WorldWideScience

Sample records for two-period crossover design

  1. A novel LC-MS/MS method for mepivacaine determination and pharmacokinetic study in a single-dose two-period crossover in healthy subjects.

    Science.gov (United States)

    Duan, Ruo-Wang; Song, Jiong; Li, Yu-Ping; Xing, Chun-Gen

    2016-12-15

    The objective of this work was to develop a simple, selective, and sensitive LC-MS/MS method for the quantitation of the mepivacaine in Chinese biological matrix. The calibration curve of mepivacaine ranged from 0.5 to 2000 ng/mL with the lower limit of quantitation being 0.5 ng/mL. This sensitivity was high enough to describe the profile of blood mepivacaine level versus time. Thereby it was very desirable for the pharmacokinetic study because of its high sensitivity and accuracy. The study used a single-dose two-period crossover design principle. For the pharmacokinetic analysis of plasma, the mean (SD) values obtained were as follows: t1/2, 1.63 (0.43) h; Cmax, 435.3 (67.4) ng/ml; AUC0-t, 1546.9 (339.7) ng/ml·h; AUC0-∞, 1982.3 (421.4) ng/ml·h; Tmax, 0.62 (0.31) h. The validated method has been successfully applied to assess the pharmacokinetic study of mepivacaine after a single administration to Chinese volunteers.

  2. Crossover Designs in Nutrition and Dietetics Research.

    Science.gov (United States)

    Harris, Jeffrey E; Raynor, Hollie A

    2017-07-01

    This article is the 12th installment in a statistical series exploring the importance of research design, epidemiologic methods, and statistical analysis as applied to nutrition and dietetics research. The purpose of this series is to assist registered dietitian nutritionists in interpreting nutrition research and aid nutrition researchers in applying scientific principles to produce high-quality nutrition research. This article focuses on the use of crossover designs in nutrition and dietetics research. The purpose is to distinguish the crossover design from the randomized clinical trial, define important terms, illustrate a 2×2 crossover design, discuss potential confounding variables in the crossover design, describe the analysis and interpretation of crossover data, present sample size considerations, provide examples of the use of the crossover design in nutrition and dietetics, and discuss additional considerations when the independent variable has more than two levels. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  3. Design, Analysis, and Presentation of Crossover Trials

    OpenAIRE

    Guyatt Gordon H; Vail Andy; Wu Ping; Chan An-Wen; Mills Edward J; Altman Douglas G

    2009-01-01

    Abstract Objective Although crossover trials enjoy wide use, standards for analysis and reporting have not been established. We reviewed methodological aspects and quality of reporting in a representative sample of published crossover trials. Methods We searched MEDLINE for December 2000 and identified all randomized crossover trials. We abstracted data independently, in duplicate, on 14 design criteria, 13 analysis criteria, and 14 criteria assessing the data presentation. Results We identif...

  4. Design and analysis of crossover trials for absorbing binary endpoints.

    Science.gov (United States)

    Nason, Martha; Follmann, Dean

    2010-09-01

    The crossover is a popular and efficient trial design used in the context of patient heterogeneity to assess the effect of treatments that act relatively quickly and whose benefit disappears with discontinuation. Each patient can serve as her own control as within-individual treatment and placebo responses are compared. Conventional wisdom is that these designs are not appropriate for absorbing binary endpoints, such as death or HIV infection. We explore the use of crossover designs in the context of these absorbing binary endpoints and show that they can be more efficient than the standard parallel group design when there is heterogeneity in individuals' risks. We also introduce a new two-period design where first period "survivors" are rerandomized for the second period. This design combines the crossover design with the parallel design and achieves some of the efficiency advantages of the crossover design while ensuring that the second period groups are comparable by randomization. We discuss the validity of the new designs and evaluate both a mixture model and a modified Mantel-Haenszel test for inference. The mixture model assumes no carryover or period effects while the Mantel-Haenszel approach conditions out period effects. Simulations are used to compare the different designs and an example is provided to explore practical issues in implementation.

  5. Bioavailability of orally administered rhGM-CSF: a single-dose, randomized, open-label, two-period crossover trial.

    Directory of Open Access Journals (Sweden)

    Wenping Zhang

    Full Text Available BACKGROUND: Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF is usually administered by injection, and its oral administration in a clinical setting has been not yet reported. Here we demonstrate the bioavailability of orally administered rhGM-CSF in healthy volunteers. The rhGM-CSF was expressed in Bombyx mori expression system (BmrhGM-CSF. METHODS AND FINDINGS: Using a single-dose, randomized, open-label, two-period crossover clinical trial design, 19 healthy volunteers were orally administered with BmrhGM-CSF (8 microg/kg and subcutaneously injected with rhGM-CSF (3.75 microg/kg respectively. Serum samples were drawn at 0.0h, 0.5h ,0.75h,1.0h,1.5h,2.0h ,3.0h,4.0h,5.0h,6.0h,8.0h,10.0h and 12.0h after administrations. The hGM-CSF serum concentrations were determined by ELISA. The AUC was calculated using the trapezoid method. The relative bioavailability of BmrhGM-CSF was determined according to the AUC ratio of both orally administered and subcutaneously injected rhGM-CSF. Three volunteers were randomly selected from 15 orally administrated subjects with ELISA detectable values. Their serum samples at the 0.0h, 1.0h, 2.0h, 3.0h and 4.0h after the administrations were analyzed by Q-Trap MS/MS TOF. The different peaks were revealed by the spectrogram profile comparison of the 1.0h, 2.0h, 3.0h and 4.0h samples with that of the 0.0h sample, and further analyzed using both Enhanced Product Ion (EPI scanning and Peptide Mass Fingerprinting Analysis. The rhGM-CSF was detected in the serum samples from 15 of 19 volunteers administrated with BmrhGM-CSF. Its bioavailability was observed at an average of 1.0%, with the highest of 3.1%. The rhGM-CSF peptide sequences in the serum samples were detected by MS analysis, and their sizes ranging from 2,039 to 7,336 Da. CONCLUSIONS: The results demonstrated that the oral administered BmrhGM-CSF was absorbed into the blood. This study provides an approach for an oral administration of

  6. The impact of nurse-driven targeted HIV screening in 8 emergency departments: study protocol for the DICI-VIH cluster-randomized two-period crossover trial.

    Science.gov (United States)

    Leblanc, Judith; Rousseau, Alexandra; Hejblum, Gilles; Durand-Zaleski, Isabelle; de Truchis, Pierre; Lert, France; Costagliola, Dominique; Simon, Tabassome; Crémieux, Anne-Claude

    2016-02-01

    In 2010, to reduce late HIV diagnosis, the French national health agency endorsed non-targeted HIV screening in health care settings. Despite these recommendations, non-targeted screening has not been implemented and only physician-directed diagnostic testing is currently performed. A survey conducted in 2010 in 29 French Emergency Departments (EDs) showed that non-targeted nurse-driven screening was feasible though only a few new HIV diagnoses were identified, predominantly among high-risk groups. A strategy targeting high-risk groups combined with current practice could be shown to be feasible, more efficient and cost-effective than current practice alone. DICI-VIH (acronym for nurse-driven targeted HIV screening) is a multicentre, cluster-randomized, two-period crossover trial. The primary objective is to compare the effectiveness of 2 strategies for diagnosing HIV among adult patients visiting EDs: nurse-driven targeted HIV screening combined with current practice (physician-directed diagnostic testing) versus current practice alone. Main secondary objectives are to compare access to specialist consultation and how early HIV diagnosis occurs in the course of the disease between the 2 groups, and to evaluate the implementation, acceptability and cost-effectiveness of nurse-driven targeted screening. The 2 strategies take place during 2 randomly assigned periods in 8 EDs of metropolitan Paris, where 42 % of France's new HIV patients are diagnosed every year. All patients aged 18 to 64, not presenting secondary to HIV exposure are included. During the intervention period, patients are invited to fill a 7-item questionnaire (country of birth, sexual partners and injection drug use) in order to select individuals who are offered a rapid test. If the rapid test is reactive, a follow-up visit with an infectious disease specialist is scheduled within 72 h. Assuming an 80 % statistical power and a 5 % type 1 error, with 1.04 and 3.38 new diagnoses per 10,000 patients in

  7. Universally optimal crossover designs under subject dropout

    OpenAIRE

    Zheng, Wei

    2013-01-01

    Subject dropout is very common in practical applications of crossover designs. However, there is very limited design literature taking this into account. Optimality results have not yet been well established due to the complexity of the problem. This paper establishes feasible, as well as necessary and sufficient conditions for a crossover design to be universally optimal in approximate design theory in the presence of subject dropout. These conditions are essentially linear equations with re...

  8. A matched crossover design for clinical trials.

    Science.gov (United States)

    Simon, Laura J; Chinchilli, Vernon M

    2007-09-01

    Two design principles are used frequently in clinical trials: 1) A subject is "matched" or "paired" with a similar subject to reduce the chance that other variables obscure the primary comparison of interest. 2) A subject serves as his/her own control by "crossing over" from one treatment to another during the course of an experiment. There are situations in which it may be advantageous to use the two design principles - crossing over and matching - simultaneously. That is, it may be advantageous to conduct a "paired crossover design," in which each subject, while paired with a similar subject, crosses over and receives each experimental treatment. In this paper, we describe two clinical trials conducted by the National Heart, Lung and Blood Institute's Asthma Clinical Research Network that used a paired 2x2 crossover design. The Beta Adrenergic Response by GEnotype (BARGE) Study compared the effects of regular use of inhaled albuterol on mildly asthmatic patients with different genotypes at the 16th position of the beta-agonist receptor gene. The Smoking Modulates Outcomes of Glucocorticoid (SMOG) Therapy in Asthma Study evaluated the hypothesis that smoking reduces the response to inhaled corticosteroids. For such paired crossover designs, the primary parameter of interest is typically the treatment-by-pairing interaction term. In evaluating the relative efficiency of the paired 2x2 crossover design to two independent crossover designs with respect to this interaction term, we show that the paired 2x2 crossover design is more efficient if the correlations between the paired members on the same treatments are greater than their correlations on different treatments. This condition should hold in most circumstances, and therefore the paired crossover design deserves serious consideration for any clinical trial in which the crossing over and matching of subjects is deemed simultaneously beneficial.

  9. Design, analysis, and presentation of crossover trials

    Directory of Open Access Journals (Sweden)

    Guyatt Gordon H

    2009-04-01

    Full Text Available Abstract Objective Although crossover trials enjoy wide use, standards for analysis and reporting have not been established. We reviewed methodological aspects and quality of reporting in a representative sample of published crossover trials. Methods We searched MEDLINE for December 2000 and identified all randomized crossover trials. We abstracted data independently, in duplicate, on 14 design criteria, 13 analysis criteria, and 14 criteria assessing the data presentation. Results We identified 526 randomized controlled trials, of which 116 were crossover trials. Trials were drug efficacy (48%, pharmacokinetic (28%, and nonpharmacologic (30%. The median sample size was 15 (interquartile range 8–38. Most (72% trials used 2 treatments and had 2 periods (64%. Few trials reported allocation concealment (17% or sequence generation (7%. Only 20% of trials reported a sample size calculation and only 31% of these considered pairing of data in the calculation. Carry-over issues were addressed in 29% of trial's methods. Most trials reported and defended a washout period (70%. Almost all trials (93% tested for treatment effects using paired data and also presented details on by-group results (95%. Only 29% presented CIs or SE so that data could be entered into a meta-analysis. Conclusion Reports of crossover trials frequently omit important methodological issues in design, analysis, and presentation. Guidelines for the conduct and reporting of crossover trials might improve the conduct and reporting of studies using this important trial design.

  10. Treadmill training with partial body weight support compared with conventional gait training for low-functioning children and adolescents with nonspastic cerebral palsy: a two-period crossover study.

    Science.gov (United States)

    Su, Ivan Y W; Chung, Kenny K Y; Chow, Daniel H K

    2013-12-01

    Partial body weight-supported treadmill training has been shown to be effective in gait training for patients with neurological disorders such as spinal cord injuries and stroke. Recent applications on children with cerebral palsy were reported, mostly on spastic cerebral palsy with single subject design. There is lack of evidence on the effectiveness of such training for nonspastic cerebral palsy, particularly those who are low functioning with limited intellectual capacity. This study evaluated the effectiveness of partial body weight-supported treadmill training for improving gross motor skills among these clients. A two-period randomized crossover design with repeated measures. A crossover design following an A-B versus a B-A pattern was adopted. The two training periods consisted of 12-week partial body weight-supported treadmill training (Training A) and 12-week conventional gait training (Training B) with a 10-week washout in between. Ten school-age participants with nonspastic cerebral palsy and severe mental retardation were recruited. The Gross Motor Function Measure-66 was administered immediately before and after each training period. Significant improvements in dimensions D and E of the Gross Motor Function Measure-66 and the Gross Motor Ability Estimator were obtained. Our findings revealed that the partial body weight-supported treadmill training was effective in improving gross motor skills for low-functioning children and adolescents with nonspastic cerebral palsy. .

  11. The Design of Cluster Randomized Crossover Trials

    Science.gov (United States)

    Rietbergen, Charlotte; Moerbeek, Mirjam

    2011-01-01

    The inefficiency induced by between-cluster variation in cluster randomized (CR) trials can be reduced by implementing a crossover (CO) design. In a simple CO trial, each subject receives each treatment in random order. A powerful characteristic of this design is that each subject serves as its own control. In a CR CO trial, clusters of subjects…

  12. The design of cluster randomized crossover trials

    NARCIS (Netherlands)

    Rietbergen, C.; Moerbeek, M.

    2011-01-01

    The inefficiency induced by between-cluster variation in cluster randomized (CR) trials can be reduced by implementing a crossover (CO) design. In a simple CO trial, each subject receives each treatment in random order. A powerful characteristic of this design is that each subject serves as its own

  13. Optimal crossover designs for the proportional model

    OpenAIRE

    Zheng, Wei

    2013-01-01

    In crossover design experiments, the proportional model, where the carryover effects are proportional to their direct treatment effects, has draw attentions in recent years. We discover that the universally optimal design under the traditional model is E-optimal design under the proportional model. Moreover, we establish equivalence theorems of Kiefer-Wolfowitz's type for four popular optimality criteria, namely A, D, E and T (trace).

  14. Pharmacokinetics of single oral dose trazodone : a randomized, two-period, cross-over trial in healthy, adult, human volunteers under fed condition

    Directory of Open Access Journals (Sweden)

    PRASHANT eKALE

    2015-10-01

    Full Text Available Objective To assess the bioequivalence of single dose trazodone hydrochloride USP 100 mg tablets administered as an oral dose under fed condition. Methods This study was an open-label, balanced, randomized, two-sequence, two-treatment, two-period, single oral dose, crossover bioequivalence study in healthy, adult, human subjects under fed conditions. After an overnight fast of at least 10 hours, the subjects were served a high fat and high calorie vegetarian breakfast, which they were required to consume within 30 minutes. A single oral dose (100 mg of either the test or the reference product was administered to the subjects. The primary pharmacokinetic parameters, maximum plasma concentration (Cmax and area under the plasma concentration–time curve (AUC from time zero to last measurable concentration (AUC0-t and extrapolated to infinity (AUC0- were compared by an analysis of variance using log-transformed data. Bioequivalence was concluded if the 90% confidence intervals (CIs of the adjusted geometric mean (gMean ratios for Cmax and AUC were within the predetermined range of 80%-125%, in accordance with regulatory requirements. Results For the test formulation, the trazodone gMean Cmax was 1480.9 ng/mL (vs. 1520.2 ng/mL for reference, AUC0-t was 18193.0 ng·h/mL (vs. 18209.8 ng·h/mL and AUC0- was 19346.3 ng·h/mL (vs. 19393.4 ng·h/mL. The 90% CIs for the ratio (test/reference were 93.0-102.0% for Cmax, 96.7-103.2% for AUC0-t and 96.1-103.5% for AUC0-. There were no deaths or serious adverse events during the conduct of the study. Conclusion Test product when compared with the Reference product meets the bioequivalence criteria with respect to the rate and extent of absorption of Trazodone under fed condition.

  15. Pharmacokinetics of single oral dose trazodone: a randomized, two-period, cross-over trial in healthy, adult, human volunteers under fed condition

    Science.gov (United States)

    Kale, Prashant; Agrawal, Yadvendra K.

    2015-01-01

    Objective: To assess the bioequivalence of single dose trazodone hydrochloride USP 100 mg tablets administered as an oral dose under fed condition. Methods:This study was an open-label, balanced, randomized, two-sequence, two-treatment, two-period, single oral dose, crossover bioequivalence study in healthy, adult, human subjects under fed conditions. After an overnight fast of at least 10 h, the subjects were served a high fat and high calorie vegetarian breakfast, which they were required to consume within 30 min. A single oral dose (100 mg) of either the test or the reference product was administered to the subjects. The primary pharmacokinetic parameters, maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUC0−t) and extrapolated to infinity (AUC0−∞) were compared by an analysis of variance using log-transformed data. Bioequivalence was concluded if the 90% confidence intervals (CIs) of the adjusted geometric mean (gMean) ratios for Cmax and AUC were within the predetermined range of 80–125%, in accordance with regulatory requirements. Results:For the test formulation, the trazodone gMean Cmax was 1480.9 ng/mL (vs. 1520.2 ng/mL for reference), AUC0−t was 18193.0 ng·h/mL (vs. 18209.8 ng·h/mL) and AUC0−∞ was 19346.3 ng·h/mL (vs. 19393.4 ng·h/mL). The 90% CIs for the ratio (test/reference) were 93.0–102.0% for Cmax, 96.7–103.2% for AUC0−t and 96.1–103.5% for AUC0−∞. There were no deaths or serious adverse events during the conduct of the study. Conclusion:Test product when compared with the Reference product meets the bioequivalence criteria with respect to the extent of absorption of trazodone under fed condition. PMID:26483693

  16. Exchangeability in the case-crossover design.

    Science.gov (United States)

    Mittleman, Murray A; Mostofsky, Elizabeth

    2014-10-01

    In cohort and case-control studies, confounding that arises as a result of differences in the distribution of determinants of the outcome between exposure groups leading to non-exchangeability are addressed by restriction, matching or with statistical models. In case-only studies, this issue is addressed by comparing each individual with his/herself. Although case-only designs use self-matching and only include individuals who develop the outcome of interest, issues of non-exchangeability are identical to those that arise in traditional case-control and cohort studies. In this review, we describe one type of case-only design, the case-crossover design, and discuss how the concept of exchangeability can be used to understand issues of confounding, carryover effects, period effects and selection bias in case-crossover studies.

  17. Double-blind, placebo-controlled, two-period, crossover trial to examine the pharmacokinetics of lisdexamfetamine dimesylate in healthy older adults

    Directory of Open Access Journals (Sweden)

    Ermer J

    2013-02-01

    Full Text Available James Ermer,1 Mary B Haffey,1,† Cynthia Richards,1 Kenneth Lasseter,2 Ben Adeyi,1 Mary Corcoran,1 Beverly Stanton,1 Patrick Martin1 1Shire Development LLC, Wayne, PA, 2Clinical Pharmacology of Miami, Inc., Miami, FL, USA†This author is now deceasedBackground: Pharmacokinetic and safety data on stimulants in older adults are limited. The objective of this study was to characterize the pharmacokinetics of lisdexamfetamine dimesylate (LDX, a d-amphetamine prodrug, in older adults.Methods: In this two-period crossover trial, healthy adults (n = 47 stratified by age (55–64, 65–74, and ≥ 75 years and gender received randomized, double-blind, single doses of LDX 50 mg or placebo. Baseline creatinine clearance, d-amphetamine and intact LDX pharmacokinetics, and safety were assessed.Results: Mean (±standard deviation baseline creatinine clearance in participants aged 55–64, 65–74, and ≥ 75 years was 102.5 ± 26.1, 105.3 ± 23.1, and 94.9 ± 27.3 mL per minute, respectively. In the groups aged 55–64, 65–74, and ≥ 75 years, the mean maximum plasma d-amphetamine concentration in men was 44.2 ± 11.1, 47.7 ± 7.0, and 53.4 ± 19.4 ng/mL, respectively; area under the concentration time curve from time 0 extrapolated to infinity (AUC0–inf was 915.0 ± 164.9, 1123.0 ± 227.0, and 1325.0 ± 464.4 ng • hour/mL; median time to reach peak plasma concentration was 4.5, 3.5, and 5.5 hours; in women, mean maximum plasma d-amphetamine concentration was 51.0 ± 6.7, 50.2 ± 6.8, and 64.3 ± 12.1 ng/mL, AUC0–inf was 1034.5 ± 154.6, 988.4 ± 80.5, and 1347.8 ± 198.9 ng • hour/mL, and median time to reach peak plasma concentration was 3.5, 4.1, and 5.5 hours, respectively. d-Amphetamine clearance was unrelated to baseline creatinine clearance. Five participants aged 55–64 years reported treatment-emergent adverse events (versus one each aged 65–74 and ≥ 75 years, and as did six women (versus one man. No trends in blood pressure or

  18. Design evaluation and optimisation in crossover pharmacokinetic studies analysed by nonlinear mixed effects models.

    Science.gov (United States)

    Nguyen, Thu Thuy; Bazzoli, Caroline; Mentré, France

    2012-05-20

    Bioequivalence or interaction trials are commonly studied in crossover design and can be analysed by nonlinear mixed effects models as an alternative to noncompartmental approach. We propose an extension of the population Fisher information matrix in nonlinear mixed effects models to design crossover pharmacokinetic trials, using a linearisation of the model around the random effect expectation, including within-subject variability and discrete covariates fixed or changing between periods. We use the expected standard errors of treatment effect to compute the power for the Wald test of comparison or equivalence and the number of subjects needed for a given power. We perform various simulations mimicking crossover two-period trials to show the relevance of these developments. We then apply these developments to design a crossover pharmacokinetic study of amoxicillin in piglets and implement them in the new version 3.2 of the r function PFIM.

  19. Linear combinations come alive in crossover designs.

    Science.gov (United States)

    Shuster, Jonathan J

    2017-10-30

    Before learning anything about statistical inference in beginning service courses in biostatistics, students learn how to calculate the mean and variance of linear combinations of random variables. Practical precalculus examples of the importance of these exercises can be helpful for instructors, the target audience of this paper. We shall present applications to the "1-sample" and "2-sample" methods for randomized short-term 2-treatment crossover studies, where patients experience both treatments in random order with a "washout" between the active treatment periods. First, we show that the 2-sample method is preferred as it eliminates "conditional bias" when sample sizes by order differ and produces a smaller variance. We also demonstrate that it is usually advisable to use the differences in posttests (ignoring baseline and post washout values) rather than the differences between the changes in treatment from the start of the period to the end of the period ("delta of delta"). Although the intent is not to provide a definitive discussion of crossover designs, we provide a section and references to excellent alternative methods, where instructors can provide motivation to students to explore the topic in greater detail in future readings or courses. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Eunice Kazue Kano

    2015-03-01

    Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

  1. Pharmacokinetic interaction between rosuvastatin and telmisartan in healthy Korean male volunteers: a randomized, open-label, two-period, crossover, multiple-dose study.

    Science.gov (United States)

    Son, Mijeong; Kim, Yukyung; Lee, Donghwan; Roh, Hyerang; Son, Hankil; Guk, Jinju; Jang, Seong Bok; Nam, Su Youn; Park, Kyungsoo

    2014-08-01

    Rosuvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, and telmisartan, an angiotensin receptor blocker, are commonly prescribed in combination for the treatment of dyslipidemia accompanied by hypertension. However, the nature of the pharmacokinetic interaction between the 2 drugs is not clearly understood. The goal of the present study was to investigate the pharmacokinetic drug-drug interaction between rosuvastatin and telmisartan in a healthy Korean population. This was a randomized, 2-part, open-label, 2-period, crossover, multiple-dose study, with each part composed of different subjects between the ages of 20 and 55 years. In part 1, each subject received rosuvastatin 20 mg with and without telmisartan 80 mg once daily for 6 consecutive days. In part 2, each subject received telmisartan 80 mg with and without rosuvastatin 20 mg once daily for 6 consecutive days. In both parts, there was a 16-day washout period between mono- and coadministration. Blood samples were collected up to 72 hours after the last dose. Adverse events (AEs) were evaluated through interviews and physical examinations. In part 1, the 90% CIs of the geometric mean ratios for the primary pharmacokinetic parameters for coadministration of the 2 drugs to monoadministration of each drug were 1.0736-1.2932 for AUCτ and 1.7442-2.3229 for Cmax,ss for rosuvastatin and 0.9942-1.1594 for AUCτ and 1.3593-1.7169 for Cmax,ss for N-desmethyl rosuvastatin, whereas in part 2, the CIs were 1.0834-1.2672 for AUCτ and 1.1534-1.5803 for Cmax,ss for telmisartan. The most frequently noted AE was cough in part 1, which occurred in 2 subjects receiving the combination therapy, and oropharyngeal pain in part 2, which occurred in 3 subjects receiving the combination therapy. All reported AEs were mild or moderate, and there was no significant difference in incidence between the treatments. These findings demonstrated that rosuvastatin and telmisartan mutually affected each other

  2. [Case-crossover design: Basic essentials and applications].

    Science.gov (United States)

    Carracedo-Martínez, Eduardo; Tobías, Aurelio; Saez, Marc; Taracido, Margarita; Figueiras, Adolfo

    2009-01-01

    Case-crossover analysis is an observational epidemiological design that was proposed by Maclure in 1991 to assess whether a given intermittent or unusual exposure may have triggered an immediate short-term, acute event. The present article outlines the basics of case-crossover designs, as well as their applications and limitations. The case-crossover design is based on exclusively selecting case subjects. To calculate relative risk, exposure during the period of time prior to the event (case period) is compared against the same subject's exposure during one or more control periods. This method is only appropriate when the exposures are transient in time and have acute short-term effects. For exposures in which there is no trend, a unidirectional approach is the most frequent and consists of selecting one or more control periods prior to the case period. When the exposure displays a time trend (e.g., air pollution), a unidirectional approach will yield biased estimates, and therefore bidirectional case-crossover designs are used, which select control time intervals preceding and subsequent to that of the event. The case-crossover design is being increasingly used across a wide range of fields, including factors triggering traffic, occupational and domestic accidents and acute myocardial infarction, and those involved in air pollution and health and pharmacoepidemiology, among others. Insofar as data-analysis is concerned, case-crossover designs can generally be regarded as matched case-control studies and consequently conditional logistic regression can be applied. Lastly, this study analyzes practical examples of distinct applications of the case-crossover design.

  3. Pharmacokinetics of venlafaxine extended release 75  mg and desvenlafaxine 50  mg in healthy CYP2D6 extensive and poor metabolizers: a randomized, open-label, two-period, parallel-group, crossover study.

    Science.gov (United States)

    Nichols, Alice I; Focht, Kristen; Jiang, Qin; Preskorn, Sheldon H; Kane, Cecelia P

    2011-01-01

    Genetically driven variations in the level of cytochrome P450 (CYP) 2D6 metabolic activity have been shown to significantly affect the pharmacokinetic behaviour of medications that are substrates of this enzyme. To evaluate the impact of CYP2D6 extensive metabolizer (EM) and poor metabolizer (PM) phenotypes on the pharmacokinetics of single doses of venlafaxine extended release (ER) and desvenlafaxine (administered as desvenlafaxine succinate). This study used a randomized, open-label, two-period, parallel-group, crossover design. The enrolled healthy subjects participated in the study for approximately 8 weeks, which included ≤ 6 weeks of screening procedures and two separate 1-week partial inpatient confinement periods (separated by a 4-day washout period), during which venlafaxine ER or desvenlafaxine was administered and blood samples were collected. Subjects were admitted to partial inpatient confinement in a laboratory setting for the two separate study periods where each study drug was individually administered. Blood samples for pharmacokinetic analyses were collected during the 120 hours following administration of each study drug. Plasma concentrations of the study drugs were measured by a third-party analyst using liquid chromatography-tandem mass spectrometry. Healthy subjects were recruited through newspaper advertisements and genotyped to determine their CYP2D6 metabolic phenotype (i.e. EM or PM) using internally developed and commercially available assays. Subjects were reimbursed for their participation in this study. Single, sequentially administered oral doses of the dual-acting, serotonin and norepinephrine reuptake inhibiting antidepressants venlafaxine ER (75  mg) and desvenlafaxine (50  mg) were administered. The main outcome measures were differences in the geometric means for area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) and peak plasma concentration (C(max)) between EMs and PMs. Comparisons were

  4. Influence analysis on crossover design experiment in bioequivalence studies.

    Science.gov (United States)

    Huang, Yufen; Ke, Bo-Shiang

    2014-01-01

    Crossover designs are commonly used in bioequivalence studies. However, the results can be affected by some outlying observations, which may lead to the wrong decision on bioequivalence. Therefore, it is essential to investigate the influence of aberrant observations. Chow and Tse in 1990 discussed this issue by considering the methods based on the likelihood distance and estimates distance. Perturbation theory provides a useful tool for the sensitivity analysis on statistical models. Hence, in this paper, we develop the influence functions via the perturbation scheme proposed by Hampel as an alternative approach on the influence analysis for a crossover design experiment. Moreover, the comparisons between the proposed approach and the method proposed by Chow and Tse are investigated. Two real data examples are provided to illustrate the results of these approaches. Our proposed influence functions show excellent performance on the identification of outlier/influential observations and are suitable for use with small sample size crossover designs commonly used in bioequivalence studies.

  5. Sequential design approaches for bioequivalence studies with crossover designs.

    Science.gov (United States)

    Potvin, Diane; DiLiberti, Charles E; Hauck, Walter W; Parr, Alan F; Schuirmann, Donald J; Smith, Robert A

    2008-01-01

    The planning of bioequivalence (BE) studies, as for any clinical trial, requires a priori specification of an effect size for the determination of power and an assumption about the variance. The specified effect size may be overly optimistic, leading to an underpowered study. The assumed variance can be either too small or too large, leading, respectively, to studies that are underpowered or overly large. There has been much work in the clinical trials field on various types of sequential designs that include sample size reestimation after the trial is started, but these have seen only little use in BE studies. The purpose of this work was to validate at least one such method for crossover design BE studies. Specifically, we considered sample size reestimation for a two-stage trial based on the variance estimated from the first stage. We identified two methods based on Pocock's method for group sequential trials that met our requirement for at most negligible increase in type I error rate.

  6. The case-crossover study design in pharmacoepidemiology.

    Science.gov (United States)

    Delaney, Joseph A 'Chris'; Suissa, Samy

    2009-02-01

    In the study of the association of transient drug exposures with acute outcomes, the case-crossover design is an efficient alternative to the case-control approach. This design based exclusively on the case series uses within-subject comparisons of drug exposures over time to estimate the rate ratio of the outcome associated with the drug under study. This design inherently removes the biasing effects of unmeasured, time-invariant confounding factors from the estimated rate ratio, but is sensitive to several assumptions. We illustrated the case-crossover design and explored its sensitivity using data from 4028 cases of gastrointestinal bleeding from the General Practice Research Database in assessing the effects of the drug warfarin. We compared the use of different time window lengths to assess exposure and considered the use of a case-time-control design to account for exposure time trends. The case-crossover approach found no excess risk of bleeding with warfarin exposure [rate ratio 0.98; 95% confidence interval (CI): 0.74-1.28] using a 1-month time window. When we restricted the analysis to subjects with truly transient drug exposure, defined by 1 to 3 prescriptions in the previous year, the rate ratio was 2.59 (95% CI: 1.42-4.74). To consider the longer 1-year exposure time window, the case-time-control approach was used and resulted in a rate ratio of 1.72 (95% CI: 1.08-2.43). In conclusion, the case-crossover design is potentially a powerful approach to assess the risk of drugs. This design is, however, highly sensitive to assumptions about intermittency of drug use and the length of the exposure time window, as demonstrated with the example of bleeding associated with warfarin use.

  7. Crossover versus parallel designs: dose-escalation design comparisons for first-in-human studies.

    Science.gov (United States)

    Yan, Zhiwu; Hosmane, Balakrishna; Locke, Charles

    2013-01-01

    We study the statistical efficiency for rising-dose designs in the context of first-in-human studies. Specifically, we identify a class of crossover designs that are appealing in terms of both subject safety and statistical efficiency and, for a three-period, two-panel design in such a class, we compare its A-efficiency relative to the corresponding parallel designs and optimal/efficient crossover designs, respectively, under various plausible models. In the meantime, we also evaluate the impact of inclusion of baseline measurements as a covariate in the statistical analysis, for both crossover and parallel studies.

  8. Pharmacokinetic and pharmacodynamic properties of a new biosimilar filgrastim TPI G-CSF in comparison to the marketed reference filgrastim Neupogen®: a double-blind, single-dose, two-period crossover trial

    Directory of Open Access Journals (Sweden)

    Niazi SK

    2015-11-01

    Full Text Available Sarfaraz K NiaziTherapeutic Proteins International, LLC, Chicago, IL, USAAbstract: Biosimilar biological products are a safe and effective alternative to branded biological agents. One of the most common uses of the therapeutic protein filgrastim, a biological drug (recombinant human granulocyte-colony stimulating factor, is to reduce the occurrence and duration of severe neutropenia and its associated serious complications. TPI G-CSF, a filgrastim product under development by Therapeutic Proteins International, LLC, is a proposed biosimilar to Amgen's marketed filgrastim, Neupogen®. To evaluate bioequivalence, we conducted a double-blind, randomized, two-period crossover study that took place at a single center and had a washout period of at least 2 weeks. The pharmacokinetic endpoints (area under the concentration-time curve from time 0 to time of the last observed/measured non-zero concentration [AUC0-t], AUC from time 0 extrapolated to infinity [AUC0-inf], and maximum observed concentration [Cmax] and the pharmacodynamic endpoints (baseline-corrected area under the effect curve from time zero to the last non-zero cell count data [AUEC0-t] and maximum observed effect [Emax] for the absolute neutrophil count were compared after administration of a subcutaneous 5 µg/kg dose of TPI G-CSF or Neupogen® in 58 healthy adults. These 58 healthy subjects (72% male, 34.8±10.5 years, 77.1±14.1 kg were randomly assigned to a treatment sequence group (TPI G-CSF-Neupogen® or Neupogen®-TPI G-CSF; subjects received a single subcutaneous injection of 5 µg/kg in each period. The 95% pharmacodynamic and 90% pharmacokinetic geometric confidence intervals of the ratio (TPI G-CSF/Neupogen® of least-squares means from the analysis of variance of the natural log-transformed data for each parameter fell within the approved bioequivalence range of 80% to 125%. There were no serious adverse events in this study. Treatment-emergent adverse events were reported

  9. Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

    Science.gov (United States)

    Choi, YoonJung; Lee, SeungHwan; Cho, Sang-Min; Kang, Won-Ho; Nam, Kyu-Yeol; Jang, In-Jin; Yu, Kyung-Sang

    2016-01-01

    Background A fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. Subjects and methods A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax) and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. Results The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94−1.01) and 0.97 (0.93−1.01), respectively. The corresponding values for losartan were 0.91 (0.81−1.02) and 1.05 (0.98−1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated. Conclusion An FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based on Cmax and AUC0–t values. The amlodipine besylate

  10. Residuals and outliers in replicate design crossover studies.

    Science.gov (United States)

    Schall, Robert; Endrenyi, Laszlo; Ring, Arne

    2010-07-01

    Outliers in bioequivalence trials may arise through various mechanisms, requiring different interpretation and handling of such data points. For example, regulatory authorities might permit exclusion from analysis of outliers caused by product or process failure, while exclusion of outliers caused by subject-by-treatment interaction generally is not acceptable. In standard 2 x 2 crossover studies it is not possible to distinguish between relevant types of outliers based on statistical criteria alone. However, in replicate design (2-treatment, 4-period) crossover studies three types of outliers can be distinguished: (i) Subject outliers are usually unproblematic, at least regarding the analysis of bioequivalence, and may require no further action; (ii) Subject-by-formulation outliers may affect the outcome of the bioequivalence test but generally cannot simply be removed from analysis; and (iii) Removal of single-data-point outliers from analysis may be justified in certain cases. As a very simple but effective diagnostic tool for the identification and classification of outliers in replicate design crossover studies we propose to calculate and plot three types of residual corresponding to the three different types of outliers that can be distinguished. The residuals are obtained from four mutually orthogonal linear contrasts of the four data points associated with each subject. If preferred, outlier tests can be applied to the resulting sets of residuals after suitable standardization.

  11. Optimal adaptive sequential designs for crossover bioequivalence studies.

    Science.gov (United States)

    Xu, Jialin; Audet, Charles; DiLiberti, Charles E; Hauck, Walter W; Montague, Timothy H; Parr, Alan F; Potvin, Diane; Schuirmann, Donald J

    2016-01-01

    In prior works, this group demonstrated the feasibility of valid adaptive sequential designs for crossover bioequivalence studies. In this paper, we extend the prior work to optimize adaptive sequential designs over a range of geometric mean test/reference ratios (GMRs) of 70-143% within each of two ranges of intra-subject coefficient of variation (10-30% and 30-55%). These designs also introduce a futility decision for stopping the study after the first stage if there is sufficiently low likelihood of meeting bioequivalence criteria if the second stage were completed, as well as an upper limit on total study size. The optimized designs exhibited substantially improved performance characteristics over our previous adaptive sequential designs. Even though the optimized designs avoided undue inflation of type I error and maintained power at ≥ 80%, their average sample sizes were similar to or less than those of conventional single stage designs.

  12. Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

    Directory of Open Access Journals (Sweden)

    Choi Y

    2016-09-01

    Full Text Available YoonJung Choi,1 SeungHwan Lee,2 Sang-Min Cho,3 Won-Ho Kang,3 Kyu-Yeol Nam,4 In-Jin Jang,1 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, 2Clinical Trials Center, Seoul National University Hospital, 3Research Institute, 4Global R&D, Korea United Pharm Inc., Seoul, Republic of Korea Background: A fixed-dose combination (FDC of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. Subjects and methods: A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. Results: The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94-1.01 and 0.97 (0.93-1.01, respectively. The corresponding values for losartan were 0.91 (0.81-1.02 and 1.05 (0.98-1.12, respectively. The incidence of adverse events was not significantly different between the two

  13. Single-dose pharmacokinetics of once-daily cyclobenzaprine extended release 30 mg versus cyclobenzaprine immediate release 10 mg three times daily in healthy young adults : a randomized, open-label, two-period crossover, single-centre study.

    Science.gov (United States)

    Darwish, Mona; Hellriegel, Edward T; Xie, Fang

    2008-01-01

    Cyclobenzaprine immediate release (CIR) has shown efficacy in the treatment of muscle spasm associated with acute, painful musculoskeletal conditions. An extended-release formulation of cyclobenzaprine (CER) has been developed to provide effective muscle spasm relief with once-daily dosing. The objective of this study was to compare the pharmacokinetics of CER and CIR. This was a single-centre study of 18 healthy young adults (aged 18-45 years). Healthy volunteers were assigned to receive either a single dose of CER 30 mg or three doses of CIR 10 mg on days 1 and 15 (separated by a 14-day washout) in an open-label, two-period crossover study. Pharmacokinetic parameters were monitored through 168 hours after the last dose in each dose period; adverse events (AEs) were monitored during the study through 3 weeks after the last dose of study drug. Cyclobenzaprine was administered as a single oral 30 mg dose of CER or three 10 mg oral doses of CIR given every 8 hours over 24 hours. Statistical tests were conducted against a two-sided alternative hypothesis at a 0.05 level of significance with equivalence limits of 80% and 125%. Measures included area under the plasma cyclobenzaprine concentration versus time curve (AUC) to 168 hours and infinity, maximum plasma cyclobenzaprine concentration (C(max)), and time to observed C(max) (t(max)). Eighteen subjects were randomized and 17 completed both periods of the study. CER exhibited a consistent concentration-time profile with a single peak, in contrast to the pharmacokinetic profile for CIR, which displayed multiple peaks and troughs over the 24-hour period. The pharmacokinetic profile of CER 30 mg was characterized by an absorption phase with a median t(max) of approximately 6 hours, compared with the initial peak of CIR (following the first dose) of about 4 hours. Mean plasma concentrations at 4 hours were comparable (12.1 ng/mL for CER; 12.4 ng/mL for CIR). Systemic cyclobenzaprine exposure (AUC and C(max)) was similar

  14. Practical approaches for design and analysis of clinical trials of infertility treatments: crossover designs and the Mantel-Haenszel method are recommended.

    Science.gov (United States)

    Takada, Michihiro; Sozu, Takashi; Sato, Tosiya

    2015-01-01

    Crossover designs have some advantages over standard clinical trial designs and they are often used in trials evaluating the efficacy of treatments for infertility. However, clinical trials of infertility treatments violate a fundamental condition of crossover designs, because women who become pregnant in the first treatment period are not treated in the second period. In previous research, to deal with this problem, some new designs, such as re-randomization designs, and analysis methods including the logistic mixture model and the beta-binomial mixture model were proposed. Although the performance of these designs and methods has previously been evaluated in large-scale clinical trials with sample sizes of more than 1000 per group, the actual sample sizes of infertility treatment trials are usually around 100 per group. The most appropriate design and analysis for these moderate-scale clinical trials are currently unclear. In this study, we conducted simulation studies to determine the appropriate design and analysis method of moderate-scale clinical trials for irreversible endpoints by evaluating the statistical power and bias in the treatment effect estimates. The Mantel-Haenszel method had similar power and bias to the logistic mixture model. The crossover designs had the highest power and the smallest bias. We recommend using a combination of the crossover design and the Mantel-Haenszel method for two-period, two-treatment clinical trials with irreversible endpoints.

  15. PHARMACOKINETIC AND BIOEQUIVALENCE COMPARISON BETWEEN EXTENDED RELEASE CAPSULES OF VENLAFAXINE HYDROCHLORIDE 150MG: AN OPEN LABEL, BALANCED, RANDOMIZED-SEQUENCE, SINGLE-DOSE, TWO-PERIOD CROSSOVER STUDY IN HEALTHY INDIAN MALE VOLUNTEERS

    Directory of Open Access Journals (Sweden)

    I.Sarath chandiran

    2011-03-01

    Full Text Available This bioequivalence study was designed to determine the pharmacokinetic, bioavailability and bioequivalence of Venlafaxine HCl 150 mg Extended Release Capsules in comparison with Effexor®-XR 150mg Extended Release Capsules after single dose administration under fed conditions in 20 healthy adult male subjects. Therefore the design of an open label, balanced, randomized, two-sequence, single dose, two way crossover study with a washout period of at least 7 days was used.Each volunteer received a 150 mg capsule of the reference or test drug respectively. On the day of dosing, blood samples were collected before dosing and at various time points up to 72 hours after dosing. Analysis of venlafaxine and its metabolite O-Desmethylvenlafaxine concentrations was performed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS method. The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the non-compartmental model. Drug safety and tolerability were assessed.The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the non-compartmental model. Drug safety and tolerability were assessed. The primary pharmacokinetic parameters (Cmax, AUC0-t and AUC0-inf 90%CI were within the 80 to 125% interval required for bioequivalence as stipulated in the current regulations of the USFDA acceptance criteria. The geometric mean ratios (Test/Reference between the two products of extended-release venlafaxine capsule under fed condition were 104.91% (92.86%-118.53% and 114.41% (103.43%-124.55% for Cmax ratios, 102.24% (95.95%-108.94% and 105.27% (96.76%-114.53% for AUC0-t ratios and 101.66% (95.73%-107.97% and 104.71% (96.13%-114.05% for AUC0-inf ratios of Venlafaxine and its metabolite O-Desmethylvenlafaxine (ODV respectively. 20 volunteers had completed both treatment periods. There was no significant difference of the Tmax parameter between the two

  16. Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers.

    Science.gov (United States)

    Parrillo-Campiglia, Susana; Ercoli, Mónica Cedres; Umpierrez, Ofelia; Rodríguez, Patricia; Márquez, Sara; Guarneri, Carolina; Estevez-Parrillo, Francisco T; Laurenz, Marilena; Estevez-Carrizo, Francisco E

    2009-10-01

    Imatinib is a tyrosine kinase inhibitor that has been established as a highly effective therapy for chronic myelogenous leukemia and gastrointestinal stromal tumors. A new generic, once-daily 400-mg tablet of imatinib has been developed by a pharmaceutical company in Argentina, where the regulatory standard for marketing authorization of an imatinib generic is in vitro dissolution testing. The aim of this study was to assess the bioequivalence of a new generic film-coated test tablet formulation versus a film-coated reference tablet formulation of imatinib 400 mg. The local manufacturer seeks to validate the in vitro performance of this new formulation with a bioequivalence study. A randomized, open-label, single-dose, fasting, 2-period, 2-sequence crossover design with a 2-week washout period was used in this study. The study population consisted of healthy male South American (Uruguayan) volunteers, who were assigned in a 1:1 ratio to a randomized sequence (test-reference or reference-test). In each period, the test or reference formulation was administered after an overnight fast. During the 72-hour follow-up period, participants were monitored for vital signs and symptoms. Blood samples were collected at 15 time points, including baseline, until 72 hours. Physical examination and laboratory tests (blood, urine) were repeated 1 week after study completion. A noncompartmental model was used to determine the pharmacokinetic parameters of imatinib. The 90% CIs of the test/reference ratios for AUC(0-infinity) and C(max) were determined; the test and reference formulations were considered bioequivalent if the 90% CIs were between 0.80 and 1.25. Adverse events were assessed by a nurse who administered a questionnaire while the healthy volunteers were admitted in the unit. The bioequivalence study was conducted in 30 Uruguayan male volunteers. Demographic characteristics (mean [SD]) included age, 27.8 (6.5) years; weight, 71.2 (9.8) kg; height, 1.71 (0.09) m; and body

  17. Relative bioavailability of generic and branded acetylcysteine effervescent tablets: A single-dose, open-label, randomized-sequence, two-period crossover study in fasting healthy Chinese male volunteers.

    Science.gov (United States)

    Liu, Yan-Mei; Liu, Yun; Lu, Chuan; Jia, Jing-Ying; Liu, Gang-Yi; Weng, Li-Ping; Wang, Jia-Yan; Li, Guo-Xiu; Wang, Wei; Li, Shui-Jun; Yu, Chen

    2010-11-01

    Acetylcysteine may be used as a muco- lytic agent for the treatment of chronic bronchitis, chronic obstructive pulmonary disease, and other pulmonary diseases complicated by the production of viscous mucus. However, little is known of its pharmacokinetic properties when given orally in healthy volunteers, particularly in a Chinese Han population. This study was conducted to provide support for the marketing of a generic product in China. The purpose of this study was to compare the pharmacokinetics and relative bioavailability of a generic test formulation and a branded reference formulation of acetylcysteine in fasting healthy Chinese male volunteers. A single-dose, open-label, randomized-sequence, 2-period crossover design with a 7-day washout period between doses was used in this study. Healthy Chinese male nonsmokers aged 18 to 40 years with a body mass index (BMI) of 19 to 25 kg/m(2) were selected. Eligible volunteers were randomly assigned to receive acetylcysteine 600 mg PO as either the test formulation (3 tablets of 200 mg each) or reference formulation (1 tablet of 600 mg) under fasting conditions. A total of 15 serial blood samples were collected over a 24-hour interval, and total plasma acetylcysteine concentrations were analyzed by a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters (C(max), T(max), t(½) AUC(0-t), and AUC(0-∞) were calculated and analyzed statistically. The 2 formulations were considered bioequivalent if the 90% CIs of the log-transformed ratios (test/reference) of C(max) and AUC were within the predetermined bioequivalence ranges (70%-143% for C(max); 80%-125% for AUC), as established by the State Food and Drug Administration of China. Tolerability was determined by vital signs, clinical laboratory tests, 12-lead ECGs, physical examinations, and interviews with the subjects about adverse events (AEs). A total of 24 healthy Chinese Han male volunteers were enrolled in and

  18. Design and numerical characterization of a crossover EBIS

    Science.gov (United States)

    Geyer, Sabrina; Langbein, A.; Meusel, Oliver; Kester, Oliver

    2015-01-01

    For the investigation of highly charged ions, a crossover EBIS (XEBIS) was developed at the University of Frankfurt. In contrast to conventional EBIS/T devices the compression of the electron beam is achieved by electrostatic focusing to a crossover point in the interaction region. This concept allows a compact and simple design. Simulations performed with EGUN show a perveance of 2.1×10-7 A/V3/2 for the realized gun system. In the interaction region the electron beam has a density of around 10 A/cm2 and a minimum radius of 0.15 mm. The XEBIS has a total length of 112 mm with a trap length of 26 mm. It is designed for electron beam energies of up to 6 keV/q. The storage capacity of the trap region is in the order of 1×108 charges. Charge state breeding studies with CBSIM indicate for the noble gases as maximal achievable charge state Ar16+, Kr30+ and Xe35+. Thus ion beam currents of around 2.04 nA assuming 50 Hz repetition rate can be expected. The emittance of the extracted beam is approximated to 8 mm mrad. After completion of the construction phase, the XEBIS will be installed for first performance investigations at a dedicated test bench, equipped with a fast Faraday Cup (FC), a retarding field spectrometer, a luminescence screen and optical diagnostics. Subsequently the XEBIS will serve as source for highly charged ions at different experimental setups.

  19. Estimation in AB/BA crossover trials with application to bioequivalence studies with incomplete and complete data designs.

    Science.gov (United States)

    Jaki, Thomas; Pallmann, Philip; Wolfsegger, Martin J

    2013-12-30

    Crossover studies are frequently used in clinical research as they allow within-subject comparisons instead of the between-subject evaluation of parallel group designs. Estimation of interesting parameters from such designs is, however, not trivial. We provide three methods for estimating treatment effects and associated standard errors from an AB/BA crossover trial. Assuming at least asymptotic normality, we can obtain the confidence intervals for single parameters as well as for differences or ratios of treatment effects. The latter is particularly useful in a pharmacokinetic context to establish bioequivalence using area under the concentration versus time curves (AUCs). In this work, we will illustrate how Fieller-type confidence intervals can be constructed for the ratio of AUCs estimated using a noncompartmental approach in a sparse sampling setting from a two-treatment, two-period, two-sequence crossover trial. In particular, we will discuss a flexible batch design, which includes traditional serial sampling and complete data designs as special cases. Via simulation, we show that the proposed intervals have nominal coverage and keep the type I error even for small sample sizes. Moreover, we illustrate the methodology in a real data example.

  20. Designer coordination polymers: dimensional crossover architectures and proton conduction.

    Science.gov (United States)

    Yamada, Teppei; Otsubo, Kazuya; Makiura, Rie; Kitagawa, Hiroshi

    2013-08-21

    Coordination polymers (CPs) have large degrees of freedom in framework compositions and in the structures and environment of the inner pores. This review focuses on the recent significant progress achieved by controlling these degrees of freedom. Two breakthroughs are reviewed for constructing sophisticated structures of CP frameworks, especially in dimensional crossover regions. The first is the synthesis of quasi one-dimensional halogen-bridged coordinative tubes by applying state-of-the-art techniques of coordination chemistry. The electronic state of the coordinative tube was studied by structural, spectroscopic and theoretical methods and found to be distinct from conventional one-dimensional systems. The second breakthrough is the achievement of a quasi-two-dimensional architecture by combining Langmuir-Blodgett and layer-by-layer methods. Two-dimensional LB CP films were prepared on liquid; the films were stacked layer by layer, and a crystalline quasi-two-dimensional structure was constructed. This review also covers the design of the environment of the inner pore, where hydrogen bond networks with various acidic sites were modified. By appropriate design of the hydrogen bond network, proton-conductive CPs are invented, which are summarized in this review. Types of proton donor sites are discussed and classified, and superprotonic conductive CPs were achieved in these investigations. These results will provide new strategies for constructing functional materials for smart devices.

  1. Using a Montessori method to increase eating ability for institutionalised residents with dementia: a crossover design.

    Science.gov (United States)

    Lin, Li-Chan; Huang, Ya-Ju; Watson, Roger; Wu, Shiao-Chi; Lee, Yue-Chune

    2011-11-01

    To investigate the efficacy of applying a Montessori intervention to improve the eating ability and nutritional status of residents with dementia in long-term care facilities. An early intervention for eating difficulties in patients with dementia can give them a better chance of maintaining independence and reduce the risk of malnutrition. An experimental crossover design was employed. Twenty-nine residents were chosen from two dementia special care units in metropolitan Taipei. To avoid contamination between participants in units using both Montessori and control interventions, two dementia special care units were randomly assigned into Montessori intervention (I1) and routine activities (I2) sequence groups. A two-period crossover design was used, with 15 residents assigned to Montessori intervention sequence I (I1, I2) and 14 residents assigned to Montessori intervention sequence II (I2, I1). On each intervention day, residents were given their assigned intervention. Montessori intervention was provided in 30-min sessions once every day, three days per week, for eight weeks. There was a two-week washout period between each intervention. There was a significant reduction in the Edinburgh Feeding Evaluation in Dementia score for the Montessori intervention period but not for the routine activities period, while the mean differences for the Eating Behavior Scale score, self-feeding frequency and self-feeding time were significantly higher than those of the routine activities period. Except for the Mini-Nutritional Assessment score post-test being significantly less than the pre-test for the routine activities period, no significant differences for any other variables were found for the routine activities period. This study confirms the efficacy of a Montessori intervention protocol on eating ability of residents with dementia. Adopting Montessori intervention protocols to maintain residents' self-feeding ability in clinical practice is recommended. Montessori

  2. A pharmacokinetic comparison of single doses of once-daily cyclobenzaprine extended-release 15 mg and 30 mg: a randomized, double-blind, two-period crossover study in healthy volunteers.

    Science.gov (United States)

    Darwish, Mona; Chang, Steven; Hellriegel, Edward T

    2009-01-01

    The purpose of this study was to compare the pharmacokinetics and tolerability of single oral doses of cyclobenzaprine extended-release (CER) 15- and 30-mg capsules. This was a randomized, double-blind, 2-period crossover study in healthy adults aged 18 to 40 years. Subjects were assigned to receive a single dose of either CER 15 mg or 30 mg on days 1 and 15, separated by a 14-day washout. Study comparisons included the plasma cyclobenzaprine AUC to 168 hours after dosing (AUC(0-168)), AUC(0-infinity), and C(max). Plasma cyclobenzaprine T(max), terminal elimination t(1/2), and adverse events (AEs) were also assessed. Sixteen subjects (9 women, 7 men) were randomized to receive cyclobenzaprine 15 mg or 30 mg; 13 (81.3%) were white and 3 (18.8%) were black. Mean age and weight were 30.2 years and 70.7 kg, respectively. The shapes of the pharmacokinetic profiles for CER 15 and 30 mg were parallel. Mean observed values for dose-dependent pharmacokinetic parameters of CER 15 and 30 mg were as follows: AUC(0-168), 318.3 and 736.6 ng . h/mL, respectively; AUC(0-infinity)), 354.1 and 779.9 ng . h/mL; and C(max), 8.3 and 19.9 ng/mL. Dose-independent parameters were comparable across doses. Median observed Tmax was 6.0 hours for both CER doses; mean t(1/2) was 33.4 hours for CER 15 mg and 32.0 hours for CER 30 mg. The bioavailability of the 2 doses, as indicated by the least squares mean AUC(0-infinity), was 330.3 ng . h/mL for CER 15 mg and 755.1 ng . h/mL for CER 30 mg. During the CER 15-mg treatment sequence, 5 subjects experienced 5 AEs (headache, dizziness, musculoskeletal pain, dermatitis, and glossodynia); during the CER 30-mg treatment sequence, 2 subjects experienced 2 AEs (somnolence and dysmenorrhea). All AEs were mild in intensity. No serious AEs occurred during the study. Once-daily CER 15 and 30 mg exhibited similarly shaped pharmacokinetic profiles. AUC(0-168), AUC(0-infinity)), and C(max) values for the 30-mg dose were approximately double those for the 15-mg

  3. An exploratory, randomized, parallel-group, open-label, relative bioavailability study with an additional two-period crossover food-effect study exploring the pharmacokinetics of two novel formulations of pexmetinib (ARRY-614

    Directory of Open Access Journals (Sweden)

    Wollenberg LA

    2015-09-01

    Full Text Available Lance A Wollenberg,1 Donald T Corson,2,3 Courtney A Nugent,1 Farran L Peterson,1 Ann M Ptaszynski,1 Alisha Arrigo,2,3 Coralee G Mannila,2,3 Kevin S Litwiler,1 Stacie J Bell1,4 1Array BioPharma, Boulder, 2Array BioPharma, Longmont, CO, 3Avista Pharma Solutions, Longmont, CO, 4Mallinckrodt Pharmaceuticals, Ellicott City, MD, USA Background: Pexmetinib (ARRY-614 is a dual inhibitor of p38 mitogen-activated protein kinase and Tie2 signaling pathways implicated in the pathogenesis of myelodysplastic syndromes. Previous clinical experience in a Phase I dose-escalation study of myelodysplastic syndrome patients using pexmetinib administered as neat powder-in-capsule (PIC exhibited high variability in pharmacokinetics and excessive pill burden, prompting an effort to improve the formulation of pexmetinib. Methods: A relative bioavailability assessment encompassed three parallel treatment cohorts of unique subjects comparing the two new formulations (12 subjects per cohort, a liquid oral suspension (LOS and liquid-filled capsule (LFC and the current clinical PIC formulation (six subjects in a fasted state. The food-effect assessment was conducted as a crossover of the LOS and LFC formulations administered under fed and fasted conditions. Subjects were divided into two groups of equal size to evaluate potential period effects on the food-effect assessment. Results: The geometric mean values of the total plasma exposures based upon area-under-the-curve to the last quantifiable sample (AUClast of pexmetinib were approximately four- and twofold higher after administration of the LFC and LOS formulations, respectively, than after the PIC formulation, when the formulations were administered in the fasted state. When the LFC formulation was administered in the fed state, pexmetinib AUClast decreased by <5% compared with the fasted state. After administration of the LOS formulation in the fed state, pexmetinib AUClast was 34% greater than observed in the fasted

  4. Effects of a 250-mL enema containing sodium phosphate on electrolyte concentrations in healthy volunteers: An open-label, randomized, controlled, two-period, crossover clinical trial*

    Science.gov (United States)

    Sédaba, Belén; Azanza, Josh R.; Campanero, Miguel A.; Garcia-Quetglas, Emilio; Muñoz, Maria Josh; Marco, Santiago

    2006-01-01

    Background: Enemas are used by individuals with constipation and are often required before certain medical diagnostic procedures and surgical interventions. However, abnormalities in serum electrolyte concentrations have been associated with enema use. Objective: The aim of this study was to determine the changes in serum electrolyte concentrations (phosphorus, calcium, sodium, and potassium) and urinary phosphorus elimination after the administration of a sodium phosphate enema. Methods: Healthy volunteers aged 35 to 70 years were eligible for this open-label, randomized, controlled, 2-period, crossover clinical trial at the Clinical Research Unit of the University Hospital of Navarra, Pamplona, Spain. The study comprised 2 one-day periods separated by a 7-day washout. All subjects were randomly assigned in a 1:1 ratio to 1 of 2 study sequences: (1) a single dose of Enema Casen® 250 mL in the first period followed by no treatment (control) in the second period, or (2) no treatment in the first period followed by a single dose of the study drug in the second period. The sequence of treatment was assigned using a randomization table that was prepared before the beginning of the study. Serum concentrations of phosphorus, sodium, potassium, and calcium were measured in both periods. Urinary phosphorus elimination was measured for 12 hours after enema administration (Ae0–12) in a subset of the subjects in the second period. Adverse events (AEs) were monitored by the investigators throughout the study. Normal ranges for the electrolytes were as follows: phosphorus, 2.5 to 5 mg/dL; calcium, 8.5 to 10.5 mg/dL; sodium, 135 to 145 mEq/L; and potassium, 3.5 to 5 mEq/L. Results: Twenty-four subjects (12 men, 12 women; mean [SD] age, 47.8 [9.6] years [range, 36–68 years]) participated in the study. All of the subjects were white and none were smokers. Twelve hours after enema administration, mean serum phosphorus and sodium concentrations increased by a mean of 1.18 mg

  5. Design evaluation and optimisation in crossover pharmacokinetic studies analysed by nonlinear mixed effects models

    OpenAIRE

    Nguyen, Thu Thuy; Bazzoli, Caroline; Mentré, France

    2012-01-01

    International audience; Bioequivalence or interaction trials are commonly studied in crossover design and can be analysed by nonlinear mixed effects models as an alternative to noncompartmental approach. We propose an extension of the population Fisher information matrix in nonlinear mixed effects models to design crossover pharmacokinetic trials, using a linearisation of the model around the random effect expectation, including within-subject variability and discrete covariates fixed or chan...

  6. The impact of anode design on fuel crossover of direct ethanol fuel cell

    Indian Academy of Sciences (India)

    Sethu Sundar Pethaiah; Jayakumar Arunkumar; Maximiano Ramos; Ahmed Al-Jumaily; Natarajan Manivannan

    2016-02-01

    Direct-ethanol fuel cells (DEFCs) hold a promising future owing to its simple balance of plant operation and potential high-energy density. The significant challenges associated with it is the fuel crossover, which limits its performance and durability. In the present work, Pt–Pd nanocomposites were fused so as to find its impact on the anode design of DEFC. The current paper aimed to address these issues optimally and it also investigated the ethanol crossover by various electrochemical characterization techniques.

  7. Bayesian analysis of time-series data under case-crossover designs: posterior equivalence and inference.

    Science.gov (United States)

    Li, Shi; Mukherjee, Bhramar; Batterman, Stuart; Ghosh, Malay

    2013-12-01

    Case-crossover designs are widely used to study short-term exposure effects on the risk of acute adverse health events. While the frequentist literature on this topic is vast, there is no Bayesian work in this general area. The contribution of this paper is twofold. First, the paper establishes Bayesian equivalence results that require characterization of the set of priors under which the posterior distributions of the risk ratio parameters based on a case-crossover and time-series analysis are identical. Second, the paper studies inferential issues under case-crossover designs in a Bayesian framework. Traditionally, a conditional logistic regression is used for inference on risk-ratio parameters in case-crossover studies. We consider instead a more general full likelihood-based approach which makes less restrictive assumptions on the risk functions. Formulation of a full likelihood leads to growth in the number of parameters proportional to the sample size. We propose a semi-parametric Bayesian approach using a Dirichlet process prior to handle the random nuisance parameters that appear in a full likelihood formulation. We carry out a simulation study to compare the Bayesian methods based on full and conditional likelihood with the standard frequentist approaches for case-crossover and time-series analysis. The proposed methods are illustrated through the Detroit Asthma Morbidity, Air Quality and Traffic study, which examines the association between acute asthma risk and ambient air pollutant concentrations.

  8. Two-stage designs for cross-over bioequivalence trials.

    Science.gov (United States)

    Kieser, Meinhard; Rauch, Geraldine

    2015-07-20

    The topic of applying two-stage designs in the field of bioequivalence studies has recently gained attention in the literature and in regulatory guidelines. While there exists some methodological research on the application of group sequential designs in bioequivalence studies, implementation of adaptive approaches has focused up to now on superiority and non-inferiority trials. Especially, no comparison of the features and performance characteristics of these designs has been performed, and therefore, the question of which design to employ in this setting remains open. In this paper, we discuss and compare 'classical' group sequential designs and three types of adaptive designs that offer the option of mid-course sample size recalculation. A comprehensive simulation study demonstrates that group sequential designs can be identified, which show power characteristics that are similar to those of the adaptive designs but require a lower average sample size. The methods are illustrated with a real bioequivalence study example.

  9. Application of Crossover Design for Conducting Rigorous Extension Evaluations

    Science.gov (United States)

    Jayaratne, K. S. U.; Bird, Carolyn L.; McClelland, Jacquelyn W.

    2013-01-01

    With the increasing demand for accountability of Extension programming, Extension professionals need to apply rigorous evaluation designs. Randomized designs are useful to eliminate selection biases of program participants and to improve the accuracy of evaluation. However, randomized control designs are not practical to apply in Extension program…

  10. Hypothesis testing and estimation in ordinal data under a simple crossover design.

    Science.gov (United States)

    Lui, Kung-Jong; Chang, Kuang-Chao

    2012-01-01

    Since each patient serves as his/her own control, the crossover design can be of use to improve power as compared with the parallel-groups design in studying noncurative treatments to certain chronic diseases. Although the research studies on the crossover design have been quite intensive, the discussions on analyzing ordinal data under such a design are truly limited. We propose using the generalized odds ratio (GOR) for paired sample data to measure the relative effect on patient responses for both treatment and period in ordinal data under a simple crossover trial. Assuming the treatment and period effects are multiplicative, we note that one can easily derive the maximum likelihood estimator (LE) in closed forms for the GOR of treatment and period effects. We develop asymptotic and exact procedures for testing treatment and period effects. We further derive asymptotic and exact interval estimators for the GOR of treatment and period effects. We use the data taken from a crossover trial to assess the clarity of leaflet instructions between two devices among asthma patients to illustrate the use of these test procedures and estimators developed here.

  11. Alterations in cardiovascular function by particulate matter in rats using a crossover design.

    Science.gov (United States)

    Chuang, Hsiao-Chi; Lin, Yin-Jyun; Chou, Charles C K; Hwang, Jing-Shiang; Chen, Chu-Chih; Yan, Yuan-Horng; Hsieh, Hui-I; Chuang, Kai-Jen; Cheng, Tsun-Jen

    2017-08-31

    The objective of this study was to investigate associations between cardiovascular effects and urban ambient particle constituents using an in vivo crossover experimental design. Ambient particles were introduced to an exposure chamber for whole-body exposure of WKY rats, where the particulate matter with an aerodynamic diameter of PM2.5) mass concentration, particle number concentration, and black carbon (BC) were monitored. Organic carbon (OC), elemental carbon (EC), and soluble ions of PM2.5 were determined. In a crossover design, rats were exposed to ambient particles or high-efficiency particle arrestance (HEPA)-filtered control air for 7 days following a 7-day washout interval. The crossover exposure between particles and HEPA-filtered air was repeated 4 times. Radiotelemetric data on blood pressure (BP) [systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP)], heart rate (HR), and heart rate viability (HRV) were subsequently obtained during the entire study. Exposure to the PM2.5 mass concentration was associated with decreases in the SBP, DBP, MAP, and HR (p PM2.5 mass concentration (p +), Cl(-), and NO3(-). Cl(-) was associated with the DBP, MAP, HR, SDNN, and RMSSD. NO3(-) was correlated with the SBP, MAP, HR, SDNN, and RMSSD. In conclusion, we observed cardiovascular responses to ambient particles in vivo using a crossover design which can reduce animal use in future environmental studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Crossover learning of gestures in two ideomotor apraxia patients: A single case experimental design study.

    Science.gov (United States)

    Shimizu, Daisuke; Tanemura, Rumi

    2017-06-01

    Crossover learning may aid rehabilitation in patients with neurological disorders. Ideomotor apraxia (IMA) is a common sequela of left-brain damage that comprises a deficit in the ability to perform gestures to verbal commands or by imitation. This study elucidated whether crossover learning occurred in two post-stroke IMA patients without motor paralysis after gesture training approximately 2 months after stroke onset. We quantitatively analysed the therapeutic intervention history and investigated whether revised action occurred during gesture production. Treatment intervention was to examine how to influence improvement and generalisation of the ability to produce the gesture. This study used an alternating treatments single-subject design, and the intervention method was errorless learning. Results indicated crossover learning in both patients. Qualitative analysis indicated that revised action occurred during the gesture-production process in one patient and that there were two types of post-revised action gestures: correct and incorrect gestures. We also discovered that even when a comparably short time had elapsed since stroke onset, generalisation was difficult. Information transfer between the left and right hemispheres of the brain via commissural fibres is important in crossover learning. In conclusion, improvements in gesture-production skill should be made with reference to the left cerebral hemisphere disconnection hypothesis.

  13. An optimal multi-period crossover design for an application in paediatric nephrology.

    Science.gov (United States)

    Matthews, John N S

    2014-02-28

    Crossover clinical trials can provide substantial benefits by eliminating inter-patient variation from treatment comparisons and by allowing multiple observations of each patient. They are particularly useful when sample sizes are necessarily small. These advantages proved particularly valuable in an assessment of clot prevention in children undergoing haemodialysis. Only small numbers of children are treated at any given time in any single dialysis unit, but each patient is obliged to attend two or three times each week, suggesting the use of a crossover trial with many periods. Standard crossover trials described in the literature (i) typically have fewer than 10 periods and (ii) are based on a model of questionable applicability to this study. This paper describes the derivation of an optimal crossover trial with 30 periods, which was used to compare two anticoagulants using nine patients. There is also a discussion of the analysis of the data obtained in the trial, which had a distribution markedly different from that anticipated when the study was designed.

  14. Case-crossover and case-time-control designs in birth defects epidemiology.

    Science.gov (United States)

    Hernández-Díaz, Sonia; Hernán, Miguel A; Meyer, Katie; Werler, Martha M; Mitchell, Allen A

    2003-08-15

    The case-crossover and the case-time-control designs can be used to evaluate the effect of intermittent exposures on the risk of acute events. To explore how birth defects epidemiology could benefit from these approaches, the authors compared them with a traditional case-control study design that evaluated the association between use of folic acid antagonists during the second and third pregnancy months and the risk of cardiovascular defects. Among 3,870 cases and 8,387 control infants in the Slone Epidemiology Center Birth Defects Study (1976-1998), the odds ratio was 2.3 (95% confidence interval (CI): 1.4, 3.9). The case-crossover approach compared folic acid antagonist use between the 2-month embryologically sensitive period (case window) and the 2 months preceding the last menstrual period (control window) among mothers of case infants (odds ratio = 1.0, 95% CI: 0.5, 2.0). Although it controls between-person confounding and avoids issues of control selection, this design may be biased by time trends of exposure prevalence during pregnancy. The case-time-control design, which adjusts for exposure time trends under certain assumptions, yielded an odds ratio of 2.9 (95% CI: 1.2, 7.2), but it requires controls. In the presence of gestational time trends of exposure, the new designs do not offer clear advantages over the case-control design.

  15. Designing quantum-dot cellular automata circuits using a robust one layer crossover scheme

    Directory of Open Access Journals (Sweden)

    Sara Hashemi

    2014-04-01

    Full Text Available Quantum-dot cellular automata (QCA is a novel nanotechnology which is considered as a solution to the scaling problems in complementary metal oxide semiconductor technology. In this Letter, a robust one layer crossover scheme is introduced. It uses only 90° QCA cells and works based on a proper clock assignment. The application of this new scheme is shown in designing a sample QCA circuit. Simulation results demonstrate that using this new scheme, significant improvements in terms of area and complexity can be achieved.

  16. Understanding the cluster randomised crossover design: a graphical illustraton of the components of variation and a sample size tutorial.

    Science.gov (United States)

    Arnup, Sarah J; McKenzie, Joanne E; Hemming, Karla; Pilcher, David; Forbes, Andrew B

    2017-08-15

    In a cluster randomised crossover (CRXO) design, a sequence of interventions is assigned to a group, or 'cluster' of individuals. Each cluster receives each intervention in a separate period of time, forming 'cluster-periods'. Sample size calculations for CRXO trials need to account for both the cluster randomisation and crossover aspects of the design. Formulae are available for the two-period, two-intervention, cross-sectional CRXO design, however implementation of these formulae is known to be suboptimal. The aims of this tutorial are to illustrate the intuition behind the design; and provide guidance on performing sample size calculations. Graphical illustrations are used to describe the effect of the cluster randomisation and crossover aspects of the design on the correlation between individual responses in a CRXO trial. Sample size calculations for binary and continuous outcomes are illustrated using parameters estimated from the Australia and New Zealand Intensive Care Society - Adult Patient Database (ANZICS-APD) for patient mortality and length(s) of stay (LOS). The similarity between individual responses in a CRXO trial can be understood in terms of three components of variation: variation in cluster mean response; variation in the cluster-period mean response; and variation between individual responses within a cluster-period; or equivalently in terms of the correlation between individual responses in the same cluster-period (within-cluster within-period correlation, WPC), and between individual responses in the same cluster, but in different periods (within-cluster between-period correlation, BPC). The BPC lies between zero and the WPC. When the WPC and BPC are equal the precision gained by crossover aspect of the CRXO design equals the precision lost by cluster randomisation. When the BPC is zero there is no advantage in a CRXO over a parallel-group cluster randomised trial. Sample size calculations illustrate that small changes in the specification of

  17. Nurse staffing level and nosocomial infections: empirical evaluation of the case-crossover and case-time-control designs.

    Science.gov (United States)

    Hugonnet, Stéphane; Villaveces, Andrés; Pittet, Didier

    2007-06-01

    The authors compared a case-crossover design, a case-time-control design, and a cohort design to evaluate the effect of nurse staffing level on the risk of nosocomial infections. They evaluated two strategies, conditional logistic regression and generalized estimating equation, to analyze the case-crossover study. The study was performed among critically ill patients in the medical intensive care unit of the University of Geneva Hospitals, Geneva, Switzerland. Of 366 patients who stayed more than 7 days in the intensive care unit between 1999 and 2002, 144 developed an infection. The main reasons for admission were infectious (35.3%), cardiovascular (32.5%), and pulmonary (19.7%) conditions. A comparison of the three study designs showed that lower nurse staffing was associated with an approximately 50% increased risk of nosocomial infections. All analyses yielded similar estimates, except that the point estimate obtained by the conditional logistic regression used in the case-crossover design was biased away from unity; the generalized estimating equation yielded unbiased results and is the most appropriate technique for case-crossover designs. The case-crossover methodology in hospital epidemiology is a promising alternative to traditional approaches, but selection of the referent periods is challenging.

  18. Challenges of clinical trial design when there is lack of clinical equipoise: use of a response-conditional crossover design.

    Science.gov (United States)

    Deng, Chunqin; Hanna, Kim; Bril, Vera; Dalakas, Marinos C; Donofrio, Peter; van Doorn, Pieter A; Hartung, Hans-Peter; Merkies, Ingemar S J

    2012-02-01

    Clinical equipoise is widely accepted as the basis of ethics in clinical research and requires investigators to be uncertain of the relative therapeutic merits of trial comparators. When clinical equipoise is in question, innovative trial designs are needed to reduce ethical tension while satisfying regulators' requirements. We report a novel response-conditional crossover study design used in a Phase 3, randomized, double-blind, placebo-controlled clinical trial of intravenous 10% caprylate-chromatography purified immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. During the initial 24-week period, patients crossed over to the alternative treatment at the first sign of deterioration or if they failed to improve or were unable to maintain improvement at any time after 6 weeks. This trial design addressed concerns about lack of equipoise raised by physicians interested in trial participation and proved acceptable to regulatory authorities. The trial design may be applicable to other studies where clinical equipoise is in question.

  19. Additional results for 'Sequential design approaches for bioequivalence studies with crossover designs'.

    Science.gov (United States)

    Montague, Timothy H; Potvin, Diane; Diliberti, Charles E; Hauck, Walter W; Parr, Alan F; Schuirmann, Donald J

    2012-01-01

    In 2008, this group published a paper on approaches for two-stage crossover bioequivalence (BE) studies that allowed for the reestimation of the second-stage sample size based on the variance estimated from the first-stage results. The sequential methods considered used an assumed GMR of 0.95 as part of the method for determining power and sample size. This note adds results for an assumed GMR = 0.90. Two of the methods recommended for GMR = 0.95 in the earlier paper have some unacceptable increases in Type I error rate when the GMR is changed to 0.90. If a sponsor wants to assume 0.90 for the GMR, Method D is recommended. Copyright © 2011 John Wiley & Sons, Ltd.

  20. Estimation of the treatment effect under an incomplete block crossover design in binary data - A conditional likelihood approach.

    Science.gov (United States)

    Lui, Kung-Jong

    2015-07-15

    A random effects logistic regression model is proposed for an incomplete block crossover trial comparing three treatments when the underlying patient response is dichotomous. On the basis of the conditional distributions, the conditional maximum likelihood estimator for the relative effect between treatments and its estimated asymptotic standard error are derived. Asymptotic interval estimator and exact interval estimator are also developed. Monte Carlo simulation is used to evaluate the performance of these estimators. Both asymptotic and exact interval estimators are found to perform well in a variety of situations. When the number of patients is small, the exact interval estimator with assuring the coverage probability larger than or equal to the desired confidence level can be especially of use. The data taken from a crossover trial comparing the low and high doses of an analgesic with a placebo for the relief of pain in primary dysmenorrhea are used to illustrate the use of estimators and the potential usefulness of the incomplete block crossover design.

  1. Design and Control of Cooperativity in Spin-Crossover in Metal–Organic Complexes: A Theoretical Overview

    Directory of Open Access Journals (Sweden)

    Hrishit Banerjee

    2017-07-01

    Full Text Available Metal organic complexes consisting of transition metal centers linked by organic ligands, may show bistability which enables the system to be observed in two different electronic states depending on external condition. One of the spectacular examples of molecular bistability is the spin-crossover phenomena. Spin-Crossover (SCO describes the phenomena in which the transition metal ion in the complex under the influence of external stimuli may show a crossover between a low-spin and high-spin state. For applications in memory devices, it is desirable to make the SCO phenomena cooperative, which may happen with associated hysteresis effect. In this respect, compounds with extended solid state structures containing metal ions connected by organic spacer linkers like linear polymers, coordination network solids are preferred candidates over isolated molecules or molecular assemblies. The microscopic understanding, design and control of mechanism driving cooperativity, however, are challenging. In this review we discuss the recent theoretical progress in this direction.

  2. The Impact of Temperature on Mortality in Tianjin, China: A Case-Crossover Design with a Distributed Lag Nonlinear Model

    Science.gov (United States)

    Barnett, Adrian G; Pan, Xiaochuan; Yu, Weiwei; Tong, Shilu

    2011-01-01

    Background: Although interest in assessing the impacts of temperature on mortality has increased, few studies have used a case-crossover design to examine nonlinear and distributed lag effects of temperature on mortality. Additionally, little evidence is available on the temperature–mortality relationship in China or on what temperature measure is the best predictor of mortality. Objectives: Our objectives were to use a distributed lag nonlinear model (DLNM) as a part of case-crossover design to examine the nonlinear and distributed lag effects of temperature on mortality in Tianjin, China and to explore which temperature measure is the best predictor of mortality. Methods: We applied the DLNM to a case-crossover design to assess the nonlinear and delayed effects of temperatures (maximum, mean, and minimum) on deaths (nonaccidental, cardiopulmonary, cardiovascular, and respiratory). Results: A U-shaped relationship was found consistently between temperature and mortality. Cold effects (i.e., significantly increased mortality associated with low temperatures) were delayed by 3 days and persisted for 10 days. Hot effects (i.e., significantly increased mortality associated with high temperatures) were acute and lasted for 3 days and were followed by mortality displacement for nonaccidental, cardiopulmonary, and cardiovascular deaths. Mean temperature was a better predictor of mortality (based on model fit) than maximum or minimum temperature. Conclusions: In Tianjin, extreme cold and hot temperatures increased the risk of mortality. The effects of cold last longer than the effects of heat. Combining the DLNM and the case-crossover design allows the case-crossover design to flexibly estimate the nonlinear and delayed effects of temperature (or air pollution) while controlling for season. PMID:21827978

  3. Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design

    Directory of Open Access Journals (Sweden)

    Brunt Ardith

    2011-05-01

    Full Text Available Abstract Background Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Methods Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6, glucose, insulin, and thiobaribituric acid reactive substance (TBARS were measured before and after of each supplementation. Results Flaxseed supplementation decreased TBARS (p = 0.0215 and HOMA-IR (p = 0.0382. Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003. Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.

  4. Randomized cluster crossover trials for reliable, efficient, comparative effectiveness testing: design of the Prevention of Arrhythmia Device Infection Trial (PADIT).

    Science.gov (United States)

    Connolly, Stuart J; Philippon, Francois; Longtin, Yves; Casanova, Amparo; Birnie, David H; Exner, Derek V; Dorian, Paul; Prakash, Ratika; Alings, Marco; Krahn, Andrew D

    2013-06-01

    Randomized clinical trials are a major advance in clinical research methodology. However, there are myriad important questions about the effectiveness of treatments used in daily practice that are not informed by the results of randomized trials. This is in part because of important limitations inherent in the methodology of randomized efficacy trials which are performed with tight control of inclusion, exclusion, treatment, and follow-up. This approach enhances evaluation of clinical efficacy (performance in controlled situations) but increases complexity and is not well suited to test clinical effectiveness (performance under conditions of actual use). The cluster crossover trial is a new concept for efficient comparative effectiveness testing. Deep tissue infection occurs in 2% of patients after arrhythmia device implantation, usually requires system extraction, and increases mortality. There is variation in antibiotic prophylaxis used to reduce implanted device infections. To efficiently evaluate the comparative effectiveness of antibiotic strategies now in use, we designed a cluster crossover clinical trial, which randomized implanting centres to 1 of 2 prophylactic antibiotic strategies, which became the standard care at the centre for 6 months, followed by crossover to the other strategy, rerandomization, and second crossover. This method greatly reduces trial complexity because it aligns study procedures with usual clinical care and increases generalizability. Pilot studies have tested the feasibility and an 10,800-patient trial, funded by the Canadian Institutes of Health Research, is now under way. The cluster crossover randomized trial design is well suited to efficiently test comparative effectiveness of existing treatments where there is variability of practice, clinical equipoise, and minimal risk.

  5. Fundamentos y aplicaciones del diseño de casos cruzados Case-crossover design: Basic essentials and applications

    Directory of Open Access Journals (Sweden)

    Eduardo Carracedo-Martínez

    2009-04-01

    Full Text Available El diseño de casos cruzados es un diseño epidemiológico observacional propuesto por Maclure en 1991 para valorar si alguna exposición intermitente o inusual ha desencadenado un evento agudo a muy corto plazo. En este trabajo se presentan los fundamentos de los diseños de casos cruzados, con sus aplicaciones y limitaciones. El diseño de casos cruzados se basa en seleccionar sólo sujetos caso. Para calcular el riesgo relativo se compara la exposición durante el periodo de tiempo previo al evento (periodo caso con la exposición del mismo sujeto en uno o varios periodos control. Este método únicamente es adecuado cuando las exposiciones son cambiantes en el tiempo, con efectos a corto plazo, y el efecto es agudo. Para exposiciones en que no existe tendencia, el planteamiento unidireccional es el más frecuente, y consiste en seleccionar uno o varios periodos control previos al momento caso. Cuando la exposición tiene una tendencia temporal (por ejemplo las de contaminación atmosférica, el planteamiento unidireccional proporciona estimaciones sesgadas, por lo que se utilizan diseños de casos cruzados bidireccionales, que seleccionan periodos de tiempo control anteriores y posteriores al del evento. Es un método que cuenta con una creciente utilización en amplios campos: desencadenantes de accidentes de tráfico, laborales y domésticos, o de infarto agudo de miocardio, contaminación atmosférica y salud, farmacoepidemiología, etc. Para el análisis de datos, generalmente se pueden considerar los diseños de casos cruzados como estudios de casos y controles emparejados, por lo que se aplica regresión logística condicional. Finalmente, en este trabajo se analizan ejemplos prácticos de diferentes aplicaciones del diseño de casos cruzados.Case-crossover analysis is an observational epidemiological design that was proposed by Maclure in 1991 to assess whether a given intermittent or unusual exposure may have triggered an immediate

  6. Macromolecular Design Strategies for Preventing Active-Material Crossover in Non-Aqueous All-Organic Redox-Flow Batteries.

    Science.gov (United States)

    Doris, Sean E; Ward, Ashleigh L; Baskin, Artem; Frischmann, Peter D; Gavvalapalli, Nagarjuna; Chénard, Etienne; Sevov, Christo S; Prendergast, David; Moore, Jeffrey S; Helms, Brett A

    2017-02-01

    Intermittent energy sources, including solar and wind, require scalable, low-cost, multi-hour energy storage solutions in order to be effectively incorporated into the grid. All-Organic non-aqueous redox-flow batteries offer a solution, but suffer from rapid capacity fade and low Coulombic efficiency due to the high permeability of redox-active species across the battery's membrane. Here we show that active-species crossover is arrested by scaling the membrane's pore size to molecular dimensions and in turn increasing the size of the active material above the membrane's pore-size exclusion limit. When oligomeric redox-active organics (RAOs) were paired with microporous polymer membranes, the rate of active-material crossover was reduced more than 9000-fold compared to traditional separators at minimal cost to ionic conductivity. This corresponds to an absolute rate of RAO crossover of less than 3 μmol cm(-2)  day(-1) (for a 1.0 m concentration gradient), which exceeds performance targets recently set forth by the battery industry. This strategy was generalizable to both high and low-potential RAOs in a variety of non-aqueous electrolytes, highlighting the versatility of macromolecular design in implementing next-generation redox-flow batteries. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Analysis of multiple exposures in the case-crossover design via sparse conditional likelihood.

    Science.gov (United States)

    Avalos, Marta; Grandvalet, Yves; Adroher, Nuria Duran; Orriols, Ludivine; Lagarde, Emmanuel

    2012-09-20

    We adapt the least absolute shrinkage and selection operator (lasso) and other sparse methods (elastic net and bootstrapped versions of lasso) to the conditional logistic regression model and provide a full R implementation. These variable selection procedures are applied in the context of case-crossover studies. We study the performances of conventional and sparse modelling strategies by simulations, then empirically compare results of these methods on the analysis of the association between exposure to medicinal drugs and the risk of causing an injurious road traffic crash in elderly drivers. Controlling the false discovery rate of lasso-type methods is still problematic, but this problem is also present in conventional methods. The sparse methods have the ability to provide a global analysis of dependencies, and we conclude that some of the variants compared here are valuable tools in the context of case-crossover studies with a large number of variables.

  8. Test Equality between Three Treatments under an Incomplete Block Crossover Design.

    Science.gov (United States)

    Lui, Kung-Jong

    2015-01-01

    Under a random effects linear additive risk model, we compare two experimental treatments with a placebo in continuous data under an incomplete block crossover trial. We develop three test procedures for simultaneously testing equality between two experimental treatments and a placebo, as well as interval estimators for the mean difference between treatments. We apply Monte Carlo simulations to evaluate the performance of these test procedures and interval estimators in a variety of situations. We note that the bivariate test procedure accounting for the dependence structure based on the F-test is preferable to the other two procedures when there is only one of the two experimental treatments has a non-zero effect vs. the placebo. We note further that when the effects of the two experimental treatments vs. a placebo are in the same relative directions and are approximately of equal magnitude, the summary test procedure based on a simple average of two weighted-least-squares (WLS) estimators can outperform the other two procedures with respect to power. When one of the two experimental treatments has a relatively large effect vs. the placebo, the univariate test procedure with using Bonferroni's equality can be still of use. Finally, we use the data about the forced expiratory volume in 1 s (FEV1) readings taken from a double-blind crossover trial comparing two different doses of formoterol with a placebo to illustrate the use of test procedures and interval estimators proposed here.

  9. Indirect fuel cell based on a redox-flow battery with a new design to avoid crossover

    Science.gov (United States)

    Siroma, Zyun; Yamazaki, Shin-ichi; Fujiwara, Naoko; Asahi, Masafumi; Nagai, Tsukasa; Ioroi, Tsutomu

    2013-11-01

    A new design of a redox flow battery (RFB), which is composed of two subcells separated by a gas phase of hydrogen, is proposed to eliminate the crossover of ionic species between the anolyte and catholyte. This idea not only increases the possible combinations of the two electrolytes, but also opens up the prospect of a revival of the old idea of an indirect fuel cell, which is composed of an RFB and two chemical reactors to regenerate the electrolytes using a fuel and oxygen. This paper describes the operation of a subcell as a component of an indirect fuel cell system. In the cycling test, oxidation/reduction of the electroactive species in each electrolyte were repeated with a hydrogen electrode as the counter electrode. This result demonstrates the possibility of this newly proposed RFB without crossover. In the operation of the subcell with a chemical reactor, a molecular catalyst (a rhodium porphyrin) was dissolved in the anolyte, and then a fuel was bubbled in the anolyte reservoir. As the electroactive species was reduced by the fuel, a steady-state oxidation current was observed at the cell. This demonstrates the negative half of the newly proposed indirect fuel cell.

  10. Crossover studies with survival outcomes.

    Science.gov (United States)

    Buyze, Jozefien; Goetghebeur, Els

    2013-12-01

    Crossover designs are well known to have major advantages when comparing the effect of two treatments which do not interact. With a right-censored survival endpoint, however, this design is quickly abandoned in favour of the more costly parallel design. Motivated by human immunodeficiency virus (HIV) prevention studies which lacked power, we evaluate what may be gained in this setting and compare parallel with crossover designs. In a heterogeneous population, we find and explain a substantial increase in power for the crossover study using a non-parametric logrank test. With frailties in a proportional hazards model, crossover designs equally lead to substantially smaller variance for the subject-specific hazard ratio (HR), while the population-averaged HR sees negligible gain. Its efficiency benefit is recovered when the population-averaged HR is reconstructed from estimated subject-specific hazard rates. We derive the time point for treatment crossover that optimizes efficiency and end with the analysis of two recent HIV prevention trials. We find that a Cellulose sulphate trial could have hardly gained efficiency from a crossover design, while a Nonoxynol-9 trial stood to gain substantial power. We conclude that there is a role for effective crossover designs in important classes of survival problems.

  11. Prescott tests of equality in binary data under a three-treatment three-period crossover design.

    Science.gov (United States)

    Zhu, Lixia; Lui, Kung-Jong

    2016-12-09

    Three test procedures accounting for patients with tied responses based on Prescott's ideas are developed for comparing three treatments under a three-period crossover trial in binary data. Monte Carlo simulation is employed to evaluate the performance of these test procedures in a variety of situations. The test procedures proposed here are noted to have power larger than those procedures, which utilize only those patients with un-tied responses. The data taken from a three-period crossover trial comparing two different doses of an analgesic with placebo for the relief of primary dysmenorrhea are used to illustrate the use of the test procedures developed here.

  12. Challenges of clinical trial design when there is lack of clinical equipoise: Use of a response-conditional crossover design

    NARCIS (Netherlands)

    C. Deng (Chunqin); K. Hanna (Kim); V. Bril (Vera); M.C. Dalakas (Marinos); P. Donofrio (Peter); P.A. van Doorn (Pieter); H.P. Hartung; I.S.J. Merkies (Ingemar)

    2012-01-01

    textabstractClinical equipoise is widely accepted as the basis of ethics in clinical research and requires investigators to be uncertain of the relative therapeutic merits of trial comparators. When clinical equipoise is in question, innovative trial designs are needed to reduce ethical tension whil

  13. Testing equality and interval estimation in binary responses when high dose cannot be used first under a three-period crossover design.

    Science.gov (United States)

    Lui, Kung-Jong; Chang, Kuang-Chao

    2015-01-01

    When comparing two doses of a new drug with a placebo, we may consider using a crossover design subject to the condition that the high dose cannot be administered before the low dose. Under a random-effects logistic regression model, we focus our attention on dichotomous responses when the high dose cannot be used first under a three-period crossover trial. We derive asymptotic test procedures for testing equality between treatments. We further derive interval estimators to assess the magnitude of the relative treatment effects. We employ Monte Carlo simulation to evaluate the performance of these test procedures and interval estimators in a variety of situations. We use the data taken as a part of trial comparing two different doses of an analgesic with a placebo for the relief of primary dysmenorrhea to illustrate the use of the proposed test procedures and estimators.

  14. A Mathematical Unification of Geometric Crossovers Defined on Phenotype Space

    OpenAIRE

    Yoon, Yourim; Kim, Yong-Hyuk; Moraglio, Alberto; Moon, Byung-Ro

    2009-01-01

    Geometric crossover is a representation-independent definition of crossover based on the distance of the search space interpreted as a metric space. It generalizes the traditional crossover for binary strings and other important recombination operators for the most frequently used representations. Using a distance tailored to the problem at hand, the abstract definition of crossover can be used to design new problem specific crossovers that embed problem knowledge in the search. This paper is...

  15. A novel approach to evaluate the pharmacokinetic biocomparability of a monoclonal antibody derived from two different cell lines using simultaneous crossover design.

    Science.gov (United States)

    Han, Chao; McIntosh, Thomas S; Geist, Brian J; Jiao, Trina; Puchalski, Thomas A; Goldberg, Kenneth M; Yang, Tong-Yuan; Pendley, Charles E; Zhou, Honghui; Davis, Hugh M

    2014-01-01

    A parallel study design with a large number of subjects has been a typical path for pharmacokinetic (PK) biocomparability assessment of biotherapeutics with long half-lives and immunogenic propensity, for example, monoclonal antibodies (mAb). A recently published innovative bioanalytical method that can quantify mAb produced from two different cell lines in the same sample opened an avenue to exploring a simultaneous crossover study design for PK biocomparability assessment of biotherapeutics. Siltuximab, a chimeric IgG1 mAb-targeting interleukin-6, was studied as an example. The pharmacokinetic biocomparability of siltuximab derived from mouse myeloma (Sp2/0) cells and Chinese hamster ovary cells was previously assessed and demonstrated in a clinical PK biocomparability study that enrolled more than 140 healthy subjects using a parallel trial design. The biocomparability was successfully shown in six cynomolgus monkeys in a preclinical proof-of-concept study using the new crossover study design supported by the analytical method. The impact of antidrug antibodies on the assessment of biocomparability was minimal. This novel approach opened up a new arena for the evaluation of PK biocomparability of biotherapeutics with unique molecular signatures such as a mAb derived from different cell lines.

  16. Assessing Different Crossover Operators for Travelling Salesman Problem

    Directory of Open Access Journals (Sweden)

    Imtiaz Hussain Khan

    2015-10-01

    Full Text Available Many crossover operators have been proposed in literature on evolutionary algorithms, however, it is still unclear which crossover operator works best for a given optimization problem. In this study, eight different crossover operators specially designed for travelling salesman problem, namely, Two-Point Crossover, Partially Mapped Crossover, Cycle Crossover, Shuffle Crossover, Edge Recombination Crossover, Uniform Order-based Crossover, Sub-tour Exchange Crossover, and Sequential Constructive Crossover are evaluated empirically. The select crossover operators were implemented to build an experimental setup upon which simulations were run. Four benchmark instances of travelling salesman problem, two symmetric (ST70 and TSP225 and two asymmetric (FTV100 and FTV170, were used to thoroughly assess the select crossover operators. The performance of these operators was analyzed in terms of solution quality and computational cost. It was found that Sequential Constructive Crossover outperformed other operators in attaining 'good' quality solution, whereas Two-Point Crossover outperformed other operators in terms of computational cost. It was also observed that the performance of different crossover operators is much better for relatively small number of cities, both in terms of solution quality and computational cost, however, for relatively large number of cities their performance greatly degrades

  17. Removal of Diethylhexyl Phthalate from Hands by Handwashing: Evidence from Experimental N-of-1 and Crossover Designs.

    Science.gov (United States)

    Lin, Pi-I D; Wu, Chia-Fang; Kou, Hwang-Shang; Huang, Tzu-Ying; Shiea, Jentaie; Wu, Ming-Tsang

    2017-03-28

    Phthalate exposure through skin is often neglected due to the small quantity and limited dermal absorption rate. However, free phthalate can be ingested by hand-to-mouth action or by contact with food. To evaluate the effectiveness in removing phthalate exposure on hand, we compare here the removal efficiency of di-(2-ethylhexyl)phthalate (DEHP) on hands by handwashing with soap-and-water versus water-only. In two three-day N-of-1 trials, residual DEHP was measured in a single female adult who washed exposed hands with soap-and-water or water-only. Subsequently, a crossover study was performed by randomly assigning another 28 subjects equally to wash with soap-and-water or with water-only, and then each one received the other treatment 24 hrs later. In the N-of-1 trials, mean DEHP removal rates range from 95.9% (SD = 0.1%) to 97.0% (SD = 2.5%) for soap-and-water handwashes, and 1.8% (SD = 0.1%) to 7.0% (SD = 0.3%) (n = 3) for water-only. In the crossover study, mean removal rate was 94.6% (SD = 6.5%) for handwashing with soap-and-water (n = 28) and 8.7% (SD = 5.7%) for water-only (n = 28). We concluded that handwashing with soap-and-water removes 80% more DEHP than handwashing with water alone, and may be a cost-effective way of removing other endocrine disruptors from hands.

  18. A Randomized Crossover Design to Assess Learning Impact and Student Preference for Active and Passive Online Learning Modules.

    Science.gov (United States)

    Prunuske, Amy J; Henn, Lisa; Brearley, Ann M; Prunuske, Jacob

    Medical education increasingly involves online learning experiences to facilitate the standardization of curriculum across time and space. In class, delivering material by lecture is less effective at promoting student learning than engaging students in active learning experience and it is unclear whether this difference also exists online. We sought to evaluate medical student preferences for online lecture or online active learning formats and the impact of format on short- and long-term learning gains. Students participated online in either lecture or constructivist learning activities in a first year neurologic sciences course at a US medical school. In 2012, students selected which format to complete and in 2013, students were randomly assigned in a crossover fashion to the modules. In the first iteration, students strongly preferred the lecture modules and valued being told "what they need to know" rather than figuring it out independently. In the crossover iteration, learning gains and knowledge retention were found to be equivalent regardless of format, and students uniformly demonstrated a strong preference for the lecture format, which also on average took less time to complete. When given a choice for online modules, students prefer passive lecture rather than completing constructivist activities, and in the time-limited environment of medical school, this choice results in similar performance on multiple-choice examinations with less time invested. Instructors need to look more carefully at whether assessments and learning strategies are helping students to obtain self-directed learning skills and to consider strategies to help students learn to value active learning in an online environment.

  19. Decomposing Multifractal Crossovers

    Science.gov (United States)

    Nagy, Zoltan; Mukli, Peter; Herman, Peter; Eke, Andras

    2017-01-01

    Physiological processes—such as, the brain's resting-state electrical activity or hemodynamic fluctuations—exhibit scale-free temporal structuring. However, impacts common in biological systems such as, noise, multiple signal generators, or filtering by transport function, result in multimodal scaling that cannot be reliably assessed by standard analytical tools that assume unimodal scaling. Here, we present two methods to identify breakpoints or crossovers in multimodal multifractal scaling functions. These methods incorporate the robust iterative fitting approach of the focus-based multifractal formalism (FMF). The first approach (moment-wise scaling range adaptivity) allows for a breakpoint-based adaptive treatment that analyzes segregated scale-invariant ranges. The second method (scaling function decomposition method, SFD) is a crossover-based design aimed at decomposing signal constituents from multimodal scaling functions resulting from signal addition or co-sampling, such as, contamination by uncorrelated fractals. We demonstrated that these methods could handle multimodal, mono- or multifractal, and exact or empirical signals alike. Their precision was numerically characterized on ideal signals, and a robust performance was demonstrated on exemplary empirical signals capturing resting-state brain dynamics by near infrared spectroscopy (NIRS), electroencephalography (EEG), and blood oxygen level-dependent functional magnetic resonance imaging (fMRI-BOLD). The NIRS and fMRI-BOLD low-frequency fluctuations were dominated by a multifractal component over an underlying biologically relevant random noise, thus forming a bimodal signal. The crossover between the EEG signal components was found at the boundary between the δ and θ bands, suggesting an independent generator for the multifractal δ rhythm. The robust implementation of the SFD method should be regarded as essential in the seamless processing of large volumes of bimodal fMRI-BOLD imaging data for

  20. Decomposing Multifractal Crossovers

    Directory of Open Access Journals (Sweden)

    Zoltan Nagy

    2017-07-01

    Full Text Available Physiological processes—such as, the brain's resting-state electrical activity or hemodynamic fluctuations—exhibit scale-free temporal structuring. However, impacts common in biological systems such as, noise, multiple signal generators, or filtering by transport function, result in multimodal scaling that cannot be reliably assessed by standard analytical tools that assume unimodal scaling. Here, we present two methods to identify breakpoints or crossovers in multimodal multifractal scaling functions. These methods incorporate the robust iterative fitting approach of the focus-based multifractal formalism (FMF. The first approach (moment-wise scaling range adaptivity allows for a breakpoint-based adaptive treatment that analyzes segregated scale-invariant ranges. The second method (scaling function decomposition method, SFD is a crossover-based design aimed at decomposing signal constituents from multimodal scaling functions resulting from signal addition or co-sampling, such as, contamination by uncorrelated fractals. We demonstrated that these methods could handle multimodal, mono- or multifractal, and exact or empirical signals alike. Their precision was numerically characterized on ideal signals, and a robust performance was demonstrated on exemplary empirical signals capturing resting-state brain dynamics by near infrared spectroscopy (NIRS, electroencephalography (EEG, and blood oxygen level-dependent functional magnetic resonance imaging (fMRI-BOLD. The NIRS and fMRI-BOLD low-frequency fluctuations were dominated by a multifractal component over an underlying biologically relevant random noise, thus forming a bimodal signal. The crossover between the EEG signal components was found at the boundary between the δ and θ bands, suggesting an independent generator for the multifractal δ rhythm. The robust implementation of the SFD method should be regarded as essential in the seamless processing of large volumes of bimodal f

  1. Coordinating two-period ordering and advertising policies in a dynamic market with stochastic demand

    Science.gov (United States)

    Wang, Junping; Wang, Shengdong; Min, Jie

    2015-03-01

    In this paper, we study the optimal two-stage advertising and ordering policies and the channel coordination issues in a supply chain composed of one manufacturer and one retailer. The manufacturer sells a short-life-cycle product through the retailer facing stochastic demand in dynamic markets characterised by price declines and product obsolescence. Following a two-period newsvendor framework, we develop two members' optimal ordering and advertising models under both the centralised and decentralised settings, and present the closed-form solutions to the developed models as well. Moreover, we design a two-period revenue-sharing contract, and develop sufficient conditions such that the channel coordination can be achieved and a win-win outcome can be guaranteed. Our analysis suggests that the centralised decision creates an incentive for the retailer to increase the advertising investments in two periods and put the purchase forward, but the decentralised decision mechanism forces the retailer to decrease the advertising investments in two periods and postpone/reduce its purchase in the first period. This phenomenon becomes more evident when demand variability is high.

  2. Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

    Science.gov (United States)

    Diaz, Francisco J; Berg, Michel J; Krebill, Ron; Welty, Timothy; Gidal, Barry E; Alloway, Rita; Privitera, Michael

    2013-12-01

    Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.

  3. Bloom Syndrome Helicase Promotes Meiotic Crossover Patterning and Homolog Disjunction.

    Science.gov (United States)

    Hatkevich, Talia; Kohl, Kathryn P; McMahan, Susan; Hartmann, Michaelyn A; Williams, Andrew M; Sekelsky, Jeff

    2017-01-09

    In most sexually reproducing organisms, crossover formation between homologous chromosomes is necessary for proper chromosome disjunction during meiosis I. During meiotic recombination, a subset of programmed DNA double-strand breaks (DSBs) are repaired as crossovers, with the remainder becoming noncrossovers [1]. Whether a repair intermediate is designated to become a crossover is a highly regulated decision that integrates several crossover patterning processes, both along chromosome arms (interference and the centromere effect) and between chromosomes (crossover assurance) [2]. Because the mechanisms that generate crossover patterning have remained elusive for over a century, it has been difficult to assess the relationship between crossover patterning and meiotic chromosome behavior. We show here that meiotic crossover patterning is lost in Drosophila melanogaster mutants that lack the Bloom syndrome helicase. In the absence of interference and the centromere effect, crossovers are distributed more uniformly along chromosomes. Crossovers even occur on the small chromosome 4, which normally never has meiotic crossovers [3]. Regulated distribution of crossovers between chromosome pairs is also lost, resulting in an elevated frequency of homologs that do not receive a crossover, which in turn leads to elevated nondisjunction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. A randomized crossover study of web-based media literacy to prevent smoking.

    Science.gov (United States)

    Shensa, Ariel; Phelps-Tschang, Jane; Miller, Elizabeth; Primack, Brian A

    2016-02-01

    Feasibly implemented Web-based smoking media literacy (SML) programs have been associated with improving SML skills among adolescents. However, prior evaluations have generally had weak experimental designs. We aimed to examine program efficacy using a more rigorous crossover design. Seventy-two ninth grade students completed a Web-based SML program based on health behavior theory and implemented using a two-group two-period crossover design. Students were randomly assigned by classroom to receive media literacy or control interventions in different sequences. They were assessed three times, at baseline (T0), an initial follow-up after the first intervention (T1) and a second follow-up after the second intervention (T2). Crossover analysis using analysis of variance demonstrated significant intervention coefficients, indicating that the SML condition was superior to control for the primary outcome of total SML (F = 11.99; P < 0.001) and for seven of the nine individual SML items. Results were consistent in sensitivity analyses conducted using non-parametric methods. There were changes in some exploratory theory-based outcomes including attitudes and normative beliefs but not others. In conclusion, while strength of the design of this study supports and extends prior findings around effectiveness of SML programs, influences on theory-based mediators of smoking should be further explored.

  5. The Ubiquity Of Crossover

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    If the word 'crossover' is unfamiliar to you, perhaps it is time to get to grips with this modern phenomenon. It is one of those vague words that one is never quite clear about; how did it start? What exactly does it mean? Crossover seems to have infiltrated our lives without us even noticing.

  6. Study design and methods for a randomized crossover trial substituting brown rice for white rice on diabetes risk factors in India.

    Science.gov (United States)

    Wedick, Nicole M; Sudha, Vasudevan; Spiegelman, Donna; Bai, Mookambika Ramya; Malik, Vasanti S; Venkatachalam, Siva Sankari; Parthasarathy, Vijayalaksmi; Vaidya, Ruchi; Nagarajan, Lakshmipriya; Arumugam, Kokila; Jones, Clara; Campos, Hannia; Krishnaswamy, Kamala; Willett, Walter; Hu, Frank B; Anjana, Ranjit Mohan; Mohan, Viswanathan

    2015-01-01

    India has the second largest number of people with diabetes in the world following China. Evidence indicates that consumption of whole grains can reduce the risk of type 2 diabetes. This article describes the study design and methods of a trial in progress evaluating the effects of substituting whole grain brown rice for polished (refined) white rice on biomarkers of diabetes risk (glucose metabolism, dyslipidemia, inflammation). This is a randomized controlled clinical trial with a crossover design conducted in Chennai, India among overweight but otherwise healthy volunteers aged 25-65 y with a body mass index ≥23 kg/m(2) and habitual rice consumption ≥200 g/day. The feasibility and cultural appropriateness of this type of intervention in the local environment will also be examined. If the intervention is efficacious, the findings can be incorporated into national-level policies which could include the provision of brown rice as an option or replacement for white rice in government institutions and food programs. This relatively simple dietary intervention has the potential to substantially diminish the burden of diabetes in Asia and elsewhere.

  7. Is saliva suitable as a biological fluid in relative bioavailability studies? Analysis of its performance in a 4 x 2 replicate crossover design.

    Science.gov (United States)

    Ruiz, M Esperanza; Fagiolino, Pietro; de Buschiazzo, Perla M; Volonté, M Guillermina

    2011-12-01

    The aim of the present study was to evaluate the suitability of saliva as a biological fluid in relative bioavailability (RBA) studies, with the focus on the statistical design and data variability. A randomized, open-label, four periods and two sequences (4 × 2) crossover RBA study in saliva of two phenytoin (PHT) 100 mg immediate-release capsules was performed. PHT is a narrow therapeutic index drug that has been widely used for epilepsy treatment for many years. Published information regarding its bioavailability is available, but plasma assessed. This study was designed and performed using saliva as the biological fluid and the simplest conditions that produce coherent results with previously published plasma studies. Pharmacokinetic parameters (C (max), T (max), AUC(0-t ), AUC(0-inf), C (max)/AUC(0-t ), K (e), and t (1/2)) for each volunteer at each period were calculated. Four different BE calculations were performed: individual bioequivalence, by the method of moments, and three average bioequivalence with data averaged over the two administrations and with data of periods 1-2 and 3-4. ANOVA calculation showed no significant subject-by-formulation interaction, period and sequence effects. The intra-subject variabilities were at least 20-fold lower than the inter-subject ones for C (max), AUC(0-t ) and AUC(0-inf). In all four BE calculations, the 90% CIs for the T/R ratios of studied pharmacokinetics parameters fell within the 80-125% range proposed by most regulatory agencies.

  8. Evaluation and Optimization of Blood Micro-Sampling Methods: Serial Sampling in a Cross-Over Design from an Individual Mouse.

    Science.gov (United States)

    Patel, Nita J; Wickremsinhe, Enaksha; Hui, Yu-Hua; Barr, Alexandar; Masterson, Nicholas; Ruterbories, Kenneth; Weller, Jennifer; Hanes, Jennifer; Kern, Tom; Perkins, Everett

    Current practices applied to mouse pharmacokinetic (PK) studies often use large numbers of animals with sporadic or composite sampling that inadequately describe PK profiles.  The purpose of this work was to evaluate and optimize blood microsampling techniques coupled with dried blood spot (DBS) and LC-MS/MS analysis to generate reliable PK data in mice.  In addition, the feasibility of cross-over designs was assessed and recommendations are presented. The work describes a comprehensive evaluation of five blood microsampling techniques (tail clip, tail vein with needle hub, submandibular, retro-orbital, and saphenous bleeding) in CD-1 mice.  The feasibility of blood sampling was evaluated based on animal observations, ease of bleeding, and ability to collect serial samples.  Methotrexate, gemfibrozil and glipizide were used as test compounds and were dosed either orally or intravenously, followed by DBS collection and LC-MS/MS analysis to compare PK with various bleeding methods. Submandibular and retro-orbital methods that required non-serial blood collections did not allow for inter-animal variability assessments and resulted in poorly described absorption and distribution kinetics.  The submandibular and tail vein with needle-hub methods were the least favorable from a technical feasibility perspective.  Serial bleeding was possible with cannulated animals or saphenous bleeding in non-cannulated animals.   Of the methods that allowed serial sampling, the saphenous method when executed as described in this report, was most practical, reproducible and provided for assessment of inter-animal variability.  It enabled the collection of complete exposure profiles from a single mouse and the conduct of an intravenous/oral cross-over study design.  This methodology can be used routinely, it promotes the 3Rs principles by achieving reductions in the number of animals used, decreased restraints and animal stress, and improved the quality of data obtained in mouse

  9. Cardiovascular responses to the ingestion of sugary drinks using a randomised cross-over study design: Does glucose attenuate the blood pressure-elevating effect of fructose?

    Science.gov (United States)

    Grasser, Erik K; Dulloo, Abdul; Montani, Jean-Pierre

    2014-07-28

    Overconsumption of sugar-sweetened beverages has been implicated in the pathogenesis of CVD. The objective of the present study was to elucidate acute haemodynamic and microcirculatory responses to the ingestion of sugary drinks made from sucrose, glucose or fructose at concentrations similar to those often found in commercial soft drinks. In a randomised cross-over study design, twelve young healthy human subjects (seven men) ingested 500 ml tap water in which was dissolved 60 g of either sucrose, glucose or fructose, or an amount of fructose equivalent to that present in sucrose (i.e. 30 g fructose). Continuous cardiovascular monitoring was performed for 30 min before and at 60 min after ingestion of sugary drinks, and measurements included beat-to-beat blood pressure (BP) and impedance cardiography. Additionally, microvascular endothelial function testing was performed after iontophoresis of acetylcholine and sodium nitroprusside using laser Doppler flowmetry. Ingestion of fructose (60 or 30 g) increased diastolic and mean BP to a greater extent than the ingestion of 60 g of either glucose or sucrose (Psugary drinks. In conclusion, ingestion of fructose, but not sucrose, increases BP in healthy human subjects. Although sucrose comprises glucose and fructose, its changes in TPR and CO are more related to glucose than to fructose.

  10. Effect of Keishibukuryogan on Endothelial Function in Patients with at Least One Component of the Diagnostic Criteria for Metabolic Syndrome: A Controlled Clinical Trial with Crossover Design

    Directory of Open Access Journals (Sweden)

    Yutaka Nagata

    2012-01-01

    Full Text Available We evaluated the effect of keishibukuryogan (KBG; Guizhi-Fuling-Wan, a traditional Japanese (Kampo formula, on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (Endo-PAT2000 in patients with metabolic syndrome-related factors by controlled clinical trial with crossover design. Ninety-two patients were assigned to group A (first KBG-treatment period, then control period; each lasting 4 weeks, with about one-year interval or group B (first control, then KBG-treatment. In forty-nine (27, group A; 22, group B patients completing all tests, the mean value of the natural logarithmic-scaled reactive hyperemia index (L_RHI increased and those of serum nonesterified fatty acid (NEFA, malondialdehyde, and soluble vascular cell adhesion molecule 1 decreased significantly during the KBG-treatment period, but not during the control period, and 4-week changes of L_RHI, NEFA, and malondialdehyde between the 2 periods showed significance. These results suggest that KBG has beneficial effect on endothelial function in patients with metabolic syndrome-related factors.

  11. A Mathematical Unification of Geometric Crossovers Defined on Phenotype Space

    CERN Document Server

    Yoon, Yourim; Moraglio, Alberto; Moon, Byung-Ro

    2009-01-01

    Geometric crossover is a representation-independent definition of crossover based on the distance of the search space interpreted as a metric space. It generalizes the traditional crossover for binary strings and other important recombination operators for the most frequently used representations. Using a distance tailored to the problem at hand, the abstract definition of crossover can be used to design new problem specific crossovers that embed problem knowledge in the search. This paper is motivated by the fact that genotype-phenotype mapping can be theoretically interpreted using the concept of quotient space in mathematics. In this paper, we study a metric transformation, the quotient metric space, that gives rise to the notion of quotient geometric crossover. This turns out to be a very versatile notion. We give many example applications of the quotient geometric crossover.

  12. Computer classes and games in virtual reality environment to reduce loneliness among students of an elderly reference center: Study protocol for a randomised cross-over design.

    Science.gov (United States)

    Antunes, Thaiany Pedrozo Campos; Oliveira, Acary Souza Bulle de; Crocetta, Tania Brusque; Antão, Jennifer Yohanna Ferreira de Lima; Barbosa, Renata Thais de Almeida; Guarnieri, Regiani; Massetti, Thais; Monteiro, Carlos Bandeira de Mello; Abreu, Luiz Carlos de

    2017-03-01

    Physical and mental changes associated with aging commonly lead to a decrease in communication capacity, reducing social interactions and increasing loneliness. Computer classes for older adults make significant contributions to social and cognitive aspects of aging. Games in a virtual reality (VR) environment stimulate the practice of communicative and cognitive skills and might also bring benefits to older adults. Furthermore, it might help to initiate their contact to the modern technology. The purpose of this study protocol is to evaluate the effects of practicing VR games during computer classes on the level of loneliness of students of an elderly reference center. This study will be a prospective longitudinal study with a randomised cross-over design, with subjects aged 50 years and older, of both genders, spontaneously enrolled in computer classes for beginners. Data collection will be done in 3 moments: moment 0 (T0) - at baseline; moment 1 (T1) - after 8 typical computer classes; and moment 2 (T2) - after 8 computer classes which include 15 minutes for practicing games in VR environment. A characterization questionnaire, the short version of the Short Social and Emotional Loneliness Scale for Adults (SELSA-S) and 3 games with VR (Random, MoviLetrando, and Reaction Time) will be used. For the intervention phase 4 other games will be used: Coincident Timing, Motor Skill Analyser, Labyrinth, and Fitts. The statistical analysis will compare the evolution in loneliness perception, performance, and reaction time during the practice of the games between the 3 moments of data collection. Performance and reaction time during the practice of the games will also be correlated to the loneliness perception. The protocol is approved by the host institution's ethics committee under the number 52305215.3.0000.0082. Results will be disseminated via peer-reviewed journal articles and conferences. This clinical trial is registered at ClinicalTrials.gov identifier: NCT

  13. Effects of a 6-month multimodal training intervention on retention of functional fitness in older adults: A randomized-controlled cross-over design

    Directory of Open Access Journals (Sweden)

    Gudlaugsson Janus

    2012-09-01

    Full Text Available Abstract Background Older adults have the highest rates of disability, functional dependence and use of healthcare resources. Training interventions for older individuals are of special interest where regular physical activity (PA has many health benefits. The main purpose of this study was to assess the immediate and long-term effects of a 6-month multimodal training intervention (MTI on functional fitness in old adults. Methods For this study, 117 participants, 71 to 90 years old, were randomized in immediate intervention group and a control group (delayed intervention group. The intervention consisted of daily endurance and twice-a-week strength training. The method was based on a randomized-controlled cross-over design. Short Physical Performance Battery (SPPB, 8 foot up-and-go test, strength performance, six min walking test (6 MW, physical activity, BMI and quality of life were obtained at baseline, after a 6-month intervention- and control phase, again after 6-month crossover- and delayed intervention phase, and after anadditional 6-month follow-up. Results After 6 months of MTI, the intervention group improved in physical performance compared with the control group via Short Physical Performance Battery (SPPB score (mean diff = 0.6, 95 % CI: 0.1, 1.0 and 8-foot up-and-go test (mean diff = −1.0 s, 95 % CI: -1.5, -0.6, and in endurance performance via 6-minute walking test (6 MW (mean diff = 44.2 meters, 95 % CI: 17.1, 71.2. In strength performance via knee extension the intervention group improved while control group declined (mean diff = 55.0 Newton, 95 % CI: 28.4, 81.7, and also in PA (mean diff = 125.9 cpm, 95 % CI: 96.0, 155.8. Long-term effects of MTI on the particpants was assesed by estimating the mean difference in the variables measured between time-point 1 and 4: SPPB (1.1 points, 95 % CI: 0.8, 1.4; 8-foot up-and-go (−0.9 s, 95 % CI: -1.2, -0.6; 6 MW (18.7 m, 95 % CI: 6.5, 31.0; knee extension (4.2 Newton

  14. Making crossovers during meiosis.

    Science.gov (United States)

    Whitby, M C

    2005-12-01

    Homologous recombination (HR) is required to promote both correct chromosome segregation and genetic variation during meiosis. For this to be successful recombination intermediates must be resolved to generate reciprocal exchanges or 'crossovers' between the homologous chromosomes (homologues) during the first meiotic division. Crossover recombination promotes faithful chromosome segregation by establishing connections (chiasmata) between the homologues, which help guide their proper bipolar alignment on the meiotic spindle. Recent studies of meiotic recombination in both the budding and fission yeasts have established that there are at least two pathways for generating crossovers. One pathway involves the resolution of fully ligated four-way DNA junctions [HJs (Holliday junctions)] by an as yet unidentified endonuclease. The second pathway appears to involve the cleavage of the precursors of ligated HJs, namely displacement (D) loops and unligated/nicked HJs, by the Mus81-Eme1/Mms4 endonuclease.

  15. Muscle ceramide content is similar after 3 weeks’ consumption of fat or carbohydrate diet in a crossover design in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Helge, J. W.; Tobin, L.; Drachmann, Tue

    2012-01-01

    This study aimed at investigating the effect of prolonged adaptation to fat- or carbohydrate-rich diet on muscle ceramide in type 2 diabetes patients, using a longitudinal crossover study. Eleven type 2 diabetes patients consumed isocaloric fat- or carbohydrate-rich diet for 3 weeks in random order...

  16. Design of a randomized controlled double-blind crossover clinical trial to assess the effects of saliva substitutes on bovine enamel and dentin in situ

    Directory of Open Access Journals (Sweden)

    Kielbassa Andrej M

    2011-04-01

    Full Text Available Abstract Background Hyposalivation is caused by various syndromes, diabetes, drugs, inflammation, infection, or radiotherapy of the salivary glands. Patients with hyposalivation often show an increased caries incidence. Moreover, hyposalivation is frequently accompanied by oral discomfort and impaired oral functions, and saliva substitutes are widely used to alleviate oral symptoms. However, preference of saliva substitutes due to taste, handling, and relief of oral symptoms has been discussed controversially. Some of the marketed products have shown demineralizing effects on dental hard tissues in vitro. This demineralizing potential is attributed to the undersaturation with respect to calcium phosphates. Therefore, it is important to modify the mineralizing potential of saliva substitutes to prevent carious lesions. Thus, the aim of the present study was to evaluate the effects of a possible remineralizing saliva substitute (SN; modified Saliva natura compared to a demineralizing one (G; Glandosane on mineral parameters of sound bovine dentin and enamel as well as on artificially demineralized enamel specimens in situ. Moreover, oral well-being after use of each saliva substitute was recorded. Methods/Design Using a randomized, double-blind, crossover, phase II/III in situ trial, volunteers with hyposalivation utilize removable dentures containing bovine specimens during the experimental period. The volunteers are divided into two groups, and are required to apply both saliva substitutes for seven weeks each. After both test periods, differences in mineral loss and lesion depth between values before and after exposure are evaluated based on microradiographs. The oral well-being of the volunteers before and after therapy is determined using questionnaires. With respect to the microradiographic analysis, equal mineral losses and lesion depths of enamel and dentin specimens during treatment with SN and G, and no differences in patients

  17. Designing dinuclear iron(II) spin crossover complexes. Structure and magnetism of dinitrile-, dicyanamido-, tricyanomethanide-, bipyrimidine- and tetrazine-bridged compounds.

    Science.gov (United States)

    Batten, Stuart R; Bjernemose, Jens; Jensen, Paul; Leita, Ben A; Murray, Keith S; Moubaraki, Boujemaa; Smith, Jonathan P; Toftlund, Hans

    2004-10-21

    In order to expand the few known examples of dinuclear iron(II) compounds displaying (weak) intradinuclear exchange coupling and spin-crossover on one or both of the iron(II) centres, various dinuclear compounds have been synthesised and assessed for their spin-crossover and exchange coupling behaviour. The key aim of the work was to prepare and structurally characterise 'weakly linked' and 'covalently bridged' systems incorporating bridging ligands such as alkyldinitriles (e.g.NC(CH(2))(4)CN), bipyrimidine (bpym), dicyanamide (dca(-)), tricyanomethanide (tcm(-)), 3,6-bis(2-pyridyl)tetrazine (bptz) and 3,6-bis(2-pyridyl)2,5-dihydrotetrazine (H(2)bptz). The 'end groups', which complete the Fe(ii)N(6) chromophores, include tris(2-pyridylmethyl)amine (tpa), di(2-pyridylethyl)(2-pyridylmethyl)amine (tpa'), 3-(2-pyridyl)pyrazole (pypzH), 1,10-phenanthroline (1,10-phen), tris(pyrazolyl)methane (tpm) and NCX(-)(X = S, Se). It was quite difficult to achieve the spin-crossover condition, many ligand combinations yielding high-spin/high-spin (HS-HS) Fe(II)Fe(II) spin states at all temperatures (300-2 K) with very weak antiferromagnetic coupling (J spin-crossover beginning above 300 K. 'Half crossover' examples, yielding HS-LS states below the spin transition, similar to those noted by Real and coworkers in some mu-bpym systems, were noted for [(1,10-phen)(NCS)(2)Fe(mu-bpym)Fe(NCS)(2)(1,10-phen)], 2, [(pypzH)(NCSe)(2)Fe(mu-bpym)Fe(NCSe)(2)(pypzH)], 4, and [(tpa)Fe(mu-H(2)bptz)Fe(tpa)](ClO(4))(4), 8. Interestingly, the mu-bptz analogue, 7, remained LS-LS at all temperatures with the start of a broad spin crossover evident above 300 K. No thermal hysteresis was evident in the spin transitions of these new dinuclear crossover species indicating a lack of intra- or interdinuclear cooperativity.

  18. A mobile application improves therapy-adherence rates in elderly patients undergoing rehabilitation: A crossover design study comparing documentation via iPad with paper-based control.

    Science.gov (United States)

    Mertens, Alexander; Brandl, Christopher; Miron-Shatz, Talya; Schlick, Christopher; Neumann, Till; Kribben, Andreas; Meister, Sven; Diamantidis, Clarissa Jonas; Albrecht, Urs-Vito; Horn, Peter; Becker, Stefan

    2016-09-01

    Medication adherence is crucial for success in the management of patients with chronic conditions. This study analyzes whether a mobile application on a tablet aimed at supporting drug intake and vital sign parameter documentation affects adherence in elderly patients.Patients with coronary heart disease and no prior knowledge of tablet computers were recruited. They received a personal introduction to the mobile application Medication Plan, installed on an Apple iPad. The study was conducted using a crossover design with 3 sequences: initial phase, interventional phase (28 days of using the app system), and comparative phase (28 days of using a paper diary). Users experienced the interventional and comparative phases alternately.A total of 24 patients (12 males; mean age 73.8 years) were enrolled in the study. The mean for subjectively assessed adherence (A14-scale; 5-point Likert scale, from "never" to "very often" which results in a score from 0 to 56) before the study was 50.0 (SD = 3.44). After both interventions there was a significant increase, which was more pronounced after the interventional phase (54.0; SD = 2.01) than after the comparative phase (52.6; SD = 2.49) (for all pairs after both interventions, P <0.001). Neither medical conditions nor the number of drug intake (amount and frequency of drug taking) per day affected subjective adherence. Logging data showed a significantly stronger adherence for the medication app than the paper system for both blood pressure recordings (P <0.001) and medication intake (P = 0.033). The majority of participants (n = 22) stated that they would like to use the medication app in their daily lives and would not need further assistance with the app.A mobile app for medication adherence increased objectively and subjectively measured adherence in elderly users undergoing rehabilitation. The findings have promising clinical implications: digital tools can assist chronic disease patients achieve adherence to

  19. Situation-specific factors predicting nonadherence to methadone maintenance treatment: a cross-sectional study using the case-crossover design in Guangzhou, China.

    Science.gov (United States)

    Gu, Jing; Xu, Huifang; Lau, Joseph T F; Chen, Long; Wang, Zixin; Hao, Chun; Hao, Yuantao

    2014-01-01

    Methadone maintenance treatment (MMT) is a key risk reduction measure for controlling HIV transmission among drug users. Studies using traditional methods exist to distinguish between drop outs and nondrop outs. However, many nondrop outs use MMT discontinuously and no study has identified situation-specific factors predicting their showing or not showing up. This study used a case-crossover design comparing situation-specific factors appearing on the last episode of attendance versus those of the last episode of nonattendance. A total of 133 participants were recruited from two MMT clinics in Guangzhou, China. Participants were asked separately whether various situation-specific factors existed in the last episodes of nonattendance and attendance of MMT. Matched odds ratios (ORs) based on conditional logistic regression analysis were presented. The results showed that the participants attended the MMT clinics on average for 25 days in the last month. Situation-specific factors significantly predicting nonattendance included: (1) physical and mental health status: in illness (OR = 33.0, P < 0.001), in a bad mood (OR = 7.5, P < 0.001), and occurrence of an unhappy event (OR = 18.0, P < 0.001); (2) other engagement: work engagement (OR = 40.0, P < 0.001), trip to other places (OR = 83.0, P < 0.001), and social activities (OR = 10.0, P = 0.012); (3) interpersonal relationship: conflicts with family (OR = 19.0, P = 0.004); and (4) structural situational factors: financial difficulty (OR = 19.0, P = 0.004) and worrying about police arrest (OR = 12.0, P = 0.003). Other factors such as interaction with drug users and heroin use were marginally significant, while reduced methadone dosage was nonsignificant. Interventions to improve MMT adherence need to consider situation-specific factors. Ancillary psychosocial services should be integrated with current MMT; MMT should also provide more flexible services to the clients. Furthermore, efforts should be taken to build up

  20. Case-crossover studies of occupational trauma: methodological caveats

    OpenAIRE

    Sorock, G; Lombardi, D; Gabel, C; Smith, G; Mittleman, M

    2001-01-01

    Objectives—The case-crossover study design was developed to examine triggers for the onset of myocardial infarction. This paper seeks to examine selected methodological issues when applying the case-crossover method to the study of traumatic injuries in the work environment.

  1. The Method Quality of Cross-Over Studies Involved in Cochrane Systematic Reviews

    OpenAIRE

    Hong Ding; Guang Li Hu; Xue Yan Zheng; Qing Chen; Diane Erin Threapleton; Zeng Huan Zhou

    2015-01-01

    Background It is possible that cross-over studies included in current systematic reviews are being inadequately assessed, because the current risk of bias tools do not consider possible biases specific to cross-over design. We performed this study to evaluate whether this was being done in cross-over studies included in Cochrane Systematic Reviews (CSRs). Methods We searched the Cochrane Library (up to 2013 issue 5) for CSRs that included at least one cross-over trial. Two authors independent...

  2. Efficacy of wearing compression garments during post-exercise period after two repeated bouts of strenuous exercise: a randomized crossover design in healthy, active males.

    Science.gov (United States)

    Goto, Kazushige; Mizuno, Sahiro; Mori, Ayaka

    2017-12-01

    The efficacy of wearing [a] compression garment (CG) between repeated bouts of exercise within a same day has not been fully understood. The present study determined the effect of wearing a CG after strenuous exercise sessions (consisting of sprint exercise, resistance exercise, drop jump) twice a day on exercise performance, muscle damage, and inflammatory responses. Eleven physically active males (age, 22.7 ± 0.9 years; height, 175.7 ± 6.7 cm; body mass, 73.6 ± 10.2 kg; BMI, 23.8 ± 2.7 kg/m(2)) performed two trials (a randomized crossover design), consisting of the trial with either wearing a whole-body CG during post-exercise period (CG trial) or the trial with wearing a normal garment without specific pressure (CON trial). Two exercise sessions were conducted in the morning (09:00-10:00, Ex1) and afternoon (14:00-15:00, Ex2). Immediately after completing 60 min of each exercise, the subjects in the CG trial changed into a whole-body CG. Time-course changes in exercise performance (bench press power, jump performances, repeated sprint ability), blood variables (lactate, glucose, myoglobin, creatine kinase, interleukin-6, leptin), and scores of subjective feeling (fatigue, muscle soreness) were compared between the CG and CON trials before Ex1 (8:40), immediately before Ex2 (14:00, 4 h after Ex1), 4 h after Ex2 (19:00), and 24 h after the onset of Ex1 (9:00). Two bouts of exercise significantly decreased performances of counter movement jump (main effect for time: P = 0.04, F = 3.75, partial η (2) = 0.27) and rebound jump (main effect for time: P = 0.00, F = 12.22, partial η (2) = 0.55), while no significant difference was observed between the two trials (interaction: P = 0.10, F = 1.96, partial η (2) = 0.16 for counter movement jump, P = 0.93, F = 0.01, partial η (2) = 0.001 for rebound jump). Repeated sprint ability (power output during 10 × 6 s maximal sprint, 30-s rest

  3. FANCM limits meiotic crossovers.

    Science.gov (United States)

    Crismani, Wayne; Girard, Chloé; Froger, Nicole; Pradillo, Mónica; Santos, Juan Luis; Chelysheva, Liudmila; Copenhaver, Gregory P; Horlow, Christine; Mercier, Raphaël

    2012-06-22

    The number of meiotic crossovers (COs) is tightly regulated within a narrow range, despite a large excess of molecular precursors. The factors that limit COs remain largely unknown. Here, using a genetic screen in Arabidopsis thaliana, we identified the highly conserved FANCM helicase, which is required for genome stability in humans and yeasts, as a major factor limiting meiotic CO formation. The fancm mutant has a threefold-increased CO frequency as compared to the wild type. These extra COs arise not from the pathway that accounts for most of the COs in wild type, but from an alternate, normally minor pathway. Thus, FANCM is a key factor imposing an upper limit on the number of meiotic COs, and its manipulation holds much promise for plant breeding.

  4. Pressure and Temperature Sensors Using Two Spin Crossover Materials

    Directory of Open Access Journals (Sweden)

    Catalin-Maricel Jureschi

    2016-02-01

    Full Text Available The possibility of a new design concept for dual spin crossover based sensors for concomitant detection of both temperature and pressure is presented. It is conjectured from numerical results obtained by mean field approximation applied to a Ising-like model that using two different spin crossover compounds containing switching molecules with weak elastic interactions it is possible to simultaneously measure P and T. When the interaction parameters are optimized, the spin transition is gradual and for each spin crossover compounds, both temperature and pressure values being identified from their optical densities. This concept offers great perspectives for smart sensing devices.

  5. Variant of partially mapped crossover for the Travelling Salesman problems

    Directory of Open Access Journals (Sweden)

    Kusum Deep

    2012-01-01

    Full Text Available In this paper a variant of partially mapped crossover (VPMX is designed using cut point positions and is tested for its performance with the existing partially mapped crossover (PMX.In order to test the performance ,two mutation operators are used. These mutation operators are inverted displacement and inversion mutations. Partially mapped crossover (PMX with inversion and with inverted displacement and a variant of partially mapped crossover (VPMX with inversion and with inverted displacement are programmed in C++ and implemented on a set of ten benchmark problems taken from the Travelling salesman problem library (TSPLIB. The results indicate that the designed variant of PMX is superior by showing a better performance in eight instances in combination with the inverted displacement mutation. In two instances PMX has obtained a better result. One is PMX with inversion mutation and the other is PMX with inverted displacement mutation.

  6. The effect of high lactose-isomaltulose on cognitive performance of young children. A double blind cross-over design study.

    Science.gov (United States)

    Taib, Mohd Nasir Mohd; Shariff, Zalilah Mohd; Wesnes, Keith A; Saad, Hazizi Abu; Sariman, Sarina

    2012-02-01

    Changes in blood glucose are hypothesized to influence cognitive performance and these changes can be affected by certain nutrients. This double-blind 4-period cross-over study evaluated the effects of a slow-release modified sucrose (isomaltulose) in combination with a high concentration of lactose on cognitive performance of 5-6 year old children. Thirty children received a standard growing upmilk (Std GUM), reformulated growing up milk (Reform GUM), standard growing up milk with lactose-isomaltulose (Iso GUM), and a standard glucose drink (Glucose). The CDR System, a computerised cognitive assessment system, was used to assess various measures of attention and memory of the children at baseline (T=0), 60 (T=1), 120 (T=2), and 180 (T=3) minutes following the intake of test products. Overall, there was a decline in performance over the morning on almost every cognitive task. Children showed better attention following consumption of Iso GUM compared to Std GUM but attention was not significantly different than Reform GUM and glucose. Also, Iso GUM conferred a beneficial effect over both Reform GUM and glucose on sensitivity index of numeric working memory with no difference observed between Iso GUM and Std GUM. Surprisingly, glucose group showed lowest decline in the sensitivity index of spatial working memory and highest speed in picture recognition, although the latter was significantly better than Reform GUM only. For speed of spatial working memory, Reform GUM had the lowest decline but was significantly different only with Std GUM. There was, however, no significant difference among conditions for continuity of attention, speed of numeric working memory and picture recognition sensitivity. Despite the small sample size, the findings are intriguing as carbohydrate composition seems to influence some aspects of cognitive performance such as attention and memory. However, further studies are needed to confirm these findings. Copyright © 2011 Elsevier Ltd. All

  7. Myofascial Induction Effects on Neck-Shoulder Pain in Breast Cancer Survivors: Randomized, Single-Blind, Placebo-Controlled Crossover Design.

    Science.gov (United States)

    Castro-Martín, Eduardo; Ortiz-Comino, Lucía; Gallart-Aragón, Tania; Esteban-Moreno, Bernabé; Arroyo-Morales, Manuel; Galiano-Castillo, Noelia

    2017-05-01

    To (1) investigate the immediate effects of myofascial induction (MI), with placebo electrotherapy as a control, on perceived pain, cervical/shoulder range of motion (ROM), and mood state in breast cancer survivors (BCSs) with shoulder/arm morbidity; and (2) examine the relationships between pain modifications and cervical/shoulder ROM on the side affected by breast cancer. Randomized, single-blind, placebo-controlled crossover study. Physical therapy laboratory. BCSs (N=21) who had a diagnosis of stage I-IIIA breast cancer and had completed adjuvant therapy (except hormonal treatment). During each session, the BCSs received either an MI (fascial unwinding) intervention focused on the upper limb area following the Pilat approach or placebo pulsed shortwave therapy (control group). Each session lasted 30 minutes, and an adequate washout period of 4 weeks between sessions was established. The visual analog scale (VAS) for pain and anxiety, shoulder-cervical goniometry for ROM, the Profile of Mood States for psychological distress, and the Attitudes Towards Massage Scale were used. An analysis of covariance (ANCOVA) revealed significant time × group interactions for VAS affected arm (P=.031) but not for VAS cervical (P=.332), VAS nonaffected arm (P=.698), or VAS anxiety (P=.266). The ANCOVA also revealed significant interactions for affected shoulder flexion (Pcervical rotation (P=.022) and affected cervical lateral flexion (P=.038) were also found. A significant negative correlation was found between changes in VAS affected arm and shoulder/arm internal rotation ROM (r=-.46; P=.03). A single MI session decreases pain intensity and improves neck-shoulder ROM to a greater degree than placebo electrotherapy for BCSs experiencing pain. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  8. Dynamics in Two Periodically Driven and Weakly Coupled Bose-Einstein Condensates

    Institute of Scientific and Technical Information of China (English)

    陈付广; 黄德斌; 郭荣伟

    2005-01-01

    In this paper, dynamics in the oscillations of the relative atomic population in two periodically driven and weakly coupled Bose-Einstein eondensates (BECs) was qualitatively studied. Using the well-known Melnikov method, the conditions of existence of the periodic and chaotic coherent atomic tunnellings were given in the model. Our results indicate the typical route from bifurcation of the limited circles to chaos, and are in agreement with the previous numerical results.

  9. Switching management by adiabatic passage in two periodically modulated nonlinear waveguides

    CERN Document Server

    Luo, Xiaobing; Yu, Xiaoguang

    2016-01-01

    We theoretically investigate light propagation in two periodically modulated nonlinear waveguides with certain propagation constant detuning between two guides. By slowly varying the amplitude of modulation, we can steer the light to the desired output waveguide when equal amounts of lights are launched into each waveguide. We also reveal that the light propagation dynamics depends sensitively on the detuning between two guides. Our findings can be explained qualitatively by means of adiabatic navigation of the extended nonlinear Floquet states.

  10. Drop cost and wavelength optimal two-period grooming with ratio 4

    CERN Document Server

    Bermond, Jean-Claude; Gionfriddo, Lucia; Quattrocchi, Gaetano; Valls, Ignasi Sau

    2009-01-01

    We study grooming for two-period optical networks, a variation of the traffic grooming problem for WDM ring networks introduced by Colbourn, Quattrocchi, and Syrotiuk. In the two-period grooming problem, during the first period of time, there is all-to-all uniform traffic among $n$ nodes, each request using $1/C$ of the bandwidth; and during the second period, there is all-to-all uniform traffic only among a subset $V$ of $v$ nodes, each request now being allowed to use $1/C'$ of the bandwidth, where $C' < C$. We determine the minimum drop cost (minimum number of ADMs) for any $n,v$ and C=4 and $C' \\in \\{1,2,3\\}$. To do this, we use tools of graph decompositions. Indeed the two-period grooming problem corresponds to minimizing the total number of vertices in a partition of the edges of the complete graph $K_n$ into subgraphs, where each subgraph has at most $C$ edges and where furthermore it contains at most $C'$ edges of the complete graph on $v$ specified vertices. Subject to the condition that the two-p...

  11. Staphylococcus aureus bacteremia: comparison of two periods and a predictive model of mortality

    Directory of Open Access Journals (Sweden)

    Lucieni de Oliveira Conterno

    2002-12-01

    Full Text Available Staphylococcus aureus is an important pathogen causing bacteremia, primarily affecting hospitalized patients. We studied the epidemiology of S. aureus bacteremia, comparing two periods (early and mid 1990s and developed a predictive model of mortality. A nested case-control was done. All 251 patients over 14 years old with positive blood cultures for S. aureus were selected. MRSA (methicillin resistant S. aureus was isolated in 63% of the cases. When comparing the two periods MRSA community-acquired bacteremia increased from 4% to 16% (p=0.01. There was no significant difference in the mortality rate between the two periods (39% and 33%, p=0.40. Intravascular catheters provoked 24% of the cases of bacteremia and were associated with the lowest rate of mortality. In a logistic regression analysis, three variables were associated with death: septic shock, source of bacteraemia and resistance to methicillin. The probability of dying among patients with MRSA and those with methicillin sensitive S. aureus bacteraemia ranged from 10% to 90% and from 4% to 76%, respectively, depending on the source of the bacteraemia and the occurrence of septic shock. The MRSA found in Brazil may be a particularly virulent strain.

  12. A prospective randomised cross-over study of the effect of insulin analogues and human insulin on the frequency of severe hypoglycaemia in patients with type 1 diabetes and recurrent hypoglycaemia (the HypoAna trial: study rationale and design

    Directory of Open Access Journals (Sweden)

    Kristensen Peter

    2012-06-01

    Full Text Available Abstract Background Severe hypoglycaemia still represents a significant problem in insulin-treated diabetes. Most patients do not experience severe hypoglycaemia often. However, 20% of patients with type 1 diabetes experience recurrent severe hypoglycaemia corresponding to at least two episodes per year. The effect of insulin analogues on glycaemic control has been documented in large trials, while their effect on the frequency of severe hypoglycaemia is less clear, especially in patients with recurrent severe hypoglycaemia. The HypoAna Trial is designed to investigate whether short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing the occurrence of severe hypoglycaemic episodes in patients with recurrent hypoglycaemia. This paper reports the study design of the HypoAna Trial. Methods/design The study is a Danish two-year investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE, multicentre, cross-over trial investigating the effect of insulin analogues versus human insulin on the frequency of severe hypoglycaemia in subjects with type 1 diabetes. Patients are randomised to treatment with basal-bolus therapy with insulin detemir / insulin aspart or human NPH insulin / human regular insulin in random order. The major inclusion criterion is history of two or more episodes of severe hypoglycaemia in the preceding year. Discussion In contrast to almost all other studies in this field the HypoAna Trial includes only patients with major problems with hypoglycaemia. The HypoAna Trial will elucidate whether basal-bolus regimen with short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing occurrence of severe hypoglycaemic episodes in hypoglycaemia prone patients with type 1 diabetes. http://www.clinicaltrials.gov: NCT00346996.

  13. Modified Order Crossover (OX Operator

    Directory of Open Access Journals (Sweden)

    Ms. Monica Sehrawat,

    2011-05-01

    Full Text Available In this work Traveling salesperson problem is taken as Domain. TSP has long been known to be NP-complete and is a standard example of such problems. Genetic Algorithm (GA is an approximate algorithmthat doesn’t always aim to find the shortest tour but to find a reasonably short tour quickly, which is a search procedure inspired by the mechanisms of biological evolution. In genetic algorithms, crossovers are used as a main search operator for TSP. Briefly speaking: the role of crossovers is to generate offspring that are better tours by preserving partial tours from the parents. There were a lot attempts to discover an appropriate crossover operator. This paper presents the strategy which used to find the nearly optimized solution to these type of problems. It is the order crossover operator (OX which was proposed by Davis, which constructs an offspring by choosing a subsequence of one parent and preserving the relative order of cities of the other parent.

  14. Coordination of Cooperative Advertising in a Two-Period Fashion and Textiles Supply Chain

    Directory of Open Access Journals (Sweden)

    Yi He

    2014-01-01

    Full Text Available Previous studies related to cooperative advertising mainly focus on the one-period supply chain. In the fashion and textiles (FT supply chain, the demand of most FT products (fashion clothing, vogue handbags, fashion shoes, and so on varies over time due to the trends of fashion. In these conditions, a decision-making framework with a multiple-period supply chain becomes more realistic. In view of this, we investigate the optimal cooperative advertising strategies in a two-period FT supply chain consisting of a manufacturer and a retailer in two different scenarios: (i each channel member makes decisions within a cooperative program; (ii the retailer is vertically integrated with a manufacturer. Also, we introduce a two-way subsidy contract to coordinate the supply chain.

  15. Intravenous Immunoglobulin for Hypogammaglobulinemia after Lung Transplantation: A Randomized Crossover Trial

    OpenAIRE

    Lederer, David J.; Nisha Philip; Debbie Rybak; Arcasoy, Selim M.; Kawut, Steven M.

    2014-01-01

    BACKGROUND: We aimed to determine the effects of treatment with intravenous immunoglobulin on bacterial infections in patients with hypogammaglobulinemia (HGG) after lung transplantation. METHODS: We performed a randomized, double-blind, placebo-controlled two-period crossover trial of immune globulin intravenous (IVIG), 10% Purified (Gamunex, Bayer, Elkhart, IN) monthly in eleven adults who had undergone lung transplantation more than three months previously. We randomized study participants...

  16. Antibiotics and oral contraceptive failure - a case-crossover study

    NARCIS (Netherlands)

    Toh, Sengwee; Mitchell, Allen A.; Anderka, Marlene; de Jong-van den Berg, Lolkje T. W.; Hernandez-Diaz, Sonia

    2011-01-01

    Background: Evidence on the association between antibiotic use and combined oral contraceptive (COC) failure is controversial. We examined the effect of concomitant antibiotic treatment on the risk of breakthrough pregnancy among COC users. Study Designs: We performed a case-crossover study of 1330

  17. Superconducting Vacuum-Gap Crossovers for High Performance Microwave Applications

    CERN Document Server

    Denis, Kevin L; Chang, Meng-Ping; Hu, Ron; U-Yen, Kongpop; Wollack, Edward

    2016-01-01

    The design and fabrication of low-loss wide-bandwidth superconducting vacuum-gap crossovers for high performance millimeter wave applications are described. In order to reduce ohmic and parasitic losses at millimeter wavelengths a vacuum gap is preferred relative to dielectric spacer. Here, vacuum-gap crossovers were realized by using a sacrificial polymer layer followed by niobium sputter deposition optimized for coating coverage over an underlying niobium signal layer. Both coplanar waveguide and microstrip crossover topologies have been explored in detail. The resulting fabrication process is compatible with a bulk micro-machining process for realizing waveguide coupled detectors, which includes sacrificial wax bonding, and wafer backside deep reactive ion etching for creation of leg isolated silicon membrane structures. Release of the vacuum gap structures along with the wax bonded wafer after DRIE is implemented in the same process step used to complete the detector fabrication

  18. Dimensional crossover in semiconductor nanostructures

    Science.gov (United States)

    McDonald, Matthew P.; Chatterjee, Rusha; Si, Jixin; Jankó, Boldizsár; Kuno, Masaru

    2016-08-01

    Recent advances in semiconductor nanostructure syntheses provide unprecedented control over electronic quantum confinement and have led to extensive investigations of their size- and shape-dependent optical/electrical properties. Notably, spectroscopic measurements show that optical bandgaps of one-dimensional CdSe nanowires are substantially (approximately 100 meV) lower than their zero-dimensional counterparts for equivalent diameters spanning 5-10 nm. But what, exactly, dictates the dimensional crossover of a semiconductor's electronic structure? Here we probe the one-dimensional to zero-dimensional transition of CdSe using single nanowire/nanorod absorption spectroscopy. We find that carrier electrostatic interactions play a fundamental role in establishing dimensional crossover. Moreover, the critical length at which this transition occurs is governed by the aspect ratio-dependent interplay between carrier confinement and dielectric contrast/confinement energies.

  19. An open-label, phase 2, single centre, randomized, crossover design bioequivalence study of AndroForte 5 testosterone cream and Testogel 1% testosterone gel in hypogonadal men: study LP101.

    Science.gov (United States)

    Wittert, G A; Harrison, R W; Buckley, M J; Wlodarczyk, J

    2016-01-01

    We compared a novel 5% testosterone (T) cream (AndroForte 5, Lawley Pharmaceuticals, Australia) with a 1% T gel (Testogel, Besins Healthcare, Australia). Using an open-label crossover design, subjects were randomized to one of two treatment sequences using either the T gel or T cream first in a 1 : 1 ratio. Each treatment period was 30 days with a 7-14 days washout period between them. On Days 1 and 30 of each treatment period blood was sampled at -15, -5 min, 0, 2, 4, 5, 6, 7, 8, 9, 10, 12 and 16 h post study drug administration. Sixteen men with established androgen deficiency aged between 29 and 73 years, who had undertaken a washout from prior testosterone therapy participated in the study. One subject failed to complete both arms and another was excluded post-completion because of a major protocol violation. Bioequivalence was established based on key pharmacokinetic (PK) variables: AUC, C(avg), C(max), T(max), % fluctuation (with and without baseline correction) for the two formulations of testosterone on Day 1 and Day 30. The ratio and 90% CI of AUC 0.99 (0.86-1.14), C(max) 1.02 (0.84-1.24) and C(avg) 0.99 (0.86-1.14) for T cream/T gel were within the predetermined bio-equivalence criteria of 80% to 125% at Day 30. There were no statistically significant differences between secondary biochemical markers: serum dihydrotestosterone (DHT), oestradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and (FSH). The two testosterone formulations were shown to be bioequivalent.

  20. 3D Framework DNA Origami with Layered Crossovers.

    Science.gov (United States)

    Hong, Fan; Jiang, Shuoxing; Wang, Tong; Liu, Yan; Yan, Hao

    2016-10-04

    Designer DNA architectures with nanoscale geometric controls provide a programmable molecular toolbox for engineering complex nanodevices. Scaffolded DNA origami has dramatically improved our ability to design and construct DNA nanostructures with finite size and spatial addressability. Here we report a novel design strategy to engineer multilayered wireframe DNA structures by introducing crossover pairs that connect neighboring layers of DNA double helices. These layered crossovers (LX) allow the scaffold or helper strands to travel through different layers and can control the relative orientation of DNA helices in neighboring layers. Using this design strategy, we successfully constructed four versions of two-layer parallelogram structures with well-defined interlayer angles, a three-layer structure with triangular cavities, and a 9- and 15-layer square lattices. This strategy provides a general route to engineer 3D framework DNA nanostructures with controlled cavities and opportunities to design host-guest networks analogs to those produced with metal organic frameworks.

  1. Methods for adjusting for bias due to crossover in oncology trials.

    Science.gov (United States)

    Ishak, K Jack; Proskorovsky, Irina; Korytowsky, Beata; Sandin, Rickard; Faivre, Sandrine; Valle, Juan

    2014-06-01

    Trials of new oncology treatments often involve a crossover element in their design that allows patients receiving the control treatment to crossover to receive the experimental treatment at disease progression or when sufficient evidence about the efficacy of the new treatment is achieved. Crossover leads to contamination of the initial randomized groups due to a mixing of the effects of the control and experimental treatments in the reference group. This is further complicated by the fact that crossover is often a very selective process whereby patients who switch treatment have a different prognosis than those who do not. Standard statistical techniques, including those that attempt to account for the treatment switch, cannot fully adjust for the bias introduced by crossover. Specialized methods such as rank-preserving structural failure time (RPSFT) models and inverse probability of censoring weighted (IPCW) analyses are designed to deal with selective treatment switching and have been increasingly applied to adjust for crossover. We provide an overview of the crossover problem and highlight circumstances under which it is likely to cause bias. We then describe the RPSFT and IPCW methods and explain how these methods adjust for the bias, highlighting the assumptions invoked in the process. Our aim is to facilitate understanding of these complex methods using a case study to support explanations. We also discuss the implications of crossover adjustment on cost-effectiveness results.

  2. An Analysis of Semantic Aware Crossover

    Science.gov (United States)

    Uy, Nguyen Quang; Hoai, Nguyen Xuan; O'Neill, Michael; McKay, Bob; Galván-López, Edgar

    It is well-known that the crossover operator plays an important role in Genetic Programming (GP). In Standard Crossover (SC), semantics are not used to guide the selection of the crossover points, which are generated randomly. This lack of semantic information is the main cause of destructive effects from SC (e.g., children having lower fitness than their parents). Recently, we proposed a new semantic based crossover known GP called Semantic Aware Crossover (SAC) [25]. We show that SAC outperforms SC in solving a class of real-value symbolic regression problems. We clarify the effect of SAC on GP search in increasing the semantic diversity of the population, thus helping to reduce the destructive effects of crossover in GP.

  3. Perinatal outcomes among immigrant mothers over two periods in a region of central Italy

    Directory of Open Access Journals (Sweden)

    Di Lallo Domenico

    2011-05-01

    Full Text Available Abstract Background The number of immigrants has increased in Italy in the last twenty years (7.2% of the Italian population, as have infants of foreign-born parents, but scanty evidence on perinatal outcomes is available. The aim of this study was to investigate whether infants of foreign-born mothers living in Italy have different odds of adverse perinatal outcomes compared to those of native-born mothers, and if such measures changed over two periods. Methods The source of this area-based study was the regional hospital discharge database that records perinatal information on all births in the Lazio region. We analysed 296,739 singleton births born between 1996-1998 and 2006-2008. The exposure variable was the mother's region of birth. We considered five outcomes of perinatal health. We estimated crude and adjusted odds ratios and 95% confidence intervals (CIs to evaluate the association between mother's region of birth and perinatal outcomes. Results Perinatal outcomes were worse among infants of immigrant compared to Italian mothers, especially for sub-Saharan and west Africans, with the following crude ORs (in 1996-1998 and 2006-2008 respectively: 1.80 (95%CI:1.44-2.28 and 1.95 (95%CI:1.72-2.21 for very preterm births, and 1.32 (95%CI:1.16-1.50 and 1.32 (95%CI:1.25-1.39 for preterm births; 1.18 (95%CI:0.99-1.40 and 1.17 (95%CI:1.03-1.34 for a low Apgar score; 1.22 (95%CI:1.15-1.31 and 1.24 (95%CI:1.17-1.32 for the presence of respiratory diseases; 1.47 (95%CI:1.30-1.66 and 1.45 (95%CI:1.34-1.57 for the need for special or intensive neonatal care/in-hospital deaths; and 1.03 (95%CI:0.93-1.15 and 1.07 (95%CI:1.00-1.15 for congenital malformations. Overall, time did not affect the odds of outcomes differently between immigrant and Italian mothers and most outcomes improved over time among all infants. None of the risk factors considered confounded the associations. Conclusion Our findings suggest that migrant status is a risk factor for

  4. Spin-crossover materials properties and applications

    CERN Document Server

    Halcrow, Malcolm A

    2013-01-01

    The phenomenon of spin-crossover has a large impact on the physical properties of a solid material, including its colour, magnetic moment, and electrical resistance. Some materials also show a structural phase change during the transition. Several practical applications of spin-crossover materials have been demonstrated including display and memory devices, electrical and electroluminescent devices, and MRI contrast agents. Switchable liquid crystals, nanoparticles, and thin films of spin-crossover materials have also been achieved. Spin-Crossover Materials: Properties and Applicat

  5. Becoming a crossover-competent DSB.

    Science.gov (United States)

    Lake, Cathleen M; Hawley, R Scott

    2016-06-01

    The proper execution of meiotic recombination (or crossing over) is essential for chromosome segregation during the first meiotic division, and thus this process is regulated by multiple, and often elaborate, mechanisms. Meiotic recombination begins with the programmed induction of DNA double-strand breaks (DSBs), of which only a subset are selected to be repaired into crossovers. This crossover selection process is carried out by a number of pro-crossover proteins that regulate the fashion in which DSBs are repaired. Here, we highlight recent studies regarding the process of DSB fate selection by a family of pro-crossover proteins known as the Zip-3 homologs.

  6. Empirical power and sample size calculations for cluster-randomized and cluster-randomized crossover studies.

    Science.gov (United States)

    Reich, Nicholas G; Myers, Jessica A; Obeng, Daniel; Milstone, Aaron M; Perl, Trish M

    2012-01-01

    In recent years, the number of studies using a cluster-randomized design has grown dramatically. In addition, the cluster-randomized crossover design has been touted as a methodological advance that can increase efficiency of cluster-randomized studies in certain situations. While the cluster-randomized crossover trial has become a popular tool, standards of design, analysis, reporting and implementation have not been established for this emergent design. We address one particular aspect of cluster-randomized and cluster-randomized crossover trial design: estimating statistical power. We present a general framework for estimating power via simulation in cluster-randomized studies with or without one or more crossover periods. We have implemented this framework in the clusterPower software package for R, freely available online from the Comprehensive R Archive Network. Our simulation framework is easy to implement and users may customize the methods used for data analysis. We give four examples of using the software in practice. The clusterPower package could play an important role in the design of future cluster-randomized and cluster-randomized crossover studies. This work is the first to establish a universal method for calculating power for both cluster-randomized and cluster-randomized clinical trials. More research is needed to develop standardized and recommended methodology for cluster-randomized crossover studies.

  7. The mechanocaloric potential of spin crossover compounds

    OpenAIRE

    Sandeman, K. G.

    2016-01-01

    We present a first evaluation of the potential for spin crossover (SCO) compounds to be considered as a new class of giant mechanocaloric effect material. From literature data on the variation of the spin crossover temperature with pressure, we estimate the maximum available adiabatic temperature change for several compounds and the relatively low pressures that may be required to observe these effects.

  8. 24 CFR 3285.701 - Electrical crossovers.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Electrical crossovers. 3285.701... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Electrical Systems and Equipment § 3285.701 Electrical crossovers. Multi-section homes with electrical wiring in more than one section...

  9. The choice in meiosis - defining the factors that influence crossover or non-crossover formation.

    Science.gov (United States)

    Youds, Jillian L; Boulton, Simon J

    2011-02-15

    Meiotic crossovers are essential for ensuring correct chromosome segregation as well as for creating new combinations of alleles for natural selection to take place. During meiosis, excess meiotic double-strand breaks (DSBs) are generated; a subset of these breaks are repaired to form crossovers, whereas the remainder are repaired as non-crossovers. What determines where meiotic DSBs are created and whether a crossover or non-crossover will be formed at any particular DSB remains largely unclear. Nevertheless, several recent papers have revealed important insights into the factors that control the decision between crossover and non-crossover formation in meiosis, including DNA elements that determine the positioning of meiotic DSBs, and the generation and processing of recombination intermediates. In this review, we focus on the factors that influence DSB positioning, the proteins required for the formation of recombination intermediates and how the processing of these structures generates either a crossover or non-crossover in various organisms. A discussion of crossover interference, assurance and homeostasis, which influence crossing over on a chromosome-wide and genome-wide scale - in addition to current models for the generation of interference - is also included. This Commentary aims to highlight recent advances in our understanding of the factors that promote or prevent meiotic crossing over.

  10. Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design

    Directory of Open Access Journals (Sweden)

    Gao Joseph

    2010-06-01

    Full Text Available Abstract Background Duration of efficacy and safety of lisdexamfetamine dimesylate (LDX was assessed in adults (18-55 years with attention-deficit/hyperactivity disorder (ADHD using the simulated adult workplace environment. Methods After open-label dose optimization (4-week with LDX, 30-70 mg/d, subjects entered a 2-week randomized, double-blind, placebo-controlled crossover phase. Efficacy assessments included the Permanent Product Measure of Performance (PERMP total score (attempted+correct measured predose and from 2 to 14 hours postdose, averaged across postdose sessions (primary and at each time point vs placebo (secondary, and ADHD Rating Scale IV (ADHD-RS-IV with adult prompts at baseline and crossover visits. Safety assessments included treatment-emergent adverse events (TEAEs, vital signs, and electrocardiograms. Results Of 127 randomized subjects, 105 were in the intention-to-treat population and 103 completed the study. While receiving LDX vs placebo, adults had greater improvement (P P ≤ .0017 for each time point and change from predose (P P Conclusions LDX significantly improved PERMP scores vs placebo and maintained improvement throughout the day from the first (2 hours to last (14 hours postdose time point vs placebo in adults with ADHD. Trial Registration ClinicalTrials.gov Identifier: NCT00697515 Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX in Adults With Attention-Deficit Hyperactivity Disorder (ADHD http://www.clinicaltrials.gov/ct2/show/NCT00697515?term=NCT00697515&rank=1

  11. Vibration Control on Multilayer Cable Moving through the Crossover Zones on Mine Hoist

    Directory of Open Access Journals (Sweden)

    Xia Peng

    2016-01-01

    Full Text Available Mine hoist is an important piece of equipment in mine hoist systems, and we achieve deep mine hoist through the multilayer winding, but the cable always undergoes severe shock and vibration during the winding process, and the dynamic load and wear would greatly reduce the lifetime of the cable and cause potential safety hazard. In this paper, we start from the course of crossing over of winding cable, use the methods of differential geometry, mechanics, and mathematical analysis, study the movements of the crossover, and derive the important formula that can reduce the vibration of cable during the course of crossover: the formula about central angle of the crossover arc. The results display that four factors contribute to central angle of the crossover arc, that is, the gap of the rope grooves, friction coefficient of the cable, and diameter of the drum and the cable. The result can provide valuable information for designing multilayer winding mine hoist.

  12. Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

    Science.gov (United States)

    Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

    2013-11-01

    An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation.

  13. Choosing appropriate analysis methods for cluster randomised cross-over trials with a binary outcome.

    Science.gov (United States)

    Morgan, Katy E; Forbes, Andrew B; Keogh, Ruth H; Jairath, Vipul; Kahan, Brennan C

    2017-01-30

    In cluster randomised cross-over (CRXO) trials, clusters receive multiple treatments in a randomised sequence over time. In such trials, there is usual correlation between patients in the same cluster. In addition, within a cluster, patients in the same period may be more similar to each other than to patients in other periods. We demonstrate that it is necessary to account for these correlations in the analysis to obtain correct Type I error rates. We then use simulation to compare different methods of analysing a binary outcome from a two-period CRXO design. Our simulations demonstrated that hierarchical models without random effects for period-within-cluster, which do not account for any extra within-period correlation, performed poorly with greatly inflated Type I errors in many scenarios. In scenarios where extra within-period correlation was present, a hierarchical model with random effects for cluster and period-within-cluster only had correct Type I errors when there were large numbers of clusters; with small numbers of clusters, the error rate was inflated. We also found that generalised estimating equations did not give correct error rates in any scenarios considered. An unweighted cluster-level summary regression performed best overall, maintaining an error rate close to 5% for all scenarios, although it lost power when extra within-period correlation was present, especially for small numbers of clusters. Results from our simulation study show that it is important to model both levels of clustering in CRXO trials, and that any extra within-period correlation should be accounted for. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Dialysis-associated hypertension treated with Telmisartan--DiaTel: a pilot, placebo-controlled, cross-over, randomized trial

    National Research Council Canada - National Science Library

    Huber, Matthias; Treutler, Till; Martus, Peter; Kurzidim, Antje; Kreutz, Reinhold; Beige, Joachim

    2013-01-01

    .... We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top...

  15. Interplay between structure-specific endonucleases for crossover control during Caenorhabditis elegans meiosis.

    Directory of Open Access Journals (Sweden)

    Takamune T Saito

    Full Text Available The number and distribution of crossover events are tightly regulated at prophase of meiosis I. The resolution of Holliday junctions by structure-specific endonucleases, including MUS-81, SLX-1, XPF-1 and GEN-1, is one of the main mechanisms proposed for crossover formation. However, how these nucleases coordinately resolve Holliday junctions is still unclear. Here we identify both the functional overlap and differences between these four nucleases regarding their roles in crossover formation and control in the Caenorhabditis elegans germline. We show that MUS-81, XPF-1 and SLX-1, but not GEN-1, can bind to HIM-18/SLX4, a key scaffold for nucleases. Analysis of synthetic mitotic defects revealed that MUS-81 and SLX-1, but not XPF-1 and GEN-1, have overlapping roles with the Bloom syndrome helicase ortholog, HIM-6, supporting their in vivo roles in processing recombination intermediates. Taking advantage of the ease of genetic analysis and high-resolution imaging afforded by C. elegans, we examined crossover designation, frequency, distribution and chromosomal morphology in single, double, triple and quadruple mutants of the structure-specific endonucleases. This revealed that XPF-1 functions redundantly with MUS-81 and SLX-1 in executing crossover formation during meiotic double-strand break repair. Analysis of crossover distribution revealed that SLX-1 is required for crossover suppression at the center region of the autosomes. Finally, analysis of chromosome morphology in oocytes at late meiosis I stages uncovered that SLX-1 and XPF-1 promote meiotic chromosomal stability by preventing formation of chromosomal abnormalities. We propose a model in which coordinate action between structure-specific nucleases at different chromosome domains, namely MUS-81, SLX-1 and XPF-1 at the arms and SLX-1 at the center region, exerts positive and negative regulatory roles, respectively, for crossover control during C. elegans meiosis.

  16. Spin-crossover molecule based thermoelectric junction

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Dibyajyoti [Chemistry and Physics of Materials Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064 (India); Parida, Prakash [Institute for Theoretical Physics, University of Regensburg, D-93040 Regensburg (Germany); Pati, Swapan K. [Theoretical Sciences Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064 (India)

    2015-05-11

    Using ab-initio numerical methods, we explore the spin-dependent transport and thermoelectric properties of a spin-crossover molecule (i.e., iron complex of 2-(1H-pyrazol-1-yl)-6-(1H-tetrazole-5-yl)pyridine) based nano-junction. We demonstrate a large magnetoresistance, efficient conductance-switching, and spin-filter activity in this molecule-based two-terminal device. The spin-crossover process also modulates the thermoelectric entities. It can efficiently switch the magnitude as well as spin-polarization of the thermocurrent. We find that thermocurrent is changed by ∼4 orders of magnitude upon spin-crossover. Moreover, it also substantially affects the thermopower and consequently, the device shows extremely efficient spin-crossover magnetothermopower generation. Furthermore, by tuning the chemical potential of electrodes into a certain range, a pure spin-thermopower can be achieved for the high-spin state. Finally, the reasonably large values of figure-of-merit in the presence and absence of phonon demonstrate a large heat-to-voltage conversion efficiency of the device. We believe that our study will pave an alternative way of tuning the transport and thermoelectric properties through the spin-crossover process and can have potential applications in generation of spin-dependent current, information storage, and processing.

  17. Solving TSP Using Advanced Crossover & Mutating Operators of Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Shruti Sharma

    2013-07-01

    Full Text Available In this paper we develops a new crossover and mutating operator, Round crossover (RX and Round mutating (RM operator, for a genetic algorithm that generates high quality solutions to the Traveling Salesman Problem (TSP. The round crossover operator constructs an offspring from a pair of parents in a circular way using better edges on the basis of their values that may be present in the parents’ structure maintaining the sequence of nodes in the parent chromosomes. The round mutation applied to the resultant chromosome after crossover by selecting a random cut point and then joining the remaining substring to first substring in circular way. The efficiency of the RX is compared as against some existing crossover operators; namely, edge recombination crossover (ERX, Order crossover (OX and partially Matched crossover (PMX for some benchmark TSPLIB instances. Experimental results show that the new crossover operator is better than the PMX, ERX and OX

  18. Design and rationale for the WARFA trial: a randomized controlled cross-over trial testing the therapeutic equivalence of branded and generic warfarin in atrial fibrillation patients in Brazil.

    Science.gov (United States)

    Freitas, Carolina Gomes; Walsh, Michael; Atallah, Álvaro Nagib

    2017-06-07

    Warfarin is a commonly used anticoagulant. Whether a given dose of the different formulations of Brazilian warfarin will result in the same effect on the international normalized ratio (INR) is uncertain. The aim of the WARFA trial is to determine whether the branded and two generic warfarins available in Brazil differ in their effect on the INR. WARFA is a cross-over RCT comparing three warfarins. The formulations tested are the branded Marevan® (Uniao Quimica/Farmoquimica) and two generic warfarin (manufactured respectively by Uniao Quimica Farmaceutica Nacional and Laboratorio Teuto Brasileiro). All of them were manufactured in Brazil, are available in all settings of the Brazilian healthcare system and were purchased from retail drugstores. Eligible participants had atrial fibrillation or flutter, had been using warfarin for at least 2 months with a therapeutic range of 2.0-3.0 and had low variability in INR results during the 1st period of the trial. Our primary outcome, for which we have an equality hypothesis, is the difference between warfarins in the mean absolute difference between two INR results, obtained after three and 4 weeks with each drug. Our secondary outcomes, that will be tested for inequality (except for the mean INR, which will be tested for equality), include the difference in the warfarin dose, and time in therapeutic range. Clinical events and adherence were also recorded and will be reported. To our knowledge, WARFA will be the first comparison of the more readily applicable INR results between branded and generic warfarins in Brazil. WARFA is important because warfarins are commonly switched between in the course of a chronic treatment in Brazil. Final results of WARFA are expected in May 2017. ClinicalTrials.gov NCT02017197 . Registered 11 December 2013.

  19. Iron(III) spin crossover compounds

    NARCIS (Netherlands)

    van Koningsbruggen, PJ; Maeda, Y; Oshio, H

    2004-01-01

    In this chapter, selected results obtained so far on Fe(III) spin crossover compounds are summarized and discussed. Fe(III) spin transition materials of ligands containing chalcogen donor atoms are considered with emphasis on those of N,N-disubstituted-dithiocarbamates, N,N-disubstituted-XY-carbamat

  20. Critical Crossover Functions for Simple Fluids: Towards the Crossover Modelling Uniqueness

    Science.gov (United States)

    Garrabos, Yves; Lecoutre, Carole; Marre, Samuel; LeNeindre, Bernard; Hahn, Inseob

    2016-11-01

    Based on a single non-universal temperature scaling factor present in a simple fluid case, a detailed analysis of non-universal parameters involved in different critical-to-classical crossover models is given. For the infinite limit of the cutoff wave number, a set of three scaling-parameters is defined for each model such that it shows all the shapes of the theoretical crossover functions overlap on the mean crossover function shapes close to the non-trivial fixed point. The analysis of corresponding links between their fluid-dependent parameters opens a route to define a parametric model of crossover equation-of-state, closely satisfying the universal features calculated from the Ising-like limit in the massive renormalization scheme.

  1. ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes.

    Directory of Open Access Journals (Sweden)

    Marco Barchi

    2008-05-01

    Full Text Available During meiosis in most sexually reproducing organisms, recombination forms crossovers between homologous maternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division. The number and distribution of crossovers are tightly controlled, but the factors that contribute to this control are poorly understood in most organisms, including mammals. Here we provide evidence that the ATM kinase or protein is essential for proper crossover formation in mouse spermatocytes. ATM deficiency causes multiple phenotypes in humans and mice, including gonadal atrophy. Mouse Atm-/- spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm(-/- meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meiotic metaphase I. Strikingly, Spo11+/-Atm-/- spermatocytes are defective in forming the obligate crossover on the sex chromosomes, even though the XY pair is usually incorporated in a sex body and is transcriptionally inactivated as in normal spermatocytes. The XY crossover defect correlates with the appearance of lagging chromosomes at metaphase I, which may trigger the extensive metaphase apoptosis that is observed in these cells. In addition, control of the number and distribution of crossovers on autosomes appears to be defective in the absence of ATM because there is an increase in the total number of MLH1 foci, which mark the sites of eventual crossover formation, and because interference between MLH1 foci is perturbed. The axes of autosomes exhibit structural defects that correlate with the positions of ongoing recombination. Together, these findings indicate that ATM plays a role in both crossover control and chromosome axis integrity and further suggests that ATM is important for coordinating these features of meiotic chromosome dynamics.

  2. The effect of physical training on patients with rheumatoid arthritis: changes in disease activity, muscle strength and aerobic capacity. A clinically controlled minimized cross-over study

    DEFF Research Database (Denmark)

    Lyngberg, K; Danneskiold-Samsøe, B; Halskov, O

    1988-01-01

    cross-over study the effect of graduated progressive training has been evaluated in 18 RA-patients with moderately active disease. The training was performed twice weekly with aerobic conditioning and strength exercises progressing to strenuous exercises over an 8-week period. The design was a crossover...

  3. Comparing effects of soybean oil- and palm olein-based mayonnaise consumption on the plasma lipid and lipoprotein profiles in human subjects: a double-blind randomized controlled trial with cross-over design.

    Science.gov (United States)

    Karupaiah, Tilakavati; Chuah, Khun-Aik; Chinna, Karuthan; Matsuoka, Ryosuke; Masuda, Yasunobu; Sundram, Kalyana; Sugano, Michihiro

    2016-08-17

    Mayonnaise is used widely in contemporary human diet with widespread use as a salad dressing or spread on breads. Vegetable oils used in its formulation may be a rich source of ω-6 PUFAs and the higher-PUFA content of mayonnaise may be beneficial in mediating a hypocholesterolemic effect. This study, therefore, evaluated the functionality of mayonnaise on cardiometabolic risk within a regular human consumption scenario. Subjects underwent a randomized double-blind crossover trial, consuming diets supplemented with 20 g/day of either soybean oil-based mayonnaise (SB-mayo) or palm olein-based mayonnaise (PO-mayo) for 4 weeks each with a 2-week wash-out period. The magnitude of changes for metabolic outcomes between dietary treatments was compared with PO-mayo serving as the control. The data was analyzed by ANCOVA using the GLM model. Analysis was adjusted for weight changes. Treatments resulted in significant reductions in TC (diff = -0.25 mmol/L; P = 0.001), LDL-C (diff = -0.17 mmol/L; P = 0.016) and HDL-C (diff = -0.12 mmol/L; P  0.05). Lipoprotein particle change was significant with large LDL particles increasing after PO-mayo (diff = +63.2 nmol/L; P = 0.007) compared to SB-mayo but small LDL particles remained unaffected. Plasma glucose, apolipoproteins and oxidative stress markers remained unchanged. Daily use with 20 g of linoleic acid-rich SB-mayo elicited reductions in TC and LDL-C concentrations without significantly changing LDL-C:HDL-C ratio or small LDL particle distributions compared to the PO-mayo diet. This clinical trial was retrospectively registered with the National Medical Research Register, National Institute of Health, Ministry of Health Malaysia, (NMRR-15-40-24035; registered on 29/01/2015; https://www.nmrr.gov.my/fwbPage.jsp?fwbPageId=ResearchISRForm&fwbAction=Update&fwbStep=10&pk.researchID=24035&fwbVMenu=3&fwbResearchAction=Update ). Ethical approval was obtained from the National University of

  4. “Beyond Morality.” Discourse on Homosexuality in Croatian Newspapers from the Sociosemiotic Perspective: Comparison of Two Periods

    Directory of Open Access Journals (Sweden)

    Sandra Antulov

    2011-06-01

    Full Text Available This paper aims to analyse and compare two newspaper articles dealing with issues of gay people in Croatia that were published in two different periods. The first article dates from the early 1990s, which was the starting point of contemporary Croatian gay activism. The second was published 16 years later, in 2008, within a different social and political context. It was the period when gay activism in Croatia had already reached some of its aims, and when the discourse on homosexuality had become more visible and acceptable in the media. In comparing these two periods, we focus on surface differences between two newspaper articles, while at the deep level we look for similarities and unchanged features. Our perspective is sociosemiotic – it will be explained in more detail in the next section. For now, it needs to be stressed that we integrate both verbal and visual elements of the two articles, explore differences and similarities in the discursive strategies of constructing and representing homosexuality, and analyse differences and similarities in aspects of utterances and utterance actors involved.

  5. Self-assembly of fully addressable DNA nanostructures from double crossover tiles.

    Science.gov (United States)

    Wang, Wen; Lin, Tong; Zhang, Suoyu; Bai, Tanxi; Mi, Yongli; Wei, Bryan

    2016-09-19

    DNA origami and single-stranded tile (SST) are two proven approaches to self-assemble finite-size complex DNA nanostructures. The construction elements appeared in structures from these two methods can also be found in multi-stranded DNA tiles such as double crossover tiles. Here we report the design and observation of four types of finite-size lattices with four different double crossover tiles, respectively, which, we believe, in terms of both complexity and robustness, will be rival to DNA origami and SST structures.

  6. Cognitive-behavioural approaches in the treatment of hypochondriasis : six single case cross-over studies

    NARCIS (Netherlands)

    Bouman, Theo; Visser, S.

    This study evaluates a cognitive and a behavioural treatment protocol for hypochondriacal complaints. In a cross-over design, six patients with a primary diagnosis of hypochondriasis were treated. Three of them first received a block of behavioural therapy (exposure in vivo and response prevention),

  7. Cognitive-behavioural approaches in the treatment of hypochondriasis : six single case cross-over studies

    NARCIS (Netherlands)

    Bouman, Theo; Visser, S.

    1992-01-01

    This study evaluates a cognitive and a behavioural treatment protocol for hypochondriacal complaints. In a cross-over design, six patients with a primary diagnosis of hypochondriasis were treated. Three of them first received a block of behavioural therapy (exposure in vivo and response prevention),

  8. A Randomized Double-Blind Crossover Study of Phase-Shift Sound Therapy for Tinnitus

    NARCIS (Netherlands)

    Heijneman, Karin M.; de Kleine, Emile; van Dijk, Pim

    2012-01-01

    Objective. The purpose of this study was to compare the efficacy of the treatment of tinnitus with a phase-shifting pure tone to that of the same tone treatment without phase shifting. Study Design. A double-blind crossover randomized controlled trial. Setting. This study was conducted at the Univer

  9. Cognitive-behavioural approaches in the treatment of hypochondriasis : six single case cross-over studies

    NARCIS (Netherlands)

    Bouman, Theo; Visser, S.

    1992-01-01

    This study evaluates a cognitive and a behavioural treatment protocol for hypochondriacal complaints. In a cross-over design, six patients with a primary diagnosis of hypochondriasis were treated. Three of them first received a block of behavioural therapy (exposure in vivo and response prevention),

  10. Hematological clozapine monitoring with a point-of-care device: A randomized cross-over trial

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Thode, Dorrit; Stenager, Elsebeth

    for several reasons, perhaps most importantly because of the mandatory hematological monitoring. The Chempaq Express Blood Counter (Chempaq XBC) is a point-of-care device providing counts of white blood cells (WBC) and granulocytes based on a capillary blood sampling. A randomized cross-over trial design...

  11. Hematological clozapine monitoring with a point-of-care device: A randomized cross-over trial

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Thode, Dorrit; Stenager, Elsebeth

    2012-01-01

    for several reasons, perhaps most importantly because of the mandatory hematological monitoring. The Chempaq Express Blood Counter (Chempaq XBC) is a point-of-care device providing counts of white blood cells (WBC) and granulocytes based on a capillary blood sampling. A randomized cross-over trial design...

  12. Psychological Factors and Pain Exacerbation in Knee Osteoarthritis : A Web Based Case-Crossover Study

    NARCIS (Netherlands)

    Erfani, Tahereh; Keefe, Francis; Bennell, Kim; Chen, J; Makovey, J; Metcalf, B; Williams, A.D.; Zhang, Y; Hunter, David

    2015-01-01

    OBJECTIVES: The pain experienced by osteoarthritis (OA) patients is neither constant nor unchanging and patients experience episodes of pain exacerbations. Using an innovative web based case-crossover design, we evaluated whether psychological factors are risk factors for pain exacerbations in patie

  13. Apparent Temperature and Cause-Specific Mortality in Copenhagen, Denmark: A Case-Crossover Analysis

    DEFF Research Database (Denmark)

    Wichmann, Janine; Jovanovic Andersen, Zorana; Ketzel, Matthias

    2011-01-01

    (max)), and respiratory, cardiovascular and cerebrovascular mortality in Copenhagen (1999-2006) using a case-crossover design. Susceptibility was investigated for age, sex, socio-economic status and place of death. For an inter-quartile range (7 °C) increase in Tapp(max), an inverse association was found...

  14. Psychological Factors and Pain Exacerbation in Knee Osteoarthritis : A Web Based Case-Crossover Study

    NARCIS (Netherlands)

    Erfani, Tahereh; Keefe, Francis; Bennell, Kim; Chen, J; Makovey, J; Metcalf, B; Williams, A.D.; Zhang, Y; Hunter, David

    2015-01-01

    OBJECTIVES: The pain experienced by osteoarthritis (OA) patients is neither constant nor unchanging and patients experience episodes of pain exacerbations. Using an innovative web based case-crossover design, we evaluated whether psychological factors are risk factors for pain exacerbations in

  15. Quantum-classical crossover in electrodynamics

    CERN Document Server

    Polonyi, J

    2006-01-01

    A classical field theory is proposed for the electric current and the electromagnetic field interpolating between microscopic and macroscopic domains. It represents a generalization of the density functional for the dynamics of the current and the electromagnetic field in the quantum side of the crossover and reproduces standard classical electrodynamics on the other side. The effective action derived in the closed time path formalism and the equations of motion follow from the variational principle. The polarization of the Dirac-see can be taken into account in the quadratic approximation of the action by the introduction of the deplacement field strengths as in conventional classical electrodynamics. Decoherence appears naturally as a simple one-loop effect in this formalism. It is argued that the radiation time arrow is generated from the quantum boundary conditions in time by decoherence at the quantum-classical crossover and the Abraham-Lorentz force arises from the accelerating charge or from other char...

  16. Het dilemma van een verleidelijk crossover boek

    Directory of Open Access Journals (Sweden)

    A. Schuurman

    2008-01-01

    Full Text Available Woud, A. van der, Een nieuwe wereld. Het ontstaan van het moderne Nederland (Amsterdam 2006The Predicament of a Seductive Crossover BookAuke van der Woud’s new book is a must for everyone interested in the second half of the nineteenth century, particularly the consequences of spatial change. His book has all the virtues and vices of a crossover book, that is one which appeals to two different audiences. It is a book based on new research written for the general reader. Therefore, it is not clear enough with regard to various scientific questions. More explicit attention for the role of industrial capitalism and the process of democracy would have enriched the book even more.

  17. Magnetic crossover effect in Nickel nanowire arrays

    Energy Technology Data Exchange (ETDEWEB)

    Ghaddar, A. [Laboratoire de Magnetisme de Bretagne, CNRS-FRE 3117, C.S. 93837, 29238 Brest, Cedex (France); Gloaguen, F. [Laboratoire de Chimie, Electrochimie Moleculaire et Chimie Analytique, CNRS-UMR 6521, C. S. 93837 Brest Cedex 3 (France); Gieraltowski, J. [Laboratoire de Magnetisme de Bretagne, CNRS-FRE 3117, C.S. 93837, 29238 Brest, Cedex (France); Tannous, C., E-mail: tannous@univ-brest.f [Laboratoire de Magnetisme de Bretagne, CNRS-FRE 3117, C.S. 93837, 29238 Brest, Cedex (France)

    2011-05-01

    A crossover effect in the magnetic reversal mechanism within arrays of Nickel nanowires whose diameter varies from 15 to 100 nm is observed around 50 nm. Hysteresis loops and FMR measurements confirm that nanowire diameter controls effectively the nanowire easy axis as well as the magnetization reversal mechanism. This might be very interesting for spintronic devices based on current-induced domain motion such as non-volatile magnetic memory elements (MRAM) and low Ohmic loss devices.

  18. Dynamical Landau theory of the glass crossover

    Science.gov (United States)

    Rizzo, Tommaso

    2016-07-01

    I introduce a dynamical field theory to describe the glassy behavior in supercooled liquids. The mean-field approximation of the theory predicts a dynamical arrest transition, as in the ideal mode-coupling theory and mean-field discontinuous spin-glass models. Instead, beyond the mean-field approximation, the theory predicts that the transition is avoided and transformed into a crossover, as observed in experiments and simulations. To go beyond mean-field, a standard perturbative loop expansion is performed at first. Approaching the ideal critical point this expansion is divergent at all orders and I show that the leading divergent term at any given order is the same as a dynamical stochastic equation, called stochastic-beta relaxation (SBR) in Europhys. Lett. 106, 56003 (2014), 10.1209/0295-5075/106/56003. At variance with the original theory, SBR can be studied beyond mean-field directly, without the need to resort to a perturbative expansion. Thus it provides a qualitative and quantitative description of the dynamical crossover. For consistency reasons, it is important to establish the connection between the dynamical field theory and SBR beyond perturbation theory. This can be done with the help of a stronger result: the dynamical field theory is exactly equivalent to a theory with quenched disorder. Qualitatively, the nonperturbative mechanism leading to the crossover is therefore the same as the mechanism of SBR. Quantitatively, SBR is equivalent to making the mean-field approximation once the quenched disorder has been generated.

  19. Is Zolpidem Associated with Increased Risk of Fractures in the Elderly with Sleep Disorders? A Nationwide Case Cross-Over Study in Taiwan

    OpenAIRE

    2015-01-01

    Background We conducted a study using a case-crossover design to clarify the risk of acute effects of zolpidem and benzodiazepine on all-sites of fractures in the elderly. Design of study Case-crossover design. Methods and Materials Elderly enrollees (n = 6010) in Taiwan’s National Health Insurance Research Database with zolpidem or benzodiazepine use were analyzed for the risk of developing fractures. Results After adjusting for medications such as antipsychotics, antidepressants, and diuret...

  20. Absence of a significant pharmacokinetic interaction between atorvastatin and fenofibrate: A randomized, crossover, study of a fixed-dose formulation in healthy Mexican subjects

    Directory of Open Access Journals (Sweden)

    Omar ePatiño-Rodríguez

    2015-01-01

    Full Text Available Several clinical trials have substantiated the efficacy of the co-administration of statins like atorvastatin and fibrates. Without information currently available about the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the effect when both drugs were co-administered. The purpose of this study was to investigate the pharmacokinetic profile of tablets containing atorvastatin 20 mg, or the combination of atorvastatin 20 mg with fenofibrate 160 mg administered to healthy Mexican volunteers. This was a randomized, two-period, two-sequence, crossover study; 36 eligible subjects aged between 20 to 50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by non-compartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC and maximum plasma drug concentration (Cmax were measured for atorvastatin as the reference and atorvastatin and fenofibrate as the test product for bioequivalence design. The estimation computed (90% confidence intervals for atorvastatin and fenofibrate combination versus atorvastatin for Cmax, AUC0-t and AUC0-∞, were 102,09, 125,95 and 120,97% respectively. These results suggest that atorvastatin and fenofibrate have no relevant clinical-pharmacokinetic drug interaction.

  1. A new crossover operator in genetic programming for object classification.

    Science.gov (United States)

    Zhang, Mengjie; Gao, Xiaoying; Lou, Weijun

    2007-10-01

    The crossover operator has been considered "the centre of the storm" in genetic programming (GP). However, many existing GP approaches to object recognition suggest that the standard GP crossover is not sufficiently powerful in producing good child programs due to the totally random choice of the crossover points. To deal with this problem, this paper introduces an approach with a new crossover operator in GP for object recognition, particularly object classification. In this approach, a local hill-climbing search is used in constructing good building blocks, a weight called looseness is introduced to identify the good building blocks in individual programs, and the looseness values are used as heuristics in choosing appropriate crossover points to preserve good building blocks. This approach is examined and compared with the standard crossover operator and the headless chicken crossover (HCC) method on a sequence of object classification problems. The results suggest that this approach outperforms the HCC, the standard crossover, and the standard crossover operator with hill climbing on all of these problems in terms of the classification accuracy. Although this approach spends a bit longer time than the standard crossover operator, it significantly improves the system efficiency over the HCC method.

  2. Optimization of three-loop missile autopilot gain under crossover frequency constraint

    Institute of Scientific and Technical Information of China (English)

    M.A. ABD-ELATIF; Long-jun QIAN; Yu-ming BO

    2016-01-01

    The open-loop crossover frequency is pointed as an important parameter for practical autopilot design. Since different gain designs may achieve the same open-loop crossover frequency, it should be neither considered as a performance objective of the optimal autopilot design-schemes nor neglected. Besides, the main assignment of the autopilot is to drive the missile to track the acceleration commands, so the autopilot gain design should be evaluated directly according to the resultant tracking performance. For this purpose, an optimal design methodology of the three-loop missile autopilot is introduced based on constraint optimization technique, where the tracking performance is established analytically as the design objective and the open-loop crossover frequency is formed as inequality constraint function, both are manipulated in terms of stable characteristic parameters of the autopilot closed-loop. The proposed technique is implemented with the assistance of a numerical optimization algorithm which automatically adjusts the design parameters. Finally, numerical simulation results are provided to demonstrate the effectiveness and feasibility of the proposed approach compared with that in some references.

  3. Dialysis-Associated Hypertension Treated with Telmisartan - DiaTel: A Pilot, Placebo-Controlled, Cross-Over, Randomized Trial: e79322

    National Research Council Canada - National Science Library

    Matthias Huber; Till Treutler; Peter Martus; Antje Kurzidim; Reinhold Kreutz; Joachim Beige

    2013-01-01

    .... We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top...

  4. Increased calcium absorption from synthetic stable amorphous calcium carbonate: Double-blind randomized crossover clinical trial in post-menopausal women

    Science.gov (United States)

    Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (C...

  5. Crossover transition in bag-like models

    Energy Technology Data Exchange (ETDEWEB)

    Ferroni, Lorenzo; Koch, Volker

    2009-03-13

    We formulate a simple model for a gas of extended hadrons at zero chemical potential by taking inspiration from the compressible bag model. We show that a crossover transition qualitatively similar to lattice QCD can be reproduced by such a system by including some appropriate additional dynamics. Under certain conditions, at high temperature, the system consist of a finite number of infinitely extended bags,which occupy the entire space. In this situation the system behaves as an ideal gas of quarks and gluons.

  6. Generalised sequential crossover of words and languages

    CERN Document Server

    Jeganathan, L; Sengupta, Ritabrata

    2009-01-01

    In this paper, we propose a new operation, Generalised Sequential Crossover (GSCO) of words, which in some sense an abstract model of crossing over of the chromosomes in the living organisms. We extend GSCO over language $L$ iteratively ($GSCO^*(L)$ as well as iterated GSCO over two languages $GSCO^*(L_1,L_2)$). Our study reveals that $GSCO^*(L)$ is subclass of regular languages for any $L$. We compare the different classes of GSCO languages with the prominent sub-regular classes.

  7. A quantum genetic algorithm with quantum crossover and mutation operations

    Science.gov (United States)

    SaiToh, Akira; Rahimi, Robabeh; Nakahara, Mikio

    2013-11-01

    In the context of evolutionary quantum computing in the literal meaning, a quantum crossover operation has not been introduced so far. Here, we introduce a novel quantum genetic algorithm that has a quantum crossover procedure performing crossovers among all chromosomes in parallel for each generation. A complexity analysis shows that a quadratic speedup is achieved over its classical counterpart in the dominant factor of the run time to handle each generation.

  8. Arabidopsis meiotic crossover hotspots overlap with H2A.Z nucleosomes at gene promoters

    Science.gov (United States)

    Choi, Kyuha; Zhao, Xiaohui; Kelly, Krystyna A.; Venn, Oliver; Higgins, James D.; Yelina, Nataliya E.; Hardcastle, Thomas J.; Ziolkowski, Piotr A.; Copenhaver, Gregory P.; Franklin, F. Chris H.; McVean, Gil; Henderson, Ian R.

    2013-01-01

    PRDM9 directs human meiotic crossover hotspots to intergenic sequence motifs, whereas budding yeast hotspots overlap low nucleosome density regions in gene promoters. To investigate hotspots in plants, which lack PRDM9, we used coalescent analysis of Arabidopsis genetic variation. Crossovers increase towards gene promoters and terminators, and hotspots are associated with active chromatin modifications, including H2A.Z, histone H3K4me3, low nucleosome density and low DNA methylation. Hotspot-enriched A-rich and CTT-repeat DNA motifs occur upstream and downstream of transcriptional start respectively. Crossovers are asymmetric around promoters and highest over CTT-motifs and H2A.Z-nucleosomes. Pollen-typing, segregation and cytogenetic analysis show decreased crossovers in the arp6 H2A.Z deposition mutant, at multiple scales. During meiosis H2A.Z and DMC1/RAD51 recombinases form overlapping chromosomal foci. As arp6 reduces DMC1/RAD51 foci, H2A.Z may promote formation or processing of meiotic DNA double-strand breaks. We propose that gene chromatin ancestrally designates hotspots within eukaryotes and PRDM9 is a derived state within vertebrates. PMID:24056716

  9. What about the leader? Crossover of emotional exhaustion and work engagement from followers to leaders.

    Science.gov (United States)

    Wirtz, Nina; Rigotti, Thomas; Otto, Kathleen; Loeb, Carina

    2017-01-01

    Although a growing body of research links leadership behavior to follower health, comparatively little is known about the health effects of being in the lead. This longitudinal study of 315 team members and 67 leaders examined the crossover of emotional exhaustion and work engagement from followers to leaders. Leader emotional self-efficacy was tested as a moderator in the crossover process. Multiple regression analyses revealed that followers' work engagement was positively related to leaders' work engagement eight months later, controlling for followers' tenure with the leader, leader gender, autonomy, workload, and work engagement at Time 1. Leaders' emotional self-efficacy did not moderate the crossover of work engagement. Followers' emotional exhaustion was not directly related to leaders' emotional exhaustion over time. We did find a significant interaction effect for follower emotional exhaustion and leader emotional self-efficacy. This study is the first to show that crossover of emotional exhaustion and work engagement can unfold over time from team members to leaders. Main theoretical implications lie in the finding that-in line with job demands-resources theory-followers' psychological states can pose a demand or resource for leaders, and influence their well-being. For practitioners, our results offer valuable insights regarding the design of organizational health interventions as well as leadership development measures. (PsycINFO Database Record

  10. Investigation of crossover processes in a unitized bidirectional vanadium/air redox flow battery

    Science.gov (United States)

    grosse Austing, Jan; Nunes Kirchner, Carolina; Komsiyska, Lidiya; Wittstock, Gunther

    2016-02-01

    In this paper the losses in coulombic efficiency are investigated for a vanadium/air redox flow battery (VARFB) comprising a two-layered positive electrode. Ultraviolet/visible (UV/Vis) spectroscopy is used to monitor the concentrations cV2+ and cV3+ during operation. The most likely cause for the largest part of the coulombic losses is the permeation of oxygen from the positive to the negative electrode followed by an oxidation of V2+ to V3+. The total vanadium crossover is followed by inductively coupled plasma mass spectroscopy (ICP-MS) analysis of the positive electrolyte after one VARFB cycle. During one cycle 6% of the vanadium species initially present in the negative electrolyte are transferred to the positive electrolyte, which can account at most for 20% of the coulombic losses. The diffusion coefficients of V2+ and V3+ through Nafion® 117 are determined as DV2+ ,N 117 = 9.05 ·10-6 cm2 min-1 and DV3+ ,N 117 = 4.35 ·10-6 cm2 min-1 and are used to calculate vanadium crossover due to diffusion which allows differentiation between vanadium crossover due to diffusion and migration/electroosmotic convection. In order to optimize coulombic efficiency of VARFB, membranes need to be designed with reduced oxygen permeation and vanadium crossover.

  11. Effects of target-controlled infusion of high-dose naloxone on pain and hyperalgesia in a human thermal injury model: a study protocol: A randomized, double-blind, placebo-controlled, crossover trial with an enriched design.

    Science.gov (United States)

    Springborg, Anders D; Jensen, Elisabeth K; Taylor, Bradley K; Werner, Mads U

    2016-11-01

    Mu-opioid-receptor antagonists have been extensively studied in experimental research as pharmacological tools uncovering mechanisms of pain modulation by the endogenous opioid system. In rodents, administration of high doses of mu-opioid-receptor antagonists after the resolution of an inflammatory injury has demonstrated reinstatement of nociceptive hypersensitivity indicating unmasking of latent sensitization. In a recent human study, pain hypersensitivity assessed as secondary hyperalgesia area (SHA), was reinstated 7 days after a mild thermal injury, in 4 out of 12 subjects after a naloxone infusion.The aims of the present study are first, to replicate our previous findings in a larger-sized study; second, to examine if high sensitizers (subjects presenting with large SHA after a thermal injury) develop a higher degree of hypersensitivity after naloxone challenge than low sensitizers (subjects presenting with restricted SHA after a thermal injury); and third to examine a dose-response relationship between 3 stable naloxone concentrations controlled by target-controlled infusion, and the unmasking of latent sensitization.Healthy participants (n = 80) underwent a screening day (day 0) with induction of a thermal skin injury (47°C, 420 seconds, 12.5 cm). Assessment of SHA was performed 1 and 2 hours after the injury. Using an enriched design, only participants belonging to the upper quartile of SHA (Q4, high sensitizers; n = 20) and the lower quartile of SHA (Q1, low sensitizers; n = 20) continued the study, comprising 4 consecutive days-days 1 to 4. Thermal skin injuries were repeated on day 1 and day 3, whereas day 2 and day 4 (7 days after day 1 and day 3, respectively) were target-controlled infusion days in which the subjects were randomly allocated to receive either naloxone (3.25 mg/kg, 4 mg/mL) or placebo (normal saline) intravenous. The primary outcome was SHA assessed by weighted-pin instrument (128 mN) 0, 1, 2, and 165 to 169

  12. Broadband Via-Less Microwave Crossover Using Microstrip-CPW Transitions

    Science.gov (United States)

    Stevenson, Thomas; U-Yen, Kongpop; Wollack, Edward; Moseley, Samuel; Hsieh, Wen-Ting

    2011-01-01

    The front-to-back interface between microstrip and CPW (coplanar waveguide) typically requires complex fabrication or has high radiation loss. The microwave crossover typically requires a complex fabrication step. The prior art in microstrip-CPW transition requires a physical vias connection between the microstrip and CPW line on a separate layer. The via-less version of this transition was designed empirically and does not have a close form solution. The prior art of the micro wave crossover requires either additional substrate or wire bond as an air bridge to isolate two microwave lines at the crossing junction. The disadvantages are high radiation loss, no analytical solution to the problem, lengthy simulation time, and complex fabrication procedures to generate air bridges or via. The disadvantage of the prior crossover is a complex fabrication procedure, which also affects the device reliability and yield. This microstrip-CPW transition is visualized as two microstrip-slotline transitions combined in a way that the radiation from two slotlines cancels each other out. The invention is designed based on analytical methods; thus, it significantly reduces the development time. The crossover requires no extra layer to cross two microwave signals and has low radiation loss. The invention is simple to fabricate and design. It produces low radiation loss and can be designed with low insertion loss, with some tradeoff with signal isolation. The microstrip-CPW transition is used as an interface to connect between the device and the circuit outside the package. The via-less microwave crossover is used to allow two signals to cross without using an extra layer or fabrication processing step to enable this function. This design allows the solution to be determined entirely though analytical techniques. In addition, a planar via-less microwave crossover using this technique was proposed. The experimental results show that the proposed crossover at 5 GHz has a minimum

  13. Research Update: The mechanocaloric potential of spin crossover compounds

    Science.gov (United States)

    Sandeman, Karl G.

    2016-11-01

    We present a first evaluation of the potential for spin crossover (SCO) compounds to be considered as a new class of giant mechanocaloric effect materials. From literature data on the variation of the spin crossover temperature with pressure, we estimate the maximum available adiabatic temperature change for several compounds and the relatively low pressures that may be required to observe these effects.

  14. Research Update: The mechanocaloric potential of spin crossover compounds

    OpenAIRE

    Sandeman, Karl G.

    2016-01-01

    We present a first evaluation of the potential for spin crossover (SCO) compounds to be considered as a new class of giant mechanocaloric effect materials. From literature data on the variation of the spin crossover temperature with pressure, we estimate the maximum available adiabatic temperature change for several compounds and the relatively low pressures that may be required to observe these effects.

  15. Deformation Crossover: from nano to meso scale

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Sheng [ORNL; Stoica, Alexandru Dan [ORNL; Wang, Xun-Li [ORNL; Liu, Chain T [ORNL; Horton Jr, Joe A [ORNL; Brown, Donald [Los Alamos National Laboratory (LANL); Clausen, B [Los Alamos National Laboratory (LANL); Liaw, Peter K [University of Tennessee, Knoxville (UTK)

    2009-01-01

    By investigating intergranular strains using in-situ high-energy x-ray and neutron diffraction, we demonstrate significantly different deformation behavior from previously observed in nanocrystalline and ultrafine-grained Ni. Little intergranular strain or texture change was found in nanocrystalline Ni indicating a grain boundary mediated deformation mechanism. A remarkable intergranular strain build-up was observed in ultrafine-grained Ni, which was attributed to dislocation activities, but the unusual angular dependence of intergranular strains gave evidence of stress relaxation by deformation twinning, as confirmed by TEM observations. From the intergranular strain evolution and the texture change, clear evidence of deformation crossovers is presented in Ni with grain sizes from nano to meso scale.

  16. Neutrino dynamics below the electroweak crossover

    Energy Technology Data Exchange (ETDEWEB)

    Ghiglieri, J.; Laine, M. [AEC, Institute for Theoretical Physics, University of Bern,Sidlerstrasse 5, CH-3012 Bern (Switzerland)

    2016-07-12

    We estimate the thermal masses and damping rates of active (m< eV) and sterile (M∼ GeV) neutrinos with thermal momenta k∼3T at temperatures below the electroweak crossover (5 GeV 130 GeV remains an option. Our differential rates are tabulated in a form suitable for studies of specific scenarios with given neutrino Yukawa matrices.

  17. Fuel cell membranes and crossover prevention

    Science.gov (United States)

    Masel, Richard I.; York, Cynthia A.; Waszczuk, Piotr; Wieckowski, Andrzej

    2009-08-04

    A membrane electrode assembly for use with a direct organic fuel cell containing a formic acid fuel includes a solid polymer electrolyte having first and second surfaces, an anode on the first surface and a cathode on the second surface and electrically linked to the anode. The solid polymer electrolyte has a thickness t:.gtoreq..times..times..times..times. ##EQU00001## where C.sub.f is the formic acid fuel concentration over the anode, D.sub.f is the effective diffusivity of the fuel in the solid polymer electrolyte, K.sub.f is the equilibrium constant for partition coefficient for the fuel into the solid polymer electrolyte membrane, I is Faraday's constant n.sub.f is the number of electrons released when 1 molecule of the fuel is oxidized, and j.sub.f.sup.c is an empirically determined crossover rate of fuel above which the fuel cell does not operate.

  18. Extended precedence preservative crossover for job shop scheduling problems

    Science.gov (United States)

    Ong, Chung Sin; Moin, Noor Hasnah; Omar, Mohd

    2013-04-01

    Job shop scheduling problems (JSSP) is one of difficult combinatorial scheduling problems. A wide range of genetic algorithms based on the two parents crossover have been applied to solve the problem but multi parents (more than two parents) crossover in solving the JSSP is still lacking. This paper proposes the extended precedence preservative crossover (EPPX) which uses multi parents for recombination in the genetic algorithms. EPPX is a variation of the precedence preservative crossover (PPX) which is one of the crossovers that perform well to find the solutions for the JSSP. EPPX is based on a vector to determine the gene selected in recombination for the next generation. Legalization of children (offspring) can be eliminated due to the JSSP representation encoded by using permutation with repetition that guarantees the feasibility of chromosomes. The simulations are performed on a set of benchmarks from the literatures and the results are compared to ensure the sustainability of multi parents recombination in solving the JSSP.

  19. Hydrophobic hydration from small to large lengthscales: Understanding and manipulating the crossover

    Science.gov (United States)

    Rajamani, Sowmianarayanan; Truskett, Thomas M.; Garde, Shekhar

    2005-07-01

    Small and large hydrophobic solutes exhibit remarkably different hydration thermodynamics. Small solutes are accommodated in water with minor perturbations to water structure, and their hydration is captured accurately by theories that describe density fluctuations in pure water. In contrast, hydration of large solutes is accompanied by dewetting of their surfaces and requires a macroscopic thermodynamic description. A unified theoretical description of these lengthscale dependencies was presented by Lum, Chandler, and Weeks [(1999) J. Phys. Chem. B 103, 4570-4577]. Here, we use molecular simulations to study lengthscale-dependent hydrophobic hydration under various thermodynamic conditions. We show that the hydration of small and large solutes displays disparate dependencies on thermodynamic variables, including pressure, temperature, and additive concentration. Understanding these dependencies allows manipulation of the small-to-large crossover lengthscale, which is nanoscopic under ambient conditions. Specifically, applying hydrostatic tension or adding ethanol decreases the crossover length to molecular sizes, making it accessible to atomistic simulations. With detailed temperature-dependent studies, we further demonstrate that hydration thermodynamics changes gradually from entropic to enthalpic near the crossover. The nanoscopic lengthscale of the crossover and its sensitivity to thermodynamic variables imply that quantitative modeling of biomolecular self-assembly in aqueous solutions requires elements of both molecular and macroscopic hydration physics. We also show that the small-to-large crossover is directly related to the Egelstaff-Widom lengthscale, the product of surface tension and isothermal compressibility, which is another fundamental lengthscale in liquids. Author contributions: S.R., T.M.T., and S.G. designed research; S.R. performed research; S.R., T.M.T., and S.G. analyzed data; and S.R., T.M.T., and S.G. wrote the paper.Abbreviations: LCW

  20. Effect of nitrogen crossover on purging strategy in PEM fuel cell systems

    DEFF Research Database (Denmark)

    Rabbani, Raja Abid; Rokni, Masoud

    2013-01-01

    conditions, making it important to investigate the dynamic performance of the system during transitory conditions. The model developed here is able to predict nitrogen crossover in excellent agreement with the design validation data of the stack. The results show that with pure recirculation, voltage...... levels from rising when compared to a fixed purge interval strategy. This model can be used as a base for control and development of anode purge strategies for automotive fuel cell systems....

  1. Acute Effects of a Spinach Extract Rich in Thylakoids on Satiety: A Randomized Controlled Crossover Trial

    OpenAIRE

    Rebello, Candida J.; Chu, Jessica; Beyl, Robbie; Edwall, Dan; Erlanson-Albertsson, Charlotte; Frank L. Greenway

    2015-01-01

    Objective: By retarding fat digestion, thylakoids, the internal photosynthetic membrane system of green plants, promote the release of satiety hormones. This study examined the effect of consuming a single dose of concentrated extract of thylakoids from spinach on satiety, food intake, lipids, and glucose compared to a placebo. Design: Sixty overweight and obese individuals enrolled in a double-blind randomized crossover study consumed the spinach extract or placebo in random order at least a...

  2. How to deal with morning bad breath: A randomized, crossover clinical trial

    OpenAIRE

    Jeronimo M Oliveira-Neto; Sandra Sato; Vinicius Pedrazzi

    2013-01-01

    Context: The absence of a protocol for the treatment of halitosis has led us to compare mouthrinses with mechanical oral hygiene procedures for treating morning breath by employing a hand-held sulfide monitor. Aims: To compare the efficacy of five modalities of treatment for controlling morning halitosis in subjects with no dental or periodontal disease. Settings and Design: This is a five-period, randomized, crossover clinical trial. Materials and Methods: Twenty volunteers were randomly ass...

  3. Contrasted patterns of crossover and non-crossover at Arabidopsis thaliana meiotic recombination hotspots.

    Directory of Open Access Journals (Sweden)

    Jan Drouaud

    2013-11-01

    Full Text Available The vast majority of meiotic recombination events (crossovers (COs and non-crossovers (NCOs cluster in narrow hotspots surrounded by large regions devoid of recombinational activity. Here, using a new molecular approach in plants, called "pollen-typing", we detected and characterized hundreds of CO and NCO molecules in two different hotspot regions in Arabidopsis thaliana. This analysis revealed that COs are concentrated in regions of a few kilobases where their rates reach up to 50 times the genome average. The hotspots themselves tend to cluster in regions less than 8 kilobases in size with overlapping CO distribution. Non-crossover (NCO events also occurred in the two hotspots but at very different levels (local CO/NCO ratios of 1/1 and 30/1 and their track lengths were quite small (a few hundred base pairs. We also showed that the ZMM protein MSH4 plays a role in CO formation and somewhat unexpectedly we also found that it is involved in the generation of NCOs but with a different level of effect. Finally, factors acting in cis and in trans appear to shape the rate and distribution of COs at meiotic recombination hotspots.

  4. Contrasted patterns of crossover and non-crossover at Arabidopsis thaliana meiotic recombination hotspots.

    Directory of Open Access Journals (Sweden)

    Jan Drouaud

    2013-11-01

    Full Text Available The vast majority of meiotic recombination events (crossovers (COs and non-crossovers (NCOs cluster in narrow hotspots surrounded by large regions devoid of recombinational activity. Here, using a new molecular approach in plants, called "pollen-typing", we detected and characterized hundreds of CO and NCO molecules in two different hotspot regions in Arabidopsis thaliana. This analysis revealed that COs are concentrated in regions of a few kilobases where their rates reach up to 50 times the genome average. The hotspots themselves tend to cluster in regions less than 8 kilobases in size with overlapping CO distribution. Non-crossover (NCO events also occurred in the two hotspots but at very different levels (local CO/NCO ratios of 1/1 and 30/1 and their track lengths were quite small (a few hundred base pairs. We also showed that the ZMM protein MSH4 plays a role in CO formation and somewhat unexpectedly we also found that it is involved in the generation of NCOs but with a different level of effect. Finally, factors acting in cis and in trans appear to shape the rate and distribution of COs at meiotic recombination hotspots.

  5. Crossovers get a boost in Brassica allotriploid and allotetraploid hybrids.

    Science.gov (United States)

    Leflon, Martine; Grandont, Laurie; Eber, Frédérique; Huteau, Virginie; Coriton, Olivier; Chelysheva, Liudmila; Jenczewski, Eric; Chèvre, Anne-Marie

    2010-07-01

    Meiotic crossovers are necessary to generate balanced gametes and to increase genetic diversity. Even if crossover number is usually constrained, recent results suggest that manipulating karyotype composition could be a new way to increase crossover frequency in plants. In this study, we explored this hypothesis by analyzing the extent of crossover variation in a set of related diploid AA, allotriploid AAC, and allotetraploid AACC Brassica hybrids. We first used cytogenetic methods to describe the meiotic behavior of the different hybrids. We then combined a cytogenetic estimation of class I crossovers in the entire genome by immunolocalization of a key protein, MutL Homolog1, which forms distinct foci on meiotic chromosomes, with genetic analyses to specifically compare crossover rates between one pair of chromosomes in the different hybrids. Our results showed that the number of crossovers in the allotriploid AAC hybrid was higher than in the diploid AA hybrid. Accordingly, the allotetraploid AACC hybrid showed an intermediate behavior. We demonstrated that this increase was related to hybrid karyotype composition (diploid versus allotriploid versus allotetraploid) and that interference was maintained in the AAC hybrids. These results could provide another efficient way to manipulate recombination in traditional breeding and genetic studies.

  6. Effects of a Worksite Weight-Control Programme in Obese Male Workers: A Randomized Controlled Crossover Trial

    Science.gov (United States)

    Iriyama, Yae; Murayama, Nobuko

    2014-01-01

    Objective: We conducted a randomized controlled crossover trial to evaluate the effects of a new worksite weight-control programme designed for men with or at risk of obesity using a combination of nutrition education and nutrition environmental interventions. Subjects and methods: Male workers with or at risk of obesity were recruited for this…

  7. The plaque inhibitory effect of a CPC mouthrinse in a 3-day plaque accumulation model - a cross-over study

    NARCIS (Netherlands)

    Versteeg, P.A.; Rosema, N.A.M.; Hoenderdos, N.L.; Slot, D.E.; van der Weijden, G.A.

    2010-01-01

    Objective:  To test the plaque inhibitory effect of an experimental 0.07% cetylpyridinium chloride (CPC) mouthrinse in a 3-day plaque accumulation model in a cross-over design. Material and Methods:  A total of 30 subjects (non-dental students), ≥18 years of age, were randomly assigned to use one of

  8. Extra virgin olive oil phenols and markers of oxidation in Greek smokers: a randomized cross-over study

    NARCIS (Netherlands)

    Moschandreas, J.; Vissers, M.N.; Wiseman, S.; Putte, van K.P.; Kafatos, A.

    2002-01-01

    Objective: To examine the effect of a low phenol olive oil and high phenol olive oil on markers of oxidation and plasma susceptibility to oxidation in normolipaemic smokers. Design: Randomized single-blind cross-over trial with two intervention periods. Setting: The Medical School and University

  9. Effects of magnetic stray fields from a 7 Tesla MRI scanner on neurocognition: a double-blind randomised crossover study

    NARCIS (Netherlands)

    van Nierop, L.E.|info:eu-repo/dai/nl/323065384; Slottje, P.|info:eu-repo/dai/nl/299345351; van Zandvoort, M.J.; de Vocht, F.; Kromhout, H.|info:eu-repo/dai/nl/074385224

    2012-01-01

    OBJECTIVE This study characterises neurocognitive domains that are affected by movement-induced time-varying magnetic fields (TVMF) within a static magnetic stray field (SMF) of a 7 Tesla (T) MRI scanner. METHODS Using a double-blind randomised crossover design, 31 healthy volunteers were tested in

  10. A Randomized, Double-Blind, Crossover Comparison of MK-0929 and Placebo in the Treatment of Adults with ADHD

    Science.gov (United States)

    Rivkin, Anna; Alexander, Robert C.; Knighton, Jennifer; Hutson, Pete H.; Wang, Xiaojing J.; Snavely, Duane B.; Rosah, Thomas; Watt, Alan P.; Reimherr, Fred W.; Adler, Lenard A.

    2012-01-01

    Objective: Preclinical models, receptor localization, and genetic linkage data support the role of D4 receptors in the etiology of ADHD. This proof-of-concept study was designed to evaluate MK-0929, a selective D4 receptor antagonist as treatment for adult ADHD. Method: A randomized, double-blind, placebo-controlled, crossover study was conducted…

  11. Extra virgin olive oil phenols and markers of oxidation in Greek smokers: a randomized cross-over study

    NARCIS (Netherlands)

    Moschandreas, J.; Vissers, M.N.; Wiseman, S.; Putte, van K.P.; Kafatos, A.

    2002-01-01

    Objective: To examine the effect of a low phenol olive oil and high phenol olive oil on markers of oxidation and plasma susceptibility to oxidation in normolipaemic smokers. Design: Randomized single-blind cross-over trial with two intervention periods. Setting: The Medical School and University Hos

  12. Randomized crossover study comparing the phosphate-binding efficacy of calcium ketoglutarate versus calcium carbonate in patients on chronic hemodialysis

    DEFF Research Database (Denmark)

    Bro, S; Rasmussen, R A; Handberg, J

    1998-01-01

    The objective of the study was to evaluate the phosphate-binding efficacy, side effects, and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis. The study design used was a randomized, crossover open trial, and the main...

  13. Effects of magnetic stray fields from a 7 Tesla MRI scanner on neurocognition: a double-blind randomised crossover study

    NARCIS (Netherlands)

    van Nierop, L.E.; Slottje, P.; van Zandvoort, M.J.; de Vocht, F.; Kromhout, H.

    2012-01-01

    OBJECTIVE This study characterises neurocognitive domains that are affected by movement-induced time-varying magnetic fields (TVMF) within a static magnetic stray field (SMF) of a 7 Tesla (T) MRI scanner. METHODS Using a double-blind randomised crossover design, 31 healthy volunteers were tested in

  14. Sexual activity as a trigger of myocardial infarction. A case-crossover analysis in the Stockholm Heart Epidemiology Programme (SHEEP)

    DEFF Research Database (Denmark)

    Möller, J; Ahlbom, A; Hulting, J

    2001-01-01

    OBJECTIVE: To investigate sexual activity as a trigger of myocardial infarction and the potential effect modification of physical fitness. DESIGN: A case-crossover study nested in the Stockholm Heart Epidemiology Programme (SHEEP). SETTING: Stockholm County from April 1993 to December 1994...

  15. Analysis of multi-step transitions in spin crossover nanochains

    Energy Technology Data Exchange (ETDEWEB)

    Chiruta, Daniel [GEMaC, Université de Versailles Saint-Quentin-en-Yvelines, CNRS-UVSQ (UMR 8635), 78035 Versailles Cedex (France); LISV, Université de Versailles Saint-Quentin-en-Yvelines, 78140 Velizy (France); Faculty of Electrical Engineering and Computer Science, Stefan cel Mare University, Suceava 720229 (Romania); Linares, Jorge, E-mail: jorge.linares@uvsq.fr [GEMaC, Université de Versailles Saint-Quentin-en-Yvelines, CNRS-UVSQ (UMR 8635), 78035 Versailles Cedex (France); Garcia, Yann, E-mail: yann.garcia@uclouvain.be [Institute of Condensed Matter and Nanosciences, Université Catholique de Louvain, Molecules, Solids and Reactivity (IMCN/MOST), Place Louis Pasteur, 1, 1348 Louvain-la-Neuve (Belgium); Dimian, Mihai [Faculty of Electrical Engineering and Computer Science, Stefan cel Mare University, Suceava 720229 (Romania); Dahoo, Pierre Richard [LATMOS, Université de Versailles-Saint-Quentin-en-Yvelines, CNRS-UPMC-UVSQ (UMR 8190), 78280 Guyancourt (France)

    2014-02-01

    The temperature driven phase transition occurring in spin crossover nanochains has been studied by an Ising-like model considering both short-range and long-range interactions. Various types of spin crossover profiles have been described in this framework, including a novel three-step transition identified in a nanosystem with eight molecules, which is modeled for the first time. A special interest has been also given to stepwise transitions accompanied by two hysteresis loops. The edge and size effects on spin crossover behavior have been investigated in order to get a deeper insight of the underlying mechanisms involved in these unusual spin transitions.

  16. The pch2Delta mutation in baker's yeast alters meiotic crossover levels and confers a defect in crossover interference.

    Directory of Open Access Journals (Sweden)

    Sarah Zanders

    2009-07-01

    Full Text Available Pch2 is a widely conserved protein that is required in baker's yeast for the organization of meiotic chromosome axes into specific domains. We provide four lines of evidence suggesting that it regulates the formation and distribution of crossover events required to promote chromosome segregation at Meiosis I. First, pch2Delta mutants display wild-type crossover levels on a small (III chromosome, but increased levels on larger (VII, VIII, XV chromosomes. Second, pch2Delta mutants show defects in crossover interference. Third, crossovers observed in pch2Delta require both Msh4-Msh5 and Mms4-Mus81 functions. Lastly, the pch2Delta mutation decreases spore viability and disrupts crossover interference in spo11 hypomorph strains that have reduced levels of meiosis-induced double-strand breaks. Based on these and previous observations, we propose a model in which Pch2 functions at an early step in crossover control to ensure that every homolog pair receives an obligate crossover.

  17. Nanoporous separator and low fuel concentration to minimize crossover in direct methanol laminar flow fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Hollinger, A.S. [Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, 1206 Green Street, Urbana, IL 61801 (United States); Maloney, R.J.; Jayashree, R.S. [Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Matthews Avenue, Urbana, IL 61801 (United States); Natarajan, D.; Markoski, L.J. [INI Power Systems, 175 Southport Drive, Suite 100, Morrisville, NC 27560 (United States); Kenis, P.J.A. [Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, 1206 Green Street, Urbana, IL 61801 (United States); Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Matthews Avenue, Urbana, IL 61801 (United States)

    2010-06-01

    Laminar flow fuel cells (LFFCs) overcome some key issues - most notably fuel crossover and water management - that typically hamper conventional polymer electrolyte-based fuel cells. Here we report two methods to further minimize fuel crossover in LFFCs: (i) reducing the cross-sectional area between the fuel and electrolyte streams, and (ii) reducing the driving force of fuel crossover, i.e. the fuel concentration gradient. First, we integrated a nanoporous tracketch separator at the interface of the fuel and electrolyte streams in a single-channel LFFC to dramatically reduce the cross-sectional area across which methanol can diffuse. Maximum power densities of 48 and 70 mW cm{sup -2} were obtained without and with a separator, respectively, when using 1 M methanol. This simple design improvement reduces losses at the cathode leading to better performance and enables thinner cells, which is attractive in portable applications. Second, we demonstrated a multichannel cell that utilizes low methanol concentrations (<300 mM) to reduce the driving force for methanol diffusion to the cathode. Using 125 mM methanol as the fuel, a maximum power density of 90 mW cm{sup -2} was obtained. This multichannel cell further simplifies the LFFC design (one stream only) and its operation, thereby extending its potential for commercial application. (author)

  18. A case-crossover study of transient risk factors influence on occupational injuries

    DEFF Research Database (Denmark)

    Oesterlund, Anna H; Lander, Flemming; Lauritsen, Jens

    2016-01-01

    BACKGROUND: The occupational injury incident rate remains relatively high in the European Union. The case-crossover study gives a unique opportunity to study transient risk factors that normally would be very difficult to approach. Studies like this have been carried out in both America and Asia......, but so far no relevant research has been conducted in Europe. METHOD: Case-crossover studies of occupational injuries were collected from PubMed and Embase and read through. Previous experiences concerning method, exposure and outcome, time-related measurements and construction of the questionnaire were...... taken into account in the preparation of a pilot study. Consequently, experiences from the pilot study were used to design the study protocol. Approximately 2000 patients with an occupational injury will be recruited from the emergency departments in Herning and Odense, Denmark. A standardised...

  19. Microelectromechanical systems integrating molecular spin crossover actuators

    Science.gov (United States)

    Manrique-Juarez, Maria D.; Rat, Sylvain; Mathieu, Fabrice; Saya, Daisuke; Séguy, Isabelle; Leïchlé, Thierry; Nicu, Liviu; Salmon, Lionel; Molnár, Gábor; Bousseksou, Azzedine

    2016-08-01

    Silicon MEMS cantilevers coated with a 200 nm thin layer of the molecular spin crossover complex [Fe(H2B(pz)2)2(phen)] (H2B(pz)2 = dihydrobis(pyrazolyl)borate and phen = 1,10-phenantroline) were actuated using an external magnetic field and their resonance frequency was tracked by means of integrated piezoresistive detection. The light-induced spin-state switching of the molecules from the ground low spin to the metastable high spin state at 10 K led to a well-reproducible shift of the cantilever's resonance frequency (Δfr = -0.52 Hz). Control experiments at different temperatures using coated as well as uncoated devices along with simple calculations support the assignment of this effect to the spin transition. This latter translates into changes in mechanical behavior of the cantilever due to the strong spin-state/lattice coupling. A guideline for the optimization of device parameters is proposed so as to efficiently harness molecular scale movements for large-scale mechanical work, thus paving the road for nanoelectromechanical systems (NEMS) actuators based on molecular materials.

  20. Standard Model thermodynamics across the electroweak crossover

    Energy Technology Data Exchange (ETDEWEB)

    Laine, M.; Meyer, M. [Institute for Theoretical Physics, Albert Einstein Center, University of Bern, Sidlerstrasse 5, CH-3012 Bern (Switzerland)

    2015-07-22

    Even though the Standard Model with a Higgs mass m{sub \\tiny H}=125 GeV possesses no bulk phase transition, its thermodynamics still experiences a “soft point” at temperatures around T=160 GeV, with a deviation from ideal gas thermodynamics. Such a deviation may have an effect on precision computations of weakly interacting dark matter relic abundances if their mass is in the few TeV range, or on leptogenesis scenarios operating in this temperature range. By making use of results from lattice simulations based on a dimensionally reduced effective field theory, we estimate the relevant thermodynamic functions across the crossover. The results are tabulated in a numerical form permitting for their insertion as a background equation of state into cosmological particle production/decoupling codes. We find that Higgs dynamics induces a non-trivial “structure” visible e.g. in the heat capacity, but that in general the largest radiative corrections originate from QCD effects, reducing the energy density by a couple of percent from the free value even at T>160 GeV.

  1. Dimensional crossover in Richtmyer-Meshkov flows

    Science.gov (United States)

    Nishihara, Katsunobu; Bhowmick, Aklant K.; Abarzhi, Snezhana

    2016-11-01

    We analyze nonlinear dynamics of large scale coherent structures in Richtmyer-Meshkov flows. Group theory based analysis is applied with a detailed consideration of RM dynamics invariant with respect to p2mm (3D rectangular), p4mm (3D square) and pm1 (2D) groups. Symmetry dictates that asymptotic solutions form a 2 parameter family for rectangular flows and a 1 parameter family for 3D square and 2D flows. For 3D square and 2D symmetry, asymptotic solutions are obtained for the 1st and 2nd order of approximation and the fastest growth rate occurs at zero bubble curvatures. Fourier amplitudes exponentially decay with increase in order showing that solutions are convergent. Both 2D and 3D square solutions are stable with respect to symmetry conserving perturbations. Isotropic 3D square solutions are universally stable, while 2D solutions are unstable to anisotropic perturbations. Furthermore, the 3D and 2D solutions cannot be continuously transformed from one to another, and the dimensional crossover is discontinuous. The work is supported by the US National Science Foundation.

  2. Species Transport Mechanisms Governing Crossover and Capacity Loss in Vanadium Redox Flow Batteries

    Science.gov (United States)

    Agar, Ertan

    Vanadium redox flow batteries (VRFBs) are an emerging energy storage technology that offers unique advantages for grid-scale energy storage due to their flexible design and decoupled power/energy feature. Despite their popularity, a series of technical challenges hinder their widespread implementation. Among these, capacity loss (i.e., loss of energy storage capability) due to the undesired species crossover across the membrane has been identified as the key issue limiting the longevity of these systems. This issue is primarily governed by the properties of the membrane and can be mitigated by using proper membrane architectures with desired features. Presently, identifying proper membrane architectures for VRFB systems is hampered by the lack of a fundamental understanding of the nature of species transport mechanisms and how they are related to the membrane properties and key operating conditions. This Ph.D. study seeks to address this critical challenge by exploring the fundamental mechanisms responsible for species transport within the membrane. The overall objective of this dissertation study is to establish a fundamental understanding of the multi-ionic transport in VRFB membranes by investigating the ionic transport mechanisms responsible for crossover, and utilize this understanding to reveal the role of membrane properties and operating conditions on the capacity loss. To achieve these goals, a combined experimental and computational study was designed. An experimentally validated, 2-D, transient VRFB model that can track the vanadium crossover and capture the related capacity loss was developed. In addition to the model, several electrochemical techniques were used to characterize different types of membrane and study the effects of various operating conditions on the species crossover. Using these computational and experimental tools, an in-depth understanding of the species transport mechanisms within the membrane and how they are related to membrane

  3. New Variations of Order Crossover for Travelling Salesman Problem

    Directory of Open Access Journals (Sweden)

    Kusum Deep

    2011-01-01

    Full Text Available Davis presented the order crossover operator for solving the travelling salesman problem (TSP using genetic algorithm and has described two basic variants of this order crossover operator. In order to improve the efficiency and validity of these variants, in this paper three new variations of the order crossover operator are presented. These are programmed in C++ and implemented on a set of benchmark test problems taken from TSPLIB.The analysis of results based on the numerical and graphical analysis indicated that the new variations of the order crossover proposed in this paper have a definite supremacy over the existing variants for TSP with number of cities less than or equal to 100 as well as greater than 100 for some instances.

  4. Hysteretic behavior of spin-crossover noise driven system

    Energy Technology Data Exchange (ETDEWEB)

    Gudyma, Iurii [Department of General Physics, Chernivtsi National University, Chernivtsi 58012 (Ukraine); Maksymov, Artur, E-mail: maxyartur@gmail.com [Department of General Physics, Chernivtsi National University, Chernivtsi 58012 (Ukraine); Advanced Materials Research Institute, University of New Orleans, LA 70148 (United States); Dimian, Mihai [Department of Electrical and Computer Engineering, Howard University, Washington DC, 20059 (United States); Faculty of Electrical Engineering and Computer Science, Stefan cel Mare University, Suceava 720229 (Romania)

    2016-04-01

    The influence of white Gaussian noise on hysteretic behavior of spin-crossover system is analyzed in the framework of stochastic Langevin dynamics. Various stochastic simulations are performed and several important properties of spin-transition in spin-crossover system driven by noise are reproduced. The numerical results are tested against the stationary probability function and the associated dynamic potential obtained from Fokker–Planck equation corresponding to spin-crossover Langevin dynamics. The dependence of light-induced optical hysteresis width and non-hysteretic transition curve slope on the noise intensity is illustrated. The role of low-spin and high-spin phase stabilities in the hysteretic behavior of noise-driven spin-crossover system is discussed.

  5. Electronic bidirectional valve circuit prevents crossover distortion and threshold effect

    Science.gov (United States)

    Kernick, A.

    1966-01-01

    Four-terminal network forms a bidirectional valve which will switch or alternate an ac signal without crossover distortion or threshold effect. In this network, an isolated control signal is sufficient for circuit turn-on.

  6. Research Update: The mechanocaloric potential of spin crossover compounds

    Directory of Open Access Journals (Sweden)

    Karl G. Sandeman

    2016-11-01

    Full Text Available We present a first evaluation of the potential for spin crossover (SCO compounds to be considered as a new class of giant mechanocaloric effect materials. From literature data on the variation of the spin crossover temperature with pressure, we estimate the maximum available adiabatic temperature change for several compounds and the relatively low pressures that may be required to observe these effects.

  7. SPECIFIC AND CROSS-OVER EFFECTS OF FOAM ROLLING ON ANKLE DORSIFLEXION RANGE OF MOTION

    Science.gov (United States)

    Beardsley, Chris

    2016-01-01

    ABSTRACT Background Flexibility is an important physical quality. Self-myofascial release (SMFR) methods such as foam rolling (FR) increase flexibility acutely but how long such increases in range of motion (ROM) last is unclear. Static stretching (SS) also increases flexibility acutely and produces a cross-over effect to contralateral limbs. FR may also produce a cross-over effect to contralateral limbs but this has not yet been identified. Purpose To explore the potential cross-over effect of SMFR by investigating the effects of a FR treatment on the ipsilateral limb of 3 bouts of 30 seconds on changes in ipsilateral and contralateral ankle DF ROM and to assess the time-course of those effects up to 20 minutes post-treatment. Methods A within- and between-subject design was carried out in a convenience sample of 26 subjects, allocated into FR (n=13) and control (CON, n=13) groups. Ankle DF ROM was recorded at baseline with the in-line weight-bearing lunge test for both ipsilateral and contralateral legs and at 0, 5, 10, 15, 20 minutes following either a two-minute seated rest (CON) or 3 3 30 seconds of FR of the plantar flexors of the dominant leg (FR). Repeated measures ANOVA was used to examine differences in ankle DF ROM. Results No significant between-group effect was seen following the intervention. However, a significant within-group effect (p<0.05) in the FR group was seen between baseline and all post-treatment time-points (0, 5, 10, 15 and 20 minutes). Significant within-group effects (p<0.05) were also seen in the ipsilateral leg between baseline and at all post-treatment time-points, and in the contralateral leg up to 10 minutes post-treatment, indicating the presence of a cross-over effect. Conclusions FR improves ankle DF ROM for at least 20 minutes in the ipsilateral limb and up to 10 minutes in the contralateral limb, indicating that FR produces a cross-over effect into the contralateral limb. The mechanism producing these cross-over effects is

  8. Crossovers from parity conserving to directed percolation universality.

    Science.gov (United States)

    Odor, Géza; Menyhárd, Nóra

    2008-10-01

    The crossover behavior of various models exhibiting phase transition to absorbing phase with parity conserving class has been investigated by numerical simulations and cluster mean-field method. In case of models exhibiting Z_2 symmetric absorbing phases (the cellular automaton version of the nonequilibrium kinetic Ising model (NEKIMCA) and a stochastic cellular automaton invented by Grassberger, Krause, and von der Twer [J. Phys. A 17, L105 (1984)]) the introduction of an external symmetry breaking field causes a crossover to kink parity conserving models characterized by dynamical scaling of the directed percolation (DP) and the crossover exponent: 1/phi approximately equal to 0.53(2) . In the case of a branching and annihilating random walk model with an even number of offspring (dual to NEKIMCA) the introduction of spontaneous particle decay destroys the parity conservation and results in a crossover to the DP class characterized by the crossover exponent: 1/phi approximately equal to 0.205(5) . The two different kinds of crossover operators cannot be mapped onto each other and the resulting models show a diversity within the DP universality class in one dimension. These subclasses differ in cluster scaling exponents.

  9. Application of genetic algorithm with approximation crossover strategy to ambiguity resolution in PD radar

    Institute of Scientific and Technical Information of China (English)

    ZhangGong; ZhuZhaoda; ZhuNingyi

    2003-01-01

    The genetic algorithm (GA) designed as a general optimization method was applied to the ambiguity resolution of pulse Doppler (PD) radar. The fitness, based on squared error for multi-PRF (pulse repeat frequency) consecutive ordered ranges, was designed. The crossover operator and the conditions of ending in GA were discussed. The relations among the probability of ambiguity resolution of this algorithm, the measurement error and the computational efficiency were analyzed.Simulation results show the GA ambiguity resolution algorithm does better than the sliding window algorithm on the probability of ambiguity resolution.

  10. The dynamical crossover in attractive colloidal systems

    Energy Technology Data Exchange (ETDEWEB)

    Mallamace, Francesco [Dipartimento di Fisica e Scienze della Terra, Università di Messina and CNISM, I-98168 Messina (Italy); Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Corsaro, Carmelo [Dipartimento di Fisica e Scienze della Terra, Università di Messina and CNISM, I-98168 Messina (Italy); Stanley, H. Eugene [Center for Polymer Studies and Department of Physics, Boston University, Boston, Massachusetts 02215 (United States); Mallamace, Domenico [Dipartimento di Scienze dell’Ambiente, della Sicurezza, del Territorio, degli Alimenti e della Salute, Università di Messina, I-98166 Messina (Italy); Chen, Sow-Hsin [Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States)

    2013-12-07

    We study the dynamical arrest in an adhesive hard-sphere colloidal system. We examine a micellar suspension of the Pluronic-L64 surfactant in the temperature (T) and volume fraction (ϕ) phase diagram. According to mode-coupling theory (MCT), this system is characterized by a cusp-like singularity and two glassy phases: an attractive glass (AG) phase and a repulsive glass (RG) phase. The T − ϕ phase diagram of this system as confirmed by a previous series of scattering data also exhibits a Percolation Threshold (PT) line, a reentrant behavior (AG-liquid-RG), and a glass-to-glass transition. The AG phase can be generated out of the liquid phase by using T and ϕ as control parameters. We utilize viscosity and nuclear magnetic resonance (NMR) techniques. NMR data confirm all the characteristic properties of the colloidal system phase diagram and give evidence of the onset of a fractal-like percolating structure at a precise threshold. The MCT scaling laws used to study the shear viscosity as a function of ϕ and T show in both cases a fragile-to-strong liquid glass-forming dynamic crossover (FSC) located near the percolation threshold where the clustering process is fully developed. These results suggest a larger thermodynamic generality for this phenomenon, which is usually studied only as a function of the temperature. We also find that the critical values of the control parameters, coincident with the PT line, define the locus of the FSC. In the region between the FSC and the glass transition lines the system dynamics are dominated by clustering effects. We thus demonstrate that it is possible, using the conceptual framework provided by extended mode-coupling theory, to describe the way a system approaches dynamic arrest, taking into account both cage and hopping effects.

  11. Efficacy of the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program among patients with mild cognitive impairment: a randomized controlled crossover trial.

    Science.gov (United States)

    Han, Ji Won; Son, Kyung Lak; Byun, Hye Jin; Ko, Ji Won; Kim, Kayoung; Hong, Jong Woo; Kim, Tae Hyun; Kim, Ki Woong

    2017-06-06

    Spaced retrieval training (SRT) is a nonpharmacological intervention for mild cognitive impairment (MCI) and dementia that trains the learning and retention of target information by recalling it over increasingly long intervals. We recently developed the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program as a convenient, self-administered tablet-based SRT program. We also demonstrated the utility of USMART for improving memory in individuals with MCI through an open-label uncontrolled trial. This study had an open-label, single-blind, randomized, controlled, two-period crossover design. Fifty patients with MCI were randomized into USMART-usual care and usual care-USMART treatment sequences. USMART was completed or usual care was provided biweekly over a 4-week treatment period with a 2-week washout period between treatment periods. Primary outcome measures included the Word List Memory Test, Word List Recall Test (WLRT), and Word List Recognition Test. Outcomes were measured at baseline, week 5, and week 11 by raters who were blinded to intervention type. An intention-to-treat analysis and linear mixed modeling were used. Of 50 randomized participants, 41 completed the study (18% dropout rate). The USMART group had larger improvements in WLRT score (effect size = 0.49, p = 0.031) than the usual care group. There were no significant differences in other primary or secondary measures between the USMART and usual care groups. Moreover, no USMART-related adverse events were reported. The 4-week USMART modestly improved information retrieval in older people with MCI, and was well accepted with minimal technical support. ClinicalTrials.gov NCT01688128 . Registered 12 September 2012.

  12. A single-dose, randomized, cross-over, two-way, open-label study for comparing the absorption of boswellic acids and its lecithin formulation.

    Science.gov (United States)

    Riva, Antonella; Morazzoni, Paolo; Artaria, Christian; Allegrini, Pietro; Meins, Jürgen; Savio, Daniele; Appendino, Giovanni; Schubert-Zsilavecz, Manfred; Abdel-Tawab, Mona

    2016-11-15

    The oral administration of the gum resin extracts of Indian frankincense (Boswellia serrata Roxb. ex Colebr) results in very low plasma concentrations of boswellic acids (BAs), being far below the pharmacologically active concentrations required in vitro for anti-inflammatory activity. For that reason the use of Indian frankincense in clinical practice and pharmaceutical development has substantially lagged behind. Recently the application of new formulation technologies resulted in a formulation of frankincense extract with lecithin, which revealed improved absorption and tissue penetration of BAs in a rodent study, leading for the first time to plasma concentrations of BAs in the range of their anti-inflammatory activity. In order to verify these encouraging results in humans, the absorption of a standardized Boswellia serrata extract (BE) and its lecithin formulation (CSP) was comparatively investigated in healthy volunteers. According to a randomized cross-over design with two treatments, two sequences and two periods, 12 volunteers alternatively received the lecithin-formulated Boswellia extract (CSP) or the non-formulated Boswellia extract (BE) at a dosage of 2×250mg capsules. The plasma concentrations of the six major BAs (KBA, AKBA, βBA, αBA, AβBA, AαBA) were determined using LC/MS. With the exception of KBA, a significantly higher (both in terms of weight-to-weight and molar comparison) and quicker absorption of BAs from the lecithin formulation was observed, leading to Cmax in the range required for the interaction with their molecular targets. These findings pave the way to further studies evaluating the clinical potential of BAs, and verify the beneficial effect of lecithin formulation to improve the absorption of poorly soluble phytochemicals. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  13. A comparative, cross-over, double blind, randomized study for bioequivalence assessment between two formulations of valsartan capsules vs. tablets

    Directory of Open Access Journals (Sweden)

    Milena Pérez

    2006-06-01

    Full Text Available Introduction: Bioequivalence or compared equivalence studies are used to demonstrate claims that the new product, named generic product, will have the same bioavailability as the reference product, named brand product. If two products are bioequivalent it means that they would expect to have the same efficacy and security. Bioequivalence is established by the statistical estimation of significant differences or not in the pharmacokinetics parameters of area under the curve (AUC and maximum concentration (Cmax. In this case, bioequivalence will be evaluated and the bioavailability of Valsartan will be compared. Valsartan is an agent antihypertensive and specific angiotensin II antagonist acting on the AT1 receptor subtype. Objective: The aim of this study was to evaluate the bioequivalence of two pharmaceutical products whose active principle is Valsartan, based on the comparison of the pharmacokinetic measures of rate and extent (in terms of required time in which valsartan reaches the sanguineous circulation after a oral dose to 15 volunteers. Metodology: This was a randomized crossover double blind single-dose study on 15 male healthy volunteers aged between 19 and 28 years. The study was performed in two periods. Each treatment period consisted of a single-dose of 320 mg valsartan, with a wash-out time of 8 days between the first and second period. Plasma concentrations of valsartan were evaluated by HPLC/UV with method of addition of valsartan standard and losartan as internal standard. Results: Valsartan tablets formulation showed this pharmacokinetic parameters: AUC 44,893 µg/mlxh, Cmax 6,430.3 µg/ml and Tmax 2 h. Valsartan capsules formulation showed this pharmacokinetic parameters: AUC 44,963 µg/mlxh, Cmax 5,831.4 µg/ml and Tmax 2.5 h. Conclusion: The study showed no statistically significant differences in the plasma concentration levels after administration of the two formulations of valsartan: 80 mg tablets and 80 mg capsules. So

  14. A comparative, cross-over, double blind, randomized study for bioequivalence assessment between two formulations of valsartan capsules vs. tablets.

    Directory of Open Access Journals (Sweden)

    Milena Pérez

    2009-11-01

    Full Text Available Introduction: Bioequivalence or compared equivalence studies are used to demonstrate claims that the new product, named generic product, will have the same bioavailability as the reference product, named brand product. If two products are bioequivalent it means that they would expect to have the same efficacy and security. Bioequivalence is established by the statistical estimation of significant differences or not in the pharmacokinetics parameters of area under the curve (AUC and maximum concentration (Cmax. In this case, bioequivalence will be evaluated and the bioavailability of valsartan will be compared. Valsartan is an agent antihypertensive and specific angiotensin II antagonist acting on the AT1 receptor subtype. Objective: The aim of this study was to evaluate the bioequivalence of two pharmaceutical products whose active principle is Valsartan, based on the comparison of the pharmacokinetic measures of rate and extent (in terms of required time in which valsartan reaches the sanguineous circulation after a oral dose to 15 volunteers. Metodology: This was a randomized crossover double blind single-dose study on 15 male healthy volunteers aged between 19 and 28 years. The study was performed in two periods. Each treatment period consisted of a single-dose of 320 mg valsartan, with a wash-out time of 8 days between the first and second period. Plasma concentrations of valsartan were evaluated by HPLC/UV with method of addition of valsartan standard and losartan as internal standard. Results: Valsartan tablets formulation showed this pharmacokinetic parameters: AUC 44,893 µg/mlxh, Cmax 6,430.3 µg/ml and Tmax 2 h. Valsartan capsules formulation showed this pharmacokinetic parameters: AUC 44,963 µg/mlxh, Cmax 5,831.4 µg/ml and Tmax 2.5 h. Conclusion: The study showed no statistically significant differences in the plasma concentration levels after administration of the two formulations of valsartan: 80 mg tablets and 80 mg capsules. So

  15. Correcting for GPS Multipath Error in LIDAR Surveys Using Crossover Analysis

    Science.gov (United States)

    Borsa, A. A.; Bills, B. G.; Fricker, H. A.; Minster, J. B.

    2003-12-01

    The quality of the range measurement from an airborne Light Detection and Ranging (LIDAR) survey is largely dependent on the accuracy of the GPS trajectory for the aircraft. GPS elevation error - which today is largely due to multipath effects at the aircraft and the GPS base station - contributes a major portion of the LIDAR vertical error budget. The usual practice of quoting an RMS value for the GPS component of the error budget implies that GPS noise is Gaussian, yet the true nature of the noise signal is time-varying with significant power at long periods. GPS noise with a 3-cm RMS can easily have more than 10 cm of total variability on a time scale of tens of minutes to several hours. We show examples from an airborne LIDAR survey over the open-pit Hector Mine where repeated flyovers of an area used for ground truth revealed large elevation biases between passes that could not be resolved by adjusting the (non-GPS) parameters of the LIDAR system. As part of the post-processing of a large kinematic GPS survey of the salar de Uyuni, Bolivia, we have developed an algorithm to correct time-varying GPS error using elevation mismatches at crossovers between vehicle paths. The survey was originally designed to incorporate a large number of crossovers for the purpose of determining survey repeatability, and we were later able to exploit the crossover difference observations to solve for a model of the actual error signal generating those differences. We give results from tests with synthetic noise and topography data indicating that this method removes more than two-thirds of the added noise from the topographic signal, and we show the excellent results obtained for the salar de Uyuni survey data. We believe that airborne LIDAR surveys incorporating crossovers at regular intervals can also benefit from the application of this algorithm.

  16. Detection of crossover time scales in multifractal detrended fluctuation analysis

    Science.gov (United States)

    Ge, Erjia; Leung, Yee

    2013-04-01

    Fractal is employed in this paper as a scale-based method for the identification of the scaling behavior of time series. Many spatial and temporal processes exhibiting complex multi(mono)-scaling behaviors are fractals. One of the important concepts in fractals is crossover time scale(s) that separates distinct regimes having different fractal scaling behaviors. A common method is multifractal detrended fluctuation analysis (MF-DFA). The detection of crossover time scale(s) is, however, relatively subjective since it has been made without rigorous statistical procedures and has generally been determined by eye balling or subjective observation. Crossover time scales such determined may be spurious and problematic. It may not reflect the genuine underlying scaling behavior of a time series. The purpose of this paper is to propose a statistical procedure to model complex fractal scaling behaviors and reliably identify the crossover time scales under MF-DFA. The scaling-identification regression model, grounded on a solid statistical foundation, is first proposed to describe multi-scaling behaviors of fractals. Through the regression analysis and statistical inference, we can (1) identify the crossover time scales that cannot be detected by eye-balling observation, (2) determine the number and locations of the genuine crossover time scales, (3) give confidence intervals for the crossover time scales, and (4) establish the statistically significant regression model depicting the underlying scaling behavior of a time series. To substantive our argument, the regression model is applied to analyze the multi-scaling behaviors of avian-influenza outbreaks, water consumption, daily mean temperature, and rainfall of Hong Kong. Through the proposed model, we can have a deeper understanding of fractals in general and a statistical approach to identify multi-scaling behavior under MF-DFA in particular.

  17. A Link between Meiotic Prophase Progression and CrossoverControl

    Energy Technology Data Exchange (ETDEWEB)

    Carlton, Peter M.; Farruggio, Alfonso P.; Dernburg, Abby F.

    2005-07-06

    During meiosis, most organisms ensure that homologous chromosomes undergo at least one exchange of DNA, or crossover, to link chromosomes together and accomplish proper segregation. How each chromosome receives a minimum of one crossover is unknown. During early meiosis in Caenorhabditis elegans and many other species, chromosomes adopt a polarized organization within the nucleus, which normally disappears upon completion of homolog synapsis. Mutations that impair synapsis even between a single pair of chromosomes in C. elegans delay this nuclear reorganization. We quantified this delay by developing a classification scheme for discrete stages of meiosis. Immunofluorescence localization of RAD-51 protein revealed that delayed meiotic cells also contained persistent recombination intermediates. Through genetic analysis, we found that this cytological delay in meiotic progression requires double-strand breaks and the function of the crossover-promoting heteroduplex HIM-14 (Msh4) and MSH-5. Failure of X chromosome synapsis also resulted in impaired crossover control on autosomes, which may result from greater numbers and persistence of recombination intermediates in the delayed nuclei. We conclude that maturation of recombination events on chromosomes promotes meiotic progression, and is coupled to the regulation of crossover number and placement. Our results have broad implications for the interpretation of meiotic mutants, as we have shown that asynapsis of a single chromosome pair can exert global effects on meiotic progression and recombination frequency.

  18. Crossover Analysis of CHANG'E-1 Laser Altimeter Data

    Science.gov (United States)

    Hu, W.; Yue, Z.; Di, K.

    2011-08-01

    This paper presents a preliminary result of crossover analysis and adjustment of Chang'E-1(CE-1) Laser Altimeter (LAM) data of the Moon for global and regional mapping applications. During the operation of Chang'E-1 from November 28, 2007 to December 4, 2008, the laser altimeter acquired 1400 orbital profiles with about 9.12 million altimetric points. In our experiment, we derived more than 1.38 million crossovers from 1395 ground tracks covering the entire lunar surface after eliminating outliers of orbits and altimetric points. A method of least-squares crossover adjustment with a series of basis functions of time (trigonometric functions and polynomials) is developed to reconcile the LAM data by minimizing the crossover residuals globally. The normal equations are very large but sparse; therefore they are stored and solved using sparse matrix technique. In a test area (0°N~60°N, 50°W~0°W), the crossover residuals are reduced from 62.1m to 32.8m, and the quality of the DEM generated from the adjusted LAM data is improved accordingly. We will optimize the method for the global adjustment to generate a high precision consistent global DEM, which can be used as absolute control for lunar mapping with orbital images.

  19. A link between meiotic prophase progression and crossover control.

    Directory of Open Access Journals (Sweden)

    Peter M Carlton

    2006-02-01

    Full Text Available During meiosis, most organisms ensure that homologous chromosomes undergo at least one exchange of DNA, or crossover, to link chromosomes together and accomplish proper segregation. How each chromosome receives a minimum of one crossover is unknown. During early meiosis in Caenorhabditis elegans and many other species, chromosomes adopt a polarized organization within the nucleus, which normally disappears upon completion of homolog synapsis. Mutations that impair synapsis even between a single pair of chromosomes in C. elegans delay this nuclear reorganization. We quantified this delay by developing a classification scheme for discrete stages of meiosis. Immunofluorescence localization of RAD-51 protein revealed that delayed meiotic cells also contained persistent recombination intermediates. Through genetic analysis, we found that this cytological delay in meiotic progression requires double-strand breaks and the function of the crossover-promoting heteroduplex HIM-14 (Msh4 and MSH-5. Failure of X chromosome synapsis also resulted in impaired crossover control on autosomes, which may result from greater numbers and persistence of recombination intermediates in the delayed nuclei. We conclude that maturation of recombination events on chromosomes promotes meiotic progression, and is coupled to the regulation of crossover number and placement. Our results have broad implications for the interpretation of meiotic mutants, as we have shown that asynapsis of a single chromosome pair can exert global effects on meiotic progression and recombination frequency.

  20. Navigation Constellation Design Using a Multi-Objective Genetic Algorithm

    Science.gov (United States)

    2015-03-26

    the mutation and crossover functions specified that certain design parameters be integer values [17]. Equation 21 represents the variables that...been used to force certain design variables to be integer values. Understanding the MATLAB code for the mutation and crossover functions is not...NAVIGATION CONSTELLATION DESIGN USING A MULTI-OBJECTIVE GENETIC ALGORITHM THESIS MARCH 2015

  1. A 12-month randomized crossover study on the effects of Lanreotide Autogel and Octreotide long-acting repeatable on GH and IGF-l in patients with acromegaly

    DEFF Research Database (Denmark)

    Andries, Magdalene; Glintborg, Dorte; Kvistborg, Annette

    2007-01-01

    of acromegaly in a randomized study design. Material and methods Twelve acromegalic patients were included and 10 patients completed treatment with LAN or OCT for 6 months and were then switched to the opposite treatment modality for 6 months without a washout period in a randomized crossover design. GH and IGF...

  2. Invited commentary: application of case-crossover methods to investigate triggers of preterm birth.

    Science.gov (United States)

    Darrow, Lyndsey A

    2010-11-15

    Properties of the case-crossover design have appeal for investigation of acute triggers of preterm birth. Measured and unmeasured time-invariant risk factors are controlled by design, such that maternal race, socioeconomic status, and other personal factors will not confound the exposure-preterm birth association. In this issue of the Journal, Basu et al. (Am J Epidemiol. 2010;172(10):1108-1117) apply the case-crossover approach to assess the short-term relation between ambient apparent temperature and preterm birth. Novel application of the design to preterm birth, a "fatal" event exhibiting dramatic within-subject changes in risk, merits a review of the assumptions underlying the design. Implications of the referent time periods selected and the potential for confounding by seasonal patterns of conception are discussed in this commentary. The provocative associations observed by Basu et al. between high ambient apparent temperature and preterm birth should stimulate follow-up analyses and could ultimately have important public health implications. Future research can also help delineate the relative strengths and weaknesses of different temporal analytic strategies for investigating short-term associations between various exposures and preterm birth.

  3. Relativistic BCS-BEC Crossover at Quark Level

    Directory of Open Access Journals (Sweden)

    Zhuang P.

    2010-10-01

    Full Text Available The non-relativistic G0G formalism of BCS-BEC crossover at finite temperature is extended to relativistic fermion systems. The theory recovers the BCS mean field approximation at zero temperature and the non-relativistic results in a proper limit. For massive fermions, when the coupling strength increases, there exist two crossovers from the weak coupling BCS superfluid to the non-relativistic BEC state and then to the relativistic BEC state. For color superconductivity at moderate baryon density, the matter is in the BCS-BEC crossover region, and the behavior of the pseudogap is quite similar to that found in high temperature superconductors.

  4. Pressure effect on hysteresis in spin-crossover solid materials

    Energy Technology Data Exchange (ETDEWEB)

    Gudyma, Iurii, E-mail: yugudyma@gmail.com [Department of General Physics, Chernivtsi National University, Chernivtsi 58012 (Ukraine); Ivashko, Victor [Department of General Physics, Chernivtsi National University, Chernivtsi 58012 (Ukraine); Dimian, Mihai [Department of Electrical and Computer Engineering, Howard University, Washington DC 20059 (United States); Faculty of Electrical Engineering and Computer Science & Integrated Center for Research, Development and Innovation in Advanced Materials, Nanotechnologies, and Distributed Systems for fabrication and control, Stefan cel Mare University, Suceava 720229 (Romania)

    2016-04-01

    A generalized microscopic Ising-like model is proposed to describe behavior of compressible spin-crossover solids with two states: low-spin and high-spin. The model was solved in mean-field approximation and shows hysteretic behavior at low energy difference between the states. We study the thermal transition between states under external hydrostatic pressure taking into account the changes in the volume of spin-crossover molecules in different states. Depending on the applied pressure, a spin-crossover system can have three types of behavior of molecular fraction in the high-spin state: hysteretic, second-order phase transition and no-phase transition. For the hysteretic regime, it is shown that the transition temperature under pressure is increased while the width of the hysteresis reduced.

  5. An Improved Genetic Algorithm with Quasi-Gradient Crossover

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ling Zhang; Li Du; Guang-Wei Zhang; Qiang Miao; Zhong-Lai Wang

    2008-01-01

    The convergence of genetic algorithm is mainly determined by its core operation crossover operation. When the objective function is a multiple hump function, traditional genetic algorithms are easily trapped into local optimum, which is called premature conver gence. In this paper, we propose a new genetic algorithm with improved arithmetic crossover operation based on gradient method. This crossover operation can generate offspring along quasi-gradient direction which is the Steepest descent direction of the value of objective function. The selection operator is also simplified, every individual in the population is given an opportunity to get evolution to avoid complicated selection algorithm. The adaptive mutation operator and the elitist strategy are also applied in this algorithm. The case 4 indicates this algorithm can faster converge to the global optimum and is more stable than the conventional genetic algorithms.

  6. Dimensional crossover of the dephasing time in disordered mesoscopic rings

    Science.gov (United States)

    Treiber, M.; Yevtushenko, O. M.; Marquardt, F.; von Delft, J.; Lerner, I. V.

    2009-11-01

    We study dephasing by electron interactions in a small disordered quasi-one-dimensional (1D) ring weakly coupled to leads. We use an influence functional for quantum Nyquist noise to describe the crossover for the dephasing time τφ(T) from diffusive or ergodic 1D (τφ-1∝T2/3,T1) to zero-dimensional (0D) behavior (τφ-1∝T2) as T drops below the Thouless energy. The crossover to 0D, predicted earlier for two-dimensional and three-dimensional systems, has so far eluded experimental observation. The ring geometry holds promise of meeting this long-standing challenge, since the crossover manifests itself not only in the smooth part of the magnetoconductivity but also in the amplitude of Altshuler-Aronov-Spivak oscillations. This allows signatures of dephasing in the ring to be cleanly extracted by filtering out those of the leads.

  7. A new crossover sine model based on trigonometric model and its application to the crossover lattice equation of state

    Science.gov (United States)

    Lee, Yongjin; Shin, Moon Sam; Kim, Hwayong

    2008-12-01

    In this study, a new crossover sine model (CSM) n was developed from a trigonometric model [M. E. Fisher, S. Zinn, and P. J. Upton, Phys. Rev. B 59, 14533 (1999)]. The trigonometric model is a parametric formulation model that is used to represent the thermodynamic variables near a critical point. Although there are other crossover models based on this trigonometric model, such as the CSM and the analytical sine model, which is an analytic formulation of the CSM, the new sine model (NSM) employs a different approach from these two models in terms of the connections between the parametric variables of the trigonometric model and thermodynamic variables. In order to test the performance of the NSM, the crossover lattice equation of state [M. S. Shin, Y. Lee, and H. Kim, J. Chem. Thermodyn. 40, 174 (2008)] was applied using the NSM for correlations of various pure fluids and fluid mixtures. The results showed that over a wide range of states, the crossover lattice fluid (xLF)/NSM yields the saturated properties of pure fluids and the phase behavior of binary mixtures more accurately than the original lattice equation of state. Moreover, a comparison with the crossover lattice equation of state using the CSM (xLF/CSM) showed that the new model presents good correlation results that are comparable to the xLF/CSM.

  8. Triggers for Preeclampsia Onset: a Case-Crossover Study.

    Science.gov (United States)

    Ford, Jane B; Schemann, Kathrin; Patterson, Jillian A; Morris, Jonathan; Herbert, Robert D; Roberts, Christine L

    2016-11-01

    Risk factors for preeclampsia are well established, whereas, the triggers associated with timing of preeclampsia onset are not. The aim of this study was to establish whether recent infection or other triggers were associated with timing of preeclampsia onset. We used a case-crossover design with preeclampsia cases serving as their own controls. Women with singleton pregnancies of ≥20 weeks gestation presenting at three hospitals were eligible for inclusion. Exposures to potential triggers were identified via guided questionnaire. Infective episodes included symptoms lasting >24 h. Preeclampsia was defined as hypertension (BP ≥140 mmHg and/or ≥90 mmHg) and proteinuria (protein/creatinine ratio ≥30 mg/mmol). Conditional logistic regression was used to compare the odds of exposure to potential triggers in the case windows (1-7 days preceding diagnosis of preeclampsia) and control windows (8-14 days prior to diagnosis); unadjusted odds ratios (ORs) are reported. Among 286 recruited women, 25 (8.7%) reported a new infection in the 7 days prior to preeclampsia onset and 21 (7.3%) in the 8-14 days prior. There was no significant association between onset of infection in the 7 days prior and preeclampsia diagnosis (OR 1.24, 95% CI 0.65, 2.34). Consumption of caffeine (OR 0.51, 95% CI 0.33, 0.77), spicy food (OR 0.49, 95% CI 0.30, 0.81), and alcohol (OR 0.26, 95% CI 0.10, 0.71) were strongly inversely associated with preeclampsia onset. Recent infection does not appear to trigger preeclampsia. Decreased consumption of caffeine, spicy food, and alcohol may be prodromal markers. Such behaviours may be early markers of imminent preeclampsia. © 2016 John Wiley & Sons Ltd.

  9. A randomized crossover trial of tenoxicam compared with rofecoxib for postoperative dental pain control.

    Science.gov (United States)

    Zacharias, M; De Silva, R K; Herbison, P; Templer, P

    2004-12-01

    Two non-steroidal anti-inflammatory drugs, tenoxicam and rofecoxib, were compared for the control of postoperative pain following surgical extraction of bilaterally and symmetrically impacted wisdom teeth performed under intravenous sedation and local anaesthesia. Thirty-five young fit adult patients received each analgesic treatment for four days in a randomized, crossover design. The results suggest statistically better pain relief for the selective COX-2 inhibitor rofecoxib compared to tenoxicam, a traditional NSAID. There were side-effects with both treatments. Abdominal discomfort was significantly more common following rofecoxib compared to tenoxicam. Both analgesics were acceptable to most participants in the trial.

  10. Escitalopram in painful polyneuropathy: A randomized, placebo-controlled, cross-over trial

    DEFF Research Database (Denmark)

    Otto, Marit; Bach, Flemming W; Jensen, Troels S

    2008-01-01

    Serotonin (5-HT) is involved in pain modulation via descending pathways in the central nervous system. The aim of this study was to test if escitalopram, a selective serotonin reuptake inhibitor (SSRI), would relieve pain in polyneuropathy. The study design was a randomized, double-blind, placebo......-controlled cross-over trial. The daily dose of escitalopram was 20mg once daily. During the two treatment periods of 5 weeks duration, patients rated pain relief (primary outcome variable) on a 6-point ordered nominal scale. Secondary outcome measures comprised total pain and different pain symptoms (touch...

  11. Synthesis and characterization of 1D iron(II) spin crossover coordination polymers with hysteresis.

    Science.gov (United States)

    Bauer, Wolfgang; Lochenie, Charles; Weber, Birgit

    2014-02-07

    Purposeful ligand design was used for the synthesis of eight new 1D iron(II) spin crossover coordination polymers aiming for cooperative spin transitions with hysteresis. The results from magnetic measurements and X-ray structure analysis show that the combination of rigid linkers and a hydrogen bond network between the 1D chains is a promising tool to reach this goal. Five of the eight new samples show a cooperative spin transition with hysteresis with up to 43 K wide hysteresis loops.

  12. A typical example of a photomagnetic study carried out on a spin-crossover material

    Indian Academy of Sciences (India)

    Jean-François Létard; Chiara Carbonera; Emilie Courcot; José Sanchez Costa

    2006-11-01

    The light-induced excited spin state trapping (LIESST) is a well known phenomenon in an iron(II) spin-crossover (SCO) material which offers some interesting prospects in data storage. In this work, we present a typical investigation of the photomagnetic properties of a SCO material. At the surface of the sample, the light-induced phenomenon is investigated by using a home-built reflectivity set up and in bulk material by using a quantum design SQUID magnetometer coupled to a light source.

  13. Superradiance at the localization-delocalization crossover in tubular chlorosomes

    CERN Document Server

    Molina, Rafael A; Somoza, Alejandro; Chen, Lipeng; Zhao, Yang

    2016-01-01

    We study the effect of disorder on spectral properties of tubular chlorosomes in green sulfur bacteria Cf. aurantiacus. Employing a Frenkel-exciton Hamiltonian with diagonal and off-diagonal disorder consistent with spectral and structural studies, we analyze excitonic localization and spectral statistics of the chlorosomes. A size-dependent localization-delocalization crossover is found to occur as a function of the excitonic energy. The crossover energy region coincides with the more optically active states with maximized superradiance, and is, consequently, more conducive for energy transfer.

  14. Application of Generalised sequential crossover of languages to generalised splicing

    CERN Document Server

    Jeganathan, L; Sengupta, Ritabrata

    2009-01-01

    This paper outlines an application of iterated version of generalised sequential crossover of two languages (which in some sense, an abstraction of the crossover of chromosomes in living organisms) in studying some classes of the newly proposed generalised splicing ($GS$) over two languages. It is proved that, for $X,Y \\in \\{FIN, REG, LIN, CF, CS, RE \\}, \\sg \\in FIN$, the subclass of generalized splicing languages namely $GS(X,Y,\\sg)$, (which is a subclass of the class $GS(X,Y,FIN)$) is always regular.

  15. Fractal-to-nonfractal crossover for viscous fingers

    Science.gov (United States)

    Lee, Jysoo; Coniglio, Antonio; Stanley, H. Eugene

    1990-04-01

    We propose a position-space renormalization-group approach to the problem of viscous fingering in the absence of surface tension, with arbitrary viscosity ratio between the injected and displaced fluid. We find there are only two fixed points, the Eden and the diffusion-limited aggregation (DLA) points. The Eden point, which corresponds to a compact cluster with nonfractal surface, is stable in all directions, while the DLA fixed point is a saddle point. Hence if the viscosity of the injected fluid is not zero, the system must eventually cross over to a compact cluster. We also calculate the crossover exponent φ and crossover radius R×, and discuss possible experimental measurements.

  16. Computational Fluid Dynamics Simulation of a Quadrupole Magnetic Sorter Flow Channel: Effect of Splitter Position on Nonspecific Crossover.

    Science.gov (United States)

    Sajja, V S K; Kennedy, David J; Todd, Paul W; Hanley, Thomas R

    2011-10-01

    In the Quadrupole Magnetic Sorter (QMS) magnetic particles enter a vertical flow annulus and are separated from non-magnetic particles by radial deflection into an outer annulus where the purified magnetic particles are collected via a flow splitter. The purity of magnetically isolated particles in QMS is affected by the migration of nonmagnetic particles across transport lamina in the annular flow channel. Computational Fluid Dynamics (CFD) simulations were used to predict the flow patterns, pressure drop and nonspecific crossover in QMS flow channel for the isolation of pancreatic islets of Langerhans. Simulation results were compared with the experimental results to validate the CFD model. Results of the simulations were used to show that one design gives up to 10% less nonspecific crossover than another and this model can be used to optimise the flow channel design to achieve maximum purity of magnetic particles.

  17. Shaped Beam Pattern Synthesis of Antenna Arrays Using Composite Differential Evolution with Eigenvector-Based Crossover Operator

    Directory of Open Access Journals (Sweden)

    Sotirios K. Goudos

    2015-01-01

    Full Text Available This paper addresses the problem of designing shaped beam patterns with arbitrary arrays subject to constraints. The constraints could include the sidelobe level suppression in specified angular intervals, the mainlobe halfpower beamwidth, and the predefined number of elements. In this paper, we propose a new Differential Evolution algorithm, which combines Composite DE with an eigenvector-based crossover operator (CODE-EIG. This operator utilizes eigenvectors of covariance matrix of individual solutions, which makes the crossover rotationally invariant. We apply this novel design method to shaped beam pattern synthesis for linear and conformal arrays. We compare this algorithm with other popular algorithms and DE variants. The results show CODE-EIG outperforms the other DE algorithms in terms of statistical results and convergence speed.

  18. Individual hemoglobin mass response to normobaric and hypobaric "live high-train low": A one-year crossover study.

    Science.gov (United States)

    Hauser, Anna; Troesch, Severin; Saugy, Jonas J; Schmitt, Laurent; Cejuela-Anta, Roberto; Faiss, Raphael; Steiner, Thomas; Robinson, Neil; Millet, Grégoire P; Wehrlin, Jon P

    2017-08-01

    The purpose of this research was to compare individual hemoglobin mass (Hbmass) changes following a live high-train low (LHTL) altitude training camp under either normobaric hypoxia (NH) or hypobaric hypoxia (HH) conditions in endurance athletes. In a crossover design with a one-year washout, 15 male triathletes randomly performed two 18-day LHTL training camps in either HH or NH. All athletes slept at 2,250 meters and trained at altitudes training camp. Hbmass increased similarly in HH (916-957 g, 4.5 ± 2.2%, P train low using a same-subject crossover design. The main findings indicate that hypobaric and normobaric hypoxia evoked a similar mean increase in Hbmass following 18 days of live high-train low. Notable variability and reproducibility in individual Hbmass responses between athletes was observed, indicating the importance of evaluating individual Hbmass response to altitude training. Copyright © 2017 the American Physiological Society.

  19. Bloom syndrome helicase in meiosis: Pro-crossover functions of an anti-crossover protein.

    Science.gov (United States)

    Hatkevich, Talia; Sekelsky, Jeff

    2017-09-01

    The functions of the Bloom syndrome helicase (BLM) and its orthologs are well characterized in mitotic DNA damage repair, but their roles within the context of meiotic recombination are less clear. In meiotic recombination, multiple repair pathways are used to repair meiotic DSBs, and current studies suggest that BLM may regulate the use of these pathways. Based on literature from Saccharomyces cerevisiae, Arabidopsis thaliana, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans, we present a unified model for a critical meiotic role of BLM and its orthologs. In this model, BLM and its orthologs utilize helicase activity to regulate the use of various pathways in meiotic recombination by continuously disassembling recombination intermediates. This unwinding activity provides the meiotic program with a steady pool of early recombination substrates, increasing the probability for a DSB to be processed by the appropriate pathway. As a result of BLM activity, crossovers are properly placed throughout the genome, promoting proper chromosomal disjunction at the end of meiosis. This unified model can be used to further refine the complex role of BLM and its orthologs in meiotic recombination. © 2017 WILEY Periodicals, Inc.

  20. Modulating crossover positioning by introducing large structural changes in chromosomes

    NARCIS (Netherlands)

    Ederveen, A.; Lai, Y.; Van Driel, M.A.; Gerats, T.; Peters, J.L.

    2015-01-01

    Background Crossing over assures the correct segregation of the homologous chromosomes to both poles of the dividing meiocyte. This exchange of DNA creates new allelic combinations thus increasing the genetic variation present in offspring. Crossovers are not uniformly distributed along chromosomes;

  1. Semiclassical genetic algorithm with quantum crossover and mutation operations

    CERN Document Server

    SaiToh, Akira; Nakahara, Mikio

    2012-01-01

    In order for finding a good individual for a given fitness function in the context of evolutionary computing, we introduce a novel semiclassical quantum genetic algorithm. It has both of quantum crossover and quantum mutation procedures unlike conventional quantum genetic algorithms. A complexity analysis shows a certain improvement over its classical counterpart.

  2. Theoretical Study of Spin Crossover in 30 Iron Complexes

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2016-01-01

    Spin crossover was studied in 30 iron complexes using density functional theory to quantify the direction and magnitude of dispersion, relativistic effects, zero-point energies, and vibrational entropy. Remarkably consistent entropy−enthalpy compensation was identified. Zero-point energies favor ...

  3. Case-Crossover Analysis of Air Pollution Health Effects: A Systematic Review of Methodology and Application

    Science.gov (United States)

    Carracedo-Martínez, Eduardo; Taracido, Margarita; Tobias, Aurelio; Saez, Marc; Figueiras, Adolfo

    2010-01-01

    Background Case-crossover is one of the most used designs for analyzing the health-related effects of air pollution. Nevertheless, no one has reviewed its application and methodology in this context. Objective We conducted a systematic review of case-crossover (CCO) designs used to study the relationship between air pollution and morbidity and mortality, from the standpoint of methodology and application. Data sources and extraction A search was made of the MEDLINE and EMBASE databases. Reports were classified as methodologic or applied. From the latter, the following information was extracted: author, study location, year, type of population (general or patients), dependent variable(s), independent variable(s), type of CCO design, and whether effect modification was analyzed for variables at the individual level. Data synthesis The review covered 105 reports that fulfilled the inclusion criteria. Of these, 24 addressed methodological aspects, and the remainder involved the design’s application. In the methodological reports, the designs that yielded the best results in simulation were symmetric bidirectional CCO and time-stratified CCO. Furthermore, we observed an increase across time in the use of certain CCO designs, mainly symmetric bidirectional and time-stratified CCO. The dependent variables most frequently analyzed were those relating to hospital morbidity; the pollutants most often studied were those linked to particulate matter. Among the CCO-application reports, 13.6% studied effect modification for variables at the individual level. Conclusions The use of CCO designs has undergone considerable growth; the most widely used designs were those that yielded better results in simulation studies: symmetric bidirectional and time-stratified CCO. However, the advantages of CCO as a method of analysis of variables at the individual level are put to little use. PMID:20356818

  4. 49 CFR 236.203 - Hand operated crossover between main tracks; protection.

    Science.gov (United States)

    2010-10-01

    ...) Electric locking of the switches of the crossover. Signals governing movements over either switch shall... crossover is occupied by a train, locomotive or car in such a manner as to foul the main track. It shall not... electric locking releases....

  5. Altered Crossover Distribution and Frequency in Spermatocytes of Infertile Men with Azoospermia.

    Directory of Open Access Journals (Sweden)

    He Ren

    Full Text Available During meiosis, homologous chromosomes pair to facilitate the exchange of DNA at crossover sites along the chromosomes. The frequency and distribution of crossover formation are tightly regulated to ensure the proper progression of meiosis. Using immunofluorescence techniques, our group and others have studied the meiotic proteins in spermatocytes of infertile men, showing that this population displays a reduced frequency of crossovers compared to fertile men. An insufficient number of crossovers is thought to promote chromosome missegregation, in which case the faulty cell may face meiotic arrest or contribute to the production of aneuploid sperm. Increasing evidence in model organisms has suggested that the distribution of crossovers may also be important for proper chromosome segregation. In normal males, crossovers are shown to be rare near centromeres and telomeres, while frequent in subtelomeric regions. Our study aims to characterize the crossover distribution in infertile men with non-obstructive (NOA and obstructive azoospermia (OA along chromosomes 13, 18 and 21. Eight of the 16 NOA men and five of the 21 OA men in our study displayed reduced crossover frequency compared to control fertile men. Seven NOA men and nine OA men showed altered crossover distributions on at least one of the chromosome arms studied compared to controls. We found that although both NOA and OA men displayed altered crossover distributions, NOA men may be at a higher risk of suffering both altered crossover frequencies and distributions compared to OA men. Our data also suggests that infertile men display an increase in crossover formation in regions where they are normally inhibited, specifically near centromeres and telomeres. Finally, we demonstrated a decrease in crossovers near subtelomeres, as well as increased average crossover distance to telomeres in infertile men. As telomere-guided mechanisms are speculated to play a role in crossover formation in

  6. Crossover patterning by the beam-film model: analysis and implications.

    Directory of Open Access Journals (Sweden)

    Liangran Zhang

    2014-01-01

    Full Text Available Crossing-over is a central feature of meiosis. Meiotic crossover (CO sites are spatially patterned along chromosomes. CO-designation at one position disfavors subsequent CO-designation(s nearby, as described by the classical phenomenon of CO interference. If multiple designations occur, COs tend to be evenly spaced. We have previously proposed a mechanical model by which CO patterning could occur. The central feature of a mechanical mechanism is that communication along the chromosomes, as required for CO interference, can occur by redistribution of mechanical stress. Here we further explore the nature of the beam-film model, its ability to quantitatively explain CO patterns in detail in several organisms, and its implications for three important patterning-related phenomena: CO homeostasis, the fact that the level of zero-CO bivalents can be low (the "obligatory CO", and the occurrence of non-interfering COs. Relationships to other models are discussed.

  7. Increasing incidence of colorectal cancer in the province of Salamanca: comparison of two periods: 2004-2006 and 2010-2012

    Directory of Open Access Journals (Sweden)

    Héctor Miguel Marcos-Prieto

    Full Text Available Objectives: To compare incidence, mortality and epidemiological characteristics of patients diagnosed with colorectal cancer (CRC in the province of Salamanca over two different periods: 2010-2012 and 2004-2006. Methods: Retrospective observational study. We include all diagnosed cases of CRC according to histopathological criteria from 01/01/2004 to 31/12/2006 and from 01/01/2010 to 31/12/2012. The studied variables were sex, age, date of diagnosis and tumor location. Cumulative incidence and specific incidence in different age groups were measured and compared between the two periods. The age rates were adjusted to the standard world population so that the results could be compared with those of other populations. Results: We detected 38% more cases of CRC in the 2010-2012 period than in 2004-2006. Variables distribution (sex, age at diagnosis and location was similar in both groups. More than twice as many colonoscopies were performed in 2010-2012 than in 2004-2006. Population mortality due to CRC also increased, although much less importantly than the incidence of this condition. Conclusions: There has been a clear increase in CRC incidence in the province of Salamanca from 2004-2006 to 2010-2012 which is not related to the ageing of the population. The remarkable increase in colonoscopies may have been an important factor for the increased detection.

  8. Two periods of total testicular regression are peculiar events of the annual reproductive cycle of the black Myotis bat, Myotis nigricans (Chiroptera: Vespertilionidae).

    Science.gov (United States)

    Beguelini, Mateus R; Góes, Rejane M; Taboga, Sebastião R; Morielle-Versute, Eliana

    2014-01-01

    Myotis nigricans presents few and controversial reproductive data, which indicate geographical variation in reproduction. Thus, this study aimed to evaluate the seasonal modifications in testicular and epididymal morphologies in a tropical environment, submitting these organs to morphometric and immunohistochemical analysis. The observations revealed that this species presents two peaks of spermatogenic activity followed by two periods of total testicular regression (a quiescent pre-pubertal-like morphology, where only Sertoli cells and spermatogonia could be observed), in the same annual reproductive cycle, which seem to be only indirectly influenced by abiotic factors. This testicular behaviour seems to be synchronised with the caput and corpus epididymidis, but not with the cauda epididymidis, which presents aspects of sperm storage in May-June. The control of this variation seems to be directly linked to the expression of the androgen receptor, since, throughout the year, it is high in periods of testicular recrudescence and low in periods of deactivation. It is not thought to be directly linked to apoptosis, which is more pronounced in periods of recrudescence than in periods of regression.

  9. The antiplaque efficacy of propolis-based herbal toothpaste: A crossover clinical study

    Science.gov (United States)

    Bhat, Nagesh; Bapat, Salil; Asawa, Kailash; Tak, Mridula; Chaturvedi, Pulkit; Gupta, Vivek V.; George, Pradeep P.

    2015-01-01

    Background: In recent years, herbal products have been suggested as an economic, safe and probably effective alternative for prevention and control of various oral diseases. But still there are some products which need to be evaluated. Of lately, Propolis is one such product. To assess and compare the efficacy of herbal dentifrice containing Propolis with Miswak and Colgate total toothpastes in controlling plaque formation. Materials and Methods: A double blind, randomized, crossover study design was conducted among thirty healthy dental students. After oral prophylaxis all subjects were given a washout product for one week period. Subjects were then made to brush with (washout product) for 1 minute followed by 1 minute brushing with assigned test product. The baseline MGMPI plaque scores were recorded. Subjects were then refrained from oral hygiene for 24 hours, and were recalled to be re-disclosed and re-measured for plaque formation. This procedure was repeated according to crossover design after a washout period of (2 week). Statistical tests used were Krukalwallis and Wilcoxon sign rank test. Results: There was a significant difference in 24 hour score between the test products evaluated. When the change from baseline to 24 hours was analyzed, the test product Propolis resulted in a consistently and significantly (p < 0.05) lower MGMPI mean scores than the Colgate Total and Miswak toothpastes. Conclusion: Propolis was found to be safe and effective in reducing plaque accumulation when compared to Miswak and Colgate total toothpaste. PMID:26283831

  10. Diagnostic Crossover in Anorexia Nervosa and Bulimia Nervosa: Implications for DSM-V

    Science.gov (United States)

    Eddy, Kamryn T.; Dorer, David J.; Franko, Debra L.; Tahilani, Kavita; Thompson-Brenner, Heather; Herzog, David B.

    2011-01-01

    Objective The Diagnostic and Statistical Manual of Mental Disorders (DSM) is designed primarily as a clinical tool. Yet high rates of diagnostic “crossover” among the anorexia nervosa subtypes and bulimia nervosa may reflect problems with the validity of the current diagnostic schema, thereby limiting its clinical utility. This study was designed to examine diagnostic crossover longitudinally in anorexia nervosa and bulimia nervosa to inform the validity of the DSM-IV-TR eating disorders classification system. Method A total of 216 women with a diagnosis of anorexia nervosa or bulimia nervosa were followed for 7 years; weekly eating disorder symptom data collected using the Eating Disorder Longitudinal Interval Follow-Up Examination allowed for diagnoses to be made throughout the follow-up period. Results Over 7 years, the majority of women with anorexia nervosa experienced diagnostic crossover: more than half crossed between the restricting and binge eating/purging anorexia nervosa subtypes over time; one-third crossed over to bulimia nervosa but were likely to relapse into anorexia nervosa. Women with bulimia nervosa were unlikely to cross over to anorexia nervosa. Conclusions These findings support the longitudinal distinction of anorexia nervosa and bulimia nervosa but do not support the anorexia nervosa subtyping schema. PMID:18198267

  11. What's Mine Is Yours: The Crossover of Day-Specific Self-Esteem

    Science.gov (United States)

    Neff, Angela; Sonnentag, Sabine; Niessen, Cornelia; Unger, Dana

    2012-01-01

    This diary study examines the daily crossover of self-esteem within working couples. By integrating self-esteem research into the crossover framework, we hypothesized that the day-specific self-esteem experienced by one partner after work crosses over to the other partner. Furthermore, we proposed that this daily crossover process is moderated by…

  12. What's Mine Is Yours: The Crossover of Day-Specific Self-Esteem

    Science.gov (United States)

    Neff, Angela; Sonnentag, Sabine; Niessen, Cornelia; Unger, Dana

    2012-01-01

    This diary study examines the daily crossover of self-esteem within working couples. By integrating self-esteem research into the crossover framework, we hypothesized that the day-specific self-esteem experienced by one partner after work crosses over to the other partner. Furthermore, we proposed that this daily crossover process is moderated by…

  13. The short-term effects of air pollutants on respiratory disease mortality in Wuhan, China: comparison of time-series and case-crossover analyses

    Science.gov (United States)

    Ren, Meng; Li, Na; Wang, Zhan; Liu, Yisi; Chen, Xi; Chu, Yuanyuan; Li, Xiangyu; Zhu, Zhongmin; Tian, Liqiao; Xiang, Hao

    2017-01-01

    Few studies have compared different methods when exploring the short-term effects of air pollutants on respiratory disease mortality in Wuhan, China. This study assesses the association between air pollutants and respiratory disease mortality with both time-series and time-stratified–case-crossover designs. The generalized additive model (GAM) and the conditional logistic regression model were used to assess the short-term effects of air pollutants on respiratory disease mortality. Stratified analyses were performed by age, sex, and diseases. A 10 μg/m3 increment in SO2 level was associated with an increase in relative risk for all respiratory disease mortality of 2.4% and 1.9% in the case-crossover and time-series analyses in single pollutant models, respectively. Strong evidence of an association between NO2 and daily respiratory disease mortality among men or people older than 65 years was found in the case-crossover study. There was a positive association between air pollutants and respiratory disease mortality in Wuhan, China. Both time-series and case-crossover analyses consistently reveal the association between three air pollutants and respiratory disease mortality. The estimates of association between air pollution and respiratory disease mortality from the case–crossover analysis displayed greater variation than that from the time-series analysis.

  14. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch.

    Science.gov (United States)

    Zhang, Chao; Li, Haiyan; Xiong, Xin; Zhai, Suodi; Wei, Yudong; Zhang, Shuang; Zhang, Yuanyuan; Xu, Lin; Liu, Li

    2017-01-01

    We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet(®)) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax), extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration-time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations.

  15. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch

    Directory of Open Access Journals (Sweden)

    Zhang C

    2017-03-01

    Full Text Available Chao Zhang,1 Haiyan Li,2 Xin Xiong,1 Suodi Zhai,1 Yudong Wei,2 Shuang Zhang,2 Yuanyuan Zhang,1 Lin Xu,2 Li Liu1 1Department of Pharmacy, 2Institute of Clinical Trial, Peking University Third Hospital, Beijing, People’s Republic of China Abstract: We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE/gestodene (GSD transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet® were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax, extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations. Keywords: pharmacokinetics, safety, ethinylestradiol/gestodene, transdermal contraceptive patch

  16. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch

    Science.gov (United States)

    Zhang, Chao; Li, Haiyan; Xiong, Xin; Zhai, Suodi; Wei, Yudong; Zhang, Shuang; Zhang, Yuanyuan; Xu, Lin; Liu, Li

    2017-01-01

    We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet®) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax), extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations.

  17. A randomised, controlled, crossover study of the effect of diet on angiopoietin-like protein 4 (ANGPTL4) through modification of the gut microbiome

    DEFF Research Database (Denmark)

    Blædel, Trine; Holm, Jacob B.; Sundekilde, Ulrik Kræmer

    2016-01-01

    . The study had a crossover design with three arms, where participants were given a standardised isoenergetic diet supplemented with inulin powder, whole-fat milk or water (control). Plasma and urine samples were collected before and after each intervention period. Faecal samples and adipose tissue biopsies...

  18. Double-Blind, Placebo-Controlled, Crossover Study of the Efficacy and Safety of Lisdexamfetamine Dimesylate in College Students with ADHD

    Science.gov (United States)

    DuPaul, George J.; Weyandt, Lisa L.; Rossi, Joseph S.; Vilardo, Brigid A.; O'Dell, Sean M.; Carson, Kristen M.; Verdi, Genevieve; Swentosky, Anthony

    2012-01-01

    Objective: To evaluate stimulant medication on symptoms and functioning for college students with ADHD using double-blind, placebo-controlled, crossover design. Method: Participants included 24 college students with ADHD and 26 college students without psychopathology. Lisdexamfetamine dimesylate (LDX) was examined for ADHD participants over five…

  19. Effect of knee joint icing on knee extension strength and knee pain early after total knee arthroplasty: a randomized cross-over study

    DEFF Research Database (Denmark)

    Holm, Bente; Husted, Henrik; Kehlet, Henrik

    2012-01-01

    Objective: To investigate the acute effect of knee joint icing on knee extension strength and knee pain in patients shortly after total knee arthroplasty.Design: A prospective, single-blinded, randomized, cross-over study.Setting: A fast-track orthopaedic arthroplasty unit at a university hospital...

  20. Lack of Interaction between Sensing-Intuitive Learning Styles and Problem-First versus Information-First Instruction: A Randomized Crossover Trial

    Science.gov (United States)

    Cook, David A.; Thompson, Warren G.; Thomas, Kris G.; Thomas, Matthew R.

    2009-01-01

    Background: Adaptation to learning styles has been proposed to enhance learning. Objective: We hypothesized that learners with sensing learning style would perform better using a problem-first instructional method while intuitive learners would do better using an information-first method. Design: Randomized, controlled, crossover trial. Setting:…

  1. Extensively hydrolysed casein formula supplemented with Lactobacillus rhamnosus GG maintains hypoallergenic status : randomised double-blind, placebo-controlled crossover trial

    NARCIS (Netherlands)

    Muraro, Antonella; Hoekstra, Maarten O.; Meijer, Yolanda; Lifschitz, Carlos; Wampler, Jennifer L.; Harris, Cheryl; Scalabrin, Deolinda M. F.

    2012-01-01

    Objective: To evaluate the hypoallergenicity of an extensively hydrolysed (EH) casein formula supplemented with Lactobacillus rhamnosus GG (LGG). Design: A prospective, randomised, double-blind, placebo-controlled crossover trial. Setting: Two study sites in Italy and The Netherlands. Study particip

  2. In-Country TEFL/Crossover Tropical Agricultural Training Manual. Trainee Edition. Training for Development. Peace Corps Information Collection & Exchange Training Manual No. T-37A.

    Science.gov (United States)

    Franck, Carl R.; And Others

    Correlated to the trainer's manual for the same course, this trainee's manual has been designed for Peace Corps trainees coming to Thailand without stateside agricultural training. Although it was developed for the training of Test of English as a Foreign Language (TEFL)/Crossovers, the majority of sessions are appropriate for other Peace Corps…

  3. Influence of a user-adaptive prosthetic knee on quality of life, balance confidence, and measures of mobility: a randomised cross-over trial

    NARCIS (Netherlands)

    Prinsen, Erik Christiaan; Nederhand, Marcus Johannes; Rietman, Johan Swanik; Koopman, Hubertus F.J.M.

    2015-01-01

    Objective: To study the influence of a transition from a non-microprocessor controlled to the Rheo Knee® II on quality of life, balance confidence and measures of mobility. Design: Randomised crossover trial. Setting: Research department of a rehabilitation centre. Subjects: Persons with a

  4. Double-Blind, Placebo-Controlled, Crossover Study of the Efficacy and Safety of Lisdexamfetamine Dimesylate in College Students with ADHD

    Science.gov (United States)

    DuPaul, George J.; Weyandt, Lisa L.; Rossi, Joseph S.; Vilardo, Brigid A.; O'Dell, Sean M.; Carson, Kristen M.; Verdi, Genevieve; Swentosky, Anthony

    2012-01-01

    Objective: To evaluate stimulant medication on symptoms and functioning for college students with ADHD using double-blind, placebo-controlled, crossover design. Method: Participants included 24 college students with ADHD and 26 college students without psychopathology. Lisdexamfetamine dimesylate (LDX) was examined for ADHD participants over five…

  5. Influence of a user-adaptive prosthetic knee on quality of life, balance confidence, and measures of mobility: a randomised cross-over trial

    NARCIS (Netherlands)

    Prinsen, E.C.; Nederhand, M.J.; Rietman, J.S.; Koopman, H.F.J.M.

    2015-01-01

    Objective: To study the influence of a transition from a non-microprocessor controlled to the Rheo Knee® II on quality of life, balance confidence and measures of mobility. Design: Randomised crossover trial. Setting: Research department of a rehabilitation centre. Subjects: Persons with a tra

  6. Comparison of the Carbon System Parameters at the Global CO2 Survey Crossover Locations in the North and South Pacific Ocean, 1990-1996

    Energy Technology Data Exchange (ETDEWEB)

    Feely, Richard A [NOAA, Pacific Marine Environmental Laboratory (PMEL); Lamb, Marilyn F. [NOAA, Pacific Marine Environmental Laboratory (PMEL); Greeley, Dana J. [NOAA, Pacific Marine Environmental Laboratory (PMEL); Wanninkhof, Rik [NOAA, Atlantic Oceanographic and Meteorological Laboratory (AOML)

    1999-10-01

    As a collaborative program to measure global ocean carbon inventories and provide estimates of the anthropogenic carbon dioxide (C02) uptake by the oceans. the National Oceanic and Atmospheric Administration and the U.S. Department of Energy have sponsored the collection of ocean carbon measurements as part of the World Ocean Circulation Experiment and Ocean-Atmosphere Carbon Exchange Study cruises. The cruises discussed here occurred in the North and South Pacific from 1990 through 1996. The carbon parameters from these 30 crossover locations have been compared to ensure that a consistent global data set emerges from the survey cruises. !'he results indicate that for dissolved inorganic carbon. fugacity of C02• and pH. the a~:,rreements at most crossover locations are well within the design specifications for the global CO) survey: whereas. in the case of total alkaliniry. the agreement between crossover locations is not as close.

  7. Mathematical Interpretation between Genotype and Phenotype Spaces and Induced Geometric Crossovers

    CERN Document Server

    Yoon, Yourim; Moraglio, Alberto; Moon, Byung-Ro

    2009-01-01

    In this paper, we present that genotype-phenotype mapping can be theoretically interpreted using the concept of quotient space in mathematics. Quotient space can be considered as mathematically-defined phenotype space in the evolutionary computation theory. The quotient geometric crossover has the effect of reducing the search space actually searched by geometric crossover, and it introduces problem knowledge in the search by using a distance better tailored to the specific solution interpretation. Quotient geometric crossovers are directly applied to the genotype space but they have the effect of the crossovers performed on phenotype space. We give many example applications of the quotient geometric crossover.

  8. Thermodynamics of ultracold Bose gases at a dimensional crossover

    Science.gov (United States)

    Labouvie, Ralf; Vogler, Andreas; Guarrera, Vera; Ott, Herwig

    2013-05-01

    We have studied the thermodynamics of ultracold Bose gases in the crossover from a three-dimensional to a one-dimensional regime. In our experiment, we use a focused electron-beam to probe in situ atomic density distributions with high temporal and spatial resolution. Starting with a Bose-Einstein-Condensate in a single beam optical dipole trap we can create one-dimensional systems by loading the atoms in a two-dimensional blue-detuned optical lattice. With increasing strength of the lattices we go from a three-dimensional into a one-dimensional system. Furthermore we tune the interaction strengths of the one-dimensional quantum-gases from weak (quasi-condensate) to strong (Tonks-Girardeau). By measuring the density profiles and applying an inverse Abel-Transformation we extract the equation of states of these systems and characterize the crossover from the three-dimensional to the one-dimensional regime.

  9. Dimensionality crossover in critical behaviour of ultrathin ferromagnetic films

    Energy Technology Data Exchange (ETDEWEB)

    Prudnikov, Pavel V., E-mail: prudnikp@univer.omsk.su; Prudnikov, Vladimir V.; Menshikova, Maria A.; Piskunova, Natalia I.

    2015-08-01

    We propose the model which takes account of magnetocrystalline anisotropy effects in thin magnetic films. The dimensionality crossover from two-dimensional monolayer to three-dimensional system in multilayer magnetic films is studied using a Monte Carlo technique. Finite-size scaling is applied for the determination of the critical characteristics as a function of film thickness. The transition to intermediate planar phase is discussed. - Highlights: • We make Monte Carlo simulations in a anisotropy Heisenberg films. • Anisotropy effects lead to dimensionality crossover in Heisenberg films. • The transition to intermediate XY-like phase for 14–19 ML was discovered. • The critical exponents agree with experiments for Ni and Co films.

  10. Tuning the quantum critical crossover in quantum dots

    Science.gov (United States)

    Murthy, Ganpathy

    2005-03-01

    Quantum dots with large Thouless number g embody a regime where both disorder and interactions can be treated nonperturbatively using large-N techniques (with N=g) and quantum phase transitions can be studied. Here we focus on dots where the noninteracting Hamiltonian is drawn from a crossover ensemble between two symmetry classes, where the crossover parameter introduces a new, tunable energy scale independent of and much smaller than the Thouless energy. We show that the quantum critical regime, dominated by collective critical fluctuations, can be accessed at the new energy scale. The nonperturbative physics of this regime can only be described by the large-N approach, as we illustrate with two experimentally relevant examples. G. Murthy, PRB 70, 153304 (2004). G. Murthy, R. Shankar, D. Herman, and H. Mathur, PRB 69, 075321 (2004)

  11. Dynamical Crossover in Complex Networks near the Percolation Transition

    Science.gov (United States)

    Kawasaki, Fumiya; Yakubo, Kousuke

    2011-10-01

    The return probability P0(t) of random walkers is investigated numerically for several scale-free fractal networks. Our results show that P0(t) is proportional to t-ds/2 with the non-integer spectral dimension ds as in the case of non-scale free fractal networks. We also study how the diffusion process is affected by the structural crossover from a fractal to a small-world architecture in a network near the percolation transition. It is elucidated that the corresponding dynamical crossover is scaled only by the unique characteristic time tξ regardless of whether the network is scale free or not. In addition, the scaling relation ds= 2Df/dw is found to be valid even for scale-free fractal networks, where Df and dw are the fractal and the walk dimensions. These results suggest that qualitative properties of P0(t) are irrelevant to the scale-free nature of networks.

  12. Hot Neutron Stars with Hadron-Quark Crossover

    Science.gov (United States)

    Masuda, Kota; Hatsuda, Tetsuo; Takatsuka, Tatsuyuki

    2016-12-01

    The effects of the hadron-quark crossover on the bulk properties of cold and hot neutron stars (NSs) are studied. We suggested a new phenomenological equation of state (EOS), which interpolates the two phases at around 3 times the nuclear matter density (ρ0), and found that the cold NSs with the gravitational mass larger than 2M⊙ can be sustained. This is in sharp contrast to the case of the first-order hadron-quark transition where the quark matter inevitably leads to soft EOS. The interpolated EOS is also generalized to the supernova matter at finite temperature to describe the hot NSs at birth. The hadron-quark crossover is found to decrease the central temperature of the hot NSs under isentropic condition due to the color degrees of freedom.

  13. Guest effect on nanopatterned spin-crossover thin films.

    Science.gov (United States)

    Bartual-Murgui, Carlos; Akou, Amal; Salmon, Lionel; Molnár, Gábor; Thibault, Christophe; Real, Jose Antonio; Bousseksou, Azzedine

    2011-12-02

    Nanopatterned thin films of the metal-organic framework {Fe(bpac)[Pt(CN)4]} (bpac=bis(4-pyridyl)acetylene) are elaborated by the combination of a sequential assembly process and a lithographic method. Raman microspectroscopy is used to probe the temperature dependence of the spin state of the iron(II) ions in the films (40-90 nm in thickness), and reveals an incomplete but cooperative spin transition comparable to that of the bulk material. Adsorption/desorption of pyridine guest molecules is found to have a substantial influence on the spin-crossover properties of the thin layers. This interplay between host-guest and spin-crossover properties in thin films and nanopatterns demonstrates the potential ability of using this kind of material as a microsensor.

  14. Chiral Relaxation Time at the Chiral Crossover of Quantum Chromodynamics

    CERN Document Server

    Ruggieri, M; Chernodub, M

    2016-01-01

    We study microscopic processes responsible for chirality flips in the thermal bath of Quantum Chromodynamics at finite temperature and zero baryon chemical potential. We focus on the temperature range where the crossover from chirally broken phase to quark-gluon plasma takes place, namely $T \\simeq (150, 200)$ MeV. The processes we consider are quark-quark scatterings mediated by collective excitations with the quantum number of pions and $\\sigma$-meson, hence we refer to these processes simply as \\sugg{to} one-pion (one-$\\sigma$) exchange\\sugg{s}. We use a Nambu-Jona-Lasinio model to compute equilibrium properties of the thermal bath, as well as the relevant scattering kernel to be used in the collision integral to estimate the chiral relaxation time $\\tau$. We find $\\tau\\simeq 0.1 \\div 1$ fm/c around the chiral crossover.

  15. Net baryon fluctuations from a crossover equation of state

    Energy Technology Data Exchange (ETDEWEB)

    Kapusta, J.; Albright, M. [University of Minnesota, School of Physics and Astronomy, Minneapolis, MN (United States); Young, C. [Michigan State University, National Superconducting Cyclotron Laboratory, East Lansing, MI (United States)

    2016-08-15

    We have constructed an equation of state which smoothly interpolates between an excluded-volume hadron resonance gas at low energy density to a plasma of quarks and gluons at high energy density. This crossover equation of state agrees very well with lattice calculations at both zero and nonzero baryon chemical potential. We use it to compute the variance, skewness, and kurtosis of fluctuations of baryon number, and compare to measurements of proton number fluctuations in central Au-Au collisions as measured by the STAR Collaboration in a beam energy scan at the Relativistic Heavy-Ion Collider. The crossover equation of state can reproduce the data if the fluctuations are frozen out at temperatures well below than the average chemical freeze-out. (orig.)

  16. Net Baryon Fluctuations from a Crossover Equation of State

    CERN Document Server

    Kapusta, J; Young, C

    2016-01-01

    We have constructed an equation of state which smoothly interpolates between an excluded volume hadron resonance gas at low energy density to a plasma of quarks and gluons at high energy density. This crossover equation of state agrees very well with lattice calculations at both zero and nonzero baryon chemical potential. We use it to compute the variance, skewness, and kurtosis of fluctuations of baryon number, and compare to measurements of proton number fluctuations in central Au-Au collisions as measured by the STAR collaboration in a beam energy scan at the Relativistic Heavy Ion Collider. The crossover equation of state can reproduce the data if the fluctuations are frozen out at temperatures well below than the average chemical freeze-out.

  17. Cascading dynamics on random networks: Crossover in phase transition

    Science.gov (United States)

    Liu, Run-Ran; Wang, Wen-Xu; Lai, Ying-Cheng; Wang, Bing-Hong

    2012-02-01

    In a complex network, random initial attacks or failures can trigger subsequent failures in a cascading manner, which is effectively a phase transition. Recent works have demonstrated that in networks with interdependent links so that the failure of one node causes the immediate failures of all nodes connected to it by such links, both first- and second-order phase transitions can arise. Moreover, there is a crossover between the two types of transitions at a critical system-parameter value. We demonstrate that these phenomena can occur in the more general setting where no interdependent links are present. A heuristic theory is derived to estimate the crossover and phase-transition points, and a remarkable agreement with numerics is obtained.

  18. Strategy Uniform Crossover Adaptation Evolution in a Minority Game

    Institute of Scientific and Technical Information of China (English)

    杨伟松; 汪秉宏; 全宏俊; 胡进锟

    2003-01-01

    We propose a new adaptation minority game for understanding the complex dynamical behaviour characterized by agent interactions competing limited resources in many natural and social systems. Intelligent agents may modify a part of their strategies periodically, depending on the strategyperformances. In the present model, the strategies will be updated according to a uniform-crossover variation process inspired by genetic evolution algorithm in biology. The performances of the agents in our model are calculated for different parameter conditions. It has been found that the new system may evolve via the strategy uniform crossover adaptation mechanism into a frozen equilibrium state in which the performance of the system may reach the best limit, implying the strongest cooperation among agents and the most effective utilization of the social resources.

  19. Viscous fingering near the percolation threshold: Double-crossover phenomena

    Science.gov (United States)

    Nagatani, Takashi; Stanley, H. Eugene

    1991-03-01

    Viscous fingering at a nonzero viscosity ratio on percolating clusters is considered to study morphological changes of patterns formed by the injected fluid in porous media. A fraction P of bonds is filled by the displaced fluid, while the others (1-P) are blocked, where P is the usual percolation probability. Fluid with a low viscosity is injected into the percolating cluster filled by the displaced fluid with high viscosity. Morphological changes of patterns of the injected fluid are described in terms of crossover phenomena by making use of a four-parameter position-space renormalization-group method. It is found that when μI/μD>μI/μD>>(P-Pc) the other double crossover appears from the DLA on an incipient percolation cluster through the invasion percolation to the dense structure, where μI/μD is the viscosity ratio and Pc the critical percolation probability.

  20. Thermodynamic characterization of two novel spin-crossover complexes

    Institute of Scientific and Technical Information of China (English)

    DING Bin; WANG Hongmei; YI Long; CHENG Peng; LI Licun; ZHAI Yuping; LIAO Daizheng; YAN Shiping; JIANG Zonghui

    2003-01-01

    Two novel FeⅡspin crossover complexes [Fe(L1)3](BF4)2·5H2O (1) and [Fe(L2)3](BF4)2·2H2O (2) with 4-NHR-1,2,4-triazole (R = isopropyl, L1; cyclohexyl, L2) were synthesized. 1 and 2 remain white at room temperature, whereas they turn purple at liquid temperature. Variable temperature optical detection and magnetic susceptibilities measurement show that the spin-crossover phenomenon for 1 was observed between 120 K and 170 K. The hysteresis loop is about 10 K. The Tc temperature of 2 is 190 K, but no thermal hysteresis loop was found. The molar thermodynamic functions and the microscopic parameters were obtained from the theoretical analysis in terms of the domain model, two level Ising model and regular solution model, respectively.

  1. An inverted crossover resonance within one Zeeman manifold

    CERN Document Server

    Salter, Liam A

    2016-01-01

    We detect and describe inverted crossover resonances in $\\pi$-driven four-level systems where $\\Delta F$ can be zero. The signal is observed through sub-Doppler frequency modulation spectroscopy of the $(6s^{2})$ $^{1}S_{0}$ $-$ $(6s6p)$ $^{3}P_{1}$ transition in $^{171}$Yb, where the nuclear spin $I=1/2$. The resonance is inherently insensitive to first-order Zeeman shifts. Optical frequency measurements of the $F'=1/2$ hyperfine line recorded over several weeks demonstrate a statistical uncertainty of $2\\times10^{-11}$. The inverted crossover resonance found with the $F'=3/2$ line is used for 556 nm laser frequency stabilization and this light cools $^{171}$Yb atoms in a two-stage magneto-optical trap. We test the atomic cloud temperatures on the frequency instability of the light.

  2. Single-crossover recombination and ancestral recombination trees.

    Science.gov (United States)

    Baake, Ellen; von Wangenheim, Ute

    2014-05-01

    We consider the Wright-Fisher model for a population of [Formula: see text] individuals, each identified with a sequence of a finite number of sites, and single-crossover recombination between them. We trace back the ancestry of single individuals from the present population. In the [Formula: see text] limit without rescaling of parameters or time, this ancestral process is described by a random tree, whose branching events correspond to the splitting of the sequence due to recombination. With the help of a decomposition of the trees into subtrees, we calculate the probabilities of the topologies of the ancestral trees. At the same time, these probabilities lead to a semi-explicit solution of the deterministic single-crossover equation. The latter is a discrete-time dynamical system that emerges from the Wright-Fisher model via a law of large numbers and has been waiting for a solution for many decades.

  3. Reporting of cross-over clinical trials of analgesic treatments for chronic pain: Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks systematic review and recommendations.

    Science.gov (United States)

    Gewandter, Jennifer S; McDermott, Michael P; McKeown, Andrew; Hoang, Kim; Iwan, Katarzyna; Kralovic, Sarah; Rothstein, Daniel; Gilron, Ian; Katz, Nathaniel P; Raja, Srinivasa N; Senn, Stephen; Smith, Shannon M; Turk, Dennis C; Dworkin, Robert H

    2016-11-01

    Cross-over trials are typically more efficient than parallel group trials in that the sample size required to yield a desired power is substantially smaller. It is important, however, to consider some issues specific to cross-over trials when designing and reporting them, and when evaluating the published results of such trials. This systematic review evaluated the quality of reporting and its evolution over time in articles of cross-over clinical trials of pharmacologic treatments for chronic pain published between 1993 and 2013. Seventy-six (61%) articles reported a within-subject primary analysis, or if no primary analysis was identified, reported at least 1 within-subject analysis, which is required to achieve the gain in power associated with the cross-over design. For 39 (31%) articles, it was unclear whether analyses conducted were within-subject or between-group. Only 36 (29%) articles reported a method to accommodate missing data (eg, last observation carried forward, n = 29), and of those, just 14 included subjects in the analysis who provided data from only 1 period. Of the articles that identified a within-subject primary analysis, 21 (51%) provided sufficient information for the results to be included in a meta-analysis (ie, estimates of the within-subject treatment effect and variability). These results and others presented in this article demonstrate deficiencies in reporting of cross-over trials for analgesic treatments. Clearer reporting in future trials could improve readers' ability to critically evaluate the results, use these data in meta-analyses, and plan future trials. Recommendations for proper reporting of cross-over trials that apply to any condition are provided.

  4. Crossover and thermodynamic representation in the extended η model for fractal growth

    Science.gov (United States)

    Nagatani, Takashi; Stanley, H. Eugene

    1990-10-01

    The η model for the dielectric breakdown is extended to the case where double power laws apply. It is shown that a crossover phenomenon between the diffusion-limited aggregation (DLA) fractal and the η fractal occurs in the extended η model. Through the use of the dimensional analysis, a dimensionless parameter is found to govern the crossover. It is shown that when η1 the inverse crossover from the η fractal to the DLA fractal appears. It is also shown that the crossover radius is controlled by changing the applied field. The global flow diagram in the two-parameter space is obtained by using a two-parameter position-space renormalization-group approach. The crossover exponent and the crossover radius are calculated. The crossover phenomenon is described in terms of a thermodynamic representation of the two-phase equilibrium.

  5. The spatial regulation of meiotic recombination hotspots: are all DSB hotspots crossover hotspots?

    Science.gov (United States)

    Serrentino, Maria-Elisabetta; Borde, Valérie

    2012-07-15

    A key step for the success of meiosis is programmed homologous recombination, during which crossovers, or exchange of chromosome arms, take place. Crossovers increase genetic diversity but their main function is to ensure accurate chromosome segregation. Defects in crossover number and position produce aneuploidies that represent the main cause of miscarriages and chromosomal abnormalities such as Down's syndrome. Recombination is initiated by the formation of programmed double strand breaks (DSBs), which occur preferentially at places called DSB hotspots. Among all DSBs generated, only a small fraction is repaired by crossover, the other being repaired by other homologous recombination pathways. Crossover maps have been generated in a number of organisms, defining crossover hotspots. With the availability of genome-wide maps of DSBs as well as the ability to measure genetically the repair outcome at several hotspots, it is becoming more and more clear that not all DSB hotspots behave the same for crossover formation, suggesting that chromosomal features distinguish different types of hotspots.

  6. The frequency crossover for the Goos-Hanchen shift

    OpenAIRE

    Araujo, Manoel; Carvalho, Silvania; De Leo, Stefano

    2014-01-01

    For total reflection, the Goos-Hanchen (GH) shift is proportional to the wavelength of the laser beam. At critical angles, such a shift is instead proportional to the square root of the product of the beam waist and wavelength. By using the stationary phase method (SPM) and, when necessary, numerical calculations, we present a detailed analysis of the frequency crossover for the GH shift. The study, done in different incidence regions, sheds new light on the validity of the analytic formulas ...

  7. Crossover from Nonequilibrium Fractal Growth to Equilibrium Compact Growth

    DEFF Research Database (Denmark)

    Sørensen, Erik Schwartz; Fogedby, Hans C.; Mouritsen, Ole G.

    1988-01-01

    Solidification controlled by vacancy diffusion is studied by Monte Carlo simulations of a two-dimensional Ising model defined by a Hamiltonian which models a thermally driven fluid-solid phase transition. The nonequilibrium morphology of the growing solid is studied as a function of time as the s...... as the system relaxes into equilibrium described by a temperature. At low temperatures the model exhibits fractal growth at early times and crossover to compact solidification as equilibrium is approached....

  8. Hyperon puzzle, hadron-quark crossover and massive neutron stars

    Energy Technology Data Exchange (ETDEWEB)

    Masuda, Kota [The University of Tokyo, Department of Physics, Tokyo (Japan); Nishina Center, RIKEN, Theoretical Research Division, Wako (Japan); Hatsuda, Tetsuo [Nishina Center, RIKEN, Theoretical Research Division, Wako (Japan); The University of Tokyo, Kavli IPMU (WPI), Chiba (Japan); Takatsuka, Tatsuyuki [Nishina Center, RIKEN, Theoretical Research Division, Wako (Japan)

    2016-03-15

    Bulk properties of cold and hot neutron stars are studied on the basis of the hadron-quark crossover picture where a smooth transition from the hadronic phase to the quark phase takes place at finite baryon density. By using a phenomenological equation of state (EOS) ''CRover'', which interpolates the two phases at around 3 times the nuclear matter density (ρ{sub 0}), it is found that the cold NSs with the gravitational mass larger than 2M {sub CircleDot} can be sustained. This is in sharp contrast to the case of the first-order hadron-quark transition. The radii of the cold NSs with the CRover EOS are in the narrow range (12.5 ± 0.5) km which is insensitive to the NS masses. Due to the stiffening of the EOS induced by the hadron-quark crossover, the central density of the NSs is at most 4 ρ{sub 0} and the hyperon-mixing barely occurs inside the NS core. This constitutes a solution of the long-standing hyperon puzzle. The effect of color superconductivity (CSC) on the NS structures is also examined with the hadron-quark crossover. For the typical strength of the diquark attraction, a slight softening of the EOS due to two-flavor CSC (2SC) takes place and the maximum mass is reduced by about 0.2M {sub CircleDot}. The CRover EOS is generalized to the supernova matter at finite temperature to describe the hot NSs at birth. The hadron-quark crossover is found to decrease the central temperature of the hot NSs under isentropic condition. The gravitational energy release and the spin-up rate during the contraction from the hot NS to the cold NS are also estimated. (orig.)

  9. Ternary and senary representations using DNA double-crossover tiles

    CERN Document Server

    Kim, Byeonghoon; Son, Junyoung; Kim, Junghoon; Hwang, Si Un; Dugasani, Sreekantha Reddy; Kim, Min Hyeok; Kim, Byung-Dong; Chang, Iksoo; Liu, Wing Kam; Kim, Moon Ki; Park, Sung Ha

    2016-01-01

    The information capacity of double-crossover (DX) tiles was successfully increased beyond a binary representation to higher base representations. By controlling the length and the position of DNA hairpins on the DX tile, ternary and senary (base-3 and base-6) digit representations were realized and verified by atomic force microscopy (AFM). Also, normal mode analysis (NMA) was carried out to study the mechanical characteristics of each structure.

  10. Surface and Size Effects in Spin-Crossover Nanocrystals

    Science.gov (United States)

    Gudyma, Iurii; Ivashko, Victor; Bobák, Andrej

    2017-02-01

    We perform Monte Carlo simulations to analyze the surface and size effects in spin-crossover nanocrystals using an Ising-like model including surface and core intermolecular interactions. The consequences of downsizing effect on the transition temperature and the width of hysteresis as finger of the system cooperativity are discussed. The critical temperature is calculated using the real-space renormalization method. The obtained results are in agreement with the experimental data.

  11. Light slowdown in the vicinity of cross-over resonances

    CERN Document Server

    Perdian, M; Zaremba, J; Zielinska-Kaniasty, S

    2004-01-01

    Pulse propagation is considered in an inhomogeneously broadened medium of three-level atoms in a V-configuration, dressed by a counter-propagating pump pulse. A significant signal slowdown is demonstrated in this of the three frequency windows of a reduced absorption and a steep normal dispersion, which is due to a cross-over resonance. Particular properties of the group index in the vicinity of such a resonance are demonstrated in the case of closely spaced upper levels.

  12. Optimized Crossover Genetic Algorithm for Vehicle Routing Problem with Time Windows

    Directory of Open Access Journals (Sweden)

    H. Nazif

    2010-01-01

    Full Text Available Problem statement: In this study, we considered the application of a genetic algorithm to vehicle routing problem with time windows where a set of vehicles with limits on capacity and travel time are available to service a set of customers with demands and earliest and latest time for serving. The objective is to find routes for the vehicles to service all the customers at a minimal cost without violating the capacity and travel time constraints of the vehicles and the time window constraints set by the customers. Approach: We proposed a genetic algorithm using an optimized crossover operator designed by a complete undirected bipartite graph that finds an optimal set of delivery routes satisfying the requirements and giving minimal total cost. Various techniques have also been introduced into the proposed algorithm to further enhance the solutions quality. Results: We tested our algorithm with benchmark instances and compared it with some other heuristics in the literature. The results showed that the proposed algorithm is competitive in terms of the quality of the solutions found. Conclusion/Recommendations: This study presented a genetic algorithm for solving vehicle routing problem with time windows using an optimized crossover operator. From the results, it can be concluded that the proposed algorithm is competitive when compared with other heuristics in the literature.

  13. A semi-parametric approach to the frequency of occurrence under a simple crossover trial.

    Science.gov (United States)

    Lui, Kung-Jong; Chang, Kuang-Chao

    2016-02-01

    To analyze the frequency of occurrence for an event of interest in a crossover design, we propose a semi-parametric approach. We develop two point estimators and four interval estimators in closed forms for the treatment effect under a random effects multiplicative risk model. Using Monte Carlo simulations, we evaluate these estimators and compare the four interval estimators with the classical interval estimator suggested elsewhere in a variety of situations. We note that the point estimator using the ratio of two arithmetic averages of mean frequencies under a multiplicative risk model can be comparable to the point estimator using the ratio of two geometric averages of mean frequencies. We note that as long as the number of patients per group is large, all the four interval estimators developed here can perform well. We also note that the classical interval estimator derived under the commonly assumed Poisson distribution for the frequency data can be conservative and lose precision if the Poisson distribution assumption is violated. We use a double-blind randomized crossover trial comparing salmeterol with a placebo in exacerbations of asthma to illustrate the practical use of these estimators. © The Author(s) 2012.

  14. Master crossover functions for one-component fluids.

    Science.gov (United States)

    Garrabos, Yves; Lecoutre, Carole; Palencia, Fabien; Le Neindre, Bernard; Erkey, Can

    2008-02-01

    By introducing three well-defined dimensionless numbers, we establish the link between the scale dilatation method able to estimate master (i.e., unique) singular behaviors of the one-component fluid subclass and the universal crossover functions recently estimated [Garrabos and Bervillier, Phys. Rev. E 74, 021113 (2006)] from the bounded results of the massive renormalization scheme applied to the Phi(d)(4)(n) model of scalar order parameter (n=1) and three dimensions (d=3), representative of the Ising-like universality class. The master (i.e., rescaled) crossover functions are then able to fit the singular behaviors of any one-component fluid without adjustable parameter, using only one critical energy scale factor, one critical length scale factor, and two dimensionless asymptotic scale factors, which characterize the fluid critical interaction cell at its liquid-gas critical point. An additional adjustable parameter accounts for quantum effects in light fluids at the critical temperature. The effective extension of the thermal field range along the critical isochore where the master crossover functions seems to be valid corresponds to a correlation length greater than three times the effective range of the microscopic short-range molecular interaction.

  15. The sphaleron rate through the electroweak cross-over

    DEFF Research Database (Denmark)

    D'Onofrio, Michela; Rummukainen, Kari; Tranberg, Anders

    2012-01-01

    Using lattice simulations, we measure the sphaleron rate in the Standard Model as a function of temperature through the electroweak cross-over, for the Higgs masses m(H) = 115 and m(H) = 160GeV. We pay special attention to the shutting off of the baryon rate as the temperature is lowered. This qu......Using lattice simulations, we measure the sphaleron rate in the Standard Model as a function of temperature through the electroweak cross-over, for the Higgs masses m(H) = 115 and m(H) = 160GeV. We pay special attention to the shutting off of the baryon rate as the temperature is lowered....... This quantity enters computations of Baryogenesis via Leptogenesis, where non-zero lepton number is converted into non-zero baryon number by equilibrium sphaleron transitions. Combining existing numerical methods applicable in the symmetric and broken electroweak phases, we find the temperature dependence...... of the sphaleron rate at very high temperature, through the electroweak cross-over transition, and deep into the broken phase....

  16. Design

    DEFF Research Database (Denmark)

    Volf, Mette

    This publication is unique in its demystification and operationalization of the complex and elusive nature of the design process. The publication portrays the designer’s daily work and the creative process, which the designer is a part of. Apart from displaying the designer’s work methods...... and design parameters, the publication shows examples from renowned Danish design firms. Through these examples the reader gets an insight into the designer’s reality....

  17. Pharmacodynamic differences between canagliflozin and dapagliflozin: results of a randomized, double-blind, crossover study.

    Science.gov (United States)

    Sha, S; Polidori, D; Farrell, K; Ghosh, A; Natarajan, J; Vaccaro, N; Pinheiro, J; Rothenberg, P; Plum-Mörschel, L

    2015-02-01

    To compare the pharmacodynamic effects of the highest approved doses of the sodium glucose co-transporter 2 (SGLT2) inhibitors canagliflozin and dapagliflozin on urinary glucose excretion (UGE), renal threshold for glucose excretion (RTG ) and postprandial plasma glucose (PPG) excursion in healthy participants in a randomized, double-blind, two-period crossover study. In each treatment period, participants (n = 54) received canagliflozin 300 mg or dapagliflozin 10 mg for 4 days (20 min before breakfast). A mixed-meal tolerance test (600 kcal; 75 g glucose) was performed at baseline and on day 4 of each treatment period to assess changes in incremental PPG (PPGΔAUC0-2 h ). We measured 24-h UGE and plasma glucose on day 4 to determine 24-h mean RTG . Canagliflozin 300 mg and dapagliflozin 10 mg had similar effects on UGE and RTG for 4 h after dosing, but canagliflozin was associated with higher UGE and greater RTG reductions for the remainder of the day. Mean 24-h UGE was ∼25% higher with canagliflozin than with dapagliflozin (51.4 vs. 40.8 g), and 24-h mean RTG was ∼0.4 mmol/l (7 mg/dl) lower with canagliflozin than with dapagliflozin (3.79 vs. 4.17 mmol/l; p canagliflozin delayed and reduced PPG excursion (between-treatment difference in PPGΔAUC0-2 h from baseline expressed as a percentage of baseline mean, -10.2%; p = 0.0122). Canagliflozin and dapagliflozin were generally well tolerated. In healthy participants, canagliflozin 300 mg provided greater 24-h UGE, a lower RTG and smaller PPG excursions than dapagliflozin 10 mg. © 2014 The Authors. Diabetes, Obesity and Metabolism published by JohnWiley & Sons Ltd.

  18. Intravenous immunoglobulin for hypogammaglobulinemia after lung transplantation: a randomized crossover trial.

    Directory of Open Access Journals (Sweden)

    David J Lederer

    Full Text Available BACKGROUND: We aimed to determine the effects of treatment with intravenous immunoglobulin on bacterial infections in patients with hypogammaglobulinemia (HGG after lung transplantation. METHODS: We performed a randomized, double-blind, placebo-controlled two-period crossover trial of immune globulin intravenous (IVIG, 10% Purified (Gamunex, Bayer, Elkhart, IN monthly in eleven adults who had undergone lung transplantation more than three months previously. We randomized study participants to three doses of IVIG (or 0.1% albumin solution (placebo given four weeks apart followed by a twelve week washout and then three doses of placebo (or IVIG. The primary outcome was the number of bacterial infections within each treatment period. RESULTS: IVIG had no effect on the number of bacterial infections during the treatment period (3 during IVIG and 1 during placebo; odds ratio 3.5, 95% confidence interval 0.4 to 27.6, p = 0.24. There were no effects on other infections, use of antibiotics, or lung function. IVIG significantly increased trough IgG levels at all time points (least square means, 765.3 mg/dl during IVIG and 486.3 mg/dl during placebo, p<0.001. Four serious adverse events (resulting in hospitalization occurred during the treatment periods (3 during active treatment and 1 during the placebo period, p = 0.37. Chills, flushing, and nausea occurred during one infusion of IVIG. CONCLUSIONS: Treatment with IVIG did not reduce the short-term risk of bacterial infection in patients with HGG after lung transplantation. The clinical efficacy of immunoglobulin supplementation in HGG related to lung transplantation over the long term or with recurrent infections is unknown. TRIAL REGISTRATION: Clinicaltrials.gov NCT00115778.

  19. Expiratory Positive Airway Pressure for Sleep Apnea after Stroke: A Randomized, Crossover Trial.

    Science.gov (United States)

    Wheeler, Natalie C; Wing, Jeffrey J; O'Brien, Louise M; Hughes, Rebecca; Jacobs, Teresa; Claflin, Edward; Chervin, Ronald D; Brown, Devin L

    2016-09-15

    Obstructive sleep apnea (OSA) is common after stroke and predicts poor outcomes. Continuous positive airway pressure (CPAP) treats OSA but is generally poorly tolerated by stroke patients. We assessed whether nasal expiratory positive airway pressure (EPAP), an alternative to CPAP, may be an effective option after acute stroke. We conducted a randomized, controlled, two-period crossover study in which each acute ischemic stroke patient received 1 night of EPAP and 1 night without EPAP while OSA was monitored with a validated device, the Watch-PAT 200. Linear repeated- measures analyses were conducted. Sample size calculations indicated that 18 subjects would be required to detect a 10-point or larger average reduction in the apnea-hypopnea index (AHI, the primary outcome), with use of EPAP, with power ≥ 80% and α = 0.05. Among the 19 subjects who completed the protocol, nasal EPAP treatment was associated with a nonsignificant absolute difference in AHI of -5.73 events/h in the primary analysis (p = 0.183, 95% confidence interval -14.4, 2.97) and a nonsignificant absolute difference in AHI of -5.43 events/h in the subgroup of patients who used nasal EPAP for ≥ 3 h (p = 0.314, 95% confidence interval -16.6, 5.76). This study suggests that EPAP is not an effective alternative to CPAP in acute stroke patients with OSA. Further work is needed to identify other more effective alternatives. ClinicalTrials.gov, ID: NCT01703663. © 2016 American Academy of Sleep Medicine.

  20. Crossover between cooper-pair condensation and Bose condensation. Kupa tsui gyoshuku to Bose gyoshuku no crossover

    Energy Technology Data Exchange (ETDEWEB)

    Miyake, K. (Osaka Univ., Osaka (Japan). Faculty of Engineering and Science)

    1992-06-05

    When the effective attractions acting among electrons are strengthened gradually, the superconducting state at low temperature is thought to cross over from Cooper pairs condensation to the state of dielectronic compound boson Bose condensation. Firstly, the ground state is discussed. Nozieres {ampersand} Schmitt-Rink (NSR) have proposed a framework for discussion of transition temperature crossover by introducing the effect of pair fluctuation having finite moment. T {sub c} can be expressed by BCS expression for weak coupling, and by ideal Bose gas transition temperature expression for strong coupling. For the middle of the two extremity limits, NSR obtain numerical solution for a three dimensional case to show the transition temperature and smooth transition of chemical potential at the temperature. Namely, the NSR theory seems to be able to express the crossover of the transition temperature consistently. It has, however, difficulty in the application to two dimensional problems. 14 refs., 3 figs.

  1. Controlling fuel crossover and hydration in ultrathin proton exchange membrane-based fuel cells using Pt-nanosheet catalysts

    DEFF Research Database (Denmark)

    Wang, Rujie; Zhang, Wenjing (Angela); He, Gaohong

    2014-01-01

    An ultra-thin proton exchange membrane with Pt-nanosheet catalysts was designed for a self-humidifying fuel cell running on H2 and O2. In this design, an ultra-thin Nafion membrane was used to reduce ohmic resistance. Pt nanocatalysts were uniformly anchored on exfoliated, layered double hydroxide...... (LDH) nanosheets by chemical vapor deposition. After embedding Pt-LDH nanocatalysts in 9 mm-thick Nafion membranes, exfoliated LDH nanosheets effectively captured crossovered H2 and O2 through the membranes. Meanwhile, Pt nanocatalysts on LDH nanosheets catalyzed reactions between captured H2 and O2...

  2. Model-based analyses of bioequivalence crossover trials using the stochastic approximation expectation maximisation algorithm.

    Science.gov (United States)

    Dubois, Anne; Lavielle, Marc; Gsteiger, Sandro; Pigeolet, Etienne; Mentré, France

    2011-09-20

    In this work, we develop a bioequivalence analysis using nonlinear mixed effects models (NLMEM) that mimics the standard noncompartmental analysis (NCA). We estimate NLMEM parameters, including between-subject and within-subject variability and treatment, period and sequence effects. We explain how to perform a Wald test on a secondary parameter, and we propose an extension of the likelihood ratio test for bioequivalence. We compare these NLMEM-based bioequivalence tests with standard NCA-based tests. We evaluate by simulation the NCA and NLMEM estimates and the type I error of the bioequivalence tests. For NLMEM, we use the stochastic approximation expectation maximisation (SAEM) algorithm implemented in monolix. We simulate crossover trials under H(0) using different numbers of subjects and of samples per subject. We simulate with different settings for between-subject and within-subject variability and for the residual error variance. The simulation study illustrates the accuracy of NLMEM-based geometric means estimated with the SAEM algorithm, whereas the NCA estimates are biased for sparse design. NCA-based bioequivalence tests show good type I error except for high variability. For a rich design, type I errors of NLMEM-based bioequivalence tests (Wald test and likelihood ratio test) do not differ from the nominal level of 5%. Type I errors are inflated for sparse design. We apply the bioequivalence Wald test based on NCA and NLMEM estimates to a three-way crossover trial, showing that Omnitrope®; (Sandoz GmbH, Kundl, Austria) powder and solution are bioequivalent to Genotropin®; (Pfizer Pharma GmbH, Karlsruhe, Germany). NLMEM-based bioequivalence tests are an alternative to standard NCA-based tests. However, caution is needed for small sample size and highly variable drug.

  3. Retention of laryngoscopy skills in medical students: a randomised, cross-over study of the Macintosh, A.P. Advance(™) , C-MAC(®) and Airtraq(®) laryngoscopes.

    Science.gov (United States)

    Hunter, I; Ramanathan, V; Balasubramanian, P; Evans, D A; Hardman, J G; McCahon, R A

    2016-10-01

    In addition to being effective and easy to learn how to use, the ideal laryngoscope should be associated with minimal reduction in skill performance during gaps in practice over time. We compared the time taken to intubate the trachea of a manikin by novice medical students immediately after training, and then after 1 month, with no intervening practice. We designed a two-period, four-group, randomised, cross-over trial to compare the Macintosh, Venner(™) A.P. Advance(™) with difficult airway blade, C-MAC(®) with D-Blade and Airtraq(®) with wireless video-viewer. A bougie was used to aid intubation with the Macintosh and the C-MAC. After training, there was no significant difference in median (IQR [range]) intubation time using the videolaryngoscopes compared with the Macintosh, which took 30 (26.5-35 [12-118])s. One month later, the intubation time was longer using the C-MAC (41 (29.5-52 [20-119])s; p = 0.002) and A.P. Advance (40 (28.5-57.5 [21-107])s; p = 0.0003)m compared with the Macintosh (27 (21-29 [16-90])s); there was no difference using the Airtraq (27 (20.5-32.5 [15-94])s; p = 0.258) compared with the Macintosh. While skill acquisition after a brief period of learning and practice was equal for each laryngoscope, performance levels differed after 1 month without practice. In particular, the consistency of performance using the C-MAC and A.P. Advance was worse compared with the Macintosh and the Airtraq. While the clinical significance of this is doubtful, we believe that reliable and consistent performance at laryngoscopy is desirable; for the devices that we tested, this requires regular practice.

  4. Fine-Scale Crossover Rate Variation on the Caenorhabditis elegans X Chromosome

    Science.gov (United States)

    Bernstein, Max R.; Rockman, Matthew V.

    2016-01-01

    Meiotic recombination creates genotypic diversity within species. Recombination rates vary substantially across taxa, and the distribution of crossovers can differ significantly among populations and between sexes. Crossover locations within species have been found to vary by chromosome and by position within chromosomes, where most crossover events occur in small regions known as recombination hotspots. However, several species appear to lack hotspots despite significant crossover heterogeneity. The nematode Caenorhabditis elegans was previously found to have the least fine-scale variation in crossover distribution among organisms studied to date. It is unclear whether this pattern extends to the X chromosome given its unique compaction through the pachytene stage of meiotic prophase in hermaphrodites. We generated 798 recombinant nested near-isogenic lines (NILs) with crossovers in a 1.41 Mb region on the left arm of the X chromosome to determine if its recombination landscape is similar to that of the autosomes. We find that the fine-scale variation in crossover rate is lower than that of other model species, and is inconsistent with hotspots. The relationship of genomic features to crossover rate is dependent on scale, with GC content, histone modifications, and nucleosome occupancy being negatively associated with crossovers. We also find that the abundances of 4- to 6-bp DNA motifs significantly explain crossover density. These results are consistent with recombination occurring at unevenly distributed sites of open chromatin. PMID:27172189

  5. Imperfect targeted advertising with two-period competition%不完美定向广告的两阶段竞争模型

    Institute of Scientific and Technical Information of China (English)

    邹翔; 仲伟俊; 梅姝娥

    2014-01-01

    A two-period model is developed to investigate the competitive effects of targeted advertising with imperfect targeting in a duopolistic market.In the first period two firms compete in price in order to recognize customers. In the second period targeted advertising plays an informative role and acts as a price discrimination device.The firms’optimal advertising and pricing strategies under imperfect targeting are compared with those under perfect targeting. Equilibrium decisions show that under imperfect targeting when the advertising cost is low enough both firms will choose to target ads at the rivals’old segments.This equilibrium which could not exist under perfect targeting results in two opposite results.When cost is high the effect of mis-targeting will soften price competition and increase profits on the contrary when cost is low enough it will lead to aggressive price competition and profit loss with the increase of imperfect targeting so firms may have incentives to reduce the mis-targeting degree.%研究了双寡头市场条件下,基于不完美定向的定向广告竞争模型。通过两阶段博弈来描述新产品或升级产品引入时不完美定向对企业广告及定价决策带来的影响。第一阶段通过价格竞争辨识消费者,第二阶段广告作为传递产品信息和价格歧视的工具。比较分析不完美定向与完美定向情况下企业的广告和定价策略,均衡结果显示:在不完美定向条件下,当广告成本足够低时,会出现在完美定向情境下不可能出现的均衡,即两企业均会选择向对方的优势市场投入广告。这一均衡的存在会导致2种相反的结果:当广告成本较高时,不完美定向能缓和价格竞争并增加企业利润;但当广告成本足够低时,随着不完美定向程度的增加,反而会加剧市场竞争并导致企业利润损失,因此,企业有动机降低定向误差的程度。

  6. No Improved Performance With Repeated-Sprint Training in Hypoxia Versus Normoxia: A Double-Blind and Crossover Study.

    Science.gov (United States)

    Montero, David; Lundby, Carsten

    2017-02-01

    Few recent studies indicate that short-term repeated-sprint (RS) training in hypoxia (RSH) improves RS performance compared with identical training under normoxic conditions (RSN) in endurance-trained subjects. To determine the effects of RSH against RSN on RS performance under normoxic and moderate hypoxic conditions, using a randomized, doubleblind, crossover experimental design. Fifteen endurance-trained male subjects (age 25 ± 4 y) performed 4 wk of RS training (3 sessions/wk) in normobaric hypoxia (RSH, FiO2 = 13.8%) and normoxia (RSN, FiO2 = 20.9%) in a crossover manner. Before and after completion of training, RS tests were performed on a cycle ergometer with no prior exercise (RSNE), after an incremental exercise test (RSIE), and after a time-trial test (RSTT) in normoxia and hypoxia. Peak power outputs at the incremental exercise test and time-trial performance were unaltered by RSH in normoxia and hypoxia. RS performance was generally enhanced by RSH, as well as RSN, but there were no additional effects of RSH over RSN on peak and mean sprint power output and the number of repeated sprints performed in the RSNE, RSIE, and RSTT trials under normoxic and hypoxic conditions. The present double-blind crossover study indicates that RSH does not improve RS performance compared with RSN in normoxic and hypoxic conditions in endurance-trained subjects. Therefore, caution should be exercised when proposing RSH as an advantageous method to improve exercise performance.

  7. Modelling and experimental studies on a direct methanol fuel cell working under low methanol crossover and high methanol concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, V.B.; Pinto, A.M.F.R. [Centro de Estudos de Fenomenos de Transporte, Departamento de Eng. Quimica, Faculdade de Engenharia da Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto (Portugal); Rangel, C.M. [Instituto Nacional de Energia e Geologia, Fuel Cells and Hydrogen, Estrada do Paco do Lumiar, 1649-038 Lisboa (Portugal)

    2009-08-15

    A number of issues need to be resolved before DMFC can be commercially viable such as the methanol crossover and water crossover which must be minimised in portable DMFCs. The main gain of this work is to systematically vary commercial MEA materials and check their influence on the cell performance of a direct methanol fuel cell operating at close to room temperature. A detailed experimental study on the performance of an <> developed DMFC with 25 cm{sup 2} of active membrane area, working near the ambient conditions is described. Tailored MEAs (membrane-electrode assemblies), with different structures and combinations of gas diffusion layers (GDLs), were designed and tested in order to select optimal working conditions at high methanol concentration levels without sacrificing performance. The experimental polarization and power density curves were successfully compared with the predictions of a steady state, one-dimensional model accounting for coupled heat and mass transfer, along with the electrochemical reactions occurring in the DMFC recently developed by the same authors. The influence of the anode gas diffusion layer media, the membrane thickness and the MEA properties on the cell performance are explained under the light of the predicted methanol crossover rate across the membrane. A tailored MEA build-up with the common available commercial materials was proposed to achieve relatively low methanol crossover, operating at high methanol concentrations. The use of adequate materials for the gas diffusion layers (carbon paper at the anode GDL and carbon cloth at the cathode GDL) enables the use of thinner membranes enhancing the water back diffusion which is essential to work at high methanol concentrations. (author)

  8. Counter-regulatory hormone responses to spontaneous hypoglycaemia during treatment with insulin Aspart or human soluble insulin. A double-blinded randomised cross-over study

    DEFF Research Database (Denmark)

    Brock-Jacobsen, Iben; Vind, B F; Korsholm, L

    2011-01-01

    as compared with more blunted insulin peaks using human soluble insulin. Conclusion: Although insulin Aspart treatment was associated with clear postprandial insulin peaks, no improvement in glycaemic control was obtained and no difference in the hypoglycaemic frequency was observed. However, insulin Aspart......To compare insulin Aspart and human insulin with respect to glycaemic control, hypoglycaemic frequency and counter-regulatory responses to spontaneous hypoglycaemia. Methods: Glycaemic control, hypoglycaemic frequency, p-insulin concentrations, insulin dosages and patients’ satisfaction were...... examined in a randomized, double-blinded cross-over study for two periods of 8 weeks. Sixteen patients with type 1 diabetes were subjected to three daily injections of human soluble insulin or Aspart in addition to Neutral Protamine Hagedorn (NPH) insulin twice daily. Each intervention period was followed...

  9. Hysteretic Four-Step Spin Crossover within a Three-Dimensional Porous Hofmann-like Material

    Energy Technology Data Exchange (ETDEWEB)

    Clements, John E.; Price, Jason R.; Neville, Suzanne M.; Kepert, Cameron J. (Sydney); (Aust. Synch.)

    2016-10-21

    Materials that display multiple stepped spin crossover (SCO) transitions with accompanying hysteresis present the opportunity for ternary, quaternary, and quinary electronic switching and data storage but are rare in existence. Herein, we present the first report of a four-step hysteretic SCO framework. Single-crystal structure analysis of a porous 3D Hofmann-like material showed long-range ordering of spin states: HS, HS0.67LS0.33, HS0.5LS0.5, HS0.33LS0.67, and LS. These detailed structural studies provide insight into how multistep SCO materials can be rationally designed through control of host–host and host–guest interactions.

  10. A Crossover from High Stiffness to High Hardness: The Case of Osmium and Its Borides

    Science.gov (United States)

    Bian, Yongming; Liu, Xiaomei; Li, Anhu; Liang, Yongcheng

    2016-09-01

    Transition-metal light-element compounds are currently raising great expectations for hard and superhard materials. Using the widely attracting osmium (Os) and its borides (OsB, Os2B3 and OsB2) as prototypes, we demonstrate by first-principles calculations that heavy transition metals, which possess high stiffness but low hardness, can be converted into highly hard materials by incorporating of light elements to form compounds. Such a crossover is a manifestation that the underlying sources of high stiffness and high hardness are fundamentally different. The stiffness is related to elastic deformation that is closely associated with valence electron density, whereas the hardness depends strongly on plastic deformation that is determined by bonding nature. Therefore, the incorporation of light atoms into transition metal should be a valid pathway of designing hard and superhard materials. This strategy is in principle also applicable to other transition-metal borides, carbides, and nitrides.

  11. Randomized placebo-controlled crossover trial of tadalafil in Raynaud's phenomenon secondary to systemic sclerosis.

    Science.gov (United States)

    Schiopu, Elena; Hsu, Vivien M; Impens, Ann J; Rothman, Jennifer A; McCloskey, Deborah A; Wilson, Julianne E; Phillips, Kristine; Seibold, James R

    2009-10-01

    Raynaud's phenomenon (RP) is an important clinical feature of systemic sclerosis (SSc) for which consistently effective therapies are lacking. The study was designed to assess the safety, tolerability, and efficacy of tadalafil, a selective, long acting type V cyclic GMP phosphodiesterase (PDE-5) inhibitor, in this clinical syndrome. We performed a prospective, randomized, double-blind, placebo-controlled, crossover study comparing oral tadalafil at a fixed dose of 20 mg daily for a period of 4 weeks versus placebo in women with RP secondary to SSc. Thirty-nine subjects completed the study and were evaluable. There were no statistically significant differences in Raynaud Condition Score (RCS), frequency of RP episodes, or duration of RP episodes between treatment groups. Placebo response was a confounding factor. Tadalafil was well tolerated. Tadalafil appears to be safe and well tolerated but lacks efficacy in comparison to placebo as a treatment for RP secondary to SSc.

  12. Single water entropy: hydrophobic crossover and application to drug binding.

    Science.gov (United States)

    Sasikala, Wilbee D; Mukherjee, Arnab

    2014-09-11

    Entropy of water plays an important role in both chemical and biological processes e.g. hydrophobic effect, molecular recognition etc. Here we use a new approach to calculate translational and rotational entropy of the individual water molecules around different hydrophobic and charged solutes. We show that for small hydrophobic solutes, the translational and rotational entropies of each water molecule increase as a function of its distance from the solute reaching finally to a constant bulk value. As the size of the solute increases (0.746 nm), the behavior of the translational entropy is opposite; water molecules closest to the solute have higher entropy that reduces with distance from the solute. This indicates that there is a crossover in translational entropy of water molecules around hydrophobic solutes from negative to positive values as the size of the solute is increased. Rotational entropy of water molecules around hydrophobic solutes for all sizes increases with distance from the solute, indicating the absence of crossover in rotational entropy. This makes the crossover in total entropy (translation + rotation) of water molecule happen at much larger size (>1.5 nm) for hydrophobic solutes. Translational entropy of single water molecule scales logarithmically (Str(QH) = C + kB ln V), with the volume V obtained from the ellipsoid of inertia. We further discuss the origin of higher entropy of water around water and show the possibility of recovering the entropy loss of some hypothetical solutes. The results obtained are helpful to understand water entropy behavior around various hydrophobic and charged environments within biomolecules. Finally, we show how our approach can be used to calculate the entropy of the individual water molecules in a protein cavity that may be replaced during ligand binding.

  13. Towards Analyzing Crossover Operators in Evolutionary Search via General Markov Chain Switching Theorem

    CERN Document Server

    Yu, Yang; Zhou, Zhi-Hua

    2011-01-01

    Evolutionary algorithms (EAs), simulating the evolution process of natural species, are used to solve optimization problems. Crossover (also called recombination), originated from simulating the chromosome exchange phenomena in zoogamy reproduction, is widely employed in EAs to generate offspring solutions, of which the effectiveness has been examined empirically in applications. However, due to the irregularity of crossover operators and the complicated interactions to mutation, crossover operators are hard to analyze and thus have few theoretical results. Therefore, analyzing crossover not only helps in understanding EAs, but also helps in developing novel techniques for analyzing sophisticated metaheuristic algorithms. In this paper, we derive the General Markov Chain Switching Theorem (GMCST) to facilitate theoretical studies of crossover-enabled EAs. The theorem allows us to analyze the running time of a sophisticated EA from an easy-to-analyze EA. Using this tool, we analyze EAs with several crossover o...

  14. Crossover between tetrahedral and hexagonal structures in liquid water

    Energy Technology Data Exchange (ETDEWEB)

    Chara, Osvaldo [Instituto de Fisica de Liquidos y Sistemas Biologicos (IFLYSIB), CONICET - Universidad Nacional de La Plata (Argentina); McCarthy, Andres N., E-mail: amccarthy@iflysib.unlp.edu.a [Instituto de Fisica de Liquidos y Sistemas Biologicos (IFLYSIB), CONICET - Universidad Nacional de La Plata (Argentina); Grigera, J. Raul [Instituto de Fisica de Liquidos y Sistemas Biologicos (IFLYSIB), CONICET - Universidad Nacional de La Plata (Argentina)

    2011-01-17

    It is widely accepted that liquid water structure is comprised of two closely interweaved components; i.e. tetrahedral (low density) and hexagonal (high density) structures. The relative amount of these components is temperature and pressure dependent. We propose an order parameter, based on the radial distribution function, that quantifies the relative structural composition at any defined temperature and pressure, thus establishing the crossover point in structural dominance. At 300 K this point lies close to 2 kbar, pressure at which water looses most of its 'anomalous' properties.

  15. Goldstone and Higgs Hydrodynamics in the BCS–BEC Crossover

    Directory of Open Access Journals (Sweden)

    Luca Salasnich

    2017-06-01

    Full Text Available We discuss the derivation of a low-energy effective field theory of phase (Goldstone and amplitude (Higgs modes of the pairing field from a microscopic theory of attractive fermions. The coupled equations for Goldstone and Higgs fields are critically analyzed in the Bardeen–Cooper–Schrieffer (BCS-to-Bose–Einstein condensate (BEC crossover—both in three spatial dimensions and in two spatial dimensions. The crucial role of pair fluctuations is investigated, and the beyond-mean-field Gaussian theory of the BCS–BEC crossover is compared with available experimental data of the two-dimensional ultracold Fermi superfluid.

  16. The frequency crossover for the Goos-Hanchen shift

    CERN Document Server

    Araujo, Manoel; De Leo, Stefano

    2014-01-01

    For total reflection, the Goos-Hanchen (GH) shift is proportional to the wavelength of the laser beam. At critical angles, such a shift is instead proportional to the square root of the product of the beam waist and wavelength. By using the stationary phase method (SPM) and, when necessary, numerical calculations, we present a detailed analysis of the frequency crossover for the GH shift. The study, done in different incidence regions, sheds new light on the validity of the analytic formulas found in literature.

  17. High-Resolution Mapping of Crossover and Non-crossover Recombination Events by Whole-Genome Re-sequencing of an Avian Pedigree.

    Directory of Open Access Journals (Sweden)

    Linnéa Smeds

    2016-05-01

    Full Text Available Recombination is an engine of genetic diversity and therefore constitutes a key process in evolutionary biology and genetics. While the outcome of crossover recombination can readily be detected as shuffled alleles by following the inheritance of markers in pedigreed families, the more precise location of both crossover and non-crossover recombination events has been difficult to pinpoint. As a consequence, we lack a detailed portrait of the recombination landscape for most organisms and knowledge on how this landscape impacts on sequence evolution at a local scale. To localize recombination events with high resolution in an avian system, we performed whole-genome re-sequencing at high coverage of a complete three-generation collared flycatcher pedigree. We identified 325 crossovers at a median resolution of 1.4 kb, with 86% of the events localized to <10 kb intervals. Observed crossover rates were in excellent agreement with data from linkage mapping, were 52% higher in male (3.56 cM/Mb than in female meiosis (2.28 cM/Mb, and increased towards chromosome ends in male but not female meiosis. Crossover events were non-randomly distributed in the genome with several distinct hot-spots and a concentration to genic regions, with the highest density in promoters and CpG islands. We further identified 267 non-crossovers, whose location was significantly associated with crossover locations. We detected a significant transmission bias (0.18 in favour of 'strong' (G, C over 'weak' (A, T alleles at non-crossover events, providing direct evidence for the process of GC-biased gene conversion in an avian system. The approach taken in this study should be applicable to any species and would thereby help to provide a more comprehensive portray of the recombination landscape across organism groups.

  18. Crossover Interference on Nucleolus Organizing Region-Bearing Chromosomes in Arabidopsis

    Science.gov (United States)

    Lam, Sandy Y.; Horn, Sarah R.; Radford, Sarah J.; Housworth, Elizabeth A.; Stahl, Franklin W.; Copenhaver, Gregory P.

    2005-01-01

    In most eukaryotes, crossovers are not independently distributed along the length of a chromosome. Instead, they appear to avoid close proximity to one another—a phenomenon known as crossover interference. Previously, for three of the five Arabidopsis chromosomes, we measured the strength of interference and suggested a model wherein some crossovers experience interference while others do not. Here we show, using the same model, that the fraction of interference-insensitive crossovers is significantly smaller on the remaining two chromosomes. Since these two chromosomes bear the Arabidopsis NOR domains, the possibility that these chromosomal regions influence interference is discussed. PMID:15802520

  19. Force Display and Bi-Lateral Master-Slave Control with an Internal Model under the Consideration of Human Cross-Over Model

    Science.gov (United States)

    Kawahata, Nagakatsu; Nishizawa, Masanori; Itoh, Youichirou; Yoshida, Hiroaki

    Human behavior for controlling machines is quite adaptive but restrictive in gain, phase, frequency bandwidth and so on. It is often assumed by a cross-over model especially for compensatory tracking task. Force display system is increasingly important in robotics, remote manipulations, machine handling and etc. The control system design for force display and/or bi-lateral master-slave manipulator is not so easy because of gain limits, mechanical vibration, human-induced oscillation and others. Proposed is a control system design for force display and/or bi-lateral master-slave manipulator based on model-following control under the concept of human crossover model in compensatory tracking. Experimental results are also shown for an actual force display device designed by the proposed method.

  20. Dimensional BCS-BEC crossover in ultracold Fermi gases

    Energy Technology Data Exchange (ETDEWEB)

    Boettcher, Igor

    2014-12-10

    We investigate thermodynamics and phase structure of ultracold Fermi gases, which can be realized and measured in the laboratory with modern trapping techniques. We approach the subject from a both theoretical and experimental perspective. Central to the analysis is the systematic comparison of the BCS-BEC crossover of two-component fermions in both three and two dimensions. A dimensional reduction can be achieved in experiments by means of highly anisotropic traps. The Functional Renormalization Group (FRG) allows for a description of both cases in a unified theoretical framework. In three dimensions we discuss with the FRG the influence of high momentum particles onto the density, extend previous approaches to the Unitary Fermi Gas to reach quantitative precision, and study the breakdown of superfluidity due to an asymmetry in the population of the two fermion components. In this context we also investigate the stability of the Sarma phase. For the two-dimensional system scattering theory in reduced dimension plays an important role. We present both the theoretically as well as experimentally relevant aspects thereof. After a qualitative analysis of the phase diagram and the equation of state in two dimensions with the FRG we describe the experimental determination of the phase diagram of the two-dimensional BCS-BEC crossover in collaboration with the group of S. Jochim at PI Heidelberg.

  1. Indication of BCS-BEC crossover behavior in halo nuclei

    CERN Document Server

    Hagino, K; Sagawa, H; Schuck, P

    2006-01-01

    We investigate the spatial structure of two-neutron wave function in a Borromean nucleus $^{11}$Li using a three-body model in which two valence neutrons interact with each other by a density-dependent contact force. The behavior of the neutron Cooper pair at different densities is simulated by calculating the two-neutron wave function at several distances between the core nucleus and the center of mass of the two neutrons. We find that the neutron pair wave function in $^{11}$Li has an oscillation at normal density, while it becomes a well localized single peak in the dilute density region around the nuclear surface. These features are in close analogue to the BCS-BEC crossover of the Cooper pair wave function found in the infinite nuclear matter. The present results also provide a unified picture of the di-neutron and the cigar-like configurations in Borromian nuclei as a manifestation of the BCS-BEC crossover phenomenon.

  2. Ordering and dimensional crossovers in metallic glasses and liquids

    Science.gov (United States)

    Chen, David Z.; An, Qi; Goddard, William A.; Greer, Julia R.

    2017-01-01

    The atomic-level structures of liquids and glasses are amorphous, lacking long-range order. We characterize the atomic structures by integrating radial distribution functions (RDF) from molecular dynamics (MD) simulations for several metallic liquids and glasses: C u46Z r54 , N i80A l20 , N i33.3Z r66.7 , and P d82S i18 . Resulting cumulative coordination numbers (CN) show that metallic liquids have a dimension of d =2.55 ±0.06 from the center atom to the first coordination shell and metallic glasses have d =2.71 ±0.04 , both less than 3. Between the first and second coordination shells, both phases crossover to a dimension of d =3 , as for a crystal. Observations from discrete atom center-of-mass position counting are corroborated by continuously counting Cu glass- and liquid-phase atoms on an artificial grid, which accounts for the occupied atomic volume. Results from Cu grid analysis show short-range d =2.65 for Cu liquid and d =2.76 for Cu glass. Cu grid structures crossover to d =3 at ξ ˜8 Å (˜3 atomic diameters). We study the evolution of local structural dimensions during quenching and discuss its correlation with the glass transition phenomenon.

  3. Cross-over studies underestimate energy compensation: The example of sucrose-versus sucralose-containing drinks.

    Science.gov (United States)

    Gadah, Nouf S; Brunstrom, Jeffrey M; Rogers, Peter J

    2016-12-01

    The vast majority of preload-test-meal studies that have investigated the effects on energy intake of disguised nutrient or other food/drink ingredient manipulations have used a cross-over design. We argue that this design may underestimate the effect of the manipulation due to carry-over effects. To test this we conducted comparable cross-over (n = 69) and parallel-groups (n = 48) studies testing the effects of sucrose versus low-calorie sweetener (sucralose) in a drink preload on test-meal energy intake. The parallel-groups study included a baseline day in which only the test meal was consumed. Energy intake in that meal was used to control for individual differences in energy intake in the analysis of the effects of sucrose versus sucralose on energy intake on the test day. Consistent with our prediction, the effect of consuming sucrose on subsequent energy intake was greater when measured in the parallel-groups study than in the cross-over study (respectively 64% versus 36% compensation for the 162 kcal difference in energy content of the sucrose and sucralose drinks). We also included a water comparison group in the parallel-groups study (n = 24) and found that test-meal energy intake did not differ significantly between the water and sucralose conditions. Together, these results confirm that consumption of sucrose in a drink reduces subsequent energy intake, but by less than the energy content of the drink, whilst drink sweetness does not increase food energy intake. Crucially, though, the studies demonstrate that study design affects estimated energy compensation.

  4. Design

    DEFF Research Database (Denmark)

    Jensen, Ole B.; Pettiway, Keon

    2017-01-01

    by designers, planners, etc. (staging from above) and mobile subjects (staging from below). A research agenda for studying situated practices of mobility and mobilities design is outlined in three directions: foci of studies, methods and approaches, and epistemologies and frames of thinking. Jensen begins...... with a brief description of how movement is studied within social sciences after the “mobilities turn” versus the idea of physical movement in transport geography and engineering. He then explains how “mobilities design” was derived from connections between traffic and architecture. Jensen concludes......In this chapter, Ole B. Jensen takes a situational approach to mobilities to examine how ordinary life activities are structured by technology and design. Using “staging mobilities” as a theoretical approach, Jensen considers mobilities as overlapping, actions, interactions and decisions...

  5. A randomized, crossover pharmacokinetic study comparing generic tacrolimus vs. the reference formulation in subpopulations of kidney transplant patients.

    Science.gov (United States)

    Bloom, R D; Trofe-Clark, J; Wiland, A; Alloway, R R

    2013-01-01

    An exploratory, post hoc analysis was performed using data from a prospective, multicenter, open-label, randomized, two-period (14 d per period), two-sequence, crossover, steady-state pharmacokinetic study comparing generic tacrolimus (Sandoz) vs. reference tacrolimus in stable renal transplant patients receiving their pre-study twice-daily dose. Pharmacokinetic parameters were compared in 68 patients according to gender, African American ethnicity, the presence or absence of diabetes, and use of steroids. The ratios of tacrolimus AUC0-12 h , Cmax , and C12 with generic vs. reference tacrolimus were calculated using the geometric mean (GM) of dose-normalized values at days 14 and 28. Mean (SD) tacrolimus dose at baseline was 5.7 (4.2) mg/d. There were no consistent differences in dose-normalized AUC0-12 h , C12 , Cmax, or tmax between the generic and reference preparations within subpopulations. The 90% confidence intervals (CI) for the ratios of dose-normalized AUC0-12 h and C12 with generic vs. reference tacrolimus were within 80-125% for all subpopulations, as were 90% CIs for Cmax other than for females, African Americans, and non-diabetics, which is not unexpected given the wide variability of tacrolimus Cmax and the small subpopulation sizes. These exploratory results suggest that this generic tacrolimus preparation would be expected to offer comparable bioavailability to the reference drug in these patient subpopulations.

  6. Design

    DEFF Research Database (Denmark)

    Volf, Mette

    Design - proces & metode iBog®  er enestående i sit fokus på afmystificering og operationalisering af designprocessens flygtige og komplekse karakter. Udgivelsen går bag om designerens daglige arbejde og giver et indblik i den kreative skabelsesproces, som designeren er en del af. Udover et bredt...... indblik i designerens arbejdsmetoder og designparametre giver Design - proces & metode en række eksempler fra anerkendte designvirksomheder, der gør det muligt at komme helt tæt på designerens virkelighed....

  7. Design

    Science.gov (United States)

    Buchanan, Richard; Cross, Nigel; Durling, David; Nelson, Harold; Owen, Charles; Valtonen, Anna; Boling, Elizabeth; Gibbons, Andrew; Visscher-Voerman, Irene

    2013-01-01

    Scholars representing the field of design were asked to identify what they considered to be the most exciting and imaginative work currently being done in their field, as well as how that work might change our understanding. The scholars included Richard Buchanan, Nigel Cross, David Durling, Harold Nelson, Charles Owen, and Anna Valtonen. Scholars…

  8. Design

    Science.gov (United States)

    Buchanan, Richard; Cross, Nigel; Durling, David; Nelson, Harold; Owen, Charles; Valtonen, Anna; Boling, Elizabeth; Gibbons, Andrew; Visscher-Voerman, Irene

    2013-01-01

    Scholars representing the field of design were asked to identify what they considered to be the most exciting and imaginative work currently being done in their field, as well as how that work might change our understanding. The scholars included Richard Buchanan, Nigel Cross, David Durling, Harold Nelson, Charles Owen, and Anna Valtonen. Scholars…

  9. Apparent temperature and acute myocardial infarction hospital admissions in Copenhagen, Denmark: a case-crossover study

    Directory of Open Access Journals (Sweden)

    Wichmann Janine

    2012-03-01

    Full Text Available Abstract Background The influence of temperature on acute myocardial infarction (AMI has not been investigated as extensively as the effects of broader outcomes of morbidity and mortality. Sixteen studies reported inconsistent results and two considered confounding by air pollution. We addressed some of the methodological limitations of the previous studies in this study. Methods This is the first study of the association between the daily 3-hour maximum apparent temperature (Tappmax and AMI hospital admissions in Copenhagen. The study period covered 1 January 1999-31 December 2006, stratified in warm (April - September and cold (October - March periods. A case-crossover epidemiology study design was applied. Models were adjusted for public holidays and influenza, confounding by PM10, NO2 and CO was investigated, the lag and non-linear effects of Tappmax was examined, effect modification by age, sex and SES was explored, and the results of the case-crossover models were compared to those of the generalised additive Poisson time-series and generalised estimating equation models. Results 14 456 AMI hospital admissions (12 995 people occurred during the study period. For an inter-quartile range (6 or 7°C increase in the 5-day cumulative average of Tappmax, a 4% (95% CI:-2%; 10% and 9% (95% CI: 3%; 14% decrease in the AMI admission rate was observed in the warm and cold periods, respectively. The 19-65 year old group, men and highest SES group seemed to be more susceptible in the cold period. Conclusion An increase in Tappmax is associated with a decrease in AMI admissions during the colder months.

  10. Fluoropolymer-coated dacron versus PTFE grafts for femorofemoral crossover bypass: randomised trial

    DEFF Research Database (Denmark)

    Eiberg, J P; Røder, Ole Christian; Stahl-Madsen, Morten

    2006-01-01

    To investigate whether patency of a thin walled 8 mm fluoropassivated Dacron graft was similar to that of a standard 8mm PTFE graft for femorofemoral crossover bypass surgery.......To investigate whether patency of a thin walled 8 mm fluoropassivated Dacron graft was similar to that of a standard 8mm PTFE graft for femorofemoral crossover bypass surgery....

  11. Crossover of angular dependent magnetoresistance with the metal-insulator transition in colossal magnetoresistive manganite films

    DEFF Research Database (Denmark)

    Chen, Yunzhong; Sun, J.R.; Zhao, T.Y.;

    2009-01-01

    directions was observed with the appearance of magnetic-field-induced metal-insulator transition, which further led to a sign crossover in the AMR effect. The AMR crossover may give a direct evidence of the drastic modification of electronic structure or possible orbital reconstruction with the magnetic...

  12. Natural variation and dosage of the HEI10 meiotic E3 ligase control Arabidopsis crossover recombination

    Science.gov (United States)

    Ziolkowski, Piotr A.; Underwood, Charles J.; Lambing, Christophe; Martinez-Garcia, Marina; Lawrence, Emma J.; Ziolkowska, Liliana; Griffin, Catherine; Choi, Kyuha; Franklin, F. Chris H.; Martienssen, Robert A.; Henderson, Ian R.

    2017-01-01

    During meiosis, homologous chromosomes undergo crossover recombination, which creates genetic diversity and balances homolog segregation. Despite these critical functions, crossover frequency varies extensively within and between species. Although natural crossover recombination modifier loci have been detected in plants, causal genes have remained elusive. Using natural Arabidopsis thaliana accessions, we identified two major recombination quantitative trait loci (rQTLs) that explain 56.9% of crossover variation in Col×Ler F2 populations. We mapped rQTL1 to semidominant polymorphisms in HEI10, which encodes a conserved ubiquitin E3 ligase that regulates crossovers. Null hei10 mutants are haploinsufficient, and, using genome-wide mapping and immunocytology, we show that transformation of additional HEI10 copies is sufficient to more than double euchromatic crossovers. However, heterochromatic centromeres remained recombination-suppressed. The strongest HEI10-mediated crossover increases occur in subtelomeric euchromatin, which is reminiscent of sex differences in Arabidopsis recombination. Our work reveals that HEI10 naturally limits Arabidopsis crossovers and has the potential to influence the response to selection. PMID:28223312

  13. Solution Theory of Ginzburg-Landau Theory on BCS-BEC Crossover

    Directory of Open Access Journals (Sweden)

    Shuhong Chen

    2014-01-01

    Full Text Available We establish strong solution theory of time-dependent Ginzburg-Landau (TDGL systems on BCS-BEC crossover. By the properties of Besov, Sobolev spaces, and Fourier functions and the method of bootstrapping argument, we deduce that the global existence of strong solutions to time-dependent Ginzburg-Landau systems on BCS-BEC crossover in various spatial dimensions.

  14. A single-item inventory model for expected inventory order crossovers

    NARCIS (Netherlands)

    Riezebos, J.; Gaalman, G.J.C.

    2009-01-01

    Expected inventory order crossovers Occur if at the moment of ordering it is expected that orders will not arrive in the sequence they are ordered. Recent research has shown that (it) expected inventory order crossovers will be encountered more frequently in future, and that (b) use of a myopic

  15. 50 CFR 660.320 - Open access fishery-crossover provisions.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Open access fishery-crossover provisions... West Coast Groundfish-Open Access Fisheries § 660.320 Open access fishery—crossover provisions. (a) Operating in both limited entry and open access fisheries. See provisions at § 660.60, subpart C....

  16. Effect of oral administration of freshly pressed juice of Echinacea purpurea on the number of various subpopulations of B- and T-lymphocytes in healthy volunteers: results of a double-blind, placebo-controlled cross-over study

    DEFF Research Database (Denmark)

    Schwarz, Evelyn; Parlesak, Alexandr; Henneicke-von-Zeppelin, H. H.

    2005-01-01

    -40 years) participated in the study. They received either a commercially available pressed juice of E. purpurea herbs or placebo juice using a double-blind placebo-controlled cross-over design with two treatment periods of 14 days. The total number of lymphocytes and 12 subgroups of lymphocytes were......-Mann-Whitney-U-test, which is claimed to be optimal for the evaluation of the results of studies with a cross-over design, a significant difference was found for the number of CD8 + -T-lymphocytes and natural killer cells corresponding to either a decrease during treatment with verum or an increase in the number......BACKGROUND: In a recent double-blind placebo-controlled crossover-study the "immune stimulatory" effects (activation of macrophages leading to enhanced phagocytosis and production of several cytokines) of Echinacea purpurea preparations (EPP) which were observed in vitro experiments and following...

  17. Crossover between spin swapping and Hall effect in disordered systems

    KAUST Repository

    Saidaoui, Hamed Ben Mohamed

    2015-07-16

    We theoretically study the crossover between spin Hall effect and spin swapping, a recently predicted phenomenon that consists of the interchange between the current flow and its spin polarization directions [M. B. Lifshits and M. I. Dyakonov, Phys. Rev. Lett. 103, 186601 (2009)]. Using a tight-binding model with spin-orbit coupled disorder, spin Hall effect, spin relaxation, and spin swapping are treated on equal footing. We demonstrate that spin swapping and spin Hall effect present very different dependencies as a function of the spin-orbit coupling and disorder strengths and confirm that the former exceeds the latter in the parameter range considered. Three setups are proposed for the experimental observation of the spin swapping effect.

  18. Crossover from nucleation to spinodal decomposition in a condensing vapor.

    Science.gov (United States)

    Wedekind, Jan; Chkonia, Guram; Wölk, Judith; Strey, Reinhard; Reguera, David

    2009-09-21

    The mechanism controlling the initial step of a phase transition has a tremendous influence on the emerging phase. We study the crossover from a purely nucleation-controlled transition toward spinodal decomposition in a condensing Lennard-Jones vapor using molecular dynamics simulations. We analyze both the kinetics and at the same time the thermodynamics by directly reconstructing the free energy of cluster formation. We estimate the location of the spinodal, which lies at much deeper supersaturations than expected. Moreover, the nucleation barriers we find differ only by a constant from the classical nucleation theory predictions and are in very good agreement with semiempirical scaling relations. In the regime from very small barriers to the spinodal, growth controls the rate of the transition but not its nature because the activation barrier has not yet vanished. Finally, we discuss in detail the influence of the chosen reaction coordinate on the interpretation of such simulation results.

  19. Factors underlying restricted crossover localization in barley meiosis.

    Science.gov (United States)

    Higgins, James D; Osman, Kim; Jones, Gareth H; Franklin, F Chris H

    2014-01-01

    Meiotic recombination results in the formation of cytological structures known as chiasmata at the sites of genetic crossovers (COs). The formation of at least one chiasma/CO between homologous chromosome pairs is essential for accurate chromosome segregation at the first meiotic division as well as for generating genetic variation. Although DNA double-strand breaks, which initiate recombination, are widely distributed along the chromosomes, this is not necessarily reflected in the chiasma distribution. In many species there is a tendency for chiasmata to be distributed in favored regions along the chromosomes, whereas in others, such as barley and some other grasses, chiasma localization is extremely pronounced. Localization of chiasma to the distal regions of barley chromosomes restricts the genetic variation available to breeders. Studies reviewed herein are beginning to provide an explanation for chiasma localization in barley. Moreover, they suggest a potential route to manipulating chiasma distribution that could be of value to plant breeders.

  20. Crossover behavior in the distance dependence of hydrophobic force law

    CERN Document Server

    Samanta, Tuhin; Bagchi, Biman

    2016-01-01

    Understanding about both the range and the strength of the effective force between two hydrophobic surfaces suspended in water is important in many areas of natural science but unfortunately has remained imperfect. Even the experimental observations have not been explained quantitatively. Here we find by varying distance (d) between two hydrophobic walls in computer simulations of water that the force exhibits a bi-exponential distance dependence. The long range part of the force can be fitted to an exponential force law with correlation length of 2 nm while the short range part displays a correlation length of only 0.5 nm. The crossover from shorter range to longer range force law is rather sharp. We show that the distance dependence of the tetrahedrality order parameter provides a reliable marker of the force law, and exhibits similar distance dependence.

  1. Critical velocity in the BEC-BCS crossover.

    Science.gov (United States)

    Weimer, Wolf; Morgener, Kai; Singh, Vijay Pal; Siegl, Jonas; Hueck, Klaus; Luick, Niclas; Mathey, Ludwig; Moritz, Henning

    2015-03-01

    We map out the critical velocity in the crossover from Bose-Einstein condensation to Bardeen-Cooper-Schrieffer superfluidity with ultracold ^{6}Li gases. A small attractive potential is dragged along lines of constant column density. The rate of the induced heating increases steeply above a critical velocity v_{c}. In the same samples, we measure the speed of sound v_{s} by exciting density waves and compare the results to the measured values of v_{c}. We perform numerical simulations in the Bose-Einstein condensation regime and find very good agreement, validating the approach. In the strongly correlated regime our measurements of v_{c} provide a testing ground for theoretical approaches.

  2. A crossover in anisotropic nanomechanochemistry of van der Waals crystals

    Energy Technology Data Exchange (ETDEWEB)

    Shimamura, Kohei [Department of Physics, Kumamoto University, Kumamoto 860-8555 (Japan); Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, Department of Computer Science, Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089-0242 (United States); Graduate School of System Informatics, Kobe University, Kobe 657-8501 (Japan); Misawa, Masaaki [Department of Physics, Kumamoto University, Kumamoto 860-8555 (Japan); Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, Department of Computer Science, Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089-0242 (United States); Li, Ying [Argonne Leadership Computing Facility, Argonne National Laboratory, Argonne, Illinois 60439 (United States); Kalia, Rajiv K.; Nakano, Aiichiro; Vashishta, Priya [Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, Department of Computer Science, Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089-0242 (United States); Shimojo, Fuyuki [Department of Physics, Kumamoto University, Kumamoto 860-8555 (Japan)

    2015-12-07

    In nanoscale mechanochemistry, mechanical forces selectively break covalent bonds to essentially control chemical reactions. An archetype is anisotropic detonation of layered energetic molecular crystals bonded by van der Waals (vdW) interactions. Here, quantum molecular dynamics simulations reveal a crossover of anisotropic nanomechanochemistry of vdW crystal. Within 10{sup −13} s from the passage of shock front, lateral collision produces NO{sub 2} via twisting and bending of nitro-groups and the resulting inverse Jahn-Teller effect, which is mediated by strong intra-layer hydrogen bonds. Subsequently, as we transition from heterogeneous to homogeneous mechanochemical regimes around 10{sup −12} s, shock normal to multilayers becomes more reactive, producing H{sub 2}O assisted by inter-layer N-N bond formation. These time-resolved results provide much needed atomistic understanding of nanomechanochemistry that underlies a wider range of technologies.

  3. Electrostatic spin crossover effect in polar magnetic molecules.

    Science.gov (United States)

    Baadji, Nadjib; Piacenza, Manuel; Tugsuz, Tugba; Della Sala, Fabio; Maruccio, Giuseppe; Sanvito, Stefano

    2009-10-01

    The magnetic configuration of a nanostructure can be altered by an external magnetic field, by spin-transfer torque or by its magnetoelastic response. Here, we explore an alternative route, namely the possibility of switching the sign of the exchange coupling between two magnetic centres by means of an electric potential. This general effect, which we name electrostatic spin crossover, occurs in insulating molecules with super-exchange magnetic interaction and inversion symmetry breaking. As an example we present the case of a family of di-cobaltocene-based molecules. The critical fields for switching, calculated from first principles, are of the order of 1 V nm(-1) and can be achieved in two-terminal devices. More crucially, such critical fields can be engineered with an appropriate choice of substituents to add to the basic di-cobaltocene unit. This suggests that an easy chemical strategy for achieving the synthesis of suitable molecules is possible.

  4. Persistent User Bias in Case-Crossover Studies in Pharmacoepidemiology

    DEFF Research Database (Denmark)

    Hallas, Jesper; Pottegård, Anton; Wang, Shirley

    2016-01-01

    , sex, and index date, and exposure over the preceding 12 months was ascertained. For retinal detachment, the case-crossover odds ratio was 1.60 (95% confidence interval (CI): 1.42, 1.80) for statins, 1.40 (95% CI: 1.02, 1.92) for thyroxine, and 1.53 (95% CI: 1.04, 2.24) for insulin. Estimates...... for the retinal detachment controls were similar, leading to near-null case-time-control estimates for all 3 medication classes. For wrist fracture and stroke, the odds ratios were higher for cases than for controls, and case-time-control odds ratios were consistently above unity, thus implying significant...

  5. Control in the middle (CIM) for three-period crossover studies.

    Science.gov (United States)

    Shuster, Jonathan; Anton, Stephen D; Theriaque, Douglas; Yoon, Saunjoo

    2011-09-01

    Three-period crossover studies can be efficient and convenient methods of conducting Phase II clinical trials. Non-randomly placing control in the middle (CIM) has not been practiced but may be extremely useful in studies testing herbal products for which placebos are not available, or for distinguishing between behavioral and biological effects. Furthermore, this design can serve as a valuable addition to classical studies of either (a) two competing treatments or (b) treatment versus placebo versus an open label "nothing" as the control. Therefore, we propose rigorous designs that will help practitioners efficiently answer research questions where (1) two active treatments need to be compared against each other with treatment vs. placebo comparisons being of secondary importance; (2) a single active treatment needs to be tested where no placebo is available; or (3) the placebo effect is of interest in a treatment vs. placebo trial. For studies where no placebo is available, deception will be required, with participants told that in one randomly selected period (#1 or #3) they will receive the active treatment, and that they will receive a new experimental inert placebo in the other period. Assuming this design is approved by an ethics committee, it can be very useful in biomedical research.

  6. EXPLORATION/EXPLOITATION TRADEOFF WITH CELL-SHIFT AND HEURISTIC CROSSOVER FOR EVOLUTIONARY ALGORITHMS

    Institute of Scientific and Technical Information of China (English)

    Xinchao ZHAO; Junling HAO

    2007-01-01

    In order to tradeoff exploration/exploitation and inspired by cell genetic algorithm a cellshift crossover operator for evolutionary algorithm(EA) is proposed in this paper.The definition domain is divided into n-dimension cubic sub-domains(cell) and each individual locates at an ndimensional cube.Cell-shift crossover first exchanges the cell numbers of the crossover pair if they are in the different cells(exploration)and subsequently shift the first individual from its initial place to the other individual's cell place.If they are already in the same cell heuristic crossover(exploitation) is used.Cell-shift/heuristic crossover adaptively executes exploration/exploitation search with the vary of genetic diversity.The cell-shift EA has excellent performance in terms of efficiency and efficacy on ten usually used optimization benchmarks when comparing with the recent well-known FEP evolutionary algorithm.

  7. Hybrid Genetic Algorithm with Multiparents Crossover for Job Shop Scheduling Problems

    Directory of Open Access Journals (Sweden)

    Noor Hasnah Moin

    2015-01-01

    Full Text Available The job shop scheduling problem (JSSP is one of the well-known hard combinatorial scheduling problems. This paper proposes a hybrid genetic algorithm with multiparents crossover for JSSP. The multiparents crossover operator known as extended precedence preservative crossover (EPPX is able to recombine more than two parents to generate a single new offspring distinguished from common crossover operators that recombine only two parents. This algorithm also embeds a schedule generation procedure to generate full-active schedule that satisfies precedence constraints in order to reduce the search space. Once a schedule is obtained, a neighborhood search is applied to exploit the search space for better solutions and to enhance the GA. This hybrid genetic algorithm is simulated on a set of benchmarks from the literatures and the results are compared with other approaches to ensure the sustainability of this algorithm in solving JSSP. The results suggest that the implementation of multiparents crossover produces competitive results.

  8. Crossover phenomena in non-Newtonian viscous fingers at a finite viscosity ratio

    Science.gov (United States)

    Nagatani, Takashi

    1990-04-01

    A viscous fingering of non-Newtonian fluids at a finite viscosity ratio is considered in order to study the effect of non-Newtonian fluid on crossover phenomena. The crossover from the fractal pattern to the dense structure is investigated by using a two-parameter position-space renormalization-group method. The global flow diagrams in two-parameter space are obtained. It is found that there are two nontrivial fixed points: the fractal point and the Eden point. When the viscosity ratio is finite, the pattern must eventually cross over to the dense structure. The dependences of the crossover phenomena on the parameter k, which describes the different non-Newtonian fluids, are shown. It is found that the non-Newtonian fluids have important effects on the fractal point and the crossover line but the crossover exponent is independent of the non-Newtonian property.

  9. Relativistic description of BCS-BEC crossover in nuclear matter

    Science.gov (United States)

    Sun, Bao Yuan; Toki, Hiroshi; Meng, Jie

    2010-01-01

    We study theoretically the di-neutron spatial correlations and the crossover from superfluidity of neutron Cooper pairs in the S10 pairing channel to Bose-Einstein condensation (BEC) of di-neutron pairs for both symmetric and neutron matter in the microscopic relativistic pairing theory. We take the bare nucleon-nucleon interaction Bonn-B in the particle-particle channel and the effective interaction PK1 of the relativistic mean-field approach in the particle-hole channel. It is found that the spatial structure of neutron Cooper pair wave function evolves continuously from BCS-type to BEC-type as density decreases. We see a strong concentration of the probability density revealed for the neutron pairs in the fairly small relative distance around 1.5 fm and the neutron Fermi momentum kFn ∈ [ 0.6 , 1.0 ] fm-1. However, from the effective chemical potential and the quasiparticle excitation spectrum, there is no evidence for the appearance of a true BEC state of neutron pairs at any density. The most BEC-like state may appear at kFn ∼ 0.2 fm-1 by examining the density correlation function. From the coherence length and the probability distribution of neutron Cooper pairs as well as the ratio between the neutron pairing gap and the kinetic energy at the Fermi surface, some features of the BCS-BEC crossover are seen in the density regions, 0.05 fm-1

  10. Pharmacokinetic Dose Proportionality Between Two Strengths (12.5 mg and 25 mg) of Doxylamine Hydrogen Succinate Film-Coated Tablets in Fasting State: A Single-Dose, Randomized, Two-Period Crossover Study in Healthy Volunteers

    OpenAIRE

    Videla, Sebastián; Cebrecos, Jesús; Lahjou, Mounia; Wagner, France; Guibord, Pascal; Xu, Zhengguo; Cabot, Anna; Encabo, Mercedes; Encina, Gregorio; Sicard, Eric; Sans, Artur

    2013-01-01

    Background Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. No data on the dose proportionality of the pharmacokinetics of doxylamine are available, although this drug has been marketed in European countries for more than 50 years. Objective The objective of this study was to evaluate and compare the dose proportionality between two marketed strengths (12.5 mg and 25 mg) of doxylamine hydrogen succinat...

  11. Antipsychotic Drugs and the Risk of Ventricular Arrhythmia and/or Sudden Cardiac Death: A Nation‐wide Case‐Crossover Study

    OpenAIRE

    2015-01-01

    Background Antipsychotics have been linked to prolongation of the QT interval. However, little is known about the risk of ventricular arrhythmia (VA) and/or sudden cardiac death (SCD) associated with individual antipsychotic drug use. This study was designed to investigate the association between specific antipsychotic drugs and the risk of VA and/or SCD. Methods and Results We conducted a case‐crossover study using a nation‐wide population‐based sample obtained from Taiwan's National Health ...

  12. Articaine and mepivacaine buccal infiltration in securing mandibular first molar pulp anesthesia following mepivacaine inferior alveolar nerve block: A randomized, double-blind crossover study

    OpenAIRE

    Giath Gazal; Abdullah Muteb Alharbi; Khalid HidayatAllah Al-Samadani; Mohammad Dib Kanaa

    2015-01-01

    Aims: A crossover double-blind, randomized study was designed to explore the efficacy of 2% mepivacaine with 1:100,000 adrenaline buccal infiltration and 4% articaine with 1:100,000 adrenaline buccal infiltration following 2% mepivacaine with 1:100,000 adrenaline inferior alveolar nerve block (IANB) for testing pulp anesthesia of mandibular first molar teeth in adult volunteers. Materials and Methods: A total of 23 healthy adult volunteers received two regimens with at least 1-week apart; one...

  13. 49 CFR 213.353 - Turnouts, crossovers, and lift rail assemblies or other transition devices on moveable bridges.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Turnouts, crossovers, and lift rail assemblies or... SAFETY STANDARDS Train Operations at Track Classes 6 and Higher § 213.353 Turnouts, crossovers, and lift... shall be at least 11/2 inches wide. (d) For all turnouts and crossovers, and lift rail assemblies or...

  14. Dynamics in Two Periodically Driven and Weakly Coupled Bose-Einstein Condensates%二周期驱动及弱耦合玻丝-爱因斯坦凝聚模型的动力学性质

    Institute of Scientific and Technical Information of China (English)

    陈付广; 黄德斌; 郭荣伟

    2005-01-01

    In this paper, dynamics in the oscillations of the relative atomic population in two periodically driven and weakly coupled Bose-Einstein condensates (BECs) was qualitatively studied. Using the well-known Melnikov method, the conditions of existence of the periodic and chaotic coherent atomic tunnellings were given in the model. Our results indicate the typical route from bifurcation of the limited circles to chaos, and are in agreement with the previous numerical results.

  15. Genetic crossovers are predicted accurately by the computed human recombination map.

    Directory of Open Access Journals (Sweden)

    Pavel P Khil

    2010-01-01

    Full Text Available Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the positions of crossovers with the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributions of crossovers with the distributions expected from the calculated recombination rate maps. Here we show that a population-averaged hotspot map computed from linkage disequilibrium data predicts well present-day genetic crossovers. We find that computed hotspot maps accurately estimate both the strength and the position of meiotic hotspots. An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations. In summary, we find that by combining several computed population-specific maps we can capture the variation in individual hotspots to generate a hotspot map that can predict almost all present-day genetic crossovers.

  16. 3792 Preston: Another Two-period Case

    Science.gov (United States)

    Benishek, Vladimir; Pilcher, Frederick; Montaigut, Romain; Leroy, Arnaud; Carbognani, Albino; Pravec, Petr

    2017-04-01

    Photometric observations of the main-belt asteroid 3792 Preston during its 2016 apparition carried out from Europe and North America clearly revealed the existence of a secondary rotational lightcurve component. Although certain shallow attenuations that could represent satellite mutual eclipse/occultation events were detected on several occasions, the attempts to determine a unique orbital period from the available data were unsuccessful.

  17. Effect of oral administration of freshly pressed juice of Echinacea purpurea on the number of various subpopulations of B- and T-lymphocytes in healthy volunteers: results of a double-blind, placebo-controlled cross-over study

    DEFF Research Database (Denmark)

    Schwarz, Evelyn; Parlesak, Alexandr; Henneicke-von-Zeppelin, H. H.;

    2005-01-01

    BACKGROUND: In a recent double-blind placebo-controlled crossover-study the "immune stimulatory" effects (activation of macrophages leading to enhanced phagocytosis and production of several cytokines) of Echinacea purpurea preparations (EPP) which were observed in vitro experiments and following......-40 years) participated in the study. They received either a commercially available pressed juice of E. purpurea herbs or placebo juice using a double-blind placebo-controlled cross-over design with two treatment periods of 14 days. The total number of lymphocytes and 12 subgroups of lymphocytes were...

  18. Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: A centre randomised, cross-over, open-label study in the Netherlands

    NARCIS (Netherlands)

    F.W. Rozendaal (Frans); P.E. Spronk (Peter); F.F. Snellen (Ferdinand); A. Schoen (Adri); A.R.H. van Zanten (Arthur); N.A. Foudraine (Norbert); P.G.H. Mulder (Paul); J. Bakker (Jan)

    2009-01-01

    textabstractObjective: Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia. Design: Centre randomised, open-label, crossover, 'real-life' study. Setting: 15 Dutch hospitals. Patie

  19. A Comparative Study of Adaptive Crossover Operators for Genetic Algorithms to Resolve the Traveling Salesman Problem

    CERN Document Server

    Abdoun, Otman

    2012-01-01

    Genetic algorithm includes some parameters that should be adjusting so that the algorithm can provide positive results. Crossover operators play very important role by constructing competitive Genetic Algorithms (GAs). In this paper, the basic conceptual features and specific characteristics of various crossover operators in the context of the Traveling Salesman Problem (TSP) are discussed. The results of experimental comparison of more than six different crossover operators for the TSP are presented. The experiment results show that OX operator enables to achieve a better solutions than other operators tested.

  20. Crossover replantation as a salvage procedure following bilateral transhumeral upper limb amputation: a case report.

    Science.gov (United States)

    Ozçelik, Ismail Bülent; Mersa, Berkan; Kabakaş, Fatih; Saçak, Bülent; Kuvat, Samet Vasfi

    2011-04-01

    Cross-over replantation is a salvage option for cases with bilateral extremity amputations where the wound conditions do not enable an orthotopic replantation. Here, we present a 24-year-old patient who applied to our center with bilateral transhumeral amputations. Due to the wound conditions, a cross-over replantation was performed. 24 months after the initial operation, the patient exhibits good protective sensation at the distal levels and function to some degree, whereas the active range of motion is not as promising as previously expected. In this article, we present this case together with its immediate and long-term outcomes and the consequences of the cross-over replantation.

  1. Measurement of Wave Chaotic Eigenfunctions in the Time-Reversal Symmetry-Breaking Crossover Regime

    CERN Document Server

    Chung, S H; Wu, D H; Bridgewater, A; Anlage, S M; Chung, Seok-Hwan; Gokirmak, Ali; Wu, Dong-Ho; Anlage, Steven M.

    1999-01-01

    We present experimental results on eigenfunctions of a wave chaotic system in the continuous crossover regime between time-reversal symmetric and time-reversal symmetry-broken states. The statistical properties of the eigenfunctions of a two-dimensional microwave resonator are analyzed as a function of an experimentally determined time-reversal symmetry breaking parameter. We test four theories of eigenfunction statistics in the crossover regime. We also find a universal correlation between the one-point and two-point statistical parameters for the crossover eigenfunctions.

  2. Is Zolpidem Associated with Increased Risk of Fractures in the Elderly with Sleep Disorders? A Nationwide Case Cross-Over Study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Yih-Jing Tang

    Full Text Available We conducted a study using a case-crossover design to clarify the risk of acute effects of zolpidem and benzodiazepine on all-sites of fractures in the elderly.Case-crossover design.Elderly enrollees (n = 6010 in Taiwan's National Health Insurance Research Database with zolpidem or benzodiazepine use were analyzed for the risk of developing fractures.After adjusting for medications such as antipsychotics, antidepressants, and diuretics, or comorbidities such as hypertension, osteoarthritis, osteoporosis, rheumatoid arthritis and depression, neither zolpidem nor benzodiazepine was found to be associated with increased risk in all-sites fractures. Subjects without depression were found to have an increased risk of fractures. Diazepam is the only benzodiazepine with increased risk of fractures after adjusting for medications and comorbidities. Hip and spine were particular sites for increased fracture risk, but following adjustment for comorbidities, the associations were found to be insignificant.Neither zolpidem nor benzodiazepine was associated with increased risk of all-site fractures in this case cross-over study after adjusting for medications or comorbidities in elderly individuals with insomnia. Clinicians should balance the benefits and risks for prescribing zolpidem or benzodiazepine in the elderly accordingly.

  3. The dynamic crossover in water does not require bulk water.

    Science.gov (United States)

    Turton, David A; Corsaro, Carmelo; Martin, David F; Mallamace, Francesco; Wynne, Klaas

    2012-06-14

    Many of the anomalous properties of water may be explained by invoking a second critical point that terminates the coexistence line between the low- and high-density amorphous states in the liquid. Direct experimental evidence of this point, and the associated polyamorphic liquid-liquid transition, is elusive as it is necessary for liquid water to be cooled below its homogeneous-nucleation temperature. To avoid crystallization, water in the eutectic LiCl solution has been studied but then it is generally considered that "bulk" water cannot be present. However, recent computational and experimental studies observe cooperative hydration in which case it is possible that sufficient hydrogen-bonded water is present for the essential characteristics of water to be preserved. For femtosecond optical Kerr-effect and nuclear magnetic resonance measurements, we observe in each case a fractional Stokes-Einstein relation with evidence of the dynamic crossover appearing near 220 K and 250 K respectively. Spectra obtained in the glass state also confirm the complex nature of the hydrogen-bonding modes reported for neat room-temperature water and support predictions of anomalous diffusion due to "worm-hole" structure.

  4. Thermopower of molecular junctions: Tunneling to hopping crossover in DNA

    Science.gov (United States)

    Korol, Roman; Kilgour, Michael; Segal, Dvira

    2016-12-01

    We study the electrical conductance G and the thermopower S of single-molecule junctions and reveal signatures of different transport mechanisms: off-resonant tunneling, on-resonant coherent (ballistic) motion, and multi-step hopping. These mechanisms are identified by studying the behavior of G and S while varying molecular length and temperature. Based on a simple one-dimensional model for molecular junctions, we derive approximate expressions for the thermopower in these different regimes. Analytical results are compared to numerical simulations, performed using a variant of Büttiker's probe technique, the so-called voltage-temperature probe, which allows us to phenomenologically introduce environmentally induced elastic and inelastic electron scattering effects, while applying both voltage and temperature biases across the junction. We further simulate the thermopower of GC-rich DNA sequences with mediating A:T blocks and manifest the tunneling-to-hopping crossover in both the electrical conductance and the thermopower, in accord with measurements by Li et al. [Nat. Commun. 7, 11294 (2016)].

  5. Catalytic Activity Control via Crossover between Two Different Microstructures

    KAUST Repository

    Zhou, Yuheng

    2017-09-08

    Metal nanocatalysts hold great promise for a wide range of heterogeneous catalytic reactions, while the optimization strategy of catalytic activity is largely restricted by particle size or shape control. Here, we demonstrate that a reversible microstructural control through the crossover between multiply-twinned nanoparticle (MTP) and single crystal (SC) can be readily achieved by solvent post-treatment on gold nanoparticles (AuNPs). Polar solvents (e.g. water, methanol) direct the transformation from MTP to SC accompanied by the disappearance of twinning and stacking faults. A reverse transformation from SC to MTP is achieved in non-polar solvent (e.g. toluene) mixed with thiol ligands. The transformation between two different microstructures is directly observed by in-situ TEM and leads to a drastic modulation of catalytic activity towards the gas-phase selective oxidation of alcohols. There is a quasi-linear relationship between TOFs and MTP concentrations. Based on the combined experimental and theoretical investigations of alcohol chemisorption on these nanocatalysts, we propose that the exposure of {211}-like microfacets associated with twin boundaries and stack faults accounts for the strong chemisorption of alcohol molecules on MTP AuNPs and thus the exceptionally high catalytic activity.

  6. Long Term Outcomes of Femorofemoral Crossover Bypass Grafts.

    Science.gov (United States)

    Park, Keun-Myoung; Park, Yang-Jin; Kim, Young-Wook; Hyun, Dongho; Park, Kwang Bo; Do, Young-Soo; Kim, Dong-Ik

    2017-06-01

    Femorofemoral crossover bypass (FCB) is a good procedure for patients with unilateral iliac artery disease. There are many articles about the results of FCB, but most of them were limited to 5 years follow-up. The purpose of our study was to analysis the results of FCB with a 10-year follow-up period. Between January 1995 and December 2010, 133 patients were operated in Samsung Medical Center (median follow-up: 58.8 months). We retrospectively analysed patient characteristics, the preoperative treatment, the operative procedure, and material used. The indications for FCB were claudication in 110 and critical limb ischemia in 23 patients. Three patients were died due to myocardiac infarction, intracranial hemorrhage, and acute respiratory failure within 30 days after surgery. The one-year primary and secondary patency rates were 89% and 97%, the 5-year primary and secondary patency rates were 70% and 85%, and the 10-year primary and secondary patency rates were 31% and 67%. The 5-year and 10-year limb salvage rates were 97% and 95%, respectively. Our long term analysis suggests that FCB might be a valuable alternative treatment modality in patients with unilateral iliac artery disease.

  7. Crossover Phenomena in Detrended Fluctuation Analysis Used in Financial Markets

    Institute of Scientific and Technical Information of China (English)

    MA Shi-Hao

    2009-01-01

    A systematic analysis of Shanghai and Japan stock indices for the period of Jan.1984 to Dec.2005 is performed.After stationarity is verified by ADF (Augmented Dickey-Fuller) test, the power spectrum of the data exhibits a power law decay as a whole characterized by 1/fβ processes with possible long range correlations.Subsequently, by using the method of detrended fluctuation analysis (DFA) of the genera/volatility in the stock markets, we find that the long-range correlations are occurred among the return series and the crossover phenomena exhibit in the results obviously.Further, Shanghai stock market shows long-range correlations in short time scale and shows short-range correlations in long time scale.Whereas, for Japan stock market, the data behaves oppositely absolutely.Last, we compare the varying of scale exponent in large volatility between two stock markets.All results obtained may indicate the possibility of characteristic of multifractal scaling behavior of the financial markets.

  8. Quantum-to-classical crossover near quantum critical point.

    Science.gov (United States)

    Vasin, M; Ryzhov, V; Vinokur, V M

    2015-12-21

    A quantum phase transition (QPT) is an inherently dynamic phenomenon. However, while non-dissipative quantum dynamics is described in detail, the question, that is not thoroughly understood is how the omnipresent dissipative processes enter the critical dynamics near a quantum critical point (QCP). Here we report a general approach enabling inclusion of both adiabatic and dissipative processes into the critical dynamics on the same footing. We reveal three distinct critical modes, the adiabatic quantum mode (AQM), the dissipative classical mode [classical critical dynamics mode (CCDM)], and the dissipative quantum critical mode (DQCM). We find that as a result of the transition from the regime dominated by thermal fluctuations to that governed by the quantum ones, the system acquires effective dimension d + zΛ(T), where z is the dynamical exponent, and temperature-depending parameter Λ(T) ∈ [0, 1] decreases with the temperature such that Λ(T = 0) = 1 and Λ(T → ∞) = 0. Our findings lead to a unified picture of quantum critical phenomena including both dissipation- and dissipationless quantum dynamic effects and offer a quantitative description of the quantum-to-classical crossover.

  9. Crossover from retro to specular Andreev reflections in bilayer graphene

    Science.gov (United States)

    Efetov, Dmitri K.; Efetov, Konstantin B.

    2016-08-01

    Ongoing experimental progress in the preparation of ultraclean graphene/superconductor (SC) interfaces enabled the recent observation of specular interband Andreev reflections (ARs) at bilayer graphene (BLG )/NbSe2 van der Waals interfaces [Efetov et al., Nat. Phys. 12, 328 (2016), 10.1038/nphys3583]. Motivated by this experiment we theoretically study the differential conductance across a BLG/SC interface at the continuous transition from high to ultralow Fermi energies EF in BLG. Using the Bogoliubov-de Gennes equations and the Blonder-Tinkham-Klapwijk formalism we derive analytical expressions for the differential conductance across the BLG/SC interface. We find a characteristic signature of the crossover from intraband retro (high EF) to interband specular (low EF) ARs that manifests itself in a strongly suppressed interfacial conductance when the excitation energy |ɛ |=| EF|<Δ (the SC gap). The sharpness of these conductance dips is strongly dependent on the size of the potential step at the BLG/SC interface U0.

  10. Tuning size and thermal hysteresis in bistable spin crossover nanoparticles.

    Science.gov (United States)

    Galán-Mascarós, José Ramón; Coronado, Eugenio; Forment-Aliaga, Alicia; Monrabal-Capilla, María; Pinilla-Cienfuegos, Elena; Ceolin, Marcelo

    2010-06-21

    Nanoparticles of iron(II) triazole salts have been prepared from water-organic microemulsions. The mean size of the nanoparticles can be tuned down to 6 nm in diameter, with a narrow size distribution. A sharp spin transition from the low spin (LS) to the high spin (HS) state is observed above room temperature, with a 30-40-K-wide thermal hysteresis. The same preparation can yield second generation nanoparticles containing molecular alloys by mixing triazole with triazole derivatives, or from metallic mixtures of iron(II) and zinc(II). In these nanoparticles of 10-15 nm, the spin transition "moves" towards lower temperatures, reaching a 316 K limit for the cooling down transition and maintaining a thermal hysteresis over 15-20-K-wide. The nanoparticles were characterized by dynamic light scattering, TEM, and AFM, after deposition on gold or silicon surfaces. The spin transition was characterized by magnetic susceptibility measurements and EXAFS (in solid samples after solvent removal) and also by the color change between the LS (violet) and HS (colorless) states in an organic solvent suspension. The discovery of bistable magnetic nanoparticles of 6 nm with a wide thermal hysteresis above room temperature showcases the actual possibilities of spin crossover materials for nanotechnological applications.

  11. Blinded placebo crossover study of gabapentin in primary orthostatic tremor.

    Science.gov (United States)

    Rodrigues, Julian P; Edwards, Dylan J; Walters, Susan E; Byrnes, Michelle L; Thickbroom, Gary W; Stell, Rick; Mastaglia, Frank L

    2006-07-01

    Primary orthostatic tremor (OT) is a rare but disabling condition characterized by leg tremor and feelings of instability during stance. Previous studies have reported a reduction in OT symptoms with gabapentin treatment. In this study, we report on the benefits of gabapentin treatment in a double-blind placebo-controlled crossover study of 6 OT patients. First, the maximally effective gabapentin dosage (600-2,700 mg/day) for each patient was determined during an initial dose-titration phase. Patients were then studied 7 days after drug withdrawal and again after two 2-week periods of treatment with either gabapentin or placebo, using force platform posturography to quantify postural sway and tremor. Other medications for OT were continued unchanged. Symptomatic response was assessed by a patient-rated severity scale and quality of life (QOL) questionnaire. All patients reported an increase in symptoms during the washout phase and symptom reduction (50%-75%) during gabapentin treatment. Tremor amplitude was reduced to 79% +/- 11% and sway area to 71% +/- 11% of the placebo state. QOL improved in all patients, no adverse drug effects were noted, and symptomatic benefit was maintained at follow-up (mean = 19 months). The findings confirm that gabapentin is an effective treatment for OT, reducing both tremor and postural instability and improving quality of life, and support its use as add-on or first-line therapy for OT.

  12. Spray-Drying to Get Spin-Crossover Materials

    Directory of Open Access Journals (Sweden)

    Nathalie Daro

    2017-01-01

    Full Text Available Spin-crossover (SCO triazole-based coordination polymers can be synthesized by micelle techniques, which almost always lead to rod-shaped nanoparticles. In order to notably reach new morphologies, we explore here the potentiality of the spray-drying (SD method to get SCO materials. Three SCO coordination polymers and a mononuclear complex are investigated. In all cases, the SD method obtains particles definitely showing SCO. The features of the latter are yet always different from those of the referenced materials, in the sense that SCO is more gradual and incomplete, in adequacy with the poor crystallinity of the powders obtained by SD. In the case of coordination polymers, the particles are preferentially spherical. Indications of possible polymorphism and/or new materials induced by the use of the SD method are evidenced. In the case of the mononuclear complex, the SD method has allowed reproducing, in a quick and easy way, the well-known bulk compound. This exploratory work demonstrates the relevance of the concept and opens the way to a systematic scrutiny of all the experimental parameters to tune the size, morphology, and properties of the SD-synthesized SCO particles.

  13. Crossover Method for Interactive Genetic Algorithms to Estimate Multimodal Preferences

    Directory of Open Access Journals (Sweden)

    Misato Tanaka

    2013-01-01

    Full Text Available We apply an interactive genetic algorithm (iGA to generate product recommendations. iGAs search for a single optimum point based on a user’s Kansei through the interaction between the user and machine. However, especially in the domain of product recommendations, there may be numerous optimum points. Therefore, the purpose of this study is to develop a new iGA crossover method that concurrently searches for multiple optimum points for multiple user preferences. The proposed method estimates the locations of the optimum area by a clustering method and then searches for the maximum values of the area by a probabilistic model. To confirm the effectiveness of this method, two experiments were performed. In the first experiment, a pseudouser operated an experiment system that implemented the proposed and conventional methods and the solutions obtained were evaluated using a set of pseudomultiple preferences. With this experiment, we proved that when there are multiple preferences, the proposed method searches faster and more diversely than the conventional one. The second experiment was a subjective experiment. This experiment showed that the proposed method was able to search concurrently for more preferences when subjects had multiple preferences.

  14. Separable Roles for a Caenorhabditis elegans RMI1 Homolog in Promoting and Antagonizing Meiotic Crossovers Ensure Faithful Chromosome Inheritance

    Science.gov (United States)

    Jagut, Marlène; Hamminger, Patricia; Woglar, Alexander; Millonigg, Sophia; Paulin, Luis; Mikl, Martin; Dello Stritto, Maria Rosaria; Tang, Lois; Habacher, Cornelia; Tam, Angela; Gallach, Miguel; von Haeseler, Arndt; Villeneuve, Anne M.; Jantsch, Verena

    2016-01-01

    During the first meiotic division, crossovers (COs) between homologous chromosomes ensure their correct segregation. COs are produced by homologous recombination (HR)-mediated repair of programmed DNA double strand breaks (DSBs). As more DSBs are induced than COs, mechanisms are required to establish a regulated number of COs and to repair remaining intermediates as non-crossovers (NCOs). We show that the Caenorhabditis elegans RMI1 homolog-1 (RMH-1) functions during meiosis to promote both CO and NCO HR at appropriate chromosomal sites. RMH-1 accumulates at CO sites, dependent on known pro-CO factors, and acts to promote CO designation and enforce the CO outcome of HR-intermediate resolution. RMH-1 also localizes at NCO sites and functions in parallel with SMC-5 to antagonize excess HR-based connections between chromosomes. Moreover, RMH-1 also has a major role in channeling DSBs into an NCO HR outcome near the centers of chromosomes, thereby ensuring that COs form predominantly at off-center positions. PMID:27011106

  15. Development of anode zone using dual-anode system to reduce organic matter crossover in membraneless microbial fuel cells.

    Science.gov (United States)

    Kim, Jisu; Kim, Bongkyu; An, Junyeong; Lee, Yoo Seok; Chang, In Seop

    2016-08-01

    To prevent the occurrence of the organic crossover in membraneless microbial fuel cells (ML-MFCs), dual-anode MFC (DA-MFC) was designed from multi-anode concept to ensure anode zone. The anode zone addressed increase the utilization of organic matter in ML-MFCs, as the result, the organic crossover was prevented and performance of MFCs were enhanced. The maximum power of the DA-MFC was 0.46mW, which is about 1.56 times higher than the ML-MFC (0.29mW). Furthermore, the DA-MFC had advantage in correlation of organic substance concentration and dissolved oxygen concentration, and even electric over-potential. In addition, in terms of cathode fouling, the DA-MFC showed clearer surface. Hence, the anode zone should be considered in the advanced ML-MFC for practically use in wastewater treatment process, and also for scale-up of MFCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Separable Roles for a Caenorhabditis elegans RMI1 Homolog in Promoting and Antagonizing Meiotic Crossovers Ensure Faithful Chromosome Inheritance.

    Science.gov (United States)

    Jagut, Marlène; Hamminger, Patricia; Woglar, Alexander; Millonigg, Sophia; Paulin, Luis; Mikl, Martin; Dello Stritto, Maria Rosaria; Tang, Lois; Habacher, Cornelia; Tam, Angela; Gallach, Miguel; von Haeseler, Arndt; Villeneuve, Anne M; Jantsch, Verena

    2016-03-01

    During the first meiotic division, crossovers (COs) between homologous chromosomes ensure their correct segregation. COs are produced by homologous recombination (HR)-mediated repair of programmed DNA double strand breaks (DSBs). As more DSBs are induced than COs, mechanisms are required to establish a regulated number of COs and to repair remaining intermediates as non-crossovers (NCOs). We show that the Caenorhabditis elegans RMI1 homolog-1 (RMH-1) functions during meiosis to promote both CO and NCO HR at appropriate chromosomal sites. RMH-1 accumulates at CO sites, dependent on known pro-CO factors, and acts to promote CO designation and enforce the CO outcome of HR-intermediate resolution. RMH-1 also localizes at NCO sites and functions in parallel with SMC-5 to antagonize excess HR-based connections between chromosomes. Moreover, RMH-1 also has a major role in channeling DSBs into an NCO HR outcome near the centers of chromosomes, thereby ensuring that COs form predominantly at off-center positions.

  17. Thermal hysteresis kinetic effects of spin crossover nanoparticulated systems studied by FORC diagram method on an Ising-like model

    Energy Technology Data Exchange (ETDEWEB)

    Atitoaie, Alexandru, E-mail: atitoaie@phys-iasi.ro [Department. of Physics, “Alexandru Ioan Cuza” University, 700506 Iasi (Romania); National Institute of Research and Development for Technical Physics, Iasi (Romania); Stoleriu, Laurentiu [Department. of Physics, “Alexandru Ioan Cuza” University, 700506 Iasi (Romania); Tanasa, Radu [Department. of Physics, “Alexandru Ioan Cuza” University, 700506 Iasi (Romania); Department of Engineering, University of Cambridge, CB2 1PZ Cambridge (United Kingdom); Stancu, Alexandru; Enachescu, Cristian [Department. of Physics, “Alexandru Ioan Cuza” University, 700506 Iasi (Romania)

    2016-04-01

    The scientific community is manifesting a high research interest on spin crossover compounds and their recently synthesized nanoparticles, due to their various appealing properties, such as the bistability between a diamagnetic low spin state and a paramagnetic high spin state (HS), inter-switchable by temperature or pressure changes, light irradiation or magnetic field. The utility of these compounds showing hysteresis covers a broad area of applications, from the development of more efficient designs of temperature and pressure sensors to automotive and aeronautic industries and even a new type of molecular actuators. We are proposing in this work a study regarding the kinetic effects and the distribution of reversible and irreversible components on the thermal hysteresis of spin crossover nanoparticulated systems. We are considering here tridimensional systems with different sizes and also systems of nanoparticles with a Gaussian size distribution. The correlations between the kinetics of the thermal hysteresis, the distributions of sizes and intermolecular interactions and the transition temperature distributions were established by using the FORC (First Order Reversal Curves) method using a Monte Carlo technique within an Ising-like system.

  18. The Effect of Vitamin E-Modified Dialyzers on Acute Intra-dialytic Symptoms: A Comparative Crossover Study

    Directory of Open Access Journals (Sweden)

    Tanimu Danlami

    2000-01-01

    Full Text Available We performed a crossover study to compare the effect of vitamin E-modified dialyzers on acute intra-dialytic symptoms, with other membranes. Twenty patients on hemodialysis were studied. They were divided into two equal groups of low-flux (C15NL, E15NL and high-flux (F60, EE15NL membrane dialyzers. Within each group, a vitamin E-modified dialyzer was compared with another dialyzer in a crossover design over a two-month period. All study patients were seen during each dialysis session by a physician and the occurrence of intra-dialytic symptoms were recorded. There was a significant overall improvement in the incidence of acute intra-dialytic symptoms with the use of vitamin E-modified dialyzers as compared with the other membranes. This effect was more for cuprophane than polysulfone. The occurrence of hypotensive episodes did not differ. Our study indicates that we can achieve a reduction in the incidence of acute intra-dialytic symptoms with the use of vitamin E-modified membrane as compared to cuprophane and polysulfone.

  19. Studies on Methanol Crossover in Liquid-Feed Direct Methanol Pem Fuel Cells

    Science.gov (United States)

    Narayanan, S. R.

    1995-01-01

    The performance of liquid feed direct methanol fuel cells using various types of Nafion membranes as the solid polymer electrolyte have been studied. The rate of fuel crossover and electrical performance has been measured for cells with Nafion membranes of various thicknesses and equivalent weights. The crossover rate is found to decrease with increasing thickness and applied current. The dependence of crossover rate on current density can be understood in terms of a simple linear diffusion model which suggests that the crossover rate can be influenced by the electrode structure in addition to the membrane. The studies suggest that Nafion EW 1500 is a very promising alternate to Nafion EW 1100 for direct methanol fuel cells.

  20. Fragile-strong fluid crossover and universal relaxation times in a confined hard-disk fluid.

    Science.gov (United States)

    Yamchi, Mahdi Zaeifi; Ashwin, S S; Bowles, Richard K

    2012-11-30

    We show that a system of hard disks confined to a narrow channel exhibits a fragile-strong fluid crossover located at the maximum of the isobaric heat capacity and that the relaxation times for different channel widths fall onto a single master curve when rescaled by the relaxation times and temperatures of the crossover. Calculations of the configurational entropy and the inherent structure equation of state find that the crossover is related to properties of the jamming landscape for the model but that the Adam-Gibbs relation does not predict the relaxation behavior. We also show that a facilitated dynamics description of the system, where kinetically excited regions are identified with local packing arrangements of the disks, successfully describes the fragile-strong crossover.

  1. Direct observation in 3d of structural crossover in binary hard sphere mixtures

    Science.gov (United States)

    Statt, Antonia; Pinchaipat, Rattachai; Turci, Francesco; Evans, Robert; Royall, C. Patrick

    2016-04-01

    For binary fluid mixtures of spherical particles in which the two species are sufficiently different in size, the dominant wavelength of oscillations of the pair correlation functions is predicted to change from roughly the diameter of the large species to that of the small species along a sharp crossover line in the phase diagram [C. Grodon et al., J. Chem. Phys. 121, 7869 (2004)]. Using particle-resolved colloid experiments in 3d we demonstrate that crossover exists and that its location in the phase diagram is in quantitative agreement with the results of both theory and our Monte-Carlo simulations. In contrast with previous work [J. Baumgartl et al., Phys. Rev. Lett. 98, 198303 (2007)], where a correspondence was drawn between crossover and percolation of both species, in our 3d study we find that structural crossover is unrelated to percolation.

  2. Phase transition and crossover in diffusion-limited aggregation with reaction times

    Science.gov (United States)

    Nagatani, Takashi; Stanley, H. Eugene

    1990-09-01

    A generalized diffusion-limited aggregation (DLA) with reaction times that has been proposed by Bunde and Miyazima [Phys. Rev. A 38, 2099 (1988)] is considered. Crossover from the DLA to the diffusion-limited self-avoiding walk (DLSAW) is investigated by using the two-parameter position-space renormalization-group method. The crossover exponent and the crossover radius are calculated. The geometrical phase transition between DLA and DLSAW found by Bunde and Miyajima is analyzed by making use of the three-parameter position-space renormalization-group method. A global flow diagram in the three-parameter space is obtained. Above the percolation threshold all the renormalization flows are merged into the DLA point. Below the threshold all the renormalization flows are merged into the DLSAW point. When the reaction time is large, the double-crossover phenomenon occurs below the threshold.

  3. Pharmacokinetics of fixed-dose combination of tenofovir disoproxil fumarate, lamivudine, and efavirenz: results of a randomized, crossover, bioequivalence study.

    Science.gov (United States)

    Abhyankar, Dhiraj; Shedage, Ashish; Gole, Milind; Raut, Preeti

    2016-06-17

    The objective of this study was to assess the bioequivalence between a fixed-dose combination of tenofovir disoproxil fumarate/lamivudine/efavirenz 300/300/600 mg and the individual innovator products. A randomized, balanced, open-label, two-sequence, two-treatment, two-period, single dose, crossover study in 48 healthy adults was conducted. Dosing was separated by a washout period of 32 days. Twenty-seven blood samples were collected in each period from pre-dose to 72 h post-dose. The data of 45 subjects were analyzed for pharmacokinetics and safety. Ninety percent CIs of geometric mean ratio on Cmax, AUC0-t, and AUC0-inf for tenofovir and lamivudine and on Cmax and AUC0-72 for efavirenz were within the acceptance criteria (80-125%). For tenofovir disoproxil fumarate, the Tmax, Kel, and t1/2 values for the test and reference products were 1.02 versus 0.91 h, 0.04 versus 0.04/h, 18.67 versus 18.46 h, respectively. For lamivudine, the Tmax, Kel, and t1/2 values were: 1.38 versus 1.30 h, 0.21 versus 0.19/h, 3.44 versus 3.91 h, respectively. For efavirenz, the Tmax values for the test and reference products were 3.71 and 3.65 h, respectively. Both the treatments were well tolerated. Our findings suggest that the tested formulation is bioequivalent to the innovators' formulations, and both treatments were well tolerated.

  4. Crossover replantation after bilateral traumatic lower limb amputations: a case report

    OpenAIRE

    Fang Jun; Li Huazhuang; Dou Honglei; Chen Jingchun; Xu Aiping; Liu Wenguo; Ding Gang

    2012-01-01

    Abstract Introduction Replantation of a limb to the contralateral stump after bilateral traumatic amputations is rare. To the best of our knowledge, there are only a few reports of crossover lower limb replantation in the literature. Case presentation We treated a 37-year-old Chinese woman with bilateral lower limb crush injuries sustained in a traffic accident. Her lower limb injuries were at different anatomic levels. We performed emergency bilateral amputations followed by crossover replan...

  5. Neckties and Cerebrovascular Reactivity in Young Healthy Males: A Pilot Randomised Crossover Trial

    Directory of Open Access Journals (Sweden)

    Mark Rafferty

    2011-01-01

    Full Text Available Background. A necktie may elevate intracranial pressure through compression of venous return. We hypothesised that a tight necktie would deleteriously alter cerebrovascular reactivity. Materials and Methods. A necktie was simulated using bespoke apparatus comprising pneumatic inner-tube with aneroid pressure-gauge. Using a randomised crossover design, cerebrovascular reactivity was measured with the “pseudo-tie” worn inflated or deflated for 5 minutes (simulating tight/loose necktie resp.. Reactivity was calculated using breath hold index (BHI and paired “t” testing used for comparative analysis. Results. We enrolled 40 healthy male volunteers. There was a reduction in cerebrovascular reactivity of 0.23 units with “tight” pseudotie (BHI loose 1.44 (SD 0.48; BHI tight 1.21 (SD 0.38 P<.001. Conclusion. Impairment in cerebrovascular reactivity was found with inflated pseudo-tie. However, mean BHI is still within a range of considered normal. The situation may differ in patients with vascular risk factors, and confirmatory work is recommended.

  6. A crossover comparison of extended release felodipine with prolonged action nifedipine in hypertension.

    Science.gov (United States)

    Moncica, I; Oh, P I; ul Qamar, I; Scolnik, D; Arbus, G S; Hebert, D; Balfe, J W; Koren, G

    1995-01-01

    In a crossover design, control of blood pressure by extended release felodipine was compared with control by prolonged action nifedipine in 21 children with renal hypertension. Compliance with once daily felodipine was higher than with nifedipine, at 95.6 (SEM 2.7)% v 78.9 (6.0)% (p = 0.02). Mean diastolic blood pressure was lower during the day with felodipine than with nifedipine, at 77.6 (2.4) v 84.4 (2.8) mm Hg (p = 0.05). Similarly, blood pressure load (the percentage of the day during which the child had blood pressure exceeding the upper limits of normal for age) was lower for felodipine than for nifedipine: 43.5 (5.5)% v 61.3 (6.3)%. There was an opposite trend during the night, though this did not reach statistical significance. These data suggest that once a day felodipine is effective in children with hypertension. This may be because of improved compliance. PMID:7574861

  7. Music intervention during daily weaning trials-A 6 day prospective randomized crossover trial.

    Science.gov (United States)

    Liang, Zhan; Ren, Dianxu; Choi, JiYeon; Happ, Mary Beth; Hravnak, Marylyn; Hoffman, Leslie A

    2016-12-01

    To examine the effect of patient-selected music intervention during daily weaning trials for patients on prolonged mechanical ventilation. Using a crossover repeated measures design, patients were randomized to music vs no music on the first intervention day. Provision of music was alternated for 6 days, resulting in 3 music and 3 no music days. During weaning trials on music days, data were obtained for 30min prior to music listening and continued for 60min while patients listened to selected music (total 90min). On no music days, data were collected for 90min. Outcome measures were heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2), blood pressure (BP), dyspnea and anxiety assessed with a visual analog scale (VAS-D, VAS-A) and weaning duration (meanh per day on music and non-music days). Of 31 patients randomized, 23 completed the 6-day intervention. When comparisons were made between the 3 music and 3 no music days, there were significant decreases in RR and VAS-D and a significant increase in daily weaning duration on music days (pmusic days (pmusic during daily weaning trials is a simple, low-cost, potentially beneficial intervention for patients on prolonged mechanical ventilation. Further study is indicated to test ability of this intervention to promote weaning success and benefits earlier in the weaning process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Deqi sensation in placebo acupuncture: a crossover study on chinese medicine students.

    Science.gov (United States)

    Liang, Zhao-Hui; Xie, Chang-Cai; Li, Zi-Ping; Zhu, Xiao-Ping; Lu, Ai-Ping; Fu, Wen-Bin

    2013-01-01

    Objective. To evaluate the similarity of deqi sensation of real and noninvasive placebo acupuncture in healthy people with knowledge of Chinese medicine. Methods. In a crossover design, volunteers recruited from Chinese medicine college students were randomized to two groups to receive two phases of intervention with a one-week washout interval. In Group A, the participants were firstly treated by real acupuncture and then by sham needle, and the treatment sequence was reversed in Group B. VAS for pain intensity and deqi sensation was evaluated as outcomes. Results. Sixty-three volunteers were recruited and 60 were included and finished the study. In Group A, VAS was higher in Phase I than in Phase II (P = 0.017). Only treatment methods were selected as factor to VAS difference (P = 0.046) in ANOVA test. More positive deqi was reported in Group A in Phase I when treated by real acupuncture (P = 0.039), but the difference was not significant in Phase II (P = 0.301). Conclusion. The noninvasive placebo acupuncture device can effetely simulate the deqi sensation as real acupuncture, but it is less likely to evoke the active effect of deqi in real practice. This trial is registered with Chinese Clinical Trial Registry: ChiCTR-ORC-09000505.

  9. Deqi Sensation in Placebo Acupuncture: A Crossover Study on Chinese Medicine Students

    Directory of Open Access Journals (Sweden)

    Zhao-hui Liang

    2013-01-01

    Full Text Available Objective. To evaluate the similarity of deqi sensation of real and noninvasive placebo acupuncture in healthy people with knowledge of Chinese medicine. Methods. In a crossover design, volunteers recruited from Chinese medicine college students were randomized to two groups to receive two phases of intervention with a one-week washout interval. In Group A, the participants were firstly treated by real acupuncture and then by sham needle, and the treatment sequence was reversed in Group B. VAS for pain intensity and deqi sensation was evaluated as outcomes. Results. Sixty-three volunteers were recruited and 60 were included and finished the study. In Group A, VAS was higher in Phase I than in Phase II (P=0.017. Only treatment methods were selected as factor to VAS difference (P=0.046 in ANOVA test. More positive deqi was reported in Group A in Phase I when treated by real acupuncture (P=0.039, but the difference was not significant in Phase II (P=0.301. Conclusion. The noninvasive placebo acupuncture device can effetely simulate the deqi sensation as real acupuncture, but it is less likely to evoke the active effect of deqi in real practice. This trial is registered with Chinese Clinical Trial Registry: ChiCTR-ORC-09000505.

  10. Captopril does not Potentiate Post-Exercise Hypotension: A Randomized Crossover Study.

    Science.gov (United States)

    Queiroz, Andréia Cristiane Carrenho; Sousa, Julio Cesar Silva; Silva, Natan Daniel; Tobaldini, Eleonora; Ortega, Katia Coelho; de Oliveira, Edilamar Menezes; Brum, Patricia Chakur; Montano, Nicola; Mion, Decio; Tinucci, Taís; de Moraes Forjaz, Claudia Lucia

    2017-04-01

    To evaluate whether captopril (3×50 mg/day) potentiates post-resistance exercise hypotension (PREH) in hypertensives (HT), 12 HT men received captopril and placebo for 4 weeks each in a double-blinded, randomized-crossover design. On each therapy, subjects underwent 2 sessions: Control (C - rest) and Resistance Exercise (RE - 7 exercises, 3 sets to moderate fatigue, 50% of 1 RM -repetition maximum). Measurements were taken before and after 30-60 min (Post1) and 7 h (Post2), and ambulatory blood pressure (BP) was monitored for 24 h. There were no differences in PREH characteristics and mechanisms between the placebo and captopril periods. At Post1, systolic/diastolic BP decreased significantly and similarly after RE with both therapies (Placebo=-13±2/-9±1 mmHg vs. Captopril=-12±2/-10±1 mmHg, PCaptopril: +13±2 bpm, +35±4 nu, 17±5 ml, -3±1 ms/mmHg, Pcaptopril did not potentiate the magnitude and duration of PREH in HT men, and it did not influence PREH mechanisms. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Probing photoinduced spin states in spin-crossover molecules with neutron scattering

    Science.gov (United States)

    Ridier, K.; Craig, G. A.; Damay, F.; Fennell, T.; Murrie, M.; Chaboussant, G.

    2017-03-01

    We report a neutron-scattering investigation of the spin-crossover compound [Fe (ptz) 6] (BF4)2 , which undergoes an abrupt thermal spin transition from high spin (HS), S =2 , to low spin (LS), S =0 , around 135 K. The HS magnetic state can be restored at low temperature under blue/green light irradiation. We have developed a specially designed optical setup for neutron scattering to address the magnetic properties of the light-induced HS state. By using neutron diffraction, we demonstrate that significant HS/LS ratios (of up to 60%) can be obtained with this experimental setup on a sample volume considered large (400 mg), while a complete recovery of the LS state is achieved using near-infrared light. Finally, with inelastic neutron scattering (INS) we have observed magnetic transitions arising from the photo-induced metastable HS S =2 state split by crystal-field and spin-orbit coupling. We interpret the INS data assuming a spin-only model with a zero-field splitting of the S =2 ground state. The obtained parameters are D ≈-1.28 ±0.03 meV and |E |≈0.08 ±0.03 meV. The present results show that in situ magnetic inelastic neutron-scattering investigations on a broad range of photomagnetic materials are now possible.

  12. Video game playing increases food intake in adolescents: a randomized crossover study.

    Science.gov (United States)

    Chaput, Jean-Philippe; Visby, Trine; Nyby, Signe; Klingenberg, Lars; Gregersen, Nikolaj T; Tremblay, Angelo; Astrup, Arne; Sjödin, Anders

    2011-06-01

    Video game playing has been linked to obesity in many observational studies. However, the influence of this sedentary activity on food intake is unknown. The objective was to examine the acute effects of sedentary video game play on various components of energy balance. With the use of a randomized crossover design, 22 healthy, normal-weight, male adolescents (mean ± SD age: 16.7 ± 1.1 y) completed two 1-h experimental conditions, namely video game play and rest in a sitting position, followed by an ad libitum lunch. The endpoints were spontaneous food intake, energy expenditure, stress markers, appetite sensations, and profiles of appetite-related hormones. Heart rate, systolic and diastolic blood pressures, sympathetic tone, and mental workload were significantly higher during the video game play condition than during the resting condition (P libitum energy intake after video game play exceeded that measured after rest by 335 kJ (P food intake associated with video game play was observed without increased sensations of hunger and was not compensated for during the rest of the day. Finally, the profiles of glucose, insulin, cortisol, and ghrelin did not suggest an up-regulation of appetite during the video game play condition. A single session of video game play in healthy male adolescents is associated with an increased food intake, regardless of appetite sensations. The trial was registered at clinicaltrials.gov as NCT01013246.

  13. Enhanced kangaroo mother care for heel lance in preterm neonates: a crossover trial.

    Science.gov (United States)

    Johnston, C C; Filion, F; Campbell-Yeo, M; Goulet, C; Bell, L; McNaughton, K; Byron, J

    2009-01-01

    To test if enhancing maternal skin-to-skin contact, or kangaroo mother care (KMC) by adding rocking, singing and sucking is more efficacious than simple KMC for procedural pain in preterm neonates. Preterm neonates (n=90) between 32 0/7 and 36 0/7 weeks' gestational age participated in a single-blind randomized crossover design. The infant was held in KMC with the addition of rocking, singing and sucking or the infant was held in KMC without additional stimulation. The Premature Infant Pain Profile was the primary outcome with time to recover as the secondary outcome. A repeated-measures analysis of covariance was employed for analyses. There were no significant differences in any of the 30 s time periods over the 2 min of blood sampling nor in time to return to baseline. Compared to historical controls of the same age in incubator, the pain scores were lower and comparable to other studies of KMC. There were site differences related to lower scores with the use of sucrose in one site and higher scores in younger, sicker infants in another site. The sensorial stimulations from skin-to-skin contact that include tactile, olfactory sensations from the mother are sufficient to decrease pain response in premature neonates. Other studies showing that rocking, sucking and music were efficacious were independent of skin-to-skin contact, which, when used alone has been shown to be effective as reported across studies.

  14. Synthetic food colourings and 'hyperactivity': a double-blind crossover study.

    Science.gov (United States)

    Rowe, K S

    1988-04-01

    Of 220 children referred for suspected 'hyperactivity', 55 were subjected to a 6 week trial of the Feingold diet. Forty (72.7%) demonstrated improved behaviour and 26 (47.3%) remained improved following liberalization of the diet over a period of 3-6 months. The parents of 14 children claimed that a particular cluster of behaviours was associated with the ingestion of foods containing synthetic colourings. A double-blind crossover study, employing a single-subject repeated measures design was conducted, using eight of these children. Subjects were maintained on a diet free from synthetic additives and were challenged daily for 18 weeks with either placebo (during lead-in and washout periods) or 50 mg of either tartrazine or carmoisine, each for 2 separate weeks. Two significant reactors were identified whose behavioural pattern featured extreme irritability, restlessness and sleep disturbance. One of the reactors did not have inattention as a feature. The findings raise the issue of whether the strict criteria for inclusion in studies concerned with 'hyperactivity' based on 'attention deficit disorder' may miss children who indicate behavioural changes associated with the ingestion of food colourings. Moreover, for further studies, the need to construct a behavioural rating instrument specifically validated for dye challenge is suggested.

  15. Crossover versus Stabilometric Platform for the Treatment of Balance Dysfunction in Parkinson's Disease: A Randomized Study.

    Science.gov (United States)

    Frazzitta, G; Bossio, F; Maestri, R; Palamara, G; Bera, R; Ferrazzoli, D

    2015-01-01

    Balance dysfunctions are a major challenge in the treatment of Parkinson's disease (PD). Previous studies have shown that rehabilitation can play a role in their treatment. In this study, we have compared the efficacy of two different devices for balance training: stabilometric platform and crossover. We have enrolled 60 PD patients randomly assigned to two groups. The first one (stabilometric group) performed a 4-week cycle of balance training, using the stabilometric platform, whereas the second one (crossover group) performed a 4-week cycle of balance training, using the crossover. The outcome measures used were Unified Parkinson's Disease Rating Scale (UPDRS) part II, Berg Balance Scale (BBS), Timed Up and Go (TUG), and Six Minutes Walking Test (6MWT). Results showed that TUG, BBS, and UPDRS II improved in both groups. There was not difference in the efficacy of the two balance treatments. Patients in both groups improved also the meters walked in the 6MWT at the end of rehabilitation, but the improvement was better for patients performing crossover training. Our results show that the crossover and the stabilometric platform have the same effect on balance dysfunction of Parkinsonian patients, while crossover gets better results on the walking capacity.

  16. Automated process flowsheet synthesis for membrane processes using genetic algorithm: role of crossover operators

    KAUST Repository

    Shafiee, Alireza

    2016-06-25

    In optimization-based process flowsheet synthesis, optimization methods, including genetic algorithms (GA), are used as advantageous tools to select a high performance flowsheet by ‘screening’ large numbers of possible flowsheets. In this study, we expand the role of GA to include flowsheet generation through proposing a modified Greedysub tour crossover operator. Performance of the proposed crossover operator is compared with four other commonly used operators. The proposed GA optimizationbased process synthesis method is applied to generate the optimum process flowsheet for a multicomponent membrane-based CO2 capture process. Within defined constraints and using the random-point crossover, CO2 purity of 0.827 (equivalent to 0.986 on dry basis) is achieved which results in improvement (3.4%) over the simplest crossover operator applied. In addition, the least variability in the converged flowsheet and CO2 purity is observed for random-point crossover operator, which approximately implies closeness of the solution to the global optimum, and hence the consistency of the algorithm. The proposed crossover operator is found to improve the convergence speed of the algorithm by 77.6%.

  17. Coherent transport through spin-crossover magnet Fe2 complexes

    Science.gov (United States)

    Huang, Jing; Xie, Rong; Wang, Weiyi; Li, Qunxiang; Yang, Jinlong

    2015-12-01

    As one of the most promising building blocks in molecular spintronics, spin crossover (SCO) complexes have attracted increasing attention due to their magnetic bistability between the high-spin (HS) and low-spin (LS) states. Here, we explore the electronic structures and transport properties of SCO magnet Fe2 complexes with three different spin-pair configurations, namely [LS-LS], [LS-HS], and [HS-HS], by performing extensive density functional theory calculations combined with the non-equilibrium Green's function technique. Our calculations clearly reveal that the SCO magnet Fe2 complexes should display two-step spin transitions triggered by external stimuli, i.e. temperature or light, which confirm the previous phenomenological model and agree well with previous experimental measurements. Based on the calculated transport results, we observe a nearly perfect spin-filtering effect and negative differential resistance (NDR) behavior integrated in the SCO magnet Fe2 junction with the [HS-HS] configuration. The current through the [HS-HS] SCO magnet Fe2 complex under a small bias voltage is mainly contributed by the spin-down electrons, which is significantly larger than those of the [LS-LS] and [LS-HS] cases. The bias-dependent transmissions are responsible for the observed NDR effect. These theoretical findings suggest that SCO Fe2 complexes hold potential applications in molecular spintronic devices.As one of the most promising building blocks in molecular spintronics, spin crossover (SCO) complexes have attracted increasing attention due to their magnetic bistability between the high-spin (HS) and low-spin (LS) states. Here, we explore the electronic structures and transport properties of SCO magnet Fe2 complexes with three different spin-pair configurations, namely [LS-LS], [LS-HS], and [HS-HS], by performing extensive density functional theory calculations combined with the non-equilibrium Green's function technique. Our calculations clearly reveal that the SCO

  18. Randomized Polypill crossover trial in people aged 50 and over.

    Directory of Open Access Journals (Sweden)

    David S Wald

    Full Text Available BACKGROUND: A Polypill is proposed for the primary prevention of cardiovascular disease in people judged to be at risk on account of their age alone. Its efficacy in reducing cholesterol and blood pressure is uncertain. METHODS: We conducted a randomized double-blind placebo-controlled crossover trial of a Polypill among individuals aged 50+ without a history of cardiovascular disease and compared the reductions with those predicted from published estimates of the effects of the individual drugs. Participants took the Polypill (amlodipine 2.5 mg, losartan 25 mg, hydrochlorothiazide 12.5 mg and simvastatin 40 mg each evening for 12 weeks and a placebo each evening for 12 weeks in random sequence. The mean within-person differences in blood pressure and low density lipoprotein (LDL cholesterol at the end of each 12 week period were determined. RESULTS: 84 out of 86 participants completed both treatment periods. The mean systolic blood pressure was reduced by 17.9 mmHg (95% CI, 15.7-20.1 on the Polypill, diastolic blood pressure by 9.8 mmHg (8.1-11.5, and LDL cholesterol by 1.4 mmol/L (1.2-1.6, reductions of 12%, 11%, and 39% respectively. The results were almost identical to those predicted; 18.4 mmHg, 9.7 mmHg, and 1.4 mmol/L respectively. CONCLUSION: The Polypill resulted in the predicted reductions in blood pressure and LDL cholesterol. Long term reductions of this magnitude would have a substantial effect in preventing heart attacks and strokes. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN36672232.

  19. Pharmacokinetic-pharmacodynamic crossover comparison of two levodopa extension strategies.

    Science.gov (United States)

    LeWitt, Peter A; Jennings, Danna; Lyons, Kelly E; Pahwa, Rajesh; Rabinowicz, Adrian L; Wang, James; Guarnieri, Maria; Hubble, Jean P; Murck, Harold

    2009-07-15

    Controlled-release carbidopa and levodopa (CL-CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L-dopa) effects. In a randomized, open-label crossover study of 17 PD subjects with wearing-off responses, we compared 8-hour L-dopa pharmacokinetics (PK) and clinical effects after two doses of CL-CR (50 and 200 mg, respectively) and CLE (37.7, 150, 200 mg, respectively). PK analysis revealed the anticipated near-equivalent mean L-dopa area-under-the-concentration-curve values (639,490 ng min/mL for two doses of CLE, and 662,577 for CL-CR, P = 0.86). The mean hourly fluctuation index for L-dopa concentration was 235% for CLE and 196% for CL-CR (P = 0.004). The mean maximal concentration for the first CLE dose was 1,926 +/- 760 ng/mL and for CL-CR, 1,840 +/- 889 (P = 0.33). During the PK studies, the mean time that L-dopa concentration was > or =1,000 ng/mL for CLE was 291 +/- 88 minutes and for CL-CR, 306 +/- 86 (P = 0.33). The mean percent-time in "off" state was 18% for CLE and 28% for CL-CR (P = 0.017), "on state without dyskinesia" was 64% for CLE and 65% for CL-CR (P = 0.803), and "on state with nontroublesome dyskinesia" was 18% for CLE and 7% for CL-CR (P = 0.03). Despite less "off" time with CLE, both formulations demonstrated similar mean PK values and marked intersubject PK variability.

  20. Randomized crossover comparison of adhesively coupled colostomy pouching systems.

    Science.gov (United States)

    Berg, Kirsten; Seidler, Heidi

    2005-03-01

    Ostomy pouching systems affect well being and quality of life, making selection of the appropriate system a key element of ostomy care. Several innovative adhesively coupled, two-piece systems are on the market. They feature flexible low profiles, allowing pouch removal/replacement without changing the skin barrier or wafer. This facilitates inspection or pouch changes without disrupting peristomal skin. Because few controlled trials compare pouching system effectiveness, a prospective, randomized open-label, crossover study was conducted. Under the supervision of ostomy care nurses in six outpatient clinics in Germany, clinical performance of and patient preferences for two adhesively coupled, closed-end pouching systems were compared during normal use. One is a gelatin/pectin-based skin barrier sealed to the pouch with a company-specific adhesive coupling technology (System E); the other, a grooved base plate wafer adhesive pouch coupling system (System F). Seventeen attributes and seven end-of-study measures that included comfort, flexibility, wear time, ease of removal, and overall performance were assessed. Informed, consenting participants were randomly assigned to use one system for five skin barrier/wafer changes or up to 15 days and subsequently switched to the alternative system for a similar period. The 39 participants used a total of 1,645 pouches and 342 skin barriers. All were found safe as determined by incidence and nature of the reported peristomal skin problems, subject withdrawals, and adverse events for both systems. However, System E provided longer pouch wear times (P System E on 10 of the 17 attributes (P System Fon none. More participants preferred System E on all seven end-of-study measures, five significantly (comfort, flexibility, wear time, ease of removal, and overall performance; (P < 0.02). These participant-reported, ostomy-related outcomes underscore the importance of product evaluation and selection for persons with an ostomy.

  1. A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study

    Directory of Open Access Journals (Sweden)

    Dash Chiranjeev

    2012-07-01

    Full Text Available Abstract Background Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown. Methods Attrition (dropouts and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥ 85% of the prescribed treatment packets are the main outcome measures reported. Results There was a high rate of dropout (51% from the study, and the rates were significantly higher among smokers (64% than non-smokers (36%. Among participants who completed the study the rate of compliance was 72%. The highest rates of dropouts occurred between the first and second treatment visits in both smokers (38% dropout and non-smokers (18% dropout. Throughout the study smokers were more likely to dropout than non-smokers. Black tea treatment was associated with the highest rates of dropout among smokers (37%, but was associated with the lowest rate of dropout among non-smokers (4%. Conclusions In a study conducted to test the feasibility of a four-treatment crossover tea trial, a high rate of dropout among smokers and non-smokers was observed. Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials. Trial registration number ISRCTN70410203

  2. A meta-analysis combining parallel and cross-over randomized controlled trials to assess impact of iodine fortified foods on urinary iodine concentration among children.

    Science.gov (United States)

    Athe, Ramesh; Mendu, Vishnu Vardhana Rao; Krishnapillai, Madhavan Nair

    2015-01-01

    The purpose of this analysis was to combine evidence from parallel and cross-over randomized controlled trials to assess the impact of iodine fortified foods on urinary iodine concentration (UIC) in children. A structured search for studies on iodine intervention studies on MEDLINE, Pro Quest, and the Cochrane Library from Jan, 1990 to Dec, 2012 was carried out. Carry-over effect was estimated by general linear model. We explored two methods to pool continuous outcomes in a meta-analysis by combining parallel and cross-over trial designs. The standard mean difference was calculated for net change in UIC. Fixed or random-effects models were used to summaries fortified food response data. Meta-regression and covariate meta-analysis were performed to explore the influ-ence of confounders on the net pooled effect on UIC. The overall pooled estimate, which combined parallel with cross-over trials in the absence of carry-over effect of UIC from 9 studies, showed a significant increase in the fortified group compared with the control group (n=3448; standard mean difference=2.02 μg/L; 95% CI: 1.30, 2.73; I2=99%, τ2=1.81, p<0.01). Meta-regression analysis indicated that dose of the feeding was positively related to the effect size (regression coefficient=0.014; 95% CI: 0.003, 0.026; p<0.019). The net pooled effect size after removing the confounders was 1.59 (95% CI: 0.953, 2.23) μg/L. There was an association between intakes of io-dine fortified foods and UIC in children. These results suggest that we can combine parallel with cross-over trials for meta-analysis for nutrients such as iodine when absorption is high.

  3. Covariance and crossover matrix guided differential evolution for global numerical optimization.

    Science.gov (United States)

    Li, YongLi; Feng, JinFu; Hu, JunHua

    2016-01-01

    Differential evolution (DE) is an efficient and robust evolutionary algorithm and has wide application in various science and engineering fields. DE is sensitive to the selection of mutation and crossover strategies and their associated control parameters. However, the structure and implementation of DEs are becoming more complex because of the diverse mutation and crossover strategies that use distinct parameter settings during the different stages of the evolution. A novel strategy is used in this study to improve the crossover and mutation operations. The crossover matrix, instead of a crossover operator and its control parameter CR, is proposed to implement the function of the crossover operation. Meanwhile, Gaussian distribution centers the best individuals found in each generation based on the proposed covariance matrix, which is generated between the best individual and several better individuals. Improved mutation operator based on the crossover matrix is randomly selected to generate the trial population. This operator is used to generate high-quality solutions to improve the capability of exploitation and enhance the preference of exploration. In addition, the memory population is randomly chosen from previous generation and used to control the search direction in the novel mutation strategy. Accordingly, the diversity of the population is improved. Thus, CCDE, which is a novel efficient and simple DE variant, is presented in this paper. CCDE has been tested on 30 benchmarks and 5 real-world optimization problems from the IEEE Congress on Evolutionary Computation (CEC) 2014 and CEC 2011, respectively. Experimental and statistical results demonstrate the effectiveness of CCDE for global numerical and engineering optimization. CCDE can solve the test benchmark functions and engineering problems more successfully than the other DE variants and algorithms from CEC 2014.

  4. Peer Assessment Enhances Student Learning: The Results of a Matched Randomized Crossover Experiment in a College Statistics Class.

    Science.gov (United States)

    Sun, Dennis L; Harris, Naftali; Walther, Guenther; Baiocchi, Michael

    2015-01-01

    Feedback has a powerful influence on learning, but it is also expensive to provide. In large classes it may even be impossible for instructors to provide individualized feedback. Peer assessment is one way to provide personalized feedback that scales to large classes. Besides these obvious logistical benefits, it has been conjectured that students also learn from the practice of peer assessment. However, this has never been conclusively demonstrated. Using an online educational platform that we developed, we conducted an in-class matched-set, randomized crossover experiment with high power to detect small effects. We establish that peer assessment causes a small but significant gain in student achievement. Our study also demonstrates the potential of web-based platforms to facilitate the design of high-quality experiments to identify small effects that were previously not detectable.

  5. Analysis of dual-end-pumped Nd3+-doped index-crossover gain guided-index antiguided fiber laser

    Science.gov (United States)

    Shen, Xiao; Wei, Wei; Zou, Hui; Zhang, Liaolin

    2016-05-01

    A dual-end pumped Nd3+-doped index-crossover gain guided-index antiguided (IGG-IAG) fiber laser is analyzed in theory. Pump light propagation and output laser characteristics are both explored by solving the related rate equations. Simulation results show that pump power confined in the IGG-IAG fiber core is larger and more uniform than that of the gain-guided and index-antiguided(GG-IAG) fiber, and the optimum fiber length and the output power of the IGG-IAG fiber laser are both larger than that of GG-IAG fiber laser. The relationship between threshold pump power and doped concentration, fiber length, fiber radius is researched respectively. The analysis results give out a method for the optimal design of the IGG-IAG fiber laser.

  6. Crossover from 3D to 2D quantum transport in Bi2Se3/In2Se3 superlattices.

    Science.gov (United States)

    Zhao, Yanfei; Liu, Haiwen; Guo, Xin; Jiang, Ying; Sun, Yi; Wang, Huichao; Wang, Yong; Li, Han-Dong; Xie, Mao-Hai; Xie, Xin-Cheng; Wang, Jian

    2014-09-10

    The topological insulator/normal insulator (TI/NI) superlattices (SLs) with multiple Dirac channels are predicted to offer great opportunity to design novel materials and investigate new quantum phenomena. Here, we report first transport studies on the SLs composed of TI Bi2Se3 layers sandwiched by NI In2Se3 layers artificially grown by molecular beam epitaxy (MBE). The transport properties of two kinds of SL samples show convincing evidence that the transport dimensionality changes from three-dimensional (3D) to two-dimensional (2D) when decreasing the thickness of building block Bi2Se3 layers, corresponding to the crossover from coherent TI transport to separated TI channels. Our findings provide the possibility to realizing "3D surface states" in TI/NI SLs.

  7. Peer Assessment Enhances Student Learning: The Results of a Matched Randomized Crossover Experiment in a College Statistics Class.

    Directory of Open Access Journals (Sweden)

    Dennis L Sun

    Full Text Available Feedback has a powerful influence on learning, but it is also expensive to provide. In large classes it may even be impossible for instructors to provide individualized feedback. Peer assessment is one way to provide personalized feedback that scales to large classes. Besides these obvious logistical benefits, it has been conjectured that students also learn from the practice of peer assessment. However, this has never been conclusively demonstrated. Using an online educational platform that we developed, we conducted an in-class matched-set, randomized crossover experiment with high power to detect small effects. We establish that peer assessment causes a small but significant gain in student achievement. Our study also demonstrates the potential of web-based platforms to facilitate the design of high-quality experiments to identify small effects that were previously not detectable.

  8. A Non-Symmetrical Solution Applying a Genetic Algorithm with Natural Crossover for the Structural Optimization of Truss Structures

    Directory of Open Access Journals (Sweden)

    Alvarado-Cárdenas R.

    2012-07-01

    Full Text Available In this research it is proposed a genetic algorithm with “natural crossover” that was applied to a continuous-discrete representation in order to optimize truss structures. The objective is to reduce the weight by restraining node displacement and limiting the cross sections to use. The solutions are combined applying two types of crossovers to the same representation, thus allowing to effectively explore the search space. The results are validated by comparing those found herein against those found in current literature for the case of the design of a 70 m span bridge truss structure. Solutions obtained are lighter and with different topology. Additionally, a case study is proposed, a greenhouse roof truss structure, in order to generate an actual application that is built in a practical scale and it is loaded afterwards to verify its strength.

  9. Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study

    Directory of Open Access Journals (Sweden)

    Jenkins TM

    2012-07-01

    Full Text Available Tim M Jenkins, Trevor S Smart, Frances Hackman, Carol Cooke, Keith KC TanClinical Research, Pfizer Worldwide Research and Development, Sandwich, Kent, UKBackground: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population.Methods: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study.Results: Twenty-five adults (20–70 years of age with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1 pregabalin followed by placebo or (2 placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5–15. In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint were significantly reduced for pregabalin versus placebo, with a mean treatment difference of -0.81 (95% confidence interval: -1.45 to -0.17; P = 0.015.Conclusion: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain.Keywords: pregabalin, post-traumatic peripheral neuropathic pain, randomized

  10. Risk of injury after alcohol consumption from case-crossover studies in five countries from the America’s

    Science.gov (United States)

    Borges, Guilherme; Orozco, Ricardo; Monteiro, Maristela; Cherpitel, Cheryl; Then, Eddy Pérez; López, Víctor A.; Bassier-Paltoo, Marcia; Weil A., Donald; de Bradshaw, Aldacira M

    2012-01-01

    Aims This study aimed to: 1) provide relative risk (RR) estimates between acute alcohol use and injuries from emergency departments in the Dominican Republic, Guatemala, Guyana, Nicaragua and Panama, and 2) test whether the RR differs if two control periods for the estimates were used. Design Case-crossover methodology was used to obtain estimates of the RR of having an injury within six hours after drinking alcohol, using a pair-matching design with control periods of the same time of day the day prior to injury, and the same time of day and day of week the week prior to injury. Setting Emergency departments(EDs). Participants 2,503 injured patients from EDs were interviewed between 2010–2011, with a response rate of 92.6%. Measurements Number of drinks consumed within six hours prior to the injury and in the two control periods. Findings The RR of injury after drinking alcohol was 4.38 (95% confidence interval CI= 3.29–5.84) using as the control period the prior week, and 5.35 (CI=3.50–8.17) using as a control period the prior day. The RR was 5.08 (CI=4.15–6.23) in multiple matching. Those drinking 1–2 drinks had a RR of 4.85 (CI=3.12–7.54); those drinking 3–5 a RR of 5.00 (CI =3.47–7.18); those drinking 6–15 a RR of 4.54 (CI=3.36–6.14); and those drinking 16 or more a RR of 10.42 (CI=4.38–24.79). Conclusions As in other countries, alcohol drinking is a trigger for an injury in all five countries. The use of more than one control period give further strength to these findings from case-crossover analysis. PMID:22775508

  11. On the origin of crossover interference: A chromosome oscillatory movement (COM model

    Directory of Open Access Journals (Sweden)

    Hultén Maj A

    2011-04-01

    Full Text Available Abstract Background It is now nearly a century since it was first discovered that crossovers between homologous parental chromosomes, originating at the Prophase stage of Meiosis I, are not randomly placed. In fact, the number and distribution of crossovers are strictly regulated with crossovers/chiasmata formed in optimal positions along the length of individual chromosomes, facilitating regular chromosome segregation at the first meiotic division. In spite of much research addressing this question, the underlying mechanism(s for the phenomenon called crossover/chiasma interference is/are still unknown; and this constitutes an outstanding biological enigma. Results The Chromosome Oscillatory Movement (COM model for crossover/chiasma interference implies that, during Prophase of Meiosis I, oscillatory movements of the telomeres (attached to the nuclear membrane and the kinetochores (within the centromeres create waves along the length of chromosome pairs (bivalents so that crossing-over and chiasma formation is facilitated by the proximity of parental homologs induced at the nodal regions of the waves thus created. This model adequately explains the salient features of crossover/chiasma interference, where (1 there is normally at least one crossover/chiasma per bivalent, (2 the number is correlated to bivalent length, (3 the positions are dependent on the number per bivalent, (4 interference distances are on average longer over the centromere than along chromosome arms, and (5 there are significant changes in carriers of structural chromosome rearrangements. Conclusions The crossover/chiasma frequency distribution in humans and mice with normal karyotypes as well as in carriers of structural chromosome rearrangements are those expected on the COM model. Further studies are underway to analyze mechanical/mathematical aspects of this model for the origin of crossover/chiasma interference, using string replicas of the homologous chromosomes at the

  12. Estimation of hydrogen crossover through Nafion {sup registered} membranes in PEMFCs

    Energy Technology Data Exchange (ETDEWEB)

    Francia, Carlotta; Ijeri, Vijaykumar S.; Specchia, Stefania; Spinelli, Paolo [Department of Materials Science and Chemical Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino (Italy)

    2011-02-15

    It is well known that the membrane electrode assembly (MEA) of proton exchange membrane fuel cells (PEMFCs) can undergo deterioration, during long term operation, of both the electrode materials and the membrane. Hydrogen crossover, i.e., the undesired diffusion of the gas from the anode to the cathode through the membrane, has been ascribed as one of the main causes of deterioration of perfluorinated ionomer membranes, normally employed in PEMFCs. One of the effects of the hydrogen permeation across the membrane is the decrease of the cell's open circuit voltage (OCV), due to the reaction between the fuel and the oxidant at the cathode surface. Such reaction can lead to the production of peroxide radicals, causing the degradation of both the PEM and the catalyst layer. Hydrogen crossover increases when temperature, pressure and humidity of the cell rise. The hydrogen permeation rate through a very thin PEM is typically lower than 1 mA cm{sup -2} for a new MEA, but it can exceed 10-20 mA cm{sup -2} after long term operation. Various methods have been proposed to measure the rate of hydrogen crossover, mainly based on electrochemical tests on a single FC with a flow of nitrogen at the cathode, so that the steady state current corresponds to the oxidation of crossed hydrogen. Hydrogen crossover has been also determined indirectly by assuming that the changes in the OCV values are due to the passage of fuel from the anode to the cathode. In this paper, a simplified mathematical model for the direct determination of hydrogen crossover permeation rate is presented. Such a model is based on analytical expressions of the polarization terms and it is employed to determine the hydrogen crossover rate. The main results show that the hydrogen crossover current densities increased from 0.12 to 0.32 mA cm{sup -2}, by decreasing the thickness of the membranes and increasing the operating cell temperature. Moreover, the hydrogen crossover determined for a fresh MEA was

  13. Process of 3D wireless decentralized sensor deployment using parsing crossover scheme

    Directory of Open Access Journals (Sweden)

    Albert H.R. Ko

    2015-07-01

    Full Text Available A Wireless Sensor Networks (WSN usually consists of numerous wireless devices deployed in a region of interest, each able to collect and process environmental information and communicate with neighboring devices. It can thus be regarded as a Multi-Agent System for territorial security, where individual agents cooperate with each other to avoid duplication of effort and to exploit other agent’s capacities. The problem of sensor deployment becomes non-trivial when we consider environmental factors, such as terrain elevations. Due to the fact that all sensors are homogeneous, the chromosomes that encode sensor positions are actually interchangeable, and conventional crossover schemes such as uniform crossover would cause some redundancy as well as over-concentration in certain specific geographical area. We propose a Parsing Crossover Scheme that intends to reduce redundancy and ease geographical concentration pattern in an effort to facilitate the search. The proposed parsing crossover method demonstrates better performances than those of uniform crossover under different terrain irregularities.

  14. Dimensional analysis and prediction of dielectrophoretic crossover frequency of spherical particles

    Directory of Open Access Journals (Sweden)

    Che-Kai Yeh

    2017-06-01

    Full Text Available The manipulation of biological cells and micrometer-scale particles using dielectrophoresis (DEP is an indispensable technique for lab-on-a-chip systems for many biological and colloidal science applications. However, existing models, including the dipole model and numerical simulations based on Maxwell stress tensor (MST, cannot achieve high accuracy and high computation efficiency at the same time. The dipole model is widely used and provides adequate predictions on the crossover frequency of submicron particles, but cannot predict the crossover frequency for larger particles accurately; on the other hand, the MST method offers high accuracy for a wide variety of particle sizes and shapes, but is time-consuming and may lack predictive understanding of the interplay between key parameters. Here we present a mathematical model, using dimensional analysis and the Buckingham pi theorem, that permits high accuracy and efficiency in predicting the crossover frequency of spherical particles. The curve fitting and calculation are performed using commercial packages OriginLab and MATLAB, respectively. In addition, through this model we also can predict the conditions in which no crossover frequency exists. Also, we propose a pair of dimensionless parameters, forming a functional relation, that provide physical insights into the dependency of the crossover frequency on five key parameters. The model is verified under several scenarios using comprehensive MST simulations by COMSOL Multiphysics software (COMSOL, Inc. and some published experimental data.

  15. Flexible-to-semiflexible chain crossover on the pressure-area isotherm of a lipid bilayer

    Science.gov (United States)

    Krivonos, I. N.; Mukhin, S. I.

    2008-01-01

    We find theoretically that competition between ˜ K f q 4 and ˜ Qq 2 terms in the Fourier-transformed conformational energy of a single-lipid chain, in combination with interchain entropic repulsion in the hydrophobic part of the lipid (bi)layer, may cause a crossover on the bilayer pressure-area isotherm P( A)˜( A- A 0)-α. The crossover manifests itself in the transition from α = 5/3 to α = 3. Our microscopic model represents a single-lipid molecule as a worm-like chain with a finite irreducible cross-section area A 0, a flexural rigidity K f , and a stretching modulus Q in a parabolic potential with the self-consistent curvature B( A) formed by entropic interactions between hydrocarbon chains in the lipid layer. The crossover area A* obeys the relation Q/√ K f B( A*) ≈ 2. We predict a peculiar possibility of deducing the effective elastic moduli K f and Q of an individual hydrocarbon chain from the analysis of the isotherm with such a crossover. Also calculated is the crossover-related behavior of the area compressibility modulus K A , the equilibrium area per lipid A t , and the chain order parameter S(θ).

  16. Constructing higher order DNA origami arrays using DNA junctions of anti-parallel/parallel double crossovers

    Science.gov (United States)

    Ma, Zhipeng; Park, Seongsu; Yamashita, Naoki; Kawai, Kentaro; Hirai, Yoshikazu; Tsuchiya, Toshiyuki; Tabata, Osamu

    2016-06-01

    DNA origami provides a versatile method for the construction of nanostructures with defined shape, size and other properties; such nanostructures may enable a hierarchical assembly of large scale architecture for the placement of other nanomaterials with atomic precision. However, the effective use of these higher order structures as functional components depends on knowledge of their assembly behavior and mechanical properties. This paper demonstrates construction of higher order DNA origami arrays with controlled orientations based on the formation of two types of DNA junctions: anti-parallel and parallel double crossovers. A two-step assembly process, in which preformed rectangular DNA origami monomer structures themselves undergo further self-assembly to form numerically unlimited arrays, was investigated to reveal the influences of assembly parameters. AFM observations showed that when parallel double crossover DNA junctions are used, the assembly of DNA origami arrays occurs with fewer monomers than for structures formed using anti-parallel double crossovers, given the same assembly parameters, indicating that the configuration of parallel double crossovers is not energetically preferred. However, the direct measurement by AFM force-controlled mapping shows that both DNA junctions of anti-parallel and parallel double crossovers have homogeneous mechanical stability with any part of DNA origami.

  17. Sgs1 regulates gene conversion tract lengths and crossovers independently of its helicase activity.

    Science.gov (United States)

    Lo, Yi-Chen; Paffett, Kimberly S; Amit, Or; Clikeman, Jennifer A; Sterk, Rosa; Brenneman, Mark A; Nickoloff, Jac A

    2006-06-01

    RecQ helicases maintain genome stability and suppress tumors in higher eukaryotes through roles in replication and DNA repair. The yeast RecQ homolog Sgs1 interacts with Top3 topoisomerase and Rmi1. In vitro, Sgs1 binds to and branch migrates Holliday junctions (HJs) and the human RecQ homolog BLM, with Top3alpha, resolves synthetic double HJs in a noncrossover sense. Sgs1 suppresses crossovers during the homologous recombination (HR) repair of DNA double-strand breaks (DSBs). Crossovers are associated with long gene conversion tracts, suggesting a model in which Sgs1 helicase catalyzes reverse branch migration and convergence of double HJs for noncrossover resolution by Top3. Consistent with this model, we show that allelic crossovers and gene conversion tract lengths are increased in sgs1Delta. However, crossover and tract length suppression was independent of Sgs1 helicase activity, which argues against helicase-dependent HJ convergence. HJs may converge passively by a "random walk," and Sgs1 may play a structural role in stimulating Top3-dependent resolution. In addition to the new helicase-independent functions for Sgs1 in crossover and tract length control, we define three new helicase-dependent functions, including the suppression of chromosome loss, chromosome missegregation, and synthetic lethality in srs2Delta. We propose that Sgs1 has helicase-dependent functions in replication and helicase-independent functions in DSB repair by HR.

  18. Two measures of bilingualism in the memories of immigrants and indigenous minorities: crossover memories and codeswitching.

    Science.gov (United States)

    Altman, Carmit

    2015-04-01

    Two indices of bilingualism, crossover memories and codeswitching (CS), were explored in five groups of immigrant (English-Hebrew, Georgian-Hebrew Russian-Hebrew) and indigenous bilinguals (Arabic-Hebrew, Hebrew-English). Participants recalled memories in response to cue words and then were asked to report the language of retrieval and provide a more elaborate narrative. More memories were 'same language' memories, recalled in the language of the experimental session/cue word, but as many as 48 % of the memories were crossovers, i.e. memories reported in a language other than the language of the session/cue word. In an effort to examine the ecological validity of the self-reported language of the memories, the frequency of CS in the elaborated narratives was investigated. For the entire sample, more CS was found for self-reported crossover memories in L2 sessions. In a further analysis of CS in crossover memories, collapsed across L1 and L2 sessions, significant differences emerged between immigrants and indigenous bilinguals. Differences between immigrant and non-immigrant bilinguals are discussed in terms of the role of activation in crossover memories.

  19. Study on nature of crossover phenomena with application to gearbox fault diagnosis

    Science.gov (United States)

    Jiang, Xingxing; Li, Shunming; Wang, Yong

    2017-01-01

    Detrended Fluctuation Analysis (DFA) is a robust tool for uncovering long-range correlations hidden in the non-stationary data. Recently, crossover properties of the scaling-law curve obtained by DFA have been applied to diagnose gearbox faults. However, the nature of the crossover phenomena has not been well- explained. In this paper, an explanation for the nature of crossover phenomena is specifically given, which is conducive to discovering novel features for gearbox fault diagnosis. Firstly, an explicit exposition of the crossover phenomena is provided by analyzing the gearbox vibration signal. Secondly, the nature of crossover phenomena is specifically disclosed. Thirdly, the features with clear physical meaning are proposed to describe operating conditions of a gearbox. Then, to overcome the deficiency of feature extraction through visual observation, a piecewise-linear regression model is utilized to extract the features automatically. Lastly, several combinations of these features are used to classify the fault types. As a consequence, the proposed novel features are verified that they can well- distinguish the gearbox operating conditions with different fault types and severities, and deliver a better performance than the existing method depending on the sensitive index (SI).

  20. Factors influencing recombination frequency and distribution in a human meiotic crossover hotspot.

    Science.gov (United States)

    Jeffreys, Alec J; Neumann, Rita

    2005-08-01

    Little is known about the factors that influence the frequency and distribution of meiotic recombination events within human crossover hotspots. We now describe the detailed analysis of sperm recombination in the NID1 hotspot. Like the neighbouring MS32 hotspot, the NID1 hotspot is associated with a minisatellite, suggesting that hotspots predispose DNA to tandem repetition. Unlike MS32, crossover resolution breakpoints in NID1 avoid the minisatellite, producing a cold spot within the hotspot. This avoidance may be related to the palindromic nature of the minisatellite interfering with the generation and/or processing of recombination intermediates. The NID1 hotspot also contains a single nucleotide polymorphism (SNP) close to the centre, which appears to directly influence the frequency of crossover initiation. Quantitative gene conversion assays show that this SNP affects the frequency of gene conversion and crossover to a very similar extent, providing evidence that conversions and crossovers are triggered by the same recombination initiating events. The recombination-suppressing allele is over-transmitted to recombinant progeny, and provides the most dramatic example to date of recombination-mediated meiotic drive, of a magnitude sufficient to virtually guarantee that the recombination suppressor will eventually replace the more active allele in human populations.

  1. Anode reaction mechanism and crossover in direct dimethyl ether fuel cell

    Science.gov (United States)

    Mizutani, Itsuko; Liu, Yan; Mitsushima, Shigenori; Ota, Ken-ichiro; Kamiya, Nobuyuki

    The anode reaction mechanism and the crossover of a direct dimethyl ether fuel cell (DDMEFC) have been investigated. This was done by considering the anode products of the half-cell and DDMEFC experiments. It was found that the CO 2 current efficiency of the DDMEFC was almost 1 at 30-80 °C and that this value was higher than that of a DMFC. The main by-products of the DDMEFC were methyl formate and methanol whose amounts are negligibly small compared to CO 2. With respect to crossover, the influence of DME on the oxygen reduction reaction (ORR) was examined with a half-cell, and the amount of crossover of DME was measured while operating an actually constructed DDMEFC. From these experiments, it was found that DME does not influence the ORR as much as methanol under similar conditions. Furthermore, the amount of crossover of DME decreased with an increase in temperature and current density and it was one-half that of methanol on open circuit and at 80 °C. The CO 2 current efficiency of the DDMEFC is higher than that of a DMFC, and the influence of crossover in the DDMEFC is less than that in the DMFC. Since the temperature dependence of the reactivity of DME is larger than that of methanol, the higher output is expected for the DDMEFC at the elevated temperature. Therefore, the DDMEFC has a promising potential as a portable power source in the future.

  2. On the Crossover of Boundary Currents in an Idealized Model of the Red Sea

    KAUST Repository

    Zhai, Ping

    2015-05-01

    © 2015 American Meteorological Society. The west-to-east crossover of boundary currents has been seen in mean circulation schemes from several past models of the Red Sea. This study investigates the mechanisms that produce and control the crossover in an idealized, eddy-resolving numerical model of the Red Sea. The authors also review the observational evidence and derive an analytical estimate for the crossover latitude. The surface buoyancy loss increases northward in the idealized model, and the resultant mean circulation consists of an anticyclonic gyre in the south and a cyclonic gyre in the north. In the midbasin, the northward surface flow crosses from the western boundary to the eastern boundary. Numerical experiments with different parameters indicate that the crossover latitude of the boundary currents changes with f0, β, and the meridional gradient of surface buoyancy forcing. In the analytical estimate, which is based on quasigeostrophic, β-plane dynamics, the crossover is predicted to lie at the latitude where the net potential vorticity advection (including an eddy component) is zero. Various terms in the potential vorticity budget can be estimated using a buoyancy budget, a thermal wind balance, and a parameterization of baroclinic instability.

  3. Dimensional analysis and prediction of dielectrophoretic crossover frequency of spherical particles

    Science.gov (United States)

    Yeh, Che-Kai; Juang, Jia-Yang

    2017-06-01

    The manipulation of biological cells and micrometer-scale particles using dielectrophoresis (DEP) is an indispensable technique for lab-on-a-chip systems for many biological and colloidal science applications. However, existing models, including the dipole model and numerical simulations based on Maxwell stress tensor (MST), cannot achieve high accuracy and high computation efficiency at the same time. The dipole model is widely used and provides adequate predictions on the crossover frequency of submicron particles, but cannot predict the crossover frequency for larger particles accurately; on the other hand, the MST method offers high accuracy for a wide variety of particle sizes and shapes, but is time-consuming and may lack predictive understanding of the interplay between key parameters. Here we present a mathematical model, using dimensional analysis and the Buckingham pi theorem, that permits high accuracy and efficiency in predicting the crossover frequency of spherical particles. The curve fitting and calculation are performed using commercial packages OriginLab and MATLAB, respectively. In addition, through this model we also can predict the conditions in which no crossover frequency exists. Also, we propose a pair of dimensionless parameters, forming a functional relation, that provide physical insights into the dependency of the crossover frequency on five key parameters. The model is verified under several scenarios using comprehensive MST simulations by COMSOL Multiphysics software (COMSOL, Inc.) and some published experimental data.

  4. The effects of a prophylactic knee brace and two neoprene knee sleeves on the performance of healthy athletes: a crossover randomized controlled trial.

    Science.gov (United States)

    Mortaza, Niyousha; Ebrahimi, Ismail; Jamshidi, Ali Ashraf; Abdollah, Vahid; Kamali, Mohammad; Abas, Wan Abu Bakar Wan; Osman, Noor Azuan Abu

    2012-01-01

    Knee injury is one of the major problems in sports medicine, and the use of prophylactic knee braces is an attempt to reduce the occurrence and/or severity of injuries to the knee joint ligament(s) without inhibiting knee mobility. The aim of the present study was to examine the effect of one recently designed prophylactic knee brace and two neoprene knee sleeves upon performance of healthy athletes. Thirty-one healthy male athletes (age = 21.2 ± 1.5) volunteered as participants to examine the effect of prophylactic knee brace/sleeves on performance using isokinetic and functional tests. All subjects were tested in four conditions in a random order: 1. nonbraced (control) 2. using a neoprene knee sleeve 3. using a knee sleeve with four bilateral metal supports and 4. using a prophylactic knee brace. The study design was a crossover, randomized, controlled trial. Subjects completed single leg vertical jump, cross-over hop, and the isokinetic knee flexion and extension (at 60, 180, 300°/sec). Data were collected from the above tests and analyzed for jump height, cross-over hop distance, peak torque to body weight ratio and average power, respectively. Comparisons of these variables in the four testing conditions revealed no statistically significant difference (p>0.05). The selected prophylactic brace/sleeves did not significantly inhibit athletic performance which might verify that their structure and design have caused no complication in the normal function of the knee joint. Moreover, it could be speculated that, if the brace or the sleeves had any limiting effect, our young healthy athletic subjects were well able to generate a mean peak torque large enough to overcome this possible restriction. Further studies are suggested to investigate the long term effect of these prophylactic knee brace and sleeves as well as their possible effect on the adjacent joints to the knee.

  5. The effects of a prophylactic knee brace and two neoprene knee sleeves on the performance of healthy athletes: a crossover randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Niyousha Mortaza

    Full Text Available Knee injury is one of the major problems in sports medicine, and the use of prophylactic knee braces is an attempt to reduce the occurrence and/or severity of injuries to the knee joint ligament(s without inhibiting knee mobility. The aim of the present study was to examine the effect of one recently designed prophylactic knee brace and two neoprene knee sleeves upon performance of healthy athletes. Thirty-one healthy male athletes (age = 21.2 ± 1.5 volunteered as participants to examine the effect of prophylactic knee brace/sleeves on performance using isokinetic and functional tests. All subjects were tested in four conditions in a random order: 1. nonbraced (control 2. using a neoprene knee sleeve 3. using a knee sleeve with four bilateral metal supports and 4. using a prophylactic knee brace. The study design was a crossover, randomized, controlled trial. Subjects completed single leg vertical jump, cross-over hop, and the isokinetic knee flexion and extension (at 60, 180, 300°/sec. Data were collected from the above tests and analyzed for jump height, cross-over hop distance, peak torque to body weight ratio and average power, respectively. Comparisons of these variables in the four testing conditions revealed no statistically significant difference (p>0.05. The selected prophylactic brace/sleeves did not significantly inhibit athletic performance which might verify that their structure and design have caused no complication in the normal function of the knee joint. Moreover, it could be speculated that, if the brace or the sleeves had any limiting effect, our young healthy athletic subjects were well able to generate a mean peak torque large enough to overcome this possible restriction. Further studies are suggested to investigate the long term effect of these prophylactic knee brace and sleeves as well as their possible effect on the adjacent joints to the knee.

  6. Describing soil surface microrelief by crossover length and fractal dimension

    Directory of Open Access Journals (Sweden)

    E. Vidal Vázquez

    2007-05-01

    Full Text Available Accurate description of soil surface topography is essential because different tillage tools produce different soil surface roughness conditions, which in turn affects many processes across the soil surface boundary. Advantages of fractal analysis in soil microrelief assessment have been recognised but the use of fractal indices in practice remains challenging. There is also little information on how soil surface roughness decays under natural rainfall conditions. The objectives of this work were to investigate the decay of initial surface roughness induced by natural rainfall under different soil tillage systems and to compare the performances of a classical statistical index and fractal microrelief indices. Field experiments were performed on an Oxisol at Campinas, São Paulo State (Brazil. Six tillage treatments, namely, disc harrow, disc plow, chisel plow, disc harrow + disc level, disc plow + disc level and chisel plow + disc level were tested. Measurements were made four times, firstly just after tillage and subsequently with increasing amounts of natural rainfall. Duplicated measurements were taken per treatment and date, yielding a total of 48 experimental surfaces. The sampling scheme was a square grid with 25×25 mm point spacing and the plot size was 1350×1350 mm, so that each data set consisted of 3025 individual elevation points. Statistical and fractal indices were calculated both for oriented and random roughness conditions, i.e. after height reading have been corrected for slope and for slope and tillage tool marks. The main drawback of the standard statistical index random roughness, RR, lies in its no spatial nature. The fractal approach requires two indices, fractal dimension, D, which describes how roughness changes with scale, and crossover length, l, specifying the variance of surface microrelief at a reference scale. Fractal parameters D and l, were estimated by two independent self-affine models

  7. Multimodal Cognitive Enhancement Therapy for Patients with Mild Cognitive Impairment and Mild Dementia: A Multi- Center, Randomized, Controlled, Double-Blind, Crossover Trial.

    Science.gov (United States)

    Han, Ji Won; Lee, Hyeonggon; Hong, Jong Woo; Kim, Kayoung; Kim, Taehyun; Byun, Hye Jin; Ko, Ji Won; Youn, Jong Chul; Ryu, Seung-Ho; Lee, Nam-Jin; Pae, Chi-Un; Kim, Ki Woong

    2017-01-01

    We developed and evaluated the effect of Multimodal Cognitive Enhancement Therapy (MCET) consisting of cognitive training, cognitive stimulations, reality orientation, physical therapy, reminiscence therapy, and music therapy in combination in older people with mild cognitive impairment (MCI) or mild dementia. This study was a multi-center, double-blind, randomized, placebo-controlled, two-period cross-over study (two 8-week treatment phases separated by a 4-week wash-out period). Sixty-four participants with MCI or dementia whose Clinical Dementia Rating was 0.5 or 1 were randomized to the MCET group or the mock-therapy (placebo) group. Outcomes were measured at baseline, week 9, and week 21. Fifty-five patients completed the study. Mini-Mental State Examination (effect size = 0.47, p = 0.013) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (effect size = 0.35, p = 0.045) scores were significantly improved in the MCET compared with mock-therapy group. Revised Memory and Behavior Problems Checklist frequency (effect size = 0.38, p = 0.046) and self-rated Quality of Life - Alzheimer's Disease (effect size = 0.39, p = 0.047) scores were significantly improved in the MCET compared with mock-therapy. MCET improved cognition, behavior, and quality of life in people with MCI or mild dementia more effectively than conventional cognitive enhancing activities did.

  8. Impact of olive oil-rich diet on serum omentin and adiponectin levels: a randomized cross-over clinical trial among overweight women.

    Science.gov (United States)

    Kabiri, Akram; Hosseinzadeh-Attar, Mohammad Javad; Haghighatdoost, Fahimeh; Eshraghian, Mohammadreza; Esmaillzadeh, Ahmad

    2017-08-01

    This study aimed to investigate the effect of olive oil-rich diet on omentin and adiponectin concentrations. This cross-over randomized trial included 17 overweight women. Participants were assigned to consume either a usual (16% saturated fatty acids [SFA] and 8% monounsaturated fatty acid [MUFA]) or an olive oil-rich diet (16% MUFA and 8% SFA) for 6 weeks crossing over after a 2-week washout period. There was no significant difference in the changes of omentin between two dietary interventions. However, in the adjusted model for polyunsaturated fatty acids and fat mass, usual diet tended to decrease omentin levels whilst olive oil-rich diet tended to increase (-56.1 ± 32.0 versus 40.6 ± 32.0 ng/mL; p = .056). Adiponectin levels increased during two periods, but changes were greater during olive oil-rich diet with a trend toward significance (4.8 ± 3.0 versus 13.4 ± 3.0 μg/mL; p = .06). Consumption of olive oil-rich diet tended to increase omentin and adiponectin in comparison with the usual diet.

  9. Crossover replantation after bilateral traumatic lower limb amputations: a case report

    Directory of Open Access Journals (Sweden)

    Fang Jun

    2012-07-01

    Full Text Available Abstract Introduction Replantation of a limb to the contralateral stump after bilateral traumatic amputations is rare. To the best of our knowledge, there are only a few reports of crossover lower limb replantation in the literature. Case presentation We treated a 37-year-old Chinese woman with bilateral lower limb crush injuries sustained in a traffic accident. Her lower limb injuries were at different anatomic levels. We performed emergency bilateral amputations followed by crossover replantation. Five years later, the woman had recovered well, and had perfect movement and stability in her replanted leg. After reviewing the literature, we thought that presentation of our patient’s case might provide useful information for clinicians. Conclusions Crossover replantation should be considered when evaluating a patient with bilateral lower limb injuries, thus allowing the patient to touch the ground and stand using their own foot.

  10. Universal low-temperature crossover in two-channel Kondo models

    Science.gov (United States)

    Mitchell, Andrew K.; Sela, Eran

    2012-06-01

    An exact expression is derived for the electron Green function in two-channel Kondo models with one and two impurities, describing the crossover from non-Fermi liquid (NFL) behavior at intermediate temperatures to standard Fermi liquid (FL) physics at low temperatures. Symmetry-breaking perturbations generically present in experiment ensure the standard low-energy FL description, but the full crossover is wholly characteristic of the unstable NFL state. Distinctive conductance lineshapes in quantum dot devices should result. We exploit a connection between this crossover and one occurring in a classical boundary Ising model to calculate real-space electron densities at finite temperature. The single universal finite-temperature Green function is then extracted by inverting the integral transformation relating these Friedel oscillations to the t matrix. Excellent agreement is demonstrated between exact results and full numerical renormalization group calculations.

  11. Universal temperature crossover behavior of electrical conductance in a single oligothiophene molecular wire.

    Science.gov (United States)

    Lee, See Kei; Yamada, Ryo; Tanaka, Shoji; Chang, Gap Soo; Asai, Yoshihiro; Tada, Hirokazu

    2012-06-26

    We have observed and analyzed a universal temperature crossover behavior of electrical conductance in a single oligothiophene molecular wire. The crossover between the Arrhenius-type temperature dependence at high temperature and the temperature-invariant behavior at low temperature is found at a critical molecular wire length of 5.6 nm, where we found a change from the exponential length dependence to the length-invariant behavior. We have derived a scaling function analysis for the origin of the crossover behavior. After assuring that the analysis fits the explanation of the Keldysh Green's function calculation for the temperature dependence, we have applied it to our experimental results and found successfully that our scaling function gives a universal description of the temperature dependence for all over the temperature range.

  12. Detecting phase transitions and crossovers in Hubbard models using the fidelity susceptibility

    Science.gov (United States)

    Huang, Li; Wang, Yilin; Wang, Lei; Werner, Philipp

    2016-12-01

    A generalized version of the fidelity susceptibility of single-band and multiorbital Hubbard models is systematically studied using single-site dynamical mean-field theory in combination with a hybridization expansion continuous-time quantum Monte Carlo impurity solver. We find that the fidelity susceptibility is extremely sensitive to changes in the state of the system. It can be used as a numerically inexpensive tool to detect and characterize a broad range of phase transitions and crossovers in Hubbard models, including (orbital-selective) Mott metal-insulator transitions, magnetic phase transitions, high-spin to low-spin transitions, Fermi-liquid to non-Fermi-liquid crossovers, and spin-freezing crossovers.

  13. Correlation length and universality in the BCS-BEC crossover for energy-dependent resonance superfluidity

    Science.gov (United States)

    Musolino, S.; Chiofalo, M.-L.

    2017-07-01

    We consider the BCS-BEC crossover of a quantum Fermi gas at T = 0 in the presence of an energy-dependent Fano-Feshbach resonance, driving the system from broad to narrow limits. We choose a minimal microscopic potential reproducing the two-particle resonance physics in terms of the scattering length a and the effective range R∗ representing the resonance width, and solve the BCS mean-field equations varying a, R∗ and the density. We show that the condensate fraction manifests a universal behavior when the correlation length, measuring the pair size, is used as the crossover parameter. Generally, a negative effective range has the effect of stretching the crossover region between the two extreme regimes, as evidenced by the behavior of the chemical potential. These results can be useful in view of the more recent perspectives of realizing narrow resonances also by optical means and amenable as a base quantum Monte Carlo simulations.

  14. The Crossover between Life Expectancies at Birth and at Age One

    DEFF Research Database (Denmark)

    Canudas-Romo, Vladimir; Becker, S

    2011-01-01

    The single most used demographic measure to describe population health is life expectancy at birth, but life expectancies at ages other than zero are also used in the study of human longevity. Our intuition tells us that the longest life expectancy is that of a newborn. However, historically......, the expectation of life at age one (e1) has exceeded the expectation of life at birth (e0). The crossover between e0 and e1 only occurred in the developed world in the second half of the twentieth century. Life tables for populations that have not achieved this crossing between life expectancy at birth and at age...... one are referred to here as imbalanced. This crossover occurs when infant mortality is equal to the inverse of life expectancy at age one. This simple relation between mortality at age zero and mortality after age one divides the world into countries that have achieved the crossover in life...

  15. Experimental observation of structural crossover in binary mixtures of colloidal hard spheres.

    Science.gov (United States)

    Baumgartl, Jörg; Dullens, Roel P A; Dijkstra, Marjolein; Roth, Roland; Bechinger, Clemens

    2007-05-11

    Using confocal microscopy, we investigate the structure of binary mixtures of colloidal hard spheres with size ratio q=0.61. As a function of the packing fraction of the two particle species, we observe a marked change of the dominant wavelength in the pair-correlation function. This behavior is in excellent agreement with a recently predicted structural crossover in such mixtures. In addition, the repercussions of structural crossover on the real-space structure of a binary fluid are analyzed. We suggest a relation between crossover and the lateral extension of networks containing only equally-sized particles that are connected by nearest-neighbor bonds. This is supported by Monte Carlo simulations which are performed at different packing fractions and size ratios.

  16. Influence of the iron spin crossover in ferropericlase on the lower mantle geotherm

    CERN Document Server

    Valencia-Cardona, Juan J; Wu, Zhongqing; Houser, Christine; Yuen, David A; Wentzcovitch, Renata M

    2016-01-01

    The iron spin crossover in ferropericlase introduces anomalies in its thermodynamics and thermoelastic properties. Here we investigate how these anomalies can affect the lower mantle geotherm. The effect is examined in mantle aggregates consisting of mixtures of bridgmanite, ferropericlase, and CaSiO$_3$ perovskite, with different Mg/Si ratios varying from harzburgitic to perovskitic (Mg/Si$\\sim$1.5 to 0.8). We find that the anomalies introduced by the spin crossover increase the isentropic gradient and thus the geotherm proportionally to the amount of ferropericlase. The geotherms can be as much as $\\sim$ 200K hotter than the conventional adiabatic geotherm at deep lower mantle conditions. Aggregate elastic moduli and seismic velocities are also sensitive to the spin crossover and the geotherm, which impacts analyses of lower mantle velocities and composition.

  17. Phase transformations of under-cooled austenite of new bainitic materials for scissors crossovers

    Directory of Open Access Journals (Sweden)

    J. Pacyna

    2008-07-01

    Full Text Available The paper contains CCT diagrams presenting a transformation kinetics of under-cooled austenite from two new bainitic cast steels which the scissors crossovers for heavy-duty railway tracks (min. 230kN/axle at the speed up to 200 km/h are made of. The cooling ranges of UIC60 type railway tracks plot on the CCT diagrams indicate that there is a 100% bainitic structure in the scissors crossovers made of these cast steels as well, but mainly it would be a favourable for cracking resistance lower bainite. The achievable hardness of scissors crossovers made of new materials make it possible to use high–temperature tempering resulting in obtaining of good crack resistance. However one should provide a good quality of castings made.

  18. Is there a need for new models of the spin crossover?

    CERN Document Server

    Boca, R

    2003-01-01

    The existing models of the low-spin to high-spin transition (spin crossover) are briefly reviewed. Experimental data pointing to a need of new models are displayed. A statistical model with the distribution of the solid-state cooperativeness is outlined. A modeling is shown as well as its application to a spin crossover system [Fe(bzimpy) sub 2](ClO sub 4) sub 2 x 0.25H sub 2 O. This shows an abrupt spin crossover at temperature as high as 403 K with a hysteresis width of 12 K. The angled walls of the hysteresis loop can be followed by the outlined statistical model. Refs. 35 (author)

  19. Influence of the iron spin crossover in ferropericlase on the lower mantle geotherm

    Science.gov (United States)

    Valencia-Cardona, Juan J.; Shukla, Gaurav; Wu, Zhongqing; Houser, Christine; Yuen, David A.; Wentzcovitch, Renata M.

    2017-05-01

    The iron spin crossover in ferropericlase introduces anomalies in its thermodynamics and thermoelastic properties. Here we investigate how these anomalies can affect the lower mantle geotherm using thermodynamics properties from ab initio calculations. The anomalous effect is examined in mantle aggregates consisting of mixtures of bridgmanite, ferropericlase, and CaSiO3 perovskite, with different Mg/Si ratios varying from harzburgitic to perovskitic (Mg/Si ˜ 1.5 to 0.8). We find that the anomalies introduced by the spin crossover increase the isentropic gradient and thus the geotherm proportionally to the amount of ferropericlase. The geotherms can be as much as ˜200 K hotter than the conventional adiabatic geotherm at deep lower mantle conditions. Aggregate elastic moduli and seismic velocities are also sensitive to the spin crossover and the geotherm, which impacts analyses of lower mantle velocities and composition.

  20. Compressibility of water in magma and the prediction of density crossovers in mantle differentiation.

    Science.gov (United States)

    Agee, Carl B

    2008-11-28

    Hydrous silicate melts appear to have greater compressibility relative to anhydrous melts of the same composition at low pressures (planetary differentiation. From these compression curves, crystal-liquid density crossovers are predicted for the mantles of the Earth and Mars. For the Earth, trapped dense hydrous melts may reside atop the 410km discontinuity, and, although not required to be hydrous, atop the core-mantle boundary (CMB), in accord with seismic observations of low-velocity zones in these regions. For Mars, a density crossover at the base of the upper mantle is predicted, which would produce a low-velocity zone at a depth of approximately 1200km. If perovskite is stable at the base of the Martian mantle, then density crossovers or trapped dense hydrous melts are unlikely to reside there, and long-lived, melt-induced, low-velocity regions atop the CMB are not predicted.

  1. STAR POLYMERS IN GOOD SOLVENTS FROM DILUTE TO CONCENTRATED REGIMES: CROSSOVER APPROACH

    Directory of Open Access Journals (Sweden)

    S.B.Kiselev

    2002-01-01

    Full Text Available An introduction is given to the crossover theory of the conformational and thermodynamic properties of star polymers in good solvents. The crossover theory is tested against Monte Carlo simulation data for the structure and thermodynamics of model star polymers. In good solvent conditions, star polymers approach a "universal" limit as N → ∞, however, there are two types of approach towards this limit. In the dilute regime, a critical degree of polymerization N* is found to play a similar role as the Ginzburg number in the crossover theory for critical phenomena in simple fluids. A rescaled penetration function is found to control the free energy of star polymer solutions in the dilute and semidilute regions. This equation of state captures the scaling behaviour of polymer solutions in the dilute/semidilute regimes and also performs well in the concentrated regimes, where the details of the monomer-monomer interactions become important.

  2. BIAS IN THE CASE-CROSSOVER DESIGN: IMPLICATIONS FOR STUDIES OF AIR POLLUTION. (R827355)

    Science.gov (United States)

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

  3. Improving efficiency in cluster-randomized study design and implementation: taking advantage of a crossover

    OpenAIRE

    Reich NG; Milstone AM

    2013-01-01

    Nicholas G Reich,1 Aaron M Milstone2,3 1Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, UMass-Amherst, Amherst, MA, USA; 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 3Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA Abstract: While individually randomized trials have long provided the gold standard of clinical evidence, the use of cluster-randomized tr...

  4. Impaired alcohol metabolism after gastric bypass surgery: a case-crossover trial.

    Science.gov (United States)

    Woodard, Gavitt A; Downey, John; Hernandez-Boussard, Tina; Morton, John M

    2011-02-01

    Severe obesity remains the leading public health crisis of the industrialized world, with bariatric surgery the only effective and enduring treatment. Poor psychological adjustment has been occasionally reported postoperatively. In addition, evidence suggests that patients can metabolize alcohol differently after gastric bypass. Preoperatively and at 3 and 6 months postoperatively, 19 Roux-en-Y gastric bypass (RYGB) patients' breath alcohol content (BAC) was measured every 5 minutes after drinking 5 oz red wine to determine peak BAC and time until sober in a case-crossover design preoperatively and at 6 months postoperatively. Patients reported symptoms experienced when intoxicated and answered a questionnaire of drinking habits. The peak BAC in patients after RYGB was considerably higher at 3 months (0.059%) and 6 months (0.088%) postoperatively than matched preoperative levels (0.024%). Patients also took considerably more time to return to sober at 3 months (61 minutes) and 6 months (88 minutes) than preoperatively (49 minutes). Postoperative intoxication was associated with lower levels of diaphoresis, flushing, and hyperactivity and higher levels of dizziness, warmth, and double vision. Postoperative patients reported drinking considerably less alcohol, fewer preferred beer, and more preferred wine than before surgery. This is the first study to match preoperative and postoperative alcohol metabolism in gastric bypass patients. Post-RYGB patients have much higher peak BAC after ingesting alcohol and require more time to become sober. Patients who drink alcohol after gastric bypass surgery should exercise caution. Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  5. A Randomised Cross-Over Pharmacokinetic Bioavailability Study of Synthetic versus Kiwifruit-Derived Vitamin C

    Directory of Open Access Journals (Sweden)

    Margreet C. M. Vissers

    2013-11-01

    Full Text Available Kiwifruit are a rich source of vitamin C and also contain numerous phytochemicals, such as flavonoids, which may influence the bioavailability of kiwifruit-derived vitamin C. The aim of this study was to compare the relative bioavailability of synthetic versus kiwifruit-derived vitamin C using a randomised cross-over pharmacokinetic study design. Nine non-smoking males (aged 18–35 years received either a chewable tablet (200 mg vitamin C or the equivalent dose from gold kiwifruit (Actinidia chinensis var. Sungold. Fasting blood and urine were collected half hourly to hourly over the eight hours following intervention. The ascorbate content of the plasma and urine was determined using HPLC with electrochemical detection. Plasma ascorbate levels increased from 0.5 h after the intervention (P = 0.008. No significant differences in the plasma time-concentration curves were observed between the two interventions (P = 0.645. An estimate of the total increase in plasma ascorbate indicated complete uptake of the ingested vitamin C tablet and kiwifruit-derived vitamin C. There was an increase in urinary ascorbate excretion, relative to urinary creatinine, from two hours post intervention (P < 0.001. There was also a significant difference between the two interventions, with enhanced ascorbate excretion observed in the kiwifruit group (P = 0.016. Urinary excretion was calculated as ~40% and ~50% of the ingested dose from the vitamin C tablet and kiwifruit arms, respectively. Overall, our pharmacokinetic study has shown comparable relative bioavailability of kiwifruit-derived vitamin C and synthetic vitamin C.

  6. Is there adaptation in the ozone mortality relationship: A multi-city case-crossover analysis

    Directory of Open Access Journals (Sweden)

    Schwartz Joel

    2008-05-01

    Full Text Available Abstract Background Ozone has been associated with daily mortality, mainly in the summer period. Despite the ample literature on adaptation of inflammatory and pulmonary responses to ozone, and the link, in cohort studies, between lung function and mortality risk there has been little done to date to examine the question of adaptation in the acute mortality risk associated with ambient ozone. Methods We applied a case-crossover design in 48 US cities to examine the ozone effect by season, by month and by age groups, particularly focusing on whether there was an adaptation effect. Results We found that the same day ozone effect was highest in summer with a 0.5% (95% CI: 0.38, 0.62 increase in total mortality for 10 ppb increase in 8-hr ozone, whilst the effect decrease to null in autumn and winter. We found higher effects in the months May- July with a 0.46% (95% CI: 0.24, 0.68 increase in total mortality for 10 ppb increase in ozone in June, and a 0.65% (95% CI: 0.47, 0.82 increase in mortality during July. The effect decreased in August and became null in September. We found similar effects from the age group 51–60 up to age 80 and a lower effect in 80 years and older. Conclusion The mortality effects of ozone appear diminished later in the ozone season, reaching the null effect previously reported in winter by September. More work should address this issue and examine the biological mechanism of adaptation.

  7. How to deal with morning bad breath: A randomized, crossover clinical trial

    Directory of Open Access Journals (Sweden)

    Jeronimo M Oliveira-Neto

    2013-01-01

    Full Text Available Context: The absence of a protocol for the treatment of halitosis has led us to compare mouthrinses with mechanical oral hygiene procedures for treating morning breath by employing a hand-held sulfide monitor. Aims: To compare the efficacy of five modalities of treatment for controlling morning halitosis in subjects with no dental or periodontal disease. Settings and Design: This is a five-period, randomized, crossover clinical trial. Materials and Methods: Twenty volunteers were randomly assigned to the trial. Testing involved the use of a conventional tongue scraper, a tongue scraper joined to the back of a toothbrush′s head, two mouthrinses (0.05% cetylpyridinium chloride and 0.12% chlorhexidine digluconate and a soft-bristled toothbrush and fluoride toothpaste for practicing oral hygiene. Statistical Analysis Used: Data analysis was performed using SPSS version 17 for Windows and NCSS 2007 software (P < 0.05. The products and the periods were compared with each other using the Friedman′s test. When significant differences (P < 0.05 were determined, the products and periods were compared in pairs by using the Wilcoxon′s test and by adjusting the original significance level (0.05 for multiple comparisons by using the Bonferroni′s method. Results: The toothbrush′s tongue scraper was able to significantly reduce bad breath for up to 2 h. Chlorhexidine reduced bad breath only at the end of the second hour, an effect that lasted for 3 h. Conclusions: Mechanical tongue cleaning was able to immediately reduce bad breath for a short period, whereas chlorhexidine and mechanical oral hygiene reduced bad breath for longer periods, achieving the best results against morning breath.

  8. A case-crossover study of alcohol consumption, meals and the risk of road traffic crashes

    Directory of Open Access Journals (Sweden)

    Marchetti Riccardo

    2009-09-01

    Full Text Available Abstract Background The case-crossover (CC design has proved effective to investigate the association between alcohol use and injuries in general, but has never been applied to study alcohol use and road traffic crashes (RTCs specifically. This study aims at investigating the association between alcohol and meal consumption and the risk of RTCs using intrapersonal comparisons of subjects while driving. Methods Drivers admitted to an Italian emergency room (ER after RTCs in 2007 were interviewed about personal, vehicle, and crash characteristics as well as hourly patterns of driving, and alcohol and food intake in the 24 hours before the crash. The odds ratio (OR of a RTC was estimated through a CC, matched pair interval approach. Alcohol and meal consumption 6 and 2 hours before the RTC (case exposure window were compared with exposures in earlier control windows of analogous length. Results Of 574 patients enrolled, 326 (56.8% reported previous driving from 6 to 18 hours before the RTC and were eligible for analysis. The ORs (mutually adjusted were 2.25 (95%CI 1.11-4.57 for alcohol and 0.94 (0.47-1.88 for meals. OR for alcohol was already increased at low (1-2 units doses - 2.17 (1.03-4.57 and the trend of increase for each unit was significant - 1.64 (95%CI 1.05-2.57. In drivers at fault the OR for alcohol was 21.22 (2.31-194.79. The OR estimate for meal consumption seemed to increase in case of previous sleep deprivation, 2.06 (0.25-17.00. Conclusion Each single unit of acute alcohol consumption increases the risk of RTCs, in contrast with the 'legal' threshold allowed in some countries. Meal consumption is not associated with RTCs, but its combined effects with sleepiness need further elucidation.

  9. How air pollution influences clinical management of respiratory diseases. A case-crossover study in Milan

    Directory of Open Access Journals (Sweden)

    Santus Pierachille

    2012-10-01

    Full Text Available Abstract Background Environmental pollution is a known risk factor for multiple diseases and furthermore increases rate of hospitalisations. We investigated the correlation between emergency room admissions (ERAs of the general population for respiratory diseases and the environmental pollutant levels in Milan, a metropolis in northern Italy. Methods We collected data from 45770 ERAs for respiratory diseases. A time-stratified case-crossover design was used to investigate the association between air pollution levels and ERAs for acute respiratory conditions. The effects of air pollutants were investigated at lag 0 to lag 5, lag 0–2 and lag 3–5 in both single and multi-pollutant models, adjusted for daily weather variables. Results An increase in ozone (O3 levels at lag 3–5 was associated with a 78% increase in the number of ERAs for asthma, especially during the warm season. Exposure to carbon monoxide (CO proved to be a risk factor for pneumonia at lag 0–2 and in the warm season increased the risk of ERA by 66%. A significant association was found between ERAs for COPD exacerbation and levels of sulphur dioxide (SO2, CO, nitrate dioxide (NO2, and particulate matter (PM10 and PM2.5. The multipollutant model that includes all pollutants showed a significant association between CO (26% and ERA for upper respiratory tract diseases at lag 0–2. For chronic obstructive pulmonary disease (COPD exacerbations, only CO (OR 1.19 showed a significant association. Conclusions Exposure to environmental pollution, even at typical low levels, can increase the risk of ERA for acute respiratory diseases and exacerbation of obstructive lung diseases in the general population.

  10. Airborne pollutants and lacunar stroke: a case cross-over analysis on stroke unit admissions.

    Science.gov (United States)

    Corea, Francesco; Silvestrelli, Giorgio; Baccarelli, Andrea; Giua, Alessandra; Previdi, Paolo; Siliprandi, Giorgio; Murgia, Nicola

    2012-06-14

    Particulate air pollution is known to be associated with cardiovascular disease. The relation of particulate air pollution with cerebrovascular disease (CVD) has not been extensively studied, particularly in relation to different subtypes of stroke. A time-series study was conducted to evaluate the association between daily air pollution and acute stroke unit hospitalizations in Mantua, Italy. We analyzed 781 CVD consecutive patients living in Mantua county admitted between 2006-08. Data on stroke types, demographic variables, risk factors were available from the Lombardia Stroke Registry. Daily mean value of particulate matter with a diameter <10 µm (PM(10)), carbon monoxide, nitric oxide, nitrogen dioxide, sulphur dioxide, benzene and ozone were used in the analysis. The association between CVD, ischemic strokes subtypes and pollutants was investigated with a case-crossover design, using conditional logistic regression analysis, adjusting for temperature, humidity, barometric pressure and holidays. Among the 781 subjects admitted 75.7% had ischemic stroke, 11.7% haemorrhagic stroke 12.6% transient ischemic attack. In men admission for stroke was associated with PM(10) [odds ratio (OR) 1.01, 95%; confidence interval (CI) 1.00-1.02; P<0.05]. According to the clinical classification, lacunar anterior circulation syndrome stroke type was related to PM(10) level registered on the day of admission for both genders (OR: 1.01, 95%; CI: 1.00-1.02; P<0.05) while for total anterior circulation syndrome stroke only in men (OR: 1.04, 95%; CI 1.01-1.07; P<0.05).In conclusion, our study confirms that air pollution peaks may contribute to increase the risk of hospitalization for stroke and particulate matter seems to be a significant risk factor, especially for lacunar stroke.

  11. Crossover comparison of atenolol, enalapril, hydrochlorothiazide and isradipine for isolated systolic systemic hypertension.

    Science.gov (United States)

    Silagy, C A; McNeil, J J; McGrath, B P

    1992-11-15

    The benefit of antihypertensive therapy in reducing cardiovascular morbidity and mortality associated with isolated systolic hypertension has now been established by the Systolic Hypertension in the Elderly Program. However, there is little information about the relative effectiveness of different drug regimens in this condition. This study compared the efficacy and tolerability of 50 mg of atenolol, 10 mg of enalapril, 25 mg of hydrochlorothiazide and 2.5 mg of isradipine in the treatment of isolated systolic hypertension. After a 3-week placebo run-in phase, 24 subjects were randomized into a 4-period double-blind crossover study by use of an orthogonal latin square design. Treatment periods were of 6 weeks' duration with titration to a higher dose after 4 weeks in those not reaching goal blood pressure (BP). Each active treatment was followed by a 3-week placebo washout. Casual clinic and 24-hour ambulatory BP (Accutracker II) were measured at the end of each treatment phase. Routine biochemistry was also performed after the placebo run-in, at the end of each active treatment phase, and after the placebo run-out. Of the 24 subjects entered (mean age 72.3 years, 38% men) 20 completed the whole study. Mean +/- standard deviation of supine clinic and daytime ambulatory BP on entry were 181/79 +/- 21/9 mm Hg and 165/82 +/- 23/15 mm Hg, respectively. All drugs reduced mean casual and ambulatory BP significantly relative to placebo but only hydrochlorothiazide and enalapril produced a consistent hypotensive effect throughout the entire 24-hour period. Isradipine and enalapril exhibited a relatively greater effect on reducing systolic BP than either hydrochlorothiazide or atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Generic substitution of lamotrigine among medicaid patients with diverse indications: a cohort-crossover study.

    Science.gov (United States)

    Hartung, Daniel M; Middleton, Luke; Svoboda, Leanne; McGregor, Jessina C

    2012-08-01

    Controversy exists about the safety of substituting generic antiepileptic drugs (AEDs). Lamotrigine, the prototypical newer AED, is often used for psychiatric and neurological conditions other than epilepsy. The safety of generic substitution of lamotrigine in diverse populations of AED users is unclear. The objective of this study was to evaluate potential associations between generic substitution of lamotrigine and adverse consequences in a population of diverse users of this drug. This study was a retrospective cohort-crossover design using state Medicaid claims data from July 2006 through June 2009. Subjects were included in the cohort if they converted from brand to generic lamotrigine and had 2 years of lamotrigine use prior to conversion. The frequency of emergency department (ED) visits, hospitalizations and condition-specific ED visits or hospitalizations were recorded in the 60 days immediately following the conversion to generic lamotrigine, then compared with the incidence of the same events during a randomly selected time period indexed to one of the patient's past refills of branded lamotrigine. Multivariate conditional logistic regression was used to quantify the association between generic conversion and health services utilization while controlling for changes in lamotrigine dose and concurrent drug use. Of the 616 unique subjects included in this analysis, epilepsy was the most common diagnosis (41%), followed by bipolar disorder (32%), pain (30%) and migraine (18%). Conversion to generic lamotrigine was not associated with a statistically significant increase in the odds of an ED visit (adjusted odds ratio [AOR] = 1.35; 95% confidence interval [CI] 0.92, 1.97), hospitalization (AOR = 1.21; 95% CI 0.60, 2.50) or condition-specific encounter (AOR 1.75; 95 CI 0.87, 3.51). A statistically significant increase in ED visits, hospitalizations or condition-specific encounters was not observed following the switch from brand to generic lamotrigine

  13. Cashew consumption reduces total and LDL cholesterol: a randomized, crossover, controlled-feeding trial.

    Science.gov (United States)

    Mah, Eunice; Schulz, Jacqueline A; Kaden, Valerie N; Lawless, Andrea L; Rotor, Jose; Mantilla, Libertie B; Liska, DeAnn J

    2017-05-01

    Background: Cashews are the third most-consumed tree nut in the United States and are abundant with monounsaturated fatty acids and polyunsaturated fatty acids, which are associated with reduced cardiovascular disease risk. Although a qualified Food and Drug Administration health claim exists for nuts and heart health, cashews have been exempt from its use because cashews exceed the disqualifying amount of saturated fatty acids. Approximately one-third of the saturated fat in cashews is stearic acid, which is relatively neutral on blood lipids, thereby suggesting that cashews could have effects that are similar to those of other nuts. However, clinical data on cashews and blood lipids have been limited.Objective: We investigated the effect of reasonable intakes of cashews on serum lipids in adults with or at risk of high LDL cholesterol.Design: In a randomized, crossover, isocaloric, controlled-feeding study, 51 men and women (aged 21-73 y) with a median LDL-cholesterol concentration of 159 mg/dL (95% CI: 146, 165 mg/dL) at screening consumed typical American diets with cashews (28-64 g/d; 50% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 32% of kilocalories from total fat) or potato chips (control; 54% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 29% of kilocalories from total fat) for 28 d with a ≥2-wk washout period.Results: Consumption of the cashew diet resulted in a significantly greater median change from baseline (compared with the control, all P cashews into typical American diets decreases total cholesterol and LDL cholesterol. Results from this study provide support that the daily consumption of cashews, when substituted for a high-carbohydrate snack, may be a simple dietary strategy to help manage total cholesterol and LDL cholesterol. This study was registered at clinicaltrials.gov as NCT02769741. © 2017 American Society for Nutrition.

  14. Science Letters:Crossover randomized controlled trial of the electronic version of the Chinese SF-36

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objectives: to verify the feasibility and reliability of the electronic version of Chinese SF-36 based on the Quality-of-Life-Recorder. Design: A crossover randomized controlled trial, comparing a paper-based and an electronic version of the Chinese SF-36, was conducted. According to generated random numbers, interviewees were asked to fill out either the electronic version or the paper version first. The second version was filled in after a pause of at least 10 min. Settings and participants: One group of 100 medical students at the School of Medicine of Zhejiang University and the other group of 50 outpatients at a clinic for general practice in Hangzhou City (China) were eventually recruited in this study. Results: The acceptance of the electronic version was good (60% of medical students and 84% of outpatients preferred the electronic version). At the level of eight-scale scores, the mean-difference for each scale (except for general health) between the two versions was less than 5%. At the level of 36 questions, the percentage of "exact agreement" ranged within 64%~99%; the percentage of "global agreement" ranged within 72%~99%; 77% of the kappa coefficients demonstrated "good/excellent agreement" and 23% of the kappa coefficients demonstrated "medium agreement". Conclusion: This study, for the first time, can provide empirical basis for the confirmation of the feasibility and reliability of the electronic version of the Chinese SF-36 and may provide an impulse towards widespread deployment of the Quality-of-Life-Recorder in Chinese populations.

  15. Omega-3 fatty acids modify human cortical visual processing--a double-blind, crossover study.

    Science.gov (United States)

    Bauer, Isabelle; Crewther, David P; Pipingas, Andrew; Rowsell, Renee; Cockerell, Robyn; Crewther, Sheila G

    2011-01-01

    While cardiovascular and mood benefits of dietary omega-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are manifest, direct neurophysiological evidence of their effects on cortical activity is still limited. Hence we chose to examine the effects of two proprietary fish oil products with different EPA:DHA ratios (EPA-rich, high EPA:DHA; DHA-rich) on mental processing speed and visual evoked brain activity. We proposed that nonlinear multifocal visual evoked potentials (mfVEP) would be sensitive to any alteration of the neural function induced by omega-3 fatty acid supplementation, because the higher order kernel responses directly measure the degree of recovery of the neural system as a function of time following stimulation. Twenty-two healthy participants aged 18-34, with no known neurological or psychiatric disorder and not currently taking any nutritional supplementation, were recruited. A double-blind, crossover design was utilized, including a 30-day washout period, between two 30-day supplementation periods of the EPA-rich and DHA-rich diets (with order of diet randomized). Psychophysical choice reaction times and multi-focal nonlinear visual evoked potential (VEP) testing were performed at baseline (No Diet), and after each supplementation period. Following the EPA-rich supplementation, for stimulation at high luminance contrast, a significant reduction in the amplitude of the first slice of the second order VEP kernel response, previously related to activation in the magnocellular pathway, was observed. The correlations between the amplitude changes of short latency second and first order components were significantly different for the two supplementations. Significantly faster choice reaction times were observed psychophysically (compared with baseline performance) under the EPA-rich (but not DHA-rich) supplementation, while simple reaction times were not affected. The reduced nonlinearities observed under the EPA

  16. Omega-3 fatty acids modify human cortical visual processing--a double-blind, crossover study.

    Directory of Open Access Journals (Sweden)

    Isabelle Bauer

    Full Text Available While cardiovascular and mood benefits of dietary omega-3 fatty acids such as docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA are manifest, direct neurophysiological evidence of their effects on cortical activity is still limited. Hence we chose to examine the effects of two proprietary fish oil products with different EPA:DHA ratios (EPA-rich, high EPA:DHA; DHA-rich on mental processing speed and visual evoked brain activity. We proposed that nonlinear multifocal visual evoked potentials (mfVEP would be sensitive to any alteration of the neural function induced by omega-3 fatty acid supplementation, because the higher order kernel responses directly measure the degree of recovery of the neural system as a function of time following stimulation. Twenty-two healthy participants aged 18-34, with no known neurological or psychiatric disorder and not currently taking any nutritional supplementation, were recruited. A double-blind, crossover design was utilized, including a 30-day washout period, between two 30-day supplementation periods of the EPA-rich and DHA-rich diets (with order of diet randomized. Psychophysical choice reaction times and multi-focal nonlinear visual evoked potential (VEP testing were performed at baseline (No Diet, and after each supplementation period. Following the EPA-rich supplementation, for stimulation at high luminance contrast, a significant reduction in the amplitude of the first slice of the second order VEP kernel response, previously related to activation in the magnocellular pathway, was observed. The correlations between the amplitude changes of short latency second and first order components were significantly different for the two supplementations. Significantly faster choice reaction times were observed psychophysically (compared with baseline performance under the EPA-rich (but not DHA-rich supplementation, while simple reaction times were not affected. The reduced nonlinearities observed under the

  17. Temperature effect on the small-to-large crossover lengthscale of hydrophobic hydration.

    Science.gov (United States)

    Djikaev, Y S; Ruckenstein, E

    2013-11-14

    The thermodynamics of hydration is expected to change gradually from entropic for small solutes to enthalpic for large ones. The small-to-large crossover lengthscale of hydrophobic hydration depends on the thermodynamic conditions of the solvent such as temperature, pressure, presence of additives, etc. We attempt to shed some light on the temperature dependence of the crossover lengthscale by using a probabilistic approach to water hydrogen bonding that allows one to obtain an analytic expression for the number of bonds per water molecule as a function of both its distance to a solute and solute radius. Incorporating that approach into the density functional theory, one can examine the solute size effects on its hydration over the entire small-to-large lengthscale range at a series of different temperatures. Knowing the dependence of the hydration free energy on the temperature and solute size, one can also obtain its enthalpic and entropic contributions as functions of both temperature and solute size. These functions can provide some interesting insight into the temperature dependence of the crossover lengthscale of hydrophobic hydration. The model was applied to the hydration of spherical particles of various radii in water in the temperature range from T = 293.15 K to T = 333.15 K. The model predictions for the temperature dependence of the hydration free energy of small hydrophobes are consistent with the experimental and simulational data on the hydration of simple molecular solutes. Three alternative definitions for the small-to-large crossover length-scale of hydrophobic hydration are proposed, and their temperature dependence is obtained. Depending on the definition and temperature, the small-to-large crossover in the hydration mechanism is predicted to occur for hydrophobes of radii from one to several nanometers. Independent of its definition, the crossover length-scale is predicted to decrease with increasing temperature.

  18. Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study

    OpenAIRE

    Hansson Anita; Pålsson Gunvor; Branell Ulla-Carin; Ahrén Bo; Granfeldt Yvonne; Jönsson Tommy; Söderström Margareta; Lindeberg Staffan

    2009-01-01

    Abstract Background Our aim was to compare the effects of a Paleolithic ('Old Stone Age') diet and a diabetes diet as generally recommended on risk factors for cardiovascular disease in patients with type 2 diabetes not treated with insulin. Methods In a randomized cross-over study, 13 patients with type 2 diabetes, 3 women and 10 men, were instructed to eat a Paleolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; and a Diabetes diet designed in accorda...

  19. Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study

    OpenAIRE

    Hansson Anita; Pålsson Gunvor; Branell Ulla-Carin; Ahrén Bo; Granfeldt Yvonne; Jönsson Tommy; Söderström Margareta; Lindeberg Staffan

    2009-01-01

    Abstract Background Our aim was to compare the effects of a Paleolithic ('Old Stone Age') diet and a diabetes diet as generally recommended on risk factors for cardiovascular disease in patients with type 2 diabetes not treated with insulin. Methods In a randomized cross-over study, 13 patients with type 2 diabetes, 3 women and 10 men, were instructed to eat a Paleolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; and a Diabetes diet designed in accorda...

  20. Randomized cross-over study of patient preference for oral or intravenous vinorelbine in combination with carboplatin in the treatment of advanced NSCLC

    DEFF Research Database (Denmark)

    Jensen, Lisa Helene Toft; Østerlind, Kell Erik; Rytter, C.

    2008-01-01

    BACKGROUND: Most chemotherapeutics are administrated intravenously (iv), but some are also available in an oral (po) formulation. This study was designed with the primary objective to estimate the patients' preference for po or iv vinorelbine in combination with carboplatin for the palliative...... treatment of non-small cell lung cancer (NSCLC). Secondary aims were to evaluate toxicity, efficacy, and subjective reasons the preference. PATIENTS AND METHODS: Sixty-one patients were randomized in a cross-over trial to two cycles of carboplatin day 1 and vinorelbine day 1 and day 8 iv followed by two...

  1. Finite-Temperature Collective Dynamics of a Fermi Gas in the BEC-BCS Crossover

    Science.gov (United States)

    Wright, M. J.; Riedl, S.; Altmeyer, A.; Kohstall, C.; Guajardo, E. R. Sánchez; Denschlag, J. Hecker; Grimm, R.

    2007-10-01

    We report on experimental studies on the collective behavior of a strongly interacting Fermi gas with tunable interactions and variable temperature. A scissors mode excitation in an elliptical trap is used to characterize the dynamics of the quantum gas in terms of hydrodynamic or near-collisionless behavior. We obtain a crossover phase diagram for collisional properties, showing a large region where a nonsuperfluid strongly interacting gas shows hydrodynamic behavior. In a narrow interaction regime on the BCS side of the crossover, we find a novel temperature-dependent damping peak, suggesting a relation to the superfluid phase transition.

  2. Cross-over to quasi-condensation: mean-field theories and beyond

    Science.gov (United States)

    Henkel, Carsten; Sauer, Tim-O.; Proukakis, N. P.

    2017-06-01

    We analyze the cross-over of a homogeneous, weakly interacting Bose gas in one dimension from the ideal gas into the dense quasi-condensate phase. We review a number of mean-field theories, perturbative or self-consistent, and provide accurate evaluations of equation of state, density fluctuations, and correlation functions. A smooth crossover is reproduced by classical-field simulations based on the stochastic Gross-Pitaevskii equation and the Yang-Yang solution to the one-dimensional Bose gas.

  3. Universal crossover from ground-state to excited-state quantum criticality

    Science.gov (United States)

    Kang, Byungmin; Potter, Andrew C.; Vasseur, Romain

    2017-01-01

    We study the nonequilibrium properties of a nonergodic random quantum chain in which highly excited eigenstates exhibit critical properties usually associated with quantum critical ground states. The ground state and excited states of this system belong to different universality classes, characterized by infinite-randomness quantum critical behavior. Using strong-disorder renormalization group techniques, we show that the crossover between the zero and finite energy density regimes is universal. We analytically derive a flow equation describing the unitary dynamics of this isolated system at finite energy density from which we obtain universal scaling functions along the crossover.

  4. Crossover of two power laws in the anomalous diffusion of a two lipid membrane

    Energy Technology Data Exchange (ETDEWEB)

    Bakalis, Evangelos, E-mail: ebakalis@gmail.com, E-mail: francesco.zerbetto@unibo.it; Höfinger, Siegfried; Zerbetto, Francesco, E-mail: ebakalis@gmail.com, E-mail: francesco.zerbetto@unibo.it [Dipartimento di Chimica “G. Ciamician”, Universita’ di Bologna, Via F. Selmi 2, 40126 Bologna (Italy); Venturini, Alessandro [Institute for the Organic Synthesis and Photoreactivity, National Research Council of Italy, Via Gobetti 101, 40129 Bologna (Italy)

    2015-06-07

    Molecular dynamics simulations of a bi-layer membrane made by the same number of 1-palmitoyl-2-oleoyl-glycero-3-phospho-ethanolamine and palmitoyl-oleoyl phosphatidylserine lipids reveal sub-diffusional motion, which presents a crossover between two different power laws. Fractional Brownian motion is the stochastic mechanism that governs the motion in both regimes. The location of the crossover point is justified with simple geometrical arguments and is due to the activation of the mechanism of circumrotation of lipids about each other.

  5. The contact in the BCS–BEC crossover for finite range interacting ultracold Fermi gases

    Energy Technology Data Exchange (ETDEWEB)

    Caballero-Benítez, Santiago F., E-mail: scaballero@fisica.unam.mx; Paredes, Rosario; Romero-Rochín, Víctor

    2013-10-15

    Using mean-field theory for the Bardeen–Cooper–Schriefer (BCS) to the Bose–Einstein condensate (BEC) crossover we investigate the ground state thermodynamic properties of an interacting homogeneous Fermi gas. The interatomic interactions modelled through a finite range potential allows us to calculate the thermodynamic behaviour as a function of the potential parameters in the whole crossover region. We concentrate in studying the Contact variable, the thermodynamic conjugate of the inverse of the s-wave scattering length. Our analysis leads to predict a quantum phase transition – like in the case of large potential range. This finding is a direct consequence of the k-dependent energy gap.

  6. Dialysis-associated hypertension treated with Telmisartan--DiaTel: a pilot, placebo-controlled, cross-over, randomized trial.

    Directory of Open Access Journals (Sweden)

    Matthias Huber

    Full Text Available Treatment of hypertension in hemodialysis (HD patients is characterised by lack of evidence for both the blood pressure (BP target goal and the recommended drug class to use. Telmisartan, an Angiotensin receptor blocker (ARB that is metabolised in the liver and not excreted via HD extracorporeal circuit might be particularly suitable for HD patients. We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top of standard antihypertensive treatment excluding other Renin-Angiotensin-System (RAS blockers. In 29 patients after randomization we analysed BP after a treatment period of 8 weeks, while 13 started with telmisartan and 16 with placebo; after 8 weeks 11 continued with telmisartan and 12 with placebo after cross-over, respectively. Patients exhibited a significant reduction of systolic pre-HD BP from 141.9±21.8 before to 131.3±17.3 mmHg after the first treatment period with telmisartan or placebo. However, no average significant influence of telmisartan was observed compared to placebo. The latter may be due to a large inter-individual variability of BP responses reaching from a 40 mmHg decrease under placebo to 40 mmHg increase under telmisartan. Antihypertensive co-medication was changed for clinical reasons in 7 out of 21 patients with no significant difference between telmisartan and placebo groups. Our starting hypothesis, that telmisartan on top of standard therapy lowers systolic office BP in HD patients could not be confirmed. In conclusion, this small trial indicates that testing antihypertensive drug efficacy in HD patients is challenging due to complicated standardization of concomitant medication and other confounding factors, e.g. volume status, salt load and neurohormonal activation, that influence BP control in HD patients.Clinicaltrialsregister.eu 2005-005021-60.

  7. Do case-only designs yield consistent results between them and across different databases (DB)? Hip fractures associated with Benzodiazepines (BZD) as a case study

    NARCIS (Netherlands)

    Requena, Gema; Logie, John; Martin, Elisa; Huerta, Consuelo; González-González, Rocio; Boudiaf, Nada; Álvarez, Arturo; Bate, Andrew; García-Rodríguez, Luis A.; Reynolds, Robert; Schlienger, Raymond G.; De Groot, Mark C.H.; Klungel, Olaf H.; De Abajo, Francisco J.; Douglas, Ian

    2014-01-01

    Background: The case crossover (CXO) and selfcontrolled case series designs (SCCS) are increasingly used in pharmacoepidemiology. In both designs relative risk estimates are obtained within persons rather than between persons thus implicitly controlling for fixed confounding variables. Objectives: T

  8. Effect of combination therapy with thyroxine (T4) and 3,5,3'-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study

    DEFF Research Database (Denmark)

    Nygaard, Birte; Jensen, Ebbe Winther; Kvetny, Jan

    2009-01-01

    the effect of combination therapy with thyroxine (T(4)) and T(3) versus T(4) monotherapy in patients with hypothyroidism on stable T(4) substitution. Study design Double-blind, randomised cross-over. Fifty micrograms of the usual T(4) dose was replaced with either 20 microg T(3) or 50 microg T(4) for 12...... weeks, followed by cross-over for another 12 weeks. The T(4) dose was regulated if needed, intending unaltered serum TSH levels. Evaluation Tests for quality of life (QOL) and depression (SF-36, Beck Depression Inventory, and SCL-90-R) at baseline and after both treatment periods. Inclusion criteria......, indicating a positive effect related to the combination therapy. Forty-nine percent preferred the combination and 15% monotherapy (P=0.002). Serum TSH remained unaltered between the groups as intended. CONCLUSION: In a study design, where morning TSH levels were unaltered between groups combination therapy...

  9. AAA-ATPase FIDGETIN-LIKE 1 and Helicase FANCM Antagonize Meiotic Crossovers by Distinct Mechanisms.

    Directory of Open Access Journals (Sweden)

    Chloe Girard

    2015-07-01

    Full Text Available Meiotic crossovers (COs generate genetic diversity and are critical for the correct completion of meiosis in most species. Their occurrence is tightly constrained but the mechanisms underlying this limitation remain poorly understood. Here we identified the conserved AAA-ATPase FIDGETIN-LIKE-1 (FIGL1 as a negative regulator of meiotic CO formation. We show that Arabidopsis FIGL1 limits CO formation genome-wide, that FIGL1 controls dynamics of the two conserved recombinases DMC1 and RAD51 and that FIGL1 hinders the interaction between homologous chromosomes, suggesting that FIGL1 counteracts DMC1/RAD51-mediated inter-homologue strand invasion to limit CO formation. Further, depleting both FIGL1 and the previously identified anti-CO helicase FANCM synergistically increases crossover frequency. Additionally, we showed that the effect of mutating FANCM on recombination is much lower in F1 hybrids contrasting from the phenotype of inbred lines, while figl1 mutation equally increases crossovers in both contexts. This shows that the modes of action of FIGL1 and FANCM are differently affected by genomic contexts. We propose that FIGL1 and FANCM represent two successive barriers to CO formation, one limiting strand invasion, the other disassembling D-loops to promote SDSA, which when both lifted, leads to a large increase of crossovers, without impairing meiotic progression.

  10. Functional equation for the crossover in the model of one-dimensional Weierstrass random walks

    Science.gov (United States)

    Rudoi, Yu. G.; Kotel'nikova, O. A.

    2016-12-01

    We consider the problem of one-dimensional symmetric diffusion in the framework of Markov random walks of the Weierstrass type using two-parameter scaling for the transition probability. We construct a solution for the characteristic Lyapunov function as a sum of regular (homogeneous) and singular (nonhomogeneous) solutions and find the conditions for the crossover from normal to anomalous diffusion.

  11. Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study

    NARCIS (Netherlands)

    Dower, James I.; Geleijnse, Marianne; Kroon, Paul A.; Philo, Mark; Mensink, Marco; Kromhout, Daan; Hollman, Peter C.H.

    2016-01-01

    Scope: Cocoa, rich in flavan-3-ols, improves vascular function, but the contribution of specific flavan-3-ols is unknown. We compared the effects of pure epicatechin, a major cocoa flavan-3-ol, and chocolate. Methods and results: In a randomized crossover study, twenty healthy men (40-80 years)

  12. How leaders affect followers' work engagement and performance : Integrating Leader−Member Exchange and Crossover Theory

    NARCIS (Netherlands)

    Gutermann, D.; Lehmann-Willenbrock, N.; Boer, D.; Born, M.; Voelpel, S.C.

    Drawing on leader−member exchange and crossover theory, this study examines how leaders’ work engagement can spread to followers, highlighting the role of leader−member exchange as an underlying explanatory process. Specifically, we investigate if leaders who are highly engaged in their work have

  13. Nanoconfinement crystallization of frustrated alkyl groups: crossover of mesophase to crystalline structure.

    Science.gov (United States)

    Shi, Haifeng; Wang, Haixia; Xin, John H; Zhang, Xingxiang; Wang, Dujin

    2011-04-07

    Crossover of mesophase to crystalline structure in the nanoconfinement crystallization process of frustrated side groups elucidates the critical crystal thickness d(c) or the length scale of side groups, which defines the transition process from mesophase (hexagonal and monoclinic phase) to crystalline phase (orthorhombic phase) of confined CH(2) sequences in a given crystal size restriction.

  14. Jacobi crossover ensembles of random matrices and statistics of transmission eigenvalues

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Santosh; Pandey, Akhilesh, E-mail: skumar.physics@gmail.co, E-mail: ap0700@mail.jnu.ac.i [School of Physical Sciences, Jawaharlal Nehru University, New Delhi - 110067 (India)

    2010-02-26

    We study the transition in conductance properties of chaotic mesoscopic cavities as time-reversal symmetry is broken. We consider the Brownian motion model for transmission eigenvalues for both types of transitions, namely, orthogonal-unitary and symplectic-unitary crossovers depending on the presence or absence of spin-rotation symmetry of the electron. In both cases the crossover is governed by a Brownian motion parameter tau, which measures the extent of time-reversal symmetry breaking. It is shown that the results obtained correspond to the Jacobi crossover ensembles of random matrices. We derive the level density and the correlation functions of higher orders for the transmission eigenvalues. We also obtain the exact expressions for the average conductance, average shot-noise power and variance of conductance, as functions of tau, for the arbitrary number of modes (channels) in the two leads connected to the cavity. Moreover, we give the asymptotic result for the variance of shot-noise power for both the crossovers, the exact results being too long. In the tau -> 0 and tau -> infinity limits, the known results for the orthogonal (or symplectic) and unitary ensembles are reproduced. In the weak time-reversal symmetry breaking regime, our results are shown to be in agreement with the semiclassical predictions.

  15. Four-site cooperative spin crossover in a mononuclear FeII complex

    DEFF Research Database (Denmark)

    Lennartson, Anders; Bond, Andrew; Piligkos, Stergios;

    2012-01-01

    Round and round: A mononuclear Fe(II) complex (see picture) with an N(4)S(2) coordination set has been characterized in four polymorphic forms. Two of the polymorphs display four-site cooperative spin crossover (SCO), shown conclusively by the crystal structure of a fully ordered 1:3 high-spin/lo...

  16. Are antibiotics related to oral combination contraceptive failures in the Netherlands? A case-crossover study

    NARCIS (Netherlands)

    Koopmans, P.C.; Bos, J.H.; de Jong-van den Berg, L.T.

    Purpose To investigate whether there is an association between use of antibiotics and breakthrough pregnancy. Methods The study was performed in a population-based prescription database (IADB.nl). We computed case-crossover odds ratios of 397 cases of defined breakthrough pregnancy comparing the use

  17. Study on Different Crossover Mechanisms of Genetic Algorithm for Test Interval Optimization for Nuclear Power Plants

    Directory of Open Access Journals (Sweden)

    Molly Mehra

    2013-12-01

    Full Text Available Surveillance tests are performed periodically on standby systems of a Nuclear Power Plant (NPP, as they improve the systems’ availability on demand. High availability of safety critical systems is very essential to NPP safety, hence, careful analysis is required to schedule the surveillance activities for such systems in a cost effective way without compromising the plant safety. This forms an optimization problem wherein, two different cases can be formulated for deciding the value of Surveillance Test Interval. In one case, cost is the objective function to be minimized while unavailability is constrained to be at a given level and in another case, unavailability is minimized for a given cost level. Here, optimization is done using Genetic Algorithm (GA and real encoding has been employed as it caters well to the requirements of this problem. A detailed procedure for GA formulation is described in this paper. Two different crossover methods, arithmetical crossover and blend crossover are explored and compared in this study to arrive at the most suitable crossover method for such type of problems.

  18. Are antibiotics related to oral combination contraceptive failures in the Netherlands? A case-crossover study

    NARCIS (Netherlands)

    Koopmans, P.C.; Bos, J.H.; de Jong-van den Berg, L.T.

    2012-01-01

    Purpose To investigate whether there is an association between use of antibiotics and breakthrough pregnancy. Methods The study was performed in a population-based prescription database (IADB.nl). We computed case-crossover odds ratios of 397 cases of defined breakthrough pregnancy comparing the use

  19. Moderate alcohol consumption increases insulin sensitivity and ADIPOQ expression in postmenopausal women: A randomised, crossover trial

    NARCIS (Netherlands)

    Joosten, M.M.; Beulens, J.W.J.; Kersten, S.; Hendriks, H.F.J.

    2008-01-01

    Aims/hypothesis: To determine whether 6 weeks of daily, moderate alcohol consumption increases expression of the gene encoding adiponectin (ADIPOQ) and plasma levels of the protein, and improves insulin sensitivity in postmenopausal women. Methods: In a randomised, open-label, crossover trial conduc

  20. Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study

    NARCIS (Netherlands)

    Dower, James I.; Geleijnse, Marianne; Kroon, Paul A.; Philo, Mark; Mensink, Marco; Kromhout, Daan; Hollman, Peter C.H.

    2016-01-01

    Scope: Cocoa, rich in flavan-3-ols, improves vascular function, but the contribution of specific flavan-3-ols is unknown. We compared the effects of pure epicatechin, a major cocoa flavan-3-ol, and chocolate. Methods and results: In a randomized crossover study, twenty healthy men (40-80 years) w

  1. Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

    Science.gov (United States)

    Gilbert, Donald L.; Batterson, J. Robert; Sethuraman, Gopalan; Sallee, Floyd R.

    2004-01-01

    Objective: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. Method: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic…

  2. Epigenetic Remodeling of Meiotic Crossover Frequency in Arabidopsis thaliana DNA Methyltransferase Mutants

    NARCIS (Netherlands)

    Yelina, N.E.; Choi, K.; Chelysheva, L.; Macaulay, M.; Snoo, de B.; Wijnker, T.G.; Miller, N.; Drouaud, J.; Grelon, M.; Copenhaver, G.P.; Mezard, C.; Kelly, K.A.; Henderson, I.R.

    2012-01-01

    Meiosis is a specialized eukaryotic cell division that generates haploid gametes required for sexual reproduction. During meiosis, homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover (CO). Meiotic CO frequency varies along the physical length of chromosomes and is d

  3. Feasibility of a Web-Based Cross-Over Paleolithic Diet Intervention in the General Population

    NARCIS (Netherlands)

    Nederhof, Esther; Bikker, Esther

    2017-01-01

    Introduction: The primary aim was to investigate feasibility of a web-based cross-over Paleolithic diet intervention in the general population. The secondary aim was to calculate the sample size needed to reach a statistically significant difference in effect of a Paleolithic-like diet on

  4. The Crossover Generation: Baby Boomers and the Role of the Public Library

    Science.gov (United States)

    Williamson, Kirsty; Bannister, Marion; Sullivan, Jen

    2010-01-01

    The article explores the concept of baby boomers as a "crossover" generation, one that embodies characteristics of previous and later generations. The context is the retirement of the baby boomers and its potential impact on the public library. Ethnographic method within a constructivist framework was used, employing the techniques of focus groups…

  5. Correlation between Fragility and the Arrhenius Crossover Phenomenon in Metallic, Molecular, and Network Liquids.

    Science.gov (United States)

    Jaiswal, Abhishek; Egami, Takeshi; Kelton, K F; Schweizer, Kenneth S; Zhang, Yang

    2016-11-11

    We report the observation of a distinct correlation between the kinetic fragility index m and the reduced Arrhenius crossover temperature θ_{A}=T_{A}/T_{g} in various glass-forming liquids, identifying three distinguishable groups. In particular, for 11 glass-forming metallic liquids, we universally observe a crossover in the mean diffusion coefficient from high-temperature Arrhenius to low-temperature super-Arrhenius behavior at approximately θ_{A}≈2 which is in the stable liquid phases. In contrast, for fragile molecular liquids, this crossover occurs at much lower θ_{A}≈1.4 and usually in their supercooled states. The θ_{A} values for strong network liquids spans a wide range higher than 2. Intriguingly, the high-temperature activation barrier E_{∞} is universally found to be ∼11k_{B}T_{g} and uncorrelated with the fragility or the reduced crossover temperature θ_{A} for metallic and molecular liquids. These observations provide a way to estimate the low-temperature glassy characteristics (T_{g} and m) from the high-temperature liquid quantities (E_{∞} and θ_{A}).

  6. Influence of the spin crossover in ferropericlase on the lower mantle geotherm

    Science.gov (United States)

    Valencia-Cardona, J. J.; Shukla, G.; Qian, C.; Wu, Z.; Wentzcovitch, R. M.

    2015-12-01

    The spin crossover in ferropericlase introduces anomalies in its thermodynamics and thermoelastic properties. Here we investigate the influence of this spin crossover in the lower mantle adiabatic geotherm. The effect is investigated for lower mantle compositions consisting of mixtures of bridgmanite, ferropericlase, and CaSiO3-perovskite, for several Mg/Si ratios varying from perovskitic to pyrolitic compositions. The thermodynamics properties of (Mg,Fe)SiO3 bridgmanite and of (Mg,Fe)O ferropericlase were obtained using LDA+U plus quasiharmonic approximation QHA while LDA and the Mie-Debye-Grüneisen approach were used for Ca-perovskite. This spin crossover essentially increases the adiabatic gradient producing temperatures between those obtained by Anderson [1] and Brown and Shankland [2]. We show that aggregate moduli and seismic velocities are sensitive to the alteration in the adiabatic geotherm caused by this spin crossover, which can influence analyses of lower mantle velocities in terms of composition. [1] O. L. Anderson (1982), The Earths core and phase diagram of iron, Phil. Trans. R. Soc. Lond. A, 306, 2135. [2] J.M. Brown and T.J. Shankland (1981), Thermodynamic parameters in the Earth as determined from seismic profiles, Geophys. J. R. astr. Soc., 66, 579596.

  7. Crossover Equation of State Models Applied to the Critical Behavior of Xenon

    Science.gov (United States)

    Garrabos, Y.; Lecoutre, C.; Marre, S.; Guillaument, R.; Beysens, D.; Hahn, I.

    2015-03-01

    The turbidity () measurements of Güttinger and Cannell (Phys Rev A 24:3188-3201, 1981) in the temperature range along the critical isochore of homogeneous xenon are reanalyzed. The singular behaviors of the isothermal compressibility () and the correlation length () predicted from the master crossover functions are introduced in the turbidity functional form derived by Puglielli and Ford (Phys Rev Lett 25:143-146, 1970). We show that the turbidity data are thus well represented by the Ornstein-Zernike approximant, within 1 % precision. We also introduce a new crossover master model (CMM) of the parametric equation of state for a simple fluid system with no adjustable parameter. The CMM model and the phenomenological crossover parametric model are compared with the turbidity data and the coexisting liquid-gas density difference (). The excellent agreement observed for , , , and in a finite temperature range well beyond the Ising-like preasymptotic domain confirms that the Ising-like critical crossover behavior of xenon can be described in conformity with the universal features estimated by the renormalization-group methods. Only 4 critical coordinates of the vapor-liquid critical point are needed in the (pressure, temperature, molecular volume) phase surface of xenon.

  8. Measuring Meiotic Crossovers via Multi-Locus Genotyping of Single Pollen Grains in Barley.

    Directory of Open Access Journals (Sweden)

    Steven Dreissig

    Full Text Available The detection of meiotic crossovers in crop plants currently relies on scoring DNA markers in a segregating population or cytological visualization. We investigated the feasibility of using flow-sorted haploid nuclei, Phi29 DNA polymerase-based whole-genome-amplification (WGA and multi-locus KASP-genotyping to measure meiotic crossovers in individual barley pollen grains. To demonstrate the proof of concept, we used 24 gene-based physically mapped single nucleotide polymorphisms to genotype the WGA products of 50 single pollen nuclei. The number of crossovers per chromosome, recombination frequencies along chromosome 3H and segregation distortion were analysed and compared to a doubled haploid (DH population of the same genotype. The number of crossovers and chromosome wide recombination frequencies show that this approach is able to produce results that resemble those obtained from other methods in a biologically meaningful way. Only the segregation distortion was found to be lower in the pollen population than in DH plants.

  9. Microscopic theory of cooperative spin crossover: Interaction of molecular modes with phonons

    Energy Technology Data Exchange (ETDEWEB)

    Palii, Andrew, E-mail: andrew.palii@uv.es, E-mail: klokishner@yahoo.com; Ostrovsky, Serghei; Reu, Oleg; Klokishner, Sophia, E-mail: andrew.palii@uv.es, E-mail: klokishner@yahoo.com [Institute of Applied Physics, Academy of Sciences of Moldova, Academy Str. 5, MD-2028 Kishinev (Moldova, Republic of); Tsukerblat, Boris [Department of Chemistry, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105 (Israel); Decurtins, Silvio; Liu, Shi-Xia [Departement für Chemie und Biochemie, Universität Bern, Freiestrasse 3, CH-3012 Bern (Switzerland)

    2015-08-28

    In this article, we present a new microscopic theoretical approach to the description of spin crossover in molecular crystals. The spin crossover crystals under consideration are composed of molecular fragments formed by the spin-crossover metal ion and its nearest ligand surrounding and exhibiting well defined localized (molecular) vibrations. As distinguished from the previous models of this phenomenon, the developed approach takes into account the interaction of spin-crossover ions not only with the phonons but also a strong coupling of the electronic shells with molecular modes. This leads to an effective coupling of the local modes with phonons which is shown to be responsible for the cooperative spin transition accompanied by the structural reorganization. The transition is characterized by the two order parameters representing the mean values of the products of electronic diagonal matrices and the coordinates of the local modes for the high- and low-spin states of the spin crossover complex. Finally, we demonstrate that the approach provides a reasonable explanation of the observed spin transition in the [Fe(ptz){sub 6}](BF{sub 4}){sub 2} crystal. The theory well reproduces the observed abrupt low-spin → high-spin transition and the temperature dependence of the high-spin fraction in a wide temperature range as well as the pronounced hysteresis loop. At the same time within the limiting approximations adopted in the developed model, the evaluated high-spin fraction vs. T shows that the cooperative spin-lattice transition proves to be incomplete in the sense that the high-spin fraction does not reach its maximum value at high temperature.

  10. Microscopic theory of cooperative spin crossover: Interaction of molecular modes with phonons.

    Science.gov (United States)

    Palii, Andrew; Ostrovsky, Serghei; Reu, Oleg; Tsukerblat, Boris; Decurtins, Silvio; Liu, Shi-Xia; Klokishner, Sophia

    2015-08-28

    In this article, we present a new microscopic theoretical approach to the description of spin crossover in molecular crystals. The spin crossover crystals under consideration are composed of molecular fragments formed by the spin-crossover metal ion and its nearest ligand surrounding and exhibiting well defined localized (molecular) vibrations. As distinguished from the previous models of this phenomenon, the developed approach takes into account the interaction of spin-crossover ions not only with the phonons but also a strong coupling of the electronic shells with molecular modes. This leads to an effective coupling of the local modes with phonons which is shown to be responsible for the cooperative spin transition accompanied by the structural reorganization. The transition is characterized by the two order parameters representing the mean values of the products of electronic diagonal matrices and the coordinates of the local modes for the high- and low-spin states of the spin crossover complex. Finally, we demonstrate that the approach provides a reasonable explanation of the observed spin transition in the [Fe(ptz)6](BF4)2 crystal. The theory well reproduces the observed abrupt low-spin → high-spin transition and the temperature dependence of the high-spin fraction in a wide temperature range as well as the pronounced hysteresis loop. At the same time within the limiting approximations adopted in the developed model, the evaluated high-spin fraction vs. T shows that the cooperative spin-lattice transition proves to be incomplete in the sense that the high-spin fraction does not reach its maximum value at high temperature.

  11. Two randomized cross-over trials assessing the impact of dietary gluten or wholegrain on the gut microbiome and host metabolic health

    DEFF Research Database (Denmark)

    Ibrügger, Sabine; Gøbel, Rikke Juul; Vestergaard, Henrik

    2014-01-01

    Background: Gut microbiota composition and activity may be changed by dietary factors and possibly affect metabolic health. Dietary gluten and wholegrain are suggested to influence metabolism in a negative and positive direction, respectively. Objective: Describe the design and rational as well...... as baseline characteristics of two human intervention studies, within the Gut, Grain and Greens (3G) Center, investigating the effects of a gluten-poor and wholegrain-rich diet on microbiota composition and metabolic health. Design: The gluten and wholegrain studies had a randomized, controlled, cross......-over design each comprising two eight-week dietary intervention periods, separated by a six-week wash-out period. Each trial included 60 men and women exhibiting an increased metabolic risk. In the gluten study a gluten-poor diet was compared with a gluten-rich dietary fiber-controlled diet...

  12. Halovest dynamic loads: full crossover comparison of three vest types.

    Science.gov (United States)

    Fukui, Yasuyuki; Krag, Martin; Huston, Dryver; Ambrose, Tim; Vaccaro, Alexander R

    2002-02-01

    Ten cervical spine trauma subjects were studied during halovest treatment. Each subject wore each of three different vests. To compare the effect of vest design on loads between halo and vest during various activities. Complications during halovest use may be related to vest design, a variety of which are available. Loads between halo and vest have been shown to vary with activity type, but no comparison between vest types has been reported previously. Loads between the halo and the vest were measured during performance of activities of daily living and during load application to the halo, using custom-built four-channel transducers and a PC-based data acquisition system. Substantial variations between subjects exist in loads between the halo and the vest. At rest, neck distraction loads were significantly greater for the supine posture than for either the sitting or standing postures. Loads applied to the halo by the investigators are carried by the neck and not by the structure connecting the halo to the vest. During activities of daily living all four measured load components are generally nonzero. During activities of daily living substantial differences in loads occurred between vest types. For all activities of daily living combined, the relative neck distraction load values were as follows: 4PAD 100%, Bremer 159%, and PMT 180%. Previous evidence supports a connection between certain complications of halovest wear (such as pin loosening) and loads on the pins. This study shows that different halovests are associated with quite different loads between the vest and the halo (and thus loads on the pins and the neck). This is encouraging for prospective, clinical comparison of different halovests and for improvements in clinical performance through halovest design improvements.

  13. Acute changes of hip joint range of motion using selected clinical stretching procedures: A randomized crossover study.

    Science.gov (United States)

    Hammer, Adam M; Hammer, Roger L; Lomond, Karen V; O'Connor, Paul

    2017-09-01

    Hip adductor flexibility and strength is an important component of athletic performance and many activities of daily living. Little research has been done on the acute effects of a single session of stretching on hip abduction range of motion (ROM). The aim of this study was to compare 3 clinical stretching procedures against passive static stretching and control on ROM and peak isometric maximal voluntary contraction (MVC). Using a randomized crossover study design, a total of 40 participants (20 male and 20 female) who had reduced hip adductor muscle length attended a familiarization session and 5 testing sessions on non-consecutive days. Following the warm-up and pre-intervention measures of ROM and MVC, participants were randomly assigned 1 of 3 clinical stretching procedures (modified lunge, multidirectional, and joint mobilization) or a static stretch or control condition. Post-intervention measures of ROM and MVC were taken immediately following completion of the assigned condition. An ANOVA using a repeated measure design with the change score was conducted. All interventions resulted in small but statistically significant (p stretching was greater than control (p = 0.031). These data suggest that a single session of stretching has only a minimal effect on acute changes of hip abduction ROM. Although hip abduction is a frontal plane motion, to effectively increase the extensibility of the structures that limit abduction, integrating multi-planar stretches may be indicated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Genetic analysis of baker's yeast Msh4-Msh5 reveals a threshold crossover level for meiotic viability.

    Directory of Open Access Journals (Sweden)

    K T Nishant

    2010-08-01

    Full Text Available During meiosis, the Msh4-Msh5 complex is thought to stabilize single-end invasion intermediates that form during early stages of recombination and subsequently bind to Holliday junctions to facilitate crossover formation. To analyze Msh4-Msh5 function, we mutagenized 57 residues in Saccharomyces cerevisiae Msh4 and Msh5 that are either conserved across all Msh4/5 family members or are specific to Msh4 and Msh5. The Msh5 subunit appeared more sensitive to mutagenesis. We identified msh4 and msh5 threshold (msh4/5-t mutants that showed wild-type spore viability and crossover interference but displayed, compared to wild-type, up to a two-fold decrease in crossing over on large and medium sized chromosomes (XV, VII, VIII. Crossing over on a small chromosome, however, approached wild-type levels. The msh4/5-t mutants also displayed synaptonemal complex assembly defects. A triple mutant containing a msh4/5-t allele and mutations that decreased meiotic double-strand break levels (spo11-HA and crossover interference (pch2Δ showed synergistic defects in spore viability. Together these results indicate that the baker's yeast meiotic cell does not require the ∼90 crossovers maintained by crossover homeostasis to form viable spores. They also show that Pch2-mediated crossover interference is important to maintain meiotic viability when crossovers become limiting.

  15. Delay in the Detrended Fluctuation Analysis Crossover Point as a Risk Factor for Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Manuel Varela

    2016-01-01

    Full Text Available Detrended Fluctuation Analysis (DFA measures the complexity of a glucose time series obtained by means of a Continuous Glucose Monitoring System (CGMS and has proven to be a sensitive marker of glucoregulatory dysfunction. Furthermore, some authors have observed a crossover point in the DFA, signalling a change of dynamics, arguably dependent on the beta-insular function. We investigate whether the characteristics of this crossover point have any influence on the risk of developing type 2 diabetes mellitus (T2DM. To this end we recruited 206 patients at increased risk of T2DM (because of obesity, essential hypertension, or a first-degree relative with T2DM. A CGMS time series was obtained, from which the DFA and the crossover point were calculated. Patients were then followed up every 6 months for a mean of 17.5 months, controlling for the appearance of T2DM diagnostic criteria. The time to crossover point was a significant predictor risk of developing T2DM, even after adjusting for other variables. The angle of the crossover was not predictive by itself but became significantly protective when the model also considered the crossover point. In summary, both a delay and a blunting of the crossover point predict the development of T2DM.

  16. Delay in the Detrended Fluctuation Analysis Crossover Point as a Risk Factor for Type 2 Diabetes Mellitus

    Science.gov (United States)

    Varela, Manuel; Vigil, Luis; Rodriguez, Carmen; Vargas, Borja; García-Carretero, Rafael

    2016-01-01

    Detrended Fluctuation Analysis (DFA) measures the complexity of a glucose time series obtained by means of a Continuous Glucose Monitoring System (CGMS) and has proven to be a sensitive marker of glucoregulatory dysfunction. Furthermore, some authors have observed a crossover point in the DFA, signalling a change of dynamics, arguably dependent on the beta-insular function. We investigate whether the characteristics of this crossover point have any influence on the risk of developing type 2 diabetes mellitus (T2DM). To this end we recruited 206 patients at increased risk of T2DM (because of obesity, essential hypertension, or a first-degree relative with T2DM). A CGMS time series was obtained, from which the DFA and the crossover point were calculated. Patients were then followed up every 6 months for a mean of 17.5 months, controlling for the appearance of T2DM diagnostic criteria. The time to crossover point was a significant predictor risk of developing T2DM, even after adjusting for other variables. The angle of the crossover was not predictive by itself but became significantly protective when the model also considered the crossover point. In summary, both a delay and a blunting of the crossover point predict the development of T2DM. PMID:27294154

  17. Crossover behavior of multiscale fluctuations in Big Data: Langevin model and substorm time-scales in Earth's magnetosphere

    Science.gov (United States)

    Sharma, A. S.; Setty, V. A.

    2015-12-01

    Multiscale fluctuations in large and complex data are usually characterized by a power law with a scaling exponent but many systems require more than one exponent and thus exhibit crossover behavior. The scaling exponents, such as Hurst exponents, represent the nature of correlation in the system and the crossover shows the presence of more than one type of correlation. An accurate characterization of the crossover behavior is thus needed for a better understanding of the inherent correlations in the system, and is an important method of Big Data analysis. A multi-step process is developed for accurate computation of the crossover behavior. First the detrended fluctuation analysis is used to remove the trends in the data and the scaling exponents are computed. The crossover point is then computed by a Hyperbolic regression technique, with no prior assumptions. The time series data of the magnetic field variations during substorms in the Earth's magnetosphere is analyzed with these techniques and yields a crossover behavior with a time scale of ~4 hrs. A Langevin model derived from the data provides an excellent fit to the crossover in the scaling exponents and a good model of magnetospheric dynamics. The combination of fluctuation analysis and mathematical modeling thus yields a comprehensive approach in the analysis of Big Data.

  18. Treatment crossovers in time-to-event non-inferiority randomised trials of radiotherapy in patients with breast cancer

    Science.gov (United States)

    Parpia, Sameer; Julian, Jim A; Thabane, Lehana; Gu, Chushu; Whelan, Timothy J; Levine, Mark N

    2014-01-01

    Background In non-inferiority trials of radiotherapy in patients with early stage breast cancer, it is inevitable that some patients will cross over from the experimental arm to the standard arm prior to initiation of any treatment due to complexities in treatment planning or subject preference. Although the intention-to-treat (ITT) analysis is the preferred approach for superiority trials, its role in non-inferiority trials is still under debate. This has led to the use of alternative approaches such as the per-protocol (PP) analysis or the as-treated (AT) analysis, despite the inherent biases of such approaches. Methods Using simulations, we investigate the effect of 2%, 5% and 10% random and non-random crossovers prior to radiotherapy initiation on the ITT, PP, AT and the combination of ITT and PP analyses with respect to type I error in trials with time-to-event outcomes. We also evaluate bias and SE of the estimates from the ITT, PP and AT approaches. Results The AT approach had the best performance in terms of type I error, but was anticonservative as non-random crossover increased. The ITT and PP approaches were anticonservative under all percentages of random and non-random crossover. Similarly, lowest bias was seen with the AT approach; however, bias increased as the percentage of non-random crossover increased. The ITT and PP had poor performance in terms of bias as crossovers increased. Conclusions If minimal crossovers were to occur, we have shown that the AT approach has the lowest type I error rates and smallest opportunity for bias. Results of trials with a high number of crossovers should be interpreted with caution, especially when crossover is non-random. Attempts to prevent crossovers should be maximised. PMID:25344487

  19. Pilot crossover trial of Reiki versus rest for treating cancer-related fatigue.

    Science.gov (United States)

    Tsang, Kathy L; Carlson, Linda E; Olson, Karin

    2007-03-01

    Fatigue is an extremely common side effect experienced during cancer treatment and recovery. Limited research has investigated strategies stemming from complementary and alternative medicine to reduce cancer-related fatigue. This research examined the effects of Reiki, a type of energy touch therapy, on fatigue, pain, anxiety, and overall quality of life. This study was a counterbalanced crossover trial of 2 conditions: (1) in the Reiki condition, participants received Reiki for 5 consecutive daily sessions, followed by a 1-week washout monitoring period of no treatments, then 2 additional Reiki sessions, and finally 2 weeks of no treatments, and (2) in the rest condition, participants rested for approximately 1 hour each day for 5 consecutive days, followed by a 1-week washout monitoring period of no scheduled resting and an additional week of no treatments. In both conditions, participants completed questionnaires investigating cancer-related fatigue (Functional Assessment of Cancer Therapy Fatigue subscale [FACT-F]) and overall quality of life (Functional Assessment of Cancer Therapy, General Version [FACT-G]) before and after all Reiki or resting sessions. They also completed a visual analog scale (Edmonton Symptom Assessment System [ESAS]) assessing daily tiredness, pain, and anxiety before and after each session of Reiki or rest. Sixteen patients (13 women) participated in the trial: 8 were randomized to each order of conditions (Reiki then rest; rest then Reiki). They were screened for fatigue on the ESAS tiredness item, and those scoring greater than 3 on the 0 to 10 scale were eligible for the study. They were diagnosed with a variety of cancers, most commonly colorectal (62.5%) cancer, and had a median age of 59 years. Fatigue on the FACT-F decreased within the Reiki condition (P=.05) over the course of all 7 treatments. In addition, participants in the Reiki condition experienced significant improvements in quality of life (FACT-G) compared to those in

  20. Measuring the effect of enhanced cleaning in a UK hospital: a prospective cross-over study

    Directory of Open Access Journals (Sweden)

    Dancer Stephanie J

    2009-06-01

    Full Text Available Abstract Background Increasing hospital-acquired infections have generated much attention over the last decade. There is evidence that hygienic cleaning has a role in the control of hospital-acquired infections. This study aimed to evaluate the potential impact of one additional cleaner by using microbiological standards based on aerobic colony counts and the presence of Staphylococcus aureus including meticillin-resistant S. aureus. Methods We introduced an additional cleaner into two matched wards from Monday to Friday, with each ward receiving enhanced cleaning for six months in a cross-over design. Ten hand-touch sites on both wards were screened weekly using standardised methods and patients were monitored for meticillin-resistant S. aureus infection throughout the year-long study. Patient and environmental meticillin-resistant S. aureus isolates were characterised using molecular methods in order to investigate temporal and clonal relationships. Results Enhanced cleaning was associated with a 32.5% reduction in levels of microbial contamination at hand-touch sites when wards received enhanced cleaning (P S. aureus/S. aureus than sites further from the patient (P = 0.065. Genotyping identified indistinguishable strains from both hand-touch sites and patients. There was a 26.6% reduction in new meticillin-resistant S. aureus infections on the wards receiving extra cleaning, despite higher meticillin-resistant S. aureus patient-days and bed occupancy rates during enhanced cleaning periods (P = 0.032: 95% CI 7.7%, 92.3%. Adjusting for meticillin-resistant S. aureus patient-days and based upon nine new meticillin-resistant S. aureus infections seen during routine cleaning, we expected 13 new infections during enhanced cleaning periods rather than the four that actually occurred. Clusters of new meticillin-resistant S. aureus infections were identified 2 to 4 weeks after the cleaner left both wards. Enhanced cleaning saved the hospital £30