajoub, Aadil; Bendini, Alessandra; Fernández-Gutiérrez, Alberto; Carrasco-Pancorbo, Alegría

2018-03-24

Over the last decades, olive oil quality and authenticity control has become an issue of great importance to consumers, suppliers, retailers, and regulators in both traditional and emerging olive oil producing countries, mainly due to the increasing worldwide popularity and the trade globalization of this product. Thus, in order to ensure olive oil authentication, various national and international laws and regulations have been adopted, although some of them are actually causing an enormous debate about the risk that they can represent for the harmonization of international olive oil trade standards. Within this context, this review was designed to provide a critical overview and comparative analysis of selected regulatory frameworks for olive oil authentication, with special emphasis on the quality and purity criteria considered by these regulation systems, their thresholds and the analytical methods employed for monitoring them. To complete the general overview, recent analytical advances to overcome drawbacks and limitations of the official methods to evaluate olive oil quality and to determine possible adulterations were reviewed. Furthermore, the latest trends on analytical approaches to assess the olive oil geographical and varietal origin traceability were also examined.

Monitoring quality of care at dialysis facilities: a case for regulatory parsimony--and beyond.

PubMed

Stivelman, John C

2012-10-01

With the issuance of the new Conditions for Coverage in 2008 and the implementation of the Prospective Payment System in 2011, the Centers for Medicare & Medicaid Services has fundamentally altered the regulatory landscape of quality in the ESRD program. Although these changes-largely through use of tools comparing individual facility performance to regional and national quality expectations-have increased facility accountability for the quality of patient care in many quarters, they have also complicated both substance and process of facility adherence to quality rules in that component of the program. This editorial critically assesses the main quality tools now in use for dialysis facilities and reviews the issues arising from their conjoint use. A scheme for improving the effectiveness of each quality tool is proposed, and an assessment of their future value and effectiveness in quality improvement is offered.

Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective.

PubMed

Feltelius, Nils; Gedeborg, Rolf; Holm, Lennart; Zethelius, Björn

2017-06-01

The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers.

Ground-Water Quality Data in the Owens and Indian Wells Valleys Study Unit, 2006: Results from the California GAMA Program

USGS Publications Warehouse

Densmore, Jill N.; Fram, Miranda S.; Belitz, Kenneth

2009-01-01

delivered to consumers. Water supplied to consumers typically is treated after withdrawal from the ground, disinfected, and blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and non-regulatory thresholds established for aesthetic concerns (secondary maximum contamination levels, SMCL-CA) by CDPH. VOCs and pesticides were detected in samples from less than one-third of the grid wells; all detections were below health-based thresholds, and most were less than one-one hundredth of threshold values. All detections of perchlorate and nutrients in samples from OWENS were below health-based thresholds. Most detections of trace elements in ground-water samples from OWENS wells were below health-based thresholds. In samples from the 53 grid wells, three constituents were detected at concentrations above USEPA maximum contaminant levels: arsenic in 5 samples, uranium in 4 samples, and fluoride in 1 sample. Two constituents were detected at concentrations above CDPH notification levels (boron in 9 samples and vanadium in 1 sample), and two were above USEPA lifetime health advisory levels (molybdenum in 3 samples and strontium in 1 sample). Most of the samples from OWENS wells had concentrations of major elements, TDS, and trace elements below the non-enforceable standards set for aesthetic concerns. Samples from nine grid wells had concentrations of manganese, iron, or TDS above the SMCL-CAs.

Groundwater Quality Data in the Mojave Study Unit, 2008: Results from the California GAMA Program

USGS Publications Warehouse

Mathany, Timothy M.; Belitz, Kenneth

2009-01-01

ground water. In total, over 230 constituents and water-quality indicators (field parameters) were investigated. Three types of quality-control samples (blanks, replicates, and matrix spikes) each were collected at approximately 5-8 percent of the wells, and the results for these samples were used to evaluate the quality of the data for the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a significant source of bias in the data for the groundwater samples. Differences between replicate samples generally were within acceptable ranges, indicating acceptable analytical reproducibility. Matrix spike recoveries were within acceptable ranges for most compounds. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, untreated groundwater typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to untreated ground water. However, to provide some context for the results, concentrations of constituents measured in the untreated ground water were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and thresholds established for aesthetic and technical concerns by CDPH. Comparisons between data collected for this study and thresholds for drinking-water are for illustrative purposes only, and are not indicative of compliance or non-compliance with those thresholds. Most constituents that were detected in groundwater samples in the 59 wells in MOJO were found at concentrations below drinking-water thresholds. In MOJO's 52 grid wells, volatile organic compounds (VOCs) were detected in 40 percent of the wells, and pesticides and pesticide degradates were detected in 23 percent of the grid wel

The influence of thresholds on the risk assessment of carcinogens in food.

PubMed

Pratt, Iona; Barlow, Susan; Kleiner, Juliane; Larsen, John Christian

2009-08-01

The risks from exposure to chemical contaminants in food must be scientifically assessed, in order to safeguard the health of consumers. Risk assessment of chemical contaminants that are both genotoxic and carcinogenic presents particular difficulties, since the effects of such substances are normally regarded as being without a threshold. No safe level can therefore be defined, and this has implications for both risk management and risk communication. Risk management of these substances in food has traditionally involved application of the ALARA (As Low as Reasonably Achievable) principle, however ALARA does not enable risk managers to assess the urgency and extent of the risk reduction measures needed. A more refined approach is needed, and several such approaches have been developed. Low-dose linear extrapolation from animal carcinogenicity studies or epidemiological studies to estimate risks for humans at low exposure levels has been applied by a number of regulatory bodies, while more recently the Margin of Exposure (MOE) approach has been applied by both the European Food Safety Authority and the Joint FAO/WHO Expert Committee on Food Additives. A further approach is the Threshold of Toxicological Concern (TTC), which establishes exposure thresholds for chemicals present in food, dependent on structure. Recent experimental evidence that genotoxic responses may be thresholded has significant implications for the risk assessment of chemicals that are both genotoxic and carcinogenic. In relation to existing approaches such as linear extrapolation, MOE and TTC, the existence of a threshold reduces the uncertainties inherent in such methodology and improves confidence in the risk assessment. However, for the foreseeable future, regulatory decisions based on the concept of thresholds for genotoxic carcinogens are likely to be taken case-by-case, based on convincing data on the Mode of Action indicating that the rate limiting variable for the development of cancer

Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective

PubMed Central

Feltelius, Nils; Gedeborg, Rolf; Holm, Lennart; Zethelius, Björn

2017-01-01

Aim The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. Methods A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. Results The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. Conclusions Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers. PMID:28276780

Groundwater-Quality Data in the Colorado River Study Unit, 2007: Results from the California GAMA Program

USGS Publications Warehouse

Goldrath, Dara A.; Wright, Michael T.; Belitz, Kenneth

2010-01-01

approximately 30 percent of the wells, and the results were used to evaluate the quality of the data obtained from the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a significant source of bias in the data. Differences between replicate samples were within acceptable ranges and matrix-spike recoveries were within acceptable ranges for most compounds. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, raw groundwater typically is treated, disinfected, or blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw groundwater. However, to provide some context for the results, concentrations of constituents measured in the raw groundwater were compared to regulatory and nonregulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH) and to thresholds established for aesthetic concerns by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only and do not indicate compliance or noncompliance with those thresholds. The concentrations of most constituents detected in groundwater samples were below drinking-water thresholds. Volatile organic compounds (VOC) were detected in approximately 35 percent of grid well samples; all concentrations were below health-based thresholds. Pesticides and pesticide degradates were detected in about 20 percent of all samples; detections were below health-based thresholds. No concentrations of constituents of special interest or nutrients were detected above health-based thresholds. Most of the major and minor ion constituents sampled do not have health-based thresholds; the exception is chloride. Concentrations of chloride, sulfate, and total dis

76 FR 77128 - Alternate Tonnage Threshold for Oil Spill Response Vessels

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-12

...The Coast Guard is establishing an alternate size threshold based on the measurement system established under the International Convention on Tonnage Measurement of Ships, 1969, for Oil Spill Response Vessels (OSRVs), which are properly certificated under 46 CFR subchapter L. The present size threshold of 500 gross registered tons is based on the U.S. regulatory measurement system. This rule provides an alternative for owners and operators of offshore supply vessels (OSVs) that may result in an increase in oil spill response capacity and capability.

Microphone Handling Noise: Measurements of Perceptual Threshold and Effects on Audio Quality

PubMed Central

Kendrick, Paul; Jackson, Iain R.; Fazenda, Bruno M.; Cox, Trevor J.; Li, Francis F.

2015-01-01

A psychoacoustic experiment was carried out to test the effects of microphone handling noise on perceived audio quality. Handling noise is a problem affecting both amateurs using their smartphones and cameras, as well as professionals using separate microphones and digital recorders. The noises used for the tests were measured from a variety of devices, including smartphones, laptops and handheld microphones. The signal features that characterise these noises are analysed and presented. The sounds include various types of transient, impact noises created by tapping or knocking devices, as well as more sustained sounds caused by rubbing. During the perceptual tests, listeners auditioned speech podcasts and were asked to rate the degradation of any unwanted sounds they heard. A representative design test methodology was developed that tried to encourage everyday rather than analytical listening. Signal-to-noise ratio (SNR) of the handling noise events was shown to be the best predictor of quality degradation. Other factors such as noise type or background noise in the listening environment did not significantly affect quality ratings. Podcast, microphone type and reproduction equipment were found to be significant but only to a small extent. A model allowing the prediction of degradation from the SNR is presented. The SNR threshold at which 50% of subjects noticed handling noise was found to be 4.2 ± 0.6 dBA. The results from this work are important for the understanding of our perception of impact sound and resonant noises in recordings, and will inform the future development of an automated predictor of quality for handling noise. PMID:26473498

Comparison of image segmentation of lungs using methods: connected threshold, neighborhood connected, and threshold level set segmentation

NASA Astrophysics Data System (ADS)

Amanda, A. R.; Widita, R.

2016-03-01

The aim of this research is to compare some image segmentation methods for lungs based on performance evaluation parameter (Mean Square Error (MSE) and Peak Signal Noise to Ratio (PSNR)). In this study, the methods compared were connected threshold, neighborhood connected, and the threshold level set segmentation on the image of the lungs. These three methods require one important parameter, i.e the threshold. The threshold interval was obtained from the histogram of the original image. The software used to segment the image here was InsightToolkit-4.7.0 (ITK). This research used 5 lung images to be analyzed. Then, the results were compared using the performance evaluation parameter determined by using MATLAB. The segmentation method is said to have a good quality if it has the smallest MSE value and the highest PSNR. The results show that four sample images match the criteria of connected threshold, while one sample refers to the threshold level set segmentation. Therefore, it can be concluded that connected threshold method is better than the other two methods for these cases.

Teachers' Occupational Well-Being and Quality of Instruction: The Important Role of Self-Regulatory Patterns

ERIC Educational Resources Information Center

Klussman, Uta; Kunter, Mareike; Trautwein, Ulrich; Ludtke, Oliver; Baumert, Jurgen

2008-01-01

Teachers' occupational well-being (level of emotional exhaustion and job satisfaction) and quality of instruction are two key aspects of research on teaching that have rarely been studied together. The role of occupational engagement and resilience as two important work-related self-regulatory dimensions that predict occupational well-being and…

Ground-Water Quality Data in the Monterey Bay and Salinas Valley Basins, California, 2005 - Results from the California GAMA Program

USGS Publications Warehouse

Kulongoski, Justin T.; Belitz, Kenneth

2007-01-01

Ground-water quality in the approximately 1,000-square-mile Monterey Bay and Salinas Valley study unit was investigated from July through October 2005 as part of the California Ground-Water Ambient Monitoring and Assessment (GAMA) program. The study was designed to provide a spatially unbiased assessment of raw ground-water quality, as well as a statistically consistent basis for comparing water quality throughout California. Samples were collected from 94 public-supply wells and 3 monitoring wells in Monterey, Santa Cruz, and San Luis Obispo Counties. Ninety-one of the public-supply wells sampled were selected to provide a spatially distributed, randomized monitoring network for statistical representation of the study area. Six wells were sampled to evaluate changes in water chemistry: three wells along a ground-water flow path were sampled to evaluate lateral changes, and three wells at discrete depths from land surface were sampled to evaluate changes in water chemistry with depth from land surface. The ground-water samples were analyzed for volatile organic compounds (VOCs), pesticides, pesticide degradates, nutrients, major and minor ions, trace elements, radioactivity, microbial indicators, and dissolved noble gases (the last in collaboration with Lawrence Livermore National Laboratory). Naturally occurring isotopes (tritium, carbon-14, helium-4, and the isotopic composition of oxygen and hydrogen) also were measured to help identify the source and age of the sampled ground water. In total, 270 constituents and water-quality indicators were investigated for this study. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain water quality. In addition, regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. In this study, only six constituents, alpha radioactivity, N

Chemical quality and regulatory compliance of drinking water in Iceland.

PubMed

Gunnarsdottir, Maria J; Gardarsson, Sigurdur M; Jonsson, Gunnar St; Bartram, Jamie

2016-11-01

Assuring sufficient quality of drinking water is of great importance for public wellbeing and prosperity. Nations have developed regulatory system with the aim of providing drinking water of sufficient quality and to minimize the risk of contamination of the water supply in the first place. In this study the chemical quality of Icelandic drinking water was evaluated by systematically analyzing results from audit monitoring where 53 parameters were assessed for 345 samples from 79 aquifers, serving 74 water supply systems. Compliance to the Icelandic Drinking Water Regulation (IDWR) was evaluated with regard to parametric values, minimum requirement of sampling, and limit of detection. Water quality compliance was divided according to health-related chemicals and indicators, and analyzed according to size. Samples from few individual locations were benchmarked against natural background levels (NBLs) in order to identify potential pollution sources. The results show that drinking compliance was 99.97% in health-related chemicals and 99.44% in indicator parameters indicating that Icelandic groundwater abstracted for drinking water supply is generally of high quality with no expected health risks. In 10 water supply systems, of the 74 tested, there was an indication of anthropogenic chemical pollution, either at the source or in the network, and in another 6 water supplies there was a need to improve the water intake to prevent surface water intrusion. Benchmarking against the NBLs proved to be useful in tracing potential pollution sources, providing a useful tool for identifying pollution at an early stage. Copyright © 2016 Elsevier GmbH. All rights reserved.

Modeling the interannual variability of microbial quality metrics of irrigation water in a Pennsylvania stream.

PubMed

Hong, Eun-Mi; Shelton, Daniel; Pachepsky, Yakov A; Nam, Won-Ho; Coppock, Cary; Muirhead, Richard

2017-02-01

Knowledge of the microbial quality of irrigation waters is extremely limited. For this reason, the US FDA has promulgated the Produce Rule, mandating the testing of irrigation water sources for many farms. The rule requires the collection and analysis of at least 20 water samples over two to four years to adequately evaluate the quality of water intended for produce irrigation. The objective of this work was to evaluate the effect of interannual weather variability on surface water microbial quality. We used the Soil and Water Assessment Tool model to simulate E. coli concentrations in the Little Cove Creek; this is a perennial creek located in an agricultural watershed in south-eastern Pennsylvania. The model performance was evaluated using the US FDA regulatory microbial water quality metrics of geometric mean (GM) and the statistical threshold value (STV). Using the 90-year time series of weather observations, we simulated and randomly sampled the time series of E. coli concentrations. We found that weather conditions of a specific year may strongly affect the evaluation of microbial quality and that the long-term assessment of microbial water quality may be quite different from the evaluation based on short-term observations. The variations in microbial concentrations and water quality metrics were affected by location, wetness of the hydrological years, and seasonality, with 15.7-70.1% of samples exceeding the regulatory threshold. The results of this work demonstrate the value of using modeling to design and evaluate monitoring protocols to assess the microbial quality of water used for produce irrigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Implementation workshop of WHO guidelines on evaluation of malaria vaccines: Current regulatory concepts and issues related to vaccine quality, Pretoria, South Africa 07 Nov 2014.

PubMed

Ho, Mei Mei; Baca-Estrada, Maria; Conrad, Christoph; Karikari-Boateng, Eric; Kang, Hye-Na

2015-08-26

The current World Health Organization (WHO) guidelines on the quality, safety and efficacy of recombinant malaria vaccines targeting the pre-erythrocytic and blood stages of Plasmodium falciparum were adopted by the WHO Expert Committee on Biological Standardization in 2012 to provide guidance on the quality, nonclinical and clinical aspects of recombinant malaria vaccines. A WHO workshop was organised to facilitate implementation into African (national/regional) regulatory practices, of the regulatory evaluation principles outlined in the guidelines regarding quality aspects. The workshop was used also to share knowledge and experience on regulatory topics of chemistry, manufacturing and control with a focus on vaccines through presentations and an interactive discussion using a case study approach. The basic principles and concepts of vaccine quality including consistency of production, quality control and manufacturing process were presented and discussed in the meeting. By reviewing and practicing a case study, better understanding on the relationship between consistency of production and batch release tests of an adjuvanted pre-erythrocytic recombinant malaria vaccine was reached. The case study exercise was considered very useful to understand regulatory evaluation principles of vaccines and a suggestion was made to WHO to provide such practices also through its Global Learning Opportunities for Vaccine Quality programme. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Groundwater Quality Data for the Northern Sacramento Valley, 2007: Results from the California GAMA Program

USGS Publications Warehouse

Bennett, Peter A.; Bennett, George L.; Belitz, Kenneth

2009-01-01

to 11 percent of the wells, and the results for these samples were used to evaluate the quality of the data obtained from the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a noticeable source of bias in the data for the groundwater samples. Differences between replicate samples were within acceptable ranges for nearly all compounds, indicating acceptably low variability. Matrix-spike recoveries were within acceptable ranges for most compounds. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, raw groundwater typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw groundwater were compared with regulatory and nonregulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and with aesthetic and technical thresholds established by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only and do not indicate compliance or noncompliance with those thresholds. The concentrations of most constituents detected in groundwater samples from REDSAC were below drinking-water thresholds. Volatile organic compounds (VOC) and pesticides were detected in less than one-quarter of the samples and were generally less than a hundredth of any health-based thresholds. NDMA was detected in one grid well above the NL-CA. Concentrations of all nutrients and trace elements in samples from REDSAC wells were below the health-based thresholds except those of arsenic in three samples, which were above the USEPA maximum contaminant level (MCL-US). However

Setting limits: Using air pollution thresholds to protect and restore U.S. ecosystems

USGS Publications Warehouse

Fenn, M.E.; Lambert, K.F.; Blett, T.F.; Burns, Douglas A.; Pardo, L.H.; Lovett, Gary M.; Haeuber, R. A.; Evers, D.C.; Driscoll, C.T.; Jeffries, D.S.

2011-01-01

states and on many tribal lands. High concentrations of mercury in wildlife are also widespread and have multiple adverse effects. ??? Air quality programs, such as those stemming from the 1990 Clean Air Act Amendments, have helped decrease air pollution even as population and energy demand have increased. Yet, they do not adequately protect ecosystems from long-term damage. Moreover they do not address ammonia emissions. ??? A stronger ecosystem basis for air pollutant policies could be established through adoption of science-based thresholds. Existing monitoring programs track vital information needed to measure the response to policies, and could be expanded to include appropriate chemical and biological indicators for terrestrial and aquatic ecosystems and establishment of a national ecosystem monitoring network for mercury. The development and use of air pollution thresholds for ecosystem protection and management is increasing in the United States, yet threshold approaches remain underutilized. Ecological thresholds for air pollution, such as critical loads for nitrogen and sulfur deposition, are not currently included in the formal regulatory process for emissions controls in the United States, although they are now considered in local management decisions by the National Park Service and U.S. Forest Service. Ecological thresholds offer a scientifically sound approach to protecting and restoring U.S. ecosystems and an important tool for natural resource management and policy. ?? The Ecological Society of America.

Ground-Water Quality Data in the Upper Santa Ana Watershed Study Unit, November 2006-March 2007: Results from the California GAMA Program

USGS Publications Warehouse

Kent, Robert; Belitz, Kenneth

2009-01-01

nitrate in the study unit. In total, nearly 400 constituents and water-quality indicators were investigated for this study. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. Volatile organic compounds (VOCs) were detected in more than 80 percent of USAW grid wells. Most VOCs detected were at concentrations far less than thresholds established for drinking water to protect human health; however, six wells had VOC concentrations above health-based thresholds. Twenty-four of the 85 VOCs investigated were detected in the study unit;11 were detected in more than 10 percent of the wells. The VOCs detected above health-based thresholds in at least one well were dibromochloropropane (DBCP), tetrachloroethene (PCE), trichloroethene (TCE), carbon tetrachloride, and 1,1-dichoroethene. Pesticide compounds were detected in more than 75 percent of the grid wells. However, of the 134 different pesticide compounds investigated, 13 were detected at concentrations greater than their respective long-term method detection limits, and only 7 compounds (all herbicides or herbicide degradates) were detected in more than 10 percent of the wells. No pesticide compound was detected above its health-based threshold, although thresholds exist for fewer than half of the pesticide compounds investigat

Ground-Water Quality Data in the Santa Clara River Valley Study Unit, 2007: Results from the California GAMA Program

USGS Publications Warehouse

Montrella, Joseph; Belitz, Kenneth

2009-01-01

and age of the sampled ground water. Quality-control samples (blanks or replicates, or samples for matrix spikes) were collected from approximately 26 percent of the wells, and the analyses of these samples were used to evaluate the quality of the data for the ground-water samples. Assessment of the quality-control results showed that the quality of the environmental data was good, with low bias and low variability, and as a result, less than 0.1 percent of the analytes detected in ground-water samples were censored. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is delivered (or, supplied) to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with regulatory and non-regulatory thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. Most constituents that were detected in ground-water samples were reported at concentrations below their established health-based thresholds. VOCs, pesticides and pesticide degradates, and potential wastewater-indicator compounds were detected in about 33 percent or less of the 42 SCRV grid wells. Concentrations of all detected organic constituents were below established health-based thresholds. Perchlorate was detected in approximately 12 percent of the SCRV grid wells; all concentrations reported were below the NL-CA threshold. Additional constituents, including major ions, trace elements, and nutrients were collected at 26 wells (16 grid wells and 10 understanding wells) of the 53 wells sampled f

Detecting fatigue thresholds from electromyographic signals: A systematic review on approaches and methodologies.

PubMed

Ertl, Peter; Kruse, Annika; Tilp, Markus

2016-10-01

The aim of the current paper was to systematically review the relevant existing electromyographic threshold concepts within the literature. The electronic databases MEDLINE and SCOPUS were screened for papers published between January 1980 and April 2015 including the keywords: neuromuscular fatigue threshold, anaerobic threshold, electromyographic threshold, muscular fatigue, aerobic-anaerobictransition, ventilatory threshold, exercise testing, and cycle-ergometer. 32 articles were assessed with regard to their electromyographic methodologies, description of results, statistical analysis and test protocols. Only one article was of very good quality. 21 were of good quality and two articles were of very low quality. The review process revealed that: (i) there is consistent evidence of one or two non-linear increases of EMG that might reflect the additional recruitment of motor units (MU) or different fiber types during fatiguing cycle ergometer exercise, (ii) most studies reported no statistically significant difference between electromyographic and metabolic thresholds, (iii) one minute protocols with increments between 10 and 25W appear most appropriate to detect muscular threshold, (iv) threshold detection from the vastus medialis, vastus lateralis, and rectus femoris is recommended, and (v) there is a great variety in study protocols, measurement techniques, and data processing. Therefore, we recommend further research and standardization in the detection of EMGTs. Copyright © 2016 Elsevier Ltd. All rights reserved.

77 FR 31050 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

...-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule... threshold qualifications and corresponding rates applicable to Option Trading Permit (``OTP'') Holder and... restructure the threshold qualifications and corresponding rates applicable to OTP Holder and OTP Firm...

A systematic review of studies eliciting willingness-to-pay per quality-adjusted life year: does it justify CE threshold?

PubMed

Nimdet, Khachapon; Chaiyakunapruk, Nathorn; Vichansavakul, Kittaya; Ngorsuraches, Surachat

2015-01-01

A number of studies have been conducted to estimate willingness to pay (WTP) per quality-adjusted life years (QALY) in patients or general population for various diseases. However, there has not been any systematic review summarizing the relationship between WTP per QALY and cost-effectiveness (CE) threshold based on World Health Organization (WHO) recommendation. To systematically review willingness-to-pay per quality-adjusted-life-year (WTP per QALY) literature, to compare WTP per QALY with Cost-effectiveness (CE) threshold recommended by WHO, and to determine potential influencing factors. We searched MEDLINE, EMBASE, Psyinfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Center of Research Dissemination (CRD), and EconLit from inception through 15 July 2014. To be included, studies have to estimate WTP per QALY in health-related issues using stated preference method. Two investigators independently reviewed each abstract, completed full-text reviews, and extracted information for included studies. We compared WTP per QALY to GDP per capita, analyzed, and summarized potential influencing factors. Out of 3,914 articles founded, 14 studies were included. Most studies (92.85%) used contingent valuation method, while only one study used discrete choice experiments. Sample size varied from 104 to 21,896 persons. The ratio between WTP per QALY and GDP per capita varied widely from 0.05 to 5.40, depending on scenario outcomes (e.g., whether it extended/saved life or improved quality of life), severity of hypothetical scenarios, duration of scenario, and source of funding. The average ratio of WTP per QALY and GDP per capita for extending life or saving life (2.03) was significantly higher than the average for improving quality of life (0.59) with the mean difference of 1.43 (95% CI, 1.81 to 1.06). This systematic review provides an overview summary of all studies estimating WTP per QALY studies. The variation of ratio of WTP per QALY and GDP per

A Systematic Review of Studies Eliciting Willingness-to-Pay per Quality-Adjusted Life Year: Does It Justify CE Threshold?

PubMed Central

Nimdet, Khachapon; Chaiyakunapruk, Nathorn; Vichansavakul, Kittaya; Ngorsuraches, Surachat

2015-01-01

Background A number of studies have been conducted to estimate willingness to pay (WTP) per quality-adjusted life years (QALY) in patients or general population for various diseases. However, there has not been any systematic review summarizing the relationship between WTP per QALY and cost-effectiveness (CE) threshold based on World Health Organization (WHO) recommendation. Objective To systematically review willingness-to-pay per quality-adjusted-life-year (WTP per QALY) literature, to compare WTP per QALY with Cost-effectiveness (CE) threshold recommended by WHO, and to determine potential influencing factors. Methods We searched MEDLINE, EMBASE, Psyinfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Center of Research Dissemination (CRD), and EconLit from inception through 15 July 2014. To be included, studies have to estimate WTP per QALY in health-related issues using stated preference method. Two investigators independently reviewed each abstract, completed full-text reviews, and extracted information for included studies. We compared WTP per QALY to GDP per capita, analyzed, and summarized potential influencing factors. Results Out of 3,914 articles founded, 14 studies were included. Most studies (92.85%) used contingent valuation method, while only one study used discrete choice experiments. Sample size varied from 104 to 21,896 persons. The ratio between WTP per QALY and GDP per capita varied widely from 0.05 to 5.40, depending on scenario outcomes (e.g., whether it extended/saved life or improved quality of life), severity of hypothetical scenarios, duration of scenario, and source of funding. The average ratio of WTP per QALY and GDP per capita for extending life or saving life (2.03) was significantly higher than the average for improving quality of life (0.59) with the mean difference of 1.43 (95% CI, 1.81 to 1.06). Conclusion This systematic review provides an overview summary of all studies estimating WTP per QALY studies. The

Determination of Cost-Effectiveness Threshold for Health Care Interventions in Malaysia.

PubMed

Lim, Yen Wei; Shafie, Asrul Akmal; Chua, Gin Nie; Ahmad Hassali, Mohammed Azmi

2017-09-01

One major challenge in prioritizing health care using cost-effectiveness (CE) information is when alternatives are more expensive but more effective than existing technology. In such a situation, an external criterion in the form of a CE threshold that reflects the willingness to pay (WTP) per quality-adjusted life-year is necessary. To determine a CE threshold for health care interventions in Malaysia. A cross-sectional, contingent valuation study was conducted using a stratified multistage cluster random sampling technique in four states in Malaysia. One thousand thirteen respondents were interviewed in person for their socioeconomic background, quality of life, and WTP for a hypothetical scenario. The CE thresholds established using the nonparametric Turnbull method ranged from MYR12,810 to MYR22,840 (~US $4,000-US $7,000), whereas those estimated with the parametric interval regression model were between MYR19,929 and MYR28,470 (~US $6,200-US $8,900). Key factors that affected the CE thresholds were education level, estimated monthly household income, and the description of health state scenarios. These findings suggest that there is no single WTP value for a quality-adjusted life-year. The CE threshold estimated for Malaysia was found to be lower than the threshold value recommended by the World Health Organization. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

75 FR 52560 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-26

...-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate Effectiveness of Proposed... and then cancelled totals 500 orders or more in a particular calendar month (the ``500 Order Threshold''). The Exchange proposes to modify the calculation of the 500 Order Threshold by creating two separate...

78 FR 7828 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-04

...-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending the NYSE Arca Options Fee Schedule To Revise Qualification Thresholds for Tiered Customer...'') to revise the qualification thresholds for tiered Customer posting credits for electronic executions...

77 FR 38729 - Alternate Tonnage Threshold for Oil Spill Response Vessels

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

...The Coast Guard is establishing an alternate size threshold based on the measurement system established under the International Convention on Tonnage Measurement of Ships, 1969, for oil spill response vessels, which are properly certificated under 46 CFR chapter I, subchapter L. The present size threshold of 500 gross register tons is based on the U.S. regulatory measurement system. This final rule provides an alternative for owners and operators of offshore supply vessels that may result in an increase in oil spill response capacity and capability. This final rule adopts, without change, the interim rule amending 46 CFR part 126 published in the Federal Register on Monday, December 12, 2011.

Ground-Water Quality Data in the San Francisco Bay Study Unit, 2007: Results from the California GAMA Program

USGS Publications Warehouse

Ray, Mary C.; Kulongoski, Justin T.; Belitz, Kenneth

2009-01-01

, replicate samples, matrix spike samples) were collected for approximately one-third of the wells, and the results for these samples were used to evaluate the quality of the data for the ground-water samples. Assessment of the quality-control information from the field blanks resulted in applying 'V' codes to approximately 0.1 percent of the data collected for ground-water samples (meaning a constituent was detected in blanks as well as the corresponding environmental data). See the Appendix section 'Quality-Control-Sample Results'. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is delivered to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. VOCs were detected in about one-half of the grid wells, while pesticides were detected in about one-fifth of the grid wells. Concentrations of all VOCs and pesticides detected in samples from all SFBAY wells were below health-based thresholds. No pharmaceutical compounds were detected in any SFBAY well. One potential wastewater-indicator compound, caffeine, was detected in one grid well in SFBAY. Concentrations of most trace elements and nutrients detected in samples from all SFBAY wells were below health-based thresholds. Exceptions include nitrate, detected above the USEPA maximum contaminant level (MCL-US) in 3samples; arsenic, above the USEPA maximum contaminant level (MCL-US) in 3 samples; c

Comprehensive genomic studies: emerging regulatory, strategic, and quality assurance challenges for biorepositories.

PubMed

McDonald, Sandra A; Mardis, Elaine R; Ota, David; Watson, Mark A; Pfeifer, John D; Green, Jonathan M

2012-07-01

As part of the molecular revolution sweeping medicine, comprehensive genomic studies are adding powerful dimensions to medical research. However, their power exposes new regulatory, strategic, and quality assurance challenges for biorepositories. A key issue is that unlike other research techniques commonly applied to banked specimens, nucleic acid sequencing, if sufficiently extensive, yields data that could identify a patient. This evolving paradigm renders the concepts of anonymized and anonymous specimens increasingly outdated. The challenges for biorepositories in this new era include refined consent processes and wording, selection and use of legacy specimens, quality assurance procedures, institutional documentation, data sharing, and interaction with institutional review boards. Given current trends, biorepositories should consider these issues now, even if they are not currently experiencing sample requests for genomic analysis. We summarize our current experiences and best practices at Washington University Medical School, St Louis, MO, our perceptions of emerging trends, and recommendations.

Comprehensive Genomic Studies: Emerging Regulatory, Strategic, and Quality Assurance Challenges for Biorepositories

PubMed Central

McDonald, Sandra A.; Mardis, Elaine R.; Ota, David; Watson, Mark A.; Pfeifer, John D.; Green, Jonathan M.

2012-01-01

As part of the molecular revolution sweeping medicine, comprehensive genomic studies are adding powerful dimensions to medical research. However, their power exposes new regulatory, strategic, and quality assurance challenges for biorepositories. A key issue is that unlike other research techniques commonly applied to banked specimens, nucleic acid sequencing, if sufficiently extensive, yields data that could identify a patient. This evolving paradigm renders the concepts of anonymized and anonymous specimens increasingly outdated. The challenges for biorepositories in this new era include refined consent processes and wording, selection and use of legacy specimens, quality assurance procedures, institutional documentation, data sharing, and interaction with institutional review boards. Given current trends, biorepositories should consider these issues now, even if they are not currently experiencing sample requests for genomic analysis. We summarize our current experiences and best practices at Washington University Medical School, St Louis, MO, our perceptions of emerging trends, and recommendations. PMID:22706855

Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents).

PubMed

Calixto, J B

2000-02-01

This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs). Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.

Evaluating Quality of Decision-Making Processes in Medicines' Development, Regulatory Review, and Health Technology Assessment: A Systematic Review of the Literature

PubMed Central

Bujar, Magdalena; McAuslane, Neil; Walker, Stuart R.; Salek, Sam

2017-01-01

Introduction: Although pharmaceutical companies, regulatory authorities, and health technology assessment (HTA) agencies have been increasingly using decision-making frameworks, it is not certain whether these enable better quality decision making. This could be addressed by formally evaluating the quality of decision-making process within those organizations. The aim of this literature review was to identify current techniques (tools, questionnaires, surveys, and studies) for measuring the quality of the decision-making process across the three stakeholders. Methods: Using MEDLINE, Web of Knowledge, and other Internet-based search engines, a literature review was performed to systematically identify techniques for assessing quality of decision making in medicines development, regulatory review, and HTA. A structured search was applied using key words and a secondary review was carried out. In addition, the measurement properties of each technique were assessed and compared. Ten Quality Decision-Making Practices (QDMPs) developed previously were then used as a framework for the evaluation of techniques identified in the review. Due to the variation in studies identified, meta-analysis was inappropriate. Results: This review identified 13 techniques, where 7 were developed specifically to assess decision making in medicines' development, regulatory review, or HTA; 2 examined corporate decision making, and 4 general decision making. Regarding how closely each technique conformed to the 10 QDMPs, the 13 techniques assessed a median of 6 QDMPs, with a mode of 3 QDMPs. Only 2 techniques evaluated all 10 QDMPs, namely the Organizational IQ and the Quality of Decision Making Orientation Scheme (QoDoS), of which only one technique, QoDoS could be applied to assess decision making of both individuals and organizations, and it possessed generalizability to capture issues relevant to companies as well as regulatory authorities. Conclusion: This review confirmed a general

Evaluating Quality of Decision-Making Processes in Medicines' Development, Regulatory Review, and Health Technology Assessment: A Systematic Review of the Literature.

PubMed

Bujar, Magdalena; McAuslane, Neil; Walker, Stuart R; Salek, Sam

2017-01-01

Introduction: Although pharmaceutical companies, regulatory authorities, and health technology assessment (HTA) agencies have been increasingly using decision-making frameworks, it is not certain whether these enable better quality decision making. This could be addressed by formally evaluating the quality of decision-making process within those organizations. The aim of this literature review was to identify current techniques (tools, questionnaires, surveys, and studies) for measuring the quality of the decision-making process across the three stakeholders. Methods: Using MEDLINE, Web of Knowledge, and other Internet-based search engines, a literature review was performed to systematically identify techniques for assessing quality of decision making in medicines development, regulatory review, and HTA. A structured search was applied using key words and a secondary review was carried out. In addition, the measurement properties of each technique were assessed and compared. Ten Quality Decision-Making Practices (QDMPs) developed previously were then used as a framework for the evaluation of techniques identified in the review. Due to the variation in studies identified, meta-analysis was inappropriate. Results: This review identified 13 techniques, where 7 were developed specifically to assess decision making in medicines' development, regulatory review, or HTA; 2 examined corporate decision making, and 4 general decision making. Regarding how closely each technique conformed to the 10 QDMPs, the 13 techniques assessed a median of 6 QDMPs, with a mode of 3 QDMPs. Only 2 techniques evaluated all 10 QDMPs, namely the Organizational IQ and the Quality of Decision Making Orientation Scheme (QoDoS), of which only one technique, QoDoS could be applied to assess decision making of both individuals and organizations, and it possessed generalizability to capture issues relevant to companies as well as regulatory authorities. Conclusion: This review confirmed a general

The air quality and regional climate effects of widespread solar power generation under a changing regulatory environment

NASA Astrophysics Data System (ADS)

Millstein, D.; Zhai, P.; Menon, S.

2011-12-01

Over the past decade significant reductions of NOx and SOx emissions from coal burning power plants in the U.S. have been achieved due to regulatory action and substitution of new generation towards natural gas and wind power. Low natural gas prices, ever decreasing solar generation costs, and proposed regulatory changes, such as to the Cross State Air Pollution Rule, promise further long-run coal power plant emission reductions. Reduced power plant emissions have the potential to affect ozone and particulate air quality and influence regional climate through aerosol cloud interactions and visibility effects. Here we investigate, on a national scale, the effects on future (~2030) air quality and regional climate of power plant emission regulations in contrast to and combination with policies designed to aggressively promote solar electricity generation. A sophisticated, economic and engineering based, hourly power generation dispatch model is developed to explore the integration of significant solar generation resources (>10% on an energy basis) at various regions across the county, providing detailed estimates of substitution of solar generation for fossil fuel generation resources. Future air pollutant emissions from all sectors of the economy are scaled based on the U.S. Environmental Protection Agency's National Emission Inventory to account for activity changes based on population and economic projections derived from county level U.S. Census data and the Energy Information Administration's Annual Energy Outlook. Further adjustments are made for technological and regulatory changes applicable within various sectors, for example, emission intensity adjustments to on-road diesel trucking due to exhaust treatment and improved engine design. The future year 2030 is selected for the emissions scenarios to allow for the development of significant solar generation resources. A regional climate and air quality model (Weather Research and Forecasting, WRF model) is

[European Union regulatory and quality requirements for botanical drugs and their implications for Chinese herbal medicinal products development].

PubMed

Zhu, You-Ping

2017-06-01

This paper introduces regulatory pathways and characteristic quality requirements for marketing authorization of herbal medicinal products in the European Union（EU）, and the legal status and applications of "European Union list of herbal substances, preparations and combinations" and "European Union herbal monographs". Also introduced are Chinese herbs that have been granted the EU list entry, those with EU herbal monographs, and registered EU traditional herbal medicinal products with Chinese herbs as active ingredients. Special attention is paid to the technical details of three authorized EU herbal medicinal products (Veregen, Sativex and Episalvan) in comparison with Andrographis paniculata extract HMPL-004 that failed the phase Ⅲ clinical trial for ulcerative colitis. The paper further emphasizes the importance of enriching active fractions of herbal extracts and taking regulatory and quality considerations into account in early stage of botanical drug development. Copyright© by the Chinese Pharmaceutical Association.

Self-Regulation in Early Adolescence: Relations with Mother-Son Relationship Quality and Maternal Regulatory Support and Antagonism

ERIC Educational Resources Information Center

Moilanen, Kristin L.; Shaw, Daniel S.; Fitzpatrick, Amber

2010-01-01

The purpose of the current investigation was to examine relations among maternal regulatory support, maternal antagonism, and mother-son relationship quality in relation to boys' self-regulation during early adolescence. As part of a larger longitudinal study on 263 low-income, ethnically diverse boys, multiple informants and methods were used to…

Data Quality Objectives for Regulatory Requirements for Dangerous Waste Sampling and Analysis

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

MULKEY, C.H.

1999-07-02

This document describes sampling and analytical requirements needed to meet state and federal regulations for dangerous waste (DW). The River Protection Project (RPP) is assigned to the task of storage and interim treatment of hazardous waste. Any final treatment or disposal operations, as well as requirements under the land disposal restrictions (LDRs), fall in the jurisdiction of another Hanford organization and are not part of this scope. The requirements for this Data Quality Objective (DQO) Process were developed using the RPP Data Quality Objective Procedure (Banning 1996), which is based on the U.S. Environmental Protection Agency's (EPA) Guidance for themore » Data Quality Objectives Process (EPA 1994). Hereafter, this document is referred to as the DW DQO. Federal and state laws and regulations pertaining to waste contain requirements that are dependent upon the composition of the waste stream. These regulatory drivers require that pertinent information be obtained. For many requirements, documented process knowledge of a waste composition can be used instead of analytical data to characterize or designate a waste. When process knowledge alone is used to characterize a waste, it is a best management practice to validate the information with analytical measurements.« less

Genetic Redundancies Enhance Information Transfer in Noisy Regulatory Circuits

PubMed Central

Rodrigo, Guillermo; Poyatos, Juan F.

2016-01-01

Cellular decision making is based on regulatory circuits that associate signal thresholds to specific physiological actions. This transmission of information is subjected to molecular noise what can decrease its fidelity. Here, we show instead how such intrinsic noise enhances information transfer in the presence of multiple circuit copies. The result is due to the contribution of noise to the generation of autonomous responses by each copy, which are altogether associated with a common decision. Moreover, factors that correlate the responses of the redundant units (extrinsic noise or regulatory cross-talk) contribute to reduce fidelity, while those that further uncouple them (heterogeneity within the copies) can lead to stronger information gain. Overall, our study emphasizes how the interplay of signal thresholding, redundancy, and noise influences the accuracy of cellular decision making. Understanding this interplay provides a basis to explain collective cell signaling mechanisms, and to engineer robust decisions with noisy genetic circuits. PMID:27741249

Developing Mindfulness in College Students through Movement Based Courses: Effects on Self-Regulatory Self-Efficacy, Mood, Stress, and Sleep Quality

PubMed Central

Caldwell, Karen; Harrison, Mandy; Adams, Marianne; Quin, Rebecca H; Greeson, Jeffrey

2010-01-01

Objective This study examined whether mindfulness increased through participation in movement based courses and whether changes in self-regulatory self-efficacy, mood, and perceived stress mediated the relationship between increased mindfulness and better sleep. Participants 166 college students enrolled in the 2007-2008 academic year in 15 week classes in Pilates, Taiji quan, or GYROKINESIS®. Methods At beginning, middle, and end of the semester, participants completed measures of mindfulness, self-regulatory self-efficacy, mood, perceived stress and sleep quality. Results Total mindfulness scores and mindfulness subscales increased overall. Greater changes in mindfulness were directly related to better sleep quality at the end of the semester after adjusting for sleep disturbance at the beginning. Tired Mood, Negative Arousal, Relaxed Mood, and Perceived Stress mediated the effect of increased mindfulness on improved sleep. Conclusions Movement based courses can increase mindfulness. Increased mindfulness accounts for changes in mood and perceived stress that explain, in part, improved sleep quality. PMID:20304755

Robust Adaptive Thresholder For Document Scanning Applications

NASA Astrophysics Data System (ADS)

Hsing, To R.

1982-12-01

In document scanning applications, thresholding is used to obtain binary data from a scanner. However, due to: (1) a wide range of different color backgrounds; (2) density variations of printed text information; and (3) the shading effect caused by the optical systems, the use of adaptive thresholding to enhance the useful information is highly desired. This paper describes a new robust adaptive thresholder for obtaining valid binary images. It is basically a memory type algorithm which can dynamically update the black and white reference level to optimize a local adaptive threshold function. The results of high image quality from different types of simulate test patterns can be obtained by this algorithm. The software algorithm is described and experiment results are present to describe the procedures. Results also show that the techniques described here can be used for real-time signal processing in the varied applications.

Ground-Water Quality Data in the Coastal Los Angeles Basin Study Unit, 2006: Results from the California GAMA Program

USGS Publications Warehouse

Mathany, Timothy M.; Land, Michael; Belitz, Kenneth

2008-01-01

] and dissolved noble gases also were measured to help identify the sources and ages of the sampled ground water. Quality-control samples (blanks, replicates, and samples for matrix spikes) were collected at approximately one-fourth of the wells, and the results for these samples were used to evaluate the quality of the data for the ground-water samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a significant source of bias. Differences between replicate samples were within acceptable ranges, indicating acceptably low variability. Matrix spike recoveries were within acceptable ranges for most compounds. Assessment of the quality-control information resulted in applying ?V? codes to approximately 0.1 percent of the data collected for ground-water samples (meaning a constituent was detected in blanks as well as the corresponding environmental data). This study did not attempt to evaluate the quality of drinking water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain acceptable drinking-water quality. Regulatory thresholds are applied to the treated drinking water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA), California Department of Public Health (CDPH, formerly California Department of Health Services [CADHS]) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only, and are not indicative of compliance or non-compliance with those thresholds. VOCs were detected in alm

Ground-Water Quality Data in the Central Sierra Study Unit, 2006 - Results from the California GAMA Program

USGS Publications Warehouse

Ferrari, Matthew J.; Fram, Miranda S.; Belitz, Kenneth

2008-01-01

the results for these samples were used to evaluate the quality of the data for the ground-water samples. Results from field blanks indicated contamination was not a noticeable source of bias in the data for ground-water samples. Differences between replicate samples were within acceptable ranges, indicating acceptably low variability. Matrix spike recoveries were within acceptable ranges for most constituents. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH), and thresholds established for aesthetic concerns (Secondary Maximum Contaminant Levels, SMCL-CA) by CDPH. Therefore, any comparisons of the results of this study to drinking-water standards only is for illustrative purposes and is not indicative of compliance or non-compliance to those standards. Most constituents that were detected in ground-water samples were found at concentrations below drinking-water standards or thresholds. Six constituents? fluoride, arsenic, molybdenum, uranium, gross-alpha radioactivity, and radon-222?were detected at concentrations higher than thresholds set for health-based regulatory purposes. Three additional constituents?pH, iron and manganese?were detected at concentrations above thresholds set for aesthetic concerns. Volatile organic compounds (VOCs) and pesticides, were detected in less than one-third of the samples and generally at less than one one-hundredth of a health-based threshold.

The impact of implementation of the Canadian regulatory requirements on the quality of natural health products: the glucosamine case.

PubMed

Aghazadeh-Habashi, Ali; Duke, John; Jamali, Fakhreddin

2014-01-01

We investigated whether the recent implementation of the regulatory requirements for the entry to the Canadian market of natural products has resulted in improved quality of the available glucosamine products. Eleven available products, of which 8 had been tested in 2002 (7 had contained substantially lower than the label claim of the active ingredient), and a European pharmaceutical grade tablet were assayed for their glucosamine content. The potassium and sodium contents of the products were also tested. Nine of the 11 Canadian products and the European tablet had more than 91% of the label claim of the active ingredient, hence, met the criterion. Two products contained 71 and 78% label claim. The electrolyte contents were very variable but constituted only a small fraction of the daily requirements. Most tested glucosamine products passed the Health Canada requirements. This improvement is likely due to the publicity regarding the low quality of the products in the past and also a result, at least in part, of the introduction of the new regulatory requirements. The sub-standard quality of a few tested products is still of concern.

A low-threshold high-index-contrast grating (HCG)-based organic VCSEL

NASA Astrophysics Data System (ADS)

Shayesteh, Mohammad Reza; Darvish, Ghafar; Ahmadi, Vahid

2015-12-01

We propose a low-threshold high-index-contrast grating (HCG)-based organic vertical-cavity surface-emitting laser (OVCSEL). The device has the feasibility to apply both electrical and optical excitation. The microcavity of the laser is a hybrid photonic crystal (HPC) in which the top distributed Bragg reflector (DBR) is replaced by a sub-wavelength high-contrast-grating layer, and provides a high-quality factor. The simulated quality factor of the microcavity is shown to be as high as 282,000. We also investigate the threshold behavior and the dynamics of the OVCSEL optically pumped with sub-picosecond pulses. Results from numerical simulation show that lasing threshold is 75 nJ/cm2.

Ultracompact low-threshold organic laser.

PubMed

Deotare, Parag B; Mahony, Thomas S; Bulović, Vladimir

2014-11-25

We report an ultracompact low-threshold laser with an Alq3:DCM host:guest molecular organic thin film gain layer. The device uses a photonic crystal nanobeam cavity which provides a high quality factor to mode volume (Q/V) ratio and increased spontaneous emission factor along with a small footprint. Lasing is observed with a threshold of 4.2 μJ/cm(2) when pumped by femtosecond pulses of λ = 400 nm wavelength light. We also model the dynamics of the laser and show good agreement with the experimental data. The inherent waveguide geometry of the structure enables easy on-chip integration with potential applications in biochemical sensing, inertial sensors, and data communication.

76 FR 64983 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

...-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change... currently count toward both the $350,000 cap and the 3,500,000 thresholds, but are not themselves capped... standard fee schedule, with the exception of transactions that exceed the fee cap threshold for Specialists...

Thresholds of Toxicological Concern for cosmetics-related substances: New database, thresholds, and enrichment of chemical space.

PubMed

Yang, Chihae; Barlow, Susan M; Muldoon Jacobs, Kristi L; Vitcheva, Vessela; Boobis, Alan R; Felter, Susan P; Arvidson, Kirk B; Keller, Detlef; Cronin, Mark T D; Enoch, Steven; Worth, Andrew; Hollnagel, Heli M

2017-11-01

A new dataset of cosmetics-related chemicals for the Threshold of Toxicological Concern (TTC) approach has been compiled, comprising 552 chemicals with 219, 40, and 293 chemicals in Cramer Classes I, II, and III, respectively. Data were integrated and curated to create a database of No-/Lowest-Observed-Adverse-Effect Level (NOAEL/LOAEL) values, from which the final COSMOS TTC dataset was developed. Criteria for study inclusion and NOAEL decisions were defined, and rigorous quality control was performed for study details and assignment of Cramer classes. From the final COSMOS TTC dataset, human exposure thresholds of 42 and 7.9 μg/kg-bw/day were derived for Cramer Classes I and III, respectively. The size of Cramer Class II was insufficient for derivation of a TTC value. The COSMOS TTC dataset was then federated with the dataset of Munro and colleagues, previously published in 1996, after updating the latter using the quality control processes for this project. This federated dataset expands the chemical space and provides more robust thresholds. The 966 substances in the federated database comprise 245, 49 and 672 chemicals in Cramer Classes I, II and III, respectively. The corresponding TTC values of 46, 6.2 and 2.3 μg/kg-bw/day are broadly similar to those of the original Munro dataset. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Modeling Source Water Threshold Exceedances with Extreme Value Theory

NASA Astrophysics Data System (ADS)

Rajagopalan, B.; Samson, C.; Summers, R. S.

2016-12-01

Variability in surface water quality, influenced by seasonal and long-term climate changes, can impact drinking water quality and treatment. In particular, temperature and precipitation can impact surface water quality directly or through their influence on streamflow and dilution capacity. Furthermore, they also impact land surface factors, such as soil moisture and vegetation, which can in turn affect surface water quality, in particular, levels of organic matter in surface waters which are of concern. All of these will be exacerbated by anthropogenic climate change. While some source water quality parameters, particularly Total Organic Carbon (TOC) and bromide concentrations, are not directly regulated for drinking water, these parameters are precursors to the formation of disinfection byproducts (DBPs), which are regulated in drinking water distribution systems. These DBPs form when a disinfectant, added to the water to protect public health against microbial pathogens, most commonly chlorine, reacts with dissolved organic matter (DOM), measured as TOC or dissolved organic carbon (DOC), and inorganic precursor materials, such as bromide. Therefore, understanding and modeling the extremes of TOC and Bromide concentrations is of critical interest for drinking water utilities. In this study we develop nonstationary extreme value analysis models for threshold exceedances of source water quality parameters, specifically TOC and bromide concentrations. In this, the threshold exceedances are modeled as Generalized Pareto Distribution (GPD) whose parameters vary as a function of climate and land surface variables - thus, enabling to capture the temporal nonstationarity. We apply these to model threshold exceedance of source water TOC and bromide concentrations at two locations with different climate and find very good performance.

Ground-Water Quality Data in the Middle Sacramento Valley Study Unit, 2006 - Results from the California GAMA Program

USGS Publications Warehouse

Schmitt, Stephen J.; Fram, Miranda S.; Milby Dawson, Barbara J.; Belitz, Kenneth

2008-01-01

, replicates, laboratory matrix spikes) were collected at approximately 10 percent of the wells, and the results for these samples were used to evaluate the quality of the data for the ground-water samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a noticeable source of bias in the data for the ground-water samples. Differences between replicate samples were within acceptable ranges, indicating acceptably low variability. Matrix spike recoveries were within acceptable ranges for most constituents. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, or blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only and are not indicative of compliance or noncompliance with regulatory thresholds. Most constituents that were detected in ground-water samples were found at concentrations below drinking-water thresholds. VOCs were detected in less than one-third and pesticides and pesticide degradates in just over one-half of the grid wells, and all detections of these constituents in samples from all wells of the MSACV study unit were below health-based thresholds. All detections of trace elements in samples from MSACV grid wells were below health-based thresholds, with the exceptions of arsenic and boro

Data Quality Objectives for Regulatory Requirements for Hazardous and Radioactive Air Emissions Sampling and Analysis

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

MULKEY, C.H.

1999-07-06

This document describes the results of the data quality objective (DQO) process undertaken to define data needs for state and federal requirements associated with toxic, hazardous, and/or radiological air emissions under the jurisdiction of the River Protection Project (RPP). Hereafter, this document is referred to as the Air DQO. The primary drivers for characterization under this DQO are the regulatory requirements pursuant to Washington State regulations, that may require sampling and analysis. The federal regulations concerning air emissions are incorporated into the Washington State regulations. Data needs exist for nonradioactive and radioactive waste constituents and characteristics as identified through themore » DQO process described in this document. The purpose is to identify current data needs for complying with regulatory drivers for the measurement of air emissions from RPP facilities in support of air permitting. These drivers include best management practices; similar analyses may have more than one regulatory driver. This document should not be used for determining overall compliance with regulations because the regulations are in constant change, and this document may not reflect the latest regulatory requirements. Regulatory requirements are also expected to change as various permits are issued. Data needs require samples for both radionuclides and nonradionuclide analytes of air emissions from tanks and stored waste containers. The collection of data is to support environmental permitting and compliance, not for health and safety issues. This document does not address health or safety regulations or requirements (those of the Occupational Safety and Health Administration or the National Institute of Occupational Safety and Health) or continuous emission monitoring systems. This DQO is applicable to all equipment, facilities, and operations under the jurisdiction of RPP that emit or have the potential to emit regulated air pollutants.« less

Color difference thresholds in dentistry.

PubMed

Paravina, Rade D; Ghinea, Razvan; Herrera, Luis J; Bona, Alvaro D; Igiel, Christopher; Linninger, Mercedes; Sakai, Maiko; Takahashi, Hidekazu; Tashkandi, Esam; Perez, Maria del Mar

2015-01-01

The aim of this prospective multicenter study was to determine 50:50% perceptibility threshold (PT) and 50:50% acceptability threshold (AT) of dental ceramic under simulated clinical settings. The spectral radiance of 63 monochromatic ceramic specimens was determined using a non-contact spectroradiometer. A total of 60 specimen pairs, divided into 3 sets of 20 specimen pairs (medium to light shades, medium to dark shades, and dark shades), were selected for psychophysical experiment. The coordinating center and seven research sites obtained the Institutional Review Board (IRB) approvals prior the beginning of the experiment. Each research site had 25 observers, divided into five groups of five observers: dentists-D, dental students-S, dental auxiliaries-A, dental technicians-T, and lay persons-L. There were 35 observers per group (five observers per group at each site ×7 sites), for a total of 175 observers. Visual color comparisons were performed using a viewing booth. Takagi-Sugeno-Kang (TSK) fuzzy approximation was used for fitting the data points. The 50:50% PT and 50:50% AT were determined in CIELAB and CIEDE2000. The t-test was used to evaluate the statistical significance in thresholds differences. The CIELAB 50:50% PT was ΔEab  = 1.2, whereas 50:50% AT was ΔEab  = 2.7. Corresponding CIEDE2000 (ΔE00 ) values were 0.8 and 1.8, respectively. 50:50% PT by the observer group revealed differences among groups D, A, T, and L as compared with 50:50% PT for all observers. The 50:50% AT for all observers was statistically different than 50:50% AT in groups T and L. A 50:50% perceptibility and ATs were significantly different. The same is true for differences between two color difference formulas ΔE00 /ΔEab . Observer groups and sites showed high level of statistical difference in all thresholds. Visual color difference thresholds can serve as a quality control tool to guide the selection of esthetic dental materials, evaluate clinical performance, and

Predictive minimum description length principle approach to inferring gene regulatory networks.

PubMed

Chaitankar, Vijender; Zhang, Chaoyang; Ghosh, Preetam; Gong, Ping; Perkins, Edward J; Deng, Youping

2011-01-01

Reverse engineering of gene regulatory networks using information theory models has received much attention due to its simplicity, low computational cost, and capability of inferring large networks. One of the major problems with information theory models is to determine the threshold that defines the regulatory relationships between genes. The minimum description length (MDL) principle has been implemented to overcome this problem. The description length of the MDL principle is the sum of model length and data encoding length. A user-specified fine tuning parameter is used as control mechanism between model and data encoding, but it is difficult to find the optimal parameter. In this work, we propose a new inference algorithm that incorporates mutual information (MI), conditional mutual information (CMI), and predictive minimum description length (PMDL) principle to infer gene regulatory networks from DNA microarray data. In this algorithm, the information theoretic quantities MI and CMI determine the regulatory relationships between genes and the PMDL principle method attempts to determine the best MI threshold without the need of a user-specified fine tuning parameter. The performance of the proposed algorithm is evaluated using both synthetic time series data sets and a biological time series data set (Saccharomyces cerevisiae). The results show that the proposed algorithm produced fewer false edges and significantly improved the precision when compared to existing MDL algorithm.

Aggregate analysis of regulatory authority assessors' comments to improve the quality of periodic safety update reports.

PubMed

Jullian, Sandra; Jaskiewicz, Lukasz; Pfannkuche, Hans-Jürgen; Parker, Jeremy; Lalande-Luesink, Isabelle; Lewis, David J; Close, Philippe

2015-09-01

Marketing authorization holders (MAHs) are expected to provide high-quality periodic safety update reports (PSURs) on their pharmaceutical products to health authorities (HAs). We present a novel instrument aiming at improving quality of PSURs based on standardized analysis of PSUR assessment reports (ARs) received from the European Union HAs across products and therapeutic areas. All HA comments were classified into one of three categories: "Request for regulatory actions," "Request for medical and scientific information," or "Data deficiencies." The comments were graded according to their impact on patients' safety, the drug's benefit-risk profile, and the MAH's pharmacovigilance system. A total of 476 comments were identified through the analysis of 63 PSUR HA ARs received in 2013 and 2014; 47 (10%) were classified as "Requests for regulatory actions," 309 (65%) as "Requests for medical and scientific information," and 118 (25%) comments were related to "Data deficiencies." The most frequent comments were requests for labeling changes (35 HA comments in 19 ARs). The aggregate analysis revealed commonly raised issues and prompted changes of the MAH's procedures related to the preparation of PSURs. The authors believe that this novel instrument based on the evaluation of PSUR HA ARs serves as a valuable mechanism to enhance the quality of PSURs and decisions about optimization of the use of the products and, therefore, contributes to improve further the MAH's pharmacovigilance system and patient safety. Copyright © 2015 John Wiley & Sons, Ltd.

Regulatory affairs and biotechnology in Europe. I. Introduction into good regulatory practice.

PubMed

Tryzelaar, B

1988-01-01

The high cost and risks associated with the research and development of new drugs demand an alert as well as realistic legislative policy at both national and international levels. Registration of a new drug required before a marketing license is granted, is important for all branches of the pharmaceutical industry but is crucial for success in the innovative biotechnological sector. Innovation as such is no guarantee to be profitable. Increasing government demands have introduced uncertainty on whether new products will secure registration and have led to a disproportionate increase in the economical risks for innovative industry. Preparation and submission of an application for registration should be undertaken seriously and professionally since it has significantly more consequences than simply obtaining a marketing licence. It will influence marketing strategies and results. It is proposed--since dealing with regulatory affairs can be considered as an essential specialism--to apply a Quality Assurance approach. Activities in this context should comply with the same performance standards as developed for GMP, GLP and GCP leading to Good Regulatory Practice (GRP). By acknowledging regulatory affairs as a quality assurance means one can define a set of standard procedures within an organization to ensure that decisions are made on current and future regulations. In such a setup regulatory affairs becomes a marketing tool. This paper illustrates the complex problems found in registration activities. It underlines the necessity of introducing a GRP-approach of performance resulting in substantive evidence of regulatory efficacy.

HMMER Cut-off Threshold Tool (HMMERCTTER): Supervised classification of superfamily protein sequences with a reliable cut-off threshold.

PubMed

Pagnuco, Inti Anabela; Revuelta, María Victoria; Bondino, Hernán Gabriel; Brun, Marcel; Ten Have, Arjen

2018-01-01

Protein superfamilies can be divided into subfamilies of proteins with different functional characteristics. Their sequences can be classified hierarchically, which is part of sequence function assignation. Typically, there are no clear subfamily hallmarks that would allow pattern-based function assignation by which this task is mostly achieved based on the similarity principle. This is hampered by the lack of a score cut-off that is both sensitive and specific. HMMER Cut-off Threshold Tool (HMMERCTTER) adds a reliable cut-off threshold to the popular HMMER. Using a high quality superfamily phylogeny, it clusters a set of training sequences such that the cluster-specific HMMER profiles show cluster or subfamily member detection with 100% precision and recall (P&R), thereby generating a specific threshold as inclusion cut-off. Profiles and thresholds are then used as classifiers to screen a target dataset. Iterative inclusion of novel sequences to groups and the corresponding HMMER profiles results in high sensitivity while specificity is maintained by imposing 100% P&R self detection. In three presented case studies of protein superfamilies, classification of large datasets with 100% precision was achieved with over 95% recall. Limits and caveats are presented and explained. HMMERCTTER is a promising protein superfamily sequence classifier provided high quality training datasets are used. It provides a decision support system that aids in the difficult task of sequence function assignation in the twilight zone of sequence similarity. All relevant data and source codes are available from the Github repository at the following URL: https://github.com/BBCMdP/HMMERCTTER.

HMMER Cut-off Threshold Tool (HMMERCTTER): Supervised classification of superfamily protein sequences with a reliable cut-off threshold

PubMed Central

Pagnuco, Inti Anabela; Revuelta, María Victoria; Bondino, Hernán Gabriel; Brun, Marcel

2018-01-01

Background Protein superfamilies can be divided into subfamilies of proteins with different functional characteristics. Their sequences can be classified hierarchically, which is part of sequence function assignation. Typically, there are no clear subfamily hallmarks that would allow pattern-based function assignation by which this task is mostly achieved based on the similarity principle. This is hampered by the lack of a score cut-off that is both sensitive and specific. Results HMMER Cut-off Threshold Tool (HMMERCTTER) adds a reliable cut-off threshold to the popular HMMER. Using a high quality superfamily phylogeny, it clusters a set of training sequences such that the cluster-specific HMMER profiles show cluster or subfamily member detection with 100% precision and recall (P&R), thereby generating a specific threshold as inclusion cut-off. Profiles and thresholds are then used as classifiers to screen a target dataset. Iterative inclusion of novel sequences to groups and the corresponding HMMER profiles results in high sensitivity while specificity is maintained by imposing 100% P&R self detection. In three presented case studies of protein superfamilies, classification of large datasets with 100% precision was achieved with over 95% recall. Limits and caveats are presented and explained. Conclusions HMMERCTTER is a promising protein superfamily sequence classifier provided high quality training datasets are used. It provides a decision support system that aids in the difficult task of sequence function assignation in the twilight zone of sequence similarity. All relevant data and source codes are available from the Github repository at the following URL: https://github.com/BBCMdP/HMMERCTTER. PMID:29579071

Improvement in clinical outcomes after dry needling versus myofascial release on pain pressure thresholds, quality of life, fatigue, pain intensity, quality of sleep, anxiety, and depression in patients with fibromyalgia syndrome.

PubMed

Castro Sánchez, Adelaida M; García López, Hector; Fernández Sánchez, Manuel; Pérez Mármol, José Manuel; Aguilar-Ferrándiz, María Encarnación; Luque Suárez, Alejandro; Matarán Peñarrocha, Guillermo Adolfo

2018-04-23

To compare the effectiveness of dry needling versus myofascial release on myofascial trigger points pain in cervical muscles, quality of life, impact of symptoms pain, quality of sleep, anxiety, depression, and fatigue in patients with fibromyalgia syndrome. A single-blind randomized controlled trial was conducted. Sixty-four subjects with fibromyalgia were randomly assigned to a dry needling group or a myofascial release group. Pain pressure thresholds of myofascial trigger points were evaluated in the cervical muscles. In addition, quality of life, impact of fibromyalgia symptoms, quality of sleep, intensity of pain, anxiety and depression symptoms, impact of fatigue at baseline and post treatment after four weeks of intervention were evaluated. Significant improvement was found in most pain pressure thresholds of the myofascial trigger points in cervical muscles in the dry needling group compared to myofascial release (p < 0.05). Similarly, these differences between groups were found for the components of quality of life of physical function (F = 12.74, p = 0.001), physical role (F = 11.24, p = 0.001), body pain (F =30.26, p < 0.001), general health (F = 15.83, p < 0.001), vitality (F = 13.51, p = 0.001), social function (F = 4.73, p = 0.034), emotional role (F = 8.01, p = 0.006), and mental health (F = 4.95, p = 0.030). Similar results were achieved for total impact of FMS symptoms (F = 42.91, p < 0.001), quality of sleep (F = 11.96, p = 0.001), state anxiety (F = 7.40, p = 0.009), and trait anxiety (F = -14.63, p < 0.001), hospital anxiety and depression (F = 20.60, p < 0.001), general pain intensity (F = 29.59, p < 0.001), and fatigue (F = -25.73, p < 0.001). The dry needling therapy showed higher improvements in comparison with myofascial release therapy for pain pressure thresholds, the components of quality of life of physical role

The Use of Regulatory Air Quality Models to Develop Successful Ozone Attainment Strategies

NASA Astrophysics Data System (ADS)

Canty, T. P.; Salawitch, R. J.; Dickerson, R. R.; Ring, A.; Goldberg, D. L.; He, H.; Anderson, D. C.; Vinciguerra, T.

2015-12-01

The Environmental Protection Agency (EPA) recently proposed lowering the 8-hr ozone standard to between 65-70 ppb. Not all regions of the U.S. are in attainment of the current 75 ppb standard and it is expected that many regions currently in attainment will not meet the future, lower surface ozone standard. Ozone production is a nonlinear function of emissions, biological processes, and weather. Federal and state agencies rely on regulatory air quality models such as the Community Multi-Scale Air Quality (CMAQ) model and Comprehensive Air Quality Model with Extensions (CAMx) to test ozone precursor emission reduction strategies that will bring states into compliance with the National Ambient Air Quality Standards (NAAQS). We will describe various model scenarios that simulate how future limits on emission of ozone precursors (i.e. NOx and VOCs) from sources such as power plants and vehicles will affect air quality. These scenarios are currently being developed by states required to submit a State Implementation Plan to the EPA. Projections from these future case scenarios suggest that strategies intended to control local ozone may also bring upwind states into attainment of the new NAAQS. Ground based, aircraft, and satellite observations are used to ensure that air quality models accurately represent photochemical processes within the troposphere. We will highlight some of the improvements made to the CMAQ and CAMx model framework based on our analysis of NASA observations obtained by the OMI instrument on the Aura satellite and by the DISCOVER-AQ field campaign.

Compressively sampled MR image reconstruction using generalized thresholding iterative algorithm

NASA Astrophysics Data System (ADS)

Elahi, Sana; kaleem, Muhammad; Omer, Hammad

2018-01-01

Compressed sensing (CS) is an emerging area of interest in Magnetic Resonance Imaging (MRI). CS is used for the reconstruction of the images from a very limited number of samples in k-space. This significantly reduces the MRI data acquisition time. One important requirement for signal recovery in CS is the use of an appropriate non-linear reconstruction algorithm. It is a challenging task to choose a reconstruction algorithm that would accurately reconstruct the MR images from the under-sampled k-space data. Various algorithms have been used to solve the system of non-linear equations for better image quality and reconstruction speed in CS. In the recent past, iterative soft thresholding algorithm (ISTA) has been introduced in CS-MRI. This algorithm directly cancels the incoherent artifacts produced because of the undersampling in k -space. This paper introduces an improved iterative algorithm based on p -thresholding technique for CS-MRI image reconstruction. The use of p -thresholding function promotes sparsity in the image which is a key factor for CS based image reconstruction. The p -thresholding based iterative algorithm is a modification of ISTA, and minimizes non-convex functions. It has been shown that the proposed p -thresholding iterative algorithm can be used effectively to recover fully sampled image from the under-sampled data in MRI. The performance of the proposed method is verified using simulated and actual MRI data taken at St. Mary's Hospital, London. The quality of the reconstructed images is measured in terms of peak signal-to-noise ratio (PSNR), artifact power (AP), and structural similarity index measure (SSIM). The proposed approach shows improved performance when compared to other iterative algorithms based on log thresholding, soft thresholding and hard thresholding techniques at different reduction factors.

Threshold-based segmentation of fluorescent and chromogenic images of microglia, astrocytes and oligodendrocytes in FIJI.

PubMed

Healy, Sinead; McMahon, Jill; Owens, Peter; Dockery, Peter; FitzGerald, Una

2018-02-01

Image segmentation is often imperfect, particularly in complex image sets such z-stack micrographs of slice cultures and there is a need for sufficient details of parameters used in quantitative image analysis to allow independent repeatability and appraisal. For the first time, we have critically evaluated, quantified and validated the performance of different segmentation methodologies using z-stack images of ex vivo glial cells. The BioVoxxel toolbox plugin, available in FIJI, was used to measure the relative quality, accuracy, specificity and sensitivity of 16 global and 9 local threshold automatic thresholding algorithms. Automatic thresholding yields improved binary representation of glial cells compared with the conventional user-chosen single threshold approach for confocal z-stacks acquired from ex vivo slice cultures. The performance of threshold algorithms varies considerably in quality, specificity, accuracy and sensitivity with entropy-based thresholds scoring highest for fluorescent staining. We have used the BioVoxxel toolbox to correctly and consistently select the best automated threshold algorithm to segment z-projected images of ex vivo glial cells for downstream digital image analysis and to define segmentation quality. The automated OLIG2 cell count was validated using stereology. As image segmentation and feature extraction can quite critically affect the performance of successive steps in the image analysis workflow, it is becoming increasingly necessary to consider the quality of digital segmenting methodologies. Here, we have applied, validated and extended an existing performance-check methodology in the BioVoxxel toolbox to z-projected images of ex vivo glia cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Using satellite observations in performance evaluation for regulatory air quality modeling: Comparison with ground-level measurements

NASA Astrophysics Data System (ADS)

Odman, M. T.; Hu, Y.; Russell, A.; Chai, T.; Lee, P.; Shankar, U.; Boylan, J.

2012-12-01

Regulatory air quality modeling, such as State Implementation Plan (SIP) modeling, requires that model performance meets recommended criteria in the base-year simulations using period-specific, estimated emissions. The goal of the performance evaluation is to assure that the base-year modeling accurately captures the observed chemical reality of the lower troposphere. Any significant deficiencies found in the performance evaluation must be corrected before any base-case (with typical emissions) and future-year modeling is conducted. Corrections are usually made to model inputs such as emission-rate estimates or meteorology and/or to the air quality model itself, in modules that describe specific processes. Use of ground-level measurements that follow approved protocols is recommended for evaluating model performance. However, ground-level monitoring networks are spatially sparse, especially for particulate matter. Satellite retrievals of atmospheric chemical properties such as aerosol optical depth (AOD) provide spatial coverage that can compensate for the sparseness of ground-level measurements. Satellite retrievals can also help diagnose potential model or data problems in the upper troposphere. It is possible to achieve good model performance near the ground, but have, for example, erroneous sources or sinks in the upper troposphere that may result in misleading and unrealistic responses to emission reductions. Despite these advantages, satellite retrievals are rarely used in model performance evaluation, especially for regulatory modeling purposes, due to the high uncertainty in retrievals associated with various contaminations, for example by clouds. In this study, 2007 was selected as the base year for SIP modeling in the southeastern U.S. Performance of the Community Multiscale Air Quality (CMAQ) model, at a 12-km horizontal resolution, for this annual simulation is evaluated using both recommended ground-level measurements and non-traditional satellite

Two new competing pathways establish the threshold for cyclin-B-Cdk1 activation at the meiotic G2/M transition.

PubMed

Hiraoka, Daisaku; Aono, Ryota; Hanada, Shin-Ichiro; Okumura, Eiichi; Kishimoto, Takeo

2016-08-15

Extracellular ligands control biological phenomena. Cells distinguish physiological stimuli from weak noise stimuli by establishing a ligand-concentration threshold. Hormonal control of the meiotic G2/M transition in oocytes is essential for reproduction. However, the mechanism for threshold establishment is unclear. In starfish oocytes, maturation-inducing hormones activate the PI3K-Akt pathway through the Gβγ complex of heterotrimeric G-proteins. Akt directly phosphorylates both Cdc25 phosphatase and Myt1 kinase, resulting in activation of cyclin-B-Cdk1, which then induces meiotic G2/M transition. Here, we show that cyclin-B-Cdk1 is partially activated after subthreshold hormonal stimuli, but this triggers negative feedback, resulting in dephosphorylation of Akt sites on Cdc25 and Myt1, thereby canceling the signal. We also identified phosphatase activity towards Akt substrates that exists independent of stimuli. In contrast to these negative regulatory activities, an atypical Gβγ-dependent pathway enhances PI3K-Akt-dependent phosphorylation. Based on these findings, we propose a model for threshold establishment in which hormonal dose-dependent competition between these new pathways establishes a threshold; the atypical Gβγ-pathway becomes predominant over Cdk-dependent negative feedback when the stimulus exceeds this threshold. Our findings provide a regulatory connection between cell cycle and signal transduction machineries. © 2016. Published by The Company of Biologists Ltd.

The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP).

PubMed

Paskiet, Diane; Jenke, Dennis; Ball, Douglas; Houston, Christopher; Norwood, Daniel L; Markovic, Ingrid

2013-01-01

The Product Quality Research Institute (PQRI) is a non-profit consortium of organizations working together to generate and share timely, relevant, and impactful information that advances drug product quality and development. The collaborative activities of PQRI participants have, in the case of orally inhaled and nasal drug products (OINDPs), resulted in comprehensive and widely-accepted recommendations for leachables assessments to help ensure patient safety with respect to this class of packaged drug products. These recommendations, which include scientifically justified safety thresholds for leachables, represent a significant milestone towards establishing standardized approaches for safety qualification of leachables in OINDP. To build on the success of the OINDP effort, PQRI's Parenteral and Ophthalmic Drug Products (PODP) Leachables and Extractables Working Group was formed to extrapolate the OINDP threshold concepts and best practice recommendations to other dosage forms with high concern for interaction with packaging/delivery systems. This article considers the general aspects of leachables and their safety assessment, introduces the PODP Work Plan and initial study Protocol, discusses the laboratory studies being conducted by the PODP Chemistry Team, outlines the strategy being developed by the PODP Toxicology Team for the safety qualification of PODP leachables, and considers the issues associated with application of the safety thresholds, particularly with respect to large-volume parenterals. Lastly, the unique leachables issues associated with biologics are described. The Product Quality Research Institute (PQRI) is a non-profit consortium involving industry organizations, academia, and regulatory agencies that together provide recommendations in support of regulatory guidance to advance drug product quality. The collaborative activities of the PQRI Orally Inhaled and Nasal Drug Products Leachables and Extractables Working Group resulted in a

Optimizing Retransmission Threshold in Wireless Sensor Networks

PubMed Central

Bi, Ran; Li, Yingshu; Tan, Guozhen; Sun, Liang

2016-01-01

The retransmission threshold in wireless sensor networks is critical to the latency of data delivery in the networks. However, existing works on data transmission in sensor networks did not consider the optimization of the retransmission threshold, and they simply set the same retransmission threshold for all sensor nodes in advance. The method did not take link quality and delay requirement into account, which decreases the probability of a packet passing its delivery path within a given deadline. This paper investigates the problem of finding optimal retransmission thresholds for relay nodes along a delivery path in a sensor network. The object of optimizing retransmission thresholds is to maximize the summation of the probability of the packet being successfully delivered to the next relay node or destination node in time. A dynamic programming-based distributed algorithm for finding optimal retransmission thresholds for relay nodes along a delivery path in the sensor network is proposed. The time complexity is OnΔ·max1≤i≤n{ui}, where ui is the given upper bound of the retransmission threshold of sensor node i in a given delivery path, n is the length of the delivery path and Δ is the given upper bound of the transmission delay of the delivery path. If Δ is greater than the polynomial, to reduce the time complexity, a linear programming-based (1+pmin)-approximation algorithm is proposed. Furthermore, when the ranges of the upper and lower bounds of retransmission thresholds are big enough, a Lagrange multiplier-based distributed O(1)-approximation algorithm with time complexity O(1) is proposed. Experimental results show that the proposed algorithms have better performance. PMID:27171092

Threshold and resilience management of coupled urbanization and water environmental system in the rapidly changing coastal region.

PubMed

Li, Yangfan; Li, Yi; Wu, Wei

2016-01-01

The concept of thresholds shows important implications for environmental and resource management. Here we derived potential landscape thresholds which indicated abrupt changes in water quality or the dividing points between exceeding and failing to meet national surface water quality standards for a rapidly urbanizing city on the Eastern Coast in China. The analysis of landscape thresholds was based on regression models linking each of the seven water quality variables to each of the six landscape metrics for this coupled land-water system. We found substantial and accelerating urban sprawl at the suburban areas between 2000 and 2008, and detected significant nonlinear relations between water quality and landscape pattern. This research demonstrated that a simple modeling technique could provide insights on environmental thresholds to support more-informed decision making in land use, water environmental and resilience management. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of the evolution of the pharmaceutical regulatory environment.

PubMed

Shafiei, Nader; Ford, James L; Morecroft, Charles W; Lisboa, Paulo J; Taylor, Mark J

2013-01-01

This paper is part of a research study that is intended to identify pharmaceutical quality risks induced by the ongoing transformation in the industry. This study establishes the current regulatory context by characterizing the development of the pharmaceutical regulatory environment. The regulatory environment is one of the most important external factors that affects a company's organization, processes, and technological strategy. This is especially the case with the pharmaceutical industry, where its products affect the quality of life of the consumers. The quantitative analysis of regulatory events since 1813 and review of the associated literature resulted in identification of six factors influencing the regulatory environment, namely public health protection, public health promotion, crisis management, harmonization, innovation, and modernization. From 1813 to the 1970s the focus of regulators was centered on crisis management and public health protection-a basic mission that has remained consistent over the years. Since the 1980s a gradual move in the regulatory environment towards a greater focus on public health promotion, international harmonization, innovation, and agency modernization may be seen. The pharmaceutical industry is currently going through changes that affect the way it performs its research, manufacturing, and regulatory activities. The impact of these changes on the approaches to quality risk management requires more understanding. The authors are engaged in research to identify elements of the changes that influence pharmaceutical quality. As quality requirements are an integral part of the pharmaceutical regulations, a comprehensive understanding of these regulations is seen as the first step. The results of this study show that (i) public health protection, public health promotion, crisis management, harmonization, innovation, and modernization are factors that affect regulations in the pharmaceutical industry; (ii) the regulators' main

Rationality, practice variation and person-centred health policy: a threshold hypothesis.

PubMed

Djulbegovic, Benjamin; Hamm, Robert M; Mayrhofer, Thomas; Hozo, Iztok; Van den Ende, Jef

2015-12-01

Variation in practice of medicine is one of the major health policy issues of today. Ultimately, it is related to physicians' decision making. Similar patients with similar likelihood of having disease are often managed by different doctors differently: some doctors may elect to observe the patient, others decide to act based on diagnostic testing and yet others may elect to treat without testing. We explain these differences in practice by differences in disease probability thresholds at which physicians decide to act: contextual social and clinical factors and emotions such as regret affect the threshold by influencing the way doctors integrate objective data related to treatment and testing. However, depending on a theoretical construct each of the physician's behaviour can be considered rational. In fact, we showed that the current regulatory policies lead to predictably low thresholds for most decisions in contemporary practice. As a result, we may expect continuing motivation for overuse of treatment and diagnostic tests. We argue that rationality should take into account both formal principles of rationality and human intuitions about good decisions along the lines of Rawls' 'reflective equilibrium/considered judgment'. In turn, this can help define a threshold model that is empirically testable. © 2015 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

Rationality, practice variation and person‐centred health policy: a threshold hypothesis

PubMed Central

Hamm, Robert M.; Mayrhofer, Thomas; Hozo, Iztok; Van den Ende, Jef

2015-01-01

Abstract Variation in practice of medicine is one of the major health policy issues of today. Ultimately, it is related to physicians' decision making. Similar patients with similar likelihood of having disease are often managed by different doctors differently: some doctors may elect to observe the patient, others decide to act based on diagnostic testing and yet others may elect to treat without testing. We explain these differences in practice by differences in disease probability thresholds at which physicians decide to act: contextual social and clinical factors and emotions such as regret affect the threshold by influencing the way doctors integrate objective data related to treatment and testing. However, depending on a theoretical construct each of the physician's behaviour can be considered rational. In fact, we showed that the current regulatory policies lead to predictably low thresholds for most decisions in contemporary practice. As a result, we may expect continuing motivation for overuse of treatment and diagnostic tests. We argue that rationality should take into account both formal principles of rationality and human intuitions about good decisions along the lines of Rawls' ‘reflective equilibrium/considered judgment’. In turn, this can help define a threshold model that is empirically testable. PMID:26639018

SART-Type Half-Threshold Filtering Approach for CT Reconstruction

PubMed Central

YU, HENGYONG; WANG, GE

2014-01-01

The ℓ1 regularization problem has been widely used to solve the sparsity constrained problems. To enhance the sparsity constraint for better imaging performance, a promising direction is to use the ℓp norm (0 < p < 1) and solve the ℓp minimization problem. Very recently, Xu et al. developed an analytic solution for the ℓ1∕2 regularization via an iterative thresholding operation, which is also referred to as half-threshold filtering. In this paper, we design a simultaneous algebraic reconstruction technique (SART)-type half-threshold filtering framework to solve the computed tomography (CT) reconstruction problem. In the medical imaging filed, the discrete gradient transform (DGT) is widely used to define the sparsity. However, the DGT is noninvertible and it cannot be applied to half-threshold filtering for CT reconstruction. To demonstrate the utility of the proposed SART-type half-threshold filtering framework, an emphasis of this paper is to construct a pseudoinverse transforms for DGT. The proposed algorithms are evaluated with numerical and physical phantom data sets. Our results show that the SART-type half-threshold filtering algorithms have great potential to improve the reconstructed image quality from few and noisy projections. They are complementary to the counterparts of the state-of-the-art soft-threshold filtering and hard-threshold filtering. PMID:25530928

SART-Type Half-Threshold Filtering Approach for CT Reconstruction.

PubMed

Yu, Hengyong; Wang, Ge

2014-01-01

The [Formula: see text] regularization problem has been widely used to solve the sparsity constrained problems. To enhance the sparsity constraint for better imaging performance, a promising direction is to use the [Formula: see text] norm (0 < p < 1) and solve the [Formula: see text] minimization problem. Very recently, Xu et al. developed an analytic solution for the [Formula: see text] regularization via an iterative thresholding operation, which is also referred to as half-threshold filtering. In this paper, we design a simultaneous algebraic reconstruction technique (SART)-type half-threshold filtering framework to solve the computed tomography (CT) reconstruction problem. In the medical imaging filed, the discrete gradient transform (DGT) is widely used to define the sparsity. However, the DGT is noninvertible and it cannot be applied to half-threshold filtering for CT reconstruction. To demonstrate the utility of the proposed SART-type half-threshold filtering framework, an emphasis of this paper is to construct a pseudoinverse transforms for DGT. The proposed algorithms are evaluated with numerical and physical phantom data sets. Our results show that the SART-type half-threshold filtering algorithms have great potential to improve the reconstructed image quality from few and noisy projections. They are complementary to the counterparts of the state-of-the-art soft-threshold filtering and hard-threshold filtering.

Searching for statistically significant regulatory modules.

PubMed

Bailey, Timothy L; Noble, William Stafford

2003-10-01

The regulatory machinery controlling gene expression is complex, frequently requiring multiple, simultaneous DNA-protein interactions. The rate at which a gene is transcribed may depend upon the presence or absence of a collection of transcription factors bound to the DNA near the gene. Locating transcription factor binding sites in genomic DNA is difficult because the individual sites are small and tend to occur frequently by chance. True binding sites may be identified by their tendency to occur in clusters, sometimes known as regulatory modules. We describe an algorithm for detecting occurrences of regulatory modules in genomic DNA. The algorithm, called mcast, takes as input a DNA database and a collection of binding site motifs that are known to operate in concert. mcast uses a motif-based hidden Markov model with several novel features. The model incorporates motif-specific p-values, thereby allowing scores from motifs of different widths and specificities to be compared directly. The p-value scoring also allows mcast to only accept motif occurrences with significance below a user-specified threshold, while still assigning better scores to motif occurrences with lower p-values. mcast can search long DNA sequences, modeling length distributions between motifs within a regulatory module, but ignoring length distributions between modules. The algorithm produces a list of predicted regulatory modules, ranked by E-value. We validate the algorithm using simulated data as well as real data sets from fruitfly and human. http://meme.sdsc.edu/MCAST/paper

THRESHOLD LOGIC.

DTIC Science & Technology

synthesis procedures; a ’best’ method is definitely established. (2) ’Symmetry Types for Threshold Logic’ is a tutorial expositon including a careful...development of the Goto-Takahasi self-dual type ideas. (3) ’Best Threshold Gate Decisions’ reports a comparison, on the 2470 7-argument threshold ...interpretation is shown best. (4) ’ Threshold Gate Networks’ reviews the previously discussed 2-algorithm in geometric terms, describes our FORTRAN

A global regulatory science agenda for vaccines.

PubMed

Elmgren, Lindsay; Li, Xuguang; Wilson, Carolyn; Ball, Robert; Wang, Junzhi; Cichutek, Klaus; Pfleiderer, Michael; Kato, Atsushi; Cavaleri, Marco; Southern, James; Jivapaisarnpong, Teeranart; Minor, Philip; Griffiths, Elwyn; Sohn, Yeowon; Wood, David

2013-04-18

The Decade of Vaccines Collaboration and development of the Global Vaccine Action Plan provides a catalyst and unique opportunity for regulators worldwide to develop and propose a global regulatory science agenda for vaccines. Regulatory oversight is critical to allow access to vaccines that are safe, effective, and of assured quality. Methods used by regulators need to constantly evolve so that scientific and technological advances are applied to address challenges such as new products and technologies, and also to provide an increased understanding of benefits and risks of existing products. Regulatory science builds on high-quality basic research, and encompasses at least two broad categories. First, there is laboratory-based regulatory science. Illustrative examples include development of correlates of immunity; or correlates of safety; or of improved product characterization and potency assays. Included in such science would be tools to standardize assays used for regulatory purposes. Second, there is science to develop regulatory processes. Illustrative examples include adaptive clinical trial designs; or tools to analyze the benefit-risk decision-making process of regulators; or novel pharmacovigilance methodologies. Included in such science would be initiatives to standardize regulatory processes (e.g., definitions of terms for adverse events [AEs] following immunization). The aim of a global regulatory science agenda is to transform current national efforts, mainly by well-resourced regulatory agencies, into a coordinated action plan to support global immunization goals. This article provides examples of how regulatory science has, in the past, contributed to improved access to vaccines, and identifies gaps that could be addressed through a global regulatory science agenda. The article also identifies challenges to implementing a regulatory science agenda and proposes strategies and actions to fill these gaps. A global regulatory science agenda will enable

Validation of gamma irradiator controls for quality and regulatory compliance

NASA Astrophysics Data System (ADS)

Harding, Rorry B.; Pinteric, Francis J. A.

1995-09-01

Since 1978 the U.S. Food and Drug Administration (FDA) has had both the legal authority and the Current Good Manufacturing Practice (CGMP) regulations in place to require irradiator owners who process medical devices to produce evidence of Irradiation Process Validation. One of the key components of Irradiation Process Validation is the validation of the irradiator controls. However, it is only recently that FDA audits have focused on this component of the process validation. What is Irradiator Control System Validation? What constitutes evidence of control? How do owners obtain evidence? What is the irradiator supplier's role in validation? How does the ISO 9000 Quality Standard relate to the FDA's CGMP requirement for evidence of Control System Validation? This paper presents answers to these questions based on the recent experiences of Nordion's engineering and product management staff who have worked with several US-based irradiator owners. This topic — Validation of Irradiator Controls — is a significant regulatory compliance and operations issue within the irradiator suppliers' and users' community.

76 FR 34118 - Self-Regulatory Organizations; The Depository Trust Company; Order Granting Approval of a...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-10

... to be held in its account as a threshold to any intraday redelivery. When the counter for a security... received intraday regardless of any MSEG-related deficit. Recently, DTC was advised by the Regulatory and...

Threshold quantum cryptography

NASA Astrophysics Data System (ADS)

Tokunaga, Yuuki; Okamoto, Tatsuaki; Imoto, Nobuyuki

2005-01-01

We present the concept of threshold collaborative unitary transformation or threshold quantum cryptography, which is a kind of quantum version of threshold cryptography. Threshold quantum cryptography states that classical shared secrets are distributed to several parties and a subset of them, whose number is greater than a threshold, collaborates to compute a quantum cryptographic function, while keeping each share secretly inside each party. The shared secrets are reusable if no cheating is detected. As a concrete example of this concept, we show a distributed protocol (with threshold) of conjugate coding.

Ultralow-threshold Raman lasing with CaF2 resonators.

PubMed

Grudinin, Ivan S; Maleki, Lute

2007-01-15

We demonstrate efficient Raman lasing with CaF2 whispering-gallery-mode resonators. Continuous-wave emission threshold is shown to be possible below 1 microW with a 5mm cavity, which is to our knowledge orders of magnitude lower than in any other Raman source. Low-threshold lasing is made possible by the ultrahigh optical quality factor of the cavity, of the order of Q=5x10(10). Stokes components of up to the fifth order were observed at a pump power of 160 microW, and up to the eighth order at 1 mW. A lasing threshold of 15 microW was also observed in a 100 microm CaF2 microcavity. Potential applications are discussed.

Economic Analysis Supporting the Increase of the Unspecified Minor Military Construction Threshold

DTIC Science & Technology

2016-06-01

UNSPECIFIED MINOR MILITARY CONSTRUCTION THRESHOLD June 2016 By: Clifford L. Kelsey Advisors: Philip Candreva Amilcar Menichini...THE UNSPECIFIED MINOR MILITARY CONSTRUCTION THRESHOLD 5. FUNDING NUMBERS 6. AUTHOR(S) Clifford L. Kelsey 7. PERFORMING ORGANIZATION NAME(S) AND...words) This report analyzes the economical, technological, and environmental challenges U.S. Navy engineers face in constructing quality, usable

Implementation of a WRF-CMAQ Air Quality Modeling System in Bogotá, Colombia

NASA Astrophysics Data System (ADS)

Nedbor-Gross, R.; Henderson, B. H.; Pachon, J. E.; Davis, J. R.; Baublitz, C. B.; Rincón, A.

2014-12-01

Due to a continuous economic growth Bogotá, Colombia has experienced air pollution issues in recent years. The local environmental authority has implemented several strategies to curb air pollution that have resulted in the decrease of PM10 concentrations since 2010. However, more activities are necessary in order to meet international air quality standards in the city. The University of Florida Air Quality and Climate group is collaborating with the Universidad de La Salle to prioritize regulatory strategies for Bogotá using air pollution simulations. To simulate pollution, we developed a modeling platform that combines the Weather Research and Forecasting Model (WRF), local emissions, and the Community Multi-scale Air Quality model (CMAQ). This platform is the first of its kind to be implemented in the megacity of Bogota, Colombia. The presentation will discuss development and evaluation of the air quality modeling system, highlight initial results characterizing photochemical conditions in Bogotá, and characterize air pollution under proposed regulatory strategies. The WRF model has been configured and applied to Bogotá, which resides in a tropical climate with complex mountainous topography. Developing the configuration included incorporation of local topography and land-use data, a physics sensitivity analysis, review, and systematic evaluation. The threshold, however, was set based on synthesis of model performance under less mountainous conditions. We will evaluate the impact that differences in autocorrelation contribute to the non-ideal performance. Air pollution predictions are currently under way. CMAQ has been configured with WRF meteorology, global boundary conditions from GEOS-Chem, and a locally produced emission inventory. Preliminary results from simulations show promising performance of CMAQ in Bogota. Anticipated results include a systematic performance evaluation of ozone and PM10, characterization of photochemical sensitivity, and air

Event-based cluster synchronization of coupled genetic regulatory networks

NASA Astrophysics Data System (ADS)

Yue, Dandan; Guan, Zhi-Hong; Li, Tao; Liao, Rui-Quan; Liu, Feng; Lai, Qiang

2017-09-01

In this paper, the cluster synchronization of coupled genetic regulatory networks with a directed topology is studied by using the event-based strategy and pinning control. An event-triggered condition with a threshold consisting of the neighbors' discrete states at their own event time instants and a state-independent exponential decay function is proposed. The intra-cluster states information and extra-cluster states information are involved in the threshold in different ways. By using the Lyapunov function approach and the theories of matrices and inequalities, we establish the cluster synchronization criterion. It is shown that both the avoidance of continuous transmission of information and the exclusion of the Zeno behavior are ensured under the presented triggering condition. Explicit conditions on the parameters in the threshold are obtained for synchronization. The stability criterion of a single GRN is also given under the reduced triggering condition. Numerical examples are provided to validate the theoretical results.

78 FR 37850 - Quality Assurance Program Requirements (Operations)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0021] Quality Assurance Program Requirements (Operations... Regulatory Commission (NRC) is issuing a revision to Regulatory Guide (RG) 1.33, ``Quality Assurance Program... managerial and administrative Quality Assurance (QA) controls for nuclear power plants during operations...

Electrocardiogram signal denoising based on a new improved wavelet thresholding

NASA Astrophysics Data System (ADS)

Han, Guoqiang; Xu, Zhijun

2016-08-01

Good quality electrocardiogram (ECG) is utilized by physicians for the interpretation and identification of physiological and pathological phenomena. In general, ECG signals may mix various noises such as baseline wander, power line interference, and electromagnetic interference in gathering and recording process. As ECG signals are non-stationary physiological signals, wavelet transform is investigated to be an effective tool to discard noises from corrupted signals. A new compromising threshold function called sigmoid function-based thresholding scheme is adopted in processing ECG signals. Compared with other methods such as hard/soft thresholding or other existing thresholding functions, the new algorithm has many advantages in the noise reduction of ECG signals. It perfectly overcomes the discontinuity at ±T of hard thresholding and reduces the fixed deviation of soft thresholding. The improved wavelet thresholding denoising can be proved to be more efficient than existing algorithms in ECG signal denoising. The signal to noise ratio, mean square error, and percent root mean square difference are calculated to verify the denoising performance as quantitative tools. The experimental results reveal that the waves including P, Q, R, and S waves of ECG signals after denoising coincide with the original ECG signals by employing the new proposed method.

Quality of alcohol-based hand disinfectants and their regulatory status. Development and marketing authorisation.

PubMed

Stengele, Michael

2008-10-01

A 2005 survey showed that there are at least four legal product classifications for hand disinfectants in the European Union: medicinal products, biocidal products, cosmetics and medical devices. An internationally harmonized classification does not exist. The regulatory status of those products is defined at national level. In order to assure compliance with the regulations these four classifications provide different levels of official surveillance varying from product-specific marketing authorisations and production site audits to the obligation to just work in accordance with certain general guidelines. Biocidal product regulations cover eco-toxicological and toxicological aspects, but do not very much address to the customers' quality and efficacy expectations. In contrast, the medicinal product legislation is the most ambitious one claiming quality, safety, efficacy, and an independent benefit risk-assessment by an authority. In respect of ambition, the two remaining product categories--cosmetics and medical devices--rank between the both classifications mentioned above. For medical devices, it is the responsibility of the manufacturer to make sure the products meet defined essential requirements regarding quality, safety and performance and to have an appropriate quality assurance system implemented under third party control. For cosmetics there are some legal restrictions, but within these it is the sole responsibility of the manufacturer to ensure that the products are safe and fulfil their claims. This paper describes one way out of this increasingly complex situation, the definition of a single quality standard meeting the users' expectations as well as all legal requirements regardless of the specific sales country. This international quality standard for products would take priority over any individual national standard, to the benefit of users.

Development of Thresholds and Exceedance Probabilities for Influent Water Quality to Meet Drinking Water Regulations

NASA Astrophysics Data System (ADS)

Reeves, K. L.; Samson, C.; Summers, R. S.; Balaji, R.

2017-12-01

Drinking water treatment utilities (DWTU) are tasked with the challenge of meeting disinfection and disinfection byproduct (DBP) regulations to provide safe, reliable drinking water under changing climate and land surface characteristics. DBPs form in drinking water when disinfectants, commonly chlorine, react with organic matter as measured by total organic carbon (TOC), and physical removal of pathogen microorganisms are achieved by filtration and monitored by turbidity removal. Turbidity and TOC in influent waters to DWTUs are expected to increase due to variable climate and more frequent fires and droughts. Traditional methods for forecasting turbidity and TOC require catchment specific data (i.e. streamflow) and have difficulties predicting them under non-stationary climate. A modelling framework was developed to assist DWTUs with assessing their risk for future compliance with disinfection and DBP regulations under changing climate. A local polynomial method was developed to predict surface water TOC using climate data collected from NOAA, Normalized Difference Vegetation Index (NDVI) data from the IRI Data Library, and historical TOC data from three DWTUs in diverse geographic locations. Characteristics from the DWTUs were used in the EPA Water Treatment Plant model to determine thresholds for influent TOC that resulted in DBP concentrations within compliance. Lastly, extreme value theory was used to predict probabilities of threshold exceedances under the current climate. Results from the utilities were used to produce a generalized TOC threshold approach that only requires water temperature and bromide concentration. The threshold exceedance model will be used to estimate probabilities of exceedances under projected climate scenarios. Initial results show that TOC can be forecasted using widely available data via statistical methods, where temperature, precipitation, Palmer Drought Severity Index, and NDVI with various lags were shown to be important

Threshold automatic selection hybrid phase unwrapping algorithm for digital holographic microscopy

NASA Astrophysics Data System (ADS)

Zhou, Meiling; Min, Junwei; Yao, Baoli; Yu, Xianghua; Lei, Ming; Yan, Shaohui; Yang, Yanlong; Dan, Dan

2015-01-01

Conventional quality-guided (QG) phase unwrapping algorithm is hard to be applied to digital holographic microscopy because of the long execution time. In this paper, we present a threshold automatic selection hybrid phase unwrapping algorithm that combines the existing QG algorithm and the flood-filled (FF) algorithm to solve this problem. The original wrapped phase map is divided into high- and low-quality sub-maps by selecting a threshold automatically, and then the FF and QG unwrapping algorithms are used in each level to unwrap the phase, respectively. The feasibility of the proposed method is proved by experimental results, and the execution speed is shown to be much faster than that of the original QG unwrapping algorithm.

Evaluation of Bayesian estimation of a hidden continuous-time Markov chain model with application to threshold violation in water-quality indicators

USGS Publications Warehouse

Deviney, Frank A.; Rice, Karen; Brown, Donald E.

2012-01-01

Natural resource managers require information concerning  the frequency, duration, and long-term probability of occurrence of water-quality indicator (WQI) violations of defined thresholds. The timing of these threshold crossings often is hidden from the observer, who is restricted to relatively infrequent observations. Here, a model for the hidden process is linked with a model for the observations, and the parameters describing duration, return period, and long-term probability of occurrence are estimated using Bayesian methods. A simulation experiment is performed to evaluate the approach under scenarios based on the equivalent of a total monitoring period of 5-30 years and an observation frequency of 1-50 observations per year. Given constant threshold crossing rate, accuracy and precision of parameter estimates increased with longer total monitoring period and more-frequent observations. Given fixed monitoring period and observation frequency, accuracy and precision of parameter estimates increased with longer times between threshold crossings. For most cases where the long-term probability of being in violation is greater than 0.10, it was determined that at least 600 observations are needed to achieve precise estimates.  An application of the approach is presented using 22 years of quasi-weekly observations of acid-neutralizing capacity from Deep Run, a stream in Shenandoah National Park, Virginia. The time series also was sub-sampled to simulate monthly and semi-monthly sampling protocols. Estimates of the long-term probability of violation were unbiased despite sampling frequency; however, the expected duration and return period were over-estimated using the sub-sampled time series with respect to the full quasi-weekly time series.

Microbiological water methods: quality control measures for Federal Clean Water Act and Safe Drinking Water Act regulatory compliance.

PubMed

Root, Patsy; Hunt, Margo; Fjeld, Karla; Kundrat, Laurie

2014-01-01

Quality assurance (QA) and quality control (QC) data are required in order to have confidence in the results from analytical tests and the equipment used to produce those results. Some AOAC water methods include specific QA/QC procedures, frequencies, and acceptance criteria, but these are considered to be the minimum controls needed to perform a microbiological method successfully. Some regulatory programs, such as those at Code of Federal Regulations (CFR), Title 40, Part 136.7 for chemistry methods, require additional QA/QC measures beyond those listed in the method, which can also apply to microbiological methods. Essential QA/QC measures include sterility checks, reagent specificity and sensitivity checks, assessment of each analyst's capabilities, analysis of blind check samples, and evaluation of the presence of laboratory contamination and instrument calibration and checks. The details of these procedures, their performance frequency, and expected results are set out in this report as they apply to microbiological methods. The specific regulatory requirements of CFR Title 40 Part 136.7 for the Clean Water Act, the laboratory certification requirements of CFR Title 40 Part 141 for the Safe Drinking Water Act, and the International Organization for Standardization 17025 accreditation requirements under The NELAC Institute are also discussed.

Threshold-driven optimization for reference-based auto-planning

NASA Astrophysics Data System (ADS)

Long, Troy; Chen, Mingli; Jiang, Steve; Lu, Weiguo

2018-02-01

We study threshold-driven optimization methodology for automatically generating a treatment plan that is motivated by a reference DVH for IMRT treatment planning. We present a framework for threshold-driven optimization for reference-based auto-planning (TORA). Commonly used voxel-based quadratic penalties have two components for penalizing under- and over-dosing of voxels: a reference dose threshold and associated penalty weight. Conventional manual- and auto-planning using such a function involves iteratively updating the preference weights while keeping the thresholds constant, an unintuitive and often inconsistent method for planning toward some reference DVH. However, driving a dose distribution by threshold values instead of preference weights can achieve similar plans with less computational effort. The proposed methodology spatially assigns reference DVH information to threshold values, and iteratively improves the quality of that assignment. The methodology effectively handles both sub-optimal and infeasible DVHs. TORA was applied to a prostate case and a liver case as a proof-of-concept. Reference DVHs were generated using a conventional voxel-based objective, then altered to be either infeasible or easy-to-achieve. TORA was able to closely recreate reference DVHs in 5-15 iterations of solving a simple convex sub-problem. TORA has the potential to be effective for auto-planning based on reference DVHs. As dose prediction and knowledge-based planning becomes more prevalent in the clinical setting, incorporating such data into the treatment planning model in a clear, efficient way will be crucial for automated planning. A threshold-focused objective tuning should be explored over conventional methods of updating preference weights for DVH-guided treatment planning.

Regulatory and quality considerations for continuous manufacturing. May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Allison, Gretchen; Cain, Yanxi Tan; Cooney, Charles; Garcia, Tom; Bizjak, Tara Gooen; Holte, Oyvind; Jagota, Nirdosh; Komas, Bekki; Korakianiti, Evdokia; Kourti, Dora; Madurawe, Rapti; Morefield, Elaine; Montgomery, Frank; Nasr, Moheb; Randolph, William; Robert, Jean-Louis; Rudd, Dave; Zezza, Diane

2015-03-01

This paper assesses the current regulatory environment, relevant regulations and guidelines, and their impact on continuous manufacturing. It summarizes current regulatory experience and learning from both review and inspection perspectives. It outlines key regulatory aspects, including continuous manufacturing process description and control strategy in regulatory files, process validation, and key Good Manufacturing Practice (GMP) requirements. In addition, the paper identifies regulatory gaps and challenges and proposes a way forward to facilitate implementation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Regulatory observations in bioanalytical determinations.

PubMed

Viswanathan, C T

2010-07-01

The concept of measuring analytes in biological media is a long-established area of the quantitative sciences that is employed in many sectors. While academic research and R&D units of private firms have been in the forefront of developing complex methodologies, it is the regulatory environment that has brought the focus and rigor to the quality control of the quantitative determination of drug concentration in biological samples. In this article, the author examines the regulatory findings discovered during the course of several years of auditing bioanalytical work. The outcomes of these findings underscore the importance of quality method validation to ensure the reliability of the data generated. The failure to ensure the reliability of these data can lead to potential risks in the health management of millions of people in the USA.

CARA Risk Assessment Thresholds

NASA Technical Reports Server (NTRS)

Hejduk, M. D.

2016-01-01

Warning remediation threshold (Red threshold): Pc level at which warnings are issued, and active remediation considered and usually executed. Analysis threshold (Green to Yellow threshold): Pc level at which analysis of event is indicated, including seeking additional information if warranted. Post-remediation threshold: Pc level to which remediation maneuvers are sized in order to achieve event remediation and obviate any need for immediate follow-up maneuvers. Maneuver screening threshold: Pc compliance level for routine maneuver screenings (more demanding than regular Red threshold due to additional maneuver uncertainty).

Using generalized additive modeling to empirically identify thresholds within the ITERS in relation to toddlers' cognitive development.

PubMed

Setodji, Claude Messan; Le, Vi-Nhuan; Schaack, Diana

2013-04-01

Research linking high-quality child care programs and children's cognitive development has contributed to the growing popularity of child care quality benchmarking efforts such as quality rating and improvement systems (QRIS). Consequently, there has been an increased interest in and a need for approaches to identifying thresholds, or cutpoints, in the child care quality measures used in these benchmarking efforts that differentiate between different levels of children's cognitive functioning. To date, research has provided little guidance to policymakers as to where these thresholds should be set. Using the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B) data set, this study explores the use of generalized additive modeling (GAM) as a method of identifying thresholds on the Infant/Toddler Environment Rating Scale (ITERS) in relation to toddlers' performance on the Mental Development subscale of the Bayley Scales of Infant Development (the Bayley Mental Development Scale Short Form-Research Edition, or BMDSF-R). The present findings suggest that simple linear models do not always correctly depict the relationships between ITERS scores and BMDSF-R scores and that GAM-derived thresholds were more effective at differentiating among children's performance levels on the BMDSF-R. Additionally, the present findings suggest that there is a minimum threshold on the ITERS that must be exceeded before significant improvements in children's cognitive development can be expected. There may also be a ceiling threshold on the ITERS, such that beyond a certain level, only marginal increases in children's BMDSF-R scores are observed. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Using machine learning to examine medication adherence thresholds and risk of hospitalization.

PubMed

Lo-Ciganic, Wei-Hsuan; Donohue, Julie M; Thorpe, Joshua M; Perera, Subashan; Thorpe, Carolyn T; Marcum, Zachary A; Gellad, Walid F

2015-08-01

Quality improvement efforts are frequently tied to patients achieving ≥80% medication adherence. However, there is little empirical evidence that this threshold optimally predicts important health outcomes. To apply machine learning to examine how adherence to oral hypoglycemic medications is associated with avoidance of hospitalizations, and to identify adherence thresholds for optimal discrimination of hospitalization risk. A retrospective cohort study of 33,130 non-dual-eligible Medicaid enrollees with type 2 diabetes. We randomly selected 90% of the cohort (training sample) to develop the prediction algorithm and used the remaining (testing sample) for validation. We applied random survival forests to identify predictors for hospitalization and fit survival trees to empirically derive adherence thresholds that best discriminate hospitalization risk, using the proportion of days covered (PDC). Time to first all-cause and diabetes-related hospitalization. The training and testing samples had similar characteristics (mean age, 48 y; 67% female; mean PDC=0.65). We identified 8 important predictors of all-cause hospitalizations (rank in order): prior hospitalizations/emergency department visit, number of prescriptions, diabetes complications, insulin use, PDC, number of prescribers, Elixhauser index, and eligibility category. The adherence thresholds most discriminating for risk of all-cause hospitalization varied from 46% to 94% according to patient health and medication complexity. PDC was not predictive of hospitalizations in the healthiest or most complex patient subgroups. Adherence thresholds most discriminating of hospitalization risk were not uniformly 80%. Machine-learning approaches may be valuable to identify appropriate patient-specific adherence thresholds for measuring quality of care and targeting nonadherent patients for intervention.

Improved Bat Algorithm Applied to Multilevel Image Thresholding

PubMed Central

2014-01-01

Multilevel image thresholding is a very important image processing technique that is used as a basis for image segmentation and further higher level processing. However, the required computational time for exhaustive search grows exponentially with the number of desired thresholds. Swarm intelligence metaheuristics are well known as successful and efficient optimization methods for intractable problems. In this paper, we adjusted one of the latest swarm intelligence algorithms, the bat algorithm, for the multilevel image thresholding problem. The results of testing on standard benchmark images show that the bat algorithm is comparable with other state-of-the-art algorithms. We improved standard bat algorithm, where our modifications add some elements from the differential evolution and from the artificial bee colony algorithm. Our new proposed improved bat algorithm proved to be better than five other state-of-the-art algorithms, improving quality of results in all cases and significantly improving convergence speed. PMID:25165733

Regulatory and Quality Considerations for Continuous Manufacturing May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Allison, Gretchen; Cain, Yanxi Tan; Cooney, Charles; Garcia, Tom; Bizjak, Tara Gooen; Holte, Oyvind; Jagota, Nirdosh; Komas, Bekki; Korakianiti, Evdokia; Kourti, Dora; Madurawe, Rapti; Morefield, Elaine; Montgomery, Frank; Nasr, Moheb; Randolph, William; Robert, Jean-Louis; Rudd, Dave; Zezza, Diane

2015-03-01

This paper assesses the current regulatory environment, relevant regulations and guidelines, and their impact on continuous manufacturing. It summarizes current regulatory experience and learning from both review and inspection perspectives. It outlines key regulatory aspects, including continuous manufacturing process description and control strategy in regulatory files, process validation, and key Good Manufacturing Practice (GMP) requirements. In addition, the paper identifies regulatory gaps and challenges and proposes a way forward to facilitate implementation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Evaluating links between forest harvest and stream temperature threshold exceedances: the value of spatial and temporal data

Treesearch

Jeremiah D. Groom; Sherri L. Johnson; Joshua D. Seeds; George G. Ice

2017-01-01

We present the results of a replicated before-after-control-impact study on 33 streams to test the effectiveness of riparian rules for private and State forests at meeting temperature criteria in streams in western Oregon. Many states have established regulatory temperature thresholds, referred to as numeric criteria, to protect cold-water fishes such as salmon and...

Reference guide to odor thresholds for hazardous air pollutants listed in the Clean Air Act amendments of 1990

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

Cain, W.S.; Shoaf, C.R.; Velasquez, S.F.

1992-03-01

In response to numerous requests for information related to odor thresholds, this document was prepared by the Air Risk Information Support Center in its role in providing technical assistance to State and Local government agencies on risk assessment of air pollutants. A discussion of basic concepts related to olfactory function and the measurement of odor thresholds is presented. A detailed discussion of criteria which are used to evaluate the quality of published odor threshold values is provided. The use of odor threshold information in risk assessment is discussed. The results of a literature search and review of odor threshold informationmore » for the chemicals listed as hazardous air pollutants in the Clean Air Act amendments of 1990 is presented. The published odor threshold values are critically evaluated based on the criteria discussed and the values of acceptable quality are used to determine a geometric mean or best estimate.« less

[Strengthening health regulation in the Americas: regulatory authorities of regional reference].

PubMed

Ojeda, Lisette Pérez; Cristiá, Rafael Pérez

2016-05-01

Health technology regulation and quality assurance are critical to the development of national pharmaceutical policies, and implementing these actions is the responsibility of national regulatory authorities, whose level of development and maturity affect the quality, safety, and effectiveness of the products made available to the public. On the initiative of the regulatory authorities themselves, together with the Pan American Health Organization, the Region of the Americas promotes the strengthening of health regulation through an evaluation and certification process that allows for the designation of regulatory authorities of regional reference for drugs and biological products. Over the period from its implementation to the present, six authorities have been certified and one is in the process of obtaining certification. These authorities work jointly and promote dialogue and regulatory convergence, information-sharing to facilitate regulatory decision making, and regional cooperation to support the establishment of other authorities in the Region--actions having direct impact on access to effective and quality-assured health technologies. Their combined efforts have led to the recognition of this process of evaluation and certification by the World Health Organization (WHO). Among the actions resulting from the International Consultation on Regulatory Systems Strengthening, WHO recommended taking a close look at this model to assess its potential scale-up at the global level.

Willingness to pay per quality-adjusted life year: is one threshold enough for decision-making?: results from a study in patients with chronic prostatitis.

PubMed

Zhao, Fei-Li; Yue, Ming; Yang, Hua; Wang, Tian; Wu, Jiu-Hong; Li, Shu-Chuen

2011-03-01

To estimate the willingness to pay (WTP) per quality-adjusted life year (QALY) ratio with the stated preference data and compare the results obtained between chronic prostatitis (CP) patients and general population (GP). WTP per QALY was calculated with the subjects' own health-related utility and the WTP value. Two widely used preference-based health-related quality of life instruments, EuroQol (EQ-5D) and Short Form 6D (SF-6D), were used to elicit utility for participants' own health. The monthly WTP values for moving from participants' current health to a perfect health were elicited using closed-ended iterative bidding contingent valuation method. A total of 268 CP patients and 364 participants from GP completed the questionnaire. We obtained 4 WTP/QALY ratios ranging from $4700 to $7400, which is close to the lower bound of local gross domestic product per capita, a threshold proposed by World Health Organization. Nevertheless, these values were lower than other proposed thresholds and published empirical researches on diseases with mortality risk. Furthermore, the WTP/QALY ratios from the GP were significantly lower than those from the CP patients, and different determinants were associated with the within group variation identified by multiple linear regression. Preference elicitation methods are acceptable and feasible in the socio-cultural context of an Asian environment and the calculation of WTP/QALY ratio produced meaningful answers. The necessity of considering the QALY type or disease-specific QALY in estimating WTP/QALY ratio was highlighted and 1 to 3 times of gross domestic product/capita recommended by World Health Organization could potentially serve as a benchmark for threshold in this Asian context.

75 FR 52558 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-26

...-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate Effectiveness of Proposed... costs associated with system issues that are attributable to cancelled AON orders. A Professional order... organization in order for a member organization to be assessed the Cancellation Fee (``500 Threshold''). The...

76 FR 65555 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-21

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65583; File No. SR-ISE-2011-68] Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change to Amend the Volume Threshold for Tier-Based Rebates for Qualified Contingent Cross Orders and Solicitation Orders Executed...

76 FR 77279 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-12

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65898; File No. SR-ISE-2011-78] Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change to Amend the Threshold Levels for Tier-Based Rebates for Qualified Contingent Cross Orders and Solicitation Orders Executed...

Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?

PubMed

Del Paggio, J C; Azariah, B; Sullivan, R; Hopman, W M; James, F V; Roshni, S; Tannock, I F; Booth, C M

2017-01-01

The European Society for Medical Oncology (ESMO) recently released a magnitude of clinical benefit scale (ESMO-MCBS) for systemic therapies for solid cancers. Here, we evaluate contemporary randomized controlled trials (RCTs) against the proposed ESMO thresholds for meaningful clinical benefit. RCTs evaluating systemic therapy for breast cancer, nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer published 2011-2015 were reviewed. Data were abstracted regarding trial characteristics and outcomes, and these were applied to the ESMO-MCBS. We also determined whether RCTs were designed to detect an effect that would meet clinical benefit as defined by the ESMO-MCBS. About 277 eligible RCTs were included (40% breast, 31% NSCLC, 22% CRC, 6% pancreas). Median sample size was 532 and 83% were funded by industry. Among all 277 RCTs, the experimental therapy was statistically superior to the control arm in 138 (50%) trials: results of only 31% (43/138) of these trials met the ESMO-MCBS clinical benefit threshold. RCTs with curative intent were more likely to meet clinically meaningful thresholds than those with palliative intent [61% (19/31) versus 22% (24/107), P < 0.001]. Among the 226 RCTs for which the ESMO-MCBS could be applied, 31% (70/226) were designed to detect an effect size that could meet ESMO-MCBS thresholds. Less than one-third of contemporary RCTs with statistically significant results meet ESMO thresholds for meaningful clinical benefit, and this represents only 15% of all published trials. Investigators, funding agencies, regulatory agencies, and industry should adopt more stringent thresholds for meaningful benefit in the design of future RCTs. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Modified Discrete Grey Wolf Optimizer Algorithm for Multilevel Image Thresholding

PubMed Central

Sun, Lijuan; Guo, Jian; Xu, Bin; Li, Shujing

2017-01-01

The computation of image segmentation has become more complicated with the increasing number of thresholds, and the option and application of the thresholds in image thresholding fields have become an NP problem at the same time. The paper puts forward the modified discrete grey wolf optimizer algorithm (MDGWO), which improves on the optimal solution updating mechanism of the search agent by the weights. Taking Kapur's entropy as the optimized function and based on the discreteness of threshold in image segmentation, the paper firstly discretizes the grey wolf optimizer (GWO) and then proposes a new attack strategy by using the weight coefficient to replace the search formula for optimal solution used in the original algorithm. The experimental results show that MDGWO can search out the optimal thresholds efficiently and precisely, which are very close to the result examined by exhaustive searches. In comparison with the electromagnetism optimization (EMO), the differential evolution (DE), the Artifical Bee Colony (ABC), and the classical GWO, it is concluded that MDGWO has advantages over the latter four in terms of image segmentation quality and objective function values and their stability. PMID:28127305

Lower-upper-threshold correlation for underwater range-gated imaging self-adaptive enhancement.

PubMed

Sun, Liang; Wang, Xinwei; Liu, Xiaoquan; Ren, Pengdao; Lei, Pingshun; He, Jun; Fan, Songtao; Zhou, Yan; Liu, Yuliang

2016-10-10

In underwater range-gated imaging (URGI), enhancement of low-brightness and low-contrast images is critical for human observation. Traditional histogram equalizations over-enhance images, with the result of details being lost. To compress over-enhancement, a lower-upper-threshold correlation method is proposed for underwater range-gated imaging self-adaptive enhancement based on double-plateau histogram equalization. The lower threshold determines image details and compresses over-enhancement. It is correlated with the upper threshold. First, the upper threshold is updated by searching for the local maximum in real time, and then the lower threshold is calculated by the upper threshold and the number of nonzero units selected from a filtered histogram. With this method, the backgrounds of underwater images are constrained with enhanced details. Finally, the proof experiments are performed. Peak signal-to-noise-ratio, variance, contrast, and human visual properties are used to evaluate the objective quality of the global and regions of interest images. The evaluation results demonstrate that the proposed method adaptively selects the proper upper and lower thresholds under different conditions. The proposed method contributes to URGI with effective image enhancement for human eyes.

Advancing a Vision for Regulatory Science Training

PubMed Central

Adamo, Joan E.; Wilhelm, Erin E.

2015-01-01

Abstract Regulatory science, a complex field which draws on science, law, and policy, is a growing discipline in medical‐related applications. Competencies help define both a discipline and the criteria to measure high‐quality learning experiences. This paper identifies competencies for regulatory science, how they were developed, and broader recommendations to enhance education and training in this burgeoning field, including a multifaceted training approach. PMID:26083660

Threshold Dynamics of a Semiconductor Single Atom Maser

NASA Astrophysics Data System (ADS)

Liu, Yinyu

Photon emission from single emitters provides fundamental insight into the detailed interaction between light and matter. Here we demonstrate a semiconductor single atom maser (SeSAM) that consists of a single InAs double quantum dot (DQD) that is coupled to a high quality factor microwave cavity. A finite bias results in population inversion in the DQD, enabling sizable cavity gain and stimulated emission. We develop a pulsed-gate approach that allows the SeSAM to be tuned across the masing threshold. The cavity output power as a function of DQD current is in good agreement with single atom maser theory once a small correction for lead emission is included. Photon statistics measurements show that the second-order correlation function of intra-cavity photon number, nc, crosses over from 〈nc2 〉 /〈nc 〉 2 = 2.1 below threshold to 〈nc2 〉 /〈nc 〉 2 = 1.2 above threshold. Large fluctuations are observed at threshold. In collaboration with J. Stehlik, C. Eichler, X. Mi, T. R. Hartke, M. J. Gullans, J. M. Taylor and J. R. Petta. Supported by the NSF and the Gordon and Betty Moore Foundation's EPiQS initiative through Grant No. GBMF4535.

The regulatory pendulum in transfusion medicine.

PubMed

Farrugia, Albert

2002-10-01

Blood banking and the manufacture of blood products have been relatively outside the influence of regulatory authorities. Several developments contributed to a revision of this environment. The transmission of acquired immunodeficiency syndrome by blood products changed the perception of blood product safety and also spawned litigation and governmental inquiries. The blood banking industry has embraced, with varying degrees of enthusiasm, the principles of systematic quality management and good manufacturing practice, which has created a substantial subindustry and has contributed to a disproportionate focus on product quality. Conventional market forces have also gradually penetrated the traditional blood economies. The public and political focus has resulted in regulatory and policy efforts being concentrated on inappropriate areas. Several of the safety efforts can be arguably described as cost-ineffective while diverting attention and resources from more important issues. An improved integration into mainstream public health policy and incorporation of objectively measured risks into regulatory policy would do much to enhance the quality of the transfusion system. This can be achieved if regulators themselves are overseen through a process that ensures performance and accountability against objective and predefined standards. A further beneficial outcome from this approach could be the harmonization of blood safety and policy measures, the need for which is being felt increasingly worldwide. Copyright 2002, Elsevier Science (USA)

Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage.

PubMed

Carson, Jeffrey L; Guyatt, Gordon; Heddle, Nancy M; Grossman, Brenda J; Cohn, Claudia S; Fung, Mark K; Gernsheimer, Terry; Holcomb, John B; Kaplan, Lewis J; Katz, Louis M; Peterson, Nikki; Ramsey, Glenn; Rao, Sunil V; Roback, John D; Shander, Aryeh; Tobian, Aaron A R

2016-11-15

is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence). Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.

Threshold Concepts and Student Engagement: Revisiting Pedagogical Content Knowledge

ERIC Educational Resources Information Center

Zepke, Nick

2013-01-01

This article revisits the notion that to facilitate quality learning requires teachers in higher education to have pedagogical content knowledge. It constructs pedagogical content knowledge as a teaching and learning space that brings content and pedagogy together. On the content knowledge side, it suggests that threshold concepts, akin to a…

Holographic Associative Memory System Using A Thresholding Microchannel Spatial Light Modulator

NASA Astrophysics Data System (ADS)

Song, Q. W.; Yu, Francis T.

1989-05-01

Experimental implementation of a holographic optical associative memory system using a thresholding microchannel spatial light modulator (MSLM) is presented. The first part of the system is basically a joint transform correlator, in which a liquid crystal light valve is used as a square-law converter for the inner product of the addressing and input memories. The MSLM is used as an active element to recall the associated data. If the device is properly thresholded, the system is capable of improving the quality of the output image.

Setting limits: Using air pollution thresholds to protect and restore US ecosystems

USGS Publications Warehouse

Fenn, Mark E.; Lambert, Kathleen F.; Blett, Tamara F.; Burns, Douglas A.; Pardo, Linda H.; Lovett, Gary M.; Haeuber, Richard A.; Evers, David C.; Driscoll, Charles T.; Jeffries, Dean S.

2011-01-01

More than four decades of research provide unequivocal evidence that sulfur, nitrogen, and mercury pollution have altered, and will continue to alter, our nation's lands and waters. The emission and deposition of air pollutants harm native plants and animals, degrade water quality, affect forest productivity, and are damaging to human health. Many air quality policies limit emissions at the source but these control measures do not always consider ecosystem impacts. Air pollution thresholds at which ecological effects are observed, such as critical loads, are effective tools for assessing the impacts of air pollution on essential ecosystem services and for informing public policy. U.S. ecosystems can be more effectively protected and restored by using a combination of emissions-based approaches and science-based thresholds of ecosystem damage.

Two regulatory RNA elements affect TisB-dependent depolarization and persister formation.

PubMed

Berghoff, Bork A; Hoekzema, Mirthe; Aulbach, Lena; Wagner, E Gerhart H

2017-03-01

Bacterial survival strategies involve phenotypic diversity which is generated by regulatory factors and noisy expression of effector proteins. The question of how bacteria exploit regulatory RNAs to make decisions between phenotypes is central to a general understanding of these universal regulators. We investigated the TisB/IstR-1 toxin-antitoxin system of Escherichia coli to appreciate the role of the RNA antitoxin IstR-1 in TisB-dependent depolarization of the inner membrane and persister formation. Persisters are phenotypic variants that have become transiently drug-tolerant by arresting growth. The RNA antitoxin IstR-1 sets a threshold for TisB-dependent depolarization under DNA-damaging conditions, resulting in two sub-populations: polarized and depolarized cells. Furthermore, our data indicate that an inhibitory 5' UTR structure in the tisB mRNA serves as a regulatory RNA element that delays TisB translation to avoid inappropriate depolarization when DNA damage is low. Investigation of the persister sub-population further revealed that both regulatory RNA elements affect persister levels as well as persistence time. This work provides an intriguing example of how bacteria exploit regulatory RNAs to control phenotypic heterogeneity. © 2016 John Wiley & Sons Ltd.

75 FR 55385 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-10

...-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule... guarantee limits the increase in a Members' execution costs associating with failing to meet the volume thresholds of other exchanges and ECNs while a Member is in the process of migrating volumes from one...

Response threshold variance as a basis of collective rationality

PubMed Central

Yamamoto, Tatsuhiro

2017-01-01

Determining the optimal choice among multiple options is necessary in various situations, and the collective rationality of groups has recently become a major topic of interest. Social insects are thought to make such optimal choices by collecting individuals' responses relating to an option's value (=a quality-graded response). However, this behaviour cannot explain the collective rationality of brains because neurons can make only ‘yes/no’ responses on the basis of the response threshold. Here, we elucidate the basic mechanism underlying the collective rationality of such simple units and show that an ant species uses this mechanism. A larger number of units respond ‘yes’ to the best option available to a collective decision-maker using only the yes/no mechanism; thus, the best option is always selected by majority decision. Colonies of the ant Myrmica kotokui preferred the better option in a binary choice experiment. The preference of a colony was demonstrated by the workers, which exhibited variable thresholds between two options' qualities. Our results demonstrate how a collective decision-maker comprising simple yes/no judgement units achieves collective rationality without using quality-graded responses. This mechanism has broad applicability to collective decision-making in brain neurons, swarm robotics and human societies. PMID:28484636

Response threshold variance as a basis of collective rationality.

PubMed

Yamamoto, Tatsuhiro; Hasegawa, Eisuke

2017-04-01

Determining the optimal choice among multiple options is necessary in various situations, and the collective rationality of groups has recently become a major topic of interest. Social insects are thought to make such optimal choices by collecting individuals' responses relating to an option's value (=a quality-graded response). However, this behaviour cannot explain the collective rationality of brains because neurons can make only 'yes/no' responses on the basis of the response threshold. Here, we elucidate the basic mechanism underlying the collective rationality of such simple units and show that an ant species uses this mechanism. A larger number of units respond 'yes' to the best option available to a collective decision-maker using only the yes/no mechanism; thus, the best option is always selected by majority decision. Colonies of the ant Myrmica kotokui preferred the better option in a binary choice experiment. The preference of a colony was demonstrated by the workers, which exhibited variable thresholds between two options' qualities. Our results demonstrate how a collective decision-maker comprising simple yes/no judgement units achieves collective rationality without using quality-graded responses. This mechanism has broad applicability to collective decision-making in brain neurons, swarm robotics and human societies.

Regulatory approaches for addressing dissolved oxygen concerns at hydropower facilities

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

Peterson, Mark J.; Cada, Glenn F.; Sale, Michael J.

Low dissolved oxygen (DO) concentrations are a common water quality problem downstream of hydropower facilities. At some facilities, structural improvements (e.g. installation of weir dams or aerating turbines) or operational changes (e.g., spilling water over the dam) can be made to improve DO levels. In other cases, structural and operational approaches are too costly for the project to implement or are likely to be of limited effectiveness. Despite improvements in overall water quality below dams in recent years, many hydropower projects are unable to meet state water quality standards for DO. Regulatory agencies in the U.S. are considering or implementingmore » dramatic changes in their approach to protecting the quality of the Nation’s waters. New policies and initiatives have emphasized flexibility, increased collaboration and shared responsibility among all parties, and market-based, economic incentives. The use of new regulatory approaches may now be a viable option for addressing the DO problem at some hydropower facilities. This report summarizes some of the regulatory-related options available to hydropower projects, including negotiation of site-specific water quality criteria, use of biological monitoring, watershed-based strategies for the management of water quality, and watershed-based trading. Key decision points center on the health of the local biological communities and whether there are contributing impacts (i.e., other sources of low DO effluents) in the watershed. If the biological communities downstream of the hydropower project are healthy, negotiation for site-specific water quality standards or biocriteria (discharge performance criteria based on characteristics of the aquatic biota) might be pursued. If there are other effluent dischargers in the watershed that contribute to low DO problems, watershed-scale strategies and effluent trading may be effective. This report examines the value of regulatory approaches by reviewing their use

Properties of perimetric threshold estimates from Full Threshold, SITA Standard, and SITA Fast strategies.

PubMed

Artes, Paul H; Iwase, Aiko; Ohno, Yuko; Kitazawa, Yoshiaki; Chauhan, Balwantray C

2002-08-01

To investigate the distributions of threshold estimates with the Swedish Interactive Threshold Algorithms (SITA) Standard, SITA Fast, and the Full Threshold algorithm (Humphrey Field Analyzer; Zeiss-Humphrey Instruments, Dublin, CA) and to compare the pointwise test-retest variability of these strategies. One eye of 49 patients (mean age, 61.6 years; range, 22-81) with glaucoma (Mean Deviation mean, -7.13 dB; range, +1.8 to -23.9 dB) was examined four times with each of the three strategies. The mean and median SITA Standard and SITA Fast threshold estimates were compared with a "best available" estimate of sensitivity (mean results of three Full Threshold tests). Pointwise 90% retest limits (5th and 95th percentiles of retest thresholds) were derived to assess the reproducibility of individual threshold estimates. The differences between the threshold estimates of the SITA and Full Threshold strategies were largest ( approximately 3 dB) for midrange sensitivities ( approximately 15 dB). The threshold distributions of SITA were considerably different from those of the Full Threshold strategy. The differences remained of similar magnitude when the analysis was repeated on a subset of 20 locations that are examined early during the course of a Full Threshold examination. With sensitivities above 25 dB, both SITA strategies exhibited lower test-retest variability than the Full Threshold strategy. Below 25 dB, the retest intervals of SITA Standard were slightly smaller than those of the Full Threshold strategy, whereas those of SITA Fast were larger. SITA Standard may be superior to the Full Threshold strategy for monitoring patients with visual field loss. The greater test-retest variability of SITA Fast in areas of low sensitivity is likely to offset the benefit of even shorter test durations with this strategy. The sensitivity differences between the SITA and Full Threshold strategies may relate to factors other than reduced fatigue. They are, however, small in

Glycoconjugate Vaccines: The Regulatory Framework.

PubMed

Jones, Christopher

2015-01-01

Most vaccines, including the currently available glycoconjugate vaccines, are administered to healthy infants, to prevent future disease. The safety of a prospective vaccine is a key prerequisite for approval. Undesired side effects would not only have the potential to damage the individual infant but also lead to a loss of confidence in the respective vaccine-or vaccines in general-on a population level. Thus, regulatory requirements, particularly with regard to safety, are extremely rigorous. This chapter highlights regulatory aspects on carbohydrate-based vaccines with an emphasis on analytical approaches to ensure the consistent quality of successive manufacturing lots.

Ground-Water Quality Data in the Southern Sierra Study Unit, 2006 - Results from the California GAMA Program

USGS Publications Warehouse

Fram, Miranda S.; Belitz, Kenneth

2007-01-01

quality-control information resulted in censoring of less than 0.2 percent of the data collected for ground-water samples. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, or blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. VOCs and pesticides were detected in less than one-third of the grid wells, and all detections in samples from SOSA wells were below health-based thresholds. All detections of trace elements and nutrients in samples from SOSA wells were below health-based thresholds, with the exception of four detections of arsenic that were above the USEPA maximum contaminant level (MCL-US) and one detection of boron that was above the CDPH notification level (NL-CA). All detections of radioactive constituents were below health-based thresholds, although four samples had activities of radon-222 above the proposed MCL-US. Most of the samples from SOSA wells had concentrations of major elements, total dissolved solids, and trace elements below the non-enforceable thresholds set for aesthetic concerns. A few samples contained iron, manganese, or total dissolved solids at concentrations above the SMCL-CA thresholds.

Groundwater-Quality Data in the South Coast Interior Basins Study Unit, 2008: Results from the California GAMA Program

USGS Publications Warehouse

Mathany, Timothy M.; Kulongoski, Justin T.; Ray, Mary C.; Belitz, Kenneth

2009-01-01

], and radioactive constituents [gross alpha and gross beta radioactivity and radon-222]. Naturally occurring isotopes [stable isotopes of hydrogen, oxygen, and carbon, and activities of tritium and carbon-14] and dissolved noble gases also were measured to help identify the sources and ages of the sampled groundwater. In total, 288 constituents and water-quality indicators (field parameters) were investigated. Three types of quality-control samples (blanks, replicates, and matrix spikes) each were collected at approximately 4-11 percent of the wells, and the results for these samples were used to evaluate the quality of the data for the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a significant source of bias in the data obtained from the groundwater samples. Differences between replicate samples generally were less than 10 percent relative standard deviation, indicating acceptable analytical reproducibility. Matrix spike recoveries were within the acceptable range (70 to 130 percent) for most compounds. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, untreated groundwater typically is treated, disinfected, and/or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to untreated groundwater. However, to provide some context for the results, concentrations of constituents measured in the untreated groundwater were compared with regulatory and nonregulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH), and to nonregulatory thresholds established for aesthetic and technical concerns by CDPH. Comparisons between data collected for this study and thresholds for drinking water are for illustrative purposes only, and are not indicative of complia

Optimal thresholds for the estimation of area rain-rate moments by the threshold method

NASA Technical Reports Server (NTRS)

Short, David A.; Shimizu, Kunio; Kedem, Benjamin

1993-01-01

Optimization of the threshold method, achieved by determination of the threshold that maximizes the correlation between an area-average rain-rate moment and the area coverage of rain rates exceeding the threshold, is demonstrated empirically and theoretically. Empirical results for a sequence of GATE radar snapshots show optimal thresholds of 5 and 27 mm/h for the first and second moments, respectively. Theoretical optimization of the threshold method by the maximum-likelihood approach of Kedem and Pavlopoulos (1991) predicts optimal thresholds near 5 and 26 mm/h for lognormally distributed rain rates with GATE-like parameters. The agreement between theory and observations suggests that the optimal threshold can be understood as arising due to sampling variations, from snapshot to snapshot, of a parent rain-rate distribution. Optimal thresholds for gamma and inverse Gaussian distributions are also derived and compared.

On the Estimation of the Cost-Effectiveness Threshold: Why, What, How?

PubMed

Vallejo-Torres, Laura; García-Lorenzo, Borja; Castilla, Iván; Valcárcel-Nazco, Cristina; García-Pérez, Lidia; Linertová, Renata; Polentinos-Castro, Elena; Serrano-Aguilar, Pedro

2016-01-01

Many health care systems claim to incorporate the cost-effectiveness criterion in their investment decisions. Information on the system's willingness to pay per effectiveness unit, normally measured as quality-adjusted life-years (QALYs), however, is not available in most countries. This is partly because of the controversy that remains around the use of a cost-effectiveness threshold, about what the threshold ought to represent, and about the appropriate methodology to arrive at a threshold value. The aim of this article was to identify and critically appraise the conceptual perspectives and methodologies used to date to estimate the cost-effectiveness threshold. We provided an in-depth discussion of different conceptual views and undertook a systematic review of empirical analyses. Identified studies were categorized into the two main conceptual perspectives that argue that the threshold should reflect 1) the value that society places on a QALY and 2) the opportunity cost of investment to the system given budget constraints. These studies showed different underpinning assumptions, strengths, and limitations, which are highlighted and discussed. Furthermore, this review allowed us to compare the cost-effectiveness threshold estimates derived from different types of studies. We found that thresholds based on society's valuation of a QALY are generally larger than thresholds resulting from estimating the opportunity cost to the health care system. This implies that some interventions with positive social net benefits, as informed by individuals' preferences, might not be an appropriate use of resources under fixed budget constraints. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

75 FR 53129 - Federal Acquisition Regulation; Inflation Adjustment of Acquisition-Related Thresholds

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-30

... contractors pay very low wages and benefits, work quality can suffer and the Government may bear hidden costs because of the need to provide income assistance to low income families. The threshold for subcontracting...

Ground-Water Quality Data in the Coachella Valley Study Unit, 2007: Results from the California GAMA Program

USGS Publications Warehouse

Goldrath, Dara A.; Wright, Michael T.; Belitz, Kenneth

2009-01-01

ground water. A quality-control sample (blank, replicate, or matrix spike) was collected at approximately one quarter of the wells, and the results for these samples were used to evaluate the quality of the data for the ground-water samples. Assessment of the quality-control information resulted in V-coding less than 0.1 percent of the data collected. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is supplied to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH) and thresholds established for aesthetic purposes (secondary maximum contaminant levels, SMCL-CA) by CDPH. Most constituents detected in ground-water samples were at concentrations below drinking-water thresholds. Volatile organic compounds, pesticides, and pesticide degradates were detected in less than one-third of the grid well samples collected. All VOC and pesticide concentrations measured were below health-based thresholds. Potential waste-water indicators were detected in less than half of the wells sampled, and no detections were above health-based thresholds. Perchlorate was detected in seven grid wells; concentrations from two wells were above the CDPH maximum contaminant level (MCL-CA). Most detections of trace elements in samples collected from COA Study Unit wells were below water-quality thresholds. Exceptions include five samples of arsenic that were above the USEPA maximum contaminant level (MCL-US), two detections of boron above the CDPH notification level (NL-CA), and two detections of mol

An Auditory-Masking-Threshold-Based Noise Suppression Algorithm GMMSE-AMT[ERB] for Listeners with Sensorineural Hearing Loss

NASA Astrophysics Data System (ADS)

Natarajan, Ajay; Hansen, John H. L.; Arehart, Kathryn Hoberg; Rossi-Katz, Jessica

2005-12-01

This study describes a new noise suppression scheme for hearing aid applications based on the auditory masking threshold (AMT) in conjunction with a modified generalized minimum mean square error estimator (GMMSE) for individual subjects with hearing loss. The representation of cochlear frequency resolution is achieved in terms of auditory filter equivalent rectangular bandwidths (ERBs). Estimation of AMT and spreading functions for masking are implemented in two ways: with normal auditory thresholds and normal auditory filter bandwidths (GMMSE-AMT[ERB]-NH) and with elevated thresholds and broader auditory filters characteristic of cochlear hearing loss (GMMSE-AMT[ERB]-HI). Evaluation is performed using speech corpora with objective quality measures (segmental SNR, Itakura-Saito), along with formal listener evaluations of speech quality rating and intelligibility. While no measurable changes in intelligibility occurred, evaluations showed quality improvement with both algorithm implementations. However, the customized formulation based on individual hearing losses was similar in performance to the formulation based on the normal auditory system.

Digital audio watermarking using moment-preserving thresholding

NASA Astrophysics Data System (ADS)

Choi, DooSeop; Jung, Hae Kyung; Choi, Hyuk; Kim, Taejeong

2007-09-01

The Moment-Preserving Thresholding technique for digital images has been used in digital image processing for decades, especially in image binarization and image compression. Its main strength lies in that the binary values that the MPT produces as a result, called representative values, are usually unaffected when the signal being thresholded goes through a signal processing operation. The two representative values in MPT together with the threshold value are obtained by solving the system of the preservation equations for the first, second, and third moment. Relying on this robustness of the representative values to various signal processing attacks considered in the watermarking context, this paper proposes a new watermarking scheme for audio signals. The watermark is embedded in the root-sum-square (RSS) of the two representative values of each signal block using the quantization technique. As a result, the RSS values are modified by scaling the signal according to the watermark bit sequence under the constraint of inaudibility relative to the human psycho-acoustic model. We also address and suggest solutions to the problem of synchronization and power scaling attacks. Experimental results show that the proposed scheme maintains high audio quality and robustness to various attacks including MP3 compression, re-sampling, jittering, and, DA/AD conversion.

Assessing Personal Qualities in Medical School Admissions.

ERIC Educational Resources Information Center

Albanese, Mark A.; Snow, Mikel H.; Skochelak, Susan E.; Huggett, Kathryn N.; Farrell, Philip M.

2003-01-01

Analyzes the challenges to using academic measures (MCAT scores and GPAs) as thresholds for medical school admissions and, for applicants exceeding the threshold, using personal qualities for admission decisions; reviews the literature on using the medical school interview and other admission data to assess personal qualities of applicants;…

REGULATORY APPLICATIONS OF POREWATER TOXICITY TESTING

EPA Science Inventory

The purpose of this chapter is to evaluate the use of porewater toxicity tests in regulatory applications, including their potential use in the development of sediment quality guideline (SQG) values. Specifically, the following discussion focuses on the appropriateness and readin...

Ground-Water Quality Data in the Kern County Subbasin Study Unit, 2006 - Results from the California GAMA Program

USGS Publications Warehouse

Shelton, Jennifer L.; Pimentel, Isabel; Fram, Miranda S.; Belitz, Kenneth

2008-01-01

the wells, and the results for these samples were used to evaluate the quality of the data from the ground-water samples. Assessment of the quality-control information resulted in censoring of less than 0.4 percent of the data collected for ground-water samples. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, raw ground water typically is treated, disinfected, or blended with other waters to maintain acceptable water quality. Regulatory thresholds apply, not to the raw ground water, but to treated water that is served to the consumer. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH), and as well as with thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. VOCs and pesticides each were detected in approximately 60 percent of the grid wells, and detections of all compounds but one were below health-based thresholds. The fumigant, 1,2-dibromo-3-chloropropane (DBCP), was detected above the USEPA maximum contaminant level (MCL-US) in one sample. Detections of most inorganic constituents were also below health-based thresholds. Constituents detected above health-based thresholds include: nitrate, (MCL-US, 2 samples), arsenic (MCL-US, 2 samples), and vanadium (California notification level, NL-CA, 1 sample). All detections of radioactive constituents were below health-based thresholds, although nine samples had activities of radon-222 above the lower proposed MCL-US. Most of the samples from KERN wells had concentrations of major elements, total dissolved solids, and trace elements below the non-enforceable thresholds set for aesthetic concerns.

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

Water quality and coral bleaching thresholds: formalising the linkage for the inshore reefs of the Great Barrier Reef, Australia.

PubMed

Wooldridge, Scott A

2009-05-01

The threats of wide-scale coral bleaching and reef demise associated with anthropogenic climate change are widely known. Here, the additional role of poor water quality in lowering the thermal tolerance (i.e. bleaching 'resistance') of symbiotic reef corals is considered. In particular, a quantitative linkage is established between terrestrially-sourced dissolved inorganic nitrogen (DIN) loading and the upper thermal bleaching thresholds of inshore reefs on the Great Barrier Reef, Australia. Significantly, this biophysical linkage provides concrete evidence for the oft-expressed belief that improved coral reef management will increase the regional-scale survival prospects of corals reefs to global climate change. Indeed, for inshore reef areas with a high runoff exposure risk, it is shown that the potential benefit of this 'local' management imperative is equivalent to approximately 2.0-2.5 degrees C in relation to the upper thermal bleaching limit; though in this case, a potentially cost-prohibitive reduction in end-of-river DIN of >50-80% would be required. An integrated socio-economic modelling framework is outlined that will assist future efforts to understand (optimise) the alternate tradeoffs that the water quality/coral bleaching linkage presents.

10 CFR 63.144 - Quality assurance program change.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Quality assurance program change. 63.144 Section 63.144 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN A GEOLOGIC... assurance program information that duplicates language in quality assurance regulatory guides and quality...

Scientific and Legal Perspectives on Science Generated for Regulatory Activities

PubMed Central

Henry, Carol J.; Conrad, James W.

2008-01-01

This article originated from a conference that asked “Should scientific work conducted for purposes of advocacy before regulatory agencies or courts be judged by the same standards as science conducted for other purposes?” In the article, which focuses on the regulatory advocacy context, we argue that it can be and should be. First, we describe a set of standards and practices currently being used to judge the quality of scientific research and testing and explain how these standards and practices assist in judging the quality of research and testing regardless of why the work was conducted. These standards and practices include the federal Information Quality Act, federal Good Laboratory Practice standards, peer review, disclosure of funding sources, and transparency in research policies. The more that scientific information meets these standards and practices, the more likely it is to be of high quality, reliable, reproducible, and credible. We then explore legal issues that may be implicated in any effort to create special rules for science conducted specifically for a regulatory proceeding. Federal administrative law does not provide a basis for treating information in a given proceeding differently depending on its source or the reason for which it was generated. To the contrary, this law positively assures that interested persons have the right to offer their technical expertise toward the solution of regulatory problems. Any proposal to subject scientific information generated for the purpose of a regulatory proceeding to more demanding standards than other scientific information considered in that proceeding would clash with this law and would face significant administrative complexities. In a closely related example, the U.S. Environmental Protection Agency considered but abandoned a program to implement standards aimed at “external” information. PMID:18197313

Scientific and legal perspectives on science generated for regulatory activities.

PubMed

Henry, Carol J; Conrad, James W

2008-01-01

This article originated from a conference that asked "Should scientific work conducted for purposes of advocacy before regulatory agencies or courts be judged by the same standards as science conducted for other purposes?" In the article, which focuses on the regulatory advocacy context, we argue that it can be and should be. First, we describe a set of standards and practices currently being used to judge the quality of scientific research and testing and explain how these standards and practices assist in judging the quality of research and testing regardless of why the work was conducted. These standards and practices include the federal Information Quality Act, federal Good Laboratory Practice standards, peer review, disclosure of funding sources, and transparency in research policies. The more that scientific information meets these standards and practices, the more likely it is to be of high quality, reliable, reproducible, and credible. We then explore legal issues that may be implicated in any effort to create special rules for science conducted specifically for a regulatory proceeding. Federal administrative law does not provide a basis for treating information in a given proceeding differently depending on its source or the reason for which it was generated. To the contrary, this law positively assures that interested persons have the right to offer their technical expertise toward the solution of regulatory problems. Any proposal to subject scientific information generated for the purpose of a regulatory proceeding to more demanding standards than other scientific information considered in that proceeding would clash with this law and would face significant administrative complexities. In a closely related example, the U.S. Environmental Protection Agency considered but abandoned a program to implement standards aimed at "external" information.

Potential Implications of Recent and Proposed Changes in the Regulatory Oversight of Solid Organ Transplantation in the United States

PubMed Central

Kasiske, BL; Salkowski, N; Wey, A; Israni, AK; Snyder, JJ

2016-01-01

Every 6 months, the Scientific Registry of Transplant Recipients (SRTR) publishes evaluations of every solid organ transplant program in the US, including evaluations of 1-year patient and graft survival. The Centers for Medicare & Medicaid Services (CMS) and the Organ Procurement and Transplantation Network (OPTN) Membership and Professional Standards Committee (MPSC) use SRTR’s 1-year evaluations for regulatory review of transplant programs. Concern has been growing that the regulatory scrutiny of transplant programs with lower than expected outcomes is harmful, causing programs to undertake fewer high-risk transplants and leading to unnecessary organ discards. As a result, CMS raised its threshold for a “Condition-Level Deficiency” designation of observed relative to expected 1-year graft or patient survival from 1.50 to 1.85. Exceeding this threshold in the current SRTR outcomes report and in one of the four previous reports leads to scrutiny that may result in loss of Medicare funding. For its part, OPTN is reviewing a proposal from the MPSC to also change its performance criteria thresholds for program review, to review programs with “substantive clinical differences.” We review the details and implications of these changes in transplant program oversight. PMID:27401597

Soil thresholds and a decision tool to manage food safety of crops grown in chlordecone polluted soil in the French West Indies.

PubMed

Clostre, Florence; Letourmy, Philippe; Lesueur-Jannoyer, Magalie

2017-04-01

Due to the persistent pollution of soils by an organochlorine, chlordecone (CLD also known as Kepone © ) in the French West Indies, some crops may be contaminated beyond the European regulatory threshold, the maximum residue limit (MRL). Farmers need to be able to foresee the risk of not complying with the regulatory threshold in each field and for each crop, if not, farmers whose fields are contaminated would have to stop cultivating certain crops in the fields concerned. To help farmers make the right choices, we studied the relationship between contamination of the soil and contamination of crops. We showed that contamination of a crop by CLD depended on the crop concerned, the soil CLD content and the type of soil. We grouped crop products in three categories: (i) non-uptakers and low-uptakers, (ii) medium-uptakers, and (iii) high-uptakers, according to their level of contamination and the resulting risk of exceeding MRL. Using a simulation model, we computed the soil threshold required to ensure the risk of not complying with MRL was sufficiently low for each crop product and soil type. Threshold values ranged from 0.02 μgkg -1 for dasheen grown in nitisol to 1.7 μgkg -1 for yam grown in andosol in the high-uptake category, and from 1 μgkg -1 for lettuce grown in nitisol to 45 μgkg -1 for the leaves of spring onions grown in andosol in the medium-uptake category. Contamination of non-uptakers and low-uptakers did not depend on soil contamination. With these results, we built an easy-to-use decision support tool based on two soil thresholds (0.1 and 1 μgkg -1 ) to enable growers to adapt their cropping system and hence to be able to continue farming. Copyright © 2017 Elsevier Ltd. All rights reserved.

ADAPTIVE THRESHOLD LOGIC.

DTIC Science & Technology

The design and construction of a 16 variable threshold logic gate with adaptable weights is described. The operating characteristics of tape wound...and sizes as well as for the 16 input adaptive threshold logic gate. (Author)

Implementation guide for turbidity threshold sampling: principles, procedures, and analysis

Treesearch

Jack Lewis; Rand Eads

2009-01-01

Turbidity Threshold Sampling uses real-time turbidity and river stage information to automatically collect water quality samples for estimating suspended sediment loads. The system uses a programmable data logger in conjunction with a stage measurement device, a turbidity sensor, and a pumping sampler. Specialized software enables the user to control the sampling...

Threshold Concepts in Biochemistry

ERIC Educational Resources Information Center

Loertscher, Jennifer

2011-01-01

Threshold concepts can be identified for any discipline and provide a framework for linking student learning to curricular design. Threshold concepts represent a transformed understanding of a discipline, without which the learner cannot progress and are therefore pivotal in learning in a discipline. Although threshold concepts have been…

Water quality and bed sediment quality in the Albemarle Sound, North Carolina, 2012–14

USGS Publications Warehouse

Moorman, Michelle C.; Fitzgerald, Sharon A.; Gurley, Laura N.; Rhoni-Aref, Ahmed; Loftin, Keith A.

2017-01-23

The Albemarle Sound region was selected in 2012 as one of two demonstration sites in the Nation to test and improve the design of the National Water Quality Monitoring Council’s National Monitoring Network (NMN) for U.S. Coastal Waters and Tributaries. The goal of the NMN for U.S. Coastal Waters and Tributaries is to provide information about the health of our oceans, coastal ecosystems, and inland influences on coastal waters for improved resource management. The NMN is an integrated, multidisciplinary, and multi-organizational program using multiple sources of data and information to augment current monitoring programs.This report presents and summarizes selected water-quality and bed sediment-quality data collected as part of the demonstration project conducted in two phases. The first phase was an occurrence and distribution study to assess nutrients, metals, pesticides, cyanotoxins, and phytoplankton communities in the Albemarle Sound during the summer of 2012 at 34 sites in Albemarle Sound, nearby sounds, and various tributaries. The second phase consisted of monthly sampling over a year (March 2013 through February 2014) to assess seasonality in a more limited set of constituents including nutrients, cyanotoxins, and phytoplankton communities at a subset (eight) of the sites sampled in the first phase. During the summer of 2012, few constituent concentrations exceeded published water-quality thresholds; however, elevated levels of chlorophyll a and pH were observed in the northern embayments and in Currituck Sound. Chlorophyll a, and metals (copper, iron, and zinc) were detected above a water-quality threshold. The World Health Organization provisional guideline based on cyanobacterial density for high recreational risk was exceeded in approximately 50 percent of water samples collected during the summer of 2012. Cyanobacteria capable of producing toxins were present, but only low levels of cyanotoxins below human health benchmarks were detected. Finally

A threshold model of content knowledge transfer for socioscientific argumentation

NASA Astrophysics Data System (ADS)

Sadler, Troy D.; Fowler, Samantha R.

2006-11-01

This study explores how individuals make use of scientific content knowledge for socioscientific argumentation. More specifically, this mixed-methods study investigates how learners apply genetics content knowledge as they justify claims relative to genetic engineering. Interviews are conducted with 45 participants, representing three distinct groups: high school students with variable genetics knowledge, college nonscience majors with little genetics knowledge, and college science majors with advanced genetics knowledge. During the interviews, participants advance positions concerning three scenarios dealing with gene therapy and cloning. Arguments are assessed in terms of the number of justifications offered as well as justification quality, based on a five-point rubric. Multivariate analysis of variance results indicate that college science majors outperformed the other groups in terms of justification quality and frequency. Argumentation does not differ among nonscience majors or high school students. Follow-up qualitative analyses of interview responses suggest that all three groups tend to focus on similar, sociomoral themes as they negotiate socially complex, genetic engineering issues, but that the science majors frequently reference specific science content knowledge in the justification of their claims. Results support the Threshold Model of Content Knowledge Transfer, which proposes two knowledge thresholds around which argumentation quality can reasonably be expected to increase. Research and educational implications of these findings are discussed.

Mitochondrial threshold effects.

PubMed Central

Rossignol, Rodrigue; Faustin, Benjamin; Rocher, Christophe; Malgat, Monique; Mazat, Jean-Pierre; Letellier, Thierry

2003-01-01

The study of mitochondrial diseases has revealed dramatic variability in the phenotypic presentation of mitochondrial genetic defects. To attempt to understand this variability, different authors have studied energy metabolism in transmitochondrial cell lines carrying different proportions of various pathogenic mutations in their mitochondrial DNA. The same kinds of experiments have been performed on isolated mitochondria and on tissue biopsies taken from patients with mitochondrial diseases. The results have shown that, in most cases, phenotypic manifestation of the genetic defect occurs only when a threshold level is exceeded, and this phenomenon has been named the 'phenotypic threshold effect'. Subsequently, several authors showed that it was possible to inhibit considerably the activity of a respiratory chain complex, up to a critical value, without affecting the rate of mitochondrial respiration or ATP synthesis. This phenomenon was called the 'biochemical threshold effect'. More recently, quantitative analysis of the effects of various mutations in mitochondrial DNA on the rate of mitochondrial protein synthesis has revealed the existence of a 'translational threshold effect'. In this review these different mitochondrial threshold effects are discussed, along with their molecular bases and the roles that they play in the presentation of mitochondrial diseases. PMID:12467494

Threshold concepts in prosthetics.

PubMed

Hill, Sophie

2017-12-01

Curriculum documents identify key concepts within learning prosthetics. Threshold concepts provide an alternative way of viewing the curriculum, focussing on the ways of thinking and practicing within prosthetics. Threshold concepts can be described as an opening to a different way of viewing a concept. This article forms part of a larger study exploring what students and staff experience as difficult in learning about prosthetics. To explore possible threshold concepts within prosthetics. Qualitative, interpretative phenomenological analysis. Data from 18 students and 8 staff at two universities with undergraduate prosthetics and orthotics programmes were generated through interviews and questionnaires. The data were analysed using an interpretative phenomenological analysis approach. Three possible threshold concepts arose from the data: 'how we walk', 'learning to talk' and 'considering the person'. Three potential threshold concepts in prosthetics are suggested with possible implications for prosthetics education. These possible threshold concepts involve changes in both conceptual and ontological knowledge, integrating into the persona of the individual. This integration occurs through the development of memories associated with procedural concepts that combine with disciplinary concepts. Considering the prosthetics curriculum through the lens of threshold concepts enables a focus on how students learn to become prosthetists. Clinical relevance This study provides new insights into how prosthetists learn. This has implications for curriculum design in prosthetics education.

Ecological thresholds: The key to successful enviromental management or an important concept with no practical application?

USGS Publications Warehouse

Groffman, P.M.; Baron, Jill S.; Blett, T.; Gold, A.J.; Goodman, I.; Gunderson, L.H.; Levinson, B.M.; Palmer, Margaret A.; Paerl, H.W.; Peterson, G.D.; Poff, N.L.; Rejeski, D.W.; Reynolds, J.F.; Turner, M.G.; Weathers, K.C.; Wiens, J.

2006-01-01

An ecological threshold is the point at which there is an abrupt change in an ecosystem quality, property or phenomenon, or where small changes in an environmental driver produce large responses in the ecosystem. Analysis of thresholds is complicated by nonlinear dynamics and by multiple factor controls that operate at diverse spatial and temporal scales. These complexities have challenged the use and utility of threshold concepts in environmental management despite great concern about preventing dramatic state changes in valued ecosystems, the need for determining critical pollutant loads and the ubiquity of other threshold-based environmental problems. In this paper we define the scope of the thresholds concept in ecological science and discuss methods for identifying and investigating thresholds using a variety of examples from terrestrial and aquatic environments, at ecosystem, landscape and regional scales. We end with a discussion of key research needs in this area.

Ground-Water Quality Data in the Southeast San Joaquin Valley, 2005-2006 - Results from the California GAMA Program

USGS Publications Warehouse

Burton, Carmen A.; Belitz, Kenneth

2008-01-01

for these samples were used to evaluate the quality of the data for the ground-water samples. Assessment of the quality-control data resulted in censoring of less than 1 percent of the detections of constituents measured in ground-water samples. This study did not attempt to evaluate the quality of drinking water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain acceptable drinking-water quality. Regulatory thresholds apply to the treated water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with regulatory and other health-based thresholds established by the U.S. Environmental Protection Agency and California Department of Public Health (CDPH) and thresholds established for aesthetic concerns by CDPH. Two VOCs were detected above health-based thresholds: 1,2-dibromo-3-chloropropane (DBCP), and benzene. DBCP was detected above the U.S. Environmental Protections Agency's maximum contaminant level (MCL-US) in three grid wells and five understanding wells. Benzene was detected above the CDPH's maximum contaminant level (MCL-CA) in one grid well. All pesticide detections were below health-based thresholds. Perchlorate was detected above its maximum contaminate level for California in one grid well. Nitrate was detected above the MCL-US in six samples from understanding wells, of which one was a public supply well. Two trace elements were detected above MCLs-US: arsenic and uranium. Arsenic was detected above the MCL-US in four grid wells and two understanding wells; uranium was detected above the MCL-US in one grid well and one understanding well. Gross alpha radiation was detected above MCLs-US in five samples; four of them understanding wells, and uranium isotope activity was greater than the MCL-US for one understanding well

RSAT 2015: Regulatory Sequence Analysis Tools

PubMed Central

Medina-Rivera, Alejandra; Defrance, Matthieu; Sand, Olivier; Herrmann, Carl; Castro-Mondragon, Jaime A.; Delerce, Jeremy; Jaeger, Sébastien; Blanchet, Christophe; Vincens, Pierre; Caron, Christophe; Staines, Daniel M.; Contreras-Moreira, Bruno; Artufel, Marie; Charbonnier-Khamvongsa, Lucie; Hernandez, Céline; Thieffry, Denis; Thomas-Chollier, Morgane; van Helden, Jacques

2015-01-01

RSAT (Regulatory Sequence Analysis Tools) is a modular software suite for the analysis of cis-regulatory elements in genome sequences. Its main applications are (i) motif discovery, appropriate to genome-wide data sets like ChIP-seq, (ii) transcription factor binding motif analysis (quality assessment, comparisons and clustering), (iii) comparative genomics and (iv) analysis of regulatory variations. Nine new programs have been added to the 43 described in the 2011 NAR Web Software Issue, including a tool to extract sequences from a list of coordinates (fetch-sequences from UCSC), novel programs dedicated to the analysis of regulatory variants from GWAS or population genomics (retrieve-variation-seq and variation-scan), a program to cluster motifs and visualize the similarities as trees (matrix-clustering). To deal with the drastic increase of sequenced genomes, RSAT public sites have been reorganized into taxon-specific servers. The suite is well-documented with tutorials and published protocols. The software suite is available through Web sites, SOAP/WSDL Web services, virtual machines and stand-alone programs at http://www.rsat.eu/. PMID:25904632

An approach to predict water quality in data-sparse catchments using hydrological catchment similarity

NASA Astrophysics Data System (ADS)

Pohle, Ina; Glendell, Miriam; Stutter, Marc I.; Helliwell, Rachel C.

2017-04-01

An understanding of catchment response to climate and land use change at a regional scale is necessary for the assessment of mitigation and adaptation options addressing diffuse nutrient pollution. It is well documented that the physicochemical properties of a river ecosystem respond to change in a non-linear fashion. This is particularly important when threshold water concentrations, relevant to national and EU legislation, are exceeded. Large scale (regional) model assessments required for regulatory purposes must represent the key processes and mechanisms that are more readily understood in catchments with water quantity and water quality data monitored at high spatial and temporal resolution. While daily discharge data are available for most catchments in Scotland, nitrate and phosphorus are mostly available on a monthly basis only, as typified by regulatory monitoring. However, high resolution (hourly to daily) water quantity and water quality data exist for a limited number of research catchments. To successfully implement adaptation measures across Scotland, an upscaling from data-rich to data-sparse catchments is required. In addition, the widespread availability of spatial datasets affecting hydrological and biogeochemical responses (e.g. soils, topography/geomorphology, land use, vegetation etc.) provide an opportunity to transfer predictions between data-rich and data-sparse areas by linking processes and responses to catchment attributes. Here, we develop a framework of catchment typologies as a prerequisite for transferring information from data-rich to data-sparse catchments by focusing on how hydrological catchment similarity can be used as an indicator of grouped behaviours in water quality response. As indicators of hydrological catchment similarity we use flow indices derived from observed discharge data across Scotland as well as hydrological model parameters. For the latter, we calibrated the lumped rainfall-runoff model TUWModel using multiple

Shifts in the relationship between motor unit recruitment thresholds versus derecruitment thresholds during fatigue.

PubMed

Stock, Matt S; Mota, Jacob A

2017-12-01

Muscle fatigue is associated with diminished twitch force amplitude. We examined changes in the motor unit recruitment versus derecruitment threshold relationship during fatigue. Nine men (mean age = 26 years) performed repeated isometric contractions at 50% maximal voluntary contraction (MVC) knee extensor force until exhaustion. Surface electromyographic signals were detected from the vastus lateralis, and were decomposed into their constituent motor unit action potential trains. Motor unit recruitment and derecruitment thresholds and firing rates at recruitment and derecruitment were evaluated at the beginning, middle, and end of the protocol. On average, 15 motor units were studied per contraction. For the initial contraction, three subjects showed greater recruitment thresholds than derecruitment thresholds for all motor units. Five subjects showed greater recruitment thresholds than derecruitment thresholds for only low-threshold motor units at the beginning, with a mean cross-over of 31.6% MVC. As the muscle fatigued, many motor units were derecruited at progressively higher forces. In turn, decreased slopes and increased y-intercepts were observed. These shifts were complemented by increased firing rates at derecruitment relative to recruitment. As the vastus lateralis fatigued, the central nervous system's compensatory adjustments resulted in a shift of the regression line of the recruitment versus derecruitment threshold relationship. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

21 CFR 26.49 - Regulatory cooperation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Regulatory cooperation. 26.49 Section 26.49 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS...

21 CFR 26.18 - Regulatory collaboration.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Regulatory collaboration. 26.18 Section 26.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS...

21 CFR 26.34 - Regulatory authorities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Regulatory authorities. 26.34 Section 26.34 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS...

78 FR 26836 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-08

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69503; File No. SR-NYSEArca-2013-44] Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending Its Schedule of Fees and Charges for Exchange Services To Amend Step Up Tier 2 to Reduce the Volume Threshold Requirements Needed To...

Using Generalized Additive Modeling to Empirically Identify Thresholds within the ITERS in Relation to Toddlers' Cognitive Development

ERIC Educational Resources Information Center

Setodji, Claude Messan; Le, Vi-Nhuan; Schaack, Diana

2013-01-01

Research linking high-quality child care programs and children's cognitive development has contributed to the growing popularity of child care quality benchmarking efforts such as quality rating and improvement systems (QRIS). Consequently, there has been an increased interest in and a need for approaches to identifying thresholds, or cutpoints,…

Ground-Water Quality Data in the San Fernando-San Gabriel Study Unit, 2005 - Results from the California GAMA Program

USGS Publications Warehouse

Land, Michael; Belitz, Kenneth

2008-01-01

samples were used to evaluate the quality of the data for the ground-water samples. Assessment of the quality-control results showed that the data had very little bias or variability and resulted in censoring of less than 0.7 percent (32 of 4,484 measurements) of the data collected for ground-water samples. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, or blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. VOCs were detected in more than 90 percent (33 of 35) of grid wells. For all wells sampled for SFSG, nearly all VOC detections were below health-based thresholds, and most were less than one-tenth of the threshold values. Samples from seven wells had at least one detection of PCE, TCE, tetrachloromethane, NDMA, or 1,2,3-TCP at or above a health-based threshold. Pesticides were detected in about 90 percent (31 of 35) grid wells and all detections in samples from SFSG wells were below health-based thresholds. Major ions, trace elements, and nutrients in samples from 17 SFSG wells were all below health-based thresholds, with the exception of one detection of nitrate that was above the USEPA maximum contaminant level (MCL-US). With the exception of 14 samples having radon-222 above the proposed MCL-US, radioactive constituents were below health-based thresholds for 16 of the SFSG wells sampled. Total dissolved solids in 6 of the 24 SFSG wells that were sampled ha

Threshold factorization redux

NASA Astrophysics Data System (ADS)

Chay, Junegone; Kim, Chul

2018-05-01

We reanalyze the factorization theorems for the Drell-Yan process and for deep inelastic scattering near threshold, as constructed in the framework of the soft-collinear effective theory (SCET), from a new, consistent perspective. In order to formulate the factorization near threshold in SCET, we should include an additional degree of freedom with small energy, collinear to the beam direction. The corresponding collinear-soft mode is included to describe the parton distribution function (PDF) near threshold. The soft function is modified by subtracting the contribution of the collinear-soft modes in order to avoid double counting on the overlap region. As a result, the proper soft function becomes infrared finite, and all the factorized parts are free of rapidity divergence. Furthermore, the separation of the relevant scales in each factorized part becomes manifest. We apply the same idea to the dihadron production in e+e- annihilation near threshold, and show that the resultant soft function is also free of infrared and rapidity divergences.

Quality measurement and improvement in liver transplantation.

PubMed

Mathur, Amit K; Talwalkar, Jayant

2018-06-01

There is growing interest in the quality of health care delivery in liver transplantation. Multiple stakeholders, including patients, transplant providers and their hospitals, payers, and regulatory bodies have an interest in measuring and monitoring quality in the liver transplant process, and understanding differences in quality across centres. This article aims to provide an overview of quality measurement and regulatory issues in liver transplantation performed within the United States. We review how broader definitions of health care quality should be applied to liver transplant care models. We outline the status quo including the current regulatory agencies, public reporting mechanisms, and requirements around quality assurance and performance improvement (QAPI) activities. Additionally, we further discuss unintended consequences and opportunities for growth in quality measurement. Quality measurement and the integration of quality improvement strategies into liver transplant programmes hold significant promise, but multiple challenges to successful implementation must be addressed to optimise value. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Effectiveness of the hearing conservation program: Change in hearing threshold shift incidence among industrial workers, 1978 to 2003

NASA Astrophysics Data System (ADS)

Davies, Hugh

2005-04-01

Hearing conservation programs (HCP) are widely employed in preventing noise-induced hearing loss, but studies of their effectiveness have been rare. The impact of the implementation of hearing conservation programs was assessed in a large group of highly noise-exposed blue-collar workers by investigating time-trends in hearing-threshold shift incidence. Serial annual audiograms for employees of 14 British Columbia lumber mills for the period 1978 to 2003 were obtained from local regulatory-agency archives. Audiograms and concomitant otological medical histories were linked to subjects' work histories and noise exposure data. Multivariable Cox proportional hazard models were used to model the incidence of hearing threshold shift while controlling for age, baseline level of hearing loss, and other potential confounders. A total of 109257 audiograms were associated with 10590 subjects. Mean noise exposure in this group was 91.4 dBA(A). Mean interval between hearing tests was 566 days and mean age at first threshold shift was 44. Forty-six percent of subjects had at least one OSHA significant threshold shift during follow up. Preliminary analyses indicated a trend toward lower incidence of threshold shifts over the study period, with incidence in 5 approximately equal 5-year periods from 1978 to 2003 being 3.2%, 6.6%, 4.9%, 4.3% and 2.4%, respectively.

Comparison between intensity- duration thresholds and cumulative rainfall thresholds for the forecasting of landslide

NASA Astrophysics Data System (ADS)

Lagomarsino, Daniela; Rosi, Ascanio; Rossi, Guglielmo; Segoni, Samuele; Catani, Filippo

2014-05-01

This work makes a quantitative comparison between the results of landslide forecasting obtained using two different rainfall threshold models, one using intensity-duration thresholds and the other based on cumulative rainfall thresholds in an area of northern Tuscany of 116 km2. The first methodology identifies rainfall intensity-duration thresholds by means a software called MaCumBA (Massive CUMulative Brisk Analyzer) that analyzes rain-gauge records, extracts the intensities (I) and durations (D) of the rainstorms associated with the initiation of landslides, plots these values on a diagram, and identifies thresholds that define the lower bounds of the I-D values. A back analysis using data from past events can be used to identify the threshold conditions associated with the least amount of false alarms. The second method (SIGMA) is based on the hypothesis that anomalous or extreme values of rainfall are responsible for landslide triggering: the statistical distribution of the rainfall series is analyzed, and multiples of the standard deviation (σ) are used as thresholds to discriminate between ordinary and extraordinary rainfall events. The name of the model, SIGMA, reflects the central role of the standard deviations in the proposed methodology. The definition of intensity-duration rainfall thresholds requires the combined use of rainfall measurements and an inventory of dated landslides, whereas SIGMA model can be implemented using only rainfall data. These two methodologies were applied in an area of 116 km2 where a database of 1200 landslides was available for the period 2000-2012. The results obtained are compared and discussed. Although several examples of visual comparisons between different intensity-duration rainfall thresholds are reported in the international literature, a quantitative comparison between thresholds obtained in the same area using different techniques and approaches is a relatively undebated research topic.

Regulatory ozone modeling: status, directions, and research needs.

PubMed Central

Georgopoulos, P G

1995-01-01

The Clean Air Act Amendments (CAAA) of 1990 have established selected comprehensive, three-dimensional, Photochemical Air Quality Simulation Models (PAQSMs) as the required regulatory tools for analyzing the urban and regional problem of high ambient ozone levels across the United States. These models are currently applied to study and establish strategies for meeting the National Ambient Air Quality Standard (NAAQS) for ozone in nonattainment areas; State Implementation Plans (SIPs) resulting from these efforts must be submitted to the U.S. Environmental Protection Agency (U.S. EPA) in November 1994. The following presentation provides an overview and discussion of the regulatory ozone modeling process and its implications. First, the PAQSM-based ozone attainment demonstration process is summarized in the framework of the 1994 SIPs. Then, following a brief overview of the representation of physical and chemical processes in PAQSMs, the essential attributes of standard modeling systems currently in regulatory use are presented in a nonmathematical, self-contained format, intended to provide a basic understanding of both model capabilities and limitations. The types of air quality, emission, and meteorological data needed for applying and evaluating PAQSMs are discussed, as well as the sources, availability, and limitations of existing databases. The issue of evaluating a model's performance in order to accept it as a tool for policy making is discussed, and various methodologies for implementing this objective are summarized. Selected interim results from diagnostic analyses, which are performed as a component of the regulatory ozone modeling process for the Philadelphia-New Jersey region, are also presented to provide some specific examples related to the general issues discussed in this work. Finally, research needs related to a) the evaluation and refinement of regulatory ozone modeling, b) the characterization of uncertainty in photochemical modeling, and c

Photoacoustic signals denoising of the glucose aqueous solutions using an improved wavelet threshold method

NASA Astrophysics Data System (ADS)

Ren, Zhong; Liu, Guodong; Xiong, Zhihua

2016-10-01

The photoacoustic signals denoising of glucose is one of most important steps in the quality identification of the fruit because the real-time photoacoustic singals of glucose are easily interfered by all kinds of noises. To remove the noises and some useless information, an improved wavelet threshld function were proposed. Compared with the traditional wavelet hard and soft threshold functions, the improved wavelet threshold function can overcome the pseudo-oscillation effect of the denoised photoacoustic signals due to the continuity of the improved wavelet threshold function, and the error between the denoised signals and the original signals can be decreased. To validate the feasibility of the improved wavelet threshold function denoising, the denoising simulation experiments based on MATLAB programmimg were performed. In the simulation experiments, the standard test signal was used, and three different denoising methods were used and compared with the improved wavelet threshold function. The signal-to-noise ratio (SNR) and the root-mean-square error (RMSE) values were used to evaluate the performance of the improved wavelet threshold function denoising. The experimental results demonstrate that the SNR value of the improved wavelet threshold function is largest and the RMSE value is lest, which fully verifies that the improved wavelet threshold function denoising is feasible. Finally, the improved wavelet threshold function denoising was used to remove the noises of the photoacoustic signals of the glucose solutions. The denoising effect is also very good. Therefore, the improved wavelet threshold function denoising proposed by this paper, has a potential value in the field of denoising for the photoacoustic singals.

40 CFR 68.115 - Threshold determination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 15 2011-07-01 2011-07-01 false Threshold determination. 68.115... § 68.115 Threshold determination. (a) A threshold quantity of a regulated substance listed in § 68.130... process exceeds the threshold. (b) For the purposes of determining whether more than a threshold quantity...

Proposing an Empirically Justified Reference Threshold for Blood Culture Sampling Rates in Intensive Care Units

PubMed Central

Castell, Stefanie; Schwab, Frank; Geffers, Christine; Bongartz, Hannah; Brunkhorst, Frank M.; Gastmeier, Petra; Mikolajczyk, Rafael T.

2014-01-01

Early and appropriate blood culture sampling is recommended as a standard of care for patients with suspected bloodstream infections (BSI) but is rarely taken into account when quality indicators for BSI are evaluated. To date, sampling of about 100 to 200 blood culture sets per 1,000 patient-days is recommended as the target range for blood culture rates. However, the empirical basis of this recommendation is not clear. The aim of the current study was to analyze the association between blood culture rates and observed BSI rates and to derive a reference threshold for blood culture rates in intensive care units (ICUs). This study is based on data from 223 ICUs taking part in the German hospital infection surveillance system. We applied locally weighted regression and segmented Poisson regression to assess the association between blood culture rates and BSI rates. Below 80 to 90 blood culture sets per 1,000 patient-days, observed BSI rates increased with increasing blood culture rates, while there was no further increase above this threshold. Segmented Poisson regression located the threshold at 87 (95% confidence interval, 54 to 120) blood culture sets per 1,000 patient-days. Only one-third of the investigated ICUs displayed blood culture rates above this threshold. We provided empirical justification for a blood culture target threshold in ICUs. In the majority of the studied ICUs, blood culture sampling rates were below this threshold. This suggests that a substantial fraction of BSI cases might remain undetected; reporting observed BSI rates as a quality indicator without sufficiently high blood culture rates might be misleading. PMID:25520442

2012 Global Summit on Regulatory Science (GSRS-2012)--modernizing toxicology.

PubMed

Miller, Margaret A; Tong, Weida; Fan, Xiaohui; Slikker, William

2013-01-01

Regulatory science encompasses the tools, models, techniques, and studies needed to assess and evaluate product safety, efficacy, quality, and performance. Several recent publications have emphasized the role of regulatory science in improving global health, supporting economic development and fostering innovation. As for other scientific disciplines, research in regulatory science is the critical element underpinning the development and advancement of regulatory science as a modern scientific discipline. As a regulatory agency in the 21st century, the Food and Drug Administration (FDA) has an international component that underpins its domestic mission; foods, drugs, and devices are developed and imported to the United States from across the world. The Global Summit on Regulatory Science, an international conference for discussing innovative technologies, approaches, and partnerships that enhance the translation of basic science into regulatory applications, is providing leadership for the advancement of regulatory sciences within the global context. Held annually, this international conference provides a platform where regulators, policy makers, and bench scientists from various countries can exchange views on how to develop, apply, and implement innovative methodologies into regulatory assessments in their respective countries, as well as developing a harmonized strategy to improve global public health through global collaboration.

Academic Standards and Regulatory Frameworks: Necessary Compromises?

ERIC Educational Resources Information Center

Stowell, Marie; Falahee, Marie; Woolf, Harvey

2016-01-01

Assessment regulations in higher education, which are important for assuring threshold academic standards, reflect institutional cultures and histories, and are shaped by pragmatic concerns about quality indicators such as retention and progression rates, as well as principles of equity. This paper articulates some of the tensions that confront…

Continuous Seismic Threshold Monitoring

DTIC Science & Technology

1992-05-31

Continuous threshold monitoring is a technique for using a seismic network to monitor a geographical area continuously in time. The method provides...area. Two approaches are presented. Site-specific monitoring: By focusing a seismic network on a specific target site, continuous threshold monitoring...recorded events at the site. We define the threshold trace for the network as the continuous time trace of computed upper magnitude limits of seismic

Interaction mode between catalytic and regulatory subunits in glucosidase II involved in ER glycoprotein quality control.

PubMed

Satoh, Tadashi; Toshimori, Takayasu; Noda, Masanori; Uchiyama, Susumu; Kato, Koichi

2016-11-01

The glycoside hydrolase family 31 (GH31) α-glucosidases play vital roles in catabolic and regulated degradation, including the α-subunit of glucosidase II (GIIα), which catalyzes trimming of the terminal glucose residues of N-glycan in glycoprotein processing coupled with quality control in the endoplasmic reticulum (ER). Among the known GH31 enzymes, only GIIα functions with its binding partner, regulatory β-subunit (GIIβ), which harbors a lectin domain for substrate recognition. Although the structural data have been reported for GIIα and the GIIβ lectin domain, the interaction mode between GIIα and GIIβ remains unknown. Here, we determined the structure of a complex formed between GIIα and the GIIα-binding domain of GIIβ, thereby providing a structural basis underlying the functional extension of this unique GH31 enzyme. © 2016 The Protein Society.

A Model of Risk Analysis in Analytical Methodology for Biopharmaceutical Quality Control.

PubMed

Andrade, Cleyton Lage; Herrera, Miguel Angel De La O; Lemes, Elezer Monte Blanco

2018-01-01

One key quality control parameter for biopharmaceutical products is the analysis of residual cellular DNA. To determine small amounts of DNA (around 100 pg) that may be in a biologically derived drug substance, an analytical method should be sensitive, robust, reliable, and accurate. In principle, three techniques have the ability to measure residual cellular DNA: radioactive dot-blot, a type of hybridization; threshold analysis; and quantitative polymerase chain reaction. Quality risk management is a systematic process for evaluating, controlling, and reporting of risks that may affects method capabilities and supports a scientific and practical approach to decision making. This paper evaluates, by quality risk management, an alternative approach to assessing the performance risks associated with quality control methods used with biopharmaceuticals, using the tool hazard analysis and critical control points. This tool provides the possibility to find the steps in an analytical procedure with higher impact on method performance. By applying these principles to DNA analysis methods, we conclude that the radioactive dot-blot assay has the largest number of critical control points, followed by quantitative polymerase chain reaction, and threshold analysis. From the analysis of hazards (i.e., points of method failure) and the associated method procedure critical control points, we conclude that the analytical methodology with the lowest risk for performance failure for residual cellular DNA testing is quantitative polymerase chain reaction. LAY ABSTRACT: In order to mitigate the risk of adverse events by residual cellular DNA that is not completely cleared from downstream production processes, regulatory agencies have required the industry to guarantee a very low level of DNA in biologically derived pharmaceutical products. The technique historically used was radioactive blot hybridization. However, the technique is a challenging method to implement in a quality

Threshold friction velocity influenced by wetness of soils within the Columbia Plateau

USDA-ARS?s Scientific Manuscript database

Windblown dust impacts air quality in the Columbia Plateau of the U.S. Pacific Northwest. Wind erosion of agricultural lands, which is the predominate source of windblown dust in the region, occurs when the friction velocity exceeds the threshold friction velocity (TFV) of the surface. Soil moisture...

Does Winning a Pay-for-Performance Bonus Improve Subsequent Quality Performance? Evidence from the Hospital Quality Incentive Demonstration

PubMed Central

Ryan, Andrew; Sutton, Matthew; Doran, Tim

2014-01-01

Objective To test whether receiving a financial bonus for quality in the Premier Hospital Quality Incentive Demonstration (HQID) stimulated subsequent quality improvement. Data Hospital-level data on process-of-care quality from Hospital Compare for the treatment of acute myocardial infarction (AMI), heart failure, and pneumonia for 260 hospitals participating in the HQID from 2004 to 2006; receipt of quality bonuses in the first 3 years of HQID from the Premier Inc. website; and hospital characteristics from the 2005 American Hospital Association Annual Survey. Study Design Under the HQID, hospitals received a 1 percent bonus on Medicare payments for scoring between the 80th and 90th percentiles on a composite quality measure, and a 2 percent bonus for scoring at the 90th percentile or above. We used a regression discontinuity design to evaluate whether hospitals with quality scores just above these payment thresholds improved more in the subsequent year than hospitals with quality scores just below the thresholds. In alternative specifications, we examined samples of hospitals scoring within 3, 5, and 10 percentage point “bandwidths” of the thresholds. We used a Generalized Linear Model to estimate whether the relationship between quality and lagged quality was discontinuous at the lagged thresholds required for quality bonuses. Principal Findings There were no statistically significant associations between receipt of a bonus and subsequent quality performance, with the exception of the 2 percent bonus for AMI in 2006 using the 5 percentage point bandwidth (0.8 percentage point increase, p < .01), and the 1 percent bonus for pneumonia in 2005 using all bandwidths (3.7 percentage point increase using the 3 percentage point bandwidth, p < .05). Conclusions We found little evidence that hospitals' receipt of quality bonuses was associated with subsequent improvement in performance. This raises questions about whether winning in pay-for-performance programs

CONDITIONAL PROBABILITY ANALYSIS APPROACH FOR IDENTIFYING BIOLOGICAL THRESHOLD OF IMPACT FOR SEDIMENTATION: APPICATION TO FRESHWATER STREAMS IN OREGON COAST RANGE ECOREGION

EPA Science Inventory

A conditional probability analysis (CPA) approach has been developed for identifying biological thresholds of impact for use in the development of geographic-specific water quality criteria for protection of aquatic life. This approach expresses the threshold as the likelihood ...

Hydrodynamics of sediment threshold

NASA Astrophysics Data System (ADS)

Ali, Sk Zeeshan; Dey, Subhasish

2016-07-01

A novel hydrodynamic model for the threshold of cohesionless sediment particle motion under a steady unidirectional streamflow is presented. The hydrodynamic forces (drag and lift) acting on a solitary sediment particle resting over a closely packed bed formed by the identical sediment particles are the primary motivating forces. The drag force comprises of the form drag and form induced drag. The lift force includes the Saffman lift, Magnus lift, centrifugal lift, and turbulent lift. The points of action of the force system are appropriately obtained, for the first time, from the basics of micro-mechanics. The sediment threshold is envisioned as the rolling mode, which is the plausible mode to initiate a particle motion on the bed. The moment balance of the force system on the solitary particle about the pivoting point of rolling yields the governing equation. The conditions of sediment threshold under the hydraulically smooth, transitional, and rough flow regimes are examined. The effects of velocity fluctuations are addressed by applying the statistical theory of turbulence. This study shows that for a hindrance coefficient of 0.3, the threshold curve (threshold Shields parameter versus shear Reynolds number) has an excellent agreement with the experimental data of uniform sediments. However, most of the experimental data are bounded by the upper and lower limiting threshold curves, corresponding to the hindrance coefficients of 0.2 and 0.4, respectively. The threshold curve of this study is compared with those of previous researchers. The present model also agrees satisfactorily with the experimental data of nonuniform sediments.

I. RENAL THRESHOLDS FOR HEMOGLOBIN IN DOGS

PubMed Central

Lichty, John A.; Havill, William H.; Whipple, George H.

1932-01-01

We use the term "renal threshold for hemoglobin" to indicate the smallest amount of hemoglobin which given intravenously will effect the appearance of recognizable hemoglobin in the urine. The initial renal threshold level for dog hemoglobin is established by the methods employed at an average value of 155 mg. hemoglobin per kilo body weight with maximal values of 210 and minimal of 124. Repeated daily injections of hemoglobin will depress this initial renal threshold level on the average 46 per cent with maximal values of 110 and minimal values of 60 mg. hemoglobin per kilo body weight. This minimal or depression threshold is relatively constant if the injections are continued. Rest periods without injections cause a return of the renal threshold for hemoglobin toward the initial threshold levels—recovery threshold level. Injections of hemoglobin below the initial threshold level but above the minimal or depression threshold will eventually reduce the renal threshold for hemoglobin to its depression threshold level. We believe the depression threshold or minimal renal threshold level due to repeated hemoglobin injections is a little above the glomerular threshold which we assume is the base line threshold for hemoglobin. Our reasons for this belief in the glomerular threshold are given above and in the other papers of this series. PMID:19870016

Quality Management Program

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

Not Available

1991-10-01

According to {section} 35.32, Quality Management Program,'' of 10 CFR Part 35, Medical Use of Byproduct Material,'' applicants or licensees, as applicable, are required to establish a quality management (QM) program. This regulatory guide provides guidance to licensees and applicants for developing policies and procedures for the QM program. This guide does not restrict or limit the licensee from using other guidance that may be equally useful in developing a QM program, e.g., information available from the Joint Commission on Accreditation of Healthcare Organizations or the American College of Radiology. Any information collection activities mentioned in this regulatory guide aremore » contained as requirements in 10 CFR Part 35, which provides the regulatory basis for this guide. This information collection requirements in 10 CFR Part 35 have been cleared under OMB Clearance No. 3150-0010.« less

Bayesian Threshold Estimation

ERIC Educational Resources Information Center

Gustafson, S. C.; Costello, C. S.; Like, E. C.; Pierce, S. J.; Shenoy, K. N.

2009-01-01

Bayesian estimation of a threshold time (hereafter simply threshold) for the receipt of impulse signals is accomplished given the following: 1) data, consisting of the number of impulses received in a time interval from zero to one and the time of the largest time impulse; 2) a model, consisting of a uniform probability density of impulse time…

RSAT 2015: Regulatory Sequence Analysis Tools.

PubMed

Medina-Rivera, Alejandra; Defrance, Matthieu; Sand, Olivier; Herrmann, Carl; Castro-Mondragon, Jaime A; Delerce, Jeremy; Jaeger, Sébastien; Blanchet, Christophe; Vincens, Pierre; Caron, Christophe; Staines, Daniel M; Contreras-Moreira, Bruno; Artufel, Marie; Charbonnier-Khamvongsa, Lucie; Hernandez, Céline; Thieffry, Denis; Thomas-Chollier, Morgane; van Helden, Jacques

2015-07-01

RSAT (Regulatory Sequence Analysis Tools) is a modular software suite for the analysis of cis-regulatory elements in genome sequences. Its main applications are (i) motif discovery, appropriate to genome-wide data sets like ChIP-seq, (ii) transcription factor binding motif analysis (quality assessment, comparisons and clustering), (iii) comparative genomics and (iv) analysis of regulatory variations. Nine new programs have been added to the 43 described in the 2011 NAR Web Software Issue, including a tool to extract sequences from a list of coordinates (fetch-sequences from UCSC), novel programs dedicated to the analysis of regulatory variants from GWAS or population genomics (retrieve-variation-seq and variation-scan), a program to cluster motifs and visualize the similarities as trees (matrix-clustering). To deal with the drastic increase of sequenced genomes, RSAT public sites have been reorganized into taxon-specific servers. The suite is well-documented with tutorials and published protocols. The software suite is available through Web sites, SOAP/WSDL Web services, virtual machines and stand-alone programs at http://www.rsat.eu/. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Ultra-low threshold polariton condensation

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

Steger, Mark; Fluegel, Brian; Alberi, Kirstin

Here, we demonstrate the condensation of microcavity polaritons with a very sharp threshold occurring at a two orders of magnitude pump intensity lower than previous demonstrations of condensation. The long cavity lifetime and trapping and pumping geometries are crucial to the realization of this low threshold. Polariton condensation, or 'polariton lasing' has long been proposed as a promising source of coherent light at a lower threshold than traditional lasing, and these results indicate some considerations for optimizing designs for lower thresholds.

Ultra-low threshold polariton condensation

DOE PAGES

Steger, Mark; Fluegel, Brian; Alberi, Kirstin; ...

2017-03-13

Here, we demonstrate the condensation of microcavity polaritons with a very sharp threshold occurring at a two orders of magnitude pump intensity lower than previous demonstrations of condensation. The long cavity lifetime and trapping and pumping geometries are crucial to the realization of this low threshold. Polariton condensation, or 'polariton lasing' has long been proposed as a promising source of coherent light at a lower threshold than traditional lasing, and these results indicate some considerations for optimizing designs for lower thresholds.

Dietary Supplements: Regulatory Challenges and Research Resources.

PubMed

Dwyer, Johanna T; Coates, Paul M; Smith, Michael J

2018-01-04

Many of the scientific and regulatory challenges that exist in research on the safety, quality and efficacy of dietary supplements are common to all countries as the marketplace for them becomes increasingly global. This article summarizes some of the challenges in supplement science and provides a case study of research at the Office of Dietary Supplements at the National Institutes of Health, USA, along with some resources it has developed that are available to all scientists. It includes examples of some of the regulatory challenges faced and some resources for those who wish to learn more about them.

Dietary Supplements: Regulatory Challenges and Research Resources

PubMed Central

Dwyer, Johanna T.; Coates, Paul M.; Smith, Michael J.

2018-01-01

Many of the scientific and regulatory challenges that exist in research on the safety, quality and efficacy of dietary supplements are common to all countries as the marketplace for them becomes increasingly global. This article summarizes some of the challenges in supplement science and provides a case study of research at the Office of Dietary Supplements at the National Institutes of Health, USA, along with some resources it has developed that are available to all scientists. It includes examples of some of the regulatory challenges faced and some resources for those who wish to learn more about them. PMID:29300341

Science in the regulatory setting: a challenging but incompatible mix?

PubMed

Yetley, Elizabeth A

2007-01-01

Regulatory decisions informed by sound science have an important role in many regulatory applications involving drugs and foods, including applications related to dietary supplements. However, science is only one of many factors that must be taken into account in the regulatory decision-making process. In many cases, the scientific input to a regulatory decision must compete with other factors (e.g. economics, legal requirements, stakeholder interests) for impact on the resultant policy decision. Therefore, timely and effective articulation of the available science to support a regulatory decision can significantly affect the relative weight given to science. However, the incorporation of science into the regulatory process for dietary supplements is often fraught with challenges. The available scientific evidence has rarely been designed for the purpose of addressing regulatory questions and is often preliminary and of widely varying scientific quality. To add to the confusion, the same scientific evidence may result in what appears to be different regulatory decisions because the context in which the science is used differs. The underlying assumption is that scientists who have a basic understanding of the interface between science and policy decisions can more effectively provide scientific input into these decisions.

Air Quality and Heart Health: Managing an Emerging ...

EPA Pesticide Factsheets

Dr. Cascio will share with a broad range of federal agencies current understanding of the links between air quality and cardiovascular health. The key facts include that air pollution contributes a high attributable health burden. That certain well-defined vulnerable subpopulations are at higher risk. At-risk populations include those with heart disease, lung disease and diabetes, older adults, children and individuals living in low socioeconomic neighborhoods. There is no established threshold level for safe long-term exposure to air particle pollution, and some of the basic biological mechanisms that account for adverse health effects are now known. This knowledge is giving us insight into how we might mitigate the effects apart from the regulatory efforts to improve overall air quality. Moreover, the work that each State has done to improve air quality has resulted in improved health outcomes including cardiovascular outcomes, and longer lives. The presentation will address: 1) What do we know? 2) Who are the at-risk populations? 3) What can communities do to reduce risk? 4) What can healthcare professionals do to reduce risk of the at-risk population? And 5) What tools are available to help healthcare professionals and their patients reduce exposure and risk from air pollutants? The talk will feature a description of the Air Quality Index and associated EPA tools and health information that can be used by health care providers to educate their at-ris

Extracellular voltage threshold settings can be tuned for optimal encoding of movement and stimulus parameters

NASA Astrophysics Data System (ADS)

Oby, Emily R.; Perel, Sagi; Sadtler, Patrick T.; Ruff, Douglas A.; Mischel, Jessica L.; Montez, David F.; Cohen, Marlene R.; Batista, Aaron P.; Chase, Steven M.

2016-06-01

Objective. A traditional goal of neural recording with extracellular electrodes is to isolate action potential waveforms of an individual neuron. Recently, in brain-computer interfaces (BCIs), it has been recognized that threshold crossing events of the voltage waveform also convey rich information. To date, the threshold for detecting threshold crossings has been selected to preserve single-neuron isolation. However, the optimal threshold for single-neuron identification is not necessarily the optimal threshold for information extraction. Here we introduce a procedure to determine the best threshold for extracting information from extracellular recordings. We apply this procedure in two distinct contexts: the encoding of kinematic parameters from neural activity in primary motor cortex (M1), and visual stimulus parameters from neural activity in primary visual cortex (V1). Approach. We record extracellularly from multi-electrode arrays implanted in M1 or V1 in monkeys. Then, we systematically sweep the voltage detection threshold and quantify the information conveyed by the corresponding threshold crossings. Main Results. The optimal threshold depends on the desired information. In M1, velocity is optimally encoded at higher thresholds than speed; in both cases the optimal thresholds are lower than are typically used in BCI applications. In V1, information about the orientation of a visual stimulus is optimally encoded at higher thresholds than is visual contrast. A conceptual model explains these results as a consequence of cortical topography. Significance. How neural signals are processed impacts the information that can be extracted from them. Both the type and quality of information contained in threshold crossings depend on the threshold setting. There is more information available in these signals than is typically extracted. Adjusting the detection threshold to the parameter of interest in a BCI context should improve our ability to decode motor intent

Extracellular voltage threshold settings can be tuned for optimal encoding of movement and stimulus parameters

PubMed Central

Oby, Emily R; Perel, Sagi; Sadtler, Patrick T; Ruff, Douglas A; Mischel, Jessica L; Montez, David F; Cohen, Marlene R; Batista, Aaron P; Chase, Steven M

2018-01-01

Objective A traditional goal of neural recording with extracellular electrodes is to isolate action potential waveforms of an individual neuron. Recently, in brain–computer interfaces (BCIs), it has been recognized that threshold crossing events of the voltage waveform also convey rich information. To date, the threshold for detecting threshold crossings has been selected to preserve single-neuron isolation. However, the optimal threshold for single-neuron identification is not necessarily the optimal threshold for information extraction. Here we introduce a procedure to determine the best threshold for extracting information from extracellular recordings. We apply this procedure in two distinct contexts: the encoding of kinematic parameters from neural activity in primary motor cortex (M1), and visual stimulus parameters from neural activity in primary visual cortex (V1). Approach We record extracellularly from multi-electrode arrays implanted in M1 or V1 in monkeys. Then, we systematically sweep the voltage detection threshold and quantify the information conveyed by the corresponding threshold crossings. Main Results The optimal threshold depends on the desired information. In M1, velocity is optimally encoded at higher thresholds than speed; in both cases the optimal thresholds are lower than are typically used in BCI applications. In V1, information about the orientation of a visual stimulus is optimally encoded at higher thresholds than is visual contrast. A conceptual model explains these results as a consequence of cortical topography. Significance How neural signals are processed impacts the information that can be extracted from them. Both the type and quality of information contained in threshold crossings depend on the threshold setting. There is more information available in these signals than is typically extracted. Adjusting the detection threshold to the parameter of interest in a BCI context should improve our ability to decode motor intent, and

Extracellular voltage threshold settings can be tuned for optimal encoding of movement and stimulus parameters.

PubMed

Oby, Emily R; Perel, Sagi; Sadtler, Patrick T; Ruff, Douglas A; Mischel, Jessica L; Montez, David F; Cohen, Marlene R; Batista, Aaron P; Chase, Steven M

2016-06-01

A traditional goal of neural recording with extracellular electrodes is to isolate action potential waveforms of an individual neuron. Recently, in brain-computer interfaces (BCIs), it has been recognized that threshold crossing events of the voltage waveform also convey rich information. To date, the threshold for detecting threshold crossings has been selected to preserve single-neuron isolation. However, the optimal threshold for single-neuron identification is not necessarily the optimal threshold for information extraction. Here we introduce a procedure to determine the best threshold for extracting information from extracellular recordings. We apply this procedure in two distinct contexts: the encoding of kinematic parameters from neural activity in primary motor cortex (M1), and visual stimulus parameters from neural activity in primary visual cortex (V1). We record extracellularly from multi-electrode arrays implanted in M1 or V1 in monkeys. Then, we systematically sweep the voltage detection threshold and quantify the information conveyed by the corresponding threshold crossings. The optimal threshold depends on the desired information. In M1, velocity is optimally encoded at higher thresholds than speed; in both cases the optimal thresholds are lower than are typically used in BCI applications. In V1, information about the orientation of a visual stimulus is optimally encoded at higher thresholds than is visual contrast. A conceptual model explains these results as a consequence of cortical topography. How neural signals are processed impacts the information that can be extracted from them. Both the type and quality of information contained in threshold crossings depend on the threshold setting. There is more information available in these signals than is typically extracted. Adjusting the detection threshold to the parameter of interest in a BCI context should improve our ability to decode motor intent, and thus enhance BCI control. Further, by sweeping

Assurance of Medical Device Quality with Quality Management System: An Analysis of Good Manufacturing Practice Implementation in Taiwan

PubMed Central

Tu, Pei-Weng; Wu, Shiow-Ing

2015-01-01

The implementation of an effective quality management system has always been considered a principal method for a manufacturer to maintain and improve its product and service quality. Globally many regulatory authorities incorporate quality management system as one of the mandatory requirements for the regulatory control of high-risk medical devices. The present study aims to analyze the GMP enforcement experience in Taiwan between 1998 and 2013. It describes the regulatory implementation of medical device GMP requirement and initiatives taken to assist small and medium-sized enterprises in compliance with the regulatory requirement. Based on statistical data collected by the competent authority and industry research institutes, the present paper reports the growth of Taiwan local medical device industry after the enforcement of GMP regulation. Transition in the production, technologies, and number of employees of Taiwan medical device industry between 1998 and 2013 provides the competent authorities around the world with an empirical foundation for further policy development. PMID:26075255

Assurance of medical device quality with quality management system: an analysis of good manufacturing practice implementation in Taiwan.

PubMed

Li, Tzu-Wei; Tu, Pei-Weng; Liu, Li-Ling; Wu, Shiow-Ing

2015-01-01

The implementation of an effective quality management system has always been considered a principal method for a manufacturer to maintain and improve its product and service quality. Globally many regulatory authorities incorporate quality management system as one of the mandatory requirements for the regulatory control of high-risk medical devices. The present study aims to analyze the GMP enforcement experience in Taiwan between 1998 and 2013. It describes the regulatory implementation of medical device GMP requirement and initiatives taken to assist small and medium-sized enterprises in compliance with the regulatory requirement. Based on statistical data collected by the competent authority and industry research institutes, the present paper reports the growth of Taiwan local medical device industry after the enforcement of GMP regulation. Transition in the production, technologies, and number of employees of Taiwan medical device industry between 1998 and 2013 provides the competent authorities around the world with an empirical foundation for further policy development.

Threshold Evolution as an Analysis of the Different Pulse Frequencies in Rechargeable Systems for Spinal Cord Stimulation.

PubMed

Abejón, David; Rueda, Pablo; Vallejo, Ricardo

2016-04-01

Pulse frequency (Fc) is one of the most important parameters in neurostimulation, with Pulse Amplitude (Pw) and Amplitude (I). Up to certain Fc, increasing the number of pulses will generate action potentials in neighboring neural structures and may facilitate deeper penetration of the electromagnetic fields. In addition, changes in frequency modify the patient's sensation with stimulation. Fifty patients previously implanted with rechargeable current control spinal cord stimulation. With pulse width fixed at 300 μsec, we stimulated at 26 different Fc values between 40 and 1200 Hz and determine the influence of these changes on different stimulation thresholds: perception threshold (Tp ), therapeutic perception (Tt), and discomfort threshold (Td). Simultaneously, paresthesia coverage of the painful area and patient's sensation and satisfaction related to the quality of stimulation were recorded. Pulse Fc is inversely proportional to stimulation thresholds and this influence is statistically significant (p < 0.05). As Pulse Fc increased from 40 to 1200 Hz, the mean threshold decreases from 7.25 to 1.38 mA (Tp ), 8.17 to 1.63 (Tt ), and 9.20 to 1.85 (Td). Significant differences for Tp and Tt began at 750 Hz (Tp , Tt ) and at 650 Hz for Td. No significant influence was found regarding paresthesia coverage. As expected, Fc affects significantly patient's sensation and satisfaction. Changes in Fc affect the quality of paresthesias. Within the evaluated parameters higher frequencies are inversely proportional to stimulation thresholds and Tt. It seems that Fc is a vital parameter to achieve therapeutic success. Changes in Fc is a useful parameter to modulate the patient's sensory perception. Fc can be successfully used to adjust the quality of the paresthesias and to modify patient's subjective sensation. We showed that as the frequency increases, the patient's satisfaction with the perceived sensation decreases, suggesting that higher Fc may need to be set up at

On what basis are medical cost-effectiveness thresholds set? Clashing opinions and an absence of data: a systematic review.

PubMed

Cameron, David; Ubels, Jasper; Norström, Fredrik

2018-01-01

The amount a government should be willing to invest in adopting new medical treatments has long been under debate. With many countries using formal cost-effectiveness (C/E) thresholds when examining potential new treatments and ever-growing medical costs, accurately setting the level of a C/E threshold can be essential for an efficient healthcare system. The aim of this systematic review is to describe the prominent approaches to setting a C/E threshold, compile available national-level C/E threshold data and willingness-to-pay (WTP) data, and to discern whether associations exist between these values, gross domestic product (GDP) and health-adjusted life expectancy (HALE). This review further examines current obstacles faced with the presently available data. A systematic review was performed to collect articles which have studied national C/E thresholds and willingness-to-pay (WTP) per quality-adjusted life year (QALY) in the general population. Associations between GDP, HALE, WTP, and C/E thresholds were analyzed with correlations. Seventeen countries were identified from nine unique sources to have formal C/E thresholds within our inclusion criteria. Thirteen countries from nine sources were identified to have WTP per QALY data within our inclusion criteria. Two possible associations were identified: C/E thresholds with HALE (quadratic correlation of 0.63), and C/E thresholds with GDP per capita (polynomial correlation of 0.84). However, these results are based on few observations and therefore firm conclusions cannot be made. Most national C/E thresholds identified in our review fall within the WHO's recommended range of one-to-three times GDP per capita. However, the quality and quantity of data available regarding national average WTP per QALY, opportunity costs, and C/E thresholds is poor in comparison to the importance of adequate investment in healthcare. There exists an obvious risk that countries might either over- or underinvest in healthcare if they

Quantifying ecological thresholds from response surfaces

Treesearch

Heather E. Lintz; Bruce McCune; Andrew N. Gray; Katherine A. McCulloh

2011-01-01

Ecological thresholds are abrupt changes of ecological state. While an ecological threshold is a widely accepted concept, most empirical methods detect them in time or across geographic space. Although useful, these approaches do not quantify the direct drivers of threshold response. Causal understanding of thresholds detected empirically requires their investigation...

Bayesian estimation of dose thresholds

NASA Technical Reports Server (NTRS)

Groer, P. G.; Carnes, B. A.

2003-01-01

An example is described of Bayesian estimation of radiation absorbed dose thresholds (subsequently simply referred to as dose thresholds) using a specific parametric model applied to a data set on mice exposed to 60Co gamma rays and fission neutrons. A Weibull based relative risk model with a dose threshold parameter was used to analyse, as an example, lung cancer mortality and determine the posterior density for the threshold dose after single exposures to 60Co gamma rays or fission neutrons from the JANUS reactor at Argonne National Laboratory. The data consisted of survival, censoring times and cause of death information for male B6CF1 unexposed and exposed mice. The 60Co gamma whole-body doses for the two exposed groups were 0.86 and 1.37 Gy. The neutron whole-body doses were 0.19 and 0.38 Gy. Marginal posterior densities for the dose thresholds for neutron and gamma radiation were calculated with numerical integration and found to have quite different shapes. The density of the threshold for 60Co is unimodal with a mode at about 0.50 Gy. The threshold density for fission neutrons declines monotonically from a maximum value at zero with increasing doses. The posterior densities for all other parameters were similar for the two radiation types.

Facing regulatory challenges of on-line hemodiafiltration.

PubMed

Kümmerle, Wolfgang

2011-01-01

On-line hemodiafiltration (on-line HDF) is the result of a vision that triggered multifarious changes in very different areas. Driven by the idea to offer better medical treatment for renal patients, technological innovations were developed and established that also constituted new challenges in the field of regulatory affairs. The existing regulations predominantly addressed the quality and safety of those products needed to perform dialysis treatment which were supplied by industrial manufacturers. However, the complexity of treatment system required for the provision of on-line fluids demanded a holistic approach encompassing all components involved. Hence, focus was placed not only on single products, but much more on their interfacing, and the clinical infrastructure, in particular, had to undergo substantial changes. The overall understanding of the interaction between such factors, quite different in their nature, was crucial to overcome the arising regulatory obstacles. This essay describes the evolution of the on-line HDF procedure from the regulatory point of view. A simplified diagram demonstrates the path taken from the former regulatory understanding to the realization of necessary changes. That achievement was only possible through 'management of preview' and consequent promotion of technical and medical innovations as well as regulatory re-evaluations. Copyright © 2011 S. Karger AG, Basel.

Assessing the role of regulatory bodies in managing health professional issues and errors in Europe.

PubMed

Risso-Gill, Isabelle; Legido-Quigley, H; Panteli, D; Mckee, M

2014-08-01

This paper explores how medical regulatory bodies in nine European countries manage professional issues involving quality and patient safety, to build on limited existing information on procedures for regulating medical professionals in Europe. Twelve vignettes describing scenarios of concerns about standards of physicians were developed, covering clinical, criminal and administrative matters. Medical regulatory bodies in nine European countries were asked what action they would normally take in each situation. Their responses were related to their regulatory mandate. Responses varied greatly across participating countries. Regulators are always involved where patients are at risk or where a criminal offence is committed within the clinical setting. Non-criminal medical issues were generally handled by the employer, if any, at their discretion. Countries varied in the use of punitive measures, the extent to which they took an interest in issues arising outside professional activities, and whether they dealt with issues themselves or referred cases to another regulatory authority or took no action at all. There is little consistency across Europe on the regulation of medical professionals. There is considerable diversity in the range of topics that regulatory bodies oversee, with almost all covering health care quality and safety and others encompassing issues related to reputation, respect and trust. These inconsistencies have significant implications for professional mobility, patient safety and quality of care. © The Author 2014. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

77 FR 25872 - Oklahoma Regulatory Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-02

... air or water quality standards issued under the authority of the Clean Water Act (33 U.S.C. 1251 et seq.) or the Clean Air Act (42 U.S.C. 7401 et seq.). None of the revisions that Oklahoma proposed to... regulatory program under the Surface Mining Control and Reclamation Act of 1977 (SMCRA or the Act). Oklahoma...

Quality considerations of paediatric investigation plans for monoclonal antibodies: A regulatory perspective from the MHRA.

PubMed

Hussain, Nasir; Siapkara, Angeliki; Branch, Sarah

2015-08-15

Since the advent of the EU Paediatric Regulation in 2007, 78 of the 1688 Paediatric Investigation Plans (PIPs) have been for monoclonal antibodies (Mabs). Of these, 22 have been assessed by the MHRA. The purpose of this mini-review is to aid those researching and developing this class of drugs to better understand regulatory concerns leading to improved medicinal products for children. Three principal quality issues were identified for PIPs under Article 7 and 8: i) the level of anti-aggregation stabilisers, ii) acceptability and tolerability of administration (i.e. multiple injections, infusion time and volume), and iii) the need to develop new presentational forms (e.g. pre-filled syringe). Overall, two types of concerns were ascertained - those which are potentially avoidable (e.g. through development of new presentational forms) and others which require the evolution of new technologies in the sector (e.g. production of concentrated, stabilised preparations). Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Face verification with balanced thresholds.

PubMed

Yan, Shuicheng; Xu, Dong; Tang, Xiaoou

2007-01-01

The process of face verification is guided by a pre-learned global threshold, which, however, is often inconsistent with class-specific optimal thresholds. It is, hence, beneficial to pursue a balance of the class-specific thresholds in the model-learning stage. In this paper, we present a new dimensionality reduction algorithm tailored to the verification task that ensures threshold balance. This is achieved by the following aspects. First, feasibility is guaranteed by employing an affine transformation matrix, instead of the conventional projection matrix, for dimensionality reduction, and, hence, we call the proposed algorithm threshold balanced transformation (TBT). Then, the affine transformation matrix, constrained as the product of an orthogonal matrix and a diagonal matrix, is optimized to improve the threshold balance and classification capability in an iterative manner. Unlike most algorithms for face verification which are directly transplanted from face identification literature, TBT is specifically designed for face verification and clarifies the intrinsic distinction between these two tasks. Experiments on three benchmark face databases demonstrate that TBT significantly outperforms the state-of-the-art subspace techniques for face verification.

FUNDAMENTALS OF THRESHOLD LOGIC.

DTIC Science & Technology

These notes on threshold logic are intended as intermediary material between a completely geometric, heuristic presentation and the more formal...source material available in the literature. Basic definitions and simple properties of threshold function are developed, followed by a complete treatment

Predictive performance of rainfall thresholds for shallow landslides in Switzerland from gridded daily data

NASA Astrophysics Data System (ADS)

Leonarduzzi, Elena; Molnar, Peter; McArdell, Brian W.

2017-08-01

A high-resolution gridded daily precipitation data set was combined with a landslide inventory containing over 2000 events in the period 1972-2012 to analyze rainfall thresholds which lead to landsliding in Switzerland. We colocated triggering rainfall to landslides, developed distributions of triggering and nontriggering rainfall event properties, and determined rainfall thresholds and intensity-duration ID curves and validated their performance. The best predictive performance was obtained by the intensity-duration ID threshold curve, followed by peak daily intensity Imax and mean event intensity Imean. Event duration by itself had very low predictive power. A single country-wide threshold of Imax = 28 mm/d was extended into space by regionalization based on surface erodibility and local climate (mean daily precipitation). It was found that wetter local climate and lower erodibility led to significantly higher rainfall thresholds required to trigger landslides. However, we showed that the improvement in model performance due to regionalization was marginal and much lower than what can be achieved by having a high-quality landslide database. Reference cases in which the landslide locations and timing were randomized and the landslide sample size was reduced showed the sensitivity of the Imax rainfall threshold model. Jack-knife and cross-validation experiments demonstrated that the model was robust. The results reported here highlight the potential of using rainfall ID threshold curves and rainfall threshold values for predicting the occurrence of landslides on a country or regional scale with possible applications in landslide warning systems, even with daily data.

Detection and Modeling of High-Dimensional Thresholds for Fault Detection and Diagnosis

NASA Technical Reports Server (NTRS)

He, Yuning

2015-01-01

Many Fault Detection and Diagnosis (FDD) systems use discrete models for detection and reasoning. To obtain categorical values like oil pressure too high, analog sensor values need to be discretized using a suitablethreshold. Time series of analog and discrete sensor readings are processed and discretized as they come in. This task isusually performed by the wrapper code'' of the FDD system, together with signal preprocessing and filtering. In practice,selecting the right threshold is very difficult, because it heavily influences the quality of diagnosis. If a threshold causesthe alarm trigger even in nominal situations, false alarms will be the consequence. On the other hand, if threshold settingdoes not trigger in case of an off-nominal condition, important alarms might be missed, potentially causing hazardoussituations. In this paper, we will in detail describe the underlying statistical modeling techniques and algorithm as well as the Bayesian method for selecting the most likely shape and its parameters. Our approach will be illustrated by several examples from the Aerospace domain.

2 CFR 200.88 - Simplified acquisition threshold.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 2 Grants and Agreements 1 2014-01-01 2014-01-01 false Simplified acquisition threshold. 200.88... acquisition threshold. Simplified acquisition threshold means the dollar amount below which a non-Federal... threshold. The simplified acquisition threshold is set by the Federal Acquisition Regulation at 48 CFR...

Laboratory Rodent Diets Contain Toxic Levels of Environmental Contaminants: Implications for Regulatory Tests

PubMed Central

Rocque, Louis-Marie; Spiroux de Vendômois, Joël; Séralini, Gilles-Eric

2015-01-01

The quality of diets in rodent feeding trials is crucial. We describe the contamination with environmental pollutants of 13 laboratory rodent diets from 5 continents. Measurements were performed using accredited methodologies. All diets were contaminated with pesticides (1-6 out of 262 measured), heavy metals (2-3 out of 4, mostly lead and cadmium), PCDD/Fs (1-13 out of 17) and PCBs (5-15 out of 18). Out of 22 GMOs tested for, Roundup-tolerant GMOs were the most frequently detected, constituting up to 48% of the diet. The main pesticide detected was Roundup, with residues of glyphosate and AMPA in 9 of the 13 diets, up to 370 ppb. The levels correlated with the amount of Roundup-tolerant GMOs. Toxic effects of these pollutants on liver, neurodevelopment, and reproduction are documented. The sum of the hazard quotients of the pollutants in the diets (an estimator of risk with a threshold of 1) varied from 15.8 to 40.5. Thus the chronic consumption of these diets can be considered at risk. Efforts toward safer diets will improve the reliability of toxicity tests in biomedical research and regulatory toxicology. PMID:26133768

Is ``No-Threshold'' a ``Non-Concept''?

NASA Astrophysics Data System (ADS)

Schaeffer, David J.

1981-11-01

A controversy prominent in scientific literature that has carried over to newspapers, magazines, and popular books is having serious social and political expressions today: “Is there, or is there not, a threshold below which exposure to a carcinogen will not induce cancer?” The distinction between establishing the existence of this threshold (which is a theoretical question) and its value (which is an experimental one) gets lost in the scientific arguments. Establishing the existence of this threshold has now become a philosophical question (and an emotional one). In this paper I qualitatively outline theoretical reasons why a threshold must exist, discuss experiments which measure thresholds on two chemicals, and describe and apply a statistical method for estimating the threshold value from exposure-response data.

Double Photoionization Near Threshold

NASA Technical Reports Server (NTRS)

Wehlitz, Ralf

2007-01-01

The threshold region of the double-photoionization cross section is of particular interest because both ejected electrons move slowly in the Coulomb field of the residual ion. Near threshold both electrons have time to interact with each other and with the residual ion. Also, different theoretical models compete to describe the double-photoionization cross section in the threshold region. We have investigated that cross section for lithium and beryllium and have analyzed our data with respect to the latest results in the Coulomb-dipole theory. We find that our data support the idea of a Coulomb-dipole interaction.

Comparison of Erosion Rates Estimated by Sediment Budget Techniques and Suspended Sediment Monitoring and Regulatory Implications

NASA Astrophysics Data System (ADS)

O'Connor, M.; Eads, R.

2007-12-01

Watersheds in the northern California Coast Range have been designated as "impaired" with respect to water quality because of excessive sediment loads and/or high water temperature. Sediment budget techniques have typically been used by regulatory authorities to estimate current erosion rates and to develop targets for future desired erosion rates. This study examines erosion rates estimated by various methods for portions of the Gualala River watershed, designated as having water quality impaired by sediment under provisions of the Clean Water Act Section 303(d), located in northwest Sonoma County (~90 miles north of San Francisco). The watershed is underlain by Jurassic age sedimentary and meta-sedimentary rocks of the Franciscan formation. The San Andreas Fault passes through the western edge of watershed, and other active faults are present. A substantial portion of the watershed is mantled by rock slides and earth flows, many of which are considered dormant. The Coast Range is geologically young, and rapid rates of uplift are believed to have contributed to high erosion rates. This study compares quantitative erosion rate estimates developed at different spatial and temporal scales. It is motivated by a proposed vineyard development project in the watershed, and the need to document conditions in the project area, assess project environmental impacts and meet regulatory requirements pertaining to water quality. Erosion rate estimates were previously developed using sediment budget techniques for relatively large drainage areas (~100 to 1,000 km2) by the North Coast Regional Water Quality Control Board and US EPA and by the California Geological Survey. In this study, similar sediment budget techniques were used for smaller watersheds (~3 to 8 km2), and were supplemented by a suspended sediment monitoring program utilizing Turbidity Threshold Sampling techniques (as described in a companion study in this session). The duration of the monitoring program to date

Managing quality and compliance.

PubMed

McNeil, Alice; Koppel, Carl

2015-01-01

Critical care nurses assume vital roles in maintaining patient care quality. There are distinct facets to the process including standard setting, regulatory compliance, and completion of reports associated with these endeavors. Typically, multiple niche software applications are required and user interfaces are varied and complex. Although there are distinct quality indicators that must be tracked as well as a list of serious or sentinel events that must be documented and reported, nurses may not know the precise steps to ensure that information is properly documented and actually reaches the proper authorities for further investigation and follow-up actions. Technology advances have permitted the evolution of a singular software platform, capable of monitoring quality indicators and managing all facets of reporting associated with regulatory compliance.

Ground-Water Quality Data in the Central Eastside San Joaquin Basin 2006: Results from the California GAMA Program

USGS Publications Warehouse

Landon, Matthew K.; Belitz, Kenneth

2008-01-01

for approximately one-sixth of the wells, and the results for these samples were used to evaluate the quality of the data for the ground-water samples. Assessment of the quality-control results showed that the environmental data were of good quality, with low bias and low variability, and resulted in censoring of less than 0.3 percent of the detections found in ground-water samples. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CADPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CADPH. VOCs and pesticides were detected in approximately half of the grid wells, and all detections in samples from CESJO wells were below health-based thresholds. All detections of nutrients and major elements in grid wells also were below health-based thresholds. Most detections of constituents of special interest, trace elements, and radioactive constituents in samples from grid wells were below health-based thresholds. Exceptions included two detections of arsenic that were above the USEPA maximum contaminant level (MCL-US), one detection of lead above the USEPA action level (AL-US), and one detection of vanadium and three detections of 1,2,3-TCP that were above the CADPH notification levels (NL-CA). All detections of radioactive constituents were below health-based thresholds, although fourteen samples had activities of radon-222 above the lower proposed MCL-US. Most of th

NETWORK SYNTHESIS OF CASCADED THRESHOLD ELEMENTS.

DTIC Science & Technology

A threshold function is a switching function which can be stimulated by a single, simplified, idealized neuron, or threshold element. In this report... threshold functions are examined in the context of abstract set theory and linear algebra for the purpose of obtaining practical synthesis procedures...for networks of threshold elements. A procedure is described by which, for any given switching function, a cascade network of these elements can be

STIMULUS AND TRANSDUCER EFFECTS ON THRESHOLD

PubMed Central

Flamme, Gregory A.; Geda, Kyle; McGregor, Kara; Wyllys, Krista; Deiters, Kristy K.; Murphy, William J.; Stephenson, Mark R.

2015-01-01

Objective This study examined differences in thresholds obtained under Sennheiser HDA200 circumaural earphones using pure tone, equivalent rectangular noise bands, and 1/3 octave noise bands relative to thresholds obtained using Telephonics TDH-39P supra-aural earphones. Design Thresholds were obtained via each transducer and stimulus condition six times within a 10-day period. Study Sample Forty-nine adults were selected from a prior study to represent low, moderate, and high threshold reliability. Results The results suggested that (1) only small adjustments were needed to reach equivalent TDH-39P thresholds, (2) pure-tone thresholds obtained with HDA200 circumaural earphones had reliability equal to or better than those obtained using TDH-39P earphones, (3) the reliability of noise-band thresholds improved with broader stimulus bandwidth and was either equal to or better than pure-tone thresholds, and (4) frequency-specificity declined with stimulus bandwidths greater than one Equivalent Rectangular Band, which could complicate early detection of hearing changes that occur within a narrow frequency range. Conclusions These data suggest that circumaural earphones such as the HDA200 headphones provide better reliability for audiometric testing as compared to the TDH-39P earphones. These data support the use of noise bands, preferably ERB noises, as stimuli for audiometric monitoring. PMID:25549164

Pausing at the Threshold

ERIC Educational Resources Information Center

Morgan, Patrick K.

2015-01-01

Since about 2003, the notion of threshold concepts--the central ideas in any field that change how learners think about other ideas--have become difficult to escape at library conferences and in general information literacy discourse. Their visibility will likely only increase because threshold concepts figure prominently in the Framework for…

Prospective Evaluation of Patient Usage of Above and Below Threshold Waveforms With Traditional Spinal Cord Stimulation Devices.

PubMed

Owusu, Stephanie; Huynh, Alexander; Gruenthal, Eric; Prusik, Julia; Owusu-Sarpong, Stephane; Cherala, Rasan; Peng, Sophia; Pilitsis, Julie G; McCallum, Sarah E

2017-08-01

Spinal cord stimulation (SCS) is an efficacious therapy used to treat chronic pain. The type of SCS programming is important in improving patients' quality of life and overall satisfaction. In this study, 19 patients who underwent SCS with traditional devices were given between 4 and 6 programs including programs with stimulation below sensory threshold and above sensory threshold. Usage patterns and preferences were assessed. SCS patients were given 4-6 programs, some above sensory threshold and some below threshold immediately postoperatively after permanent implantation. Usage patterns of different programs were documented, including percent of time that the settings were used and preference for above threshold vs. below threshold settings during sleeping, walking, sitting, and vigorous activity. Improvements at three months in Oswestry disability index (ODI), numeric rating scale (NRS), Beck depression inventory (BDI), McGill pain questionnaire (MPQ), pain catastrophizing scale (PCS), insomnia severity index (ISI), and Epworth sleepiness scale (ESS) were evaluated. Patients were all trialed on above sensory threshold programs. Six weeks after implantation, most patients preferred above threshold stimulation (74%) vs. below threshold waveforms (21%). Patient diagnosis, type/location of lead or recharging burden played no role in patient preference. Above threshold patients had significantly better improvement in BDI scores than did below threshold patients (p < 0.05) at three-month follow-up but also had worse ESS scores (p < 0.05). Above threshold stimulation was preferred for walking and sitting (p < 0.05). Results indicate that when given the option between waveforms inducing paresthesias and those that do not, SCS patients tend to prefer waveforms that induce paresthesias. Among users of above threshold waveforms, there was preference for these settings during walking and sitting. There was a trend for below threshold preference in vigorous

A Continuous Threshold Expectile Model.

PubMed

Zhang, Feipeng; Li, Qunhua

2017-12-01

Expectile regression is a useful tool for exploring the relation between the response and the explanatory variables beyond the conditional mean. A continuous threshold expectile regression is developed for modeling data in which the effect of a covariate on the response variable is linear but varies below and above an unknown threshold in a continuous way. The estimators for the threshold and the regression coefficients are obtained using a grid search approach. The asymptotic properties for all the estimators are derived, and the estimator for the threshold is shown to achieve root-n consistency. A weighted CUSUM type test statistic is proposed for the existence of a threshold at a given expectile, and its asymptotic properties are derived under both the null and the local alternative models. This test only requires fitting the model under the null hypothesis in the absence of a threshold, thus it is computationally more efficient than the likelihood-ratio type tests. Simulation studies show that the proposed estimators and test have desirable finite sample performance in both homoscedastic and heteroscedastic cases. The application of the proposed method on a Dutch growth data and a baseball pitcher salary data reveals interesting insights. The proposed method is implemented in the R package cthreshER .

On what basis are medical cost-effectiveness thresholds set? Clashing opinions and an absence of data: a systematic review

PubMed Central

Cameron, David; Ubels, Jasper; Norström, Fredrik

2018-01-01

ABSTRACT Background: The amount a government should be willing to invest in adopting new medical treatments has long been under debate. With many countries using formal cost-effectiveness (C/E) thresholds when examining potential new treatments and ever-growing medical costs, accurately setting the level of a C/E threshold can be essential for an efficient healthcare system. Objectives: The aim of this systematic review is to describe the prominent approaches to setting a C/E threshold, compile available national-level C/E threshold data and willingness-to-pay (WTP) data, and to discern whether associations exist between these values, gross domestic product (GDP) and health-adjusted life expectancy (HALE). This review further examines current obstacles faced with the presently available data. Methods: A systematic review was performed to collect articles which have studied national C/E thresholds and willingness-to-pay (WTP) per quality-adjusted life year (QALY) in the general population. Associations between GDP, HALE, WTP, and C/E thresholds were analyzed with correlations. Results: Seventeen countries were identified from nine unique sources to have formal C/E thresholds within our inclusion criteria. Thirteen countries from nine sources were identified to have WTP per QALY data within our inclusion criteria. Two possible associations were identified: C/E thresholds with HALE (quadratic correlation of 0.63), and C/E thresholds with GDP per capita (polynomial correlation of 0.84). However, these results are based on few observations and therefore firm conclusions cannot be made. Conclusions: Most national C/E thresholds identified in our review fall within the WHO’s recommended range of one-to-three times GDP per capita. However, the quality and quantity of data available regarding national average WTP per QALY, opportunity costs, and C/E thresholds is poor in comparison to the importance of adequate investment in healthcare. There exists an obvious risk that

Analytical Chemistry in the Regulatory Science of Medical Devices.

PubMed

Wang, Yi; Guan, Allan; Wickramasekara, Samanthi; Phillips, K Scott

2018-06-12

In the United States, regulatory science is the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all Food and Drug Administration-regulated products. Good regulatory science facilitates consumer access to innovative medical devices that are safe and effective throughout the Total Product Life Cycle (TPLC). Because the need to measure things is fundamental to the regulatory science of medical devices, analytical chemistry plays an important role, contributing to medical device technology in two ways: It can be an integral part of an innovative medical device (e.g., diagnostic devices), and it can be used to support medical device development throughout the TPLC. In this review, we focus on analytical chemistry as a tool for the regulatory science of medical devices. We highlight recent progress in companion diagnostics, medical devices on chips for preclinical testing, mass spectrometry for postmarket monitoring, and detection/characterization of bacterial biofilm to prevent infections.

[Threshold value for reimbursement of costs of new drugs: cost-effectiveness research and modelling are essential links].

PubMed

Frederix, Geert W J; Hövels, Anke M; Severens, Johan L; Raaijmakers, Jan A M; Schellens, Jan H M

2015-01-01

There is increasing discussion in the Netherlands about the introduction of a threshold value for the costs per extra year of life when reimbursing costs of new drugs. The Medicines Committee ('Commissie Geneesmiddelen'), a division of the Netherlands National Healthcare Institute ('Zorginstituut Nederland'), advises on reimbursement of costs of new drugs. This advice is based upon the determination of therapeutic value of the drug and the results of economic evaluations. Mathematical models that predict future costs and effectiveness are often used in economic evaluations; these models can vary greatly in transparency and quality due to author assumptions. Standardisation of cost-effectiveness models is one solution to overcome the unwanted variation in quality. Discussions about the introduction of a threshold value can only be meaningful if all involved are adequately informed, and by high quality in cost-effectiveness research and, particularly, economic evaluations. Collaboration and discussion between medical specialists, patients or patient organisations, health economists and policy makers, both in development of methods and in standardisation, are essential to improve the quality of decision making.

LOGIC OF CONTROLLED THRESHOLD DEVICES.

DTIC Science & Technology

The synthesis of threshold logic circuits from several points of view is presented. The first approach is applicable to resistor-transistor networks...in which the outputs are tied to a common collector resistor. In general, fewer threshold logic gates than NOR gates connected to a common collector...network to realize a specified function such that the failure of any but the output gate can be compensated for by a change in the threshold level (and

THRESHOLD LOGIC SYNTHESIS OF SEQUENTIAL MACHINES.

DTIC Science & Technology

The application of threshold logic to the design of sequential machines is the subject of this research. A single layer of threshold logic units in...advantages of fewer components because of the use of threshold logic, along with very high-speed operation resulting from the use of only a single layer of...logic. In some instances, namely for asynchronous machines, the only delay need be the natural delay of the single layer of threshold elements. It is

76 FR 76168 - Regulatory Site Visit Training Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0824... routine manufacturing practices and to give CBER staff a better understanding of the biologics industry... quality of its regulatory efforts and interactions, by providing CBER staff with a better understanding of...

Threshold Concepts in Economics

ERIC Educational Resources Information Center

Shanahan, Martin

2016-01-01

Purpose: The purpose of this paper is to examine threshold concepts in the context of teaching and learning first-year university economics. It outlines some of the arguments for using threshold concepts and provides examples using opportunity cost as an exemplar in economics. Design/ Methodology/Approach: The paper provides an overview of the…

Methods for automatic trigger threshold adjustment

DOEpatents

Welch, Benjamin J; Partridge, Michael E

2014-03-18

Methods are presented for adjusting trigger threshold values to compensate for drift in the quiescent level of a signal monitored for initiating a data recording event, thereby avoiding false triggering conditions. Initial threshold values are periodically adjusted by re-measuring the quiescent signal level, and adjusting the threshold values by an offset computation based upon the measured quiescent signal level drift. Re-computation of the trigger threshold values can be implemented on time based or counter based criteria. Additionally, a qualification width counter can be utilized to implement a requirement that a trigger threshold criterion be met a given number of times prior to initiating a data recording event, further reducing the possibility of a false triggering situation.

Peaks Over Threshold (POT): A methodology for automatic threshold estimation using goodness of fit p-value

NASA Astrophysics Data System (ADS)

Solari, Sebastián.; Egüen, Marta; Polo, María. José; Losada, Miguel A.

2017-04-01

Threshold estimation in the Peaks Over Threshold (POT) method and the impact of the estimation method on the calculation of high return period quantiles and their uncertainty (or confidence intervals) are issues that are still unresolved. In the past, methods based on goodness of fit tests and EDF-statistics have yielded satisfactory results, but their use has not yet been systematized. This paper proposes a methodology for automatic threshold estimation, based on the Anderson-Darling EDF-statistic and goodness of fit test. When combined with bootstrapping techniques, this methodology can be used to quantify both the uncertainty of threshold estimation and its impact on the uncertainty of high return period quantiles. This methodology was applied to several simulated series and to four precipitation/river flow data series. The results obtained confirmed its robustness. For the measured series, the estimated thresholds corresponded to those obtained by nonautomatic methods. Moreover, even though the uncertainty of the threshold estimation was high, this did not have a significant effect on the width of the confidence intervals of high return period quantiles.

Establishing a regulatory value chain model: An innovative approach to strengthening medicines regulatory systems in resource-constrained settings.

PubMed

Chahal, Harinder Singh; Kashfipour, Farrah; Susko, Matt; Feachem, Neelam Sekhri; Boyle, Colin

2016-05-01

Medicines Regulatory Authorities (MRAs) are an essential part of national health systems and are charged with protecting and promoting public health through regulation of medicines. However, MRAs in resource-constrained settings often struggle to provide effective oversight of market entry and use of health commodities. This paper proposes a regulatory value chain model (RVCM) that policymakers and regulators can use as a conceptual framework to guide investments aimed at strengthening regulatory systems. The RVCM incorporates nine core functions of MRAs into five modules: (i) clear guidelines and requirements; (ii) control of clinical trials; (iii) market authorization of medical products; (iv) pre-market quality control; and (v) post-market activities. Application of the RVCM allows national stakeholders to identify and prioritize investments according to where they can add the most value to the regulatory process. Depending on the economy, capacity, and needs of a country, some functions can be elevated to a regional or supranational level, while others can be maintained at the national level. In contrast to a "one size fits all" approach to regulation in which each country manages the full regulatory process at the national level, the RVCM encourages leveraging the expertise and capabilities of other MRAs where shared processes strengthen regulation. This value chain approach provides a framework for policymakers to maximize investment impact while striving to reach the goal of safe, affordable, and rapidly accessible medicines for all.

Development of a novel regulatory pharmacovigilance prioritisation system: an evaluation of its performance at the UK Medicines and Healthcare products Regulatory Agency.

PubMed

Seabroke, Suzie; Wise, Lesley; Waller, Patrick

2013-10-01

The prioritisation of drug safety issues for further evaluation or regulatory action is critical to ensure that acceptable timelines and appropriate resource allocation are defined to meet public health and regulatory obligations. Our objective was to develop, pilot and implement a novel tool for prioritising pharmacovigilance issues within the Medicines and Healthcare products Regulatory Agency (MHRA). An initial system was developed empirically and then piloted over a 10-month period in the pharmacovigilance signal management meeting at the MHRA that discusses potential pharmacovigilance issues, and determines, through consensus, their priority and a timescale for action. The priority assigned by the tool was compared with the priority decided by collective judgement at the meeting. Once an acceptable level of concordance between the tool and the meeting had been achieved, the finalised tool was implemented into routine use at the MHRA, with an evaluation of its performance conducted after the first year. The Regulatory Pharmacovigilance Prioritisation System (RPPS) tool prioritises pharmacovigilance issues according to the following four broad categories, each with four inputs: strength of evidence, public health implications, agency regulatory obligations and public perceptions. A weighted scoring system links the inputs to a pre-defined number of points where if a threshold is reached then the points are awarded. The overall priority is determined by the sum of all points obtained from each of the inputs. The pilot study included a total of 73 pharmacovigilance issues during the 10-month study period, with an overall exact agreement between the RPPS priority and the collective judgement of the meeting of 60.3 %. Where exact agreement was not obtained, the RPPS generally prioritised the issues slightly higher than the meeting. Over the first year following implementation, the RPPS achieved an overall exact agreement of 82.2 %. Following the pilot study and

Trazodone Increases the Respiratory Arousal Threshold in Patients with Obstructive Sleep Apnea and a Low Arousal Threshold

PubMed Central

Eckert, Danny J.; Malhotra, Atul; Wellman, Andrew; White, David P.

2014-01-01

Study Objectives: The effect of common sedatives on upper airway physiology and breathing during sleep in obstructive sleep apnea (OSA) has been minimally studied. Conceptually, certain sedatives may worsen OSA in some patients. However, sleep and breathing could improve with certain sedatives in patients with OSA with a low respiratory arousal threshold. This study aimed to test the hypothesis that trazodone increases the respiratory arousal threshold in patients with OSA and a low arousal threshold. Secondary aims were to examine the effects of trazodone on upper airway dilator muscle activity, upper airway collapsibility, and breathing during sleep. Design: Patients were studied on 4 separate nights according to a within-subjects cross-over design. Setting: Sleep physiology laboratory. Patients: Seven patients with OSA and a low respiratory arousal threshold. Interventions: In-laboratory polysomnograms were obtained at baseline and after 100 mg of trazodone was administered, followed by detailed overnight physiology experiments under the same conditions. During physiology studies, continuous positive airway pressure was transiently lowered to measure arousal threshold (negative epiglottic pressure prior to arousal), dilator muscle activity (genioglossus and tensor palatini), and upper airway collapsibility (Pcrit). Measurements and Results: Trazodone increased the respiratory arousal threshold by 32 ± 6% (-11.5 ± 1.4 versus -15.3 ± 2.2 cmH2O, P < 0.01) but did not alter the apnea-hypopnea index (39 ± 12 versus 39 ± 11 events/h sleep, P = 0.94). Dilator muscle activity and Pcrit also did not systematically change with trazodone. Conclusions: Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold without major impairment in dilator muscle activity or upper airway collapsibility. However, the magnitude of change in arousal threshold was insufficient to overcome the compromised upper airway

Ground-Water Quality Data in the Southern Sacramento Valley, California, 2005 - Results from the California GAMA Program

USGS Publications Warehouse

Milby Dawson, Barbara J.; Bennett, George L.; Belitz, Kenneth

2008-01-01

) were collected at ten percent of the wells, and the results for these samples were used to evaluate the quality of the data for the ground-water samples. Assessment of the quality-control data resulted in censoring of less than 0.03 percent of the analyses of ground-water samples. This study did not evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Health Services (CADHS) (Maximum Contaminant Levels [MCLs], notification levels [NLs], or lifetime health advisories [HA-Ls]) and thresholds established for aesthetic concerns (Secondary Maximum Contaminant Levels [SMCLs]). All wells were sampled for organic constituents and selected general water quality parameters; subsets of wells were sampled for inorganic constituents, nutrients, and radioactive constituents. Volatile organic compounds were detected in 49 out of 83 wells sampled and pesticides were detected in 35 out of 82 wells; all detections were below health-based thresholds, with the exception of 1 detection of 1,2,3-trichloropropane above a NL. Of the 43 wells sampled for trace elements, 27 had no detections of a trace element above a health-based threshold and 16 had at least one detection above. Of the 18 trace elements with health-based thresholds, 3 (arsenic, barium, and boron) were detected at concentrations higher an MCL. Of the 43 wells sampled for nitrate, only 1 well had a detection above the MCL. Twenty wells were sampled for radioactive constituents; only 1 (radon-222) was measured at activiti

40 CFR 68.115 - Threshold determination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 16 2013-07-01 2013-07-01 false Threshold determination. 68.115 Section 68.115 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Regulated Substances for Accidental Release Prevention § 68.115 Threshold determination. (a) A threshold...

40 CFR 68.115 - Threshold determination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 16 2012-07-01 2012-07-01 false Threshold determination. 68.115 Section 68.115 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Regulated Substances for Accidental Release Prevention § 68.115 Threshold determination. (a) A threshold...

40 CFR 68.115 - Threshold determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Threshold determination. 68.115 Section 68.115 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Regulated Substances for Accidental Release Prevention § 68.115 Threshold determination. (a) A threshold...

40 CFR 68.115 - Threshold determination.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 16 2014-07-01 2014-07-01 false Threshold determination. 68.115 Section 68.115 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Regulated Substances for Accidental Release Prevention § 68.115 Threshold determination. (a) A threshold...

Mesenchymal Stem Cells as Therapeutics Agents: Quality and Environmental Regulatory Aspects

PubMed Central

Sabata, Roger; Verges, Josep; Zugaza, José L.; Ruiz, Adolfina; Clares, Beatriz

2016-01-01

Mesenchymal stem cells (MSCs) are one of the main stem cells that have been used for advanced therapies and regenerative medicine. To carry out the translational clinical application of MSCs, their manufacturing and administration in human must be controlled; therefore they should be considered as medicine: stem cell-based medicinal products (SCMPs). The development of MSCs as SCMPs represents complicated therapeutics due to their extreme complex nature and rigorous regulatory oversights. The manufacturing process of MSCs needs to be addressed in clean environments in compliance with requirements of Good Manufacturing Practice (GMP). Facilities should maintain these GMP conditions according to international and national medicinal regulatory frameworks that introduce a number of specifications in order to produce MSCs as safe SCMPs. One of these important and complex requirements is the environmental monitoring. Although a number of environmental requirements are clearly defined, some others are provided as recommendations. In this review we aim to outline the current issues with regard to international guidelines which impact environmental monitoring in cleanrooms and clean areas for the manufacturing of MSCs. PMID:27999600

REFLECTIONS ON THE ROLE OF THE PHARMACY REGULATORY AUTHORITY IN ENHANCING QUALITY RELATED EVENT REPORTING IN COMMUNITY PHARMACIESi

PubMed Central

Boyle, Todd A.; Bishop, Andrea C.; Mahaffey, Thomas; MacKinnon, Neil J.; Ashcroft, Darren; Zwicker, Bev; Reid, Carolyn

2016-01-01

Background Given the demanding nature of providing pharmacy services, coupled with the expanded scope of practice of the professions in jurisdictions around the world, greater commitment to continuous quality improvement through adoption of quality related event (QRE) reporting is necessary to ensure patient safety. Pharmacy regulatory authorities (PRAs) are in a unique position to enhance QRE reporting and learning through the standardization of expected practice Objective This study aims to better understand the perceived roles of PRAs in enhancing QRE reporting and learning in community pharmacies and identifying regulatory best practices to execute such roles. Methods A purposive case sampling approach was used to identify PRA staff members from two groups (deputy registrars and pharmacy inspectors) in 10 Canadian jurisdictions to participate in focus groups in the fall of 2011. Focus groups were used to explore perceptions of the role of PRAs in enhancing and promoting QRE reporting and learning, and perceived barriers to effective implementation in practice. Thematic analysis was used to analyze the qualitative data. Results Two focus groups were conducted, one with seven deputy registrars/practice managers and one with nine pharmacy inspectors. Five themes were identified, including (1) defining QRE reporting and compliance, (2) navigating role conflict, (3) educating for enhanced QRE reporting and learning, (4) promoting the positive/removing the fear of QREs, and (5) tailoring QRE reporting and learning consistency. Conclusions Overall, participants perceived a strong role for PRAs in enhancing QRE reporting and learning and providing education for pharmacies to support their compliance with reporting standards. However, PRAs must navigate the conflict inherent in both educating and promoting a process for achieving a standard while simultaneously inspecting compliance to that standard. Ensuring pharmacies have autonomy in operationalizing standards may

Reflections on the role of the pharmacy regulatory authority in enhancing quality related event reporting in community pharmacies.

PubMed

Boyle, Todd A; Bishop, Andrea C; Mahaffey, Thomas; Mackinnon, Neil J; Ashcroft, Darren M; Zwicker, Bev; Reid, Carolyn

2014-01-01

Given the demanding nature of providing pharmacy services, coupled with the expanded scope of practice of the professions in jurisdictions around the world, greater commitment to continuous quality improvement through adoption of quality-related event (QRE) reporting is necessary to ensure patient safety. Pharmacy regulatory authorities (PRAs) are in a unique position to enhance QRE reporting and learning through the standardization of expected practice. This study was aimed to gain a better understanding of the perceived roles of PRAs in enhancing QRE reporting and learning in community pharmacies, and identifying regulatory best practices to execute such roles. A purposive case sampling approach was used to identify PRA staff members from two groups (Deputy registrars and pharmacy inspectors) in 10 Canadian jurisdictions to participate in focus groups in the fall of 2011. Focus groups were used to explore perceptions of the role of PRAs in enhancing and promoting QRE reporting and learning, and perceived barriers to effective implementation in practice. Thematic analysis was used to analyze the qualitative data. Two focus groups were conducted, one with seven Deputy registrars/Practice managers, and one with nine pharmacy inspectors. Five themes were identified, including (1) defining QRE reporting and compliance, (2) navigating role conflict, (3) educating for enhanced QRE reporting and learning, (4) promoting the positive/removing the fear of QREs, and (5) tailoring QRE reporting and learning consistency. Overall, participants perceived a strong role for PRAs in enhancing QRE reporting and learning and providing education for pharmacies to support their compliance with reporting standards. However, PRAs must navigate the conflict inherent in both educating and promoting a process for achieving a standard while simultaneously inspecting compliance to that standard. Ensuring pharmacies have autonomy in operationalizing standards may help to mitigate this conflict

Quantitative evaluation method of the threshold adjustment and the flat field correction performances of hybrid photon counting pixel detectors

NASA Astrophysics Data System (ADS)

Medjoubi, K.; Dawiec, A.

2017-12-01

A simple method is proposed in this work for quantitative evaluation of the quality of the threshold adjustment and the flat-field correction of Hybrid Photon Counting pixel (HPC) detectors. This approach is based on the Photon Transfer Curve (PTC) corresponding to the measurement of the standard deviation of the signal in flat field images. Fixed pattern noise (FPN), easily identifiable in the curve, is linked to the residual threshold dispersion, sensor inhomogeneity and the remnant errors in flat fielding techniques. The analytical expression of the signal to noise ratio curve is developed for HPC and successfully used as a fit function applied to experimental data obtained with the XPAD detector. The quantitative evaluation of the FPN, described by the photon response non-uniformity (PRNU), is measured for different configurations (threshold adjustment method and flat fielding technique) and is demonstrated to be used in order to evaluate the best setting for having the best image quality from a commercial or a R&D detector.

40 CFR 98.361 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.361 Section 98...) MANDATORY GREENHOUSE GAS REPORTING Manure Management § 98.361 Reporting threshold. Livestock facilities must report GHG emissions under this subpart if the facility meets the reporting threshold as defined in 98...

40 CFR 98.361 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.361 Section 98...) MANDATORY GREENHOUSE GAS REPORTING Manure Management § 98.361 Reporting threshold. Livestock facilities must report GHG emissions under this subpart if the facility meets the reporting threshold as defined in 98...

The regulatory sciences for stem cell-based medicinal products.

PubMed

Yuan, Bao-Zhu; Wang, Junzhi

2014-06-01

Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced. More relevantly, the stem cell regulatory sciences need to be established or improved to more effectively evaluate quality, safety and efficacy of stem cell products, and for building up the appropriate regulatory framework. In this review, we summarize some new achievements in stem cell studies, especially the preclinical and clinical studies, the existing regulations, and the associated challenges, and we then propose some considerations for improving stem cell regulatory sciences with a goal of promoting the steadfast growth of the well-regulated stem cell therapies abreast of evolvement of stem cell sciences and technologies.

Setting objective thresholds for rare event detection in flow cytometry

PubMed Central

Richards, Adam J.; Staats, Janet; Enzor, Jennifer; McKinnon, Katherine; Frelinger, Jacob; Denny, Thomas N.; Weinhold, Kent J.; Chan, Cliburn

2014-01-01

The accurate identification of rare antigen-specific cytokine positive cells from peripheral blood mononuclear cells (PBMC) after antigenic stimulation in an intracellular staining (ICS) flow cytometry assay is challenging, as cytokine positive events may be fairly diffusely distributed and lack an obvious separation from the negative population. Traditionally, the approach by flow operators has been to manually set a positivity threshold to partition events into cytokine-positive and cytokine-negative. This approach suffers from subjectivity and inconsistency across different flow operators. The use of statistical clustering methods does not remove the need to find an objective threshold between between positive and negative events since consistent identification of rare event subsets is highly challenging for automated algorithms, especially when there is distributional overlap between the positive and negative events (“smear”). We present a new approach, based on the Fβ measure, that is similar to manual thresholding in providing a hard cutoff, but has the advantage of being determined objectively. The performance of this algorithm is compared with results obtained by expert visual gating. Several ICS data sets from the External Quality Assurance Program Oversight Laboratory (EQAPOL) proficiency program were used to make the comparisons. We first show that visually determined thresholds are difficult to reproduce and pose a problem when comparing results across operators or laboratories, as well as problems that occur with the use of commonly employed clustering algorithms. In contrast, a single parameterization for the Fβ method performs consistently across different centers, samples, and instruments because it optimizes the precision/recall tradeoff by using both negative and positive controls. PMID:24727143

40 CFR 98.441 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.441 Section 98...) MANDATORY GREENHOUSE GAS REPORTING Geologic Sequestration of Carbon Dioxide § 98.441 Reporting threshold. (a... amount of CO2 for long-term containment in subsurface geologic formations. There is no threshold. (b...

49 CFR 80.13 - Threshold criteria.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Threshold criteria. 80.13 Section 80.13... § 80.13 Threshold criteria. (a) To be eligible to receive Federal credit assistance under this part, a project shall meet the following five threshold criteria: (1) The project shall be consistent with the...

49 CFR 80.13 - Threshold criteria.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 1 2014-10-01 2014-10-01 false Threshold criteria. 80.13 Section 80.13... § 80.13 Threshold criteria. (a) To be eligible to receive Federal credit assistance under this part, a project shall meet the following five threshold criteria: (1) The project shall be consistent with the...

Advancing pharmaceutical quality: An overview of science and research in the U.S. FDA's Office of Pharmaceutical Quality.

PubMed

Fisher, Adam C; Lee, Sau L; Harris, Daniel P; Buhse, Lucinda; Kozlowski, Steven; Yu, Lawrence; Kopcha, Michael; Woodcock, Janet

2016-12-30

Failures surrounding pharmaceutical quality, particularly with respect to product manufacturing issues and facility remediation, account for the majority of drug shortages and product recalls in the United States. Major scientific advancements pressure established regulatory paradigms, especially in the areas of biosimilars, precision medicine, combination products, emerging manufacturing technologies, and the use of real-world data. Pharmaceutical manufacturing is increasingly globalized, prompting the need for more efficient surveillance systems for monitoring product quality. Furthermore, increasing scrutiny and accelerated approval pathways provide a driving force to be even more efficient with limited regulatory resources. To address these regulatory challenges, the Office of Pharmaceutical Quality (OPQ) in the Center for Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA) harbors a rigorous science and research program in core areas that support drug quality review, inspection, surveillance, standards, and policy development. Science and research is the foundation of risk-based quality assessment of new drugs, generic drugs, over-the-counter drugs, and biotechnology products including biosimilars. This is an overview of the science and research activities in OPQ that support the mission of ensuring that safe, effective, and high-quality drugs are available to the American public. Published by Elsevier B.V.

A Life Worth Giving? The Threshold for Permissible Withdrawal of Life Support From Disabled Newborn Infants

PubMed Central

Wilkinson, Dominic James

2011-01-01

When is it permissible to allow a newborn infant to die on the basis of their future quality of life? The prevailing official view is that treatment may be withdrawn only if the burdens in an infant's future life outweigh the benefits. In this paper I outline and defend an alternative view. On the Threshold View, treatment may be withdrawn from infants if their future well-being is below a threshold that is close to, but above the zero-point of well-being. I present four arguments in favor of the Threshold View, and identify and respond to several counterarguments. I conclude that it is justifiable in some circumstances for parents and doctors to decide to allow an infant to die even though the infant's life would be worth living. The Threshold View provides a justification for treatment decisions that is more consistent, more robust, and potentially more practical than the standard view. PMID:21337273

An integrative perspective of the anaerobic threshold.

PubMed

Sales, Marcelo Magalhães; Sousa, Caio Victor; da Silva Aguiar, Samuel; Knechtle, Beat; Nikolaidis, Pantelis Theodoros; Alves, Polissandro Mortoza; Simões, Herbert Gustavo

2017-12-14

The concept of anaerobic threshold (AT) was introduced during the nineteen sixties. Since then, several methods to identify the anaerobic threshold (AT) have been studied and suggested as novel 'thresholds' based upon the variable used for its detection (i.e. lactate threshold, ventilatory threshold, glucose threshold). These different techniques have brought some confusion about how we should name this parameter, for instance, anaerobic threshold or the physiological measure used (i.e. lactate, ventilation). On the other hand, the modernization of scientific methods and apparatus to detect AT, as well as the body of literature formed in the past decades, could provide a more cohesive understanding over the AT and the multiple physiological systems involved. Thus, the purpose of this review was to provide an integrative perspective of the methods to determine AT. Copyright © 2017 Elsevier Inc. All rights reserved.

Threshold Concepts in Finance: Student Perspectives

ERIC Educational Resources Information Center

Hoadley, Susan; Kyng, Tim; Tickle, Leonie; Wood, Leigh N.

2015-01-01

Finance threshold concepts are the essential conceptual knowledge that underpin well-developed financial capabilities and are central to the mastery of finance. In this paper we investigate threshold concepts in finance from the point of view of students, by establishing the extent to which students are aware of threshold concepts identified by…

40 CFR 98.91 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.91 Section 98...) MANDATORY GREENHOUSE GAS REPORTING Electronics Manufacturing § 98.91 Reporting threshold. (a) You must... year emission threshold in § 98.2(a)(2), follow the requirements of § 98.2(b), with one exception...

40 CFR 98.121 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.121 Section 98...) MANDATORY GREENHOUSE GAS REPORTING Fluorinated Gas Production § 98.121 Reporting threshold. You must report...). To calculate GHG emissions for comparison to the 25,000 metric ton CO2e per year emission threshold...

Monitoring air quality in mountains: Designing an effective network

USGS Publications Warehouse

Peterson, D.L.

2000-01-01

A quantitatively robust yet parsimonious air-quality monitoring network in mountainous regions requires special attention to relevant spatial and temporal scales of measurement and inference. The design of monitoring networks should focus on the objectives required by public agencies, namely: 1) determine if some threshold has been exceeded (e.g., for regulatory purposes), and 2) identify spatial patterns and temporal trends (e.g., to protect natural resources). A short-term, multi-scale assessment to quantify spatial variability in air quality is a valuable asset in designing a network, in conjunction with an evaluation of existing data and simulation-model output. A recent assessment in Washington state (USA) quantified spatial variability in tropospheric ozone distribution ranging from a single watershed to the western third of the state. Spatial and temporal coherence in ozone exposure modified by predictable elevational relationships ( 1.3 ppbv ozone per 100 m elevation gain) extends from urban areas to the crest of the Cascade Range. This suggests that a sparse network of permanent analyzers is sufficient at all spatial scales, with the option of periodic intensive measurements to validate network design. It is imperative that agencies cooperate in the design of monitoring networks in mountainous regions to optimize data collection and financial efficiencies.

Using self-organizing maps to determine observation threshold limit predictions in highly variant data

USGS Publications Warehouse

Paganoni, C.A.; Chang, K.C.; Robblee, M.B.

2006-01-01

A significant data quality challenge for highly variant systems surrounds the limited ability to quantify operationally reasonable limits on the data elements being collected and provide reasonable threshold predictions. In many instances, the number of influences that drive a resulting value or operational range is too large to enable physical sampling for each influencer, or is too complicated to accurately model in an explicit simulation. An alternative method to determine reasonable observation thresholds is to employ an automation algorithm that would emulate a human analyst visually inspecting data for limits. Using the visualization technique of self-organizing maps (SOM) on data having poorly understood relationships, a methodology for determining threshold limits was developed. To illustrate this approach, analysis of environmental influences that drive the abundance of a target indicator species (the pink shrimp, Farfantepenaeus duorarum) provided a real example of applicability. The relationship between salinity and temperature and abundance of F. duorarum is well documented, but the effect of changes in water quality upstream on pink shrimp abundance is not well understood. The highly variant nature surrounding catch of a specific number of organisms in the wild, and the data available from up-stream hydrology measures for salinity and temperature, made this an ideal candidate for the approach to provide a determination about the influence of changes in hydrology on populations of organisms.

Using self-organizing maps to determine observation threshold limit predictions in highly variant data

NASA Astrophysics Data System (ADS)

Paganoni, Christopher A.; Chang, K. C.; Robblee, Michael B.

2006-05-01

A significant data quality challenge for highly variant systems surrounds the limited ability to quantify operationally reasonable limits on the data elements being collected and provide reasonable threshold predictions. In many instances, the number of influences that drive a resulting value or operational range is too large to enable physical sampling for each influencer, or is too complicated to accurately model in an explicit simulation. An alternative method to determine reasonable observation thresholds is to employ an automation algorithm that would emulate a human analyst visually inspecting data for limits. Using the visualization technique of self-organizing maps (SOM) on data having poorly understood relationships, a methodology for determining threshold limits was developed. To illustrate this approach, analysis of environmental influences that drive the abundance of a target indicator species (the pink shrimp, Farfantepenaeus duorarum) provided a real example of applicability. The relationship between salinity and temperature and abundance of F. duorarum is well documented, but the effect of changes in water quality upstream on pink shrimp abundance is not well understood. The highly variant nature surrounding catch of a specific number of organisms in the wild, and the data available from up-stream hydrology measures for salinity and temperature, made this an ideal candidate for the approach to provide a determination about the influence of changes in hydrology on populations of organisms.

Air Quality Management Process Cycle

EPA Pesticide Factsheets

Air quality management are activities a regulatory authority undertakes to protect human health and the environment from the harmful effects of air pollution. The process of managing air quality can be illustrated as a cycle of inter-related elements.

Regulatory neutrality is essential to establishing a level playing field for accountable care organizations.

PubMed

Bacher, Gary E; Chernew, Michael E; Kessler, Daniel P; Weiner, Stephen M

2013-08-01

Accountable care organizations (ACOs) are among the most widely discussed models for encouraging movement away from fee-for-service payment arrangements. Although ACOs have the potential to slow health spending growth and improve quality of care, regulating them poses special challenges. Regulations, particularly those that affect both ACOs and Medicare Advantage plans, could inadvertently favor or disfavor certain kinds of providers or payers. Such favoritism could drive efficient organizations from the market and thus increase costs or reduce quality of and access to care. To avoid this type of outcome, we propose a general principle: Regulation of ACOs should strive to preserve a level playing field among different kinds of organizations seeking the same cost, quality, and access objectives. This is known as regulatory neutrality. We describe the implications of regulatory neutrality in four key areas: antitrust, financial solvency regulation, Medicare governance requirements, and Medicare payment models. We also discuss issues relating to short-term versus long-term perspectives--to promote the goal of regulatory neutrality and allow the most efficient organizations to prevail in the marketplace.

Influence of the hypercycle on the error threshold: a stochastic approach.

PubMed

García-Tejedor, A; Sanz-Nuño, J C; Olarrea, J; Javier de la Rubia, F; Montero, F

1988-10-21

The role of fluctuations on the error threshold of the hypercycle has been studied by a stochastic approach on a very simplified model. For this model, the master equation was derived and its unique steady state calculated. This state implies the extinction of the system. But the actual time necessary to reach the steady state may be astronomically long whereas for times of experimental interest the system could be near some quasi-stationary states. In order to explore this possibility a Gillespie simulation of the stochastic process has been carried out. These quasi-stationary states correspond to the deterministic steady states of the system. The error threshold shifts towards higher values of the quality factor Q. Moreover, information about the fluctuations around the quasi-stationary states is obtained. The results are discussed in relation to the deterministic states.

Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

PubMed

Gonçalves, Joana P; Aires, Ricardo S; Francisco, Alexandre P; Madeira, Sara C

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched

Regulatory Snapshots: Integrative Mining of Regulatory Modules from Expression Time Series and Regulatory Networks

PubMed Central

Gonçalves, Joana P.; Aires, Ricardo S.; Francisco, Alexandre P.; Madeira, Sara C.

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched

75 FR 54921 - Withdrawal of Regulatory Guides 1.38, 1.94, and 1.116

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

....116, ``Quality Assurance Requirements for Installation, Inspection, and Testing of Mechanical....116, ``Quality Assurance Requirements for Installation, Inspection, and Testing of Mechanical Equipment and Systems,'' dated May 1977. Regulatory Guide 1.38 endorses the American Society of Mechanical...

Estimating phonation threshold pressure.

PubMed

Fisher, K V; Swank, P R

1997-10-01

Phonation threshold pressure (PTP) is the minimum subglottal pressure required to initiate vocal fold oscillation. Although potentially useful clinically, PTP is difficult to estimate noninvasively because of limitations to vocal motor control near the threshold of soft phonation. Previous investigators observed, for example, that trained subjects were unable to produce flat, consistent oral pressure peaks during/pae/syllable strings when they attempted to phonate as softly as possible (Verdolini-Marston, Titze, & Druker, 1990). The present study aimed to determine if nasal airflow or vowel context affected phonation threshold pressure as estimated from oral pressure (Smitheran & Hixon, 1981) in 5 untrained female speakers with normal velopharyngeal and voice function. Nasal airflow during /p/occlusion was observed for 3 of 5 participants when they attempted to phonate near threshold pressure. When the nose was occluded, nasal airflow was reduced or eliminated during /p/;however, individuals then evidenced compensatory changes in glottal adduction and/or respiratory effort that may be expected to alter PTP estimates. Results demonstrate the importance of monitoring nasal flow (or the flow zero point in undivided masks) when obtaining PTP measurements noninvasively. Results also highlight the need to pursue improved methods for noninvasive estimation of PTP.

Regional rainfall thresholds for landslide occurrence using a centenary database

NASA Astrophysics Data System (ADS)

Vaz, Teresa; Luís Zêzere, José; Pereira, Susana; Cruz Oliveira, Sérgio; Quaresma, Ivânia

2017-04-01

Rainfall is one of the most important triggering factors for landslides occurrence worldwide. The relation between rainfall and landslide occurrence is complex and some approaches have been focus on the rainfall thresholds identification, i.e., rainfall critical values that when exceeded can initiate landslide activity. In line with these approaches, this work proposes and validates rainfall thresholds for the Lisbon region (Portugal), using a centenary landslide database associated with a centenary daily rainfall database. The main objectives of the work are the following: i) to compute antecedent rainfall thresholds using linear and potential regression; ii) to define lower limit and upper limit rainfall thresholds; iii) to estimate the probability of critical rainfall conditions associated with landslide events; and iv) to assess the thresholds performance using receiver operating characteristic (ROC) metrics. In this study we consider the DISASTER database, which lists landslides that caused fatalities, injuries, missing people, evacuated and homeless people occurred in Portugal from 1865 to 2010. The DISASTER database was carried out exploring several Portuguese daily and weekly newspapers. Using the same newspaper sources, the DISASTER database was recently updated to include also the landslides that did not caused any human damage, which were also considered for this study. The daily rainfall data were collected at the Lisboa-Geofísico meteorological station. This station was selected considering the quality and completeness of the rainfall data, with records that started in 1864. The methodology adopted included the computation, for each landslide event, of the cumulative antecedent rainfall for different durations (1 to 90 consecutive days). In a second step, for each combination of rainfall quantity-duration, the return period was estimated using the Gumbel probability distribution. The pair (quantity-duration) with the highest return period was

COUNCIL FOR REGULATORY ENVIRONMENTAL MODELING (CREM) PILOT WATER QUALITY MODEL SELECTION TOOL

EPA Science Inventory

EPA's Council for Regulatory Environmental Modeling (CREM) is currently supporting the development of a pilot model selection tool that is intended to help the states and the regions implement the total maximum daily load (TMDL) program. This tool will be implemented within the ...

40 CFR 98.231 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.231 Section 98...) MANDATORY GREENHOUSE GAS REPORTING Petroleum and Natural Gas Systems § 98.231 Reporting threshold. (a) You... § 98.232(i) emit 25,000 metric tons of CO2 equivalent or more per year. (b) For applying the threshold...

Optical ranked-order filtering using threshold decomposition

DOEpatents

Allebach, Jan P.; Ochoa, Ellen; Sweeney, Donald W.

1990-01-01

A hybrid optical/electronic system performs median filtering and related ranked-order operations using threshold decomposition to encode the image. Threshold decomposition transforms the nonlinear neighborhood ranking operation into a linear space-invariant filtering step followed by a point-to-point threshold comparison step. Spatial multiplexing allows parallel processing of all the threshold components as well as recombination by a second linear, space-invariant filtering step. An incoherent optical correlation system performs the linear filtering, using a magneto-optic spatial light modulator as the input device and a computer-generated hologram in the filter plane. Thresholding is done electronically. By adjusting the value of the threshold, the same architecture is used to perform median, minimum, and maximum filtering of images. A totally optical system is also disclosed.

Threshold-based system for noise detection in multilead ECG recordings.

PubMed

Jekova, Irena; Krasteva, Vessela; Christov, Ivaylo; Abächerli, Roger

2012-09-01

This paper presents a system for detection of the most common noise types seen on the electrocardiogram (ECG) in order to evaluate whether an episode from 12-lead ECG is reliable for diagnosis. It implements criteria for estimation of the noise corruption level in specific frequency bands, aiming to identify the main sources of ECG quality disruption, such as missing signal or limited dynamics of the QRS components above 4 Hz; presence of high amplitude and steep artifacts seen above 1 Hz; baseline drift estimated at frequencies below 1 Hz; power-line interference in a band ±2 Hz around its central frequency; high-frequency and electromyographic noises above 20 Hz. All noise tests are designed to process the ECG series in the time domain, including 13 adjustable thresholds for amplitude and slope criteria which are evaluated in adjustable time intervals, as well as number of leads. The system allows flexible extension toward application-specific requirements for the noise levels in acceptable quality ECGs. Training of different thresholds' settings to determine different positive noise detection rates is performed with the annotated set of 1000 ECGs from the PhysioNet database created for the Computing in Cardiology Challenge 2011. Two implementations are highlighted on the receiver operating characteristic (area 0.968) to fit to different applications. The implementation with high sensitivity (Se = 98.7%, Sp = 80.9%) appears as a reliable alarm when there are any incidental problems with the ECG acquisition, while the implementation with high specificity (Sp = 97.8%, Se = 81.8%) is less susceptible to transient problems but rather validates noisy ECGs with acceptable quality during a small portion of the recording.

Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold.

PubMed

Eckert, Danny J; Malhotra, Atul; Wellman, Andrew; White, David P

2014-04-01

The effect of common sedatives on upper airway physiology and breathing during sleep in obstructive sleep apnea (OSA) has been minimally studied. Conceptually, certain sedatives may worsen OSA in some patients. However, sleep and breathing could improve with certain sedatives in patients with OSA with a low respiratory arousal threshold. This study aimed to test the hypothesis that trazodone increases the respiratory arousal threshold in patients with OSA and a low arousal threshold. Secondary aims were to examine the effects of trazodone on upper airway dilator muscle activity, upper airway collapsibility, and breathing during sleep. Patients were studied on 4 separate nights according to a within-subjects cross-over design. Sleep physiology laboratory. Seven patients with OSA and a low respiratory arousal threshold. In-laboratory polysomnograms were obtained at baseline and after 100 mg of trazodone was administered, followed by detailed overnight physiology experiments under the same conditions. During physiology studies, continuous positive airway pressure was transiently lowered to measure arousal threshold (negative epiglottic pressure prior to arousal), dilator muscle activity (genioglossus and tensor palatini), and upper airway collapsibility (Pcrit). Trazodone increased the respiratory arousal threshold by 32 ± 6% (-11.5 ± 1.4 versus -15.3 ± 2.2 cmH2O, P < 0.01) but did not alter the apnea-hypopnea index (39 ± 12 versus 39 ± 11 events/h sleep, P = 0.94). Dilator muscle activity and Pcrit also did not systematically change with trazodone. Trazodone increases the respiratory arousal threshold in patients with obstructive sleep apnea and a low arousal threshold without major impairment in dilator muscle activity or upper airway collapsibility. However, the magnitude of change in arousal threshold was insufficient to overcome the compromised upper airway anatomy in these patients.

Influence of emission threshold of explosive emission cathodes on current waveform in foilless diodes

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

Wu, P.; Liu, G. Z.; Science and Technology on High Power Microwave Laboratory, Northwest Institute of Nuclear Technology, Xi'an 710024

The emission threshold of explosive emission cathodes (EECs) is an important factor for beam quality. It can affect the explosive emission delay time, the plasma expansion process on the cathode surface, and even the current amplitude when the current is not fully space-charge-limited. This paper researches the influence of the emission threshold of an annular EEC on the current waveform in a foilless diode when the current is measured by a Rogowski coil. The particle-in-cell simulation which is performed under some tolerable and necessary simplifications shows that the long explosive emission delay time of high-threshold cathodes may leave an apparentmore » peak of displacement current on the rise edge of the current waveform, and this will occur only when the electron emission starts after this peak. The experimental researches, which are performed under a diode voltage of 1 MV and a repetitive frequency of 20 Hz, demonstrate that the graphite cathode has a lower emission threshold and a longer lifetime than the stainless steel cathode according to the variation of the peak of displacement current on the rise edge of the current waveform.« less

Experimental evidence of a pathogen invasion threshold

PubMed Central

Krkošek, Martin

2018-01-01

Host density thresholds to pathogen invasion separate regions of parameter space corresponding to endemic and disease-free states. The host density threshold is a central concept in theoretical epidemiology and a common target of human and wildlife disease control programmes, but there is mixed evidence supporting the existence of thresholds, especially in wildlife populations or for pathogens with complex transmission modes (e.g. environmental transmission). Here, we demonstrate the existence of a host density threshold for an environmentally transmitted pathogen by combining an epidemiological model with a microcosm experiment. Experimental epidemics consisted of replicate populations of naive crustacean zooplankton (Daphnia dentifera) hosts across a range of host densities (20–640 hosts l−1) that were exposed to an environmentally transmitted fungal pathogen (Metschnikowia bicuspidata). Epidemiological model simulations, parametrized independently of the experiment, qualitatively predicted experimental pathogen invasion thresholds. Variability in parameter estimates did not strongly influence outcomes, though systematic changes to key parameters have the potential to shift pathogen invasion thresholds. In summary, we provide one of the first clear experimental demonstrations of pathogen invasion thresholds in a replicated experimental system, and provide evidence that such thresholds may be predictable using independently constructed epidemiological models. PMID:29410876

10 CFR 76.93 - Quality assurance.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Quality assurance. 76.93 Section 76.93 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Safety § 76.93 Quality assurance. The Corporation shall establish, maintain, and execute a quality assurance program satisfying each of...

10 CFR 76.93 - Quality assurance.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Quality assurance. 76.93 Section 76.93 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Safety § 76.93 Quality assurance. The Corporation shall establish, maintain, and execute a quality assurance program satisfying each of...

10 CFR 76.93 - Quality assurance.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Quality assurance. 76.93 Section 76.93 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Safety § 76.93 Quality assurance. The Corporation shall establish, maintain, and execute a quality assurance program satisfying each of...

10 CFR 76.93 - Quality assurance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Quality assurance. 76.93 Section 76.93 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Safety § 76.93 Quality assurance. The Corporation shall establish, maintain, and execute a quality assurance program satisfying each of...

10 CFR 76.93 - Quality assurance.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Quality assurance. 76.93 Section 76.93 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) CERTIFICATION OF GASEOUS DIFFUSION PLANTS Safety § 76.93 Quality assurance. The Corporation shall establish, maintain, and execute a quality assurance program satisfying each of...

CHOW PARAMETERS IN THRESHOLD LOGIC,

DTIC Science & Technology

respect to threshold functions, they provide the optimal test-synthesis method for completely specified 7-argument (or less) functions, reflect the...signs and relative magnitudes of realizing weights and threshold , and can be used themselves as approximating weights. Results are reproved in a

On Hierarchical Threshold Access Structures

DTIC Science & Technology

2010-11-01

One of the recent generalizations of (t, n) secret sharing for hierarchical threshold access structures is given by Tassa, where he answers the...of theoretical background. We give a conceptually simpler alternative for the understanding of the realization of hierarchical threshold access

Optical ranked-order filtering using threshold decomposition

DOEpatents

Allebach, J.P.; Ochoa, E.; Sweeney, D.W.

1987-10-09

A hybrid optical/electronic system performs median filtering and related ranked-order operations using threshold decomposition to encode the image. Threshold decomposition transforms the nonlinear neighborhood ranking operation into a linear space-invariant filtering step followed by a point-to-point threshold comparison step. Spatial multiplexing allows parallel processing of all the threshold components as well as recombination by a second linear, space-invariant filtering step. An incoherent optical correlation system performs the linear filtering, using a magneto-optic spatial light modulator as the input device and a computer-generated hologram in the filter plane. Thresholding is done electronically. By adjusting the value of the threshold, the same architecture is used to perform median, minimum, and maximum filtering of images. A totally optical system is also disclosed. 3 figs.

Variable neighborhood search for reverse engineering of gene regulatory networks.

PubMed

Nicholson, Charles; Goodwin, Leslie; Clark, Corey

2017-01-01

A new search heuristic, Divided Neighborhood Exploration Search, designed to be used with inference algorithms such as Bayesian networks to improve on the reverse engineering of gene regulatory networks is presented. The approach systematically moves through the search space to find topologies representative of gene regulatory networks that are more likely to explain microarray data. In empirical testing it is demonstrated that the novel method is superior to the widely employed greedy search techniques in both the quality of the inferred networks and computational time. Copyright © 2016 Elsevier Inc. All rights reserved.

Absolute auditory threshold: testing the absolute.

PubMed

Heil, Peter; Matysiak, Artur

2017-11-02

The mechanisms underlying the detection of sounds in quiet, one of the simplest tasks for auditory systems, are debated. Several models proposed to explain the threshold for sounds in quiet and its dependence on sound parameters include a minimum sound intensity ('hard threshold'), below which sound has no effect on the ear. Also, many models are based on the assumption that threshold is mediated by integration of a neural response proportional to sound intensity. Here, we test these ideas. Using an adaptive forced choice procedure, we obtained thresholds of 95 normal-hearing human ears for 18 tones (3.125 kHz carrier) in quiet, each with a different temporal amplitude envelope. Grand-mean thresholds and standard deviations were well described by a probabilistic model according to which sensory events are generated by a Poisson point process with a low rate in the absence, and higher, time-varying rates in the presence, of stimulation. The subject actively evaluates the process and bases the decision on the number of events observed. The sound-driven rate of events is proportional to the temporal amplitude envelope of the bandpass-filtered sound raised to an exponent. We find no evidence for a hard threshold: When the model is extended to include such a threshold, the fit does not improve. Furthermore, we find an exponent of 3, consistent with our previous studies and further challenging models that are based on the assumption of the integration of a neural response that, at threshold sound levels, is directly proportional to sound amplitude or intensity. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

New developments in supra-threshold perimetry.

PubMed

Henson, David B; Artes, Paul H

2002-09-01

To describe a series of recent enhancements to supra-threshold perimetry. Computer simulations were used to develop an improved algorithm (HEART) for the setting of the supra-threshold test intensity at the beginning of a field test, and to evaluate the relationship between various pass/fail criteria and the test's performance (sensitivity and specificity) and how they compare with modern threshold perimetry. Data were collected in optometric practices to evaluate HEART and to assess how the patient's response times can be analysed to detect false positive response errors in visual field test results. The HEART algorithm shows improved performance (reduced between-eye differences) over current algorithms. A pass/fail criterion of '3 stimuli seen of 3-5 presentations' at each test location reduces test/retest variability and combines high sensitivity and specificity. A large percentage of false positive responses can be detected by comparing their latencies to the average response time of a patient. Optimised supra-threshold visual field tests can perform as well as modern threshold techniques. Such tests may be easier to perform for novice patients, compared with the more demanding threshold tests.

Deriving freshwater safety thresholds for hexabromocyclododecane and comparison of toxicity of brominated flame retardants.

PubMed

Dong, Liang; Zheng, Lei; Yang, Suwen; Yan, Zhenguang; Jin, Weidong; Yan, Yuhong

2017-05-01

Hexabromocyclododecane (HBCD) is a brominated flame retardant used throughout the world. It has been detected in various environmental media and has been shown toxic to aquatic life. The toxic effects of HBCD to aquatic organisms in Chinese freshwater ecosystems are discussed here. Experiments were conducted with nine types of acute toxicity testing and three types of chronic toxicity testing. After comparing a range of species sensitivity distribution models, the optimal model of Bull III was used to derive the safety thresholds for HBCD. The acute safety threshold and the chronic safety threshold of HBCD for Chinese freshwater organisms were found to be 2.32mg/L and 0.128mg/L, respectively. Both values were verified by the methods of the Netherlands and the United States. HBCD was found to be less toxic compared to other widely used brominated flame retardants. The present results provide valuable information for revision of the water quality standard of HBCD in China. Copyright © 2017 Elsevier Inc. All rights reserved.

Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a systematic review.

PubMed

Daru, J; Allotey, J; Peña-Rosas, J P; Khan, K S

2017-06-01

The aim of this review was to understand the landscape of serum ferritin in diagnosing iron deficiency in the aetiology of anaemia in pregnancy. Iron deficiency in pregnancy is a major public health problem leading to the development of anaemia. Reducing the global prevalence of anaemia in women of reproductive age is a 2025 global nutrition target. Bone marrow aspiration is the gold standard test for iron deficiency but requires an invasive procedure; therefore, serum ferritin is the most clinically useful test. We undertook a systematic search of electronic databases and trial registers from inception to January 2016. Studies of iron or micronutrient supplementation in pregnancy with pre-defined serum ferritin thresholds were included. Two independent reviewers selected studies, extracted data and assessed quality. There were 76 relevant studies mainly of observational study design (57%). The most commonly used thresholds of serum ferritin for the diagnosis of iron deficiency were <12 and <15 ng mL -1 (68%). Most primary studies provided no justification for the choice of serum ferritin threshold used, but 25 studies (33%) used thresholds defined by expert consensus in a guideline development process. There were five studies (7%) using a serum ferritin threshold defining iron deficiency derived from primary studies of bone marrow aspiration. Unified international thresholds of iron deficiency for women throughout pregnancy are required for accurate assessments of the global disease burden and for evaluating effectiveness of interventions addressing this problem. © 2017 World Health Organization licensed by Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.

A simple threshold rule is sufficient to explain sophisticated collective decision-making.

PubMed

Robinson, Elva J H; Franks, Nigel R; Ellis, Samuel; Okuda, Saki; Marshall, James A R

2011-01-01

Decision-making animals can use slow-but-accurate strategies, such as making multiple comparisons, or opt for simpler, faster strategies to find a 'good enough' option. Social animals make collective decisions about many group behaviours including foraging and migration. The key to the collective choice lies with individual behaviour. We present a case study of a collective decision-making process (house-hunting ants, Temnothorax albipennis), in which a previously proposed decision strategy involved both quality-dependent hesitancy and direct comparisons of nests by scouts. An alternative possible decision strategy is that scouting ants use a very simple quality-dependent threshold rule to decide whether to recruit nest-mates to a new site or search for alternatives. We use analytical and simulation modelling to demonstrate that this simple rule is sufficient to explain empirical patterns from three studies of collective decision-making in ants, and can account parsimoniously for apparent comparison by individuals and apparent hesitancy (recruitment latency) effects, when available nests differ strongly in quality. This highlights the need to carefully design experiments to detect individual comparison. We present empirical data strongly suggesting that best-of-n comparison is not used by individual ants, although individual sequential comparisons are not ruled out. However, by using a simple threshold rule, decision-making groups are able to effectively compare options, without relying on any form of direct comparison of alternatives by individuals. This parsimonious mechanism could promote collective rationality in group decision-making.

Threshold q -voter model

NASA Astrophysics Data System (ADS)

Vieira, Allan R.; Anteneodo, Celia

2018-05-01

We introduce the threshold q -voter opinion dynamics where an agent, facing a binary choice, can change its mind when at least q0 among q neighbors share the opposite opinion. Otherwise, the agent can still change its mind with a certain probability ɛ . This threshold dynamics contemplates the possibility of persuasion by an influence group even when there is not full agreement among its members. In fact, individuals can follow their peers not only when there is unanimity (q0=q ) in the lobby group, as assumed in the q -voter model, but also, depending on the circumstances, when there is simple majority (q0>q /2 ), Byzantine consensus (q0>2 q /3 ), or any minimal number q0 among q . This realistic threshold gives place to emerging collective states and phase transitions which are not observed in the standard q voter. The threshold q0, together with the stochasticity introduced by ɛ , yields a phenomenology that mimics as particular cases the q voter with stochastic drivings such as nonconformity and independence. In particular, nonconsensus majority states are possible, as well as mixed phases. Continuous and discontinuous phase transitions can occur, but also transitions from fluctuating phases into absorbing states.

Optimal threshold estimator of a prognostic marker by maximizing a time-dependent expected utility function for a patient-centered stratified medicine.

PubMed

Dantan, Etienne; Foucher, Yohann; Lorent, Marine; Giral, Magali; Tessier, Philippe

2018-06-01

Defining thresholds of prognostic markers is essential for stratified medicine. Such thresholds are mostly estimated from purely statistical measures regardless of patient preferences potentially leading to unacceptable medical decisions. Quality-Adjusted Life-Years are a widely used preferences-based measure of health outcomes. We develop a time-dependent Quality-Adjusted Life-Years-based expected utility function for censored data that should be maximized to estimate an optimal threshold. We performed a simulation study to compare estimated thresholds when using the proposed expected utility approach and purely statistical estimators. Two applications illustrate the usefulness of the proposed methodology which was implemented in the R package ROCt ( www.divat.fr ). First, by reanalysing data of a randomized clinical trial comparing the efficacy of prednisone vs. placebo in patients with chronic liver cirrhosis, we demonstrate the utility of treating patients with a prothrombin level higher than 89%. Second, we reanalyze the data of an observational cohort of kidney transplant recipients: we conclude to the uselessness of the Kidney Transplant Failure Score to adapt the frequency of clinical visits. Applying such a patient-centered methodology may improve future transfer of novel prognostic scoring systems or markers in clinical practice.

Impact of muon detection thresholds on the separability of primary cosmic rays

NASA Astrophysics Data System (ADS)

Müller, S.; Engel, R.; Pierog, T.; Roth, M.

2018-01-01

Knowledge of the mass composition of cosmic rays in the transition region of galactic to extragalactic cosmic rays is needed to discriminate different astrophysical models on their origin, acceleration, and propagation. An important observable to separate different mass groups of cosmic rays is the number of muons in extensive air showers. We performed a CORSIKA simulation study to analyze the impact of the detection threshold of muons on the separation quality of different primary cosmic rays in the energy region of the ankle. Using only the number of muons as the composition-sensitive observable, we find a clear dependence of the separation power on the detection threshold for ideal measurements. Although the number of detected muons increases when lowering the threshold, the discrimination power is reduced. If statistical fluctuations for muon detectors of limited size are taken into account, the threshold dependence remains qualitatively the same for small distances to the shower core but is reduced for large core distances. We interpret the impact of the detection threshold of muons on the composition sensitivity in terms of a change of the correlation of the number of muons nμ with the shower maximum Xmax as function of the muon energy as a result of the underlying hadronic interactions and the shower geometry. We further investigate the role of muons produced in a shower by photon-air interactions and conclude that, in addition to the effect of the nμ -Xmax correlation, the separability of primaries is reduced as a consequence of the presence of more muons from photonuclear reactions in proton than in iron showers.

Anaerobic Threshold and Salivary α-amylase during Incremental Exercise.

PubMed

Akizuki, Kazunori; Yazaki, Syouichirou; Echizenya, Yuki; Ohashi, Yukari

2014-07-01

[Purpose] The purpose of this study was to clarify the validity of salivary α-amylase as a method of quickly estimating anaerobic threshold and to establish the relationship between salivary α-amylase and double-product breakpoint in order to create a way to adjust exercise intensity to a safe and effective range. [Subjects and Methods] Eleven healthy young adults performed an incremental exercise test using a cycle ergometer. During the incremental exercise test, oxygen consumption, carbon dioxide production, and ventilatory equivalent were measured using a breath-by-breath gas analyzer. Systolic blood pressure and heart rate were measured to calculate the double product, from which double-product breakpoint was determined. Salivary α-amylase was measured to calculate the salivary threshold. [Results] One-way ANOVA revealed no significant differences among workloads at the anaerobic threshold, double-product breakpoint, and salivary threshold. Significant correlations were found between anaerobic threshold and salivary threshold and between anaerobic threshold and double-product breakpoint. [Conclusion] As a method for estimating anaerobic threshold, salivary threshold was as good as or better than determination of double-product breakpoint because the correlation between anaerobic threshold and salivary threshold was higher than the correlation between anaerobic threshold and double-product breakpoint. Therefore, salivary threshold is a useful index of anaerobic threshold during an incremental workload.

Modeling in the quality by design environment: Regulatory requirements and recommendations for design space and control strategy appointment.

PubMed

Djuris, Jelena; Djuric, Zorica

2017-11-30

Mathematical models can be used as an integral part of the quality by design (QbD) concept throughout the product lifecycle for variety of purposes, including appointment of the design space and control strategy, continual improvement and risk assessment. Examples of different mathematical modeling techniques (mechanistic, empirical and hybrid) in the pharmaceutical development and process monitoring or control are provided in the presented review. In the QbD context, mathematical models are predominantly used to support design space and/or control strategies. Considering their impact to the final product quality, models can be divided into the following categories: high, medium and low impact models. Although there are regulatory guidelines on the topic of modeling applications, review of QbD-based submission containing modeling elements revealed concerns regarding the scale-dependency of design spaces and verification of models predictions at commercial scale of manufacturing, especially regarding real-time release (RTR) models. Authors provide critical overview on the good modeling practices and introduce concepts of multiple-unit, adaptive and dynamic design space, multivariate specifications and methods for process uncertainty analysis. RTR specification with mathematical model and different approaches to multivariate statistical process control supporting process analytical technologies are also presented. Copyright © 2017 Elsevier B.V. All rights reserved.

Variations in Daily Sleep Quality and Type 1 Diabetes Management in Late Adolescents

PubMed Central

Queen, Tara L.; Butner, Jonathan; Wiebe, Deborah; Berg, Cynthia A.

2016-01-01

Objective To determine how between- and within-person variability in perceived sleep quality were associated with adolescent diabetes management. Methods A total of 236 older adolescents with type 1 diabetes reported daily for 2 weeks on sleep quality, self-regulatory failures, frequency of blood glucose (BG) checks, and BG values. Average, inconsistent, and daily deviations in sleep quality were examined. Results Hierarchical linear models indicated that poorer average and worse daily perceived sleep quality (compared with one’s average) was each associated with more self-regulatory failures. Sleep quality was not associated with frequency of BG checking. Poorer average sleep quality was related to greater risk of high BG. Furthermore, inconsistent and daily deviations in sleep quality interacted to predict higher BG, with more consistent sleepers benefitting more from a night of high-quality sleep. Conclusions Good, consistent sleep quality during late adolescence may benefit diabetes management by reducing self-regulatory failures and risk of high BG. PMID:26994852

A threshold method for immunological correlates of protection

PubMed Central

2013-01-01

Background Immunological correlates of protection are biological markers such as disease-specific antibodies which correlate with protection against disease and which are measurable with immunological assays. It is common in vaccine research and in setting immunization policy to rely on threshold values for the correlate where the accepted threshold differentiates between individuals who are considered to be protected against disease and those who are susceptible. Examples where thresholds are used include development of a new generation 13-valent pneumococcal conjugate vaccine which was required in clinical trials to meet accepted thresholds for the older 7-valent vaccine, and public health decision making on vaccination policy based on long-term maintenance of protective thresholds for Hepatitis A, rubella, measles, Japanese encephalitis and others. Despite widespread use of such thresholds in vaccine policy and research, few statistical approaches have been formally developed which specifically incorporate a threshold parameter in order to estimate the value of the protective threshold from data. Methods We propose a 3-parameter statistical model called the a:b model which incorporates parameters for a threshold and constant but different infection probabilities below and above the threshold estimated using profile likelihood or least squares methods. Evaluation of the estimated threshold can be performed by a significance test for the existence of a threshold using a modified likelihood ratio test which follows a chi-squared distribution with 3 degrees of freedom, and confidence intervals for the threshold can be obtained by bootstrapping. The model also permits assessment of relative risk of infection in patients achieving the threshold or not. Goodness-of-fit of the a:b model may be assessed using the Hosmer-Lemeshow approach. The model is applied to 15 datasets from published clinical trials on pertussis, respiratory syncytial virus and varicella. Results

The Threshold Level--For Schools?

ERIC Educational Resources Information Center

Lauerbach, Gerda

1979-01-01

Comments on the document "Threshold Level for Modern Language Learning Schools" (J. A. Van Ek, Strasbourg, 1976) and its appropriateness as a description of learning goals for the first years of foreign language teaching. Criticizes particularly the "reduced learning" concept, on which the threshold projects are based. (IFS/WGA)

Threshold Concepts and Information Literacy

ERIC Educational Resources Information Center

Townsend, Lori; Brunetti, Korey; Hofer, Amy R.

2011-01-01

What do we teach when we teach information literacy in higher education? This paper describes a pedagogical approach to information literacy that helps instructors focus content around transformative learning thresholds. The threshold concept framework holds promise for librarians because it grounds the instructor in the big ideas and underlying…

Methods for SBS Threshold Reduction

DTIC Science & Technology

1994-01-30

We have investigated methods for reducing the threshold for stimulated Brillouin scattering (SBS) using a frequency-narrowed Cr,Tm,Ho:YAG laser...operating at 2.12 micrometers. The SBS medium was carbon disulfide. Single-focus SBS and threshold reduction by using two foci, a loop, and a ring have

10 CFR 63.144 - Quality assurance program change.

Code of Federal Regulations, 2013 CFR

2013-01-01

... assurance program information that duplicates language in quality assurance regulatory guides and quality... 10 Energy 2 2013-01-01 2013-01-01 false Quality assurance program change. 63.144 Section 63.144... REPOSITORY AT YUCCA MOUNTAIN, NEVADA Quality Assurance § 63.144 Quality assurance program change. Changes to...

10 CFR 63.144 - Quality assurance program change.

Code of Federal Regulations, 2014 CFR

2014-01-01

... assurance program information that duplicates language in quality assurance regulatory guides and quality... 10 Energy 2 2014-01-01 2014-01-01 false Quality assurance program change. 63.144 Section 63.144... REPOSITORY AT YUCCA MOUNTAIN, NEVADA Quality Assurance § 63.144 Quality assurance program change. Changes to...

10 CFR 63.144 - Quality assurance program change.

Code of Federal Regulations, 2012 CFR

2012-01-01

... assurance program information that duplicates language in quality assurance regulatory guides and quality... 10 Energy 2 2012-01-01 2012-01-01 false Quality assurance program change. 63.144 Section 63.144... REPOSITORY AT YUCCA MOUNTAIN, NEVADA Quality Assurance § 63.144 Quality assurance program change. Changes to...

Deactivating stimulation sites based on low-rate thresholds improves spectral ripple and speech reception thresholds in cochlear implant users.

PubMed

Zhou, Ning

2017-03-01

The study examined whether the benefit of deactivating stimulation sites estimated to have broad neural excitation was attributed to improved spectral resolution in cochlear implant users. The subjects' spatial neural excitation pattern was estimated by measuring low-rate detection thresholds across the array [see Zhou (2016). PLoS One 11, e0165476]. Spectral resolution, as assessed by spectral-ripple discrimination thresholds, significantly improved after deactivation of five high-threshold sites. The magnitude of improvement in spectral-ripple discrimination thresholds predicted the magnitude of improvement in speech reception thresholds after deactivation. Results suggested that a smaller number of relatively independent channels provide a better outcome than using all channels that might interact.

SPATIAL PREDICTION OF AIR QUALITY DATA

EPA Science Inventory

Site-specific air quality monitoring data have been used extensively in both scientific and regulatory programs. As such, these data provide essential information to the public, environmental managers, and the atmospheric research community. Currently, air quality management prac...

Determination of quality factors by microdosimetry

NASA Astrophysics Data System (ADS)

Al-Affan, I. A. M.; Watt, D. E.

1987-03-01

The application of microdose parameters for the specification of a revised scale of quality factors which would be applicable at low doses and dose rates is examined in terms of an original proposal by Rossi. Two important modifications are suggested to enable an absolute scale of quality factors to be constructed. Allowance should be made to allow for the dependence of the saturation threshold of lineal energy on the type of heavy charged particle. Also, an artificial saturation threshold should be introduced for electron tracks as a mean of modifying the measurements made in the microdosimeter to the more realistic site sizes of nanometer dimensions. The proposed absolute scale of quality factors nicely encompasses the high RBEs of around 3 observed at low doses for tritium β rays and is consistent with the recent recommendation of the ICRP that the quality factor for fast neutrons be increased by a factor of two, assuming that there is no biological repair for the reference radiation.

Toxicogenomics: the challenges and opportunities to identify biomarkers, signatures and thresholds to support mode-of-action.

PubMed

Currie, Richard A

2012-08-15

Toxicogenomics (TGx) can be defined as the application of "omics" techniques to toxicology and risk assessment. By identifying molecular changes associated with toxicity, TGx data might assist hazard identification and investigate causes. Early technical challenges were evaluated and addressed by consortia (e.g. ISLI/HESI and the Microarray Quality Control consortium), which demonstrated that TGx gave reliable and reproducible information. The MAQC also produced "best practice on signature generation" after conducting an extensive evaluation of different methods on common datasets. Two findings of note were the need for methods that control batch variability, and that the predictive ability of a signature changes in concert with the variability of the endpoint. The key challenge remaining is data interpretation, because TGx can identify molecular changes that are causal, associated with or incidental to toxicity. Application of Bradford Hill's tests for causation, which are used to build mode of action (MOA) arguments, can produce reasonable hypotheses linking altered pathways to phenotypic changes. However, challenges in interpretation still remain: are all pathway changes equal, which are most important and plausibly linked to toxicity? Therefore the expert judgement of the toxicologist is still needed. There are theoretical reasons why consistent alterations across a metabolic pathway are important, but similar changes in signalling pathways may not alter information flow. At the molecular level thresholds may be due to the inherent properties of the regulatory network, for example switch-like behaviours from some network motifs (e.g. positive feedback) in the perturbed pathway leading to the toxicity. The application of systems biology methods to TGx data can generate hypotheses that explain why a threshold response exists. However, are we adequately trained to make these judgments? There is a need for collaborative efforts between regulators, industry and

24 CFR 594.7 - Other threshold requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Other threshold requirements. 594.7 Section 594.7 Housing and Urban Development Regulations Relating to Housing and Urban Development... Other threshold requirements. In addition, an applicant must meet the following threshold requirements...

Maps showing predicted probabilities for selected dissolved oxygen and dissolved manganese threshold events in depth zones used by the domestic and public drinking water supply wells, Central Valley, California

USGS Publications Warehouse

Rosecrans, Celia Z.; Nolan, Bernard T.; Gronberg, JoAnn M.

2018-01-31

The purpose of the prediction grids for selected redox constituents—dissolved oxygen and dissolved manganese—are intended to provide an understanding of groundwater-quality conditions at the domestic and public-supply drinking water depths. The chemical quality of groundwater and the fate of many contaminants is influenced by redox processes in all aquifers, and understanding the redox conditions horizontally and vertically is critical in evaluating groundwater quality. The redox condition of groundwater—whether oxic (oxygen present) or anoxic (oxygen absent)—strongly influences the oxidation state of a chemical in groundwater. The anoxic dissolved oxygen thresholds of <0.5 milligram per liter (mg/L), <1.0 mg/L, and <2.0 mg/L were selected to apply broadly to regional groundwater-quality investigations. Although the presence of dissolved manganese in groundwater indicates strongly reducing (anoxic) groundwater conditions, it is also considered a “nuisance” constituent in drinking water, making drinking water undesirable with respect to taste, staining, or scaling. Three dissolved manganese thresholds, <50 micrograms per liter (µg/L), <150 µg/L, and <300 µg/L, were selected to create predicted probabilities of exceedances in depth zones used by domestic and public-supply water wells. The 50 µg/L event threshold represents the secondary maximum contaminant level (SMCL) benchmark for manganese (U.S. Environmental Protection Agency, 2017; California Division of Drinking Water, 2014), whereas the 300 µg/L event threshold represents the U.S. Geological Survey (USGS) health-based screening level (HBSL) benchmark, used to put measured concentrations of drinking-water contaminants into a human-health context (Toccalino and others, 2014). The 150 µg/L event threshold represents one-half the USGS HBSL. The resultant dissolved oxygen and dissolved manganese prediction grids may be of interest to water-resource managers, water-quality researchers, and

Rainfall thresholds for possible landslide occurrence in Italy

NASA Astrophysics Data System (ADS)

Peruccacci, Silvia; Brunetti, Maria Teresa; Gariano, Stefano Luigi; Melillo, Massimo; Rossi, Mauro; Guzzetti, Fausto

2017-08-01

The large physiographic variability and the abundance of landslide and rainfall data make Italy an ideal site to investigate variations in the rainfall conditions that can result in rainfall-induced landslides. We used landslide information obtained from multiple sources and rainfall data captured by 2228 rain gauges to build a catalogue of 2309 rainfall events with - mostly shallow - landslides in Italy between January 1996 and February 2014. For each rainfall event with landslides, we reconstructed the rainfall history that presumably caused the slope failure, and we determined the corresponding rainfall duration D (in hours) and cumulated event rainfall E (in mm). Adopting a power law threshold model, we determined cumulated event rainfall-rainfall duration (ED) thresholds, at 5% exceedance probability, and their uncertainty. We defined a new national threshold for Italy, and 26 regional thresholds for environmental subdivisions based on topography, lithology, land-use, land cover, climate, and meteorology, and we used the thresholds to study the variations of the rainfall conditions that can result in landslides in different environments, in Italy. We found that the national and the environmental thresholds cover a small part of the possible DE domain. The finding supports the use of empirical rainfall thresholds for landslide forecasting in Italy, but poses an empirical limitation to the possibility of defining thresholds for small geographical areas. We observed differences between some of the thresholds. With increasing mean annual precipitation (MAP), the thresholds become higher and steeper, indicating that more rainfall is needed to trigger landslides where the MAP is high than where it is low. This suggests that the landscape adjusts to the regional meteorological conditions. We also observed that the thresholds are higher for stronger rocks, and that forested areas require more rainfall than agricultural areas to initiate landslides. Finally, we

Identification of Effects of Regulatory Actions on Air Quality in Goods Movement Corridors in California.

PubMed

Su, Jason G; Meng, Ying-Ying; Pickett, Melissa; Seto, Edmund; Ritz, Beate; Jerrett, Michael

2016-08-16

Few studies have assessed the impact of regulatory actions on air quality improvement through a comprehensive monitoring effort. In this study, we designed saturation sampling of nitrogen oxides (NOX) for the counties of Los Angeles and Alameda (San Francisco Bay) before (2003-2007) and after (2008-2013) implementation of goods movement actions in California. We further separated the research regions into three location categories, including goods movement corridors (GMCs), nongoods movement corridors (NGMCs), and control areas (CTRLs). Linear mixed models were developed to identify whether reductions in NOX were greater in GMCs than in other areas, after controlling for potential confounding, including weather conditions (e.g., wind speed and temperature) and season of sampling. We also considered factors that might confound the relationship, including traffic and cargo volumes that may have changed due to economic downturn impacts. Compared to the pre-policy period, we found reductions of average pollutant concentrations for nitrogen dioxide (NO2) and NOX in GMCs of 6.4 and 21.7 ppb. The reductions were smaller in NGMCs (5.9 and 16.3 ppb, respectively) and in CTRLs (4.6 and 12.1 ppb, respectively). After controlling for potential confounding from weather conditions, season of sampling, and the economic downturn in 2008, the linear mixed models demonstrated that reductions in NO2 and NOX were significantly greater in GMCs compared to reductions observed in CTRLs; there were no statistically significant differences between NGMCs and CTRLs. These results indicate that policies regulating goods movement are achieving the desired outcome of improving air quality for the state, particularly in goods movement corridors where most disadvantaged communities live.

Threshold Hypothesis: Fact or Artifact?

ERIC Educational Resources Information Center

Karwowski, Maciej; Gralewski, Jacek

2013-01-01

The threshold hypothesis (TH) assumes the existence of complex relations between creative abilities and intelligence: linear associations below 120 points of IQ and weaker or lack of associations above the threshold. However, diverse results have been obtained over the last six decades--some confirmed the hypothesis and some rejected it. In this…

The Nature of Psychological Thresholds

ERIC Educational Resources Information Center

Rouder, Jeffrey N.; Morey, Richard D.

2009-01-01

Following G. T. Fechner (1966), thresholds have been conceptualized as the amount of intensity needed to transition between mental states, such as between a states of unconsciousness and consciousness. With the advent of the theory of signal detection, however, discrete-state theory and the corresponding notion of threshold have been discounted.…

Objectives, Budgets, Thresholds, and Opportunity Costs-A Health Economics Approach: An ISPOR Special Task Force Report [4].

PubMed

Danzon, Patricia M; Drummond, Michael F; Towse, Adrian; Pauly, Mark V

2018-02-01

The fourth section of our Special Task Force report focuses on a health plan or payer's technology adoption or reimbursement decision, given the array of technologies, on the basis of their different values and costs. We discuss the role of budgets, thresholds, opportunity costs, and affordability in making decisions. First, we discuss the use of budgets and thresholds in private and public health plans, their interdependence, and connection to opportunity cost. Essentially, each payer should adopt a decision rule about what is good value for money given their budget; consistent use of a cost-per-quality-adjusted life-year threshold will ensure the maximum health gain for the budget. In the United States, different public and private insurance programs could use different thresholds, reflecting the differing generosity of their budgets and implying different levels of access to technologies. In addition, different insurance plans could consider different additional elements to the quality-adjusted life-year metric discussed elsewhere in our Special Task Force report. We then define affordability and discuss approaches to deal with it, including consideration of disinvestment and related adjustment costs, the impact of delaying new technologies, and comparative cost effectiveness of technologies. Over time, the availability of new technologies may increase the amount that populations want to spend on health care. We then discuss potential modifiers to thresholds, including uncertainty about the evidence used in the decision-making process. This article concludes by discussing the application of these concepts in the context of the pluralistic US health care system, as well as the "excess burden" of tax-financed public programs versus private programs. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Clinical guidelines in the European Union: mapping the regulatory basis, development, quality control, implementation and evaluation across member states.

PubMed

Legido-Quigley, Helena; Panteli, Dimitra; Brusamento, Serena; Knai, Cécile; Saliba, Vanessa; Turk, Eva; Solé, Meritxell; Augustin, Uta; Car, Josip; McKee, Martin; Busse, Reinhard

2012-10-01

Clinical guidelines are advocated to improve the quality of care, especially for chronic diseases. However, the regulatory basis of clinical guidelines, their development, quality control, implementation and use as well as evaluation within countries across the European Union is not systematically known. Using information collected from key informants in each country by means of a structured questionnaire, this mapping exercise illustrates the varied status of guideline production in European Union countries. Most European Union countries have an established national, regional or local clinical guideline programme, and a substantial proportion have developed guidelines on the prevention and management of chronic diseases. Several countries have mechanisms in place to ensure the quality of scientific evidence used for the development of guidelines is high and that the process is consistent and transparent. Others are only now taking an interest in guideline development and are taking the first steps towards establishing ways of implementing them. The majority of countries have no legal basis for the development of guidelines and those that have well established systems mostly implement them on a voluntary basis. The process of guideline development varies in its degrees of decentralisation across countries with many different types of organisations taking on this responsibility. There is general acceptance of the value of the instrument developed by the AGREE collaboration for evaluating the methodological robustness of guidelines. However, the extent to which guidelines are implemented in Europe is unknown, as there is no systematic data collection and, in most countries, no structure to enable it. There are few examples of formal evaluations of the development, quality, implementation and use of guidelines. Our findings call for renewed efforts to respond to the severe lack of standardized guideline terminology and accessibility as well as rigorous studies to

[The analysis of threshold effect using Empower Stats software].

PubMed

Lin, Lin; Chen, Chang-zhong; Yu, Xiao-dan

2013-11-01

In many studies about biomedical research factors influence on the outcome variable, it has no influence or has a positive effect within a certain range. Exceeding a certain threshold value, the size of the effect and/or orientation will change, which called threshold effect. Whether there are threshold effects in the analysis of factors (x) on the outcome variable (y), it can be observed through a smooth curve fitting to see whether there is a piecewise linear relationship. And then using segmented regression model, LRT test and Bootstrap resampling method to analyze the threshold effect. Empower Stats software developed by American X & Y Solutions Inc has a threshold effect analysis module. You can input the threshold value at a given threshold segmentation simulated data. You may not input the threshold, but determined the optimal threshold analog data by the software automatically, and calculated the threshold confidence intervals.

Threshold altitude resulting in decompression sickness

NASA Technical Reports Server (NTRS)

Kumar, K. V.; Waligora, James M.; Calkins, Dick S.

1990-01-01

A review of case reports, hypobaric chamber training data, and experimental evidence indicated that the threshold for incidence of altitude decompression sickness (DCS) was influenced by various factors such as prior denitrogenation, exercise or rest, and period of exposure, in addition to individual susceptibility. Fitting these data with appropriate statistical models makes it possible to examine the influence of various factors on the threshold for DCS. This approach was illustrated by logistic regression analysis on the incidence of DCS below 9144 m. Estimations using these regressions showed that, under a noprebreathe, 6-h exposure, simulated EVA profile, the threshold for symptoms occurred at approximately 3353 m; while under a noprebreathe, 2-h exposure profile with knee-bends exercise, the threshold occurred at 7925 m.

Optimizing the European regulatory framework for sustainable bacteriophage therapy in human medicine.

PubMed

Verbeken, Gilbert; Pirnay, Jean-Paul; De Vos, Daniel; Jennes, Serge; Zizi, Martin; Lavigne, Rob; Casteels, Minne; Huys, Isabelle

2012-06-01

For practitioners at hospitals seeking to use natural (not genetically modified, as appearing in nature) bacteriophages for treatment of antibiotic-resistant bacterial infections (bacteriophage therapy), Europe's current regulatory framework for medicinal products hinders more than it facilitates. Although many experts consider bacteriophage therapy to be a promising complementary (or alternative) treatment to antibiotic therapy, no bacteriophage-specific framework for documentation exists to date. Decades worth of historical clinical data on bacteriophage therapy (from Eastern Europe, particularly Poland, and the former Soviet republics, particularly Georgia and Russia, as well as from today's 27 EU member states and the US) have not been taken into account by European regulators because these data have not been validated under current Western regulatory standards. Consequently, applicants carrying out standard clinical trials on bacteriophages in Europe are obliged to initiate clinical work from scratch. This paper argues for a reduced documentation threshold for Phase 1 clinical trials of bacteriophages and maintains that bacteriophages should not be categorized as classical medicinal products for at least two reasons: (1) such a categorization is scientifically inappropriate for this specific therapy and (2) such a categorization limits the marketing authorization process to industry, the only stakeholder with sufficient financial resources to prepare a complete dossier for the competent authorities. This paper reflects on the current regulatory framework for medicines in Europe and assesses possible regulatory pathways for the (re-)introduction of bacteriophage therapy in a way that maintains its effectiveness and safety as well as its inherent characteristics of sustainability and in situ self-amplification and limitation.

High-frequency (8 to 16 kHz) reference thresholds and intrasubject threshold variability relative to ototoxicity criteria using a Sennheiser HDA 200 earphone.

PubMed

Frank, T

2001-04-01

The first purpose of this study was to determine high-frequency (8 to 16 kHz) thresholds for standardizing reference equivalent threshold sound pressure levels (RETSPLs) for a Sennheiser HDA 200 earphone. The second and perhaps more important purpose of this study was to determine whether repeated high-frequency thresholds using a Sennheiser HDA 200 earphone had a lower intrasubject threshold variability than the ASHA 1994 significant threshold shift criteria for ototoxicity. High-frequency thresholds (8 to 16 kHz) were obtained for 100 (50 male, 50 female) normally hearing (0.25 to 8 kHz) young adults (mean age of 21.2 yr) in four separate test sessions using a Sennheiser HDA 200 earphone. The mean and median high-frequency thresholds were similar for each test session and increased as frequency increased. At each frequency, the high-frequency thresholds were not significantly (p > 0.05) different for gender, test ear, or test session. The median thresholds at each frequency were similar to the 1998 interim ISO RETSPLs; however, large standard deviations and wide threshold distributions indicated very high intersubject threshold variability, especially at 14 and 16 kHz. Threshold repeatability was determined by finding the threshold differences between each possible test session comparison (N = 6). About 98% of all of the threshold differences were within a clinically acceptable range of +/-10 dB from 8 to 14 kHz. The threshold differences between each subject's second, third, and fourth minus their first test session were also found to determine whether intrasubject threshold variability was less than the ASHA 1994 criteria for determining a significant threshold shift due to ototoxicity. The results indicated a false-positive rate of 0% for a threshold shift > or = 20 dB at any frequency and a false-positive rate of 2% for a threshold shift >10 dB at two consecutive frequencies. This study verified that the output of high-frequency audiometers at 0 dB HL using

From molecule to market access: drug regulatory science as an upcoming discipline.

PubMed

Gispen-de Wied, Christine C; Leufkens, Hubertus G M

2013-11-05

Regulatory science as a discipline has evolved over the past years with the object to boost and promote scientific rationale behind benefit/risk and decision making by regulatory authorities. The European Medicines Agency, EMA, the Food and Drug Administration, FDA, and the Japanese Pharmaceutical and Medical Devices Agency, PMDA, highlighted in their distinct ways the importance of regulatory science as a basis of good quality assessment in their strategic plans. The Medicines Evaluation Board, MEB, states: 'regulatory science is the science of developing and validating new standards and tools to evaluate and assess the benefit/risk of medicinal products, facilitating sound and transparent regulatory decision making'. Through analysis of regulatory frameworks itself and their effectiveness, however, regulatory science can also advance knowledge of these systems in general. The comprehensive guidance that is issued to complete an application dossier for regulatory product approval has seldomly been scrutinized for its efficiency. Since it is the task of regulatory authorities to protect and promote public health, it is understood that they take a cautious approach in regulating drugs prior to market access. In general, the authorities are among the first to be blamed if dangerous or useless drugs were allowed to the market. Yet, building a regulatory framework that is not challenged continuously in terms of deliverables for public health and cost-effectiveness, might be counterproductive in the end. Regulatory science and research can help understand how and why regulatory decisions are made, and where renewed discussions may be warranted. The MEB supports regulatory science as an R&D activity to fuel primary regulatory processes on product evaluation and vigilance, but also invests in a 'looking into the mirror' approach. Along the line of the drug life-cycle, publicly available data are reviewed and their regulatory impact highlighted. If made explicit

78 FR 7816 - Quality Assurance Program Requirements (Operations)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-04

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0021] Quality Assurance Program Requirements (Operations...), DG-1300, ``Quality Assurance Program Requirements (Operations).'' DATES: Submit comments by April 1... CFR Part 50, Appendix B, ``Quality Assurance Criteria for Nuclear power Plants and Fuel Reprocessing...

Thermotactile perception thresholds measurement conditions.

PubMed

Maeda, Setsuo; Sakakibara, Hisataka

2002-10-01

The purpose of this paper is to investigate the effects of posture, push force and rate of temperature change on thermotactile thresholds and to clarify suitable measuring conditions for Japanese people. Thermotactile (warm and cold) thresholds on the right middle finger were measured with an HVLab thermal aesthesiometer. Subjects were eight healthy male Japanese students. The effects of posture in measurement were examined in the posture of a straight hand and forearm placed on a support, the same posture without a support, and the fingers and hand flexed at the wrist with the elbow placed on a desk. The finger push force applied to the applicator of the thermal aesthesiometer was controlled at a 0.5, 1.0, 2.0 and 3.0 N. The applicator temperature was changed to 0.5, 1.0, 1.5, 2.0 and 2.5 degrees C/s. After each measurement, subjects were asked about comfort under the measuring conditions. Three series of experiments were conducted on different days to evaluate repeatability. Repeated measures ANOVA showed that warm thresholds were affected by the push force and the rate of temperature change and that cold thresholds were influenced by posture and push force. The comfort assessment indicated that the measurement posture of a straight hand and forearm laid on a support was the most comfortable for the subjects. Relatively high repeatability was obtained under measurement conditions of a 1 degrees C/s temperature change rate and a 0.5 N push force. Measurement posture, push force and rate of temperature change can affect the thermal threshold. Judging from the repeatability, a push force of 0.5 N and a temperature change of 1.0 degrees C/s in the posture with the straight hand and forearm laid on a support are recommended for warm and cold threshold measurements.

10 CFR 71.135 - Quality assurance records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Quality assurance records. 71.135 Section 71.135 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PACKAGING AND TRANSPORTATION OF RADIOACTIVE MATERIAL Quality Assurance § 71.135 Quality assurance records. The licensee, certificate holder, and applicant for a CoC...

20 CFR 418.2105 - What is the threshold?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false What is the threshold? 418.2105 Section 418... Adjustment Amount § 418.2105 What is the threshold? (a) The threshold is a level of modified adjusted gross... years 2011 through and including 2019, the modified adjusted gross income threshold is $85,000 for...

20 CFR 418.1105 - What is the threshold?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false What is the threshold? 418.1105 Section 418... What is the threshold? (a) The threshold is a level of modified adjusted gross income above which the... gross income threshold is $80,000 for individuals with a Federal income tax filing status of single...

24 CFR 599.301 - Initial determination of threshold requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Initial determination of threshold... Nominating Renewal Communities § 599.301 Initial determination of threshold requirements. (a) Two threshold... meets both of the following thresholds: (1) Eligibility of the nominated area. This threshold is met if...

RSAT 2018: regulatory sequence analysis tools 20th anniversary.

PubMed

Nguyen, Nga Thi Thuy; Contreras-Moreira, Bruno; Castro-Mondragon, Jaime A; Santana-Garcia, Walter; Ossio, Raul; Robles-Espinoza, Carla Daniela; Bahin, Mathieu; Collombet, Samuel; Vincens, Pierre; Thieffry, Denis; van Helden, Jacques; Medina-Rivera, Alejandra; Thomas-Chollier, Morgane

2018-05-02

RSAT (Regulatory Sequence Analysis Tools) is a suite of modular tools for the detection and the analysis of cis-regulatory elements in genome sequences. Its main applications are (i) motif discovery, including from genome-wide datasets like ChIP-seq/ATAC-seq, (ii) motif scanning, (iii) motif analysis (quality assessment, comparisons and clustering), (iv) analysis of regulatory variations, (v) comparative genomics. Six public servers jointly support 10 000 genomes from all kingdoms. Six novel or refactored programs have been added since the 2015 NAR Web Software Issue, including updated programs to analyse regulatory variants (retrieve-variation-seq, variation-scan, convert-variations), along with tools to extract sequences from a list of coordinates (retrieve-seq-bed), to select motifs from motif collections (retrieve-matrix), and to extract orthologs based on Ensembl Compara (get-orthologs-compara). Three use cases illustrate the integration of new and refactored tools to the suite. This Anniversary update gives a 20-year perspective on the software suite. RSAT is well-documented and available through Web sites, SOAP/WSDL (Simple Object Access Protocol/Web Services Description Language) web services, virtual machines and stand-alone programs at http://www.rsat.eu/.

ECG signal performance de-noising assessment based on threshold tuning of dual-tree wavelet transform.

PubMed

El B'charri, Oussama; Latif, Rachid; Elmansouri, Khalifa; Abenaou, Abdenbi; Jenkal, Wissam

2017-02-07

Since the electrocardiogram (ECG) signal has a low frequency and a weak amplitude, it is sensitive to miscellaneous mixed noises, which may reduce the diagnostic accuracy and hinder the physician's correct decision on patients. The dual tree wavelet transform (DT-WT) is one of the most recent enhanced versions of discrete wavelet transform. However, threshold tuning on this method for noise removal from ECG signal has not been investigated yet. In this work, we shall provide a comprehensive study on the impact of the choice of threshold algorithm, threshold value, and the appropriate wavelet decomposition level to evaluate the ECG signal de-noising performance. A set of simulations is performed on both synthetic and real ECG signals to achieve the promised results. First, the synthetic ECG signal is used to observe the algorithm response. The evaluation results of synthetic ECG signal corrupted by various types of noise has showed that the modified unified threshold and wavelet hyperbolic threshold de-noising method is better in realistic and colored noises. The tuned threshold is then used on real ECG signals from the MIT-BIH database. The results has shown that the proposed method achieves higher performance than the ordinary dual tree wavelet transform into all kinds of noise removal from ECG signal. The simulation results indicate that the algorithm is robust for all kinds of noises with varying degrees of input noise, providing a high quality clean signal. Moreover, the algorithm is quite simple and can be used in real time ECG monitoring.

Olfactory Threshold of Chlorine in Oxygen.

DTIC Science & Technology

1977-09-01

The odor threshold of chlorine in oxygen was determined. Measurements were conducted in an altitude chamber, which provided an odor-free and noise...free background. Human male volunteers, with no previous olfactory acuity testing experience, served as panelists. Threshold values were affected by...time intervals between trials and by age differences. The mean threshold value for 11 subjects was 0.08 ppm obtained by positive responses to the lowest detectable level of chlorine in oxygen, 50% of the time. (Author)

Do We Need Plant Food Supplements? A Critical Examination of Quality, Safety, Efficacy, and Necessity for a New Regulatory Framework.

PubMed

Abdel-Tawab, Mona

2018-04-01

Given the expanding market of plant food supplements (PFSs) not undergoing any pre-marketing authorization, the overall quality, safety and efficacy of PFSs were subjected to a critical examination. Although many high-quality PFSs exist on the legal market, quality concerns are in general justified. Besides economic adulteration, active ingredients dramatically differing from label claims and among products were reported in several studies. In addition, PFSs sold via the Internet may be intentionally adulterated with undeclared prescription drugs. Compared to PFSs with only one single herb, PFSs containing herbal mixtures were more involved in moderate and severe clinical courses. Although prohibited by regulation, misleading labels on PFSs are common. Above all, only vague evidence for the efficacy of PFSs exists. Notwithstanding the unproven efficacy and insufficient safety assessment, PFSs represent a relevant source for consumers to get access to herbal preparations in the United States and meanwhile also in Europe, as launching of licensed/registered European herbal medicinal products (HMPs) has steadily decreased. However, being non-vitamin, non-mineral products, PFSs are neither food nor drugs. In terms of protecting public health and providing the consumer with high-quality, effective, and safe PFSs, possibilities are shown how to deal with the many challenges of PFSs. Last but not least, suggestions are made for assigning PFSs a separate regulatory category being less regulated compared to HMPs but more strictly regulated compared to food laws including implementation of good manufacturing practices and a scientific pre-marketing review process by an expert commission. Georg Thieme Verlag KG Stuttgart · New York.

The drug regulatory and review process in Guyana.

PubMed

Woo-Ming, R B

1993-01-01

After the old "Sale of Food and Drugs" Ordinance, Cap. 144 was repealed, the new Food and Drugs Act was enacted in 1971. This new Act has considerable flexibility and gives the Minister extensive authority to make Regulations (for carrying out the purposes and provisions of the Act). The Act controls the manufacture, importation, sale, advertising, labeling, packaging, and distribution of drug samples, and the testing of drugs. The Act also controls raw materials and finished products of drugs at the point of entry into the country, with a single agency coordinating both the inspection and analytical services. Developing countries could ensure the procurement of safe, good quality, and effective drugs and devices with the enactment of a similar Food and Drugs Act only. Rapid assessment of Drug Safety, Quality and Efficacy is done through Guyana's participation in the WHO Certification Scheme on the Quality of Pharmaceutical Products moving in International Commerce. This certification scheme is highly commendable especially to third-world countries. The Food and Drug Regulations (1977) have several unique features for drug, cosmetic and device control and they allow for a system of centralized control with limited staff to enforce the legislation. In summary, enforcement of legislative control of imported pharmaceuticals and product evaluation can be considered strong points in the drug regulatory and review process in Guyana. A cautious attitude is observed so as to ensure efficacy, safety, and quality of drugs entering the market. This Drug Regulatory and Review Process is recommended for implementation by third-world countries with outdated drug legislation.(ABSTRACT TRUNCATED AT 250 WORDS)

Fronting Integrated Scientific Web Applications: Design Features and Benefits for Regulatory Environments

EPA Science Inventory

Integrated decision support systems for regulatory applications benefit from standardindustry practices such as code reuse, test-driven development, and modularization. Theseapproaches make meeting the federal government’s goals of transparency, efficiency, and quality assurance ...

Investigation of Service Quality of Measurement Reference Points for the Internet Services on Mobile Networks

NASA Astrophysics Data System (ADS)

Lipenbergs, E.; Bobrovs, Vj.; Ivanovs, G.

2016-10-01

To ensure that end-users and consumers have access to comprehensive, comparable and user-friendly information regarding the Internet access service quality, it is necessary to implement and regularly renew a set of legislative regulatory acts and to provide monitoring of the quality of Internet access services regarding the current European Regulatory Framework. The actual situation regarding the quality of service monitoring solutions in different European countries depends on national regulatory initiatives and public awareness. The service monitoring solutions are implemented using different measurement methodologies and tools. The paper investigates the practical implementations for developing a harmonising approach to quality monitoring in order to obtain objective information on the quality of Internet access services on mobile networks.

Translucency thresholds for dental materials.

PubMed

Salas, Marianne; Lucena, Cristina; Herrera, Luis Javier; Yebra, Ana; Della Bona, Alvaro; Pérez, María M

2018-05-12

To determine the translucency acceptability and perceptibility thresholds for dental resin composites using CIEDE2000 and CIELAB color difference formulas. A 30-observer panel performed perceptibility and acceptability judgments on 50 pairs of resin composites discs (diameter: 10mm; thickness: 1mm). Disc pair differences for the Translucency Parameter (ΔTP) were calculated using both color difference formulas (ΔTP 00 ranged from 0.11 to 7.98, and ΔTP ab ranged from 0.01 to 12.79). A Takagi-Sugeno-Kang (TSK) Fuzzy Approximation was used as fitting procedure. From the resultant fitting curves, the 95% confidence intervals were estimated and the 50:50% translucency perceptibility and acceptability thresholds (TPT and TAT) were calculated. Differences between thresholds were statistically analyzed using Student t tests (α=0.05). CIEDE2000 50:50% TPT was 0.62 and TAT was 2.62. Corresponding CIELAB values were 1.33 and 4.43, respectively. Translucency perceptibility and acceptability thresholds were significantly different using both color difference formulas (p=0.01 for TPT and p=0.005 for TAT). CIEDE2000 color difference formula provided a better data fit than CIELAB formula. The visual translucency difference thresholds determined with CIEDE2000 color difference formula can serve as reference values in the selection of resin composites and evaluation of its clinical performance. Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

Pressure and cold pain threshold reference values in a large, young adult, pain-free population.

PubMed

Waller, Robert; Smith, Anne Julia; O'Sullivan, Peter Bruce; Slater, Helen; Sterling, Michele; McVeigh, Joanne Alexandra; Straker, Leon Melville

2016-10-01

Currently there is a lack of large population studies that have investigated pain sensitivity distributions in healthy pain free people. The aims of this study were: (1) to provide sex-specific reference values of pressure and cold pain thresholds in young pain-free adults; (2) to examine the association of potential correlates of pain sensitivity with pain threshold values. This study investigated sex specific pressure and cold pain threshold estimates for young pain free adults aged 21-24 years. A cross-sectional design was utilised using participants (n=617) from the Western Australian Pregnancy Cohort (Raine) Study at the 22-year follow-up. The association of site, sex, height, weight, smoking, health related quality of life, psychological measures and activity with pain threshold values was examined. Pressure pain threshold (lumbar spine, tibialis anterior, neck and dorsal wrist) and cold pain threshold (dorsal wrist) were assessed using standardised quantitative sensory testing protocols. Reference values for pressure pain threshold (four body sites) stratified by sex and site, and cold pain threshold (dorsal wrist) stratified by sex are provided. Statistically significant, independent correlates of increased pressure pain sensitivity measures were site (neck, dorsal wrist), sex (female), higher waist-hip ratio and poorer mental health. Statistically significant, independent correlates of increased cold pain sensitivity measures were, sex (female), poorer mental health and smoking. These data provide the most comprehensive and robust sex specific reference values for pressure pain threshold specific to four body sites and cold pain threshold at the dorsal wrist for young adults aged 21-24 years. Establishing normative values in this young age group is important given that the transition from adolescence to adulthood is a critical temporal period during which trajectories for persistent pain can be established. These data will provide an important research

Thresholds in chemical respiratory sensitisation.

PubMed

Cochrane, Stella A; Arts, Josje H E; Ehnes, Colin; Hindle, Stuart; Hollnagel, Heli M; Poole, Alan; Suto, Hidenori; Kimber, Ian

2015-07-03

There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the

Steering healthcare service delivery: a regulatory perspective.

PubMed

Prakash, Gyan

2015-01-01

The purpose of this paper is to explore regulation in India's healthcare sector and makes recommendations needed for enhancing the healthcare service. The literature was reviewed to understand healthcare's regulatory context. To understand the current healthcare system, qualitative data were collected from state-level officials, public and private hospital staff. A patient survey was performed to assess service quality (QoS). Regulation plays a central role in driving healthcare QoS. India needs to strengthen market and institutional co-production based approaches for steering its healthcare in which delivery processes are complex and pose different challenges. This study assesses current healthcare regulation in an Indian state and presents a framework for studying and strengthening regulation. Agile regulation should be based on service delivery issues (pull approach) rather than monitoring and sanctions based regulatory environment (push approach). Healthcare pitfalls across the world seem to follow similar follies. India's complexity and experience is useful for emerging and developed economies. The author reviewed around 70 publications and synthesised them in healthcare regulatory contexts. Patient's perception of private providers could be a key input towards steering regulation. Identifying gaps across QoS dimensions would be useful in taking corrective measures.

10 CFR 71.105 - Quality assurance program.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Quality assurance program. 71.105 Section 71.105 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PACKAGING AND TRANSPORTATION OF RADIOACTIVE MATERIAL Quality Assurance § 71.105 Quality assurance program. (a) The licensee, certificate holder, and applicant for a CoC...

Fractal Approach to Erosion Threshold of Bentonites

NASA Astrophysics Data System (ADS)

Xu, Y. F.; Li, X. Y.

Bentonite has been considered as a candidate buffer material for the disposal of high-level radioactive waste (HLW) because of its low permeability, high sorption capacity, self-sealing characteristics and durability in a natural environment. Bentonite erosion caused by groundwater flow may take place at the interface of the compacted bentonite and fractured granite. Surface erosion of bentonite flocs is represented typically as an erosion threshold. Predicting the erosion threshold of bentonite flocs requires taking into account cohesion, which results from interactions between clay particles. Beyond the usual dependence on grain size, a significant correlation between erosion threshold and porosity measurements is confirmed for bentonite flocs. A fractal model for erosion threshold of bentonite flocs is proposed. Cohesion forces, the long-range van der Waals interaction between two clay particles are taken as the resource of the erosion threshold. The model verification is conducted by the comparison with experiments published in the literature. The results show that the proposed model for erosion threshold is in good agreement with the experimental data.

Self-adjusting threshold mechanism for pixel detectors

NASA Astrophysics Data System (ADS)

Heim, Timon; Garcia-Sciveres, Maurice

2017-09-01

Readout chips of hybrid pixel detectors use a low power amplifier and threshold discrimination to process charge deposited in semiconductor sensors. Due to transistor mismatch each pixel circuit needs to be calibrated individually to achieve response uniformity. Traditionally this is addressed by programmable threshold trimming in each pixel, but requires robustness against radiation effects, temperature, and time. In this paper a self-adjusting threshold mechanism is presented, which corrects the threshold for both spatial inequality and time variation and maintains a constant response. It exploits the electrical noise as relative measure for the threshold and automatically adjust the threshold of each pixel to always achieve a uniform frequency of noise hits. A digital implementation of the method in the form of an up/down counter and combinatorial logic filter is presented. The behavior of this circuit has been simulated to evaluate its performance and compare it to traditional calibration results. The simulation results show that this mechanism can perform equally well, but eliminates instability over time and is immune to single event upsets.

Quality of clinical trials: A moving target

PubMed Central

Bhatt, Arun

2011-01-01

Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials. PMID:22145122

Double Threshold Energy Detection Based Cooperative Spectrum Sensing for Cognitive Radio Networks with QoS Guarantee

NASA Astrophysics Data System (ADS)

Hu, Hang; Yu, Hong; Zhang, Yongzhi

2013-03-01

Cooperative spectrum sensing, which can greatly improve the ability of discovering the spectrum opportunities, is regarded as an enabling mechanism for cognitive radio (CR) networks. In this paper, we employ a double threshold detection method in energy detector to perform spectrum sensing, only the CR users with reliable sensing information are allowed to transmit one bit local decision to the fusion center. Simulation results will show that our proposed double threshold detection method could not only improve the sensing performance but also save the bandwidth of the reporting channel compared with the conventional detection method with one threshold. By weighting the sensing performance and the consumption of system resources in a utility function that is maximized with respect to the number of CR users, it has been shown that the optimal number of CR users is related to the price of these Quality-of-Service (QoS) requirements.

Compositional threshold for Nuclear Waste Glass Durability

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

Kruger, Albert A.; Farooqi, Rahmatullah; Hrma, Pavel R.

2013-04-24

Within the composition space of glasses, a distinct threshold appears to exist that separates "good" glasses, i.e., those which are sufficiently durable, from "bad" glasses of a low durability. The objective of our research is to clarify the origin of this threshold by exploring the relationship between glass composition, glass structure and chemical durability around the threshold region.

The Irish Cost-Effectiveness Threshold: Does it Support Rational Rationing or Might it Lead to Unintended Harm to Ireland's Health System?

PubMed

O'Mahony, James F; Coughlan, Diarmuid

2016-01-01

Ireland is one of the few countries worldwide to have an explicit cost-effectiveness threshold. In 2012, an agreement between government and the pharmaceutical industry that provided substantial savings on existing medications set the threshold at €45,000/quality-adjusted life-year (QALY). This replaced a previously unofficial threshold of €20,000/QALY. According to the agreement, drugs within the threshold will be granted reimbursement, whereas those exceeding it may still be approved following further negotiation. A number of drugs far exceeding the threshold have been approved recently. The agreement only applies to pharmaceuticals. There are four reasons for concern regarding Ireland's threshold. The absence of an explicit threshold for non-drug interventions leaves it unclear if there is parity in willingness to pay across all interventions. As the threshold resembles a price floor rather than a ceiling, in principle it only offers a weak barrier to cost-ineffective interventions. It has no empirical basis. Finally, it is probably too high given recent estimates of a threshold for the UK based on the cost effectiveness of services forgone of approximately £13,000/QALY. An excessive threshold risks causing the Irish health system unintended harm. The lack of an empirically informed threshold means the policy recommendations of cost-effectiveness analysis cannot be considered as fully evidence- based rational rationing. Policy makers should consider these issues and recent Irish legislation that defined cost effectiveness in terms of the opportunity cost of services forgone when choosing what threshold to apply once the current industry agreement expires at the end of 2015

A study of FM threshold extension techniques

NASA Technical Reports Server (NTRS)

Arndt, G. D.; Loch, F. J.

1972-01-01

The characteristics of three postdetection threshold extension techniques are evaluated with respect to the ability of such techniques to improve the performance of a phase lock loop demodulator. These techniques include impulse-noise elimination, signal correlation for the detection of impulse noise, and delta modulation signal processing. Experimental results from signal to noise ratio data and bit error rate data indicate that a 2- to 3-decibel threshold extension is readily achievable by using the various techniques. This threshold improvement is in addition to the threshold extension that is usually achieved through the use of a phase lock loop demodulator.

Threshold concepts: implications for the management of natural resources

USGS Publications Warehouse

Guntenspergen, Glenn R.; Gross, John

2014-01-01

Threshold concepts can have broad relevance in natural resource management. However, the concept of ecological thresholds has not been widely incorporated or adopted in management goals. This largely stems from the uncertainty revolving around threshold levels and the post hoc analyses that have generally been used to identify them. Natural resource managers have a need for new tools and approaches that will help them assess the existence and detection of conditions that demand management actions. Recognition of additional threshold concepts include: utility thresholds (which are based on human values about ecological systems) and decision thresholds (which reflect management objectives and values and include ecological knowledge about a system) as well as ecological thresholds. All of these concepts provide a framework for considering the use of threshold concepts in natural resource decision making.

Advanced Reactor Technologies - Regulatory Technology Development Plan (RTDP)

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

Moe, Wayne L.

regulatory importance of key DOE reactor research initiatives should be assessed early in the technology development process. Quality assurance requirements supportive of later licensing activities must also be attached to important research activities to ensure resulting data is usable in that context. Early regulatory analysis and licensing approach planning thus provides a significant benefit to the formulation of research plans and also enables the planning and development of a compatible AdvSMR licensing framework, should significant modification be required.« less

Advanced Reactor Technology -- Regulatory Technology Development Plan (RTDP)

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

Moe, Wayne Leland

regulatory importance of key DOE reactor research initiatives should be assessed early in the technology development process. Quality assurance requirements supportive of later licensing activities must also be attached to important research activities to ensure resulting data is usable in that context. Early regulatory analysis and licensing approach planning thus provides a significant benefit to the formulation of research plans and also enables the planning and development of a compatible AdvSMR licensing framework, should significant modification be required.« less

[Regulatory science: modern trends in science and education for pharmaceutical products].

PubMed

Beregovykh, V V; Piatigorskaia, N V; Aladysheva, Zh I

2012-01-01

This article reviews modern trends in development of new instruments, standards and approaches to drugs safety, efficacy and quality assessment in USA and EU that can be called by unique term--"regulatory science" which is a new concept for Russian Federation. New education programs (curricula) developed by USA and EU universities within last 3 years are reviewed. These programs were designed in order to build workforce capable to utilize science approach for drug regulation. The principal mechanisms for financing research in regulatory science used by Food and Drug Administration are analyzed. There are no such science and relevant researches in Russian Federation despite the high demand as well as needs for the system for higher education and life-long learning education of specialists for regulatory affairs (or compliance).

Vegetation Patterns and Degradation Thresholds in the Mulga Landscapes of Australia

NASA Astrophysics Data System (ADS)

Azadi, Samira; Saco, Patricia; Moreno-de las Heras, Mariano; Willgoose, Garry

2017-04-01

Drylands are often characterised by a spatially heterogeneous vegetation cover forming mosaics of patches dense vegetation within bare soil. This 'patterned' or 'patchy' vegetation cover is sensitive to human pressures. Previous work suggests that within these landscapes there is a critical vegetation cover threshold below which the landscape functionality is lost. This threshold behaviour is tightly linked to the overland flow redistribution and an increase in hydrologic connectivity that induces loss of resources (i.e., leakiness). In fact, disturbances (such as wildfire, overgrazing or harvesting activities) can disrupt the spatial structure of vegetation, increase landscape hydrologic connectivity, trigger erosion and produce a substantial loss of water. All these effects affect ecosystem functionality. Here we present the results of exploring the impact of degradation processes induced by vegetation disturbances (mainly grazing) on ecosystem functionality and connectivity in semiarid landscapes with various types of vegetation patterns. The sites are carefully selected in Mulga landscapes bioregion (New South Wales, Queensland) and in sites of Northern Territory in Australia, which display similar vegetation characteristics but with different vegetation patterns and good quality rainfall information. The analysis of vegetation patterns is derived from high resolution remote sensing images (IKONOS, QuickBird, Pleiades). Using MODIS NDVI and local precipitation data, we compute rainfall use efficiency and precipitation marginal response in order to assess the ecosystem functionality. We use vegetation binary maps and digital elevation models to estimate mean Flowlength as an indicator of structural hydrologic connectivity. We compare the trends for several sites with varying vegetation patterns (i.e., banded versus spotted patterns). Our results show that disturbances increase hydrologic connectivity and suggest threshold behaviour that affects landscape

ANALYTICAL EQUATIONS OF STORAGE RESERVOIR WATER QUALITY

EPA Science Inventory

Distribution system water quality protection is an integral aspect of public water supply management. Effective regulatory compliance requires a thorough understanding of the transport and mixing processes in storage reservoirs and their impacts on effluent water quality. This ...

A comprehensive study on regulatory requirements for development and filing of generic drugs globally

PubMed Central

Handoo, Shweta; Arora, Vandana; Khera, Deepak; Nandi, Prafulla Kumar; Sahu, Susanta Kumar

2012-01-01

The regulatory requirements of various countries of the world vary from each other. Therefore, it is challenging for the companies to develop a single drug which can be simultaneously submitted in all the countries for approval. The regulatory strategy for product development is essentially to be established before commencement of developmental work in order to avoid major surprises after submission of the application. The role of the regulatory authorities is to ensure the quality, safety, and efficacy of all medicines in circulation in their country. It not only includes the process of regulating and monitoring the drugs but also the process of manufacturing, distribution, and promotion of it. One of the primary challenges for regulatory authority is to ensure that the pharmaceutical products are developed as per the regulatory requirement of that country. This process involves the assessment of critical parameters during product development. PMID:23373001

Novel analyses of long-term data provide a scientific basis for chlorophyll-a thresholds in San Francisco Bay

NASA Astrophysics Data System (ADS)

Sutula, Martha; Kudela, Raphael; Hagy, James D.; Harding, Lawrence W.; Senn, David; Cloern, James E.; Bricker, Suzanne; Berg, Gry Mine; Beck, Marcus

2017-10-01

San Francisco Bay (SFB), USA, is highly enriched in nitrogen and phosphorus, but has been resistant to the classic symptoms of eutrophication associated with over-production of phytoplankton. Observations in recent years suggest that this resistance may be weakening, shown by: significant increases of chlorophyll-a (chl-a) and decreases of dissolved oxygen (DO), common occurrences of phytoplankton taxa that can form Harmful Algal Blooms (HAB), and algal toxins in water and mussels reaching levels of concern. As a result, managers now ask: what levels of chl-a in SFB constitute tipping points of phytoplankton biomass beyond which water quality will become degraded, requiring significant nutrient reductions to avoid impairments? We analyzed data for DO, phytoplankton species composition, chl-a, and algal toxins to derive quantitative relationships between three indicators (HAB abundance, toxin concentrations, DO) and chl-a. Quantile regressions relating HAB abundance and DO to chl-a were significant, indicating SFB is at increased risk of adverse HAB and low DO levels if chl-a continues to increase. Conditional probability analysis (CPA) showed chl-a of 13 mg m-3 as a "protective" threshold below which probabilities for exceeding alert levels for HAB abundance and toxins were reduced. This threshold was similar to chl-a of 13-16 mg m-3 that would meet a SFB-wide 80% saturation Water Quality Criterion (WQC) for DO. Higher "at risk" chl-a thresholds from 25 to 40 mg m-3 corresponded to 0.5 probability of exceeding alert levels for HAB abundance, and for DO below a WQC of 5.0 mg L-1 designated for lower South Bay (LSB) and South Bay (SB). We submit these thresholds as a basis to assess eutrophication status of SFB and to inform nutrient management actions. This approach is transferrable to other estuaries to derive chl-a thresholds protective against eutrophication.

Pain thresholds, supra-threshold pain and lidocaine sensitivity in patients with erythromelalgia, including the I848Tmutation in NaV 1.7.

PubMed

Helås, T; Sagafos, D; Kleggetveit, I P; Quiding, H; Jönsson, B; Segerdahl, M; Zhang, Z; Salter, H; Schmelz, M; Jørum, E

2017-09-01

Nociceptive thresholds and supra-threshold pain ratings as well as their reduction upon local injection with lidocaine were compared between healthy subjects and patients with erythromelalgia (EM). Lidocaine (0.25, 0.50, 1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful areas of the lower arm, in a randomized, double-blind manner, to test the effect on dynamic and static mechanical sensitivity, mechanical pain sensitivity, thermal thresholds and supra-threshold heat pain sensitivity. Heat pain thresholds and pain ratings to supra-threshold heat stimulation did not differ between EM-patients (n = 27) and controls (n = 25), neither did the dose-response curves for lidocaine. Only the subgroup of EM-patients with mutations in sodium channel subunits Na V 1.7, 1.8 or 1.9 (n = 8) had increased lidocaine sensitivity for supra-threshold heat stimuli, contrasting lower sensitivity to strong mechanical stimuli. This pattern was particularly clear in the two patients carrying the Na V 1.7 I848T mutations in whom lidocaine's hyperalgesic effect on mechanical pain sensitivity contrasted more effective heat analgesia. Heat pain thresholds are not sensitized in EM patients, even in those with gain-of-function mutations in Na V 1.7. Differential lidocaine sensitivity was overt only for noxious stimuli in the supra-threshold range suggesting that sensitized supra-threshold encoding is important for the clinical pain phenotype in EM in addition to lower activation threshold. Intracutaneous lidocaine dose-dependently blocked nociceptive sensations, but we did not identify EM patients with particular high lidocaine sensitivity that could have provided valuable therapeutic guidance. Acute pain thresholds and supra-threshold heat pain in controls and patients with erythromelalgia do not differ and have the same lidocaine sensitivity. Acute heat pain thresholds even in EM patients with the Na V 1.7 I848T mutation are normal and only nociceptor

Meeting Threshold Learning Standards through Self-Management in Group Oral Presentations: Observations on Accounting Postgraduate Students

ERIC Educational Resources Information Center

Shauki, Elvia R.; Benzie, Helen

2017-01-01

This study explores the development of student self-management skills through an oral presentation task. It is motivated by the challenge to maintain consistent quality in students' oral skills and to incorporate national accounting curriculum requirements for threshold learning standards into an accounting subject. The study has been conducted in…

Predictive performance of rainfall thresholds for shallow landslide triggering in Switzerland from daily gridded precipitation data

NASA Astrophysics Data System (ADS)

Leonarduzzi, E.; Molnar, P.; McArdell, B. W.

2017-12-01

In Switzerland floods are responsible for most of the damage caused by rainfall-triggered natural hazards (89%), followed by landslides (6%, almost 600 M USD) as reported in Hilker et al. (2009) for the period 1972-2007. A high-resolution gridded daily precipitation dataset is combined with a landslide inventory containing over 2000 events in the period 1972-2012 to analyze rainfall thresholds that lead to landsliding in Switzerland. First triggering rainfall and landslides are co-located obtaining the distributions of triggering and non-triggering rainfall event properties at the scale of the precipitation data (2*2 km2) and considering 1 day as the interarrival time to separate events. Then rainfall thresholds are obtained by maximizing true positives (accurate predictions) while minimizing false negatives (false alarms), using the True Skill Statistic. The best predictive performance is obtained by the intensity-duration ID threshold curve, followed by peak daily intensity (Imax) and mean event intensity (Imean). Event duration by itself has very low predictive power. In addition to country-wide thresholds, local ones are also defined by regionalization based on surface erodibility and local long-term climate (mean daily precipitation). Different Imax thresholds are determined for each of the regions separately. It is found that wetter local climate and lower erodibility lead to significantly higher rainfall thresholds required to trigger landslides. However, the improvement in model performance due to regionalization is marginal and much lower than what can be achieved by having a high quality landslide database. In order to validate the performance of the Imax rainfall threshold model, reference cases will be presented in which the landslide locations and timing are randomized and the landslide sample size is reduced. Jack-knife and cross-validation experiments demonstrate that the model is robust. The results highlight the potential of using rainfall I

High-order above-threshold dissociation of molecules

NASA Astrophysics Data System (ADS)

Lu, Peifen; Wang, Junping; Li, Hui; Lin, Kang; Gong, Xiaochun; Song, Qiying; Ji, Qinying; Zhang, Wenbin; Ma, Junyang; Li, Hanxiao; Zeng, Heping; He, Feng; Wu, Jian

2018-03-01

Electrons bound to atoms or molecules can simultaneously absorb multiple photons via the above-threshold ionization featured with discrete peaks in the photoelectron spectrum on account of the quantized nature of the light energy. Analogously, the above-threshold dissociation of molecules has been proposed to address the multiple-photon energy deposition in the nuclei of molecules. In this case, nuclear energy spectra consisting of photon-energy spaced peaks exceeding the binding energy of the molecular bond are predicted. Although the observation of such phenomena is difficult, this scenario is nevertheless logical and is based on the fundamental laws. Here, we report conclusive experimental observation of high-order above-threshold dissociation of H2 in strong laser fields where the tunneling-ionized electron transfers the absorbed multiphoton energy, which is above the ionization threshold to the nuclei via the field-driven inelastic rescattering. Our results provide an unambiguous evidence that the electron and nuclei of a molecule as a whole absorb multiple photons, and thus above-threshold ionization and above-threshold dissociation must appear simultaneously, which is the cornerstone of the nowadays strong-field molecular physics.

High-order above-threshold dissociation of molecules.

PubMed

Lu, Peifen; Wang, Junping; Li, Hui; Lin, Kang; Gong, Xiaochun; Song, Qiying; Ji, Qinying; Zhang, Wenbin; Ma, Junyang; Li, Hanxiao; Zeng, Heping; He, Feng; Wu, Jian

2018-02-27

Electrons bound to atoms or molecules can simultaneously absorb multiple photons via the above-threshold ionization featured with discrete peaks in the photoelectron spectrum on account of the quantized nature of the light energy. Analogously, the above-threshold dissociation of molecules has been proposed to address the multiple-photon energy deposition in the nuclei of molecules. In this case, nuclear energy spectra consisting of photon-energy spaced peaks exceeding the binding energy of the molecular bond are predicted. Although the observation of such phenomena is difficult, this scenario is nevertheless logical and is based on the fundamental laws. Here, we report conclusive experimental observation of high-order above-threshold dissociation of H 2 in strong laser fields where the tunneling-ionized electron transfers the absorbed multiphoton energy, which is above the ionization threshold to the nuclei via the field-driven inelastic rescattering. Our results provide an unambiguous evidence that the electron and nuclei of a molecule as a whole absorb multiple photons, and thus above-threshold ionization and above-threshold dissociation must appear simultaneously, which is the cornerstone of the nowadays strong-field molecular physics. Copyright © 2018 the Author(s). Published by PNAS.

Determinants of Change in the Cost-effectiveness Threshold.

PubMed

Paulden, Mike; O'Mahony, James; McCabe, Christopher

2017-02-01

The cost-effectiveness threshold in health care systems with a constrained budget should be determined by the cost-effectiveness of displacing health care services to fund new interventions. Using comparative statics, we review some potential determinants of the threshold, including the budget for health care, the demand for existing health care interventions, the technical efficiency of existing interventions, and the development of new health technologies. We consider the anticipated direction of impact that would affect the threshold following a change in each of these determinants. Where the health care system is technically efficient, an increase in the health care budget unambiguously raises the threshold, whereas an increase in the demand for existing, non-marginal health interventions unambiguously lowers the threshold. Improvements in the technical efficiency of existing interventions may raise or lower the threshold, depending on the cause of the improvement in efficiency, whether the intervention is already funded, and, if so, whether it is marginal. New technologies may also raise or lower the threshold, depending on whether the new technology is a substitute for an existing technology and, again, whether the existing technology is marginal. Our analysis permits health economists and decision makers to assess if and in what direction the threshold may change over time. This matters, as threshold changes impact the cost-effectiveness of interventions that require decisions now but have costs and effects that fall in future periods.

40 CFR 98.391 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.391 Section 98.391 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Suppliers of Petroleum Products § 98.391 Reporting threshold. Any...

40 CFR 98.241 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.241 Section 98.241 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Petrochemical Production § 98.241 Reporting threshold. You must report...

40 CFR 98.241 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.241 Section 98.241 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Petrochemical Production § 98.241 Reporting threshold. You must report...

40 CFR 98.31 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.31 Section 98.31 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Stationary Fuel Combustion Sources § 98.31 Reporting threshold...

40 CFR 98.411 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.411 Section 98.411 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Suppliers of Industrial Greenhouse Gases § 98.411 Reporting threshold...

40 CFR 98.411 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.411 Section 98.411 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Suppliers of Industrial Greenhouse Gases § 98.411 Reporting threshold...

40 CFR 98.391 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.391 Section 98.391 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Suppliers of Petroleum Products § 98.391 Reporting threshold. Any...

40 CFR 98.31 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.31 Section 98.31 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING General Stationary Fuel Combustion Sources § 98.31 Reporting threshold...

40 CFR 98.351 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.351 Section 98.351 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Industrial Wastewater Treatment § 98.351 Reporting threshold. You must...

Influence of surgical gloves on haptic perception thresholds.

PubMed

Hatzfeld, Christian; Dorsch, Sarah; Neupert, Carsten; Kupnik, Mario

2018-02-01

Impairment of haptic perception by surgical gloves could reduce requirements on haptic systems for surgery. While grip forces and manipulation capabilities were not impaired in previous studies, no data is available for perception thresholds. Absolute and differential thresholds (20 dB above threshold) of 24 subjects were measured for frequencies of 25 and 250 Hz with a Ψ-method. Effects of wearing a surgical glove, moisture on the contact surface and subject's experience with gloves were incorporated in a full-factorial experimental design. Absolute thresholds of 12.8 dB and -29.6 dB (means for 25 and 250 Hz, respectively) and differential thresholds of -12.6 dB and -9.5 dB agree with previous studies. A relevant effect of the frequency on absolute thresholds was found. Comparisons of glove- and no-glove-conditions did not reveal a significant mean difference. Wearing a single surgical glove does not affect absolute and differential haptic perception thresholds. Copyright © 2017 John Wiley & Sons, Ltd.

Identifying a Probabilistic Boolean Threshold Network From Samples.

PubMed

Melkman, Avraham A; Cheng, Xiaoqing; Ching, Wai-Ki; Akutsu, Tatsuya

2018-04-01

This paper studies the problem of exactly identifying the structure of a probabilistic Boolean network (PBN) from a given set of samples, where PBNs are probabilistic extensions of Boolean networks. Cheng et al. studied the problem while focusing on PBNs consisting of pairs of AND/OR functions. This paper considers PBNs consisting of Boolean threshold functions while focusing on those threshold functions that have unit coefficients. The treatment of Boolean threshold functions, and triplets and -tuplets of such functions, necessitates a deepening of the theoretical analyses. It is shown that wide classes of PBNs with such threshold functions can be exactly identified from samples under reasonable constraints, which include: 1) PBNs in which any number of threshold functions can be assigned provided that all have the same number of input variables and 2) PBNs consisting of pairs of threshold functions with different numbers of input variables. It is also shown that the problem of deciding the equivalence of two Boolean threshold functions is solvable in pseudopolynomial time but remains co-NP complete.

Wavelet-based adaptive thresholding method for image segmentation

NASA Astrophysics Data System (ADS)

Chen, Zikuan; Tao, Yang; Chen, Xin; Griffis, Carl

2001-05-01

A nonuniform background distribution may cause a global thresholding method to fail to segment objects. One solution is using a local thresholding method that adapts to local surroundings. In this paper, we propose a novel local thresholding method for image segmentation, using multiscale threshold functions obtained by wavelet synthesis with weighted detail coefficients. In particular, the coarse-to- fine synthesis with attenuated detail coefficients produces a threshold function corresponding to a high-frequency- reduced signal. This wavelet-based local thresholding method adapts to both local size and local surroundings, and its implementation can take advantage of the fast wavelet algorithm. We applied this technique to physical contaminant detection for poultry meat inspection using x-ray imaging. Experiments showed that inclusion objects in deboned poultry could be extracted at multiple resolutions despite their irregular sizes and uneven backgrounds.

CORRELATIONS IN LIGHT FROM A LASER AT THRESHOLD,

DTIC Science & Technology

Temporal correlations in the electromagnetic field radiated by a laser in the threshold region of oscillation (from one tenth of threshold intensity...to ten times threshold ) were measured by photoelectron counting techniques. The experimental results were compared with theoretical predictions based...shows that the intensity fluctuations at about one tenth threshold are nearly those of a Gaussian field and continuously approach those of a constant amplitude field as the intensity is increased. (Author)

The relationship between stereoacuity and stereomotion thresholds.

PubMed

Cumming, B G

1995-01-01

There are in principle at least two binocular sources of information that could be used to determine the motion of an object towards or away from an observer; such motion produces changes in binocular disparities over time and also generates different image velocities in the two eyes. It has been argued in the past that stereomotion is detected by a mechanism that is independent of that which detects static disparities. More recently this conclusion has been questioned. If stereomotion detection in fact depends upon detecting disparities, there should be a clear correlation between static stereo-detection thresholds and stereomotion thresholds. If the systems are separate, there need be no such correlation. Four types of threshold measurement were performed by means of random-dot stereograms: (1) static stereo detection/discrimination; (2) stereomotion detection in random-dot stereograms (temporally uncorrelated); (3) stereomotion detection in temporally correlated random-dot stereograms; and (4) binocular detection of frontoparallel motion. Three normal subjects and five subjects with unusually high stereoacuities were studied. In addition, two manipulations were performed that altered stereomotion thresholds: changes in mean disparity, and image defocus produced by positive spectacle lenses. Across subjects and conditions, stereomotion thresholds were well correlated with stereo-discrimination thresholds. Stereomotion was poorly correlated with binocular frontoparallel-motion thresholds. These results suggest that stereomotion is detected by means of registering changes in the output of the same disparity detectors that are used to detect static disparities.

On Regional Modeling to Support Air Quality Policies

EPA Science Inventory

We examine the use of the Community Multiscale Air Quality (CMAQ) model in simulating the changes in the extreme values of air quality that are of interest to the regulatory agencies. Year-to-year changes in ozone air quality are attributable to variations in the prevailing mete...

24 CFR 954.104 - Performance thresholds.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Performance thresholds. 954.104... DEVELOPMENT INDIAN HOME PROGRAM Applying for Assistance § 954.104 Performance thresholds. Applicants must have... HOME program must have performed adequately. In cases of previously documented deficient performance...

24 CFR 954.104 - Performance thresholds.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Performance thresholds. 954.104... DEVELOPMENT INDIAN HOME PROGRAM Applying for Assistance § 954.104 Performance thresholds. Applicants must have... HOME program must have performed adequately. In cases of previously documented deficient performance...

40 CFR 98.61 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.61 Section 98.61 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Aluminum Production § 98.61 Reporting threshold. You must report GHG...

40 CFR 98.281 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.281 Section 98.281 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Silicon Carbide Production § 98.281 Reporting threshold. You must report...

40 CFR 98.81 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.81 Section 98.81 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Cement Production § 98.81 Reporting threshold. You must report GHG...

40 CFR 98.251 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.251 Section 98.251 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Petroleum Refineries § 98.251 Reporting threshold. You must report GHG...

40 CFR 98.81 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.81 Section 98.81 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Cement Production § 98.81 Reporting threshold. You must report GHG...

40 CFR 98.201 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.201 Section 98.201 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Magnesium Production § 98.201 Reporting threshold. You must report GHG...

40 CFR 98.211 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.211 Section 98.211 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Miscellaneous Uses of Carbonate § 98.211 Reporting threshold. You must...

40 CFR 98.111 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.111 Section 98.111 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Ferroalloy Production § 98.111 Reporting threshold. You must report GHG...

40 CFR 98.451 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.451 Section 98.451 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... threshold. You must report GHG emissions under this subpart if your facility contains an electrical...

40 CFR 98.181 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.181 Section 98.181 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Lead Production § 98.181 Reporting threshold. You must report GHG...

40 CFR 98.341 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.341 Section 98.341 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Municipal Solid Waste Landfills § 98.341 Reporting threshold. You must...

40 CFR 98.271 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.271 Section 98.271 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Pulp and Paper Manufacturing § 98.271 Reporting threshold. You must...

40 CFR 98.381 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.381 Section 98.381 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Suppliers of Coal-based Liquid Fuels § 98.381 Reporting threshold. Any...

40 CFR 98.151 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.151 Section 98.151 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING HCFC-22 Production and HFC-23 Destruction § 98.151 Reporting threshold...

40 CFR 98.251 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.251 Section 98.251 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Petroleum Refineries § 98.251 Reporting threshold. You must report GHG...

40 CFR 98.311 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.311 Section 98.311 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Titanium Dioxide Production § 98.311 Reporting threshold. You must report...

40 CFR 98.471 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.471 Section 98.471 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Injection of Carbon Dioxide § 98.471 Reporting threshold. (a) You must...

40 CFR 98.271 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.271 Section 98.271 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Pulp and Paper Manufacturing § 98.271 Reporting threshold. You must...

40 CFR 98.171 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.171 Section 98.171 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Iron and Steel Production § 98.171 Reporting threshold. You must report...

40 CFR 98.111 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.111 Section 98.111 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Ferroalloy Production § 98.111 Reporting threshold. You must report GHG...

40 CFR 98.191 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.191 Section 98.191 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Lime Manufacturing § 98.191 Reporting threshold. You must report GHG...

40 CFR 98.311 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.311 Section 98.311 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Titanium Dioxide Production § 98.311 Reporting threshold. You must report...

40 CFR 98.141 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.141 Section 98.141 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Glass Production § 98.141 Reporting threshold. You must report GHG...

40 CFR 98.221 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.221 Section 98.221 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Nitric Acid Production § 98.221 Reporting threshold. You must report GHG...

40 CFR 98.191 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.191 Section 98.191 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Lime Manufacturing § 98.191 Reporting threshold. You must report GHG...

40 CFR 98.211 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.211 Section 98.211 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Miscellaneous Uses of Carbonate § 98.211 Reporting threshold. You must...

40 CFR 98.291 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.291 Section 98.291 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Soda Ash Manufacturing § 98.291 Reporting threshold. You must report GHG...

40 CFR 98.421 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.421 Section 98.421 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Suppliers of Carbon Dioxide § 98.421 Reporting threshold. Any supplier of...

40 CFR 98.61 - Reporting threshold.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Reporting threshold. 98.61 Section 98.61 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Aluminum Production § 98.61 Reporting threshold. You must report GHG...

40 CFR 98.291 - Reporting threshold.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Reporting threshold. 98.291 Section 98.291 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Soda Ash Manufacturing § 98.291 Reporting threshold. You must report GHG...