Endpoint behavior of high-energy scattering cross sections

International Nuclear Information System (INIS)

Chay, Junegone; Kim, Chul

2010-01-01

In high-energy processes near the endpoint, there emerge new contributions associated with spectator interactions. Away from the endpoint region, these new contributions are suppressed compared to the leading contribution, but the leading contribution becomes suppressed as we approach the endpoint and the new contributions become comparable. We present how the new contributions scale as we reach the endpoint and show that they are comparable to the suppressed leading contributions in deep inelastic scattering by employing a power-counting analysis. The hadronic tensor in deep inelastic scattering is shown to factorize including the spectator interactions, and it can be expressed in terms of the light cone distribution amplitudes of initial hadrons. We also consider the contribution of the spectator contributions in Drell-Yan processes. Here the spectator interactions are suppressed compared to double parton annihilation according to the power counting.

An evaluation of 10 percent and 20 percent benzocaine gels in patients with acute toothaches

Science.gov (United States)

Hersh, Elliot V.; Ciancio, Sebastian G.; Kuperstein, Arthur S.; Stoopler, Eric T.; Moore, Paul A.; Boynes, Sean G.; Levine, Steven C.; Casamassimo, Paul; Leyva, Rina; Mathew, Tanya; Shibly, Othman; Creighton, Paul; Jeffers, Gary E.; Corby, Patricia M.A.; Turetzky, Stanley N.; Papas, Athena; Wallen, Jillian; Idzik-Starr, Cynthia; Gordon, Sharon M.

2013-01-01

Background The authors evaluated the efficacy and tolerability of 10 percent and 20 percent benzocaine gels compared with those of a vehicle (placebo) gel for the temporary relief of toothache pain. They also assessed the compliance with the label dose administration directions on the part of participants with toothache pain. Methods Under double-masked conditions, 576 participants self-applied study gel to an open tooth cavity and surrounding oral tissues. Participants evaluated their pain intensity and pain relief for 120 minutes. The authors determined the amount of gel the participants applied. Results The responders’ rates (the primary efficacy parameter), defined as the percentage of participants who had an improvement in pain intensity as exhibited by a pain score reduction of at least one unit on the dental pain scale from baseline for two consecutive assessments any time between the five- and 20-minute points, were 87.3 percent, 80.7 percent and 70.4 percent, respectively, for 20 percent benzocaine gel, 10 percent benzocaine gel and vehicle gel. Both benzocaine gels were significantly (P ≤ .05) better than vehicle gel; the 20 percent benzocaine gel also was significantly (P ≤ .05) better than the 10 percent benzocaine gel. The mean amount of gel applied was 235.6 milligrams, with 88.2 percent of participants applying 400 mg or less. Conclusions Both 10 percent and 20 percent benzocaine gels were more efficacious than the vehicle gel, and the 20 percent benzocaine gel was more efficacious than the 10 percent benzocaine gel. All treatments were well tolerated by participants. Practical Implications Patients can use 10 percent and 20 percent benzocaine gels to temporarily treat toothache pain safely. PMID:23633700

Hippeastrum hybridum anthocyanins as indicators of endpoint in ...

African Journals Online (AJOL)

Anthocyanins from Hippeastrum hybridum (Amaryllis) were investigated as indicators of endpoint in acid- base titrations. Extraction of the anthocyanins was done using distilled water, methanol and methanol containing 0.5% acetic acid. The extracts were used in determination of endpoint in titrations between strong ...

SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines

Science.gov (United States)

Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas; Vandenbussche, Pierre-Yves

In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this method, most of the currently listed SPARQL endpoints in existing endpoint repositories, as well as a significant number of new SPARQL endpoints, have been discovered. Finally, we have developed a new SPARQL endpoint crawler (SpEC) for crawling and link analysis.

Planning and analyzing clinical trials with composite endpoints

CERN Document Server

Rauch, Geraldine; Kieser, Meinhard

2017-01-01

This book addresses the most important aspects of how to plan and evaluate clinical trials with a composite primary endpoint to guarantee a clinically meaningful and valid interpretation of the results. Composite endpoints are often used as primary efficacy variables for clinical trials, particularly in the fields of oncology and cardiology. These endpoints combine several variables of interest within a single composite measure, and as a result, all variables that are of major clinical relevance can be considered in the primary analysis without the need to adjust for multiplicity. Moreover, composite endpoints are intended to increase the size of the expected effects thus making clinical trials more powerful. The book offers practical advice for statisticians and medical experts involved in the planning and analysis of clinical trials. For readers who are mainly interested in the application of the methods, all the approaches are illustrated with real-world clinical trial examples, and the software codes requ...

Parametric Study of Beta-Endpoint Energy in Direct Energy Converters

Science.gov (United States)

2007-01-01

value to the endpoint energy of nickel-63 ( Ni63 ), whose endpoint energy is 66 keV. Only an approximation is sought. Nickel-63 is an easily...is known to vary from Sr90’s spectrum, where instead of peaking at approximately one third of the endpoint energy, the peak of Ni63 ’s output spectrum

The next fifty years

International Nuclear Information System (INIS)

Scaldwell, Reg

1995-01-01

The General Manager of the reactor division of Centronics, a world class manufacturer of reactor control systems and radiation detectors, describes its achievements and looks forward to speculate on what the next fifty years may mean in terms of technological development. Tables are given of the locations of Centronics Fission Chambers and of reactors controlled with Centronic Detectors. (UK)

Evaluation of early efficacy endpoints for proof-of-concept trials.

Science.gov (United States)

Chen, Cong; Sun, Linda; Li, Chih-Lin

2013-03-11

A Phase II proof-of-concept (POC) trial usually uses an early efficacy endpoint other than a clinical endpoint as the primary endpoint. Because of the advancement in bioscience and technology, which has yielded a number of new surrogate biomarkers, drug developers often have more candidate endpoints to choose from than they can handle. As a result, selection of endpoint and its effect size as well as choice of type I/II error rates are often at the center of heated debates in design of POC trials. While optimization of the trade-off between benefit and cost is the implicit objective in such a decision-making process, it is seldom explicitly accounted for in practice. In this research note, motivated by real examples from the oncology field, we provide practical measures for evaluation of early efficacy endpoints (E4) for POC trials. We further provide optimal design strategies for POC trials that include optimal Go-No Go decision criteria for initiation of Phase III and optimal resource allocation strategies for conducting multiple POC trials in a portfolio under fixed resources. Although oncology is used for illustration purpose, the same idea developed in this research note also applies to similar situations in other therapeutic areas or in early-stage drug development in that a Go-No Go decision has to rely on limited data from an early efficacy endpoint and cost-effectiveness is the main concern.

Forecasting interest rates with shifting endpoints

DEFF Research Database (Denmark)

Van Dijk, Dick; Koopman, Siem Jan; Wel, Michel van der

2014-01-01

We consider forecasting the term structure of interest rates with the assumption that factors driving the yield curve are stationary around a slowly time-varying mean or ‘shifting endpoint’. The shifting endpoints are captured using either (i) time series methods (exponential smoothing) or (ii......) long-range survey forecasts of either interest rates or inflation and output growth, or (iii) exponentially smoothed realizations of these macro variables. Allowing for shifting endpoints in yield curve factors provides substantial and significant gains in out-of-sample predictive accuracy, relative...... to stationary and random walk benchmarks. Forecast improvements are largest for long-maturity interest rates and for long-horizon forecasts....

The fifty-year-old woman and midlife stress.

Science.gov (United States)

Campbell, S

It has been assumed that the fifties are a relatively stable decade; however, women in their fifties are susceptible to many stresses, internal and external. The possibilities of widowhood, divorce, or poverty, combined with intra- and interpersonal strains, make this a time of insecurity about aging for many women. Some suggestions as to why women nonetheless cope successfully with aging are considered.

Hippeastrum hybridum anthocyanins as indicators of endpoint in acid

African Journals Online (AJOL)

Anthocyanins from Hippeastrum hybridum (Amaryllis) were investigated as indicators of endpoint in acid- base titrations. Extraction of the anthocyanins was done using distilled water, methanol and methanol containing 0.5% acetic acid. The extracts were used in determination of endpoint in titrations between strong.

Inconsistent selection and definition of local and regional endpoints in breast cancer research.

Science.gov (United States)

Moossdorff, M; van Roozendaal, L M; Schipper, R-J; Strobbe, L J A; Voogd, A C; Tjan-Heijnen, V C G; Smidt, M L

2014-12-01

Results in breast cancer research are reported using study endpoints. Most are composite endpoints (such as locoregional recurrence), consisting of several components (for example local recurrence) that are in turn composed of specific events (such as skin recurrence). Inconsistent endpoint selection and definition might lead to unjustified conclusions when comparing study outcomes. This study aimed to determine which locoregional endpoints are used in breast cancer studies, and how these endpoints and their components are defined. PubMed was searched for breast cancer studies published in nine leading journals in 2011. Articles using endpoints with a local or regional component were included and definitions were compared. Twenty-three different endpoints with a local or regional component were extracted from 44 articles. Most frequently used were disease-free survival (25 articles), recurrence-free survival (7), local control (4), locoregional recurrence-free survival (3) and event-free survival (3). Different endpoints were used for similar outcomes. Of 23 endpoints, five were not defined and 18 were defined only partially. Of these, 16 contained a local and 13 a regional component. Included events were not specified in 33 of 57 (local) and 27 of 50 (regional) cases. Definitions of local components inconsistently included carcinoma in situ and skin and chest wall recurrences. Regional components inconsistently included specific nodal sites and skin and chest wall recurrences. Breast cancer studies use many different endpoints with a locoregional component. Definitions of endpoints and events are either not provided or vary between trials. To improve transparency, facilitate trial comparison and avoid unjustified conclusions, authors should report detailed definitions of all endpoints. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Endpoints in pediatric pain studies

NARCIS (Netherlands)

M. van Dijk (Monique); I. Ceelie (Ilse); D. Tibboel (Dick)

2011-01-01

textabstractAssessing pain intensity in (preverbal) children is more difficult than in adults. Tools to measure pain are being used as primary endpoints [e.g., pain intensity, time to first (rescue) analgesia, total analgesic consumption, adverse effects, and long-term effects] in studies on the

Biomarkers and correlative endpoints for immunotherapy trials.

Science.gov (United States)

Morse, Michael A; Osada, Takuya; Hobeika, Amy; Patel, Sandip; Lyerly, H Kim

2013-01-01

Immunotherapies for lung cancer are reaching phase III clinical trial, but the ultimate success likely will depend on developing biomarkers to guide development and choosing patient populations most likely to benefit. Because the immune response to cancer involves multiple cell types and cytokines, some spatially and temporally separated, it is likely that multiple biomarkers will be required to fully characterize efficacy of the vaccine and predict eventual benefit. Peripheral blood markers of response, such as the ELISPOT assay and cytokine flow cytometry analyses of peripheral blood mononuclear cells following immunotherapy, remain the standard approach, but it is increasingly important to obtain tissue to study the immune response at the site of the tumor. Earlier clinical endpoints such as response rate and progression-free survival do not correlate with overall survival demonstrated for some immunotherapies, suggesting the need to develop other intermediary clinical endpoints. Insofar as all these biomarkers and surrogate endpoints are relevant in multiple malignancies, it may be possible to extrapolate findings to immunotherapy of lung cancer.

Fifty years of nuclear magnetic resonance

International Nuclear Information System (INIS)

Martinez Valderrama, Juan Crisostomo

1997-01-01

Short information about the main developments of nuclear magnetic resonance during their fifty existence years is presented. Beside two examples of application (HETCOR and INADEQUATE) to the structural determination of organic compounds are described

Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper

Science.gov (United States)

Herzog, Thomas J.; Armstrong, Deborah K.; Brady, Mark F.; Coleman, Robert L.; Einstein, Mark H.; Monk, Bradley J.; Mannel, Robert S.; Thigpen, J. Tate; Umpierre, Sharee A.; Villella, Jeannine A.; Alvarez, Ronald D.

2015-01-01

Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect

Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper.

Science.gov (United States)

Herzog, Thomas J; Armstrong, Deborah K; Brady, Mark F; Coleman, Robert L; Einstein, Mark H; Monk, Bradley J; Mannel, Robert S; Thigpen, J Tate; Umpierre, Sharee A; Villella, Jeannine A; Alvarez, Ronald D

2014-01-01

To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies

Transcervical, intrauterine ultrasound-guided radiofrequency ablation of uterine fibroids with the VizAblate® System: three- and six-month endpoint results from the FAST-EU study.

Science.gov (United States)

Bongers, Marlies; Brölmann, Hans; Gupta, Janesh; Garza-Leal, José Gerardo; Toub, David

This was a prospective, longitudinal, multicenter, single-arm controlled trial, using independent core laboratory validation of MRI results, to establish the effectiveness and confirm the safety of the VizAblate® System in the treatment of symptomatic uterine fibroids. The VizAblate System is a transcervical device that ablates fibroids with radiofrequency energy, guided by a built-in intrauterine ultrasound probe. Fifty consecutive women with symptomatic uterine fibroids received treatment with the VizAblate System. Patients had a minimum Menstrual Pictogram score of 120, no desire for fertility, and met additional inclusion and exclusion criteria. The VizAblate System was inserted transcervically and individual fibroids were ablated with radiofrequency energy. An integrated intrauterine ultrasound probe was used for fibroid imaging and targeting. Anesthesia was at the discretion of each investigator. The primary study endpoint was the percentage change in perfused fibroid volume, as assessed by contrast-enhanced MRI at 3 months. Secondary endpoints, reached at 6 months, included safety, percentage reductions in the Menstrual Pictogram (MP) score and the Symptom Severity Score (SSS) subscale of the Uterine Fibroid Symptom-Quality of Life questionnaire (UFS-QOL), along with the rate of surgical reintervention for abnormal uterine bleeding and the mean number of days to return to normal activity. Additional assessments included the Health-Related Quality of Life (HRQOL) subscale of the UFS-QOL, medical reintervention for abnormal uterine bleeding, and procedure times. Fifty patients were treated, representing 92 fibroids. Perfused fibroid volumes were reduced at 3 months by an average of 68.8 ± 27.8 % ( P  abnormal uterine bleeding associated with fibroids, with appropriate safety and a low reintervention rate.

Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Zhendong Yang

2015-12-01

Full Text Available Aflatoxins B1 (AFB1, deoxynivalenol (DON, fumonisin B1 (FB1, T-2 toxin (T-2, and zearalenone (ZEA are the major foodborne mycotoxins of public health concerns. In the present study, the multiple toxic endpoints of these naturally-occurring mycotoxins were evaluated in Caenorhabditis elegans model for their lethality, toxic effects on growth and reproduction, as well as influence on lifespan. We found that the lethality endpoint was more sensitive for T-2 toxicity with the EC50 at 1.38 mg/L, the growth endpoint was relatively sensitive for AFB1 toxic effects, and the reproduction endpoint was more sensitive for toxicities of AFB1, FB1, and ZEA. Moreover, the lifespan endpoint was sensitive to toxic effects of all five tested mycotoxins. Data obtained from this study may serve as an important contribution to knowledge on assessment of mycotoxin toxic effects, especially for assessing developmental and reproductive toxic effects, using the C. elegans model.

Percent Coverage

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The Percent Coverage is a spreadsheet that keeps track of and compares the number of vessels that have departed with and without observers to the numbers of vessels...

Sensitive endpoints in extended one-generation reproductive toxicity study versus two generation?

DEFF Research Database (Denmark)

Christiansen, Sofie

. The protocol includes assessment of novel endpoints of concern and developmental landmarks such as anogenital distance, nipple retention (both sensitive endpoints for anti-androgenic effects in male offspring) and mammary gland development (sensitive endpoint for oestrogen action) and may also include...... during critical period of development in contrast to the parental generation. Retrospective analysis of available two-generation studies, however, indicate that the assessment included in the study of other endpoints in the male offspring such as histopathology of reproductive organs and semen quality...

Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition.

Science.gov (United States)

Gilbert, Peter B; Gabriel, Erin E; Huang, Ying; Chan, Ivan S F

2015-09-01

A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the "principal effects" or "causal effect predictiveness (CEP)" surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the "surrogate paradox"). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect

Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition

Science.gov (United States)

Gilbert, Peter B.; Gabriel, Erin E.; Huang, Ying; Chan, Ivan S.F.

2015-01-01

A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the “principal effects” or “causal effect predictiveness (CEP)” surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the “surrogate paradox”). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of

A data-driven weighting scheme for multivariate phenotypic endpoints recapitulates zebrafish developmental cascades

Energy Technology Data Exchange (ETDEWEB)

Zhang, Guozhu, E-mail: gzhang6@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Roell, Kyle R., E-mail: krroell@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Truong, Lisa, E-mail: lisa.truong@oregonstate.edu [Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR (United States); Tanguay, Robert L., E-mail: robert.tanguay@oregonstate.edu [Department of Environmental and Molecular Toxicology, Sinnhuber Aquatic Research Laboratory, Oregon State University, Corvallis, OR (United States); Reif, David M., E-mail: dmreif@ncsu.edu [Bioinformatics Research Center, North Carolina State University, Raleigh, NC (United States); Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC (United States)

2017-01-01

Zebrafish have become a key alternative model for studying health effects of environmental stressors, partly due to their genetic similarity to humans, fast generation time, and the efficiency of generating high-dimensional systematic data. Studies aiming to characterize adverse health effects in zebrafish typically include several phenotypic measurements (endpoints). While there is a solid biomedical basis for capturing a comprehensive set of endpoints, making summary judgments regarding health effects requires thoughtful integration across endpoints. Here, we introduce a Bayesian method to quantify the informativeness of 17 distinct zebrafish endpoints as a data-driven weighting scheme for a multi-endpoint summary measure, called weighted Aggregate Entropy (wAggE). We implement wAggE using high-throughput screening (HTS) data from zebrafish exposed to five concentrations of all 1060 ToxCast chemicals. Our results show that our empirical weighting scheme provides better performance in terms of the Receiver Operating Characteristic (ROC) curve for identifying significant morphological effects and improves robustness over traditional curve-fitting approaches. From a biological perspective, our results suggest that developmental cascade effects triggered by chemical exposure can be recapitulated by analyzing the relationships among endpoints. Thus, wAggE offers a powerful approach for analysis of multivariate phenotypes that can reveal underlying etiological processes. - Highlights: • Introduced a data-driven weighting scheme for multiple phenotypic endpoints. • Weighted Aggregate Entropy (wAggE) implies differential importance of endpoints. • Endpoint relationships reveal developmental cascade effects triggered by exposure. • wAggE is generalizable to multi-endpoint data of different shapes and scales.

The impact of endpoint measures in rheumatoid arthritis clinical trials

NARCIS (Netherlands)

van der Heide, A.; Jacobs, J. W.; Dinant, H. J.; Bijlsma, J. W.

1992-01-01

In clinical trials on the effectiveness of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA), it is common to apply a large number of endpoint measures. This practice has several disadvantages. To determine which endpoint measures are most valuable, reports of

Biomechanical constraints on the feedforward regulation of endpoint stiffness.

Science.gov (United States)

Hu, Xiao; Murray, Wendy M; Perreault, Eric J

2012-10-01

Although many daily tasks tend to destabilize arm posture, it is still possible to have stable interactions with the environment by regulating the multijoint mechanics of the arm in a task-appropriate manner. For postural tasks, this regulation involves the appropriate control of endpoint stiffness, which represents the stiffness of the arm at the hand. Although experimental studies have been used to evaluate endpoint stiffness control, including the orientation of maximal stiffness, the underlying neural strategies remain unknown. Specifically, the relative importance of feedforward and feedback mechanisms has yet to be determined due to the difficulty separately identifying the contributions of these mechanisms in human experiments. This study used a previously validated three-dimensional musculoskeletal model of the arm to quantify the degree to which the orientation of maximal endpoint stiffness could be changed using only steady-state muscle activations, used to represent feedforward motor commands. Our hypothesis was that the feedforward control of endpoint stiffness orientation would be significantly constrained by the biomechanical properties of the musculoskeletal system. Our results supported this hypothesis, demonstrating substantial biomechanical constraints on the ability to regulate endpoint stiffness throughout the workspace. The ability to regulate stiffness orientation was further constrained by additional task requirements, such as the need to support the arm against gravity or exert forces on the environment. Together, these results bound the degree to which slowly varying feedforward motor commands can be used to regulate the orientation of maximum arm stiffness and provide a context for better understanding conditions in which feedback control may be needed.

A step towards standardization: A method for end-point titer determination by fluorescence index of an automated microscope. End-point titer determination by fluorescence index.

Science.gov (United States)

Carbone, Teresa; Gilio, Michele; Padula, Maria Carmela; Tramontano, Giuseppina; D'Angelo, Salvatore; Pafundi, Vito

2018-05-01

Indirect Immunofluorescence (IIF) is widely considered the Gold Standard for Antinuclear Antibody (ANA) screening. However, the high inter-reader variability remains the major disadvantage associated with ANA testing and the main reason for the increasing demand of the computer-aided immunofluorescence microscope. Previous studies proposed the quantification of the fluorescence intensity as an alternative for the classical end-point titer evaluation. However, the different distribution of bright/dark light linked to the nature of the self-antigen and its location in the cells result in different mean fluorescence intensities. The aim of the present study was to correlate Fluorescence Index (F.I.) with end-point titers for each well-defined ANA pattern. Routine serum samples were screened for ANA testing on HEp-2000 cells using Immuno Concepts Image Navigator System, and positive samples were serially diluted to assign the end-point titer. A comparison between F.I. and end-point titers related to 10 different staining patterns was made. According to our analysis, good technical performance of F.I. (97% sensitivity and 94% specificity) was found. A significant correlation between quantitative reading of F.I. and end-point titer groups was observed using Spearman's test and regression analysis. A conversion scale of F.I. in end-point titers for each recognized ANA-pattern was obtained. The Image Navigator offers the opportunity to improve worldwide harmonization of ANA test results. In particular, digital F.I. allows quantifying ANA titers by using just one sample dilution. It could represent a valuable support for the routine laboratory and an effective tool to reduce inter- and intra-laboratory variability. Copyright © 2018. Published by Elsevier B.V.

Deutsches Atomforum turns fifty

International Nuclear Information System (INIS)

Geisler, Maja

2009-01-01

Fifty years ago, the Deutsches Atomforum e. V. was founded to promote the peaceful uses of nuclear power in Germany. On July 1, 2009, the organization celebrated its fiftieth birthday in Berlin. The anniversary was celebrated in the Berlin electricity plant, Germany's oldest existing building for commercial electricity generation. DAtF President Dr. Walter Hohlefelder welcomed some 200 high-ranking guests from politics, industry, and from the nuclear community, above all, the Chancellor of the Federal Republic of Germany, Dr. Angela Merkel, and, as keynote speaker, Professor Dr. Arnulf Baring. (orig.)

Gene expression profiles in auricle skin as a possible additional endpoint for determination of sensitizers: A multi-endpoint evaluation of the local lymph node assay.

Science.gov (United States)

Tsuchiyama, Hiromi; Maeda, Akihisa; Nakajima, Mayumi; Kitsukawa, Mika; Takahashi, Kei; Miyoshi, Tomoya; Mutsuga, Mayu; Asaoka, Yoshiji; Miyamoto, Yohei; Oshida, Keiyu

2017-10-05

The murine local lymph node assay (LLNA) is widely used to test chemicals to induce skin sensitization. Exposure of mouse auricle skin to a sensitizer results in proliferation of local lymph node T cells, which has been measured by in vivo incorporation of H 3 -methyl thymidine or 5-bromo-2'-deoxyuridine (BrdU). The stimulation index (SI), the ratio of the mean proliferation in each treated group to that in the concurrent vehicle control group, is frequently used as a regulatory-authorized endpoint for LLNA. However, some non-sensitizing irritants, such as sodium dodecyl sulfate (SDS) or methyl salicylate (MS), have been reported as false-positives by this endpoint. In search of a potential endpoint to enhance the specificity of existing endpoints, we evaluated 3 contact sensitizers; (hexyl cinnamic aldehyde [HCA], oxazolone [OXA], and 2,4-dinitrochlorobenzene [DNCB]), 1 respiratory sensitizer (toluene 2,4-diisocyanate [TDI]), and 2 non-sensitizing irritants (MS and SDS) by several endpoints in LLNA. Each test substance was applied to both ears of female CBA/Ca mice daily for 3 consecutive days. The ears and auricle lymph node cells were analyzed on day 5 for endpoints including the SI value, lymph node cell count, cytokine release from lymph node cells, and histopathological changes and gene expression profiles in auricle skin. The SI values indicated that all the test substances induced significant proliferation of lymph node cells. The lymph node cell counts showed no significant changes by the non-sensitizers assessed. The inflammatory findings of histopathology were similar among the auricle skins treated by sensitizers and irritants. Gene expression profiles of cytokines IFN-γ, IL-4, and IL-17 in auricle skin were similar to the cytokine release profiles in draining lymph node cells. In addition, the gene expression of the chemokine CXCL1 and/or CXCL2 showed that it has the potential to discriminate sensitizers and non-sensitizing irritants. Our results

Right-handed currents at B→ K l+l− kinematic endpoint

Indian Academy of Sciences (India)

2017-10-09

Oct 9, 2017 ... The recent LHCb measured values of these observables are used to conclude an evidence of right-handed currents at the kinematic endpoint of this decay mode. As the conclusion is drawn at the maximum dilepton invariant mass square ( q 2 ) kinematic endpoint, it relies only on heavy quark symmetries ...

Two-temperature LATE-PCR endpoint genotyping

Directory of Open Access Journals (Sweden)

Reis Arthur H

2006-12-01

Full Text Available Abstract Background In conventional PCR, total amplicon yield becomes independent of starting template number as amplification reaches plateau and varies significantly among replicate reactions. This paper describes a strategy for reconfiguring PCR so that the signal intensity of a single fluorescent detection probe after PCR thermal cycling reflects genomic composition. The resulting method corrects for product yield variations among replicate amplification reactions, permits resolution of homozygous and heterozygous genotypes based on endpoint fluorescence signal intensities, and readily identifies imbalanced allele ratios equivalent to those arising from gene/chromosomal duplications. Furthermore, the use of only a single colored probe for genotyping enhances the multiplex detection capacity of the assay. Results Two-Temperature LATE-PCR endpoint genotyping combines Linear-After-The-Exponential (LATE-PCR (an advanced form of asymmetric PCR that efficiently generates single-stranded DNA and mismatch-tolerant probes capable of detecting allele-specific targets at high temperature and total single-stranded amplicons at a lower temperature in the same reaction. The method is demonstrated here for genotyping single-nucleotide alleles of the human HEXA gene responsible for Tay-Sachs disease and for genotyping SNP alleles near the human p53 tumor suppressor gene. In each case, the final probe signals were normalized against total single-stranded DNA generated in the same reaction. Normalization reduces the coefficient of variation among replicates from 17.22% to as little as 2.78% and permits endpoint genotyping with >99.7% accuracy. These assays are robust because they are consistent over a wide range of input DNA concentrations and give the same results regardless of how many cycles of linear amplification have elapsed. The method is also sufficiently powerful to distinguish between samples with a 1:1 ratio of two alleles from samples comprised of

Pollutant threshold concentration determination in marine ecosystems using an ecological interaction endpoint

International Nuclear Information System (INIS)

Wang, Changyou; Liang, Shengkang; Guo, Wenting; Yu, Hua; Xing, Wenhui

2015-01-01

The threshold concentrations of pollutants are determined by extrapolating single-species effect data to community-level effects. This assumes the most sensitive endpoint of the life cycle of individuals and the species sensitivity distribution from single-species toxic effect tests, thus, ignoring the ecological interactions. The uncertainties due to this extrapolation can be partially overcome using the equilibrium point of a customized ecosystem. This method incorporates ecological interactions and integrates the effects on growth, survival, and ingestion into a single effect measure, the equilibrium point excursion in the customized ecosystem, in order to describe the toxic effects on plankton. A case study showed that the threshold concentration of copper calculated with the endpoint of the equilibrium point was 10 μg L −1 , which is significantly different from the threshold calculated with a single-species endpoint. The endpoint calculated using this method provides a more relevant measure of the ecological impact than any single individual-level endpoint. - Highlights: • Ecotoxicological effect of exposure to copper was tested on a customized ecosystem. • Equilibrium point of biomasses in the customized ecosystem was used as an endpoint. • Exposure–response relationship in a community level was built on equilibrium point. • A threshold concentration incorporating ecological interactions was derived. - The equilibrium biomass incorporating ecological interactions in a customized ecosystem was used as an endpoint to calculate the threshold concentration at a community level

Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

Science.gov (United States)

Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

2014-08-12

Endpoint-based parallel data processing in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective operation through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

Improved Endpoints for Cancer Immunotherapy Trials

Science.gov (United States)

Eggermont, Alexander M. M.; Janetzki, Sylvia; Hodi, F. Stephen; Ibrahim, Ramy; Anderson, Aparna; Humphrey, Rachel; Blumenstein, Brent; Wolchok, Jedd

2010-01-01

Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. PMID:20826737

Pollutant threshold concentration determination in marine ecosystems using an ecological interaction endpoint.

Science.gov (United States)

Wang, Changyou; Liang, Shengkang; Guo, Wenting; Yu, Hua; Xing, Wenhui

2015-09-01

The threshold concentrations of pollutants are determined by extrapolating single-species effect data to community-level effects. This assumes the most sensitive endpoint of the life cycle of individuals and the species sensitivity distribution from single-species toxic effect tests, thus, ignoring the ecological interactions. The uncertainties due to this extrapolation can be partially overcome using the equilibrium point of a customized ecosystem. This method incorporates ecological interactions and integrates the effects on growth, survival, and ingestion into a single effect measure, the equilibrium point excursion in the customized ecosystem, in order to describe the toxic effects on plankton. A case study showed that the threshold concentration of copper calculated with the endpoint of the equilibrium point was 10 μg L(-1), which is significantly different from the threshold calculated with a single-species endpoint. The endpoint calculated using this method provides a more relevant measure of the ecological impact than any single individual-level endpoint. Copyright © 2015 Elsevier Ltd. All rights reserved.

A web-based endpoint adjudication system for interim analyses in clinical trials.

Science.gov (United States)

Nolen, Tracy L; Dimmick, Bill F; Ostrosky-Zeichner, Luis; Kendrick, Amy S; Sable, Carole; Ngai, Angela; Wallace, Dennis

2009-02-01

A data monitoring committee (DMC) is often employed to assess trial progress and review safety data and efficacy endpoints throughout a trail. Interim analyses performed for the DMC should use data that are as complete and verified as possible. Such analyses are complicated when data verification involves subjective study endpoints or requires clinical expertise to determine each subject's status with respect to the study endpoint. Therefore, procedures are needed to obtain adjudicated data for interim analyses in an efficient manner. In the past, methods for handling such data included using locally reported results as surrogate endpoints, adjusting analysis methods for unadjudicated data, or simply performing the adjudication as rapidly as possible. These methods all have inadequacies that make their sole usage suboptimal. For a study of prophylaxis for invasive candidiasis, adjudication of both study eligibility criteria and clinical endpoints prior to two interim analyses was required. Because the study was expected to enroll at a moderate rate and the sponsor required adjudicated endpoints to be used for interim analyses, an efficient process for adjudication was required. We created a web-based endpoint adjudication system (WebEAS) that allows for expedited review by the endpoint adjudication committee (EAC). This system automatically identifies when a subject's data are complete, creates a subject profile from the study data, and assigns EAC reviewers. The reviewers use the WebEAS to review the subject profile and submit their completed review form. The WebEAS then compares the reviews, assigns an additional review as a tiebreaker if needed, and stores the adjudicated data. The study for which this system was originally built was administratively closed after 10 months with only 38 subjects enrolled. The adjudication process was finalized and the WebEAS system activated prior to study closure. Some website accessibility issues presented initially. However

Modeling hard clinical end-point data in economic analyses.

Science.gov (United States)

Kansal, Anuraag R; Zheng, Ying; Palencia, Roberto; Ruffolo, Antonio; Hass, Bastian; Sorensen, Sonja V

2013-11-01

The availability of hard clinical end-point data, such as that on cardiovascular (CV) events among patients with type 2 diabetes mellitus, is increasing, and as a result there is growing interest in using hard end-point data of this type in economic analyses. This study investigated published approaches for modeling hard end-points from clinical trials and evaluated their applicability in health economic models with different disease features. A review of cost-effectiveness models of interventions in clinically significant therapeutic areas (CV diseases, cancer, and chronic lower respiratory diseases) was conducted in PubMed and Embase using a defined search strategy. Only studies integrating hard end-point data from randomized clinical trials were considered. For each study included, clinical input characteristics and modeling approach were summarized and evaluated. A total of 33 articles (23 CV, eight cancer, two respiratory) were accepted for detailed analysis. Decision trees, Markov models, discrete event simulations, and hybrids were used. Event rates were incorporated either as constant rates, time-dependent risks, or risk equations based on patient characteristics. Risks dependent on time and/or patient characteristics were used where major event rates were >1%/year in models with fewer health states (Models of infrequent events or with numerous health states generally preferred constant event rates. The detailed modeling information and terminology varied, sometimes requiring interpretation. Key considerations for cost-effectiveness models incorporating hard end-point data include the frequency and characteristics of the relevant clinical events and how the trial data is reported. When event risk is low, simplification of both the model structure and event rate modeling is recommended. When event risk is common, such as in high risk populations, more detailed modeling approaches, including individual simulations or explicitly time-dependent event rates, are

Bioremediation of hydrocarbon-contaminated soils: are treatability and ecotoxicity endpoints related?

International Nuclear Information System (INIS)

Visser, S.

1999-01-01

To determine if there is a relationship between biotreatability and ecotoxicity endpoints in a wide range of hydrocarbon-contaminated soils, including medium and heavy crude oil-contaminated flare pit wastes and lubrication oil contaminated soil, research was conducted. Each test material was analyzed for pH, water repellency, electrical conductivity, available N and P, total extractable hydrocarbons, oil and grease, and toxicity to seedling emergence, root elongation in barley, lettuce and canola, earthworm survival and luminescent bacteria (Microtox), prior to, and following three months of bioremediation in the laboratory. By monitoring soil respiration, progress of the bioremediation process and determination of a treatment endpoint were assessed. The time required to attain a treatment endpoint under laboratory conditions can range from 30 days to 100 days depending on the concentration of hydrocarbons and degree of weathering. Most flare pits are biotreatable, averaging a loss of 25-30% of hydrocarbons during bioremediation. Once a treatment endpoint is achieved, residual hydrocarbons contents almost always exceeds Alberta Tier I criteria for mineral oil and grease. As a result of bioremediation treatments, hydrophobicity is often reduced from severe to low. Many flare pit materials are still moderately to extremely toxic after reaching a treatment endpoint. (Abstract only)

Percent Wetland Cover

Data.gov (United States)

U.S. Environmental Protection Agency — Wetlands act as filters, removing or diminishing the amount of pollutants that enter surface water. Higher values for percent of wetland cover (WETLNDSPCT) may be...

Sample size determination in clinical trials with multiple endpoints

CERN Document Server

Sozu, Takashi; Hamasaki, Toshimitsu; Evans, Scott R

2015-01-01

This book integrates recent methodological developments for calculating the sample size and power in trials with more than one endpoint considered as multiple primary or co-primary, offering an important reference work for statisticians working in this area. The determination of sample size and the evaluation of power are fundamental and critical elements in the design of clinical trials. If the sample size is too small, important effects may go unnoticed; if the sample size is too large, it represents a waste of resources and unethically puts more participants at risk than necessary. Recently many clinical trials have been designed with more than one endpoint considered as multiple primary or co-primary, creating a need for new approaches to the design and analysis of these clinical trials. The book focuses on the evaluation of power and sample size determination when comparing the effects of two interventions in superiority clinical trials with multiple endpoints. Methods for sample size calculation in clin...

Patients’ preferences for selection of endpoints in cardiovascular clinical trials

Directory of Open Access Journals (Sweden)

Robert D. Chow

2014-02-01

Full Text Available Background: To reduce the duration and overall costs of cardiovascular trials, use of the combined endpoints in trial design has become commonplace. Though this methodology may serve the needs of investigators and trial sponsors, the preferences of patients or potential trial subjects in the trial design process has not been studied. Objective: To determine the preferences of patients in the design of cardiovascular trials. Design: Participants were surveyed in a pilot study regarding preferences among various single endpoints commonly used in cardiovascular trials, preference for single vs. composite endpoints, and the likelihood of compliance with a heart medication if patients similar to them participated in the trial design process. Participants: One hundred adult English-speaking patients, 38% male, from a primary care ambulatory practice located in an urban setting. Key results: Among single endpoints, participants rated heart attack as significantly more important than death from other causes (4.53 vs. 3.69, p=0.004 on a scale of 1–6. Death from heart disease was rated as significantly more important than chest pain (4.73 vs. 2.47, p<0.001, angioplasty/PCI/CABG (4.73 vs. 2.43, p<0.001, and stroke (4.73 vs. 2.43, p<0.001. Participants also expressed a slight preference for combined endpoints over single endpoint (43% vs. 57%, incorporation of the opinions of the study patient population into the design of trials (48% vs. 41% for researchers, and a greater likelihood of medication compliance if patient preferences were considered during trial design (67% indicated a significant to major effect. Conclusions: Patients are able to make judgments and express preferences regarding trial design. They prefer that the opinions of the study population rather than the general population be incorporated into the design of the study. This novel approach to study design would not only incorporate patient preferences into medical decision making, but

Inspiration: One Percent and Rising

Science.gov (United States)

Walling, Donovan R.

2009-01-01

Inventor Thomas Edison once famously declared, "Genius is one percent inspiration and ninety-nine percent perspiration." If that's the case, then the students the author witnessed at the International Student Media Festival (ISMF) last November in Orlando, Florida, are geniuses and more. The students in the ISMF pre-conference workshop…

Sexist Attitudes Among Emerging Adult Women Readers of Fifty Shades Fiction.

Science.gov (United States)

Altenburger, Lauren E; Carotta, Christin L; Bonomi, Amy E; Snyder, Anastasia

2017-02-01

Stereotypical sexist representations of men and women in popular culture reinforce rigid views of masculinity (e.g., males as being strong, in control, masterful, and aggressive) and femininity (e.g., women as being fragile and weak, unassertive, peaceful, irrational, and driven by emotions). The present study examined associations between the fictional series Fifty Shades-one popular culture mechanism that includes pervasive traditional gender role representations-and underlying sexist beliefs among a sample of 715 women ages 18-24 years. Analyses revealed associations between Fifty Shades readership and sexism, as measured through the Ambivalent Sexism Inventory. Namely women who reported reading Fifty Shades had higher levels of ambivalent, benevolent, and hostile sexism. Further, those who interpreted Fifty Shades as "romantic" had higher levels of ambivalent and benevolent sexism. Our findings support prior empirical studies noting associations between interacting with aspects of popular culture, such as television and video games, and individual beliefs and behaviors.

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

Science.gov (United States)

Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; Van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; De Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

2014-11-01

Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparing three novel endpoints for developmental osteotoxicity in the embryonic stem cell test

International Nuclear Information System (INIS)

Nieden, Nicole I. zur; Davis, Lesley A.; Rancourt, Derrick E.

2010-01-01

Birth defects belong to the most serious side effects of pharmaceutical compounds or environmental chemicals. In vivo, teratogens most often affect the normal development of bones, causing growth retardation, limb defects or craniofacial malformations. The embryonic stem cell test (EST) is one of the most promising models that allow the in vitro prediction of embryotoxicity, with one of its endpoints being bone tissue development. The present study was designed to describe three novel inexpensive endpoints to assess developmental osteotoxicity using the model compounds penicillin G (non-teratogenic), 5-fluorouracil (strong teratogen) and all-trans retinoic acid (bone teratogen). These three endpoints were: quantification of matrix incorporated calcium by (1) morphometric analysis and (2) measurement of calcium levels as well as (3) activity of alkaline phosphatase, an enzyme involved in matrix calcification. To evaluate our data, we have compared the concentration curves and resulting ID 50 s of the new endpoints with mRNA expression for osteocalcin. Osteocalcin is an exclusive marker found only in mineralized tissues, is regulated upon compound treatment and reliably predicts the potential of a chemical entity acting as a bone teratogen. By comparing the new endpoints to quantitative expression of osteocalcin, which we previously identified as suitable to detect developmental osteotoxicity, we were ultimately able to illustrate IMAGE analysis and Ca 2+ deposition assays as two reliable novel endpoints for the EST. This is of particular importance for routine industrial assessment of novel compounds as these two new endpoints may substitute previously used molecular read-out methods, which are often costly and time-consuming.

Observations on Three Endpoint Properties and Their Relationship to Regulatory Outcomes of European Oncology Marketing Applications.

Science.gov (United States)

Liberti, Lawrence; Stolk, Pieter; McAuslane, James Neil; Schellens, Jan; Breckenridge, Alasdair M; Leufkens, Hubert

2015-06-01

Guidance and exploratory evidence indicate that the type of endpoints and the magnitude of their outcome can define a therapy's clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes. We explored the relationship of 3 endpoint properties to regulatory outcomes by assessing 50 oncology marketing authorization applications (MAAs; reviewed from 2009 to 2013). Overall, 16 (32%) had a negative outcome. The most commonly used hard endpoints were overall survival (OS) and the duration of response or stable disease. OS was a component of 91% approved and 63% failed MAAs. The most commonly used surrogate endpoints were progression-free survival (PFS), response rate, and health-related quality of life assessments. There was no difference (p = .3801) between the approved and failed MAA cohorts in the proportion of hard endpoints used. A mean of slightly more than four surrogate endpoints were used per approved MAA compared with slightly more than two for failed MAAs. Longer OS and PFS duration outcomes were generally associated with approvals, often when not statistically significant. The approved cohort was associated with a preponderance of statistically significant (p < .05) improvements in primary endpoints (p < .0001 difference between the approved and failed groups). Three key endpoint properties (type of endpoint [hard/surrogate], magnitude of an endpoint outcome, and its statistical significance) are consistent with the European Medicines Agency guidance and, notwithstanding the contribution of unique disease-specific circumstances, are associated with a predictable positive outcome for oncology MAAs. Regulatory decisions made by the European Medicines Agency determine which new medicines will be available to European prescribers and for which therapeutic indications. Regulatory success or failure can be influenced by many factors. This study assessed three key properties of endpoints used in

Fifty years of Erlangen radiochemistry

International Nuclear Information System (INIS)

Morell, W.

2007-01-01

On June 29, 2006, the Radiochemical Laboratory of AREVA NP GmbH (formerly Siemens AG) in Erlangen celebrated its fiftieth anniversary. The occasion was marked by an event attended by more than 1,000 guests, among them Werner Gebauhr, the 85-year-old founder and first head of the Laboratory; the Managing Directors of AREVA NP GmbH, Ralf Gueldner and Ruediger Steuerlein; representatives of universities, research institutions, power utilities, and public authorities. The present head of the Radiochemical Laboratory, Wilfred Morell, sketched the highlights of the work performed over the past fifty years, which ranged from solid-state and very-high-purity materials technologies to development and service activities for nuclear technology. Manfred Erve, head of the Technical Center of AREVA NP GmbH, of which the Radiochemical Laboratory is a part, emphasized the changes in priorities over the past fifty years, which had always been met successfully by Radiochemistry. In the scientific part of the event, Wolfgang Schwarz (E.ON Kernkraftwerk GmbH, KKW Isar), Ulf Ilg (EnBW Kraftwerk AG, KKW Philippsburg), and Hans-Josef Allelein (Gesellschaft fuer Anlagen- und Reaktorsicherheit mbH) explained 3 major subject areas in which Erlangen Radio-chemistry over many years has contributed basic findings (see other articles in this atw issue). On the occasion of the anniversary, a comprehensive booklet was published under the title of '50 Jahre Radiochemie Erlangen - 1956-2006'. (orig.)

Trial endpoints for drug approval in oncology: Chemoprevention.

Science.gov (United States)

Beitz, J

2001-04-01

As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

Comparison of RNA-seq and microarray-based models for clinical endpoint prediction.

Science.gov (United States)

Zhang, Wenqian; Yu, Ying; Hertwig, Falk; Thierry-Mieg, Jean; Zhang, Wenwei; Thierry-Mieg, Danielle; Wang, Jian; Furlanello, Cesare; Devanarayan, Viswanath; Cheng, Jie; Deng, Youping; Hero, Barbara; Hong, Huixiao; Jia, Meiwen; Li, Li; Lin, Simon M; Nikolsky, Yuri; Oberthuer, André; Qing, Tao; Su, Zhenqiang; Volland, Ruth; Wang, Charles; Wang, May D; Ai, Junmei; Albanese, Davide; Asgharzadeh, Shahab; Avigad, Smadar; Bao, Wenjun; Bessarabova, Marina; Brilliant, Murray H; Brors, Benedikt; Chierici, Marco; Chu, Tzu-Ming; Zhang, Jibin; Grundy, Richard G; He, Min Max; Hebbring, Scott; Kaufman, Howard L; Lababidi, Samir; Lancashire, Lee J; Li, Yan; Lu, Xin X; Luo, Heng; Ma, Xiwen; Ning, Baitang; Noguera, Rosa; Peifer, Martin; Phan, John H; Roels, Frederik; Rosswog, Carolina; Shao, Susan; Shen, Jie; Theissen, Jessica; Tonini, Gian Paolo; Vandesompele, Jo; Wu, Po-Yen; Xiao, Wenzhong; Xu, Joshua; Xu, Weihong; Xuan, Jiekun; Yang, Yong; Ye, Zhan; Dong, Zirui; Zhang, Ke K; Yin, Ye; Zhao, Chen; Zheng, Yuanting; Wolfinger, Russell D; Shi, Tieliu; Malkas, Linda H; Berthold, Frank; Wang, Jun; Tong, Weida; Shi, Leming; Peng, Zhiyu; Fischer, Matthias

2015-06-25

Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models. We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.

A comparison of chemoembolization endpoints using angiographic versus transcatheter intraarterial perfusion/MR imaging monitoring.

Science.gov (United States)

Lewandowski, Robert J; Wang, Dingxin; Gehl, James; Atassi, Bassel; Ryu, Robert K; Sato, Kent; Nemcek, Albert A; Miller, Frank H; Mulcahy, Mary F; Kulik, Laura; Larson, Andrew C; Salem, Riad; Omary, Reed A

2007-10-01

Transcatheter arterial chemoembolization (TACE) is an established treatment for unresectable liver cancer. This study was conducted to test the hypothesis that angiographic endpoints during TACE are measurable and reproducible by comparing subjective angiographic versus objective magnetic resonance (MR) endpoints of TACE. The study included 12 consecutive patients who presented for TACE for surgically unresectable HCC or progressive hepatic metastases despite chemotherapy. All procedures were performed with a dedicated imaging system. Angiographic series before and after TACE were reviewed independently by three board-certified interventional radiologists. A subjective angiographic chemoembolization endpoint (SACE) classification scheme, modified from an established angiographic grading system in the cardiology literature, was designed to assist in reproducibly classifying angiographic endpoints. Reproducibility in SACE classification level was compared among operators, and MR imaging perfusion reduction was compared with SACE levels for each observer. Twelve patients successfully underwent 15 separate TACE sessions. SACE levels ranged from I through IV. There was moderate agreement in SACE classification (kappa = 0.46 +/- 0.12). There was no correlation between SACE level and MR perfusion reduction (r = 0.16 for one operator and 0.02 for the other two). Angiographic endpoints during TACE vary widely, have moderate reproducibility among operators, and do not correlate with functional MR imaging perfusion endpoints. Future research should aim to determine ideal angiographic and functional MR imaging endpoints for TACE according to outcome measures such as imaging response, pathologic response, and survival.

Congenital Adrenal Hyperplasia: Classification of Studies Employing Psychological Endpoints

Directory of Open Access Journals (Sweden)

Sandberg DavidE

2010-08-01

Full Text Available Psychological outcomes in persons with congenital adrenal hyperplasia (CAH have received substantial attention. The objectives of this paper were to (1 catalog psychological endpoints assessed in CAH outcome studies and (2 classify the conceptual/theoretical model shaping the research design and interpretation of CAH-related psychological effects. A total of 98 original research studies, published between 1955 and 2009, were categorized based on psychological endpoints examined as well as the research design and conceptual model guiding analysis and interpretation of data. The majority of studies (68% investigated endpoints related to psychosexual differentiation. The preponderance of studies (76% examined a direct relationship (i.e., inferring causality between prenatal androgen exposure and psychological outcomes. Findings are discussed in relation to the observed imbalance between theoretical interest in the role of prenatal androgens in shaping psychosexual differentiation and a broader conceptual model that examines the role of other potential factors in mediating or moderating the influence of CAH pathophysiology on psychological outcomes in both affected females and males. The latter approach offers to identify factors amenable to clinical intervention that enhance both health and quality of life outcomes in CAH as well as other disorders of sex development.

21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Science.gov (United States)

2010-04-01

... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... well-controlled. The applicant shall carry out any such studies with due diligence. ...

Columbia physics in the fifties: Untold tales

Directory of Open Access Journals (Sweden)

J. Sucher

2000-07-01

Full Text Available Eyvind Wichmann and I were both graduate students at Columbia University in the fifties, a decade of remarkable creativity by a star-studded physics faculty, which included some ten Nobel Laureates. I share some reminiscences about our time there and explain the role played in our relationship by an eightball.

Restoration for the future: endpoints, targets, and indicators of progress and success

Science.gov (United States)

Daniel C. Dey; Callie Jo. Schweitzer

2014-01-01

Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly described and quantitative endpoints and intermediary targets are needed to...

Considerations in choosing a primary endpoint that measures durability of virological suppression in an antiretroviral trial.

Science.gov (United States)

Gilbert, P B; Ribaudo, H J; Greenberg, L; Yu, G; Bosch, R J; Tierney, C; Kuritzkes, D R

2000-09-08

At present, many clinical trials of anti-HIV-1 therapies compare treatments by a primary endpoint that measures the durability of suppression of HIV-1 replication. Several durability endpoints are compared. Endpoints are compared by their implicit assumptions regarding surrogacy for clinical outcomes, sample size requirements, and accommodations for inter-patient differences in baseline plasma HIV-1-RNA levels and in initial treatment response. Virological failure is defined by the non-suppression of virus levels at a prespecified follow-up time T(early virological failure), or by relapse. A binary virological failure endpoint is compared with three time-to-virological failure endpoints: time from (i) randomization that assigns early failures a failure time of T weeks; (ii) randomization that extends the early failure time T for slowly responding subjects; and (iii) virological response that assigns non-responders a failure time of 0 weeks. Endpoint differences are illustrated with Agouron's trial 511. In comparing high with low-dose nelfinavir (NFV) regimens in Agouron 511, the difference in Kaplan-Meier estimates of the proportion not failing by 24 weeks is 16.7% (P = 0.048), 6.5% (P = 0.29) and 22.9% (P = 0.0030) for endpoints (i), (ii) and (iii), respectively. The results differ because NFV suppresses virus more quickly at the higher dose, and the endpoints weigh this treatment difference differently. This illustrates that careful consideration needs to be given to choosing a primary endpoint that will detect treatment differences of interest. A time from randomization endpoint is usually recommended because of its advantages in flexibility and sample size, especially at interim analyses, and for its interpretation for patient management.

A systematic comparison of recurrent event models for application to composite endpoints.

Science.gov (United States)

Ozga, Ann-Kathrin; Kieser, Meinhard; Rauch, Geraldine

2018-01-04

Many clinical trials focus on the comparison of the treatment effect between two or more groups concerning a rarely occurring event. In this situation, showing a relevant effect with an acceptable power requires the observation of a large number of patients over a long period of time. For feasibility issues, it is therefore often considered to include several event types of interest, non-fatal or fatal, and to combine them within a composite endpoint. Commonly, a composite endpoint is analyzed with standard survival analysis techniques by assessing the time to the first occurring event. This approach neglects that an individual may experience more than one event which leads to a loss of information. As an alternative, composite endpoints could be analyzed by models for recurrent events. There exists a number of such models, e.g. regression models based on count data or Cox-based models such as the approaches of Andersen and Gill, Prentice, Williams and Peterson or, Wei, Lin and Weissfeld. Although some of the methods were already compared within the literature there exists no systematic investigation for the special requirements regarding composite endpoints. Within this work a simulation-based comparison of recurrent event models applied to composite endpoints is provided for different realistic clinical trial scenarios. We demonstrate that the Andersen-Gill model and the Prentice- Williams-Petersen models show similar results under various data scenarios whereas the Wei-Lin-Weissfeld model delivers effect estimators which can considerably deviate under commonly met data scenarios. Based on the conducted simulation study, this paper helps to understand the pros and cons of the investigated methods in the context of composite endpoints and provides therefore recommendations for an adequate statistical analysis strategy and a meaningful interpretation of results.

Fifty years ago - nuclear physics at Cambridge

International Nuclear Information System (INIS)

Burcham, W.E.

1982-01-01

Fifty years ago, the Cavendish saw the first nuclear transformations using artificially accelerated particles, and was soon to provide confirmation of the discovery of the positron. In 1932, the Cavendish Laboratory under the guiding hand of Rutherford was a world focus for research and with these discoveries saw the birth of modern particle physics. (orig.).

Five criteria for using a surrogate endpoint to predict treatment effect based on data from multiple previous trials.

Science.gov (United States)

Baker, Stuart G

2018-02-20

A surrogate endpoint in a randomized clinical trial is an endpoint that occurs after randomization and before the true, clinically meaningful, endpoint that yields conclusions about the effect of treatment on true endpoint. A surrogate endpoint can accelerate the evaluation of new treatments but at the risk of misleading conclusions. Therefore, criteria are needed for deciding whether to use a surrogate endpoint in a new trial. For the meta-analytic setting of multiple previous trials, each with the same pair of surrogate and true endpoints, this article formulates 5 criteria for using a surrogate endpoint in a new trial to predict the effect of treatment on the true endpoint in the new trial. The first 2 criteria, which are easily computed from a zero-intercept linear random effects model, involve statistical considerations: an acceptable sample size multiplier and an acceptable prediction separation score. The remaining 3 criteria involve clinical and biological considerations: similarity of biological mechanisms of treatments between the new trial and previous trials, similarity of secondary treatments following the surrogate endpoint between the new trial and previous trials, and a negligible risk of harmful side effects arising after the observation of the surrogate endpoint in the new trial. These 5 criteria constitute an appropriately high bar for using a surrogate endpoint to make a definitive treatment recommendation. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Beyond Marbles: Percent Change and Social Justice

Science.gov (United States)

Denny, Flannery

2013-01-01

In the author's eighth year of teaching, she hit a wall teaching percent change. Percent change is one of the few calculations taught in math classes that shows up regularly in the media, and one that she often does in her head to make sense of the world around her. Despite this, she had been teaching percent change using textbook problems about…

Fifty years after Hiroshima

International Nuclear Information System (INIS)

Imai, R.

1997-01-01

Any discussion of the nuclear-proliferation regime in the post-Cold War era, its present role and expected function in the future must take into account the outcome of the New York Non-proliferation Treaty Review Conference held in 1995, and the four factors that shaped the twentieth century: fascism and communism, nuclear energy and environmental concerns, as well as the interaction between them. none of the factors can be handled within the boundaries of a single state. After fifty years of nuclear competition both for military and energy generation purposes, international conferences on disarmament, Non-proliferation Treaty, Comprehensive Test Ban Treaty, START negotiations and agreements, there are still remaining nuclear issues. Population growth, energy demands and supplies, all related to global environmental changes must be taken into account

Endpoint behavior of the pion distribution amplitude in QCD sum rules with nonlocal condensates

International Nuclear Information System (INIS)

Mikhailov, S. V.; Pimikov, A. V.; Stefanis, N. G.

2010-01-01

Starting from the QCD sum rules with nonlocal condensates for the pion distribution amplitude, we derive another sum rule for its derivative and its ''integral derivatives''--defined in this work. We use this new sum rule to analyze the fine details of the pion distribution amplitude in the endpoint region x∼0. The results for endpoint-suppressed and flattop (or flatlike) pion distribution amplitudes are compared with those we obtained with differential sum rules by employing two different models for the distribution of vacuum-quark virtualities. We determine the range of values of the derivatives of the pion distribution amplitude and show that endpoint-suppressed distribution amplitudes lie within this range, while those with endpoint enhancement--flat-type or Chernyak-Zhitnitsky like--yield values outside this range.

Reporting and evaluation of HIV-related clinical endpoints in two multicenter international clinical trials

DEFF Research Database (Denmark)

Lifson, A; Rhame, F; Bellosa, W

2006-01-01

adjudication between reviewers before diagnostic certainty was assigned. CONCLUSION: Important requirements for HIV trials using clinical endpoints include objective definitions of "confirmed" and "probable," a formal reporting process with adequate information and supporting source documentation, evaluation......PURPOSE: The processes for reporting and review of progression of HIV disease clinical endpoints are described for two large phase III international clinical trials. METHOD: SILCAAT and ESPRIT are multicenter randomized HIV trials evaluating the impact of interleukin-2 on disease progression...... and death in HIV-infected patients receiving antiretroviral therapy. We report definitions used for HIV progression of disease endpoints, procedures for site reporting of such events, processes for independent review of reported events by an Endpoint Review Committee (ERC), and the procedure...

Percent Wetland Cover (Future)

Data.gov (United States)

U.S. Environmental Protection Agency — Wetlands act as filters, removing or diminishing the amount of pollutants that enter surface water. Higher values for percent of wetland cover (WETLNDSPCT) may be...

Gastroenterological endpoints in drug trials for cystic fibrosis

NARCIS (Netherlands)

Bodewes, Frank A. J. A.; Verkade, Henkjan J.; Wilschanski, Micheal

2016-01-01

The phenotype of cystic fibrosis includes a wide variety of clinical and biochemical gastrointestinal presentations. These gastrointestinal characteristics of the disease have come under renewed interest as potential outcome measures and clinical endpoints for therapeutic trials in cystic fibrosis.

Reducing sample size by combining superiority and non-inferiority for two primary endpoints in the Social Fitness study.

Science.gov (United States)

Donkers, Hanneke; Graff, Maud; Vernooij-Dassen, Myrra; Nijhuis-van der Sanden, Maria; Teerenstra, Steven

2017-01-01

In randomized controlled trials, two endpoints may be necessary to capture the multidimensional concept of the intervention and the objectives of the study adequately. We show how to calculate sample size when defining success of a trial by combinations of superiority and/or non-inferiority aims for the endpoints. The randomized controlled trial design of the Social Fitness study uses two primary endpoints, which can be combined into five different scenarios for defining success of the trial. We show how to calculate power and sample size for each scenario and compare these for different settings of power of each endpoint and correlation between them. Compared to a single primary endpoint, using two primary endpoints often gives more power when success is defined as: improvement in one of the two endpoints and no deterioration in the other. This also gives better power than when success is defined as: improvement in one prespecified endpoint and no deterioration in the remaining endpoint. When two primary endpoints are equally important, but a positive effect in both simultaneously is not per se required, the objective of having one superior and the other (at least) non-inferior could make sense and reduce sample size. Copyright © 2016 Elsevier Inc. All rights reserved.

Overview of Biomarkers and Surrogate Endpoints in Drug Development

Directory of Open Access Journals (Sweden)

John A. Wagner

2002-01-01

Full Text Available There are numerous factors that recommend the use of biomarkers in drug development including the ability to provide a rational basis for selection of lead compounds, as an aid in determining or refining mechanism of action or pathophysiology, and the ability to work towards qualification and use of a biomarker as a surrogate endpoint. Examples of biomarkers come from many different means of clinical and laboratory measurement. Total cholesterol is an example of a clinically useful biomarker that was successfully qualified for use as a surrogate endpoint. Biomarkers require validation in most circumstances. Validation of biomarker assays is a necessary component to delivery of high-quality research data necessary for effective use of biomarkers. Qualification is necessary for use of a biomarker as a surrogate endpoint. Putative biomarkers are typically identified because of a relationship to known or hypothetical steps in a pathophysiologic cascade. Biomarker discovery can also be effected by expression profiling experiment using a variety of array technologies and related methods. For example, expression profiling experiments enabled the discovery of adipocyte related complement protein of 30 kD (Acrp30 or adiponectin as a biomarker for in vivo activation of peroxisome proliferator-activated receptors (PPAR γ activity.

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)

NARCIS (Netherlands)

Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; de Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

2014-01-01

Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across

SpEnD: Linked Data SPARQL Endpoints Discovery Using Search Engines

OpenAIRE

Yumusak, Semih; Dogdu, Erdogan; Kodaz, Halife; Kamilaris, Andreas

2016-01-01

In this study, a novel metacrawling method is proposed for discovering and monitoring linked data sources on the Web. We implemented the method in a prototype system, named SPARQL Endpoints Discovery (SpEnD). SpEnD starts with a "search keyword" discovery process for finding relevant keywords for the linked data domain and specifically SPARQL endpoints. Then, these search keywords are utilized to find linked data sources via popular search engines (Google, Bing, Yahoo, Yandex). By using this ...

Deep inelastic scattering near the endpoint in soft-collinear effective theory

International Nuclear Information System (INIS)

Chay, Junegone; Kim, Chul

2007-01-01

We apply the soft-collinear effective theory to deep inelastic scattering near the endpoint region. The forward scattering amplitude and the structure functions are shown to factorize as a convolution of the Wilson coefficients, the jet functions, and the parton distribution functions. The behavior of the parton distribution functions near the endpoint region is considered. It turns out that it evolves with the Altarelli-Parisi kernel even in the endpoint region, and the parton distribution function can be factorized further into a collinear part and the soft Wilson line. The factorized form for the structure functions is obtained by the two-step matching, and the radiative corrections or the evolution for each factorized part can be computed in perturbation theory. We present the radiative corrections of each factorized part to leading order in α s , including the zero-bin subtraction for the collinear part

Meeting report: Measuring endocrine-sensitive endpoints within the first years of life

DEFF Research Database (Denmark)

Arbuckle, T.E.; Hauser, R.; Swan, S.H.

2008-01-01

An international workshop tided "Assessing Endocrine-Related Endpoints within the First Years of Life" was held 30 April-1 May 2007, in Ottawa, Ontario, Canada. Representatives from a number of pregnancy cohort studies in North America and Europe presented options for measuring various endocrine......-sensitive endpoints in early life and discussed issues related to performing and using those measures. The workshop focused on measuring reproductive tract developmental endpoints [e.g., anogenital distance (AGD)], endocrine status, and infant anthropometry. To the extent possible, workshop participants strove...... on the genital exam. Although a number of outcome measures recommended during the genital exam have been associated with exposure to endocrine-disrupting chemicals, little is known about how predictive these effects are of later reproductive health or other chronic health conditions....

The Impact of Chemoembolization Endpoints on Survival in Hepatocellular Carcinoma Patients

Science.gov (United States)

Jin, Brian; Wang, Dingxin; Lewandowski, Robert J.; Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Larson, Andrew C.; Salem, Riad; Omary, Reed A.

2010-01-01

OBJECTIVE To investigate the relationship between angiographic embolic endpoints of transarterial chemoembolization (TACE) and survival in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This study retrospectively assessed 105 patients with surgically unresectable HCC who underwent TACE. Patients were classified according to a previously established subjective angiographic chemoembolization endpoint (SACE) scale. Only one patient was classified as SACE level 1 and thus excluded from all subsequent analysis. Survival was evaluated with Kaplan-Meier analysis. Multivariate analysis with Cox’s proportional hazard regression model was used to determine independent prognostic risk factors of survival. RESULTS Overall median survival was 21.1 months (95% confidence interval [CI], 15.9–26.4). Patients embolized to SACE levels 2 and 3 were aggregated and had a significantly higher median survival (25.6 months; 95% CI, 16.2–35.0) than patients embolized to SACE level 4 (17.1 months; 95% CI, 13.3–20.9) (p = 0.035). Multivariate analysis indicated that SACE level 4 (Hazard ratio [HR], 2.49; 95% CI, 1.41–4.42; p = 0.002), European Cooperative Oncology Group performance status > 0 (HR, 1.97; 95% CI, 1.15–3.37; p = 0.013), American Joint Committee on Cancer stage 3 or 4 (HR, 2.42; 95% CI, 1.27–4.60; p = 0.007), and Child-Pugh class B (HR, 1.94; 95% CI, 1.09–3.46; p = 0.025) were all independent negative prognostic indicators of survival. CONCLUSION Embolization to an intermediate, sub-stasis endpoint (SACE levels 2 and 3) during TACE improves survival compared to embolization to a higher, stasis endpoint (SACE level 4). Interventional oncologists should consider targeting these intermediate, sub-stasis angiographic endpoints during TACE. PMID:21427346

Information Systems Curricula: A Fifty Year Journey

Science.gov (United States)

Longenecker, Herbert E., Jr.; Feinstein, David; Clark, Jon D.

2013-01-01

This article presents the results of research to explore the nature of changes in skills over a fifty year period spanning the life of Information Systems model curricula. Work begun in 1999 was expanded both backwards in time, as well as forwards to 2012 to define skills relevant to Information Systems curricula. The work in 1999 was based on job…

Deterrence, denuclearization, and proliferation: Alternative visions of the next fifty years

International Nuclear Information System (INIS)

Lehman, R.F. II.

1994-01-01

The great library of Alexandria may have contained fewer volumes than the number which have been written on the subject of nuclear weapons in the Cold War. With the end of the Cold War, a new nuclear library is in the making. Much thought is being given to the next steps in nuclear policy, strategy, forces, arms control, and nonproliferation. For this very distinguished conference, however, I have been asked to look further ahead indeed, forward fifty-years. Prognostication is always a risky business. Detailed predictions beyond the shortest duration are difficult to label as ''scientific'' even in the social sciences. Forecasting ahead fifty years in an age of ever accelerating change would seem to be hopeless. Projecting the future of nuclear weapons, however, may not be as complex as one might think. Detailing the future fifty years from now is not necessary. We want to inform upcoming decisions by examining the possibilities, not write a history in advance of what is to happen. Our look forward con benefit from a brief look back fifty years. In retrospect, those years passed quickly, and with each additional year, analysts make them appear more simple than they seemed at the time. This paper contributes further to this process of oversimplification, as we say, ''for heuristic purposes.'' When in doubt, I have erred on the side of being provocative

Deterrence, denuclearization, and proliferation: Alternative visions of the next fifty years

Energy Technology Data Exchange (ETDEWEB)

Lehman, R.F. II

1994-02-12

The great library of Alexandria may have contained fewer volumes than the number which have been written on the subject of nuclear weapons in the Cold War. With the end of the Cold War, a new nuclear library is in the making. Much thought is being given to the next steps in nuclear policy, strategy, forces, arms control, and nonproliferation. For this very distinguished conference, however, I have been asked to look further ahead indeed, forward fifty-years. Prognostication is always a risky business. Detailed predictions beyond the shortest duration are difficult to label as ``scientific`` even in the social sciences. Forecasting ahead fifty years in an age of ever accelerating change would seem to be hopeless. Projecting the future of nuclear weapons, however, may not be as complex as one might think. Detailing the future fifty years from now is not necessary. We want to inform upcoming decisions by examining the possibilities, not write a history in advance of what is to happen. Our look forward con benefit from a brief look back fifty years. In retrospect, those years passed quickly, and with each additional year, analysts make them appear more simple than they seemed at the time. This paper contributes further to this process of oversimplification, as we say, ``for heuristic purposes.`` When in doubt, I have erred on the side of being provocative.

The use of intermediate endpoints in the design of type 1 diabetes prevention trials.

Science.gov (United States)

Krischer, Jeffrey P

2013-09-01

This paper presents a rationale for the selection of intermediate endpoints to be used in the design of type 1 diabetes prevention clinical trials. Relatives of individuals diagnosed with type 1 diabetes were enrolled on the TrialNet Natural History Study and screened for diabetes-related autoantibodies. Those with two or more such autoantibodies were analysed with respect to increased HbA1c, decreased C-peptide following an OGTT, or abnormal OGTT values as intermediate markers of disease progression. Over 2 years, a 10% increase in HbA1c, and a 20% or 30% decrease in C-peptide from baseline, or progression to abnormal OGTT, occurred with a frequency between 20% and 41%. The 3- to 5-year risk of type 1 diabetes following each intermediate endpoint was high, namely 47% to 84%. The lower the incidence of the endpoint being reached, the higher the risk of diabetes. A diabetes prevention trial using these intermediate endpoints would require a 30% to 50% smaller sample size than one using type 1 diabetes as the endpoint. The use of an intermediate endpoint in diabetes prevention is based on the generally held view of disease progression from initial occurrence of autoantibodies through successive immunological and metabolic changes to manifest type 1 diabetes. Thus, these markers are suitable for randomised phase 2 trials, which can more rapidly screen promising new therapies, allowing them to be subsequently confirmed in definitive phase 3 trials.

Sperm count as a surrogate endpoint for male fertility control.

Science.gov (United States)

Benda, Norbert; Gerlinger, Christoph

2007-11-30

When assessing the effectiveness of a hormonal method of fertility control in men, the classical approach used for the assessment of hormonal contraceptives in women, by estimating the pregnancy rate or using a life-table analysis for the time to pregnancy, is difficult to apply in a clinical development program. The main reasons are the dissociation of the treated unit, i.e. the man, and the observed unit, i.e. his female partner, the high variability in the frequency of male intercourse, the logistical cost and ethical concerns related to the monitoring of the trial. A reasonable surrogate endpoint of the definite endpoint time to pregnancy is sperm count. In addition to the avoidance of the mentioned problems, trials that compare different treatments are possible with reasonable sample sizes, and study duration can be shorter. However, current products do not suppress sperm production to 100 per cent in all men and the sperm count is only observed with measurement error. Complete azoospermia might not be necessary in order to achieve an acceptable failure rate compared with other forms of male fertility control. Therefore, the use of sperm count as a surrogate endpoint must rely on the results of a previous trial in which both the definitive- and surrogate-endpoint results were assessed. The paper discusses different estimation functions of the mean pregnancy rate (corresponding to the cumulative hazard) that are based on the results of sperm count trial and a previous trial in which both sperm count and time to pregnancy were assessed, as well as the underlying assumptions. Sample size estimations are given for pregnancy rate estimation with a given precision.

Comparison of methods for accurate end-point detection of potentiometric titrations

Science.gov (United States)

Villela, R. L. A.; Borges, P. P.; Vyskočil, L.

2015-01-01

Detection of the end point in potentiometric titrations has wide application on experiments that demand very low measurement uncertainties mainly for certifying reference materials. Simulations of experimental coulometric titration data and consequential error analysis of the end-point values were conducted using a programming code. These simulations revealed that the Levenberg-Marquardt method is in general more accurate than the traditional second derivative technique used currently as end-point detection for potentiometric titrations. Performance of the methods will be compared and presented in this paper.

Comparison of methods for accurate end-point detection of potentiometric titrations

International Nuclear Information System (INIS)

Villela, R L A; Borges, P P; Vyskočil, L

2015-01-01

Detection of the end point in potentiometric titrations has wide application on experiments that demand very low measurement uncertainties mainly for certifying reference materials. Simulations of experimental coulometric titration data and consequential error analysis of the end-point values were conducted using a programming code. These simulations revealed that the Levenberg-Marquardt method is in general more accurate than the traditional second derivative technique used currently as end-point detection for potentiometric titrations. Performance of the methods will be compared and presented in this paper

[Origin exploration of "the fifty-nine acupoints for febrile disease"].

Science.gov (United States)

Li, Guangyi

2017-02-12

Fifty-nine acupoints for febrile disease is recorded in Huangdi Neijing ( Huangdi's Internal Classics ). By analyzing the combination of these acupoints, the writer discovered the acupoint composition and detected their origins from Huangdi's Internal Classics , in which the terms biaoben, qijie and beishu are involved in the theoretic evidence. The writer thought the "fifty-nine acupoints for febrile disease" implied the self-evolution of some acupuncture school in ancient time, which was formed by absorbing the theoretic experiences of the other schools. It is necessary to analyze and interpret the other literatures besides Huangdi's Internal Classics and probably obtain the further reorganization on it.

Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges.

Science.gov (United States)

Angel, Juana; Steele, A Duncan; Franco, Manuel A

2014-01-01

Rotavirus (RV) is a major vaccine-preventable killer of young children worldwide. Two RV vaccines are globally commercially available and other vaccines are in different stages of development. Due to the absence of a suitable correlate of protection (CoP), all RV vaccine efficacy trials have had clinical endpoints. These trials represent an important challenge since RV vaccines have to be introduced in many different settings, placebo-controlled studies are unethical due to the availability of licensed vaccines, and comparator assessments for new vaccines with clinical endpoints are very large, complex, and expensive to conduct. A CoP as a surrogate endpoint would allow predictions of vaccine efficacy for new RV vaccines and enable a regulatory pathway, contributing to the more rapid development of new RV vaccines. The goal of this review is to summarize experiences from RV natural infection and vaccine studies to evaluate potential CoP for use as surrogate endpoints for assessment of new RV vaccines, and to explore challenges and opportunities in the field.

The Use of Tools, Modelling Methods, Data Types, and Endpoints in Systems Medicine: A Survey on Projects of the German e:Med-Programme.

Science.gov (United States)

Gietzelt, Matthias; Höfer, Thomas; Knaup-Gregori, Petra; König, Rainer; Löpprich, Martin; Poos, Alexandra; Ganzinger, Matthias

2016-01-01

Systems medicine is the consequent continuation of research efforts on the road to an individualized medicine. Thereby, systems medicine tries to offer a holistic view on the patient by combining different data sources to highlight different perspectives on the patient's health. Our research question was to identify the main data types, modelling methods, analysis tools, and endpoints currently used and studied in systems medicine. Therefore, we conducted a survey on projects with a systems medicine background. Fifty participants completed this survey. The results of the survey were analyzed using histograms and cross tables, and finally compared to results of a former literature review with the same research focus. The data types reported in this survey were widely diversified. As expected, genomic and phenotype data were used most frequently. In contrast, environmental and behavioral data were rarely used in the projects. Overall, the cross tables of the data types in the survey and the literature review showed overlapping results.

1977 flywheel technology symposium proceedings. [Fifty-two papers

Energy Technology Data Exchange (ETDEWEB)

Chang, G.C.; Stone, R.G. (eds.)

1978-03-01

Fifty-two papers, four paper abstracts, and four brief summaries of panel discussions are presented on flywheel energy storage technology. A separate abstract was prepared for each of 41 papers for inclusion in DOE Energy Research Abstracts (ERA). Eleven papers were processed previously for inclusion in the data base. (PMA)

A Conceptual Model for Solving Percent Problems.

Science.gov (United States)

Bennett, Albert B., Jr.; Nelson, L. Ted

1994-01-01

Presents an alternative method to teaching percent problems which uses a 10x10 grid to help students visualize percents. Offers a means of representing information and suggests different approaches for finding solutions. Includes reproducible student worksheet. (MKR)

The Algebra of the Cumulative Percent Operation.

Science.gov (United States)

Berry, Andrew J.

2002-01-01

Discusses how to help students avoid some pervasive reasoning errors in solving cumulative percent problems. Discusses the meaning of ."%+b%." the additive inverse of ."%." and other useful applications. Emphasizes the operational aspect of the cumulative percent concept. (KHR)

Young Women's Perceptions of the Relationship in Fifty Shades of Grey.

Science.gov (United States)

Bonomi, Amy E; Nichols, Emily M; Carotta, Christin L; Kiuchi, Yuya; Perry, Samantha

2016-02-01

Millions of women are interacting with Fifty Shades of Grey-a best-selling novel and film. Yet, to date, no social science study has been undertaken to examine women's perceptions of the Fifty Shades relationship narrative in its film adaptation-what they deem appealing, what they deem unappealing, and what they would welcome or resist in their own relationship. In the present study, we used focus groups to examine women's perceptions of the relationship patterns in the Fifty Shades of Grey film. Focus groups were conducted with 35 young adult women (randomly sampled from the registrar's office of a large Midwestern university) immediately after watching the Fifty Shades film with the study team at a local theater within two days of the film's release. Seven semistructured questions concentrating on reactions to the relationship patterns between Christian Grey and Anastasia Steele depicted in the Fifty Shades film were asked, including general reactions, appealing and unappealing characteristics, romantic and dangerous elements, and aspects that participants would tolerate (or not tolerate) in their own relationships. While participants assessed parts of the relationship between Christian and Anastasia as exciting and romantic, they consistently indicated an unappealing lack of health in the relationship. Participants expressed grave concerns over Christian's stalking, controlling, manipulative, and emotionally abusive behavior, anger in sexual interactions, and neglect of Anastasia's needs. At the same time, they sympathized with and rationalized Christian's behaviors as a function of his personality, needs, and abilities. A small contingent implicated Anastasia in the unhealthy relationship process, whereas a broader majority of participants highlighted the challenges with trying to "speak up" in an unhealthy relationship like Christian and Anastasia's. When asked where participants would draw the line in their own relationship, participants indicated they would

Development of Cardiovascular and Neurodevelopmental Metrics as Sublethal Endpoints for the Fish Embryo Toxicity Test.

Science.gov (United States)

Krzykwa, Julie C; Olivas, Alexis; Jeffries, Marlo K Sellin

2018-06-19

The fathead minnow fish embryo toxicity (FET) test has been proposed as a more humane alternative to current toxicity testing methods, as younger organisms are thought to experience less distress during toxicant exposure. However, the FET test protocol does not include endpoints that allow for the prediction of sublethal adverse outcomes, limiting its utility relative to other test types. Researchers have proposed the development of sublethal endpoints for the FET test to increase its utility. The present study 1) developed methods for previously unmeasured sublethal metrics in fathead minnows (i.e., spontaneous contraction frequency and heart rate) and 2) investigated the responsiveness of several sublethal endpoints related to growth (wet weight, length, and growth-related gene expression), neurodevelopment (spontaneous contraction frequency, and neurodevelopmental gene expression), and cardiovascular function and development (pericardial area, eye size and cardiovascular related gene expression) as additional FET test metrics using the model toxicant 3,4-dichloroaniline. Of the growth, neurological and cardiovascular endpoints measured, length, eye size and pericardial area were found to more responsive than the other endpoints, respectively. Future studies linking alterations in these endpoints to longer-term adverse impacts are needed to fully evaluate the predictive power of these metrics in chemical and whole effluent toxicity testing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Endpoints and cutpoints in head and neck oncology trials: methodical background, challenges, current practice and perspectives.

Science.gov (United States)

Hezel, Marcus; von Usslar, Kathrin; Kurzweg, Thiemo; Lörincz, Balazs B; Knecht, Rainald

2016-04-01

This article reviews the methodical and statistical basics of designing a trial, with a special focus on the process of defining and choosing endpoints and cutpoints as the foundations of clinical research, and ultimately that of evidence-based medicine. There has been a significant progress in the treatment of head and neck cancer in the past few decades. Currently available treatment options can have a variety of different goals, depending e.g. on tumor stage, among other factors. The outcome of a specific treatment in clinical trials is measured using endpoints. Besides classical endpoints, such as overall survival or organ preservation, other endpoints like quality of life are becoming increasingly important in designing and conducting a trial. The present work is based on electronic research and focuses on the solid methodical and statistical basics of a clinical trial, on the structure of study designs and on the presentation of various endpoints.

Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

Energy Technology Data Exchange (ETDEWEB)

Huang Qihong; Jin Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D.; Stoltz, James H.; Jayadev, Supriya; Blanchard, Kerry T

2004-05-18

Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1 mg/kg per day for 1, 7 and 14 days), methapyrilene (100 mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and

Is Doubling of Serum Creatinine a Valid Clinical 'Hard' Endpoint in Clinical Nephrology Trials?

NARCIS (Netherlands)

Lambers Heerspink, H. J.; Perkovic, V.; de Zeeuw, D.

2011-01-01

The composite of end stage renal disease (ESRD), doubling of serum creatinine and (renal) death, is a frequently used endpoint in randomized clinical trials in nephrology. Doubling of serum creatinine is a well-accepted part of this endpoint because a doubling of serum creatinine reflects a large

Protocol of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project: formal consensus method for the development of guidelines for standardised time-to-event endpoints' definitions in cancer clinical trials.

Science.gov (United States)

Bellera, Carine A; Pulido, Marina; Gourgou, Sophie; Collette, Laurence; Doussau, Adélaïde; Kramar, Andrew; Dabakuyo, Tienhan Sandrine; Ouali, Monia; Auperin, Anne; Filleron, Thomas; Fortpied, Catherine; Le Tourneau, Christophe; Paoletti, Xavier; Mauer, Murielle; Mathoulin-Pélissier, Simone; Bonnetain, Franck

2013-03-01

In randomised phase III cancer clinical trials, the most objectively defined and only validated time-to-event endpoint is overall survival (OS). The appearance of new types of treatments and the multiplication of lines of treatment have resulted in the use of surrogate endpoints for overall survival such as progression-free survival (PFS), or time-to-treatment failure. Their development is strongly influenced by the necessity of reducing clinical trial duration, cost and number of patients. However, while these endpoints are frequently used, they are often poorly defined and definitions can differ between trials which may limit their use as primary endpoints. Moreover, this variability of definitions can impact on the trial's results by affecting estimation of treatments' effects. The aim of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project is to provide recommendations for standardised definitions of time-to-event endpoints in randomised cancer clinical trials. We will use a formal consensus methodology based on experts' opinions which will be obtained in a systematic manner. Definitions will be independently developed for several cancer sites, including pancreatic, breast, head and neck and colon cancer, as well as sarcomas and gastrointestinal stromal tumours (GISTs). The DATECAN project should lead to the elaboration of recommendations that can then be used as guidelines by researchers participating in clinical trials. This process should lead to a standardisation of the definitions of commonly used time-to-event endpoints, enabling appropriate comparisons of future trials' results. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fifty years of Cuba's medical diplomacy: from idealism to pragmatism.

Science.gov (United States)

Feinsilver, Julie M

2010-01-01

Medical diplomacy, the collaboration between countries to simultaneously produce health benefits and improve relations, has been a cornerstone of Cuban foreign policy since the outset of the revolution fifty years ago. It has helped Cuba garner symbolic capital (goodwill, influence, and prestige) well beyond what would have been possible for a small, developing country, and it has contributed to making Cuba a player on the world stage. In recent years, medical diplomacy has been instrumental in providing considerable material capital (aid, credit, and trade), as the oil-for-doctors deals with Venezuela demonstrates. This has helped keep the revolution afloat in trying economic times. What began as the implementation of the one of the core values of the revolution, namely health as a basic human right for all peoples, has continued as both an idealistic and a pragmatic pursuit. This article examines the factors that enabled Cuba to conduct medical diplomacy over the past fifty years, the rationale behind the conduct of this type of soft power politics, the results of that effort, and the mix of idealism and pragmatism that has characterized the experience. Moreover, it presents a typology of medical diplomacy that Cuba has used over the past fifty years.

Individuals versus organisms versus populations in the definition of ecological assessment endpoints.

Science.gov (United States)

Suter, Glenn W; Norton, Susan B; Fairbrother, Anne

2005-11-01

Discussions and applications of the policies and practices of the U.S. Environmental Protection Agency (USEPA) in ecological risk assessment will benefit from continued clarification of the concepts of assessment endpoints and of levels of biological organization. First, assessment endpoint entities and attributes can be defined at different levels of organization. Hence, an organism-level attribute, such as growth or survival, can be applied collectively to a population-level entity such as the brook trout in a stream. Second, assessment endpoints for ecological risk assessment are often mistakenly described as "individual level," which leads to the idea that such assessments are intended to protect individuals. Finally, populations play a more important role in risk assessments than is generally recognized. Organism-level attributes are used primarily for population-level assessments. In addition, the USEPA and other agencies already are basing management decisions on population or community entities and attributes such as production of fisheries, abundance of migratory bird populations, and aquatic community composition.

Determination of percent calcium carbonate in calcium chromate

International Nuclear Information System (INIS)

Middleton, H.W.

1979-01-01

The precision, accuracy and reliability of the macro-combustion method is superior to the Knorr alkalimetric method, and it is faster. It also significantly reduces the calcium chromate waste accrual problem. The macro-combustion method has been adopted as the official method for determination of percent calcium carbonate in thermal battery grade anhydrous calcium chromate and percent calcium carbonate in quicklime used in the production of calcium chromate. The apparatus and procedure can be used to measure the percent carbonate in inorganic materials other than calcium chromate. With simple modifications in the basic apparatus and procedure, the percent carbon and hydrogen can be measured in many organic material, including polymers and polymeric formulations. 5 figures, 5 tables

Helicopter EMS: Research Endpoints and Potential Benefits

Directory of Open Access Journals (Sweden)

Stephen H. Thomas

2012-01-01

Full Text Available Patients, EMS systems, and healthcare regions benefit from Helicopter EMS (HEMS utilization. This article discusses these benefits in terms of specific endpoints utilized in research projects. The endpoint of interest, be it primary, secondary, or surrogate, is important to understand in the deployment of HEMS resources or in planning further HEMS outcomes research. The most important outcomes are those which show potential benefits to the patients, such as functional survival, pain relief, and earlier ALS care. Case reports are also important “outcomes” publications. The benefits of HEMS in the rural setting is the ability to provide timely access to Level I or Level II trauma centers and in nontrauma, interfacility transport of cardiac, stroke, and even sepsis patients. Many HEMS crews have pharmacologic and procedural capabilities that bring a different level of care to a trauma scene or small referring hospital, especially in the rural setting. Regional healthcare and EMS system's benefit from HEMS by their capability to extend the advanced level of care throughout a region, provide a “backup” for areas with limited ALS coverage, minimize transport times, make available direct transport to specialized centers, and offer flexibility of transport in overloaded hospital systems.

Exposing the cancer genome atlas as a SPARQL endpoint.

Science.gov (United States)

Deus, Helena F; Veiga, Diogo F; Freire, Pablo R; Weinstein, John N; Mills, Gordon B; Almeida, Jonas S

2010-12-01

The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. Copyright © 2010 Elsevier Inc. All rights reserved.

Exposing the cancer genome atlas as a SPARQL endpoint

Science.gov (United States)

Deus, Helena F.; Veiga, Diogo F.; Freire, Pablo R.; Weinstein, John N.; Mills, Gordon B.; Almeida, Jonas S.

2011-01-01

The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. PMID:20851208

Alternate Endpoints for Deep Vadose Zone Environments: Challenges, Opportunities, and Progress - 13036

International Nuclear Information System (INIS)

Wellman, Dawn M.; Freshley, Mark D.; Truex, Michael J.; Lee, M. Hope

2013-01-01

Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical to achieve. Use of risk-informed alternate endpoints provide a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable establishing a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

Alternate Endpoints for Deep Vadose Zone Environments: Challenges, Opportunities, and Progress - 13036

Energy Technology Data Exchange (ETDEWEB)

Wellman, Dawn M.; Freshley, Mark D.; Truex, Michael J.; Lee, M. Hope [Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA, 99352 (United States)

2013-07-01

Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical to achieve. Use of risk-informed alternate endpoints provide a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable establishing a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

Multiple-endpoint assay provides a detailed mechanistic view of responses to herbicide exposure in Chlamydomonas reinhardtii

International Nuclear Information System (INIS)

Nestler, Holger; Groh, Ksenia J.; Schönenberger, René; Behra, Renata; Schirmer, Kristin; Eggen, Rik I.L.; Suter, Marc J.-F.

2012-01-01

The release of herbicides into the aquatic environment raises concerns about potential detrimental effects on ecologically important non-target species, such as unicellular algae, necessitating ecotoxicological risk assessment. Algal toxicity tests based on growth, a commonly assessed endpoint, are integrative, and hence do not provide information about underlying toxic mechanisms and effects. This limitation may be overcome by measuring more specific biochemical and physiological endpoints. In the present work, we developed and applied a novel multiple-endpoint assay, and analyzed the effects of the herbicides paraquat, diuron and norflurazon, each representing a specific mechanism of toxic action, on the single celled green alga Chlamydomonas reinhardtii. The endpoints added to assessment of growth were pigment content, maximum and effective photosystem II quantum yield, ATP content, esterase and oxidative activity. All parameters were measured at 2, 6 and 24 h of exposure, except for growth and pigment content, which were determined after 6 and 24 h only. Effective concentrations causing 50% of response (EC50s) and lowest observable effect concentrations (LOECs) were determined for all endpoints and exposure durations where possible. The assay provided a detailed picture of the concentration- and time-dependent development of effects elicited by the analyzed herbicides, thus improving the understanding of the underlying toxic mechanisms. Furthermore, the response patterns were unique to the respective herbicide and reflected the different mechanisms of toxicity. The comparison of the endpoint responses and sensitivities revealed that several physiological and biochemical parameters reacted earlier or stronger to disturbances than growth. Overall, the presented multiple-endpoint assay constitutes a promising basis for investigating stressor and toxicant effects in green algae.

Multiple-endpoint assay provides a detailed mechanistic view of responses to herbicide exposure in Chlamydomonas reinhardtii

Energy Technology Data Exchange (ETDEWEB)

Nestler, Holger [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); Groh, Ksenia J.; Schoenenberger, Rene; Behra, Renata [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); Schirmer, Kristin [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); EPF Lausanne, School of Architecture, Civil and Environmental Engineering, 1015 Lausanne (Switzerland); Eggen, Rik I.L. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); Suter, Marc J.-F., E-mail: suter@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland)

2012-04-15

The release of herbicides into the aquatic environment raises concerns about potential detrimental effects on ecologically important non-target species, such as unicellular algae, necessitating ecotoxicological risk assessment. Algal toxicity tests based on growth, a commonly assessed endpoint, are integrative, and hence do not provide information about underlying toxic mechanisms and effects. This limitation may be overcome by measuring more specific biochemical and physiological endpoints. In the present work, we developed and applied a novel multiple-endpoint assay, and analyzed the effects of the herbicides paraquat, diuron and norflurazon, each representing a specific mechanism of toxic action, on the single celled green alga Chlamydomonas reinhardtii. The endpoints added to assessment of growth were pigment content, maximum and effective photosystem II quantum yield, ATP content, esterase and oxidative activity. All parameters were measured at 2, 6 and 24 h of exposure, except for growth and pigment content, which were determined after 6 and 24 h only. Effective concentrations causing 50% of response (EC50s) and lowest observable effect concentrations (LOECs) were determined for all endpoints and exposure durations where possible. The assay provided a detailed picture of the concentration- and time-dependent development of effects elicited by the analyzed herbicides, thus improving the understanding of the underlying toxic mechanisms. Furthermore, the response patterns were unique to the respective herbicide and reflected the different mechanisms of toxicity. The comparison of the endpoint responses and sensitivities revealed that several physiological and biochemical parameters reacted earlier or stronger to disturbances than growth. Overall, the presented multiple-endpoint assay constitutes a promising basis for investigating stressor and toxicant effects in green algae.

Detection of Bordetella pertussis from Clinical Samples by Culture and End-Point PCR in Malaysian Patients.

Science.gov (United States)

Ting, Tan Xue; Hashim, Rohaidah; Ahmad, Norazah; Abdullah, Khairul Hafizi

2013-01-01

Pertussis or whooping cough is a highly infectious respiratory disease caused by Bordetella pertussis. In vaccinating countries, infants, adolescents, and adults are relevant patients groups. A total of 707 clinical specimens were received from major hospitals in Malaysia in year 2011. These specimens were cultured on Regan-Lowe charcoal agar and subjected to end-point PCR, which amplified the repetitive insertion sequence IS481 and pertussis toxin promoter gene. Out of these specimens, 275 were positive: 4 by culture only, 6 by both end-point PCR and culture, and 265 by end-point PCR only. The majority of the positive cases were from ≤3 months old patients (77.1%) (P 0.05). Our study showed that the end-point PCR technique was able to pick up more positive cases compared to culture method.

Percent voluntary inactivation and peak force predictions with the interpolated twitch technique in individuals with high ability of voluntary activation

International Nuclear Information System (INIS)

Herda, Trent J; Walter, Ashley A; Hoge, Katherine M; Stout, Jeffrey R; Costa, Pablo B; Ryan, Eric D; Cramer, Joel T

2011-01-01

The purpose of this study was to examine the sensitivity and peak force prediction capability of the interpolated twitch technique (ITT) performed during submaximal and maximal voluntary contractions (MVCs) in subjects with the ability to maximally activate their plantar flexors. Twelve subjects performed two MVCs and nine submaximal contractions with the ITT method to calculate percent voluntary inactivation (%VI). Additionally, two MVCs were performed without the ITT. Polynomial models (linear, quadratic and cubic) were applied to the 10–90% VI and 40–90% VI versus force relationships to predict force. Peak force from the ITT MVC was 6.7% less than peak force from the MVC without the ITT. Fifty-eight percent of the 10–90% VI versus force relationships were best fit with nonlinear models; however, all 40–90% VI versus force relationships were best fit with linear models. Regardless of the polynomial model or the contraction intensities used to predict force, all models underestimated the actual force from 22% to 28%. There was low sensitivity of the ITT method at high contraction intensities and the predicted force from polynomial models significantly underestimated the actual force. Caution is warranted when interpreting the % VI at high contraction intensities and predicted peak force from submaximal contractions

The Asthma Control Questionnaire as a clinical trial endpoint

DEFF Research Database (Denmark)

Barnes, P J; Casale, T B; Dahl, Ronald

2014-01-01

these component endpoints; however, there is no consensus on the optimal instrument for use in clinical trials. The Asthma Control Questionnaire (ACQ) has been shown to be a valid, reliable instrument that allows accurate and reproducible assessment of asthma control that compares favourably with other commonly...

Endpoint singularities in unintegrated parton distributions

CERN Document Server

Hautmann, F

2007-01-01

We examine the singular behavior from the endpoint region x -> 1 in parton distributions unintegrated in both longitudinal and transverse momenta. We identify and regularize the singularities by using the subtraction method, and compare this with the cut-off regularization method. The counterterms for the distributions with subtractive regularization are given in coordinate space by compact all-order expressions in terms of eikonal-line operators. We carry out an explicit calculation at one loop for the unintegrated quark distribution. We discuss the relation of the unintegrated parton distributions in subtractive regularization with the ordinary parton distributions.

Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

International Nuclear Information System (INIS)

Methy, Nicolas; Bedenne, Laurent; Bonnetain, Franck

2010-01-01

Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position N1) to the least relevant in their opinion. Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS. DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than

Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists.

Science.gov (United States)

Methy, Nicolas; Bedenne, Laurent; Bonnetain, Franck

2010-06-10

Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion.Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS.DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69

Endpoint in plasma etch process using new modified w-multivariate charts and windowed regression

Science.gov (United States)

Zakour, Sihem Ben; Taleb, Hassen

2017-09-01

Endpoint detection is very important undertaking on the side of getting a good understanding and figuring out if a plasma etching process is done in the right way, especially if the etched area is very small (0.1%). It truly is a crucial part of supplying repeatable effects in every single wafer. When the film being etched has been completely cleared, the endpoint is reached. To ensure the desired device performance on the produced integrated circuit, the high optical emission spectroscopy (OES) sensor is employed. The huge number of gathered wavelengths (profiles) is then analyzed and pre-processed using a new proposed simple algorithm named Spectra peak selection (SPS) to select the important wavelengths, then we employ wavelet analysis (WA) to enhance the performance of detection by suppressing noise and redundant information. The selected and treated OES wavelengths are then used in modified multivariate control charts (MEWMA and Hotelling) for three statistics (mean, SD and CV) and windowed polynomial regression for mean. The employ of three aforementioned statistics is motivated by controlling mean shift, variance shift and their ratio (CV) if both mean and SD are not stable. The control charts show their performance in detecting endpoint especially W-mean Hotelling chart and the worst result is given by CV statistic. As the best detection of endpoint is given by the W-Hotelling mean statistic, this statistic will be used to construct a windowed wavelet Hotelling polynomial regression. This latter can only identify the window containing endpoint phenomenon.

26 CFR 301.6226(b)-1 - 5-percent group.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 18 2010-04-01 2010-04-01 false 5-percent group. 301.6226(b)-1 Section 301.6226... ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6226(b)-1 5-percent group. (a) In general. All members of a 5-percent group shall join in filing any petition for judicial review. The...

Using an Ecosystem Approach to complement protection schemes based on organism-level endpoints

International Nuclear Information System (INIS)

Bradshaw, Clare; Kapustka, Lawrence; Barnthouse, Lawrence; Brown, Justin; Ciffroy, Philippe; Forbes, Valery; Geras'kin, Stanislav; Kautsky, Ulrik; Bréchignac, François

2014-01-01

Radiation protection goals for ecological resources are focussed on ecological structures and functions at population-, community-, and ecosystem-levels. The current approach to radiation safety for non-human biota relies on organism-level endpoints, and as such is not aligned with the stated overarching protection goals of international agencies. Exposure to stressors can trigger non-linear changes in ecosystem structure and function that cannot be predicted from effects on individual organisms. From the ecological sciences, we know that important interactive dynamics related to such emergent properties determine the flows of goods and services in ecological systems that human societies rely upon. A previous Task Group of the IUR (International Union of Radioecology) has presented the rationale for adding an Ecosystem Approach to the suite of tools available to manage radiation safety. In this paper, we summarize the arguments for an Ecosystem Approach and identify next steps and challenges ahead pertaining to developing and implementing a practical Ecosystem Approach to complement organism-level endpoints currently used in radiation safety. - Highlights: • An Ecosystem Approach to radiation safety complements the organism-level approach. • Emergent properties in ecosystems are not captured by organism-level endpoints. • The proposed Ecosystem Approach better aligns with management goals. • Practical guidance with respect to system-level endpoints is needed. • Guidance on computational model selection would benefit an Ecosystem Approach

Use of endpoint adjudication to improve the quality and validity of endpoint assessment for medical device development and post marketing evaluation: Rationale and best practices. A report from the cardiac safety research consortium.

Science.gov (United States)

Seltzer, Jonathan H; Heise, Ted; Carson, Peter; Canos, Daniel; Hiatt, Jo Carol; Vranckx, Pascal; Christen, Thomas; Cutlip, Donald E

2017-08-01

This white paper provides a summary of presentations, discussions and conclusions of a Thinktank entitled "The Role of Endpoint Adjudication in Medical Device Clinical Trials". The think tank was cosponsored by the Cardiac Safety Research Committee, MDEpiNet and the US Food and Drug Administration (FDA) and was convened at the FDA's White Oak headquarters on March 11, 2016. Attention was focused on tailoring best practices for evaluation of endpoints in medical device clinical trials, practical issues in endpoint adjudication of therapeutic, diagnostic, biomarker and drug-device combinations, and the role of adjudication in regulatory and reimbursement issues throughout the device lifecycle. Attendees included representatives from medical device companies, the FDA, Centers for Medicare and Medicaid Services (CMS), end point adjudication specialist groups, clinical research organizations, and active, academically based adjudicators. The manuscript presents recommendations from the think tank regarding (1) rationale for when adjudication is appropriate, (2) best practices establishment and operation of a medical device adjudication committee and (3) the role of endpoint adjudication for post market evaluation in the emerging era of real world evidence. Copyright © 2017. Published by Elsevier Inc.

Restoration for the future: Setting endpoints and targets and selecting indicators of progress and success

Science.gov (United States)

Daniel C. Dey; Callie Jo Schweitzer; John M. Kabrick

2014-01-01

Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly written and quantitative endpoints and intermediary targets need to be...

First Fifty Years of Chemoresistive Gas Sensors

Directory of Open Access Journals (Sweden)

Giovanni Neri

2015-01-01

Full Text Available The first fifty years of chemoresistive sensors for gas detection are here reviewed, focusing on the main scientific and technological innovations that have occurred in the field over the course of these years. A look at advances made in fundamental and applied research and leading to the development of actual high performance chemoresistive devices is presented. The approaches devoted to the synthesis of novel semiconducting materials with unprecedented nanostructure and gas-sensing properties have been also presented. Perspectives on new technologies and future applications of chemoresistive gas sensors have also been highlighted.

Nuclear fission discovered fifty years ago

International Nuclear Information System (INIS)

Weis, M.

1988-01-01

Fifty years ago, Otto Hahn, Lise Meitner and Fritz Strassmann discovered the process of nuclear fission which, more than other scientific discoveries to date, profoundly has changed the world and continues to influence our life significantly: This discovery made the up to then incontestable physicists' view of the atom as an inseparable whole suddenly shatter to pieces. It has brought about the invaluable advantages of a peaceful utilization of nuclear energy, and at the same time put scientists in the position to build the most terrible weapon ever, threatening mankind and earth with complete destruction. All this certainly is reason enough to recall the scientists, their work and the spirit of the time. (orig.) [de

Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

Directory of Open Access Journals (Sweden)

Bonnetain Franck

2010-06-01

Full Text Available Abstract Background Overall survival (OS is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL. Methods In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1 to the least relevant in their opinion. Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Results Response rate was 30% (24/80 in the first round and 20% (16/80 in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS. DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings

Characterization of the uranium--2 weight percent molybdenum alloy

International Nuclear Information System (INIS)

Hemperly, V.C.

1976-01-01

The uranium-2 wt percent molybdenum alloy was prepared, processed, and age hardened to meet a minimum 930-MPa yield strength (0.2 percent) with a minimum of 10 percent elongation. These mechanical properties were obtained with a carbon level up to 300 ppM in the alloy. The tensile-test ductility is lowered by the humidity of the laboratory atmosphere

Importance of glomerular filtration rate change as surrogate endpoint for the future incidence of end-stage renal disease in general Japanese population: community-based cohort study.

Science.gov (United States)

Kanda, Eiichiro; Usui, Tomoko; Kashihara, Naoki; Iseki, Chiho; Iseki, Kunitoshi; Nangaku, Masaomi

2018-04-01

Because of the necessity for extended period and large costs until the event occurs, surrogate endpoints are indispensable for implementation of clinical studies to improve chronic kidney disease (CKD) patients' prognosis. Subjects with serum creatinine level for a baseline period over 1-3 years were enrolled (n = 69,238) in this community-based prospective cohort study in Okinawa, Japan, and followed up for 15 years. The endpoint was end-stage renal disease (ESRD). The percent of estimated glomerular filtration rate (%eGFR) change was calculated on the basis of the baseline period. Subjects had a mean ± SD age, 55.59 ± 14.69 years; eGFR, 80.15 ± 21.15 ml/min/1.73 m 2 . Among the subjects recruited, 15.81% had a low eGFR (<60 ml/min/1.73 m 2 ) and 36.1/100,000 person years developed ESRD. Cox proportional hazards models adjusted for baseline characteristics showed that the risk of ESRD tended to be high with high rates of decrease in %eGFR changes over 2 or 3 years in the high- and low-eGFR groups. The specificities and positive predictive values for ESRD based on a cutoff value of %eGFR change of less than -30% over 2 or 3 years were high in the high- and low-eGFR groups. %eGFR change tends to be associated with the risk of ESRD. %eGFR change of less than -30% over 2 or 3 years can be a candidate surrogate endpoint for ESRD in the general Japanese population.

Endpoint-based parallel data processing with non-blocking collective instructions in a parallel active messaging interface of a parallel computer

Science.gov (United States)

Archer, Charles J; Blocksome, Michael A; Cernohous, Bob R; Ratterman, Joseph D; Smith, Brian E

2014-11-11

Endpoint-based parallel data processing with non-blocking collective instructions in a PAMI of a parallel computer is disclosed. The PAMI is composed of data communications endpoints, each including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task. The compute nodes are coupled for data communications through the PAMI. The parallel application establishes a data communications geometry specifying a set of endpoints that are used in collective operations of the PAMI by associating with the geometry a list of collective algorithms valid for use with the endpoints of the geometry; registering in each endpoint in the geometry a dispatch callback function for a collective operation; and executing without blocking, through a single one of the endpoints in the geometry, an instruction for the collective operation.

Nuclear spin: Fifty years of ups and downs

Energy Technology Data Exchange (ETDEWEB)

Pines, A. [Lawrence Berkeley National Lab., CA (United States)

1996-12-31

Rumors of its demise notwithstanding, nuclear magnetic resonance (NMR) continues to flourish fifty years after our birth. The lecture will be a reminiscence about moments of excitation, coherence and relaxation in the history of NMR which produced, among other developments, spin echoes and time reversal, Fourier transform and multidimensional spectroscopy, magnetic resonance imaging, and high resolution solid state NMR. Applications of modern NMR spectroscopy cut across the boundaries of physics, chemistry, materials, biology and medicine.

Energetic endpoints provide early indicators of life history effects in a freshwater gastropod exposed to the fungicide, pyraclostrobin

International Nuclear Information System (INIS)

Fidder, Bridgette N.; Reátegui-Zirena, Evelyn G.; Olson, Adric D.; Salice, Christopher J.

2016-01-01

Organismal energetics provide important insights into the effects of environmental toxicants. We aimed to determine the effects of pyraclostrobin on Lymnaea stagnalis by examining energy allocation patterns and life history traits. Juvenile snails exposed to pyraclostrobin decreased feeding rate and increased apparent avoidance behaviors at environmentally relevant concentrations. In adults, we found that sublethal concentrations of pyraclostrobin did not affect reproductive output, however, there were significant effects on developmental endpoints with longer time to hatch and decreased hatching success in pyraclostrobin-exposed egg masses. Further, there were apparent differences in developmental effects depending on whether mothers were also exposed to pyraclostrobin suggesting this chemical can exert intergenerational effects. Pyraclostrobin also affected protein and carbohydrate content of eggs in mothers that were exposed to pyraclostrobin. Significant effects on macronutrient content of eggs occurred at lower concentrations than effects on gross endpoints such as hatching success and time to hatch suggesting potential value for these endpoints as early indicators of ecologically relevant stress. These results provide important insight into the effects of a common fungicide on important endpoints for organismal energetics and life history. - Highlights: • We exposed a freshwater snail to relevant concentrations of pyraclostrobin. • We monitored energetic and life history endpoints. • Pyraclostrobin affected feeding, hatching success and egg macronutrient content. • Energetic-based endpoints may provide valuable insight to toxic effects. - The fungicide pyraclostrobin at environmentally relevant concentrations effects a range of life history and energetic endpoints in the freshwater snail, Lymnaea stagnalis.

Adaptive endpoint detection of seismic signal based on auto-correlated function

International Nuclear Information System (INIS)

Fan Wanchun; Shi Ren

2000-01-01

There are certain shortcomings for the endpoint detection by time-waveform envelope and/or by checking the travel table (both labelled as the artificial detection method). Based on the analysis of the auto-correlation function, the notion of the distance between auto-correlation functions was quoted, and the characterizations of the noise and the signal with noise were discussed by using the distance. Then, the method of auto-adaptable endpoint detection of seismic signal based on auto-correlated similarity was summed up. The steps of implementation and determining of the thresholds were presented in detail. The experimental results that were compared with the methods based on artificial detecting show that this method has higher sensitivity even in a low SNR circumstance

The relationships between percent body fat and other ...

African Journals Online (AJOL)

The relationships between percent body fat and other anthropometric nutritional predictors among male and female children in Nigeria. ... A weak significant positive correlation was observed between the percent body fat and height – armspan ratio ... There was evidence of overweight and obesity in both children. The mid ...

Time-dependent efficacy of longitudinal biomarker for clinical endpoint.

Science.gov (United States)

Kolamunnage-Dona, Ruwanthi; Williamson, Paula R

2018-06-01

Joint modelling of longitudinal biomarker and event-time processes has gained its popularity in recent years as they yield more accurate and precise estimates. Considering this modelling framework, a new methodology for evaluating the time-dependent efficacy of a longitudinal biomarker for clinical endpoint is proposed in this article. In particular, the proposed model assesses how well longitudinally repeated measurements of a biomarker over various time periods (0,t) distinguish between individuals who developed the disease by time t and individuals who remain disease-free beyond time t. The receiver operating characteristic curve is used to provide the corresponding efficacy summaries at various t based on the association between longitudinal biomarker trajectory and risk of clinical endpoint prior to each time point. The model also allows detecting the time period over which a biomarker should be monitored for its best discriminatory value. The proposed approach is evaluated through simulation and illustrated on the motivating dataset from a prospective observational study of biomarkers to diagnose the onset of sepsis.

Abdominal pain endpoints currently recommended by the FDA and EMA for adult patients with irritable bowel syndrome may not be reliable in children.

Science.gov (United States)

Saps, M; Lavigne, J V

2015-06-01

The Food and Drug Administration (FDA) recommended ≥30% decrease on patient-reported outcomes for pain be considered clinically significant in clinical trials for adults with irritable bowel syndrome. This percent change approach may not be appropriate for children. We compared three alternate approaches to determining clinically significant reductions in pain among children. 80 children with functional abdominal pain participated in a study of the efficacy of amitriptyline. Endpoints included patient-reported estimates of feeling better, and pain Visual Analog Scale (VAS). The minimum clinically important difference in pain report was calculated as (i) mean change in VAS score for children reporting being 'better'; (ii) percent changes in pain (≥30% and ≥50%) on the VAS; and (iii) statistically reliable changes on the VAS for 68% and 95% confidence intervals. There was poor agreement between the three approaches. 43.6% of the children who met the FDA ≥30% criterion for clinically significant change did not achieve a reliable level of improvement (95% confidence interval). Children's self-reported ratings of being better may not be statistically reliable. A combined approach in which children must report improvement as better and achieve a statistically significant change may be more appropriate for outcomes in clinical trials. © 2015 John Wiley & Sons Ltd.

Verifying Elimination Programs with a Special Emphasis on Cysticercosis Endpoints and Postelimination Surveillance

Directory of Open Access Journals (Sweden)

Sukwan Handali

2012-01-01

Full Text Available Methods are needed for determining program endpoints or postprogram surveillance for any elimination program. Cysticercosis has the necessary effective strategies and diagnostic tools for establishing an elimination program; however, tools to verify program endpoints have not been determined. Using a statistical approach, the present study proposed that taeniasis and porcine cysticercosis antibody assays could be used to determine with a high statistical confidence whether an area is free of disease. Confidence would be improved by using secondary tests such as the taeniasis coproantigen assay and necropsy of the sentinel pigs.

DMPD: Fifty years of interferon research: aiming at a moving target. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available mmunity. 2006 Sep;25(3):343-8. (.png) (.svg) (.html) (.csml) Show Fifty years of interferon research: aiming at a moving target. Pubm...edID 16979566 Title Fifty years of interferon research: aiming at a moving target.

Root length of aquatic plant, Lemna minor L., as an optimal toxicity endpoint for biomonitoring of mining effluents.

Science.gov (United States)

Gopalapillai, Yamini; Vigneault, Bernard; Hale, Beverley A

2014-10-01

Lemna minor, a free-floating macrophyte, is used for biomonitoring of mine effluent quality under the Metal Mining Effluent Regulations (MMER) of the Environmental Effects Monitoring (EEM) program in Canada and is known to be sensitive to trace metals commonly discharged in mine effluents such as Ni. Environment Canada's standard toxicity testing protocol recommends frond count (FC) and dry weight (DW) as the 2 required toxicity endpoints-this is similar to other major protocols such as those by the US Environmental Protection Agency (USEPA) and the Organisation for Economic Co-operation and Development (OECD)-that both require frond growth or biomass endpoints. However, we suggest that similar to terrestrial plants, average root length (RL) of aquatic plants will be an optimal and relevant endpoint. As expected, results demonstrate that RL is the ideal endpoint based on the 3 criteria: accuracy (i.e., toxicological sensitivity to contaminant), precision (i.e., lowest variance), and ecological relevance (metal mining effluents). Roots are known to play a major role in nutrient uptake in conditions of low nutrient conditions-thus having ecological relevance to freshwater from mining regions. Root length was the most sensitive and precise endpoint in this study where water chemistry varied greatly (pH and varying concentrations of Ca, Mg, Na, K, dissolved organic carbon, and an anthropogenic organic contaminant, sodium isopropyl xanthates) to match mining effluent ranges. Although frond count was a close second, dry weight proved to be an unreliable endpoint. We conclude that toxicity testing for the floating macrophyte should require average RL measurement as a primary endpoint. © 2014 SETAC.

Fiction or not? Fifty Shades is associated with health risks in adolescent and young adult females.

Science.gov (United States)

Bonomi, Amy E; Nemeth, Julianna M; Altenburger, Lauren E; Anderson, Melissa L; Snyder, Anastasia; Dotto, Irma

2014-09-01

No prior study has empirically characterized the association between health risks and reading popular fiction depicting violence against women. Fifty Shades--a blockbuster fiction series--depicts pervasive violence against women, perpetuating a broader social narrative that normalizes these types of risks and behaviors in women's lives. The present study characterized the association between health risks in women who read and did not read Fifty Shades; while our cross-sectional study design precluded causal determinations, an empirical representation of the health risks in women consuming the problematic messages in Fifty Shades is made. Females ages 18 to 24 (n=715), who were enrolled in a large Midwestern university, completed a cross-sectional online survey about their health behaviors and Fifty Shades' readership. The analysis included 655 females (219 who read at least the first Fifty Shades novel and 436 who did not read any part of Fifty Shades). Age- and race-adjusted multivariable models characterized Fifty Shades' readers and nonreaders on intimate partner violence victimization (experiencing physical, sexual and psychological abuse, including cyber-abuse, at some point during their lifetime); binge drinking (consuming five or more alcoholic beverages on six or more days in the last month); sexual practices (having five or more intercourse partners and/or one or more anal sex partner during their lifetime); and using diet aids or fasting for 24 or more hours at some point during their lifetime. One-third of subjects read Fifty Shades (18.6%, or 122/655, read all three novels, and 14.8%, or 97/655, read at least the first novel but not all three). In age- and race-adjusted models, compared with nonreaders, females who read at least the first novel (but not all three) were more likely than nonreaders to have had, during their lifetime, a partner who shouted, yelled, or swore at them (relative risk [RR]=1.25) and who delivered unwanted calls/text messages

Impact of confinement housing on study end-points in the calf model of cryptosporidiosis.

Science.gov (United States)

Graef, Geneva; Hurst, Natalie J; Kidder, Lance; Sy, Tracy L; Goodman, Laura B; Preston, Whitney D; Arnold, Samuel L M; Zambriski, Jennifer A

2018-04-01

Diarrhea is the second leading cause of death in children confinement housing, and Interval Collection (IC), which permits use of box stalls. CFC mimics human challenge model methodology but it is unknown if confinement housing impacts study end-points and if data gathered via this method is suitable for generalization to human populations. Using a modified crossover study design we compared CFC and IC and evaluated the impact of housing on study end-points. At birth, calves were randomly assigned to confinement (n = 14) or box stall housing (n = 9), or were challenged with 5 x 107 C. parvum oocysts, and followed for 10 days. Study end-points included fecal oocyst shedding, severity of diarrhea, degree of dehydration, and plasma cortisol. Calves in confinement had no significant differences in mean log oocysts enumerated per gram of fecal dry matter between CFC and IC samples (P = 0.6), nor were there diurnal variations in oocyst shedding (P = 0.1). Confinement housed calves shed significantly more oocysts (P = 0.05), had higher plasma cortisol (P = 0.001), and required more supportive care (P = 0.0009) than calves in box stalls. Housing method confounds study end-points in the calf model of cryptosporidiosis. Due to increased stress data collected from calves in confinement housing may not accurately estimate the efficacy of chemotherapeutics targeting C. parvum.

Implementation of minimally invasive and objective humane endpoints in the study of murine Plasmodium infections

DEFF Research Database (Denmark)

Dellavalle, B; Kirchhoff, J; Maretty, L

2014-01-01

SUMMARY Defining appropriate and objective endpoints for animal research can be difficult. Previously we evaluated and implemented a body temperature (BT) of ECM) and were interested in a similar endpoint for a model of severe malarial...... anaemia (SMA). Furthermore, we investigate the potential of a minimally invasive, non-contact infrared thermometer for repeated BT measurement. ECM was induced with Plasmodium berghei ANKA infection in C57Bl/6 mice. SMA was induced with Plasmodium chabaudi AS infection in A/J mice. Our previous published...... endpoint was applied in ECM and 30 °C was pre-determined as the lowest permitted limit for termination in SMA according to consultation with the Danish Animal Inspectorate. Infrared thermometer was compared with the rectal probe after cervical dislocation, ECM and SMA. Linear regression analysis of rectal...

Population modelling to compare chronic external radiotoxicity between individual and population endpoints in four taxonomic groups

International Nuclear Information System (INIS)

Alonzo, Frédéric; Hertel-Aas, Turid; Real, Almudena; Lance, Emilie; Garcia-Sanchez, Laurent; Bradshaw, Clare; Vives i Batlle, Jordi; Oughton, Deborah H.; Garnier-Laplace, Jacqueline

2016-01-01

In this study, we modelled population responses to chronic external gamma radiation in 12 laboratory species (including aquatic and soil invertebrates, fish and terrestrial mammals). Our aim was to compare radiosensitivity between individual and population endpoints and to examine how internationally proposed benchmarks for environmental radioprotection protected species against various risks at the population level. To do so, we used population matrix models, combining life history and chronic radiotoxicity data (derived from laboratory experiments and described in the literature and the FREDERICA database) to simulate changes in population endpoints (net reproductive rate R_0, asymptotic population growth rate λ, equilibrium population size N_e_q) for a range of dose rates. Elasticity analyses of models showed that population responses differed depending on the affected individual endpoint (juvenile or adult survival, delay in maturity or reduction in fecundity), the considered population endpoint (R_0, λ or N_e_q) and the life history of the studied species. Among population endpoints, net reproductive rate R_0 showed the lowest EDR_1_0 (effective dose rate inducing 10% effect) in all species, with values ranging from 26 μGy h"−"1 in the mouse Mus musculus to 38,000 μGy h"−"1 in the fish Oryzias latipes. For several species, EDR_1_0 for population endpoints were lower than the lowest EDR_1_0 for individual endpoints. Various population level risks, differing in severity for the population, were investigated. Population extinction (predicted when radiation effects caused population growth rate λ to decrease below 1, indicating that no population growth in the long term) was predicted for dose rates ranging from 2700 μGy h"−"1 in fish to 12,000 μGy h"−"1 in soil invertebrates. A milder risk, that population growth rate λ will be reduced by 10% of the reduction causing extinction, was predicted for dose rates ranging from 24 μGy h"−"1

A duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains.

Science.gov (United States)

Benacer, Douadi; Zain, Siti Nursheena Mohd; Lewis, John W; Khalid, Mohd Khairul Nizam Mohd; Thong, Kwai Lin

2017-01-01

This study aimed to develop a duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains. Primers were designed to target the rrs (LG1/LG2) and ligB (LP1/LP2) genes to confirm the presence of the Leptospira genus and the pathogenic species, respectively. The assay showed 100% specificity against 17 Leptospira strains with a limit of detection of 23.1pg/µl of leptospiral DNA and sensitivity of 103 leptospires/ml in both spiked urine and water. Our duplex endpoint PCR assay is suitable for rapid early detection of Leptospira with high sensitivity and specificity.

Radiometric titration of officinal radiopharmaceuticals using radioactive kryptonates as end-point indicators. I

International Nuclear Information System (INIS)

Toelgyessy, J.; Dillinger, P.; Harangozo, M.; Jombik, J.

1980-01-01

A method for the determination of salicylic, acetylsalicylic and benzoic acids in officinal pharmaceutical based on radiometric titration with 0.1 mol.l -1 NaOH was developed. The end-point was detected with the aid of radioactive glass kryptonate. After the end-point, the excess titrant attacks the glass surface layers and this results in releasing 85 Kr, and consequently, in decreasing the radioactivity of the kryptonate employed. The radioactive kryptonate used as an indicator was prepared by the bombardment of glass with accelerated 85 Kr ions. The developed method is simple, accurate and correct. (author)

Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

OpenAIRE

Bonnetain Franck; Bedenne Laurent; Methy Nicolas

2010-01-01

Abstract Background Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opin...

A New Test Unit for Disintegration End-Point Determination of Orodispersible Films.

Science.gov (United States)

Low, Ariana; Kok, Si Ling; Khong, Yuet Mei; Chan, Sui Yung; Gokhale, Rajeev

2015-11-01

No standard time or pharmacopoeia disintegration test method for orodispersible films (ODFs) exists. The USP disintegration test for tablets and capsules poses significant challenges for end-point determination when used for ODFs. We tested a newly developed disintegration test unit (DTU) against the USP disintegration test. The DTU is an accessory to the USP disintegration apparatus. It holds the ODF in a horizontal position, allowing top-view of the ODF during testing. A Gauge R&R study was conducted to assign relative contributions of the total variability from the operator, sample or the experimental set-up. Precision was compared using commercial ODF products in different media. Agreement between the two measurement methods was analysed. The DTU showed improved repeatability and reproducibility compared to the USP disintegration system with tighter standard deviations regardless of operator or medium. There is good agreement between the two methods, with the USP disintegration test giving generally longer disintegration times possibly due to difficulty in end-point determination. The DTU provided clear end-point determination and is suitable for quality control of ODFs during product developmental stage or manufacturing. This may facilitate the development of a standardized methodology for disintegration time determination of ODFs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

7 CFR 762.129 - Percent of guarantee and maximum loss.

Science.gov (United States)

2010-01-01

... loss. (a) General. The percent of guarantee will not exceed 90 percent based on the credit risk to the lender and the Agency both before and after the transaction. The Agency will determine the percentage of... PLP lenders will not be less than 80 percent. (d) Maximum loss. The maximum amount the Agency will pay...

Fifty challenging problems in probability with solutions

CERN Document Server

Mosteller, Frederick

1987-01-01

Can you solve the problem of ""The Unfair Subway""? Marvin gets off work at random times between 3 and 5 p.m. His mother lives uptown, his girlfriend downtown. He takes the first subway that comes in either direction and eats dinner with the one he is delivered to. His mother complains that he never comes to see her, but he says she has a 50-50 chance. He has had dinner with her twice in the last 20 working days. Explain. Marvin's adventures in probability are one of the fifty intriguing puzzles that illustrate both elementary ad advanced aspects of probability, each problem designed to chall

Imaging biomarkers as surrogate endpoints for drug development

International Nuclear Information System (INIS)

Richter, Wolf S.

2006-01-01

The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

A seasonal variation of the three Leading diagnoses over fifty ...

African Journals Online (AJOL)

A seasonal variation of the three Leading diagnoses over fifty months at the Duk Lost. Boys Clinic, South Sudan reed, williama, Dannan, Tomb, Friedman Danielc, MD, Manyok gabrield, Connor Barbarae, MD, reed Davidf, MD. Introduction. The Duk Lost Boys Clinic, a Primary Health Care Clinic in Duk Payuel, is the only ...

Can joint sound assess soft and hard endpoints of the Lachman test?: A preliminary study.

Science.gov (United States)

Hattori, Koji; Ogawa, Munehiro; Tanaka, Kazunori; Matsuya, Ayako; Uematsu, Kota; Tanaka, Yasuhito

2016-05-12

The Lachman test is considered to be a reliable physical examination for anterior cruciate ligament (ACL) injury. Patients with a damaged ACL demonstrate a soft endpoint feeling. However, examiners judge the soft and hard endpoints subjectively. The purpose of our study was to confirm objective performance of the Lachman test using joint auscultation. Human and porcine knee joints were examined. Knee joint sound during the Lachman test (Lachman sound) was analyzed by fast Fourier transformation. As quantitative indices of Lachman sound, the peak sound as the maximum relative amplitude (acoustic pressure) and its frequency were used. The mean Lachman peak sound for healthy volunteer knees was 86.9 ± 12.9 Hz in frequency and -40 ± 2.5 dB in acoustic pressure. The mean Lachman peak sound for intact porcine knees was 84.1 ± 9.4 Hz and -40.5 ± 1.7 dB. Porcine knees with ACL deficiency had a soft endpoint feeling during the Lachman test. The Lachman peak sounds of porcine knees with ACL deficiency were dispersed into four distinct groups, with center frequencies of around 40, 160, 450, and 1600. The Lachman peak sound was capable of assessing soft and hard endpoints of the Lachman test objectively.

A patient and community-centered approach selecting endpoints for a randomized trial of a novel advance care planning tool

Directory of Open Access Journals (Sweden)

Bridges JFP

2018-02-01

Full Text Available John FP Bridges,1,2 Norah L Crossnohere,2 Anne L Schuster,1 Judith A Miller,3 Carolyn Pastorini,3,† Rebecca A Aslakson2,4,5 1Department of Health Policy and Management, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 2Department of Health, Behavior, and Society, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 3Patient-Centered Outcomes Research Institute (PCORI Project, Baltimore, MD, 4Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, MD, 5Armstrong Institute for Patient Safety and Quality, The Johns Hopkins School of Medicine, Baltimore, MD, USA †Carolyn Pastorini passed away on August 24, 2015 Background: Despite a movement toward patient-centered outcomes, best practices on how to gather and refine patients’ perspectives on research endpoints are limited. Advanced care planning (ACP is inherently patient centered and would benefit from patient prioritization of endpoints for ACP-related tools and studies.Objective: This investigation sought to prioritize patient-centered endpoints for the content and evaluation of an ACP video being developed for patients undergoing major surgery. We also sought to highlight an approach using complementary engagement and research strategies to document priorities and preferences of patients and other stakeholders.Materials and methods: Endpoints identified from a previously published environmental scan were operationalized following rating by a caregiver co-investigator, refinement by a patient co-investigator, review by a stakeholder committee, and validation by patients and family members. Finalized endpoints were taken to a state fair where members of the public who indicated that they or a loved one had undergone major surgery prioritized their most relevant endpoints and provided comments.Results: Of the initial 50 ACP endpoints identified from the review, 12 endpoints were selected for public

Deutsches Atomforum turns fifty; 50 Jahre Deutsches Atomforum

Energy Technology Data Exchange (ETDEWEB)

Geisler, Maja [Deutsches Atomforum e.V., Berlin (Germany). Bereich Oeffentlichkeitsarbeit, Informationskreis KernEnergie

2009-07-15

Fifty years ago, the Deutsches Atomforum e. V. was founded to promote the peaceful uses of nuclear power in Germany. On July 1, 2009, the organization celebrated its fiftieth birthday in Berlin. The anniversary was celebrated in the Berlin electricity plant, Germany's oldest existing building for commercial electricity generation. DAtF President Dr. Walter Hohlefelder welcomed some 200 high-ranking guests from politics, industry, and from the nuclear community, above all, the Chancellor of the Federal Republic of Germany, Dr. Angela Merkel, and, as keynote speaker, Professor Dr. Arnulf Baring. (orig.)

[Wide support for oocyte donation and banking in the Netherlands].

Science.gov (United States)

Bos, Annelies M E; Klapwijk, Petra; Fauser, Bart C J M

2012-01-01

To assess the general consensus on the cryopreservation of oocytes and the introduction of oocyte banking facilities in the Netherlands. Poll investigation A poll with the use of an online questionnaire was conducted among nearly 19,000 participants of the Dutch EenVandaag opinion panel in May 2011. The poll results were adjusted to the Dutch population based on data from the Dutch Central Office for Statistics for age, gender, education, marital status, geographical area and political preference (measured according to the lower house elections of 2010). The primary endpoints were the percentages of supporters of oocyte freezing for own future use and of the concept of introducing oocyte banking facilities in The Netherlands. The secondary endpoints were the demographic differences between supporters and opponents. Approximately half of 18.911 participants supported oocyte freezing (47%). Fifty-percent of all participants supported oocyte banking in the Netherlands. Supporters of oocyte freezing were mainly women ≤ 45 years of age, who are highly educated and have no children. Four percent of the participating women aged ≤ 45 years would seriously consider obtaining donor oocytes from an available oocyte banking facility. Twelve percent of the participating women ≤ 45 years of age said they would definitely donate their oocytes or would seriously consider donating. Thirty-seven percent of all participants were against the introduction of oocyte banking facilities. The most important arguments against oocyte freezing were that women should reproduce during normal reproductive years and that it was not medically necessary. Poll results showed much support for oocyte freezing and for the introduction of oocyte banking facilities in the Netherlands. In addition, the poll shows that oocyte banking facilities would fulfil a need in the population.

Free Energy, Enthalpy and Entropy from Implicit Solvent End-Point Simulations.

Science.gov (United States)

Fogolari, Federico; Corazza, Alessandra; Esposito, Gennaro

2018-01-01

Free energy is the key quantity to describe the thermodynamics of biological systems. In this perspective we consider the calculation of free energy, enthalpy and entropy from end-point molecular dynamics simulations. Since the enthalpy may be calculated as the ensemble average over equilibrated simulation snapshots the difficulties related to free energy calculation are ultimately related to the calculation of the entropy of the system and in particular of the solvent entropy. In the last two decades implicit solvent models have been used to circumvent the problem and to take into account solvent entropy implicitly in the solvation terms. More recently outstanding advancement in both implicit solvent models and in entropy calculations are making the goal of free energy estimation from end-point simulations more feasible than ever before. We review briefly the basic theory and discuss the advancements in light of practical applications.

Free Energy, Enthalpy and Entropy from Implicit Solvent End-Point Simulations

Directory of Open Access Journals (Sweden)

Federico Fogolari

2018-02-01

Full Text Available Free energy is the key quantity to describe the thermodynamics of biological systems. In this perspective we consider the calculation of free energy, enthalpy and entropy from end-point molecular dynamics simulations. Since the enthalpy may be calculated as the ensemble average over equilibrated simulation snapshots the difficulties related to free energy calculation are ultimately related to the calculation of the entropy of the system and in particular of the solvent entropy. In the last two decades implicit solvent models have been used to circumvent the problem and to take into account solvent entropy implicitly in the solvation terms. More recently outstanding advancement in both implicit solvent models and in entropy calculations are making the goal of free energy estimation from end-point simulations more feasible than ever before. We review briefly the basic theory and discuss the advancements in light of practical applications.

A yeast screening system for simultaneously monitoring multiple genetic endpoints

International Nuclear Information System (INIS)

Dixon, M.L.; Mortimer, R.K.

1986-01-01

Mutation, recombination, and mitochondrial deficiencies have been proposed to have roles in the carcinogenic process. The authors describe a diploid strain of the yeast Saccharomyces cerevisiae capable of detecting this wide spectrum of genetic changes. The markers used for monitoring these events have been especially well characterized genetically. Ultraviolet light was chosen as a model carcinogenic agent to test this system. In addition to highly significant increases in the frequencies of each genetic change, increases in the absolute numbers of each change indicated induction and not selective survival. The relative amounts of each type of genetic change varied with dose. The wide spectrum of endpoints monitored in the XD83 yeast system may allow the detection of certain carcinogens and other genetically toxic agents which have escaped detection in more limited systems. Since only one strain is required to simultaneously monitor these genetic changes, this assay system should facilitate comparisons of the induced changes and be more efficient than using multiple strains to monitor the same endpoints. (Auth.)

Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.

Science.gov (United States)

Finder, Jonathan; Mayer, Oscar Henry; Sheehan, Daniel; Sawnani, Hemant; Abresch, R Ted; Benditt, Joshua; Birnkrant, David J; Duong, Tina; Henricson, Erik; Kinnett, Kathi; McDonald, Craig M; Connolly, Anne M

2017-08-15

Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

Can a fifty percent increase in public sector wages improve the position of public sector employees in the long run? An assessment of the public-private income gap in Hungary

OpenAIRE

Szilvia Hamori; Anna Lovasz

2011-01-01

We provide a detailed descriptive analysis of the long-term effects of the 50 percent public sector wage increase initiated by the government in 2002 in order to improve the relative situation of public sector workers. The aim of this policy was to attract high quality workers to the public sector, and to counteract the problem of "brain drain," the loss of high-skilled workers to abroad. To study the effects on the public-private income gap - and on high-skilled workers in particular - we em...

On weighted hardy inequalities on semiaxis for functions vanishing at the endpoints

Directory of Open Access Journals (Sweden)

Stepanov Vladimir

1997-01-01

Full Text Available We study the weighted Hardy inequalities on the semiaxis of the form for functions vanishing at the endpoints together with derivatives up to the order . The case is completely characterized.

An evaluation of culture results during treatment for tuberculosis as surrogate endpoints for treatment failure and relapse.

Directory of Open Access Journals (Sweden)

Patrick P J Phillips

Full Text Available It is widely acknowledged that new regimens are urgently needed for the treatment of tuberculosis. The primary endpoint in the Phase III trials is a composite outcome of failure at the end of treatment or relapse after stopping treatment. Such trials are usually both long and expensive. Valid surrogate endpoints measured during or at the end of treatment could dramatically reduce both the time and cost of assessing the effectiveness of new regimens. The objective of this study was to evaluate sputum culture results on solid media during treatment as surrogate endpoints for poor outcome. Data were obtained from twelve randomised controlled trials conducted by the British Medical Research Council in the 1970s and 80s in East Africa and East Asia, consisting of 6974 participants and 49 different treatment regimens. The month two culture result was shown to be a poor surrogate in East Africa but a good surrogate in Hong Kong. In contrast, the month three culture was a good surrogate in trials conducted in East Africa but not in Hong Kong. As well as differences in location, ethnicity and probable strain of Mycobacteria tuberculosis, Hong Kong trials more often evaluated regimens with rifampicin throughout and intermittent regimens, and patients in East African trials more often presented with extensive cavitation and were slower to convert to culture negative during treatment. An endpoint that is a summary measure of the longitudinal profile of culture results over time or that is able to detect the presence of M. tuberculosis later in treatment is more likely to be a better endpoint for a phase II trial than a culture result at a single time point and may prove to be an acceptable surrogate. More data are needed before any endpoint can be used as a surrogate in a confirmatory phase III trial.

Does Asset Allocation Policy Explain 40, 90, 100 Percent of Performance?

OpenAIRE

Roger G. Ibbotson; Paul D. Kaplan

2001-01-01

Does asset allocation policy explain 40 percent, 90 percent, or 100 percent of performance? According to some well-known studies, more than 90 percent of the variability of a typical plan sponsor's performance over time is attributable to asset allocation. However, few people want to explain variability over time. Instead, an analyst might want to know how important it is in explaining the differences in return from one fund to another, or what percentage of the level of a typical fund's retu...

Does bisphenol A induce superfeminization in Marisa cornuarietis? Part I: intra- and inter-laboratory variability in test endpoints.

Science.gov (United States)

Forbes, Valery E; Selck, Henriette; Palmqvist, Annemette; Aufderheide, John; Warbritton, Ryan; Pounds, Nadine; Thompson, Roy; van der Hoeven, Nelly; Caspers, Norbert

2007-03-01

It has been claimed that bisphenol A (BPA) induces superfeminization in the freshwater gastropod, Marisa cornuarietis. To explore the reproducibility of prior work, here we present results from a three-laboratory study, the objectives of which were to determine the mean and variability in test endpoints (i.e., adult fecundity, egg hatchability, and juvenile growth) under baseline conditions and to identify the sources of variability. A major source of variability for all of the measured endpoints was due to differences within and among individuals. With few exceptions, variability among laboratories and among replicate tanks within laboratories contributed little to the observed variability in endpoints. The results highlight the importance of obtaining basic knowledge of husbandry requirements and baseline information on life-history traits of potential test species prior to designing toxicity test protocols. Understanding of the levels and sources of endpoint variability is essential so that statistically robust and ecologically relevant tests of chemicals can be conducted.

Representasi Perempuan Dalam Film (Analisis Semiotika Representasi Perempuan Dalam Film “Fifty Shades of Grey”)

OpenAIRE

Aviomeita, Friska

2016-01-01

This study entitled "Representation of Women In Film ( Roland Barthes Semiotics Analysis In the film Fifty Shades of Grey ) " . The purpose of this study to find out how women are represented in the film " Fifty Shades of Grey " by denotation , connotation and myths . Film has always influenced and shaped the public based on the contents of the message behind it. Messages or values contained in the film may affect the audience. In this study, researchers used several theorie...

The Texas Ten Percent Plan's Impact on College Enrollment

Science.gov (United States)

Daugherty, Lindsay; Martorell, Paco; McFarlin, Isaac, Jr.

2014-01-01

The Texas Ten Percent Plan (TTP) provides students in the top 10 percent of their high-school class with automatic admission to any public university in the state, including the two flagship schools, the University of Texas at Austin and Texas A&M. Texas created the policy in 1997 after a federal appellate court ruled that the state's previous…

Serum urate as surrogate endpoint for flares in people with gout

DEFF Research Database (Denmark)

Stamp, Lisa K; Birger Morillon, Melanie; Taylor, William J

2018-01-01

Objectives The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical tr...

Radiological endpoints relevant to ecological risk assessment

International Nuclear Information System (INIS)

Harrison, F.

1997-01-01

Because of the potential risk from radiation due to the releases of radionuclides from anthropogenic activities, considerable research was performed to determine for humans the levels of dose received, their responses to the doses and mechanisms of action of radioactivity on living matter. More recently, there is an increased interest in the effects of radioactivity on non-human species. There are differences in approach between risk assessment for humans and ecosystems. For protection of humans, the focus is the individual and the endpoint of primary concern is cancer induction. For protection of ecosystems, the focus is on population stability and the endpoint of concern is reproductive success for organisms important ecologically and economically. For these organisms, information is needed on their responses to irradiation and the potential impact of the doses absorbed on their reproductive success. Considerable information is available on the effects of radiation on organisms from different phyla and types of ecosystems. Databases useful for assessing risk from exposures of populations to radioactivity are the effects of irradiation on mortality, fertility and sterility, the latter two of which are important components of reproductive success. Data on radiation effects on mortality are available both from acute and chronic irradiation. In relation to radiation effects, reproductive success for a given population is related to a number of characteristics of the species, including inherent radiosensitivity of reproductive tissues and early life stages, processes occurring during gametogenesis, reproductive strategy and exposure history. The available data on acute and chronic radiation doses is reviewed for invertebrates, fishes and mammals. The information reviewed indicates that wide ranges in responses with species can be expected. Parameters that most likely contribute to inherent radiosensitivity are discussed. (author)

Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

DEFF Research Database (Denmark)

Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

2007-01-01

endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...... level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties...... of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...

Deep vadose zone remediation: technical and policy challenges, opportunities, and progress in achieving cleanup endpoints

International Nuclear Information System (INIS)

Wellman, D.M.; Freshley, M.D.; Truex, M.J.; Lee, M.H.

2013-01-01

Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical. Use of risk-informed alternate endpoints provides a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable the establishment of a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

Deep vadose zone remediation: technical and policy challenges, opportunities, and progress in achieving cleanup endpoints

Energy Technology Data Exchange (ETDEWEB)

Wellman, D.M.; Freshley, M.D.; Truex, M.J.; Lee, M.H. [Pacific Northwest National Laboratory, Richland, Washington (United States)

2013-07-01

Current requirements for site remediation and closure are standards-based and are often overly conservative, costly, and in some cases, technically impractical. Use of risk-informed alternate endpoints provides a means to achieve remediation goals that are permitted by regulations and are protective of human health and the environment. Alternate endpoints enable the establishment of a path for cleanup that may include intermediate remedial milestones and transition points and/or regulatory alternatives to standards-based remediation. A framework is presented that is centered around developing and refining conceptual models in conjunction with assessing risks and potential endpoints as part of a system-based assessment that integrates site data with scientific understanding of processes that control the distribution and transport of contaminants in the subsurface and pathways to receptors. This system-based assessment and subsequent implementation of the remediation strategy with appropriate monitoring are targeted at providing a holistic approach to addressing risks to human health and the environment. This holistic approach also enables effective predictive analysis of contaminant behavior to provide defensible criteria and data for making long-term decisions. Developing and implementing an alternate endpoint-based approach for remediation and waste site closure presents a number of challenges and opportunities. Categories of these challenges include scientific and technical, regulatory, institutional, and budget and resource allocation issues. Opportunities exist for developing and implementing systems-based approaches with respect to supportive characterization, monitoring, predictive modeling, and remediation approaches. (authors)

Population modelling to compare chronic external radiotoxicity between individual and population endpoints in four taxonomic groups.

Science.gov (United States)

Alonzo, Frédéric; Hertel-Aas, Turid; Real, Almudena; Lance, Emilie; Garcia-Sanchez, Laurent; Bradshaw, Clare; Vives I Batlle, Jordi; Oughton, Deborah H; Garnier-Laplace, Jacqueline

2016-02-01

In this study, we modelled population responses to chronic external gamma radiation in 12 laboratory species (including aquatic and soil invertebrates, fish and terrestrial mammals). Our aim was to compare radiosensitivity between individual and population endpoints and to examine how internationally proposed benchmarks for environmental radioprotection protected species against various risks at the population level. To do so, we used population matrix models, combining life history and chronic radiotoxicity data (derived from laboratory experiments and described in the literature and the FREDERICA database) to simulate changes in population endpoints (net reproductive rate R0, asymptotic population growth rate λ, equilibrium population size Neq) for a range of dose rates. Elasticity analyses of models showed that population responses differed depending on the affected individual endpoint (juvenile or adult survival, delay in maturity or reduction in fecundity), the considered population endpoint (R0, λ or Neq) and the life history of the studied species. Among population endpoints, net reproductive rate R0 showed the lowest EDR10 (effective dose rate inducing 10% effect) in all species, with values ranging from 26 μGy h(-1) in the mouse Mus musculus to 38,000 μGy h(-1) in the fish Oryzias latipes. For several species, EDR10 for population endpoints were lower than the lowest EDR10 for individual endpoints. Various population level risks, differing in severity for the population, were investigated. Population extinction (predicted when radiation effects caused population growth rate λ to decrease below 1, indicating that no population growth in the long term) was predicted for dose rates ranging from 2700 μGy h(-1) in fish to 12,000 μGy h(-1) in soil invertebrates. A milder risk, that population growth rate λ will be reduced by 10% of the reduction causing extinction, was predicted for dose rates ranging from 24 μGy h(-1) in mammals to 1800 μGy h(-1) in

Comparison of mammalian and fish cell line cytotoxicity: impact of endpoint and exposure duration

International Nuclear Information System (INIS)

Guelden, Michael; Moerchel, Sabine; Seibert, Hasso

2005-01-01

Comparisons of acute toxic concentrations of chemicals to fish in vivo and cytotoxic concentrations to fish cell lines in vitro reveal rather good correlations of the toxic potencies in vitro and in vivo, but a clearly lower sensitivity of the fish cells. To examine whether the low sensitivity is specific for fish cells, cytotoxic potencies of reference chemicals from the Multicenter Evaluation of In Vitro Cytotoxicity program (MEIC) reported for the fish cell lines R1 and RTG-2 were compared with those obtained with the mouse Balb/c 3T3 cell line. Cytotoxic potencies (EC 50 values) for MEIC reference chemicals were determined with exponentially growing Balb/c 3T3 cells using three different test protocols. To assess both endpoints, cell proliferation and cell survival, EC 50 values were measured for the decrease in final cell protein after 24 and 72 h of exposure and for the reduction of cell protein increase during 24 h of exposure. EC 50 values obtained with the fish cell lines R1 and RTG-2 using cell survival as endpoint were taken from the MEIC data base. The comparison of cytotoxic potencies shows that, in general, the fish cell lines and the mammalian cell line are almost equally sensitive towards the cytotoxic action of chemicals. The mammalian cell line assay, however, becomes considerably more sensitive, by factors of 3.4-8.5, than the fish cell line assays, if cell growth instead of cell survival is used as endpoint. It is concluded, that cell proliferation might be a better endpoint than cell survival and that mammalian cell lines might be suited to assess fish acute toxicity

Designing quantitative structure activity relationships to predict specific toxic endpoints for polybrominated diphenyl ethers in mammalian cells.

Science.gov (United States)

Rawat, S; Bruce, E D

2014-01-01

Polybrominated diphenyl ethers (PBDEs) are known as effective flame retardants and have vast industrial application in products like plastics, building materials and textiles. They are found to be structurally similar to thyroid hormones that are responsible for regulating metabolism in the body. Structural similarity with the hormones poses a threat to human health because, once in the system, PBDEs have the potential to affect thyroid hormone transport and metabolism. This study was aimed at designing quantitative structure-activity relationship (QSAR) models for predicting toxic endpoints, namely cell viability and apoptosis, elicited by PBDEs in mammalian cells. Cell viability was evaluated quantitatively using a general cytotoxicity bioassay using Janus Green dye and apoptosis was evaluated using a caspase assay. This study has thus modelled the overall cytotoxic influence of PBDEs at an early and a late endpoint by the Genetic Function Approximation method. This research was a twofold process including running in vitro bioassays to collect data on the toxic endpoints and modeling the evaluated endpoints using QSARs. Cell viability and apoptosis responses for Hep G2 cells exposed to PBDEs were successfully modelled with an r(2) of 0.97 and 0.94, respectively.

Analysis association of milk fat and protein percent in quantitative ...

African Journals Online (AJOL)

Analysis association of milk fat and protein percent in quantitative trait locus ... African Journal of Biotechnology ... Protein and fat percent as content of milk are high-priority criteria for financial aims and selection of programs in dairy cattle.

Cortical plasticity as a new endpoint measurement for chronic pain

Directory of Open Access Journals (Sweden)

Zhuo Min

2011-07-01

Full Text Available Abstract Animal models of chronic pain are widely used to investigate basic mechanisms of chronic pain and to evaluate potential novel drugs for treating chronic pain. Among the different criteria used to measure chronic pain, behavioral responses are commonly used as the end point measurements. However, not all chronic pain conditions can be easily measured by behavioral responses such as the headache, phantom pain and pain related to spinal cord injury. Here I propose that cortical indexes, that indicate neuronal plastic changes in pain-related cortical areas, can be used as endpoint measurements for chronic pain. Such cortical indexes are not only useful for those chronic pain conditions where a suitable animal model is lacking, but also serve as additional screening methods for potential drugs to treat chronic pain in humans. These cortical indexes are activity-dependent immediate early genes, electrophysiological identified plastic changes and biochemical assays of signaling proteins. It can be used to evaluate novel analgesic compounds that may act at peripheral or spinal sites. I hope that these new cortical endpoint measurements will facilitate our search for new, and more effective, pain medicines, and help to reduce false lead drug targets.

Dependence of QSAR models on the selection of trial descriptor sets: a demonstration using nanotoxicity endpoints of decorated nanotubes.

Science.gov (United States)

Shao, Chi-Yu; Chen, Sing-Zuo; Su, Bo-Han; Tseng, Yufeng J; Esposito, Emilio Xavier; Hopfinger, Anton J

2013-01-28

Little attention has been given to the selection of trial descriptor sets when designing a QSAR analysis even though a great number of descriptor classes, and often a greater number of descriptors within a given class, are now available. This paper reports an effort to explore interrelationships between QSAR models and descriptor sets. Zhou and co-workers (Zhou et al., Nano Lett. 2008, 8 (3), 859-865) designed, synthesized, and tested a combinatorial library of 80 surface modified, that is decorated, multi-walled carbon nanotubes for their composite nanotoxicity using six endpoints all based on a common 0 to 100 activity scale. Each of the six endpoints for the 29 most nanotoxic decorated nanotubes were incorporated as the training set for this study. The study reported here includes trial descriptor sets for all possible combinations of MOE, VolSurf, and 4D-fingerprints (FP) descriptor classes, as well as including and excluding explicit spatial contributions from the nanotube. Optimized QSAR models were constructed from these multiple trial descriptor sets. It was found that (a) both the form and quality of the best QSAR models for each of the endpoints are distinct and (b) some endpoints are quite dependent upon 4D-FP descriptors of the entire nanotube-decorator complex. However, other endpoints yielded equally good models only using decorator descriptors with and without the decorator-only 4D-FP descriptors. Lastly, and most importantly, the quality, significance, and interpretation of a QSAR model were found to be critically dependent on the trial descriptor sets used within a given QSAR endpoint study.

Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

DEFF Research Database (Denmark)

Lassere, Marissa N; Johnson, Kent R; Boers, Maarten

2007-01-01

endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. RESULTS: The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation...... of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. CONCLUSION: Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery...... are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization...

Serum Predictors of Percent Lean Mass in Young Adults.

Science.gov (United States)

Lustgarten, Michael S; Price, Lori L; Phillips, Edward M; Kirn, Dylan R; Mills, John; Fielding, Roger A

2016-08-01

Lustgarten, MS, Price, LL, Phillips, EM, Kirn, DR, Mills, J, and Fielding, RA. Serum predictors of percent lean mass in young adults. J Strength Cond Res 30(8): 2194-2201, 2016-Elevated lean (skeletal muscle) mass is associated with increased muscle strength and anaerobic exercise performance, whereas low levels of lean mass are associated with insulin resistance and sarcopenia. Therefore, studies aimed at obtaining an improved understanding of mechanisms related to the quantity of lean mass are of interest. Percent lean mass (total lean mass/body weight × 100) in 77 young subjects (18-35 years) was measured with dual-energy x-ray absorptiometry. Twenty analytes and 296 metabolites were evaluated with the use of the standard chemistry screen and mass spectrometry-based metabolomic profiling, respectively. Sex-adjusted multivariable linear regression was used to determine serum analytes and metabolites significantly (p ≤ 0.05 and q ≤ 0.30) associated with the percent lean mass. Two enzymes (alkaline phosphatase and serum glutamate oxaloacetate aminotransferase) and 29 metabolites were found to be significantly associated with the percent lean mass, including metabolites related to microbial metabolism, uremia, inflammation, oxidative stress, branched-chain amino acid metabolism, insulin sensitivity, glycerolipid metabolism, and xenobiotics. Use of sex-adjusted stepwise regression to obtain a final covariate predictor model identified the combination of 5 analytes and metabolites as overall predictors of the percent lean mass (model R = 82.5%). Collectively, these data suggest that a complex interplay of various metabolic processes underlies the maintenance of lean mass in young healthy adults.

Sodium chloride as a reference substance for the three growth endpoints used in the Lemna minor L. (1753 test

Directory of Open Access Journals (Sweden)

Aline Andrade Godoy

2017-01-01

Full Text Available Lemna sp. growth inhibition test standardized protocols suggest the use of compounds such as 3,5-dichlorophenol as reference substances for checking the test organism’s sensitivity routinely. However, this and other recommended chemicals present risks to human health and to the environment. Sodium chloride (NaCl appears as a less toxic alternative reference substance which has been successfully used in routine ecotoxicological tests. However, the evaluation of this compound in multiple growth endpoints used in the L. minor test, which is required for recommending it as a reference substance for this test organism, has not yet been reported. In the present study, NaCl was tested with L. minor for the growth endpoints frond number, total frond area and fresh weight. Results showed acceptable sensitivity and reproducibility (coefficient of variance < 15.0% for all three of the measured endpoints. Statistically significant differences were observed between the EC50 values calculated based on the three endpoints (p < 0.05. Total frond area was the most sensitive one, with average EC50 value of 2742.80 ± 245.7 mg L-1. It was anticipated that NaCl can be a suitable alternative reference substance and that total frond area should be the endpoint of choice for sensitivity toxicity tests using NaCl.

Fifty Shades a way readers put sex back in their lives

DEFF Research Database (Denmark)

Knudsen, Gry Høngsmark

2014-01-01

This is a guest blog from Gry Høngsmark Knudsen, a former student, who visited my “Women’s Economy” class this winter to report on her project about the reception of Fifty Shades of Grey. We all enjoyed her report, so I asked her to write a short blog for Double X Readers....

EDITORIAL: Semiconductor lasers: the first fifty years Semiconductor lasers: the first fifty years

Science.gov (United States)

Calvez, S.; Adams, M. J.

2012-09-01

Anniversaries call for celebrations. Since it is now fifty years since the first semiconductor lasers were reported, it is highly appropriate to celebrate this anniversary with a Special Issue dedicated to the topic. The semiconductor laser now has a major effect on our daily lives since it has been a key enabler in the development of optical fibre communications (and hence the internet and e-mail), optical storage (CDs, DVDs, etc) and barcode scanners. In the early 1960s it was impossible for most people (with the exception of very few visionaries) to foresee any of these future developments, and the first applications identified were for military purposes (range-finders, target markers, etc). Of course, many of the subsequent laser applications were made possible by developments in semiconductor materials, in the associated growth and fabrication technology, and in the increased understanding of the underlying fundamental physics. These developments continue today, so that the subject of semiconductor lasers, although mature, is in good health and continues to grow. Hence, we can be confident that the pervasive influence of semiconductor lasers will continue to develop as optoelectronics technology makes further advances into other sectors such as healthcare, security and a whole host of applications based on the global imperatives to reduce energy consumption, minimise environmental impact and conserve resources. The papers in this Special Issue are intended to tell some of the story of the last fifty years of laser development as well as to provide evidence of the current state of semiconductor laser research. Hence, there are a number of papers where the early developments are recalled by authors who played prominent parts in the story, followed by a selection of papers from authors who are active in today's exciting research. The twenty-fifth anniversary of the semiconductor laser was celebrated by the publication of a number of papers dealing with the early

Choice of futility boundaries for group sequential designs with two endpoints

Directory of Open Access Journals (Sweden)

Svenja Schüler

2017-08-01

Full Text Available Abstract Background In clinical trials, the opportunity for an early stop during an interim analysis (either for efficacy or for futility may relevantly save time and financial resources. This is especially important, if the planning assumptions required for power calculation are based on a low level of evidence. For example, when including two primary endpoints in the confirmatory analysis, the power of the trial depends on the effects of both endpoints and on their correlation. Assessing the feasibility of such a trial is therefore difficult, as the number of parameter assumptions to be correctly specified is large. For this reason, so-called ‘group sequential designs’ are of particular importance in this setting. Whereas the choice of adequate boundaries to stop a trial early for efficacy has been broadly discussed in the literature, the choice of optimal futility boundaries has not been investigated so far, although this may have serious consequences with respect to performance characteristics. Methods In this work, we propose a general method to construct ‘optimal’ futility boundaries according to predefined criteria. Further, we present three different group sequential designs for two endpoints applying these futility boundaries. Our methods are illustrated by a real clinical trial example and by Monte-Carlo simulations. Results By construction, the provided method of choosing futility boundaries maximizes the probability to correctly stop in case of small or opposite effects while limiting the power loss and the probability of stopping the study ‘wrongly’. Our results clearly demonstrate the benefit of using such ‘optimal’ futility boundaries, especially compared to futility boundaries commonly applied in practice. Conclusions As the properties of futility boundaries are often not considered in practice and unfavorably chosen futility boundaries may imply bad properties of the study design, we recommend assessing the

Energy metabolism and biotransformation as endpoints to pre-screen hepatotoxicity using a liver spheroid model

International Nuclear Information System (INIS)

Xu Jinsheng; Purcell, Wendy M.

2006-01-01

The current study investigated liver spheroid culture as an in vitro model to evaluate the endpoints relevant to the status of energy metabolism and biotransformation after exposure to test toxicants. Mature rat liver spheroids were exposed to diclofenac, galactosamine, isoniazid, paracetamol, m-dinitrobenzene (m-DNB) and 3-nitroaniline (3-NA) for 24 h. Pyruvate uptake, galactose biotransformation, lactate release and glucose secretion were evaluated after exposure. The results showed that pyruvate uptake and lactate release by mature liver spheroids in culture were maintained at a relatively stable level. These endpoints, together with glucose secretion and galactose biotransformation, were related to and could reflect the status of energy metabolism and biotransformation in hepatocytes. After exposure, all of the test agents significantly reduced glucose secretion, which was shown to be the most sensitive endpoint of those evaluated. Diclofenac, isoniazid, paracetamol and galactosamine reduced lactate release (P < 0.01), but m-DNB increased lactate release (P < 0.01). Diclofenac, isoniazid and paracetamol also reduced pyruvate uptake (P < 0.01), while galactosamine had little discernible effect. Diclofenac, galactosamine, paracetamol and m-DNB also reduced galactose biotransformation (P < 0.01), by contrast, isoniazid did not. The metabolite of m-DNB, 3-NA, which served as a negative control, did not cause significant changes in lactate release, pyruvate uptake or galactose biotransformation. It is concluded that pyruvate uptake, galactose biotransformation, lactate release and glucose secretion can be used as endpoints for evaluating the status of energy metabolism and biotransformation after exposure to test agents using the liver spheroid model to pre-screen hepatotoxicity

What history tells us XIII. Fifty years of the Central Dogma

Indian Academy of Sciences (India)

2008-05-14

May 14, 2008 ... Home; Journals; Journal of Biosciences; Volume 33; Issue 2. What history tells us XIII. Fifty years of the Central Dogma. Michel Morange. Series Volume 33 Issue 2 June 2008 pp 171-175. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/jbsc/033/02/0171-0175 ...

Muscle Synergies Heavily Influence the Neural Control of Arm Endpoint Stiffness and Energy Consumption.

Science.gov (United States)

Inouye, Joshua M; Valero-Cuevas, Francisco J

2016-02-01

Much debate has arisen from research on muscle synergies with respect to both limb impedance control and energy consumption. Studies of limb impedance control in the context of reaching movements and postural tasks have produced divergent findings, and this study explores whether the use of synergies by the central nervous system (CNS) can resolve these findings and also provide insights on mechanisms of energy consumption. In this study, we phrase these debates at the conceptual level of interactions between neural degrees of freedom and tasks constraints. This allows us to examine the ability of experimentally-observed synergies--correlated muscle activations--to control both energy consumption and the stiffness component of limb endpoint impedance. In our nominal 6-muscle planar arm model, muscle synergies and the desired size, shape, and orientation of endpoint stiffness ellipses, are expressed as linear constraints that define the set of feasible muscle activation patterns. Quadratic programming allows us to predict whether and how energy consumption can be minimized throughout the workspace of the limb given those linear constraints. We show that the presence of synergies drastically decreases the ability of the CNS to vary the properties of the endpoint stiffness and can even preclude the ability to minimize energy. Furthermore, the capacity to minimize energy consumption--when available--can be greatly affected by arm posture. Our computational approach helps reconcile divergent findings and conclusions about task-specific regulation of endpoint stiffness and energy consumption in the context of synergies. But more generally, these results provide further evidence that the benefits and disadvantages of muscle synergies go hand-in-hand with the structure of feasible muscle activation patterns afforded by the mechanics of the limb and task constraints. These insights will help design experiments to elucidate the interplay between synergies and the mechanisms

Kinetic titration with differential thermometric determination of the end-point.

Science.gov (United States)

Sajó, I

1968-06-01

A method has been described for the determination of concentrations below 10(-4)M by applying catalytic reactions and using thermometric end-point determination. A reference solution, identical with the sample solution except for catalyst, is titrated with catalyst solution until the rates of reaction become the same, as shown by a null deflection on a galvanometer connected via bridge circuits to two opposed thermistors placed in the solutions.

Fourier-transform infrared spectroscopy as a novel approach to providing effect-based endpoints in duckweed toxicity testing.

Science.gov (United States)

Hu, Li-Xin; Ying, Guang-Guo; Chen, Xiao-Wen; Huang, Guo-Yong; Liu, You-Sheng; Jiang, Yu-Xia; Pan, Chang-Gui; Tian, Fei; Martin, Francis L

2017-02-01

Traditional duckweed toxicity tests only measure plant growth inhibition as an endpoint, with limited effects-based data. The present study aimed to investigate whether Fourier-transform infrared (FTIR) spectroscopy could enhance the duckweed (Lemna minor L.) toxicity test. Four chemicals (Cu, Cd, atrazine, and acetochlor) and 4 metal-containing industrial wastewater samples were tested. After exposure of duckweed to the chemicals, standard toxicity endpoints (frond number and chlorophyll content) were determined; the fronds were also interrogated using FTIR spectroscopy under optimized test conditions. Biochemical alterations associated with each treatment were assessed and further analyzed by multivariate analysis. The results showed that comparable x% of effective concentration (ECx) values could be achieved based on FTIR spectroscopy in comparison with those based on traditional toxicity endpoints. Biochemical alterations associated with different doses of toxicant were mainly attributed to lipid, protein, nucleic acid, and carbohydrate structural changes, which helped to explain toxic mechanisms. With the help of multivariate analysis, separation of clusters related to different exposure doses could be achieved. The present study is the first to show successful application of FTIR spectroscopy in standard duckweed toxicity tests with biochemical alterations as new endpoints. Environ Toxicol Chem 2017;36:346-353. © 2016 SETAC. © 2016 SETAC.

Reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.

Science.gov (United States)

Takayama-Ito, Mutsuyo; Lim, Chang-Kweng; Nakamichi, Kazuo; Kakiuchi, Satsuki; Horiya, Madoka; Posadas-Herrera, Guillermo; Kurane, Ichiro; Saijo, Masayuki

2017-03-01

Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

12 CFR 741.4 - Insurance premium and one percent deposit.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Insurance premium and one percent deposit. 741... Insurance premium and one percent deposit. (a) Scope. This section implements the requirements of Section... payment of an insurance premium. (b) Definitions. For purposes of this section: (1) Available assets ratio...

Fifty years experiences in nuclear engineering education at Tokyo Institute of Technology

International Nuclear Information System (INIS)

Fujii, Yasuhiko; Saito, Masaki; Aritomi, Masanori

2008-01-01

Nuclear engineering education has been initiated in 1957 at the graduate school of Tokyo Institute of Technology. Educational activities have been conducted for fifty years under the support of the Research Laboratory for Nuclear Reactors. In the past fifty years, about 1000 Master students and 200 Doctoral students and 200 Doctoral students graduated from our Nuclear Engineering Department at Tokyo Institute of Technology. Many of them found their jobs in nuclear industries and institutes. International course of nuclear engineering was initiated in 1994, and so far about 90 students from 15 overseas countries have graduated from our Master and Doctoral Programs. In 2003, our proposal of 'Innovative Nuclear Energy System for the Sustainable World' was adopted as the Center of Excellent Program sponsored by Ministry of Education, Science and Technology. Recently a collaborative education network has been developed among Kanazawa University, Fukui University, Ibaraki University, Okayama University, Tokyo Institute of Technology and Japan Atomic Energy Agency. (author)

Verification of models for ballistic movement time and endpoint variability.

Science.gov (United States)

Lin, Ray F; Drury, Colin G

2013-01-01

A hand control movement is composed of several ballistic movements. The time required in performing a ballistic movement and its endpoint variability are two important properties in developing movement models. The purpose of this study was to test potential models for predicting these two properties. Twelve participants conducted ballistic movements of specific amplitudes using a drawing tablet. The measured data of movement time and endpoint variability were then used to verify the models. This study was successful with Hoffmann and Gan's movement time model (Hoffmann, 1981; Gan and Hoffmann 1988) predicting more than 90.7% data variance for 84 individual measurements. A new theoretically developed ballistic movement variability model, proved to be better than Howarth, Beggs, and Bowden's (1971) model, predicting on average 84.8% of stopping-variable error and 88.3% of aiming-variable errors. These two validated models will help build solid theoretical movement models and evaluate input devices. This article provides better models for predicting end accuracy and movement time of ballistic movements that are desirable in rapid aiming tasks, such as keying in numbers on a smart phone. The models allow better design of aiming tasks, for example button sizes on mobile phones for different user populations.

Energetic endpoints provide early indicators of life history effects in a freshwater gastropod exposed to the fungicide, pyraclostrobin.

Science.gov (United States)

Fidder, Bridgette N; Reátegui-Zirena, Evelyn G; Olson, Adric D; Salice, Christopher J

2016-04-01

Organismal energetics provide important insights into the effects of environmental toxicants. We aimed to determine the effects of pyraclostrobin on Lymnaea stagnalis by examining energy allocation patterns and life history traits. Juvenile snails exposed to pyraclostrobin decreased feeding rate and increased apparent avoidance behaviors at environmentally relevant concentrations. In adults, we found that sublethal concentrations of pyraclostrobin did not affect reproductive output, however, there were significant effects on developmental endpoints with longer time to hatch and decreased hatching success in pyraclostrobin-exposed egg masses. Further, there were apparent differences in developmental effects depending on whether mothers were also exposed to pyraclostrobin suggesting this chemical can exert intergenerational effects. Pyraclostrobin also affected protein and carbohydrate content of eggs in mothers that were exposed to pyraclostrobin. Significant effects on macronutrient content of eggs occurred at lower concentrations than effects on gross endpoints such as hatching success and time to hatch suggesting potential value for these endpoints as early indicators of ecologically relevant stress. These results provide important insight into the effects of a common fungicide on important endpoints for organismal energetics and life history. Copyright © 2015 Elsevier Ltd. All rights reserved.

Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema.

Science.gov (United States)

Lassere, Marissa N; Johnson, Kent R; Boers, Maarten; Tugwell, Peter; Brooks, Peter; Simon, Lee; Strand, Vibeke; Conaghan, Philip G; Ostergaard, Mikkel; Maksymowych, Walter P; Landewe, Robert; Bresnihan, Barry; Tak, Paul-Peter; Wakefield, Richard; Mease, Philip; Bingham, Clifton O; Hughes, Michael; Altman, Doug; Buyse, Marc; Galbraith, Sally; Wells, George

2007-03-01

There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders. After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval.

26 CFR 1.1348-2 - Computation of the fifty-percent maximum tax on earned income.

Science.gov (United States)

2010-04-01

... compensation for A's personal services rendered by him in his laundry business would be $12,000. The net... earned income. 1.1348-2 Section 1.1348-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... account in determining the net profits of a trade or business in which both personal services and capital...

Near fifty percent sodium substituted lanthanum manganites—A potential magnetic refrigerant for room temperature applications

Energy Technology Data Exchange (ETDEWEB)

Sethulakshmi, N.; Anantharaman, M. R., E-mail: mraiyer@yahoo.com [Department of Physics, Cochin University of Science and Technology, Cochin 682022, Kerala (India); Al-Omari, I. A. [Department of Physics, Sultan Qaboos University, PC 123 Muscat, Sultanate of Oman (Oman); Suresh, K. G. [Department of Physics, Indian Institute of Technology Bombay, Powai, Mumbai 400076 (India)

2014-03-03

Nearly half of lanthanum sites in lanthanum manganites were substituted with monovalent ion-sodium and the compound possessed distorted orthorhombic structure. Ferromagnetic ordering at 300 K and the magnetic isotherms at different temperature ranges were analyzed for estimating magnetic entropy variation. Magnetic entropy change of 1.5 J·kg{sup −1}·K{sup −1} was observed near 300 K. An appreciable magnetocaloric effect was also observed for a wide range of temperatures near 300 K for small magnetic field variation. Heat capacity was measured for temperatures lower than 300 K and the adiabatic temperature change increases with increase in temperature with a maximum of 0.62 K at 280 K.

Matter power spectrum and the challenge of percent accuracy

International Nuclear Information System (INIS)

Schneider, Aurel; Teyssier, Romain; Potter, Doug; Stadel, Joachim; Reed, Darren S.; Onions, Julian; Pearce, Frazer R.; Smith, Robert E.; Springel, Volker; Scoccimarro, Roman

2016-01-01

Future galaxy surveys require one percent precision in the theoretical knowledge of the power spectrum over a large range including very nonlinear scales. While this level of accuracy is easily obtained in the linear regime with perturbation theory, it represents a serious challenge for small scales where numerical simulations are required. In this paper we quantify the precision of present-day N -body methods, identifying main potential error sources from the set-up of initial conditions to the measurement of the final power spectrum. We directly compare three widely used N -body codes, Ramses, Pkdgrav3, and Gadget3 which represent three main discretisation techniques: the particle-mesh method, the tree method, and a hybrid combination of the two. For standard run parameters, the codes agree to within one percent at k ≤1 h Mpc −1 and to within three percent at k ≤10 h Mpc −1 . We also consider the bispectrum and show that the reduced bispectra agree at the sub-percent level for k ≤ 2 h Mpc −1 . In a second step, we quantify potential errors due to initial conditions, box size, and resolution using an extended suite of simulations performed with our fastest code Pkdgrav3. We demonstrate that the simulation box size should not be smaller than L =0.5 h −1 Gpc to avoid systematic finite-volume effects (while much larger boxes are required to beat down the statistical sample variance). Furthermore, a maximum particle mass of M p =10 9 h −1 M ⊙ is required to conservatively obtain one percent precision of the matter power spectrum. As a consequence, numerical simulations covering large survey volumes of upcoming missions such as DES, LSST, and Euclid will need more than a trillion particles to reproduce clustering properties at the targeted accuracy.

49 CFR 173.182 - Barium azide-50 percent or more water wet.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Barium azide-50 percent or more water wet. 173.182 Section 173.182 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS... Class 1 and Class 7 § 173.182 Barium azide—50 percent or more water wet. Barium azide—50 percent or more...

78 FR 49530 - Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics; Public Workshop

Science.gov (United States)

2013-08-14

...] Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics; Public Workshop AGENCY: Food and Drug... for Drug Evaluation and Research, in cosponsorship with the American College of Gastroenterology, the... American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, and the Pediatric IBD...

Mathematical card magic fifty-two new effects

CERN Document Server

Mulcahy, Colm

2013-01-01

Mathematical card effects offer both beginning and experienced magicians an opportunity to entertain with a minimum of props. Featuring mostly original creations, Mathematical Card Magic: Fifty-Two New Effects presents an entertaining look at new mathematically based card tricks. Each chapter contains four card effects, generally starting with simple applications of a particular mathematical principle and ending with more complex ones. Practice a handful of the introductory effects and, in no time, you'll establish your reputation as a "mathemagician." Delve a little deeper into each chapter and the mathematics gets more interesting. The author explains the mathematics as needed in an easy-to-follow way. He also provides additional details, background, and suggestions for further explorations.Suitable for recreational math buffs and amateur card lovers or as a text in a first-year seminar, this color book offers a diverse collection of new mathemagic principles and effects.

Confirmatory versus explorative endpoint analysis: Decision-making on the basis of evidence available from market authorization and early benefit assessment for oncology drugs.

Science.gov (United States)

Niehaus, Ines; Dintsios, Charalabos-Markos

2018-03-26

The early benefit assessment of pharmaceuticals in Germany and their preceding market authorization pursue different objectives. This is reflected by the inclusion of varying confirmatory endpoints within the evaluation of oncology drugs in early benefit assessment versus market authorization, with both relying on the same evidence. Data from assessments up to July 2015 are used to estimate the impact of explorative in comparison to confirmatory endpoints on market authorization and early benefit assessment by contrasting the benefit-risk ratio of EMA and the benefit-harm balance of the HTA jurisdiction. Agreement between market authorization and early benefit assessment is examined by Cohen's kappa (k). 21 of 41 assessments were considered in the analysis. Market authorization is more confirmatory than early benefit assessment because it includes a higher proportion of primary endpoints. The latter implies a primary endpoint to be relevant for the benefit-harm balance in only 67% of cases (0.078). Explorative mortality endpoints reached the highest agreement regarding the mutual consideration for the risk-benefit ratio and the benefit-harm balance (0.000). For explorative morbidity endpoints (-0.600), quality of life (-0.600) and side effects (-0.949) no agreement is ascertainable. To warrant a broader confirmatory basis for decisions supported by HTA, closer inter-institutional cooperation of approval authorities and HTA jurisdictions by means of reliable joint advice for manufacturers regarding endpoint definition would be favorable. Copyright © 2018 Elsevier B.V. All rights reserved.

Fifty years in fusion and the way forward

International Nuclear Information System (INIS)

Jacquinot, J.

2010-01-01

This particular 'Fusion Pioneers Memorial lecture' was given 50 years after the first historical FEC conference in 1958. It was a unique occasion to perform a global reflection on thermonuclear fusion which is summarized in this paper. We first consider the case for fusion energy then move on to the scientific achievements during the past five decades. Finally, the lessons drawn from the past give a framework to consider the challenges ahead of us. The 1958 pioneers had the vision of the vital importance of international collaboration to succeed in this unique endeavour. Fifty years later, this vision has amply proven its worth. Looking at the way forward, this vision constitutes a strong basis to harness fusion energy in the decades to come.

Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration

DEFF Research Database (Denmark)

Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo

2013-01-01

Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...

Free-time and fixed end-point multi-target optimal control theory: Application to quantum computing

International Nuclear Information System (INIS)

Mishima, K.; Yamashita, K.

2011-01-01

Graphical abstract: The two-state Deutsch-Jozsa algortihm used to demonstrate the utility of free-time and fixed-end point multi-target optimal control theory. Research highlights: → Free-time and fixed-end point multi-target optimal control theory (FRFP-MTOCT) was constructed. → The features of our theory include optimization of the external time-dependent perturbations with high transition probabilities, that of the temporal duration, the monotonic convergence, and the ability to optimize multiple-laser pulses simultaneously. → The advantage of the theory and a comparison with conventional fixed-time and fixed end-point multi-target optimal control theory (FIFP-MTOCT) are presented by comparing data calculated using the present theory with those published previously [K. Mishima, K. Yamashita, Chem. Phys. 361 (2009) 106]. → The qubit system of our interest consists of two polar NaCl molecules coupled by dipole-dipole interaction. → The calculation examples show that our theory is useful for minor adjustment of the external fields. - Abstract: An extension of free-time and fixed end-point optimal control theory (FRFP-OCT) to monotonically convergent free-time and fixed end-point multi-target optimal control theory (FRFP-MTOCT) is presented. The features of our theory include optimization of the external time-dependent perturbations with high transition probabilities, that of the temporal duration, the monotonic convergence, and the ability to optimize multiple-laser pulses simultaneously. The advantage of the theory and a comparison with conventional fixed-time and fixed end-point multi-target optimal control theory (FIFP-MTOCT) are presented by comparing data calculated using the present theory with those published previously [K. Mishima, K. Yamashita, Chem. Phys. 361, (2009), 106]. The qubit system of our interest consists of two polar NaCl molecules coupled by dipole-dipole interaction. The calculation examples show that our theory is useful for minor

A clinical study on the feasibility of autologous cord blood transfusion for anemia of prematurity.

Science.gov (United States)

Khodabux, Chantal M; von Lindern, Jeannette S; van Hilten, Joost A; Scherjon, Sicco; Walther, Frans J; Brand, Anneke

2008-08-01

The objective was to investigate the use of autologous red blood cells (RBCs) derived from umbilical cord blood (UCB), as an alternative for allogeneic transfusions in premature infants admitted to a tertiary neonatal center. UCB collection was performed at deliveries of less than 32 weeks of gestation and processed into autologous RBC products. Premature infants requiring a RBC transfusion were randomly assigned to an autologous or allogeneic product. The primary endpoint was an at least 50 percent reduction in allogeneic transfusion needs. Fifty-seven percent of the collections harvested enough volume (> or =15 mL) for processing. After being processed, autologous products (> or =10 mL/kg) were available for 36 percent of the total study population and for 27 percent of the transfused infants and could cover 58 percent (range, 25%-100%) of the transfusion needs within the 21-day product shelf life. Availability of autologous products depended most on the gestational age. Infants born between 24 and 28 weeks had the lowest availability (17%). All products, however, would be useful in view of their high (87%) transfusion needs. Availability was highest (48%) for the infants born between 28 and 30 weeks. For 42 percent of the infants with transfusion needs in this group, autologous products were available. For the infants born between 30 and 32 weeks, autologous products were available for 36 percent of the infants. Transfusion needs in this group were, however, much lower (19%) compared to the other gestational groups. Autologous RBCs derived from UCB could not replace 50 percent of allogeneic transfusions due to the low UCB volumes collected and subsequent low product availability.

Domain analysis of computational science - Fifty years of a scientific computing group

Energy Technology Data Exchange (ETDEWEB)

Tanaka, M.

2010-02-23

I employed bibliometric- and historical-methods to study the domain of the Scientific Computing group at Brookhaven National Laboratory (BNL) for an extended period of fifty years, from 1958 to 2007. I noted and confirmed the growing emergence of interdisciplinarity within the group. I also identified a strong, consistent mathematics and physics orientation within it.

The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints.

Science.gov (United States)

Shiboski, C H; Patton, L L; Webster-Cyriaque, J Y; Greenspan, D; Traboulsi, R S; Ghannoum, M; Jurevic, R; Phelan, J A; Reznik, D; Greenspan, J S

2009-07-01

The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points.

Is automated kinetic measurement superior to end-point for advanced oxidation protein product?

Science.gov (United States)

Oguz, Osman; Inal, Berrin Bercik; Emre, Turker; Ozcan, Oguzhan; Altunoglu, Esma; Oguz, Gokce; Topkaya, Cigdem; Guvenen, Guvenc

2014-01-01

Advanced oxidation protein product (AOPP) was first described as an oxidative protein marker in chronic uremic patients and measured with a semi-automatic end-point method. Subsequently, the kinetic method was introduced for AOPP assay. We aimed to compare these two methods by adapting them to a chemistry analyzer and to investigate the correlation between AOPP and fibrinogen, the key molecule responsible for human plasma AOPP reactivity, microalbumin, and HbA1c in patients with type II diabetes mellitus (DM II). The effects of EDTA and citrate-anticogulated tubes on these two methods were incorporated into the study. This study included 93 DM II patients (36 women, 57 men) with HbA1c levels > or = 7%, who were admitted to the diabetes and nephrology clinics. The samples were collected in EDTA and in citrate-anticoagulated tubes. Both methods were adapted to a chemistry analyzer and the samples were studied in parallel. In both types of samples, we found a moderate correlation between the kinetic and the endpoint methods (r = 0.611 for citrate-anticoagulated, r = 0.636 for EDTA-anticoagulated, p = 0.0001 for both). We found a moderate correlation between fibrinogen-AOPP and microalbumin-AOPP levels only in the kinetic method (r = 0.644 and 0.520 for citrate-anticoagulated; r = 0.581 and 0.490 for EDTA-anticoagulated, p = 0.0001). We conclude that adaptation of the end-point method to automation is more difficult and it has higher between-run CV% while application of the kinetic method is easier and it may be used in oxidative stress studies.

Matter power spectrum and the challenge of percent accuracy

Energy Technology Data Exchange (ETDEWEB)

Schneider, Aurel; Teyssier, Romain; Potter, Doug; Stadel, Joachim; Reed, Darren S. [Institute for Computational Science, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Onions, Julian; Pearce, Frazer R. [School of Physics and Astronomy, University of Nottingham, Nottingham NG7 2RD (United Kingdom); Smith, Robert E. [Department of Physics and Astronomy, University of Sussex, Brighton, BN1 9QH (United Kingdom); Springel, Volker [Heidelberger Institut für Theoretische Studien, 69118 Heidelberg (Germany); Scoccimarro, Roman, E-mail: aurel@physik.uzh.ch, E-mail: teyssier@physik.uzh.ch, E-mail: dpotter@physik.uzh.ch, E-mail: stadel@physik.uzh.ch, E-mail: julian.onions@nottingham.ac.uk, E-mail: reed@physik.uzh.ch, E-mail: r.e.smith@sussex.ac.uk, E-mail: volker.springel@h-its.org, E-mail: Frazer.Pearce@nottingham.ac.uk, E-mail: rs123@nyu.edu [Center for Cosmology and Particle Physics, Department of Physics, New York University, NY 10003, New York (United States)

2016-04-01

Future galaxy surveys require one percent precision in the theoretical knowledge of the power spectrum over a large range including very nonlinear scales. While this level of accuracy is easily obtained in the linear regime with perturbation theory, it represents a serious challenge for small scales where numerical simulations are required. In this paper we quantify the precision of present-day N -body methods, identifying main potential error sources from the set-up of initial conditions to the measurement of the final power spectrum. We directly compare three widely used N -body codes, Ramses, Pkdgrav3, and Gadget3 which represent three main discretisation techniques: the particle-mesh method, the tree method, and a hybrid combination of the two. For standard run parameters, the codes agree to within one percent at k ≤1 h Mpc{sup −1} and to within three percent at k ≤10 h Mpc{sup −1}. We also consider the bispectrum and show that the reduced bispectra agree at the sub-percent level for k ≤ 2 h Mpc{sup −1}. In a second step, we quantify potential errors due to initial conditions, box size, and resolution using an extended suite of simulations performed with our fastest code Pkdgrav3. We demonstrate that the simulation box size should not be smaller than L =0.5 h {sup −1}Gpc to avoid systematic finite-volume effects (while much larger boxes are required to beat down the statistical sample variance). Furthermore, a maximum particle mass of M {sub p}=10{sup 9} h {sup −1}M{sub ⊙} is required to conservatively obtain one percent precision of the matter power spectrum. As a consequence, numerical simulations covering large survey volumes of upcoming missions such as DES, LSST, and Euclid will need more than a trillion particles to reproduce clustering properties at the targeted accuracy.

United States home births increase 20 percent from 2004 to 2008.

Science.gov (United States)

MacDorman, Marian F; Declercq, Eugene; Mathews, T J

2011-09-01

After a gradual decline from 1990 to 2004, the percentage of births occurring at home increased from 2004 to 2008 in the United States. The objective of this report was to examine the recent increase in home births and the factors associated with this increase from 2004 to 2008. United States birth certificate data on home births were analyzed by maternal demographic and medical characteristics. In 2008, there were 28,357 home births in the United States. From 2004 to 2008, the percentage of births occurring at home increased by 20 percent from 0.56 percent to 0.67 percent of United States births. This rise was largely driven by a 28 percent increase in the percentage of home births for non-Hispanic white women, for whom more than 1 percent of births occur at home. At the same time, the risk profile for home births has been lowered, with substantial drops in the percentage of home births of infants who are born preterm or at low birthweight, and declines in the percentage of home births that occur to teen and unmarried mothers. Twenty-seven states had statistically significant increases in the percentage of home births from 2004 to 2008; only four states had declines. The 20 percent increase in United States home births from 2004 to 2008 is a notable development that will be of interest to practitioners and policymakers. (BIRTH 38:3 September 2011). © 2011, Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc.

Alternative Endpoints and Approaches for the Remediation of Contaminated Groundwater at Complex Sites - 13426

International Nuclear Information System (INIS)

Deeb, Rula A.; Hawley, Elisabeth L.

2013-01-01

The goal of United States (U.S.) Department of Energy's (DOE)'s environmental remediation programs is to restore groundwater to beneficial use, similar to many other Federal and state environmental cleanup programs. Based on past experience, groundwater remediation to pre-contamination conditions (i.e., drinking water standards or non-detectable concentrations) can be successfully achieved at many sites. At a subset of the most complex sites, however, complete restoration is not likely achievable within the next 50 to 100 years using today's technology. This presentation describes several approaches used at complex sites in the face of these technical challenges. Many complex sites adopted a long-term management approach, whereby contamination was contained within a specified area using active or passive remediation techniques. Consistent with the requirements of their respective environmental cleanup programs, several complex sites selected land use restrictions and used risk management approaches to accordingly adopt alternative cleanup goals (alternative endpoints). Several sites used long-term management designations and approaches in conjunction with the alternative endpoints. Examples include various state designations for groundwater management zones, technical impracticability (TI) waivers or greater risk waivers at Superfund sites, and the use of Monitored Natural Attenuation (MNA) or other passive long-term management approaches over long time frames. This presentation will focus on findings, statistics, and case studies from a recently-completed report for the Department of Defense's Environmental Security Technology Certification Program (ESTCP) (Project ER-0832) on alternative endpoints and approaches for groundwater remediation at complex sites under a variety of Federal and state cleanup programs. The primary objective of the project was to provide environmental managers and regulators with tools, metrics, and information needed to evaluate

Alternative Endpoints and Approaches for the Remediation of Contaminated Groundwater at Complex Sites - 13426

Energy Technology Data Exchange (ETDEWEB)

Deeb, Rula A.; Hawley, Elisabeth L. [ARCADIS, U.S., 2000 Powell St., 7th Floor, Emeryville, California 94608 (United States)

2013-07-01

The goal of United States (U.S.) Department of Energy's (DOE)'s environmental remediation programs is to restore groundwater to beneficial use, similar to many other Federal and state environmental cleanup programs. Based on past experience, groundwater remediation to pre-contamination conditions (i.e., drinking water standards or non-detectable concentrations) can be successfully achieved at many sites. At a subset of the most complex sites, however, complete restoration is not likely achievable within the next 50 to 100 years using today's technology. This presentation describes several approaches used at complex sites in the face of these technical challenges. Many complex sites adopted a long-term management approach, whereby contamination was contained within a specified area using active or passive remediation techniques. Consistent with the requirements of their respective environmental cleanup programs, several complex sites selected land use restrictions and used risk management approaches to accordingly adopt alternative cleanup goals (alternative endpoints). Several sites used long-term management designations and approaches in conjunction with the alternative endpoints. Examples include various state designations for groundwater management zones, technical impracticability (TI) waivers or greater risk waivers at Superfund sites, and the use of Monitored Natural Attenuation (MNA) or other passive long-term management approaches over long time frames. This presentation will focus on findings, statistics, and case studies from a recently-completed report for the Department of Defense's Environmental Security Technology Certification Program (ESTCP) (Project ER-0832) on alternative endpoints and approaches for groundwater remediation at complex sites under a variety of Federal and state cleanup programs. The primary objective of the project was to provide environmental managers and regulators with tools, metrics, and information needed

End-point construction and systematic titration error in linear titration curves-complexation reactions

NARCIS (Netherlands)

Coenegracht, P.M.J.; Duisenberg, A.J.M.

The systematic titration error which is introduced by the intersection of tangents to hyperbolic titration curves is discussed. The effects of the apparent (conditional) formation constant, of the concentration of the unknown component and of the ranges used for the end-point construction are

Fifty years of sociological leadership at Social Science and Medicine.

Science.gov (United States)

Timmermans, Stefan; Tietbohl, Caroline

2018-01-01

In this review article, we examine some of the conceptual contributions of sociology of health and illness over the past fifty years. Specifically, we focus on research dealing with medicalization, the management of stigma, research on adherence and compliance, and patient-doctor interaction. We show how these themes that originated within sociology, diffused in other disciplines. Sociology in Social Science and Medicine started as an applied research tradition but morphed into a robust, stand-alone social science tradition. Copyright © 2017 Elsevier Ltd. All rights reserved.

FIFTY-FIVE GALLON DRUM STANDARD STUDY

International Nuclear Information System (INIS)

Puigh, R.J.

2009-01-01

Fifty-five gallon drums are routinely used within the U.S. for the storage and eventual disposal of fissionable materials as Transuranic or low-level waste. To support these operations, criticality safety evaluations are required. A questionnaire was developed and sent to selected Endusers at Hanford, Idaho National Laboratory, Lawrence Livermore National Laboratory, Oak Ridge and the Savannah River Site to solicit current practices. This questionnaire was used to gather information on the kinds of fissionable materials packaged into drums, the models used in performing criticality safety evaluations in support of operations involving these drums, and the limits and controls established for the handling and storage of these drums. The completed questionnaires were reviewed and clarifications solicited through individual communications with each Enduser to obtain more complete and consistent responses. All five sites have similar drum operations involving thousands to tens of thousands of fissionable material waste drums. The primary sources for these drums are legacy (prior operations) and decontamination and decommissioning wastes at all sites except Lawrence Livermore National Laboratory. The results from this survey and our review are discussed in this paper

Fifty years of continuous improvement: (What has DOE done for analytical chemistry?)

Energy Technology Data Exchange (ETDEWEB)

Shults, W.D.

1993-11-01

Over the past fifty years, analytical scientist within the DOE complex have had a tremendous impact on the field of analytical chemistry. This paper suggests six ``high impact`` research/development areas that either originated within or were brought to maturity within the DOE laboratories. ``High impact`` means they lead to new subdisciplines or to new ways of doing business.

Fifty years with nuclear fission

International Nuclear Information System (INIS)

Behrens, J.W.; Carlson, A.D.

1989-01-01

The news of the discovery of nucler fission, by Otto Hahn and Fritz Strassmann in Germany, was brought to the United States by Niels Bohr in January 1939. Since its discovery, the United States, and the world for that matter, has never been the same. It therefore seemed appropriate to acknowledge the fiftieth anniversary of its discovery by holding a topical meeting entitled, ''Fifty years with nuclear fission,'' in the United States during the year 1989. The objective of the meeting was to bring together pioneers of the nuclear industry and other scientists and engineers to report on reminiscences of the past and on the more recent developments in fission science and technology. The conference highlighted the early pioneers of the nuclear industry by dedicating a full day (April 26), consisting of two plenary sessions, at the National Academy of Sciences (NAS) in Washington, DC. More recent developments in fission science and technology in addition to historical reflections were topics for two full days of sessions (April 27 and 28) at the main sites of the NIST in Gaithersburg, Maryland. The wide range of topics covered by Volume 2 of this topical meeting included plenary invited, and contributed sessions entitled, Nuclear fission -- a prospective; reactors II; fission science II; medical and industrial applications by by-products; reactors and safeguards; general research, instrumentation, and by-products; and fission data, astrophysics, and space applications. The individual papers have been cataloged separately

How I Love My 80 Percenters

Science.gov (United States)

Maturo, Anthony J.

2002-01-01

Don't ever take your support staff for granted. By support staff, I mean the people in personnel, logistics, and finance; the ones who can make things happen with a phone call or a signature, or by the same token frustrate you to no end by their inaction; these are people you must depend on. I've spent a lot of time thinking about how to cultivate relationships with my support staff that work to the advantage of both of us. The most important thing that have learned working with people, any people--and I will tell you how I learned this in a minute--is there are some folks you just can't motivate, so forget it, don't try; others you certainly can with a little psychology and some effort; and the best of the bunch, what I call the 80 percenters, you don't need to motivate because they're already on the team and performing beautifully. The ones you can't change are rocks. Face up to it, and just kick them out of your way. I have a reputation with the people who don't want to perform or be part of the team. They don't come near me. If someone's a rock, I pick up on it right away, and I will walk around him or her to find someone better. The ones who can be motivated I take time to nurture. I consider them my projects. A lot of times these wannabes are people who want to help but don't know how. Listen, you can work with them. Lots of people in organizations have the mindset that all that matters are the regulations. God forbid if you ever work outside those regulations. They've got one foot on that regulation and they're holding it tight like a baby holds a blanket. What you're looking for is that first sign that their minds are opening. Usually you hear it in their vocabulary. What used to sound like "We can't do that ... the regulations won't allow it ... we have never done this before," well, suddenly that changes to "We have options ... let's take a look at the options ... let me research this and get back to you." The 80 percenters you want to nurture too, but

Mesoscale simulation of semiflexible chains. I. Endpoint distribution and chain dynamics

Science.gov (United States)

Groot, Robert D.

2013-06-01

The endpoint distribution and dynamics of semiflexible fibers are studied by numerical simulation. A brief overview is given over the analytical theory of flexible and semiflexible polymers. In particular, a closed expression is given for the relaxation spectrum of wormlike chains, which determines polymer diffusion and rheology. Next a simulation model for wormlike chains with full hydrodynamic interaction is described, and relations for the bending and torsion modulus are given. Two methods are introduced to include torsion stiffness into the model. The model is validated by simulating single chains in a heat bath, and comparing the endpoint distribution of the chains with established Monte Carlo results. It is concluded that torsion stiffness leads to a slightly shorter effective persistence length for a given bending stiffness. To further validate the simulation model, polymer diffusion is studied for fixed persistence length and varying polymer length N. The diffusion constant shows crossover from Rouse (D ∝ N-1) to reptation behaviour (D ∝ N-2). The terminal relaxation time obtained from the monomer displacement is consistent with the theory of wormlike chains. The probability for chain crossing has also been studied. This probability is so low that it does not influence the present results.

Comparison of earthworm responses to petroleum hydrocarbon exposure in aged field contaminated soil using traditional ecotoxicity endpoints and 1H NMR-based metabolomics

International Nuclear Information System (INIS)

Whitfield Åslund, Melissa; Stephenson, Gladys L.; Simpson, André J.; Simpson, Myrna J.

2013-01-01

1 H NMR metabolomics and conventional ecotoxicity endpoints were used to examine the response of earthworms exposed to petroleum hydrocarbons (PHCs) in soil samples collected from a site that was contaminated with crude oil from a pipeline failure in the mid-1990s. The conventional ecotoxicity tests showed that the soils were not acutely toxic to earthworms (average survival ≥90%), but some soil samples impaired reproduction endpoints by >50% compared to the field control soil. Additionally, metabolomics revealed significant relationships between earthworm metabolic profiles (collected after 2 or 14 days of exposure) and soil properties including soil PHC concentration. Further comparisons by partial least squares regression revealed a significant relationship between the earthworm metabolomic data (collected after only 2 or 14 days) and the reproduction endpoints (measured after 63 days). Therefore, metabolomic responses measured after short exposure periods may be predictive of chronic, ecologically relevant toxicity endpoints for earthworms exposed to soil contaminants. -- Highlights: •Earthworm response to petroleum hydrocarbon exposure in soil is examined. •Metabolomics shows significant changes to metabolic profile after 2 days. •Significant relationships observed between metabolomic and reproduction endpoints. •Metabolomics may have value as a rapid screening tool for chronic toxicity. -- Earthworm metabolomic responses measured after 2 and 14 days are compared to traditional earthworm ecotoxicity endpoints (survival and reproduction) in petroleum hydrocarbon contaminated soil

QED contribution to the color-singlet J/ψ production in Υ decay near the endpoint

International Nuclear Information System (INIS)

Liu Xiaohui

2010-01-01

A recent study indicates that the α 2 α s 2 order QED processes of Υ→J/ψ+X decay are compatible with those of QCD processes. However, in the endpoint region, the nonrelativistic QED calculation breaks down since the collinear degrees of freedom are missing under the framework of this effective theory. In this paper we apply the soft-collinear effective theory (SCET) to study the color-singlet QED process at the kinematic limit. Within this approach we are able to sum the kinematic logarithms by running operators using the renormalization group equations of soft-collinear effective theory, which will lead to a dramatic change in the momentum distribution near the endpoint and the spectrum shape consistent with the experimental results.

Extracting gluino endpoints with event topology patterns

Energy Technology Data Exchange (ETDEWEB)

Pietsch, N. [Hamburg Univ. (Germany). Inst. fuer Experimentalphysik; Reuter, J.; Sakurai, K.; Wiesler, D. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

2012-06-15

In this paper we study the gluino dijet mass edge measurement at the LHC in a realistic situation including both SUSY and combinatorical backgrounds together with effects of initial and final state radiation as well as a finite detector resolution. Three benchmark scenarios are examined in which the dominant SUSY production process and also the decay modes are different. Several new kinematical variables are proposed to minimize the impact of SUSY and combinatorial backgrounds in the measurement. By selecting events with a particular number of jets and leptons, we attempt to measure two distinct gluino dijet mass edges originating from wino g {yields} jjW and bino g {yields}jjB decay modes, separately. We determine the endpoints of distributions of proposed and existing variables and show that those two edges can be disentangled and measured within good accuracy, irrespective of the presence of ISR, FSR, and detector effects.

The history of fifty years of institute of electrical engineers 1947-1996

International Nuclear Information System (INIS)

1997-07-01

This book starts with the survey of a century of Korea electrical industry. It includes a business of electric power and electrical machinery industry. Next, it deals with the survey of fifty years of Korea institute electrical engineers. Then, it enumerates the articles of association, organization, board members, the role of the administrative organization, study and institute business activities in detail.

Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data

NARCIS (Netherlands)

Mauguen, Audrey; Pignon, Jean-Pierre; Burdett, Sarah; Domerg, Caroline; Fisher, David; Paulus, Rebecca; Mandrekar, Samithra J.; Belani, Chandra P.; Shepherd, Frances A.; Eisen, Tim; Pang, Herbert; Collette, Laurence; Sause, William T.; Dahlberg, Suzanne E.; Crawford, Jeffrey; O'Brien, Mary; Schild, Steven E.; Parmar, Mahesh; Tierney, Jayne F.; Le Pechoux, Cécile; Michiels, Stefan; Burdett, S.; Fisher, D.; Le Péchoux, C.; Mauguen, A.; Michiels, S.; Pignon, J. P.; Tierney, J. F.; Belani, C. P.; Collette, L.; Dahlberg, S.; Eisen, T.; Mandrekar, S.; O'Brien, M.; Parmar, M.; Pang, H.; Paulus, R.; Crawford, J.; Sause, W.; Schild, S. E.; Shepherd, F.; Arriagada, R.; Atagi, S.; Auperin, A.; Ball, D.; Baumann, M.; Behrendt, K.; Belderbos, J.; Koning, C. C. E.; Uitterhoeve, A.

2013-01-01

The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We

New formula for calculation of cobalt-60 percent depth dose

International Nuclear Information System (INIS)

Tahmasebi Birgani, M. J.; Ghorbani, M.

2005-01-01

On the basis of percent depth dose calculation, the application of - dosimetry in radiotherapy has an important role to play in reducing the chance of tumor recurrence. The aim of this study is to introduce a new formula for calculating the central axis percent depth doses of Cobalt-60 beam. Materials and Methods: In the present study, based on the British Journal of Radiology table, nine new formulas are developed and evaluated for depths of 0.5 - 30 cm and fields of (4*4) - (45*45) cm 2 . To evaluate the agreement between the formulas and the table, the average of the absolute differences between the values was used and the formula with the least average was selected as the best fitted formula. The Microsoft Excel 2000 and the Data fit 8.0 soft wares were used to perform the calculations. Results: The results of this study indicated that one amongst the nine formulas gave a better agreement with the percent depth doses listed in the table of British Journal of Radiology . The new formula has two parts in terms of log (A/P). The first part as a linear function with the depth in the range of 0.5 to 5 cm and the other one as a second order polynomial with the depth in the range of 6 to 30 cm. The average of - the differences between the tabulated and the calculated data using the formula (Δ) is equal to 0.3 152. Discussion and Conclusion: Therefore, the calculated percent depth dose data based on this formula has a better agreement with the published data for Cobalt-60 source. This formula could be used to calculate the percent depth dose for the depths and the field sizes not listed in the British Journal of Radiology table

End-point impedance measurements across dominant and nondominant hands and robotic assistance with directional damping.

Science.gov (United States)

Erden, Mustafa Suphi; Billard, Aude

2015-06-01

The goal of this paper is to perform end-point impedance measurements across dominant and nondominant hands while doing airbrush painting and to use the results for developing a robotic assistance scheme. We study airbrush painting because it resembles in many ways manual welding, a standard industrial task. The experiments are performed with the 7 degrees of freedom KUKA lightweight robot arm. The robot is controlled in admittance using a force sensor attached at the end-point, so as to act as a free-mass and be passively guided by the human. For impedance measurements, a set of nine subjects perform 12 repetitions of airbrush painting, drawing a straight-line on a cartoon horizontally placed on a table, while passively moving the airbrush mounted on the robot's end-point. We measure hand impedance during the painting task by generating sudden and brief external forces with the robot. The results show that on average the dominant hand displays larger impedance than the nondominant in the directions perpendicular to the painting line. We find the most significant difference in the damping values in these directions. Based on this observation, we develop a "directional damping" scheme for robotic assistance and conduct a pilot study with 12 subjects to contrast airbrush painting with and without robotic assistance. Results show significant improvement in precision with both dominant and nondominant hands when using robotic assistance.

Using quantitative structure-activity relationships (QSAR) to predict toxic endpoints for polycyclic aromatic hydrocarbons (PAH).

Science.gov (United States)

Bruce, Erica D; Autenrieth, Robin L; Burghardt, Robert C; Donnelly, K C; McDonald, Thomas J

2008-01-01

Quantitative structure-activity relationships (QSAR) offer a reliable, cost-effective alternative to the time, money, and animal lives necessary to determine chemical toxicity by traditional methods. Additionally, humans are exposed to tens of thousands of chemicals in their lifetimes, necessitating the determination of chemical toxicity and screening for those posing the greatest risk to human health. This study developed models to predict toxic endpoints for three bioassays specific to several stages of carcinogenesis. The ethoxyresorufin O-deethylase assay (EROD), the Salmonella/microsome assay, and a gap junction intercellular communication (GJIC) assay were chosen for their ability to measure toxic endpoints specific to activation-, induction-, and promotion-related effects of polycyclic aromatic hydrocarbons (PAH). Shape-electronic, spatial, information content, and topological descriptors proved to be important descriptors in predicting the toxicity of PAH in these bioassays. Bioassay-based toxic equivalency factors (TEF(B)) were developed for several PAH using the quantitative structure-toxicity relationships (QSTR) developed. Predicting toxicity for a specific PAH compound, such as a bioassay-based potential potency (PP(B)) or a TEF(B), is possible by combining the predicted behavior from the QSTR models. These toxicity estimates may then be incorporated into a risk assessment for compounds that lack toxicity data. Accurate toxicity predictions are made by examining each type of endpoint important to the process of carcinogenicity, and a clearer understanding between composition and toxicity can be obtained.

Radiometric titration of officinal radiopharmaceuticals using radioactive kryptonates as end-point indicators. I. Salicylic, acetylosalicylic, benzoic acids

Energy Technology Data Exchange (ETDEWEB)

Toelgyessy, J; Dillinger, P [Slovenska Vysoka Skola Technicka, Bratislava (Czechoslovakia). Chemickotechnologicka Fakulta; Harangozo, M; Jombik, J [Komenskeho Univ., Bratislava (Czechoslovakia). Farmaceuticka Fakulta

1980-01-01

A method for the determination of salicylic, acetylsalicylic and benzoic acids in officinal pharmaceutical based on radiometric titration with 0.1 mol.l/sup -1/ NaOH was developed. The end-point was detected with the aid of radioactive glass kryptonate. After the end-point, the excess titrant attacks the glass surface layers and this results in releasing /sup 85/Kr, and consequently, in decreasing the radioactivity of the kryptonate employed. The radioactive kryptonate used as an indicator was prepared by the bombardment of glass with accelerated /sup 85/Kr ions. The developed method is simple, accurate and correct.

The decision book fifty models for strategic thinking

CERN Document Server

Krogerus, Mikael

2011-01-01

Most of us face the same questions every day: What do I want? And how can I get it? How can I live more happily and work more efficiently? A worldwide bestseller, The Decision Book distils into a single volume the fifty best decision-making models used on MBA courses and elsewhere that will help you tackle these important questions - from the well known (the Eisenhower matrix for time management) to the less familiar but equally useful (the Swiss Cheese model). It will even show you how to remember everything you will have learned by the end of it. Stylish and compact, this little black book is a powerful asset. Whether you need to plot a presentation, assess someone's business idea or get to know yourself better, this unique guide will help you simplify any problem and take steps towards the right decision.

Fifty years of 'Atoms for Peace'

International Nuclear Information System (INIS)

Heller, W.

2004-01-01

Fifty years ago, on December 8, 1953, the then U.S. President, Dwight D. Eisenhower, in his famous speech before the General Assembly of the United Nations proclaimed his 'Atoms for Peace' program, which was to initiate a policy of international cooperation. The event had been preceded by a policy of the United States intended to guarantee to the United States the monopoly in the production and use of nuclear weapons, which ultimately failed because of the resistance of the Soviet Union. The doctrine of a technological monopoly in the nuclear field was to be changed in favor of cooperative ventures under the rigorous control of the United States. The 1954 Atomic Energy Act clearly formulated the will to cooperate. Following a U.S. initiative, the International Atomic Energy Agency (IAEA) was founded in 1956 to assist in transfers of nuclear technology and assume controlling functions to prevent abuse for non-peaceful purposes. Quite a number of countries used the 'Atoms for Peace' offer to develop nuclear power in very close cooperation with American industry and depending on U.S. nuclear fuel supply. On the whole, 'Atoms for Peace' has paved the way to a worldwide peaceful use of nuclear power. (orig.)

The Kramers problem: Fifty years of development

International Nuclear Information System (INIS)

Mel'nikov, V.O.

1990-09-01

In the last fifty years the seminal work by Kramers of 1940 has been greatly extended both by elaboration of new theoretical approaches and through applications to new experimental systems. The most interesting case turns out to be the regime of weak-to-medium damping, in which case the Fokker-Planck equation can be reduced to an equation or to a system of integral equations of the Wiener-Hopf type. Exact solutions can then be given for the escape rate from single- and double-well potentials. This general scheme can be naturally extended to include quantum penetration through a semiclassical barrier and the effect of quantum noise. Finally, we consider the Brownian motion in a tilted washboard potential using Josephson junctions as an illustrative example. In that context we calculate (i) fluctuation-induced voltage-current characteristics, (ii) the lifetime of a zero-voltage state, (iii) the lifetime of the running state, (iv) partial probabilities of the phase jumps by 2πn (n is an integer) and (v) retrapping current distribution in both classical and quantum regimes. (author). 61 refs, 17 figs

The role of categorization and scale endpoint comparisons in numerical information processing: A two-process model.

Science.gov (United States)

Tao, Tao; Wyer, Robert S; Zheng, Yuhuang

2017-03-01

We propose a two-process conceptualization of numerical information processing to describe how people form impressions of a score that is described along a bounded scale. According to the model, people spontaneously categorize a score as high or low. Furthermore, they compare the numerical discrepancy between the score and the endpoint of the scale to which it is closer, if they are not confident of their categorization, and use implications of this comparison as a basis for judgment. As a result, their evaluation of the score is less extreme when the range of numbers along the scale is large (e.g., from 0 to 100) than when it is small (from 0 to 10). Six experiments support this two-process model and demonstrate its generalizability. Specifically, the magnitude of numbers composing the scale has less impact on judgments (a) when the score being evaluated is extreme, (b) when individuals are unmotivated to engage in endpoint comparison processes (i.e., they are low in need for cognition), and (c) when they are unable to do so (i.e., they are under cognitive load). Moreover, the endpoint to which individuals compare the score can depend on their regulatory focus. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

A Comparison of Real-Time and Endpoint Cell Viability Assays for Improved Synthetic Lethal Drug Validation.

Science.gov (United States)

Single, Andrew; Beetham, Henry; Telford, Bryony J; Guilford, Parry; Chen, Augustine

2015-12-01

Cell viability assays fulfill a central role in drug discovery studies. It is therefore important to understand the advantages and disadvantages of the wide variety of available assay methodologies. In this study, we compared the performance of three endpoint assays (resazurin reduction, CellTiter-Glo, and nuclei enumeration) and two real-time systems (IncuCyte and xCELLigence). Of the endpoint approaches, both the resazurin reduction and CellTiter-Glo assays showed higher cell viabilities when compared directly to stained nuclei counts. The IncuCyte and xCELLigence real-time systems were comparable, and both were particularly effective at tracking the effects of drug treatment on cell proliferation at sub-confluent growth. However, the real-time systems failed to evaluate contrasting cell densities between drug-treated and control-treated cells at full growth confluency. Here, we showed that using real-time systems in combination with endpoint assays alleviates the disadvantages posed by each approach alone, providing a more effective means to evaluate drug toxicity in monolayer cell cultures. Such approaches were shown to be effective in elucidating the toxicity of synthetic lethal drugs in an isogenic pair of MCF10A breast cell lines. © 2015 Society for Laboratory Automation and Screening.

Comparing and combining biomarkers as principle surrogates for time-to-event clinical endpoints.

Science.gov (United States)

Gabriel, Erin E; Sachs, Michael C; Gilbert, Peter B

2015-02-10

Principal surrogate endpoints are useful as targets for phase I and II trials. In many recent trials, multiple post-randomization biomarkers are measured. However, few statistical methods exist for comparison of or combination of biomarkers as principal surrogates, and none of these methods to our knowledge utilize time-to-event clinical endpoint information. We propose a Weibull model extension of the semi-parametric estimated maximum likelihood method that allows for the inclusion of multiple biomarkers in the same risk model as multivariate candidate principal surrogates. We propose several methods for comparing candidate principal surrogates and evaluating multivariate principal surrogates. These include the time-dependent and surrogate-dependent true and false positive fraction, the time-dependent and the integrated standardized total gain, and the cumulative distribution function of the risk difference. We illustrate the operating characteristics of our proposed methods in simulations and outline how these statistics can be used to evaluate and compare candidate principal surrogates. We use these methods to investigate candidate surrogates in the Diabetes Control and Complications Trial. Copyright © 2014 John Wiley & Sons, Ltd.

76 FR 51993 - Draft Guidance for Industry on Standards for Clinical Trial Imaging Endpoints; Availability

Science.gov (United States)

2011-08-19

... clinical trials of therapeutic drugs and biological products. The draft guidance describes standards... important imaging endpoint is used in a clinical trial of a therapeutic drug or biological product... Services to the Chairman of [[Page 51994

Assessment of sublethal endpoints after chronic exposure of the nematode Caenorhabditis elegans to palladium, platinum and rhodium.

Science.gov (United States)

Schertzinger, Gerhard; Zimmermann, Sonja; Grabner, Daniel; Sures, Bernd

2017-11-01

The aim of this study was to investigate chronic effects of the platinum-group elements (PGE) palladium (Pd), platinum (Pt) and rhodium (Rh) on the nematode Caenorhabditis elegans. Aquatic toxicity testing was carried out according to ISO 10872 by determining 96 h EC 50 values for sublethal endpoints, including growth, fertility and reproduction. Single PGE standard solutions were used as metal source. Based on the EC 50 values for Pt, reproduction (96 h EC 50  = 497 μg/L) was the most sensitive endpoint followed by fertility (96 h EC 50  = 726 μg/L) and growth (96 h EC 50  = 808 μg/L). For Pd, no precise EC 50 values could be calculated due to bell-shaped concentration response curves, but the 96 h EC 50 for reproduction ranged between 10 and 100 μg/L. Pd and Pt had effects on all endpoints. With raising element concentrations reproduction was inhibited first. At a certain concentration, fertility was also affected, which in turn had an additional effect on reproduction. Growth inhibition can also lead to a loss of fertility if the worms do not reach an appropriate body size to become fertile. Rhodium showed no inhibition of any endpoint between concentrations of 100 to 10,000 μg Rh/L. The results of this study allow the following order of PGE with respect to decreasing toxicity to C. elegans: Pd > Pt » Rh. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relationship between breast sound speed and mammographic percent density

Science.gov (United States)

Sak, Mark; Duric, Nebojsa; Boyd, Norman; Littrup, Peter; Myc, Lukasz; Faiz, Muhammad; Li, Cuiping; Bey-Knight, Lisa

2011-03-01

Despite some shortcomings, mammography is currently the standard of care for breast cancer screening and diagnosis. However, breast ultrasound tomography is a rapidly developing imaging modality that has the potential to overcome the drawbacks of mammography. It is known that women with high breast densities have a greater risk of developing breast cancer. Measuring breast density is accomplished through the use of mammographic percent density, defined as the ratio of fibroglandular to total breast area. Using an ultrasound tomography (UST) prototype, we created sound speed images of the patient's breast, motivated by the fact that sound speed in a tissue is proportional to the density of the tissue. The purpose of this work is to compare the acoustic performance of the UST system with the measurement of mammographic percent density. A cohort of 251 patients was studied using both imaging modalities and the results suggest that the volume averaged breast sound speed is significantly related to mammographic percent density. The Spearman correlation coefficient was found to be 0.73 for the 175 film mammograms and 0.69 for the 76 digital mammograms obtained. Since sound speed measurements do not require ionizing radiation or physical compression, they have the potential to form the basis of a safe, more accurate surrogate marker of breast density.

Statement to the fifty-fifth session of the United Nations General Assembly

International Nuclear Information System (INIS)

ElBaradei, M.

2000-01-01

In his statement to the fifty-fifth session of the United Nations General Assembly, the Director General of the IAEA briefly presented the three fundamental functions of the IAEA, namely: its role as a catalyst for the development and transfer of peaceful nuclear technologies, the efforts to prevent the proliferation of nuclear weapons and move towards nuclear disarmament, and the work to build and maintain a global nuclear safety regime

Experience with high percent step load decrease from full power in NPP Krsko

International Nuclear Information System (INIS)

Vukovic, V.

2000-01-01

The control system of NPP Kriko, is designed to automatically control the reactor in the power range between 15 and 100 percent of rated power for the following designed transients; - 10 percent step change in load; 5 percent per minute loading and unloading; step full load decrease with the aid of automatically initiated and controlled steam dump. Because station operation below 15 percent of rated power is designed for a period of time during startup or standby conditions, automatic control below 15 percent is not provided. The steam dump accomplishes the following functional tasks: it permits the nuclear plants to accept a sudden 95 percent loss of load without incurring reactor trip; it removes stored energy and residual heat following a reactor trip and brings the plant to equilibrium no-load conditions without actuation of the steam generator safety valves; it permits control of the steam generator pressure at no-load conditions and permits a manually controlled cooldown of the plant. The first two functional tasks are controlled by Tavg. The third is controlled by steam pressure. Interlocks minimise any possibility of an inadvertent actuation of steam dump system. This paper discusses relationships between designed (described) characteristics of plant and the data which are obtained during startup and/or first ten years of operation. (author)

School Designed To Use 80 Percent Less Energy

Science.gov (United States)

American School and University, 1975

1975-01-01

The new Terraset Elementary School in Reston, Virginia, uses earth as a cover for the roof area and for about 80 percent of the wall area. A heat recovery system will be used with solar collectors playing a primary role in heating and cooling. (Author/MLF)

Fifty years with nuclear fission

International Nuclear Information System (INIS)

Behrens, J.W.; Carlson, A.D.

1989-01-01

The news of the discovery of nuclear fission, by Otto Hahn and Fritz Strassmann in Germany, was brought to the United States by Niels Bohr in January 1939. Since its discovery, the United States, and the world for that matter, has never been the same. It therefore seemed appropriate to acknowledge the fifieth anniversary of its discovery by holding a topical meeting entitled, ''Fifty Years with Nuclear Fission,'' in the United States during the year 1989. The objective of the meeting was to bring together pioneers of the nuclear industry and other scientists and engineers to report on reminiscences of the past and on the more recent development in fission science and technology. The conference highlighted the early pioneers of the nuclear industry by dedicated a full day (April 26), consisting of two plenary sessions, at the National Academy of Sciences (NAS) in Washington, DC. More recent developments in fission science and technology in addition to historical reflections were topics for two fully days of sessions (April 27 and 28) at the main site of the NIST in Gaithersburg, Maryland. The wide range of topics covered in this Volume 1 by this topical meeting included plenary invited, and contributed sessions entitled: Preclude to the First Chain Reaction -- 1932 to 1942; Early Fission Research -- Nuclear Structure and Spontaneous Fission; 50 Years of Fission, Science, and Technology; Nuclear Reactors, Secure Energy for the Future; Reactors 1; Fission Science 1; Safeguards and Space Applications; Fission Data; Nuclear Fission -- Its Various Aspects; Theory and Experiments in Support of Theory; Reactors and Safeguards; and General Research, Instrumentation, and By-Product. The individual papers have been cataloged separately

Is Overall Mortality the Right Composite Endpoint in Clinical Trials of Acute Respiratory Distress Syndrome?

Science.gov (United States)

Villar, Jesús; Martínez, Domingo; Mosteiro, Fernando; Ambrós, Alfonso; Añón, José M; Ferrando, Carlos; Soler, Juan A; Montiel, Raquel; Vidal, Anxela; Conesa-Cayuela, Luís A; Blanco, Jesús; Arrojo, Regina; Solano, Rosario; Capilla, Lucía; Del Campo, Rafael; Civantos, Belén; Fernández, María Mar; Aldecoa, César; Parra, Laura; Gutiérrez, Andrea; Martínez-Jiménez, Chanel; González-Martín, Jesús M; Fernández, Rosa L; Kacmarek, Robert M

2018-06-01

Overall mortality in patients with acute respiratory distress syndrome is a composite endpoint because it includes death from multiple causes. In most acute respiratory distress syndrome trials, it is unknown whether reported deaths are due to acute respiratory distress syndrome or the underlying disease, unrelated to the specific intervention tested. We investigated the causes of death after contracting acute respiratory distress syndrome in a large cohort. A secondary analysis from three prospective, multicenter, observational studies. A network of multidisciplinary ICUs. We studied 778 patients with moderate-to-severe acute respiratory distress syndrome treated with lung-protective ventilation. None. We examined death in the ICU from individual causes. Overall ICU mortality was 38.8% (95% CI, 35.4-42.3). Causes of acute respiratory distress syndrome modified the risk of death. Twenty-three percent of deaths occurred from refractory hypoxemia due to nonresolving acute respiratory distress syndrome. Most patients died from causes unrelated to acute respiratory distress syndrome: 48.7% of nonsurvivors died from multisystem organ failure, and cancer or brain injury was involved in 37.1% of deaths. When quantifying the true burden of acute respiratory distress syndrome outcome, we identified 506 patients (65.0%) with one or more exclusion criteria for enrollment into current interventional trials. Overall ICU mortality of the "trial cohort" (21.3%) was markedly lower than the parent cohort (relative risk, 0.55; 95% CI, 0.43-0.70; p respiratory distress syndrome patients are not directly related to lung damage but to extrapulmonary multisystem organ failure. It would be challenging to prove that specific lung-directed therapies have an effect on overall survival.

Measuring titratable alkalinity by single versus double endpoint titration: An evaluation in two cyprinodont species and implications for characterizing net H+ flux in aquatic organisms.

Science.gov (United States)

Brix, Kevin V; Wood, Chris M; Grosell, Martin

2013-01-01

In this study, Na(+) uptake and acid-base balance in the euryhaline pupfish Cyprinodon variegatus variegatus were characterized when fish were exposed to pH 4.5 freshwater (7mM Na(+)). Similar to the related cyprinodont, Fundulus heteroclitus, Na(+) uptake was significantly inhibited when exposed to low pH water. However, it initially appeared that C. v. variegatus increased apparent net acid excretion at low pH relative to circumneutral pH. This result is opposite to previous observations for F. heteroclitus under similar conditions where fish were observed to switch from apparent net H(+) excretion at circumneutral pH to apparent net H(+) uptake at low pH. Further investigation revealed disparate observations between these studies were the result of using double endpoint titrations to measure titratable alkalinity fluxes in the current study, while the earlier study utilized single endpoint titrations to measure these fluxes (i.e.,. Cyprinodon acid-base transport is qualitatively similar to Fundulus when characterized using single endpoint titrations). This led to a comparative investigation of these two methods. We hypothesized that either the single endpoint methodology was being influenced by a change in the buffer capacity of the water (e.g., mucus being released by the fish) at low pH, or the double endpoint methodology was not properly accounting for ammonia flux by the fish. A series of follow-up experiments indicated that buffer capacity of the water did not change significantly, that excretion of protein (a surrogate for mucus) was actually reduced at low pH, and that the double endpoint methodology does not properly account for NH(3) excretion by fish under low pH conditions. As a result, it overestimates net H(+) excretion during low pH exposure. After applying the maximum possible correction for this error (i.e., assuming that all ammonia is excreted as NH(3)), the double endpoint methodology indicates that net H(+) transport was reduced to

Dose and dose rate extrapolation factors for malignant and non-malignant health endpoints after exposure to gamma and neutron radiation

Energy Technology Data Exchange (ETDEWEB)

Tran, Van; Little, Mark P. [National Cancer Institute, Radiation Epidemiology Branch, Rockville, MD (United States)

2017-11-15

Murine experiments were conducted at the JANUS reactor in Argonne National Laboratory from 1970 to 1992 to study the effect of acute and protracted radiation dose from gamma rays and fission neutron whole body exposure. The present study reports the reanalysis of the JANUS data on 36,718 mice, of which 16,973 mice were irradiated with neutrons, 13,638 were irradiated with gamma rays, and 6107 were controls. Mice were mostly Mus musculus, but one experiment used Peromyscus leucopus. For both types of radiation exposure, a Cox proportional hazards model was used, using age as timescale, and stratifying on sex and experiment. The optimal model was one with linear and quadratic terms in cumulative lagged dose, with adjustments to both linear and quadratic dose terms for low-dose rate irradiation (<5 mGy/h) and with adjustments to the dose for age at exposure and sex. After gamma ray exposure there is significant non-linearity (generally with upward curvature) for all tumours, lymphoreticular, respiratory, connective tissue and gastrointestinal tumours, also for all non-tumour, other non-tumour, non-malignant pulmonary and non-malignant renal diseases (p < 0.001). Associated with this the low-dose extrapolation factor, measuring the overestimation in low-dose risk resulting from linear extrapolation is significantly elevated for lymphoreticular tumours 1.16 (95% CI 1.06, 1.31), elevated also for a number of non-malignant endpoints, specifically all non-tumour diseases, 1.63 (95% CI 1.43, 2.00), non-malignant pulmonary disease, 1.70 (95% CI 1.17, 2.76) and other non-tumour diseases, 1.47 (95% CI 1.29, 1.82). However, for a rather larger group of malignant endpoints the low-dose extrapolation factor is significantly less than 1 (implying downward curvature), with central estimates generally ranging from 0.2 to 0.8, in particular for tumours of the respiratory system, vasculature, ovary, kidney/urinary bladder and testis. For neutron exposure most endpoints, malignant and

National Land Cover Database (NLCD) Percent Developed Imperviousness Collection

Data.gov (United States)

U.S. Geological Survey, Department of the Interior — The National Land Cover Database (NLCD) Percent Developed Imperviousness Collection is produced through a cooperative project conducted by the Multi-Resolution Land...

Predicting treatment effect from surrogate endpoints and historical trials: an extrapolation involving probabilities of a binary outcome or survival to a specific time.

Science.gov (United States)

Baker, Stuart G; Sargent, Daniel J; Buyse, Marc; Burzykowski, Tomasz

2012-03-01

Using multiple historical trials with surrogate and true endpoints, we consider various models to predict the effect of treatment on a true endpoint in a target trial in which only a surrogate endpoint is observed. This predicted result is computed using (1) a prediction model (mixture, linear, or principal stratification) estimated from historical trials and the surrogate endpoint of the target trial and (2) a random extrapolation error estimated from successively leaving out each trial among the historical trials. The method applies to either binary outcomes or survival to a particular time that is computed from censored survival data. We compute a 95% confidence interval for the predicted result and validate its coverage using simulation. To summarize the additional uncertainty from using a predicted instead of true result for the estimated treatment effect, we compute its multiplier of standard error. Software is available for download. © 2011, The International Biometric Society No claim to original US government works.

7 CFR 402.4 - Catastrophic Risk Protection Endorsement Provisions.

Science.gov (United States)

2010-01-01

..., adoption or marriage, are considered to be family members) and others who live under the same roof. Limited... equal to fifty percent (50%) of your approved yield indemnified at fifty-five percent (55%) of the... will pay a premium subsidy equal to the premium established for the coverage provided under this...

Õige valu õiges kohas. Lahinguväljal näeme! Noor veri vemmeldab : Slide-Fifty

Index Scriptorium Estoniae

2006-01-01

9.-10. juunil Järvakandis toimuval festivalil Rabarock esinevatest ansamblitest: The Skreppers, Metsatöll, Slide Fifty (vt. www. rabarock. ee, www.skreppers.com, www.metsatoll.ee, www.slidefifty.com)

Fifty Cases of Parkinson's Disease Treated by Acupuncture Combined with Madopar

Institute of Scientific and Technical Information of China (English)

REN Xiao-ming

2008-01-01

objective;To search for an effective therapy for trealing motor disorder due to Parkinson's disease(PD).Methods;Fifty cases in a treatrnent group were treated by acupuncture combined with madopar,and 30 cases in a control group treated by madopar only.Results;A total effective rate of 92%was achieved with obvious alleviation of motor disorder in the treatment group,which was significantly higher than that in the control group(P＜0.05).Conclusion;Acupuncture can enhance therapeutic effects of western medicine and lessen the dose of the medicine needed.

A covariant open bosonic string field theory including the endpoint and middlepoint interaction

International Nuclear Information System (INIS)

Liu, B.G.; Northwest Univ., Xian; Chen, Y.X.

1988-01-01

Extending the usual endpoint and midpoint interactions, we introduce numerous kinds of interactions, labelled by a parameter λ and obtain a non-commutative and associative string field algebra by adding up all interactions. With this algebra we develop a covariant open bosonic string field theory, which reduces to Witten's open bosonic string field theory under a special string length choice. (orig.)

Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study.

Directory of Open Access Journals (Sweden)

Laura K Erdman

Full Text Available Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance.We studied children with WHO-defined clinical pneumonia (n = 155 within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30, other infiltrates (n = 31, or normal chest x-ray (n = 94. Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis.Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8, 80.8% specificity (72.6-87.1, positive likelihood ratio 4.9 (3.4-7.1, negative likelihood ratio 0

Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study

Science.gov (United States)

Erdman, Laura K.; D’Acremont, Valérie; Hayford, Kyla; Kilowoko, Mary; Kyungu, Esther; Hongoa, Philipina; Alamo, Leonor; Streiner, David L.; Genton, Blaise; Kain, Kevin C.

2015-01-01

Background Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. Methods We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. Results Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5–98.8), 80.8% specificity (72.6–87.1), positive likelihood ratio 4.9 (3.4–7

Experience in thyroid scintigraphy with Ethiopian patients

International Nuclear Information System (INIS)

Demena, Solomon

1993-01-01

One thousand and thirty seven thyroid scintigraphy examinations done in the Nuclear Medicine Unit of Tikur Anbesma Hospital, Addis Abeba, Ethiopia between December 1984 and September 1989 were analyzed to assess their diagnostic value. Thirty one percent of the referrals were to investigate clinically detectable solitary nodules, and of these fifty-six percent had ''cold'' nodules and twenty-three percent ''hot'' nodules. Fifty-five percent of the referrals for evaluation of goitre were for multi nodular goitres and twelve percent for diffuse. Thirteen of fifty-three cases with suspected ectopic thyroid tissue were positive. Little useful information was obtained in the evaluation of goitre. It is concluded that thyroid scintigraphy was an unnecessary investigation in the evaluation of goitres in euthyroid patients. Its primary role was in the investigation of the solitary nodule, ectopic thyroid tissue and the retresternal goitre. Therefore, only selected patients should be investigated with thyroid scintigraphy

Fifty years of fuzzy logic and its applications

CERN Document Server

Rishe, Naphtali; Kandel, Abraham

2015-01-01

This book presents a comprehensive report on the evolution of Fuzzy Logic since its formulation in Lotfi Zadeh’s seminal paper on “fuzzy sets,” published in 1965. In addition, it features a stimulating sampling from the broad field of research and development inspired by Zadeh’s paper. The chapters, written by pioneers and prominent scholars in the field, show how fuzzy sets have been successfully applied to artificial intelligence, control theory, inference, and reasoning. The book also reports on theoretical issues; features recent applications of Fuzzy Logic in the fields of neural networks, clustering, data mining, and software testing; and highlights an important paradigm shift caused by Fuzzy Logic in the area of uncertainty management. Conceived by the editors as an academic celebration of the fifty years’ anniversary of the 1965 paper, this work is a must-have for students and researchers willing to get an inspiring picture of the potentialities, limitations, achievements and accomplishments...

Diabetes mellitus during pregnancy: a study of fifty cases

International Nuclear Information System (INIS)

Randhawa, M. S.; Moin, S.; Shoaib, F.

2003-01-01

To review and critically evaluated the incidence, epidemiology, clinical pattern, diagnosis, management, complications and outcome of diabetes mellitus during pregnancy in hospital based study. Results: Total number of women delivered were 11271. Fifty cases of diabetes mellitus during pregnancy were studied. Mostly the patients were more than 30 years of age, multiparous ladies with gestational diabetes in 80% of cases, Type-II diabetes in 16% and only in 4% Type-I diabetes was reported. Insulin was required in 40% of patients. Eight women out of 50 had spontaneous miscarriage, 5 underwent preterm delivery while 36 reached term with one intrauterine death. Total number of babies delivered alive were 41. There was one stillbirth and 3 neonatal deaths. Conclusion: Management of diabetes mellitus in pregnancy involves teamwork of obstetricians, physicians and neonatologists. (author)

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative

DEFF Research Database (Denmark)

Myles, P S; Boney, O; Botti, M

2018-01-01

Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus...

Patient-specific dosimetric endpoints based treatment plan quality control in radiotherapy

International Nuclear Information System (INIS)

Song, Ting; Zhou, Linghong; Staub, David; Chen, Mingli; Lu, Weiguo; Tian, Zhen; Jia, Xun; Li, Yongbao; Jiang, Steve B; Gu, Xuejun

2015-01-01

In intensity modulated radiotherapy (IMRT), the optimal plan for each patient is specific due to unique patient anatomy. To achieve such a plan, patient-specific dosimetric goals reflecting each patient’s unique anatomy should be defined and adopted in the treatment planning procedure for plan quality control. This study is to develop such a personalized treatment plan quality control tool by predicting patient-specific dosimetric endpoints (DEs). The incorporation of patient specific DEs is realized by a multi-OAR geometry-dosimetry model, capable of predicting optimal DEs based on the individual patient’s geometry. The overall quality of a treatment plan is then judged with a numerical treatment plan quality indicator and characterized as optimal or suboptimal. Taking advantage of clinically available prostate volumetric modulated arc therapy (VMAT) treatment plans, we built and evaluated our proposed plan quality control tool. Using our developed tool, six of twenty evaluated plans were identified as sub-optimal plans. After plan re-optimization, these suboptimal plans achieved better OAR dose sparing without sacrificing the PTV coverage, and the dosimetric endpoints of the re-optimized plans agreed well with the model predicted values, which validate the predictability of the proposed tool. In conclusion, the developed tool is able to accurately predict optimally achievable DEs of multiple OARs, identify suboptimal plans, and guide plan optimization. It is a useful tool for achieving patient-specific treatment plan quality control. (paper)

New drugs and patient-centred end-points in old age: setting the wheels in motion.

Science.gov (United States)

Mangoni, Arduino A; Pilotto, Alberto

2016-01-01

Older patients with various degrees of frailty and disability, a key population target of pharmacological interventions in acute and chronic disease states, are virtually neglected in pre-marketing studies assessing the efficacy and safety of investigational drugs. Moreover, aggressively pursuing established therapeutic targets in old age, e.g. blood pressure, serum glucose or cholesterol concentrations, is not necessarily associated with the beneficial effects, and the acceptable safety, reported in younger patient cohorts. Measures of self-reported health and functional status might represent additional, more meaningful, therapeutic end-points in the older population, particularly in patients with significant frailty and relatively short life expectancy, e.g. in the presence of cancer and/or neurodegenerative disease conditions. Strategies enhancing early knowledge about key pharmacological characteristics of investigational drugs targeting older adults are discussed, together with the rationale for incorporating non-traditional, patient-centred, end-points in this ever-increasing group.

Hairy black holes and the endpoint of AdS{sub 4} charged superradiance

Energy Technology Data Exchange (ETDEWEB)

Dias, Óscar J.C.; Masachs, Ramon [STAG research centre and Mathematical Sciences, University of Southampton,Southampton (United Kingdom)

2017-02-24

We construct hairy black hole solutions that merge with the anti-de Sitter (AdS{sub 4}) Reissner-Nordström black hole at the onset of superradiance. These hairy black holes have, for a given mass and charge, higher entropy than the corresponding AdS{sub 4}-Reissner-Nordström black hole. Therefore, they are natural candidates for the endpoint of the charged superradiant instability. On the other hand, hairy black holes never dominate the canonical and grand-canonical ensembles. The zero-horizon radius of the hairy black holes is a soliton (i.e. a boson star under a gauge transformation). We construct our solutions perturbatively, for small mass and charge, so that the properties of hairy black holes can be used to testify and compare with the endpoint of initial value simulations. We further discuss the near-horizon scalar condensation instability which is also present in global AdS{sub 4}-Reissner-Nordström black holes. We highlight the different nature of the near-horizon and superradiant instabilities and that hairy black holes ultimately exist because of the non-linear instability of AdS.

National Land Cover Database (NLCD) Percent Tree Canopy Collection

Data.gov (United States)

U.S. Geological Survey, Department of the Interior — The National Land Cover Database (NLCD) Percent Tree Canopy Collection is a product of the U.S. Forest Service (USFS), and is produced through a cooperative project...

Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)

DEFF Research Database (Denmark)

Parving, Hans-Henrik; Brenner, Barry M; McMurray, John J V

2012-01-01

Patients with type 2 diabetes are at enhanced risk for macro- and microvascular complications. Albuminuria and/or reduced kidney function further enhances the vascular risk. We initiated the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Aliskiren, a novel direct renin...

78 FR 73199 - Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs...

Science.gov (United States)

2013-12-05

... exposure measures is suitable for documenting BE (e.g., transdermal delivery systems and certain rectal and... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-1464] Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted...

A randomized, phase II study of the anti-insulin-like growth factor receptor type 1 (IGF-1R) monoclonal antibody robatumumab (SCH 717454) in patients with advanced colorectal cancer

International Nuclear Information System (INIS)

Lin, Edward H; Lenz, Heinz-Josef; Saleh, Mansoor N; Mackenzie, Mary J; Knost, James A; Pathiraja, Kumudu; Langdon, Ronald B; Yao, Siu-Long; Lu, Brian D

2014-01-01

Overexpression of insulin-like growth factor receptor type 1 (IGF-1R) may promote tumor development and progression in some cancer patients. Our objective was to assess tumor uptake of fluorodeoxyglucose by positron-emission tomography in patients with chemotherapy-refractory colorectal cancer treated with an anti-insulin-like growth factor receptor type 1 (anti-IGF-1R) monoclonal antibody, robatumumab. This was a randomized, open-label study with two periods (P1 and P2). Patients were randomized 3:1 into treatment arms R/R and C/R that received, respectively, one cycle of 0.3 mg/kg robatumumab or one or more cycles of second-line chemotherapy in P1, followed in either case by 10 mg/kg robatumumab biweekly in P2. The primary measure of fluorodeoxyglucose uptake was maximum standardized uptake value (SUV max ). The primary endpoint was the proportion of patients in the R/R arm having a mean percent decrease from baseline in SUV max (DiSUV) greater than 20% 12–14 days postdose in P2. Secondary endpoints included Response Evaluation Criteria in Solid Tumors (RECIST)-defined tumor response and pharmacodynamic measures of target engagement. Among 41 patients who were evaluable for the primary endpoint, seven (17%, 95% CI 7%–32%) had DiSUV greater than 20%. Fifty robatumumab-treated patients were evaluable for RECIST-defined tumor response and six (12%) had stable disease lasting greater than or equal to 7 weeks in P2. Pharmacodynamic endpoints indicated target engagement after dosing with 10 mg/kg robatumumab, but not 0.3 mg/kg. The most frequently reported adverse events were fatigue/asthenia, nausea, anorexia, and gastrointestinal disturbances. In this study, few patients with chemotherapy-refractory colorectal cancer appeared to benefit from treatment with the IGF-1R antagonist robatumumab

Improvement in latent variable indirect response modeling of multiple categorical clinical endpoints: application to modeling of guselkumab treatment effects in psoriatic patients.

Science.gov (United States)

Hu, Chuanpu; Randazzo, Bruce; Sharma, Amarnath; Zhou, Honghui

2017-10-01

Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23. A Phase 2b study was conducted in 238 patients with psoriasis for which disease severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA) scores. A latent variable Type I IDR model was developed to evaluate the therapeutic effect of guselkumab dosing on 75, 90 and 100% improvement of PASI scores from baseline and PGA scores, with placebo effect empirically modeled. The results showed that the joint model is able to describe the observed data better with fewer parameters compared with the common approach of separately modeling the endpoints.

Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

Science.gov (United States)

Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J

2017-05-01

Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

Ranking Tehran’s Stock Exchange Top Fifty Stocks Using Fundamental Indexes and Fuzzy TOPSIS

Directory of Open Access Journals (Sweden)

E. S. Saleh

2017-08-01

Full Text Available Investment through the purchase of securities, constitute an important part of countries economic exchange. Therefore, making decisions about investing in a particular stock has become one of the most controversial areas of economic and financial research and various institutions have began to rank companies stock and determine priorities of stock purchase to investment. The current research, with the determination of important required indexes for companies ranking based on their shares value on the Tehran stock exchange, can greatly help to the accurate ranking of fifty premier listed companies. Initial ranking indicators are extracted and then a decision-making group (exchange experts with the use of the Delphi method and also non-parametric statistic methods, determines the final indexes. Then, by using Fuzzy ANP, weight criteria are obtained with taking into account their interaction with each other. Finally, using fuzzy TOPSIS and information extraction about the premier fifty listed companies of Tehran stock exchange in 2014 are ranked with the software "Rahavard Novin”. Sensitivity analysis to criteria weight and relevant analysis presentation was conducted at the end of the study procedures.

Modeling percent tree canopy cover: a pilot study

Science.gov (United States)

John W. Coulston; Gretchen G. Moisen; Barry T. Wilson; Mark V. Finco; Warren B. Cohen; C. Kenneth Brewer

2012-01-01

Tree canopy cover is a fundamental component of the landscape, and the amount of cover influences fire behavior, air pollution mitigation, and carbon storage. As such, efforts to empirically model percent tree canopy cover across the United States are a critical area of research. The 2001 national-scale canopy cover modeling and mapping effort was completed in 2006,...

Women in Management - A Movement from the Fifties to the New Millenium

OpenAIRE

Parikh Indira J; Engineer Mahrukh

2002-01-01

"Women in Management - A Movement from the Fifties to the New Millennium", views the evolution and changes that have occurred from the 1950s onwards and looks at new opportunities for women managers in the new millennium. Women in Management are coming of age. The transformation of the Indian woman from an enigmatic figure, covered in meters of fabric, to todays educated, successful and accomplished professional has not been without great personal sacrifices. These are women who have broken t...

The Henderson Question? The Melbourne Institute and fifty years of welfare policy

OpenAIRE

R. G. Gregory

2013-01-01

We discuss selected research contributions of the Melbourne Institute of Applied Economics and Social Research, to fifty years of welfare policy for those of work force age and focus particularly on the policy focus of R. F. Henderson, the inaugural director. Following the spirit of his 1960s poverty research, government, in the mid-1970s, doubled unemployment allowances in real terms and increased pensions by approximately forty per cent. Both income support payments were to be indexed by av...

The Impact of Multiple Endpoint Dependency on "Q" and "I"[superscript 2] in Meta-Analysis

Science.gov (United States)

Thompson, Christopher Glen; Becker, Betsy Jane

2014-01-01

A common assumption in meta-analysis is that effect sizes are independent. When correlated effect sizes are analyzed using traditional univariate techniques, this assumption is violated. This research assesses the impact of dependence arising from treatment-control studies with multiple endpoints on homogeneity measures "Q" and…

Nuclear magnetic resonance evaluation of fifty children with cancer

International Nuclear Information System (INIS)

Cohen, M.D.; Klatte, E.C.; Smith, J.A.; Carr, B.E.; Martin-Simmerman, P.

1985-01-01

Fifty children with cancer have been studied by MR. The patients studied include ten with lymphoma, nine with neuroblastoma, five with rhabdomyosarcoma, six with leukemia, five with Ewings sarcoma, four with Wilms tumor and several with other miscellaneous tumors. The results of scanning show that MR is well tolerated by children. Primary tumor has been identified in every case. Metastases have been identified in many patients. MR has proved helpful in identifying the organ of origin of a tumor. Because of excellent vessel visualization it is helpful in planning surgical resection of a tumor. In addition, in a number of patients MR has proved helpful in monitoring the response of tumor to nonsurgical therapy. With continued improvement in image quality it is believed that MR has a major role to play in pediatric tumor imaging [fr

CRED Cumulative Map of Percent Scleractinian Coral Cover at Sarigan

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Saipan

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Tutuila

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Anatahan

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Alamagan

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Agrihan

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Pagan

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Asuncion

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Aguijan

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

Completion of the first approach to critical for the seven percent critical experiment

International Nuclear Information System (INIS)

Barber, A. D.; Harms, G. A.

2009-01-01

The first approach-to-critical experiment in the Seven Percent Critical Experiment series was recently completed at Sandia. This experiment is part of the Seven Percent Critical Experiment which will provide new critical and reactor physics benchmarks for fuel enrichments greater than five weight percent. The inverse multiplication method was used to determine the state of the system during the course of the experiment. Using the inverse multiplication method, it was determined that the critical experiment went slightly supercritical with 1148 fuel elements in the fuel array. The experiment is described and the results of the experiment are presented. (authors)

WHK Student Internship Enrollment, Mentor Participation Up More than 50 Percent | Poster

Science.gov (United States)

By Nancy Parrish, Staff Writer The Werner H. Kirsten Student Internship Program (WHK SIP) has enrolled the largest class ever for the 2013–2014 academic year, with 66 students and 50 mentors. This enrollment reflects a 53 percent increase in students and a 56 percent increase in mentors, compared to 2012–2013 (43 students and 32 mentors), according to Julie Hartman, WHK SIP

Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.

Directory of Open Access Journals (Sweden)

Amory Koch

Full Text Available Acute radiation sickness (ARS following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS developed at the Veterinary Sciences Department (VSD of the Armed Forces Radiobiology Research Institute (AFRRI to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male TBI model (6-14 Gy, 60Co γ-rays at 0.6 Gy min-1, which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated, 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors. In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2-4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies.

An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay

International Nuclear Information System (INIS)

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

2005-01-01

The original local lymph node assay (LLNA) is based on the use of radioactive labelling to measure cell proliferation. Other endpoints for the assessment of proliferation are also authorized by the OECD Guideline 429 provided there is appropriate scientific support, including full citations and description of the methodology (OECD, 2002. OECD Guideline for the Testing of Chemicals; Skin Sensitization: Local Lymph Node Assay, Guideline 429. Paris, adopted 24th April 2002.). Here, we describe the outcome of the second round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in nine laboratories in Europe. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products (Swissmedic) in Bern. Ear-draining lymph node (LN) weight and cell counts were used to assess LN cell proliferation instead of [3H]TdR incorporation. In addition, the acute inflammatory skin reaction was measured by ear weight determination of circular biopsies of the ears to identify skin irritation properties of the test items. The statistical analysis was performed in the department of statistics at the university of Bern. Similar to the EC 3 values defined for the radioactive method, threshold values were calculated for the endpoints measured in this modification of the LLNA. It was concluded that all parameters measured have to be taken into consideration for the categorisation of compounds due to their sensitising potencies. Therefore, an assessment scheme has been developed which turned out to be of great importance to consistently assess sensitisation versus irritancy based on the data of the different parameters. In contrast to the radioactive method, irritants have been picked up by all the laboratories applying this assessment scheme

The Proton Synchrotron, going strong at fifty years

CERN Multimedia

Django Manglunki

It was on the evening of 24 November 1959 that an incredulous Hildred Blewett, on detachment to CERN from the Brookhaven laboratory, exclaimed “Yes! We’re through transition!” The first beam of ten billion protons had not only broken through the 5.2 GeV barrier but gone on all the way to 24 GeV, the machine’s top energy at that time.   An operational screenshot from the PS, taken on its 50th anniversary. The three white peaks depict different phases (cycles) of the PS’s operation. In the first and third cycle, the PS is producing a very low-intensity beam for LHC commissioning. In the second cycle, protons are being spilled out for use in the East Area. Fifty years ago the PS, the first strong-focusing proton synchrotron using alternating gradient technology, first began to circulate beams at an unprecedented level of energy. Over the years, a complex of linear and circular accelerators and storage rings grew up around the PS. In the mid-1990s ...

Adaptive endpoint detection of seismic signal based on auto-correlated function

International Nuclear Information System (INIS)

Fan Wanchun; Shi Ren

2001-01-01

Based on the analysis of auto-correlation function, the notion of the distance between auto-correlation function was quoted, and the characterization of the noise and the signal with noise were discussed by using the distance. Then, the method of auto- adaptable endpoint detection of seismic signal based on auto-correlated similarity was summed up. The steps of implementation and determining of the thresholds were presented in detail. The experimental results that were compared with the methods based on artificial detecting show that this method has higher sensitivity even in a low signal with noise ratio circumstance

Prediction of Tungsten CMP Pad Life Using Blanket Removal Rate Data and Endpoint Data Obtained from Process Temperature and Carrier Motor Current Measurments

International Nuclear Information System (INIS)

Hetherington, Dale L.; Stein, David J.

1999-01-01

Several techniques to predict pad failure during tungsten CMP were investigated for a specific consumable set. These techniques include blanket polish rate measurements and metrics derived from two endpoint detection schemes. Blanket polish rate decreased significantly near pad failure. Metrics from the thermal endpoint technique included change in peak temperature, change in the time to reach peak temperature, and the change in the slope of the temperature trace just prior to peak temperature all as a function of pad life. Average carrier motor current before endpoint was also investigated. Changes in these metrics were observed however these changes, excluding time to peak process temperature, were either not consistent between pads or too noisy to be reliable predictors of pad failure

Effects of un-ionized ammonia on histological, endocrine, and whole organism endpoints in slimy sculpin (Cottus cognatus)

Energy Technology Data Exchange (ETDEWEB)

Spencer, P. [Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, S7N 5B3 (Canada)], E-mail: paula.spencer@usask.ca; Pollock, R.; Dube, M. [Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, S7N 5B3 (Canada)

2008-12-11

Ammonia is known to be an important toxicant in aquatic environments. Although ammonia toxicity has been well studied in many fish species, effects of chronic exposure on slimy sculpin (Cottus cognatus), a critical biomonitoring species for northern aquatic habitats, are not well known. Further, with increasing mining development in Canada's north, this information is critical to better predict potential effects of mine effluent discharges on northern fish species. Slimy sculpin were exposed to six concentrations of un-ionized ammonia (NH{sub 3}) relevant to concentrations found in northern mining effluents: control (0 ppm), 0.278 ppm, 0.556 ppm, 0.834 ppm, 1.112 ppm, and 1.668 ppm. An LC{sub 50} of 1.529 ppm was calculated from mortality data. Histopathological examination of gills indicated significant tissue damage, measured as lamellar fusion and epithelial lifting, at 0.834 ppm, 1.112 ppm, and 1.668 ppm. Using gill endpoints, NOEC and LOEC were calculated as 0.556 ppm and 0.834 ppm, respectively. An EC{sub 50} of 0.775 ppm was determined for lamellar fusion and an EC{sub 50} of 0.842 ppm for epithelial lifting. Hemorrhage of gills was present in mortalities, which occurred at 1.668 ppm of un-ionized ammonia. A significant decrease in liver somatic index (LSI) was seen in both male and female fish at 0.834 ppm and 1.112 ppm, respectively. Gonadosomatic index (GSI) in female fish significantly increased at 1.668 ppm un-ionized ammonia with an associated significant increase in total wholebody testosterone concentrations. GSI in male fish also significantly increased at 1.668 ppm but no differences were seen in testosterone concentrations. No significant differences were seen in gonad histopathological assessments or condition factor. Gill histopathology endpoints may be a more sensitive indicator for detecting effects in slimy sculpin exposed to ammonia than traditional chronic endpoints. Results from this study indicate that ammonia concentrations commonly

A comparison of methods of determining the 100 percent survival of preserved red cells

International Nuclear Information System (INIS)

Valeri, C.R.; Pivacek, L.E.; Ouellet, R.; Gray, A.

1984-01-01

Studies were done to compare three methods to determine the 100 percent survival value from which to estimate the 24-hour posttransfusion survival of preserved red cells. The following methods using small aliquots of 51 Cr-labeled autologous preserved red cells were evaluated: First, the 125 I-albumin method, which is an indirect measurement of the recipient's red cell volume derived from the plasma volume measured using 125 I-labeled albumin and the total body hematocrit. Second, the body surface area method (BSA) in which the recipient's red cell volume is derived from a body surface area nomogram. Third, an extrapolation method, which extrapolates to zero time the radioactivity associated with the red cells in the recipient's circulation from 10 to 20 or 15 to 30 minutes after transfusion. The three methods gave similar results in all studies in which less than 20 percent of the transfused red cells were nonviable (24-hour posttransfusion survival values of between 80-100%), but not when more than 20 percent of the red cells were nonviable. When 21 to 35 percent of the transfused red cells were nonviable (24-hour posttransfusion survivals of 65 to 79%), values with the 125 I-albumin method and the body surface area method were about 5 percent lower (p less than 0.001) than values with the extrapolation method. When greater than 35 percent of the red cells were nonviable (24-hour posttransfusion survival values of less than 65%), values with the 125 I-albumin method and the body surface area method were about 10 percent lower (p less than 0.001) than those obtained by the extrapolation method

Chloride and sulphate toxicity to Hydropsyche exocellata (Trichoptera, Hydropsychidae): Exploring intraspecific variation and sub-lethal endpoints

Energy Technology Data Exchange (ETDEWEB)

Sala, Miquel [Centre Tecnològic Forestal de Catalunya - CTFC, Solsona, Catalunya (Spain); Faria, Melissa [CESAM, Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro (Portugal); Sarasúa, Ignacio [Technische Universität München, Munich, Bayern (Germany); Barata, Carlos [Institute of Environmental Assessment and Water Research (IDAEA-CSIC), Barcelona (Spain); Bonada, Núria [Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Universitat de Barcelona (UB), Diagonal 643, 08028 Barcelona, Catalonia (Spain); Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Institut de Recerca de la Biodiversitat (IRBio), Universitat de Barcelona - UB, Diagonal 643, 08028 Barcelona, Catalonia (Spain); Brucet, Sandra [Aquatic Ecology Group, BETA Tecnio Centre, University of Vic - Central University of Catalonia, Vic, Catalonia (Spain); Catalan Institution for Research and Advanced Studies, ICREA, Barcelona 08010 (Spain); Llenas, Laia; Ponsá, Sergio [Aquatic Ecology Group, BETA Tecnio Centre, University of Vic - Central University of Catalonia, Vic, Catalonia (Spain); Prat, Narcís [Grup de Recerca Freshwater Ecology and Management (FEM), Departament d' Ecologia, Facultat de Biologia, Universitat de Barcelona (UB), Diagonal 643, 08028 Barcelona, Catalonia (Spain); Soares, Amadeu M.V.M. [CESAM, Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro (Portugal); and others

2016-10-01

The rivers and streams of the world are becoming saltier due to human activities. In spite of the potential damage that salt pollution can cause on freshwater ecosystems, this is an issue that is currently poorly managed. Here we explored intraspecific differences in the sensitivity of freshwater fauna to two major ions (Cl{sup −} and SO{sub 4}{sup 2−}) using the net-spinning caddisfly Hydropsyche exocellata Dufour 1841 (Trichoptera, Hydropsychidae) as a model organism. We exposed H. exocellata to saline solutions (reaching a conductivity of 2.5 mS cm{sup −1}) with Cl{sup −}:SO{sub 4}{sup 2−} ratios similar to those occurring in effluents coming from the meat, mining and paper industries, which release dissolved salts to rivers and streams in Spain. We used two different populations, coming from low and high conductivity streams. To assess toxicity, we measured sub-lethal endpoints: locomotion, symmetry of the food-capturing nets and oxidative stress biomarkers. According to biomarkers and net building, the population historically exposed to lower conductivities (B10) showed higher levels of stress than the population historically exposed to higher conductivities (L102). However, the differences between populations were not strong. For example, net symmetry was lower in the B10 than in the L102 only 48 h after treatment was applied, and biomarkers showed a variety of responses, with no discernable pattern. Also, treatment effects were rather weak, i.e. only some endpoints, and in most cases only in the B10 population, showed a significant response to treatment. The lack of consistent differences between populations and treatments could be related to the high salt tolerance of H. exocellata, since both populations were collected from streams with relatively high conductivities. The sub-lethal effects tested in this study can offer an interesting and promising tool to monitor freshwater salinization by combining physiological and behavioural bioindicators

Chloride and sulphate toxicity to Hydropsyche exocellata (Trichoptera, Hydropsychidae): Exploring intraspecific variation and sub-lethal endpoints

International Nuclear Information System (INIS)

Sala, Miquel; Faria, Melissa; Sarasúa, Ignacio; Barata, Carlos; Bonada, Núria; Brucet, Sandra; Llenas, Laia; Ponsá, Sergio; Prat, Narcís; Soares, Amadeu M.V.M.

2016-01-01

The rivers and streams of the world are becoming saltier due to human activities. In spite of the potential damage that salt pollution can cause on freshwater ecosystems, this is an issue that is currently poorly managed. Here we explored intraspecific differences in the sensitivity of freshwater fauna to two major ions (Cl"− and SO_4"2"−) using the net-spinning caddisfly Hydropsyche exocellata Dufour 1841 (Trichoptera, Hydropsychidae) as a model organism. We exposed H. exocellata to saline solutions (reaching a conductivity of 2.5 mS cm"−"1) with Cl"−:SO_4"2"− ratios similar to those occurring in effluents coming from the meat, mining and paper industries, which release dissolved salts to rivers and streams in Spain. We used two different populations, coming from low and high conductivity streams. To assess toxicity, we measured sub-lethal endpoints: locomotion, symmetry of the food-capturing nets and oxidative stress biomarkers. According to biomarkers and net building, the population historically exposed to lower conductivities (B10) showed higher levels of stress than the population historically exposed to higher conductivities (L102). However, the differences between populations were not strong. For example, net symmetry was lower in the B10 than in the L102 only 48 h after treatment was applied, and biomarkers showed a variety of responses, with no discernable pattern. Also, treatment effects were rather weak, i.e. only some endpoints, and in most cases only in the B10 population, showed a significant response to treatment. The lack of consistent differences between populations and treatments could be related to the high salt tolerance of H. exocellata, since both populations were collected from streams with relatively high conductivities. The sub-lethal effects tested in this study can offer an interesting and promising tool to monitor freshwater salinization by combining physiological and behavioural bioindicators. - Highlights: • We assessed Cl

Coulometric Titration of Ethylenediaminetetraacetate (EDTA) with Spectrophotometric Endpoint Detection: An Experiment for the Instrumental Analysis Laboratory

Science.gov (United States)

Williams, Kathryn R.; Young, Vaneica Y.; Killian, Benjamin J.

2011-01-01

Ethylenediaminetetraacetate (EDTA) is commonly used as an anticoagulant in blood-collection procedures. In this experiment for the instrumental analysis laboratory, students determine the quantity of EDTA in commercial collection tubes by coulometric titration with electrolytically generated Cu[superscript 2+]. The endpoint is detected…

Chevy Corvette: Icon Of American Life In The Fifties

Directory of Open Access Journals (Sweden)

Wishnoebroto Wishnoebroto

2007-11-01

Full Text Available Cars not only function simply as a mean of transportation. Like paintings, the design of a car could represent a certain cultural and social phenomenon of a country. The design of Chevrolet (Chevy Corvette is very different compared to its competitors in the 50s. The size, engine, weight, and the materials of this car were chosen based on the assumption that speed and agility is on top of everything. It was not surprising that in the 50s, the year when the first Corvette was designed and launched, The US was involved in a cold war with the Soviets. Arm race and competition to be the first was the major issue and Corvette was the first car that suggests this spirit. This paper tries to show the distinctiveness of Corvette and how it can be used to explain the character of American people in the fifties. 

On weighted hardy inequalities on semiaxis for functions vanishing at the endpoints

Directory of Open Access Journals (Sweden)

Vladimir Stepanov

1997-01-01

Full Text Available We study the weighted Hardy inequalities on the semiaxis of the form ‖Fu‖2≤C‖F(kv‖2  (1 for functions vanishing at the endpoints together with derivatives up to the order k−1. The case k=2 is completely characterized.

Hausdorff dimension of exponential parameter rays and their endpoints

International Nuclear Information System (INIS)

Bailesteanu, Mihai; Balan, Horia Vlad; Schleicher, Dierk

2008-01-01

We investigate the set I of parameters κ for which the singular value of z map e z + κ converges to ∞. The set I consists of uncountably many parameter rays, plus landing points of some of these rays (Förster et al 2008 Proc Am. Math. Soc. 136 at press (Preprint math.DS/0311427)). We show that the parameter rays have Hausdorff dimension 1, which implies (Qiu 1994 Acta Math. Sin. (N.S.) 10 362–8) that the ray endpoints in I alone have dimension 2. Analogous results were known for dynamical planes of exponential maps (Karpińska 1999 C. R. Acad. Sci. Paris Sér. I: Math. 328 1039–44; Schleicher and Zimmer 2003 J. Lond. Math. Soc. 67 380–400); our result shows that this also holds in parameter space

Low dose response analysis through a cytogenetic end-point

International Nuclear Information System (INIS)

Bojtor, I.; Koeteles, G.J.

1998-01-01

The effects of low doses were studied on human lymphocytes of various individuals. The frequency of micronuclei in cytokinesis-blocked cultured lymphocytes was taken as end-point. The probability distribution of radiation-induced increment was statistically proved and identified as to be asymmetric when the blood samples had been irradiated with doses of 0.01-0.05 Gy of X-rays, similarly to that in unirradiated control population. On the contrary, at or above 1 Gy the corresponding normal curve could be accepted only reflecting an approximately symmetrical scatter of the increments about their mean value. It was found that the slope as well as the closeness of correlation of the variables considerably changed when lower and lower dose ranges had been selected. Below approximately 0.2 Gy even an unrelatedness was found betwen the absorbed dose and the increment

Biomarkers of intermediate endpoints in environmental and occupational health

DEFF Research Database (Denmark)

Knudsen, Lisbeth E; Hansen, Ase M

2007-01-01

The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers...... of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal...... health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained...

SU-D-204-01: A Methodology Based On Machine Learning and Quantum Clustering to Predict Lung SBRT Dosimetric Endpoints From Patient Specific Anatomic Features

Energy Technology Data Exchange (ETDEWEB)

Lafata, K; Ren, L; Wu, Q; Kelsey, C; Hong, J; Cai, J; Yin, F [Duke University Medical Center, Durham, NC (United States)

2016-06-15

Purpose: To develop a data-mining methodology based on quantum clustering and machine learning to predict expected dosimetric endpoints for lung SBRT applications based on patient-specific anatomic features. Methods: Ninety-three patients who received lung SBRT at our clinic from 2011–2013 were retrospectively identified. Planning information was acquired for each patient, from which various features were extracted using in-house semi-automatic software. Anatomic features included tumor-to-OAR distances, tumor location, total-lung-volume, GTV and ITV. Dosimetric endpoints were adopted from RTOG-0195 recommendations, and consisted of various OAR-specific partial-volume doses and maximum point-doses. First, PCA analysis and unsupervised quantum-clustering was used to explore the feature-space to identify potentially strong classifiers. Secondly, a multi-class logistic regression algorithm was developed and trained to predict dose-volume endpoints based on patient-specific anatomic features. Classes were defined by discretizing the dose-volume data, and the feature-space was zero-mean normalized. Fitting parameters were determined by minimizing a regularized cost function, and optimization was performed via gradient descent. As a pilot study, the model was tested on two esophageal dosimetric planning endpoints (maximum point-dose, dose-to-5cc), and its generalizability was evaluated with leave-one-out cross-validation. Results: Quantum-Clustering demonstrated a strong separation of feature-space at 15Gy across the first-and-second Principle Components of the data when the dosimetric endpoints were retrospectively identified. Maximum point dose prediction to the esophagus demonstrated a cross-validation accuracy of 87%, and the maximum dose to 5cc demonstrated a respective value of 79%. The largest optimized weighting factor was placed on GTV-to-esophagus distance (a factor of 10 greater than the second largest weighting factor), indicating an intuitively strong

Angiographic core laboratory reproducibility analyses: implications for planning clinical trials using coronary angiography and left ventriculography end-points.

Science.gov (United States)

Steigen, Terje K; Claudio, Cheryl; Abbott, David; Schulzer, Michael; Burton, Jeff; Tymchak, Wayne; Buller, Christopher E; John Mancini, G B

2008-06-01

To assess reproducibility of core laboratory performance and impact on sample size calculations. Little information exists about overall reproducibility of core laboratories in contradistinction to performance of individual technicians. Also, qualitative parameters are being adjudicated increasingly as either primary or secondary end-points. The comparative impact of using diverse indexes on sample sizes has not been previously reported. We compared initial and repeat assessments of five quantitative parameters [e.g., minimum lumen diameter (MLD), ejection fraction (EF), etc.] and six qualitative parameters [e.g., TIMI myocardial perfusion grade (TMPG) or thrombus grade (TTG), etc.], as performed by differing technicians and separated by a year or more. Sample sizes were calculated from these results. TMPG and TTG were also adjudicated by a second core laboratory. MLD and EF were the most reproducible, yielding the smallest sample size calculations, whereas percent diameter stenosis and centerline wall motion require substantially larger trials. Of the qualitative parameters, all except TIMI flow grade gave reproducibility characteristics yielding sample sizes of many 100's of patients. Reproducibility of TMPG and TTG was only moderately good both within and between core laboratories, underscoring an intrinsic difficulty in assessing these. Core laboratories can be shown to provide reproducibility performance that is comparable to performance commonly ascribed to individual technicians. The differences in reproducibility yield huge differences in sample size when comparing quantitative and qualitative parameters. TMPG and TTG are intrinsically difficult to assess and conclusions based on these parameters should arise only from very large trials.

Effects of short- and long-term exposures to copper on lethal and reproductive endpoints of the harpacticoid copepod Tigriopus fulvus.

Science.gov (United States)

Biandolino, Francesca; Parlapiano, Isabella; Faraponova, Olga; Prato, Ermelinda

2018-01-01

The long-term exposure provides a realistic measurement of the effects of toxicants on aquatic organisms. The harpacticoid copepod Tigriopus fulvus has a wide geographical distribution and is considered as an ideal model organism for ecotoxicological studies for its good sensitivity to different toxicants. In this study, acute, sub-chronic and chronic toxicity tests based on lethal and reproductive responses of Tigriopus fulvus to copper were performed. The number of moults during larval development was chosen as an endpoint for sub-chronic test. Sex ratio, inhibitory effect on larval development, hatching time, fecundity, brood number, nauplii/brood, total newborn production, etc, were calculated in the chronic test (28d). Lethal effect of copper to nauplii showed the LC50-48h of 310 ± 72µgCu/L (mean ± sd). It was observed a significant inhibition of larval development at sublethal copper concentrations, after 4 and 7 d. After 4d, the EC50 value obtained for the endpoint in "moult naupliar reduction" was of 55.8 ± 2.5µgCu/L (mean ± sd). The EC50 for the inhibition of naupliar development into copepodite stage, was of 21.7 ± 4.4µgCu/L (mean ± sd), after 7 days. Among the different traits tested, copper did not affect sex ratio and growth, while fecundity and total nauplii production were the most sensitive endpoints. The reproductive endpoints offer the advantage of being detectable at very low pollutant concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.

Infrared skin damage thresholds from 1319-nm continuous-wave laser exposures

Science.gov (United States)

Oliver, Jeffrey W.; Vincelette, Rebecca; Noojin, Gary D.; Clark, Clifton D.; Harbert, Corey A.; Schuster, Kurt J.; Shingledecker, Aurora D.; Kumru, Semih S.; Maughan, Justin; Kitzis, Naomi; Buffington, Gavin D.; Stolarski, David J.; Thomas, Robert J.

2013-12-01

A series of experiments were conducted in vivo using Yucatan miniature pigs (Sus scrofa domestica) to determine thermal damage thresholds to the skin from 1319-nm continuous-wave Nd:YAG laser irradiation. Experiments employed exposure durations of 0.25, 1.0, 2.5, and 10 s and beam diameters of ˜0.6 and 1 cm. Thermal imagery data provided a time-dependent surface temperature response from the laser. A damage endpoint of fifty percent probability of a minimally visible effect was used to determine threshold for damage at 1 and 24 h postexposure. Predicted thermal response and damage thresholds are compared with a numerical model of optical-thermal interaction. Resultant trends with respect to exposure duration and beam diameter are compared with current standardized exposure limits for laser safety. Mathematical modeling agreed well with experimental data, predicting that though laser safety standards are sufficient for exposures <10 s, they may become less safe for very long exposures.

Lethal and sublethal endpoints observed for Artemia exposed to two reference toxicants and an ecotoxicological concern organic compound.

Science.gov (United States)

Manfra, Loredana; Canepa, Sara; Piazza, Veronica; Faimali, Marco

2016-01-01

Swimming speed alteration and mortality assays with the marine crustacean Artemia franciscana were carried out. EC50 and LC50 values after 24-48h exposures were calculated for two reference toxicants, copper sulphate pentahydrate (CuSO4·5H2O) and Sodium Dodecyl Sulphate (SDS), and an ecotoxicological concern organic compound, Diethylene Glycol (DEG). Different end-points have been evaluated, in order to point out their sensitivity levels. The swimming speed alteration (SSA) was compared to mortality values and also to the hatching rate inhibition (literature data). SSA resulted to be more sensitive than the mortality and with a sensitivity comparable to (or even higher than) the hatching rate endpoint. Copyright © 2015 Elsevier Inc. All rights reserved.

L'etat, c'est moi. Fifty years of history and philosophy of evolutionary biology.

Science.gov (United States)

Ruse, Michael

2016-01-01

I reflect on my fifty-year history as a philosopher of biology, showing how it has taken me from rather narrow analytic studies, through the history of ideas, and now on to issues to do with science and religion. I argue that moral concerns were and still are a major motivation behind what I do and write. Copyright: © 2016 by Fabrizio Serra editore, Pisa · Roma.

Age-specific association between percent body fat and pulmonary ...

African Journals Online (AJOL)

This study describes the association between percent body fat and pulmonary function among apparently normal twenty male children tidal volume aged 4 years and twenty male children aged 10 years in Ogbomoso. The mean functional residual capacity of the lung in male children aged 10 years was significantly higher ...

Secondary efficacy endpoints of the pentavalent rotavirus vaccine against gastroenteritis in sub-Saharan Africa.

Science.gov (United States)

Tapia, Milagritos D; Armah, George; Breiman, Robert F; Dallas, Michael J; Lewis, Kristen D C; Sow, Samba O; Rivers, Stephen B; Levine, Myron M; Laserson, Kayla F; Feikin, Daniel R; Victor, John C; Ciarlet, Max; Neuzil, Kathleen M; Steele, A Duncan

2012-04-27

The efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), was evaluated in a double-blind, placebo-controlled, multicenter Phase III clinical trial conducted (April 2007-March 2009) in 3 low-income countries in Africa: Ghana, Kenya, and Mali. In total, 5468 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age; concomitant administration with routine EPI vaccines, including OPV, was allowed. HIV-infected infants were not excluded. The primary endpoint, vaccine efficacy (VE) against severe-rotavirus gastroenteritis (RVGE), as measured by Vesikari scoring system (VSS, score ≥11), from ≥14 days following Dose 3 through a follow-up period of nearly 2 years in the combined 3 African countries, and secondary endpoints by total follow-up period have been previously reported. In this study, we report post hoc subgroup analyses on secondary endpoints of public health importance. VE against RVGE of any severity was 49.2% (95%CI: 29.9, 63.5) through the first year of life and 30.5% (95%CI: 16.7, 42.2) through the complete follow-up period. VE against severe-gastroenteritis of any etiology was 21.5% (95%CI: vaccine-contained G and P types (G1-G4, P1A[8]), (ii) non-vaccine G types (G8, G9, G10), and (iii) non-vaccine P types (P1B[4], P2A[6]) was 34.0% (95%CI:11.2, 51.2), 81.8% (95%CI:16.5, 98.0) and 40.7% (95%CI:8.4, 62.1), respectively. There was a trend towards higher VE with higher disease severity, although in some cases the numbers were small. In African countries with high under-5 mortality rates, PRV significantly reduced RVGE through nearly 2 years of follow-up; more modest reductions were observed against gastroenteritis of any etiology. PRV provides protection against severe-RVGE caused by diverse rotavirus genotypes, including those not contained in the vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

Approving cancer treatments based on endpoints other than overall survival: an analysis of historical data using the PACE Continuous Innovation Indicators™ (CII).

Science.gov (United States)

Brooks, Neon; Campone, Mario; Paddock, Silvia; Shortenhaus, Scott; Grainger, David; Zummo, Jacqueline; Thomas, Samuel; Li, Rose

2017-01-01

There is an active debate about the role that endpoints other than overall survival (OS) should play in the drug approval process. Yet the term 'surrogate endpoint' implies that OS is the only critical metric for regulatory approval of cancer treatments. We systematically analyzed the relationship between U.S. Food and Drug Administration (FDA) approval and publication of OS evidence to understand better the risks and benefits of delaying approval until OS evidence is available. Using the PACE Continuous Innovation Indicators (CII) platform, we analyzed the effects of cancer type, treatment goal, and year of approval on the lag time between FDA approval and publication of first significant OS finding for 53 treatments approved between 1952 and 2016 for 10 cancer types (n = 71 approved indications). Greater than 59% of treatments were approved before significant OS data for the approved indication were published. Of the drugs in the sample, 31% had lags between approval and first published OS evidence of 4 years or longer. The average number of years between approval and first OS evidence varied by cancer type and did not reliably predict the eventual amount of OS evidence accumulated. Striking the right balance between early access and minimizing risk is a central challenge for regulators worldwide. We illustrate that endpoints other than OS have long helped to provide timely access to new medicines, including many current standards of care. We found that many critical drugs are approved many years before OS data are published, and that OS may not be the most appropriate endpoint in some treatment contexts. Our examination of approved treatments without significant OS data suggests contexts where OS may not be the most relevant endpoint and highlights the importance of using a wide variety of fit-for-purpose evidence types in the approval process.

Identification of a novel percent mammographic density locus at 12q24.

Science.gov (United States)

Stevens, Kristen N; Lindstrom, Sara; Scott, Christopher G; Thompson, Deborah; Sellers, Thomas A; Wang, Xianshu; Wang, Alice; Atkinson, Elizabeth; Rider, David N; Eckel-Passow, Jeanette E; Varghese, Jajini S; Audley, Tina; Brown, Judith; Leyland, Jean; Luben, Robert N; Warren, Ruth M L; Loos, Ruth J F; Wareham, Nicholas J; Li, Jingmei; Hall, Per; Liu, Jianjun; Eriksson, Louise; Czene, Kamila; Olson, Janet E; Pankratz, V Shane; Fredericksen, Zachary; Diasio, Robert B; Lee, Adam M; Heit, John A; DeAndrade, Mariza; Goode, Ellen L; Vierkant, Robert A; Cunningham, Julie M; Armasu, Sebastian M; Weinshilboum, Richard; Fridley, Brooke L; Batzler, Anthony; Ingle, James N; Boyd, Norman F; Paterson, Andrew D; Rommens, Johanna; Martin, Lisa J; Hopper, John L; Southey, Melissa C; Stone, Jennifer; Apicella, Carmel; Kraft, Peter; Hankinson, Susan E; Hazra, Aditi; Hunter, David J; Easton, Douglas F; Couch, Fergus J; Tamimi, Rulla M; Vachon, Celine M

2012-07-15

Percent mammographic density adjusted for age and body mass index (BMI) is one of the strongest risk factors for breast cancer and has a heritable component that remains largely unidentified. We performed a three-stage genome-wide association study (GWAS) of percent mammographic density to identify novel genetic loci associated with this trait. In stage 1, we combined three GWASs of percent density comprised of 1241 women from studies at the Mayo Clinic and identified the top 48 loci (99 single nucleotide polymorphisms). We attempted replication of these loci in 7018 women from seven additional studies (stage 2). The meta-analysis of stage 1 and 2 data identified a novel locus, rs1265507 on 12q24, associated with percent density, adjusting for age and BMI (P = 4.43 × 10(-8)). We refined the 12q24 locus with 459 additional variants (stage 3) in a combined analysis of all three stages (n = 10 377) and confirmed that rs1265507 has the strongest association in the 12q24 region (P = 1.03 × 10(-8)). Rs1265507 is located between the genes TBX5 and TBX3, which are members of the phylogenetically conserved T-box gene family and encode transcription factors involved in developmental regulation. Understanding the mechanism underlying this association will provide insight into the genetics of breast tissue composition.

SERIAL PERCENT-FREE PSA IN COMBINATION WITH PSA FOR POPULATION-BASED EARLY DETECTION OF PROSTATE CANCER

Science.gov (United States)

Ankerst, Donna Pauler; Gelfond, Jonathan; Goros, Martin; Herrera, Jesus; Strobl, Andreas; Thompson, Ian M.; Hernandez, Javier; Leach, Robin J.

2016-01-01

PURPOSE To characterize the diagnostic properties of serial percent-free prostate-specific antigen (PSA) in relation to PSA in a multi-ethnic, multi-racial cohort of healthy men. MATERIALS AND METHODS 6,982 percent-free PSA and PSA measures were obtained from participants in a 12 year+ Texas screening study comprising 1625 men who never underwent biopsy, 497 who underwent one or more biopsies negative for prostate cancer, and 61 diagnosed with prostate cancer. Area underneath the receiver-operating-characteristic-curve (AUC) for percent-free PSA, and the proportion of patients with fluctuating values across multiple visits were determined according to two thresholds (under 15% versus 25%) were evaluated. The proportion of cancer cases where percent-free PSA indicated a positive test before PSA > 4 ng/mL did and the number of negative biopsies that would have been spared by percent-free PSA testing negative were computed. RESULTS Percent-free PSA fluctuated around its threshold of PSA tested positive earlier than PSA in 71.4% (34.2%) of cancer cases, and among men with multiple negative biopsies and a PSA > 4 ng/mL, percent-free PSA would have tested negative in 31.6% (65.8%) instances. CONCLUSIONS Percent-free PSA should accompany PSA testing in order to potentially spare unnecessary biopsies or detect cancer earlier. When near the threshold, both tests should be repeated due to commonly observed fluctuation. PMID:26979652

Pharmaceutics, Drug Delivery and Pharmaceutical Technology: A New Test Unit for Disintegration End-Point Determination of Orodispersible Films.

Science.gov (United States)

Low, Ariana; Kok, Si Ling; Khong, Yuetmei; Chan, Sui Yung; Gokhale, Rajeev

2015-11-01

No standard time or pharmacopoeia disintegration test method for orodispersible films (ODFs) exists. The USP disintegration test for tablets and capsules poses significant challenges for end-point determination when used for ODFs. We tested a newly developed disintegration test unit (DTU) against the USP disintegration test. The DTU is an accessory to the USP disintegration apparatus. It holds the ODF in a horizontal position, allowing top-view of the ODF during testing. A Gauge R&R study was conducted to assign relative contributions of the total variability from the operator, sample or the experimental set-up. Precision was compared using commercial ODF products in different media. Agreement between the two measurement methods was analysed. The DTU showed improved repeatability and reproducibility compared to the USP disintegration system with tighter standard deviations regardless of operator or medium. There is good agreement between the two methods, with the USP disintegration test giving generally longer disintegration times possibly due to difficulty in end-point determination. The DTU provided clear end-point determination and is suitable for quality control of ODFs during product developmental stage or manufacturing. This may facilitate the development of a standardized methodology for disintegration time determination of ODFs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3893-3903, 2015. Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Muscular variations during axillary dissection: A clinical study in fifty patients

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Upasna

2015-01-01

Methods: The anatomy of axilla regarding muscular variations was studied in 50 patients who had an axillary dissection for the staging and treatment of invasive primary breast cancer over one year. Results: In a period of one year, two patients (4% with axillary arch and one patient (2% with absent pectoralis major and minor muscles among fifty patients undergoing axillary surgery for breast cancer were identified. Conclusions: Axillary arch when present should always be identified and formally divided to allow adequate exposure of axillary contents, in order to achieve a complete lymphatic dissection. Complete absence of pectoralis major and minor muscles precludes the insertion of breast implants and worsens the prognosis of breast cancer.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Kauai, 2005

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Niihau, 2005

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Stingray Shoals

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Molokai, 2005

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Ofu & Olosega

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Ta'u

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Guam, 2003

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

Defining clinically important perioperative blood loss and transfusion for the Standardised Endpoints for Perioperative Medicine (StEP) collaborative: a protocol for a scoping review.

Science.gov (United States)

Bartoszko, Justyna; Vorobeichik, Leon; Jayarajah, Mohandas; Karkouti, Keyvan; Klein, Andrew A; Lamy, Andre; Mazer, C David; Murphy, Mike; Richards, Toby; Englesakis, Marina; Myles, Paul S; Wijeysundera, Duminda N

2017-06-30

'Standardised Endpoints for Perioperative Medicine' (StEP) is an international collaboration undertaking development of consensus-based consistent definitions for endpoints in perioperative clinical trials. Inconsistency in endpoint definitions can make interpretation of trial results more difficult, especially if conflicting evidence is present. Furthermore, this inconsistency impedes evidence synthesis and meta-analyses. The goals of StEP are to harmonise definitions for clinically meaningful endpoints and specify standards for endpoint reporting in clinical trials. To help inform this endeavour, we aim to conduct a scoping review to systematically characterise the definitions of clinically important endpoints in the existing published literature on perioperative blood loss and transfusion. The scoping review will be conducted using the widely adopted framework developed by Arksey and O'Malley, with modifications from Levac. We refined our methods with guidance from research librarians as well as researchers and clinicians with content expertise. The electronic literature search will involve several databases including Medline, PubMed-not-Medline and Embase. Our review has three objectives, namely to (1) identify definitions of significant blood loss and transfusion used in previously published large perioperative randomised trials; (2) identify previously developed consensus-based definitions for significant blood loss and transfusion in perioperative medicine and related fields; and (3) describe the association between different magnitudes of blood loss and transfusion with postoperative outcomes. The multistage review process for each question will involve two reviewers screening abstracts, reading full-text articles and performing data extraction. The abstracted data will be organised and subsequently analysed in an iterative process. This scoping review of the previously published literature does not require research ethics approval. The results will be used

Updated standardized endpoint definitions for transcatheter aortic valve implantation: The Valve Academic Research Consortium-2 consensus document

NARCIS (Netherlands)

A.P. Kappetein (Arie Pieter); S.J. Head (Stuart); P. Généreux (Philippe); N. Piazza (Nicolo); N.M. van Mieghem (Nicolas); E.H. Blackstone (Eugene); T.G. Brott (Thomas); D.J. Cohen (David J.); D.E. Cutlip (Donald); G.A. van Es (Gerrit Anne); R.T. Hahn (Rebecca); A.J. Kirtane (Ajay); M. Krucoff (Mitchell); S. Kodali (Susheel); M.J. Mack (Michael); R. Mehran (Roxana); J. Rodés-Cabau (Josep); P. Vranckx (Pascal); J.G. Webb (John); S.W. Windecker (Stephan); P.W.J.C. Serruys (Patrick); M.B. Leon (Martin)

2012-01-01

textabstractObjectives: The aim of the current Valvular Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI)- clinical endpoints to make them more suitable to the present and future needs of clinical trials.

Cadmium phytotoxicity: Quantitative sensitivity relationships between classical endpoints and antioxidative enzyme biomarkers

International Nuclear Information System (INIS)

Rosa Correa, Albertina Xavier da; Roerig, Leonardo Rubi; Verdinelli, Miguel A.; Cotelle, Sylvie; Ferard, Jean-Francois; Radetski, Claudemir Marcos

2006-01-01

In this work, cadmium phytotoxicity and quantitative sensitivity relationships between different hierarchical endpoints in plants cultivated in a contaminated soil were studied. Thus, germination rate, biomass growth and antioxidative enzyme activity (i.e. superoxide dismutase, peroxidase, catalase and glutathione reductase) in three terrestrial plants (Avena sativa L., Brassica campestris L. cv. Chinensis, Lactuca sativa L. cv. hanson) were analyzed. Plant growth tests were carried out according to an International Standard Organization method and the results were analyzed by ANOVA followed by Williams' test. The concentration of Cd 2+ that had the smallest observed significant negative effect (LOEC) on plant biomass was 6.25, 12.5 and 50 mg Cd/kg dry soil for lettuce, oat and Chinese cabbage, respectively. Activity of all enzymes studied increased significantly compared to enzyme activity in plant controls. For lettuce, LOEC values (mg Cd/kg dry soil) for enzymic activity ranged from 0.05 (glutathione reductase) to 0.39 (catalase). For oat, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (for superoxide dismutase and glutathione reductase) to 0.39 (for catalase and peroxidase). For Chinese cabbage, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (peroxidase, catalase and glutathione reductase) to 0.39 (superoxide dismutase). Classical (i.e. germination and biomass) and biochemical (i.e. enzyme activity) endpoints were compared to establish a sensitivity ranking, which was: enzyme activity > biomass > germination rate. For cadmium-soil contamination, the determination of quantitative sensitivity relationships (QSR) between classical and antioxidative enzyme biomarkers showed that the most sensitive plant species have, generally, the lowest QSR values

Analysis association of milk fat and protein percent in quantitative ...

African Journals Online (AJOL)

SAM

2014-05-14

May 14, 2014 ... African Journal of Biotechnology. Full Length ... quantitative trait locus (QTLs) on chromosomes 1, 6, 7 and 20 in ... Protein and fat percent as content of milk are high-priority criteria for financial aims and selection of programs ...

A conscious mouse model of gastric ileus using clinically relevant endpoints

Directory of Open Access Journals (Sweden)

Shao Yuanlin

2005-06-01

Full Text Available Abstract Background Gastric ileus is an unsolved clinical problem and current treatment is limited to supportive measures. Models of ileus using anesthetized animals, muscle strips or isolated smooth muscle cells do not adequately reproduce the clinical situation. Thus, previous studies using these techniques have not led to a clear understanding of the pathophysiology of ileus. The feasibility of using food intake and fecal output as simple, clinically relevant endpoints for monitoring ileus in a conscious mouse model was evaluated by assessing the severity and time course of various insults known to cause ileus. Methods Delayed food intake and fecal output associated with ileus was monitored after intraperitoneal injection of endotoxin, laparotomy with bowel manipulation, thermal injury or cerulein induced acute pancreatitis. The correlation of decreased food intake after endotoxin injection with gastric ileus was validated by measuring gastric emptying. The effect of endotoxin on general activity level and feeding behavior was also determined. Small bowel transit was measured using a phenol red marker. Results Each insult resulted in a transient and comparable decrease in food intake and fecal output consistent with the clinical picture of ileus. The endpoints were highly sensitive to small changes in low doses of endotoxin, the extent of bowel manipulation, and cerulein dose. The delay in food intake directly correlated with delayed gastric emptying. Changes in general activity and feeding behavior were insufficient to explain decreased food intake. Intestinal transit remained unchanged at the times measured. Conclusion Food intake and fecal output are sensitive markers of gastric dysfunction in four experimental models of ileus. In the mouse, delayed gastric emptying appears to be the major cause of the anorexic effect associated with ileus. Gastric dysfunction is more important than small bowel dysfunction in this model. Recovery of

Age-related changes in the macula. A histopathological study of fifty Indian donor eyes

OpenAIRE

Biswas Jyotirmay; Raman Rajiv

2002-01-01

PURPOSE: Age-related macular degeneration (ARMD) is clinically less common in India compared to the West. Therefore, clinicians are unfamiliar with histopathologic evidence of age-related macular changes in the Indian population. METHODS: Fifty consecutive human donor eyes removed for corneal grafting were studied for gross, microscopic and histochemical features of age-related changes in the macula in the Indian population. A horizontal block was cut from the globe including the optic disc, ...

Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone

OpenAIRE

Palmerini, E.; Jones, R. L.; Marchesi, E.; Paioli, A.; Cesari, M.; Longhi, A.; Meazza, C.; Coccoli, L.; Fagioli, F.; Asaftei, S.; Grignani, G.; Tamburini, A.; Pollack, S. M.; Picci, P.; Ferrari, S.

2016-01-01

Background Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Methods Patients receiving G 900?mg/m2 d 1, 8; D 75?mg/m2 d 8, every 21?days were eligible. Primary end-point: progression-free survival (PFS) at 4?months; secondary end-point: overall survival (OS) and response rate. Results Fifty-one patients w...

The effect of adherence to statin therapy on cardiovascular mortality: quantification of unmeasured bias using falsification end-points

Directory of Open Access Journals (Sweden)

Maarten J. Bijlsma

2016-04-01

Full Text Available Abstract Background To determine the clinical effectiveness of statins on cardiovascular mortality in practice, observational studies are needed. Control for confounding is essential in any observational study. Falsification end-points may be useful to determine if bias is present after adjustment has taken place. Methods We followed starters on statin therapy in the Netherlands aged 46 to 100 years over the period 1996 to 2012, from initiation of statin therapy until cardiovascular mortality or censoring. Within this group (n = 49,688, up to 16 years of follow-up, we estimated the effect of adherence to statin therapy (0 = completely non-adherent, 1 = fully adherent on ischemic heart diseases and cerebrovascular disease (ICD10-codes I20-I25 and I60-I69 as well as respiratory and endocrine disease mortality (ICD10-codes J00-J99 and E00-E90 as falsification end points, controlling for demographic factors, socio-economic factors, birth cohort, adherence to other cardiovascular medications, and diabetes using time-varying Cox regression models. Results Falsification end-points indicated that a simpler model was less biased than a model with more controls. Adherence to statins appeared to be protective against cardiovascular mortality (HR: 0.70, 95 % CI 0.61 to 0.81. Conclusions Falsification end-points helped detect overadjustment bias or bias due to competing risks, and thereby proved to be a useful technique in such a complex setting.

Investigation of allergenicity of some cosmetic mixtures by using ex vivo local lymph node assay-BrdU endpoints.

Science.gov (United States)

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

2014-01-01

Balsam of Peru and fragrance mix are commonly used in cosmetic products. Allergy to fragrance is the most common cause of cosmetic contact dermatitis. In the present study, ex vivo local lymph node assay-5-bromo-2'-deoxyuridine (LLNA-BrdU) was used to evaluate the dermal sensitization potential of these cosmetic mixtures. The stimulation index values and estimated concentration (EC3) values were calculated and the potency classification was found for each mixture. At the same time, in order to measure the irritant effect without having to use additional animals, a combination of ex vivo LLNA-BrdU and the irritancy assay was conducted. Th1 [interleukin (IL)-2, interferon-γ] and Th2 cytokine (IL-4, IL-5) releases from lymph node cell culture were investigated as non-radioactive endpoints. According to the results of ex vivo LLNA-BrdU assays, EC3 values were found to be 3.09% (moderate) for balsam of Peru and 4.44% (moderate) for fragrance mix. Cytokine analysis results indicate that both Th1 and Th2 cytokines are involved in the regulation of murine contact allergy and can be considered as useful endpoints. In conclusion, according to our results, fragrance mix and balsam of Peru can be considered as moderate sensitizers; however, in high concentrations, both of them have irritation properties. The cytokines investigated can be considered as the endpoints of the ex vivo LLNA-BrdU assay. © 2014 S. Karger AG, Basel.

Fifty years of fat: news coverage of trends that predate obesity prevalence.

Science.gov (United States)

Davis, Brennan; Wansink, Brian

2015-07-10

Obesity prevalence has risen in fifty years. While people generally expect media mentions of health risks like obesity prevalence to follow health risk trends, food consumption trends may precede obesity prevalence trends. Therefore, this research investigates whether media mentions of food predate obesity prevalence. Fifty years of non-advertising articles in the New York Times (and 17 years for the London Times) are coded for the mention of less healthy (5 salty and 5 sweet snacks) and healthy (5 fruits and 5 vegetables) food items by year and then associated with annual obesity prevalence in subsequent years. Time-series generalized linear models test whether food-related mentions predate or postdate obesity prevalence in each country. United States obesity prevalence is positively associated with New York Times mentions of sweet snacks (b = 55.2, CI = 42.4 to 68.1, p = .000) and negatively associated with mentions of fruits (b = -71.28, CI -91.5 to -51.1, p = .000) and vegetables (b = -13.6, CI = -17.5 to -9.6, p = .000). Similar results are found for the United Kingdom and The London Times. Importantly, the "obesity followed mentions" models are stronger than the "obesity preceded mentions" models. It may be possible to estimate a nation's future obesity prevalence (e.g., three years from now) based on how frequently national media mention sweet snacks (positively related) and vegetables or fruits (negatively related) today. This may provide public health officials and epidemiologists with new tools to more quickly assess the effectiveness of current obesity interventions based on what is mentioned in the media today.

Study of extraterrestrial disposal of radioactive wastes. Part 3: Preliminary feasibility screening study of space disposal of the actinide radioactive wastes with 1 percent and 0.1 percent fission product contamination

Science.gov (United States)

Hyland, R. E.; Wohl, M. L.; Finnegan, P. M.

1973-01-01

A preliminary study was conducted of the feasibility of space disposal of the actinide class of radioactive waste material. This waste was assumed to contain 1 and 0.1 percent residual fission products, since it may not be feasible to completely separate the actinides. The actinides are a small fraction of the total waste but they remain radioactive much longer than the other wastes and must be isolated from human encounter for tens of thousands of years. Results indicate that space disposal is promising but more study is required, particularly in the area of safety. The minimum cost of space transportation would increase the consumer electric utility bill by the order of 1 percent for earth escape and 3 percent for solar escape. The waste package in this phase of the study was designed for normal operating conditions only; the design of next phase of the study will include provisions for accident safety. The number of shuttle launches per year required to dispose of all U.S. generated actinide waste with 0.1 percent residual fission products varies between 3 and 15 in 1985 and between 25 and 110 by 2000. The lower values assume earth escape (solar orbit) and the higher values are for escape from the solar system.

Influence of nutrient medium composition on uranium toxicity and choice of the most sensitive growth related endpoint in Lemna minor.

Science.gov (United States)

Horemans, Nele; Van Hees, May; Saenen, Eline; Van Hoeck, Arne; Smolders, Valérie; Blust, Ronny; Vandenhove, Hildegarde

2016-01-01

Uranium (U) toxicity is known to be highly dependent on U speciation and bioavailability. To assess the impact of uranium on plants, a growth inhibition test was set up in the freshwater macrophyte Lemna minor. First growth media with different compositions were tested in order to find a medium fit for testing U toxicity in L. minor. Following arguments were used for medium selection: the ability to sustain L. minor growth, a high solubility of U in the medium and a high percentage of the more toxic U-species namely UO2(2+). Based on these selection criteria a with a low phosphate concentration of 0.5 mg L(-1) and supplemented with 5 mM MES (2-(N-morpholino)ethanesulfonic acid) to ensure pH stability was chosen. This medium also showed highest U toxicity compared to the other tested media. Subsequently a full dose response curve for U was established by exposing L. minor plants to U concentrations ranging from 0.05 μM up to 150 μM for 7 days. Uranium was shown to adversely affect growth of L. minor in a dose dependent manner with EC10, EC30 and EC50 values ranging between 1.6 and 4.8 μM, 7.7-16.4 μM and 19.4-37.2 μM U, respectively, depending on the growth endpoint. Four different growth related endpoints were tested: frond area, frond number, fresh weight and dry weight. Although differences in relative growth rates and associated ECx-values calculated on different endpoints are small (maximal twofold difference), frond area is recommended to be used to measure U-induced growth effects as it is a sensitive growth endpoint and easy to measure in vivo allowing for measurements over time. Copyright © 2015 Elsevier Ltd. All rights reserved.

46 CFR 42.20-7 - Flooding standard: Type “B” vessel, 60 percent reduction.

Science.gov (United States)

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Flooding standard: Type âBâ vessel, 60 percent reduction... DOMESTIC AND FOREIGN VOYAGES BY SEA Freeboards § 42.20-7 Flooding standard: Type “B” vessel, 60 percent... applied to the following flooding standards: (1) If the vessel is 225 meters (738 feet) or less in length...

[Trends in the mortality of liver cancer in Qidong, China: an analysis of fifty years].

Science.gov (United States)

Chen, Jian-guo; Zhu, Jian; Zhang, Yong-hui; Chen, Yong-sheng; Ding, Lu-lu; Lu, Jian-hua; Zhu, Yuan-rong

2012-07-01

To describe and analyze the charecteristics and trends of liver cancer mortality during the past fifty years in Qidong, China. Retrospective mortality survey was conducted to get the data on liver cancer death in the period of 1958-1971, and the data from 1972 to 2007 were obtained from the records of cancer registration in Qidong. The crude mortality rate (CR) of liver cancer, and age-standardized rate by Chinese population (CASR) and by world population (WASR) were calculated and analyzed. The total percent changes (PC) and annual percent changes (APC) were used for evaluating the increasing trends of the mortality. The sex-specific rate, age-specific rate, truncated rate of the age group 35 - 64, cumulative rate of the age group 0-74, cumulative risk, period-rate, and the rate for age-birth cohort were compared. The natural death rate in Qidong residents for the past five-decade period experienced a wave interval of 8.62‰ in 1958 down to 5.37‰ in 1979, and up to 7.75‰ in 2007. The mortality rate for all-site cancers was increased from 56.69 per 100, 000 to 234.97 per 100, 000. The mortality rate of liver cancer, being 20.45 per 100, 100 in 1958 was increased to 49.04 per 100, 000 in 1972, and up to 69.29 per 100, 000 in 2007. According to the registration data of 1972 - 2007, the death from liver cancer was accounted for 34.88% of all deaths due to cancers, with a CR of 58.86 per 100, 000, CASR of 38.36 per 100, 000, and WASR, 49.37 Per 100, 000 in Qidong. The truncated rate for the age group 35 - 64 was 117.08 per 100, 000, and the cumulative rate for the age group 0-74 and the cumulative risk were 5.15% and 5.02%, respectively. The CRs for males was 90.52 per 100, 000 and for females was 27.93 per 100, 000, with a sex ratio of 3.24:1. For the period of 1972 - 2007, the PC for CR was 49.71%, and APC was +1.41%, showing an increasing variation tendency. The APCs for CASR and WASR, however, were decreasing, with a percentage of -1.11%, and -0

Endpoint design for future renal denervation trials - Novel implications for a new definition of treatment response to renal denervation.

Science.gov (United States)

Lambert, Thomas; Nahler, Alexander; Rohla, Miklos; Reiter, Christian; Grund, Michael; Kammler, Jürgen; Blessberger, Hermann; Kypta, Alexander; Kellermair, Jörg; Schwarz, Stefan; Starnawski, Jennifer A; Lichtenauer, Michael; Weiss, Thomas W; Huber, Kurt; Steinwender, Clemens

2016-10-01

Defining an adequate endpoint for renal denervation trials represents a major challenge. A high inter-individual and intra-individual variability of blood pressure levels as well as a partial or total non-adherence on antihypertensive drugs hamper treatment evaluations after renal denervation. Blood pressure measurements at a single point in time as used as primary endpoint in most clinical trials on renal denervation, might not be sufficient to discriminate between patients who do or do not respond to renal denervation. We compared the traditional responder classification (defined as systolic 24-hour blood pressure reduction of -5mmHg six months after renal denervation) with a novel definition of an ideal respondership (based on a 24h blood pressure reduction at no point in time, one, or all follow-up timepoints). We were able to re-classify almost a quarter of patients. Blood pressure variability was substantial in patients traditionally defined as responders. On the other hand, our novel classification of an ideal respondership seems to be clinically superior in discriminating sustained from pseudo-response to renal denervation. Based on our observations, we recommend that the traditional response classification should be reconsidered and possibly strengthened by using a composite endpoint of 24h-BP reductions at different follow-up-visits. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Fifty years of mathematical physics selected works of Ludwig Faddeev

CERN Document Server

Faddeev, Ludwig; Niemi, Antti J

2016-01-01

This unique volume summarizes with a historical perspective several of the major scientific achievements of Ludwig Faddeev, with a foreword by Nobel Laureate C N Yang. The volume that spans over fifty years of Faddeev's career begins where he started his own scientific research, in the subject of scattering theory and the three-body problem. It then continues to describe Faddeev's contributions to automorphic functions, followed by an extensive account of his many fundamental contributions to quantum field theory including his original article on ghosts with Popov. Faddeev's contributions to soliton theory and integrable models are then described, followed by a survey of his work on quantum groups. The final scientific section is devoted to Faddeev's contemporary research including articles on his long-term interest in constructing knotted solitons and understanding confinement. The volume concludes with his personal view on science and mathematical physics in particular.

Towards better environmental performance of wastewater sludge treatment using endpoint approach in LCA methodology

Directory of Open Access Journals (Sweden)

Isam Alyaseri

2017-03-01

Full Text Available The aim of this study is to use the life cycle assessment method to measure the environmental performance of the sludge incineration process in a wastewater treatment plant and to propose an alternative that can reduce the environmental impact. To show the damages caused by the treatment processes, the study aimed to use an endpoint approach in evaluating impacts on human health, ecosystem quality, and resources due to the processes. A case study was taken at Bissell Point Wastewater Treatment Plant in Saint Louis, Missouri, U.S. The plant-specific data along with literature data from technical publications were used to build an inventory, and then analyzed the environmental burdens from sludge handling unit in the year 2011. The impact assessment method chosen was ReCipe 2008. The existing scenario (dewatering-multiple hearth incineration-ash to landfill was evaluated and three alternative scenarios (fluid bed incineration and anaerobic digestion with and without land application with energy recovery from heat or biogas were proposed and analyzed to find the one with the least environmental impact. The existing scenario shows that the most significant impacts are related to depletion in resources and damage to human health. These impacts mainly came from the operation phase (electricity and fuel consumption and emissions related to combustion. Alternatives showed better performance than the existing scenario. Using ReCipe endpoint methodology, and among the three alternatives tested, the anaerobic digestion had the best overall environmental performance. It is recommended to convert to fluid bed incineration if the concerns were more about human health or to anaerobic digestion if the concerns were more about depletion in resources. The endpoint approach may simplify the outcomes of this study as follows: if the plant is converted to fluid bed incineration, it could prevent an average of 43.2 DALYs in human life, save 0.059 species in the area

Phase II Trials for Heterogeneous Patient Populations with a Time-to-Event Endpoint.

Science.gov (United States)

Jung, Sin-Ho

2017-07-01

In this paper, we consider a single-arm phase II trial with a time-to-event end-point. We assume that the study population has multiple subpopulations with different prognosis, but the study treatment is expected to be similarly efficacious across the subpopulations. We review a stratified one-sample log-rank test and present its sample size calculation method under some practical design settings. Our sample size method requires specification of the prevalence of subpopulations. We observe that the power of the resulting sample size is not very sensitive to misspecification of the prevalence.

Giant Magnetic Fluctuations at the Critical Endpoint in Insulating HoMnO3

Science.gov (United States)

Choi, Y. J.; Lee, N.; Sharma, P. A.; Kim, S. B.; Vajk, O. P.; Lynn, J. W.; Oh, Y. S.; Cheong, S.-W.

2013-04-01

Although abundant research has focused recently on the quantum criticality of itinerant magnets, critical phenomena of insulating magnets in the vicinity of critical endpoints (CEP’s) have rarely been revealed. Here we observe an emergent CEP at 2.05 T and 2.2 K with a suppressed thermal conductivity and concomitant strong critical fluctuations evident via a divergent magnetic susceptibility (e.g., χ''(2.05T,2.2K)/χ''(3T,2.2K)≈23,500%, comparable to the critical opalescence in water) in the hexagonal insulating antiferromagnet HoMnO3.

Endpoint Distinctiveness Facilitates Analogical Mapping in Pigeons

Science.gov (United States)

Hagmann, Carl Erick; Cook, Robert G.

2015-01-01

Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, reassignment, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal map of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons’ capacity for more advanced types of analogical reasoning. PMID:25447511

Radiological impacts analysis with use of new endpoint as complementary safety indicators

International Nuclear Information System (INIS)

Peralta Vital, J.L.; Gil Castillo, R.; Fleitas Estevez, G.G.; Olivera Acosta, J.

2015-01-01

The paper shows the new safety indicators on risk assessment (safety assessment) to radioactive waste environmental management implementation (concentrations and fluxes of naturally occurring radioactive materials (NORM)). The endpoint obtained, allow the best analysis of the radiological impact associated to radioactive waste isolation system. The common safety indicators for safety assessment purpose, dose and risk, are very time dependent, increasing the uncertainties in the results for long term assessment. The complementary and new proposed endpoints are more stable and they are not affected by changes in the critical group, pathways, etc. The NORM values on facility site were obtained as result of national surveys, the natural concentrations of U, Ra, Th, K has been associated with the variation of the lithologies in 3 geographical areas of the Country (Occidental, Central and Oriental). The results obtained are related with the safety assessment topics and allowed to apply the new complementary safety indicators, by comparisons between the natural concentrations and fluxes on site and its calculated values for the conceptual repository design. In order to normalize the concentration results, the analysis was realized adopting the criteria of the Repository Equivalent Rock Volume (RERV). The preliminary comparison showed that the calculated concentrations and fluxes in the Cuban conceptual radioactive waste repository are not higher than the natural values in the host rock. According to the application of new safety indicators, the reference disposal facility does not increase the natural activity concentration and fluxes in the environment. In order to implement these new safety indicator it has been used the current 226 Ra inventory of the Repository and the 226 Ra as natural concentration on the site. (authors)

Cadmium phytotoxicity: Quantitative sensitivity relationships between classical endpoints and antioxidative enzyme biomarkers

Energy Technology Data Exchange (ETDEWEB)

Rosa Correa, Albertina Xavier da [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil); Roerig, Leonardo Rubi [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil); Verdinelli, Miguel A. [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil); Cotelle, Sylvie [Centre des Sciences de l' Environnement, Universite de Metz, 57000 Metz (France); Ferard, Jean-Francois [Centre des Sciences de l' Environnement, Universite de Metz, 57000 Metz (France); Radetski, Claudemir Marcos [Centro de Ciencias Tecnologicas da Terra e do Mar, Universidade do Vale do Itajai, Rua Uruguai, 458, 88302-202 Itajai SC (Brazil)]. E-mail: radetski@univali.br

2006-03-15

In this work, cadmium phytotoxicity and quantitative sensitivity relationships between different hierarchical endpoints in plants cultivated in a contaminated soil were studied. Thus, germination rate, biomass growth and antioxidative enzyme activity (i.e. superoxide dismutase, peroxidase, catalase and glutathione reductase) in three terrestrial plants (Avena sativa L., Brassica campestris L. cv. Chinensis, Lactuca sativa L. cv. hanson) were analyzed. Plant growth tests were carried out according to an International Standard Organization method and the results were analyzed by ANOVA followed by Williams' test. The concentration of Cd{sup 2+} that had the smallest observed significant negative effect (LOEC) on plant biomass was 6.25, 12.5 and 50 mg Cd/kg dry soil for lettuce, oat and Chinese cabbage, respectively. Activity of all enzymes studied increased significantly compared to enzyme activity in plant controls. For lettuce, LOEC values (mg Cd/kg dry soil) for enzymic activity ranged from 0.05 (glutathione reductase) to 0.39 (catalase). For oat, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (for superoxide dismutase and glutathione reductase) to 0.39 (for catalase and peroxidase). For Chinese cabbage, LOEC values (mg Cd/kg dry soil) ranged from 0.19 (peroxidase, catalase and glutathione reductase) to 0.39 (superoxide dismutase). Classical (i.e. germination and biomass) and biochemical (i.e. enzyme activity) endpoints were compared to establish a sensitivity ranking, which was: enzyme activity > biomass > germination rate. For cadmium-soil contamination, the determination of quantitative sensitivity relationships (QSR) between classical and antioxidative enzyme biomarkers showed that the most sensitive plant species have, generally, the lowest QSR values.

A comparison of height and weight velocity as a part of the composite endpoint in pediatric HIV.

Science.gov (United States)

Benjamin, Daniel K; Miller, Wiliam C; Benjamin, Daniel K; Ryder, Robert W; Weber, David J; Walter, Emmanuel; McKinney, Ross E

2003-11-07

HIV adversely affects growth in children. Pediatric AIDS Clinical Trial Group (PACTG) protocols often use weight velocity [changes in weight z-score for age (WAZ)] as a part of the composite endpoint for phase II and III clinical trials. However, WAZ and height velocity (HAZ) have not been critically compared for their utility as part of the composite endpoint. HAZ and WAZ were compared to predict laboratory and clinical progression of HIV in a retrospective cohort study of HIV-infected children with data from PACTG Protocol 300. In both bivariable and multivariable analyses, changes in HAZ were more closely linked to subsequent progression than WAZ. Children with improved HAZ were somewhat less likely to exhibit virological failure [odds ratio (OR), 0.76; 95% confidence interval (CI) 0.51-1.14], than children with improved WAZ (OR, 1.45; 95% CI, 0.99,2.11). Children who had improved HAZ were less likely to exhibit immunological failure (OR, 0.7; 95% CI, 0.49-1.00), than children with improved WAZ (OR, 1.13; 95% CI, 0.82-1.57). Children who had improved HAZ were less likely to have other forms of clinical progression of HIV (OR, 0.55; 95% CI, 0.31-0.99), than children who had improved WAZ (OR, 1.0; 95% CI, 1.58-1.94). Increases in HAZ were associated with reduced risk of subsequent clinical progression and subsequent immune reconstitution and weakly associated with declines in HIV RNA. Changes in WAZ were not associated with laboratory outcomes relevant to pediatric HIV infection. Height velocity should be considered as a component of a composite clinical endpoint in future PACTG trials.

26 CFR 1.414(r)-4 - Qualified separate line of business-fifty-employee and notice requirements.

Science.gov (United States)

2010-04-01

...-employee and notice requirements. 1.414(r)-4 Section 1.414(r)-4 Internal Revenue INTERNAL REVENUE SERVICE... Bonus Plans, Etc. § 1.414(r)-4 Qualified separate line of business—fifty-employee and notice... business (as determined under § 1.414(r)-3) satisfies the 50-employee and notice requirements of § 1.414(r...

Impact of copula directional specification on multi-trial evaluation of surrogate endpoints

Science.gov (United States)

Renfro, Lindsay A.; Shang, Hongwei; Sargent, Daniel J.

2014-01-01

Evaluation of surrogate endpoints using patient-level data from multiple trials is the gold standard, where multi-trial copula models are used to quantify both patient-level and trial-level surrogacy. While limited consideration has been given in the literature to copula choice (e.g., Clayton), no prior consideration has been given to direction of implementation (via survival versus distribution functions). We demonstrate that evenwith the “correct” copula family, directional misspecification leads to biased estimates of patient-level and trial-level surrogacy. We illustrate with a simulation study and a re-analysis of disease-free survival as a surrogate for overall survival in early stage colon cancer. PMID:24905465

Investigation of Rheological Impacts on the Defense Waste Processing Facility's Sludge Slurry Feed as Insoluble Solids and Wash Endpoints are Adjusted

International Nuclear Information System (INIS)

Fellinger, T. L.; Howard, S.J.; Lee, M.C.; Galloway, R.H.

2006-01-01

The Savannah River Site (SRS) is currently pursuing an aggressive program to empty its High Level Waste (HLW) tanks and immobilize its radioactive waste into a durable borosilicate glass in the Defense Waste Processing Facility (DWPF). To create a batch of feed for the DWPF, several tanks of radioactive sludge slurry are combined into one of the million gallon (i.e. 3.79 E06 liters) feed tanks for DWPF. Once these sludge slurries are combined, the soluble sodium and weight percent total solids are adjusted by a 'washing' process. The 'washing' process involves diluting the soluble sodium of the sludge slurry with inhibited water (0.015 M NaOH and 0.015 M NaNO 2 ) and allowing the sludge slurry to settle into two layers. The two layers in the tank consist of a clear supernate on top and a layer of settled sludge solids on the bottom. The clear supernate layer is then decanted to another hold tank. This 'washing' process is repeated until the desired wash endpoint (i.e. sodium concentration in the supernate) and weight percent total solids are achieved. A final washed batch of feed consists of approximately 500,000 gallons (i.e. 1.89 E06 liters). DWPF has already processed three batches of feed and is currently processing a fourth. Prior to processing a batch of feed in the DWPF, it must be well characterized. Samples of the prepared feed batch are sent to the Savannah River National Laboratory (SRNL) for this characterization. As a part of the SRNL characterization for the fourth batch, rheology measurements were performed. Measurements were performed at different weight percent insoluble solids loadings to mimic potential facility processing scenarios (i.e. mixing/pumping of concentrated sludge slurry). In order to determine the influence of the soluble Na on the rheological properties of the sample, the supernate of the 'as received' sample was adjusted from 1 M soluble Na to 0.5 M soluble Na by using a lab scale version of the 'washing' process. Rheology

EnviroAtlas - Cleveland, OH - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Austin, TX - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Portland, ME - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Woodbine, IA - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Milwaukee, WI - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Tampa, FL - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Pittsburgh, PA - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Phoenix, AZ - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Durham, NC - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Portland, OR - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Paterson, NJ - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Memphis, TN - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Fresno, CA - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas Estimated Percent Tree Cover Along Walkable Roads Web Service

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

Amazing 7-day, super-simple, scripted guide to teaching or learning percents

CERN Document Server

Hernandez, Lisa

2014-01-01

Welcome to The Amazing 7-Day, Super-Simple, Scripted Guide to Teaching or Learning Percents. I have attempted to do just what the title says: make learning percents super simple. I have also attempted to make it fun and even ear-catching. The reason for this is not that I am a frustrated stand-up comic, but because in my fourteen years of teaching the subject, I have come to realize that my jokes, even the bad ones, have a crazy way of sticking in my students' heads. And should I use a joke (even a bad one) repetitively, the associations become embedded in their brains, many times to their cha

Inconsistent approaches of the G-BA regarding acceptance of primary study endpoints as being relevant to patients - an analysis of three disease areas: oncological, metabolic, and infectious diseases

Directory of Open Access Journals (Sweden)

Thomas Staab

2016-11-01

Full Text Available Abstract Background Previous evaluations of oncological medicines in the German early benefit assessment (EBA procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA. Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas. Methods Medicines for oncological, metabolic and infectious diseases with EBAs finalised before 25 January 2016 were evaluated. Respective manufacturer’s dossiers, regulatory assessments, G-BA appraisals and oral hearing minutes were reviewed, and PEPs were examined to determine whether they were considered relevant to patients by the G-BA. Furthermore, the acceptance of symptomatic vs asymptomatic PEPs was also analysed. Results A total of 65 EBAs were evaluated. Mortality PEPs were widely accepted as patient-relevant but were only used in a minority of EBAs and exclusively in oncological diseases. Morbidity PEPs constituted around 72 % of assessed PEPs, but were excluded from the EBA in over half of the corresponding assessments as they were not considered patient-relevant. Symptomatic endpoints were largely deemed patient-relevant, whereas acceptance of asymptomatic endpoints varied between therapeutic areas. Conclusions This evaluation identified inconsistencies in patient relevance of morbidity-related PEPs as well as in acceptance of asymptomatic endpoints by the G-BA in all three disease areas examined. Better harmonisation between the regulatory authorities and the G-BA is still required after 5 years of AMNOG health technology assessment in Germany.

MFT homogeneity study at TNX: Final report on the low weight percent solids concentration

International Nuclear Information System (INIS)

Jenkins, W.J.

1993-01-01

A statistical design and analysis of both elemental analyses and weight percent solids analyses data was utilized to evaluate the MFT homogeneity at low heel levels and low agitator speed at both high and low solids feed concentrations. The homogeneity was also evaluated at both low and high agitator speed at the 6000+ gallons static level. The dynamic level portion of the test simulated feeding the Melter from the MFT to evaluate the uniformity of the solids slurry composition (Frit-PHA-Sludge) entering the melter from the MFT. This final report provides the results and conclusions from the second half of the study, the low weight percent solids concentration portion, as well as a comparison with the results from the first half of the study, the high weight percent solids portion

Circulations, debates and appropriations of the Fifty Shades of Grey in Argentina

Directory of Open Access Journals (Sweden)

Karina Felitti

2018-01-01

Full Text Available This article studies the social effects of the circulation and reception of the phenomenon of Fifty Shades of Grey in Argentina, in the context of sexualization of culture, postfeminism and the local agenda on gender policies. It analyzes the discussions that it aroused in the academy and the feminist militancy, its repercussions in the press and in the market of erotic goods and services, and the opinions and experiences of a set of readers. It is a qualitative study that combines textual analysis and in-depth interviews. Similarities are observed with analyzes carried out in other countries and also we pointed local specificities related to the discussions on gender violence, its manifestations and women’s agency.

Evaluating Equating Results: Percent Relative Error for Chained Kernel Equating

Science.gov (United States)

Jiang, Yanlin; von Davier, Alina A.; Chen, Haiwen

2012-01-01

This article presents a method for evaluating equating results. Within the kernel equating framework, the percent relative error (PRE) for chained equipercentile equating was computed under the nonequivalent groups with anchor test (NEAT) design. The method was applied to two data sets to obtain the PRE, which can be used to measure equating…

BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints.

Science.gov (United States)

Zhou, Heng; Lee, J Jack; Yuan, Ying

2017-09-20

We propose a flexible Bayesian optimal phase II (BOP2) design that is capable of handling simple (e.g., binary) and complicated (e.g., ordinal, nested, and co-primary) endpoints under a unified framework. We use a Dirichlet-multinomial model to accommodate different types of endpoints. At each interim, the go/no-go decision is made by evaluating a set of posterior probabilities of the events of interest, which is optimized to maximize power or minimize the number of patients under the null hypothesis. Unlike other existing Bayesian designs, the BOP2 design explicitly controls the type I error rate, thereby bridging the gap between Bayesian designs and frequentist designs. In addition, the stopping boundary of the BOP2 design can be enumerated prior to the onset of the trial. These features make the BOP2 design accessible to a wide range of users and regulatory agencies and particularly easy to implement in practice. Simulation studies show that the BOP2 design has favorable operating characteristics with higher power and lower risk of incorrectly terminating the trial than some existing Bayesian phase II designs. The software to implement the BOP2 design is freely available at www.trialdesign.org. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Raita Bank, 2001

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Eleven-Mile Bank

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Gardner Pinnacles, 2003

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at French Frigate Shoals

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

An overview of techniques for linking high-dimensional molecular data to time-to-event endpoints by risk prediction models.

Science.gov (United States)

Binder, Harald; Porzelius, Christine; Schumacher, Martin

2011-03-01

Analysis of molecular data promises identification of biomarkers for improving prognostic models, thus potentially enabling better patient management. For identifying such biomarkers, risk prediction models can be employed that link high-dimensional molecular covariate data to a clinical endpoint. In low-dimensional settings, a multitude of statistical techniques already exists for building such models, e.g. allowing for variable selection or for quantifying the added value of a new biomarker. We provide an overview of techniques for regularized estimation that transfer this toward high-dimensional settings, with a focus on models for time-to-event endpoints. Techniques for incorporating specific covariate structure are discussed, as well as techniques for dealing with more complex endpoints. Employing gene expression data from patients with diffuse large B-cell lymphoma, some typical modeling issues from low-dimensional settings are illustrated in a high-dimensional application. First, the performance of classical stepwise regression is compared to stage-wise regression, as implemented by a component-wise likelihood-based boosting approach. A second issues arises, when artificially transforming the response into a binary variable. The effects of the resulting loss of efficiency and potential bias in a high-dimensional setting are illustrated, and a link to competing risks models is provided. Finally, we discuss conditions for adequately quantifying the added value of high-dimensional gene expression measurements, both at the stage of model fitting and when performing evaluation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Science.gov (United States)

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

2013-01-01

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

Neutralization Assay for Zika and Dengue Viruses by Use of Real-Time-PCR-Based Endpoint Assessment.

Science.gov (United States)

Wilson, Heather L; Tran, Thomas; Druce, Julian; Dupont-Rouzeyrol, Myrielle; Catton, Michael

2017-10-01

The global spread and infective complications of Zika virus (ZKV) and dengue virus (DENV) have made them flaviviruses of public health concern. Serological diagnosis can be challenging due to antibody cross-reactivity, particularly in secondary flavivirus infections or when there is a history of flavivirus vaccination. The virus neutralization assay is considered to be the most specific assay for measurement of anti-flavivirus antibodies. This study describes an assay where the neutralization endpoint is measured by real-time PCR, providing results within 72 h. It demonstrated 100% sensitivity (24/24 ZKV and 15/15 DENV) and 100% specificity (11/11 specimens) when testing well-characterized sera. In addition, the assay was able to determine the correct DENV serotype in 91.7% of cases. The high sensitivity and specificity of the real-time PCR neutralization assay makes it suitable to use as a confirmatory test for sera that are reactive in commercial IgM/IgG enzyme immunoassays. Results are objective and the PCR-based measurement of the neutralization endpoint lends itself to automation so that throughput may be increased in times of high demand. Copyright © 2017 American Society for Microbiology.

Testing of an End-Point Control Unit Designed to Enable Precision Control of Manipulator-Coupled Spacecraft

Science.gov (United States)

Montgomery, Raymond C.; Ghosh, Dave; Tobbe, Patrick A.; Weathers, John M.; Manouchehri, Davoud; Lindsay, Thomas S.

1994-01-01

This paper presents an end-point control concept designed to enable precision telerobotic control of manipulator-coupled spacecraft. The concept employs a hardware unit (end-point control unit EPCU) that is positioned between the end-effector of the Space Shuttle Remote Manipulator System and the payload. Features of the unit are active compliance (control of the displacement between the end-effector and the payload), to allow precision control of payload motions, and inertial load relief, to prevent the transmission of loads between the end-effector and the payload. This paper presents the concept and studies the active compliance feature using a simulation and hardware. Results of the simulation show the effectiveness of the EPCU in smoothing the motion of the payload. Results are presented from initial, limited tests of a laboratory hardware unit on a robotic arm testbed at the l Space Flight Center. Tracking performance of the arm in a constant speed automated retraction and extension maneuver of a heavy payload with and without the unit active is compared for the design speed and higher speeds. Simultaneous load reduction and tracking performance are demonstrated using the EPCU.

Traditional and new composite endpoints in heart failure clinical trials : facilitating comprehensive efficacy assessments and improving trial efficiency

NARCIS (Netherlands)

Anker, Stefan D. t; Schroeder, Stefan; Atar, Dan; Bax, Jeroen J.; Ceconi, Claudio; Cowie, Martin R.; AdamCrisp,; Dominjon, Fabienne; Ford, Ian; Ghofrani, Hossein-Ardeschir; Gropper, Savion; Hindricks, Gerhard; Hlatky, Mark A.; Holcomb, Richard; Honarpour, Narimon; Jukema, J. Wouter; Kim, Albert M.; Kunz, Michael; Lefkowitz, Martin; Le Floch, Chantal; Landmesser, Ulf; McDonagh, Theresa A.; McMurray, John J.; Merkely, Bela; Packer, Milton; Prasad, Krishna; Revkin, James; Rosano, Giuseppe M. C.; Somaratne, Ransi; Stough, Wendy Gattis; Voors, Adriaan A.; Ruschitzka, Frank

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and

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

Science.gov (United States)

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

2005-08-15

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

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

International Nuclear Information System (INIS)

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

2005-01-01

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

A Portable Automatic Endpoint Detection System for Amplicons of Loop Mediated Isothermal Amplification on Microfluidic Compact Disk Platform

Directory of Open Access Journals (Sweden)

Shah Mukim Uddin

2015-03-01

Full Text Available In recent years, many improvements have been made in foodborne pathogen detection methods to reduce the impact of food contamination. Several rapid methods have been developed with biosensor devices to improve the way of performing pathogen detection. This paper presents an automated endpoint detection system for amplicons generated by loop mediated isothermal amplification (LAMP on a microfluidic compact disk platform. The developed detection system utilizes a monochromatic ultraviolet (UV emitter for excitation of fluorescent labeled LAMP amplicons and a color sensor to detect the emitted florescence from target. Then it processes the sensor output and displays the detection results on liquid crystal display (LCD. The sensitivity test has been performed with detection limit up to 2.5 × 10−3 ng/µL with different DNA concentrations of Salmonella bacteria. This system allows a rapid and automatic endpoint detection which could lead to the development of a point-of-care diagnosis device for foodborne pathogens detection in a resource-limited environment.

Evaluation of Gene Expression Endpoints in the Context of a Xenopus laevis Metamorphosis-based Bioassay to Detect Thyroid Hormone Disruptors

Science.gov (United States)

This study accentuates the need to examine multiple tissues and provides critical information required for optimization of exposure regimens and endpoint assessments that focus on the detection of disruption in TH-regulatory systems.

Endpoint distinctiveness facilitates analogical mapping in pigeons.

Science.gov (United States)

Hagmann, Carl Erick; Cook, Robert G

2015-03-01

Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due to endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal mapping of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons' capacity for more advanced types of analogical reasoning. This article is part of a Special Issue entitled: Tribute to Tom Zentall. Copyright © 2014 Elsevier B.V. All rights reserved.

A multiple endpoint analysis of the effects of chronic exposure to sediment contaminated with Deepwater Horizon oil on juvenile Southern flounder and their associated microbiomes

International Nuclear Information System (INIS)

Brown-Peterson, Nancy J.; Krasnec, Michelle; Takeshita, Ryan; Ryan, Caitlin N.; Griffitt, Kimberly J.; Lay, Claire; Mayer, Gregory D.; Bayha, Keith M.; Hawkins, William E.; Lipton, Ian; Morris, Jeffrey

2015-01-01

Highlights: • Juvenile southern flounder were exposed to sediment mixed with different amount of oil from the Deepwater Horizon spill. • The exposure was performed for 32 days, with growth and survival assessed throughout. • After the termination of the experiment, the survivors were examined at multiple endpoints, including histopathology and microbiome analysis. • The results indicated that the flounder were adversely affected at each endpoint examined. • Growth and survival were significantly reduced. • Histopathology found effects on gills and livers of exposed fish. • The microbiomes of the exposed fish were significantly altered by the exposure to sediment-associated oil in both gills and intestines. - Abstract: Exposure to oiled sediments can negatively impact the health of fish species. Here, we examine the effects of chronic exposure of juvenile southern flounder, Paralichthys lethostigma, to a sediment-oil mixture. Oil:sediment mixtures are persistent over time and can become bioavailable following sediment perturbation or resuspension. Juvenile flounder were exposed for 32 days under controlled laboratory conditions to five concentrations of naturally weathered Macondo MC252 oil mixed into uncontaminated, field-collected sediments. The percent composition of individual polycyclic aromatic hydrocarbons (PAHs) of the weathered oil did not change after mixing with the sediment. Spiked exposure sediments contained 0.04–395 mg/kg tPAH50 (sum of 50 individual PAH concentration measurements). Mortality increased with both exposure duration and concentration of sediment-associated PAHs, and flounder exposed to concentrations above 8 mg/kg tPAH50 showed significantly reduced growth over the course of the experiment. Evident histopathologic changes were observed in liver and gill tissues of fish exposed to more than 8 mg/kg tPAH50. All fish at these concentrations showed hepatic intravascular congestion, macrovesicular hepatic vacoulation

A multiple endpoint analysis of the effects of chronic exposure to sediment contaminated with Deepwater Horizon oil on juvenile Southern flounder and their associated microbiomes

Energy Technology Data Exchange (ETDEWEB)

Brown-Peterson, Nancy J., E-mail: nancy.brown-peterson@usm.edu [Department of Coastal Sciences, The University of Southern Mississippi, 703 East Beach Dr., Ocean Springs, MS 39564 (United States); Krasnec, Michelle, E-mail: MKrasnec@stratusconsulting.com [Abt Associates, 1881 Ninth Street, Suite 201, Boulder, Colorado 80302 (United States); Takeshita, Ryan, E-mail: RTakeshita@stratusconsulting.com [Abt Associates, 1881 Ninth Street, Suite 201, Boulder, Colorado 80302 (United States); Ryan, Caitlin N., E-mail: Caitlin.ryan@ttu.edu [The Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409 (United States); Griffitt, Kimberly J., E-mail: kim.griffitt@gmail.com [Department of Coastal Sciences, The University of Southern Mississippi, 703 East Beach Dr., Ocean Springs, MS 39564 (United States); Lay, Claire, E-mail: claymsc@stratusconsulting.com [Abt Associates, 1881 Ninth Street, Suite 201, Boulder, Colorado 80302 (United States); Mayer, Gregory D., E-mail: greg.mayer@ttu.edu [The Institute of Environmental and Human Health, Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409 (United States); Bayha, Keith M., E-mail: kmbayha@gmail.com [Department of Coastal Sciences, The University of Southern Mississippi, 703 East Beach Dr., Ocean Springs, MS 39564 (United States); Hawkins, William E., E-mail: william.hawkins@usm.edu [Department of Coastal Sciences, The University of Southern Mississippi, 703 East Beach Dr., Ocean Springs, MS 39564 (United States); Lipton, Ian, E-mail: ianlipton@stratusconsulting.com [Abt Associates, 1881 Ninth Street, Suite 201, Boulder, Colorado 80302 (United States); Morris, Jeffrey, E-mail: JMorrisMSCanyon252@stratusconsulting.com [Abt Associates, 1881 Ninth Street, Suite 201, Boulder, Colorado 80302 (United States); and others

2015-08-15

Highlights: • Juvenile southern flounder were exposed to sediment mixed with different amount of oil from the Deepwater Horizon spill. • The exposure was performed for 32 days, with growth and survival assessed throughout. • After the termination of the experiment, the survivors were examined at multiple endpoints, including histopathology and microbiome analysis. • The results indicated that the flounder were adversely affected at each endpoint examined. • Growth and survival were significantly reduced. • Histopathology found effects on gills and livers of exposed fish. • The microbiomes of the exposed fish were significantly altered by the exposure to sediment-associated oil in both gills and intestines. - Abstract: Exposure to oiled sediments can negatively impact the health of fish species. Here, we examine the effects of chronic exposure of juvenile southern flounder, Paralichthys lethostigma, to a sediment-oil mixture. Oil:sediment mixtures are persistent over time and can become bioavailable following sediment perturbation or resuspension. Juvenile flounder were exposed for 32 days under controlled laboratory conditions to five concentrations of naturally weathered Macondo MC252 oil mixed into uncontaminated, field-collected sediments. The percent composition of individual polycyclic aromatic hydrocarbons (PAHs) of the weathered oil did not change after mixing with the sediment. Spiked exposure sediments contained 0.04–395 mg/kg tPAH50 (sum of 50 individual PAH concentration measurements). Mortality increased with both exposure duration and concentration of sediment-associated PAHs, and flounder exposed to concentrations above 8 mg/kg tPAH50 showed significantly reduced growth over the course of the experiment. Evident histopathologic changes were observed in liver and gill tissues of fish exposed to more than 8 mg/kg tPAH50. All fish at these concentrations showed hepatic intravascular congestion, macrovesicular hepatic vacoulation

Gauge evolution of elementary particles physics during the last fifty years

International Nuclear Information System (INIS)

Khodjaev, L.Sh

2002-01-01

Gauge evolution of the elementary particle physics has been remarked by outstanding and exiting discoveries during the last fifty years of X X century. We review a new tendency in the development of the modern elementary particle physics. The phenomenological basis for the formulation of Standard Model has been reviewed. The Standard Model based on the fundamental postulates has been formulated. The concept of the fundamental symmetries has been introduced to look for not fundamental particles but fundamental symmetries. The Standard Model is renormalizable and therefore potentially consistent in all energy scales. The Standard Model in principle can describe the properties of the Universe beginning at 10 -43 sec. after Big Bang. In searching of more general theory obvious program is to searching the first of all global symmetries and then learn consequences connected with the localization of these global symmetries

Matter power spectrum and the challenge of percent accuracy

OpenAIRE

Schneider, Aurel; Teyssier, Romain; Potter, Doug; Stadel, Joachim; Onions, Julian; Reed, Darren S.; Smith, Robert E.; Springel, Volker; Pearce, Frazer R.; Scoccimarro, Roman

2015-01-01

Future galaxy surveys require one percent precision in the theoretical knowledge of the power spectrum over a large range including very nonlinear scales. While this level of accuracy is easily obtained in the linear regime with perturbation theory, it represents a serious challenge for small scales where numerical simulations are required. In this paper we quantify the precision of present-day $N$-body methods, identifying main potential error sources from the set-up of initial conditions to...

Optimal descriptor as a translator of eclectic data into endpoint prediction: mutagenicity of fullerene as a mathematical function of conditions.

Science.gov (United States)

Toropov, Andrey A; Toropova, Alla P

2014-06-01

The experimental data on the bacterial reverse mutation test on C60 nanoparticles (TA100) is examined as an endpoint. By means of the optimal descriptors calculated with the Monte Carlo method a mathematical model of the endpoint has been built up. The model is the mathematical function of (i) dose (g/plate); (ii) metabolic activation (i.e. with S9 mix or without S9 mix); and (iii) illumination (i.e. dark or irradiation). The statistical quality of the model is the following: n=10, r(2)=0.7549, q(2)=0.5709, s=7.67, F=25 (Training set); n=5, r(2)=0.8987, s=18.4 (Calibration set); and n=5, r(2)=0.6968, s=10.9 (Validation set). Copyright © 2013 Elsevier Ltd. All rights reserved.

Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints.

Science.gov (United States)

Zhu, Wenbo; Jin, Pengfei; Li, Jing-Xin; Zhu, Feng-Cai; Liu, Pei

2017-09-01

Inactivated Enterovirus 71 (EV71) vaccines showed significant efficacy against the diseases associated with EV71 and a neutralizing antibody (NTAb) titer of 1:16-1:32 was suggested as the correlates of the vaccine protection. This paper aims to further estimate the immunological surrogate endpoints for the protection of inactivated EV71 vaccines and the effect factors. Pre-vaccination NTAb against EV71 at baseline (day 0), post-vaccination NTAb against EV71 at day 56, and the occurrence of laboratory-confirmed EV71-associated diseases during a 24-months follow-up period were collected from a phase 3 efficacy trial of an inactivated EV71 vaccine. We used the mixed-scaled logit model and the absolute sigmoid function by some extensions in continuous models to estimate the immunological surrogate endpoint for the EV71 vaccine protection, respectively. For children with a negative baseline of EV71 NTAb titers, an antibody level of 26.6 U/ml (1:30) was estimated to provide at least a 50% protection for 12 months, and an antibody level of 36.2 U/ml (1:42) may be needed to achieve a 50% protective level of the population for 24 months. Both the pre-vaccination NTAb level and the vaccine protective period could affect the estimation of the immunological surrogate for EV71 vaccine. A post-vaccination NTAb titer of 1:42 or more may be needed for long-term protection. NCT01508247.

An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: 2nd round.

Science.gov (United States)

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

2005-08-15

The original local lymph node assay (LLNA) is based on the use of radioactive labelling to measure cell proliferation. Other endpoints for the assessment of proliferation are also authorized by the OECD Guideline 429 provided there is appropriate scientific support, including full citations and description of the methodology (OECD, 2002. OECD Guideline for the Testing of Chemicals; Skin Sensitization: Local Lymph Node Assay, Guideline 429. Paris, adopted 24th April 2002.). Here, we describe the outcome of the second round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in nine laboratories in Europe. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products (Swissmedic) in Bern. Ear-draining lymph node (LN) weight and cell counts were used to assess LN cell proliferation instead of [3H]TdR incorporation. In addition, the acute inflammatory skin reaction was measured by ear weight determination of circular biopsies of the ears to identify skin irritation properties of the test items. The statistical analysis was performed in the department of statistics at the university of Bern. Similar to the EC(3) values defined for the radioactive method, threshold values were calculated for the endpoints measured in this modification of the LLNA. It was concluded that all parameters measured have to be taken into consideration for the categorisation of compounds due to their sensitising potencies. Therefore, an assessment scheme has been developed which turned out to be of great importance to consistently assess sensitisation versus irritancy based on the data of the different parameters. In contrast to the radioactive method, irritants have been picked up by all the laboratories applying this assessment scheme.

Daikenchuto stimulates colonic motility after laparoscopic-assisted colectomy.

Science.gov (United States)

Yaegashi, Mizunori; Otsuka, Koki; Itabashi, Tetsuya; Kimura, Toshimoto; Kato, Kuniyuki; Fujii, Hitoshi; Koeda, Keisuke; Sasaki, Akira; Wakabayashi, Go

2014-01-01

Paralytic ileus after laparoscopic-assisted surgery often occurs. We investigated whether daikenchuto (DKT), a traditional Japanese herbal medicine, improves intestinal motility in patients undergoing laparoscopic-assisted colectomy for colon cancer. Fifty-four patients who underwent colectomy at Iwate Medical University Hospital between October 2010 and March 2012 were randomized to either the DKT group (7.5 g/day, p.o.) or the control group (lactobacillus preparation, 3g/day, p.o.). Primary endpoints included time to first flatus, bowel movement, and tolerance of diet after extubation. Secondary endpoints were WBC count, C-reactive protein (CRP) level, length of hospital stay, and postoperative ileus. Colonic transit time was measured using radiopaque markers and abdominal radiographs. Fifty-one patients (DKT, 26 vs. control, 25) were included in the per-protocol analysis. The DKT group had significantly faster time until first flatus (67.5 +/- 13.6h vs. 77.9 +/- 11.8h, P DKT accelerates colonic motility in patients undergoing laparoscopic-assisted colectomy for colon cancer.

Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Vance, Sean; Suri, Jaipreet S. [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Mahan, Meredith [Public Health Science, Henry Ford Hospital, Detroit, Michigan (United States); Munkarah, Adnan [Division of Gynecologic Oncology, Department of Women' s Health Services, Henry Ford Hospital, Detroit, Michigan (United States)

2014-02-01

Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

Center-Within-Trial Versus Trial-Level Evaluation of Surrogate Endpoints

Science.gov (United States)

Renfro, Lindsay A.; Shi, Qian; Xue, Yuan; Li, Junlong; Shang, Hongwei; Sargent, Daniel J.

2014-01-01

Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer. PMID:25061255

One hundred and fifty years of combustion of fossil hydrocarbons: The emergent alternatives

International Nuclear Information System (INIS)

Laine, Jorge

2009-01-01

After one hundred fifty years of drilling first commercial petroleum wells that led to the intensive use of liquid fuels to move transport vehicles, we are arriving at the peak of the world-wide petroleum reserves. Yet, we still have a good portion for spending, with the hope that the consequences will be better than in the first part, which has implied several wars and deteriorations of the environment. This assay brings a review about the history of fossil fuels and with the prospective of the emergent energetic alternatives, placing emphasis on bioenergy as an alternative for the transition between the actual combustion age and the new age of clean energy.

Atoms for peace plus fifty

International Nuclear Information System (INIS)

Eisenhower, S.

2003-01-01

One of Dwight Eisenhower's most significant political legacies stemmed from his management of the nuclear question. Five decades after Eisenhower's 'Atoms for Peace' speech before the United Nations, the nuclear dilemma persists but the world is a different, and I would submit, a better place today than it might have been had that vision not been articulated, or its proposals not advanced. The 'Atoms for Peace' speech had a number of objectives, but it is over arching goal was to propose a set of ideas, a nuclear strategy, which would call on the Soviets to cooperate internationally for the betterment of mankind. This would reengage the Soviets in discussions on nuclear matters at a time when arms control talks had stalled, but it would also offer hope, and a practical set of ideas, to the developing world. 'Atoms for Peace' spawned many developments, including the establishment of the International Atomic Energy Agency, and eventually the Nuclear Non-Proliferation Treaty. While 'Atoms for Peace', as well as the institutions it created, has come under fire in recent years, it is hard to imagine what the world would have been like without it. Largely through the international Atomic Energy Agency, nations around the world have participated in research and development programs, including the use of nuclear energy in important civilian applications. Nuclear electric power accounts for nearly one-fifth of the world's electricity - reducing global tensions by replacing oil in many applications, and providing much of the world's electricity that is generated without the release of greenhouse gases or other destructive emissions. Many other nuclear and radiation-related technologies, especially radiopharmaceuticals and medical advances involving radiation, have resulted in large part from research spawned by 'Atoms for Peace'. Millions of lives have been saved in the process. While the 'nuclear dilemma' remains a challenge almost as complex as it was fifty years ago, the

Elementary School-Based Influenza Vaccination: Evaluating Impact on Respiratory Illness Absenteeism and Laboratory-Confirmed Influenza

Science.gov (United States)

Kjos, Sonia A.; Irving, Stephanie A.; Meece, Jennifer K.; Belongia, Edward A.

2013-01-01

Background Studies of influenza vaccine effectiveness in schools have assessed all-cause absenteeism rather than laboratory-confirmed influenza. We conducted an observational pilot study to identify absences due to respiratory illness and laboratory-confirmed influenza in schools with and without school-based vaccination. Methods A local public health agency initiated school-based influenza vaccination in two Wisconsin elementary schools during October 2010 (exposed schools); two nearby schools served as a comparison group (non-exposed schools). Absences due to fever or cough illness were monitored for 12 weeks. During the 4 weeks of peak influenza activity, parents of absent children with fever/cough illness were contacted and offered influenza testing. Results Parental consent for sharing absenteeism data was obtained for 937 (57%) of 1,640 students. Fifty-two percent and 28%, respectively, of all students in exposed and non-exposed schools were vaccinated. Absences due to fever or cough illness were significantly lower in the exposed schools during seven of 12 surveillance weeks. Twenty-seven percent of students at exposed schools and 39% at unexposed schools had one or more days of absence due to fever/cough illness (pabsenteeism due to fever or cough illness, but not absenteeism for other reasons. Although nonspecific, absence due to fever or cough illness may be a useful surrogate endpoint in school-based studies if identification of laboratory confirmed influenza is not feasible. PMID:23991071

Tied Up In Knots: Irony, Ambiguity, and the 'Difficult' Pleasures of FIFTY SHADES OF GREY

OpenAIRE

McCulloch, Richard

2016-01-01

Upon its release in February 2015, Sam Taylor-Johnson’s Fifty Shades of Grey met with vehement critical derision, finding itself reproached on both artistic and ideological grounds. While the precise focus of this indignation varied between reviews, complaints broadly fell into three categories: (1) it isn’t titillating enough (2) it\\ud is misogynistic, and (3) the love story and characters are clichéd and unrealistic.\\ud \\ud In this article, however, I demonstrate that the film is far more s...

Evaluation of biological endpoints in crop plants after exposure to non-steroidal anti-inflammatory drugs (NSAIDs): implications for phytotoxicological assessment of novel contaminants.

Science.gov (United States)

Schmidt, Wiebke; Redshaw, Clare H

2015-02-01

Human pharmaceuticals have been detected in the terrestrial environment at µg to mg kg(-1) concentrations. Repeated application of sewage sludge (biosolids) and increasing reclaimed wastewater use for irrigation could lead to accumulation of these novel contaminants in soil systems. Despite this, potential phytotoxicological effects on higher plants have rarely been evaluated. These studies aimed to test effects upon germination, development, growth and physiology of two crop plants, namely radish (Raphanus sativus Spakler 3) and lettuce (Lactuca sativa All Year Around), after exposure to different, but structurally related non-steroidal anti-inflammatory drugs (NSAIDs) at environmentally relevant concentrations. A range of biological endpoints comprising biomass, length, water content, specific root and shoot length, root to shoot ratio, daily progress of stages of cell elongation and organ emergence (primary root, hypocotyl elongation, cotyledon emergence, cotyledon opening, and no change), as well as photosynthetic measurements were evaluated. Compounds from the fenamic acid class were found to affect R. sativus root endpoints (root length and water content), while ibuprofen affected early root development of L. sativa. In general, phytotoxicological effects on root endpoints demonstrated that impacts upon higher plants are not only compound specific, but also differ between plant species. It was found that the usage of a wide range of biological endpoints (all simple, cost-effective and ecologically relevant) were beneficial in detecting differences in plant responses to NSAID exposure. Due to paucity and discrepancy within the few previously available phytotoxicological studies with pharmaceuticals, it is now essential to allocate time and resources to consider development of suitable chronic toxicity tests, and some suggestions regarding this are presented. Copyright © 2014 Elsevier Inc. All rights reserved.

Celebrating fifty years of research and applications in reminiscence and life review: State of the art and new directions

NARCIS (Netherlands)

Westerhof, Gerben Johan; Bohlmeijer, Ernst Thomas

2014-01-01

Fifty years ago, psychiatrist Robert Butler (1963) published an influential article on the recollection and evaluation of personal memories in later life. We discuss the major insights and applications in psychological gerontology that were inspired by Butler. Reminiscence and life review serve to

The anomaly of Marquesan ceramics : a fifty year retrospective

International Nuclear Information System (INIS)

Allen, M.S.; Dickinson, W.R.; Huebert, J.M.

2012-01-01

Fifty years ago pioneering archaeologist Robert Suggs reported a small number of pottery sherds from the Marquesas Islands. The first such finds in East Polynesia, at the time they were considered indicative of both a Marquesan homeland and local ceramic manufacture. In the intervening years, additional sherds have been recovered from three other Marquesan localities resulting in a total of 14 specimens. Prior petrographic studies demonstrate unambiguously that some derive from Fiji. Others have been interpreted historically as representative of an indigenous Marquesan ceramic industry. Here we bring together key petrographic analyses from Polynesia, recent chronological assessments of the Marquesan sequence, and insights from new field research to reassess the origins and chronology of Marquesan pottery. We suggest that there is little support for an indigenous Marquesan ceramic industry, and most likely all of the specimens are imports. With respect to the timing of ceramic arrivals, three hypotheses are explored: 1) with founding settlers, 2) as a component of long-distance exchange networks operating between the 12th to 16th centuries AD, or 3) as late prehistoric or historic imports. The preponderance of evidence points to the second alternative, although the other two cannot be completely discounted for the assemblage as a whole. (author). 63 refs., 5 figs., 3 tabs.

Transgenerational endpoints provide increased sensitivity and insight into multigenerational responses of Lymnaea stagnalis exposed to cadmium.

Science.gov (United States)

Reátegui-Zirena, Evelyn G; Fidder, Bridgette N; Olson, Adric D; Dawson, Daniel E; Bilbo, Thomas R; Salice, Christopher J

2017-05-01

Ecotoxicology provides data to inform environmental management. Many testing protocols do not consider offspring fitness and toxicant sensitivity. Cadmium (Cd) is a well-studied and ubiquitous toxicant but little is known about the effects on offspring of exposed parents (transgenerational effects). This study had three objectives: to identify endpoints related to offspring performance; to determine whether parental effects would manifest as a change in Cd tolerance in offspring and how parental exposure duration influenced the manifestation of parental effects. Adult snails were exposed to Cd 0, 25, 50, 100, 200 and 400 μg Cd/L for eight weeks. There were effects on adult endpoints (e.g., growth, reproduction) but only at the highest concentrations (>100 μg/L). Alternatively, we observed significant transgenerational effects at all Cd concentrations. Surprisingly, we found increased Cd tolerance in hatchlings from all parental Cd exposure concentrations even though eggs and hatchlings were in Cd-free conditions for 6 weeks. Explicit consideration of offspring performance adds value to current toxicity testing protocols. Parental exposure duration has important implications for offspring effects and that contaminant concentrations that are not directly toxic to parents can cause transgenerational changes in resistance that have significant implications for toxicity testing and adaptive responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

EnviroAtlas - Des Moines, IA - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - Green Bay, WI - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - New York, NY - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

EnviroAtlas - New Bedford, MA - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

Application of process analytical technology for monitoring freeze-drying of an amorphous protein formulation: use of complementary tools for real-time product temperature measurements and endpoint detection.

Science.gov (United States)

Schneid, Stefan C; Johnson, Robert E; Lewis, Lavinia M; Stärtzel, Peter; Gieseler, Henning

2015-05-01

Process analytical technology (PAT) and quality by design have gained importance in all areas of pharmaceutical development and manufacturing. One important method for monitoring of critical product attributes and process optimization in laboratory scale freeze-drying is manometric temperature measurement (MTM). A drawback of this innovative technology is that problems are encountered when processing high-concentrated amorphous materials, particularly protein formulations. In this study, a model solution of bovine serum albumin and sucrose was lyophilized at both conservative and aggressive primary drying conditions. Different temperature sensors were employed to monitor product temperatures. The residual moisture content at primary drying endpoints as indicated by temperature sensors and batch PAT methods was quantified from extracted sample vials. The data from temperature probes were then used to recalculate critical product parameters, and the results were compared with MTM data. The drying endpoints indicated by the temperature sensors were not suitable for endpoint indication, in contrast to the batch methods endpoints. The accuracy of MTM Pice data was found to be influenced by water reabsorption. Recalculation of Rp and Pice values based on data from temperature sensors and weighed vials was possible. Overall, extensive information about critical product parameters could be obtained using data from complementary PAT tools. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

40 CFR 60.1445 - What are the emission limits for air curtain incinerators that burn 100 percent yard waste?

Science.gov (United States)

2010-07-01

... curtain incinerators that burn 100 percent yard waste? 60.1445 Section 60.1445 Protection of Environment... Air Curtain Incinerators That Burn 100 Percent Yard Waste § 60.1445 What are the emission limits for air curtain incinerators that burn 100 percent yard waste? If your air curtain incinerator combusts...

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African Journals Online (AJOL)

Mr Olusoji

Conclusion: Fifty four percent of the participants would not accept blood transfusion in pregnancy, however, if it ... Global Burden of Disease 2000 considered only ... pregnancy; and 45% percent were agreeable to blood .... and Child Count.

Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema

NARCIS (Netherlands)

Lassere, Marissa N.; Johnson, Kent R.; Boers, Maarten; Tugwell, Peter; Brooks, Peter; Simon, Lee; Strand, Vibeke; Conaghan, Philip G.; Ostergaard, Mikkel; Maksymowych, Walter P.; Landewe, Robert; Bresnihan, Barry; Tak, Paul-Peter; Wakefield, Richard; Mease, Philip; Bingham, Clifton O.; Hughes, Michael; Altman, Doug; Buyse, Marc; Galbraith, Sally; Wells, George

2007-01-01

OBJECTIVE: There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to

40 CFR 62.15375 - What are the emission limits for air curtain incinerators that burn 100 percent yard waste?

Science.gov (United States)

2010-07-01

... curtain incinerators that burn 100 percent yard waste? 62.15375 Section 62.15375 Protection of Environment... Combustion Units Constructed on or Before August 30, 1999 Air Curtain Incinerators That Burn 100 Percent Yard Waste § 62.15375 What are the emission limits for air curtain incinerators that burn 100 percent yard...

40 CFR 62.15380 - How must I monitor opacity for air curtain incinerators that burn 100 percent yard waste?

Science.gov (United States)

2010-07-01

... curtain incinerators that burn 100 percent yard waste? 62.15380 Section 62.15380 Protection of Environment... Combustion Units Constructed on or Before August 30, 1999 Air Curtain Incinerators That Burn 100 Percent Yard Waste § 62.15380 How must I monitor opacity for air curtain incinerators that burn 100 percent yard...

40 CFR 60.1920 - What are the emission limits for air curtain incinerators that burn 100 percent yard waste?

Science.gov (United States)

2010-07-01

... curtain incinerators that burn 100 percent yard waste? 60.1920 Section 60.1920 Protection of Environment... or Before August 30, 1999 Model Rule-Air Curtain Incinerators That Burn 100 Percent Yard Waste § 60.1920 What are the emission limits for air curtain incinerators that burn 100 percent yard waste? If...

CRED Cumulative Map of Percent Scleractinian Coral Cover at Kure Atoll, 2002-2004

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Laysan Island, 2002-2004

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Palmyra Atoll, 2002-2004

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Lisianski Island, 2001-2004

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Maro Reef, 2001-2004

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Baker Island, 2002-2004

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

Does One Know the Properties of a MICE Solid or Liquid Absorber to Better than 0.3 Percent?

International Nuclear Information System (INIS)

Green, Michael A.; Yang, Stephanie Q.

2006-01-01

This report discusses the report discusses whether the MICE absorbers can be characterized to ±0.3 percent, so that one predict absorber ionization cooling within the absorber. This report shows that most solid absorbers can be characterized to much better than ±0.3 percent. The two issues that dominate the characterization of the liquid cryogen absorbers are the dimensions of the liquid in the vessel and the density of the cryogenic liquid. The thickness of the window also plays a role. This report will show that a liquid hydrogen absorber can be characterized to better than ±0.3 percent, but a liquid helium absorber cannot be characterized to better and ±1 percent

40 CFR 60.1450 - How must I monitor opacity for air curtain incinerators that burn 100 percent yard waste?

Science.gov (United States)

2010-07-01

... curtain incinerators that burn 100 percent yard waste? 60.1450 Section 60.1450 Protection of Environment... Air Curtain Incinerators That Burn 100 Percent Yard Waste § 60.1450 How must I monitor opacity for air curtain incinerators that burn 100 percent yard waste? (a) Use EPA Reference Method 9 in appendix A of...

40 CFR 60.1925 - How must I monitor opacity for air curtain incinerators that burn 100 percent yard waste?

Science.gov (United States)

2010-07-01

... curtain incinerators that burn 100 percent yard waste? 60.1925 Section 60.1925 Protection of Environment... or Before August 30, 1999 Model Rule-Air Curtain Incinerators That Burn 100 Percent Yard Waste § 60.1925 How must I monitor opacity for air curtain incinerators that burn 100 percent yard waste? (a) Use...

Venice: Fifty years after the great flood of November 4, 1966

Science.gov (United States)

Rizzoli, P. M.

2017-12-01

Fifty years ago Venice and its lagoon suffered the most devastating flood in their millennial history. The causes of the increasingly recurring floods will be examined, namely the man-induced subsidence in the period 1925-1970 and the storm surges of the Adriatic sea. The engineering solution designed for their protection , named the MOSE system, will be discussed in detail. The MOSE was started in 2003 and is near completion. It consists of four barriers , invisible in normal conditions, which will close the inlets to the lagoon under the prediction of a forthcoming flood. Finally, the perspective of the MOSE capability of protecting the city under scenarios of future global sea level rise will be assessed. This assessment must critically take into account that Venice and its lagoon are confined in the northernmost corner of the semi-enclosed, marginal Mediterranean sea for which the uncertainties of future sea level rise greatly exceed the uncertainties of the global averages.

What makes a champion! over fifty extraordinary individuals share their insights

CERN Document Server

2014-01-01

What drives great and successful individuals — be they athletes, artists, or scientists — or businesses, to achieve the extraordinary? Over fifty champions from all walks of life, brought together by Allan Snyder, draw on their experiences to explore the secrets of success in this inspiring, revealing and thought-provoking book. Hear from the authors what made a McDonalds' branch become the most successful in the world; how a cottage business is catapulted into a world brand; how a visual artist's works crosses almost every medium imaginable; how an Ernst and Young setup becomes a top-notch employer; or why many geniuses or brilliant individuals never become champions, while many 'ordinary' individuals do; why many people don't know about their talent; what constitutes a champion outcome; and the neurological explanation for championship. Straddling academia and practitioners in all fields — government, entertainment, sports, business, arts, education, medicine, media — the authors include business...

Comparison of content in phenolic compounds, polyphenol oxidase and peroxidase in grains of fifty sorghum cultivars from Burkina Faso.

NARCIS (Netherlands)

Dicko, M.H.; Hilhorst, M.H.; Gruppen, H.; Traore, A.S.; Laane, N.C.M.; Berkel, van W.J.H.; Voragen, A.G.J.

2002-01-01

Analysis of fifty sorghum [Sorghum bicolor (L.) Moench] varieties used in Burkina Faso showed that they have different contents of phenolic compounds, peroxidase (POX), and polyphenol oxidase (PPO). Most of the varieties (82%) had a tannin content less than 0.25% (w/w). POX specific activity was

Basal area or stocking percent: which works best in controlling density in natural shortleaf pine stands

Science.gov (United States)

Ivan L. Sander

1986-01-01

Results from a shortleaf pine thinning study in Missouri show that continually thinning a stand to the same basal area will eventually create an understocked stand and reduce yields. Using stocking percent to control thinning intensity allows basal area to increase as stands get older. The best yield should occur when shortleaf pine is repeatedly thinned to 60 percent...

Log-gamma directed polymer with fixed endpoints via the replica Bethe Ansatz

International Nuclear Information System (INIS)

Thiery, Thimothée; Le Doussal, Pierre

2014-01-01

We study the model of a discrete directed polymer (DP) on a square lattice with homogeneous inverse gamma distribution of site random Boltzmann weights, introduced by Seppalainen (2012 Ann. Probab. 40 19–73). The integer moments of the partition sum, Z n -bar , are studied using a transfer matrix formulation, which appears as a generalization of the Lieb–Liniger quantum mechanics of bosons to discrete time and space. In the present case of the inverse gamma distribution the model is integrable in terms of a coordinate Bethe Ansatz, as discovered by Brunet. Using the Brunet-Bethe eigenstates we obtain an exact expression for the integer moments of Z n -bar for polymers of arbitrary lengths and fixed endpoint positions. Although these moments do not exist for all integer n, we are nevertheless able to construct a generating function which reproduces all existing integer moments and which takes the form of a Fredholm determinant (FD). This suggests an analytic continuation via a Mellin–Barnes transform and we thereby propose a FD ansatz representation for the probability distribution function (PDF) of Z and its Laplace transform. In the limit of a very long DP, this ansatz yields that the distribution of the free energy converges to the Gaussian unitary ensemble (GUE) Tracy-Widom distribution up to a non-trivial average and variance that we calculate. Our asymptotic predictions coincide with a result by Borodin et al (2013 Commun. Math. Phys. 324 215–32) based on a formula obtained by Corwin et al (2011 arXiv:1110.3489) using the geometric Robinson–Schensted–Knuth (gRSK) correspondence. In addition we obtain the dependence on the endpoint position and the exact elastic coefficient at a large time. We argue the equivalence between our formula and that of Borodin et al. As we will discuss, this provides a connection between quantum integrability and tropical combinatorics. (paper)

The Research of Dr. Joanne Simpson: Fifty Years Investigating Hurricanes, Tropical Clouds and Cloud Systems

Science.gov (United States)

Tao, W. -K.; Halverson, J.; Adler, R.; Garstang, M.; Houze, R., Jr.; LeMone, M.; Pielke, R., Sr.; Woodley, W.; O'C.Starr, David (Technical Monitor)

2001-01-01

This AMS Meteorological Monographs is dedicated to Dr. Joanne Simpson for her many pioneering research efforts in tropical meteorology during her fifty-year career. Dr. Simpson's major areas of scientific research involved the "hot tower" hypothesis and its role in hurricanes, structure and maintenance of trade winds, air-sea interaction, and observations and the mechanism for hurricanes and waterspouts. She was also a pioneer in cloud modeling with the first one-dimensional model and had the first cumulus model on a computer. She also played a major role in planning and leading observational experiments on convective cloud systems. The launch of the Tropical Rainfall Measuring Mission (TRMM) satellite, a joint U.S.-Japan project, in November of 1997 made it possible for quantitative measurements of tropical rainfall to be obtained on a continuous basis over the entire global tropics. Dr. Simpson was the TRAM Project Scientist from 1986 until its launch in 1997. Her efforts during this crucial period ensured that the mission was both well planned scientifically and well engineered as well as within budget. In this paper, Dr. J. Simpson's nine specific accomplishments during her fifty-year career: (1) hot tower hypothesis, (2) hurricanes, (3) airflow and clouds over heated islands, (4) cloud models, (5) trade winds and their role in cumulus development, (6) air-sea interaction, (7) cloud-cloud interactions and mergers, (8) waterspouts, and (9) TRMM science, will be described and discussed.

TEM investigation of irradiated U-7 weight percent Mo dispersion fuel

International Nuclear Information System (INIS)

Van den Berghe, S.

2009-01-01

In the FUTURE experiment, fuel plates containing U-7 weight percent Mo atomized powder were irradiated in the BR2 reactor. At a burn-up of approximately 33 percent 235 U (6.5 percent FIMA or 1.41 10 21 fissions/cm 3 meat), the fuel plates showed an important deformation and the irradiation was stopped. The plates were submitted to detailed PIE at the Laboratory for High and Medium level Activity. The results of these examinations were reported in the scientific report of last year and published in open literature. Since then, the microstructural aspects of the FUTURE fuel were studied in more detail using transmission electron microscopy (TEM), in an attempt to understand the nature of the interaction phase and the fission gas behavior in the atomized U(Mo) fuel. The FUTURE experiment is regarded as the definitive proof that the classical atomized U(Mo) dispersion fuel is not stable under irradiation, at least in the conditions required for normal operation of plate-type fuel. The main cause for the instability was identified to be the irradiation behavior of the U(Mo)-Al interaction phase which is formed between the U(Mo) particles and the pure aluminum matrix during irradiation. It is assumed to become amorphous under irradiation and as such cannot retain the fission gas in stable bubbles. As a consequence, gas filled voids are generated between the interaction layer and the matrix, resulting in fuel plate pillowing and failure. The objective of the TEM investigation was the confirmation of this assumption of the amorphisation of the interaction phase. A deeper understanding of the actual nature of this layer and the fission gas behaviour in these fuels in general can allow a more oriented search for a solution to the fuel failures

Patient-reported outcomes in insomnia: development of a conceptual framework and endpoint model.

Science.gov (United States)

Kleinman, Leah; Buysse, Daniel J; Harding, Gale; Lichstein, Kenneth; Kalsekar, Anupama; Roth, Thomas

2013-01-01

This article describes qualitative research conducted with patients with clinical diagnoses of insomnia and focuses on the development of a conceptual framework and endpoint model that identifies a hierarchy and interrelationships of potential outcomes in insomnia research. Focus groups were convened to discuss how patients experience insomnia and to generate items for patient-reported questionnaires on insomnia and associated daytime consequences. Results for the focus group produced two conceptual frameworks: one for sleep and one for daytime impairment. Each conceptual framework consists of hypothesized domains and items in each domain based on patient language taken from the focus group. These item pools may ultimately serve as a basis to develop new questionnaires to assess insomnia.

40 CFR 63.5885 - How do I calculate percent reduction to demonstrate compliance for continuous lamination/casting...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 12 2010-07-01 2010-07-01 true How do I calculate percent reduction to... Pollutants: Reinforced Plastic Composites Production Testing and Initial Compliance Requirements § 63.5885 How do I calculate percent reduction to demonstrate compliance for continuous lamination/casting...

"Double crap!" abuse and harmed identity in Fifty Shades of Grey.

Science.gov (United States)

Bonomi, Amy E; Altenburger, Lauren E; Walton, Nicole L

2013-09-01

While intimate partner violence (IPV) affects 25% of women and impairs health, current societal conditions-including the normalization of abuse in popular culture such as novels, film, and music-create the context to support such violence. Fifty Shades of Grey, a best-selling novel, depicts a "romantic" and "erotic" relationship involving 28-year-old megamillionaire, Christian Grey, and a 22-year-old college student, Anastasia Steele. We argue that the relationship is characterized by IPV, which is harmful to Anastasia. All authors engaged in iterative readings of the text, and wrote narrative summaries to elucidate themes. Validity checks included double review of the first eight chapters of the novel to establish consistency in our analysis approach, iterative discussions in-person and electronically to arbitrate discrepancies, and review of our analysis with other abuse and sexual practice experts. To characterize IPV, we used the U.S. Centers for Disease Control and Prevention's definitions of emotional abuse (intimidation/threats; isolation; stalking; and humiliation) and sexual violence (forced sex acts/contact against a person's will, including using alcohol/drugs or intimidation/pressure). To characterize harm, we used Smith's conceptualizations of perceived threat, managing, altered identity, yearning, entrapment, and disempowerment experienced by abused women. Emotional abuse is present in nearly every interaction, including: stalking (Christian deliberately follows Anastasia and appears in unusual places, uses a phone and computer to track Anastasia's whereabouts, and delivers expensive gifts); intimidation (Christian uses intimidating verbal and nonverbal behaviors, such as routinely commanding Anastasia to eat and threatening to punish her); and isolation (Christian limits Anastasia's social contact). Sexual violence is pervasive-including using alcohol to compromise Anastasia's consent, as well as intimidation (Christian initiates sexual encounters

A model for growth of beta-phase particles in zirconium-2.5 wt percent niobium

International Nuclear Information System (INIS)

Chow, C.K.; Liner, Y.; Rigby, G.L.

1984-08-01

The kinetics of the α → β phase change in Zr-2.5 percent Nb pressure-tube material at constant temperature have been studied. The volume-fraction change of the β phase due to diffusion in an infinite α-phase matrix was considered, and a mathematical model with a numerical solution was developed to predict the transient spherical growth of the β-phase region. This model has been applied to Zr-2.5 wt percent Nb, and the calculated results compared to experiment

26 CFR 1.46-9 - Requirements for taxpayers electing an extra one-half percent additional investment credit.

Science.gov (United States)

2010-04-01

... percent additional investment credit for property described in section 46(a)(2)(D). Paragraph (c) of this...-half percent additional investment credit. 1.46-9 Section 1.46-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY INCOME TAX INCOME TAXES Rules for Computing Credit for Investment in...

Environmentally acceptable endpoints for PAHs at a manufactured gas plant site

Energy Technology Data Exchange (ETDEWEB)

Stroo, H.F.; Jensen, R.; Loehr, R.C.; Nakles, D.V.; Fairbrother, A.; Liban, C.B. [ThermoRetec Corp., Carson, CA (USA)

2000-09-01

Samples from a former manufactured gas plant (MGP) site in Santa Barbara, CA were tested to evaluate the environmentally acceptable endpoints (EAE) process for setting risk-based cleanup criteria. The research was part of an ongoing effort to develop and demonstrate a protocol for assessing risk-based criteria for MGP sites that incorporates the availability of polycyclic aromatic hydrocarbons (PAHs). Six soil samples were subjected to a battery of physical and biological tests that focused on determining the 'availability' of the soil-bound contaminants to groundwater, ecological receptors, and human receptors. Results demonstrated that sorption to soil, matrix effects, aging, and treatment can significantly reduce chemical availability. Including these reduced availability results in risk assessment calculations yielded environmentally protective cleanup levels almost 3-10 times greater than levels derived using California default risk assessment assumptions. Using an EAE-based approach for MGP soils, especially those containing lampblack, could provide more realistic risk assessment. 23 refs., 6 tabs.

How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

Directory of Open Access Journals (Sweden)

Carolin Vegvari

Full Text Available Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements.

Importance of soil-water relation in assessment endpoint in bioremediated soils: Plant growth and soil physical properties

International Nuclear Information System (INIS)

Li, X.; Sawatsky, N.

1995-01-01

Much effort has been focused on defining the end-point of bioremediated soils by chemical analysis (Alberta Tier 1 or CCME Guideline for Contaminated Soils) or toxicity tests. However, these tests do not completely assess the soil quality, or the capability of soil to support plant growth after bioremediation. This study compared barley (Hordeum vulgare) growth on: (i) non-contaminated, agricultural topsoil, (2) oil-contaminated soil (4% total extractable hydrocarbons, or TEH), and (3) oil-contaminated soil treated by bioremediation (< 2% TEH). Soil physical properties including water retention, water uptake, and water repellence were measured. The results indicated that the growth of barley was significantly reduced by oil-contamination of agricultural topsoil. Furthermore, bioremediation did not improve the barley yield. The lack of effects from bioremediation was attributed to development of water repellence in hydrocarbon contaminated soils. There seemed to be a critical water content around 18% to 20% in contaminated soils. Above this value the water uptake by contaminated soil was near that of the agricultural topsoil. For lower water contents, there was a strong divergence in sorptivity between contaminated and agricultural topsoil. For these soils, water availability was likely the single most important parameter controlling plant growth. This parameter should be considered in assessing endpoint of bioremediation for hydrocarbon contaminated soils

Examination of temperature-induced shape memory of uranium--5.3-to 6.9 weight percent niobium alloys

International Nuclear Information System (INIS)

Hemperly, V.C.

1976-01-01

The uranium-niobium alloy system was examined in the range of 5.3-to-6.9 weight percent niobium with respect to shape memory, mechanical properties, metallography, Coefficients of linear thermal expansion, and differential thermal analysis. Shape memory increased with increasing niobium levels in the study range. There were no useful correlations found between shape memory and the other tests. Coefficients of linear thermal expansion tests of as-quenched 5.8 and 6.2 weight percent niobium specimens, but not 5.3 and 6.9 weight percent niobium specimens, had a contraction component on heating, but the phenomenon was not a contributor to shape memory

Development and Cross-Validation of Equation for Estimating Percent Body Fat of Korean Adults According to Body Mass Index

Directory of Open Access Journals (Sweden)

Hoyong Sung

2017-06-01

Full Text Available Background : Using BMI as an independent variable is the easiest way to estimate percent body fat. Thus far, few studies have investigated the development and cross-validation of an equation for estimating the percent body fat of Korean adults according to the BMI. The goals of this study were the development and cross-validation of an equation for estimating the percent fat of representative Korean adults using the BMI. Methods : Samples were obtained from the Korea National Health and Nutrition Examination Survey between 2008 and 2011. The samples from 2008-2009 and 2010-2011 were labeled as the validation group (n=10,624 and the cross-validation group (n=8,291, respectively. The percent fat was measured using dual-energy X-ray absorptiometry, and the body mass index, gender, and age were included as independent variables to estimate the measured percent fat. The coefficient of determination (R², standard error of estimation (SEE, and total error (TE were calculated to examine the accuracy of the developed equation. Results : The cross-validated R² was 0.731 for Model 1 and 0.735 for Model 2. The SEE was 3.978 for Model 1 and 3.951 for Model 2. The equations developed in this study are more accurate for estimating percent fat of the cross-validation group than those previously published by other researchers. Conclusion : The newly developed equations are comparatively accurate for the estimation of the percent fat of Korean adults.

Food Safety: Recommendations for Determining Doneness in Consumer Egg Dish Recipes and Measurement of Endpoint Temperatures When Recipes Are Followed

Directory of Open Access Journals (Sweden)

Sandria Godwin

2016-06-01

Full Text Available Many consumers do not follow recommended food safety practices for cooking egg dishes, such as pies, quiches, and casseroles, potentially leading to foodborne illnesses such as Salmonellosis. The United States Department of Agriculture (USDA recommends cooking egg mixtures until the center reaches 71 °C (160 °F. The objectives of this study were to determine what endpoint temperature information consumers receive from egg dish recipes, and if recipes would lead to safe temperatures when followed. Egg dish recipes (n = 226 from 65 websites, 50 cookbooks, and nine magazine titles (multiple issues of each were analyzed. Time was the most frequently used indicator, given in 92% of the recipes, with 15% using only time. Other indicators included: set (89, browned (76, clean toothpick/knife (60, puffed (27, and jiggled (13. Only two recipes indicated final endpoint temperatures. Three recipes (a pie, a quiche, and an egg casserole were chosen and prepared in triplicate to see if they would reach recommended temperatures. The pie and quiche were still liquid at 71 °C, and were well over the recommended temperature when cooked according to instructions, but the egg casserole was not consistently above 71 °C, when the recipe instructions indicated it was done and the center was light brown and “jiggled” This research indicates that consumers are not receiving information on endpoint temperatures in egg recipes, but the likelihood of foodborne illness is low since most dishes probably be cooked past the recommended temperature before the consumer considers them done unless there are many inclusions that may absorb liquid and reduce the appearance of liquid in the dish.

Food Safety: Recommendations for Determining Doneness in Consumer Egg Dish Recipes and Measurement of Endpoint Temperatures When Recipes Are Followed

Science.gov (United States)

Godwin, Sandria; Maughan, Curtis; Chambers, Edgar

2016-01-01

Many consumers do not follow recommended food safety practices for cooking egg dishes, such as pies, quiches, and casseroles, potentially leading to foodborne illnesses such as Salmonellosis. The United States Department of Agriculture (USDA) recommends cooking egg mixtures until the center reaches 71 °C (160 °F). The objectives of this study were to determine what endpoint temperature information consumers receive from egg dish recipes, and if recipes would lead to safe temperatures when followed. Egg dish recipes (n = 226) from 65 websites, 50 cookbooks, and nine magazine titles (multiple issues of each) were analyzed. Time was the most frequently used indicator, given in 92% of the recipes, with 15% using only time. Other indicators included: set (89), browned (76), clean toothpick/knife (60), puffed (27), and jiggled (13). Only two recipes indicated final endpoint temperatures. Three recipes (a pie, a quiche, and an egg casserole) were chosen and prepared in triplicate to see if they would reach recommended temperatures. The pie and quiche were still liquid at 71 °C, and were well over the recommended temperature when cooked according to instructions, but the egg casserole was not consistently above 71 °C, when the recipe instructions indicated it was done and the center was light brown and “jiggled” This research indicates that consumers are not receiving information on endpoint temperatures in egg recipes, but the likelihood of foodborne illness is low since most dishes probably be cooked past the recommended temperature before the consumer considers them done unless there are many inclusions that may absorb liquid and reduce the appearance of liquid in the dish. PMID:28231140

Food Safety: Recommendations for Determining Doneness in Consumer Egg Dish Recipes and Measurement of Endpoint Temperatures When Recipes Are Followed.

Science.gov (United States)

Godwin, Sandria; Maughan, Curtis; Chambers, Edgar

2016-06-23

Many consumers do not follow recommended food safety practices for cooking egg dishes, such as pies, quiches, and casseroles, potentially leading to foodborne illnesses such as Salmonellosis. The United States Department of Agriculture (USDA) recommends cooking egg mixtures until the center reaches 71 °C (160 °F). The objectives of this study were to determine what endpoint temperature information consumers receive from egg dish recipes, and if recipes would lead to safe temperatures when followed. Egg dish recipes ( n = 226) from 65 websites, 50 cookbooks, and nine magazine titles (multiple issues of each) were analyzed. Time was the most frequently used indicator, given in 92% of the recipes, with 15% using only time. Other indicators included: set (89), browned (76), clean toothpick/knife (60), puffed (27), and jiggled (13). Only two recipes indicated final endpoint temperatures. Three recipes (a pie, a quiche, and an egg casserole) were chosen and prepared in triplicate to see if they would reach recommended temperatures. The pie and quiche were still liquid at 71 °C, and were well over the recommended temperature when cooked according to instructions, but the egg casserole was not consistently above 71 °C, when the recipe instructions indicated it was done and the center was light brown and "jiggled" This research indicates that consumers are not receiving information on endpoint temperatures in egg recipes, but the likelihood of foodborne illness is low since most dishes probably be cooked past the recommended temperature before the consumer considers them done unless there are many inclusions that may absorb liquid and reduce the appearance of liquid in the dish.

Forest ownership dynamics of southern forests

Science.gov (United States)

Brett J. Butler; David N. Wear

2013-01-01

Key FindingsPrivate landowners hold 86 percent of the forest area in the South; two-thirds of this area is owned by families or individuals.Fifty-nine percent of family forest owners own between 1 and 9 acres of forest land, but 60 percent of family-owned forests are in holdings of 100 acres or more.Two-...

Women, Work and Age: A Report on Older Women and Employment.

Science.gov (United States)

Stentzel, Cathy; Steenland, Sally, Ed.

Fifty-four percent of all midlife and older American women are in the work force. Like their younger counterparts, most older women work in nonprofessional occupations. Regardless of their age, working women earn less than men. Sixty-five percent of working women aged 45 to 64 are married; 30 percent are widowed, divorced, or separated; and 5…

EnviroAtlas - Minneapolis/St. Paul, MN - Estimated Percent Tree Cover Along Walkable Roads

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates tree cover along walkable roads. The road width is estimated for each road and percent tree cover is calculated in a 8.5 meter...

A PHYSIOLOGICALLY BASED COMPUTATIONAL MODEL OF THE BPG AXIS IN FATHEAD MINNOWS: PREDICTING EFFECTS OF ENDOCRINE DISRUPTING CHEMICAL EXPOSURE ON REPRODUCTIVE ENDPOINTS

Science.gov (United States)

This presentation describes development and application of a physiologically-based computational model that simulates the brain-pituitary-gonadal (BPG) axis and other endpoints important in reproduction such as concentrations of sex steroid hormones, 17-estradiol, testosterone, a...

End-point detection in potentiometric titration by continuous wavelet transform.

Science.gov (United States)

Jakubowska, Małgorzata; Baś, Bogusław; Kubiak, Władysław W

2009-10-15

The aim of this work was construction of the new wavelet function and verification that a continuous wavelet transform with a specially defined dedicated mother wavelet is a useful tool for precise detection of end-point in a potentiometric titration. The proposed algorithm does not require any initial information about the nature or the type of analyte and/or the shape of the titration curve. The signal imperfection, as well as random noise or spikes has no influence on the operation of the procedure. The optimization of the new algorithm was done using simulated curves and next experimental data were considered. In the case of well-shaped and noise-free titration data, the proposed method gives the same accuracy and precision as commonly used algorithms. But, in the case of noisy or badly shaped curves, the presented approach works good (relative error mainly below 2% and coefficients of variability below 5%) while traditional procedures fail. Therefore, the proposed algorithm may be useful in interpretation of the experimental data and also in automation of the typical titration analysis, specially in the case when random noise interfere with analytical signal.

Austrian Business Cycle Theory: Are 100 Percent Reserves Sufficient to Prevent a Business Cycle?

Directory of Open Access Journals (Sweden)

Philipp Bagus

2010-02-01

Full Text Available Authors in the Austrian tradition have made the credit expansion of a fractional reserve banking system as the prime cause of business cycles. Authors such as Selgin (1988 and White (1999 have argued that a solution to this problem would be a free banking system. They maintain that the competition between banks would limit the credit expansion effectively. Other authors such as Rothbard (1991 and Huerta de Soto (2006 have gone further and advocated a 100 percent reserve banking system ruling out credit expansion altogether. In this article it is argued that a 100 percent reserve system can still bring about business cycles through excessive maturity mismatching between deposits and loans.

The richness of discovery : Amoco's first fifty years in Canada (1948-1998)

International Nuclear Information System (INIS)

McKenzie-Brown, P.

1998-01-01

A review of Amoco's first fifty years of operations in Canada, including investments, discoveries, and policies was presented. While no claim is made for this attractively produced slim volume to be a definitive history, it does manage to shed light on some of the great achievements and outstanding deeds of the people behind the company. The book provides a glimpse into how Amoco contributed to the growth of the Canadian petroleum industry in diverse areas including the manufacturing sector, the petroleum service sector, oil field technology, oil field infrastructure and petrochemical development. The company enjoyed spectacular success during the 1950s and 1960s. As evidence of that success, in 1997 Amoco Canada was the largest Canadian producer and exporter of natural gas and NGLs, the largest cold producer of heavy oil, the second largest in situ producer of heavy oil, and one of the 10 largest producers of conventional oil. refs., tabs., figs

Organ Transplantation and the Uniform Anatomical Gift Act: A Fifty-Year Perspective.

Science.gov (United States)

Sadler, Blair L; Sadler, Alfred M

2018-03-01

Fifty years ago this summer, the Uniform Anatomical Gift Act was adopted by the National Conference of Commissioners on Uniform State Laws and approved by the American Bar Association. The UAGA has provided a sound and stable legal platform on which to base an effective nationwide organ donation system. The cardinal principles of altruism, autonomy, and public trust are still important. At a time when confidence and trust in our government and many private institutions has declined, maintaining trust and confidence in our health care system and its commitment to "first, do no harm" has never been more important. Any policies that override these core ethical principles could cause irreparable damage to the public's faith in our transplant system. While progress has been made to increase organ registration and the number of organs transplanted, much more must be done to realize the potential of life-saving therapy without jeopardizing ethical principles. © 2018 The Hastings Center.

German Atomic Energy Act turns fifty

International Nuclear Information System (INIS)

Schneider, Horst

2009-01-01

The German Atomic Energy Act entered into force on January 1, 1960. It turns fifty at the beginning of 2010. Is this a reason to celebrate or rather the opposite? Lawyers, in principle, can view old pieces of legislation from 2 perspectives: On the one hand, aged laws are treated in a spirit of veneration and are celebrated as proven. On the other hand, an anniversary of this kind can be a welcome reason for demands to abolish or, at least, fundamentally renew that law. Over the past half century, the German Atomic Energy Act went through stormy and varied phases both of a legal and a political character. Its 50 th anniversary is likely to spark off very conflicting evaluations as well. A review of legal history shows that the German or, rather, the Federal German Atomic Energy Act (AtG) was not a first-of-its-kind piece of legislation but stemmed from the 1957 EURATOM Treaty, in a way representing a latecomer of that treaty. The Atomic Energy Act experienced a number of important developments throughout its history: - In 1975, compulsory licensing of fuel element factories was introduced. - The back end of the fuel cycle, especially final storage, were incorporated in the Atomic Energy Act comprehensively first in 1976. - In 1985, legislators decided in favor of unlimited nuclear liability. - In 1994 and 1998, only some innovations in special items were introduced under the headings of environmental impact assessment and suitability for repository storage because the controversy about nuclear power did not permit a fundamental alignment towards a more comprehensive modern safety law. - The decision to opt out of the peaceful uses of nuclear power in 2002 drew the final line so far of decisions about directions of nuclear law in a major amendment. In parallel, the decisions by the Federal Constitutional Court and the Federal Administrative Court in the late 1970s and, above all, the 1980s provided important assistance which has remained valid to this day. What is

Cumulative percent energy deposition of photon beam incident on different targets, simulated by Monte Carlo

International Nuclear Information System (INIS)

Kandic, A.; Jevremovic, T.; Boreli, F.

1989-01-01

Monte Carlo simulation (without secondary radiation) of the standard photon interactions (Compton scattering, photoelectric absorption and pair protection) for the complex slab's geometry is used in numerical code ACCA. A typical ACCA run will yield: (a) transmission of primary photon radiation differential in energy, (b) the spectrum of energy deposited in the target as a function of position and (c) the cumulative percent energy deposition as a function of position. A cumulative percent energy deposition of photon monoenergetic beam incident on simplest and complexity tissue slab and Fe slab are presented in this paper. (author). 5 refs.; 2 figs

Evaluation of concomitant use of non-specific immunopotentiator on 172 cases of primary lung cancer (Stage III, IV) treated with radiation combined with chemotherapy

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Kimura, Shuji; Imajo, Yoshinari; Hamada, Fumio; Miyaji, Chihiro

1982-01-01

The clinical effect of concomitant use of non-specific immunopotentiator OK-432 and/or PSK was studied about 172 cases of primary lung cancer (Stage III, IV). In 91 cases in stage III, fifty percent survival period was found to be 11.5 months for 63 cases with OK-432 and/or PSK, and 7.5 months for 28 cases without immunotherapy, respectively. In 81 cases in stage IV, fifty percent survival period was found to be 6.7 months for 45 cases with OK-432 and/or PSK, and 3.3 months for 36 cases without immunotherapy, respectively. (author)

Radial growth and percent of latewood in Scots pine provenance trials in Western and Central Siberia

Directory of Open Access Journals (Sweden)

S. R. Kuzmin

2016-12-01

Full Text Available Percent of latewood of Boguchany and Suzun Scots pine climatypes has been studied in two provenance trials (place of origin and trial place. For Boguchany climatype the place of origin is south taiga of Central Siberia (Krasnoyarsk Krai, the place of trial is forest-steppe zone of Western Siberia (Novosibirsk Oblast and vice versa for Suzun climatype – forest-steppe zone of Western Siberia is the place of origin, south taiga is the place of trial. Comparison of annual average values of latewood percent of Boguchany climatype in south taiga and forest-steppe revealed the same numbers – 19 %. Annual variability of this trait in south taiga is distinctly lower and equal to 17 %, in forest-steppe – 35 %. Average annual values of latewood percent of Suzun climatype in the place of origin and trial place are close (20 and 21 %. Variability of this trait for Suzun climatype is higher than for Boguchany and equal to 23 % in south taiga and 42 % in forest-steppe. Climatic conditions in southern taiga in Central Siberia in comparison with forest-steppe in Western Siberia make differences between climatypes stronger. Differences between climatypes are expressed in different age of maximal increments of diameter, different tree ring width and latewood percent values and in different latewood reaction to weather conditions.

Hazardous waste transportation risk assessment for the US Department of Energy Environmental Restoration and Waste Management Programmatic Environmental Impact Statement -- human health endpoints

International Nuclear Information System (INIS)

Hartmann, H.M.; Policastro, A.J.; Lazaro, M.A.

1994-01-01

In this presentation, a quantitative methodology for assessing the risk associated with the transportation of hazardous waste (HW) is proposed. The focus is on identifying air concentrations of HW that correspond to specific human health endpoints

FINANCIAL PROBLEMS OF BOTTOM 40 PERCENT BUMIPUTERA IN MALAYSIA: A POSSIBLE SOLUTION THROUGH WAQF-BASED CROWDFUNDING

OpenAIRE

Abidullah ABID; Muhammad Hakimi Mohd SHAFIAI

2017-01-01

Low savings by the bottom 40 percent Bumiputera triggered low wealth accumulation and greater wealth inequality. The issue behind the low savings is the increase in food prices, taxes, and interest rates for the borrowers. In response to these problems, the Malaysian government provides cash transfer BRIM as one of redistributive measures. However, it is still not enough as many of the bottom 40 percent are neglected to avail the facility. In such circumstances, the role of community-based ca...

Choosing relevant endpoints for older breast cancer patients in clinical trials: an overview of all current clinical trials on breast cancer treatment

NARCIS (Netherlands)

de Glas, N. A.; Hamaker, M. E.; Kiderlen, M.; de Craen, A. J. M.; Mooijaart, S. P.; van de Velde, C. J. H.; van Munster, B. C.; Portielje, J. E. A.; Liefers, G. J.; Bastiaannet, E.

2014-01-01

With the ongoing ageing of western societies, the proportion of older breast cancer patients will increase. For several years, clinicians and researchers in geriatric oncology have urged for new clinical trials that address patient-related endpoints such as functional decline after treatment of

An Ode to Stuart Hall's "The Supply of Demand": The Case of Post-Secondary Education in Ontario Fifty Years Later

Science.gov (United States)

FitzGerald Murphy, Maggie

2016-01-01

Despite the fact that over fifty years have passed since its publication, Stuart Hall's article "The Supply of Demand" (1960), is remarkably relevant today. The central message that society must not be blinded by "prosperity" such that it no longer envisions and demands a better world is especially pertinent in light of the…

48 CFR 836.606-73 - Application of 6 percent architect-engineer fee limitation.

Science.gov (United States)

2010-10-01

... architect-engineer fee limitation. 836.606-73 Section 836.606-73 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Architect-Engineer Services 836.606-73 Application of 6 percent architect-engineer fee limitation...

Correlation of Hip Fracture with Other Fracture Types: Toward a Rational Composite Hip Fracture Endpoint

Science.gov (United States)

Colón-Emeric, Cathleen; Pieper, Carl F.; Grubber, Janet; Van Scoyoc, Lynn; Schnell, Merritt L; Van Houtven, Courtney Harold; Pearson, Megan; Lafleur, Joanne; Lyles, Kenneth W.; Adler, Robert A.

2016-01-01

Purpose With ethical requirements to the enrollment of lower risk subjects, osteoporosis trials are underpowered to detect reduction in hip fractures. Different skeletal sites have different levels of fracture risk and response to treatment. We sought to identify fracture sites which cluster with hip fracture at higher than expected frequency; if these sites respond to treatment similarly, then a composite fracture endpoint could provide a better estimate of hip fracture reduction. Methods Cohort study using Veterans Affairs and Medicare administrative data. Male Veterans (n=5,036,536) aged 50-99 years receiving VA primary care between1999-2009 were included. Fractures were ascertained using ICD9 and CPT codes and classified by skeletal site. Pearson correlation coefficients, logistic regression and kappa statistics, were used to describe the correlation between each fracture type and hip fracture within individuals, without regards to the timing of the events. Results 595,579 (11.8%) men suffered 1 or more fractures and 179,597 (3.6%) suffered 2 or more fractures during the time under study. Of those with one or more fractures, rib was the most common site (29%), followed by spine (22%), hip (21%) and femur (20%). The fracture types most highly correlated with hip fracture were pelvic/acetabular (Pearson correlation coefficient 0.25, p<0.0001), femur (0.15, p<0.0001), and shoulder (0.11, p<0.0001). Conclusions Pelvic, acetabular, femur, and shoulder fractures cluster with hip fractures within individuals at greater than expected frequency. If we observe similar treatment risk reductions within that cluster, subsequent trials could consider use of a composite endpoint to better estimate hip fracture risk. PMID:26151123

How "humane" is your endpoint? Refining the science-driven approach for termination of animal studies of chronic infection.

OpenAIRE

Nuno H Franco; Margarida Correia-Neves; I Anna S Olsson

2012-01-01

Public concern on issues such as animal welfare or the scientific validity and clinical value of animal research is growing, resulting in increasing regulatory demands for animal research. Abiding to the most stringent animal welfare standards, while having scientific objectives as the main priority, is often challenging. To do so, endpoints of studies involving severe, progressive diseases need to be established considering how early in the disease process the scientific objectives can be ac...

Pilot study on quantitative assessment of muscle imbalance: differences of muscle synergies, equilibrium-point trajectories, and endpoint stiffness in normal and pathological upper-limb movements.

Science.gov (United States)

Oku, Takanori; Uno, Kanna; Nishi, Tomoki; Kageyama, Masayuki; Phatiwuttipat, Pipatthana; Koba, Keitaro; Yamashita, Yuto; Murakami, Kenta; Uemura, Mitsunori; Hirai, Hiroaki; Miyazaki, Fumio; Naritomi, Hiroaki

2014-01-01

This paper proposes a novel method for assessment of muscle imbalance based on muscle synergy hypothesis and equilibrium point (EP) hypothesis of motor control. We explain in detail the method for extracting muscle synergies under the concept of agonist-antagonist (AA) muscle pairs and for estimating EP trajectories and endpoint stiffness of human upper limbs in a horizontal plane using an electromyogram. The results of applying this method to the reaching movement of one normal subject and one hemiplegic subject suggest that (1) muscle synergies (the balance among coactivation of AA muscle pairs), particularly the synergies that contributes to the angular directional kinematics of EP and the limb stiffness, are quite different between the normal subject and the hemiplegic subject; (2) the concomitant EP trajectory is also different between the normal and hemiplegic subjects, corresponding to the difference of muscle synergies; and (3) the endpoint (hand) stiffness ellipse of the hemiplegic subject becomes more elongated and orientation of the major axis rotates clockwise more than that of the normal subject. The level of motor impairment would be expected to be assessed from a comparison of these differences of muscle synergies, EP trajectories, and endpoint stiffness among normal and pathological subjects using the method.

Urban percent impervious surface and its relationship with land surface temperature in Yantai City, China

International Nuclear Information System (INIS)

Yu, Xinyang; Lu, Changhe

2014-01-01

This study investigated percent impervious surface area (PISA) extracted by a four-endmember normalized spectral mixture analysis (NSMA) method and evaluated the reliability of PISA as an indicator of land surface temperature (LST). Landsat Thematic Mapper (TM) and Enhanced Thematic Mapper Plus (ETM+) images for Yantai city, eastern China obtained from USGS were used as the main data source. The results demonstrated that four-endmember NSMA method performed better than the typical three-endmember one, and there was a strong linear relationship between LST and PISA for the two images, which suggest percent impervious surface area provides an alternative parameter for analyzing LST quantitatively in urban areas

End-Point Contact Force Control with Quantitative Feedback Theory for Mobile Robots

Directory of Open Access Journals (Sweden)

Shuhuan Wen

2012-12-01

Full Text Available Robot force control is an important issue for intelligent mobile robotics. The end-point stiffness of a robot is a key and open problem in the research community. The control strategies are mostly dependent on both the specifications of the task and the environment of the robot. Due to the limited stiffness of the end-effector, we may adopt inherent torque to feedback the oscillations of the controlled force. This paper proposes an effective control strategy which contains a controller using quantitative feedback theory. The nested loop controllers take into account the physical limitation of the system's inner variables and harmful interference. The biggest advantage of the method is its simplicity in both the design process and the implementation of the control algorithm in engineering practice. Taking the one-link manipulator as an example, numerical experiments are carried out to verify the proposed control method. The results show the satisfactory performance.

Evaluation of the influence of percent labeling of 99mTc-MIBI on nuclear medicine procedures in Recife, Pernambuco State, Brazil

International Nuclear Information System (INIS)

Pereira, Jucilene Maria

2003-08-01

The aim of this work was to evaluate the influence of percent labeling of the radiopharmaceutical 99m Tc-MIBI on the procedures adopted by the nuclear medicine clinics in Recife, Pernambuco State, Brazil, and their possible interference with image quality in myocardial perfusion examinations. This work was performed at two nuclear medicine services in Recife that use pharmaceuticals provided by two different manufacturers: Cardiolite, provided by Dupont and Cardiosyd, provided by SYDMA. The pH, percent labeling and stability of samples of 99m Tc-MIBI and the percent uptake in heart and liver of a number of patients were evaluated. The results showed that the pH values measured in all samples of both radiopharmaceuticals were within the limits recommended. In 48% of the Cardiolite samples, the percent labeling was less than 90%, which is the minimum recommended limit. On the other hand, 87,5% of the Cardiosyd samples measured values above 98%. Both radiopharmaceuticals had good labeling stability, even in samples with low percent labeling efficiencies. In spite of the higher percent labeling of Cardiosyd its heart uptake is similar to that observed with the Cardiolite, even when the percent labeling is lower than 90%. On the other hand, the image quality, according to physicians, evaluation was poorer for Cardiosyd images, due to high noise and poor sharpness. (author)

Comparison endpoint study of process plasma and secondary electron beam exciter optical emission spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Stephan Thamban, P. L.; Yun, Stuart; Padron-Wells, Gabriel; Hosch, Jimmy W.; Goeckner, Matthew J. [Department of Mechanical Engineering, University of Texas at Dallas, 800W Campbell Road, Richardson, Texas 75080 (United States); Department of Electrical Engineering, University of Texas at Dallas, 800W Campbell Road, Richardson, Texas 75080 (United States); Verity Instruments, Inc., 2901 Eisenhower Street, Carrollton, Texas 75007 (United States); Department of Mathematical Sciences, University of Texas at Dallas, 800 W Campbell Road, Richardson, Texas 75080 (United States)

2012-11-15

Traditionally process plasmas are often studied and monitored by optical emission spectroscopy. Here, the authors compare experimental measurements from a secondary electron beam excitation and direct process plasma excitation to discuss and illustrate its distinctiveness in the study of process plasmas. They present results that show excitations of etch process effluents in a SF{sub 6} discharge and endpoint detection capabilities in dark plasma process conditions. In SF{sub 6} discharges, a band around 300 nm, not visible in process emission, is observed and it can serve as a good indicator of etch product emission during polysilicon etches. Based on prior work reported in literature the authors believe this band is due to SiF{sub 4} gas phase species.

64 Percent of Asian and Pacific Islander Treatment Admissions Name Alcohol as Their Problem

Science.gov (United States)

Data Spotlight May 28, 2013 64 Percent of Asian and Pacific Islander Treatment Admissions Name Alcohol as ... common problem in the United States. 1 When Asians and Pacific Islanders (APIs) go to treatment, alcohol ...

Fire forbids fifty-fifty forest

Science.gov (United States)

Staal, Arie; Hantson, Stijn; Holmgren, Milena; Pueyo, Salvador; Bernardi, Rafael E.; Flores, Bernardo M.; Xu, Chi; Scheffer, Marten

2018-01-01

Recent studies have interpreted patterns of remotely sensed tree cover as evidence that forest with intermediate tree cover might be unstable in the tropics, as it will tip into either a closed forest or a more open savanna state. Here we show that across all continents the frequency of wildfires rises sharply as tree cover falls below ~40%. Using a simple empirical model, we hypothesize that the steepness of this pattern causes intermediate tree cover (30‒60%) to be unstable for a broad range of assumptions on tree growth and fire-driven mortality. We show that across all continents, observed frequency distributions of tropical tree cover are consistent with this hypothesis. We argue that percolation of fire through an open landscape may explain the remarkably universal rise of fire frequency around a critical tree cover, but we show that simple percolation models cannot predict the actual threshold quantitatively. The fire-driven instability of intermediate states implies that tree cover will not change smoothly with climate or other stressors and shifts between closed forest and a state of low tree cover will likely tend to be relatively sharp and difficult to reverse. PMID:29351323

Fire forbids fifty-fifty forest.

Science.gov (United States)

van Nes, Egbert H; Staal, Arie; Hantson, Stijn; Holmgren, Milena; Pueyo, Salvador; Bernardi, Rafael E; Flores, Bernardo M; Xu, Chi; Scheffer, Marten

2018-01-01

Recent studies have interpreted patterns of remotely sensed tree cover as evidence that forest with intermediate tree cover might be unstable in the tropics, as it will tip into either a closed forest or a more open savanna state. Here we show that across all continents the frequency of wildfires rises sharply as tree cover falls below ~40%. Using a simple empirical model, we hypothesize that the steepness of this pattern causes intermediate tree cover (30‒60%) to be unstable for a broad range of assumptions on tree growth and fire-driven mortality. We show that across all continents, observed frequency distributions of tropical tree cover are consistent with this hypothesis. We argue that percolation of fire through an open landscape may explain the remarkably universal rise of fire frequency around a critical tree cover, but we show that simple percolation models cannot predict the actual threshold quantitatively. The fire-driven instability of intermediate states implies that tree cover will not change smoothly with climate or other stressors and shifts between closed forest and a state of low tree cover will likely tend to be relatively sharp and difficult to reverse.

CRED Cumulative Map of Percent Scleractinian Coral Cover at Pearl and Hermes Atoll, 2002-2004

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral overlaid on bathymetry.

Tranexamic Acid Reduced the Percent of Total Blood Volume Lost During Adolescent Idiopathic Scoliosis Surgery.

Science.gov (United States)

Jones, Kristen E; Butler, Elissa K; Barrack, Tara; Ledonio, Charles T; Forte, Mary L; Cohn, Claudia S; Polly, David W

2017-01-01

Multilevel posterior spine fusion is associated with significant intraoperative blood loss. Tranexamic acid is an antifibrinolytic agent that reduces intraoperative blood loss. The goal of this study was to compare the percent of total blood volume lost during posterior spinal fusion (PSF) with or without tranexamic acid in patients with adolescent idiopathic scoliosis (AIS). Thirty-six AIS patients underwent PSF in 2011-2014; the last half (n=18) received intraoperative tranexamic acid. We retrieved relevant demographic, hematologic, intraoperative and outcomes information from medical records. The primary outcome was the percent of total blood volume lost, calculated from estimates of intraoperative blood loss (numerator) and estimated total blood volume per patient (denominator, via Nadler's equations). Unadjusted outcomes were compared using standard statistical tests. Tranexamic acid and no-tranexamic acid groups were similar (all p>0.05) in mean age (16.1 vs. 15.2 years), sex (89% vs. 83% female), body mass index (22.2 vs. 20.2 kg/m2), preoperative hemoglobin (13.9 vs. 13.9 g/dl), mean spinal levels fused (10.5 vs. 9.6), osteotomies (1.6 vs. 0.9) and operative duration (6.1 hours, both). The percent of total blood volume lost (TBVL) was significantly lower in the tranexamic acid-treated vs. no-tranexamic acid group (median 8.23% vs. 14.30%, p = 0.032); percent TBVL per level fused was significantly lower with tranexamic acid than without it (1.1% vs. 1.8%, p=0.048). Estimated blood loss (milliliters) was similar across groups. Tranexamic acid significantly reduced the percentage of total blood volume lost versus no tranexamic acid in AIS patients who underwent PSF using a standardized blood loss measure.Level of Evidence: 3. Institutional Review Board status: This medical record chart review (minimal risk) study was approved by the University of Minnesota Institutional Review Board.

Clinical endpoint adjudication in a contemporary all-comers coronary stent investigation: methodology and external validation.

Science.gov (United States)

Vranckx, Pascal; McFadden, Eugene; Cutlip, Donald E; Mehran, Roxana; Swart, Michael; Kint, P P; Zijlstra, Felix; Silber, Sigmund; Windecker, Stephan; Serruys, Patrick W C J

2013-01-01

Globalisation in coronary stent research calls for harmonization of clinical endpoint definitions and event adjudication. Little has been published about the various processes used for event adjudication or their impact on outcome reporting. We performed a validation of the clinical event committee (CEC) adjudication process on 100 suspected events in the RESOLUTE All-comers trial (Resolute-AC). Two experienced Clinical Research Organisations (CRO) that had already extensive internal validation processes in place, participated in the study. After initial adjudication by the primary-CEC, events were cross-adjudicated by an external-CEC using the same definitions. Major discrepancies affecting the primary end point of target-lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), or clinically-indicated target-lesion revascularization (CI-TLR), were analysed by an independent oversight committee who provided recommendations for harmonization. Discordant adjudications were reconsidered by the primary CEC. Subsequently, the RAC database was interrogated for cases that based on these recommendations merited re-adjudication and these cases were also re-adjudicated by the primary CEC. Final discrepancies in adjudication of individual components of TLF occurred in 7 out of 100 events in 5 patients. Discrepancies for the (hierarchical) primary endpoint occurred in 5 events (2 cardiac deaths and 3 TV-MI). After application of harmonization recommendations to the overall RAC population (n=2292), the primary CEC adjudicated 3 additional clinical-TLRs and considered 1 TV-MI as no event. A harmonization process provided a high level of concordance for event adjudication and improved accuracy for final event reporting. These findings suggest it is feasible to pool clinical event outcome data across clinical trials even when different CECs are responsible for event adjudication. Copyright © 2012 Elsevier Inc. All rights reserved.

40 CFR 62.14815 - What are the emission limitations for air curtain incinerators that burn 100 percent wood wastes...

Science.gov (United States)

2010-07-01

... air curtain incinerators that burn 100 percent wood wastes, clean lumber and/or yard waste? 62.14815... Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Air Curtain Incinerators That Burn 100 Percent Wood Wastes, Clean Lumber And/or...

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

Science.gov (United States)

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

2014-03-01

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

Automatic sorting of toxicological information into the IUCLID (International Uniform Chemical Information Database) endpoint-categories making use of the semantic search engine Go3R.

Science.gov (United States)

Sauer, Ursula G; Wächter, Thomas; Hareng, Lars; Wareing, Britta; Langsch, Angelika; Zschunke, Matthias; Alvers, Michael R; Landsiedel, Robert

2014-06-01

The knowledge-based search engine Go3R, www.Go3R.org, has been developed to assist scientists from industry and regulatory authorities in collecting comprehensive toxicological information with a special focus on identifying available alternatives to animal testing. The semantic search paradigm of Go3R makes use of expert knowledge on 3Rs methods and regulatory toxicology, laid down in the ontology, a network of concepts, terms, and synonyms, to recognize the contents of documents. Search results are automatically sorted into a dynamic table of contents presented alongside the list of documents retrieved. This table of contents allows the user to quickly filter the set of documents by topics of interest. Documents containing hazard information are automatically assigned to a user interface following the endpoint-specific IUCLID5 categorization scheme required, e.g. for REACH registration dossiers. For this purpose, complex endpoint-specific search queries were compiled and integrated into the search engine (based upon a gold standard of 310 references that had been assigned manually to the different endpoint categories). Go3R sorts 87% of the references concordantly into the respective IUCLID5 categories. Currently, Go3R searches in the 22 million documents available in the PubMed and TOXNET databases. However, it can be customized to search in other databases including in-house databanks. Copyright © 2013 Elsevier Ltd. All rights reserved.

Oral cancer: a retrospective study of 100 Danish cases

DEFF Research Database (Denmark)

Pinholt, E M; Rindum, J; Pindborg, J J

1997-01-01

One hundred Danes with oral cancer who were collected consecutively from 1986 to 1991 were evaluated retrospectively. The study included subjective and objective observations in 56% men and in 44% women. M:F ratio was 1.2:1. Fifty percent of the patients were non-smokers. Nine percent were women...

Determining significant endpoints for ecological risk analyses. 1997 annual progress report

Energy Technology Data Exchange (ETDEWEB)

Hinton, T.G.; Congdon, J.; Rowe, C.; Scott, D. [Univ. of Georgia, Aiken, SC (US). Savannah River Ecology Lab.; Bedford, J.; Whicker, F.W. [Colorado State Univ., Fort Collins, CO (US)

1997-11-01

'This report summarizes the first year''s progress of research funded under the Department of Energy''s Environmental Management Science Program. The research was initiated to better determine ecological risks from toxic and radioactive contaminants. More precisely, the research is designed to determine the relevancy of sublethal cellular damage to the performance of individuals and to identify characteristics of non-human populations exposed to chronic, low-level radiation, as is typically found on many DOE sites. The authors propose to establish a protocol to assess risks to non-human species at higher levels of biological organization by relating molecular damage to more relevant responses that reflect population health. They think that they can achieve this by coupling changes in metabolic rates and energy allocation patterns to meaningful population response variables, and by using novel biological dosimeters in controlled, manipulative dose/effects experiments. They believe that a scientifically defensible endpoint for measuring ecological risks can only be determined once its understood the extent to which molecular damage from contaminant exposure is detrimental at the individual and population levels of biological organization.'

Simultaneous small-sample comparisons in longitudinal or multi-endpoint trials using multiple marginal models

DEFF Research Database (Denmark)

Pallmann, Philip; Ritz, Christian; Hothorn, Ludwig A

2018-01-01

, however only asymptotically. In this paper, we show how to make the approach also applicable to small-sample data problems. Specifically, we discuss the computation of adjusted P values and simultaneous confidence bounds for comparisons of randomised treatment groups as well as for levels......Simultaneous inference in longitudinal, repeated-measures, and multi-endpoint designs can be onerous, especially when trying to find a reasonable joint model from which the interesting effects and covariances are estimated. A novel statistical approach known as multiple marginal models greatly...... simplifies the modelling process: the core idea is to "marginalise" the problem and fit multiple small models to different portions of the data, and then estimate the overall covariance matrix in a subsequent, separate step. Using these estimates guarantees strong control of the family-wise error rate...

Determination of the Acidity of Oils Using Paraformaldehyde as a Thermometric End-Point Indicator

Directory of Open Access Journals (Sweden)

Carneiro Mário J. D.

2002-01-01

Full Text Available The determination of the acidity of oils by catalytic thermometric titrimetry using paraformaldehyde as the thermometric end-point indicator was investigated. The sample solvent was a 1:1 (v/v mixture of toluene and 2-propanol and the titrant was 0.1 mol L-1 aqueous sodium hydroxide. Paraformaldehyde, being insoluble in the sample solvent, does not present the inconvenience of other indicators that change the properties of the solvent due to composition changes. The titration can therefore be done effectively in the same medium as the standard potentiometric and visual titration methods. The results of the application of the method to both non-refined and refined oils are presented herein. The proposed method has advantages in relation to the potentiometric method in terms of speed and simplicity.

A cooperative effort to pass tobacco control ordinances in Wichita, Kansas.

Science.gov (United States)

Pippert, K; Jecha, L; Coen, S; MacDonald, P; Francisco, J; Pickard, S

1995-01-01

In October 1993, the Tobacco-Free Wichita Coalition proposed ordinances to the Wichita City Council that would tightly control access of minors to tobacco and prohibit smoking in public places. The subsequent successful change in local health policy required the collaborative efforts of local and state organizations and health agencies. A simple random telephone survey commissioned and financed by the coalition demonstrated that 76 percent (95 percent CI = 72 percent to 80 percent) of adult Wichita-Sedgwick County residents favored enforced penalties for merchants selling tobacco to minors, and 62 percent (95 percent CI = 58 percent to 66 percent) favored a ban on tobacco vending machines. Fifty-four percent (95 percent CI = 50 percent to 58 percent) favored a smoking ban in all public places.

Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.

Directory of Open Access Journals (Sweden)

Astrid Yeo

Full Text Available Darapladib, a lipoprotein-associated phospholipase A2 (Lp-PLA2 inhibitor, failed to demonstrate efficacy for the primary endpoints in two large phase III cardiovascular outcomes trials, one in stable coronary heart disease patients (STABILITY and one in acute coronary syndrome (SOLID-TIMI 52. No major safety signals were observed but tolerability issues of diarrhea and odor were common (up to 13%. We hypothesized that genetic variants associated with Lp-PLA2 activity may influence efficacy and tolerability and therefore performed a comprehensive pharmacogenetic analysis of both trials. We genotyped patients within the STABILITY and SOLID-TIMI 52 trials who provided a DNA sample and consent (n = 13,577 and 10,404 respectively, representing 86% and 82% of the trial participants using genome-wide arrays with exome content and performed imputation using a 1000 Genomes reference panel. We investigated baseline and change from baseline in Lp-PLA2 activity, two efficacy endpoints (major coronary events and myocardial infarction as well as tolerability parameters at genome-wide and candidate gene level using a meta-analytic approach. We replicated associations of published loci on baseline Lp-PLA2 activity (APOE, CELSR2, LPA, PLA2G7, LDLR and SCARB1 and identified three novel loci (TOMM5, FRMD5 and LPL using the GWAS-significance threshold P≤5E-08. Review of the PLA2G7 gene (encoding Lp-PLA2 within these datasets identified V279F null allele carriers as well as three other rare exonic null alleles within various ethnic groups, however none of these variants nor any other loci associated with Lp-PLA2 activity at baseline were associated with any of the drug response endpoints. The analysis of darapladib efficacy endpoints, despite low power, identified six low frequency loci with main genotype effect (though with borderline imputation scores and one common locus (minor allele frequency 0.24 with genotype by treatment interaction effect passing the GWAS

The Biomarker-Surrogacy Evaluation Schema: a review of the biomarker-surrogate literature and a proposal for a criterion-based, quantitative, multidimensional hierarchical levels of evidence schema for evaluating the status of biomarkers as surrogate endpoints.

Science.gov (United States)

Lassere, Marissa N

2008-06-01

There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Section 2 is a systematic, historical review of the biomarker-surrogate endpoint literature with special reference to the nomenclature, the systems of classification and statistical methods developed for their evaluation. In Section 3 an explicit, criterion-based, quantitative, multidimensional hierarchical levels of evidence schema - Biomarker-Surrogacy Evaluation Schema - is proposed to evaluate and co-ordinate the multiple dimensions (biological, epidemiological, statistical, clinical trial and risk-benefit evidence) of the biomarker clinical endpoint relationships. The schema systematically evaluates and ranks the surrogacy status of biomarkers and surrogate endpoints using defined levels of evidence. The schema incorporates the three independent domains: Study Design, Target Outcome and Statistical Evaluation. Each domain has items ranked from zero to five. An additional category called Penalties incorporates additional considerations of biological plausibility, risk-benefit and generalizability. The total score (0-15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. The term ;surrogate' is restricted to markers attaining Levels 1 or 2 only. Surrogacy status of markers can then be directly compared within and across different areas of medicine to guide individual, trial-based or drug-development decisions. This schema would facilitate communication between clinical, researcher, regulatory, industry and consumer participants necessary for evaluation of the biomarker-surrogate-clinical endpoint relationship in their different settings.

Map of percent scleractinian coral cover and sand along camera tow tracks in west Hawaii

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This map displays optical validation observation locations and percent coverage of scleractinian coral and sand overlaid on bathymetry and landsat imagery northwest...

Proceedings of the fifty sixth congress of Indian Society of Theoretical and Applied Mechanics: souvenir

International Nuclear Information System (INIS)

Pradhan, V.H.

2011-01-01

The fifty sixth congress of Indian Society of Theoretical and Applied Mechanics had been organized from December 19-21, 2011. Mathematics has been playing a key role in the development of society right from the use of geometry in land measurement to satellite launching. The appropriate mathematical tools are right answers to real world problems which has increase many fold because of the advancement in various branches of applied sciences, engineering and technologies with the advanced development of high speed super digital computers. The topics such as wireless communication, health systems, financing, budgeting, planning, management and decision making which plays important role in day to day lives have been covered in this meet. Papers relevant to INIS have been indexed separately

Comparative evaluation of PSA-Density, percent free PSA and total PSA

OpenAIRE

Ströbel, Greta

2010-01-01

BACKGROUND The objective of this study was to evaluate the prostate specific antigen (PSA) density (PSAD) (the quotient of PSA and prostate volume) compared with the percent free PSA (%fPSA) and total PSA (tPSA) in different total PSA (tPSA) ranges from 2 ng/mL to 20 ng/mL. Possible cut-off levels depending on the tPSA should be established. METHODS In total, 1809 men with no pretreatment of the prostate were enrolled between 1996 and 2004. Total and free PSA were measured with t...

European Community Can Reduce CO2 Emissions by Sixty Percent : A Feasibility Study

NARCIS (Netherlands)

Mot, E.; Bartelds, H.; Esser, P.M.; Huurdeman, A.J.M.; Laak, P.J.A. van de; Michon, S.G.L.; Nielen, R.J.; Baar, H.J.W. de

1993-01-01

Carbon dioxide (CO2) emissions in the European Community (EC) can be reduced by roughly 60 percent. A great many measures need to be taken to reach this reduction, with a total annual cost of ECU 55 milliard. Fossil fuel use is the main cause of CO2 emissions into the atmosphere; CO2 emissions are

End-Point Immobilization of Recombinant Thrombomodulin via Sortase-Mediated Ligation

Science.gov (United States)

Jiang, Rui; Weingart, Jacob; Zhang, Hailong; Ma, Yong; Sun, Xue-Long

2012-01-01

We report an enzymatic end-point modification and immobilization of recombinant human thrombomodulin (TM), a cofactor for activation of anticoagulant protein C pathway via thrombin. First, a truncated TM mutant consisting of epidermal growth factor-like domains 4–6 (TM456) with a conserved pentapeptide LPETG motif at its C-terminal was expressed and purified in E. coli. Next, the truncated TM456 derivative was site-specifically modified with N-terminal diglycine containing molecules such as biotin and the fluorescent probe dansyl via sortase A (SrtA) mediated ligation (SML). The successful ligations were confirmed by SDS-PAGE and fluorescence imaging. Finally, the truncated TM456 was immobilized onto N-terminal diglycine-functionalized glass slide surface via SML directly. Alternatively, the truncated TM456 was biotinylated via SML and then immobilized onto streptavidin-functionalized glass slide surface indirectly. The successful immobilizations were confirmed by fluorescence imaging. The bioactivity of the immobilized truncated TM456 was further confirmed by protein C activation assay, in which enhanced activation of protein C by immobilized recombinant TM was observed. The sortase A-catalyzed surface ligation took place under mild conditions and is rapid occurring in a single step without prior chemical modification of the target protein. This site-specific covalent modification leads to molecules being arranged in a definitively ordered fashion and facilitating the preservation of the protein’s biological activity. PMID:22372933

Student Loan Default Rates in Minnesota, 2007

Science.gov (United States)

Grimes, Tricia

2010-01-01

While Minnesota undergraduates are more likely to take out student loans, they are substantially less likely than their peers nationally to default on federal student loans. Fifty-four percent of Minnesota undergraduates took out student loans in 2007-2008, compared to 39 percent of undergraduates across the U.S. Minnesota undergraduates were also…

Objectively-determined intensity- and domain-specific physical activity and sedentary behavior in relation to percent body fat.

Science.gov (United States)

Scheers, Tineke; Philippaerts, Renaat; Lefevre, Johan

2013-12-01

This study examined the independent and joint associations of overall, intensity-specific and domain-specific physical activity and sedentary behavior with bioelectrical impedance-determined percent body fat. Physical activity was measured in 442 Flemish adults (41.4 ± 9.8 years) using the SenseWear Armband and an electronic diary. Two-way analyses of covariance investigated the interaction of physical activity and sedentary behavior with percent body fat. Multiple linear regression analyses, adjusted for potential confounders, examined the associations of intensity-specific and domain-specific physical activity and sedentary behavior with percent body fat. Results showed a significant main effect for physical activity in both genders and for sedentary behavior in women, but no interaction effects. Light activity was positively (β = 0.41 for men and 0.43 for women) and moderate (β = -0.64 and -0.41), vigorous (β = -0.21 and -0.24) and moderate-to-vigorous physical activity (MVPA) inversely associated with percent body fat, independent of sedentary time. Regarding domain-specific physical activity, significant associations were present for occupation, leisure time and household chores, irrespective of sedentary time. The positive associations between body fat and total and domain-specific sedentary behavior diminished after MVPA was controlled for. MVPA during leisure time, occupation and household chores may be essential to prevent fat gain. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The interpolation method based on endpoint coordinate for CT three-dimensional image

International Nuclear Information System (INIS)

Suto, Yasuzo; Ueno, Shigeru.

1997-01-01

Image interpolation is frequently used to improve slice resolution to reach spatial resolution. Improved quality of reconstructed three-dimensional images can be attained with this technique as a result. Linear interpolation is a well-known and widely used method. The distance-image method, which is a non-linear interpolation technique, is also used to convert CT value images to distance images. This paper describes a newly developed method that makes use of end-point coordinates: CT-value images are initially converted to binary images by thresholding them and then sequences of pixels with 1-value are arranged in vertical or horizontal directions. A sequence of pixels with 1-value is defined as a line segment which has starting and end points. For each pair of adjacent line segments, another line segment was composed by spatial interpolation of the start and end points. Binary slice images are constructed from the composed line segments. Three-dimensional images were reconstructed from clinical X-ray CT images, using three different interpolation methods and their quality and processing speed were evaluated and compared. (author)

EnviroAtlas - Percent Urban Land Cover by 12-Digit HUC for the Conterminous United States

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset estimates the percent urban land for each 12-digit hydrologic unit code (HUC) in the conterminous United States. For the purposes of this...

A Comparison of the Outcomes for Cartilage Defects of the Knee Treated With Biologic Resurfacing Versus Focal Metallic Implants.

Science.gov (United States)

Pascual-Garrido, Cecilia; Daley, Erika; Verma, Nikhil N; Cole, Brian J

2017-02-01

To compare the results of focal metallic resurfacing with biologic procedures in patients more than 35 years of age with isolated, full thickness defects of the femoral condyle. A total of 61 patients met the selection criteria resulting in 30 patients treated with biological procedures, including debridement, microfracture, osteochondral autograft transplantation, osteochondral allograft, and autologous chondrocyte implantation (BIO group), and 32 patients treated with focal metallic resurfacing (CAP group). The BIO and CAP groups were matched according to treatment location, defect grade and size, and age profile. Outcomes included Western Ontario and McMaster Osteoarthritis Index (WOMAC), Short Form-12, and satisfaction. The primary combination endpoint was determined as a 20% improvement (minimum clinically important difference-20) on WOMAC pain and function at 2 years and no additional index lesion-related surgical intervention. Safety and effectiveness were also reported. Thirty patients in the BIO group (mean age of 44.6, range 35-64) had an average follow-up of 2.6 years and 32 patients in the CAP group (mean age 47.9, range 37-68) were followed for 2.0 years. Fifty-three percent in the BIO group and 75% in the CAP group achieved success per the endpoint definition. The mean total WOMAC score improved significantly for both groups (BIO: 57-78; P metal resurfacing procedures for the treatment of isolated focal chondral lesions of the femoral condyle in the knee. Focal metallic resurfacing results in similar clinical outcomes and provides excellent success rates at short-term follow-up. Level III comparative study. Copyright © 2016. Published by Elsevier Inc.

The Use of Gas Chromatography and Mass Spectrometry to Introduce General Chemistry Students to Percent Mass and Atomic Mass Calculations

Science.gov (United States)

Pfennig, Brian W.; Schaefer, Amy K.

2011-01-01

A general chemistry laboratory experiment is described that introduces students to instrumental analysis using gas chromatography-mass spectrometry (GC-MS), while simultaneously reinforcing the concepts of mass percent and the calculation of atomic mass. Working in small groups, students use the GC to separate and quantify the percent composition…

40 CFR 62.14820 - How must I monitor opacity for air curtain incinerators that burn 100 percent wood wastes, clean...

Science.gov (United States)

2010-07-01

... curtain incinerators that burn 100 percent wood wastes, clean lumber, and/or yard waste? 62.14820 Section... Requirements for Commercial and Industrial Solid Waste Incineration Units That Commenced Construction On or Before November 30, 1999 Air Curtain Incinerators That Burn 100 Percent Wood Wastes, Clean Lumber And/or...

Personal Best Time, Percent Body Fat, and Training Are Differently Associated with Race Time for Male and Female Ironman Triathletes

Science.gov (United States)

Knechtle, Beat; Wirth, Andrea; Baumann, Barbara; Knechtle, Patrizia; Rosemann, Thomas

2010-01-01

We studied male and female nonprofessional Ironman triathletes to determine whether percent body fat, training, and/or previous race experience were associated with race performance. We used simple linear regression analysis, with total race time as the dependent variable, to investigate the relationship among athletes' percent body fat, average…

The First Fifty ABO Blood Group Incompatible Kidney Transplantations: The Rotterdam Experience

Directory of Open Access Journals (Sweden)

Madelon van Agteren

2014-01-01

Full Text Available This study describes the single center experience and long-term results of ABOi kidney transplantation using a pretransplantation protocol involving immunoadsorption combined with rituximab, intravenous immunoglobulins, and triple immune suppression. Fifty patients received an ABOi kidney transplant in the period from 2006 to 2012 with a follow-up of at least one year. Eleven antibody mediated rejections were noted of which 5 were mixed antibody and cellular mediated rejections. Nine cellular mediated rejections were recorded. Two grafts were lost due to rejection in the first year. One-year graft survival of the ABOi grafts was comparable to 100 matched ABO compatible renal grafts, 96% versus 99%. At 5-year follow-up, the graft survival was 90% in the ABOi versus 97% in the control group. Posttransplantation immunoadsorption was not an essential part of the protocol and no association was found between antibody titers and subsequent graft rejection. Steroids could be withdrawn safely 3 months after transplantation. Adverse events specifically related to the ABOi protocol were not observed. The currently used ABOi protocol shows good short and midterm results despite a high rate of antibody mediated rejections in the first years after the start of the program.

27 CFR 30.61 - Table 1, showing the true percent of proof spirit for any indication of the hydrometer at...

Science.gov (United States)

2010-04-01

... percent of proof spirit for any indication of the hydrometer at temperatures between zero and 100 degrees... true percent of proof spirit for any indication of the hydrometer at temperatures between zero and 100... hydrometer likely to occur in practice at temperatures between zero and 100 degrees Fahrenheit and shall be...

Comparison of Anaesthetic Efficacy of 4 percent Articaine Primary Buccal Infiltration Versus 2 percent Lidocaine Inferior Alveolar Nerve Block in Symptomatic Mandibular First Molar Teeth

International Nuclear Information System (INIS)

Zain, M.; Khattak, S. U. R.; Shah, S. A.; Fayyaz, M.; Sikandar, H.

2016-01-01

Objective: To evaluate success of pulpal anaesthesia of mandibular 1st molar by using 4 percentage articaine in buccal infiltration versus 2 percentage lidocaine in inferior alveolar nerve block. Study Design: Randomized control trial. Place and Duration of Study: Department of Operative Dentistry, Sardar Begum Dental College, Gandhara University, Peshawar, from March to August 2014. Methodology: One hundred and fifty-six emergency patients, who had 1st molar diagnosed with irreversible pulpitis, participated in the study. Subjects were divided into two groups by random allocation. One group received 4 percentage articaine buccal infiltration and the other group received inferior alveolar nerve block of 2 percentage lidocaine. Subjects self-reported pain response was recorded on Heft Parker Visual Analogue Scale after local anaesthetic administration during access cavity preparation and pulp extirpation. Results: Mean age of subjects was 31.46 ±10.994 years. The success rate of 4 percentage buccal infiltration was 76.9 percentage; whereas the success rate of 2 percentage lidocaine inferior alveolar nerve block was 62.8 percentage. There was no statistically significant difference between the two groups. Conclusion: 4 percentage articaine buccal infiltration can be considered a viable alternative to 2 percentage lidocaine inferior alveolar nerve block in securing successful pulpal anaesthesia for endodontic therapy. (author)

Predicting the outcome of oral food challenges with hen's egg through skin test end-point titration.

Science.gov (United States)

Tripodi, S; Businco, A Di Rienzo; Alessandri, C; Panetta, V; Restani, P; Matricardi, P M

2009-08-01

Oral food challenge (OFC) is the diagnostic 'gold standard' of food allergies but it is laborious and time consuming. Attempts to predict a positive OFC through specific IgE assays or conventional skin tests so far gave suboptimal results. To test whether skin test with titration curves predict with enough confidence the outcome of an oral food challenge. Children (n=47; mean age 6.2 +/- 4.2 years) with suspected and diagnosed allergic reactions to hen's egg (HE) were examined through clinical history, physical examination, oral food challenge, conventional and end-point titrated skin tests with HE white extract and determination of serum specific IgE against HE white. Predictive decision points for a positive outcome of food challenges were calculated through receiver operating characteristic (ROC) analysis for HE white using IgE concentration, weal size and end-point titration (EPT). OFC was positive (Sampson's score >or=3) in 20/47 children (42.5%). The area under the ROC curve obtained with the EPT method was significantly bigger than the one obtained by measuring IgE-specific antibodies (0.99 vs. 0.83, P<0.05) and weal size (0.99 vs. 0.88, P<0.05). The extract's dilution that successfully discriminated a positive from a negative OFC (sensitivity 95%, specificity 100%) was 1 : 256, corresponding to a concentration of 5.9 microg/mL of ovotransferrin, 22.2 microg/mL of ovalbumin, and 1.4 microg/mL of lysozyme. EPT is a promising approach to optimize the use of skin prick tests and to predict the outcome of OFC with HE in children. Further studies are needed to test whether this encouraging finding can be extended to other populations and food allergens.

Residual volume on land and when immersed in water: effect on percent body fat.

Science.gov (United States)

Demura, Shinichi; Yamaji, Shunsuke; Kitabayashi, Tamotsu

2006-08-01

There is a large residual volume (RV) error when assessing percent body fat by means of hydrostatic weighing. It has generally been measured before hydrostatic weighing. However, an individual's maximal exhalations on land and in the water may not be identical. The aims of this study were to compare residual volumes and vital capacities on land and when immersed to the neck in water, and to examine the influence of the measurement error on percent body fat. The participants were 20 healthy Japanese males and 20 healthy Japanese females. To assess the influence of the RV error on percent body fat in both conditions and to evaluate the cross-validity of the prediction equation, another 20 males and 20 females were measured using hydrostatic weighing. Residual volume was measured on land and in the water using a nitrogen wash-out technique based on an open-circuit approach. In water, residual volume was measured with the participant sitting on a chair while the whole body, except the head, was submerged . The trial-to-trial reliabilities of residual volume in both conditions were very good (intraclass correlation coefficient > 0.98). Although residual volume measured under the two conditions did not agree completely, they showed a high correlation (males: 0.880; females: 0.853; P body fat computed using residual volume measured in both conditions was very good for both sexes (males: r = 0.902; females: r = 0.869, P body fat: -3.4 to 2.2% for males; -6.3 to 4.4% for females). We conclude that if these errors are of no importance, residual volume measured on land can be used when assessing body composition.