Between-Batch Pharmacokinetic Variability Inflates Type I Error Rate in Conventional Bioequivalence Trials: A Randomized Advair Diskus Clinical Trial.

PubMed

Burmeister Getz, E; Carroll, K J; Mielke, J; Benet, L Z; Jones, B

2017-03-01

We previously demonstrated pharmacokinetic differences among manufacturing batches of a US Food and Drug Administration (FDA)-approved dry powder inhalation product (Advair Diskus 100/50) large enough to establish between-batch bio-inequivalence. Here, we provide independent confirmation of pharmacokinetic bio-inequivalence among Advair Diskus 100/50 batches, and quantify residual and between-batch variance component magnitudes. These variance estimates are used to consider the type I error rate of the FDA's current two-way crossover design recommendation. When between-batch pharmacokinetic variability is substantial, the conventional two-way crossover design cannot accomplish the objectives of FDA's statistical bioequivalence test (i.e., cannot accurately estimate the test/reference ratio and associated confidence interval). The two-way crossover, which ignores between-batch pharmacokinetic variability, yields an artificially narrow confidence interval on the product comparison. The unavoidable consequence is type I error rate inflation, to ∼25%, when between-batch pharmacokinetic variability is nonzero. This risk of a false bioequivalence conclusion is substantially higher than asserted by regulators as acceptable consumer risk (5%). © 2016 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of The American Society for Clinical Pharmacology and Therapeutics.

Small cause - big effect: improvement in interface design results in improved data quality - a multicenter crossover study.

PubMed

Ahlbrandt, Janko; Henrich, Michael; Hartmann, Bernd A; Bundschuh, Bettina B; Schwarz, Julia; Klasen, Joachim; Röhrig, Rainer

2012-01-01

In Germany the core data set for anesthesia version 3.0 was recently introduced for external quality assurance, which includes five surgical tracer procedures. We found a low rate of correctly documented tracers when compared to procedure data (OPS-Codes) documented separately. Examination revealed that the graphical user interface (GUI) contravened the dialogue principles as defined in EN ISO 9241-110. We worked with the manufacturer to implement small improvements and roll out the software. A crossover study was conducted at a university hospital and a municipal hospital chain with five hospitals. All study sites and surgical tracer procedures combined, we found an improvement from 42% to 65% (p<0.001; N=34,610) correctly documented anesthesias. We also saw improvements for most of the observed surgical tracer procedures at all hospitals. Our results show the big effect small changes to the GUI can have on data quality. They also raise the question, if highly flexible and parameterized clinical documentation systems are suited to achieve high usability. Finding the right balance between GUIs designed by usability experts and the flexibility of parameterization by administrators will be a difficult task for the future and subject to further research.

The Effect of Music Therapy Services on Classroom Behaviours of Newly Arrived Refugee Students in Australia--A Pilot Study

ERIC Educational Resources Information Center

Baker, Felicity; Jones, Carolyn

2006-01-01

This pilot study examined the effects of a short-term music therapy program on the classroom behaviours of newly arrived refugee students who were attending an intensive "English as a Second Language" secondary school. A cross-over design with two five-week intervention periods was employed with group music therapy sessions conducted one…

X-Chromosome Control of Genome-Scale Recombination Rates in House Mice.

PubMed

Dumont, Beth L

2017-04-01

Sex differences in recombination are widespread in mammals, but the causes of this pattern are poorly understood. Previously, males from two interfertile subspecies of house mice, Mus musculus musculus and M. m. castaneus , were shown to exhibit a ∼30% difference in their global crossover frequencies. Much of this crossover rate divergence is explained by six autosomal loci and a large-effect locus on the X chromosome. Intriguingly, the allelic effects at this X-linked locus are transgressive, with the allele conferring increased crossover rate being transmitted by the low crossover rate M. m. castaneus parent. Despite the pronounced divergence between males, females from these subspecies exhibit similar crossover rates, raising the question of how recombination is genetically controlled in this sex. Here, I analyze publicly available genotype data from early generations of the Collaborative Cross, an eight-way panel of recombinant inbred strains, to estimate crossover frequencies in female mice with sex-chromosome genotypes of diverse subspecific origins. Consistent with the transgressive influence of the X chromosome in males, I show that females inheriting an M. m. castaneus X possess higher average crossover rates than females lacking the M. m. castaneus X chromosome. The differential inheritance of the X chromosome in males and females provides a simple genetic explanation for sex-limited evolution of this trait. Further, the presence of X-linked and autosomal crossover rate modifiers with antagonistic effects hints at an underlying genetic conflict fueled by selection for distinct crossover rate optima in males and females. Copyright © 2017 by the Genetics Society of America.

New and old ways to control meiotic recombination.

PubMed

Phadnis, Naina; Hyppa, Randy W; Smith, Gerald R

2011-10-01

The unique segregation of homologs, rather than sister chromatids, at the first meiotic division requires the formation of crossovers (COs) between homologs by meiotic recombination in most species. Crossovers do not form at random along chromosomes. Rather, their formation is carefully controlled, both at the stage of formation of DNA double-strand breaks (DSBs) that can initiate COs and during the repair of these DSBs. Here, we review control of DSB formation and two recently recognized controls of DSB repair: CO homeostasis and CO invariance. Crossover homeostasis maintains a constant number of COs per cell when the total number of DSBs in a cell is experimentally or stochastically reduced. Crossover invariance maintains a constant CO density (COs per kb of DNA) across much of the genome despite strong DSB hotspots in some intervals. These recently uncovered phenomena show that CO control is even more complex than previously suspected. Copyright © 2011 Elsevier Ltd. All rights reserved.

Five Years of Cenosumab Exposure in Women With Postmenopausal Osteoporosis: Results From the First Two Years of the FREEDOM Extension

PubMed Central

Papapoulos, Socrates; Chapurlat, Roland; Libanati, Cesar; Brandi, Maria Luisa; Brown, Jacques P; Czerwiński, Edward; Krieg, Marc-Antoine; Man, Zulema; Mellström, Dan; Radominski, Sebastião C; Reginster, Jean-Yves; Resch, Heinrich; Ivorra, José A Román; Roux, Christian; Vittinghoff, Eric; Austin, Matthew; Daizadeh, Nadia; Bradley, Michelle N; Grauer, Andreas; Cummings, Steven R; Bone, Henry G

2012-01-01

The 3-year FREEDOM trial assessed the efficacy and safety of 60 mg denosumab every 6 months for the treatment of postmenopausal women with osteoporosis. Participants who completed the FREEDOM trial were eligible to enter an extension to continue the evaluation of denosumab efficacy and safety for up to 10 years. For the extension results presented here, women from the FREEDOM denosumab group had 2 more years of denosumab treatment (long-term group) and those from the FREEDOM placebo group had 2 years of denosumab exposure (cross-over group). We report results for bone turnover markers (BTMs), bone mineral density (BMD), fracture rates, and safety. A total of 4550 women enrolled in the extension (2343 long-term; 2207 cross-over). Reductions in BTMs were maintained (long-term group) or occurred rapidly (cross-over group) following denosumab administration. In the long-term group, lumbar spine and total hip BMD increased further, resulting in 5-year gains of 13.7% and 7.0%, respectively. In the cross-over group, BMD increased at the lumbar spine (7.7%) and total hip (4.0%) during the 2-year denosumab treatment. Yearly fracture incidences for both groups were below rates observed in the FREEDOM placebo group and below rates projected for a “virtual untreated twin” cohort. Adverse events did not increase with long-term denosumab administration. Two adverse events in the cross-over group were adjudicated as consistent with osteonecrosis of the jaw. Five-year denosumab treatment of women with postmenopausal osteoporosis maintained BTM reduction and increased BMD, and was associated with low fracture rates and a favorable risk/benefit profile. © 2012 American Society for Bone and Mineral Research PMID:22113951

A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study

PubMed Central

2012-01-01

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 PMID:22800470

Correlation between Fragility and the Arrhenius Crossover Phenomenon in Metallic, Molecular, and Network Liquids.

PubMed

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}).

Correlation between Fragility and the Arrhenius Crossover Phenomenon in Metallic, Molecular, and Network Liquids

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

Jaiswal, Abhishek; Egami, Takeshi; Kelton, K. F.

2016-11-10

In this paper, 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 valuesmore » for strong network liquids spans a wide range higher than 2. Intriguingly, the high-temperature activation barrier E ∞ is universally found to be ~11k BT g and uncorrelated with the fragility or the reduced crossover temperature θ A for metallic and molecular liquids. Finally, 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).« less

Deep brain stimulation for treatment-resistant major depressive disorder: a comparison of two targets and long-term follow-up

PubMed Central

Raymaekers, S; Luyten, L; Bervoets, C; Gabriëls, L; Nuttin, B

2017-01-01

We previously found that electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) alleviates depressive symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we tested the hypothesis that electrical stimulation in either IC/BST or in the inferior thalamic peduncle (ITP) effectively reduces depressive symptoms in treatment-resistant major depressive disorder (TRD). In a double-blind crossover design, the effects of electrical stimulation at both targets were compared in TRD patients. The 17-item Hamilton Depression Rating scale (HAM-D) was the primary outcome measure. During the first crossover, patients received IC/BST stimulation versus no stimulation in random order (2 × 1 weeks). During the second crossover (3 × 2 months), patients received IC/BST versus ITP versus no stimulation. Patients and evaluators were blinded for stimulation conditions. All patients (n=7) were followed up for at least 3 years (3–8 years) after implantation. Six patients completed the first crossover and five patients completed the second. During the first crossover, mean (s.d.) HAM-D scores were 21.5 (2.7) for no stimulation and 11.5 (8.8) for IC/BST stimulation. During the second crossover, HAM-D scores were 15.4 (7.5) for no stimulation, 7.6 (3.8) for IC/BST stimulation and 11.2 (7.5) for ITP stimulation. The final sample size was too small to statistically analyze this second crossover. At last follow-up, only one patient preferred ITP over IC/BST stimulation. Two patients, with a history of suicide attempts before implantation, committed suicide during the follow-up phases of this study. Our data indicate that, in the long term, both ITP and IC/BST stimulation may alleviate depressive symptoms in patients suffering from TRD. PMID:29087373

Deep brain stimulation for treatment-resistant major depressive disorder: a comparison of two targets and long-term follow-up.

PubMed

Raymaekers, S; Luyten, L; Bervoets, C; Gabriëls, L; Nuttin, B

2017-10-31

We previously found that electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) alleviates depressive symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we tested the hypothesis that electrical stimulation in either IC/BST or in the inferior thalamic peduncle (ITP) effectively reduces depressive symptoms in treatment-resistant major depressive disorder (TRD). In a double-blind crossover design, the effects of electrical stimulation at both targets were compared in TRD patients. The 17-item Hamilton Depression Rating scale (HAM-D) was the primary outcome measure. During the first crossover, patients received IC/BST stimulation versus no stimulation in random order (2 × 1 weeks). During the second crossover (3 × 2 months), patients received IC/BST versus ITP versus no stimulation. Patients and evaluators were blinded for stimulation conditions. All patients (n=7) were followed up for at least 3 years (3-8 years) after implantation. Six patients completed the first crossover and five patients completed the second. During the first crossover, mean (s.d.) HAM-D scores were 21.5 (2.7) for no stimulation and 11.5 (8.8) for IC/BST stimulation. During the second crossover, HAM-D scores were 15.4 (7.5) for no stimulation, 7.6 (3.8) for IC/BST stimulation and 11.2 (7.5) for ITP stimulation. The final sample size was too small to statistically analyze this second crossover. At last follow-up, only one patient preferred ITP over IC/BST stimulation. Two patients, with a history of suicide attempts before implantation, committed suicide during the follow-up phases of this study. Our data indicate that, in the long term, both ITP and IC/BST stimulation may alleviate depressive symptoms in patients suffering from TRD.

Can the Farnsworth D15 Color Vision Test Be Defeated through Practice?

PubMed

Ng, Jason S; Liem, Sophia C

2018-05-01

This study suggests that it is possible for some patients with severe red-green color vision deficiency to do perfectly on the Farnsworth D15 test after practicing it. The Farnsworth D15 is a commonly used test to qualify people for certain occupations. For patients with color vision deficiency, there may be high motivation to try to pass the test through practice to gain entry into a particular occupation. There is no evidence in the literature on whether it is possible for patients to learn to pass the D15 test through practice. Ten subjects with inherited red-green color vision deficiency and 15 color-normal subjects enrolled in the study. All subjects had anomaloscope testing, color vision book tests, and a Farnsworth D15 at an initial visit. For the D15, the number of major crossovers was determined for each subject. Failing the D15 was determined as greater than 1 major crossover. Subjects with color vision deficiency practiced the D15 as long as desired to achieve a perfect score and then returned for a second visit for D15 testing. A paired t test was used to analyze the number of major crossovers at visit 1 versus visit 2. Color-normal subjects did not have any major crossovers. Subjects with color vision deficiency had significantly (P < .001) fewer major crossovers on the D15 test at visit 2 (mean/SD = 2.5/3.0), including five subjects with dichromacy that achieved perfect D15 performance, compared to visit 1 (mean/SD = 8.7/1.3). Practice of the Farnsworth D15 test can lead to perfect performance for some patients with color vision deficiency, and this should be considered in certain cases where occupational entry is dependent on D15 testing.

Automatic Combination of Operators in a Genetic Algorithm to Solve the Traveling Salesman Problem.

PubMed

Contreras-Bolton, Carlos; Parada, Victor

2015-01-01

Genetic algorithms are powerful search methods inspired by Darwinian evolution. To date, they have been applied to the solution of many optimization problems because of the easy use of their properties and their robustness in finding good solutions to difficult problems. The good operation of genetic algorithms is due in part to its two main variation operators, namely, crossover and mutation operators. Typically, in the literature, we find the use of a single crossover and mutation operator. However, there are studies that have shown that using multi-operators produces synergy and that the operators are mutually complementary. Using multi-operators is not a simple task because which operators to use and how to combine them must be determined, which in itself is an optimization problem. In this paper, it is proposed that the task of exploring the different combinations of the crossover and mutation operators can be carried out by evolutionary computing. The crossover and mutation operators used are those typically used for solving the traveling salesman problem. The process of searching for good combinations was effective, yielding appropriate and synergic combinations of the crossover and mutation operators. The numerical results show that the use of the combination of operators obtained by evolutionary computing is better than the use of a single operator and the use of multi-operators combined in the standard way. The results were also better than those of the last operators reported in the literature.

Automatic Combination of Operators in a Genetic Algorithm to Solve the Traveling Salesman Problem

PubMed Central

2015-01-01

Genetic algorithms are powerful search methods inspired by Darwinian evolution. To date, they have been applied to the solution of many optimization problems because of the easy use of their properties and their robustness in finding good solutions to difficult problems. The good operation of genetic algorithms is due in part to its two main variation operators, namely, crossover and mutation operators. Typically, in the literature, we find the use of a single crossover and mutation operator. However, there are studies that have shown that using multi-operators produces synergy and that the operators are mutually complementary. Using multi-operators is not a simple task because which operators to use and how to combine them must be determined, which in itself is an optimization problem. In this paper, it is proposed that the task of exploring the different combinations of the crossover and mutation operators can be carried out by evolutionary computing. The crossover and mutation operators used are those typically used for solving the traveling salesman problem. The process of searching for good combinations was effective, yielding appropriate and synergic combinations of the crossover and mutation operators. The numerical results show that the use of the combination of operators obtained by evolutionary computing is better than the use of a single operator and the use of multi-operators combined in the standard way. The results were also better than those of the last operators reported in the literature. PMID:26367182

Lubiprostone decreases the small bowel transit time by capsule endoscopy: an exploratory, randomised, double-blind, placebo-controlled 3-way crossover study.

PubMed

Matsuura, Mizue; Inamori, Masahiko; Endo, Hiroki; Matsuura, Tetsuya; Kanoshima, Kenji; Inoh, Yumi; Fujita, Yuji; Umezawa, Shotaro; Fuyuki, Akiko; Uchiyama, Shiori; Higurashi, Takuma; Ohkubo, Hidenori; Sakai, Eiji; Iida, Hiroshi; Nonaka, Takashi; Futagami, Seiji; Kusakabe, Akihiko; Maeda, Shin; Nakajima, Atsushi

2014-01-01

The aim of this study was to investigate the usefulness of lubiprostone for bowel preparation and as a propulsive agent in small bowel endoscopy. Six healthy male volunteers participated in this randomized, 3-way crossover study. The subjects received a 24 μg tablet of lubiprostone 60 minutes prior to the capsule ingestion for capsule endoscopy (CE) and a placebo tablet 30 minutes before the capsule ingestion (L-P regimen), a placebo tablet 60 minutes prior to CE and a 24 μg tablet of lubiprostone 30 minutes prior to CE (P-L regimen), or a placebo tablet 60 minutes prior to r CE and a placebo tablet again 30 minutes prior to CE (P-P regimen). The quality of the capsule endoscopic images and the amount of water in the small bowel were assessed on 5-point scale. The median SBTT was 178.5 (117-407) minutes in the P-P regimen, 122.5 (27-282) minutes in the L-P regimen, and 110.5 (11-331) minutes in the P-L regimen (P = 0.042). This study showed that the use of lubiprostone significantly decreased the SBTT. We also confirmed that lubiprostone was effective for inducing water secretion into the small bowel during CE.

Efficacy and safety of mini-dose glucagon for treatment of nonsevere hypoglycemia in adults with type 1 diabetes

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to evaluate low-dose glucagon to treat mild hypoglycemia in ambulatory adults with type 1 diabetes (T1D). This was a randomized crossover trial (two 3-week periods) conducted at five U.S. diabetes clinics. Twenty adults with T1D using an insulin pump and continuous gluc...

Telerehabilitation in poststroke anomia.

PubMed

Agostini, Michela; Garzon, Martina; Benavides-Varela, Silvia; De Pellegrin, Serena; Bencini, Giulia; Rossi, Giulia; Rosadoni, Sara; Mancuso, Mauro; Turolla, Andrea; Meneghello, Francesca; Tonin, Paolo

2014-01-01

Anomia, a word-finding difficulty, is a frequent consequence of poststroke linguistic disturbance, associated with fluent and nonfluent aphasia that needs long-term specific and intensive speech rehabilitation. The present study explored the feasibility of telerehabilitation as compared to a conventional face-to-face treatment of naming, in patients with poststroke anomia. Five aphasic chronic patients participated in this study characterized by: strictly controlled crossover design; well-balanced lists of words in picture-naming tasks where progressive phonological cues were provided; same kind of the treatment in the two ways of administration. ANOVA was used to compare naming accuracy in the two types of treatment, at three time points: baseline, after treatment, and followup. The results revealed no main effect of treatment type (P = 0.844) indicating that face-to-face and tele-treatment yielded comparable results. Moreover, there was a significant main effect of time (P = 0.0004) due to a better performance immediately after treatment and in the followup when comparing them to baseline. These preliminary results show the feasibility of teletreatment applied to lexical deficits in chronic stroke patients, extending previous work on telerehabilitation and opening new vistas for future studies on teletreatment of language functions.

Experimental investigation of cross-over jets in a rib-roughened trailing-edge cooling channel

NASA Astrophysics Data System (ADS)

Xue, Fei

Increasing the rotor inlet temperature can dramatically increase the efficiency and power output of the gas turbine engine. However, the melting point of turbine blade material limits the realistic upper bound of the rotor inlet temperature. As a result, the development of high temperature turbine blade material and advanced turbine blade cooling technology determines the future of turbine blade engine. Adding impingement jet holes and rib turbulators in the inner cooling channel of the gas turbine blades are two effective ways to enhance the cooling effects. The purpose of this study is to figure out the influence of different combinations of jet holes and rib turbulators on the heat transfer efficiency. A tabletop scale test model is used in the study to simulate the cooling cavity of trailing edge and its feed channel in a real gas turbine blade. The Dimensional Analysis Theory is used in the study to eliminate the influence of scaling. Two different crossover slots are tested with 5 different rib arrangements, and each of the test geometries is tested for 6 jet Reynolds numbers ranging from 10,000 to 36,000. The two different crossover slots are the crossover slots with 0 and 5 degree tilt angles. The four different rib arrangements are ribs with 0 degree, 45 degree, 90 degree and 135 degree angles of attack with respect to the flow direction. Furthermore, a smooth test section (no ribs) was also tested. The steady state liquid crystal thermography is used to quantify the heat transfer performance of the target areas. The variation of Nusselt number versus Reynolds number is plotted for each of the 10 geometries. Also, the variation of Nusselt number versus Reynolds number are compared for different rib angles of attack with the same crossover slot tilt angle, and between different crossover slots tilt angles with the same rib angle. The results show that, the area-weighted average Nusselt number increases monotonically with the Reynolds number; the target areas near the open end have a larger Nusselt number comparing with the ones near the close end; the 90 degree rib angle has the highest Nusselt number among the 4 rib angles of attack and the smooth wall channel; the crossover slots with 0 degree tilt angle produce higher convective heat transfer coefficients than the crossover slots with 5 degree tilt angle. Possible physical explanations for the result are offered by the author.

Workaholism and relationship quality: a spillover-crossover perspective.

PubMed

Bakker, Arnold B; Demerouti, Evangelia; Burke, Ronald

2009-01-01

This study of 168 dual-earner couples examined the relationship between workaholism and relationship satisfaction. More specifically, on the basis of the literature, it was hypothesized that workaholism is positively related to work-family conflict. In addition, the authors predicted that workaholism is related to reduced support provided to the partner, through work-family conflict, and that individuals who receive considerable support from their partners are more satisfied with their relationship. Finally, the authors hypothesized direct crossover of relationship satisfaction between partners. The results of structural equation modeling analyses using the matched responses of both partners supported these hypotheses. Moreover, in line with predictions, the authors found that gender did not affect the strength of the relationships in the proposed model. The authors discuss workplace interventions as possible ways to help workaholics and their partners.

Ambient temperature and coronary heart disease mortality in Beijing, China: a time series study

PubMed Central

2012-01-01

Background Many studies have examined the association between ambient temperature and mortality. However, less evidence is available on the temperature effects on coronary heart disease (CHD) mortality, especially in China. In this study, we examined the relationship between ambient temperature and CHD mortality in Beijing, China during 2000 to 2011. In addition, we compared time series and time-stratified case-crossover models for the non-linear effects of temperature. Methods We examined the effects of temperature on CHD mortality using both time series and time-stratified case-crossover models. We also assessed the effects of temperature on CHD mortality by subgroups: gender (female and male) and age (age > =65 and age < 65). We used a distributed lag non-linear model to examine the non-linear effects of temperature on CHD mortality up to 15 lag days. We used Akaike information criterion to assess the model fit for the two designs. Results The time series models had a better model fit than time-stratified case-crossover models. Both designs showed that the relationships between temperature and group-specific CHD mortality were non-linear. Extreme cold and hot temperatures significantly increased the risk of CHD mortality. Hot effects were acute and short-term, while cold effects were delayed by two days and lasted for five days. The old people and women were more sensitive to extreme cold and hot temperatures than young and men. Conclusions This study suggests that time series models performed better than time-stratified case-crossover models according to the model fit, even though they produced similar non-linear effects of temperature on CHD mortality. In addition, our findings indicate that extreme cold and hot temperatures increase the risk of CHD mortality in Beijing, China, particularly for women and old people. PMID:22909034

Pulmonary rehabilitation after total laryngectomy: a randomized cross-over clinical trial comparing two different heat and moisture exchangers (HMEs).

PubMed

Herranz, Jesús; Espiño, María Alvarez; Morado, Carolina Ogen

2013-09-01

Post-laryngectomy heat and moisture exchanger (HME) use is known to have a beneficial effect on tracheal climate, pulmonary symptoms and related aspects. This study aims to investigate differences in clinical effects between the first and second generation Provox HMEs. The second generation (Provox XtraHME) has better humidification properties than the first generation (Provox HME), and has been shown to further improve tracheal climate. Forty-five laryngectomized patients, who were already using an HME, participated in a prospective, randomized cross-over clinical study in which each HME was used for 6 weeks. Results showed that for most parameters studied, the second generation HME performed equally well or better than the first generation HME. The improvement in tracheal climate translated into patients reporting significantly less tracheal dryness with the second generation than with the first generation (p = 0.039). Using an HME with better humidification properties is related to a reduction in tracheal dryness in our study population.

Ultrastable light sources in the crossover from superradiance to lasing

NASA Astrophysics Data System (ADS)

Xu, Minghui; Tieri, David; Holland, Murray

2013-05-01

We theoretically investigate the crossover from steady-state superradiance to optical lasing. An exact solution of the quantum master equation is difficult to obtain due to the exponential scaling of the Hilbert space dimension with system size. However, since Lindblad operators in the master equation are invariant under SU(4) transformations, we are able to reduce the exponential scaling of the problem to cubic by expanding the density matrix in terms of an SU(4) basis. In this way, we obtain exact quantum solutions of the superradiance-laser crossover. We use this theory to investigate the potential for ultrastable lasers in the millihertz linewidth regime, and find the behavior of important observables, such as intensity, linewidth, spin-correlation, and entanglement. This work was supported by the DARPA QUASAR program and NSF.

Omega-3/Omega-6 Fatty Acids for Attention Deficit Hyperactivity Disorder: A Randomized Placebo-Controlled Trial in Children and Adolescents

ERIC Educational Resources Information Center

Johnson, Mats; Ostlund, Sven; Fransson, Gunnar; Kadesjo, Bjorn; Gillberg, Christopher

2009-01-01

Objective: The aim of the study was to assess omega 3/6 fatty acids (eye q) in attention deficit hyperactivity disorder (ADHD). Method: The study included a randomized, 3-month, omega 3/6 placebo-controlled, one-way crossover trial with 75 children and adolescents (8-18 years), followed by 3 months with omega 3/6 for all. Investigator-rated ADHD…

The influence of transcutaneous electrical nerve stimulation parameters on the level of pain perceived by participants with painful diabetic neuropathy: A crossover study.

PubMed

Upton, Gabrielle A; Tinley, Paul; Al-Aubaidy, Hayder; Crawford, Rachel

This pilot study aimed to investigate and compare the perceived pain relief effectiveness of two different modes of TENS in people with painful diabetic neuropathy (PDN). A cross-over study was conducted at Charles Sturt University, Orange. Five participants with PDN were assessed with a McGill Pain Questionnaire before and after each of the two TENS treatments. Participants were randomly allocated to Traditional TENS (80Hz, 200ms) or Acupuncture-like TENS (2Hz, 200ms) and the treatments were applied daily for 30min over ten days. Following a seven day washout period, the alternate mode of TENS was carried out using the same method. Wilcoxon Signed Rank tests were used to statistically analyse the results. All five participants reported personally meaningful pain relief during one or both of the TENS treatments. The Wilcoxon signed rank testing showed no statistical significance, p=1, likely due to the small sample size. Acupuncture-like TENS had a large effect size (z=-1.625, r=0.514), whilst Traditional TENS produced a medium effect size (z=-1.214, r=0.384). No adverse effects were reported. Acupuncture-like TENS may be more effective for PDN than traditional TENS. A larger scale replication of this pilot study is warranted. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Quasi-experimental designs in practice-based research settings: design and implementation considerations.

PubMed

Handley, Margaret A; Schillinger, Dean; Shiboski, Stephen

2011-01-01

Although randomized controlled trials are often a gold standard for determining intervention effects, in the area of practice-based research (PBR), there are many situations in which individual randomization is not possible. Alternative approaches to evaluating interventions have received increased attention, particularly those that can retain elements of randomization such that they can be considered "controlled" trials. Methodological design elements and practical implementation considerations for two quasi-experimental design approaches that have considerable promise in PBR settings--the stepped-wedge design, and a variant of this design, a wait-list cross-over design, are presented along with a case study from a recent PBR intervention for patients with diabetes. PBR-relevant design features include: creation of a cohort over time that collects control data but allows all participants (clusters or patients) to receive the intervention; staggered introduction of clusters; multiple data collection points; and one-way cross-over into the intervention arm. Practical considerations include: randomization versus stratification, training run in phases; and extended time period for overall study completion. Several design features of practice based research studies can be adapted to local circumstances yet retain elements to improve methodological rigor. Studies that utilize these methods, such as the stepped-wedge design and the wait-list cross-over design, can increase the evidence base for controlled studies conducted within the complex environment of PBR.

An Evaluation of the Effectiveness of a "Five Ways to Well-Being" Group Run with People with Learning Disabilities

ERIC Educational Resources Information Center

Mahoney-Davies, Gerwyn; Dixon, Clare; Tynan, Hannah; Mann, Sian

2017-01-01

Background: The "Five Ways to Well-being" document presents five ways in which people in the general population may be able to improve their well-being. This study evaluates the use of a "Five Ways to Well-being" group in a population of people with learning disabilities. Materials and Methods: Twelve participants who attend a…

The effect of nabilone on neuropsychological functions related to driving ability: an extended case series.

PubMed

Kurzthaler, Ilsemarie; Bodner, Thomas; Kemmler, Georg; Entner, Tanja; Wissel, Joerg; Berger, Thomas; Fleischhacker, W Wolfgang

2005-06-01

The primary goal of this prospective extended case series was to obtain the first data about the potential influence of nabilone intake on driving ability related neuropsychological functions. Six patients were investigated within a placebo controlled, double-blind crossover study of this synthetic cannabinoid (2 mg/day) in patients with multiple sclerosis and spasticity associated pain. Five neuropsychological functions (reaction time, working memory, divided attention, psychomotor speed and mental flexibility) were assessed. No indication was found of a deterioration of any of the five investigated neuropsychological functions during the 4-week treatment period with nabilone. Copyright 2005 John Wiley & Sons, Ltd.

Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized, double-masked, crossover study.

PubMed

Asp, Michelle L; Collene, Angela L; Norris, Leigh E; Cole, Rachel M; Stout, Michael B; Tang, Szu-Yu; Hsu, Jason C; Belury, Martha A

2011-08-01

Metabolic effects of dietary fat quality in people with type 2 diabetes are not well-understood. The study objective was to evaluate effects of conjugated linoleic acid (CLA) and safflower (SAF) oils on glycemia, blood lipids, and inflammation. The hypothesis we tested is that dietary oils improve glycemia, lipids, and inflammatory markers in a time-dependent way that follows accumulation of linoleic acid and CLA isomers in serum of subjects supplemented with dietary oils. Fifty-five post-menopausal, obese women with type 2 diabetes enrolled, and 35 completed this randomized, double-masked crossover study. Treatments were 8 g daily of CLA and SAF for 16 weeks each. We used a multiple testing procedure with pre-determined steps analysis to determine the earliest time that a significant effect was detected. CLA did not alter measured metabolic parameters. SAF decreased HbA1c (-0.64 ± 0.18%, p = 0.0007) and C-reactive protein (-13.6 ± 8.2 mg/L, p = 0.0472), increased QUICKI (0.0077 ± 0.0035, p = 0.0146) with a minimum time to effect observed 16 weeks after treatment. SAF increased HDL cholesterol (0.12 ± 0.05 mmol/L, p = 0.0228) with the minimum time to detect an effect of SAF at 12 weeks. The minimum time to detect an increase of c9t11-CLA, t10c12-CLA, and linoleic acid in serum of women supplemented CLA or SAF, respectively, was four weeks. We conclude that 8 g of SAF daily improved glycemia, inflammation, and blood lipids, indicating that small changes in dietary fat quality may augment diabetes treatments to improve risk factors for diabetes-related complications. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized, double-masked, crossover study

PubMed Central

Asp, Michelle L.; Collene, Angela L.; Norris, Leigh E.; Cole, Rachel M.; Stout, Michael B.; Tang, Szu-Yu; Hsu, Jason C.; Belury, Martha A.

2011-01-01

Background & Aims Metabolic effects of dietary fat quality in people with type 2 diabetes are not well-understood. The study objective was to evaluate effects of conjugated linoleic acid (CLA) and safflower (SAF) oils on glycemia, blood lipids, and inflammation. The hypothesis we tested is SAF oil improves glycemic and inflammatory markers in a time dependent way that follows accumulation of linoleic acid and CLA isomers in serum of subjects supplemented with dietary oils. Methods Fifty-five post-menopausal, obese women with type 2 diabetes enrolled, and 35 completed this randomized, double-masked crossover study. Treatments were eight grams daily of CLA and SAF for 16 weeks each. We used a multiple testing procedure with predetermined step analysis to determine when the earliest time to effect was significant. Results CLA did not alter measured metabolic parameters. SAF decreased HbA1c (−0.64±0.18%, p<0.0007) and C-reactive protein (−13.6±8.2mg/L, p<0.0472), increased QUICKI (0.0077±0.0035, p<0.0146) with a minimum time to effect observed 16 weeks after treatment. SAF increased HDL cholesterol (0.12±0.05mmol/L, p<0.0228) with the minimum time to detect an effect of SAF at 12 weeks. The minimum time to detect an increase of c9t11-CLA, t10c12-CLA and linoleic acid in serum of women supplemented CLA or SAF respectively was four weeks. Conclusions We conclude that eight grams of SAF daily improved glycemia, inflammation, and blood lipids indicating that small changes in dietary fat quality may augment diabetes treatments to improve risk factors for diabetes-related complications. PMID:21295383

The role of crossover operator in evolutionary-based approach to the problem of genetic code optimization.

PubMed

Błażej, Paweł; Wnȩtrzak, Małgorzata; Mackiewicz, Paweł

2016-12-01

One of theories explaining the present structure of canonical genetic code assumes that it was optimized to minimize harmful effects of amino acid replacements resulting from nucleotide substitutions and translational errors. A way to testify this concept is to find the optimal code under given criteria and compare it with the canonical genetic code. Unfortunately, the huge number of possible alternatives makes it impossible to find the optimal code using exhaustive methods in sensible time. Therefore, heuristic methods should be applied to search the space of possible solutions. Evolutionary algorithms (EA) seem to be ones of such promising approaches. This class of methods is founded both on mutation and crossover operators, which are responsible for creating and maintaining the diversity of candidate solutions. These operators possess dissimilar characteristics and consequently play different roles in the process of finding the best solutions under given criteria. Therefore, the effective searching for the potential solutions can be improved by applying both of them, especially when these operators are devised specifically for a given problem. To study this subject, we analyze the effectiveness of algorithms for various combinations of mutation and crossover probabilities under three models of the genetic code assuming different restrictions on its structure. To achieve that, we adapt the position based crossover operator for the most restricted model and develop a new type of crossover operator for the more general models. The applied fitness function describes costs of amino acid replacement regarding their polarity. Our results indicate that the usage of crossover operators can significantly improve the quality of the solutions. Moreover, the simulations with the crossover operator optimize the fitness function in the smaller number of generations than simulations without this operator. The optimal genetic codes without restrictions on their structure minimize the costs about 2.7 times better than the canonical genetic code. Interestingly, the optimal codes are dominated by amino acids characterized by polarity close to its average value for all amino acids. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A randomized, open-label 3-way crossover study to investigate the relative bioavailability and bioequivalence of crushed sildenafil 20 mg tablets mixed with apple sauce, extemporaneously prepared suspension (EP), and intact sildenafil 20 mg tablets in healthy volunteers under fasting conditions.

PubMed

Gao, Xiang; Ndongo, Marie-Noella; Checchio, Tina M; Cook, Jack; Duncan, Barbara; LaBadie, Robert R

2015-01-01

The relative bioavailability and bioequivalence of 20-mg doses of a pediatric formulation of sildenafil extemporaneous preparation suspension (EP; 10 mg/mL), the sildenafil 20-mg intact tablet and the crushed sildenafil 20-mg tablet mixed with apple sauce were assessed in a single-dose, randomized, open-label, 3-way crossover study with 18 healthy adult volunteers. Blood samples were collected at predefined times and analyzed for sildenafil plasma concentrations. Natural log-transformed sildenafil pharmacokinetic parameters (Cmax , AUClast , and AUCinf ) were used to estimate relative bioavailability and construct 90% confidence intervals (CI) using a mixed-effects model. Bioequivalence was concluded among the three formulations with one exception, in which the EP suspension showed a 15% decrease in Cmax with a lower 90% CI of 76% compared with the intact tablet. The 15% decrease in sildenafil Cmax is not considered to be clinically relevant. Therefore, the EP suspension is considered to be an appropriate pediatric formulation. All 3 formulations were well tolerated in healthy adult volunteers. © 2014, The American College of Clinical Pharmacology.

The management of xerostomia in patients on haemodialysis: comparison of artificial saliva and chewing gum.

PubMed

Bots, Casper P; Brand, Henk S; Veerman, Enno C I; Valentijn-Benz, Marianne; Van Amerongen, Barbara M; Nieuw Amerongen, Arie V; Valentijn, Robert M; Vos, Pieter F; Bijlsma, Joost A; Bezemer, Pieter D; ter Wee, Piet M

2005-04-01

Many patients on haemodialysis (HD) therapy suffer from a dry mouth and xerostomia. This can be relieved by mechanical and gustatory stimulation or palliative care. The aim of this crossover study was to investigate the effect and preferences of a sugar-free chewing gum (Freedent White) and a xanthan gum-based artificial saliva (Xialine) in the management of xerostomia in chronic HD patients. Sixty-five HD patients participated in a 6-week crossover trial. The artificial saliva was rated significantly lower than the chewing gum for effectiveness, taste and a global assessment. No preference differences were found for gender and age, although older subjects rated the artificial saliva with a higher mark. Thirty-nine subjects (60%) preferred chewing gum, 15% (n=10) preferred the artificial saliva. Therefore, both chewing gum and artificial saliva could play an important role in the palliative care of xerostomia in HD patients.

The educational, racial and gender crossovers in life satisfaction: Findings from the longitudinal Health and Retirement Study.

PubMed

Zhang, Wei; Braun, Kathryn L; Wu, Yan Yan

2017-11-01

To examine variations in life satisfaction by education, gender, and race/ethnicity over a period of eight years among middle-aged and older Americans. Mixed-effects models were used to analyze five waves (2006, 2008, 2010, 2012 and 2014) of longitudinal data from 16,163 participants born 1890-1953 in the U.S. Health and Retirement Study. Life satisfaction was higher in older adults, and the Great Recession had great impact on life satisfaction. Crossover interactions were found by gender, education, and race/ethnicity. Higher education was associated with higher life satisfaction for both genders, with stronger effects for females. Hispanics had the higher level of life satisfaction than non-Hispanic Whites and African Americans. Longitudinal evidence revealed disparities in life satisfaction. The racial/ethnic differences in the impact of education suggest that the economic and health returns of education vary by social group. Researchers should continue to examine reasons for these disparities. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of conjugated linoleic acid and high oleic acid safflower oil in the treatment of children with HPV-induced laryngeal papillomatosis: a randomized, double-blinded and crossover preliminary study.

PubMed

Louw, Louise

2012-10-12

Surgery is the mainstay therapy for HPV-induced laryngeal papillomatosis (LP) and adjuvant therapies are palliative at best. Research revealed that conjugated-linoleic acid (CLA) may improve the outcome of virally-induced diseases. The effects of Clarinol™ G-80 (CLA) and high oleic safflower oil (HOSF) on children with LP (concomitant with surgery) were evaluated. A randomized, double-blinded, crossover and reference-oil controlled trial was conducted at a South African medical university. Study components included clinical, HPV type/load and lymphocyte/cytokine analyses, according to routine laboratory methods. Overall: ten children enrolled; eight completed the trial; five remained randomized; seven received CLA first; all treatments remained double-blinded. Children (4 to 12 years) received 2.5 ml p/d CLA (8 weeks) and 2.5 ml p/d HOSF (8 weeks) with a washout period (6 weeks) in-between. The one-year trial included a post-treatment period (30 weeks) and afterwards was a one-year follow-up period. Changes in numbers of surgical procedures for improved disease outcome, total/anatomical scores (staging system) for papillomatosis prevention/viral inhibition, and lymphocyte/cytokine counts for immune responses between baselines and each treatment/end of trial were measured. After each treatment all the children were in remission (no surgical procedures); after the trial two had recurrence (surgical procedures in post-treatment period); after the follow-up period three had recurrence (several surgical procedures) and five recovered (four had no surgical procedures). Effects of CLA (and HOSF to a lesser extent) were restricted to mildly/moderately aggressive papillomatosis. Children with low total scores (seven/less) and reduced infections (three/less laryngeal sub-sites) recovered after the trial. No harmful effects were observed. The number of surgical procedures during the trial (n6/available records) was significantly lower [(p 0.03) (95% CI 1.1; 0)]. Changes in scores between baselines and CLA treatments (n8) were significantly lower: total scores [(p 0.02) (95% CI -30.00; 0.00)]; anatomical scores [(p 0.008) (95% CI -33.00: -2.00)]. Immune enhancement could not be demonstrated. These preliminary case and group findings pave the way for further research on the therapeutic potential of adjuvant CLA in the treatment of HPV-induced LP.

Consumption of restructured meat products with added walnuts has a cholesterol-lowering effect in subjects at high cardiovascular risk: a randomised, crossover, placebo-controlled study.

PubMed

Olmedilla-Alonso, B; Granado-Lorencio, F; Herrero-Barbudo, C; Blanco-Navarro, I; Blázquez-García, S; Pérez-Sacristán, B

2008-04-01

Diet and lifestyle are modifiable factors involved in the development and prevention of non-communicable diseases, including cardiovascular disease. Nut consumption, particularly walnut intake, has been inversely related to incident coronary heart disease (CHD) in observational studies and to improved lipid profiles in short-term feeding trials. To assess the potential functional effect associated with the regular consumption of walnut-enriched restructured meat products in subjects at risk for cardiovascular disease (CVD). A crossover single-dose bioavailability study (n = 3) using gamma-tocopherol as exposure marker and a crossover unblinded dietary intervention study (5 weeks) in subjects at risk (n = 25). Dietary intervention consisted of regular consumption of the meat product, with or without walnuts, five times per week for five weeks with a 1-month washout in between. Overnight fasting blood samples were collected on days 0, 12, 21, 28 and 35, coinciding with blood pressure and body weight recordings. Participants were asked to complete a diet record throughout the study. The functional effects were assessed using clinically relevant and related biomarkers of CHD: serum total, HDL and LDL cholesterol, triacylglycerols, homocysteine, vitamins B(6) and B(12), folic acid, alpha-tocopherol and platelet function test (obturation time). The regular consumption of walnut-enriched meat products compared with that of the restructured meat products without added walnuts provokes a decrease in total cholesterol of 6.8 mg/dl (CI(95%): -12.8, -0.85). Compared to baseline (mixed diet), meat products with walnuts decreased total cholesterol (-10.7 mg/dl, CI(95%): -17.1, -4.2), LDL cholesterol (-7.6 mg/dl, CI(95%): -2.2, -13.0) and body weight (-0.5 kg, CI(95%): -0.1, -0.9) and increased gamma-tocopherol (8.9 mg/dl, CI(95%): 1.0, 16.8). The restructured meat products with added walnuts supplied in this study can be considered functional foods for subjects at high risk for CVD, as their regular consumption provokes a reduction in total cholesterol of 4.5% with respect to baseline values (mixed diet) and 3% with respect to the restructured meat without walnuts.

Peer Assessment Enhances Student Learning: The Results of a Matched Randomized Crossover Experiment in a College Statistics Class.

PubMed

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.

Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users

PubMed Central

Webster, Lynn R.; Smith, Michael D.; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M.

2017-01-01

Abstract Objective. To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets. Methods. A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (Emax; primary endpoint) using drug liking visual analog scale (VAS) score, Emax using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking. Results. Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking Emax was significantly lower (P < 0.0001) compared with IN morphine ER. Overall drug liking and TDA Emax values were significantly lower (P < 0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2). Conclusions. All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine. PMID:27651510

Risk of injury after alcohol consumption from case-crossover studies in five countries from the America’s

PubMed Central

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

Levothyroxine soft capsules demonstrate bioequivalent pharmacokinetic exposure with the European reference tablets in healthy volunteers under fasting conditions.

PubMed

Al-Numani, Dina; Scarsi, Claudia; Ducharme, Murray P

2016-02-01

To assess the bioequivalence (BE) potential under fasting conditions between levothyroxine soft capsules and the European reference tablet formulation. Two studies were conducted to assess the BE potential as per European regulations. Study 1 was a two-way crossover BE study comparing a high strength of levothyroxine soft capsules versus levothyroxine tablets (200 μg), while study 2 was a three-way crossover dosage form proportionality study between low, medium, and high strengths of soft capsules. 70 healthy adult subjects participated in the two studies. Each treatment consisted of a 600-μg dose of levothyroxine sodium, administered under fasting conditions. Blood samples were collected for levothyroxine (T4) assay prior to dosing and up to 72 hours post dose. A washout of 35 days separated treatments in each study. Pharmacokinetics was assessed using noncompartmental methods. A total of 61 subjects completed the studies. Baseline-adjusted total T4 ratios (test/reference) and 90% confidence intervals (CIs) between soft capsules and tablets were within 80.00 - 125.00%. Comparison of the three strengths of soft capsules indicated pharmacokinetic equivalence between them (ratios and 90% CIs were contained within 80.00 - 125.00%). Overall, levothyroxine sodium was well tolerated with all products when given as single oral doses of 600 μg, except for 1 serious adverse event of secondary bacteremia reported in study 2, deemed not to be related to treatment. Levothyroxine soft capsules meet BE criteria in terms of systemic exposure when compared to a European reference tablet under fasting conditions in healthy volunteers.

Preventing gastric sieving by blending a solid/water meal enhances satiation in healthy humans.

PubMed

Marciani, Luca; Hall, Nicholas; Pritchard, Susan E; Cox, Eleanor F; Totman, John J; Lad, Mita; Hoad, Caroline L; Foster, Tim J; Gowland, Penny A; Spiller, Robin C

2012-07-01

Separation of solids and liquids within the stomach allows faster gastric emptying of liquids compared with solids, a phenomenon known as sieving. We tested the hypothesis that blending a solid and water meal would abolish sieving, preventing the early rapid decrease in gastric volume and thereby enhancing satiety. We carried out 2 separate studies. Study 1 was a 2-way, crossover, satiety study of 22 healthy volunteers who consumed roasted chicken and vegetables with a glass of water (1008 kJ) or the same blended to a soup. They completed satiety visual analogue scales at intervals for 3 h. Study 2 was a 2-way, crossover, mechanistic study of 18 volunteers who consumed the same meals and underwent an MRI to assess gastric emptying, gallbladder contraction, and small bowel water content (SBWC) at intervals for 3 h. In Study 1, the soup meal was associated with reduced hunger (P = 0.02). In Study 2, the volume of the gastric contents after the soup meal decreased more slowly than after the solid/liquid meal (P = 0.0003). The soup meal caused greater gallbladder contraction (P < 0.04). SBWC showed a biphasic response with an initial "gastric" phase during which SBWC was greater when the solid/liquid meal was consumed (P < 0.001) and a later "small bowel" phase when SBWC was greater when the soup meal was consumed (P < 0.01). Blending the solid/liquid meal to a soup delayed gastric emptying and increased the hormonal response to feeding, which may contribute to enhanced postprandial satiety.

Antiseptic Body Washes for Reducing the Transmission of Methicillin-Resistant Staphylococcus aureus: A Cluster Crossover Study.

PubMed

Harris, Patrick N A; Le, Bich Diep; Tambyah, Paul; Hsu, Li Yang; Pada, Surinder; Archuleta, Sophia; Salmon, Sharon; Mukhopadhyay, Amartya; Dillon, Jasmine; Ware, Robert; Fisher, Dale A

2015-04-01

Background.  Limiting the spread of methicillin-resistant Staphylococcus aureus (MRSA) within healthcare facilities where the organism is highly endemic is a challenge. The use of topical antiseptic agents may help interrupt the transmission of MRSA and reduce the risk of clinical infection. Octenidine dihydrochloride is a topical antiseptic that exhibits in vitro efficacy against a wide variety of bacteria, including S aureus. Methods.  We conducted a prospective cluster crossover study to compare the use of daily octenidine body washes with soap and water in patients identified by active surveillance cultures to be MRSA-colonized, to prevent the acquisition of MRSA in patients with negative screening swabs. Five adult medical and surgical wards and 2 intensive care units were selected. The study involved an initial 6-month phase using octenidine or soap washes followed by a crossover in each ward to the alternative product. The primary and secondary outcomes were the rates of new MRSA acquisitions and MRSA clinical infections, respectively. Results.  A total of 10 936 patients admitted for ≥48 hours was included in the analysis. There was a small reduction in MRSA acquisition in the intervention group compared with controls (3.0% vs 3.3%), but this reduction was not significant (odds ratio, 0.89; 95% confidence interval, .72-1.11; P = .31). There were also no significant differences in clinical MRSA infection or incidence of MRSA bacteremia. Conclusions.  This study suggests that the targeted use of routine antiseptic washes may not in itself be adequate to reduce the transmission of MRSA in an endemic hospital setting.

Design and evaluation of modified centerline rumble strips : final report.

DOT National Transportation Integrated Search

2017-03-08

A centerline rumble strip (CLRS) is primarily installed on the centerline of undivided two-lane and two-way roadways : to alert drivers that they are moving out of their intended travel lane. The main purpose of CLRSs is to reduce crossover : collisi...

Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study

PubMed Central

Jenkins, Tim M; Smart, Trevor S; Hackman, Frances; Cooke, Carol; Tan, Keith KC

2012-01-01

Background: 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. PMID:22888270

Mitochondrial Haplotype Diversity in Zambian Lions: Bridging a Gap in the Biogeography of an Iconic Species

PubMed Central

Curry, Caitlin J.; White, Paula A.; Derr, James N.

2015-01-01

Analysis of DNA sequence diversity at the 12S to 16S mitochondrial genes of 165 African lions (Panthera leo) from five main areas in Zambia has uncovered haplotypes which link Southern Africa with East Africa. Phylogenetic analysis suggests Zambia may serve as a bridge connecting the lion populations in southern Africa to eastern Africa, supporting earlier hypotheses that eastern-southern Africa may represent the evolutionary cradle for the species. Overall gene diversity throughout the Zambian lion population was 0.7319 +/- 0.0174 with eight haplotypes found; three haplotypes previously described and the remaining five novel. The addition of these five novel haplotypes, so far only found within Zambia, nearly doubles the number of haplotypes previously reported for any given geographic location of wild lions. However, based on an AMOVA analysis of these haplotypes, there is little to no matrilineal gene flow (Fst = 0.47) when the eastern and western regions of Zambia are considered as two regional sub-populations. Crossover haplotypes (H9, H11, and Z1) appear in both populations as rare in one but common in the other. This pattern is a possible result of the lion mating system in which predominately males disperse, as all individuals with crossover haplotypes were male. The determination and characterization of lion sub-populations, such as done in this study for Zambia, represent a higher-resolution of knowledge regarding both the genetic health and connectivity of lion populations, which can serve to inform conservation and management of this iconic species. PMID:26674533

Mitochondrial Haplotype Diversity in Zambian Lions: Bridging a Gap in the Biogeography of an Iconic Species.

PubMed

Curry, Caitlin J; White, Paula A; Derr, James N

2015-01-01

Analysis of DNA sequence diversity at the 12S to 16S mitochondrial genes of 165 African lions (Panthera leo) from five main areas in Zambia has uncovered haplotypes which link Southern Africa with East Africa. Phylogenetic analysis suggests Zambia may serve as a bridge connecting the lion populations in southern Africa to eastern Africa, supporting earlier hypotheses that eastern-southern Africa may represent the evolutionary cradle for the species. Overall gene diversity throughout the Zambian lion population was 0.7319 +/- 0.0174 with eight haplotypes found; three haplotypes previously described and the remaining five novel. The addition of these five novel haplotypes, so far only found within Zambia, nearly doubles the number of haplotypes previously reported for any given geographic location of wild lions. However, based on an AMOVA analysis of these haplotypes, there is little to no matrilineal gene flow (Fst = 0.47) when the eastern and western regions of Zambia are considered as two regional sub-populations. Crossover haplotypes (H9, H11, and Z1) appear in both populations as rare in one but common in the other. This pattern is a possible result of the lion mating system in which predominately males disperse, as all individuals with crossover haplotypes were male. The determination and characterization of lion sub-populations, such as done in this study for Zambia, represent a higher-resolution of knowledge regarding both the genetic health and connectivity of lion populations, which can serve to inform conservation and management of this iconic species.

Effects of befloxatone, a reversible selective monoamine oxidase-A inhibitor, on psychomotor function and memory in healthy subjects.

PubMed

Warot, D; Berlin, I; Patat, A; Durrieu, G; Zieleniuk, I; Puech, A J

1996-10-01

Befloxatone is a new reversible and selective monoamine oxidase (MAO-A) inhibitor that has been shown to have antidepressant activity in various animal models. To assess the effects of single oral doses of befloxatone (5, 10, and 20 mg) on psychomotor performance and memory, a randomized, double-blind, five-way, crossover study with both placebo and amitriptyline (50 mg) was carried out in 15 healthy male volunteers. Psychomotor and cognitive functions were evaluated using both objective measures, including Critical Flicker Frequency (CFF), Choice Reaction Time (CRT), Digit Symbol Substitution Test (DSST), and a picture memory test and subjective measures, including Visual Analog Scales (VAS) and Addiction Research Center Inventory (ARCI), before and 2, 4, and 8 hours after administration. Pupil diameter was recorded by videopupillography. Single doses of befloxatone from 5 to 20 mg did not result in any detrimental effects on skilled performance and memory. In contrast, amitriptyline significantly impaired arousal (CFF), speed of reaction (CRT), information processing (DSST) and long-term memory (delayed free recall of pictures) and produced subjective sedation from 2 to 8 hours after administration. At the doses studied amitriptyline induced miosis but befloxatone did not modify pupil diameter. There was no evidence in this study to suggest that befloxatone, at the doses studied, has any sedative or amnesic effects in healthy subjects.

Scaling in the aggregation dynamics of a magnetorheological fluid.

PubMed

Domínguez-García, P; Melle, Sonia; Pastor, J M; Rubio, M A

2007-11-01

We present experimental results on the aggregation dynamics of a magnetorheological fluid, namely, an aqueous suspension of micrometer-sized superparamagnetic particles, under the action of a constant uniaxial magnetic field using video microscopy and image analysis. We find a scaling behavior in several variables describing the aggregation kinetics. The data agree well with the Family-Vicsek scaling ansatz for diffusion-limited cluster-cluster aggregation. The kinetic exponents z and z' are obtained from the temporal evolution of the mean cluster size S(t) and the number of clusters N(t), respectively. The crossover exponent Delta is calculated in two ways: first, from the initial slope of the scaling function; second, from the evolution of the nonaggregated particles, n1(t). We report on results of Brownian two-dimensional dynamics simulations and compare the results with the experiments. Finally, we discuss the differences obtained between the kinetic exponents in terms of the variation in the crossover exponent and relate this behavior to the physical interpretation of the crossover exponent.

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

PubMed

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

2002-10-01

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. Randomized single-blind cross-over trial with two intervention periods. The Medical School and University Hospital of the University of Crete, Heraklion, Crete, Greece. Twenty-five healthy males and females completed the study. Each intervention was of three weeks duration and intervention periods were separated by a two week washout. Seventy grams of extra virgin olive oil was supplied to each subject per day in the intervention periods. The olive oils supplied differed in their phenol content by 18.6 mg/day. Two fasting venous blood samples were taken at the end of each intervention period. The markers of antioxidant capacity measured in fasting plasma samples (total plasma resistance to oxidation, concentrations of protein carbonyl as a marker of protein oxidation, malondialdehyde and lipid hydroperoxides as markers of lipid oxidation and the ferric reducing ability of plasma) did not differ significantly between the low and high phenol olive oil diets. No effect of olive oil phenols on markers of oxidation in smokers was detected. It may be that the natural concentrations of phenols in olive oil are too low to produce an effect in the post-absorptive phase. Possible reasons for period effects and interactions between diet and administration period need attention to aid further cross-over trials of this kind. Unilever Research Vlaardingen, The Netherlands.

An insight into the performance of road barriers - redistribution of barrier-relevant crashes.

PubMed

Zou, Yaotian; Tarko, Andrew P

2016-11-01

Unlike most of traffic safety treatments that prevent crashes, road barriers reduce the severity of crash outcomes by replacing crashes with a high risk of severe injury and fatality (such as median crossover head-on collisions or collisions with high-hazard objects) with less risky events (such as collisions with barriers). This "crash conversion" is actually more complex than one-to-one replacement and it has not been studied yet. The published work estimated the reduction of selected types of crashes (typically, median crossover collisions) or the overall effect of barriers on crash severity. The objective of this study was to study the probabilities of various types of crash events possible under various road and barrier scenarios. The estimated probabilities are conditional given that at least one vehicle left the travelled way and the resulted crash had been recorded. The results are meant to deliver a useful insight onto the conversion of crashes by barriers from more to less risky to help better understand the mechanism of crash severity reduction. Such knowledge should allow engineers more accurate estimation of barriers' benefits and help researchers evaluate barriers' performance to improve the barrier's design. Seven barrier-relevant crash events possible after a vehicle departs the road could be identified based on the existing crash data and their probabilities estimated given the presence and location of three types of barriers: median concrete barriers, median and roadside W-beam steel guardrails, and high-tension median cable barriers. A multinomial logit model with variable outcomes was estimated based on 2049 barrier-relevant crashes occurred between 2003 and 2012 on 1258 unidirectional travelled ways in Indiana. The developed model allows calculating the changes in the probabilities of the barrier-relevant crash events. The results of this study indicated that road departures lead to less frequent crossings of unprotected (no barriers) medians 50-80ft. wide than for narrower medians 30-50ft wide. This benefit decreased with an increase in rollovers inside the median. Although our data indicated no median crossover events when a median barrier was present, the risk of crossovers, although low, is still present and could manifest itself if the sample were larger. The presence of barriers near a travelled way was associated with a higher risk of redirecting errant vehicles back to the roadway where they could collide with other vehicles continuing on the road. As expected, cable barriers installed on the far-side edge of a median were associated with a lower probability of being hit by errant vehicles and of redirecting vehicles into traffic than the nearside cable barriers. On the other hand, the probability of off-road non-barrier crashes was higher because vehicles penetrating the median from the unprotected side were exposed to median ditches and similar obstacles. The roadside guardrails were confirmed to reduce the percentage of hazardous off-road crashes. The results of this study facilitate a more transparent evaluation of the safety effect of road barriers. Copyright © 2016 Elsevier Ltd. All rights reserved.

An approach to checking case-crossover analyses based on equivalence with time-series methods.

PubMed

Lu, Yun; Symons, James Morel; Geyh, Alison S; Zeger, Scott L

2008-03-01

The case-crossover design has been increasingly applied to epidemiologic investigations of acute adverse health effects associated with ambient air pollution. The correspondence of the design to that of matched case-control studies makes it inferentially appealing for epidemiologic studies. Case-crossover analyses generally use conditional logistic regression modeling. This technique is equivalent to time-series log-linear regression models when there is a common exposure across individuals, as in air pollution studies. Previous methods for obtaining unbiased estimates for case-crossover analyses have assumed that time-varying risk factors are constant within reference windows. In this paper, we rely on the connection between case-crossover and time-series methods to illustrate model-checking procedures from log-linear model diagnostics for time-stratified case-crossover analyses. Additionally, we compare the relative performance of the time-stratified case-crossover approach to time-series methods under 3 simulated scenarios representing different temporal patterns of daily mortality associated with air pollution in Chicago, Illinois, during 1995 and 1996. Whenever a model-be it time-series or case-crossover-fails to account appropriately for fluctuations in time that confound the exposure, the effect estimate will be biased. It is therefore important to perform model-checking in time-stratified case-crossover analyses rather than assume the estimator is unbiased.

Associations between Eating Competence and Cardiovascular Disease Biomarkers

ERIC Educational Resources Information Center

Psota, Tricia L.; Lohse, Barbara; West, Sheila G.

2007-01-01

Objective: Explore the relationship between eating competence (EC) and biomarkers of risk for cardiovascular disease (CVD). Design: Secondary analysis of data collected for a larger, 2-way crossover clinical trial. Setting: Outpatient clinical research center. Participants: Forty-eight hypercholesterolemic (LDL cholesterol [greater than or equal]…

Regulation of human retinal blood flow by endothelin-1.

PubMed

Polak, Kaija; Luksch, Alexandra; Frank, Barbara; Jandrasits, Kerstin; Polska, Elzbieta; Schmetterer, Leopold

2003-05-01

There is evidence from in vitro and animal studies that endothelin is a major regulator of retinal blood flow. We set out to characterize the role of the endothelin-system in the blood flow control of the human retina. Two studies in healthy subjects were performed. The study design was randomized, placebo-controlled, double-masked, balanced, two-way crossover in protocol A and three way-way crossover in protocol B. In protocol A 18 healthy male subjects received intravenous endothelin-1 (ET-1) in a dose of 2.5 ng kg (-1)min(-1) for 30 min or placebo on two different study days and retinal vessel diameters were measured. In protocol B 12 healthy male subjects received ET-1 in stepwise increasing doses of 0, 1.25, 2.5 and 5 ng kg (-1)min(-1) (each infusion step over 20 min) in co-infusion with the specific ET(A)-receptor antagonist BQ123 (60 microg min (-1)) or placebo or BQ123 alone investigating retinal vessel diameters, retinal blood velocity and retinal blood flow. Measurements of retinal vessel size were done with the Zeiss retinal vessel analyzer. Measurements of blood velocities were done with bi-directional laser Doppler velocimetry. From these measurements retinal blood flow was calculated. In protocol A exogenous ET-1 tended to decrease retinal arterial diameter, but this effect was not significant versus placebo. No effect on retinal venous diameter was seen. In protocol B retinal venous blood velocity and retinal blood flow was significantly reduced after administration of exogenous ET-1. These effects were significantly blunted when BQ-123 was co-administered. By contrast, BQ-123 alone had no effect on retinal hemodynamic parameters. Concluding, BQ123 antagonizes the effects of exogenously administered ET-1 on retinal blood flow in healthy subjects. In addition, the results of the present study are compatible with the hypothesis that ET-1 exerts its vasoconstrictor effects in the retina mainly on the microvessels.

Deltoid Injections of Risperidone Long-acting Injectable in Patients with Schizophrenia

PubMed Central

Quiroz, Jorge A.; Rusch, Sarah; Thyssen, An; Kushner, Stuart

2011-01-01

Background Risperidone long-acting injectable was previously approved for treatment of schizophrenia as biweekly injections in the gluteal muscle only. We present data on local injection-site tolerability and safety of risperidone long-acting injectable and comparability of systemic exposure of deltoid versus gluteal injections. Methods Risperidone long-acting injectable was administered in an open-label, single-dose, two-way crossover study, with patients randomized to receive either 25mg gluteal/37.5mg deltoid crossover in two treatment periods or 50mg gluteal/50mg deltoid injections crossover; each treatment period was separated by an 85-day observation period (Study 1) and an open-label, multiple-dose study (4 sequential 37.5mg or 50mg deltoid injections every 2 weeks) (Study 2). The pharmacokinetic results from both the studies have already been published. Results In Study 1 (n=170), the majority of patients had no local injection-site findings, based on investigator and patient-rated evaluations. In Study 2 (n=53), seven of the 51 patients who received at least two deltoid injections discontinued (primary endpoint). However, none of the discontinuations were due to injection-site related reasons. The 90-percent upper confidence limit of the true proportion of injection-site issue withdrawals was 5.7 percent. No moderate or severe injection-site reactions were reported. Conclusion Intramuscular injections via the deltoid and gluteal sites are equivalent routes of administration of risperidone long-acting injectable with respect to local injection-site tolerability. The overall safety and tolerability profile of risperidone long-acting injectable was comparable when administered as an intramuscular injection in the deltoid (37.5mg and 50mg) and gluteal (25mg and 50mg) sites. PMID:21779538

Elementary excitations and crossover phenomenon in liquids.

PubMed

Iwashita, T; Nicholson, D M; Egami, T

2013-05-17

The elementary excitations of vibration in solids are phonons. But in liquids phonons are extremely short lived and marginalized. In this Letter through classical and ab initio molecular dynamics simulations of the liquid state of various metallic systems we show that different excitations, the local configurational excitations in the atomic connectivity network, are the elementary excitations in high temperature metallic liquids. We also demonstrate that the competition between the configurational excitations and phonons determines the so-called crossover phenomenon in liquids. These discoveries open the way to the explanation of various complex phenomena in liquids, such as fragility and the rapid increase in viscosity toward the glass transition, in terms of these excitations.

A pilot study assessing the effectiveness of a glycerin suppository in controlled colostomy emptying.

PubMed

McClees, Nancy; Mikolaj, Eda L; Carlson, Sharon L; Pryor-McCann, Joan

2004-01-01

The focus of this research was to explore another way for the patient to manage their colostomy. It was hoped that by inserting a glycerin suppository into the colostomy one would be able to evacuate the lower large intestine more effectively and efficiently. To determine if persons with a sigmoid colostomy could obtain fecal continence by instituting a daily self-administered bowel-stimulating suppository. Randomized crossover comparative study comparing usual ostomy emptying practice with emptying with a glycerine suppository to stimulate controlled emptying. Adult males and females with a sigmoid colostomy were studied in their homes. The instruments included a profile questionnaire, a take-home diary, crossover and end-of-study questionnaires, and an exit questionnaire. Subjects were randomized to their usual pouching method or to the experimental suppository method for 14 days each. There was no difference in fecal output, fecal volume, or flatus between the 2 groups. The action of the suppository was affected by its failure to remain in the bowel for an adequate amount of time. Further research is needed to determine if an adjunct device/method to hold the suppository in place would produce successful results.

Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects

PubMed Central

Pantaleon, Carmela; Iverson, Matthew; Smith, Michael D.; Kinzler, Eric R.; Aigner, Stefan

2018-01-01

Objective To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), abuse-deterrent formulation of morphine sulfate after oral and intranasal administration. Methods This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of abuse potential, was also evaluated. Results Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal abuse potential compared with ER morphine.

Effects of conjugated linoleic acid and high oleic acid safflower oil in the treatment of children with HPV-induced laryngeal papillomatosis: a randomized, double-blinded and crossover preliminary study

PubMed Central

2012-01-01

Background Surgery is the mainstay therapy for HPV-induced laryngeal papillomatosis (LP) and adjuvant therapies are palliative at best. Research revealed that conjugated-linoleic acid (CLA) may improve the outcome of virally-induced diseases. The effects of Clarinol™ G-80 (CLA) and high oleic safflower oil (HOSF) on children with LP (concomitant with surgery) were evaluated. Design A randomized, double-blinded, crossover and reference-oil controlled trial was conducted at a South African medical university. Study components included clinical, HPV type/load and lymphocyte/cytokine analyses, according to routine laboratory methods. Participants Overall: ten children enrolled; eight completed the trial; five remained randomized; seven received CLA first; all treatments remained double-blinded. Intervention Children (4 to 12 years) received 2.5 ml p/d CLA (8 weeks) and 2.5 ml p/d HOSF (8 weeks) with a washout period (6 weeks) in-between. The one-year trial included a post-treatment period (30 weeks) and afterwards was a one-year follow-up period. Main outcome measures Changes in numbers of surgical procedures for improved disease outcome, total/anatomical scores (staging system) for papillomatosis prevention/viral inhibition, and lymphocyte/cytokine counts for immune responses between baselines and each treatment/end of trial were measured. Findings After each treatment all the children were in remission (no surgical procedures); after the trial two had recurrence (surgical procedures in post-treatment period); after the follow-up period three had recurrence (several surgical procedures) and five recovered (four had no surgical procedures). Effects of CLA (and HOSF to a lesser extent) were restricted to mildly/moderately aggressive papillomatosis. Children with low total scores (seven/less) and reduced infections (three/less laryngeal sub-sites) recovered after the trial. No harmful effects were observed. The number of surgical procedures during the trial (n6/available records) was significantly lower [(p 0.03) (95% CI 1.1; 0)]. Changes in scores between baselines and CLA treatments (n8) were significantly lower: total scores [(p 0.02) (95% CI −30.00; 0.00)]; anatomical scores [(p 0.008) (95% CI −33.00: -2.00)]. Immune enhancement could not be demonstrated. Conclusions These preliminary case and group findings pave the way for further research on the therapeutic potential of adjuvant CLA in the treatment of HPV-induced LP. PMID:23061633

Cognitive and physiological effects of an "energy drink": an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractions.

PubMed

Scholey, Andrew B; Kennedy, David O

2004-11-01

Both glucose and caffeine can improve aspects of cognitive performance and, in the case of caffeine, mood. There are few studies investigating the effects of the two substances in combination. We assessed the mood, cognitive and physiological effects of a soft drink containing caffeine and glucose as well as flavouring levels of herbal extracts. The effects of different drink fractions were also evaluated. Using a randomised, double-blind, balanced, five-way crossover design, 20 participants who were overnight fasted and caffeine-deprived received 250 ml drinks containing 37.5 g glucose; 75 mg caffeine; ginseng and ginkgo biloba at flavouring levels; a whole drink (containing all these substances) or a placebo (vehicle). Participants were assessed in each drink condition, separated by a 7-day wash-out period. Cognitive, psychomotor and mood assessment took place immediately prior to the drink then 30 min thereafter. The primary outcome measures included five aspects of cognitive performance from the Cognitive Drug Research assessment battery. Mood, heart rate and blood glucose levels were also monitored. Compared with placebo, the whole drink resulted in significantly improved performance on "secondary memory" and "speed of attention" factors. There were no other cognitive or mood effects. This pattern of results would not be predicted from the effects of glucose and caffeine in isolation, either as seen here or from the literature addressing the effects of the substances in isolation. These data suggest that there is some degree of synergy between the cognition-modulating effects of glucose and caffeine which merits further investigation.

Antiseptic Body Washes for Reducing the Transmission of Methicillin-Resistant Staphylococcus aureus: A Cluster Crossover Study

PubMed Central

Harris, Patrick N. A.; Le, Bich Diep; Tambyah, Paul; Hsu, Li Yang; Pada, Surinder; Archuleta, Sophia; Salmon, Sharon; Mukhopadhyay, Amartya; Dillon, Jasmine; Ware, Robert; Fisher, Dale A.

2015-01-01

Background. Limiting the spread of methicillin-resistant Staphylococcus aureus (MRSA) within healthcare facilities where the organism is highly endemic is a challenge. The use of topical antiseptic agents may help interrupt the transmission of MRSA and reduce the risk of clinical infection. Octenidine dihydrochloride is a topical antiseptic that exhibits in vitro efficacy against a wide variety of bacteria, including S aureus. Methods. We conducted a prospective cluster crossover study to compare the use of daily octenidine body washes with soap and water in patients identified by active surveillance cultures to be MRSA-colonized, to prevent the acquisition of MRSA in patients with negative screening swabs. Five adult medical and surgical wards and 2 intensive care units were selected. The study involved an initial 6-month phase using octenidine or soap washes followed by a crossover in each ward to the alternative product. The primary and secondary outcomes were the rates of new MRSA acquisitions and MRSA clinical infections, respectively. Results. A total of 10 936 patients admitted for ≥48 hours was included in the analysis. There was a small reduction in MRSA acquisition in the intervention group compared with controls (3.0% vs 3.3%), but this reduction was not significant (odds ratio, 0.89; 95% confidence interval, .72–1.11; P = .31). There were also no significant differences in clinical MRSA infection or incidence of MRSA bacteremia. Conclusions. This study suggests that the targeted use of routine antiseptic washes may not in itself be adequate to reduce the transmission of MRSA in an endemic hospital setting. PMID:26125031

Quasi-One-Dimensional Ultracold Fermi Gases

NASA Astrophysics Data System (ADS)

Revelle, Melissa C.

Ultracold atoms have become an essential tool in studying condensed matter phenomena. The advantage of atomic physics experiments is that they provide an easily tunable system. This experiment uses the lowest two ground state hyperfine levels of fermionic lithium. Having two different states creates a pseudo-spin- 1/2 system and allows us to emulate electronic systems, such as superconductors and crystal lattices. In our experiment, we can control the ratio between these two states resulting in either a spin-balanced or a spin-imbalanced gas. Imposing an imbalance is analogous to applying a magnetic field to a superconductor which causes the electrons in the material to align to the field (thus breaking the electron pairs which cause superconductivity). This motivates us to understand the phases created when a spin-imbalance is created and the effect of changing the atomic interactions. In a 3D system, we find where superfluidity is suppressed throughout the BEC to BCS crossover. Using phase separation as a guide, we probe the dimensional crossover between 1D and 3D. The phase separation in 1D is inverted from that in 3D, which provides a unique characteristic to distinguish between the dimensions. By varying the tunneling between tubes and the atomic interactions in a 2D optical lattice, we control whether the system is 1D, 3D, or in between. Using the properties of a 3D gas as a guide, we directly observe when the gas has crossed over from being dominated by 1D-like behavior to 3D. In this way, we have found a universal value for the dimensional crossover. The 1D-3D crossover paves the way to search for the exotic FFLO (Fulde-Ferrell-Larkin-Ovchinnikov) superconductor. While most superconductors do not coexist with magnetism, the FFLO phase requires large magnetic fields to support its pairing mechanism. Additionally, this phase is more likely to be found in lower dimensional systems. However, at low dimensions, the effect of temperature fluctuations on the phase is destabilizing, but these temperature effects are reduced with higher dimensionality. Thus, the quasi-1D regime is the optimal region of parameter space to find this phase. The search for direct evidence of FFLO continues in this regime.

Evaluation of herbal cannabis characteristics by medical users: a randomized trial

PubMed Central

Ware, Mark A; Ducruet, Thierry; Robinson, Ann R

2006-01-01

Background Cannabis, in herbal form, is widely used as self-medication by patients with diseases such as HIV/AIDS and multiple sclerosis suffering from symptoms including pain, muscle spasticity, stress and insomnia. Valid clinical studies of herbal cannabis require a product which is acceptable to patients in order to maximize adherence to study protocols. Methods We conducted a randomized controlled crossover trial of 4 different herbal cannabis preparations among 8 experienced and authorized cannabis users with chronic pain. Preparations were varied with respect to grind size, THC content and humidity. Subjects received each preparation on a separate day and prepared the drug in their usual way in a dedicated and licensed clinical facility. They were asked to evaluate the products based on appearance (smell, colour, humidity, grind size, ease of preparation and overall appearance) and smoking characteristics (burn rate, hotness, harshness and taste). Five-point Likert scores were assigned to each characteristic. Scores were compared between preparations using ANOVA. Results Seven subjects completed the study, and the product with highest THC content (12%), highest humidity (14%) and largest grind size (10 mm) was rated highest overall. Significant differences were noted between preparations on overall appearance and colour (p = 0.003). Discussion While the small size of the study precludes broad conclusions, the study shows that medical cannabis users can appreciate differences in herbal product. A more acceptable cannabis product may increase recruitment and retention in clinical studies of medical cannabis. PMID:17101054

Studies on Methanol Crossover in Liquid-Feed Direct Methanol Pem Fuel Cells

NASA Technical Reports Server (NTRS)

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.

Effect of sex, age and genetics on crossover interference in cattle

PubMed Central

Wang, Zhiying; Shen, Botong; Jiang, Jicai; Li, Jinquan; Ma, Li

2016-01-01

Crossovers generated by homologous recombination ensure proper chromosome segregation during meiosis. Crossover interference results in chiasmata being more evenly distributed along chromosomes, but the mechanism underlying crossover interference remains elusive. Based on large pedigrees of Holstein and Jersey cattle with genotype data, we extracted three-generation families, including 147,327 male and 71,687 female meioses in Holstein, and 108,163 male and 37,008 female meioses in Jersey, respectively. We identified crossovers in these meioses and fitted the Housworth-Stahl “interference-escape” model to study crossover interference patterns in the cattle genome. Our result reveals that the degree of crossover interference is stronger in females than in males. We found evidence for inter-chromosomal variation in the level of crossover interference, with smaller chromosomes exhibiting stronger interference. In addition, crossover interference levels decreased with maternal age. Finally, sex-specific GWAS analyses identified one locus near the NEK9 gene on chromosome 10 to have a significant effect on crossover interference levels. This locus has been previously associated with recombination rate in cattle. Collectively, this large-scale analysis provided a comprehensive description of crossover interference across chromosome, sex and age groups, identified associated candidate genes, and produced useful insights into the mechanism of crossover interference. PMID:27892966

Oligofructose promotes satiety in healthy human: a pilot study.

PubMed

Cani, P D; Joly, E; Horsmans, Y; Delzenne, N M

2006-05-01

The administration of a fermentable dietary fibre (oligofructose) in rats increases satietogenic gut peptides and lowered spontaneous energy intake. The aim of the study was to assess the relevance of those effects of oligofructose on satiety and energy intake in humans. Single-blinded, crossover, placebo-controlled design, pilot study. Volunteers included five men and five women aged 21-39 years, BMI ranging from 18.5 to 27.4 kg/m(2), were randomly assigned as described below. Subjects were included in two 2-week experimental phases during which they received either fibre (oligofructose (OFS)) or placebo (dextrine maltose (DM)); a 2-week washout period was included between crossover phases. In total, 8 g OFS or 8 g DM were ingested twice daily (16 g/day in total). Energy intake, hunger, satiety, fullness and prospective food consumption were assessed with analogue scales at the end of each experimental phase. During breakfast, OFS significantly increases the satiety (P=0.04) without any difference on other sensations as compared to DM treatment periods. After lunch, no significant differences are observed between treatment period. At dinner, OFS significantly increases satiety (P=0.04), reduces hunger (P=0.04) and prospective food consumption (P=0.05). The energy intake at breakfast and lunch are significantly lower (P=0.01, 0.03, respectively) after OFS treatment than after DM treatment. Total energy intake per day is 5% lower during OFS than in DM period. Oligofructose treatment increases satiety following breakfast and dinner, reduces hunger and prospective food consumption following dinner. This pilot study presents a rationale to propose oligofructose supplements in the management of food intake in overweight and obese patients.

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

ERIC Educational Resources Information Center

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…

Associations between urinary biomarkers of oxidative stress and air pollutants observed in a randomized crossover exposure to steel mill emissions.

PubMed

Pelletier, Guillaume; Rigden, Marc; Kauri, Lisa Marie; Shutt, Robin; Mahmud, Mamun; Cakmak, Sabit; Kumarathasan, Premkumari; Thomson, Errol M; Vincent, Renaud; Broad, Gayle; Liu, Ling; Dales, Robert

2017-04-01

The effects of industrial air pollution on human health have not been as thoroughly investigated as those of urban air pollution which originates mostly from automotive transport. To better assess the health impacts of point sources of industrial air pollution, a randomized crossover exposure study was conducted. Sixty one young and healthy volunteers were randomly assigned to spend five consecutive eight-hour days near a steel mill or at a location five kilometres away. After a nine or sixteen-day washout period, volunteers spent another five consecutive days at the second site. Meteorological conditions and air pollutants were monitored at both exposure sites. On each exposure day, the first morning urine was collected along with a second urine sample obtained immediately before leaving the exposure site at the end of the day. Urinary levels of biomarkers of oxidative stress 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage), malondialdehyde (MDA, a biomarker of lipid peroxidation), 8-isoprostane (8-IsoP, a bioactive metabolite resulting from the peroxidation of arachidonic acid) and Vascular Endothelial Growth Factor (VEGF, involved in response to oxidative stress) were measured. According to mixed-effects linear regression models, intra-individual variations in 8-OHdG urinary levels were significantly associated with exposure site, but surprisingly, lower levels were observed at the steel mill site. Delayed, temporally-defined associations with specific air pollutants were observed for 8-OHdG, 8-IsoP and VEGF. However, these associations were subtle, presented complex patterns and their biological consequences remain unclear. Crown Copyright © 2016. Published by Elsevier GmbH. All rights reserved.

Stress Crossover in Newlywed Marriage: A Longitudinal and Dyadic Perspective

ERIC Educational Resources Information Center

Neff, Lisa A.; Karney, Benjamin R.

2007-01-01

Studies of stress and marital quality often assess stress as an intrapersonal phenomenon, examining how spouses' stress may influence their own relationship well-being. Yet spouses' stress also may influence partners' relationship evaluations, a phenomenon referred to as stress crossover. This study examined stress crossover, and conditions that…

76 FR 10086 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-23

... automatic signals as well as the circuit controllers from five hand-operated switches and one hand-operated crossover. The hand-operated switches will remain in the application area without signal protection. The... submitting written views, data, or comments. FRA does not anticipate scheduling a public hearing in...

Language Minority Crossover Students: A Program To Address a New Challenge at Bergen Community College.

ERIC Educational Resources Information Center

Altano, Brian

In response to the conflicting needs of English as a Second Language (ESL) students in English Basic Skills (EBS) courses at Bergen Community College, a project has been proposed to provide a more comprehensive program. The plan of operation is divided into five components: (1) identification, testing, and placement; (2) orientation and…

Guar sprinkled on food: effect on glycaemic control, plasma lipids and gut hormones in non-insulin dependent diabetic patients.

PubMed

Fuessl, H S; Williams, G; Adrian, T E; Bloom, S R

1987-01-01

The effects of guar granules sprinkled over food on carbohydrate and lipid metabolism were studied in a double-blind cross-over trial in 18 patients with non-insulin-dependent diabetes mellitus (mean +/- SEM age 61.3 +/- 2.5 years). Five-gram guar granules (Guarem, Rybar Laboratories, Amersham, Bucks) were sprinkled over food at each main meal for 4 weeks, and during a 4-week placebo period (separated by a 2-week 'wash-out' period), 5 g wheat bran was taken in the same way. Diabetic treatment was not changed during the study. Mean fasting plasma glucose (FPG) concentration and glycosylated haemoglobin (HbA1) concentration after treatment were significantly lower than after the placebo period (FPG 8.29 +/- 0.47 vs 8.78 +/- 0.53 mmol/l, p less than 0.05; HbA1: 8.70 +/- 0.39 vs 9.09 +/- 0.39%, p less than 0.05). There was a 50% reduction in the incremental area under the postprandial glycaemic curve when guar was eaten with a standardized test meal. Total plasma cholesterol decreased from 5.79 +/- 0.29 to 5.19 +/- 0.22 mmol/l (p less than 0.05) after the guar treatment period. Guar ingestion reduced postprandial insulin and enteroglucagon responses, the latter significantly so, but had no apparent effect on gastric inhibitory polypeptide, pancreatic glucagon, gastrin, and pancreatic polypeptide.

mlh3 mutations in baker’s yeast alter meiotic recombination outcomes by increasing noncrossover events genome-wide

PubMed Central

Al-Sweel, Najla; Raghavan, Vandana; Khondakar, Nabila; Manhart, Carol M.; Surtees, Jennifer A.

2017-01-01

Mlh1-Mlh3 is an endonuclease hypothesized to act in meiosis to resolve double Holliday junctions into crossovers. It also plays a minor role in eukaryotic DNA mismatch repair (MMR). To understand how Mlh1-Mlh3 functions in both meiosis and MMR, we analyzed in baker’s yeast 60 new mlh3 alleles. Five alleles specifically disrupted MMR, whereas one (mlh3-32) specifically disrupted meiotic crossing over. Mlh1-mlh3 representatives for each class were purified and characterized. Both Mlh1-mlh3-32 (MMR+, crossover-) and Mlh1-mlh3-45 (MMR-, crossover+) displayed wild-type endonuclease activities in vitro. Msh2-Msh3, an MSH complex that acts with Mlh1-Mlh3 in MMR, stimulated the endonuclease activity of Mlh1-mlh3-32 but not Mlh1-mlh3-45, suggesting that Mlh1-mlh3-45 is defective in MSH interactions. Whole genome recombination maps were constructed for wild-type and MMR+ crossover-, MMR- crossover+, endonuclease defective and null mlh3 mutants in an S288c/YJM789 hybrid background. Compared to wild-type, all of the mlh3 mutants showed increases in the number of noncrossover events, consistent with recombination intermediates being resolved through alternative recombination pathways. Our observations provide a structure-function map for Mlh3 that reveals the importance of protein-protein interactions in regulating Mlh1-Mlh3’s enzymatic activity. They also illustrate how defective meiotic components can alter the fate of meiotic recombination intermediates, providing new insights for how meiotic recombination pathways are regulated. PMID:28827832

Case-crossover study of Burkholderia cepacia complex bloodstream infection associated with contaminated intravenous bromopride.

PubMed

Martins, Ianick Souto; Pellegrino, Flávia Lúcia Piffano Costa; Freitas, Andrea d'Avila; Santos, Marisa da Silva; Ferraiuoli, Giovanna Ianini d'Alemeida; Vasques, Márcia Regina Guimarães; Amorim, Efigenia Lourdes Teixeira; Oliveira, Sandra; Nouér, Simone Aranha; Cardoso, Fernando Luiz Lopes; Mascarenhas, Luiz Affonso; Magalhães, Ana Cristina Gouveia; Cleinman, Isabella Barbosa; Figueiredo, Agnes Marie Sá; Moreira, Beatriz Meurer

2010-05-01

To investigate an outbreak of healthcare-associated Burkholderia cepacia complex (BCC) primary bloodstream infections (BCC-BSI). Case-crossover study in a public hospital, a university hospital and a private hospital in Rio de Janeiro, Brazil, from March 2006 to May 2006. Twenty-five patients with BCC-BSI. After determining the date BCC-BSI symptoms started for each patient, 3 time intervals of data collection were defined, each one with a duration of 3 days: the case period, starting just before BCC-BSI symptoms onset; the control period, starting 6 days before BCC-BSI symptoms onset; and the washout period, comprising the 3 days between the case period and the control period. Exposures evaluated were intravascular solutions and invasive devices and procedures. Potential risk factors were identified by using the McNemar chi(2) adjusted test. Cultures of samples of potentially contaminated solutions were performed. BCC strain typing was performed by pulsed-field gel electrophoresis using SpeI. The statistical analysis revealed that the use of bromopride and dipyrone was associated with BCC-BSI. A total of 21 clinical isolates from 17 (68%) of the 25 patients and an isolate obtained from the bromopride vial were available for strain typing. Six pulsotypes were detected. A predominant pulsotype (A) accounted for 11 isolates obtained from 11 patients (65%) in the 3 study hospitals. Our investigation, using a case-crossover design, of an outbreak of BCC-BSI infections concluded it was polyclonal but likely caused by infusion of contaminated bromopride. The epidemiological finding was validated by microbiological analysis. After recall of contaminated bromopride vials by the manufacturer, the outbreak was controlled.

Association of Situational and Environmental Factors With Last Episode of Unprotected Anal Intercourse Among MSM in Hong Kong: A Case-Crossover Analysis.

PubMed

Lau, Joseph T F; Mo, Phoenix K H; Gu, Jing; Hao, Chun; Lai, CoCo H Y

2016-02-01

This study investigates event-specific factors that differentiate the last episodes of unprotected anal intercourse (UAI) from protected anal intercourse (PAI) with regular partner (RP) among 213 men who have sex with men (MSM) who did not use condoms consistently using case-crossover analysis. Factors positively associated with the last episode of UAI with RP included: two situational factors (i.e., participant's suggestion to have UAI, alcohol use) and three environmental/setting factors (i.e., sex took place overseas, during a weekday and not at home). Negative associations with an episode of UAI with RP included: five situational factors (i.e., discussion about condom use prior to sex, RP's suggestion to have PAI, participant's suggestion to have PAI, perception that RP would like to use a condom, participant's planning to use a condom) and two environmental/setting factors (i.e., condoms placed at the venue where sex took place, partner possessed a condom). Thus, these significant event-specific factors explained under which circumstances some MSM would use and would not use condoms during anal sex with RP.

A randomized, double-blind, crossover, placebo-controlled comparative clinical trial of arginine aspartate plus adenosine monophosphate for the intermittent treatment of male erectile dysfunction.

PubMed

Neuzillet, Y; Hupertan, V; Cour, F; Botto, H; Lebret, T

2013-03-01

Efficacy and safety of l-arginine aspartate 8 g combined with 200 mg of adenosine monophosphate (AA) with placebo (PL) alone for intermittent treatment of mild-to-moderate erectile dysfunction (ED) were compared. The study design was a double-blind, PL-controlled, two-way crossover randomized clinical trial with 26 patients. Efficacy was assessed by International Index of Erectile Function (IIEF) and two additional validated questionnaires [the Erection Hardness Score (EHS) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). During each crossover period, separated by a 2-week wash-out period, drugs were administered orally, 1-2 h before sexual intercourse. Primary endpoint was a change in the IIEF. Secondary endpoints were patient and investigator assessments of treatment success. Investigators' and patients' assessment of efficacy was significantly improved by the combination vs. PL (p = 0.01 and p = 0.04 respectively]. EHS and EDITS questionnaires were both improved by the combination (p = 0.015 and p = 0.017 respectively). There was no significant difference in terms of tolerance between AA and PL or severe adverse events. ED patients demonstrated significant improvements in all IIEF domains with the exception of the Sexual Desire and Orgasmic Domains when treated with AA compared with PL. This pilot phase II study showed that the on-demand oral administration at a high dosage of l-arginine aspartate-adenosine monophosphate combination may be effective in patients with mild-to-moderate ED, is very well tolerated and could be tested as a safe first-line therapy in a larger size phase III study. © 2012 American Society of Andrology and European Academy of Andrology.

Changing Racial/Ethnic Disparities in Heavy Drinking Trajectories Through Young Adulthood: A Comparative Cohort Study.

PubMed

Williams, Edwina; Mulia, Nina; Karriker-Jaffe, Katherine J; Lui, Camillia K

2018-01-01

There is evidence of racial/ethnic differences in the age at which young adults age out of heavy drinking. Some studies have found Black and Hispanic drinkers engage in more frequent heavy drinking than White people beyond adulthood. Yet, the alcohol-related disparities literature has produced contradictory findings on whether an age-crossover effect is evident among racial/ethnic groups; that is, whether racial/ethnic minorities' drinking levels or trajectories are lower than White people at young ages but later exceed (or crossover) those of White people. This study extends this scant literature by assessing whether racial/ethnic differences in heavy drinking have changed over time (possibly accounting for mixed findings from prior research); and tests for an age-crossover effect in heavy drinking using longitudinal data from 2 cohorts born 20 years apart. Data are from the 1979 (n = 10,963) and 1997 (n = 8,852) cohorts of the National Longitudinal Survey of Youth (NLSY). Generalized estimating equations were used to model trajectories of heavy drinking frequency from ages 17 to 31. Racial/ethnic differences were determined using sex-stratified models and 3-way interactions of race/ethnicity with age, age-squared, and cohort. Racial/ethnic differences in heavy drinking trajectories have changed over time in men and women. In the older NLSY cohort, Hispanic men and Black women surpassed White men's and women's heavy drinking frequency by age 31. This crossover was absent in the younger cohort, where trajectories of all racial-sex groups converged by age 31. Normative trajectories have changed in Hispanics and White people of both sexes, with a delay in age of peak frequency, and greater levels of heavy drinking in the younger cohort of women. Changes in heavy drinking trajectories over time suggest the need for targeted interventions during young adulthood. While disparities in young adult heavy drinking were no longer apparent in the more recent birth cohort, continued monitoring is important. Copyright © 2017 by the Research Society on Alcoholism.

Relationship between the acid-inhibitory effects of two proton pump inhibitors and CYP2C19 genotype in Japanese subjects: a randomized two-way crossover study.

PubMed

Furuta, K; Adachi, K; Ohara, S; Morita, T; Tanimura, T; Koshino, K; Kinoshita, Y

2010-01-01

This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotypes. A total of 23 Helicobacter pylori-negative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19 poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.

Arousability and Fall Risk During Forced Awakenings From Nocturnal Sleep Among Healthy Males Following Administration of Zolpidem 10 mg and Doxepin 6 mg: A Randomized, Placebo-Controlled, Four-Way Crossover Trial.

PubMed

Drake, Christopher L; Durrence, Heith; Cheng, Philip; Roth, Thomas; Pillai, Vivek; Peterson, Edward L; Singh, Meeta; Tran, Kieulinh Michelle

2017-07-01

To examine and compare the arousability threshold and fall risk upon awakening of doxepin (6 mg) versus zolpidem (10 mg). A total of 52 healthy adult males were included in a double-blind, placebo-controlled, four-way crossover study. The experimental procedure included four nights with polysomnography in the lab (zolpidem, doxepin, and their respective placebo conditions). Arousability was measured using an auditory awakening threshold delivered at the peak-plasma concentration for the active hypnotics and at matched times for the respective placebo conditions. Fall risk during the night was measured following awakening using the Berg Balance Scale and the Tandem Walk Task. Both arousability and fall risk were lower in the doxepin condition compared to the zolpidem condition. Furthermore, arousability and fall risk for doxepin did not differ significantly from the placebo conditions. A significantly greater proportion of participants in the zolpidem condition (63.5%) did not wake until receiving the loudest tone (110 dB) as compared to the doxepin (17.6%) and placebo conditions (17.3%, 5.8%). Results suggest that zolpidem has greater risks for balance and awakening threshold compared with low-dose doxepin. Future prospective studies should extend results to clinical samples with population-level risk of injury and arousability. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Evaluation of a 12-Hour Sustained-Release Acetaminophen (Paracetamol) Formulation: A Randomized, 3-Way Crossover Pharmacokinetic and Safety Study in Healthy Volunteers.

PubMed

Yue, Yong; Collaku, Agron; Liu, Dongzhou J

2018-01-01

Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (T C≥4μg/mL ). Key secondary outcomes were area under the plasma concentration-time curve (AUC) from time 0 to time t, when plasma acetaminophen was detectable (AUC 0-t ), AUC from 0 to infinity (AUC 0-inf ), and maximum plasma acetaminophen concentration (C max ). T C≥4μg/mL from 2000-mg SR acetaminophen was similar to that from 2 doses of IR acetaminophen, whereas T C≥4μg/mL for 1500-mg SR acetaminophen was significantly shorter than that for IR acetaminophen (P = .004). The extent of acetaminophen absorption from 2000-mg SR and 2 doses of the IR formulation was similar and within bioequivalence limits with regard to AUC 0-12 , AUC 0-t , and AUC 0-inf . The extent of acetaminophen absorption from 1500-mg SR was significantly lower than that from IR acetaminophen. The 2000-mg SR represents a potential candidate formulation for 12-hour dosing with acetaminophen. © 2017, The American College of Clinical Pharmacology.

Learning as a Machine: Crossovers between Humans and Machines

ERIC Educational Resources Information Center

Hildebrandt, Mireille

2017-01-01

This article is a revised version of the keynote presented at LAK '16 in Edinburgh. The article investigates some of the assumptions of learning analytics, notably those related to behaviourism. Building on the work of Ivan Pavlov, Herbert Simon, and James Gibson as ways of "learning as a machine," the article then develops two levels of…

An evidence-based review of pregabalin for the treatment of fibromyalgia.

PubMed

Arnold, Lesley M; Choy, Ernest; Clauw, Daniel J; Oka, Hiroshi; Whalen, Ed; Semel, David; Pauer, Lynne; Knapp, Lloyd

2018-04-16

Pregabalin, an α2-δ agonist, is approved for the treatment of fibromyalgia (FM) in the United States, Japan, and 37 other countries. The purpose of this article was to provide an in-depth, evidence-based summary of pregabalin for FM as demonstrated in randomized, placebo-controlled clinical studies, including open-label extensions, meta-analyses, combination studies and post-hoc analyses of clinical study data. PubMed was searched using the term "pregabalin AND fibromyalgia" and the Cochrane Library with the term "pregabalin". Both searches were conducted on 2 March 2017 with no other date limits set. Eleven randomized, double-blind, placebo-controlled clinical studies were identified including parallel group, two-way crossover and randomized withdrawal designs. One was a neuroimaging study. Five open-label extensions were also identified. Evidence of efficacy was demonstrated across the studies identified with significant and clinically relevant improvements in pain, sleep quality and patient status. The safety and tolerability profile of pregabalin is consistent across all the studies identified, including in adolescents, with dizziness and somnolence the most common adverse events reported. These efficacy and safety data are supported by meta-analyses (13 studies). Pregabalin in combination with other pharmacotherapies (7 studies) is also efficacious. Post-hoc analyses have demonstrated the onset of pregabalin efficacy as early as 1-2 days after starting treatment, examined the effect of pregabalin on other aspects of sleep beyond quality, and shown it is effective irrespective of the presence of a wide variety of patient demographic and clinical characteristics. Pregabalin is a treatment option for FM; its clinical utility has been comprehensively demonstrated.

An Ecological Approach of Constraint Induced Movement Therapy for 2-3-Year-Old Children: A Randomized Control Trial

ERIC Educational Resources Information Center

Eliasson, Ann-Christin; Shaw, Karin; Berg, Elisabeth; Krumlinde-Sundholm, Lena

2011-01-01

The aim was to evaluate the effect of Eco-CIMT in young children with unilateral cerebral palsy in a randomized controlled crossover design. The training was implemented within the regular pediatric services, provided by the child's parents and/or preschool teacher and supervised by the child's regular therapist. Methods: Twenty-five children…

School Desegregation in Greenville, Mississippi: A Staff Report of the U.S. Commission on Civil Rights.

ERIC Educational Resources Information Center

Commission on Civil Rights, Washington, DC.

This is a report of school desegregation in Greenville, Mississippi. In 1964, five years before ordered to do so by a federal judge, Greenville initiated its own plan for majority-to-minority crossover of students on a "freedom of choice" basis. The school board also initiated a voluntary teacher transfer program that met with…

Bioequivalence of fixed-dose combination RIN®-150 to each reference drug in loose combination.

PubMed

Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Damle, B

2015-03-01

RIN(®)-150 is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg) and isoniazid (INH, 75 mg) developed for the treatment of tuberculosis. This study was conducted at a single center: the Pfizer Clinical Research Unit in Singapore. To demonstrate bioequivalence of each drug component between RIN-150 and individual products in a loose combination. This was a randomized, open-label, single-dose, two-way crossover study. Subjects received single doses of RIN-150 or two individual reference products under fasting conditions in a crossover fashion, with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC). Of 28 subjects enrolled, 26 completed the study. The adjusted geometric mean ratios of Cmax and AUClast between the FDC and single-drug references and 90% confidence intervals were respectively 91.63% (90%CI 83.13-101.01) and 95.45% (90%CI 92.07-98.94) for RMP, and 107.58% (90%CI 96.07-120.47) and 103.45% (90%CI 99.33-107.75) for INH. Both formulations were generally well tolerated in this study. The RIN-150 FDC tablet formulation is bioequivalent to the two single-drug references for RMP and INH at equivalent doses.

Bioequivalence of fixed-dose combination Myrin®-P Forte and reference drugs in loose combination.

PubMed

Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Naqvi, A; Jafri, I

2013-12-01

Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB). This study was conducted at a single centre--the Pfizer Clinical Research Unit in Singapore. To demonstrate the bioequivalence of each drug component of the Myrin-P Forte FDC and the individual product in loose combination. In a randomized, open-label, single-dose, two-way, crossover study, subjects received single doses of Myrin-P Forte or four individual products under fasting conditions in a crossover fashion with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (C(max)) and the area under plasma concentration-time curve (AUC). Of 36 subjects enrolled, 35 completed the study. The adjusted geometric mean ratios and 90% confidence intervals for C(max) and AUC values were completely contained within bioequivalence limits (80%, 125%) for all four drugs in both formulations. Both treatments were generally well tolerated in the study. The Myrin-P Forte FDC tablet formulation is bioequivalent to the four single-drug references for RMP, INH, EMB hydrochloride and PZA at equivalent doses.

Confidence intervals for distinguishing ordinal and disordinal interactions in multiple regression.

PubMed

Lee, Sunbok; Lei, Man-Kit; Brody, Gene H

2015-06-01

Distinguishing between ordinal and disordinal interaction in multiple regression is useful in testing many interesting theoretical hypotheses. Because the distinction is made based on the location of a crossover point of 2 simple regression lines, confidence intervals of the crossover point can be used to distinguish ordinal and disordinal interactions. This study examined 2 factors that need to be considered in constructing confidence intervals of the crossover point: (a) the assumption about the sampling distribution of the crossover point, and (b) the possibility of abnormally wide confidence intervals for the crossover point. A Monte Carlo simulation study was conducted to compare 6 different methods for constructing confidence intervals of the crossover point in terms of the coverage rate, the proportion of true values that fall to the left or right of the confidence intervals, and the average width of the confidence intervals. The methods include the reparameterization, delta, Fieller, basic bootstrap, percentile bootstrap, and bias-corrected accelerated bootstrap methods. The results of our Monte Carlo simulation study suggest that statistical inference using confidence intervals to distinguish ordinal and disordinal interaction requires sample sizes more than 500 to be able to provide sufficiently narrow confidence intervals to identify the location of the crossover point. (c) 2015 APA, all rights reserved).

The effect of glucose dose and fasting interval on cognitive function: a double-blind, placebo-controlled, six-way crossover study.

PubMed

Owen, Lauren; Scholey, Andrew B; Finnegan, Yvonne; Hu, Henglong; Sünram-Lea, Sandra I

2012-04-01

Previous research has identified a number of factors that appear to moderate the behavioural response to glucose administration. These include physiological state, dose, types of cognitive tasks used and level of cognitive demand. Another potential moderating factor is the length of the fasting interval prior to a glucose load. Therefore, we aimed to examine the effect of glucose dose and fasting interval on mood and cognitive function. The current study utilised a double-blind, placebo-controlled, balanced, six period crossover design to examine potential interactions between length of fasting interval (2 versus 12 hours) and optimal dose for cognition enhancement. Results demonstrated that the higher dose (60 g) increased working memory performance following an overnight fast, whereas the lower dose (25 g) enhanced working memory performance following a 2-h fast. The data suggest that optimal glucose dosage may differ under different conditions of depleted blood glucose resources. In addition, glucoregulation was observed to be a moderating factor. However, further research is needed to develop a model of the moderating and mediating factors under which glucose facilitation is best achieved.

Quantum corrections crossover and ferromagnetism in magnetic topological insulators.

PubMed

Bao, Lihong; Wang, Weiyi; Meyer, Nicholas; Liu, Yanwen; Zhang, Cheng; Wang, Kai; Ai, Ping; Xiu, Faxian

2013-01-01

Revelation of emerging exotic states of topological insulators (TIs) for future quantum computing applications relies on breaking time-reversal symmetry and opening a surface energy gap. Here, we report on the transport response of Bi2Te3 TI thin films in the presence of varying Cr dopants. By tracking the magnetoconductance (MC) in a low doping regime we observed a progressive crossover from weak antilocalization (WAL) to weak localization (WL) as the Cr concentration increases. In a high doping regime, however, increasing Cr concentration yields a monotonically enhanced anomalous Hall effect (AHE) accompanied by an increasing carrier density. Our results demonstrate a possibility of manipulating bulk ferromagnetism and quantum transport in magnetic TI, thus providing an alternative way for experimentally realizing exotic quantum states required by spintronic applications.

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

PubMed

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 C max 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.

Self-noise models of five commercial strong-motion accelerometers

USGS Publications Warehouse

Ringler, Adam; Evans, John R.; Hutt, Charles R.

2015-01-01

To better characterize the noise of a number of commonly deployed accelerometers in a standardized way, we conducted noise measurements on five different models of strong‐motion accelerometers. Our study was limited to traditional accelerometers (Fig. 1) and is in no way exhaustive.

Pharmacokinetics of two 6-mercaptopurine liquid formulations in children with acute lymphoblastic leukemia.

PubMed

Tolbert, Jaszianne A; Bai, Shasha; Abdel-Rahman, Susan M; August, Keith J; Weir, Scott J; Kearns, Gregory L; Neville, Kathleen A

2017-08-01

A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts. Group 1 (n = 11; five males) received a 5 mg/ml liquid formulation and the marketed 50 mg 6-MP tablet on separate occasions, and Group 2 (n = 11; five males) received a 50 mg/ml liquid formulation and the marketed tablet. The usual prescribed 6-MP dose (25-115 mg/m 2 ) was given after an 8-hr fast. Serial blood samples were collected over 8 hr postdose. Plasma 6-MP concentrations were determined using a good laboratory practice (GLP)-validated liquid chromatography-tandem mass spectrometry method. PK parameters were calculated using noncompartmental analysis and compared within and between cohorts, and thiopurine methyltransferase (TPMT) genotype was analyzed. No patient had a TPMT genotype reflective of a poor metabolizer phenotype. Comparison of PK parameters between 5 and 50 mg/ml treatments revealed significant differences (P <0.05) in AUC N (where AUC is area under the curve), C maxN , and T max . Comparisons within each group revealed significant differences in AUC 0-∞ and T max in the 5 mg/ml group. Pharmacokinetic profiles of 6-MP established in healthy adults with the approved liquid formulation may not reflect the PK profile in children with ALL. Formulation-specific differences in PK may significantly impact the dose-exposure profile in these children and must be considered. © 2017 Wiley Periodicals, Inc.

Intranasal abuse potential of an abuse-deterrent oxycodone formulation compared to oxycodone immediate release and placebo in nondependent, recreational opioid users.

PubMed

Setnik, Beatrice; Schoedel, Kerri; Bartlett, Cindy; Dick, Chris; Hakim, Nasrat; Geoffroy, Pierre

To assess the intranasal (IN) human abuse potential of ELI-200, a novel immediate-release (IR) oxycodone formulation containing sequestered naltrexone. Randomized, double-blind, double-dummy, active and placebo-controlled, five-way crossover study. Pharmacodynamics, safety, and pharmacokinetics (PKs) were evaluated for up to 36 hours postdose. Single site in Canada (INC Research Toronto). Healthy male and female nondependent recreational opioid users underwent a naloxone challenge and drug discrimination qualification test. Single IN dose of ground ELI-200 (30-mg oxycodone hydrochloride [HCl]/3-mg naltrexone HCl), crushed 30-mg oxycodone HCl IR (Roxicodone®), placebo, fixed placebo, and single oral dose of intact ELI-200 (30mg/3mg). Peak effect (E max ) for bipolar Drug Liking (0-100 point visual analog scale). Of the 44 randomized subjects, 37 completed all five treatment periods. All active treatments showed significantly higher (p<0.001) median Drug Liking E max relative to placebo. Significant reductions (p<0.001) in median Drug Liking [E max ] were observed for IN ELI-200 [56.0] compared to IN oxycodone IR [100.0]. Secondary positive or objective measures (High, Good Drug Effects, Overall Drug Liking, Take Drug Again, and maximum pupil constriction) showed significantly lower E max for IN ELI-200 (p<0.001) compared to IN oxycodone IR. IN administration of ELI-200 demonstrated significantly decreased effects on subjective and physiologic measures, and greater nasal irritation, compared to IN oxycodone IR. These findings, along with the PK profile of naltrexone, demonstrated that when ELI-200 capsules were ground and administered intranasally, the naltrexone component was rapidly released and conferred meaningful abuse-deterrent properties.

Electroacupuncture prevents endothelial dysfunction induced by ischemia-reperfusion injury via a cyclooxygenase-2-dependent mechanism: A randomized controlled crossover trial

PubMed Central

Park, Jimin; Woo, Jong Shin; Leem, Jungtae; Park, Jun Hyeong; Lee, Sanghoon; Chung, Hyemoon; Lee, Jung Myung; Kim, Jin-Bae; Kim, Woo-Shik; Kim, Kwon Sam; Kim, Weon

2017-01-01

Objective Exploring clinically effective methods to reduce ischemia-reperfusion (IR) injury in humans is critical. Several drugs have shown protective effects, but studies using other interventions have been rare. Electroacupuncture (EA) has induced similar protection in several animal studies but no study has investigated how the effects could be translated and reproduced in humans. This study aimed to explore the potential effect and mechanisms of EA in IR-induced endothelial dysfunction in humans. Methods This is a prospective, randomized, crossover, sham-controlled trial consisting of two protocols. Protocol 1 was a crossover study to investigate the effect of EA on IR-induced endothelial dysfunction. Twenty healthy volunteers were randomly assigned to EA or sham EA (sham). Flow mediated dilation (FMD) of the brachial artery (BA), nitroglycerin-mediated endothelial independent dilation, blood pressure before and after IR were measured. In protocol 2, seven volunteers were administered COX-2 inhibitor celecoxib (200 mg orally twice daily) for five days. After consumption, volunteers underwent FMD before and after IR identical to protocol 1. Results In protocol 1, baseline BA diameter, Pre-IR BA diameter and FMD were similar between the two groups (p = NS). After IR, sham group showed significantly blunted FMD (Pre-IR: 11.41 ± 3.10%, Post-IR: 4.49 ± 2.04%, p < 0.001). However, EA protected this blunted FMD (Pre-IR: 10.96 ± 5.30%, Post-IR: 9.47 ± 5.23%, p = NS, p < 0.05 compared with sham EA after IR). In protocol 2, this protective effect was completely abolished by pre-treatment with celecoxib (Pre-IR: 11.05 ± 3.27%; Post-IR: 4.20 ± 1.68%, p = 0.001). Conclusion EA may prevent IR-induced endothelial dysfunction via a COX-2 dependent mechanism. PMID:28591155

A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study.

PubMed

Ridha, Basil H; Crutch, Sebastian; Cutler, Dawn; Frost, Christopher; Knight, William; Barker, Suzie; Epie, Norah; Warrington, Elizabeth K; Kukkastenvehmas, Riitta; Douglas, Jane; Rossor, Martin N

2018-05-01

The study investigated whether donepezil exerts symptomatic benefit in patients with posterior cortical atrophy (PCA), an atypical variant of Alzheimer's disease. A single-centre, double-blind, placebo-controlled, cross-over clinical trial was performed to assess the efficacy of donepezil in patients with PCA. Each patient received either donepezil (5 mg once daily in the first 6 weeks and 10 mg once daily in the second 6 weeks) or placebo for 12 weeks. After a 2-week washout period, each patient received the other treatment arm during the following 12 weeks followed by another 2-week washout period. The primary outcome was the Mini-Mental State Examination (MMSE) at 12 weeks. Secondary outcome measures were five neuropsychological tests reflecting parieto-occipital function. Intention-to-treat analysis was used. For each outcome measure, carry-over effects were first assessed. If present, then analysis was restricted to the first 12-week period. Otherwise, the standard approach to the analysis of a 2 × 2 cross-over trial was used. Eighteen patients (13 females) were recruited (mean age 61.6 years). There was a protocol violation in one patient, who subsequently withdrew from the study due to gastrointestinal side effects. There was statistically significant (p < 0.05) evidence of a carry-over effect on MMSE. Therefore, the analysis of treatment effect on MMSE was restricted to the first 12-week period. Treatment effect at 6 weeks was statistically significant (difference = 2.5 in favour of donepezil, 95% CI 0.1 to 5.0, p < 0.05). Treatment effect at 12 weeks was close, but not statistically significant (difference = 2.0 in favour of donepezil, 95% CI -0.1 to 4.5, p > 0.05). There were no statistically significant treatment effects on any of the five neuropsychological tests, except for digit span at 12 weeks (higher by 0.5 digits in favour of placebo, 95% CI 0.1 to 0.9). Gastrointestinal side effects occurred most frequently, affecting 13/18 subjects (72%), and were the cause of study discontinuation in one subject. Nightmares and vivid dreams occurred in 8/18 subjects (44%), and were statistically more frequent during treatment with donepezil. In this small study, there was no statistically significant treatment effect of donepezil on the primary outcome measure (MMSE score at 12 weeks) in PCA patients, who appear to be particularly susceptible to the development of nightmares and vivid dreams when treated. Trial registration: Current Controlled Trials ISRCTN22636071 . Retrospectively registered 19 May 2010.

A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome.

PubMed

Peterson, P K; Pheley, A; Schroeppel, J; Schenck, C; Marshall, P; Kind, A; Haugland, J M; Lambrecht, L J; Swan, S; Goldsmith, S

1998-04-27

To provide a preliminary assessment of the efficacy and safety of fludrocortisone acetate treatment of chronic fatigue syndrome. A placebo-controlled, double-blind, random-allocation crossover trial of 6 weeks of fludrocortisone. An outpatient clinical trials unit. Twenty-five participants with chronic fatigue syndrome (mean age, 40 years; 19 [76%] women; mean duration of illness, 7.0 years) were recruited from a research and clinic registry. Five patients withdrew from the trial. All participants were scheduled to receive fludrocortisone acetate (0.1-0.2 mg) or a placebo for 6 weeks in each treatment. Self-administered questionnaires were completed at the beginning and end of each treatment arm that asked patients to rate the severity of their symptoms on a visual analogue scale. The Medical Outcomes Study 36-Item Short-Form Health Survey, a reaction time test, and a treadmill exercise test were used to assess functional status. Blood pressure, heart rate, and plasma norepinephrine levels were obtained at baseline. Blood pressure and heart rate were recorded at the end of the exercise test and monitored at all subsequent visits. At baseline, the study participants reported symptom severity greater than 5 for most symptoms, and all had evidence of marked functional impairments. No improvement was observed in the severity of any symptom or in any test of function for the 20 participants who completed both arms of the trial. Blood pressure and heart rate readings were unaffected by treatment, and plasma norepinephrine levels did not differ from those of a healthy control group. The incidence of adverse experiences was similar in the fludrocortisone and placebo arms of the trial. Low-dose fludrocortisone does not provide sufficient benefit to be evident in a preliminary blinded trial of unselected patients with chronic fatigue syndrome.

Evaluation of eLearning for the teaching of undergraduate ophthalmology at medical school: a randomised controlled crossover study.

PubMed

Petrarca, Caroline A; Warner, Julia; Simpson, Andrew; Petrarca, Robert; Douiri, Abdel; Byrne, David; Jackson, Timothy L

2018-05-25

To compare ophthalmology teaching delivered by eLearning with traditional lectures, in terms of undergraduate performance and satisfaction. Randomised controlled crossover study at King's College London Medical School with 245 third year medical students. The ophthalmology syllabus was divided into ten topics. Five topics were randomised to be taught by traditional lectures and five by electronic learning (eLearning). For the second rotation of students the topics were crossed over, so that those topics taught by traditional lectures were taught by eLearning and vice versa. At the end of each rotation the students sat an optional online mock examination containing 100 questions (ten on each topic). Students' examination performance was compared between the two teaching methods. Student satisfaction was assessed using an online satisfaction survey. Outcome measures were the mean percentage of correct answers across all ten topics, student satisfaction and self-assessed knowledge. The mean examination score for questions taught by eLearning was 58% (95% CI, 55.7-59.6), versus 55% (95% CI 53.1-56.8) for traditional lectures (P = 0.047). Across all topics students were more satisfied with eLearning than traditional lectures, with 87% (95% CI 84.5-88.4) rating eLearning as 'excellent' or 'good' versus 65% (95% CI 62.0-67.4) for lectures (p < 0.0001). Overall 180 (75.6%) preferred eLearning compared to traditional lectures, with 166 (69.7%) rating eLearning 'much better' or 'better,' 61 (25.6%) 'neutral' and 11 (4.6%) 'worse' or 'much worse.' Student satisfaction and examination performance are both enhanced by ophthalmology eLearning. Similar eLearning modules may be suitable for other specialties and postgraduate learning.

The Kondo problem. II. Crossover from asymptotic freedom to infrared slavery

NASA Astrophysics Data System (ADS)

Schlottmann, P.

1982-04-01

In the preceding paper we transformed the s-d Hamiltonian onto a resonance level with a large perturbation and derived the scaling equations for the vertices, the invariant coupling, and the resonance width. The scaling equations are integrated under the assumption that the energy dependence of the resonance width can be neglected. The transcendental equation obtained in this way for the renormalized resonance width is solved in the relevant limits and allows a calculation of the static and dynamical susceptibility. At high temperatures the perturbation expansion for the relaxation rate and the susceptibility is reproduced up to third order in Jρ. At low temperatures the lifetime and χ0 remain finite and vary according to a Fermi-liquid theory. The approximation scheme interpolates in this way between the asymptotic freedom and the infrared slavery, yielding a smooth crossover. The present results are in quantitative agreement with previous ones obtained with the relaxation-kernel method by Götze and Schlottmann. The advantages and drawbacks of the method are discussed. The calculation of the dynamical susceptibility is extended to nonzero external magnetic fields. The quasielastic peak of χ''(ω)ω is suppressed at low temperatures and large magnetic fields and shoulders develop at ω=+/-B.

An Herbal Drug, Gongjin-dan, Ameliorates Acute Fatigue Caused by Short-Term Sleep-Deprivation: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Clinical Trial.

PubMed

Son, Mi Ju; Im, Hwi-Jin; Ku, Boncho; Lee, Jun-Hwan; Jung, So Young; Kim, Young-Eun; Lee, Sung Bae; Kim, Jun Young; Son, Chang-Gue

2018-01-01

Introduction: Gongjin-dan (GJD) is an herbal drug commonly used in Korea and China to combat fatigue, but there are only few clinical studies on its effectiveness and experimental studies on its mechanism of action, and no randomized controlled trial of GJD on the efficacy and mechanism of action has been reported. Here, we performed an exploratory study to evaluate both questions regarding GJD use in humans. Methods: A randomized, double-blinded, placebo-controlled, crossover clinical trial was conducted in the Republic of Korea. Healthy male participants were recruited and randomly allocated to groups receiving GJD-placebo or placebo-GJD in sequence. Fatigue was artificially induced by sleep deprivation for 2 nights. The primary outcome was a change in serum cortisol level; levels of biomarkers for stress hormones as well as oxidative stress and immunologic factors were also assessed, and questionnaires on fatigue and sleep quality were conducted. Results: Twelve and 11 participants were assigned to the GJD-placebo and placebo-GJD groups, respectively. Of all 23 participants, depending on crossover design, we analyzed a total of 20 participants for GJD, and 21 for placebo. An increase in serum cortisol appeared to be attenuated by GJD administration ( p = 0.25), but the effect was not statistically significant; a similar pattern was observed in salivary cortisol levels ( p = 0.14). Overall, GJD showed a tendency to reduce fatigue according to the Brief Fatigue Inventory (BFI, p = 0.07) and the Fatigue Severity Scale (FSS, p = 0.13) questionnaires. BFI and FSS scores in the first stage (before the crossover), however, were significantly improved (BFI, p = 0.02; FSS, p = 0.05) after GJD treatment (relative to placebo). GJD also seemed to improve sleep quality as assessed by the Leeds Sleep Evaluation Questionnaire ( p = 0.06), with a significant improvement specifically in the condition "Getting To Sleep" ( p = 0.02). Five participants experienced minor adverse events, but no adverse events were specific to the GJD administration period. Conclusions: This trial produced the first clinical evidence that GJD might have anti-fatigue properties, especially under sleep deprivation; however, the investigation of cortisol-mediated mechanisms requires further larger-scale studies in the future. World Health Organization International Clinical Trials Registry Platform KCT0001681 (http://apps.who.int/trialsearch/Trial2.aspx?TrialID=KCT0001681).

Menstrual cycle phase and single tablet antiretroviral medication adherence in women with HIV.

PubMed

Hessol, Nancy A; Holman, Susan; Minkoff, Howard; Cohen, Mardge H; Golub, Elizabeth T; Kassaye, Seble; Karim, Roksana; Sosanya, Oluwakemi; Shaheen, Christopher; Merhi, Zaher

2016-01-01

Suboptimal adherence to antiretroviral (ARV) therapy among HIV-infected individuals is associated with increased risk of progression to AIDS and the development of HIV resistance to ARV medications. To examine whether the luteal phase of the menstrual cycle is independently associated with suboptimal adherence to single tablet regimen (STR) ARV medication, data were analyzed from a multicenter cohort study of HIV-infected women who reported regular menstrual cycles and were taking an STR. In a cross-sectional analysis, suboptimal adherence to an STR among women in their follicular phase was compared with suboptimal adherence among women in their luteal phase. In two-way crossover analyses, whereby the same woman was assessed for STR medication adherence in both her follicular and luteal phases, the estimated exact conditional odds of non-adherence to an STR was measured. In adjusted logistic regression analysis of the cross-sectional data (N=327), women with ≤12 years of education were more than three times more likely to have suboptimal adherence (OR=3.6, p=.04) compared to those with >12 years of education. Additionally, women with Center for Epidemiological Studies Depression Scale (CES-D) scores ≥23 were 2.5-times more likely to have suboptimal adherence (OR=2.6, p=.02) compared to those with CES-D scores <23. In conditional logistic regression analyses of the crossover data (N=184), having childcare responsibilities was associated with greater odds of ≤95% adherence. Menstrual cycle phase was not associated with STR adherence in either the cross-sectional or crossover analyses. The lack of association between phase of the menstrual cycle and adherence to an STR in HIV-infected women means attention can be given to other more important risk factors for suboptimal adherence, such as depression, level of education, and childcare responsibilities.

Predictive display design for the vehicles with time delay in dynamic response

NASA Astrophysics Data System (ADS)

Efremov, A. V.; Tiaglik, M. S.; Irgaleev, I. H.; Efremov, E. V.

2018-02-01

The two ways for the improvement of flying qualities are considered: the predictive display (PD) and the predictive display integrated with the flight control system (FCS). The both ways allow to transforming the controlled element dynamics in the crossover frequency range, to improve the accuracy of tracking and to suppress the effect of time delay in the vehicle response too. The technique for optimization of the predictive law is applied to the landing task. The results of the mathematical modeling and experimental investigations carried out for this task are considered in the paper.

On the equivalence of case-crossover and time series methods in environmental epidemiology.

PubMed

Lu, Yun; Zeger, Scott L

2007-04-01

The case-crossover design was introduced in epidemiology 15 years ago as a method for studying the effects of a risk factor on a health event using only cases. The idea is to compare a case's exposure immediately prior to or during the case-defining event with that same person's exposure at otherwise similar "reference" times. An alternative approach to the analysis of daily exposure and case-only data is time series analysis. Here, log-linear regression models express the expected total number of events on each day as a function of the exposure level and potential confounding variables. In time series analyses of air pollution, smooth functions of time and weather are the main confounders. Time series and case-crossover methods are often viewed as competing methods. In this paper, we show that case-crossover using conditional logistic regression is a special case of time series analysis when there is a common exposure such as in air pollution studies. This equivalence provides computational convenience for case-crossover analyses and a better understanding of time series models. Time series log-linear regression accounts for overdispersion of the Poisson variance, while case-crossover analyses typically do not. This equivalence also permits model checking for case-crossover data using standard log-linear model diagnostics.

Effects of Subsensory Noise and Fatigue on Knee Landing and Cross-over Cutting Biomechanics in Male Athletes.

PubMed

Qu, Xingda; Jiang, Jianxin; Hu, Xinyao

2018-06-01

The objective of this study was to examine the effects of subsensory noise and fatigue on knee biomechanics during the athletic task of landing followed by cross-over cutting. A total of 32 healthy male athletes participated in the study. They were evenly divided into 2 groups: no fatigue group and fatigue group. Fatigue was induced to the lower extremity by a repetitive squatting exercise in the fatigue group. Subsensory noise was generated by linear miniature vibrators bilaterally placed around the knee joints. During data collection, the participants were instructed to perform landing followed by cross-over cutting in both the subsensory on and off conditions. Dependent variables were selected to assess knee biomechanics in the phases of landing and cross-over cutting, separately. Results showed that fatigue resulted in larger knee flexion during landing and larger knee internal rotation during cross-over cutting. Subsensory noise was found to reduce knee rotation impulse during cross-over cutting. These findings suggest that cross-over cutting is more dangerous than landing in the fatigue condition, and subsensory noise may lead to changes in knee biomechanics consistent with reduced risk of anterior cruciate ligament injuries, but the changes may be task-specific.

An investigation of the safety and pharmacokinetics of the novel TRPV1 antagonist XEN-D0501 in healthy subjects

PubMed Central

Round, Patrick; Priestley, Anthony; Robinson, Jan

2011-01-01

AIMS XEN-D0501, a novel TRPV1 antagonist, is being developed to treat overactive bladder. This study investigated the safety and pharmacokinetics of repeat-dose XEN-D0501 in healthy subjects. METHODS The study was conducted in two parts. Part 1 was a double-blind, randomized, placebo-controlled, two-way crossover study in three cohorts of 12 young male subjects. Each subject received XEN-D0501 and placebo (in random order) twice daily for 13 days, with a final single dose on day 14. Doses of 1, 2.5 and 5 mg XEN-D0501 were investigated. Part 2 was an open-label, randomized, two-way crossover study in male and female subjects (45 to 65 years). Subjects received single doses of 5 mg XEN-D0501 under fasted and fed conditions in random order. Blood sampling and safety assessments were conducted throughout the study. RESULTS XEN-D0501 was rapidly absorbed (tmax generally 0.5–4 h post dose). XEN-D0501 exposure increased less than proportionally to dose over the range studied and exhibited minimal accumulation with twice daily dosing. Food had no clinically relevant effects on the pharmacokinetics of XEN-D0501. There were no severe or serious adverse events and all doses were well tolerated. A dose-related increase in body temperature was seen with XEN-D0501 which attenuated over time. Differences from placebo in mean maximum core body temperatures were 0.22°C, 0.5°C and 0.74°C following 1 mg, 2.5 mg and 5 mg twice daily XEN-D0501. The observed increase in body temperature was not considered to be of clinical concern. CONCLUSIONS XEN-D0501 appeared safe and well tolerated at doses up to 5 mg twice daily for 14 days in healthy subjects. PMID:21676011

Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

PubMed

Muir, J F; Bertin, L; Georges, D

1992-11-01

We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

Open circuit voltage durability study and model of catalyst coated membranes at different humidification levels

NASA Astrophysics Data System (ADS)

Kundu, Sumit; Fowler, Michael W.; Simon, Leonardo C.; Abouatallah, Rami; Beydokhti, Natasha

Fuel cell material durability is an area of extensive research today. Chemical degradation of the ionomer membrane is one important degradation mechanism leading to overall failure of fuel cells. This study examined the effects of relative humidity on the chemical degradation of the membrane during open circuit voltage testing. Five Gore™ PRIMEA ® series 5510 catalyst coated membranes were degraded at 100%, 75%, 50%, and 20% RH. Open circuit potential and cumulative fluoride release were monitored over time. Additionally scanning electron microscopy images were taken at end of the test. The results showed that with decreasing RH fluoride release rate increased as did performance degradation. This was attributed to an increase in gas crossover with a decrease in RH. Further, it is also shown that interruptions in testing may heavily influence cumulative fluoride release measurements where frequent stoppages in testing will cause fluoride release to be underestimated. SEM analysis shows that degradation occurred in the ionomer layer close to the cathode catalyst. A chemical degradation model of the ionomer membrane was used to model the results. The model was able to predict fluoride release trends, including the effects of interruptions, showing that changes in gas crossover with RH could explain the experimental results.

The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease

PubMed Central

Gimeno-Santos, Elena; Raste, Yogini; Demeyer, Heleen; Louvaris, Zafeiris; de Jong, Corina; Rabinovich, Roberto A.; Hopkinson, Nicholas S.; Polkey, Michael I.; Vogiatzis, Ioannis; Tabberer, Maggie; Dobbels, Fabienne; Ivanoff, Nathalie; de Boer, Willem I.; van der Molen, Thys; Kulich, Karoly; Serra, Ignasi; Basagaña, Xavier; Troosters, Thierry; Puhan, Milo A.; Karlsson, Niklas

2015-01-01

No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD. Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts. 236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”. After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test–retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity. Daily and clinical visit “PROactive physical activity in COPD” instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients. PMID:26022965

The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease.

PubMed

Gimeno-Santos, Elena; Raste, Yogini; Demeyer, Heleen; Louvaris, Zafeiris; de Jong, Corina; Rabinovich, Roberto A; Hopkinson, Nicholas S; Polkey, Michael I; Vogiatzis, Ioannis; Tabberer, Maggie; Dobbels, Fabienne; Ivanoff, Nathalie; de Boer, Willem I; van der Molen, Thys; Kulich, Karoly; Serra, Ignasi; Basagaña, Xavier; Troosters, Thierry; Puhan, Milo A; Karlsson, Niklas; Garcia-Aymerich, Judith

2015-10-01

No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled "amount" and "difficulty". After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.Daily and clinical visit "PROactive physical activity in COPD" instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients. Copyright ©ERS 2015.

Assessment of bioequivalence of rifampicin, isoniazid and pyrazinamide in a four drug fixed dose combination with separate formulations at the same dose levels.

PubMed

Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

2002-02-21

Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.

Crossover from capillary fingering to viscous fingering in a rough fracture

NASA Astrophysics Data System (ADS)

Hu, R.; Chen, Y.; Wu, D. S.

2017-12-01

Controlled by the competition between capillary and viscous forces, the displacement patterns of one fluid displacing another more viscous one exhibit capillary fingering, viscous fingering, and the crossover between the two. Although extensive studies have investigated viscous and capillary fingerings in porous and fractured media, a few studies focused on the crossover in rough fractures, and how viscous and capillary forces affect the crossover remains unclear. Using a transparent fracture visualization system, we studied how the competition impacts the crossover in a horizontal rough fracture. Drainage experiments of water displacing oil were conducted at seven flow rates (capillary number log10Ca ranging from -7.07 to -3.07) and four viscosity ratios (M = 1/1000, 1/500, 1/100 and 1/50). We consistently observed lower invading fluid saturations in the crossover zone. In addition, we proposed a phase diagram for the displacement patterns in a rough fracture that is consistent with similar studies in porous media. Based on real-time imaging and statistical analysis of the invasion morphology, we showed that the competition between the capillary and viscous forces is responsible for the saturation reduction in the crossover zone. In this zone, finger propagation toward the outlet (characteristic of viscous fingering) as well as void-filling in the transverse and backward directions (characteristic of capillary fingering), are both suppressed. Therefore, the invading fluid tends to occupy larger apertures with higher characteristic front velocity, promoting void-filling toward the outlet with thinner finger growth and resulting in a larger volume of defending fluid left behind.

5D perspective on Higgs production at the boundary of a warped extra dimension

NASA Astrophysics Data System (ADS)

Malm, Raoul; Neubert, Matthias; Novotny, Kristiane; Schmell, Christoph

2014-01-01

A comprehensive, five-dimensional calculation of Higgs-boson production in gluon fusion is performed for both the minimal and the custodially protected Randall-Sundrum (RS) model, with Standard Model fields propagating in the bulk and the scalar sector confined on or near the IR brane. For the first time, an exact expression for the gg → h amplitude in terms of the five-dimensional fermion propagator is derived, which includes the full dependence on the Higgs-boson mass. Various results in the literature are reconciled and shown to correspond to different incarnations of the RS model, in which the Higgs field is either localized on the IR brane or is described in terms of a narrow bulk state. The results in the two scenarios differ in a qualitative way: the gg → h amplitude is suppressed in models where the scalar sector is localized on the IR brane, while it tends to be enhanced in bulk Higgs models. In both cases, effects of higher-dimensional operators contributing to the gg → h amplitude at tree level are shown to be numerically suppressed under reasonable assumptions. There is no smooth cross-over between the two scenarios, since the effective field-theory description breaks down in the transition region. A detailed phenomenological analysis of Higgs production in various RS scenarios is presented, and for each scenario the regions of parameter space already excluded by LHC data are derived.

Does topical amethocaine gel reduce pain from heel prick blood sampling in premature infants? A randomized double-blind cross-over controlled study

PubMed Central

Patel, Amita; Czerniawski, Barbara; Gray, Shari; Lui, Eric

2003-01-01

BACKGROUND: Heel prick blood sampling is the most common painful invasive procedure performed on neonates. Currently, there are no effective ways to provide pain relief from this painful procedure. OBJECTIVE: To assess the efficacy of the topical anesthetic amethocaine 4% gel (Ametop, Smith & Nephew Inc, St Laurent) in reducing the pain of heel prick blood sampling in neonates. METHODS: A randomized, double-blind, placebo controlled, crossover trial was conducted. Neonates between 33 to 37 weeks’ gestational age in their first seven days of life were eligible. Heel prick blood sampling was performed on each participant twice. Each infant was randomly assigned to receive either amethocaine 4% gel or placebo to the heel for the first prick, and then received the alternative agent for the second prick. Prick pain was assessed using both Premature Infant Pain Profile (PIPP) and Neonatal Infant Pain Scale (NIPS). Squeeze pain was assessed by NIPS. RESULTS: Ten babies were recruited. There were no significant differences in the average PIPP and NIPS scores between the treatment and placebo groups for both prick and squeeze pains from heel prick blood sampling. For prick pain, linear-regression showed significant correlation between the PIPP and NIPS scores. No adverse reactions were observed after application of either the active or placebo agents. CONCLUSION: Topical amethocaine 4% gel is not shown to reduce prick and squeeze pains significantly from heel prick blood sampling in neonates between 33 to 37 weeks’ gestational age. Further studies are needed to find ways to provide effective pain relief from this common procedure. PMID:20020001

Pharmacokinetic Interaction of Abacavir (1592U89) and Ethanol in Human Immunodeficiency Virus-Infected Adults

PubMed Central

McDowell, James A.; Chittick, Gregory E.; Stevens, Cristina Pilati; Edwards, Kathleen D.; Stein, Daniel S.

2000-01-01

While in vitro results at clinically relevant concentrations do not predict abacavir (1592U89) interactions with drugs highly metabolized by cytochrome P450, the potential does exist for a pharmacokinetic interaction between abacavir and ethanol, as both are metabolized by alcohol dehydrogenase. Twenty-five subjects were enrolled in an open-label, randomized, three-way-crossover, phase I study of human immunodeficiency virus-infected male subjects. The three treatments were administration of (i) 600 mg of abacavir, (ii) 0.7 g of ethanol per kg of body weight, and (iii) 600 mg of abacavir and 0.7 g of ethanol per kg. Twenty-four subjects completed the study with no unexpected adverse events reported. Ethanol pharmacokinetic parameters were unchanged with abacavir coadministration. The geometric least squares mean area under the concentration curve extrapolated to infinite time for abacavir increased 41% (from 11.07 to 15.62 μg · h/ml), and the half-life increased 26% (from 1.42 to 1.79 h) in the presence of ethanol (mean ethanol maximum concentration in plasma of 498 μg/ml). The percentages of abacavir dose recovered in urine as abacavir and its two major metabolites were each altered in the presence of ethanol, but there was no change in the total percentage (≈50%) of administered dose recovered in the 12-h collection interval. In conclusion, while a single 600-mg dose of abacavir does not alter blood ethanol concentration, ethanol does increase plasma abacavir concentrations. PMID:10817729

Effects of rabeprazole, 20 mg, or esomeprazole, 20 mg, on 24-h intragastric pH and serum gastrin in healthy subjects.

PubMed

Warrington, S; Baisley, K; Boyce, M; Tejura, B; Morocutti, A; Miller, N

2002-07-01

To compare the antisecretory effects of rabeprazole and esomeprazole in an open, randomized, two-way crossover, clinical pharmacology study. Twenty-four healthy subjects (14 men, 10 women; mean age 26.8 years) received rabeprazole 20 mg or esomeprazole 20 mg daily on days 1-5, with a 14-day 'wash-out'. Intragastric pH was recorded continuously, and serum gastrin measured, on days 0, 1 and 5. On day 0, mean intragastric pH AUC was significantly higher before the esomeprazole than before the rabeprazole treatment in four of the five time intervals analysed. On days 1 and 5, mean intragastric pH AUC was higher after rabeprazole than esomeprazole during 5-11, 14-24 and 0-24 h after dosing. Mean pH AUC in the first 5 h after dosing on day 5 was higher after esomeprazole than rabeprazole (P=0.012). On day 1, mean per cent times pH > 3 and > 4 were significantly greater after rabeprazole than esomeprazole during 0-14, 14-24 and 0-24 h. On day 5, mean serum gastrin AUC0-4 was higher (P = 0.017) after rabeprazole than esomeprazole (335 vs. 316 pg/mL.h). In this clinical pharmacology study, rabeprazole 20 mg daily was more effective than esomeprazole 20 mg daily in increasing intragastric pH and maintaining pH > 3 and > 4. On day 5, mean pH AUC was higher after esomeprazole than rabeprazole.

Anatomy of charge-exchange straggling

NASA Astrophysics Data System (ADS)

Sigmund, P.; Osmani, O.; Schinner, A.

2014-11-01

We have studied charge-exchange straggling theoretically for swift krypton and silicon ions and five target gases in the MeV/u energy regime. We find a pronounced two-peak structure for all ion-target combinations. The peak at the highest energy appears around the velocity where the bare ion and the one-electron ion are equally abundant in the equilibrium charge distribution. Correspondingly, the low-energy peak appears near the cross-over between the charge fractions of the two- and the three-electron ion. The possibility of further peaks at lower energies is discussed. Our findings are compared with recent experimental results on straggling of krypton beams.

On the temperature dependence of the Adam-Gibbs equation around the crossover region in the glass transition

NASA Astrophysics Data System (ADS)

Duque, Michel; Andraca, Adriana; Goldstein, Patricia; del Castillo, Luis Felipe

2018-04-01

The Adam-Gibbs equation has been used for more than five decades, and still a question remains unanswered on the temperature dependence of the chemical potential it includes. Nowadays, it is a well-known fact that in fragile glass formers, actually the behavior of the system depends on the temperature region it is being studied. Transport coefficients change due to the appearance of heterogeneity in the liquid as it is supercooled. Using the different forms for the logarithmic shift factor and the form of the configurational entropy, we evaluate this temperature dependence and present a discussion on our results.

Logical NAND and NOR Operations Using Algorithmic Self-assembly of DNA Molecules

NASA Astrophysics Data System (ADS)

Wang, Yanfeng; Cui, Guangzhao; Zhang, Xuncai; Zheng, Yan

DNA self-assembly is the most advanced and versatile system that has been experimentally demonstrated for programmable construction of patterned systems on the molecular scale. It has been demonstrated that the simple binary arithmetic and logical operations can be computed by the process of self assembly of DNA tiles. Here we report a one-dimensional algorithmic self-assembly of DNA triple-crossover molecules that can be used to execute five steps of a logical NAND and NOR operations on a string of binary bits. To achieve this, abstract tiles were translated into DNA tiles based on triple-crossover motifs. Serving as input for the computation, long single stranded DNA molecules were used to nucleate growth of tiles into algorithmic crystals. Our method shows that engineered DNA self-assembly can be treated as a bottom-up design techniques, and can be capable of designing DNA computer organization and architecture.

Spillover and Crossover of Exhaustion and Life Satisfaction among Dual-Earner Parents

ERIC Educational Resources Information Center

Demerouti, Evangelia; Bakker, Arnold B.; Schaufeli, Wilmar B.

2005-01-01

This study integrates spillover research of stress transferring from work to home and crossover research of strains transferring from one spouse to another. A spillover and crossover model was tested among 191 (couples of) dual-earner parents. For both males and females, it was hypothesized that (self-reported and partners' rating of)…

Effect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans: a crossover double-blind study.

PubMed

Yamane, Ayaka; Higuchi, Hitoshi; Tomoyasu, Yumiko; Ishii-Maruhama, Minako; Maeda, Shigeru; Miyawaki, Takuya

2015-04-01

Recently, attention has been paid to dexmedetomidine, a selective α-2 adrenoceptor agonist, as a possible additive for local anesthesia. However, the effect of locally injected dexmedetomidine on the anesthetic action in humans has not fully been clarified. Thus, the purpose of the present study was to evaluate the effect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans. Twenty healthy volunteers were included in the present crossover double-blinded study. Lidocaine solution or lidocaine plus dexmedetomidine solution was submucosally injected into the alveolar mucosa in a crossover and double-blinded manner. The local anesthetic effect of the solutions was evaluated by measuring the current perception threshold (CPT) in the oral mucosa for 120 minutes after injection. Furthermore, the sedation level, blood pressure, and heart rate of the volunteers were evaluated. For statistical analysis, the Wilcoxon signed rank test and 2-way repeated measures analysis of variation were used. The CPT was increased with the 2 solutions and peaked 10 minutes after injection. CPT values 10 and 20 minutes after injection of lidocaine plus dexmedetomidine solution were considerably higher than those with lidocaine solution. The duration of an important increase in the CPT after injection with lidocaine plus dexmedetomidine solution was longer than that with lidocaine. Furthermore, the area under the time curve of CPT was considerably higher with lidocaine plus dexmedetomidine solution than with lidocaine solution. No volunteer showed a change in sedation level, blood pressure, or heart rate after injection with either test solution throughout the experiment. The present study showed that a combination of dexmedetomidine plus lidocaine considerably enhances the local anesthetic potency of lidocaine without any major influences on the cardiovascular system when locally injected into the oral mucosa. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Switching to nilotinib versus imatinib dose escalation in patients with chronic myeloid leukaemia in chronic phase with suboptimal response to imatinib (LASOR): a randomised, open-label trial.

PubMed

Cortes, Jorge E; De Souza, Carmino Antonio; Ayala, Manuel; Lopez, Jose Luis; Bullorsky, Eduardo; Shah, Sandip; Huang, Xiaojun; Babu, K Govind; Abdulkadyrov, Kudrat; de Oliveira, José Salvador Rodrigues; Shen, Zhi-Xiang; Sacha, Tomasz; Bendit, Israel; Liang, Zhizhou; Owugah, Tina; Szczudlo, Tomasz; Khanna, Sadhvi; Fellague-Chebra, Rafik; le Coutre, Philipp D

2016-12-01

Optimal management of patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response remains undetermined. This study aimed to investigate the safety and efficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic response on imatinib. We did a phase 3, open-label, randomised trial in patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response to imatinib according to the 2009 European LeukemiaNet criteria, in Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries). Eligible patients were aged 18 years or older with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase and Eastern Cooperative Oncology Group performance status of 0-2. Before enrolment, all patients had received 3-18 months of imatinib 400 mg once daily and had a suboptimal cytogenetic response according to 2009 ELN recommendations, established through bone marrow cytogenetics. By use of an interactive response technology using fixed blocks, we randomly assigned patients (1:1) to switch to nilotinib 400 mg twice per day or an escalation of imatinib dose to 600 mg once per day (block size of 4). Investigators and participants were not blinded to study treatment. Crossover was allowed for loss of response or intolerance at any time, or for patients with no complete cytogenetic response at 6 months. The primary endpoint was complete cytogenetic response at 6 months in the intention-to-treat population. Efficacy endpoints were based on the intention-to-treat population, with all patients assessed according to the treatment group to which they were randomised (regardless of crossover); the effect of crossover was assessed in post-hoc analyses, in which responses achieved after crossover were excluded. We present the final results at 24 months' follow-up. This study is registered with ClinicalTrials.gov (NCT00802841). Between July 7, 2009, and Aug 29, 2012, we enrolled 191 patients. 96 patients were randomly assigned to nilotinib and 95 patients were randomly assigned to imatinib. Complete cytogenetic response at 6 months was achieved by 48 of 96 patients in the nilotinib group (50%, 95·18% CI 40-61) and 40 of 95 in the imatinib group (42%, 32-53%; difference 7·9% in favour of nilotinib; 95% CI -6·2 to 22·0, p=0·31). Excluding responses achieved after crossover, 48 (50%) of 96 patients in the nilotinib group and 34 (36%) of 95 patients in the imatinib group achieved complete cytogenic response at 6 months (nominal p=0·058). Grade 3-4 non-haematological adverse events occurring in more than one patient were headache (nilotinib group, n=2 [2%, including 1 after crossover to imatinib]; imatinib group, n=1 [1%]), blast cell crisis (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%]), and QT prolongation (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%, after crossover to nilotinib]). Serious adverse events on assigned treatment were reported in 11 (11%) of 96 patients in the nilotinib group and nine (10%) of 93 patients in the imatinib group. Seven (7%) of 96 patients died in the nilotinib group and five (5%) of 93 patients died in the imatinib group; no deaths were treatment-related. While longer-term analyses are needed to establish whether the clinical benefits observed with switching to nilotinib are associated with improved long-term survival outcomes, our results suggest that patients with suboptimal cytogenetic response are more likely to achieve improved cytogenetic and molecular responses with switching to nilotinib than with imatinib dose escalation, although the difference was not statistically significant when responses achieved after crossover were included. Novartis Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increased calcium absorption from synthetic stable amorphous calcium carbonate: double-blind randomized crossover clinical trial in postmenopausal women.

PubMed

Vaisman, Nachum; Shaltiel, Galit; Daniely, Michal; Meiron, Oren E; Shechter, Assaf; Abrams, Steven A; Niv, Eva; Shapira, Yami; Sagi, Amir

2014-10-01

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 (CCC) using the dual stable isotope technique. The study was conducted in the Unit of Clinical Nutrition, Tel Aviv Sourasky Medical Center, Israel. The study population included 15 early postmenopausal women aged 54.9 ± 2.8 (mean ± SD) years with no history of major medical illness or metabolic bone disorder, excess calcium intake, or vitamin D deficiency. Standardized breakfast was followed by randomly provided CCC or ACC capsules containing 192 mg elemental calcium labeled with 44Ca at intervals of at least 3 weeks. After swallowing the capsules, intravenous CaCl2 labeled with 42Ca on was administered on each occasion. Fractional calcium absorption (FCA) of ACC and CCC was calculated from the 24-hour urine collection following calcium administration. The results indicated that FCA of ACC was doubled (± 0.96 SD) on average compared to that of CCC (p < 0.02). The higher absorption of the synthetic stable ACC may serve as a more efficacious way of calcium supplementation. © 2014 American Society for Bone and Mineral Research.

Five Ways to Facilitate the Teacher Assistant's Work in the Classroom

ERIC Educational Resources Information Center

Tobin, Ruthanne

2006-01-01

A teacher and a teacher assistant, working together in an inclusive grade-six classroom, provided an invaluable insider perspective on the kind of context that leads to effective support for all students. Findings from this case study revealed five ways in which the teacher could facilitate the work of the teacher assistant, by: 1) focusing on…

Multimodal Cognitive Enhancement Therapy for Patients with Mild Cognitive Impairment and Mild Dementia: A Multi- Center, Randomized, Controlled, Double-Blind, Crossover Trial.

PubMed

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.

Double-blind, placebo-controlled study of nicergoline in the treatment of pruritus in patients receiving maintenance hemodialysis.

PubMed

Bousquet, J; Rivory, J P; Maheut, M; Michel, F B; Mion, C

1989-04-01

Pruritus is a common symptom among patients undergoing long-term hemodialysis. The effect of nicergoline, an ergoline, on pruritus was studied in products released during dialysis. In a first experiment series, 20 age-matched normal individuals, 25 patients receiving hemodialysis without pruritus, and 15 patients receiving hemodialysis with pruritus had intradermal tests with 500 micrograms of papaverine. All patients with pruritus had a small papaverine skin test response, and mean values were significantly (p less than 0.0001, Mann-Whitney U test) smaller in patients with pruritus. All patients with pruritus entered in a crossover, double-blind trial with nicergoline. In a first period of six dialyses, they received either nicergoline (daily oral dose, 30 mg, and intravenous dose during dialyses, 5 mg) or placebo. In the second period of six dialyses, patients received the crossover treatment. Nicergoline was effective in 13/15 patients, eight of these patients having a complete remission of pruritus. When nicergoline was stopped, patients relapsed within 24 to 48 hours. All patients who improved during the trial were then treated with a daily dose of 30 mg of nicergoline for 6 months. Seven patients had a complete remission, five had moderate symptoms, and one patient relapsed. This study demonstrated that some hemodialyzed patients with pruritus of unknown etiology had improvement with nicergoline.

Mobile Application vs Paper Pictorial Blood Assessment Chart to Track Menses in Young Women: A Randomized Cross-over Design.

PubMed

Jacobson, Amanda E; Vesely, Sara K; Haamid, Fareeda; Christian-Rancy, Myra; O'Brien, Sarah H

2018-04-01

Heavy menstrual bleeding is a common symptom reported by approximately 30% of women. The Pictorial Blood Assessment Chart (PBAC) score is often used to quantify severity of menstrual bleeding. However, the traditional PBAC paper diary might be subject to recall bias and compliance issues, especially in adolescents. We developed a mobile application (app) version of the PBAC score and evaluated patient satisfaction and compliance with app reporting vs paper reporting. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This study was a randomized cross-over study of 25 postmenarchal female adolescents and young women ages 13-21 years. Participants agreed to track bleeding in 2 consecutive menstrual cycles and were randomized to use the PBAC paper diary or mobile app format first. At the end of each cycle, a satisfaction survey and system usability scale (app only) was used to assess the acceptability of the format used. Twenty-five participants had a median age of 15 years. Cross-over analysis showed that satisfaction level was significantly higher for the app (P < .001). Twenty of 25 (80%) participants preferred the app over the paper diary. For the app, 20 of 25 participants (80%) had high compliance for reporting bleeding, with a mean of 2 app entries per day. Participants' PBAC scores did not vary significantly between the paper diary (median, 95) and mobile app (median, 114). All paper diaries met definition for high compliance. There was no significant period or carryover effect. This study showed that a PBAC app compared with the paper diary was the preferred method of recording menstrual bleeding in adolescents and showed feasibility as a research data collection tool. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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. © 2013, The International Biometric Society.

Design, Analysis, and Reporting of Crossover Trials for Inclusion in a Meta-Analysis.

PubMed

Li, Tianjing; Yu, Tsung; Hawkins, Barbara S; Dickersin, Kay

2015-01-01

To evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines. We searched MEDLINE, EMBASE, and Cochrane's CENTRAL register for randomized crossover trials for a systematic review and network meta-analysis we are conducting. Two individuals independently screened the search results for eligibility and abstracted data from each included report. We identified 83 crossover trials eligible for inclusion. Issues affecting the risk of bias in crossover trials, such as carryover, period effects and missing data, were often ignored. Some trials failed to accommodate the within-individual differences in the analysis. For a large proportion of the trials, the authors tabulated the results as if they arose from a parallel design. Precision estimates properly accounting for the paired nature of the design were often unavailable from the study reports; consequently, to include trial findings in a meta-analysis would require further manipulation and assumptions. The high proportion of poorly reported analyses and results has the potential to affect whether crossover data should or can be included in a meta-analysis. There is pressing need for reporting guidelines for crossover trials.

Stepped wedge designs: insights from a design of experiments perspective.

PubMed

Matthews, J N S; Forbes, A B

2017-10-30

Stepped wedge designs (SWDs) have received considerable attention recently, as they are potentially a useful way to assess new treatments in areas such as health services implementation. Because allocation is usually by cluster, SWDs are often viewed as a form of cluster-randomized trial. However, since the treatment within a cluster changes during the course of the study, they can also be viewed as a form of crossover design. This article explores SWDs from the perspective of crossover trials and designed experiments more generally. We show that the treatment effect estimator in a linear mixed effects model can be decomposed into a weighted mean of the estimators obtained from (1) regarding an SWD as a conventional row-column design and (2) a so-called vertical analysis, which is a row-column design with row effects omitted. This provides a precise representation of "horizontal" and "vertical" comparisons, respectively, which to date have appeared without formal description in the literature. This decomposition displays a sometimes surprising way the analysis corrects for the partial confounding between time and treatment effects. The approach also permits the quantification of the loss of efficiency caused by mis-specifying the correlation parameter in the mixed-effects model. Optimal extensions of the vertical analysis are obtained, and these are shown to be highly inefficient for values of the within-cluster dependence that are likely to be encountered in practice. Some recently described extensions to the classic SWD incorporating multiple treatments are also compared using the experimental design framework. Copyright © 2017 John Wiley & Sons, Ltd.

Visualizing and quantifying the crossover from capillary fingering to viscous fingering in a rough fracture

NASA Astrophysics Data System (ADS)

Chen, Yi-Feng; Fang, Shu; Wu, Dong-Sheng; Hu, Ran

2017-09-01

Immiscible fluid-fluid displacement in permeable media is important in many subsurface processes, including enhanced oil recovery and geological CO2 sequestration. Controlled by capillary and viscous forces, displacement patterns of one fluid displacing another more viscous one exhibit capillary and viscous fingering, and crossover between the two. Although extensive studies investigated viscous and capillary fingering in porous media, a few studies focused on the crossover in rough fractures, and how viscous and capillary forces affect the crossover remains unclear. Using a transparent fracture-visualization system, we studied how the two forces impact the crossover in a horizontal rough fracture. Drainage experiments of water displacing oil were conducted at seven flow rates (capillary number log10Ca ranging from -7.07 to -3.07) and four viscosity ratios (M=1/1000,1/500,1/100 and 1/50). We consistently observed lower invading fluid saturations in the crossover zone. We also proposed a phase diagram for the displacement patterns in a rough fracture that is consistent with similar studies in porous media. Based on real-time imaging and statistical analysis of the invasion morphology, we showed that the competition between capillary and viscous forces is responsible for the saturation reduction in the crossover zone. In this zone, finger propagation toward the outlet (characteristic of viscous fingering) as well as void-filling in the transverse/backward directions (characteristic of capillary fingering), are both suppressed. Therefore, the invading fluid tends to occupy larger apertures with higher characteristic front velocity, promoting void-filling toward the outlet with thinner finger growth and resulting in a larger volume of defending fluid left behind.

Development and evaluation of a study design typology for human research.

PubMed

Carini, Simona; Pollock, Brad H; Lehmann, Harold P; Bakken, Suzanne; Barbour, Edward M; Gabriel, Davera; Hagler, Herbert K; Harper, Caryn R; Mollah, Shamim A; Nahm, Meredith; Nguyen, Hien H; Scheuermann, Richard H; Sim, Ida

2009-11-14

A systematic classification of study designs would be useful for researchers, systematic reviewers, readers, and research administrators, among others. As part of the Human Studies Database Project, we developed the Study Design Typology to standardize the classification of study designs in human research. We then performed a multiple observer masked evaluation of active research protocols in four institutions according to a standardized protocol. Thirty-five protocols were classified by three reviewers each into one of nine high-level study designs for interventional and observational research (e.g., N-of-1, Parallel Group, Case Crossover). Rater classification agreement was moderately high for the 35 protocols (Fleiss' kappa = 0.442) and higher still for the 23 quantitative studies (Fleiss' kappa = 0.463). We conclude that our typology shows initial promise for reliably distinguishing study design types for quantitative human research.

Short term clinical efficacy of new meridol HALITOSIS tooth & tongue gel in combination with a tongue cleaner to reduce oral malodor.

PubMed

Wilhelm, D; Himmelmann, A; Krause, C; Wilhelm, K-P

2013-01-01

This study evaluated the short term efficacy of tongue cleaning with meridol HALITOSIS tooth & tongue gel in comparison to mechanical tongue cleaning alone and untreated after five and 60 minutes in patients with an oral cause of bad breath. Fifty-four male and female subjects with an intra-oral cause of halitosis (organoleptic ratings > or = 2 and volatile sulphur compounds > or = 50 ppb) participated in this crossover study and were assigned to six different treatment sequences (ABC, ACB, BAC, BCA, CAB, CBA) with no treatment (A), mechanical tongue cleaning alone (B), and tongue cleaning with tooth & tongue gel applied to the tongue cleaner (C). Efficacy was assessed by organoleptic ratings and volatile sulphur compound measurements five and 60 minutes after treatment Cleaning the tongue with tooth & tongue gel applied onto the tongue cleaner resulted in significantly reduced organoleptic ratings (p < 0.001 for the five-minute assessment; p = 0.001 for the 60-minute assessment) and volatile sulphur compounds (H2S + CH3SH: p = 0.005 for the five-minute assessment; p = 0.003 for the 60-minute assessment) compared to no treatment at the five- and 60-minute assessment time points, while mechanical tongue cleaning alone was less effective in reducing organoleptic ratings (p = 0.008 for the five-minute assessment; p = 0.144 for the 60-minute assessment) and volatile sulphur compounds (H2S + CH3SH: p = 0.261 for the five-minute assessment; p = 0.365 for the 60-minute assessment). Single tongue cleaning with meridol HALITOSIS tooth & tongue gel had a positive effect on halitosis five and 60 minutes after treatment. Tongue cleaning with tooth & tongue gel in combination with other oral hygiene procedures is a promising approach to control halitosis.

Viscosity minima in binary mixtures of ionic liquids + molecular solvents.

PubMed

Tariq, M; Shimizu, K; Esperança, J M S S; Canongia Lopes, J N; Rebelo, L P N

2015-05-28

The viscosity (η) of four binary mixtures (ionic liquids plus molecular solvents, ILs+MSs) was measured in the 283.15 < T/K < 363.15 temperature range. Different IL/MS combinations were selected in such a way that the corresponding η(T) functions exhibit crossover temperatures at which both pure components present identical viscosity values. Consequently, most of the obtained mixture isotherms, η(x), exhibit clear viscosity minima in the studied T-x range. The results are interpreted using auxiliary molecular dynamics (MD) simulation data in order to correlate the observed η(T,x) trends with the interactions in each mixture, including the balance between electrostatic forces and hydrogen bonding.

Safety and economic impacts of converting two-way frontage roads to one-way : methodology and findings.

DOT National Transportation Integrated Search

2011-01-01

In the research documented here, researchers develop information to communicate the safety and : economic impacts of converting frontage roads from two-way to one-way. Researchers studied five : locations in Texas where frontage roads were converted ...

NON-HOMOGENEOUS POISSON PROCESS MODEL FOR GENETIC CROSSOVER INTERFERENCE.

PubMed

Leu, Szu-Yun; Sen, Pranab K

2014-01-01

The genetic crossover interference is usually modeled with a stationary renewal process to construct the genetic map. We propose two non-homogeneous, also dependent, Poisson process models applied to the known physical map. The crossover process is assumed to start from an origin and to occur sequentially along the chromosome. The increment rate depends on the position of the markers and the number of crossover events occurring between the origin and the markers. We show how to obtain parameter estimates for the process and use simulation studies and real Drosophila data to examine the performance of the proposed models.

Crossover ensembles of random matrices and skew-orthogonal polynomials

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

Kumar, Santosh, E-mail: skumar.physics@gmail.com; Pandey, Akhilesh, E-mail: ap0700@mail.jnu.ac.in

2011-08-15

Highlights: > We study crossover ensembles of Jacobi family of random matrices. > We consider correlations for orthogonal-unitary and symplectic-unitary crossovers. > We use the method of skew-orthogonal polynomials and quaternion determinants. > We prove universality of spectral correlations in crossover ensembles. > We discuss applications to quantum conductance and communication theory problems. - Abstract: In a recent paper (S. Kumar, A. Pandey, Phys. Rev. E, 79, 2009, p. 026211) we considered Jacobi family (including Laguerre and Gaussian cases) of random matrix ensembles and reported exact solutions of crossover problems involving time-reversal symmetry breaking. In the present paper we givemore » details of the work. We start with Dyson's Brownian motion description of random matrix ensembles and obtain universal hierarchic relations among the unfolded correlation functions. For arbitrary dimensions we derive the joint probability density (jpd) of eigenvalues for all transitions leading to unitary ensembles as equilibrium ensembles. We focus on the orthogonal-unitary and symplectic-unitary crossovers and give generic expressions for jpd of eigenvalues, two-point kernels and n-level correlation functions. This involves generalization of the theory of skew-orthogonal polynomials to crossover ensembles. We also consider crossovers in the circular ensembles to show the generality of our method. In the large dimensionality limit, correlations in spectra with arbitrary initial density are shown to be universal when expressed in terms of a rescaled symmetry breaking parameter. Applications of our crossover results to communication theory and quantum conductance problems are also briefly discussed.« less

The pharmacokinetic and pharmacodynamic effects of SL65.1498, a GABA-A alpha2,3 selective agonist, in comparison with lorazepam in healthy volunteers.

PubMed

de Haas, S L; Franson, K L; Schmitt, J A J; Cohen, A F; Fau, J B; Dubruc, C; van Gerven, J M A

2009-08-01

Benzodiazepines are effective short-term treatments for anxiety disorders, but their use is limited by undesirable side effects related to Central Nervous System impairment and tolerance development. SL65.1498 is a new compound that acts in vitro as a full agonist at the gamma-aminobutyric acid(A) 2 and 3 receptor and as a partial agonist at the 1 and 5 receptor subtypes. It is thought that the compound could be anxiolytic by its activation at the alpha2 and alpha3 receptor subtypes, without causing unfavourable side effects, which are believed to be mediated by the alpha1 and alpha5 subtypes. This study was a double-blind, five-way cross-over study to investigate the effects of three doses of SL65.1498 in comparison with placebo and lorazepam 2 mg in healthy volunteers. The objective was to select a dose level (expected to be therapeutically active), free of any significant deleterious effect. Psychomotor and cognitive effects were measured using a validated battery of measurements, including eye movements, body sway, memory tests, reaction-time assessments, and visual analogue scales. The highest dose of SL65.1498 showed slight effects on saccadic peak velocity and smooth pursuit performance, although to a much lesser extent than lorazepam. In contrast to lorazepam, none of the SL65.1498 doses affected body sway, visual analogue scale alertness, attention, or memory tests. This study showed that the three doses of SL65.1498 were well tolerated and induced no impairments on memory, sedation, psychomotor, and cognitive functions.

Numerical Investigations of the Thermal, Pressure and Size Effects on 2D Spin Crossover Nanoparticles

NASA Astrophysics Data System (ADS)

Harlé, C.; Allal, S. E.; Sohier, D.; Dufaud, T.; Caballero, R.; de Zela, F.; Dahoo, P. R.; Boukheddaden, K.; Linares, J.

2017-12-01

In the framework of the Ising-like model, the thermal and pressure effects on the spin crossover systems are evaluated through two-states fictitious spin operators σ with eigenvalues 𝜎 = -1 and 𝜎 = +1 respectively associated with the low-spin (LS) and highspin (HS) states of each spin-crossover (SCO) molecule. Based on each configurational state, the macroscopic SCO system, is described by the following variables: m=Σ σi, s=Σ σi σj and c=Σ σk standing respectively for the total magnetization, the short-range correlations and surface magnetization. To solve this problem, we first determine the density of macrostates d[m][s][c], giving the number of microscopic configurations with the same m, s and c values. In this contribution, two different ways have been performed to calculate this important quantity: (i) the entropic sampling method, based on Monte Carlo simulations and (ii) a new algorithm based on specific dynamic programming. These two methods were tested on the 2D SCO nanoparticles for which, we calculated the average magnetization < σ> taking into account for short-, long-range interactions as well as for the interaction between surface molecules with their surrounding matrix. We monitored the effect of the pressure, temperature and size on the properties of the SCO nanoparticles.

Evolutionarily diverse determinants of meiotic DNA break and recombination landscapes across the genome

PubMed Central

Fowler, Kyle R.; Sasaki, Mariko; Milman, Neta

2014-01-01

Fission yeast Rec12 (Spo11 homolog) initiates meiotic recombination by forming developmentally programmed DNA double-strand breaks (DSBs). DSB distributions influence patterns of heredity and genome evolution, but the basis of the highly nonrandom choice of Rec12 cleavage sites is poorly understood, largely because available maps are of relatively low resolution and sensitivity. Here, we determined DSBs genome-wide at near-nucleotide resolution by sequencing the oligonucleotides attached to Rec12 following DNA cleavage. The single oligonucleotide size class allowed us to deeply sample all break events. We find strong evidence across the genome for differential DSB repair accounting for crossover invariance (constant cM/kb in spite of DSB hotspots). Surprisingly, about half of all crossovers occur in regions where DSBs occur at low frequency and are widely dispersed in location from cell to cell. These previously undetected, low-level DSBs thus play an outsized and crucial role in meiosis. We further find that the influence of underlying nucleotide sequence and chromosomal architecture differs in multiple ways from that in budding yeast. DSBs are not strongly restricted to nucleosome-depleted regions, as they are in budding yeast, but are nevertheless spatially influenced by chromatin structure. Our analyses demonstrate that evolutionarily fluid factors contribute to crossover initiation and regulation. PMID:25024163

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

PubMed Central

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. PMID:28084399

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

PubMed

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

2017-01-13

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/m 3 increment in SO 2 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 NO 2 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.

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

NASA Astrophysics Data System (ADS)

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.

Energy expenditure in people with transtibial amputation walking with crossover and energy storing prosthetic feet: A randomized within-subject study.

PubMed

McDonald, Cody L; Kramer, Patricia A; Morgan, Sara J; Halsne, Elizabeth G; Cheever, Sarah M; Hafner, Brian J

2018-05-01

Energy storing feet are unable to reduce the energy required for normal locomotion among people with transtibial amputation. Crossover feet, which incorporate aspects of energy storing and running specific feet, are designed to maximize energy return while providing stability for everyday activities. Do crossover prosthetic feet reduce the energy expenditure of walking across a range of speeds, when compared with energy storing feet among people with transtibial amputation due to non-dysvascular causes? A randomized within-subject study was conducted with a volunteer sample of twenty-seven adults with unilateral transtibial amputation due to non-dysvascular causes. Participants were fit with two prostheses. One had an energy storing foot (Össur Variflex) and the other a crossover foot (Össur Cheetah Xplore). Other components, including sockets, suspension, and interface were standardized. Energy expenditure was measured with a portable respirometer (Cosmed K4b2) while participants walked on a treadmill at self-selected slow, comfortable, and fast speeds with each prosthesis. Gross oxygen consumption rates (VO 2  ml/min) were compared between foot conditions. Energy storing feet were used as the baseline condition because they are used by most people with a lower limb prosthesis. Analyses were performed to identify people who may benefit from transition to crossover feet. On average, participants had lower oxygen consumption in the crossover foot condition compared to the energy storing foot condition at each self-selected walking speed, but this difference was not statistically significant. Participants with farther six-minute walk test distances, higher daily step counts, and higher Medicare Functional Classification Levels at baseline were more likely to use less energy in the crossover foot. Crossover feet may be most beneficial for people with higher activity levels and physical fitness. Further research is needed to examine the effect of crossover feet on energy expenditure during high-level activities. Copyright © 2018 Elsevier B.V. All rights reserved.

Broadband Via-Less Microwave Crossover Using Microstrip-CPW Transitions

NASA Technical Reports Server (NTRS)

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 isolation of 32 dB. It also has low in-band insertion loss and return loss of 1.2 dB and 18 dB, respectively, over more than 44 percent of bandwidth at room temperature. This microstrip-CPW transition requires the microstrip line to be split into two sections. Each section is connected to a microstrip quarter-wavelength openended stub. A slotline is also placed perpendicular to the microstrip section. The slot is connected to a grounded-end quarter-wavelength slotline and generates a microstrip-slotline transition. When two of these sections are placed in parallel and with the microstrip section combined at transition, a microstrip- CPW transition is formed. The slotline radiation is suppressed as two slots are excited with the electric field in an opposite direction, which cancels the radiation in far field. The invention on the crossover consists of the invented microstrip-CPW transitions combined back-to-back and a microstrip low-pass filter. One signal is crossed through to the microstrip layer, while the other signal is crossed through the CPW line located on the ground plane of the microstrip line. The microstrip low-pass filter produces a narrow line at the crossing point to enhance the system isolation. It also produces broadband response in the operating frequency band. The microstrip-CPW transition allows a microwave signal to travel from microstrip line to CPW line with low radiation loss. The crossover allows two microwave signals to cross with minimal parasitic coupling.

Are Emotions Transmitted From Work to Family? A Crossover Model of Psychological Contract Breach.

PubMed

Liang, Huai-Liang

2018-01-01

Based on affective events theory and the crossover model, this study examines the effect of psychological contract breach on employee dysfunctional behavior and partner family undermining and explores the crossover effect of employee dysfunctional behavior on partner family undermining in work-family issues. This study collected 370 employee-partner dyads (277 male employees, 93 female employees, M age = 43.59 years) from a large manufacturing organization. The results of this study support the conception that employees' psychological contract breach results in frustration in the workplace. In addition, mediation analysis results reveal that psychological contract breach relates to employee dysfunctional behavior in the workplace. The findings show that partners' psychological strain mediates the relationship between employee dysfunctional behavior and partner family undermining. Furthermore, these findings provide investigations for the crossover model to display the value of psychological contract breach in family issues.

Two-way crossover bioequivalence study of alendronate sodium tablets in healthy, non-smoking male volunteers under fasted conditions.

PubMed

Thudi, Nageshwar Rao; Gagnon, Stéphanie; Hussain, Saleh; Abolfathi, Zohreh; Singla, Ajay; Pai, Raveendra; Kumar, Sudershan; Monif, Tausif

2009-01-01

This study was conducted in order to assess the bioequivalence of two different formulations containing 70 mg alendronate sodium (CAS 121268-17-5) under fasted conditions. One hundred twenty-two healthy male volunteers were enrolled in an open label, randomized, crossover design with a wash-out period of 20 days in one study center. Urine samples were collected up to 36 h post-dose, and the concentrations of alendronic acid were determined using a high performance liquid chromatographic method with pre-derivatization and fluorescence detection (HPLC/FL) method. The mean Ae(0-t) were 604.24 +/- 348.73 microg and 627.36 +/- 327.99 microg, while the mean R(max) were 193.87 +/- 114.68 microg/h and 202.00 +/- 107.83 microg/h for the test and reference formulations, respectively. The T(max) of the test and reference tablets were 1.26 +/- 0.58 h and 1.26 +/- 0.51 h, respectively. No significant differences of pharmacokinetic parameters between the two studied formulations were found. The 90% confidence intervals for the primary target parameters, intra-individual ratios for Ae(0-t) and R(max) of alendronic acid, were between 0.86-1.00 and 0.85-1.01, respectively, and thus within the acceptance range for bioequivalence criteria. In the light of the present study it can be concluded that the test formulation is bioequivalent to the reference formulation.

Endoscopic evaluation of the comparative effects of acetylsalicylic acid and choline magnesium trisalicylate on human gastric and duodenal mucosa.

PubMed

Kilander, A; Dotevall, G

1983-02-01

A new salicylate product, choline magnesium trisalicylate (Trilisate tablets), and acetylsalicylic acid were compared for their local effects in equipotent doses on the gastroduodenal mucosa in a randomized, double-blind, cross-over study, using 10 healthy volunteers. After five-day periods of administration, gastroduodenoscopy was performed and photographs were obtained. All subjects given acetylsalicylic acid developed multiple mucosal lesions, but in only four subjects given choline magnesium trisalicylate were slight mucosal changes noted. Mean serum salicylate levels were similar in the two groups. Our data suggest that the risk of developing mucosal lesions is much less during treatment with choline magnesium trisalicylate than with acetylsalicylic acid.

Fasting Reduces the Incidence of Delayed-Type Vomiting Associated with Doxorubicin Treatment in Dogs with Lymphoma.

PubMed

Withers, Sita S; Kass, Philip H; Rodriguez, Carlos O; Skorupski, Katherine A; O'Brien, Danielle; Guerrero, Teri A; Sein, Kristen D; Rebhun, Robert B

2014-05-12

Fasting reduces gastrointestinal cellular proliferation rates through G 1 cycle blockade and can promote cellular protection of normal but not cancer cells through altered cell signaling including down-regulation of insulin-like growth factor 1 (IGF-1). Consequently, the purpose of this study was to determine the effects of fasting on delayed-type chemotherapy-induced nausea and vomiting in dogs receiving doxorubicin. This prospective randomized crossover study involved intended administration of two doses of doxorubicin. Cancer-bearing dogs were randomized to be fasted for 24 hours beginning at 6 P.M. the night before the first or second doxorubicin administration, and all treatments were administered within an hour before or after 12 P.M. Dogs were fed normally before the alternate dose. Circulating IGF-1 concentrations were determined from serum samples obtained immediately before each doxorubicin treatment. Data from 35 doses were available from 20 dogs enrolled. Dogs that were fasted exhibited a significantly lower incidence of vomiting, when compared to fed dogs (10% compared to 67%, P = .020). Furthermore, among the 15 dogs that completed crossover dosing, vomiting was abrogated in four of five dogs that experienced doxorubicin-induced vomiting when fed normally (P = .050). No differences in other gastrointestinal, constitutional, or bone marrow toxicities or serum IGF-1 levels were observed. Copyright © 2014 Elsevier Inc. All rights reserved.

Transcranial Direct Current Stimulation Improves Audioverbal Memory in Stroke Patients

PubMed Central

Kazuta, Toshinari; Takeda, Kotaro; Osu, Rieko; Tanaka, Satoshi; Oishi, Ayako; Kondo, Kunitsugu; Liu, Meigen

2017-01-01

Objective The aim of this study was to investigate whether anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance in stroke patients. Design Twelve stroke patients with audioverbal memory impairment participated in a single-masked, crossover, and sham-controlled experiment. The anodal or sham transcranial direct current stimulation was applied during the Rey Auditory Verbal Learning Test, which evaluates the ability to recall a list of 15 heard words over five trials. The number of correctly recalled words was compared between the anodal and sham conditions and the influence of transcranial direct current stimulation on serial position effect of the 15 words was also examined. Results The increase in the number of correctly recalled words from the first to the fifth trial was significantly greater in the anodal condition than in the sham condition (P < 0.01). There was a significant difference (P < 0.01) between the anodal and sham conditions in the number of correctly recalled words within the first five words (primacy region) over the second to fifth trial trials, but not in the middle (next five words) or recency (last five words) regions. Conclusions Anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance and induced the primacy effect in stroke patients. PMID:28085735

Transcranial Direct Current Stimulation Improves Audioverbal Memory in Stroke Patients.

PubMed

Kazuta, Toshinari; Takeda, Kotaro; Osu, Rieko; Tanaka, Satoshi; Oishi, Ayako; Kondo, Kunitsugu; Liu, Meigen

2017-08-01

The aim of this study was to investigate whether anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance in stroke patients. Twelve stroke patients with audioverbal memory impairment participated in a single-masked, crossover, and sham-controlled experiment. The anodal or sham transcranial direct current stimulation was applied during the Rey Auditory Verbal Learning Test, which evaluates the ability to recall a list of 15 heard words over five trials. The number of correctly recalled words was compared between the anodal and sham conditions and the influence of transcranial direct current stimulation on serial position effect of the 15 words was also examined. The increase in the number of correctly recalled words from the first to the fifth trial was significantly greater in the anodal condition than in the sham condition (P < 0.01). There was a significant difference (P < 0.01) between the anodal and sham conditions in the number of correctly recalled words within the first five words (primacy region) over the second to fifth trial trials, but not in the middle (next five words) or recency (last five words) regions. Anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance and induced the primacy effect in stroke patients.

Nifedipine--a calcium channel blocker--in asthmatic patients. Interaction with terbutaline.

PubMed

Svedmyr, K; Löfdahl, C G; Svedmyr, N

1984-01-01

Seven asthmatic patients were studied in a single-blind randomized, crossover study after oral administration of 20 mg nifedipine or placebo. Four increasing doses of i.v. terbutaline were then given with 30 min interval. The study was concluded with inhalation of five terbutaline puffs. FEV1 measurements 30 min after intake of nifedipine did not show any difference compared to placebo. During the terbutaline treatment, however, there was a more pronounced bronchodilation after nifedipine than after placebo (P less than 0.05). Terbutaline-induced skeletal muscle tremor was similar after nifedipine and placebo pretreatments. After nifedipine intake there was a decrease of diastolic blood pressure and a reflexogenic tachycardia. Thus, this study showed a small potentiation of the beta 2-adrenoceptor mediated bronchodilation, which is of importance when treating patients with simultaneous asthma and hypertension or angina pectoris.

Cathodal transcranial direct current stimulation in children with dystonia: a sham-controlled study.

PubMed

Young, Scott J; Bertucco, Matteo; Sanger, Terence D

2014-02-01

Increased motor cortex excitability is a common finding in dystonia, and transcranial direct current stimulation can reduce motor cortex excitability. In an earlier study, we found that cathodal direct-current stimulation decreased motor overflow for some children with dystonia. To investigate this observation further, we performed a sham-controlled, double-blind, crossover study of 14 children with dystonia. We found a significant reduction in overflow following real stimulation, when participants performed the experimental task with the hand contralateral to the cathode. While these results suggest that cathodal stimulation may help some children to reduce involuntary overflow, the size of the effect is small. Further research will need to investigate ways to increase the magnitude of the effect of cathodal transcranial direct current stimulation.

Deanol acetamidobenzoate treatment in choreiform movement disorders.

PubMed

Tarsy, D; Bralower, M

1977-12-01

Deanol acetamidobenzoate was administered in double-blind, crossover fashion with placebo to five patients with tardive dyskinesia, three patients with Huntington's chorea, and one patient with posthemiplegic chorea. No significant effect on dyskinesia was observed. Preliminary administration of physostigmine salicylate to patients with tardive dyskinesia had a variable effect, while benztropine mesylate produced no change. Since the status of deanol as an effective precursor of acetylcholine is uncertain, further trials with putative cholinergic agents remain warranted in choreiform syndromes.

Local and sex-specific biases in crossover vs. noncrossover outcomes at meiotic recombination hot spots in mice

PubMed Central

de Boer, Esther; Jasin, Maria; Keeney, Scott

2015-01-01

Meiotic recombination initiated by programmed double-strand breaks (DSBs) yields two types of interhomolog recombination products, crossovers and noncrossovers, but what determines whether a DSB will yield a crossover or noncrossover is not understood. In this study, we analyzed the influence of sex and chromosomal location on mammalian recombination outcomes by constructing fine-scale recombination maps in both males and females at two mouse hot spots located in different regions of the same chromosome. These include the most comprehensive maps of recombination hot spots in oocytes to date. One hot spot, located centrally on chromosome 1, behaved similarly in male and female meiosis: Crossovers and noncrossovers formed at comparable levels and ratios in both sexes. In contrast, at a distal hot spot, crossovers were recovered only in males even though noncrossovers were obtained at similar frequencies in both sexes. These findings reveal an example of extreme sex-specific bias in recombination outcome. We further found that estimates of relative DSB levels are surprisingly poor predictors of relative crossover frequencies between hot spots in males. Our results demonstrate that the outcome of mammalian meiotic recombination can be biased, that this bias can vary depending on location and cellular context, and that DSB frequency is not the only determinant of crossover frequency. PMID:26251527

Demonstration of an anti-hyperalgesic effect of a novel pan-Trk inhibitor PF-06273340 in a battery of human evoked pain models.

PubMed

Loudon, Peter; Siebenga, Pieter; Gorman, Donal; Gore, Katrina; Dua, Pinky; van Amerongen, Guido; Hay, Justin L; Groeneveld, Geert Jan; Butt, Richard P

2018-02-01

Inhibitors of nerve growth factor (NGF) reduce pain in several chronic pain indications. NGF signals through tyrosine kinase receptors of the tropomyosin-related kinase (Trk) family and the unrelated p75 receptor. PF-06273340 is a small molecule inhibitor of Trks A, B and C that reduces pain in nonclinical models, and the present study aimed to investigate the pharmacodynamics of this first-in-class molecule in humans. A randomized, double-blind, single-dose, placebo- and active-controlled five-period crossover study was conducted in healthy human subjects (NCT02260947). Subjects received five treatments: PF-06273340 50 mg, PF-06273340 400 mg, pregabalin 300 mg, ibuprofen 600 mg and placebo. The five primary endpoints were the pain detection threshold for the thermal pain tests and the pain tolerance threshold for the cold pressor, electrical stair and pressure pain tests. The trial had predefined decision rules based on 95% confidence that the PF-06273340 effect was better than that of placebo. Twenty subjects entered the study, with 18 completing all five periods. The high dose of PF-06273340 met the decision rules on the ultraviolet (UV) B skin thermal pain endpoint [least squares (LS) mean vs. placebo: 1.13, 95% confidence interval: 0.64-1.61], but not on the other four primary endpoints. The low dose did not meet the decision criteria for any of the five primary endpoints. Pregabalin (cold pressor and electrical stair tests) and ibuprofen (UVB thermal pain) showed significant analgesic effects on expected endpoints. The study demonstrated, for the first time, the translation of nonclinical effects into man in an inflammatory pain analgesic pharmacodynamic endpoint using a pan-Trk inhibitor. © 2017 The British Pharmacological Society.

Ecological momentary assessment for chronic pain in fibromyalgia using a smartphone: a randomized crossover study.

PubMed

Garcia-Palacios, A; Herrero, R; Belmonte, M A; Castilla, D; Guixeres, J; Molinari, G; Baños, R M

2014-07-01

Daily diaries are a useful way of measuring fluctuations in pain-related symptoms. However, traditional diaries do not assure the gathering of data in real time, not solving the problem of retrospective assessment. Ecological momentary assessment (EMA) by means of electronic diaries helps to improve repeated assessment. However, it is important to test its feasibility in specific populations in order to reach a wider number of people who could benefit from these procedures. The present study compares the compliance and acceptability of an electronic diary running on a smartphone using a crossover design for a sample with a specific pain condition, fibromyalgia and low familiarity with technology. Forty-seven participants were randomly assigned to one of two conditions: (1) paper diary - smartphone diary and (2) smartphone diary - paper diary, using each assessment method for 1 week. The findings of this study showed that the smartphone diary made it possible to gather more accurate and complete ratings. Besides, this method was well accepted by a sample of patients with fibromyalgia referred by a public hospital, with an important proportion of participants with low level of education and low familiarity with technology. The findings of this study support the use of smartphones for EMA even in specific populations with a specific pain condition, fibromyalgia and with low familiarity with technology. These methods could help clinicians and researchers to gather more accurate ratings of relevant pain-related variables even in populations with low familiarity with technology.

A Randomized, Two-Way Crossover Study to Evaluate the Pharmacokinetics of Caffeine Delivered Using Caffeinated Chewing Gum Versus a Marketed Caffeinated Beverage in Healthy Adult Volunteers.

PubMed

Sadek, Paul; Pan, Xiao; Shepherd, Phil; Malandain, Elise; Carney, John; Coleman, Hugh

2017-12-01

Background: This study was conducted to compare the pharmacokinetics of caffeine delivered using caffeinated chewing gum to that delivered using a marketed caffeinated beverage (instant coffee) in 16 healthy adult volunteers. Materials and Methods: This was a controlled open-label, randomized, two-period crossover study. Caffeinated chewing gum and a serving of instant coffee, each containing ∼50 mg caffeine, were administered with blood samples collected before and up to 24 hours after administration starts. Plasma caffeine levels were analyzed using validated liquid chromatography coupled with tandem mass spectrometry methodology. Results: There were no statistical differences between the two caffeine products in t max ( p  = 0.3308) and k a ( p  = 0.3894). Although formulated at ∼50 mg caffeine each, mean dose released from chewing gum was ∼18% less than beverage. Dose-normalized area under the concentration-time curve (AUC) 0-t , AUC 0-∞ , and C max was similar between products. Although the criteria were not set a priori and the study was not powered for concluding bioequivalence, the 90% confidence intervals fell within the bioequivalence limit of 80% to 125%. Conclusions: Existing scientific literature on caffeine, based mostly on data from caffeinated beverages, can be leveraged to support the safety of caffeine delivered by chewing gum and current maximum safe caffeine dose advice should be applicable irrespective of delivery method.

Immediate acid-suppressing effects of ranitidine hydrochloride and rabeprazole sodium following initial administration and reintroduction: A randomized, cross-over study using wireless pH monitoring capsules.

PubMed

Ono, Shouko; Kato, Mototsugu; Ono, Yuji; Imai, Aki; Yoshida, Takeshi; Shimizu, Yuichi; Asaka, Masahiro

2009-04-01

Histamine 2 receptor antagonists and proton-pump inhibitors, drugs that are widely used for the treatment of acid-related diseases, have different clinical characteristics. The objective of this study was to compare the acid-suppressing effects of ranitidine hydrochloride and those of rabeprazole sodium at the first administration and re-administration after withdrawal. The study was designed as an open-label, randomized, two-way cross-over trial. Seven Helicobacter pylori-negative healthy volunteers were enrolled in this study. Ranitidine hydrochloride (300 mg/day) or rabeprazole sodium (20 mg/day) was administered from days 1 to 7 and from days 11 to 13. The percentage of time with gastric pH < 4 and the median gastric pH were evaluated for 15 consecutive days by a Bravo capsule fixed to the stomach. On day 1, there was no significant difference between the acid-suppressing effects of the two drugs (ranitidine vs rabeprazole: not significant). Although rabeprazole sodium maintained a potent and stable effect from days 2 to 7 (ranitidine vs rabeprazole: P < 0.05), the effect of ranitidine hydrochloride was attenuated after day 4. In addition, the effect of ranitidine hydrochloride at re-administration was attenuated (days 11, 12, and 13 vs pre-administration: not significant). In view of our observations, we expect symptoms associated with gastric acidity to be more adequately controlled with rabeprazole sodium in the short term when compared to ranitidine hydrochloride.

A Case Study of Controlling Crossover in a Selection Hyper-heuristic Framework Using the Multidimensional Knapsack Problem.

PubMed

Drake, John H; Özcan, Ender; Burke, Edmund K

2016-01-01

Hyper-heuristics are high-level methodologies for solving complex problems that operate on a search space of heuristics. In a selection hyper-heuristic framework, a heuristic is chosen from an existing set of low-level heuristics and applied to the current solution to produce a new solution at each point in the search. The use of crossover low-level heuristics is possible in an increasing number of general-purpose hyper-heuristic tools such as HyFlex and Hyperion. However, little work has been undertaken to assess how best to utilise it. Since a single-point search hyper-heuristic operates on a single candidate solution, and two candidate solutions are required for crossover, a mechanism is required to control the choice of the other solution. The frameworks we propose maintain a list of potential solutions for use in crossover. We investigate the use of such lists at two conceptual levels. First, crossover is controlled at the hyper-heuristic level where no problem-specific information is required. Second, it is controlled at the problem domain level where problem-specific information is used to produce good-quality solutions to use in crossover. A number of selection hyper-heuristics are compared using these frameworks over three benchmark libraries with varying properties for an NP-hard optimisation problem: the multidimensional 0-1 knapsack problem. It is shown that allowing crossover to be managed at the domain level outperforms managing crossover at the hyper-heuristic level in this problem domain.

A Crossover Study of Risperidone in Children, Adolescents and Adults with Mental Retardation

ERIC Educational Resources Information Center

Hellings, Jessica A.; Zarcone, Jennifer R.; Reese, R. Matthew; Valdovinos, Maria G.; Marquis, Janet G.; Fleming, Kandace K.; Schroeder, Stephen R.

2006-01-01

Risperidone has shown safety and efficacy for aggressive and destructive behaviors in short-term studies. This longer-duration study includes a broad sample. Forty subjects, aged 8-56 years (mean=22), all with mental retardation and 36 with autism spectrum disorders participated in this 22-week crossover study, with 24 weeks of open maintenance…

Predictive Factors for Patients Undergoing ASD Device Occlusion Who "Crossover" to Surgery.

PubMed

Mulukutla, Venkatachalam; Qureshi, Athar M; Pignatelli, Ricardo; Ing, Frank F

2018-03-01

The aim of this study was to define characteristics of those patients who are referred for device closure of an Atrial septal defect (ASD), but identified to "crossover" surgery. All patients who underwent surgical and device (Amplatzer or Helex occluder) closures of secundum ASDs from 2001 to 2010 were reviewed and organized into three groups: surgical closure, device closure, and "crossover" group. 369 patients underwent ASD closure (265 device, 104 surgical). 42 of the 265 patients referred for device closure "crossed over" to the surgical group at various stages of the catheterization procedure. The device group had defect size measuring 14.2 mm (mean) and an ASD index (Defect Size (mm)/BSA) of 14.0 compared to the corresponding values in the surgical group (20.1 mm, ASD index 25.9) (P < 0.001) and in the "crossover" group (20.7 mm, 22.6 ASD index) (P < 0.001). 79 patients in the device group had a deficient rim, and 86% were located in the retroaortic region. 33 patients in the "crossover" group had deficient rims with 70% deficiency in the posterior/inferior rim. The device group with deficient rims had an ASD index of 14.7 compared with the crossover group ASD index of 23.8 (P < 0.001). Comparing the device and "crossover" groups, an ASD index greater than 23.7 had a 90% specificity in "crossing over" to surgery. The crossover and surgical groups had statistically larger ASD defect size indexes compared with the device group. Deficient rim in the posterior/inferior rim is associated with a large ASD size index which is a predictive factor for crossing over to surgery. Catheterization did not negatively impact surgical results in the "crossover" group.

A Randomized Crossover Trial on Acute Stress-Related Physiological Responses to Mountain Hiking

PubMed Central

Grafetstätter, Carina; Hartl, Arnulf; Kopp, Martin

2017-01-01

Green exercise, defined as physical activity in natural environments, might have positive effects on stress-related physiological measures. Little is known about the acute effects of green exercise bouts lasting longer than 60 min. Therefore, the aim of the present study was to analyze the acute effects of a three-hour green exercise intervention (mountain hiking) on stress-related physiological responses. Using a randomized crossover design, 42 healthy participants were exposed to three different conditions in a field-based experiment: outdoor mountain hiking, indoor treadmill walking, and sedentary control condition (three hours each). At baseline and at follow-up (five minutes after the condition), stress-related physiological responses (salivary cortisol, blood pressure, and heart rate variability) were measured. Salivary cortisol decreased in all conditions, but showed a larger decrease after both mountain hiking and treadmill walking compared to the sedentary control situation (partial η2 = 0.10). No differences were found between mountain hiking and treadmill walking in salivary cortisol. In heart rate variability and blood pressure, changes from baseline to follow-up did not significantly differ between the three conditions. The results indicate that three hours of hiking indoors or outdoors elicits positive effects on salivary cortisol concentration. Environmental effects seem to play a minor role in salivary cortisol, blood pressure, and heart rate variability. PMID:28800067

Phase I study evaluating the safety, tolerability and pharmacokinetics of a novel oral dissolvable film containing dexamethasone versus Fortecortin dexamethasone tablets.

PubMed

Diamant, Zuzana; Samuelsson Palmgren, Gabriella; Westrin, Bengt; Bjermer, Leif

2017-01-01

Introduction : Systemic corticosteroids are anti-inflammatory agents with dexamethasone among the most potent in the class. Within (respiratory) allergy, systemic corticosteroids are usually applied in medical emergencies. In these situations, patients may experience physical or logistic problems taking tablets. To fulfil a practical unmet need for outpatients, Dexa ODF, an oral dissolvable film containing dexamethasone, was developed. Objectives : We compared the safety, tolerability and pharmacokinetics (PK) of Dexa ODF with Fortecortin tablets in healthy subjects. Methods : Thirty subjects participated in this open label, two-way, cross-over study, consisting of two treatment visits separated by 5-10 days. On both treatment visits, subjects randomly received one single dose of Dexa ODF (one strip; 8 mg dexamethasone) or one single dose of Fortecortin (two 4 mg tablets). Safety evaluations and blood sampling for PK were conducted until 48 h post-dose and bioequivalence analysis was performed on AUC(0-t), AUC(0-∞) and Cmax. Results : All subjects were dosed. Forty-five adverse events (AEs) were reported by 17 subjects and approximately 50% were deemed 'possibly treatment related' (14 on Dexa ODF; 12 on Fortecortin) with no significant difference between treatments. For all three bioequivalence parameters the 90% CIs were within the acceptance limits of bioequivalence (0.8;1.25). Conclusion : We demonstrated good tolerability and bioequivalence of Dexa ODF (8 mg dexamethasone) compared to Fortecortin tablets (2 × 4 mg dexamethasone). Dexa ODF is currently under development as an innovative treatment for use within respiratory and allergic conditions, including emergencies.

Metabolic and anti-inflammatory benefits of eccentric endurance exercise - a pilot study.

PubMed

Drexel, H; Saely, C H; Langer, P; Loruenser, G; Marte, T; Risch, L; Hoefle, G; Aczel, S

2008-04-01

Eccentric endurance exercise (e.g. hiking downwards) is less strenuous than concentric exercise (e.g. hiking upwards) but its potential to reduce cardiovascular risk is unknown. We randomly allocated 45 healthy sedentary individuals (16 men and 29 women, mean age 48 years) to one of two groups, one beginning with two months of hiking upwards, the other with two months of hiking downwards the same route, with a crossover for a further two months. For the opposite way, a cable car was used where compliance was recorded electronically. The difference in altitude was 540 metres; the distance was covered three to five times a week. Fasting and postprandial metabolic profiles were obtained at baseline and after the two month periods of eccentric and concentric exercise, respectively. Forty-two of the 45 participants completed the study; the compliance rate was therefore 93%. Compared with baseline, eccentric exercise lowered total cholesterol (by 4.1%; P = 0.026), low-density lipoprotein (LDL) cholesterol (by 8.4%, P = 0.001), Apolipoprotein B/Apolipoprotein A1 ratio (by 10.9%, P < 0.001), homeostasis model assessment of insulin resistance scores (by 26.2%, P = 0.017) and C-reactive protein (by 30.0%; P = 0.007); the magnitude of these changes was comparable to that of concentric exercise. Eccentric exercise improved glucose tolerance (by 6.2%, P = 0.023), whereas concentric exercise improved triglyceride tolerance (by 14.9%, P = 0.022). Eccentric endurance exercise is a promising new exercise modality with favourable metabolic and anti-inflammatory effects and is well applicable to sedentary individuals.

Effects of desloratadine and alcohol coadministration on psychomotor performance.

PubMed

Scharf, Martin; Berkowitz, David

2007-02-01

This study was set up to evaluate the effects of desloratadine 7.5 mg daily, with and without alcohol, on sedation and psychomotor performance. In a double-blind, placebo-controlled, four-way crossover trial, 25 adult patients were randomized to desloratadine 7.5 mg, desloratadine 7.5 mg plus alcohol, placebo, or placebo plus alcohol. Alcohol was weight adjusted to an average blood alcohol concentration of 0.1%. Assessments included the modified Romberg test, Stanford Sleepiness Scale, Digit Symbol Substitution Test, Serial Add Subtract Reaction Time Test, and the Psychomotor Vigilance Test. The primary variable was the mean score of each of the five tests averaged over the treatment period, expressed as the mean percent change from baseline. Across these assessments, differences between desloratadine alone or with alcohol versus placebo alone or without alcohol, were not significant, whereas most differences between desloratadine and placebo alone versus desloratadine and placebo with alcohol were significant (p < 0.01). Thus, with or without alcohol, desloratadine 7.5 mg does not increase sedation or impair psychomotor performance. Most adverse events (AEs) were mild-to-moderate in severity, with the most frequently reported individual AEs being headache, fatigue, nausea, vomiting, and dry mouth. The study does have potential limitations. The measures used are restricted to a particular profile of the known effects of alcohol only, and the relatively high doses of alcohol used alone demonstrate effects on psychomotor function and attention. A single dose of desloratadine does not potentiate alcohol-mediated CNS impairment. Desloratadine alone or in combination with alcohol was safe and well tolerated.

Cardiovascular benefits from ancient grain bread consumption: findings from a double-blinded randomized crossover intervention trial.

PubMed

Sereni, Alice; Cesari, Francesca; Gori, Anna Maria; Maggini, Niccolò; Marcucci, Rossella; Casini, Alessandro; Sofi, Francesco

2017-02-01

Ancient grain varieties have been shown to have some beneficial effects on health. Forty-five clinically healthy subjects were included in a randomized, double-blinded crossover trial aimed at evaluating the effect of a replacement diet with bread derived from ancient grain varieties versus modern grain variety on cardiovascular risk profile. After 8 weeks of intervention, consumption of bread obtained by the ancient varieties showed a significant amelioration of various cardiovascular parameters. Indeed, the ancient varieties were shown to result in a significant reduction of total cholesterol, low-density lipoprotein (LDL)-cholesterol and blood glucose, whereas no significant differences during the phase with the modern variety were reported. Moreover, a significant increase in circulating endothelial progenitor cells were reported after the consumption of products made from the ancient "Verna" variety. The present results suggest that a dietary consumption of bread obtained from ancient grain varieties was effective in reducing cardiovascular risk factors.

SV40 host-substituted variants: a new look at the monkey DNA inserts and recombinant junctions.

PubMed

Singer, Maxine; Winocour, Ernest

2011-04-10

The available monkey genomic data banks were examined in order to determine the chromosomal locations of the host DNA inserts in 8 host-substituted SV40 variant DNAs. Five of the 8 variants contained more than one linked monkey DNA insert per tandem repeat unit and in all cases but one, the 19 monkey DNA inserts in the 8 variants mapped to different locations in the monkey genome. The 50 parental DNAs (32 monkey and 18 SV40 DNA segments) which spanned the crossover and flanking regions that participated in monkey/monkey and monkey/SV40 recombinations were characterized by substantial levels of microhomology of up to 8 nucleotides in length; the parental DNAs also exhibited direct and inverted repeats at or adjacent to the crossover sequences. We discuss how the host-substituted SV40 variants arose and the nature of the recombination mechanisms involved. Copyright © 2011 Elsevier Inc. All rights reserved.

A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the Pharmacokinetic and Pharmacodynamic Interaction Between Nebivolol and Valsartan in Healthy Volunteers at Steady State

PubMed Central

Chen, Chun Lin; Desai-Krieger, Daksha; Ortiz, Stephan; Kerolous, Majid; Wright, Harold M.; Ghahramani, Parviz

2015-01-01

Combining different classes of antihypertensives is more effective for reducing blood pressure (BP) than increasing the dose of monotherapies. The aims of this phase I study were to investigate pharmacokinetic and pharmacodynamic interactions between nebivolol, a vasodilatory β1-selective blocker, and valsartan, an angiotensin II receptor blocker, and to assess safety and tolerability of the combination. This was a single-center, randomized, open-label, multiple-dose, 3-way crossover trial in 30 healthy adults aged 18–45 years. Participants were randomized into 1 of 6 treatment sequences (1:1:1:1:1:1) consisting of three 7-day treatment periods followed by a 7-day washout. Once-daily oral treatments comprised nebivolol (20 mg), valsartan (320 mg), and nebivolol–valsartan combination (20/320 mg). Outcomes included AUC0-τ,ss, Cmax,ss, Tmax,ss, changes in BP, pulse rate, plasma angiotensin II, plasma renin activity, 24-hour urinary aldosterone, and adverse events. Steady-state pharmacokinetic interactions were observed but deemed not clinically significant. Systolic and diastolic BP reduction was significantly greater with nebivolol–valsartan combination than with either monotherapy. The mean pulse rate associated with nebivolol and nebivolol–valsartan treatments was consistently lower than that associated with valsartan monotherapy. A sharp increase in mean day 7 plasma renin activity and plasma angiotensin II that occurred in valsartan-treated participants was significantly attenuated with concomitant nebivolol administration. Mean 24-hour urine aldosterone at day 7 was substantially decreased after combined treatment, as compared with either monotherapy. All treatments were safe and well tolerated. In conclusion, nebivolol and valsartan coadministration led to greater reductions in BP compared with either monotherapy; nebivolol and valsartan lower BP through complementary mechanisms. PMID:25853236

A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the Pharmacokinetic and Pharmacodynamic Interaction Between Nebivolol and Valsartan in Healthy Volunteers at Steady State.

PubMed

Chen, Chun Lin; Desai-Krieger, Daksha; Ortiz, Stephan; Kerolous, Majid; Wright, Harold M; Ghahramani, Parviz

2015-01-01

Combining different classes of antihypertensives is more effective for reducing blood pressure (BP) than increasing the dose of monotherapies. The aims of this phase I study were to investigate pharmacokinetic and pharmacodynamic interactions between nebivolol, a vasodilatory β1-selective blocker, and valsartan, an angiotensin II receptor blocker, and to assess safety and tolerability of the combination. This was a single-center, randomized, open-label, multiple-dose, 3-way crossover trial in 30 healthy adults aged 18-45 years. Participants were randomized into 1 of 6 treatment sequences (1:1:1:1:1:1) consisting of three 7-day treatment periods followed by a 7-day washout. Once-daily oral treatments comprised nebivolol (20 mg), valsartan (320 mg), and nebivolol-valsartan combination (20/320 mg). Outcomes included AUC0-τ,ss, Cmax,ss, Tmax,ss, changes in BP, pulse rate, plasma angiotensin II, plasma renin activity, 24-hour urinary aldosterone, and adverse events. Steady-state pharmacokinetic interactions were observed but deemed not clinically significant. Systolic and diastolic BP reduction was significantly greater with nebivolol-valsartan combination than with either monotherapy. The mean pulse rate associated with nebivolol and nebivolol-valsartan treatments was consistently lower than that associated with valsartan monotherapy. A sharp increase in mean day 7 plasma renin activity and plasma angiotensin II that occurred in valsartan-treated participants was significantly attenuated with concomitant nebivolol administration. Mean 24-hour urine aldosterone at day 7 was substantially decreased after combined treatment, as compared with either monotherapy. All treatments were safe and well tolerated. In conclusion, nebivolol and valsartan coadministration led to greater reductions in BP compared with either monotherapy; nebivolol and valsartan lower BP through complementary mechanisms.

Nonlinear Rheology in a Model Biological Tissue

NASA Astrophysics Data System (ADS)

Matoz-Fernandez, D. A.; Agoritsas, Elisabeth; Barrat, Jean-Louis; Bertin, Eric; Martens, Kirsten

2017-04-01

The rheological response of dense active matter is a topic of fundamental importance for many processes in nature such as the mechanics of biological tissues. One prominent way to probe mechanical properties of tissues is to study their response to externally applied forces. Using a particle-based model featuring random apoptosis and environment-dependent division rates, we evidence a crossover from linear flow to a shear-thinning regime with an increasing shear rate. To rationalize this nonlinear flow we derive a theoretical mean-field scenario that accounts for the interplay of mechanical and active noise in local stresses. These noises are, respectively, generated by the elastic response of the cell matrix to cell rearrangements and by the internal activity.

Studies of the structure of massive hybrid stars within a modified NJL model

NASA Astrophysics Data System (ADS)

Li, Cheng-Ming; Zhang, Jin-Li; Yan, Yan; Huang, Yong-Feng; Zong, Hong-Shi

2018-05-01

In this paper, we use the equation of state based on a modification of the 2 +1 flavors Nambu-Jona-Lasinio (NJL) model to study the quark matter of hybrid stars. For comparison, we utilize five EOSs of the relativistic mean-field (RMF) model to describe the hadronic phase. With the three-window crossover interpolation approach, we try to construct relatively soft hybrid EOSs but find the maximum masses of hybrid stars do not differ much. The results are quite close to the 2 solar mass, which is consistent with the mass constraint of PSR J 0348 +0432 . Furthermore, it is noteworthy that the heaviest stable stars have central densities higher than that of the deconfinement transition, suggesting a pure quark core in the hybrid star.

kinesiotaping reduces pain and modulates sensory function in patients with focal dystonia: a randomized crossover pilot study.

PubMed

Pelosin, Elisa; Avanzino, Laura; Marchese, Roberta; Stramesi, Paola; Bilanci, Martina; Trompetto, Carlo; Abbruzzese, Giovanni

2013-10-01

Pain is one of the most common and disabling "nonmotor" symptoms in patients with dystonia. No recent study evaluated the pharmacological or physical therapy approaches to specifically treat dystonic pain symptoms. To evaluate the effectiveness of KinesioTaping in patients with cervical dystonia (CD) and focal hand dystonia (FHD) on self-reported pain (primary objective) and on sensory functions (secondary objective). Twenty-five dystonic patients (14 with CD and 11 FHD) entered a randomized crossover pilot study. The patients were randomized to 14-day treatment with KinesioTaping or ShamTaping over neck (in CD) or forearm muscles (in FHD), and after a 30-day washout period, they received the other treatment. The were 3 visual analog scales (VASs) for usual pain, worst pain, and pain relief. Disease severity changes were evaluated by means of the Toronto Western Spasmodic Torticollis Rating Scale (CD) and the Writer's Cramp Rating Scale (FHD). Furthermore, to investigate possible KinesioTaping-induced effects on sensory functions, we evaluated the somatosensory temporal discrimination threshold. Treatment with KinesioTape induced a decrease in the subjective sensation of pain and a modification in the ability of sensory discrimination, whereas ShamTaping had no effect. A significant, positive correlation was found in both groups of patients between the improvement in the subjective sensation of pain and the reduction of somatosensory temporal discrimination threshold values induced by KinesioTaping. These preliminary results suggest that KinesioTaping may be useful in treating pain in patients with dystonia.

Short-term effects of ozone air pollution on hospital admissions for myocardial infarction: A time-stratified case-crossover study in Taipei.

PubMed

Chiu, Hui-Fen; Weng, Yi-Hao; Chiu, Ya-Wen; Yang, Chun-Yuh

2017-01-01

This study was undertaken to determine whether there was a correlation between ambient ozone (O 3 ) levels and number of hospital admissions for myocardial infarction (MI) in Taipei, Taiwan. Hospital admissions for MI and ambient air pollution data for Taipei were obtained for the period from 2006 to 2010. The relative risk (RR) of hospital admissions for MI was estimated using a time-stratified case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased RR for a number of MI admissions was significantly associated with higher O 3 levels both on warm days (>23°C) and on cool days (<23°C). This observation was accompanied by an interquartile range elevation correlated with a 7% (95% CI = 2%-12%) and 17% (95% CI = 11%-25%) rise in number of MI admissions, respectively. In the two-pollutant models, no significant associations between ambient O 3 concentrations and number of MI admissions were observed on warm days. However, on cool days, correlation between ambient O 3 after inclusion of each of the other five pollutants, particulate matter (PM 10 or PM 2.5 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ) or carbon monoxide (CO), and number of MI admissions remained significant. This study provides evidence that higher levels of ambient O 3 increase the RR of number of hospital admissions for MI.

Risk perception, experience, and objective risk: a cross-national study with European emergency survivors.

PubMed

Knuth, Daniela; Kehl, Doris; Hulse, Lynn; Schmidt, Silke

2014-07-01

Understanding public risk perceptions and their underlying processes is important in order to learn more about the way people interpret and respond to hazardous emergency events. Direct experience with an involuntary hazard has been found to heighten the perceived risk of experiencing the same hazard and its consequences in the future, but it remains unclear if cross-over effects are possible (i.e., experience with one hazard influencing perceived risk for other hazards also). Furthermore, the impact of objective risk and country of residence on perceived risk is not well understood. As part of the BeSeCu (Behavior, Security, and Culture) Project, a sample of 1,045 survivors of emergencies from seven European countries (i.e., Germany, the Czech Republic, Poland, Sweden, Spain, Turkey, and Italy) was drawn. Results revealed heightened perceived risk for emergency events (i.e., domestic and public fires, earthquakes, floods, and terrorist attacks) when the event had been experienced previously plus some evidence of cross-over effects, although these effects were not so strong. The largest country differences in perceived risk were observed for earthquakes, but this effect was significantly reduced by taking into account the objective earthquake risk. For fires, floods, terrorist attacks, and traffic accidents, only small country differences in perceived risk were found. Further studies including a larger number of countries are welcomed. © 2013 Society for Risk Analysis.

Acute psychotropic effects of oral cannabis extract with a defined content of Delta9-tetrahydrocannabinol (THC) in healthy volunteers.

PubMed

Kaufmann, R M; Kraft, B; Frey, R; Winkler, D; Weiszenbichler, S; Bäcker, C; Kasper, S; Kress, H G

2010-01-01

The medical use of cannabinoids is limited mainly by their undesirable effects. With respect to acute psychotropic effects, the aim of this study is the comparison of an oral cannabis extract and low-dose diazepam in a cross-over experiment in drug-naïve healthy women. Sixteen healthy females participated in this randomized, double-blind, active comparator-controlled, single-dose, balanced 2-way cross-over study. Cannabis extract with standardised Delta (9)-tetrahydrocannabinol (THC) content (20 mg) or active placebo (5 mg diazepam) was administered orally. Subjects were assessed by self- and observer-rated visual analogue scales (VAS), the BRIEF PSYCHIATRIC RATING SCALE (BPRS) and three psychomotor tests up to 6 h after administration. VAS showed significantly elevated fatigue, drowsiness, dizziness, and "feeling high" after cannabis as compared to baseline and diazepam. BPRS scores were significantly higher after cannabis intake. Only in one psychomotor test a decrease of psychomotor activity after cannabis was evident. One subject in the cannabis condition experienced severe transient psychotic symptoms. Orally administered cannabis produced significant central depressant side-effects compared to diazepam, mostly subjective effects (VAS) but marginal effects in psychomotor performance in 15 healthy females. Regarding the medical use of cannabis, a rigorous benefit-risk analysis and an exact psychiatric assessment before and during treatment are necessary. (c) Georg Thieme Verlag KG Stuttgart . New York.

Impact of post-meal and one-time daily exercise in patient with type 2 diabetes mellitus: a randomized crossover study.

PubMed

Pahra, Daizy; Sharma, Nitasha; Ghai, Sandhya; Hajela, Abhishek; Bhansali, Shobhit; Bhansali, Anil

2017-01-01

To evaluate the effectiveness of short-timed post-meal and one-time daily exercise on glycemic control in patients with T2DM. Sixty-four T2DM patients were randomised into crossover design. Group A (n = 32) underwent post-meal exercise (moderate-intensity brisk walking covering 1500-1600 steps for 15 min, starting 15 min after each meal) from d1 to d60 followed by one-time daily exercise (45 min pre-breakfast brisk walking at stretch covering 4500-4800 steps) from d61 to d120, while it was vice versa for the group B (n = 32). The five-point blood glucose profile was performed on d1, d30, d60, d90 and d120, and HbA1c on d1, d60 and d120. Fitness wrist band was used for step-counting to ensure the intensity of exercise and compliance to exercise protocol. Group A patients showed a significant improvement in five point blood glucose profile and HbA1c after performing post-meal exercise (p < 0.001), which was mitigated after switchover to one-time daily exercise (p < 0.001). While, group B patients showed improvement in glucose profile and HbA1c (p < 0.001) after performing post-meal exercise, as compared to one-time daily exercise. Further, on pooled analysis (post-meal versus one-time daily exercise group) the beneficial effect of post-meal exercise on glucose profile and HbA1c was consistent as compared to one time daily exercise and the significance persisted on comparison between the two groups. No hypoglycemic events were noted between the groups during the study period. Post-meal exercise is more effective than routine one-time daily exercise for glycemic control in T2DM patients.

The effect of five day dosing with THCV on THC-induced cognitive, psychological and physiological effects in healthy male human volunteers: A placebo-controlled, double-blind, crossover pilot trial.

PubMed

Englund, Amir; Atakan, Zerrin; Kralj, Aleksandra; Tunstall, Nigel; Murray, Robin; Morrison, Paul

2016-02-01

Cannabis is mostly grown under illegal and unregulated circumstances, which seems to favour a product increasingly high in its main cannabinoid ∆-9-tetrahydrocannabinol (THC). ∆-9-tetrahydrocannabivarin (THCV) is a relatively untested cannabinoid which is said to be a cannabinoid receptor neutral antagonist, and may inhibit the effects of THC. To explore the safety and tolerability of repeated THCV administration and its effects on symptoms normally induced by THC in a sample of healthy volunteers. Ten male cannabis users (<25 use occasions) were recruited for this within-subjects, placebo-controlled, double-blind, cross-over pilot study. 10mg oral pure THCV or placebo were administered daily for five days, followed by 1mg intravenous THC on the fifth day. THCV was well tolerated and subjectively indistinguishable from placebo. THC did not significantly increase psychotic symptoms, paranoia or impair short-term memory, while still producing significant intoxicating effects. Delayed verbal recall was impaired by THC and only occurred under placebo condition (Z=-2.201, p=0.028), suggesting a protective effect of THCV. THCV also inhibited THC-induced increased heart rate (Z=-2.193, p=0.028). Nine out of ten participants reported THC under THCV condition (compared to placebo) to be subjectively weaker or less intense (χ(2)=6.4, p=0.011). THCV in combination with THC significantly increased memory intrusions (Z=-2.155, p=0.031). In this first study of THC and THCV, THCV inhibited some of the well-known effects of THC, while potentiating others. These findings need to be interpreted with caution due to a small sample size and lack of THC-induced psychotomimetic and memory-impairing effect, probably owing to the choice of dose. © The Author(s) 2015.

Antibiotic rotation strategies to reduce antimicrobial resistance in Gram-negative bacteria in European intensive care units: study protocol for a cluster-randomized crossover controlled trial.

PubMed

van Duijn, Pleun J; Bonten, Marc J M

2014-07-10

Intensive care units (ICU) are epicenters for the emergence of antibiotic-resistant Gram-negative bacteria (ARGNB) because of high rates of antibiotic usage, rapid patient turnover, immunological susceptibility of acutely ill patients, and frequent contact between healthcare workers and patients, facilitating cross-transmission.Antibiotic stewardship programs are considered important to reduce antibiotic resistance, but the effectiveness of strategies such as, for instance, antibiotic rotation, have not been determined rigorously. Interpretation of available studies on antibiotic rotation is hampered by heterogeneity in implemented strategies and suboptimal study designs. In this cluster-randomized, crossover trial the effects of two antibiotic rotation strategies, antibiotic mixing and cycling, on the prevalence of ARGNB in ICUs are determined. Antibiotic mixing aims to create maximum antibiotic heterogeneity, and cycling aims to create maximum antibiotic homogeneity during consecutive periods. This is an open cluster-randomized crossover study of mixing and cycling of antibiotics in eight ICUs in five European countries. During cycling (9 months) third- or fourth-generation cephalosporins, piperacillin-tazobactam and carbapenems will be rotated during consecutive 6-week periods as the primary empiric treatment in patients suspected of infection caused by Gram-negative bacteria. During mixing (9 months), the same antibiotics will be rotated for each consecutive antibiotic course. Both intervention periods will be preceded by a baseline period of 4 months. ICUs will be randomized to consecutively implement either the mixing and then cycling strategy, or vice versa. The primary outcome is the ICU prevalence of ARGNB, determined through monthly point-prevalence screening of oropharynx and perineum. Secondary outcomes are rates of acquisition of ARGNB, bacteremia and appropriateness of therapy, length of stay in the ICU and ICU mortality. Results will be adjusted for intracluster correlation, and patient- and ICU-level variables of case-mix and infection-prevention measures using advanced regression modeling. This trial will determine the effects of antibiotic mixing and cycling on the unit-wide prevalence of ARGNB in ICUs. ClinicalTrials.gov NCT01293071 December 2010.

Evaluation of chlorhexidine 0.05% with the adjunct of fluoride 0.05% in the inhibition of plaque formation: a double blind, crossover, plaque regrowth study.

PubMed

De Siena, F; Del Fabbro, M; Corbella, S; Taschieri, S; Weinstein, R

2013-08-01

The aim of this study was to evaluate the effect of mouthrinses containing 0.05% chlorhexidine + 0.05% fluoride solution on early dental plaque regrowth. Thirty periodontally healthy subjects were included in the study. A crossover 4-day plaque regrowth protocol was adopted. The test product was initially used in 15 patients, while a placebo was administered to the other 15 patients. Then, after a washout period, each patient used the other product. No other oral hygiene manoeuvre was allowed. Full-mouth plaque and bleeding scores (FMPS and FMBS) were evaluated at baseline and after 4 days. All subjects completed the study. The mean age was 27 ± 8.4 years. Five patients were smokers with a mean daily consumption of 1 ± 2.5 cigarettes. FMPS at baseline was 8.0 ± 4.4 for control group and 7.9 ± 3.8 for test group, without significant difference. After the 4-day plaque regrowth the mean FMPS significantly increased to 31.9 ± 16.5 and 36.3 ± 16.1 for control and test group, respectively (no significant difference between the two groups). The test product was safe and well tolerated by subjects. The similar outcomes of the two experimental groups suggest that the two products have an equivalent effect on early dental plaque regrowth. Studies with longer follow-up are needed to clarify whether there is a beneficial long-term effect of daily rinses with the tested solution. © 2012 John Wiley & Sons A/S.

Coffee inhibition of CYP3A4 in vitro was not translated to a grapefruit-like pharmacokinetic interaction clinically.

PubMed

Dresser, George K; Urquhart, Brad L; Proniuk, Julianne; Tieu, Alvin; Freeman, David J; Arnold, John Malcolm; Bailey, David G

2017-10-01

Grapefruit can augment oral medication bioavailability through irreversible (mechanism-based) inhibition of intestinal CYP3A4. Supplementary data from our recent coffee-drug interaction clinical study showed some subjects had higher area under the plasma drug concentration - time curve (AUC) and plasma peak drug concentration (Cmax) of the CYP3A4 probe felodipine compared to aqueous control. It was hypothesized that coffee might interact like grapefruit in responsive individuals. Beans from six geographical locations were consistently brewed into coffee that was separated chromatographically to a methanolic fraction for in vitro inhibition testing of CYP3A4 metabolism of felodipine at 1% coffee strength. The effect of simultaneous incubation and 10-min preincubation with coffee fractions determined whether coffee had direct and mechanism-based inhibitory activity. A subsequent five-way randomized balanced controlled crossover clinical study evaluated the clinical pharmacokinetic interaction with single-dose felodipine. Grapefruit juice, water, or three of the in vitro tested coffees were ingested at 300 mL alone 1 h before and then with felodipine. In vitro, all six coffees decreased felodipine metabolism for both simultaneous and preincubation exposure compared to corresponding control. Five coffees demonstrated mechanism-based inhibition. Grapefruit increased felodipine AUC 0-8 (25 vs. 13 ng.h/mL, P < 0.001) and Cmax (5.8 vs. 2.7 ng/mL, P < 0.001) and decreased dehydrofelodipine/felodipine AUC 0-8 ratio (0.84 vs. 1.29, P < 0.001), while the three coffees caused no change in these parameters compared to water. Despite high in vitro potency of CYP3A4 inhibition, the coffees did not cause a clinical pharmacokinetic interaction possibly from insufficient amount of inhibitor(s) in coffee reaching intestinal CYP3A4 during the absorption phase of felodipine. The results of this study highlight the need for follow-up clinical testing when in vitro results indicate the possibility of an interaction. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

A systematic review identifies shortcomings in the reporting of crossover trials in chronic painful conditions.

PubMed

Straube, Sebastian; Werny, Benedikt; Friede, Tim

2015-12-01

To investigate the reporting of study features of interest in abstracts and full texts of journal publications of crossover trials in chronic painful conditions. Systematic review based on a MEDLINE (PubMed) search (January 1990-August 2014). Ninety-eight publications on crossover studies with 3,513 study participants were eligible for inclusion. Double-blind status and randomized allocation to treatment groups are commonly reported in both abstracts and full texts (90 of 98 publications and 82 of 98 publications, respectively). Adverse events are reported in both abstract and full text in 49 of 98 publications and in the full text only in 44 of 98. A breakdown of results by treatment period is provided only in 23 of 98 publications, and if so, is reported only in the full text, never in the abstract. There is a time trend for the reporting of randomization in abstracts; it is more likely to be reported in recent studies (P = 0.0094). No time trends are detected in the reporting of double-blind status (P = 0.1087) and adverse events (P = 0.6084). The reporting of adverse events in the abstract and the reporting of results specified by crossover period in the full texts of journal publications on crossover pain trials should be improved. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Perron, Justin K., E-mail: jperron@csusm.edu; Joint Quantum Institute, National Institute of Standards and Technology, Gaithersburg, Maryland 20899; National Institute of Standards and Technology, Gaithersburg, Maryland 20899

Pauli-spin blockade (PSB) is a transport phenomenon in double quantum dots that allows for a type of spin to charge conversion often used to probe fundamental physics such as spin relaxation and singlet-triplet coupling. In this paper, we theoretically explore Pauli-spin blockade as a function of magnetic field B applied parallel to the substrate. In the well-studied low magnetic field regime, where PSB occurs in the forward (1, 1) → (0, 2) tunneling direction, we highlight some aspects of PSB that are not discussed in detail in existing literature, including the change in size of both bias triangles measured inmore » the forward and reverse biasing directions as a function of B. At higher fields, we predict a crossover to “reverse PSB” in which current is blockaded in the reverse direction due to the occupation of a spin singlet as opposed to the traditional triplet blockade that occurs at low fields. The onset of reverse PSB coincides with the development of a tail like feature in the measured bias triangles and occurs when the Zeeman energy of the polarized triplet equals the exchange energy in the (0, 2) charge configuration. In Si quantum dots, these fields are experimentally accessible; thus, this work suggests a way to observe a crossover in magnetic field to qualitatively different behavior.« less

Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.

PubMed

Coelingh Bennink, Herjan J T; Zimmerman, Yvette; Laan, Ellen; Termeer, Hanneke M M; Appels, Nicole; Albert, Adelin; Fauser, Bart C J M; Thijssen, Jos H H; van Lunsen, Rik H W

2017-11-01

To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m 2 ) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC. Copyright © 2016 Pantarhei Bioscience. Published by Elsevier Inc. All rights reserved.

Spin state switching in iron coordination compounds

PubMed Central

Gaspar, Ana B; Garcia, Yann

2013-01-01

Summary The article deals with coordination compounds of iron(II) that may exhibit thermally induced spin transition, known as spin crossover, depending on the nature of the coordinating ligand sphere. Spin transition in such compounds also occurs under pressure and irradiation with light. The spin states involved have different magnetic and optical properties suitable for their detection and characterization. Spin crossover compounds, though known for more than eight decades, have become most attractive in recent years and are extensively studied by chemists and physicists. The switching properties make such materials potential candidates for practical applications in thermal and pressure sensors as well as optical devices. The article begins with a brief description of the principle of molecular spin state switching using simple concepts of ligand field theory. Conditions to be fulfilled in order to observe spin crossover will be explained and general remarks regarding the chemical nature that is important for the occurrence of spin crossover will be made. A subsequent section describes the molecular consequences of spin crossover and the variety of physical techniques usually applied for their characterization. The effects of light irradiation (LIESST) and application of pressure are subjects of two separate sections. The major part of this account concentrates on selected spin crossover compounds of iron(II), with particular emphasis on the chemical and physical influences on the spin crossover behavior. The vast variety of compounds exhibiting this fascinating switching phenomenon encompasses mono-, oligo- and polynuclear iron(II) complexes and cages, polymeric 1D, 2D and 3D systems, nanomaterials, and polyfunctional materials that combine spin crossover with another physical or chemical property. PMID:23504535

Local and sex-specific biases in crossover vs. noncrossover outcomes at meiotic recombination hot spots in mice.

PubMed

de Boer, Esther; Jasin, Maria; Keeney, Scott

2015-08-15

Meiotic recombination initiated by programmed double-strand breaks (DSBs) yields two types of interhomolog recombination products, crossovers and noncrossovers, but what determines whether a DSB will yield a crossover or noncrossover is not understood. In this study, we analyzed the influence of sex and chromosomal location on mammalian recombination outcomes by constructing fine-scale recombination maps in both males and females at two mouse hot spots located in different regions of the same chromosome. These include the most comprehensive maps of recombination hot spots in oocytes to date. One hot spot, located centrally on chromosome 1, behaved similarly in male and female meiosis: Crossovers and noncrossovers formed at comparable levels and ratios in both sexes. In contrast, at a distal hot spot, crossovers were recovered only in males even though noncrossovers were obtained at similar frequencies in both sexes. These findings reveal an example of extreme sex-specific bias in recombination outcome. We further found that estimates of relative DSB levels are surprisingly poor predictors of relative crossover frequencies between hot spots in males. Our results demonstrate that the outcome of mammalian meiotic recombination can be biased, that this bias can vary depending on location and cellular context, and that DSB frequency is not the only determinant of crossover frequency. © 2015 de Boer et al.; Published by Cold Spring Harbor Laboratory Press.

Assessment of levothyroxine sodium bioavailability: recommendations for an improved methodology based on the pooled analysis of eight identically designed trials with 396 drug exposures.

PubMed

Walter-Sack, Ingeborg; Clanget, Christof; Ding, Reinhard; Goeggelmann, Christoph; Hinke, Vera; Lang, Matthias; Pfeilschifter, Johannes; Tayrouz, Yorki; Wegscheider, Karl

2004-01-01

Assessment of dosage form performance in delivering endogenous compounds, such as hormones, in vivo requires a specific approach. Assessment of relative bioavailability of levothyroxine sodium (L-T4) from eight solid preparations, compared with a liquid formulation, by using pharmacological doses, and critical evaluation of trial methodology based on the pooled analysis of individual data. Eight open-label, randomised, single-dose, crossover phase I studies using eight solid L-T4 dosage forms (25, 50, 75, 100, 125, 150, 175, 200 microg per tablet; administered total doses 600, 625 or 700 microg) and a liquid formulation; assessment of relative bioavailability by 90% confidence intervals for the relative area under the concentration-time curve (AUC) of total thyroxine (TT4), i.e. protein-bound plus free thyroxine, calculated by using the recommended log AUC four-way analysis of variance models for crossover designs. For the pooled analysis, general linear models were applied to assess the validity of model assumptions, to identify potential sources of effect modification, to discuss alternative modelling approaches with respect to endogenous hormone secretion and to give recommendations for future designs and sample sizes. One hundred and sixty-nine healthy males; 29 of these individuals participating in two studies. Single oral doses of L-T4 tablets and the liquid formulation administered after fasting, separated by at least 6 weeks; a total of 396 drug exposures. TT4 AUC from 0 to 48 hours and peak plasma concentration with and without baseline correction. Each study demonstrated equivalence of the tablets to the drinking solution, independent of the chosen analysis model. Sequence effects that could devalidate the chosen crossover approach were not found. Period effects with changing directions that could best be explained by seasonal variation were detected. While the pre-specified method of baseline correction of simply subtracting individual time-zero TT4 values was disadvantageous, the analysis of total AUC could be improved considerably by covariate adjustment for baseline TT4. With this approach, sample sizes could have been substantially reduced or, alternatively, the recommended equivalence ranges could be reduced to +/-6%. Using a single pharmacological dose of L-T4 in two-period crossover designs is a safe and reliable procedure to assess L-T4 dosage form performance. With an adequate statistical modelling approach, the design is efficient and allows general conclusions with moderate sample sizes.

Design, analysis, and testing of high frequency passively damped struts

NASA Technical Reports Server (NTRS)

Yiu, Y. C.; Davis, L. Porter; Napolitano, Kevin; Ninneman, R. Rory

1993-01-01

Objectives of the research are: (1) to develop design requirements for damped struts to stabilize control system in the high frequency cross-over and spill-over range; (2) to design, fabricate and test viscously damped strut and viscoelastically damped strut; (3) to verify accuracy of design and analysis methodology of damped struts; and (4) to design and build test apparatus, and develop data reduction algorithm to measure strut complex stiffness. In order to meet the stringent performance requirements of the SPICE experiment, the active control system is used to suppress the dynamic responses of the low order structural modes. However, the control system also inadvertently drives some of the higher order modes unstable in the cross-over and spill-over frequency range. Passive damping is a reliable and effective way to provide damping to stabilize the control system. It also improves the robustness of the control system. Damping is designed into the SPICE testbed as an integral part of the control-structure technology.

Six different roles for crossover inhibition in the retina: correcting the nonlinearities of synaptic transmission.

PubMed

Werblin, Frank S

2010-03-01

Early retinal studies categorized ganglion cell behavior as either linear or nonlinear and rectifying as represented by the familiar X- and Y-type ganglion cells in cat. Nonlinear behavior is in large part a consequence of the rectifying nonlinearities inherent in synaptic transmission. These nonlinear signals underlie many special functions in retinal processing, including motion detection, motion in motion, and local edge detection. But linear behavior is also required for some visual processing tasks. For these tasks, the inherently nonlinear signals are "linearized" by "crossover inhibition." Linearization utilizes a circuitry whereby nonlinear ON inhibition adds with nonlinear OFF excitation or ON excitation adds with OFF inhibition to generate a more linear postsynaptic voltage response. Crossover inhibition has now been measured in most bipolar, amacrine, and ganglion cells. Functionally crossover inhibition enhances edge detection, allows ganglion cells to recognize luminance-neutral patterns with their receptive fields, permits ganglion cells to distinguish contrast from luminance, and maintains a more constant conductance during the light response. In some cases, crossover extends the operating range of cone-driven OFF ganglion cells into the scotopic levels. Crossover inhibition is also found in neurons of the lateral geniculate nucleus and V1.

Variation and Evolution of the Meiotic Requirement for Crossing Over in Mammals.

PubMed

Dumont, Beth L

2017-01-01

The segregation of homologous chromosomes at the first meiotic division is dependent on the presence of at least one well-positioned crossover per chromosome. In some mammalian species, however, the genomic distribution of crossovers is consistent with a more stringent baseline requirement of one crossover per chromosome arm. Given that the meiotic requirement for crossing over defines the minimum frequency of recombination necessary for the production of viable gametes, determining the chromosomal scale of this constraint is essential for defining crossover profiles predisposed to aneuploidy and understanding the parameters that shape patterns of recombination rate evolution across species. Here, I use cytogenetic methods for in situ imaging of crossovers in karyotypically diverse house mice (Mus musculus domesticus) and voles (genus Microtus) to test how chromosome number and configuration constrain the distribution of crossovers in a genome. I show that the global distribution of crossovers in house mice is thresholded by a minimum of one crossover per chromosome arm, whereas the crossover landscape in voles is defined by a more relaxed requirement of one crossover per chromosome. I extend these findings in an evolutionary metaanalysis of published recombination and karyotype data for 112 mammalian species and demonstrate that the physical scale of the genomic crossover distribution has undergone multiple independent shifts from one crossover per chromosome arm to one per chromosome during mammalian evolution. Together, these results indicate that the chromosomal scale constraint on crossover rates is itself a trait that evolves among species, a finding that casts light on an important source of crossover rate variation in mammals. Copyright © 2017 by the Genetics Society of America.

Comparison of automated and manual vital sign collection at hospital wards.

PubMed

Wood, Jeffrey; Finkelstein, Joseph

2013-01-01

Using a cross-over study design, vital signs were collected from 60 patients by 6 nurses. Each nurse was randomly assigned for manual vital sign collection in 5 patients and for automated data collection in other 5 patients. The mean time taken for vital signs information to be available in EMR was significantly (p <0.004) lower after automated data collection (158.7±67.0) than after the manual collection (4079.8±7091.8 s). The nursing satisfaction score of collecting vital signs was significantly lower (p<0.007) for the manual way (10.3±3.9) than for the automated way (16.5±3.4). We found that 30% of vital sign records were transmitted to EMR with at least one error after manual data collection whereas there wasno transmission error with automated data collection. Allparticipating nurses stated that the automated vital sign collection can improve their efficiency and save their time for direct patient care.

Effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of carbamazepine in healthy volunteers.

PubMed

Malhotra, S; Dixit, R K; Garg, S K

2002-01-01

The effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of a single dose of carbamazepine was studied. In a two-way cross-over design with a 1 week washout period, 10 healthy volunteers were randomized to received 200 mg carbamazepine orally with 300 ml of Coca-Cola or water. Blood samples were collected at 0, 0.5, 1, 2, 3, 6, 9, 12, 24, 48 and 72 h after drug administration. Plasma carbamazepine levels were higher with Coca-Cola as compared to water. The AUC0-infinity and Cmax of carbamazepine were significantly enhanced after Coca-Cola while tmax was achieved earlier with Coca-Cola. The results of the study indicate that concomitant administration of Coca-Cola enhances the rate and extent of absorption of carbamazepine.

Localization of an ataxia-telangiectasia gene by linkage disequilibrium in the Costa Rican population

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

Uhrhammer, N.A.; Lange, E.; Gatti, R.A.

1994-09-01

Linkage disequilibrium (LD) was studied in 27 Costa Rican families with ataxia-telangiectasia. Previous studies indicate that the ATA and ATC gene(s) are on chromosome 11q22.3, between D11S1819 and D11S927. We studied the ordered loci D11-S1816, S1817, S1343, S1819, S384, S535, S1295, S1818, S927, S1300 and S1004 by PCR and Southern blotting. We noted moderate LD at the more distant markers S1816, S1300, and S1004. LD was higher at markers closer to A-T, and also where A-T was associated with rarer alleles. This broad region of disequilibrium did not by itself contribute to further localization of the A-T gene(s). We analyzedmore » 54 affected chromosomal haplotypes. The most common haplotype occurred 34 times, including some that had recombined outside the known A-T region. Other haplotypes occurred seven times, five times, two occurred twice, and the four remaining were unique. The most common haplotype had `broken` at S927 in five different patients, placing A-T proximal to this marker. We looked for recombination events in 15 of the families to further localize A-T. We observed one family with a recombination event placing A-T distal to S1819. A second family appears to either not link to 11q22.3 or to have a double-crossover between the markers S384 and S927; two affected sibs share haplotypes for the entire region studied, and a normal sib shared the same two haplotypes. Since all or part of this A-T haplotype occurs in 32 other, unrelated, Costa Rican patients, we anticipate a double-crossover in the 1600 kb between the informative flanking markers. All other families show segregation patterns consistent with placing A-T at 11q22.3. These results demonstrate that the major A-T gene in the Costa Rican population is located between S1819 and S927 at 11q22.3.« less

The effect of food on the pharmacokinetics of oral ibrutinib in healthy participants and patients with chronic lymphocytic leukemia.

PubMed

de Jong, Jan; Sukbuntherng, Juthamas; Skee, Donna; Murphy, Joe; O'Brien, Susan; Byrd, John C; James, Danelle; Hellemans, Peter; Loury, David J; Jiao, Juhui; Chauhan, Vijay; Mannaert, Erik

2015-05-01

To assess ibrutinib pharmacokinetics under fasted and fed conditions, impact of food-intake timing, and the safety and tolerability. Three studies were analyzed. Study 1 was a randomized, open-label, single-dose, four-way crossover study in 44 healthy participants. Study 2 was a randomized, repeat-dose crossover study in 16 patients with previously treated chronic lymphocytic leukemia (CLL). Ibrutinib dose was 420 mg in both studies. Study 3 was an open-label, sequential study to assess the effect of a standard breakfast on ibrutinib 560 mg in eight healthy participants. Administration of single-dose ibrutinib under fasting conditions (study 1) resulted in approximately 60 % of exposure compared with drug intake either 30 min before, 30 min after (fed), or 2 h after a high-fat meal. Similar food effect was observed (study 3) when ibrutinib was given 30 min before meal. In CLL patients (study 2), the C max and AUC under fasting conditions were 43 and 61 %, respectively, relative to fed conditions. When administered once-daily in uncontrolled food-intake conditions (≥30 min before or 2 h after), exposures were slightly (≈30 %) lower than in fed condition. When corrected for repeated dosing, pharmacokinetic parameters in healthy participants and patients were comparable. Ibrutinib was generally well tolerated in all settings studied. Ibrutinib administered in fasted condition reduces exposure to approximately 60 % as compared with dosing in proximity to food-intake, regardless of timing/type of meal. Because repeated drug intake in fasted condition is unlikely, no food restrictions may be needed to administer ibrutinib.

The Effectiveness of Music in Pediatric Healthcare: A Systematic Review of Randomized Controlled Trials

PubMed Central

Treurnicht Naylor, Karline; Kingsnorth, Shauna; Lamont, Andrea; McKeever, Patricia; Macarthur, Colin

2011-01-01

The aim of this study was to systematically review the effectiveness of music on pediatric health-related outcomes. Five electronic databases were searched for randomized controlled/crossover trial designs published between 1984 and 2009. Eligible studies used music as a therapy or intervention, included participants 1 to 18 years, and focused on at least one health-related outcome (with the exclusion of procedural pain). Seventeen studies met the inclusion criteria. Quantitative synthesis was hampered by an inability to aggregate data arising from heterogeneity of interventions, outcomes and measurement tools. Qualitative synthesis revealed significant improvements in one or more health outcomes within four of seven trials involving children with learning and developmental disorders; two of three trials involving children experiencing stressful life events; and four of five trials involving children with acute and/or chronic physical illness. No significant effects were found for two trials involving children with mood disorders and related psychopathology. These findings offer limited qualitative evidence to support the effectiveness of music on health-related outcomes for children and adolescents with clinical diagnoses. Recommendations for establishing a consensus on research priorities and addressing methodological limitations are put forth to support the continued advancement of this popular intervention. PMID:20976017

Eating marshmallows reduces ileostomy output: a randomized crossover trial.

PubMed

Clarebrough, E; Guest, G; Stupart, D

2015-12-01

Anecdotally, many ostomates believe that eating marshmallows can reduce ileostomy effluent. There is a plausible mechanism for this, as the gelatine contained in marshmallows may thicken small bowel fluid, but there is currently no evidence that this is effective. This was a randomized crossover trial. Adult patients with well-established ileostomies were included. Ileostomy output was measured for 1 week during which three marshmallows were consumed three times daily, and for one control week where marshmallows were not eaten. There was a 2-day washout period. Patients were randomly allocated to whether the control or intervention week occurred first. In addition, a questionnaire was administered regarding patient's subjective experience of their ileostomy function. Thirty-one participants were recruited; 28 completed the study. There was a median reduction in ileostomy output volume of 75 ml per day during the study period (P = 0.0054, 95% confidence interval 23.4-678.3) compared with the control week. Twenty of 28 subjects (71%) experienced a reduction in their ileostomy output, two had no change and six reported an increase. During the study period, participants reported fewer ileostomy bag changes (median five per day vs six in the control period, P = 0.0255). Twenty of 28 (71%) reported that the ileostomy effluent was thicker during the study week (P = 0.023). Overall 19 (68%) participants stated they would use marshmallows in the future if they wanted to reduce or thicken their ileostomy output. Eating marshmallows leads to a small but statistically significant reduction in ileostomy output. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Effect of sodium chloride- and sodium bicarbonate-rich mineral water on blood pressure and metabolic parameters in elderly normotensive individuals: a randomized double-blind crossover trial.

PubMed

Schorr, U; Distler, A; Sharma, A M

1996-01-01

To examine the effect of sodium chloride- and sodium bicarbonate-rich mineral water on blood pressure and parameters of glucose and lipid metabolism in elderly normotensive individuals. We examined 21 healthy men and women aged 60-72 years in a randomized, placebo-controlled, double-blind crossover trial. After reducing dietary salt intake to below 100 mmol/day, study participants were randomly assigned to drink 1.5 l daily of a sodium chloride-rich (sodium 84.5 mmol/l, chloride 63.7 mmol/l, bicarbonate 21.9 mmol/l), a sodium bicarbonate-rich (sodium 39.3 mmol/l, chloride 6.5 mmol/l, bicarbonate 48.8 mmol/l) and a low-sodium (placebo: sodium, chloride and bicarbonate < 0.02 mmol/l) mineral water for 4 weeks each in a three-phase crossover order. Each phase was separated by a 2-week washout period in which the study participants remained on a low-salt diet. Compliance was assessed by biweekly urinary electrolyte excretion and five study participants were excluded from analysis for failing to complete the trial or to fulfil the compliance criteria. Mean arterial blood pressure was significantly lower during the periods of consuming low-sodium -7.0 +/- 7.2 mmHg, P < 0.001) or sodium bicarbonate-rich (-5.7 +/- 6.4 mmHg, P < 0.05) water than at baseline. In contrast, blood pressure during the phase of drinking sodium chloride-rich water was identical to that at baseline. Ambulatory 24 h blood pressure, oral glucose tolerance and plasma lipids were not affected by the different regimens. Urinary calcium excretion was significantly reduced by drinking low-sodium or sodium bicarbonate-rich water but was unchanged under the sodium chloride-rich water. Consumption of sodium chloride-rich mineral water can abolish the blood pressure reduction induced by dietary salt restriction in elderly individuals. Sodium bicarbonate-rich mineral water in conjunction with a low-salt diet may have a beneficial effect on calcium homeostasis.

Efficacy of maropitant for preventing vomiting associated with motion sickness in dogs.

PubMed

Benchaoui, H A; Siedek, E M; De La Puente-Redondo, V A; Tilt, N; Rowan, T G; Clemence, R G

2007-09-29

Maropitant is a neurokinin-1 inhibitor that acts to prevent and treat vomiting by blocking stimuli to the final common pathway in the emetic centre of the brain. The field efficacy and safety of a single oral dose of maropitant were investigated for the prevention of vomiting in dogs with a history of motion sickness resulting from transportation by car in two blinded, placebo-controlled studies. In an exploratory study designed as a two-way crossover trial with 17 dogs, 10 of the dogs given the placebo vomited during a car journey but only three of the dogs vomited under maropitant treatment. In a larger multicentred parallel design study, 69 of 105 dogs treated with the placebo vomited during the journey compared with 15 of 106 dogs treated with maropitant (P < 0.0001).

The Value of Supplementing Science Education with Outdoor Instruction for Sixth Grade Students

NASA Astrophysics Data System (ADS)

Jackson, Devin Joseph Guilford

Science education is moving away from memorization of facts to inquiry based learning. Adding outdoor instruction can be an effective way to promote this exploratory method of learning. The limited number of empirical studies available have shown significant increase in attitudes and learning with outdoor science instruction. An eight-week quasi-experimental teacher research study was conducted to further this research and assess the value of schoolyard science instruction on student engagement and learning. Participants were 60 students in two sixth grade middle school Earth Science classes. A crossover study design was used with two classes alternating as experimental and control groups. NASA Global Precipitation Measurement mission curriculum was used (NASA/GPM, 2011). While the results did not show a clear increase in student engagement and content knowledge, the study adds to the body of knowledge on outdoor instruction and identifies limitations to consider in future studies.

Spin Crossover and the Magnetic P- T Phase Diagram of Hematite at High Hydrostatic Pressures and Cryogenic Temperatures

NASA Astrophysics Data System (ADS)

Gavriliuk, A. G.; Struzhkin, V. V.; Mironovich, A. A.; Lyubutin, I. S.; Troyan, I. A.; Chow, P.; Xiao, Y.

2018-02-01

The magnetic properties of the α-Fe2O3 hematite at a high hydrostatic pressure have been studied by synchrotron Mössbauer spectroscopy (nuclear forward scattering (NFS)) on iron nuclei. Time-domain NFS spectra of hematite have been measured in a diamond anvil cell in the pressure range of 0-72 GPa and the temperature range of 36-300 K in order to study the magnetic properties at a phase transition near a critical pressure of 50 GPa. In addition, Raman spectra at room temperature have been studied in the pressure range of 0-77 GPa. Neon has been used as a pressure-transmitting medium. The appearance of an intermediate electronic state has been revealed at a pressure of 48 GPa. This state is probably related to the spin crossover in Fe3+ ions at their transition from the high-spin state (HS, S = 5/2) to a low-spin one (LS, S = 1/2). It has been found that the transient pressure range of the HS-LS crossover is extended from 48 to 55 GPa and is almost independent of the temperature. This surprising result differs fundamentally from other cases of the spin crossover in Fe3+ ions observed in other crystals based on iron oxides. The transition region of spin crossover appears because of thermal fluctuations between HS and LS states in the critical pressure range and is significantly narrowed at cooling because of the suppression of thermal excitations. The magnetic P- T phase diagram of α-Fe2O3 at high pressures and low temperatures in the spin crossover region has been constructed according to the results of measurements.

Investigation of Sustained Detonation Devices: the Pulse Detonation Engine-Crossover System and the Rotating Detonation Engine System

NASA Astrophysics Data System (ADS)

Driscoll, Robert B.

An experimental study is conducted on a Pulse Detonation Engine-Crossover System to investigate the feasibility of repeated, shock-initiated combustion and characterize the initiation performance. A PDE-crossover system can decrease deflagration-to-detonation transition length while employing a single spark source to initiate a multi-PDE system. Visualization of a transferred shock wave propagating through a clear channel reveals a complex shock train behind the leading shock. Shock wave Mach number and decay rate remains constant for varying crossover tube geometries and operational frequencies. A temperature gradient forms within the crossover tube due to forward flow of high temperature ionized gas into the crossover tube from the driver PDE and backward flow of ionized gas into the crossover tube from the driven PDE, which can cause intermittent auto-ignition of the driver PDE. Initiation performance in the driven PDE is strongly dependent on initial driven PDE skin temperature in the shock wave reflection region. An array of detonation tubes connected with crossover tubes is developed using optimized parameters and successful operation utilizing shock-initiated combustion through shock wave reflection is achieved and sustained. Finally, an air-breathing, PDE-Crossover System is developed to characterize the feasibility of shock-initiated combustion within an air-breathing pulse detonation engine. The initiation effectiveness of shock-initiated combustion is compared to spark discharge and detonation injection through a pre-detonator. In all cases, shock-initiated combustion produces improved initiation performance over spark discharge and comparable detonation transition run-up lengths relative to pre-detonator initiation. A computational study characterizes the mixing processes and injection flow field within a rotating detonation engine. Injection parameters including reactant flow rate, reactant injection area, placement of the fuel injection, and fuel injection distribution are varied to assess the impact on mixing. Decreasing reactant injection areas improves fuel penetration into the cross-flowing air stream, enhances turbulent diffusion of the fuel within the annulus, and increases local equivalence ratio and fluid mixedness. Staggering fuel injection holes produces a decrease in mixing when compared to collinear fuel injection. Finally, emulating nozzle integration by increasing annulus back-pressure increases local equivalence ratio in the injection region due to increased convection residence time.

Exchangeability in the case-crossover design

PubMed Central

Mittleman, Murray A; Mostofsky, Elizabeth

2014-01-01

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. PMID:24756878

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

PubMed

Oliveira-Neto, Jeronimo M; Sato, Sandra; Pedrazzi, Vinícius

2013-11-01

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. To compare the efficacy of five modalities of treatment for controlling morning halitosis in subjects with no dental or periodontal disease. This is a five-period, randomized, crossover clinical trial. 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. 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. 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. 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.

Protein from Meat or Vegetable Sources in Meals Matched for Fiber Content has Similar Effects on Subjective Appetite Sensations and Energy Intake-A Randomized Acute Cross-Over Meal Test Study.

PubMed

Nielsen, Lone V; Kristensen, Marlene D; Klingenberg, Lars; Ritz, Christian; Belza, Anita; Astrup, Arne; Raben, Anne

2018-01-16

Higher-protein meals decrease hunger and increase satiety compared to lower-protein meals. However, no consensus exists about the different effects of animal and vegetable proteins on appetite. We investigated how a meal based on vegetable protein (fava beans/split peas) affected ad libitum energy intake and appetite sensations, compared to macronutrient-balanced, iso-caloric meals based on animal protein (veal/pork or eggs). Thirty-five healthy men were enrolled in this acute cross-over study. On each test day, participants were presented with one of four test meals (~3550 kilojoules (kJ) 19% of energy from protein), based on fava beans/split peas (28.5 g fiber), pork/veal or eggs supplemented with pea fiber to control for fiber content (28.5 g fiber), or eggs without supplementation of fiber (6.0 g fiber). Subjective appetite sensations were recorded at baseline and every half hour until the ad libitum meal three hours later. There were no differences in ad libitum energy intake across test meals ( p > 0.05). Further, no differences were found across meals for hunger, satiety, fullness, prospective food consumption, or composite appetite score (all p > 0.05). Iso-caloric, macronutrient-balanced, fiber-matched meals based on vegetable protein (fava beans/split peas) or animal protein (veal/pork or eggs) had similar effects on ad libitum energy intake and appetite sensations.

Protein from Meat or Vegetable Sources in Meals Matched for Fiber Content has Similar Effects on Subjective Appetite Sensations and Energy Intake—A Randomized Acute Cross-Over Meal Test Study

PubMed Central

Nielsen, Lone V.; Kristensen, Marlene D.; Klingenberg, Lars; Belza, Anita

2018-01-01

Higher-protein meals decrease hunger and increase satiety compared to lower-protein meals. However, no consensus exists about the different effects of animal and vegetable proteins on appetite. We investigated how a meal based on vegetable protein (fava beans/split peas) affected ad libitum energy intake and appetite sensations, compared to macronutrient-balanced, iso-caloric meals based on animal protein (veal/pork or eggs). Thirty-five healthy men were enrolled in this acute cross-over study. On each test day, participants were presented with one of four test meals (~3550 kilojoules (kJ) 19% of energy from protein), based on fava beans/split peas (28.5 g fiber), pork/veal or eggs supplemented with pea fiber to control for fiber content (28.5 g fiber), or eggs without supplementation of fiber (6.0 g fiber). Subjective appetite sensations were recorded at baseline and every half hour until the ad libitum meal three hours later. There were no differences in ad libitum energy intake across test meals (p > 0.05). Further, no differences were found across meals for hunger, satiety, fullness, prospective food consumption, or composite appetite score (all p > 0.05). Iso-caloric, macronutrient-balanced, fiber-matched meals based on vegetable protein (fava beans/split peas) or animal protein (veal/pork or eggs) had similar effects on ad libitum energy intake and appetite sensations. PMID:29337861

Gender differences in plantar loading during three soccer-specific tasks.

PubMed

Sims, E L; Hardaker, W M; Queen, R M

2008-04-01

Examine the effect of gender on plantar loading during three football-specific tasks. Thirty-four athletes (17 men, 17 women) ran an agility course five times while wearing the Nike Vitoria hard ground cleat. Plantar loading data were recorded during a side cut, a cross-over cut and a forward acceleration task using Pedar-X insoles. Controlled laboratory study. No history of lower extremity injury in the past 6 months, no previous foot or ankle surgery, not currently wearing foot orthotics and play a cleated sport at least two times per week. Contact area, maximum force and the force-time integral (FTI) in the medial and lateral midfoot, medial, middle and lateral forefoot as well as the hallux. A univariate ANCOVA (alpha = 0.05) was performed on each dependent variable (covariate was course speed). Significant gender differences existed in the force and force-time integral beneath the lateral midfoot and forefoot during the cross-over cut task as well as in the middle forefoot during the side cut task with the men demonstrating an increased force. No significant differences existed in the loading on the medial side of the foot during any tasks. The results of this study indicate that the increase in plantar loading on the lateral portion of the midfoot and forefoot in men could be one possible explanation for the increased incidence of fifth metatarsal stress fractures in men. Gender differences in loading patterns need to be considered when comparing different movements as well as different footwear conditions.

Randomized controlled trial of nettle sting for treatment of base-of-thumb pain.

PubMed Central

Randall, C; Randall, H; Dobbs, F; Hutton, C; Sanders, H

2000-01-01

There are numerous published references to use of nettle sting for arthritis pain but no randomized controlled trials have been reported. We conducted a randomized controlled double-blind crossover study in 27 patients with osteoarthritic pain at the base of the thumb or index finger. Patients applied stinging nettle leaf (Urtica dioica) daily for one week to the painful area. The effect of this treatment was compared with that of placebo, white deadnettle leaf (Lamium album), for one week after a five-week washout period. Observations of pain and disability were recorded for the twelve weeks of the study. After one week's treatment with nettle sting, score reductions on both visual analogue scale (pain) and health assessment questionnaire (disability) were significantly greater than with placebo (P = 0.026 and P = 0.0027). PMID:10911825

Bioequivalence of HTX-019 (aprepitant IV) and fosaprepitant in healthy subjects: a Phase I, open-label, randomized, two-way crossover evaluation.

PubMed

Ottoboni, Tom; Keller, Mary Rose; Cravets, Matt; Clendeninn, Neil; Quart, Barry

2018-01-01

Fosaprepitant, an intravenous (IV) aprepitant prodrug for chemotherapy-induced nausea and vomiting prophylaxis, is associated with systemic and infusion-site reactions attributed in part to its surfactant, polysorbate 80. HTX-019 is an IV aprepitant formulation free of polysorbate 80 and other synthetic surfactants. This open-label, single-dose, randomized, two-way crossover bioequivalence study compared pharmacokinetics and safety of HTX-019 and fosaprepitant. Healthy subjects received single-dose HTX-019 (130 mg) or fosaprepitant (150 mg) IV over 30 min, with ≥7-day washout between doses. Blood samples were evaluated for pharmacokinetics and bioequivalence; safety evaluation included treatment-emergent adverse events (TEAEs) and serious adverse events. Ninety-seven of one hundred enrolled subjects completed the study. Baseline characteristics were comparable between treatment sequences. For HTX-019, mean (percent coefficient of variation) area under the curve (AUC) from time 0 to time of last measurable plasma concentration (AUC 0-t ), AUC from time 0 to infinity (AUC 0-inf ), and plasma concentration at 12 h (C 12 h ) for HTX-019 were 43,729 h*ng/mL (32.7), 45,460 h*ng/mL (36.8), and 988.4 ng/mL (27.5), respectively; corresponding fosaprepitant values were 44,130 h*ng/mL (32.0), 46,163 h*ng/mL (36.6), and 1,022 ng/mL (28.5). Also, 90% CIs (94.186-101.354) were within bioequivalence bounds (80%-125%). Within 1 h following infusion start, one (1%) HTX-019 recipient reported one TEAE, while 20 (20%) fosaprepitant recipients reported 32 TEAEs. Dyspnea occurred in three fosaprepitant recipients (at <1 min in two subjects and at 18 min in one subject, considered study drug related) and one HTX-019 recipient (at 120 h, associated with a respiratory tract infection and considered not related to the study drug). No severe TEAEs, serious adverse events, or deaths occurred; all TEAEs resolved. HTX-019 was bioequivalent to fosaprepitant and may provide a safer alternative to fosaprepitant for chemotherapy-induced nausea and vomiting prophylaxis.

Bioequivalence of HTX-019 (aprepitant IV) and fosaprepitant in healthy subjects: a Phase I, open-label, randomized, two-way crossover evaluation

PubMed Central

Ottoboni, Tom; Keller, Mary Rose; Cravets, Matt; Clendeninn, Neil; Quart, Barry

2018-01-01

Introduction Fosaprepitant, an intravenous (IV) aprepitant prodrug for chemotherapy-induced nausea and vomiting prophylaxis, is associated with systemic and infusion-site reactions attributed in part to its surfactant, polysorbate 80. HTX-019 is an IV aprepitant formulation free of polysorbate 80 and other synthetic surfactants. Materials and methods This open-label, single-dose, randomized, two-way crossover bioequivalence study compared pharmacokinetics and safety of HTX-019 and fosaprepitant. Healthy subjects received single-dose HTX-019 (130 mg) or fosaprepitant (150 mg) IV over 30 min, with ≥7-day washout between doses. Blood samples were evaluated for pharmacokinetics and bioequivalence; safety evaluation included treatment-emergent adverse events (TEAEs) and serious adverse events. Ninety-seven of one hundred enrolled subjects completed the study. Results Baseline characteristics were comparable between treatment sequences. For HTX-019, mean (percent coefficient of variation) area under the curve (AUC) from time 0 to time of last measurable plasma concentration (AUC0−t), AUC from time 0 to infinity (AUC0−inf), and plasma concentration at 12 h (C12 h) for HTX-019 were 43,729 h*ng/mL (32.7), 45,460 h*ng/mL (36.8), and 988.4 ng/mL (27.5), respectively; corresponding fosaprepitant values were 44,130 h*ng/mL (32.0), 46,163 h*ng/mL (36.6), and 1,022 ng/mL (28.5). Also, 90% CIs (94.186–101.354) were within bioequivalence bounds (80%–125%). Within 1 h following infusion start, one (1%) HTX-019 recipient reported one TEAE, while 20 (20%) fosaprepitant recipients reported 32 TEAEs. Dyspnea occurred in three fosaprepitant recipients (at <1 min in two subjects and at 18 min in one subject, considered study drug related) and one HTX-019 recipient (at 120 h, associated with a respiratory tract infection and considered not related to the study drug). No severe TEAEs, serious adverse events, or deaths occurred; all TEAEs resolved. Conclusion HTX-019 was bioequivalent to fosaprepitant and may provide a safer alternative to fosaprepitant for chemotherapy-induced nausea and vomiting prophylaxis. PMID:29535504

Mood spillover and crossover among dual-earner couples: a cell phone event sampling study.

PubMed

Song, Zhaoli; Foo, Maw-Der; Uy, Marilyn A

2008-03-01

In this study, the authors examined affective experiences of dual-earner couples. More specifically, the authors explored how momentary moods can spill over between work and family and cross over from one spouse to another. Fifty couples used their cell phones to provide reports of their momentary moods over 8 consecutive days. Results show significant spillover and crossover effects for both positive and negative moods. Work orientation moderated negative mood spillover from work to home, and the presence of children in the family decreased negative mood crossover between spouses. Crossover was observed when spouses were physically together and when the time interval between the spouses' reports was short. With this study, the authors contribute to the work and family research by examining the nature of mood transfers among dual-earner couples, including the direction, valence, and moderators of these transfers across work and family domains. The authors also contribute to the event sampling methodology by introducing a new method of using cell phones to collect momentary data. Copyright 2008 APA

Comparative bioavailability study of cefuroxime axetil (equivalent to 500 mg cefuroxime/tablet) tablets (Zednad® versus Zinnat®) in healthy male volunteers.

PubMed

Asiri, Y A; Al-Hadiya, B M; Kadi, A A; Al-Khamis, K I; Mowafy, H A; El-Sayed, Y M

2011-09-01

This study was performed to investigate the bioequivalence of cefuroxime axetil tablets between a generic test product (A) Zednad® Tablet (500 mg cefuroxime/ tablet, Diamond Pharma, Syria), and the Reference Product (B) Zinnat® Tablet (500 mg cefuroxime/tablet, GlaxoSmithKline, Saudi Arabia). The bioavailability study was carried out for 24 healthy male volunteers. The subjects received 1 Zednad® Tablet (500 mg/ tablet) and 1 Zinnat® Tablet (500 mg/tablet) in a randomized, two-way crossover design fashion on 2 treatment days, after an overnight fast of at least 10 h, with a washout period of 7 days. 24 volunteers plus 2 alternatives completed the crossover. The bioanalysis of clinical plasma samples was accomplished by HPLC method, which was developed and validated in accordance with international guidelines. Pharmacokinetic parameters, determined by standard non-compartmental methods, and ANOVA statistics were calculated using SAS Statistical Software. The significance of a sequence effect was tested using the subjects nested in sequence as the error term. The 90% confidence intervals for the ratio between the test and reference product pharmacokinetic parameters of AUC0→t, AUC0→∞, and Cmax were calculated and found to be within the confidence limits of 80.00 - 125.00% for AUC0→t, AUC0→∞ and Cmax. The study demonstrated that the test product (A) was found bioequivalent to the reference product (B) following an oral dose of 500 mg tablet. Therefore, the two formulations were considered to be bioequivalent.

PM₁₀ exposure and non-accidental mortality in Asian populations: a meta-analysis of time-series and case-crossover studies.

PubMed

Park, Hye Yin; Bae, Sanghyuk; Hong, Yun-Chul

2013-01-01

We investigated the association between particulate matter less than 10 µm in aerodynamic diameter (PM₁₀) exposure and non-accidental mortality in Asian populations by meta-analysis, using both time-series and case-crossover analysis. Among the 819 published studies searched from PubMed and EMBASE using key words related to PM₁₀ exposure and non-accidental mortality in Asian countries, 8 time-series and 4 case-crossover studies were selected for meta-analysis after exclusion by selection criteria. We obtained the relative risk (RR) and 95% confidence intervals (CI) of non-accidental mortality per 10 µg/m³ increase of daily PM₁₀ from each study. We used Q statistics to test the heterogeneity of the results among the different studies and evaluated for publication bias using Begg funnel plot and Egger test. Testing for heterogeneity showed significance (p<0.001); thus, we applied a random-effects model. RR (95% CI) per 10 µg/m³ increase of daily PM₁₀ for both the time-series and case-crossover studies combined, time-series studies relative risk only, and case-crossover studies only, were 1.0047 (1.0033 to 1.0062), 1.0057 (1.0029 to 1.0086), and 1.0027 (1.0010 to 1.0043), respectively. The non-significant Egger test suggested that this analysis was not likely to have a publication bias. We found a significant positive association between PM₁₀ exposure and non-accidental mortality among Asian populations. Continued investigations are encouraged to contribute to the health impact assessment and public health management of air pollution in Asian countries.

No correlation between germline mutation at repeat DNA and meiotic crossover in male mice exposed to X-rays or cisplatin.

PubMed

Barber, R; Plumb, M; Smith, A G; Cesar, C E; Boulton, E; Jeffreys, A J; Dubrova, Y E

2000-12-20

To test the hypothesis that mouse germline expanded simple tandem repeat (ESTR) mutations are associated with recombination events during spermatogenesis, crossover frequencies were compared with germline mutation rates at ESTR loci in male mice acutely exposed to 1Gy of X-rays or to 10mg/kg of the anticancer drug cisplatin. Ionising radiation resulted in a highly significant 2.7-3.6-fold increase in ESTR mutation rate in males mated 4, 5 and 6 weeks after exposure, but not 3 weeks after exposure. In contrast, irradiation had no effect on meiotic crossover frequencies assayed on six chromosomes using 25 polymorphic microsatellite loci spaced at approximately 20cM intervals and covering 421cM of the mouse genome. Paternal exposure to cisplatin did not affect either ESTR mutation rates or crossover frequencies, despite a report that cisplatin can increase crossover frequency in mice. Correlation analysis did not reveal any associations between the paternal ESTR mutation rate and crossover frequency in unexposed males and in those exposed to X-rays or cisplatin. This study does not, therefore, support the hypothesis that mutation induction at mouse ESTR loci results from a general genome-wide increase in meiotic recombination rate.

Crossover study of amputee stair ascent and descent biomechanics using Genium and C-Leg prostheses with comparison to non-amputee control.

PubMed

Lura, Derek J; Wernke, Matthew W; Carey, Stephanie L; Kahle, Jason T; Miro, Rebecca M; Highsmith, M Jason

2017-10-01

This study was a randomized crossover of stair ambulation of Transfemoral Amputees (TFAs) using the Genium and C-Leg prosthetic knees. TFAs typically have difficulty ascending and descending stairs, limiting community mobility. The objective of this study was to determine the relative efficacy of the Genium and C-Leg prostheses for stair ascent and descent, and their absolute efficacy relative to non-amputees. Twenty TFAs, and five non-amputees participated in the study. TFAs were randomized to begin the study with the Genium or C-Leg prosthesis. Informed consent was obtained from all participants prior to data collection and the study was listed on clinicaltrials.gov (#NCT01473662). After fitting, accommodation, and training, participants were asked to demonstrate their preferred gait pattern for stair ascent and descent and a step-over-step pattern if able. TFAs then switched prosthetic legs and repeated fitting, accommodation, training, and testing. An eight camera Vicon optical motion analysis system, and two AMTI force plates were used to track and analyze the participants' gait patterns, knee flexion angles, knee moment normalized by body weight, and swing time. For stair descent, no significant differences were found between prostheses. For stair ascent, Genium use resulted in: increased ability to use a step-over-step gait pattern (p=0.03), increased prosthetic side peak knee flexion (p<0.01), and increased swing duration (p<0.01). Changes in contralateral side outcomes and in knee moment were not significant. Overall the Genium knee decreased deficiency in gait patterns for stair ascent relative to the C-Leg, by enabling gait patterns that more closely resembled non-amputees. Copyright © 2017 Elsevier B.V. All rights reserved.

Work-family enrichment, work-family conflict, and marital satisfaction: a dyadic analysis.

PubMed

van Steenbergen, Elianne F; Kluwer, Esther S; Karney, Benjamin R

2014-04-01

This study was designed to examine whether spouses' work-to-family (WF) enrichment experiences account for their own and their partner's marital satisfaction, beyond the effects of WF conflict. Data were collected from both partners of 215 dual-earner couples with children. As hypothesized, structural equation modeling revealed that WF enrichment experiences accounted for variance in individuals' marital satisfaction, over and above WF conflict. In line with our predictions, this positive link between individuals' WF enrichment and their marital satisfaction was mediated by more positive marital behavior, and more positive perceptions of the partner's behavior. Furthermore, evidence for crossover was found. Husbands who experienced more WF enrichment were found to show more marital positivity (according to their wives), which related to increased marital satisfaction in their wives. No evidence of such a crossover effect from wives to husbands was found. The current findings not only highlight the added value of studying positive spillover and crossover effects of work into the marriage, but also suggest that positive spillover and crossover effects on marital satisfaction might be stronger than negative spillover and crossover are. These results imply that organizational initiatives of increasing job enrichment may make employees' marital life happier and can contribute to a happy, healthy, and high-performing workforce.

Is ambient air pollution associated with onset of sudden infant death syndrome: a case-crossover study in the UK

PubMed Central

Ayres, Jon G; Mohammed, Nuredin I

2018-01-01

Objectives Air pollution has been associated with increased mortality and morbidity in several studies with indications that its effect could be more severe in children. This study examined the relationship between short-term variations in criteria air pollutants and occurrence of sudden infant death syndrome (SIDS). Design We used a case-crossover study design which is widely applied in air pollution studies and particularly useful for estimating the risk of a rare acute outcome associated with short-term exposure. Setting The study used data from the West Midlands region in the UK. Participants We obtained daily time series data on SIDS mortality (ICD-9: 798.0 or ICD-10: R95) for the period 1996–2006 with a total of 211 SIDS events. Primary outcome measures Daily counts of SIDS events. Results For an IQR increase in previous day pollutant concentration, the percentage increases (95% CI) in SIDS were 16 (6 to 27) for PM10, 1 (−7 to 10) for SO2, 5 (−4 to 14) for CO, −17 (−27 to –6) for O3, 16 (2 to 31) for NO2 and 2 (−3 to 8) for NO after controlling for average temperature and national holidays. PM10 and NO2 showed relatively consistent association which persisted across different lag structures and after adjusting for copollutants. Conclusions The results indicated ambient air pollutants, particularly PM10 and NO2, may show an association with increased SIDS mortality. Thus, future studies are recommended to understand possible mechanistic explanations on the role of air pollution on SIDS incidence and the ways in which we might reduce pollution exposure among infants. PMID:29654005

Is ambient air pollution associated with onset of sudden infant death syndrome: a case-crossover study in the UK.

PubMed

Litchfield, Ian J; Ayres, Jon G; Jaakkola, Jouni J K; Mohammed, Nuredin I

2018-04-12

Air pollution has been associated with increased mortality and morbidity in several studies with indications that its effect could be more severe in children. This study examined the relationship between short-term variations in criteria air pollutants and occurrence of sudden infant death syndrome (SIDS). We used a case-crossover study design which is widely applied in air pollution studies and particularly useful for estimating the risk of a rare acute outcome associated with short-term exposure. The study used data from the West Midlands region in the UK. We obtained daily time series data on SIDS mortality (ICD-9: 798.0 or ICD-10: R95) for the period 1996-2006 with a total of 211 SIDS events. Daily counts of SIDS events. For an IQR increase in previous day pollutant concentration, the percentage increases (95% CI) in SIDS were 16 (6 to 27) for PM 10 , 1 (-7 to 10) for SO 2 , 5 (-4 to 14) for CO, -17 (-27 to -6) for O 3 , 16 (2 to 31) for NO 2 and 2 (-3 to 8) for NO after controlling for average temperature and national holidays. PM 10 and NO 2 showed relatively consistent association which persisted across different lag structures and after adjusting for copollutants. The results indicated ambient air pollutants, particularly PM 10 and NO 2 , may show an association with increased SIDS mortality. Thus, future studies are recommended to understand possible mechanistic explanations on the role of air pollution on SIDS incidence and the ways in which we might reduce pollution exposure among infants. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Procedures for assessing psychological predictors of injuries in circus artists: a pilot prospective study.

PubMed

Shrier, Ian; Raglin, John S; Levitan, Emily B; Mittleman, Murray A; Steele, Russell J; Powell, Janette

2014-06-11

Research on psychological risk factors for injury has focused on stable traits. Our objective was to test the feasibility of a prospective longitudinal study designed to examine labile psychological states as risk factors of injury. We measured psychological traits at baseline (mood, ways of coping and anxiety), and psychological states every day (1-item questions on anxiety, sleep, fatigue, soreness, self-confidence) before performances in Cirque du Soleil artists of the show "O". Additional questions were added once per week to better assess anxiety (20-item) and mood. Questionnaires were provided in English, French, Russian and Japanese. Injury and exposure data were extracted from electronic records that are kept as part of routine business practices. The 43.9% (36/82) recruitment rate was more than expected. Most artists completed the baseline questionnaires in 15 min, a weekly questionnaire in <2 min and a daily questionnaire in <1 min. We improved the formatting of some questions during the study, and adapted the wording of other questions to improve clarity. There were no dropouts during the entire study, suggesting the questionnaires were appropriate in content and length. Results for sample size calculations depend on the number of artists followed and the minimal important difference in injury rates, but in general, preclude a purely prospective study with daily data collection because of the long follow-up required. However, a prospective nested case-crossover design with data collection bi-weekly and at the time of injury appears feasible. A prospective study collecting psychological state data from subjects who train and work regularly together is feasible, but sample size calculations suggest that the optimal study design would use prospective nested case-crossover methodology.

Procedures for assessing psychological predictors of injuries in circus artists: a pilot prospective study

PubMed Central

2014-01-01

Background Research on psychological risk factors for injury has focused on stable traits. Our objective was to test the feasibility of a prospective longitudinal study designed to examine labile psychological states as risk factors of injury. Methods We measured psychological traits at baseline (mood, ways of coping and anxiety), and psychological states every day (1-item questions on anxiety, sleep, fatigue, soreness, self-confidence) before performances in Cirque du Soleil artists of the show “O”. Additional questions were added once per week to better assess anxiety (20-item) and mood. Questionnaires were provided in English, French, Russian and Japanese. Injury and exposure data were extracted from electronic records that are kept as part of routine business practices. Results The 43.9% (36/82) recruitment rate was more than expected. Most artists completed the baseline questionnaires in 15 min, a weekly questionnaire in <2 min and a daily questionnaire in <1 min. We improved the formatting of some questions during the study, and adapted the wording of other questions to improve clarity. There were no dropouts during the entire study, suggesting the questionnaires were appropriate in content and length. Results for sample size calculations depend on the number of artists followed and the minimal important difference in injury rates, but in general, preclude a purely prospective study with daily data collection because of the long follow-up required. However, a prospective nested case-crossover design with data collection bi-weekly and at the time of injury appears feasible. Conclusion A prospective study collecting psychological state data from subjects who train and work regularly together is feasible, but sample size calculations suggest that the optimal study design would use prospective nested case-crossover methodology. PMID:24920527

Control of Meiotic Crossovers: From Double-Strand Break Formation to Designation

PubMed Central

Gray, Stephen

2017-01-01

Meiosis, the mechanism of creating haploid gametes, is a complex cellular process observed across sexually reproducing organisms. Fundamental to meiosis is the process of homologous recombination, whereby DNA double-strand breaks are introduced into the genome and are subsequently repaired to generate either noncrossovers or crossovers. Although homologous recombination is essential for chromosome pairing during prophase I, the resulting crossovers are critical for maintaining homolog interactions and enabling accurate segregation at the first meiotic division. Thus, the placement, timing, and frequency of crossover formation must be exquisitely controlled. In this review, we discuss the proteins involved in crossover formation, the process of their formation and designation, and the rules governing crossovers, all within the context of the important landmarks of prophase I. We draw together crossover designation data across organisms, analyze their evolutionary divergence, and propose a universal model for crossover regulation. PMID:27648641

Investigation of iron spin crossover pressure in Fe-bearing MgO using hybrid functional

NASA Astrophysics Data System (ADS)

Cheng, Ya; Wang, Xianlong; Zhang, Jie; Yang, Kaishuai; Zhang, Chuanguo; Zeng, Zhi; Lin, Haiqin

2018-04-01

Pressure-induced spin crossover behaviors of Fe-bearing MgO were widely investigated by using an LDA  +  U functional for describing the strongly correlated Fe–O bonding. Moreover, the simulated spin crossover pressures depend on the applied U values, which are sensitive to environments and parameters. In this work, the spin crossover pressures of (Mg1‑x ,Fe x )O are investigated by using the hybrid functional with a uniform parameter. Our results indicate that the spin crossover pressures increase with increasing iron concentration. For example, the spin crossover pressure of (Mg0.03125,Fe0.96875)O and FeO was 56 GPa and 127 GPa, respectively. The calculated crossover pressures agreed well with the experimental observations. Therefore, the hybrid functional should be an effective method for describing the pressure-induced spin crossover behaviors in transition metal oxides.

Efficacy and tolerability of ramelteon in a double-blind, placebo-controlled, crossover study in Japanese patients with chronic primary insomnia.

PubMed

Kohsaka, Masako; Kanemura, Takashi; Taniguchi, Mitsutaka; Kuwahara, Hiroo; Mikami, Akira; Kamikawa, Kunihisa; Uno, Hideki; Ogawa, Atsushi; Murasaki, Mitsukuni; Sugita, Yoshiro

2011-10-01

The aim of this study was to evaluate the efficacy and safety of ramelteon 4, 8, 16 or 32 mg and placebo in Japanese patients with chronic insomnia using a randomized, double-blind, five-period crossover design. A total of 65 Japanese patients with chronic primary insomnia received ramelteon or placebo for two nights each in sleep laboratories. Changes in sleep parameters were assessed objectively by polysomnography and subjectively by postsleep questionnaires. Safety and tolerability was evaluated by assessment of the occurrence of adverse events, next-day residual effects and laboratory and ECG investigations. Ramelteon 8 and 32 mg significantly shortened the mean latency to persistent sleep in comparison with placebo, and there was a statistically significant trend for linear dose-response for this sleep parameter. Overall changes in sleep architecture were modest (<3% changes vs placebo), with increases in stage 1 and decreases in stage 3/4. Ramelteon was well tolerated, the most common adverse effect being somnolence, which was similar to placebo at doses up to 8 mg, but increased with higher doses. Next-day residual effects occurred no more frequently with ramelteon at any dose than with placebo. When compared with sleep latency data from a similarly-designed US study, there was no evidence of any ethnic differences in the efficacy of ramelteon between Japanese and US patients. Overall, ramelteon 8 mg showed the most favorable balance between sleep-promoting effects and tolerability. The unique efficacy profile of ramelteon, promoting sleep initiation without affecting other sleep parameters, may be due to its circadian shifting effect.

Academic Crossover Study, University of Hawaii Community Colleges, Fall 1999.

ERIC Educational Resources Information Center

Hawaii Univ., Honolulu. Office of the Chancellor for Community Colleges.

The academic crossover study was developed to answer two questions: (1) What is the course-taking pattern of the different groups of academic majors? (e.g. what is proportion of academic load taken outside the major); and (2) What is the client-serving pattern of the different subject disciplines? (e.g. what are the groups of students served by…

Good Effective School Improvement Practices in Spain.

ERIC Educational Resources Information Center

Murillo, F. Javier

2002-01-01

Presents case studies of five effective school improvement (ESI) programs developed in Spain. Identified characteristics of the Spanish education system that affect the way ESI programs are carried out and developed descriptions of the five programs and lessons learned from them. (SLD)

Randomized, blinded, placebo- and positive-controlled crossover study to determine the effect of multiple doses of apixaban on the QTc interval.

PubMed

Frost, Charles; Nepal, Sunil; Byon, Wonkyung; Moore, Kenneth; Reeves, Richard A; Boyd, Rebecca; LaCreta, Frank

2015-05-01

Apixaban is an oral, direct factor Xa inhibitor indicated for the prevention and treatment of thromboembolic disease. This randomized, blinded, 4-way crossover study investigated the potential effect of apixaban on the QTc interval. Forty healthy subjects (39 completers) each received 3 days of the following treatments: blinded apixaban 10 mg once daily (QD), 50 mg QD (supratherapeutic), matched apixaban placebo QD, and a single dose of open-label moxifloxacin 400 mg on Day 3, preceded by 2 days of placebo QD. Triplicate electrocardiograms obtained over 24 hours on Days -1 (baseline) and 3 were read by a blinded third party. The mean placebo-adjusted, time-matched, Fridericia-corrected change from baseline QTc (ΔΔQTcF) for apixaban and moxifloxacin was estimated at each time point. The maximum ΔΔQTcF was 1.51 milliseconds (one-sided upper 95% confidence interval [CI] 3.71 milliseconds) after apixaban 50 mg QD, 1.36 milliseconds (one-sided upper 95%CI 3.54 milliseconds) after apixaban 10 mg QD, and 10.21 milliseconds (lower 95%CI 8.07 milliseconds) after moxifloxacin. Concentration-response analysis suggested no evidence of a positive relationship between apixaban concentration and ΔQTcF. Apixaban doses up to 50 mg QD for 3 days were well tolerated and did not prolong the QTc interval in healthy subjects. © 2015, The American College of Clinical Pharmacology.

The Satiating Properties of Pork are not Affected by Cooking Methods, Sousvide Holding Time or Mincing in Healthy Men—A Randomized Cross-Over Meal Test Study

PubMed Central

Kehlet, Ursula; Mitra, Bhaskar; Aaslyng, Margit D.

2017-01-01

Low temperature long time (LTLT) sous-vide cooking may modify meat proteins in a way that could promote satiety. We investigated the effects of (1) cooking method (LTLT 58 °C vs. oven 160 °C), (2) LTLT holding time (17 h vs. 72 min), and (3) pork structure, LTLT 58 °C for 17 h (minced vs. roast) on appetite regulation and in vitro protein digestibility. In a cross-over study, 37 healthy men consumed four meals containing pork: LTLT-cooked roast, 58 °C, 72 min; LTLT-cooked roast, 58 °C, 17 h; and, oven-cooked roast, 160 °C to a core temperature of 58 °C and LTLT-cooked minced patties, 58 °C, 17 h. Ad libitum energy intake (EI) after three hours was the primary endpoint. Moreover, subjective appetite sensations were assessed. Protein digestibility was determined in an in vitro simulated digestion model. Ad libitum EI did not differ between the meals. Furthermore, appetite ratings were not clearly affected. LTLT cooking for 72 min increased the proteolytic rate in the early gastric phase during digestion as compared to LTLT cooking for 17 h or oven cooking. In conclusion, LTLT cooking, LTLT holding time, and pork structure did not affect ad libitum EI. However, LTLT cooking at 58 °C for 72 min seemed to enhance in vitro protein digestibility. PMID:28846600

The Satiating Properties of Pork are not Affected by Cooking Methods, Sousvide Holding Time or Mincing in Healthy Men-A Randomized Cross-Over Meal Test Study.

PubMed

Kehlet, Ursula; Mitra, Bhaskar; Ruiz Carrascal, Jorge; Raben, Anne; Aaslyng, Margit D

2017-08-26

Low temperature long time (LTLT) sous-vide cooking may modify meat proteins in a way that could promote satiety. We investigated the effects of (1) cooking method (LTLT 58 °C vs. oven 160 °C), (2) LTLT holding time (17 h vs. 72 min), and (3) pork structure, LTLT 58 °C for 17 h (minced vs. roast) on appetite regulation and in vitro protein digestibility. In a cross-over study, 37 healthy men consumed four meals containing pork: LTLT-cooked roast, 58 °C, 72 min; LTLT-cooked roast, 58 °C, 17 h; and, oven-cooked roast, 160 °C to a core temperature of 58 °C and LTLT-cooked minced patties, 58 °C, 17 h. Ad libitum energy intake (EI) after three hours was the primary endpoint. Moreover, subjective appetite sensations were assessed. Protein digestibility was determined in an in vitro simulated digestion model. Ad libitum EI did not differ between the meals. Furthermore, appetite ratings were not clearly affected. LTLT cooking for 72 min increased the proteolytic rate in the early gastric phase during digestion as compared to LTLT cooking for 17 h or oven cooking. In conclusion, LTLT cooking, LTLT holding time, and pork structure did not affect ad libitum EI. However, LTLT cooking at 58 °C for 72 min seemed to enhance in vitro protein digestibility.

Effects of breaking up sitting on adolescents' postprandial glucose after consuming meals varying in energy: a cross-over randomised trial.

PubMed

Fletcher, Elly A; Salmon, Jo; McNaughton, Sarah A; Orellana, Liliana; Wadley, Glenn D; Bruce, Clinton; Dempsey, Paddy C; Lacy, Kathleen E; Dunstan, David W

2018-03-01

To explore the impact of uninterrupted sitting versus sitting with resistance-type activity breaks on adolescents' postprandial glucose responses while consuming a diet varying in energy. Cross-over randomised trial. Thirteen healthy participants (16.4±1.3years) completed a four-treatment cross-over trial: (1) uninterrupted sitting+high-energy diet; (2) sitting with breaks+high-energy diet; (3) uninterrupted sitting+standard-energy diet; and (4) sitting with breaks+standard-energy diet. For all four conditions, two identical meals were consumed; at 0h and 3h. A continuous glucose monitoring system (CGM) recorded interstitial glucose concentrations every five minutes. Linear mixed models examined differences in glucose positive incremental area under the curve (iAUC) and total AUC between the sitting and diet conditions for the first meal, second meal and entire trial period. Compared to the uninterrupted sitting conditions, the breaks condition elicited a 36.0mmol/L/h (95%CI 6.6-65.5) and 35.9mmol/L/h (95%CI 6.6-65.5) lower iAUC response after the first and second meal, respectively, but not for the entire trial period or for total AUC. Compared to the standard-energy diet, the high-energy diet elicited a 55.0mmol/L/h (95%CI 25.8-84.2) and 75.7mmol/L/h (95%CI 8.6-142.7) higher iAUC response after the first meal and entire trial, respectively. Similar response to the high-energy diet were observed for total AUC. According to iAUC, interrupting sitting had a significant effect on lowering postprandial glucose for both dietary conditions, however, it was not significant when examining total AUC. Larger studies are needed to confirm these findings. ACTRN12615001145594. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Residual effects of middle-of-the-night administration of zaleplon and zolpidem on driving ability, memory functions, and psychomotor performance.

PubMed

Verster, Joris C; Volkerts, Edmund R; Schreuder, Antonia H C M L; Eijken, Erik J E; van Heuckelum, Janet H G; Veldhuijzen, Dieuwke S; Verbaten, Marinus N; Paty, Isabelle; Darwish, Mona; Danjou, Philippe; Patat, Alain

2002-12-01

Thirty healthy volunteers participated in this two-part study. Part 1 was a single-blind, two-period crossover design to determine the effects of a single dose of ethanol (0.03% < BAC < 0.05%) or ethanol-placebo on driving ability, memory, and psychomotor performance. Part 2 was a double-blind, five-period crossover design to measure the effects of a middle-of-the-night administration of zaleplon 10 or 20 mg, zolpidem 10 or 20 mg, or placebo on driving ability 4 hours after administration and memory and psychomotor performance 6 hours after administration. The on-the-road driving test consisted of operating an instrumented automobile over a 100-km highway circuit at a constant speed (95 km/h) while maintaining a steady lateral position between the right lane boundaries. The standard deviation of lateral position (SDLP) was the primary performance parameter of the driving test. The psychomotor and memory test battery consisted of the Word Learning Test, the Critical Tracking Test, the Divided Attention Test, and the Digit Symbol Substitution Test. Data for each part were analyzed separately using ANOVA for crossover designs. Zaleplon 10 and 20 mg did not significantly impair driving ability 4 hours after middle-of-the-night administration. Relative to placebo, after zolpidem 10 mg, SDLP was significantly elevated, but the magnitude of the difference was small and not likely to be of clinical importance. Memory and psychomotor test performance was unaffected after both doses of zaleplon and zolpidem 10 mg. In contrast, zolpidem 20 mg significantly increased SDLP and speed variability. Further, zolpidem 20 mg significantly impaired performance on all psychomotor and memory tests. Finally, driving performance, Digit Symbol Substitution Test, Divided Attention Test, and immediate and delayed free recall of the Word Learning Test were significantly impaired after ethanol. The results show that zaleplon (10 and 20 mg) is a safe hypnotic devoid of next-morning residual impairment when used in the middle of the night.

Chorionic gonadotropin in weight control. A double-blind crossover study.

PubMed

Young, R L; Fuchs, R J; Woltjen, M J

1976-11-29

Two hundred two patients participated in a double-blind random cross-over study of the effectiveness of human chorionic gonadotropin (HCG) vs placebo in a wieght reduction program. Serial measurements were made of weight, skin-fold thickness, dropout rates, reasons for dropping out, and patient subjective response. There was no statistically significant difference between those receiving HCG vs placebo during any phase of this study (P greater than .1).

Video-game based therapy performed by children with cerebral palsy: a cross-over randomized controlled trial and a cross-sectional quantitative measure of physical activity.

PubMed

Zoccolillo, L; Morelli, D; Cincotti, F; Muzzioli, L; Gobbetti, T; Paolucci, S; Iosa, M

2015-12-01

Previous studies reported controversial results about the efficacy of video-game based therapy (VGT) in improving neurorehabilitation outcomes in children with cerebral palsy (CP). Primary aim was to investigate the effectiveness of VGT with respect to conventional therapy (CT) in improving upper limb motor outcomes in a group of children with CP. Secondary aim was to quantify if VGT leads children to perform a higher number of movements. A cross-over randomized controlled trial (RCT) for investigating the primary aim and a cross-sectional study for investigating the secondary aim of this study. Outpatients. clinical diagnosis of CP, age between 4 and 14 years, level of GMFC between I and IV. QI<35, severe comorbidities, incapacity to stand even with an external support. Twenty-two children with CP (6.89±1.91-year old) were enrolled in a cross-over RCT with 16 sessions of VGT (using Xbox with Kinect device) and then 16 of CT or vice versa. Upper limb functioning was assessed using the Quality of Upper Extremities Skills Test (QUEST) and hand abilities using Abilhand-kids score. According to the secondary aim of this study a secondary cross-sectional study has been performed. Eight children with CP (6.50±1.60-year old) were enrolled into a trial in which five wireless triaxial accelerometers were positioned on their forearms, legs and trunk for quantifying the physical activity during VGT vs. CT. QUEST scores significantly improved only after VGT (P=0.003), and not after CT (P=0.056). The reverse occurred for Abilhand-kids scores (P=0.165 vs. P=0.013, respectively). Quantity of performed movements was three times higher in VGT than in CT (+198%, P=0.027). VGT resulted effective in improving the motor functions of upper limb extremities in children with CP, conceivably for the increased quantity of limb movements, but failed in improving the manual abilities for performing activities of daily living which benefited more from CT. VGT performed using the X-Box with Kinect device could enhance the number of upper limb movements in children with CP during rehabilitation and in turn improving upper limb motor skills, but CT remained superior for improving performances in manual activities of daily living.

Home-based balance training using the Wii balance board: a randomized, crossover pilot study in multiple sclerosis.

PubMed

Prosperini, Luca; Fortuna, Deborah; Giannì, Costanza; Leonardi, Laura; Marchetti, Maria Rita; Pozzilli, Carlo

2013-01-01

To evaluate the effectiveness of a home-based rehabilitation of balance using the Nintendo Wii Balance Board System (WBBS) in patients affected by multiple sclerosis (MS). In this 24-week, randomized, 2-period crossover pilot study, 36 patients having an objective balance disorder were randomly assigned in a 1:1 ratio to 2 counterbalanced arms. Group A started a 12-week period of home-based WBBS training followed by a 12-week period without any intervention; group B received the treatment in reverse order. As endpoints, we considered the mean difference (compared with baseline) in force platform measures (i.e., the displacement of body center of pressure in 30 seconds), 4-step square test (FSST), 25-foot timed walking test (25-FWT), and 29-item MS Impact Scale (MSIS-29), as evaluated after 12 weeks and at the end of the 24-week study period. The 2 groups did not differ in baseline characteristics. Repeated-measures analyses of variance showed significant time × treatment effects, indicating that WBBS was effective in ameliorating force platform measures (F = 4.608, P = .016), FSST (F = 3.745, P = .034), 25-FWT (F = 3.339, P = .048), and MSIS-29 (F = 4.282, P = .023). Five adverse events attributable to the WBSS training (knee or low back pain) were recorded, but only 1 patient had to retire from the study. A home-based WBBS training might potentially provide an effective, engaging, balance rehabilitation solution for people with MS. However, the risk of WBBS training-related injuries should be carefully balanced with benefits. Further studies, including cost-effectiveness analyses, are warranted to establish whether WBBS may be useful in the home setting.

Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study.

PubMed

Hoang, Thanh D; Olsen, Cara H; Mai, Vinh Q; Clyde, Patrick W; Shakir, Mohamed K M

2013-05-01

Patients previously treated with desiccated thyroid extract (DTE), when being switched to levothyroxine (L-T₄), occasionally did not feel as well despite adequate dosing based on serum TSH levels. Our objective was to investigate the effectiveness of DTE compared with L-T₄ in hypothyroid patients. We conducted a randomized, double-blind, crossover study at a tertiary care center. Patients (n = 70, age 18-65 years) diagnosed with primary hypothyroidism on a stable dose of L-T₄ for 6 months were included in the study. Patients were randomized to either DTE or L-T₄ for 16 weeks and then crossed over for the same duration. Biochemical and neurocognitive tests at baseline and at the end of each treatment period were evaluated. There were no differences in symptoms and neurocognitive measurements between the 2 therapies. Patients lost 3 lb on DTE treatment (172.9 ± 36.4 lb vs 175.7 ± 37.7 lb, P < .001). At the end of the study, 34 patients (48.6%) preferred DTE, 13 (18.6%) preferred L-T₄, and 23 (32.9%) had no preference. In the subgroup analyses, those patients who preferred DTE lost 4 lb during the DTE treatment, and their subjective symptoms were significantly better while taking DTE as measured by the general health questionnaire-12 and thyroid symptom questionnaire (P < .001 for both). Five variables were predictors of preference for DTE. DTE therapy did not result in a significant improvement in quality of life; however, DTE caused modest weight loss and nearly half (48.6%) of the study patients expressed preference for DTE over L-T₄. DTE therapy may be relevant for some hypothyroid patients.

Short, frequent, 5-days-per-week, in-center hemodialysis versus 3-days-per week treatment: a randomized crossover pilot trial through the Midwest Pediatric Nephrology Consortium.

PubMed

Laskin, Benjamin L; Huang, Guixia; King, Eileen; Geary, Denis F; Licht, Christoph; Metlay, Joshua P; Furth, Susan L; Kimball, Tom; Mitsnefes, Mark

2017-08-01

No controlled trials in children with end-stage kidney disease have assessed the benefits of more frequently administered hemodialysis (HD). We conducted a multicenter, crossover pilot trial to determine if short, more frequent (5 days per week) in-center HD was feasible and associated with improvements in blood pressure compared with three conventional HD treatments per week. Because adult studies have not controlled for the weekly duration of dialysis, we fixed the total treatment time at 12 h a week of dialysis during two 3-month study periods; only frequency varied from 5 to 3 days per week between study periods. Eight children (median age 16.7 years) consented at three children's hospitals. The prespecified primary composite outcome was a sustained 10% decrease in systolic blood pressure and/or a decrease in antihypertensive medications relative to each study period's baseline. Among the six patients completing both study periods, five (83.3%) experienced the primary outcome during HD performed 5 days per week but not 3 days per week; one of the six (16.7%) achieved that outcome during 3-day but not 5-day (p = 0.22) per week HD. During 5-day HD, all patients had significantly more treatments during which their pre-HD systolic (p = 0.01) or diastolic (p = 0.01) blood pressure was 10% lower than baseline. We observed that more frequent HD sessions per week was feasible and associated with improved blood pressure control, but barriers to changing thrice-weekly standard of care include financial reimbursement and the time demands associated with more frequent treatments.

Effects of lorazepam on visual perceptual abilities.

PubMed

Pompéia, S; Pradella-Hallinan, M; Manzano, G M; Bueno, O F A

2008-04-01

To evaluate the effects of an acute dose of the benzodiazepine (BZ) lorazepam in young healthy volunteers on five distinguishable visual perception abilities determined by previous factor-analytic studies. This was a double-blind, cross-over design study of acute oral doses of lorazepam (2 mg) and placebo in young healthy volunteers. We focused on a set of paper-and-pencil tests of visual perceptual abilities that load on five correlated but distinguishable factors (Spatial Visualization, Spatial Relations, Perceptual Speed, Closure Speed, and Closure Flexibility). Some other tests (DSST, immediate and delayed recall of prose; measures of subjective mood alterations) were used to control for the classic BZ-induced effects. Lorazepam impaired performance in the DSST and delayed recall of prose, increased subjective sedation and impaired tasks of all abilities except Spatial Visualization and Closure Speed. Only impairment in Perceptual Speed (Identical Pictures task) and delayed recall of prose were not explained by sedation. Acute administration of lorazepam, in a dose that impaired episodic memory, selectively affected different visual perceptual abilities before and after controlling for sedation. Central executive demands and sedation did not account for results, so impairment in the Identical Pictures task may be attributed to lorazepam's visual processing alterations. 2008 John Wiley & Sons, Ltd.

A two-step spin crossover mononuclear iron(II) complex with a [HS-LS-LS] intermediate phase.

PubMed

Bonnet, Sylvestre; Siegler, Maxime A; Costa, José Sánchez; Molnár, Gábor; Bousseksou, Azzedine; Spek, Anthony L; Gamez, Patrick; Reedijk, Jan

2008-11-21

The two-step spin crossover of a new mononuclear iron(ii) complex is studied by magnetic, crystallographic and calorimetric methods revealing two successive first-order phase transitions and an ordered intermediate phase built by the repetition of the unprecedented [HS-LS-LS] motif.

Isotretinoin conundrum: a randomized, openlabel, crossover study in Mexico to evaluate the bioavailability and bioequivalence of three pharmaceutical preparations of isotretinoin in healthy participants.

PubMed

Piñeyro-Garza, Everardo; Gómez-Silva, Magdalena; Gamino Peña, María Elena; Palmer, Jonathan; Berber, Arturo

2015-10-01

The oral retinoid agent isotretinoin (13-cis-retinoic acid) is approved for the treatment of severe recalcitrant cystic acne. For registrational renewal of Oratane® in Mexico (isotretinoin; Laboratorios Dermatologicos Darier S.A. de C.V., Mexico), it was necessary to establish bioequivalence to the reference product Roaccutan® (Isotretinoin; Roche, Mannheim, Germany). Three prior studies failed to establish the bioequivalence of Oratane to Mexican-sourced Roaccutan. However, 13 studies demonstrated the bioequivalence of Oratane to Roaccutane® from multiple sources. This study compared the bioavailability of Oratane with that of Mexicansourced Roaccutan and Australian-sourced Roaccutane. Study participants received each of the three agents in a randomized, open-label, 6-sequence, 3-way crossover study with a 2-week washout period between treatments. Pharmacokinetic analysis revealed that peak plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 (dosing) to infinite time (AUC0-∞) were lower for Roaccutan than for Roaccutane and Oratane (Cmax: 1,023.35, 1,223.08, and 1,224.25 ng/mL, respectively; AUC0-∞: 13,653.65, 15,681.35 and 15,733.55 ng/mL x h, respectively). The 90% CIs (test/reference) for the ratios of the geometric means indicated that Oratane was bioequivalent to Roaccutane but not to Roaccutan. In addition, Roaccutane (R2) was not bioequivalent to Roaccutan (R1; R1/R2 90% CIs: Cmax, 76.12 - 91.04; AUC0-t, 82.19 - 91.13; AUC0-∞, 82.94 - 91.57). Oratane and Australian-sourced Roaccutane could be considered bioequivalent, but neither formulation was found to be bioequivalent to Mexican-sourced Roaccutan.

Women's Ways of Knowing in Information Technology-Related Subjects: A Community College Case Study

ERIC Educational Resources Information Center

Liu, Dejang

2011-01-01

Belenky et al. (1997) found five ways of women's knowing (silent knowing, receiving knowing, subjective knowing, procedural knowing, and constructed knowing) according to the study conducted on women who majored in the social sciences and liberal arts. This study is built on the same model found by Belenky et al.'s study to collect open-ended…

Core structure of two-dimensional Fermi gas vortices in the BEC-BCS crossover region

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

Madeira, Lucas; Gandolfi, Stefano; Schmidt, Kevin E.

2017-05-02

We report T = 0 diffusion Monte Carlo results for the ground-state and vortex excitation of unpolarized spin-1/2 fermions in a two-dimensional disk. We investigate how vortex core structure properties behave over the BEC-BCS crossover. We calculate the vortex excitation energy, density pro les, and vortex core properties related to the current. We nd a density suppression at the vortex core on the BCS side of the crossover and a depleted core on the BEC limit. Size-effect dependencies in the disk geometry were carefully studied.

Evaluating the effectiveness of personal response system technology on millennial student learning.

PubMed

McCurry, Mary K; Hunter Revell, Susan M

2011-08-01

As nurse educators, we must explore new technologies that capitalize on the characteristics of millennial learners. One such technology, the personal response system (PRS), is an effective way to promote active learning and increase comprehension. Few nursing studies have examined the benefits of PRS technology on student outcomes. The purpose of this study was to evaluate the effectiveness of PRS technology on learning outcomes in two sections of an undergraduate nursing research course. A crossover design compared class quiz averages between and within groups. Findings related to between and within class quiz scores were mixed, whereas the effectiveness of in-class PRS questions on paper-and-pencil quiz scores and PRS-targeted quiz items was significant. Knowledge gained from this study can be used to enhance our ability to actively engage our technologically savvy undergraduate students. By threading technology into the undergraduate curriculum, learning outcomes may be improved. Copyright 2011, SLACK Incorporated.

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

ERIC Educational Resources Information Center

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…

Challenging Fiction: Exploring Meaning-Making Processes in the Crossover between Social Media and Drama in Education

ERIC Educational Resources Information Center

Knudsen, Kristian Nødtvedt

2018-01-01

The aim of this study was to explore how meaning-making activity can be expressed and shaped in the crossover between drama in education and social media. This study concerns the use of empirical material from an educational drama project called #iLive, which was designed and implemented, on four different occasions with a total of 89 students…

Mutations in the N Terminus of the Brome Mosaic Virus Polymerase Affect Genetic RNA-RNA Recombination

PubMed Central

Figlerowicz, M.; Nagy, P. D.; Tang, N.; Kao, C. C.; Bujarski, J. J.

1998-01-01

Previously, we have observed that mutations in proteins 1a and 2a, the two virally encoded components of the brome mosaic virus (BMV) replicase, can affect the frequency of recombination and the locations of RNA recombination sites (P. D. Nagy, A. Dzianott, P. Ahlquist, and J. J. Bujarski, J. Virol. 69:2547–2556, 1995; M. Figlerowicz, P. D. Nagy, and J. J. Bujarski, Proc. Natl. Acad. Sci. USA 94:2073–2078, 1997). Also, it was found before that the N-terminal domain of 2a, the putative RNA polymerase protein, participates in the interactions between 1a and 2a (C. C. Kao, R. Quadt, R. P. Hershberger, and P. Ahlquist, J. Virol. 66:6322–6329, 1992; E. O’Reilly, J. Paul, and C. C. Kao, J. Virol. 71:7526–7532, 1997). In this work, we examine how mutations within the N terminus of 2a influence RNA recombination in BMV. Because of the likely electrostatic character of 1a-2a interactions, five 2a mutants, MF1 to MF5, were generated by replacing clusters of acidic amino acids with their neutral counterparts. MF2 and MF5 retained nearly wild-type levels of 1a-2a interaction and were infectious in Chenopodium quinoa. However, compared to that in wild-type virus, the frequency of nonhomologous recombination in both MF2 and MF5 was markedly decreased. Only in MF2 was the frequency of homologous recombination reduced and the occurrence of imprecise homologous recombination increased. In MF5 there was also a 3′ shift in the positions of homologous crossovers. The observed effects of MF2 and MF5 reveal that the 2a N-terminal domain participates in different ways in homologous and in nonhomologous BMV RNA recombination. This work maps specific locations within the N terminus involved in 1a-2a interaction and in recombination and further suggests that the mechanisms of the two types of crossovers in BMV are different. PMID:9765466

Mutations in the N terminus of the brome mosaic virus polymerase affect genetic RNA-RNA recombination.

PubMed

Figlerowicz, M; Nagy, P D; Tang, N; Kao, C C; Bujarski, J J

1998-11-01

Previously, we have observed that mutations in proteins 1a and 2a, the two virally encoded components of the brome mosaic virus (BMV) replicase, can affect the frequency of recombination and the locations of RNA recombination sites (P. D. Nagy, A. Dzianott, P. Ahlquist, and J. J. Bujarski, J. Virol. 69:2547-2556, 1995; M. Figlerowicz, P. D. Nagy, and J. J. Bujarski, Proc. Natl. Acad. Sci. USA 94:2073-2078, 1997). Also, it was found before that the N-terminal domain of 2a, the putative RNA polymerase protein, participates in the interactions between 1a and 2a (C. C. Kao, R. Quadt, R. P. Hershberger, and P. Ahlquist, J. Virol. 66:6322-6329, 1992; E. O'Reilly, J. Paul, and C. C. Kao, J. Virol. 71:7526-7532, 1997). In this work, we examine how mutations within the N terminus of 2a influence RNA recombination in BMV. Because of the likely electrostatic character of 1a-2a interactions, five 2a mutants, MF1 to MF5, were generated by replacing clusters of acidic amino acids with their neutral counterparts. MF2 and MF5 retained nearly wild-type levels of 1a-2a interaction and were infectious in Chenopodium quinoa. However, compared to that in wild-type virus, the frequency of nonhomologous recombination in both MF2 and MF5 was markedly decreased. Only in MF2 was the frequency of homologous recombination reduced and the occurrence of imprecise homologous recombination increased. In MF5 there was also a 3' shift in the positions of homologous crossovers. The observed effects of MF2 and MF5 reveal that the 2a N-terminal domain participates in different ways in homologous and in nonhomologous BMV RNA recombination. This work maps specific locations within the N terminus involved in 1a-2a interaction and in recombination and further suggests that the mechanisms of the two types of crossovers in BMV are different.

A compartmentalized signaling network mediates crossover control in meiosis

PubMed Central

Zhang, Liangyu; Köhler, Simone; Rillo-Bohn, Regina

2018-01-01

During meiosis, each pair of homologous chromosomes typically undergoes at least one crossover (crossover assurance), but these exchanges are strictly limited in number and widely spaced along chromosomes (crossover interference). The molecular basis for this chromosome-wide regulation remains mysterious. A family of meiotic RING finger proteins has been implicated in crossover regulation across eukaryotes. Caenorhabditis elegans expresses four such proteins, of which one (ZHP-3) is known to be required for crossovers. Here we investigate the functions of ZHP-1, ZHP-2, and ZHP-4. We find that all four ZHP proteins, like their homologs in other species, localize to the synaptonemal complex, an unusual, liquid crystalline compartment that assembles between paired homologs. Together they promote accumulation of pro-crossover factors, including ZHP-3 and ZHP-4, at a single recombination intermediate, thereby patterning exchanges along paired chromosomes. These proteins also act at the top of a hierarchical, symmetry-breaking process that enables crossovers to direct accurate chromosome segregation. PMID:29521627

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

PubMed

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. Copyright © 2012. Published by Elsevier Inc.

The Effects of Aroma Foot Massage on Blood Pressure and Anxiety in Japanese Community-Dwelling Men and Women: A Crossover Randomized Controlled Trial

PubMed Central

Tomooka, Kiyohide; Ohira, Tetsuya; Ogino, Keiki; Tanigawa, Takeshi

2016-01-01

Objectives The aim of this study was to investigate the effects of aroma foot massage on blood pressure, anxiety, and health-related quality of life (QOL) in Japanese community-dwelling men and women using a crossover randomized controlled trial. Methods Fifty-seven eligible participants (5 men and 52 women) aged 27 to 72 were randomly divided into 2 intervention groups (group A: n = 29; group B: n = 28) to participate in aroma foot massages 12 times during the 4-week intervention period. Systolic and diastolic blood pressure (SBP and DBP, respectively), heart rate, state anxiety, and health-related QOL were measured at the baseline, 4-week follow-up, and 8-week follow-up. The effects of the aroma foot massage intervention on these factors and the proportion of participants with anxiety were analyzed using a linear mixed-effect model for a crossover design adjusted for participant and period effects. Furthermore, the relationship between the changes in SBP and state anxiety among participants with relieved anxiety was assessed using a linear regression model. Results Aroma foot massage significantly decreased the mean SBP (p = 0.02), DBP (p = 0.006), and state anxiety (p = 0.003) as well as the proportion of participants with anxiety (p = 0.003). Although it was not statistically significant (p = 0.088), aroma foot massage also increased the score of mental health-related QOL. The change in SBP had a significant and positive correlation with the change in state anxiety (p = 0.01) among participants with relieved anxiety. Conclusion The self-administered aroma foot massage intervention significantly decreased the mean SBP and DBP as well as the state anxiety score, and tended to increase the mental health-related QOL scores. The results suggest that aroma foot massage may be an easy and effective way to improve mental health and blood pressure. Trial Registration University Hospital Medical Information Network 000014260 PMID:27010201

The Effects of Aroma Foot Massage on Blood Pressure and Anxiety in Japanese Community-Dwelling Men and Women: A Crossover Randomized Controlled Trial.

PubMed

Eguchi, Eri; Funakubo, Narumi; Tomooka, Kiyohide; Ohira, Tetsuya; Ogino, Keiki; Tanigawa, Takeshi

2016-01-01

The aim of this study was to investigate the effects of aroma foot massage on blood pressure, anxiety, and health-related quality of life (QOL) in Japanese community-dwelling men and women using a crossover randomized controlled trial. Fifty-seven eligible participants (5 men and 52 women) aged 27 to 72 were randomly divided into 2 intervention groups (group A: n = 29; group B: n = 28) to participate in aroma foot massages 12 times during the 4-week intervention period. Systolic and diastolic blood pressure (SBP and DBP, respectively), heart rate, state anxiety, and health-related QOL were measured at the baseline, 4-week follow-up, and 8-week follow-up. The effects of the aroma foot massage intervention on these factors and the proportion of participants with anxiety were analyzed using a linear mixed-effect model for a crossover design adjusted for participant and period effects. Furthermore, the relationship between the changes in SBP and state anxiety among participants with relieved anxiety was assessed using a linear regression model. Aroma foot massage significantly decreased the mean SBP (p = 0.02), DBP (p = 0.006), and state anxiety (p = 0.003) as well as the proportion of participants with anxiety (p = 0.003). Although it was not statistically significant (p = 0.088), aroma foot massage also increased the score of mental health-related QOL. The change in SBP had a significant and positive correlation with the change in state anxiety (p = 0.01) among participants with relieved anxiety. The self-administered aroma foot massage intervention significantly decreased the mean SBP and DBP as well as the state anxiety score, and tended to increase the mental health-related QOL scores. The results suggest that aroma foot massage may be an easy and effective way to improve mental health and blood pressure. University Hospital Medical Information Network 000014260.

Comparison of application of various crossovers in solving inhomogeneous minimax problem modified by Goldberg model

NASA Astrophysics Data System (ADS)

Kobak, B. V.; Zhukovskiy, A. G.; Kuzin, A. P.

2018-05-01

This paper considers one of the classical NP complete problems - an inhomogeneous minimax problem. When solving such large-scale problem, there appear difficulties in obtaining an exact solution. Therefore, let us propose getting an optimum solution in an acceptable time. Among a wide range of genetic algorithm models, let us choose the modified Goldberg model, which earlier was successfully used by authors in solving NP complete problems. The classical Goldberg model uses a single-point crossover and a singlepoint mutation, which somewhat decreases the accuracy of the obtained results. In the article, let us propose using a full two-point crossover with various mutations previously researched. In addition, the work studied the necessary probability to apply it to the crossover in order to obtain results that are more accurate. Results of the computation experiment showed that the higher the probability of a crossover, the higher the quality of both the average results and the best solutions. In addition, it was found out that the higher the values of the number of individuals and the number of repetitions, the closer both the average results and the best solutions to the optimum. The paper shows how the use of a full two-point crossover increases the accuracy of solving an inhomogeneous minimax problem, while the time for getting the solution increases, but remains polynomial.

Principal Sensemaking of Inclusion: A Multi-Case Study of Five Urban School Principals

ERIC Educational Resources Information Center

DeMatthews, David Edward

2012-01-01

This study examined how five principals working in one urban school district made sense of inclusion. I employed a multi-case study guided by the theoretical framework of sensemaking. Weick's sensemaking theory was useful in examining the way principals made sense of inclusion. Each of the seven characteristics of Weick's sensemaking…

Individual and crossover effects of stress on adjustment in medical student marriages.

PubMed

Katz, J; Monnier, J; Libet, J; Shaw, D; Beach, S R

2000-07-01

High-stress individuals may benefit from social support, although their support providers may be adversely affected via stress crossover effects. Individual and crossover effects of perceived stress within medical student marriages (n = 30) were investigated. Perceived spousal support was positively associated with individuals' own marital and emotional adjustment, attenuating stress effects. With regard to crossover effects, medical students' perceived stress was significantly associated with their spouses' emotional adjustment. Further, medical students' own emotional adjustment fully mediated this crossover effect. Results suggest that the contagion of negative affect may serve as a key mechanism through which stress crossover effects operate in marriage.

Evaluation of the Safety, Tolerability, and Pharmacokinetics of Gammaplex® 10% Versus Gammaplex® 5% in Subjects with Primary Immunodeficiency.

PubMed

Wasserman, Richard L; Melamed, Isaac R; Stein, Mark R; Jolles, Stephen; Norton, Miranda; Moy, James N

2017-04-01

This phase 3, multicenter, open-label, randomized, two-period, crossover bioequivalence trial evaluated the safety, tolerability, and pharmacokinetics of intravenous immunoglobulins (IVIGs) Gammaplex 5% and Gammaplex 10% in 33 adults and 15 children with primary immunodeficiency diseases (PIDs). Eligible adults received five Gammaplex 5% infusions followed by five Gammaplex 10% infusions, or vice versa, stratified by a 21- or 28-day dosing regimen. Pediatric subjects received five Gammaplex 10% infusions only. The primary objective, to demonstrate the bioequivalence of Gammaplex 10% and Gammaplex 5% at the 28-day dosing interval, was met based on the Gammaplex 10%/Gammaplex 5% ratio of area under the concentration versus time curve (AUC 0-28 ) values. Throughout the study, total immunoglobulin G trough levels were well maintained, with total values generally ≥600 mg/dL (minimum level for study inclusion). At the dosing schedules and infusion rates used in this study, safety and tolerability were comparable and acceptable in adult and pediatric PID subjects treated with Gammaplex 10% and 5%. In this study, the first direct comparison of 5% IVIG and 10% IVIG products in PID subjects, the pharmacokinetic analysis demonstrated bioequivalence of Gammaplex 10% and Gammaplex 5% at the 28-day dosing interval. The Gammaplex 10% formulation was safe and well tolerated in pediatric and adult PID subjects. Based on the results from this bridging study in PID subjects, Gammaplex 10% could be expected to have a therapeutic effect similar to the licensed Gammaplex 5%, which has demonstrated efficacy and tolerability in patients with PID and idiopathic thrombocytopenic purpura.

Two Formulations of Venlafaxine are Bioequivalent when Administered as Open Capsule Mixed with Applesauce to Healthy Subjects.

PubMed

Jain, Renu T; Panda, J; Srivastava, A

2011-09-01

Venlafaxine is a unique antidepressant approved for treatment of various depressive disorders. A single dose, cross-over bioequivalence study was performed with two different formulations of venlafaxine 150 mg extended-release capsules in which the contents of capsule were mixed with applesauce and administered to healthy subjects under fed condition. A total of 24 healthy adult male subjects participated in this randomized, single-dose, non-blinded, two-way crossover study conducted at a single centre and 23 subjects completed the study as per the study protocol. After an overnight fast of 10 h, a high-fat and high-calorie breakfast was served 30 min before dosing. The subjects then received a single dose of either formulation administered with apple sauce followed by 240 ml of water as per randomized schedule in each period separated by a washout period of 7 days. A series of blood samples were collected upto 72 h for estimation of venlafaxine and its active metabolite, O-desmethylvenlafaxine. The quantification of venlafaxine and O-desmethylvenlafaxine was done by LC-MS/MS method and pharmacokinetic and statistical analysis by WinNonlin(®) 5.2 and SAS(®) 9.1.3. The results of the study demonstrated bioequivalence of two formulations as the 90% confidence interval for the intra-individual mean ratio of log-transformed C(max), AUC(0-t) and AUC(0-inf) of the test to the reference formulation were found within the defined bioequivalence range of 80.00%-125.00%. Both the formulations were well tolerated. This alternative mode of administration may provide benefits to patients who have difficulty in swallowing the capsule as a whole.

Two Formulations of Venlafaxine are Bioequivalent when Administered as Open Capsule Mixed with Applesauce to Healthy Subjects

PubMed Central

Jain, Renu T.; Panda, J.; Srivastava, A.

2011-01-01

Venlafaxine is a unique antidepressant approved for treatment of various depressive disorders. A single dose, cross-over bioequivalence study was performed with two different formulations of venlafaxine 150 mg extended-release capsules in which the contents of capsule were mixed with applesauce and administered to healthy subjects under fed condition. A total of 24 healthy adult male subjects participated in this randomized, single-dose, non-blinded, two-way crossover study conducted at a single centre and 23 subjects completed the study as per the study protocol. After an overnight fast of 10 h, a high-fat and high-calorie breakfast was served 30 min before dosing. The subjects then received a single dose of either formulation administered with apple sauce followed by 240 ml of water as per randomized schedule in each period separated by a washout period of 7 days. A series of blood samples were collected upto 72 h for estimation of venlafaxine and its active metabolite, O-desmethylvenlafaxine. The quantification of venlafaxine and O-desmethylvenlafaxine was done by LC-MS/MS method and pharmacokinetic and statistical analysis by WinNonlin® 5.2 and SAS® 9.1.3. The results of the study demonstrated bioequivalence of two formulations as the 90% confidence interval for the intra-individual mean ratio of log-transformed Cmax, AUC0-t and AUC0-inf of the test to the reference formulation were found within the defined bioequivalence range of 80.00%-125.00%. Both the formulations were well tolerated. This alternative mode of administration may provide benefits to patients who have difficulty in swallowing the capsule as a whole. PMID:22923863

Acute triggers of myocardial infarction: A case-crossover study.

PubMed

Ghiasmand, Maryam; Moghadamnia, Mohammad Taghi; Pourshaikhian, Majid; Kazemnejad Lili, Ehsan

2017-12-01

Acute myocardial infarction (AMI) is one of the most preventable non-communicable diseases in human. Identifying triggers of myocardial infarction (MI) and prevention ways of exposure-induced complications can reduce morbidity and mortality in people at risk. The aim of this study was to identify the emotional, environmental, physical and chemical dimensions of acute triggers in patients with AMI. This case-crossover study was conducted on 269 patients with AMI, hospitalized at two remedial centers in Rasht in 2015. The study samples were selected by convenient sampling method. Data were collected using researcher-made questionnaire through interviews. Hazard and control periods for each trigger and its effects on the development of MI were studied. The collected data were analyzed using descriptive and analytical statistical methods, Cochran test, and generalized estimating equation (GEE) model with logistics function default in SPSS version 21, and p  < 0.05 was considered statistically significant. The results showed that quarrel ( P  = 0.008, OR = 2.01) and hearing the sudden news ( P  = 0.001, OR = 2.19) were the most common emotional triggers. Respiratory infections ( P  = 0.0001, OR = 6.78) and exposure to hot or cold weather ( P  = 0.005, OR = 2.19) were the most frequent environmental triggers. Doing heavy activities ( P  = 0.005, OR = 1.66) and sexual activities ( P  = 0.003, OR = 2.36) were among the most common physical triggers. High-fat foods consumption and overeating ( P  = 0.0001, OR = 3.79) were the most frequent chemical triggers of AMI. It seems that given the importance of the triggers in the incidence of AMI, planning is necessary to train vulnerable individuals to reduce exposure to triggers.

Hadron-quark crossover and hot neutron stars at birth

NASA Astrophysics Data System (ADS)

Masuda, Kota; Hatsuda, Tetsuo; Takatsuka, Tatsuyuki

2016-02-01

We construct a new isentropic equation of state (EOS) at finite temperature, "CRover," on the basis of the hadron-quark crossover at high density. By using the new EOS, we study the structure of hot neutron stars at birth with typical lepton fraction (Y_l=0.3-0.4) and typical entropy per baryon (hat {S}=1{-}2). Due to the gradual appearance of quark degrees of freedom at high density, the temperature T and the baryon density ρ at the center of hot neutron stars with hadron-quark crossover are found to be smaller than those without the crossover by a factor of two or more. Typical energy release due to the contraction of a hot neutron star to a cold neutron star with mass M=1.4 M_{⊙} is shown to be about 0.04 M_{⊙}, with a spin-up rate of about 14%.

Tuning across the BCS-BEC crossover in superconducting Fe1+ySexTe1-x : An angle-resolved photoemission study

NASA Astrophysics Data System (ADS)

Rinott, Shahar; Ribak, Amit; Chashka, Khanan; Randeria, Mohit; Kanigel, Amit

The crossover from Bardeen-Cooper-Schrieffer (BCS) superconductivity to Bose-Einstein condensation (BEC) was never realized in quantum materials. It is difficult to realize because, unlike in ultra cold atoms, one cannot tune the pairing interaction. We realize the BCS-BEC crossover in a nearly compensated semimetal Fe1+ySexTe1-x by tuning the Fermi energy ɛF via chemical doping, which permits us to systematically change Δ /ɛF from 0 . 16 to 0 . 50 , where Δ is the superconducting (SC) gap. We use angle-resolved photoemission spectroscopy to measure the Fermi energy, the SC gap and characteristic changes in the SC state electronic dispersion as the system evolves from a BCS to a BEC regime. Our results raise important questions about the crossover in multi-band superconductors which go beyond those addressed in the context of cold atoms.

Low temperature thermoelectric properties of Bi2-xSbxTeSe2 crystals near the n-p crossover

NASA Astrophysics Data System (ADS)

Fuccillo, M. K.; Charles, M. E.; Hor, Y. S.; Jia, Shuang; Cava, R. J.

2012-07-01

Seebeck coefficients, electrical resistivities, thermal conductivities and figure of merit ZT of Bi2-xSbxTeSe2 crystals (x=0.8, 0.9, 1.0, 1.1, and 1.2) measured along the hexagonal basal plane are presented. The crystals gradually change from n- to p-type with increasing Sb content, with the crossover lying in the region between x=1.0 and 1.1. The crossover is accounted for by a simple (p-n) electron-hole compensation model, as supported by carrier concentrations determined from Hall measurements. ZT was found to be maximized near the crossover on the p-type side, with the high electrical resistance of the Se-rich crystals apparently the limiting factor in the performance. These materials may serve as a basis for future nanostructuring or doping studies.

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

PubMed

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 (c) 2016 APA, all rights reserved).

DNA methylation epigenetically silences crossover hot spots and controls chromosomal domains of meiotic recombination in Arabidopsis.

PubMed

Yelina, Nataliya E; Lambing, Christophe; Hardcastle, Thomas J; Zhao, Xiaohui; Santos, Bruno; Henderson, Ian R

2015-10-15

During meiosis, homologous chromosomes undergo crossover recombination, which is typically concentrated in narrow hot spots that are controlled by genetic and epigenetic information. Arabidopsis chromosomes are highly DNA methylated in the repetitive centromeres, which are also crossover-suppressed. Here we demonstrate that RNA-directed DNA methylation is sufficient to locally silence Arabidopsis euchromatic crossover hot spots and is associated with increased nucleosome density and H3K9me2. However, loss of CG DNA methylation maintenance in met1 triggers epigenetic crossover remodeling at the chromosome scale, with pericentromeric decreases and euchromatic increases in recombination. We used recombination mutants that alter interfering and noninterfering crossover repair pathways (fancm and zip4) to demonstrate that remodeling primarily involves redistribution of interfering crossovers. Using whole-genome bisulfite sequencing, we show that crossover remodeling is driven by loss of CG methylation within the centromeric regions. Using cytogenetics, we profiled meiotic DNA double-strand break (DSB) foci in met1 and found them unchanged relative to wild type. We propose that met1 chromosome structure is altered, causing centromere-proximal DSBs to be inhibited from maturation into interfering crossovers. These data demonstrate that DNA methylation is sufficient to silence crossover hot spots and plays a key role in establishing domains of meiotic recombination along chromosomes. © 2015 Yelina et al.; Published by Cold Spring Harbor Laboratory Press.

An alternative approach for neural network evolution with a genetic algorithm: crossover by combinatorial optimization.

PubMed

García-Pedrajas, Nicolás; Ortiz-Boyer, Domingo; Hervás-Martínez, César

2006-05-01

In this work we present a new approach to crossover operator in the genetic evolution of neural networks. The most widely used evolutionary computation paradigm for neural network evolution is evolutionary programming. This paradigm is usually preferred due to the problems caused by the application of crossover to neural network evolution. However, crossover is the most innovative operator within the field of evolutionary computation. One of the most notorious problems with the application of crossover to neural networks is known as the permutation problem. This problem occurs due to the fact that the same network can be represented in a genetic coding by many different codifications. Our approach modifies the standard crossover operator taking into account the special features of the individuals to be mated. We present a new model for mating individuals that considers the structure of the hidden layer and redefines the crossover operator. As each hidden node represents a non-linear projection of the input variables, we approach the crossover as a problem on combinatorial optimization. We can formulate the problem as the extraction of a subset of near-optimal projections to create the hidden layer of the new network. This new approach is compared to a classical crossover in 25 real-world problems with an excellent performance. Moreover, the networks obtained are much smaller than those obtained with classical crossover operator.

Effects of Ethnic Attributes on the Quality of Family Planning Services in Lima, Peru: A Randomized Crossover Trial

PubMed Central

Planas, Maria-Elena; García, Patricia J.; Bustelo, Monserrat; Carcamo, Cesar P.; Martinez, Sebastian; Nopo, Hugo; Rodriguez, Julio; Merino, Maria-Fernanda; Morrison, Andrew

2015-01-01

Most studies reporting ethnic disparities in the quality of healthcare come from developed countries and rely on observational methods. We conducted the first experimental study to evaluate whether health providers in Peru provide differential quality of care for family planning services, based on the indigenous or mestizo (mixed ethnoracial ancestry) profile of the patient. In a crossover randomized controlled trial conducted in 2012, a sample of 351 out of the 408 public health establishments in Metropolitan Lima, Peru were randomly assigned to receive unannounced simulated patients enacting indigenous and mestizo profiles (sequence-1) or mestizo and then indigenous profiles (sequence-2), with a five week wash-out period. Both ethnic profiles used the same scripted scenario for seeking contraceptive advice but had distinctive cultural attributes such as clothing, styling of hair, make-up, accessories, posture and patterns of movement and speech. Our primary outcome measure of quality of care is the proportion of technical tasks performed by providers, as established by Peruvian family planning clinical guidelines. Providers and data analysts were kept blinded to the allocation. We found a non-significant mean difference of -0·7% (p = 0·23) between ethnic profiles in the percentage of technical tasks performed by providers. However we report large deficiencies in the compliance with quality standards of care for both profiles. Differential provider behaviour based on the patient's ethnic profiles compared in the study did not contribute to deficiencies in family planning outcomes observed. The study highlights the need to explore other determinants for poor compliance with quality standards, including demand and supply side factors, and calls for interventions to improve the quality of care for family planning services in Metropolitan Lima. PMID:25671664

The effects of topical diclofenac, topical flurbiprofen, and humidity on corneal sensitivity in normal dogs.

PubMed

Dorbandt, Daniel M; Labelle, Amber L; Mitchell, Mark A; Hamor, Ralph E

2017-03-01

To determine the immediate and chronic effects of topical 0.1% diclofenac and 0.03% flurbiprofen on corneal sensitivity in normal canine eyes. Eighteen normal, nonbrachycephalic dogs. A prospective, randomized, masked, crossover study was performed. To determine the immediate effects associated with treatment, the study drug was instilled into the eye every 5 min for five doses, and corneal sensitivity of treated and untreated eyes was obtained prior to treatment and every 15 min post-treatment for 60 min. To determine the chronic effects, the study drug was instilled every 12 h for 30 days, and corneal sensitivity of treated and untreated eyes was obtained prior to treatment on days 0 and 30. A washout period of at least 30 days occurred between drug crossover. Ambient temperature and humidity were measured throughout the study. After multiple instillations, there was no difference in corneal sensitivity between eyes over time for diclofenac (P = 0.67) or flurbiprofen (P = 0.54), with a median sensitivity of 25 mm (1.8 g/mm 2 ). After chronic dosing, there was no difference in corneal sensitivity between eyes over time for diclofenac (P = 0.82) or flurbiprofen (P = 0.56), with a median sensitivity of 35 mm (1.0 g/mm 2 ). Decreasing ambient humidity was associated with an increase in sensitivity measurements (P = 0.0001). Neither diclofenac nor flurbiprofen had an effect on corneal sensitivity after multiple-drops or twice-daily dosing for 30 days. Ambient humidity may have an effect on corneal sensitivity measurements, with a longer filament length eliciting a blink response at lower humidity. © 2016 American College of Veterinary Ophthalmologists.

Effects of ethnic attributes on the quality of family planning services in Lima, Peru: a randomized crossover trial.

PubMed

Planas, Maria-Elena; García, Patricia J; Bustelo, Monserrat; Carcamo, Cesar P; Martinez, Sebastian; Nopo, Hugo; Rodriguez, Julio; Merino, Maria-Fernanda; Morrison, Andrew

2015-01-01

Most studies reporting ethnic disparities in the quality of healthcare come from developed countries and rely on observational methods. We conducted the first experimental study to evaluate whether health providers in Peru provide differential quality of care for family planning services, based on the indigenous or mestizo (mixed ethnoracial ancestry) profile of the patient. In a crossover randomized controlled trial conducted in 2012, a sample of 351 out of the 408 public health establishments in Metropolitan Lima, Peru were randomly assigned to receive unannounced simulated patients enacting indigenous and mestizo profiles (sequence-1) or mestizo and then indigenous profiles (sequence-2), with a five week wash-out period. Both ethnic profiles used the same scripted scenario for seeking contraceptive advice but had distinctive cultural attributes such as clothing, styling of hair, make-up, accessories, posture and patterns of movement and speech. Our primary outcome measure of quality of care is the proportion of technical tasks performed by providers, as established by Peruvian family planning clinical guidelines. Providers and data analysts were kept blinded to the allocation. We found a non-significant mean difference of -0.7% (p = 0.23) between ethnic profiles in the percentage of technical tasks performed by providers. However we report large deficiencies in the compliance with quality standards of care for both profiles. Differential provider behaviour based on the patient's ethnic profiles compared in the study did not contribute to deficiencies in family planning outcomes observed. The study highlights the need to explore other determinants for poor compliance with quality standards, including demand and supply side factors, and calls for interventions to improve the quality of care for family planning services in Metropolitan Lima.

Balloon-Assisted Tracking Use Reduces Radial Artery Access Failure in an Experienced Radial Center and is Feasible During Primary PCI for STEMI.

PubMed

Obaid, Daniel; Hailan, Ahmed; Chase, Alexander; Dorman, Stephen; Jenkins, Geraint; Raybould, Adrian; Ramsey, Mark; Thomas, Phillip; Smith, David; Ionescu, Adrian

2017-07-01

This prospective study assesses balloon-assisted tracking (BAT) in reducing radial access failure during percutaneous coronary intervention (PCI). Arterial spasm prevents PCI from the radial artery in a small percentage of cases. A total of 2223 consecutive patients undergoing PCI from the radial approach were analyzed. Radial access failure mode and requirement for crossover to femoral access during a 12-month run-in period were compared with the following 14-month period with routine BAT usage. During the 14-month study period, 1334 radial PCIs were attempted. Twenty-six patients switched to femoral at an early stage, while 76 encountered radial spasm and underwent successful BAT in 69 cases (91%), giving a total crossover rate to femoral of 33/1334 (2.5%). Utilizing BAT rather than a femoral puncture reduced our institution's radial-femoral crossover rate from 7.6% to 2.5% (P<.01), which is also significantly lower than the radial-femoral crossover rate in the 12 months before BAT implementation (6.1%; P<.01). Mean procedure times were similar for those requiring BAT compared with conventional radial access (51.3 ± 21.3 min vs 47.9 ± 23.7 min; P=.23), and those crossing straight to femoral (BAT not attempted) (60.7 ± 31.9 min; P=.10). Mean first device/balloon time for the BAT-assisted primary PCI cases (22.6 ± 9.4 min) was similar to cases that had radial difficulties and converted to femoral without attempting BAT (25.8 ± 13.4 min; P=.54). BAT allowed catheter passage despite radial spasm in 91% of cases, significantly reducing the institution's rate of femoral crossover. During radial spasm in primary PCI, using BAT did not delay reperfusion compared with femoral crossover.

Impact of yoga way of life on organizational performance

PubMed Central

Adhia, Hasmukh; Nagendra, HR; Mahadevan, B

2010-01-01

Background: Organizational performance can be attributed to a number of factors. However, there are certain organizational factors, the presence or absence of which can determine the success or failure of the organization. There are different ways in which organizations try to improve their performance by working on such factors. In the research presented in this article, an attempt is made to find out whether adoption of the Yoga Way of Life by managers can have a positive impact on such organizational performance indicators. Aims: To measure effect of yoga way of life on five different indicators through an empirical study. Materials and Methods: The five indicators are job satisfaction, job involvement, goal orientation, affective organizational commitment and organizational citizenship behavior. Statistics Analysis: Pre- and post-data was measured using self-reported questionnaire. Independent T-test (Paired) and Pearson’s correlation test were conducted using SPSS. Results and Conclusion: The results of the study show that Yoga has a significant positive impact on four out of five of these indicators. Only job involvement does not show significant improvement. The construct used for measuring job involvement had a Chronbach alpha of 0.613, which is an indicator of moderate reliability, which could be the main reason for not getting positive result. PMID:21170231

Kinetic nanofriction: a mechanism transition from quasi-continuous to ballistic-like Brownian regime

PubMed Central

2012-01-01

Surface diffusion of mobile adsorbates is not only the key to control the rate of dynamical processes on solid surfaces, e.g. epitaxial growth, but also of fundamental importance for recent technological applications, such as nanoscale electro-mechanical, tribological, and surface probing devices. Though several possible regimes of surface diffusion have been suggested, the nanoscale surface Brownian motion, especially in the technologically important low friction regimes, remains largely unexplored. Using molecular dynamics simulations, we show for the first time, that a C60 admolecule on a graphene substrate exhibits two distinct regimes of nanoscale Brownian motion: a quasi-continuous and a ballistic-like. A crossover between these two regimes is realized by changing the temperature of the system. We reveal that the underlying physical origin for this crossover is a mechanism transition of kinetic nanofriction arising from distinctive ways of interaction between the admolecule and the graphene substrate in these two regimes due to the temperature change. Our findings provide insight into surface mass transport and kinetic friction control at the nanoscale. PMID:22353343

Dimensional crossover and cold-atom realization of topological Mott insulators

PubMed Central

Scheurer, Mathias S.; Rachel, Stephan; Orth, Peter P.

2015-01-01

Interacting cold-atomic gases in optical lattices offer an experimental approach to outstanding problems of many body physics. One important example is the interplay of interaction and topology which promises to generate a variety of exotic phases such as the fractionalized Chern insulator or the topological Mott insulator. Both theoretically understanding these states of matter and finding suitable systems that host them have proven to be challenging problems. Here we propose a cold-atom setup where Hubbard on-site interactions give rise to spin liquid-like phases: weak and strong topological Mott insulators. They represent the celebrated paradigm of an interacting and topological quantum state with fractionalized spinon excitations that inherit the topology of the non-interacting system. Our proposal shall help to pave the way for a controlled experimental investigation of this exotic state of matter in optical lattices. Furthermore, it allows for the investigation of a dimensional crossover from a two-dimensional quantum spin Hall insulating phase to a three-dimensional strong topological insulator by tuning the hopping between the layers. PMID:25669431

A Randomized Crossover Study of Web-Based Media Literacy to Prevent Smoking

ERIC Educational Resources Information Center

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

2016-01-01

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…

Father Influences on Employed Mothers' Work-Family Balance

ERIC Educational Resources Information Center

Fagan, Jay; Press, Julie

2008-01-01

This study employed the ecological systems perspective and gender ideology theory to examine the influence of fathers' paid work-family crossover and family involvement on self-reports of work-family balance by employed mothers with children under the age of 13 (N = 179). Multiple regression analyses revealed that fathers' crossover factors had a…

Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

ERIC Educational Resources Information Center

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…

The crossover of daily work engagement: test of an actor-partner interdependence model.

PubMed

Bakker, Arnold B; Xanthopoulou, Despoina

2009-11-01

This study of 62 dyads of employees (N = 124) examined the crossover of work engagement-a positive, fulfilling, work-related state of mind that is characterized by vigor, dedication, and absorption. We hypothesized that work engagement crosses over from an employee (the actor) to his or her colleague (the partner) on a daily basis. The frequency of daily communication was expected to moderate the crossover of daily work engagement, which in turn would relate to colleagues' daily performance. Participants first filled in a general questionnaire and then completed a diary study over 5 consecutive workdays. The hypotheses were tested with multilevel analyses, using an actor-partner interdependence model. Results confirmed the crossover of daily work engagement, but only on days when employees within a dyad interacted more frequently than usual. Moreover, we found that actor's work engagement (particularly vigor), when frequently communicated, had a positive indirect relationship with partner's performance through partner's work engagement. Finally, results showed that actor's vigor was negatively related to partner's performance when communication was low. However, this negative effect was counteracted when mediated by the vigor of the partner.

Testing equality and interval estimation of the generalized odds ratio in ordinal data under a three-period crossover design.

PubMed

Lui, Kung-Jong; Chang, Kuang-Chao; Lin, Chii-Dean

2017-06-01

The crossover design can be of use to save the number of patients or improve power of a parallel groups design in studying treatments to noncurable chronic diseases. We propose using the generalized odds ratio for paired sample data to measure the relative effects in ordinal data between treatments and between periods. We show that one can apply the commonly used asymptotic and exact test procedures for stratified analysis in epidemiology to test non-equality of treatments in ordinal data, as well as obtain asymptotic and exact interval estimators for the generalized odds ratio under a three-period crossover design. We further show that one can apply procedures for testing the homogeneity of the odds ratio under stratified sampling to examine whether there are treatment-by-period interactions. We use the data taken from a three-period crossover trial studying the effects of low and high doses of an analgesic versus a placebo for the relief of pain in primary dysmenorrhea to illustrate the use of these test procedures and estimators proposed here.

A Feminist Case Study of Five Women Preschool Practitioners' Engagement in the Collaborative Inquiry Process

ERIC Educational Resources Information Center

Black, Felicia V.

2013-01-01

The purpose of this feminist case study was two-fold: (1) to describe the ways that Collaborative Inquiry (CI) can be proposed as a counter-discourse of professional development that acknowledges the multiple forms of personal and professional knowledge among five women preschool practitioners, and (2) to explore alternative constructs of the…

Situational and contextual factors that increase the risk of harm when students drink: case-control and case-crossover investigation.

PubMed

Connor, Jennie; Cousins, Kimberly; Samaranayaka, Ari; Kypri, Kypros

2014-07-01

Better understanding of the circumstances of alcohol-related adverse events experienced by university students could identify opportunities for prevention. We aimed to identify situational and contextual factors associated with unintentional injury, assault, unsafe sex, sexual assault and drink-driving/riding amongst university students. We conducted a Web-based survey of full-time students aged 17-25 years at five New Zealand universities (n = 2683) and carried out between- and within-subjects comparisons (case-control and case-crossover, respectively) of situational and contextual characteristics of events in the last seven days and control drinking occasions. The response fraction was 49%. For the seven days preceding the survey, 4.9% of women and 7.4% of men reported at least one of the defined events while they were drinking or soon after. The number of drinking locations and getting drunker than expected were strongly associated with risk of an event in both case-control and case-crossover models, independent of consumption. Total number of drinks, drinking later and into the morning, and drinking with close friends were also associated with increased risk in the case-control analysis. No gender difference was seen after controlling for drinking and contextual factors. Strategies to reduce the duration and volume of alcohol consumption, including earlier closing of licensed premises, should be considered as countermeasures for alcohol-related adverse events. The use of two different comparison groups for the circumstances of adverse events when drinking can strengthen inferences about the contribution of contextual factors. © 2014 Australasian Professional Society on Alcohol and other Drugs.

Spin crossover in ferropericlase and velocity heterogeneities in the lower mantle

NASA Astrophysics Data System (ADS)

Wu, Z.; Wentzcovitch, R. M.

2014-12-01

Ferropericlase (Fp) is believed to be the second most abundant phase in the lower mantle. Since the discovery of the high spin (HS) to low spin (LS) crossover in iron in Fp [1], this phenomenon has been investigated extensively experimentally and theoretically. This is a broad and smooth crossover that takes place throughout most of the lower mantle and does not produce an obvious signature in radial velocity or density profiles [2]. Therefore, the spin transition has been generally considered to be invisible to seismic waves. This study, however, shows that it can produce a peculiar effect on lateral velocity heterogeneities at certain depths[3]. Deciphering the origin of seismic velocity heterogeneities in the mantle is crucial to understanding internal structures and processes at work in the Earth. The spin crossover in iron introduces unfamiliar effects on seismic velocities. First principles calculations indicate that anti-correlation between shear velocity (VS) and bulk sound velocity (Vφ) in the mantle, usually interpreted as compositional heterogeneity, can also be produced in homogeneous aggregates containing Fp. The spin crossover also suppresses thermally induced heterogeneity in VP but not in VS. This effect is observed in tomographic models at conditions where the spin crossover in Fp is expected in the lower mantle. In addition, the one-of-a-kind signature of this spin crossover in the RS/P () heterogeneity ratio might be a useful "fingerprint" to detect the presence of Fp in the lower mantle. [1] Badro J, et al. (2003) Science 300(5620):789-791. [2] Wu Z, Justo J. F., and Wentzcovitch R. M., (2013). Phys. Rev. Lett. 110. 228501-5 [3]Wu Z., and Wentzcovitch R. M., (2014) Proc Natl Acad Sci USA. www.pnas.org/cgi/doi/10.1073/pnas.1322427111

Tunable Magnetic Alignment between Trapped Exciton-Polariton Condensates.

PubMed

Ohadi, H; Del Valle-Inclan Redondo, Y; Dreismann, A; Rubo, Y G; Pinsker, F; Tsintzos, S I; Hatzopoulos, Z; Savvidis, P G; Baumberg, J J

2016-03-11

Tunable spin correlations are found to arise between two neighboring trapped exciton-polariton condensates which spin polarize spontaneously. We observe a crossover from an antiferromagnetic to a ferromagnetic pair state by reducing the coupling barrier in real time using control of the imprinted pattern of pump light. Fast optical switching of both condensates is then achieved by resonantly but weakly triggering only a single condensate. These effects can be explained as the competition between spin bifurcations and spin-preserving Josephson coupling between the two condensates, and open the way to polariton Bose-Hubbard ladders.

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

PubMed Central

Oliveira-Neto, Jeronimo M.; Sato, Sandra; Pedrazzi, Vinícius

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 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. PMID:24554886

Tuning porosity and radial mechanical properties of DNA origami nanotubes via crossover design

NASA Astrophysics Data System (ADS)

Ma, Zhipeng; Kawai, Kentaro; Hirai, Yoshikazu; Tsuchiya, Toshiyuki; Tabata, Osamu

2017-06-01

DNA origami nanotubes are utilized as structural platforms for the fabrication of various micro/nanosystems for drug delivery, optical or biological sensing, and even nanoscale robots. Their radial structural and mechanical properties, which play a crucial role in the effective use of micro/nanosystems, have not been fully studied. In particular, the effects of crossovers, which are basic structures for rationally assembling double-stranded DNA (dsDNA) helices into a nanotube configuration, have not yet been characterized experimentally. To investigate the effects of crossovers on the porosity and the radial mechanical properties of DNA origami nanotubes, we fabricated a DNA origami nanotube with varied crossover designs along the nanotube axis. The radial geometry of the DNA origami nanotube is experimentally characterized by both atomic force microscopy (AFM) and electron cryomicroscopy (cryo-EM). Moreover, the radial mechanical properties of the DNA origami nanotube including the radial modulus are directly measured by force-distance-based AFM. These measurements reveal that the porosity and the radial modulus of DNA origami nanotubes can be tuned by adjusting the crossover design, which enables the optimal design and construction of DNA origami nanostructures for various applications.

50 CFR 660.320 - Open access fishery-crossover provisions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Open access fishery-crossover provisions... West Coast Groundfish-Open Access Fisheries § 660.320 Open access fishery—crossover provisions. The crossover provisions listed at § 660.60(h)(7), apply to vessels fishing in the open access fishery. [76 FR...

50 CFR 660.320 - Open access fishery-crossover provisions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 13 2013-10-01 2013-10-01 false Open access fishery-crossover provisions... West Coast Groundfish-Open Access Fisheries § 660.320 Open access fishery—crossover provisions. The crossover provisions listed at § 660.60(h)(7), apply to vessels fishing in the open access fishery. [76 FR...

50 CFR 660.320 - Open access fishery-crossover provisions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 13 2012-10-01 2012-10-01 false Open access fishery-crossover provisions... West Coast Groundfish-Open Access Fisheries § 660.320 Open access fishery—crossover provisions. The crossover provisions listed at § 660.60(h)(7), apply to vessels fishing in the open access fishery. [76 FR...

Mosquito larval source management for controlling malaria

PubMed Central

Tusting, Lucy S; Thwing, Julie; Sinclair, David; Fillinger, Ulrike; Gimnig, John; Bonner, Kimberly E; Bottomley, Christian; Lindsay, Steven W

2015-01-01

Background Malaria is an important cause of illness and death in people living in many parts of the world, especially sub-Saharan Africa. Long-lasting insecticide treated bed nets (LLINs) and indoor residual spraying (IRS) reduce malaria transmission by targeting the adult mosquito vector and are key components of malaria control programmes. However, mosquito numbers may also be reduced by larval source management (LSM), which targets mosquito larvae as they mature in aquatic habitats. This is conducted by permanently or temporarily reducing the availability of larval habitats (habitat modification and habitat manipulation), or by adding substances to standing water that either kill or inhibit the development of larvae (larviciding). Objectives To evaluate the effectiveness of mosquito LSM for preventing malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CABS Abstracts; and LILACS up to 24 October 2012. We handsearched the Tropical Diseases Bulletin from 1900 to 2010, the archives of the World Health Organization (up to 11 February 2011), and the literature database of the Armed Forces Pest Management Board (up to 2 March 2011). We also contacted colleagues in the field for relevant articles. Selection criteria We included cluster randomized controlled trials (cluster-RCTs), controlled before-and-after trials with at least one year of baseline data, and randomized cross-over trials that compared LSM with no LSM for malaria control. We excluded trials that evaluated biological control of anopheline mosquitoes with larvivorous fish. Data collection and analysis At least two authors assessed each trial for eligibility. We extracted data and at least two authors independently determined the risk of bias in the included studies. We resolved all disagreements through discussion with a third author. We analyzed the data using Review Manager 5 software. Main results We included 13 studies; four cluster-RCTs, eight controlled before-and-after trials, and one randomized cross-over trial. The included studies evaluated habitat modification (one study), habitat modification with larviciding (two studies), habitat manipulation (one study), habitat manipulation plus larviciding (two studies), or larviciding alone (seven studies) in a wide variety of habitats and countries. Malaria incidence In two cluster-RCTs undertaken in Sri Lanka, larviciding of abandoned mines, streams, irrigation ditches, and rice paddies reduced malaria incidence by around three-quarters compared to the control (RR 0.26, 95% CI 0.22 to 0.31, 20,124 participants, two trials, moderate quality evidence). In three controlled before-and-after trials in urban and rural India and rural Kenya, results were inconsistent (98,233 participants, three trials, very low quality evidence). In one trial in urban India, the removal of domestic water containers together with weekly larviciding of canals and stagnant pools reduced malaria incidence by three quarters. In one trial in rural India and one trial in rural Kenya, malaria incidence was higher at baseline in intervention areas than in controls. However dam construction in India, and larviciding of streams and swamps in Kenya, reduced malaria incidence to levels similar to the control areas. In one additional randomized cross-over trial in the flood plains of the Gambia River, where larval habitats were extensive and ill-defined, larviciding by ground teams did not result in a statistically significant reduction in malaria incidence (2039 participants, one trial). Parasite prevalence In one cluster-RCT from Sri Lanka, larviciding reduced parasite prevalence by almost 90% (RR 0.11, 95% CI 0.05 to 0.22, 2963 participants, one trial, moderate quality evidence). In five controlled before-and-after trials in Greece, India, the Philippines, and Tanzania, LSM resulted in an average reduction in parasite prevalence of around two-thirds (RR 0.32, 95% CI 0.19 to 0.55, 8041 participants, five trials, moderate quality evidence). The interventions in these five trials included dam construction to reduce larval habitats, flushing of streams, removal of domestic water containers, and larviciding. In the randomized cross-over trial in the flood plains of the Gambia River, larviciding by ground teams did not significantly reduce parasite prevalence (2039 participants, one trial). Authors’ conclusions In Africa and Asia, LSM is another policy option, alongside LLINs and IRS, for reducing malaria morbidity in both urban and rural areas where a sufficient proportion of larval habitats can be targeted. Further research is needed to evaluate whether LSM is appropriate or feasible in parts of rural Africa where larval habitats are more extensive. PMID:23986463

Recent Studies on Methanol Crossover in Liquid-Feed Direct Methanol Fuel Cells

NASA Technical Reports Server (NTRS)

Valdez, T. I.; Narayanan, S. R.

2000-01-01

In this work, the effects of methanol crossover and airflow rates on the cathode potential of an operating direct methanol fuel cell are explored. Techniques for quantifying methanol crossover in a fuel cell and for separating the electrical performance of each electrode in a fuel cell are discussed. The effect of methanol concentration on cathode potential has been determined to be significant. The cathode is found to be mass transfer limited when operating on low flow rate air and high concentrations of methanol. Improvements in cathode structure and operation at low methanol concentration have been shown to result in improved cell performance.

Comparative efficacy of maropitant and selected drugs in preventing emesis induced by centrally or peripherally acting emetogens in dogs.

PubMed

Sedlacek, H S; Ramsey, D S; Boucher, J F; Eagleson, J S; Conder, G A; Clemence, R G

2008-12-01

Maropitant (Cerenia; a novel, selective neurokinin(1) receptor antagonist), chlorpromazine, metoclopramide and ondansetron were compared in two randomized, placebo-controlled studies for efficacy in preventing emesis induced by emetogens acting centrally (apomorphine; Study 1) or peripherally (syrup of ipecac; Study 2) in dogs. In each study, ten male and ten female beagles were treated in a five-treatment, five-period crossover design. The five treatments were 0.9% saline (0.1 mL/kg), maropitant (1 mg/kg), metoclopramide (0.5 mg/kg), or chlorpromazine (0.5 mg/kg) all administered subcutaneously, or ondansetron (0.5 mg/kg) administered intravenously. One hour posttreatment dogs were challenged with apomorphine at 0.1 mg/kg intravenously (Study 1) or syrup of ipecac at 0.5 mL/kg orally (Study 2). Following emetogen challenge, dogs were observed for 30 min (Study 1) or 1 h (Study 2) for emesis. No clinical signs, other than those related to emesis, were observed. Efficacy of maropitant in preventing emesis induced centrally by apomorphine was not different (P > 0.05) from metoclopramide or chlorpromazine but was superior (P < 0.0001) to ondansetron. Efficacy of maropitant in preventing emesis induced by syrup of ipecac was not different (P > 0.05) from ondansetron but was superior (P

Meiotic recombination protein Rec12: functional conservation, crossover homeostasis and early crossover/non-crossover decision

PubMed Central

Kan, Fengling; Davidson, Mari K.; Wahls, Wayne P.

2011-01-01

In fission yeast and other eukaryotes, Rec12 (Spo11) is thought to catalyze the formation of dsDNA breaks (DSBs) that initiate homologous recombination in meiosis. Rec12 is orthologous to the catalytic subunit of topoisomerase VI (Top6A). Guided by the crystal structure of Top6A, we engineered the rec12 locus to encode Rec12 proteins each with a single amino acid substitution in a conserved residue. Of 21 substitutions, 10 significantly reduced or abolished meiotic DSBs, gene conversion, crossover recombination and the faithful segregation of chromosomes. Critical residues map within the metal ion-binding pocket toprim (E179A, D229A, D231A), catalytic region 5Y-CAP (R94A, D95A, Y98F) and the DNA-binding interface (K201A, G202E, R209A, K242A). A subset of substitutions reduced DSBs but maintained crossovers, demonstrating crossover homeostasis. Furthermore, a strong separation of function mutation (R304A) suggests that the crossover/non-crossover decision is established early by a protein–protein interaction surface of Rec12. Fission yeast has multiple crossovers per bivalent, and chromosome segregation was robust above a threshold of about one crossover per bivalent, below which non-disjunction occurred. These results support structural and functional conservation among Rec12/Spo11/Top6A family members for the catalysis of DSBs, and they reveal how Rec12 regulates other features of meiotic chromosome dynamics. PMID:21030440

Dental Students' Preference with Regard to Tactile or Visual Determination of Injection Site for an Inferior Alveolar Nerve Block in Children: A Crossover Randomized Clinical Trial.

PubMed

Ramazani, Nahid; Iranmanesh, Seyed Masoud

2016-01-01

Instruction of local anesthesia injection in an important part of dental education curricula. This study was performed to compare dental students' preference with regard to tactile or visual determination of injection site for an inferior alveolar nerve block (IANB) in children. This crossover randomized clinical trial was conducted on dental students of Zahedan Dental School who took the first practical course of pediatric dentistry in the first academic semester of 2013-14 (n=42). They were randomly divided into two groups. During the first phase, group I was instructed to find the needle insertion point for an IANB via tactile method and group II was instructed to do it visually. In the second phase, the groups received instructions for the alternate technique. Both instructions were done using live demonstrations by the same instructor and immediately after instruction the learners practiced an IANB using the taught method. A five-point Likert scale questionnaire was then filled out by the students. The preference score was determined by calculating the mean of item scores. Data were analyzed using Mann-Whitney U and Wilcoxon Singed Rank tests in SPSS 19 at P=0.05 level of significance. Thirty-eight students completed the study. By using the visual method to perform an IANB, students gained a significantly higher mean preference score (P=0.020). There was a significant difference in the preference of male students (P=0.008). Instruction of IANB by visual identification of needle insertion point is more desirable by students.

Traditional and pyramidal resistance training systems improve muscle quality and metabolic biomarkers in older women: A randomized crossover study.

PubMed

Ribeiro, Alex S; Schoenfeld, Brad J; Souza, Mariana F; Tomeleri, Crisieli M; Venturini, Danielle; Barbosa, Décio S; Cyrino, Edilson S

2016-06-15

The purpose of this study was to compare the effect of RT performed in a pyramid (PR) and traditional (TD) straight set training system on muscle quality and metabolic biomarkers in older women. Twenty-five physically independent older women (67.6±5.1years, 65.9±11.1kg, 154.7±5.8cm) performed a RT program in TD and PR training systems in a balanced crossover design. Measurements of muscle quality, serum levels of C-reactive protein (CRP), glucose (GLU), total cholesterol, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and triglycerides (TG) were obtained at different moments. The TD program consisted of 3 sets of 8-12 repetitions maximum (RM) with a constant weight for the 3 sets, whereas the PR training consisted of 3 sets of 12/10/8 RM with incremental weight for each set. The training was performed in 2 phases of 8weeks each, with a 12-week washout period between phases. Significant (P<0.05) improvements were observed in both groups for muscle quality (TD=+8.6% vs. PR=+6.8%), GLU (TD=-4.5% vs. PR=-1.9%), TG (TD=-18.0% vs. PR=-11.7%), HDL-C (TD=+10.6 vs. PR=+7.8%), LDL-C (TD=-23.3% vs. PR=-21.0%), and CRP (TD=-19.4% vs. PR=-14.3%) with no differences between training systems. These results suggest that RT improves muscle quality and metabolic biomarkers of older women independently of the training system. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of photobiomodulation therapy (pulsed LASER 904 nm) on muscle oxygenation and performance in exercise-induced skeletal muscle fatigue in young women: a pilot study

NASA Astrophysics Data System (ADS)

Oliveira, Murilo X.; Toma, Renata L.; Jones, Brett J. L.; Cyprien, Thomas P.; Tier, Matthew R.; Wallace, Cameron A.; Renno, Ana C. M.; Sabapathy, Surendran; Laakso, E.-Liisa

2017-02-01

Photobiomodulation therapy (PBMt) has been used to increase muscle performance and improve recovery when applied before exercise. We aimed to evaluate the effects of PBMt using LASER on muscle oxygenation and performance. The study was a randomized, participant and assessor-blinded, within-subject crossover trial with placebo control to test the viability of the methods. Five physically active young women were randomly assigned to either placebo, or active PBMt (12 diode cluster probe; 904 nm; 60 mW; 250 Hz; 43.2 J per site, 129.6 J total) in contact over rectus femoris (RF) muscle of the dominant limb immediately before an isokinetic fatigue protocol. A one-week wash-out period preceded cross-over. Electromyography and isokinetic performance measures were evaluated. Absolute concentrations of deoxygenated haemoglobin and myoglobin (deoxy[Hb + Mb]) of the RF, an index of local microvascular fractional O2 extraction, was monitored continuously by near-infrared spectroscopy (NIRS). Total haemoglobin concentration as an indicator of microvascular haematocrit was calculated as the sum of the deoxy[Hb + Mb] and oxy[Hb + Mb] signals. PBMt pre-conditioning reduced time to peak torque when compared to placebo (P<0.05). PBMt resulted in a noticeably reduced trend in deoxy[Hb + Mb] during exercise compared to placebo (P>0.05). PBMt before exercise improves indicators of muscle performance, potentially by increasing local matching of bulk and microvascular O2 delivery relative to skeletal muscle O2 utilisation. Further work is required to understand the effect of PBMt on haemodynamic and metabolic characteristics of muscle.

A 2-way cross-over, open-labeled trial to compare efficacy and safety of insulin Aspart and Novolin R delivered with CSII in 21 Chinese diabetic patients.

PubMed

Bi, Yu-fang; Zhao, Lie-bin; Li, Xiao-ying; Wang, Wei-qing; Sun, Shou-yue; Chen, Yu-hong; Hong, Jie; Su, Ting-wei; Liu, Jian-min; Ning, Guang

2007-10-05

Subcutaneous absorption is accelerated by the monomeric conformation of insulin Aspart, which provides good glycemic control with a lower risk of hypoglycemia and less body weight increase. In the present study we investigated the efficacy and safety of a rapid-acting human insulin analogue (insulin Aspart) delivered with continuous subcutaneous insulin infusion (CSII) into Chinese diabetic patients. A total of 21 patients with type 1 or type 2 diabetes were recruited for the 2-way cross-over, open-labeled trial, and then randomized to Group A (n = 10, treated with insulin Aspart) or Group B (n = 11, treated with Novolin R). Insulin Aspart and Novolin R were administered by CSII. Capillary glucose concentrations were measured at 8 time points, pre-prandial and postprandial, bedtime (10 pm), midnight (2 am) every day during the treatment. The average capillary glucose profiles for the day were much better controlled in Group A than in Group B (P < 0.01). The blood glucose levels were particularly better controlled in Group A than in Group B at pre-breakfast ((6.72 +/- 1.24) mmol/L vs (7.84 +/- 1.58) mmol/L, P = 0.014), post-breakfast ((8.96 +/- 2.41) mmol/L vs (11.70 +/- 3.11) mmol/L, P = 0.0028), post-supper ((8.15 +/- 2.10) mmol/L vs (10.07 +/- 2.36) mmol/L, P = 0.008), bed time ((7.73 +/- 1.72) mmol/L vs (9.39 +/- 2.05) mmol/L, P = 0.007) and midnight ((6.32 +/- 1.16) mmol/L vs (7.48 +/- 1.36) mmol/L, P = 0.0049). There was no significant difference in the frequency of hypoglycemic episodes between the two groups. Insulin Aspart results in better control of blood glucose levels than regular human insulin (Novolin R) in diabetic patients during delivery by CSII.

Effect of bread gluten content on gastrointestinal function: a crossover MRI study on healthy humans.

PubMed

Coletta, Marina; Gates, Fred K; Marciani, Luca; Shiwani, Henna; Major, Giles; Hoad, Caroline L; Chaddock, Gemma; Gowland, Penny A; Spiller, Robin C

2016-01-14

Gluten is a crucial functional component of bread, but the effect of increasing gluten content on gastrointestinal (GI) function remains uncertain. Our aim was to investigate the effect of increasing gluten content on GI function and symptoms in healthy participants using the unique capabilities of MRI. A total of twelve healthy participants completed this randomised, mechanistic, open-label, three-way crossover study. On days 1 and 2 they consumed either gluten-free bread (GFB), or normal gluten content bread (NGCB) or added gluten content bread (AGCB). The same bread was consumed on day 3, and MRI scans were performed every 60 min from fasting baseline up to 360 min after eating. The appearance of the gastric chime in the images was assessed using a visual heterogeneity score. Gastric volumes, the small bowel water content (SBWC), colonic volumes and colonic gas content and GI symptoms were measured. Fasting transverse colonic volume after the 2-d preload was significantly higher after GFB compared with NGCB and AGCB with a dose-dependent response (289 (SEM 96) v. 212 (SEM 74) v. 179 (SEM 87) ml, respectively; P=0·02). The intragastric chyme heterogeneity score was higher for the bread with increased gluten (AGCB 6 (interquartile range (IQR) 0·5) compared with GFB 3 (IQR 0·5); P=0·003). However, gastric half-emptying time was not different between breads nor were study day GI symptoms, postprandial SBWC, colonic volume and gas content. This MRI study showed novel mechanistic insights in the GI responses to different breads, which are poorly understood notwithstanding the importance of this staple food.

Effects of Silexan on the Serotonin-1A Receptor and Microstructure of the Human Brain: A Randomized, Placebo-Controlled, Double-Blind, Cross-Over Study with Molecular and Structural Neuroimaging

PubMed Central

Baldinger, Pia; Höflich, Anna S.; Mitterhauser, Markus; Hahn, Andreas; Rami-Mark, Christina; Spies, Marie; Wadsak, Wolfgang; Lanzenberger, Rupert

2015-01-01

Background: Recently, Silexan, a patented active substance comprised of an essential oil produced from Lavandula angustifolia flowers, has been authorized in Germany as a medicinal product for the treatment of states of restlessness related to anxious mood. Its efficacy has been shown in several forms of anxiety disorders. Findings from preclinical and clinical studies attribute a major role to the serotonin-1A receptor in the pathogenesis and treatment of anxiety. Methods: To elucidate the effect of Silexan on serotonin-1A receptor binding, 17 healthy men underwent 2 positron emission tomography measurements using the radioligand [carbonyl-11C]WAY-100635 following the daily intake of 160mg Silexan or placebo for a minimum of 8 weeks (randomized, double-blind, cross-over design). Additionally, structural magnetic resonance imaging and voxel-based morphometry analysis was performed to determine potential effects on gray matter microstructure. Results: Serotonin-1A receptor binding potential was shown to be significantly reduced following the intake of Silexan compared with placebo in 2 large clusters encompassing the temporal gyrus, the fusiform gyrus and the hippocampus on one hand as well as the insula and anterior cingulate cortex on the other hand. No effects of Silexan on gray matter volume could be detected in this investigation. Conclusion: This positron emission tomography study proposes an involvement of the serotonin-1A receptor in the anxiolytic effects of Silexan. The study was registered in the International Standard Randomized Controlled Trial Number Register as ISRCTN30885829 (http://www.controlled-trials.com/isrctn/). PMID:25522403

Bioequivalence of two commercial preparations of escitalopram oxalate/clonazepam using a liquid chromatography-electrospray mass spectrometry method.

PubMed

Agarwal, Sangita; Gowda, Kadajji Veeran; Selvan, Perumal Senthamil; Chattaraj, Tapas Kumar; Pal, Tapan Kumar

2008-01-01

A randomized, two-way crossover study was conducted in 24 fasting healthy male volunteers of Indian origin to compare the bioavailability of two brands of a fixed dose combination of escitalopram oxalate (CAS 219861-08-2) 10 mg and clonazepam (CAS 1622-61-3) 0.5 mg tablets, using Estomine-zee as test and a commercially available formulation as the reference product. The pharmacokinetics of escitalopram oxalate and clonazepam individually after oral administration of tablet formulation has been extensively evaluated in adult volunteers. However, no published data are available regarding the pharmacokinetics and bioavailability of this particular fixed dose combination. The trial was designed as a randomized, balanced, open-label, 2-period cross-over study. The drug was administered with 240 ml of water after a 10-h overnight fasting on two treatment days separated by a 21-day washout period. After dosing, serial blood samples were collected for a period of 96 h. Plasma harvested from blood was analyzed by simple rapid, selective and validated liquid chromatography-electrospray mass spectrometry (LC-ESI-MS/ MS) using diazepam (CAS 439-14-5) as an internal standard. The calibration curves were found to be linear in the range of 1-25 ng/ml and 1-10 ng/ml for escitalopram oxalate and clonazepam, respectively, with a mean correlation coefficient of more than 0.99. No statistically significant differences were obtained between the two products with respect to the mean concentration-time profiles or in the pharmacokinetic parameters, including the area under the serum concentration-time curve from the present study. Based on the statistical inferences, it was concluded that the test product is bioequivalent to the reference product. Both preparations were well tolerated with no adverse reactions throughout the study.

Clinical pharmacokinetics of Icotinib, an anti-cancer drug: evaluation of dose proportionality, food effect, and tolerability in healthy subjects.

PubMed

Liu, Dongyang; Jiang, Ji; Zhang, Li; Tan, Fenlai; Wang, Yingxiang; Zhang, Don; Hu, Pei

2014-04-01

Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3.5 h after single dose and then declined with a mean t1/2β of 6.02-7.83 h. Over the dose range of 100-600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100-600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects.

Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults.

PubMed

White, John R; Padowski, Jeannie M; Zhong, Yili; Chen, Gang; Luo, Shaman; Lazarus, Philip; Layton, Matthew E; McPherson, Sterling

2016-01-01

There is a paucity of data describing the impact of type of beverage (coffee versus energy drink), different rates of consumption and different temperature of beverages on the pharmacokinetic disposition of caffeine. Additionally, there is concern that inordinately high levels of caffeine may result from the rapid consumption of cold energy drinks. The objective of this study was to compare the pharmacokinetics of caffeine under various drink temperature, rate of consumption and vehicle (coffee versus energy drink) conditions. Five caffeine (dose = 160 mg) conditions were evaluated in an open-label, group-randomized, crossover fashion. After the administration of each caffeine dose, 10 serial plasma samples were harvested. Caffeine concentration was measured via liquid chromatography-mass spectrometry (LC-MS), and those concentrations were assessed by non-compartmental pharmacokinetic analysis. The calculated mean pharmacokinetic parameters were analyzed statistically by one-way repeated measures analysis of variance (RM ANOVA). If differences were found, each group was compared to the other by all pair-wise multiple comparison. Twenty-four healthy subjects ranging in age from 18 to 30 completed the study. The mean caffeine concentration time profiles were similar with overlapping SDs at all measured time points. The ANOVA revealed significant differences in mean Cmax and Vd ss/F, but no pair-wise comparisons reached statistical significance. No other differences in pharmacokinetic parameters were found. The results of this study are consistent with previous caffeine pharmacokinetic studies and suggest that while rate of consumption, temperature of beverage and vehicle (coffee versus energy drink) may be associated with slightly different pharmacokinetic parameters, the overall impact of these variables is small. This study suggests that caffeine absorption and exposure from coffee and energy drink is similar irrespective of beverage temperature or rate of consumption.

Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults

PubMed Central

White, John R.; Padowski, Jeannie M.; Zhong, Yili; Chen, Gang; Luo, Shaman; Lazarus, Philip; Layton, Matthew E.; McPherson, Sterling

2016-01-01

Abstract Context: There is a paucity of data describing the impact of type of beverage (coffee versus energy drink), different rates of consumption and different temperature of beverages on the pharmacokinetic disposition of caffeine. Additionally, there is concern that inordinately high levels of caffeine may result from the rapid consumption of cold energy drinks. Objective: The objective of this study was to compare the pharmacokinetics of caffeine under various drink temperature, rate of consumption and vehicle (coffee versus energy drink) conditions. Materials: Five caffeine (dose = 160 mg) conditions were evaluated in an open-label, group-randomized, crossover fashion. After the administration of each caffeine dose, 10 serial plasma samples were harvested. Caffeine concentration was measured via liquid chromatography–mass spectrometry (LC–MS), and those concentrations were assessed by non-compartmental pharmacokinetic analysis. The calculated mean pharmacokinetic parameters were analyzed statistically by one-way repeated measures analysis of variance (RM ANOVA). If differences were found, each group was compared to the other by all pair-wise multiple comparison. Results: Twenty-four healthy subjects ranging in age from 18 to 30 completed the study. The mean caffeine concentration time profiles were similar with overlapping SDs at all measured time points. The ANOVA revealed significant differences in mean C max and V d ss/F, but no pair-wise comparisons reached statistical significance. No other differences in pharmacokinetic parameters were found. Discussion: The results of this study are consistent with previous caffeine pharmacokinetic studies and suggest that while rate of consumption, temperature of beverage and vehicle (coffee versus energy drink) may be associated with slightly different pharmacokinetic parameters, the overall impact of these variables is small. Conclusion: This study suggests that caffeine absorption and exposure from coffee and energy drink is similar irrespective of beverage temperature or rate of consumption. PMID:27100333

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

ERIC Educational Resources Information Center

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…

Five Secondary Teachers: Creating and Presenting a Teaching Persona

ERIC Educational Resources Information Center

Davis, Janine Schank

2011-01-01

This qualitative study investigates the ways that five secondary teachers developed and presented personae. The researcher collected and analyzed data using a theoretical frame based in social psychology, including Goffman's Presentation of Self in Everyday Life (1959), and Miles and Huberman's (1994) three-step approach to qualitative data…

Five Exciting, Enriching Outdoor Study Days in the Life of Delaware Valley Middle School Sixth Graders.

ERIC Educational Resources Information Center

Palermo, Scott D.; Sewall, Susan B.

1988-01-01

Discusses some of the variables involved in the development of five environmental education days by the Delaware Valley (Pennsylvania) Middle School. Recounts some of the ways that support was generated for programs from school administrators and community resources people. (TW)

The Crossover Time as an Evaluation of Ocean Models Against Persistence

NASA Astrophysics Data System (ADS)

Phillipson, L. M.; Toumi, R.

2018-01-01

A new ocean evaluation metric, the crossover time, is defined as the time it takes for a numerical model to equal the performance of persistence. As an example, the average crossover time calculated using the Lagrangian separation distance (the distance between simulated trajectories and observed drifters) for the global MERCATOR ocean model analysis is found to be about 6 days. Conversely, the model forecast has an average crossover time longer than 6 days, suggesting limited skill in Lagrangian predictability by the current generation of global ocean models. The crossover time of the velocity error is less than 3 days, which is similar to the average decorrelation time of the observed drifters. The crossover time is a useful measure to quantify future ocean model improvements.

An Investigation of How a Physics Professional Development Course Influenced the Teaching Practices of Five Elementary School Teachers

ERIC Educational Resources Information Center

Harlow, Danielle B.

2014-01-01

This paper reports the results of an investigation of how a professional development content course based on the Physics and Everyday Thinking (PET) curriculum affected the teaching practices of five case study elementary school teachers. The findings of this study highlight different ways that teachers use what they learn in content courses to…

Homeless Families with Children: Programmatic Responses of Five Communities. Volume I: Cross-Site Comparisons and Findings.

ERIC Educational Resources Information Center

Macro Systems, Inc., Silver Spring, MD.

An exploratory study was conducted to examine the ways in which existing programs or service delivery systems have adapted to meet the needs of homeless families with children. Key issues and model and innovative approaches were identified prior to study site visits in five cities: (1) Atlanta (Georgia); (2) Baltimore (Maryland); (3) Boston…

Evaluation of 5 Hour Energy Drink on the Blood Pressure and Electrocardiograph Parameters on Young Healthy Volunteers: A Randomized, Double Blind, Crossover, Placebo-Controlled Trial

DTIC Science & Technology

2014-02-11

Travis AFB CA INSTITUTIONAL REVIEW BOARD (IRB) ()~\\) Non-Exempt Study Final Report p3YVJ (Please 1J!J!£ all information. Use additional pages if...QTc interval after acute and chronic consumption. METHODS: This was a randomized, placebo controlled, crossover study enrolling young healthy volunteers...not on any medications. Subjects received the study drink (5 Hour Energy shot or placebo) twice daily separated by approximately 7 hours for the

A crossover-crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and semen quality in men with inflammatory bowel disease.

PubMed

Nassan, Feiby L; Coull, Brent A; Skakkebaek, Niels E; Williams, Michelle A; Dadd, Ramace; Mínguez-Alarcón, Lidia; Krawetz, Stephen A; Hait, Elizabeth J; Korzenik, Joshua R; Moss, Alan C; Ford, Jennifer B; Hauser, Russ

2016-10-01

Phthalates are widely used chemicals with ubiquitous exposure. Dibutyl-phthalate (DBP), a male reproductive toxicant in animals, is understudied in humans. Some mesalamine medications used to treat inflammatory bowel disease (IBD) have DBP in their coating, whereas other mesalamine formulations do not. Taking advantage of differences in mesalamine formulations, we investigated whether high-DBP exposure from mesalamine medications was associated with decreased semen parameters. 73 men with IBD taking mesalamine participated in a crossover-crossback prospective study. Men taking non-DBP containing mesalamine at baseline i.e., background exposure, crossed-over for four months to high-DBP mesalamine and then crossed-back for four months to their non-DBP mesalamine (B1HB2-arm;Background1-High-Background2) and vice versa for men taking high-DBP mesalamine at baseline (H1BH2-arm;High1-Background-High2). Men provided up to six semen samples (2: baseline, 2: crossover and 2: crossback). We estimated crossover, crossback and carryover effects using linear mixed models adjusted for abstinence time, age, season and duration on high-DBP mesalamine at baseline. Semen parameters in B1HB2-arm (26 men, 133 samples) decreased after high-DBP mesalamine exposure (crossover versus baseline), especially motility parameters, and continued to decrease further even after crossback to non-DBP mesalamine (crossback versus crossover). The cumulative carryover effect of high-DBP (crossback versus baseline) was a decrease of % total sperm motility by 7.61(CI:-13.1, -2.15), % progressive sperm motility by 4.23(CI:-8.05, -0.4) and motile sperm count by 26.0% (CI:-46.2%, 1.7%). However, H1BH2-arm (47 men, 199 samples) had no significant change during crossover or crossback. Men newly exposed to high-DBP mesalamine for four months had a cumulative reduction in several semen parameters, primarily sperm motility, that was more pronounced and statistically significant even after exposure ended for four months. Copyright © 2016 Elsevier Ltd. All rights reserved.

Platelet aggregation, eicosanoid production and thrombogenic ratio in individuals at high cardiovascular risk consuming meat enriched in walnut paste. A crossover, placebo-controlled study.

PubMed

Canales, Amaia; Bastida, Sara; Librelottto, Josana; Nus, Meritxell; Sánchez-Muniz, Francisco J; Benedi, Juana

2009-07-01

Walnut consumption produces beneficial cardiovascular effects. The aim of the present study is to compare the effects of meat enriched in walnut paste (WM) and low-fat meat (LM) consumptions on platelet aggregation, plasma thromboxane A2 (TXA2, measured as TXB2), prostacyclin I2 (PGI2, as 6-keto-PGF1alpha) and the thrombogenic ratio (TXB2/6-keto-PGF1alpha) in volunteers at high CVD risk. Twenty-two adults were placed on a random, non-blinded crossover study involving two test periods (five portions WM/week for 5 week; five portions LM/week for 5 week) separated by a 4- to 6-week washout period. The participants were asked to complete a diet record throughout the study. Platelet aggregation, plasma TXB2, 6-keto-PGF1alpha production and the TXB2/6-keto-PGF1alpha ratio were determined at baseline and at weeks 3 and 5 for the two dietary periods. The WM diet contains a lower SFA content, a higher concentration of PUFA and a more favourable n-6/n-3 ratio than the LM diet. Significant time x treatment interactions were observed for TXB2 (P = 0.048) and the TXB2/6-keto-PGF1alpha ratio (P = 0.028). The WM diet significantly increased the level of 6-keto-PGF1alpha (P = 0.037) and decreased the TXB2/6-keto-PGF1alpha ratio (P = 0.048). At week 5, significant differences (P < 0.05) between treatments were found for maximum aggregation rate, TXB2 values and the TXB2/6-keto-PGF1alpha ratio. The effects on TXB2 and the TXB2/6-keto-PGF1alpha ratio were time-course dependent (P = 0.019 and 0.011, respectively). The WM and LM diets reduced TXB2 levels most (P = 0.050) in obese individuals, while the TXB2/6-keto-PGF1alpha ratio decreased most (P = 0.066) in volunteers whose serum cholesterol levels were > or = 2200 mg/l. The WM diet should be considered a functional meat because it improves the thrombogenic status mainly in individuals with high-cholesterol levels or high BMI.

Effects of Food on the Pharmacokinetics of Omega-3-Carboxylic Acids in Healthy Japanese Male Subjects: A Phase I, Randomized, Open-label, Three-period, Crossover Trial.

PubMed

Shimada, Hitoshi; Nilsson, Catarina; Noda, Yoshinori; Kim, Hyosung; Lundström, Torbjörn; Yajima, Toshitaka

2017-09-01

Omega-3-carboxylic acids (OM3-CA) contain omega-3 free fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as carboxylic acids. Food intake is known to affect the bioavailability of ethyl ester fatty acid formulations. We conducted a phase I study to investigate the effects of the timing of OM3-CA administration relative to food intake on the pharmacokinetics of EPA and DHA. In this randomized, open-label, three-period crossover study, Japanese healthy male subjects were administered 4×1 g OM3-CA capsules with continued fasting, before a meal, or after a meal. All subjects fasted for ≥10 h prior to drug/meal administration. The primary objective was to examine the effect of meal timing on the pharmacokinetics of EPA and DHA after OM3-CA administration. The secondary objectives were to examine the safety and tolerability of OM3-CA. A total of 42 Japanese subjects was enrolled in the study. The baseline-adjusted maximum concentration and area under the concentration-time curve from 0 to 72 h for EPA, DHA, and EPA +DHA were lower in the fasting and before meal conditions than in the after meal condition. The maximum total EPA, total DHA, and total EPA+DHA concentrations were reached later when administered in fasting conditions than in fed conditions, indicating slower absorption in fasting conditions. Diarrhea was reported by five, six, and no subjects in the fasting, before meal, and after meal conditions, respectively. The timing of OM3-CA administration relative to food intake influences the systemic bioavailability of EPA and DHA in healthy Japanese male subjects. NCT02372344.

Lubiprostone improves visualization of small bowel for capsule endoscopy: a double-blind, placebo-controlled 2-way crossover study.

PubMed

Matsuura, Mizue; Inamori, Masahiko; Inou, Yumi; Kanoshima, Kenji; Higurashi, Takuma; Ohkubo, Hidenori; Iida, Hiroshi; Endo, Hiroki; Nonaka, Takashi; Kusakabe, Akihiko; Maeda, Shin; Nakajima, Atsushi

2017-06-01

 Lubiprostone has been reported to be an anti-constipation drug. The aim of the study was to investigate the usefulness of lubiprostone both for bowel preparation and as a propulsive agent in small bowel endoscopy.  This was a double-blind, placebo-controlled, 2-way crossover study of subjects who volunteered to undergo capsule endoscopy (CE). A total of 20 subjects (16 male and 4 female volunteers) were randomly assigned to receive a 24-μg tablet of lubiprostone 120 minutes prior to capsule ingestion for CE (L regimen), or a placebo tablet 120 minutes prior to capsule ingestion for CE (P regimen). Main outcome was gastric transit time (GTT) and small-bowel transit time (SBTT). Secondary outcome was adequacy of small-bowel cleansing and the fluid score in the small bowel. The quality of the capsule endoscopic images and fluid in the small bowel were assessed on 5-point scale.  The capsule passed into the small bowel in all cases. Median GTT was 57.3 (3 - 221) minutes for the P regimen and 61.3 (10 - 218) minutes for the L regimen ( P  = 0.836). Median SBTT was 245.0 (164 - 353) minutes for the P regimen and 228.05 (116 - 502) minutes for the L regimen ( P  = 0.501). The image quality score in the small bowel was 3.05 ± 1.08 for the P regimen and 3.80 ± 0.49 for the L regimen ( P  < 0.001). The fluid score in the small bowel was 2.04 ± 1.58 for the P regimen and 2.72 ± 1.43 for the L regimen ( P  < 0.001). There was a significant difference between the 2 regimens with regard to image quality. The fluid score was more plentiful for the L regimen than for the P regimen. There were no cases of capsule retention or serious adverse events in this study.  Our study showed that use of lubiprostone prior to CE significantly improved visualization of the small bowel during CE as a result of inducing fluid secretion into the small bowel.

Proper time regularization and the QCD chiral phase transition

PubMed Central

Cui, Zhu-Fang; Zhang, Jin-Li; Zong, Hong-Shi

2017-01-01

We study the QCD chiral phase transition at finite temperature and finite quark chemical potential within the two flavor Nambu–Jona-Lasinio (NJL) model, where a generalization of the proper-time regularization scheme is motivated and implemented. We find that in the chiral limit the whole transition line in the phase diagram is of second order, whereas for finite quark masses a crossover is observed. Moreover, if we take into account the influence of quark condensate to the coupling strength (which also provides a possible way of how the effective coupling varies with temperature and quark chemical potential), it is found that a CEP may appear. These findings differ substantially from other NJL results which use alternative regularization schemes, some explanation and discussion are given at the end. This indicates that the regularization scheme can have a dramatic impact on the study of the QCD phase transition within the NJL model. PMID:28401889

Comparative bioavailability study of clonazepam after oral administration of two tablet formulations.

PubMed

Chauhan, B L; Sane, S P; Revankar, S N; Rammamurthy, L; Doshi, B; Bhatt, A D; Bhate, V R; Kulkarni, R D

2000-10-01

To assess the bioavailability of clonazepam from two brands of 2 mg tablet formulations--Epitril and reference brand. A two-way randomised cross-over bioavailability study was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of clonazepam by high performance liquid chromatography (HPLC) method. The mean Cmax, Tmax t1/2 beta and AUC (0-48) for Epitril were: 16.31 +/- 3.07 ng/mL, 1.63 +/- 0.48 h, 46.97 +/- 12.26 h and 207.70 +/- 57.07 ng/ml.h; for reference brand were 19.75 +/- 5.95 ng/mL, 1.42 +/- 0.29 h, 46.88 +/- 11.29 h and 215.70 +/- 50.89 ng/ml.h respectively. These were comparable and the differences were not statistically significant. Based on above pharmacokinetic parameters, Epitril was bioequivalent to reference brand.

Pharmacokinetics in Healthy Volunteers of Sumatriptan 25-mg Oral Tablet Versus 25-mg Extemporaneous Suppository.

PubMed

Desai, Hiral D; Shriley, Kara L; Penzak, Scott R; Strom, J Grady; Hon, Yuen Yi; Spratlin, Vicky; Jann, Michael W

2003-01-01

The pharmacokinetics of an extemporaneous 25-mg suppository formulation of sumatriptan were compared to those of the marketed 25-mg oral tablet. Sixteen healthy volunteers enrolled in this open-label, two-way crossover study. Fifteen subjects completed the study. The pharmacokinetics of the suppository and the oral tablet were significantly different. Tmax was observed at 0.5 hours in 12 of 15 subjects with the extemporaneous suppository, compared with the range of 0.75 hours to 1.5 hours in 13 of 15 subjects with the oral tablet. The mean Cmax and area under the plasma concentration time curve were 5.4-fold and fourfold greater for the suppository than for the oral tablet. Both formulations were well tolerated, with mild headache experienced in only three subjects. Based upon its pharmacokinetic profile, the extemporaneous suppository may represent a useful alternative therapeutic administartion route for some patients.

Rhombic-Shaped Nanostructures and Mechanical Properties of 2D DNA Origami Constructed with Different Crossover/Nick Designs.

PubMed

Ma, Zhipeng; Huang, Yunfei; Park, Seongsu; Kawai, Kentaro; Kim, Do-Nyun; Hirai, Yoshikazu; Tsuchiya, Toshiyuki; Yamada, Hirofumi; Tabata, Osamu

2018-01-01

DNA origami methods enable the fabrication of various nanostructures and nanodevices, but their effective use depends on an understanding of their structural and mechanical properties and the effects of basic structural features. Frequency-modulation atomic force microscopy is introduced to directly characterize, in aqueous solution, the crossover regions of sets of 2D DNA origami based on different crossover/nick designs. Rhombic-shaped nanostructures formed under the influence of flexible crossovers placed between DNA helices are observed in DNA origami incorporating crossovers every 3, 4, or 6 DNA turns. The bending rigidity of crossovers is determined to be only one-third of that of the DNA helix, based on interhelical electrostatic forces reported elsewhere, and the measured pitches of the 3-turn crossover design rhombic-shaped nanostructures undergoing negligible bending. To evaluate the robustness of their structural integrity, they are intentionally and simultaneously stressed using force-controlled atomic force microscopy. DNA crossovers are verified to have a stabilizing effect on the structural robustness, while the nicks have an opposite effect. The structural and mechanical properties of DNA origami and the effects of crossovers and nicks revealed in this paper can provide information essential for the design of versatile DNA origami structures that exhibit specified and desirable properties. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

49 CFR 213.353 - Turnouts, crossovers, and lift rail assemblies or other transition devices on moveable bridges.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 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...

49 CFR 213.353 - Turnouts, crossovers, and lift rail assemblies or other transition devices on moveable bridges.

Code of Federal Regulations, 2010 CFR

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...

How Crossover Speeds up Building Block Assembly in Genetic Algorithms.

PubMed

Sudholt, Dirk

2017-01-01

We reinvestigate a fundamental question: How effective is crossover in genetic algorithms in combining building blocks of good solutions? Although this has been discussed controversially for decades, we are still lacking a rigorous and intuitive answer. We provide such answers for royal road functions and OneMax, where every bit is a building block. For the latter, we show that using crossover makes every ([Formula: see text]+[Formula: see text]) genetic algorithm at least twice as fast as the fastest evolutionary algorithm using only standard bit mutation, up to small-order terms and for moderate [Formula: see text] and [Formula: see text]. Crossover is beneficial because it can capitalize on mutations that have both beneficial and disruptive effects on building blocks: crossover is able to repair the disruptive effects of mutation in later generations. Compared to mutation-based evolutionary algorithms, this makes multibit mutations more useful. Introducing crossover changes the optimal mutation rate on OneMax from [Formula: see text] to [Formula: see text]. This holds both for uniform crossover and k-point crossover. Experiments and statistical tests confirm that our findings apply to a broad class of building block functions.

Ocular hemodynamic effects of nitrovasodilators in healthy subjects.

PubMed

Schmidl, D; Polska, E; Kiss, B; Sacu, S; Garhofer, G; Schmetterer, L

2010-01-01

Nitric oxide (NO) plays a key role in the regulation of ocular blood flow and may be an interesting therapeutic target in ocular ischemic disease. In the present study, we hypothesized that NO-releasing drugs may increase blood flow to the head of the optic nerve and also in the choroid. The study employed a randomized, placebo-controlled, double blind, four-way crossover design. On separate study days, 12 healthy subjects received infusions of nitroglycerin, isosorbide dinitrate, sodium nitroprusside, or placebo. All three study drugs reduced the mean arterial pressure (MAP) and ocular perfusion pressure (OPP) (P < 0.001). None of the administered drugs increased the ocular hemodynamic variables. By contrast, vascular resistance decreased dose dependently during administration of the study drugs (P < 0.001). These results indicate that systemic administration of NO-donor drugs is associated with a decrease in vascular resistance in the ocular vasculature. However, because these drugs also reduce blood pressure, they do not improve perfusion to the posterior eye pole.

Short-term effects of particulate matter constituents on daily hospitalizations and mortality in five South-European cities: results from the MED-PARTICLES project.

PubMed

Basagaña, Xavier; Jacquemin, Bénédicte; Karanasiou, Angeliki; Ostro, Bart; Querol, Xavier; Agis, David; Alessandrini, Ester; Alguacil, Juan; Artiñano, Begoña; Catrambone, Maria; de la Rosa, Jesús D; Díaz, Julio; Faustini, Annunziata; Ferrari, Silvia; Forastiere, Francesco; Katsouyanni, Klea; Linares, Cristina; Perrino, Cinzia; Ranzi, Andrea; Ricciardelli, Isabella; Samoli, Evangelia; Zauli-Sajani, Stefano; Sunyer, Jordi; Stafoggia, Massimo

2015-02-01

Few recent studies examined acute effects on health of individual chemical species in the particulate matter (PM) mixture, and most of them have been conducted in North America. Studies in Southern Europe are scarce. The aim of this study is to examine the relationship between particulate matter constituents and daily hospital admissions and mortality in five cities in Southern Europe. The study included five cities in Southern Europe, three cities in Spain: Barcelona (2003-2010), Madrid (2007-2008) and Huelva (2003-2010); and two cities in Italy: Rome (2005-2007) and Bologna (2011-2013). A case-crossover design was used to link cardiovascular and respiratory hospital admissions and total, cardiovascular and respiratory mortality with a pre-defined list of 16 PM10 and PM2.5 constituents. Lags 0 to 2 were examined. City-specific results were combined by random-effects meta-analysis. Most of the elements studied, namely EC, SO4(2-), SiO2, Ca, Fe, Zn, Cu, Ti, Mn, V and Ni, showed increased percent changes in cardiovascular and/or respiratory hospitalizations, mainly at lags 0 and 1. The percent increase by one interquartile range (IQR) change ranged from 0.69% to 3.29%. After adjustment for total PM levels, only associations for Mn, Zn and Ni remained significant. For mortality, although positive associations were identified (Fe and Ti for total mortality; EC and Mg for cardiovascular mortality; and NO3(-) for respiratory mortality) the patterns were less clear. The associations found in this study reflect that several PM constituents, originating from different sources, may drive previously reported results between PM and hospital admissions in the Mediterranean area. Copyright © 2014 Elsevier Ltd. All rights reserved.

The kinetochore prevents centromere-proximal crossover recombination during meiosis

PubMed Central

Vincenten, Nadine; Kuhl, Lisa-Marie; Lam, Isabel; Oke, Ashwini; Kerr, Alastair RW; Hochwagen, Andreas; Fung, Jennifer; Keeney, Scott; Vader, Gerben; Marston, Adèle L

2015-01-01

During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes. DOI: http://dx.doi.org/10.7554/eLife.10850.001 PMID:26653857

Magnetization reversal dynamics in Co nanowires with competing magnetic anisotropies

NASA Astrophysics Data System (ADS)

Pal, Semanti; Saha, Susmita; Polley, Debanjan; Barman, Anjan

2011-12-01

We present the magnetization reversal dynamics of Co nanowires with competing magnetic anisotropies. The aspect ratio ( R) of the nanowires is varied between 2.5 and 60, and we observe a cross-over of the directions of the magnetic easy and hard axes at R=6.8. Micromagnetic simulations qualitatively reproduce the observed cross-over and give detailed insight into the reversal mechanisms associated with the cross-over. The reversal mechanism for a field applied along the long axis of the nanowire exhibits a quasi-coherent rotation mode and a corkscrew-like mode, respectively, above and below the cross-over, with the formation of a Bloch domain near the cross-over region. For a field applied along the short axis, the reversal occurs by nucleation and propagation of reversed domains from the two ends of the nanowires for very high values of the aspect ratio down to the cross-over region, but it transforms into quasi-coherent rotation mode for smaller aspect ratios (below the cross-over region).

Caffeine ingestion changes time-motion and technical-tactical aspects in simulated boxing matches: A randomized double-blind PLA-controlled crossover study.

PubMed

Coswig, Victor Silveira; Gentil, Paulo; Irigon, Francine; Del Vecchio, Fabrício Boscolo

2018-05-08

The number of offensive actions and glycolytic energy in combat sports both increase with caffeine (CAF) ingestion. In addition, the effects of CAF on technical-tactical and time-motion analysis and physiological parameters in boxing are unknown. This study aimed to investigate the effects of CAF ingestion on physiological parameters and the notational analysis of boxing matches. Ten male boxers were recruited; the participants ingested 6 mg kg -1 BM of CAF or placebo (PLA) 30 min prior to the match in a crossover design. Heart rate (HR) and rate of perceived exertion (RPE) were collected before and after each of three 2 min rounds, interspersed by 1-min recovery; the matches were recorded for notational analysis. A two-way ANOVA for repeated measures was used for the physiological variables, and a three-way ANOVA with repeated measures was used for technical-tactical and time-motion variables. Statistical differences were found for HR and RPE between rounds (F (6, 54)  = 131.3, p = .001; [Formula: see text] = 0.93 and F (2, 18)  = 40.6, p = .001; [Formula: see text] = 0.81, respectively) but not between conditions (F (1, 9)  = 0.46; p = .51; [Formula: see text] = 0.05 and F (1, 9)  = 0.02, p = .89; [Formula: see text] = 0.002, respectively). The CAF condition induced a greater duration of interaction blocks (CAF = 6.5 ± 1.8 s; PLA = 4.4 ± 0.9 s; p = .01). Effort:pause ratio was 4.4 s:8.7 s (approx. 1:2) for PLA and 6.5 s:9.4 s (1:1.44) for CAF, which were significantly different (p < .05). In conclusion, 6 mg kg -1 BM of CAF prior to simulated boxing matches induces a greater duration of high-intensity actions, with no effects on internal load markers.

Hydrogeologic controls on ground-water discharge to the Washington METRO subway tunnel near the Medical Center station and Crossover, Montgomery County, Maryland

USGS Publications Warehouse

Greene, Earl A.; Shapiro, Allen M.; LaMotte, Andrew E.

2004-01-01

Excessive water intrusion has been observed inside several of the Washington Metropolitan Area Transit Authority subway tunnels, with the worst leakage occurring along the Red Line tunnels and stations north of Dupont Circle in Washington, D.C. These tunnels were constructed in bedrock that contains permeable (water-bearing) joints and fractures. Excessive water leakage through the walls and water inside the underground facilities has damaged mechanical and electrical components in the tunnel, and has escalated the deterioration rate of the rail system. The U.S. Geological Survey and the Washington Metropolitan Area Transit Authority have worked cooperatively on a study from 200003 to describe and quantify the factors controlling ground-water flow into the Red Line subway tunnel near the Medical Center Station and Crossover in Montgomery County, Maryland. The Red Line near the Medical Center Station and Crossover passes through or beneath the gneissic Sykesville Formation and the biotite-hornblende tonalite member of the Georgetown Intrusive Suite, both of which contain numerous fractures. The mapped foliation and joints of the Sykesville Formation in the vicinity of the Medical Center Station and Crossover are generally orientated north-south. Fractures in the Sykesville Formation in outcrops appear to be poorly connected. In the biotite-hornblende tonalite member of the Georgetown Intrusive Suite, the general orientation of the mapped foliation and joints is east-west. In contrast to the fractures in the Sykesville Formation, the fractures in the Georgetown Intrusive Suite in outcrops appear to be more numerous and have a greater degree of connectivity. Fractures intersecting four bedrock wells near the Medical Center Station and Crossover that were drilled into the biotite-hornblende tonalite member of the Georgetown Intrusive Suite show an east-west orientation matching the foliation and joints shown on geologic maps. The excessive water intrusion at the Medical Center Station and Crossover could be the result of its location within the Georgetown Intrusive Suite. The abrupt changes in the mapped directions of ground-water flow based on the hydraulic heads at the contact between the Sykesville Formation and biotite-hornblende tonalite member of the Georgetown Intrusive Suite could also be the result of the change in fracturing between these two lithologies. Saprolite, a residual of soft, red/brown to gray clay from decomposed crystalline rock, overlies the bedrock and varies from about 20 to 55 feet thick, depending on location. On the basis of a slug test conducted in the lower part of the saprolite near the Medical Center Station and Crossover, transmissivity and storativity of the saprolite were estimated to be 10 feet squared per day and 10-6 , respectively. The transmissivity of fractures intersecting bedrock boreholes drilled in the biotite-hornblende tonalite member of the Georgetown Intrusive Suite varies over five orders of magnitude, from a maximum of approximately 10 feet squared per day to the detection limit of the in situ testing apparatus, which is approximately 10-4 feet squared per day. In general, the transmissivity of fractures intersecting the boreholes increases with depth. The low transmissivity of bedrock fractures in close proximity to the saprolite is likely to be caused by the fractures being filled with byproducts of rock weathering, resulting in reduced permeability. 2 Hydrogeologic Controls on Ground-Water Discharge to the Washington METRO Subway Tunnel The bulk transmissivity of the bedrock aquifer is approximately 3.7 feet squared per day, as determined from an aquifer test conducted by pumping a 240-foot-deep borehole and monitoring the drawdown over 3 days in the pumped borehole and several observation boreholes. In general, the hydraulic head decreases with depth in bedrock boreholes, indicating the potential for downward ground-water flow. Based on hydraulic head values mea

Work-Family Conflict within the Family: Crossover Effects, Perceived Parent-Child Interaction Quality, Parental Self-Efficacy, and Life Role Attributions

ERIC Educational Resources Information Center

Cinamon, Rachel Gali; Weisel, Amatzia; Tzuk, Kineret

2007-01-01

To better understand the work-family interface within the family domain, this study investigated crossover effects of two types of work-family conflict among 120 participants (60 married couples), these conflicts' relations with parental self-efficacy and perceived quality of parent-child interaction, and the contribution of attributions of…

Automatic identification of vessel crossovers in retinal images

NASA Astrophysics Data System (ADS)

Sánchez, L.; Barreira, N.; Penedo, M. G.; Cancela, B.

2015-02-01

Crossovers and bifurcations are interest points of the retinal vascular tree useful to diagnose diseases. Specifically, detecting these interest points and identifying which of them are crossings will give us the opportunity to search for arteriovenous nicking, this is, an alteration of the vessel tree where an artery is crossed by a vein and the former compresses the later. These formations are a clear indicative of hypertension, among other medical problems. There are several studies that have attempted to define an accurate and reliable method to detect and classify these relevant points. In this article, we propose a new method to identify crossovers. Our approach is based on segmenting the vascular tree and analyzing the surrounding area of each interest point. The minimal path between vessel points in this area is computed in order to identify the connected vessel segments and, as a result, to distinguish between bifurcations and crossovers. Our method was tested using retinographies from public databases DRIVE and VICAVR, obtaining an accuracy of 90%.

Kinetic roughening and porosity scaling in film growth with subsurface lateral aggregation.

PubMed

Reis, F D A Aarão

2015-06-01

We study surface and bulk properties of porous films produced by a model in which particles incide perpendicularly to a substrate, interact with deposited neighbors in its trajectory, and aggregate laterally with probability of order a at each position. The model generalizes ballisticlike models by allowing attachment to particles below the outer surface. For small values of a, a crossover from uncorrelated deposition (UD) to correlated growth is observed. Simulations are performed in 1+1 and 2+1 dimensions. Extrapolation of effective exponents and comparison of roughness distributions confirm Kardar-Parisi-Zhang roughening of the outer surface for a>0. A scaling approach for small a predicts crossover times as a(-2/3) and local height fluctuations as a(-1/3) at the crossover, independent of substrate dimension. These relations are different from all previously studied models with crossovers from UD to correlated growth due to subsurface aggregation, which reduces scaling exponents. The same approach predicts the porosity and average pore height scaling as a(1/3) and a(-1/3), respectively, in good agreement with simulation results in 1+1 and 2+1 dimensions. These results may be useful for modeling samples with desired porosity and long pores.

Chiral crossover transition in a finite volume

NASA Astrophysics Data System (ADS)

Shi, Chao; Jia, Wenbao; Sun, An; Zhang, Liping; Zong, Hongshi

2018-02-01

Finite volume effects on the chiral crossover transition of strong interactions at finite temperature are studied by solving the quark gap equation within a cubic volume of finite size L. With the anti-periodic boundary condition, our calculation shows the chiral quark condensate, which characterizes the strength of dynamical chiral symmetry breaking, decreases as L decreases below 2.5 fm. We further study the finite volume effects on the pseudo-transition temperature {T}{{c}} of the crossover, showing a significant decrease in {T}{{c}} as L decreases below 3 fm. Supported by National Natural Science Foundation of China (11475085, 11535005, 11690030, 51405027), the Fundamental Research Funds for the Central Universities (020414380074), China Postdoctoral Science Foundation (2016M591808) and Open Research Foundation of State Key Lab. of Digital Manufacturing Equipment & Technology in Huazhong University of Science & Technology (DMETKF2015015)

Organic-aqueous crossover coating process for the desmopressin orally disintegrating microparticles.

PubMed

Kim, Ju-Young; Hwang, Kyu-Mok; Park, Chun-Woong; Rhee, Yun-Seok; Park, Eun-Seok

2015-02-01

The purpose of the present study was to prepare desmopressin orally disintegrating microparticles (ODMs) using organic-aqueous crossover coating process which featured an organic sub-coating followed by an aqueous active coating. Sucrose beads and hydroxypropyl cellulose (HPC) were used as inert cores and a coating material, respectively. Characterizations including size distribution analysis, in-vitro release studies and in-vitro disintegration studies were performed. A pharmacokinetic study of the ODMs was also conducted in eight beagle dogs. It was found that sucrose beads should be coated using organic solvents to preserve their original morphology. For the active coating, the aqueous coating solution should be used for drug stability. When sucrose beads were coated using organic-aqueous crossover coating process, double-layer ODMs with round shapes were produced with detectable impurities below limit of US Pharmacopeia. The median size of ODMs was 195.6 μm, which was considered small enough for a good mouthfeel. The ODMs dissolved in artificial saliva within 15 s because of hydrophilic materials including sucrose and HPC in the ODMs. Because of its fast-dissolving properties, 100% release of the drug was reached within 5 min. Pharmacokinetic parameters including Cmax and AUC24 indicated bioequivalence of the ODMs and the conventional immediate release tablets. Therefore, by using the organic-aqueous crossover coating process, double-layer ODMs were successively prepared with small size, round shapes and good drug stability.

Computer Analysis of 400 HZ Aircraft Electrical Generator Test Data.

DTIC Science & Technology

1980-06-01

Data Acquisition System. ............ 6 3 Voltage Waveform with Data Points. ....... 19 14 Zero Crossover Interpolation. ........ 20 5 Numerical...difference between successive positive-sloped zero crossovers of the waveform. However, the exact time of zero crossover is not known. This is because...data sampling and the generator output are not synchronized. This unsynchronization means that data points which correspond with an exact zero crossover

Interim analyses in 2 x 2 crossover trials.

PubMed

Cook, R J

1995-09-01

A method is presented for performing interim analyses in long term 2 x 2 crossover trials with serial patient entry. The analyses are based on a linear statistic that combines data from individuals observed for one treatment period with data from individuals observed for both periods. The coefficients in this linear combination can be chosen quite arbitrarily, but we focus on variance-based weights to maximize power for tests regarding direct treatment effects. The type I error rate of this procedure is controlled by utilizing the joint distribution of the linear statistics over analysis stages. Methods for performing power and sample size calculations are indicated. A two-stage sequential design involving simultaneous patient entry and a single between-period interim analysis is considered in detail. The power and average number of measurements required for this design are compared to those of the usual crossover trial. The results indicate that, while there is minimal loss in power relative to the usual crossover design in the absence of differential carry-over effects, the proposed design can have substantially greater power when differential carry-over effects are present. The two-stage crossover design can also lead to more economical studies in terms of the expected number of measurements required, due to the potential for early stopping. Attention is directed toward normally distributed responses.

Dynamic crossover in deeply cooled water confined in MCM-41 at 4 kbar and its relation to the liquid-liquid transition hypothesis

NASA Astrophysics Data System (ADS)

Wang, Zhe; Le, Peisi; Ito, Kanae; Leão, Juscelino B.; Tyagi, Madhusudan; Chen, Sow-Hsin

2015-09-01

With quasi-elastic neutron scattering, we study the single-particle dynamics of the water confined in a hydrophilic silica material, MCM-41, at 4 kbar. A dynamic crossover phenomenon is observed at 219 K. We compare this dynamic crossover with the one observed at ambient pressure and find that (a) above the crossover temperature, the temperature dependence of the characteristic relaxation time at ambient pressure exhibits a more evident super-Arrhenius behavior than that at 4 kbar. Especially, at temperatures below about 230 K, the relaxation time at 4 kbar is even smaller than that at ambient pressure. This feature is different from many other liquids. (b) Below the crossover temperature, the Arrhenius behavior found at ambient pressure has a larger activation energy compared to the one found at 4 kbar. We ascribe the former to the difference between the local structure of the low-density liquid (LDL) phase and that of the high-density liquid (HDL) phase, and the latter to the difference between the strength of the hydrogen bond of the LDL and that of the HDL. Therefore, we conclude that the phenomena observed in this paper are consistent with the LDL-to-HDL liquid-liquid transition hypothesis.

Dynamic crossover in deeply cooled water confined in MCM-41 at 4 kbar and its relation to the liquid-liquid transition hypothesis

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

Wang, Zhe; Le, Peisi; Ito, Kanae

With quasi-elastic neutron scattering, we study the single-particle dynamics of the water confined in a hydrophilic silica material, MCM-41, at 4 kbar. A dynamic crossover phenomenon is observed at 219 K. We compare this dynamic crossover with the one observed at ambient pressure and find that (a) above the crossover temperature, the temperature dependence of the characteristic relaxation time at ambient pressure exhibits a more evident super-Arrhenius behavior than that at 4 kbar. Especially, at temperatures below about 230 K, the relaxation time at 4 kbar is even smaller than that at ambient pressure. This feature is different from manymore » other liquids. (b) Below the crossover temperature, the Arrhenius behavior found at ambient pressure has a larger activation energy compared to the one found at 4 kbar. We ascribe the former to the difference between the local structure of the low-density liquid (LDL) phase and that of the high-density liquid (HDL) phase, and the latter to the difference between the strength of the hydrogen bond of the LDL and that of the HDL. Therefore, we conclude that the phenomena observed in this paper are consistent with the LDL-to-HDL liquid-liquid transition hypothesis.« less

Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

PubMed

Liu, Dongzhou J; Collaku, Agron

2018-01-01

Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

Effect of aggregation form on bioavailability of zeaxanthin in humans: a randomised cross-over study.

PubMed

Hempel, Judith; Fischer, Anja; Fischer, Monique; Högel, Josef; Bosy-Westphal, Anja; Carle, Reinhold; Schweiggert, Ralf M

2017-11-01

Carotenoid bioavailability from plant and animal food is highly variable depending on numerous factors such as the physical deposition form of carotenoids. As the carotenoid zeaxanthin is believed to play an important role in eye and brain health, we sought to compare the human bioavailability of an H-aggregated with that of a J-aggregated deposition form of zeaxanthin encapsulated into identical formulation matrices. A randomised two-way cross-over study with sixteen participants was designed to compare the post-prandial bioavailability of an H-aggregated zeaxanthin and a J-aggregated zeaxanthin dipalmitate formulation, both delivering 10 mg of free zeaxanthin. Carotenoid levels in TAG-rich lipoprotein fractions were analysed over 9·5 h after test meal consumption. Bioavailability from the J-aggregated formulation (AUC=55·9 nmol h/l) was 23 % higher than from the H-aggregated one (AUC=45·5 nmol h/l), although being only marginally significant (P=0·064). Furthermore, the same formulations were subjected to an internationally recognised in vitro digestion protocol to reveal potential strengths and weaknesses of simulated digestions. In agreement with our human study, liberation of zeaxanthin from the J-aggregated formulation into the simulated duodenal fluids was superior to that from the H-aggregated form. However, micellization rate (bioaccessibility) of the J-aggregated zeaxanthin dipalmitate was lower than that of the H-aggregated zeaxanthin, being contradictory to our in vivo results. An insufficient ester cleavage during simulated digestion was suggested to be the root cause for these observations. In brief, combining our in vitro and in vivo observations, the effect of the different aggregation forms on human bioavailability was lower than expected.

Qualitative Inquiry and Research Design: Choosing among Five Approaches [with CD-ROM]. Second Edition

ERIC Educational Resources Information Center

Creswell, John W.

2006-01-01

This new version explores the philosophical underpinnings, history, and key elements of each of five qualitative inquiry approaches: narrative research, phenomenology, grounded theory, ethnography, and case study. Using an accessible and engaging writing style, the author compares theoretical frameworks, ways to employ standards of quality, and…

Does a crossover age effect exist for African American and Hispanic binge drinkers? Findings from the 2010-2013 National Study on Drug Use and Health

PubMed Central

Zapolski, Tamika C. B.; Baldwin, Patrick; Banks, Devin E.; Stump, Timothy E.

2017-01-01

Background Among general population studies, lower rates of binge drinking tend to be found among African Americans and Hispanics compared to Whites. However, among older adult populations, minority groups have been shown to be at higher risk for binge drinking, suggesting the presence of a crossover effect from low to high risk as a function of age. Aims To date, limited research has examined the crossover effect among African American and Hispanic populations compared to non-Hispanic Whites across large developmental time frames or explored variation in risk based on income or gender. The current study aimed to fill these gaps in the literature. Methods Data were compiled from the 2010-2013 National Survey on Drug Use and Health surveys, which provide annual, nationally representative data on substance use behaviors among individuals age 12 and older. Hispanic, non-Hispanic African American, and non-Hispanic White respondents were included (N = 205,198) in the analyses. Results A crossover effect was found for African American males and females among the lowest income level (i.e., incomes less than $20,000). Specifically, after controlling for education and marital status, compared to Whites, risk for binge drinking was lower for African American males at ages 18-24 and for females at ages 18-34, but higher for both African American males and females at ages 50 to 64. No crossover effect was found for Hispanic respondents. Conclusions Although African Americans are generally at lower risk for binge drinking, risk appears to increase disproportionately with age among those who are impoverished. Social determinants of health prevalent within low-income African American communities (e.g., lower education, violence exposure, housing insecurity) and potential areas for intervention programming are discussed. PMID:28423479

Calorimetric indications of a cooperativity onset in the crossover region of dynamic glass transition for benzoin isobutylether

NASA Astrophysics Data System (ADS)

Kahle, S.; Schröter, K.; Hempel, E.; Donth, E.

1999-10-01

Heat capacity spectroscopy (HCS), dielectric spectroscopy, and shear viscosity data are reported for liquid benzoin isobutylether (BIBE). Dielectric and viscosity peculiarities indicate the crossover region of dynamic glass transition at T=(-8±8) °C where the extrapolated Johari Goldstein β relaxation intersects the main transition trace in an Arrhenius plot. Although HCS does not reach the crossover frequency of order ω=2×106 rad/s, the linear decrease of the square root of cooperativity as calculated from HCS data at lower frequencies indicates a cooperativity onset in the crossover temperature-frequency range. As BIBE belongs to another dielectric crossover scenario as the substances where such an onset could previously be observed, it seems that the cooperativity onset is a general property of the crossover region.

A curve fitting method for solving the flutter equation. M.S. Thesis

NASA Technical Reports Server (NTRS)

Cooper, J. L.

1972-01-01

A curve fitting approach was developed to solve the flutter equation for the critical flutter velocity. The psi versus nu curves are approximated by cubic and quadratic equations. The curve fitting technique utilized the first and second derivatives of psi with respect to nu. The method was tested for two structures, one structure being six times the total mass of the other structure. The algorithm never showed any tendency to diverge from the solution. The average time for the computation of a flutter velocity was 3.91 seconds on an IBM Model 50 computer for an accuracy of five per cent. For values of nu close to the critical root of the flutter equation the algorithm converged on the first attempt. The maximum number of iterations for convergence to the critical flutter velocity was five with an assumed value of nu relatively distant from the actual crossover.

Changing the Way We Teach by Changing the College: Leading the Way Together.

ERIC Educational Resources Information Center

Lape, Douglas H.; Hart, Patricia K.

1997-01-01

Reviews the responses of five leadership groups (presidents, chief financial officers, deans of liberal studies, chairs of social sciences and media services directors) from 29 community colleges in Michigan regarding the planning, curriculum design, and cost-effectiveness of distance education. Indicates that all groups have favorable views of…

"He Was Born that Way": Parental Constructions of Giftedness

ERIC Educational Resources Information Center

Mudrak, Jiri

2011-01-01

The article presents results of a multiple-case study that examined the ways in which parents perceived and influenced the development of five children who showed extraordinary potential in various domains, such as school, sports or music. Semi-structured interviews were used to collect information about the children's development and were…

Circuit Design Optimization Using Genetic Algorithm with Parameterized Uniform Crossover

NASA Astrophysics Data System (ADS)

Bao, Zhiguo; Watanabe, Takahiro

Evolvable hardware (EHW) is a new research field about the use of Evolutionary Algorithms (EAs) to construct electronic systems. EHW refers in a narrow sense to use evolutionary mechanisms as the algorithmic drivers for system design, while in a general sense to the capability of the hardware system to develop and to improve itself. Genetic Algorithm (GA) is one of typical EAs. We propose optimal circuit design by using GA with parameterized uniform crossover (GApuc) and with fitness function composed of circuit complexity, power, and signal delay. Parameterized uniform crossover is much more likely to distribute its disruptive trials in an unbiased manner over larger portions of the space, then it has more exploratory power than one and two-point crossover, so we have more chances of finding better solutions. Its effectiveness is shown by experiments. From the results, we can see that the best elite fitness, the average value of fitness of the correct circuits and the number of the correct circuits of GApuc are better than that of GA with one-point crossover or two-point crossover. The best case of optimal circuits generated by GApuc is 10.18% and 6.08% better in evaluating value than that by GA with one-point crossover and two-point crossover, respectively.

Distinct age and self-rated health crossover mortality effects for African Americans: Evidence from a national cohort study.

PubMed

Roth, David L; Skarupski, Kimberly A; Crews, Deidra C; Howard, Virginia J; Locher, Julie L

2016-05-01

The predictive effects of age and self-rated health (SRH) on all-cause mortality are known to differ across race and ethnic groups. African American adults have higher mortality rates than Whites at younger ages, but this mortality disparity diminishes with advancing age and may "crossover" at about 75-80 years of age, when African Americans may show lower mortality rates. This pattern of findings reflects a lower overall association between age and mortality for African Americans than for Whites, and health-related mechanisms are typically cited as the reason for this age-based crossover mortality effect. However, a lower association between poor SRH and mortality has also been found for African Americans than for Whites, and it is not known if the reduced age and SRH associations with mortality for African Americans reflect independent or overlapping mechanisms. This study examined these two mortality predictors simultaneously in a large epidemiological study of 12,181 African Americans and 17,436 Whites. Participants were 45 or more years of age when they enrolled in the national REasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007. Consistent with previous studies, African Americans had poorer SRH than Whites even after adjusting for demographic and health history covariates. Survival analysis models indicated statistically significant and independent race*age, race*SRH, and age*SRH interaction effects on all-cause mortality over an average 9-year follow-up period. Advanced age and poorer SRH were both weaker mortality risk factors for African Americans than for Whites. These two effects were distinct and presumably tapped different causal mechanisms. This calls into question the health-related explanation for the age-based mortality crossover effect and suggests that other mechanisms, including behavioral, social, and cultural factors, should be considered in efforts to better understand the age-based mortality crossover effect and other longevity disparities. Copyright © 2016. Published by Elsevier Ltd.

Phenomenological model of spin crossover in molecular crystals as derived from atom-atom potentials.

PubMed

Sinitskiy, Anton V; Tchougréeff, Andrei L; Dronskowski, Richard

2011-08-07

The method of atom-atom potentials, previously applied to the analysis of pure molecular crystals formed by either low-spin (LS) or high-spin (HS) forms (spin isomers) of Fe(II) coordination compounds (Sinitskiy et al., Phys. Chem. Chem. Phys., 2009, 11, 10983), is used to estimate the lattice enthalpies of mixed crystals containing different fractions of the spin isomers. The crystals under study were formed by LS and HS isomers of Fe(phen)(2)(NCS)(2) (phen = 1,10-phenanthroline), Fe(btz)(2)(NCS)(2) (btz = 5,5',6,6'-tetrahydro-4H,4'H-2,2'-bi-1,3-thiazine), and Fe(bpz)(2)(bipy) (bpz = dihydrobis(1-pyrazolil)borate, and bipy = 2,2'-bipyridine). For the first time the phenomenological parameters Γ pertinent to the Slichter-Drickamer model (SDM) of several materials were independently derived from the microscopic model of the crystals with use of atom-atom potentials of intermolecular interaction. The accuracy of the SDM was checked against the numerical data on the enthalpies of mixed crystals. Fair semiquantitative agreement with the experimental dependence of the HS fraction on temperature was achieved with use of these values. Prediction of trends in Γ values as a function of chemical composition and geometry of the crystals is possible with the proposed approach, which opens a way to rational design of spin crossover materials with desired properties. This journal is © the Owner Societies 2011

Urinary excretion of Citrus flavanones and their major catabolites after consumption of fresh oranges and pasteurized orange juice: A randomized cross-over study.

PubMed

Aschoff, Julian K; Riedl, Ken M; Cooperstone, Jessica L; Högel, Josef; Bosy-Westphal, Anja; Schwartz, Steven J; Carle, Reinhold; Schweiggert, Ralf M

2016-12-01

Orange juice contains flavanones including hesperidin and narirutin, albeit at lower concentrations as compared to orange fruit. Therefore, we compared bioavailability and colonic catabolism of flavanones from orange juice to a 2.4-fold higher dose from fresh oranges. Following a randomized two-way cross-over design, 12 healthy subjects consumed a test meal comprising either fresh oranges or pasteurized orange juice, delivering 1774 and 751 μmol of total Citrus flavanones, respectively. Deglucuronidated and desulfated hesperetin, naringenin, and the flavanone catabolites 3-(3'-hydroxy-4'-methoxyphenyl)propionic acid, 3-(3'-hydroxyphenyl)hydracrylic acid, 4-hydroxyhippuric acid, and hippuric acid were quantitated in 24-h urine by UHPLC-MS/MS. Differences in urinary hesperetin excretion were found to be nonsignificant (p = 0.5209) both after consumption of orange fruit (21.6 ± 8.0 μmol) and juice (18.3 ± 7.2 μmol). By analogy, postprandial flavanone catabolite excretions were highly similar between treatments. Excretion of 3-(3'-hydroxy-4'-methoxyphenyl)propionic acid was inversely related to that of hesperetin, illustrating the catabolite/precursor relationship. Despite 2.4-fold higher doses, excretion of flavanones from ingested fresh orange fruit did not differ from that following orange juice consumption, possibly due to a saturation of absorption or their entrapment in the fiber-rich matrix of the fruit. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis.

PubMed

Medhi, Darpan; Goldman, Alastair Sh; Lichten, Michael

2016-11-18

The budding yeast genome contains regions where meiotic recombination initiates more frequently than in others. This pattern parallels enrichment for the meiotic chromosome axis proteins Hop1 and Red1. These proteins are important for Spo11-catalyzed double strand break formation; their contribution to crossover recombination remains undefined. Using the sequence-specific VMA1 -derived endonuclease (VDE) to initiate recombination in meiosis, we show that chromosome structure influences the choice of proteins that resolve recombination intermediates to form crossovers. At a Hop1-enriched locus, most VDE-initiated crossovers, like most Spo11-initiated crossovers, required the meiosis-specific MutLγ resolvase. In contrast, at a locus with lower Hop1 occupancy, most VDE-initiated crossovers were MutLγ-independent. In pch2 mutants, the two loci displayed similar Hop1 occupancy levels, and VDE-induced crossovers were similarly MutLγ-dependent. We suggest that meiotic and mitotic recombination pathways coexist within meiotic cells, and that features of meiotic chromosome structure determine whether one or the other predominates in different regions.

Skating crossovers on a motorized flywheel: a preliminary experimental design to test effect on speed and on crossovers.

PubMed

Smith, Aynsley M; Krause, David A; Stuart, Michael J; Montelpare, William J; Sorenson, Matthew C; Link, Andrew A; Gaz, Daniel V; Twardowski, Casey P; Larson, Dirk R; Stuart, Michael B

2013-12-01

Ice hockey requires frequent skater crossovers to execute turns. Our investigation aimed to determine the effectiveness of training crossovers on a motorized, polyethylene high-resistance flywheel. We hypothesized that high school hockey players training on the flywheel would perform as well as their peers training on ice. Participants were 23 male high-school hockey players (age 15-19 years). The study used an experimental prospective design to compare players who trained for 9 sessions on the 22-foot flywheel with players who trained for 9 sessions on a similarly sized on-ice circle. Both groups were compared with control subjects who were randomly selected from the same participant pool as those training on ice. All players were tested before and after their 3-week training regimens, and control subjects were asked to not practice crossovers between testing. Group 1 trained in a hockey training facility housing the flywheel, and group 2 trained in the ice hockey arena where testing occurred. Primary outcome measures tested in both directions were: (a) speed (time in seconds) required to skate crossovers for 3 laps of a marked face-off circle, (b) cadence of skating crossovers on the similarly sized circles, and (c) a repeat interval speed test, which measures anaerobic power. No significant changes were found between groups in on-ice testing before and after training. Among the group 1 players, 7 of 8 believed they benefited from flywheel training. Group 2 players, who trained on ice, did not improve performance significantly over group 1 players. Despite the fact that no significant on-ice changes in performance were observed in objective measures, players who trained on the flywheel subjectively reported that the flywheel is an effective cost-effective alternative to training on ice. This is a relevant finding when placed in context with limited availability of on-ice training.

Ruxolitinib reduces JAK2 p.V617F allele burden in patients with polycythemia vera enrolled in the RESPONSE study.

PubMed

Vannucchi, Alessandro Maria; Verstovsek, Srdan; Guglielmelli, Paola; Griesshammer, Martin; Burn, Timothy C; Naim, Ahmad; Paranagama, Dilan; Marker, Mahtab; Gadbaw, Brian; Kiladjian, Jean-Jacques

2017-07-01

In patients with polycythemia vera (PV), an elevated JAK2 p.V617F allele burden is associated with indicators of more severe disease (e.g., leukocytosis, splenomegaly, and increased thrombosis risk); however, correlations between allele burden reductions and clinical benefit in patients with PV have not been extensively evaluated in a randomized trial. This exploratory analysis from the multicenter, open-label, phase 3 Randomized Study of Efficacy and Safety in Polycythemia Vera With JAK Inhibitor INCB018424 Versus Best Supportive Care trial evaluated the long-term effect of ruxolitinib treatment on JAK2 p.V617F allele burden in patients with PV. Evaluable JAK2 p.V617F-positive patients randomized to ruxolitinib (n = 107) or best available therapy (BAT) who crossed over to ruxolitinib at week 32 (n = 97) had consistent JAK2 p.V617F allele burden reductions throughout the study. At all time points measured (up to weeks 208 [ruxolitinib-randomized] and 176 [ruxolitinib crossover]), mean changes from baseline over time in JAK2 p.V617F allele burden ranged from -12.2 to -40.0% (ruxolitinib-randomized) and -6.3 to -17.8% (ruxolitinib crossover). Complete or partial molecular response was observed in 3 patients (ruxolitinib-randomized, n = 2; ruxolitinib crossover, n = 1) and 54 patients (ruxolitinib-randomized, n = 33; ruxolitinib crossover, n = 20; BAT, n = 1), respectively. Among patients treated with interferon as BAT (n = 13), the mean maximal reduction in allele burden from baseline was 25.6% after crossover to ruxolitinib versus 6.6% before crossover. Collectively, the data from this exploratory analysis suggest that ruxolitinib treatment for up to 4 years provides progressive reductions in JAK2 p.V617F allele burden in patients with PV who are resistant to or intolerant of hydroxyurea. The relationship between allele burden changes and clinical outcomes in patients with PV remains unclear.

Comparison of text messaging data collection vs face-to-face interviews for public health surveys: a cluster randomized crossover study of care-seeking for childhood pneumonia and diarrhoea in rural China.

PubMed

van Velthoven, Michelle Helena; Wang, Wei; Wu, Qiong; Li, Ye; Scherpbier, Robert W; Du, Xiaozhen; Chen, Li; Zhang, Yanfeng; Car, Josip; Rudan, Igor

2018-06-01

To compare text messaging and face-to-face interviews to conduct a survey on childhood diarrhoea and pneumonia. Caregivers of young children able to send text messages in Zhao County in rural China were included in this crossover study. Villages (clusters) were randomized into two groups using the ratio 1:1.6 to account for an expected higher drop-out in group 2. In group 1, participants first completed the face-to-face and then text messaging survey; this order was reversed in group 2. We determined data equivalence of 17 questions that were answered by participants who were the same person in both surveys. For the text messaging survey, we assessed the overall and item response rate. We included 1014 participants between 16 and 28 March 2013: 371 in 15 villages in group 1 and 643 in 27 villages in group 2. A total of 662 (65.3%) out of 1014 participants responded (first text message question) and a significantly higher proportion who did not respond were from rural areas ( P  = 0.005). Of 651 participants willing to participate, 356 (54.7%) completed the text messaging survey, which was marginally significantly different between the groups ( P  = 0.05). In total, 409 participants took part in both surveys: 183 in group 1 and 226 in group 2. There was a significantly higher proportion of caregivers from rural areas in Zhao County in the non-responder group compared to the responder group ( P  = 0.004). Kappas were substantial for six (0.61-0.80), moderate for two (0.58 and 0.60), and fair for three questions (0.31, 0.35 and 0.37). The proportion of agreement was >90% for five questions; 80.0%-90.0% for five questions; 70.0%, 65.0% and 45.5%. The remaining questions had too small numbers to calculate these values. This study shows that text messaging data collection produces data similar to data from face-to-face interviews in a middle-income setting, but the response rate was insufficient for use in public health surveys. Improving the response rate is important, because text message surveys could be of greater value in rural remote areas due to the cost-saving potential.

Technology-Based Healthcare for Nursing Education Within The Netherlands: Past, Present and Future.

PubMed

Koster, Ybranda; van Houwelingen, Cornelis T M

2017-01-01

At the present time, nearly all Dutch nursing schools are searching for suitable ways to implement technology-based healthcare in their curriculum. Some Universities chose elective education, others a mandatory solution. Several studies were executed to determine competencies needed by nurses in order to work with technology-based healthcare. In 2016 a nationwide new curriculum for nurses has been published. Providing technology-based healthcare is included under the core competencies of this new curriculum. All baccalaureate nursing educational institutes must implement this new curriculum at the start of 2016 which will have a huge impact on the implementation of technology-based healthcare in the education programs. In the future, technology centers from Universities will collaborate and specialize, partner with technology companies and crossovers between information and communication technology and healthcare education will be expanded.

Pharmacokinetic and pharmacodynamic interactions between zolpidem and caffeine.

PubMed

Cysneiros, R M; Farkas, D; Harmatz, J S; von Moltke, L L; Greenblatt, D J

2007-07-01

The kinetic and dynamic interaction of caffeine and zolpidem was evaluated in a double-blind, single-dose, six-way crossover study of 7.5 mg zolpidem (Z) or placebo (P) combined with low-dose caffeine (250 mg), high-dose caffeine (500 mg), or placebo. Caffeine coadministration modestly increased maximum plasma concentration (C(max)) and area under the plasma concentration-time curve of zolpidem by 30-40%, whereas zolpidem did not significantly affect the pharmacokinetics of caffeine or its metabolites. Compared to P+P, Z+P significantly increased sedation, impaired digit-symbol substitution test performance, slowed tapping speed and reaction time, increased EEG relative beta amplitude, and impaired delayed recall. Caffeine partially, but not completely, reversed most pharmacodynamic effects of zolpidem. Thus, caffeine only incompletely reverses zolpidem's sedative and performance-impairing effects, and cannot be considered as an antidote to benzodiazepine agonists.

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

Ono, Shota, E-mail: shota-o@gifu-u.ac.jp; Department of Physics, Graduate School of Engineering, Yokohama National University, Yokohama 240-8501; Tanikawa, Kousei

Revealing a universal relation between geometrical structures and electronic properties of capped carbon nanotubes (CNTs) is one of the current objectives in nanocarbon community. Here, we investigate the local curvature of capped CNTs and define the cap region by a crossover behavior of the curvature energy versus the number of carbon atoms integrated from the tip to the tube region. Clear correlations among the energy gap of the cap localized states, the curvature energy, the number of carbon atoms in the cap region, and the number of specific carbon clusters are observed. The present analysis opens the way to understandmore » the cap states.« less

The joy of six: how to control your crossovers.

PubMed

Globus, Samuel T; Keeney, Scott

2012-03-30

Meiotic cells tightly regulate the number and distribution of crossovers to promote accurate chromosome segregation. Yokoo and colleagues uncover a metazoan-specific, cyclin-like protein that is crucial for crossover formation. They utilize this protein's unique properties to explore a remarkable example of biological numerology, whereby nearly every meiotic cell in C. elegans makes precisely six crossovers, one for each of its six chromosome pairs. Copyright © 2012 Elsevier Inc. All rights reserved.

An improved genetic algorithm and its application in the TSP problem

NASA Astrophysics Data System (ADS)

Li, Zheng; Qin, Jinlei

2011-12-01

Concept and research actuality of genetic algorithm are introduced in detail in the paper. Under this condition, the simple genetic algorithm and an improved algorithm are described and applied in an example of TSP problem, where the advantage of genetic algorithm is adequately shown in solving the NP-hard problem. In addition, based on partial matching crossover operator, the crossover operator method is improved into extended crossover operator in order to advance the efficiency when solving the TSP. In the extended crossover method, crossover operator can be performed between random positions of two random individuals, which will not be restricted by the position of chromosome. Finally, the nine-city TSP is solved using the improved genetic algorithm with extended crossover method, the efficiency of whose solution process is much higher, besides, the solving speed of the optimal solution is much faster.

Observing large-scale temporal variability of ocean currents by satellite altimetry - With application to the Antarctic circumpolar current

NASA Technical Reports Server (NTRS)

Fu, L.-L.; Chelton, D. B.

1985-01-01

A new method is developed for studying large-scale temporal variability of ocean currents from satellite altimetric sea level measurements at intersections (crossovers) of ascending and descending orbit ground tracks. Using this method, sea level time series can be constructed from crossover sea level differences in small sample areas where altimetric crossovers are clustered. The method is applied to Seasat altimeter data to study the temporal evolution of the Antarctic Circumpolar Current (ACC) over the 3-month Seasat mission (July-October 1978). The results reveal a generally eastward acceleration of the ACC around the Southern Ocean with meridional disturbances which appear to be associated with bottom topographic features. This is the first direct observational evidence for large-scale coherence in the temporal variability of the ACC. It demonstrates the great potential of satellite altimetry for synoptic observation of temporal variability of the world ocean circulation.

A novel mechanism important for the alignment of microtubules.

PubMed

Wightman, Raymond; Turner, Simon R

2008-04-01

Using a live-cell imaging approach to study individual micro-tubules, we have compared microtubule behavior between net-like and aligned cortical arrays. In contrast to previous studies, a steep angled collision between the growing end of a microtubule and a preexisting microtubule was found to favor crossover. Frequencies of microtubule crossovers, bundling and catastrophes are similar regardless of whether the cell exhibited a net-like or aligned microtubule array. In the predominantly aligned array of petiole cells, severing occurs at the sites of microtubule crossovers and serves to remove unaligned microtubules and to increase microtubule density. Severing was observed to be rare in net-like arrays. Microtubule severing is carried out by the katanin enzyme. In this addendum, we present new insights into the possible mechanism of crossing over and preliminary data looking at organization of the array in a katanin mutant.

Expected precision of Europa Clipper gravity measurements

NASA Astrophysics Data System (ADS)

Verma, Ashok K.; Margot, Jean-Luc

2018-11-01

The primary gravity science objective of NASA's Clipper mission to Europa is to confirm the presence or absence of a global subsurface ocean beneath Europa's Icy crust. Gravity field measurements obtained with a radio science investigation can reveal much about Europa's interior structure. Here, we conduct extensive simulations of the radio science measurements with the anticipated spacecraft trajectory and attitude (17F12v2) and assets on the spacecraft and the ground, including antenna orientations and beam patterns, transmitter characteristics, and receiver noise figures. In addition to two-way Doppler measurements, we also include radar altimeter crossover range measurements. We concentrate on ± 2 h intervals centered on the closest approach of each of the 46 flybys. Our covariance analyses reveal the precision with which the tidal Love number k2, second-degree gravity coefficients Cbar20 and Cbar22 , and higher-order gravity coefficients can be determined. The results depend on the Deep Space Network (DSN) assets that are deployed to track the spacecraft. We find that some DSN allocations are sufficient to conclusively confirm the presence or absence of a global ocean. Given adequate crossover range performance, it is also possible to evaluate whether the ice shell is hydrostatic.

In silico modelling of directed evolution: Implications for experimental design and stepwise evolution.

PubMed

Wedge, David C; Rowe, William; Kell, Douglas B; Knowles, Joshua

2009-03-07

We model the process of directed evolution (DE) in silico using genetic algorithms. Making use of the NK fitness landscape model, we analyse the effects of mutation rate, crossover and selection pressure on the performance of DE. A range of values of K, the epistatic interaction of the landscape, are considered, and high- and low-throughput modes of evolution are compared. Our findings suggest that for runs of or around ten generations' duration-as is typical in DE-there is little difference between the way in which DE needs to be configured in the high- and low-throughput regimes, nor across different degrees of landscape epistasis. In all cases, a high selection pressure (but not an extreme one) combined with a moderately high mutation rate works best, while crossover provides some benefit but only on the less rugged landscapes. These genetic algorithms were also compared with a "model-based approach" from the literature, which uses sequential fixing of the problem parameters based on fitting a linear model. Overall, we find that purely evolutionary techniques fare better than do model-based approaches across all but the smoothest landscapes.

Increased Erythrocyte Eicosapentaenoic Acid and Docosahexaenoic Acid Are Associated With Improved Attention and Behavior in Children With ADHD in a Randomized Controlled Three-Way Crossover Trial.

PubMed

Milte, Catherine M; Parletta, Natalie; Buckley, Jonathan D; Coates, Alison M; Young, Ross M; Howe, Peter R C

2015-11-01

To investigate effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on attention, literacy, and behavior in children with ADHD. Ninety children were randomized to consume supplements high in EPA, DHA, or linoleic acid (control) for 4 months each in a crossover design. Erythrocyte fatty acids, attention, cognition, literacy, and Conners' Parent Rating Scales (CPRS) were measured at 0, 4, 8, 12 months. Fifty-three children completed the treatment. Outcome measures showed no significant differences between the three treatments. However, in children with blood samples (n = 76-46), increased erythrocyte EPA + DHA was associated with improved spelling (r = .365, p < .001) and attention (r = -.540, p < .001) and reduced oppositional behavior (r = -.301, p < .003), hyperactivity (r = -.310, p < .001), cognitive problems (r = -.326, p < .001), Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) hyperactivity (r = -.270, p = .002) and DSM-IV inattention (r = -.343, p < .001). Increasing erythrocyte DHA and EPA via dietary supplementation may improve behavior, attention, and literacy in children with ADHD. © The Author(s) 2013.

Nonlocal equation for the superconducting gap parameter

NASA Astrophysics Data System (ADS)

Simonucci, S.; Strinati, G. Calvanese

2017-08-01

The properties are considered in detail of a nonlocal (integral) equation for the superconducting gap parameter, which is obtained by a coarse-graining procedure applied to the Bogoliubov-de Gennes (BdG) equations over the whole coupling-versus-temperature phase diagram associated with the superfluid phase. It is found that the limiting size of the coarse-graining procedure, which is dictated by the range of the kernel of this integral equation, corresponds to the size of the Cooper pairs over the whole coupling-versus-temperature phase diagram up to the critical temperature, even when Cooper pairs turn into composite bosons on the BEC side of the BCS-BEC crossover. A practical method is further implemented to solve numerically this integral equation in an efficient way, which is based on a novel algorithm for calculating the Fourier transforms. Application of this method to the case of an isolated vortex, throughout the BCS-BEC crossover and for all temperatures in the superfluid phase, helps clarifying the nature of the length scales associated with a single vortex and the kinds of details that are in practice disposed off by the coarse-graining procedure on the BdG equations.

Induced interaction in a Fermi gas with a BEC-BCS crossover

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

Yu Zengqiang; Huang Kun; Yin Lan

2009-05-15

We study the effect of the induced interaction on the superfluid transition temperature of a Fermi gas with a Bose-Einstein condensation-Bardeen-Cooper-Schrieffer (BEC-BCS) crossover. The Gorkov-Melik-Barkhudarov theory about the induced interaction is extended from the BCS side to the entire crossover and the pairing fluctuation is treated in the approach by Nozieres and Schmitt-Rink. At unitarity, the induced interaction reduces the transition temperature by about 20%. In the BCS limit, the transition temperature is reduced by a factor of about 2.22, as found by Gorkov and Melik-Barkhudarov. Our result shows that the effect of the induced interaction is important both onmore » the BCS side and in the unitary region.« less

Scan-rate and vacuum pressure dependence of the nucleation and growth dynamics in a spin-crossover single crystal: the role of latent heat.

PubMed

Ridier, Karl; Rat, Sylvain; Salmon, Lionel; Nicolazzi, William; Molnár, Gábor; Bousseksou, Azzedine

2018-04-04

Using optical microscopy we studied the vacuum pressure dependence (0.1-1000 mbar) of the nucleation and growth dynamics of the thermally induced first-order spin transition in a single crystal of the spin-crossover compound [Fe(HB(tz)3)2] (tz = 1,2,4-triazol-1-yl). A crossover between a quasi-static hysteresis regime and a temperature-scan-rate-dependent kinetic regime is evidenced around 5 mbar due to the change of the heat exchange coupling between the crystal and its external environment. Remarkably, the absorption/dissipation rate of latent heat was identified as the key factor limiting the switching speed of the crystal.

Cross-over endocytosis of claudins is mediated by interactions via their extracellular loops.

PubMed

Gehne, Nora; Lamik, Agathe; Lehmann, Martin; Haseloff, Reiner F; Andjelkovic, Anuska V; Blasig, Ingolf E

2017-01-01

Claudins (Cldns) are transmembrane tight junction (TJ) proteins that paracellularly seal endo- and epithelial barriers by their interactions within the TJs. However, the mechanisms allowing TJ remodeling while maintaining barrier integrity are largely unknown. Cldns and occludin are heterophilically and homophilically cross-over endocytosed into neighboring cells in large, double membrane vesicles. Super-resolution microscopy confirmed the presence of Cldns in these vesicles and revealed a distinct separation of Cldns derived from opposing cells within cross-over endocytosed vesicles. Colocalization of cross-over endocytosed Cldn with the autophagosome markers as well as inhibition of autophagosome biogenesis verified involvement of the autophagosomal pathway. Accordingly, cross-over endocytosed Cldns underwent lysosomal degradation as indicated by lysosome markers. Cross-over endocytosis of Cldn5 depended on clathrin and caveolin pathways but not on dynamin. Cross-over endocytosis also depended on Cldn-Cldn-interactions. Amino acid substitutions in the second extracellular loop of Cldn5 (F147A, Q156E) caused impaired cis- and trans-interaction, as well as diminished cross-over endocytosis. Moreover, F147A exhibited an increased mobility in the membrane, while Q156E was not as mobile but enhanced the paracellular permeability. In conclusion, the endocytosis of TJ proteins depends on their ability to interact strongly with each other in cis and trans, and the mobility of Cldns in the membrane is not necessarily an indicator of barrier permeability. TJ-remodeling via cross-over endocytosis represents a general mechanism for the degradation of transmembrane proteins in cell-cell contacts and directly links junctional membrane turnover to autophagy.

Concord grape juice, cognitive function, and driving performance: a 12-wk, placebo-controlled, randomized crossover trial in mothers of preteen children.

PubMed

Lamport, Daniel J; Lawton, Clare L; Merat, Natasha; Jamson, Hamish; Myrissa, Kyriaki; Hofman, Denise; Chadwick, Helen K; Quadt, Frits; Wightman, JoLynne D; Dye, Louise

2016-03-01

Daily consumption of Concord grape juice (CGJ) over 3-4 mo has been shown to improve memory function in adults with mild cognitive impairment and reduce blood pressure in hypertensive adults. These benefits likely result from the high concentration of polyphenols in CGJ. Increased stress can impair cognitive function and elevate blood pressure. Thus, we examined the potential beneficial effect of CGJ in individuals with somewhat stressful and demanding lifestyles. We sought to examine the effects of the daily consumption of CGJ for 12 wk on cognitive function, driving performance, and blood pressure in healthy, middle-aged working mothers. Twenty-five healthy mothers (aged 40-50 y) of preteen children who were employed for ≥30 h/wk consumed 12 ounces (355 mL) of either CGJ (containing 777 mg total polyphenols) or an energy-, taste-, and appearance-matched placebo daily for 12 wk according to a randomized crossover design with a 4-wk washout. Verbal and spatial memory, executive function, attention, blood pressure, and mood were assessed at baseline and at 6 and 12 wk. Immediately after the cognitive battery, a subsample of 17 women completed a driving performance assessment at the University of Leeds Driving Simulator. The 25-min driving task required participants to match the speed and direction of a lead vehicle. Significant improvements in immediate spatial memory and driving performance were observed after CGJ relative to placebo. There was evidence of an enduring effect of CGJ such that participants who received CGJ in arm 1 maintained better performance in the placebo arm. Cognitive benefits associated with the long-term consumption of flavonoid-rich grape juice are not exclusive to adults with mild cognitive impairment. Moreover, these cognitive benefits are apparent in complex everyday tasks such as driving. Effects may persist beyond the cessation of flavonoid consumption, and future studies should carefully consider the length of washout within crossover designs. This trial was registered at clinicaltrials.gov as NCT01411631. © 2016 American Society for Nutrition.

Effects of alcohol ethoxylate and pluronic detergents on the development of pasture bloat in cattle and sheep.

PubMed

Stanford, K; Wang, Y; Berg, B P; Majak, W; McCartney, D H; Baron, V; McAllister, T A

2001-01-01

A series of studies was conducted to determine the efficacy and possible modes of action of a water-soluble mixture of alcohol ethoxylate and pluronic detergents (AEPD; Blocare 4511, ANCARE, Auckland, NZ) in preventing pasture bloat in ruminants grazing or fed freshly harvested alfalfa. Ten cannulated Suffolk wethers were offered freshly harvested alfalfa; five were given a daily intraruminal dose of 40 ml of 50% AEPD (vol/vol) 1 h before feeding, and five (controls) were dosed with water. Viscosity of ruminal fluid was reduced (P < 0.001) in AEPD-treated wethers, relative to the controls, for the first 2 h after feeding but not at 4 h after feeding and beyond. Treatment with AEPD did not affect dry matter (DM) intake, digestibility of DM, acid detergent fiber, or neutral detergent fiber, or N digestion and retention, implying that AEPD likely would not affect milk production. In a crossover grazing study, five of the wethers were given AEPD in drinking water (0.1%, vol/vol); treatment with AEPD was 100% effective for preventing bloat in sheep grazing early-bloom alfalfa for 4 h daily. Replicate grazing studies were conducted with cattle in Lethbridge, AB; Lacombe, AB; and Kamloops, BC. Treated animals received AEPD in the water (0.06%, vol/vol) and grazed vegetative alfalfa for 6 h daily. As it did with sheep, AEPD treatment effectively precluded the bloat observed in control animals. Consequently, AEPD may be a valuable tool for alfalfa pasture-based dairy production although further study is required to develop an integrated model for optimal administration under a variety of climatic conditions.

Highway driving performance and cognitive functioning the morning after bedtime and middle-of-the-night use of gaboxadol, zopiclone and zolpidem.

PubMed

Leufkens, Tim R M; Lund, Jesper S; Vermeeren, Annemiek

2009-12-01

Gaboxadol is a selective extrasynaptic GABA(A) receptor agonist previously in development for the treatment of insomnia. Due to its short half-life (1.5-2 h) it is expected to be free from residual effects the next morning. The present study assessed the residual effects of evening and middle-of-the-night administration of 15 mg of gaboxadol on cognitive, psychomotor and driving performance. Twenty-eight healthy volunteers entered the study with 25 (12 women; mean age 31.4 years) completing a double-blind, placebo-controlled, active-referenced five-way cross-over study. Each treatment night subjects ingested one capsule at 23:00 hours and one at 04:00 hours. Treatments were placebo at both times, 15 mg gaboxadol or 7.5 mg zopiclone followed by placebo, and placebo followed by 15 mg gaboxadol or 10 mg zolpidem. Effects on cognition and psychomotor performance were assessed between 07:30 and 08:30 hours and on driving between 09:00 and 10:00 hours. Driving, as measured by standard deviation of lateral position in an on-the-road driving test, was almost significantly (P < 0.07) impaired after evening administration of gaboxadol for the all-subjects-completed set (n = 25) but significantly (P < 0.05) in the full analysis set (n = 28). Effects of all other active treatments on driving were significant. Evening administration of gaboxadol had minor effects on divided attention only, whereas middle-of-the-night administration impaired performance significantly in all tests except memory. Zolpidem and zopiclone impaired performance significantly in every test except tracking after zopiclone; 15 mg of gaboxadol can produce minor residual effects on driving after evening administration. Administration later at night is associated with moderately impairing residual effects on driving and psychomotor performance but not on memory.

The new insight into dynamic crossover in glass forming liquids from the apparent enthalpy analysis

NASA Astrophysics Data System (ADS)

Martinez-Garcia, Julio Cesar; Martinez-Garcia, Jorge; Rzoska, Sylwester J.; Hulliger, Jürg

2012-08-01

One of the most intriguing phenomena in glass forming systems is the dynamic crossover (TB), occurring well above the glass temperature (Tg). So far, it was estimated mainly from the linearized derivative analysis of the primary relaxation time τ(T) or viscosity η(T) experimental data, originally proposed by Stickel et al. [J. Chem. Phys. 104, 2043 (1996), 10.1063/1.470961; Stickel et al. J. Chem. Phys. 107, 1086 (1997)], 10.1063/1.474456. However, this formal procedure is based on the general validity of the Vogel-Fulcher-Tammann equation, which has been strongly questioned recently [T. Hecksher et al. Nature Phys. 4, 737 (2008), 10.1038/nphys1033; P. Lunkenheimer et al. Phys. Rev. E 81, 051504 (2010), 10.1103/PhysRevE.81.051504; J. C. Martinez-Garcia et al. J. Chem. Phys. 134, 024512 (2011)], 10.1063/1.3514589. We present a qualitatively new way to identify the dynamic crossover based on the apparent enthalpy space (H_a^' = {{dln τ }/{d({1/T})}}) analysis via a new plot ln H_a^' vs. 1/T supported by the Savitzky-Golay filtering procedure for getting an insight into the noise-distorted high order derivatives. It is shown that depending on the ratio between the "virtual" fragility in the high temperature dynamic domain (mhigh) and the "real" fragility at Tg (the low temperature dynamic domain, m = mlow) glass formers can be splitted into two groups related to f < 1 and f > 1, (f = mhigh/mlow). The link of this phenomenon to the ratio between the apparent enthalpy and activation energy as well as the behavior of the configurational entropy is indicated.

Elevated mutation rate during meiosis in Saccharomyces cerevisiae.

PubMed

Rattray, Alison; Santoyo, Gustavo; Shafer, Brenda; Strathern, Jeffrey N

2015-01-01

Mutations accumulate during all stages of growth, but only germ line mutations contribute to evolution. While meiosis contributes to evolution by reassortment of parental alleles, we show here that the process itself is inherently mutagenic. We have previously shown that the DNA synthesis associated with repair of a double-strand break is about 1000-fold less accurate than S-phase synthesis. Since the process of meiosis involves many programmed DSBs, we reasoned that this repair might also be mutagenic. Indeed, in the early 1960's Magni and Von Borstel observed elevated reversion of recessive alleles during meiosis, and found that the revertants were more likely to be associated with a crossover than non-revertants, a process that they called "the meiotic effect." Here we use a forward mutation reporter (CAN1 HIS3) placed at either a meiotic recombination coldspot or hotspot near the MAT locus on Chromosome III. We find that the increased mutation rate at CAN1 (6 to 21 -fold) correlates with the underlying recombination rate at the locus. Importantly, we show that the elevated mutation rate is fully dependent upon Spo11, the protein that introduces the meiosis specific DSBs. To examine associated recombination we selected for random spores with or without a mutation in CAN1. We find that the mutations isolated this way show an increased association with recombination (crossovers, loss of crossover interference and/or increased gene conversion tracts). Polζ appears to contribute about half of the mutations induced during meiosis, but is not the only source of mutations for the meiotic effect. We see no difference in either the spectrum or distribution of mutations between mitosis and meiosis. The correlation of hotspots with elevated mutagenesis provides a mechanism for organisms to control evolution rates in a gene specific manner.

Pairwise Maximum Entropy Models for Studying Large Biological Systems: When They Can Work and When They Can't

PubMed Central

Roudi, Yasser; Nirenberg, Sheila; Latham, Peter E.

2009-01-01

One of the most critical problems we face in the study of biological systems is building accurate statistical descriptions of them. This problem has been particularly challenging because biological systems typically contain large numbers of interacting elements, which precludes the use of standard brute force approaches. Recently, though, several groups have reported that there may be an alternate strategy. The reports show that reliable statistical models can be built without knowledge of all the interactions in a system; instead, pairwise interactions can suffice. These findings, however, are based on the analysis of small subsystems. Here, we ask whether the observations will generalize to systems of realistic size, that is, whether pairwise models will provide reliable descriptions of true biological systems. Our results show that, in most cases, they will not. The reason is that there is a crossover in the predictive power of pairwise models: If the size of the subsystem is below the crossover point, then the results have no predictive power for large systems. If the size is above the crossover point, then the results may have predictive power. This work thus provides a general framework for determining the extent to which pairwise models can be used to predict the behavior of large biological systems. Applied to neural data, the size of most systems studied so far is below the crossover point. PMID:19424487

Topoisomerase II Mediates Meiotic Crossover Interference

PubMed Central

Zhang, Liangran; Wang, Shunxin; Yin, Shen; Hong, Soogil; Kim, Keun P.; Kleckner, Nancy

2014-01-01

Summary Spatial patterning is a ubiquitous feature of biological systems. Meiotic crossovers provide an interesting example, defined by the classical phenomenon of crossover interference. Here, analysis of crossover patterns in budding yeast identifies a molecular pathway for interference. Topoisomerase II (Topo II) plays a central role, thus identifying a new function for this critical molecule. SUMOylation [of TopoII and axis component Red1] and ubiquitin-mediated removal of SUMOylated proteins are also required. These and other findings support the hypothesis that crossover interference involves accumulation, relief and redistribution of mechanical stress along the protein/DNA meshwork of meiotic chromosome axes, with TopoII required to adjust spatial relationships among DNA segments. PMID:25043020

Interparental Violence and the Mediating Role of Parental Availability in Children's Trauma Related Symptoms.

PubMed

Visser, Margreet; Schoemaker, Kim; de Schipper, Clasien; Lamers-Winkelman, Francien; Finkenauer, Catrin

This cross-sectional study examined the hypothesis that parental psychopathology in Interparental Violence (IPV) families crosses over to children, because parental psychopathology spills over to parental functioning. In a high-risk sample of IPV exposed families, we tested whether parental psychopathology spills over to parental availability, which, in turn, shows a crossover effect to children's trauma-related symptoms. The study population consisted of 78 IPV exposed children (4-12 years), and their 65 custodial parents referred to outpatient Children's Trauma Centers in the Netherlands for intervention. Consistent with our hypotheses, parental psychopathology was negatively related to parental availability, suggesting a spillover effect. Although parental psychopathology was not associated with children's trauma-related symptoms directly, we found evidence for the predicted indirect, crossover effects. We found an indirect crossover effect from parental psychopathology to children's trauma-related anxiety, depression, and anger, through the spillover effect of parental availability. Clinical implications for treatment and study limitations are discussed.

EffenDys-Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Patients With Advanced Cancer: A Multicenter, Open-Label, Randomized, Morphine-Controlled, Crossover, Phase II Trial.

PubMed

Simon, Steffen T; Kloke, Marianne; Alt-Epping, Bernd; Gärtner, Jan; Hellmich, Martin; Hein, Rebecca; Piel, Maren; Cornely, Oliver A; Nauck, Friedemann; Voltz, Raymond

2016-11-01

Episodic breathlessness is a frequent and burdensome symptom in cancer patients but pharmacological treatment is limited. To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl in comparison to immediate-release morphine for the relief of episodic breathlessness. Phase II, investigator-initiated, multicenter, open-label, randomized, morphine-controlled, crossover trial with open-label titration of fentanyl buccal tablet (FBT) in inpatients with incurable cancer. The primary outcome was time to onset of meaningful breathlessness relief. Secondary outcomes were efficacy (breathlessness intensity difference at 10 and 30 minutes; sum of breathlessness intensity difference at 15 and 60 minutes), feasibility, and safety. Study was approved by local ethics committees. Twenty-five of 1341 patients were eligible, 10 patients agreed to participate (four female, mean age 58 ± 11, mean Karnofsky score 67 ± 11). Two patients died before final visits and two patients dropped-out because of disease progression leaving six patients for analysis with 61 episodes of breathlessness. Mean time to onset was for FBT 12.7 ± 10.0 and for immediate-release morphine 23.6 ± 15.1 minutes with a mean difference of -10.9 minutes (95% CI = -24.5 to 2.7, P = 0.094). Efficacy measures were predominately in favor for FBT. Both interventions were safe. Feasibility failed because of too much study demands for a very ill patient group. The description of a faster and greater relief of episodic breathlessness by transmucosal fentanyl versus morphine justifies further evaluation by a full-powered trial. Copyright © 2016. Published by Elsevier Inc.

The effect of angiotensin-converting enzyme inhibitors of left atrial pressure in dogs with mitral valve regurgitation.

PubMed

Ishikawa, T; Tanaka, R; Suzuki, S; Miyaishi, Y; Akagi, H; Iino, Y; Fukushima, R; Yamane, Y

2010-01-01

Despite many epidemiological reports concerning the efficacy of angiotensin-converting enzyme (ACE) inhibitors in dogs with mitral regurgitation (MR), the hemodynamic effects of ACE inhibitor administration have not been fully evaluated. To document left atrial pressure (LAP) in dogs with MR administered ACE inhibitors, in order to obtain interesting information about daily LAP changes with administration of ACE inhibitors. Five healthy Beagle dogs weighing 9.8 to 14.2 kg (2 males and 3 females; aged 2 years). Experimental, crossover, and interventional study. Chordae tendineae rupture was induced, and a radiotelemetry transmitter catheter was inserted into the left atrium. LAP was recorded for 72 consecutive hours during which each of 3 ACE inhibitors--nalapril (0.5 mg/kg/d), temocapril (0.1 mg/kg/d), and alacepril (3.0 mg/kg/d)--were administered in a crossover study. Averaged diurnal LAP was significantly, but slightly reduced by alacepril (P = .03, 19.03 +/- 3.01-18.24 +/- 3.07 mmHg). The nightly drops in LAP caused by alacepril and enalapril were significantly higher than the daily drops (P = .03, -0.98 +/- 0.19 to -0.07 +/- 0.25 mmHg, and P = .03, -0.54 +/- 0.21-0.02 +/- 0.17 mmHg, respectively), despite the fact that the oral administrations were given in the morning. Systolic blood pressure (122.7 +/- 14.4-117.4 +/- 13.1 mmHg, P = .04) and systemic vascular resistance (5800 +/- 2685-5144 +/- 2077 dyne x s/cm5, P = .03) were decreased by ACE inhibitors. ACE inhibitors decrease LAP minimally, despite reductions in left ventricular afterload. ACE inhibitors should not be used to decrease LAP.

Dental Students’ Preference with Regard to Tactile or Visual Determination of Injection Site for an Inferior Alveolar Nerve Block in Children: A Crossover Randomized Clinical Trial

PubMed Central

Iranmanesh, Seyed Masoud

2016-01-01

Objectives: Instruction of local anesthesia injection in an important part of dental education curricula. This study was performed to compare dental students’ preference with regard to tactile or visual determination of injection site for an inferior alveolar nerve block (IANB) in children. Materials and Methods: This crossover randomized clinical trial was conducted on dental students of Zahedan Dental School who took the first practical course of pediatric dentistry in the first academic semester of 2013–14 (n=42). They were randomly divided into two groups. During the first phase, group I was instructed to find the needle insertion point for an IANB via tactile method and group II was instructed to do it visually. In the second phase, the groups received instructions for the alternate technique. Both instructions were done using live demonstrations by the same instructor and immediately after instruction the learners practiced an IANB using the taught method. A five-point Likert scale questionnaire was then filled out by the students. The preference score was determined by calculating the mean of item scores. Data were analyzed using Mann-Whitney U and Wilcoxon Singed Rank tests in SPSS 19 at P=0.05 level of significance. Results: Thirty-eight students completed the study. By using the visual method to perform an IANB, students gained a significantly higher mean preference score (P=0.020). There was a significant difference in the preference of male students (P=0.008). Conclusions: Instruction of IANB by visual identification of needle insertion point is more desirable by students. PMID:27536327

Marked antioxidant effect of orange juice intake and its phytomicronutrients in a preliminary randomized cross-over trial on mild hypercholesterolemic men.

PubMed

Constans, Joël; Bennetau-Pelissero, Catherine; Martin, Jean-François; Rock, Edmond; Mazur, Andrzej; Bedel, Aurélie; Morand, Christine; Bérard, Annie M

2015-12-01

Blond orange juice is the most consumed fruit juice in the world. It is a source of hesperidin, a bioavailable flavonoid reported to exhibit potential vascular protective actions. However, the specific impact on vascular function of Citrus phytomicronutrients, is unknown. For the first time, we investigated the effects of blond orange juice compared with a control beverage mimicking the composition of orange juice (including Vitamin C but no phytomicronutrients), on antioxidant markers, cardiovascular risk factors and endothelial function. Twenty five male volunteers with two cardiovascular risk factors (age over 50 years and LDL-cholesterol between 130 and 190 mg/L) were enrolled in a randomized cross-over study. They received 3 times daily 200 mL of either blond orange juice or control beverage for 4 weeks, spaced by a 5-week wash-out. Endothelial function (flow mediated dilatation and plasma markers), oxidative status, lipid profile and inflammatory markers were assessed. Daily intakes of orange juice significantly led to a marked antioxidant effect which was correlated to hesperetin plasma levels and related with a decrease in reactive oxygen species. A tendency towards reduction of endothelial dysfunction and modest increase in plasma apoA-I concentration were also observed. This allows further experiments demonstrating the specific effect of phytomicronutrients from orange juice. These findings suggest that daily intake of nutritionally relevant dose of blond orange juice may contribute for a significant antioxidant effect through the phytochemicals contained in. Orange juice may be associated to other healthy foods to achieve a significant effect on the vascular function. This study is recorded in ClinicalTrials.com as NCT00539916. Copyright © 2014. Published by Elsevier Ltd.

Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man.

PubMed

Bukara, Katarina; Schueller, Laurent; Rosier, Jan; Martens, Mark A; Daems, Tinne; Verheyden, Loes; Eelen, Siemon; Van Speybroeck, Michiel; Libanati, Cristian; Martens, Johan A; Van Den Mooter, Guy; Frérart, Françoise; Jolling, Koen; De Gieter, Marjan; Bugarski, Branko; Kiekens, Filip

2016-11-01

Formulating poorly water soluble drugs using ordered mesoporous silica materials is an emerging approach to tackle solubility-related bioavailability problems. The current study was conducted to assess the bioavailability-enhancing potential of ordered mesoporous silica in man. In this open-label, randomized, two-way cross-over study, 12 overnight fasted healthy volunteers received a single dose of fenofibrate formulated with ordered mesoporous silica or a marketed product based on micronized fenofibrate. Plasma concentrations of fenofibric acid, the pharmacologically active metabolite of fenofibrate, were monitored up to 96h post-dose. The rate (C max /dose increased by 77%; t max reduced by 0.75h) and extent of absorption (AUC 0-24h /dose increased by 54%) of fenofibrate were significantly enhanced following administration of the ordered mesoporous silica based formulation. The results of this study serve as a proof of concept in man for this novel formulation approach. Copyright © 2016 Elsevier B.V. All rights reserved.

How job and family demands impact change in perceived stress: A dyadic study.

PubMed

Smoktunowicz, Ewelina; Cieślak, Roman

2018-01-07

The aim of this two-wave study has been to test the spillover and crossover of job and family demands on changes in perceived stress at work and in the family. Specifically, we proposed that demands from one domain (work or family) spilled over to another domain through interrrole conflict (work-family/family-work conflict) and context-specific self-efficacy. Additionally, we hypothesized that changes in perceived stress were impacted not only by a person's own demands through interrole conflict but also by the demands of one's significant other, in the process of crossover. The study was of dyadic design and it was conducted online, among 130 heterosexual couples, at 2 time points separated by 3 months interval. Hypotheses were verified by means of the path analysis. No support was found for the spillover of job and family demands on changes in perceived stress through interrole conflict and self-efficacy, neither for women nor for men. With regard to the crossover, no support was found for the actor effects, i.e., a person's demands did not impact changes in one's own work- and family-related perceived stress but partial support was found for the partner effects, i.e., women's job demands were associated with men's changes in work and family-related stress through women's work-family conflict, and men's family demands were associated with women's change in family-related perceived stress through men's family-work conflict. The study is a longitudinal test of the Spillover-Crossover model and Work-Home Resources model demonstrating that job and family demands are transmitted across domains and across partners in the intimate relationships through the interrole conflict but the nature of this crossover is different for men and women. Int J Occup Med Environ Health 2018;31(2)199-215. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

The School-Community Integrated Learning Pathway: Exploring a New Way to Prepare and Induct Final-Year Preservice Teachers

ERIC Educational Resources Information Center

Hudson, Suzanne; Hudson, Peter; Adie, Lenore

2015-01-01

Universities and teacher employment bodies seek new, cost-effective ways for graduating classroom-ready teachers. This study involved 32 final-year preservice teachers in an innovative school--university partnership teacher education programme titled, the School-Community Integrated Learning (SCIL) pathway. Data were collected using a five-part…

Towards Understanding the Two Way Interaction Effects of Extraversion and Openness to Experience on Career Commitment

ERIC Educational Resources Information Center

Arora, Ridhi; Rangnekar, Santosh

2016-01-01

In this study, we examined potential two-way interaction effects of the Big Five personality traits extraversion and openness to experience on career commitment measured in terms of three components of career identity, career resilience, and career planning. Participants included 450 managers from public and private sector organizations in North…

Computer-Enriched Instruction (CEI) Is Better for Preview Material Instead of Review Material: An Example of a Biostatistics Chapter, the Central Limit Theorem

ERIC Educational Resources Information Center

See, Lai-Chu; Huang, Yu-Hsun; Chang, Yi-Hu; Chiu, Yeo-Ju; Chen, Yi-Fen; Napper, Vicki S.

2010-01-01

This study examines the timing using computer-enriched instruction (CEI), before or after a traditional lecture to determine cross-over effect, period effect, and learning effect arising from sequencing of instruction. A 2 x 2 cross-over design was used with CEI to teach central limit theorem (CLT). Two sequences of graduate students in nursing…

Melatonin versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial

ERIC Educational Resources Information Center

Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

2011-01-01

Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant…

Universality-class crossover by a nonorder field introduced to the pair contact process with diffusion

NASA Astrophysics Data System (ADS)

Park, Su-Chan

2017-09-01

The one-dimensional pair contact process with diffusion (PCPD), an interacting particle system with diffusion, pair annihilation, and creation by pairs, has defied consensus about the universality class to which it belongs. An argument by Hinrichsen [Physica A 361, 457 (2006), 10.1016/j.physa.2005.06.101] claims that freely diffusing particles in the PCPD should play the same role as frozen particles when it comes to the critical behavior. Therefore, the PCPD is claimed to have the same critical phenomena as a model with infinitely many absorbing states that belongs to the directed percolation (DP) universality class. To investigate if diffusing particles are really indistinguishable from frozen particles in the sense of the renormalization group, we study numerically a variation of the PCPD by introducing a nonorder field associated with infinitely many absorbing states. We find that a crossover from the PCPD to DP occurs due to the nonorder field. By studying a similar model, we exclude the possibility that the mere introduction of a nonorder field to one model can entail a nontrivial crossover to another model in the same universality class, thus we attribute the observed crossover to the difference of the universality class of the PCPD from the DP class.

Role of confinements on the melting of Wigner molecules in quantum dots

NASA Astrophysics Data System (ADS)

Bhattacharya, Dyuti; Filinov, Alexei V.; Ghosal, Amit; Bonitz, Michael

2016-03-01

We explore the stability of a Wigner molecule (WM) formed in confinements with different geometries emulating the role of disorder and analyze the melting (or crossover) of such a system. Building on a recent calculation [D. Bhattacharya, A. Ghosal, Eur. Phys. J. B 86, 499 (2013)] that discussed the effects of irregularities on the thermal crossover in classical systems, we expand our studies in the untested territory by including both the effects of quantum fluctuations and of disorder. Our results, using classical and quantum (path integral) Monte Carlo techniques, unfold complementary mechanisms that drive the quantum and thermal crossovers in a WM and show that the symmetry of the confinement plays no significant role in determining the quantum crossover scale n X . This is because the zero-point motion screens the boundary effects within short distances. The phase diagram as a function of thermal and quantum fluctuations determined from independent criteria is unique, and shows "melting" from the WM to both the classical and quantum "liquids". An intriguing signature of weakening liquidity with increasing temperature, T, is found in the extreme quantum regime. The crossover is associated with production of defects. However, these defects appear to play distinct roles in driving the quantum and thermal "melting". Our analyses carry serious implications for a variety of experiments on many-particle systems - semiconductor heterostructure quantum dots, trapped ions, nanoclusters, colloids and complex plasma.

Crossover and maximal fat-oxidation points in sedentary healthy subjects: methodological issues.

PubMed

Gmada, N; Marzouki, H; Haboubi, M; Tabka, Z; Shephard, R J; Bouhlel, E

2012-02-01

Our study aimed to assess the influence of protocol on the crossover point and maximal fat-oxidation (LIPOX(max)) values in sedentary, but otherwise healthy, young men. Maximal oxygen intake was assessed in 23 subjects, using a progressive maximal cycle ergometer test. Twelve sedentary males (aged 20.5±1.0 years) whose directly measured maximal aerobic power (MAP) values were lower than their theoretical maximal values (tMAP) were selected from this group. These individuals performed, in random sequence, three submaximal graded exercise tests, separated by three-day intervals; work rates were based on the tMAP in one test and on MAP in the remaining two. The third test was used to assess the reliability of data. Heart rate, respiratory parameters, blood lactate, the crossover point and LIPOX(max) values were measured during each of these tests. The crossover point and LIPOX(max) values were significantly lower when the testing protocol was based on tMAP rather than on MAP (P<0.001). Respiratory exchange ratios were significantly lower with MAP than with tMAP at 30, 40, 50 and 60% of maximal aerobic power (P<0.01). At the crossover point, lactate and 5-min postexercise oxygen consumption (EPOC(5 min)) values were significantly higher using tMAP rather than MAP (P<0.001). During the first 5 min of recovery, EPOC(5 min) and blood lactate were significantly correlated (r=0.89; P<0.001). Our data show that, to assess the crossover point and LIPOX(max) values for research purposes, the protocol must be based on the measured MAP rather than on a theoretical value. Such a determination should improve individualization of training for initially sedentary subjects. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Associations of daily pediatric asthma emergency department visits with air pollution in Newark, NJ: utilizing time-series and case-crossover study designs.

PubMed

Gleason, Jessie A; Fagliano, Jerald A

2015-10-01

Asthma is one of the most common chronic diseases affecting children. This study assesses the associations of ozone and fine particulate matter (PM2.5) with pediatric emergency department visits in the urban environment of Newark, NJ. Two study designs were utilized and evaluated for usability. We obtained daily emergency department visits among children aged 3-17 years with a primary diagnosis of asthma during April to September for 2004-2007. Both a time-stratified case-crossover study design with bi-directional control sampling and a time-series study design were utilized. Lagged effects (1-d through 5-d lag, 3-d average, and 5-d average) of ozone and PM2.5 were explored and a dose-response analysis comparing the bottom 5th percentile of 3-d average lag ozone with each 5 percentile increase was performed. Associations of interquartile range increase in same-day ozone were similar between the time-series and case-crossover study designs (RR = 1.08, 95% CI 1.04-1.12) and (OR = 1.10, 95% CI 1.06-1.14), respectively. Similar associations were seen for 1-day lag and 3-day average lag ozone levels. PM2.5 was not associated with the outcome in either study design. Dose-response assessment indicated a statistically significant and increasing association around 50-55 ppb consistent for both study designs. Ozone was statistically positively associated with pediatric asthma ED visits in Newark, NJ. Our results were generally comparable across the time-series and case-crossover study designs, indicating both are useful to assess local air pollution impacts.

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

PubMed

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. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Geosat crossover analysis in the tropical Pacific. Part 1: Constrained sinusoidal crossover adjustment

NASA Technical Reports Server (NTRS)

Tai, Chang-Kou

1988-01-01

A new method (constrained sinusoidal crossover adjustment) for removing the orbit error in satellite altimetry is tested (using crossovers accumulated in the first 91 days of the Geosat non-repeat era in the tropical Pacific) and found to have excellent qualities. Two features distinguish the new method from the conventional bias-and-tilt crossover adjustment. First, a sine wave (with wavelength equaling the circumference of the Earth) is used to represent the orbit error for each satellite revolution, instead of the bias-and-tilt (and curvature, if necessary) approach for each segment of the satellite ground track. Secondly, the indeterminacy of the adjustment process is removed by a simple constraint minimizing the amplitudes of the sine waves, rather than by fixing selected tracks. Overall the new method is more accurate, more efficient, and much less cumbersome than the old. The idea of restricting the crossover adjustment to crossovers between tracks that are less than certain days apart in order to preserve the large-scale long-term oceanic variability is also tested with inconclusive results because the orbit error was unusually nonstationary in the initial 91 days of the GEOSAT mission.

Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis

PubMed Central

Medhi, Darpan; Goldman, Alastair SH; Lichten, Michael

2016-01-01

The budding yeast genome contains regions where meiotic recombination initiates more frequently than in others. This pattern parallels enrichment for the meiotic chromosome axis proteins Hop1 and Red1. These proteins are important for Spo11-catalyzed double strand break formation; their contribution to crossover recombination remains undefined. Using the sequence-specific VMA1-derived endonuclease (VDE) to initiate recombination in meiosis, we show that chromosome structure influences the choice of proteins that resolve recombination intermediates to form crossovers. At a Hop1-enriched locus, most VDE-initiated crossovers, like most Spo11-initiated crossovers, required the meiosis-specific MutLγ resolvase. In contrast, at a locus with lower Hop1 occupancy, most VDE-initiated crossovers were MutLγ-independent. In pch2 mutants, the two loci displayed similar Hop1 occupancy levels, and VDE-induced crossovers were similarly MutLγ-dependent. We suggest that meiotic and mitotic recombination pathways coexist within meiotic cells, and that features of meiotic chromosome structure determine whether one or the other predominates in different regions. DOI: http://dx.doi.org/10.7554/eLife.19669.001 PMID:27855779

The exposure-crossover design is a new method for studying sustained changes in recurrent events.

PubMed

Redelmeier, Donald A

2013-09-01

To introduce a new design that explores how an acute exposure might lead to a sustained change in the risk of a recurrent outcome. The exposure-crossover design uses self-matching to control within-person confounding due to genetics, personality, and all other stable patient characteristics. The design is demonstrated using population-based individual-level health data from Ontario, Canada, for three separate medical conditions (n > 100,000 for each) related to the risk of a motor vehicle crash (total outcomes, >2,000 for each). The exposure-crossover design yields numerical risk estimates during the baseline interval before an intervention, the induction interval immediately ahead of the intervention, and the subsequent interval after the intervention. Accompanying graphs summarize results, provide an intuitive display to readers, and show risk comparisons (absolute and relative). Self-matching increases statistical efficiency, reduces selection bias, and yields quantitative analyses. The design has potential limitations related to confounding, artifacts, pragmatics, survivor bias, statistical models, potential misunderstandings, and serendipity. The exposure-crossover design may help in exploring selected questions in epidemiology science. Copyright © 2013 Elsevier Inc. All rights reserved.

Superfluid density of states and pseudogap phenomenon in the BCS-BEC crossover regime of a superfluid Fermi gas

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

Watanabe, Ryota; Tsuchiya, Shunji; CREST

2010-10-15

We investigate single-particle excitations and strong-coupling effects in the BCS-BEC crossover regime of a superfluid Fermi gas. Including phase and amplitude fluctuations of the superfluid order parameter within a T-matrix theory, we calculate the superfluid density of states (DOS), as well as single-particle spectral weight, over the entire BCS-BEC crossover region below the superfluid transition temperature T{sub c}. We clarify how the pseudogap in the normal state evolves into the superfluid gap, as one passes through T{sub c}. While the pseudogap in DOS continuously evolves into the superfluid gap in the weak-coupling BCS regime, the superfluid gap in the crossovermore » region is shown to appear in DOS after the pseudogap disappears below T{sub c}. In the phase diagram with respect to the temperature and interaction strength, we determine the region where strong pairing fluctuations dominate over single-particle properties of the system. Our results would be useful for the study of strong-coupling phenomena in the BCS-BEC crossover regime of a superfluid Fermi gas.« less

Single-crossover recombination in discrete time.

PubMed

von Wangenheim, Ute; Baake, Ellen; Baake, Michael

2010-05-01

Modelling the process of recombination leads to a large coupled nonlinear dynamical system. Here, we consider a particular case of recombination in discrete time, allowing only for single crossovers. While the analogous dynamics in continuous time admits a closed solution (Baake and Baake in Can J Math 55:3-41, 2003), this no longer works for discrete time. A more general model (i.e. without the restriction to single crossovers) has been studied before (Bennett in Ann Hum Genet 18:311-317, 1954; Dawson in Theor Popul Biol 58:1-20, 2000; Linear Algebra Appl 348:115-137, 2002) and was solved algorithmically by means of Haldane linearisation. Using the special formalism introduced by Baake and Baake (Can J Math 55:3-41, 2003), we obtain further insight into the single-crossover dynamics and the particular difficulties that arise in discrete time. We then transform the equations to a solvable system in a two-step procedure: linearisation followed by diagonalisation. Still, the coefficients of the second step must be determined in a recursive manner, but once this is done for a given system, they allow for an explicit solution valid for all times.

Meiotic recombination hotspots - a comparative view.

PubMed

Choi, Kyuha; Henderson, Ian R

2015-07-01

During meiosis homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover. Meiotic recombination has a profound effect on patterns of genetic variation and is an important tool during crop breeding. Crossovers initiate from programmed DNA double-stranded breaks that are processed to form single-stranded DNA, which can invade a homologous chromosome. Strand invasion events mature into double Holliday junctions that can be resolved as crossovers. Extensive variation in the frequency of meiotic recombination occurs along chromosomes and is typically focused in narrow hotspots, observed both at the level of DNA breaks and final crossovers. We review methodologies to profile hotspots at different steps of the meiotic recombination pathway that have been used in different eukaryote species. We then discuss what these studies have revealed concerning specification of hotspot locations and activity and the contributions of both genetic and epigenetic factors. Understanding hotspots is important for interpreting patterns of genetic variation in populations and how eukaryotic genomes evolve. In addition, manipulation of hotspots will allow us to accelerate crop breeding, where meiotic recombination distributions can be limiting. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol

PubMed Central

2010-01-01

Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Methods Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-over, repeat-dose study. Results Pharmacokinetic parameters for ibuprofen and paracetamol were similar for the combination and monotherapy tablets (values falling within the 80% to 125% acceptable bioequivalence range) except for the rate of absorption of paracetamol from the combination (tmax), which was significantly faster compared with monotherapy (median difference 10 minutes; p < 0.05). Mean plasma concentrations of both drugs were higher, earlier, following administration of the combination tablet compared with monotherapy. Mean plasma levels at 10 and 20 minutes were 6.64 μg.mL-1 and 16.81 μg.mL-1, respectively, for ibuprofen from the combination, compared with 0.58 μg.mL-1 and 9.00 μg.mL-1, respectively, for monotherapy. For paracetamol, mean plasma levels at 10 and 20 minutes were 5.43 μg.mL-1 and 14.54 μg.mL-1, respectively, for the combination compared with 0.33 μg.mL-1 and 9.19 μg.mL-1, respectively, for monotherapy. The rate of absorption of both ibuprofen and paracetamol was significantly delayed when the combination tablet was administered in the fed versus fasted state; median delay was 25 minutes for ibuprofen (p > 0.05) and 55 minutes for paracetamol (p < 0.001). The pharmacokinetic parameters were comparable irrespective of whether the combination tablet was given twice or three times daily; systemic exposure was, however, approximately 1.4 times greater for both drugs when given three times daily. Conclusions Administration of ibuprofen and paracetamol in a fixed-dose combination tablet does not significantly alter the pharmacokinetic profiles of either drug, except for enhancing the rate of paracetamol absorption, offering potential therapeutic benefits in relation to the onset of analgesia. Concentrations of both drugs reached previously reported therapeutic levels when the combination tablet was administrated in the fed or fasted state. Three times daily dosing may offer enhanced therapeutic effect for longer than twice daily dosing. PMID:20602760

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

Code of Federal Regulations, 2014 CFR

2014-10-01

...) 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. ...

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

Code of Federal Regulations, 2013 CFR

2013-10-01

...) 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. ...

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

Code of Federal Regulations, 2012 CFR

2012-10-01

...) 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. ...

24 CFR 3285.701 - Electrical crossovers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 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 require...

24 CFR 3285.701 - Electrical crossovers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 24 Housing and Urban Development 5 2013-04-01 2013-04-01 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 require...

24 CFR 3285.701 - Electrical crossovers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 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 require...

24 CFR 3285.701 - Electrical crossovers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 5 2012-04-01 2012-04-01 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 require...

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

Code of Federal Regulations, 2011 CFR

2011-10-01

...) 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. ...

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

Code of Federal Regulations, 2010 CFR

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. ...

Quantum anharmonic oscillator plus delta-function potential: a molecular view of pairing formation and breaking in the coordinate space

NASA Astrophysics Data System (ADS)

Sumaryada, Tony; Maha Putra, Bima; Pramudito, Sidikrubadi

2017-05-01

We propose an alternative way to describe the pairing formation and breaking via a quantum anharmonic oscillator with a delta-function potential model. Unlike BCS theory, which describes the pairing formation in the momentum space, this model works in the coordinate space and is able to give a molecular view of pairing formation and breaking in the coordinate space. By exploring the dynamical interplay between the intrinsic factor (dissociation energy) and external factor (pairing strength) of this system additional information was gained, including the critical pairing strength and critical scattering length, which might relate to the BCS-BEC crossover phenomena and halo state formation. Although only the energetic aspect of pairing is described by this model, its simplicity and pedagogical steps might help undergraduate students to understand the pairing problem in a simple way.

A randomized double-blind crossover study of indoor air filtration and acute changes in cardiorespiratory health in a First Nations community.

PubMed

Weichenthal, S; Mallach, G; Kulka, R; Black, A; Wheeler, A; You, H; St-Jean, M; Kwiatkowski, R; Sharp, D

2013-06-01

Few studies have examined indoor air quality in First Nations communities and its impact on cardiorespiratory health. To address this need, we conducted a crossover study on a First Nations reserve in Manitoba, Canada, including 37 residents in 20 homes. Each home received an electrostatic air filter and a placebo filter for 1 week in random order, and lung function, blood pressure, and endothelial function measures were collected at the beginning and end of each week. Indoor air pollutants were monitored throughout the study period. Indoor PM2.5 decreased substantially during air filter weeks relative to placebo (mean difference: 37 μg/m(3) , 95% CI: 10, 64) but remained approximately five times greater than outdoor concentrations owing to a high prevalence of indoor smoking. On average, air filter use was associated with a 217-ml (95% CI: 23, 410) increase in forced expiratory volume in 1 s, a 7.9-mm Hg (95% CI: -17, 0.82) decrease in systolic blood pressure, and a 4.5-mm Hg (95% CI: -11, 2.4) decrease in diastolic blood pressure. Consistent inverse associations were also observed between indoor PM2.5 and lung function. In general, our findings suggest that reducing indoor PM2.5 may contribute to improved lung function in First Nations communities. Indoor air quality is known to contribute to adverse cardiorespiratory health, but few studies have examined indoor air quality in First Nations communities. Our findings suggest that indoor PM2.5 may contribute to reduced lung function and that portable air filters may help to alleviate these effects by effectively reducing indoor levels of particulate matter. © Her Majesty the Queen in Right of Canada 2012. Reproduced with the permission of the Minister of Health Canada.

Dietary sodium restriction for mild hypertension in general practice.

PubMed Central

Watt, G C; Edwards, C; Hart, J T; Hart, M; Walton, P; Foy, C J

1983-01-01

Eighteen patients with stable mild hypertension (mean blood pressure 144/93 mm Hg) restricted their sodium intake for eight weeks while taking part in a double blind randomised crossover trial of slow sodium and placebo tablets. Mean 24 hour urinary sodium excretion was 143 mmol(mEq) during the period on slow sodium and 87 mmol during the period on placebo. Five patients were unable to reduce their sodium intake below 120 mmol, but the others had a mean 24 hour urinary sodium excretion of 59 mmol during the period on placebo. There was no significant difference in blood pressure between the slow sodium and placebo treatment periods, although the study had a power of 99% to detect a difference of 5 mm Hg in mean arterial pressure between the two periods. Moderate dietary sodium restriction does not lower blood pressure in patients with this degree of hypertension. PMID:6401551

Integrated pharmacokinetics and pharmacodynamics of Ro 48-8684, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects.

PubMed

van Gerven, J M; Roncari, G; Schoemaker, R C; Massarella, J; Keesmaat, P; Kooyman, H; Heizmann, P; Zell, M; Cohen, A F; Dingemanse, J

1997-11-01

This study aimed to investigate the pharmacodynamics and pharmacokinetics of ascending doses of Ro 48-8684, compared with midazolam, in healthy subjects during first administration to man. The study was double-blind and five-way crossover (three ascending doses, placebo, fixed midazolam dose), performed in two groups of five males. Ro 48-8684 was infused in doses of 0.1-0.3-1 mg in the first group, and 1-3-10 mg in the second, with different infusion rates (expressed as mg min(-1)) among doses. Midazolam was infused at 0.1 mg(-1) kg. Infusions were stopped after 20 min or if sedation became too strong for proper performance of saccadic eye movements. Pharmacokinetics and pharmacodynamics and their relationships were evaluated as described in the companion article. Ro 48-8684 caused dose-dependent sedation. No serious adverse events occurred. The volume of distribution and clearance of Ro 48-8684 were larger than of midazolam (337+/-114 vs 50+/-121 and 2.4+/-0.5 vs 0.47+/-0.11 l min(-1), resp). The recovery of saccadic eye movements from equal levels of sedation was on average almost half an hour faster for Ro 48-8684 than for midazolam, with considerable interindividual differences (range 2, 55 min). The doses of Ro 48-8684 leading to the same clinical endpoint as midazolam were comparable, but the corresponding predicted effect compartment concentrations of Ro 48-8684 were on average 2.6 times lower (range 1.5, 4.9 times). The slope of the linear concentration-effect-relationship for saccadic peak velocity was on average 2.2 times steeper for 10 mg Ro 48-8684 than for midazolam (range 1.3, 3.3). The slope decreased on average 4.4-fold (range 1.6, 7.3 times), with doses of Ro 48-8684 increasing from 1 to 10 mg. The metabolite Ro 61-2466 had a longer half-life than the parent compound Ro 48-8684. The influence of this metabolite during prolonged administration should be further investigated. These results show that Ro 48-8684 has a considerably shorter duration of action than midazolam. There may be a reduction of sensitivity to Ro 48-8684 with repeated administration of rising doses due to as yet undetermined factors.

Genetic algorithms and their use in Geophysical Problems

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

Parker, Paul B.

1999-04-01

Genetic algorithms (GAs), global optimization methods that mimic Darwinian evolution are well suited to the nonlinear inverse problems of geophysics. A standard genetic algorithm selects the best or ''fittest'' models from a ''population'' and then applies operators such as crossover and mutation in order to combine the most successful characteristics of each model and produce fitter models. More sophisticated operators have been developed, but the standard GA usually provides a robust and efficient search. Although the choice of parameter settings such as crossover and mutation rate may depend largely on the type of problem being solved, numerous results show thatmore » certain parameter settings produce optimal performance for a wide range of problems and difficulties. In particular, a low (about half of the inverse of the population size) mutation rate is crucial for optimal results, but the choice of crossover method and rate do not seem to affect performance appreciably. Optimal efficiency is usually achieved with smaller (< 50) populations. Lastly, tournament selection appears to be the best choice of selection methods due to its simplicity and its autoscaling properties. However, if a proportional selection method is used such as roulette wheel selection, fitness scaling is a necessity, and a high scaling factor (> 2.0) should be used for the best performance. Three case studies are presented in which genetic algorithms are used to invert for crustal parameters. The first is an inversion for basement depth at Yucca mountain using gravity data, the second an inversion for velocity structure in the crust of the south island of New Zealand using receiver functions derived from teleseismic events, and the third is a similar receiver function inversion for crustal velocities beneath the Mendocino Triple Junction region of Northern California. The inversions demonstrate that genetic algorithms are effective in solving problems with reasonably large numbers of free parameters and with computationally expensive objective function calculations. More sophisticated techniques are presented for special problems. Niching and island model algorithms are introduced as methods to find multiple, distinct solutions to the nonunique problems that are typically seen in geophysics. Finally, hybrid algorithms are investigated as a way to improve the efficiency of the standard genetic algorithm.« less

Genetic algorithms and their use in geophysical problems

NASA Astrophysics Data System (ADS)

Parker, Paul Bradley

Genetic algorithms (GAs), global optimization methods that mimic Darwinian evolution are well suited to the nonlinear inverse problems of geophysics. A standard genetic algorithm selects the best or "fittest" models from a "population" and then applies operators such as crossover and mutation in order to combine the most successful characteristics of each model and produce fitter models. More sophisticated operators have been developed, but the standard GA usually provides a robust and efficient search. Although the choice of parameter settings such as crossover and mutation rate may depend largely on the type of problem being solved, numerous results show that certain parameter settings produce optimal performance for a wide range of problems and difficulties. In particular, a low (about half of the inverse of the population size) mutation rate is crucial for optimal results, but the choice of crossover method and rate do not seem to affect performance appreciably. Also, optimal efficiency is usually achieved with smaller (<50) populations. Lastly, tournament selection appears to be the best choice of selection methods due to its simplicity and its autoscaling properties. However, if a proportional selection method is used such as roulette wheel selection, fitness scaling is a necessity, and a high scaling factor (>2.0) should be used for the best performance. Three case studies are presented in which genetic algorithms are used to invert for crustal parameters. The first is an inversion for basement depth at Yucca mountain using gravity data, the second an inversion for velocity structure in the crust of the south island of New Zealand using receiver functions derived from teleseismic events, and the third is a similar receiver function inversion for crustal velocities beneath the Mendocino Triple Junction region of Northern California. The inversions demonstrate that genetic algorithms are effective in solving problems with reasonably large numbers of free parameters and with computationally expensive objective function calculations. More sophisticated techniques are presented for special problems. Niching and island model algorithms are introduced as methods to find multiple, distinct solutions to the nonunique problems that are typically seen in geophysics. Finally, hybrid algorithms are investigated as a way to improve the efficiency of the standard genetic algorithm.

Bio-Inspired Genetic Algorithms with Formalized Crossover Operators for Robotic Applications.

PubMed

Zhang, Jie; Kang, Man; Li, Xiaojuan; Liu, Geng-Yang

2017-01-01

Genetic algorithms are widely adopted to solve optimization problems in robotic applications. In such safety-critical systems, it is vitally important to formally prove the correctness when genetic algorithms are applied. This paper focuses on formal modeling of crossover operations that are one of most important operations in genetic algorithms. Specially, we for the first time formalize crossover operations with higher-order logic based on HOL4 that is easy to be deployed with its user-friendly programing environment. With correctness-guaranteed formalized crossover operations, we can safely apply them in robotic applications. We implement our technique to solve a path planning problem using a genetic algorithm with our formalized crossover operations, and the results show the effectiveness of our technique.

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.

PubMed

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.

Extended precedence preservative crossover for job shop scheduling problems

NASA Astrophysics Data System (ADS)

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.

Genetic Recombination at the Buff Spore Color Locus in SORDARIA BREVICOLLIS. II. Analysis of Flanking Marker Behavior in Crosses between Buff Mutants.

PubMed

Sang, H; Whitehouse, H L

1983-02-01

Aberrant asci containing one or more wild-type spores were selected from crosses between pairs of alleles of the buff locus in the presence of closely linked flanking markers. Data were obtained relating to the site of aberrant segregation and the position of any associated crossover giving recombination of flanking markers. Aberrant segregation at a proximal site within the buff gene may be associated with a crossover proximal to the site of aberrant segregation or, with equal frequency, with a crossover distal to the site of the second mutant present in the cross. Similarly, segregation at a distal site may be associated with a crossover distal to the site or, with lower frequency, with a crossover proximal to the site of the proximal mutant present in the cross. Crossovers between the alleles were rare. This evidence for the relationship between hybrid DNA and crossing over is discussed in terms of current models for the mechanism of recombination.

Predicting critical temperatures of iron(II) spin crossover materials: Density functional theory plus U approach

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

Zhang, Yachao, E-mail: yczhang@nano.gznc.edu.cn

2014-12-07

A first-principles study of critical temperatures (T{sub c}) of spin crossover (SCO) materials requires accurate description of the strongly correlated 3d electrons as well as much computational effort. This task is still a challenge for the widely used local density or generalized gradient approximations (LDA/GGA) and hybrid functionals. One remedy, termed density functional theory plus U (DFT+U) approach, introduces a Hubbard U term to deal with the localized electrons at marginal computational cost, while treats the delocalized electrons with LDA/GGA. Here, we employ the DFT+U approach to investigate the T{sub c} of a pair of iron(II) SCO molecular crystals (αmore » and β phase), where identical constituent molecules are packed in different ways. We first calculate the adiabatic high spin-low spin energy splitting ΔE{sub HL} and molecular vibrational frequencies in both spin states, then obtain the temperature dependent enthalpy and entropy changes (ΔH and ΔS), and finally extract T{sub c} by exploiting the ΔH/T − T and ΔS − T relationships. The results are in agreement with experiment. Analysis of geometries and electronic structures shows that the local ligand field in the α phase is slightly weakened by the H-bondings involving the ligand atoms and the specific crystal packing style. We find that this effect is largely responsible for the difference in T{sub c} of the two phases. This study shows the applicability of the DFT+U approach for predicting T{sub c} of SCO materials, and provides a clear insight into the subtle influence of the crystal packing effects on SCO behavior.« less

Effect of environmental noise and music on dexmedetomidine-induced sedation in dogs

PubMed Central

Seddighi, Reza M.; Ng, Zenithson; Sun, Xiaocun; Rezac, DJ

2017-01-01

Background Previous studies in human patients suggest depth of sedation may be affected by environmental noise or music; however, related data in domestic animals is limited. The objective of the current study was to investigate the effect of noise and music on dexmedetomidine-induced (DM- 10 µg/kg, IM) sedation in 10 dogs. Methods In a crossover design, post-DM injection dogs were immediately subjected to recorded human voices at either 55–60 decibel (dB) (Noise 1) or 80–85 dB (Noise 2); classical music at 45–50 dB (Music); or background noise of 40–45 dB (Control+). Control− included IM saline injection and exposure to 40–45 dB background noise. Sedation was assessed via monitoring spontaneous behavior and accelerometry (delta-g) throughout three 20-min evaluation periods: baseline, noise exposure, and post-treatment. Sedation was further assessed during two restraint tests at 30 min (R1) and 40 min (R2) post-injection. A mixed model for crossover design was used to determine the effect of noise exposure and time on either spontaneous behavior scores or delta-g. The restraint scores were analyzed using a two-way repeated measures ANOVA. Results Spontaneous behavior scores indicated less sedation during Noise 2 compared to Control+ (P = 0.05). R2 restraint scores for all DM treatments except Noise 2 indicated significantly higher sedation than Control− [C+ (P = 0.003), M (P = 0.014) and N1 (P = 0.044)]. Discussion Results suggest that the quality of sedation is negatively impacted by high-intensity noise conditions (80–85 dB), but exposure to music did not improve sedation in this population of research dogs. PMID:28785527

Dynamic and thermodynamic crossover scenarios in the Kob-Andersen mixture: Insights from multi-CPU and multi-GPU simulations.

PubMed

Coslovich, Daniele; Ozawa, Misaki; Kob, Walter

2018-05-17

The physical behavior of glass-forming liquids presents complex features of both dynamic and thermodynamic nature. Some studies indicate the presence of thermodynamic anomalies and of crossovers in the dynamic properties, but their origin and degree of universality is difficult to assess. Moreover, conventional simulations are barely able to cover the range of temperatures at which these crossovers usually occur. To address these issues, we simulate the Kob-Andersen Lennard-Jones mixture using efficient protocols based on multi-CPU and multi-GPU parallel tempering. Our setup enables us to probe the thermodynamics and dynamics of the liquid at equilibrium well below the critical temperature of the mode-coupling theory, [Formula: see text]. We find that below [Formula: see text] the analysis is hampered by partial crystallization of the metastable liquid, which nucleates extended regions populated by large particles arranged in an fcc structure. By filtering out crystalline samples, we reveal that the specific heat grows in a regular manner down to [Formula: see text] . Possible thermodynamic anomalies suggested by previous studies can thus occur only in a region of the phase diagram where the system is highly metastable. Using the equilibrium configurations obtained from the parallel tempering simulations, we perform molecular dynamics and Monte Carlo simulations to probe the equilibrium dynamics down to [Formula: see text]. A temperature-derivative analysis of the relaxation time and diffusion data allows us to assess different dynamic scenarios around [Formula: see text]. Hints of a dynamic crossover come from analysis of the four-point dynamic susceptibility. Finally, we discuss possible future numerical strategies to clarify the nature of crossover phenomena in glass-forming liquids.

Meatballs with 3% and 6% dietary fibre from rye bran or pea fibre - Effects on sensory quality and subjective appetite sensations.

PubMed

Kehlet, Ursula; Pagter, Mette; Aaslyng, Margit D; Raben, Anne

2017-03-01

This study investigated dose-response effects of rye bran and pea fibre added to meatballs on sensory quality and subjective appetite sensations. Pea fibre or rye bran was added to meatballs in doses ranging from 3g to 6g dietary fibre per 100g. In a sensory profile, a trained panel (n=9) evaluated the meatballs in terms of odour, appearance, texture and flavour attributes. In a cross-over appetite study, 27 healthy men were served five test meals. Subjective appetite sensations were assessed over a 4-hour period. The addition of rye bran to the meatballs increased the grainy odour, texture and flavour. Pea fibre resulted in a more crumbly, firm and gritty texture with increasing doses of fibre. The sensory changes followed a dose-response relationship. Subjective appetite sensations were not affected by the addition of fibre. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of the effects of firocoxib, carprofen and vedaprofen in a sodium urate crystal induced synovitis model of arthritis in dogs.

PubMed

Hazewinkel, Herman A W; van den Brom, Walter E; Theyse, Lars F H; Pollmeier, Matthias; Hanson, Peter D

2008-02-01

A randomized, placebo-controlled, four-period cross-over laboratory study involving eight dogs was conducted to confirm the effective analgesic dose of firocoxib, a selective COX-2 inhibitor, in a synovitis model of arthritis. Firocoxib was compared to vedaprofen and carprofen, and the effect, defined as a change in weight bearing measured via peak ground reaction, was evaluated at treatment dose levels. A lameness score on a five point scale was also assigned to the affected limb. Peak vertical ground reaction force was considered to be the most relevant measurement in this study. The firocoxib treatment group performed significantly better than placebo at the 3 h post-treatment time point and significantly better than placebo and carprofen at the 7 h post-treatment time point. Improvement in lameness score was also significantly better in the dogs treated with firocoxib than placebo and carprofen at both the 3 and 7 h post-treatment time points.

The effects of bilastine compared with cetirizine, fexofenadine, and placebo on allergen-induced nasal and ocular symptoms in patients exposed to aeroallergen in the Vienna Challenge Chamber.

PubMed

Horak, Friedrich; Zieglmayer, Petra; Zieglmayer, René; Lemell, Patrick

2010-05-01

This double-blind cross-over study compared the potential of bilastine, cetirizine, and fexofenadine to relieve the symptoms of allergic rhinitis. Seventy-five allergic volunteers were challenged with grass pollen in the Vienna Challenge Chamber (VCC) on two consecutive days of allergen provocation; 6 h on day 1 and 4 h day 2. Bilastine 20 mg, cetirizine 10 mg, fexofenadine 120 mg, or placebo were taken orally 2 h after the start of provocation on day 1 only. Total nasal symptom scores, the global symptom scores, nasal secretions, and eye symptoms were assessed on both day 1 and day 2. Bilastine had a rapid onset of action, within 1 h, and a long duration of action, greater than 26 h. Cetirizine was similar. Fexofenadine was similar on day 1 but less effective on day 2, indicating a shorter duration of action. Bilastine, like cetirizine and fexofenadine, was safe and well tolerated in this study.

How Regrouping Alerts in Computerized Physician Order Entry Layout Influences Physicians' Prescription Behavior: Results of a Crossover Randomized Trial.

PubMed

Wipfli, Rolf; Ehrler, Frederic; Bediang, Georges; Bétrancourt, Mireille; Lovis, Christian

2016-06-02

As demonstrated in several publications, low positive predictive value alerts in computerized physician order entry (CPOE) induce fatigue and may interrupt physicians unnecessarily during prescription of medication. Although it is difficult to increase the consideration of medical alerts by physician through an improvement of their predictive value, another approach consists to act on the way they are presented. The interruption management model inspired us to propose an alternative alert display strategy of regrouping the alerts in the screen layout, as a possible solution for reducing the interruption in physicians' workflow. In this study, we compared 2 CPOE designs based on a particular alert presentation strategy: one design involved regrouping the alerts in a single place on the screen, and in the other, the alerts were located next to the triggering information. Our objective was to evaluate experimentally whether the new design led to fewer interruptions in workflow and if it affected alert handling. The 2 CPOE designs were compared in a controlled crossover randomized trial. All interactions with the system and eye movements were stored for quantitative analysis. The study involved a group of 22 users consisting of physicians and medical students who solved medical scenarios containing prescription tasks. Scenario completion time was shorter when the alerts were regrouped (mean 117.29 seconds, SD 36.68) than when disseminated on the screen (mean 145.58 seconds, SD 75.07; P=.045). Eye tracking revealed that physicians fixated longer on alerts in the classic design (mean 119.71 seconds, SD 76.77) than in the centralized alert design (mean 70.58 seconds, SD 33.53; P=.001). Visual switches between prescription and alert areas, indicating interruption, were reduced with centralized alerts (mean 41.29, SD 21.26) compared with the classic design (mean 57.81, SD 35.97; P=.04). Prescription behavior (ie, prescription changes after alerting), however, did not change significantly between the 2 strategies of display. The After-Scenario Questionnaire (ASQ) that was filled out after each scenario showed that overall satisfaction was significantly rated lower when alerts were regrouped (mean 4.37, SD 1.23) than when displayed next to the triggering information (mean 5.32, SD 0.94; P=.02). Centralization of alerts in a table might be a way to motivate physicians to manage alerts more actively, in a meaningful way, rather than just being interrupted by them. Our study could not provide clear recommendations yet, but provides objective data through a cognitive psychological approach. Future tests should work on standardized scenarios that would enable to not only measure physicians' behavior (visual fixations and handling of alerts) but also validate those actions using clinical criteria.

The unusual magnetism of nanoparticle LaCoO3.

PubMed

Durand, A M; Belanger, D P; Hamil, T J; Ye, F; Chi, S; Fernandez-Baca, J A; Booth, C H; Abdollahian, Y; Bhat, M

2015-05-08

Bulk and nanoparticle powders of LaCoO3 (LCO) were synthesized and their magnetic and structural properties were studied using SQUID magnetometry and neutron diffraction. The bulk and large nanoparticles exhibit weak ferromagnetism (FM) below T ≈ 85 K and a crossover from strong to weak antiferromagnetic (AFM) correlations near a transition expressed in the lattice parameters, To≈40 K. This crossover does not occur in the smallest nanoparticles; instead, the magnetic behavior is predominantly ferromagnetic. The amount of FM in the nanoparticles depends on the amount of Co3O4 impurity phase, which induces tensile strain on the LCO lattice. A core-interface model is introduced, with the core region exhibiting the AFM crossover and with FM in the interface region near surfaces and impurity phases.

The unusual magnetism of nanoparticle LaCoO 3

DOE PAGES

Durand, A. M.; Belanger, D. P.; Hamil, T. J.; ...

2015-04-15

Bulk and nanoparticle powders of LaCoO 3 (LCO) were synthesized and their magnetic and structural properties were studied using SQUID magnetometry and neutron diffraction. The bulk and large nanoparticles exhibit weak ferromagnetism (FM) below T≈85K and a crossover from strong to weak antiferromagnetic (AFM) correlations near a transition expressed in the lattice parameters, To ≈ 40 K. This crossover does not occur in the smallest nanoparticles; instead, the magnetic behavior is predominantly ferromagnetic. The amount of FM in the nanoparticles depends on the amount of Co 3O 4 impurity phase, which induces tensile strain on the LCO lattice. A core-interfacemore » model is introduced, with the core region exhibiting the AFM crossover and with FM in the interface region near surfaces and impurity phases.« less

The unusual magnetism of nanoparticle LaCoO3

NASA Astrophysics Data System (ADS)

Durand, A. M.; Belanger, D. P.; Hamil, T. J.; Ye, F.; Chi, S.; Fernandez-Baca, J. A.; Booth, C. H.; Abdollahian, Y.; Bhat, M.

2015-05-01

Bulk and nanoparticle powders of LaCoO3 (LCO) were synthesized and their magnetic and structural properties were studied using SQUID magnetometry and neutron diffraction. The bulk and large nanoparticles exhibit weak ferromagnetism (FM) below T ≈ 85 K and a crossover from strong to weak antiferromagnetic (AFM) correlations near a transition expressed in the lattice parameters, To≈40 K. This crossover does not occur in the smallest nanoparticles; instead, the magnetic behavior is predominantly ferromagnetic. The amount of FM in the nanoparticles depends on the amount of Co3O4 impurity phase, which induces tensile strain on the LCO lattice. A core-interface model is introduced, with the core region exhibiting the AFM crossover and with FM in the interface region near surfaces and impurity phases.

Dynamical Crossovers in Prethermal Critical States.

PubMed

Chiocchetta, Alessio; Gambassi, Andrea; Diehl, Sebastian; Marino, Jamir

2017-03-31

We study the prethermal dynamics of an interacting quantum field theory with an N-component order parameter and O(N) symmetry, suddenly quenched in the vicinity of a dynamical critical point. Depending on the initial conditions, the evolution of the order parameter, and of the response and correlation functions, can exhibit a temporal crossover between universal dynamical scaling regimes governed, respectively, by a quantum and a classical prethermal fixed point, as well as a crossover from a Gaussian to a non-Gaussian prethermal dynamical scaling. Together with a recent experiment, this suggests that quenches may be used in order to explore the rich variety of dynamical critical points occurring in the nonequilibrium dynamics of a quantum many-body system. We illustrate this fact by using a combination of renormalization group techniques and a nonperturbative large-N limit.

Relative Bioavailabilities of Lisdexamfetamine Dimesylate and d-Amphetamine in Healthy Adults in an Open-Label, Randomized, Crossover Study After Mixing Lisdexamfetamine Dimesylate With Food or Drink

PubMed Central

Ermer, James; Corcoran, Mary; Lasseter, Kenneth

2016-01-01

Background: This open-label, crossover study examined lisdexamfetamine dimesylate (LDX) and d-amphetamine pharmacokinetics in healthy adults after administration of an intact LDX capsule or after the capsule was emptied into orange juice or yogurt and the contents consumed. Methods: Healthy adult volunteers (N = 30) were administered a 70-mg LDX capsule or the contents of a 70-mg capsule mixed with yogurt or orange juice using a 3-way crossover design. Blood samples were collected serially for up to 96 hours after dose. Pharmacokinetic endpoints included maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from zero to infinity (AUC0–∞) or to last assessment (AUClast). Relative LDX and d-amphetamine bioavailabilities from the contents of a 70-mg LDX capsule mixed with orange juice or yogurt were compared with those from the intact LDX capsule using bioequivalence-testing procedures. Results: Geometric least squares mean ratios (90% confidence intervals [CIs]) for d-amphetamine (active moiety) were within the prespecified bioequivalence range (0.80–1.25) when the contents of a 70-mg LDX capsule were mixed with orange juice [Cmax: 0.971 (0.945, 0.998); AUC0–∞: 0.986 (0.955, 1.019); AUClast: 0.970 (0.937, 1.004)] or yogurt [Cmax: 0.970 (0.944, 0.997); AUC0–∞: 0.945 (0.915, 0.976); AUClast: 0.944 (0.912, 0.977)]. Geometric least squares mean ratios (90% CIs) for LDX (inactive prodrug) were below the accepted range when the contents of a 70-mg LDX capsule were mixed with orange juice [Cmax: 0.641 (0.582, 0.707); AUC0–∞: 0.716 (0.647, 0.792); AUClast: 0.708 (0.655, 0.766)]; the lower 90% CI for Cmax [0.828 (0.752, 0.912)] was below the accepted range when the contents of a 70-mg LDX capsule were mixed with yogurt. Conclusions: Relative bioavailability of d-amphetamine (the active moiety) did not differ across administrations, which suggests that emptying an LDX capsule into orange juice or yogurt and consuming it is an alternative to intact capsules. PMID:27661399

Empirical mode decomposition and long-range correlation analysis of sunspot time series

NASA Astrophysics Data System (ADS)

Zhou, Yu; Leung, Yee

2010-12-01

Sunspots, which are the best known and most variable features of the solar surface, affect our planet in many ways. The number of sunspots during a period of time is highly variable and arouses strong research interest. When multifractal detrended fluctuation analysis (MF-DFA) is employed to study the fractal properties and long-range correlation of the sunspot series, some spurious crossover points might appear because of the periodic and quasi-periodic trends in the series. However many cycles of solar activities can be reflected by the sunspot time series. The 11-year cycle is perhaps the most famous cycle of the sunspot activity. These cycles pose problems for the investigation of the scaling behavior of sunspot time series. Using different methods to handle the 11-year cycle generally creates totally different results. Using MF-DFA, Movahed and co-workers employed Fourier truncation to deal with the 11-year cycle and found that the series is long-range anti-correlated with a Hurst exponent, H, of about 0.12. However, Hu and co-workers proposed an adaptive detrending method for the MF-DFA and discovered long-range correlation characterized by H≈0.74. In an attempt to get to the bottom of the problem in the present paper, empirical mode decomposition (EMD), a data-driven adaptive method, is applied to first extract the components with different dominant frequencies. MF-DFA is then employed to study the long-range correlation of the sunspot time series under the influence of these components. On removing the effects of these periods, the natural long-range correlation of the sunspot time series can be revealed. With the removal of the 11-year cycle, a crossover point located at around 60 months is discovered to be a reasonable point separating two different time scale ranges, H≈0.72 and H≈1.49. And on removing all cycles longer than 11 years, we have H≈0.69 and H≈0.28. The three cycle-removing methods—Fourier truncation, adaptive detrending and the proposed EMD-based method—are further compared, and possible reasons for the different results are given. Two numerical experiments are designed for quantitatively evaluating the performances of these three methods in removing periodic trends with inexact/exact cycles and in detecting the possible crossover points.

Influence diagnostics for count data under AB-BA crossover trials.

PubMed

Hao, Chengcheng; von Rosen, Dietrich; von Rosen, Tatjana

2017-12-01

This paper aims to develop diagnostic measures to assess the influence of data perturbations on estimates in AB-BA crossover studies with a Poisson distributed response. Generalised mixed linear models with normally distributed random effects are utilised. We show that in this special case, the model can be decomposed into two independent sub-models which allow to derive closed-form expressions to evaluate the changes in the maximum likelihood estimates under several perturbation schemes. The performance of the new influence measures is illustrated by simulation studies and the analysis of a real dataset.

49 CFR 218.107 - Additional operational requirements for hand-operated crossover switches.

Code of Federal Regulations, 2011 CFR

2011-10-01

...-operated crossover switches. 218.107 Section 218.107 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.107 Additional operational requirements for hand-operated crossover switches. (a) Each railroad shall adopt and comply with an operating rule which...

49 CFR 218.103 - Hand-operated switches, including crossover switches.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Hand-operated switches, including crossover switches. 218.103 Section 218.103 Transportation Other Regulations Relating to Transportation (Continued... Equipment, Switches, and Fixed Derails § 218.103 Hand-operated switches, including crossover switches. (a)(1...

49 CFR 218.107 - Additional operational requirements for hand-operated crossover switches.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-operated crossover switches. 218.107 Section 218.107 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.107 Additional operational requirements for hand-operated crossover switches. (a) Each railroad shall adopt and comply with an operating rule which...

49 CFR 218.107 - Additional operational requirements for hand-operated crossover switches.

Code of Federal Regulations, 2014 CFR

2014-10-01

...-operated crossover switches. 218.107 Section 218.107 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.107 Additional operational requirements for hand-operated crossover switches. (a) Each railroad shall adopt and comply with an operating rule which...

49 CFR 218.103 - Hand-operated switches, including crossover switches.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Hand-operated switches, including crossover switches. 218.103 Section 218.103 Transportation Other Regulations Relating to Transportation (Continued... Equipment, Switches, and Fixed Derails § 218.103 Hand-operated switches, including crossover switches. (a)(1...

49 CFR 218.107 - Additional operational requirements for hand-operated crossover switches.

Code of Federal Regulations, 2012 CFR

2012-10-01

...-operated crossover switches. 218.107 Section 218.107 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.107 Additional operational requirements for hand-operated crossover switches. (a) Each railroad shall adopt and comply with an operating rule which...

49 CFR 218.103 - Hand-operated switches, including crossover switches.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Hand-operated switches, including crossover switches. 218.103 Section 218.103 Transportation Other Regulations Relating to Transportation (Continued... Equipment, Switches, and Fixed Derails § 218.103 Hand-operated switches, including crossover switches. (a)(1...

49 CFR 218.103 - Hand-operated switches, including crossover switches.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Hand-operated switches, including crossover switches. 218.103 Section 218.103 Transportation Other Regulations Relating to Transportation (Continued... Equipment, Switches, and Fixed Derails § 218.103 Hand-operated switches, including crossover switches. (a)(1...

49 CFR 218.107 - Additional operational requirements for hand-operated crossover switches.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-operated crossover switches. 218.107 Section 218.107 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.107 Additional operational requirements for hand-operated crossover switches. (a) Each railroad shall adopt and comply with an operating rule which...

49 CFR 218.103 - Hand-operated switches, including crossover switches.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Hand-operated switches, including crossover switches. 218.103 Section 218.103 Transportation Other Regulations Relating to Transportation (Continued... Equipment, Switches, and Fixed Derails § 218.103 Hand-operated switches, including crossover switches. (a)(1...

A randomized, double-blind, placebo-controlled, crossover trial evaluating the effect of intranasal insulin on cognition and mood in individuals with treatment-resistant major depressive disorder.

PubMed

Cha, Danielle S; Best, Michael W; Bowie, Christopher R; Gallaugher, Laura Ashley; Woldeyohannes, Hanna O; Soczynska, Joanna K; Lewis, Gary; MacQueen, Glenda; Sahakian, Barbara J; Kennedy, Sidney H; Lui, Jane P; Mansur, Rodrigo B; McIntyre, Roger S

2017-03-01

Cognitive dysfunction in major depressive disorder (MDD) is identified as a primary therapeutic target; no current treatment is approved for the treatment of cognitive dysfunction in MDD. We examined whether intranasal insulin offered a beneficial effect across measures of cognitive function in adults with MDD. Thirty-five adults (18-65 years of age: 47.09±9.89) meeting criteria for a major depressive episode as per the Diagnostic and Statistical Manual (DSM)-IV-Treatment Revised were included in this randomized, double blind, placebo-controlled, crossover design study. Subjects were not stratified based on baseline cognitive deficit. Subjects were randomized to 4 weeks of either intranasal insulin 40 International Units (IU) taken four times a day (i.e., morning, afternoon, evening, and before bed) (QID) (n=19) or placebo (n=16). No between group differences were observed in change from baseline on total Montgomery Åsberg Depression Rating Scale (MADRS) score (25.98±2.81), in either of the Positive or Negative subscales of the Positive and Negative Affect Schedule (PANAS), or on a global index of neurocognition. The possibility of practice and/or carry over effect could not be excluded. Methodological refinement (e.g., stratification of subjects based on baseline cognitive deficit) may have augmented assay sensitivity. Intranasal insulin did not demonstrate statistically significant improvements on overall mood, aspects of emotional processing, neurocognitive function, or self-reported quality of life patient reported outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

Ready-Made Versus Custom-Made Mandibular Repositioning Devices in Sleep Apnea: A Randomized Clinical Trial.

PubMed

Johal, Ama; Haria, Priya; Manek, Seema; Joury, Easter; Riha, Renata

2017-02-15

To compare the effectiveness of a custom-made (MRDc) versus ready-made (MRDr) mandibular repositioning devices (MRD) in the management of obstructive sleep apnea (OSA). A randomized crossover trial design was adopted in which patients with a confirmed diagnosis of OSA were randomly allocated to receive either a 3-month period of ready-made or custom-made MRD, with an intervening washout period of 2 weeks, prior to crossover. Treatment outcomes included both objective sleep monitoring and patient-centered measures (daytime sleepiness, partner snoring and quality of life). Twenty-five patients, with a mild degree of OSA (apnea-hypopnea index of 13.3 [10.9-25] events/h) and daytime sleepiness (Epworth Sleepiness Scale of 11 [6-16]), completed both arms of the trial. The MRDc achieved a complete treatment response in 64% of participants, compared with 24% with the MRDr (p < 0.001). A significant difference was observed in treatment failures, when comparing the MRDr (36%) with the MRDc (4%). Excessive daytime sleepiness (Epworth Sleepiness Scale ≥ 10) persisted in 33% (MRDc) and 66% (MRDr) of OSA subjects, following treatment. A statistically significant improvement was observed in quality of life scales following MRDc therapy only. Significant differences were observed in relation to both the number of nights per week (p = 0.004) and hours per night (p = 0.006) between the two different designs of device. The study demonstrates the significant clinical effectiveness of a custom-made mandibular repositioning device, particularly in terms of patient compliance and tolerance, in the treatment of OSA. © 2017 American Academy of Sleep Medicine

Experimentally manipulated sleep duration in adolescents with asthma: Feasibility and preliminary findings.

PubMed

Meltzer, Lisa J; Faino, Anna; Szefler, Stanley J; Strand, Matthew; Gelfand, Erwin W; Beebe, Dean W

2015-12-01

To examine the impact of sleep duration on lung function and asthma symptoms in adolescents. Ten adolescents with asthma (60% female, 60% Caucasian, mean age = 13.7 years, range 12-17) completed a 3-week randomized, cross-over sleep manipulation protocol. Following a week of self-selected sleep duration, adolescents were randomized to a five-night deficient sleep opportunity (6.5 hr in bed) or a healthy sleep opportunity (10 hr in bed) obtained by systematically changing bedtimes. Wake time remained consistent across all 3 weeks (including weekends). Daily reports of sleep patterns and asthma symptoms, actigraphy, and daily peak expiratory flow rates (PEFR), as well as weekly spirometry and exhaled nitric oxide were collected. Participants averaged 3.2 hr less sleep (P < 0.001) per night in the short sleep condition versus the long sleep condition. Further, they had an 8.4% decrease overnight in PEFR (P = 0.007), and reported more asthma symptoms interfering with activities in the past 24 hr (P = 0.02) in the short sleep condition than the long sleep condition. No significant differences between experimental weeks were found for weekly spirometry or exhaled nitric oxide. This pilot study demonstrated the feasibility of a cross-over sleep manipulation protocol in adolescents with asthma. Since overnight decrease in PEFR is a marker of nocturnal asthma, and has been associated with the severity of daytime airflow limitation, these early-stage results suggest that shortened sleep duration may exacerbate adolescent asthma and associated functional impairments. © 2015 Wiley Periodicals, Inc.

Technology Use in Science Instruction (TUSI): Aligning the Integration of Technology in Science Instruction in Ways Supportive of Science Education Reform

ERIC Educational Resources Information Center

Campbell, Todd; Abd-Hamid, Nor Hashidah

2013-01-01

This study describes the development of an instrument to investigate the extent to which technology is integrated in science instruction in ways aligned to science reform outlined in standards documents. The instrument was developed by: (a) creating items consistent with the five dimensions identified in science education literature, (b)…

Coping as Part of Motivational Resilience in School: A Multidimensional Measure of Families, Allocations, and Profiles of Academic Coping

ERIC Educational Resources Information Center

Skinner, Ellen; Pitzer, Jennifer; Steele, Joel

2013-01-01

A study was designed to examine a multidimensional measure of children's coping in the academic domain as part of a larger model of motivational resilience. Using items tapping multiple ways of dealing with academic problems, including five adaptive ways (strategizing, help-seeking, comfort-seeking, self-encouragement, and commitment) and six…

Open-label, randomized, single-dose, crossover study to evaluate the pharmacokinetics and safety differences between two docetaxel products, CKD-810 and Taxotere injection, in patients with advanced solid cancer.

PubMed

Cho, Eun Kyung; Park, Ji-Young; Lee, Kyung Hee; Song, Hong Suk; Min, Young Joo; Kim, Yeul Hong; Kang, Jin-Hyoung

2014-01-01

The aim of this study was to compare CKD-810 (test docetaxel) with Taxotere(®) (reference docetaxel) in terms of pharmacokinetics and safety for patients with advanced or metastatic carcinoma. A randomized, open-label, two-way crossover study was conducted in eligible patients. Patients received with reference or test drugs of 75 mg/m(2) docetaxel by intravenous infusion for 60 min in the first period and the alternative drug in the second period with a washout of 3 weeks. Plasma concentrations of docetaxel were determined by validated high-performance liquid chromatography coupled to tandem mass spectrometry detection. Pharmacokinetic parameters, including the maximum plasma concentration (C(max)) and the area under the concentration-time curve (AUC), were determined by non-compartmental analysis. A total of 44 patients were included in the study, 21 patients received test drug and 23 received reference drug for the first cycle. The C(max) of docetaxel was 2,658.77 ng/mL for test drug and 2,827.60 ng/mL for reference drug, and two drugs showed no difference with a statistical significance. Time to reach C(max) (T(max)) of CKD-810 (0.94 h) versus reference docetaxel (0.97 h) was also not significantly different. Other pharmacokinetic parameters including the plasma AUC, elimination half-life, and total body clearance exhibited similar values without a significant difference. The most common grade 3 or 4 toxicity was neutropenia (CKD-810 19.5 or 29.3 %; reference docetaxel 14.6 or 41.5 %). Febrile neutropenia was experienced by only one patient in each group. Two patients died of progression of disease during the study. Docetaxel anhydrous CKD-810 use with patients suffering advanced or metastatic solid malignancies was equivalent to reference docetaxel in terms of pharmacokinetic parameters and safety profile. Additionally, the test and reference drug met the regulatory criteria for pharmacokinetic equivalence.

Does postprandial itopride intake affect the rate of gastric emptying? A crossover study using the continuous real time 13C breath test (BreathID system).

PubMed

Nonaka, Takashi; Kessoku, Takaomi; Ogawa, Yuji; Yanagisawa, Shogo; Shiba, Tadahiko; Sahaguchi, Takashi; Atsukawa, Kazuhiro; Takahashi, Hisao; Sekino, Yusuke; Iida, Hiroshi; Hosono, Kunihiro; Endo, Hiroki; Sakamoto, Yasunari; Koide, Tomoko; Takahashi, Hirokazu; Tokoro, Chikako; Abe, Yasunobu; Maeda, Shin; Nakajima, Atsushi; Inamori, Masahiko

2011-01-01

The aim of this study was to determine whether oral Itopride hydrochloride (itopride) intake might have any effect on the rate of gastric emptying, using a novel non-invasive technique for measuring the rate of gastric emptying, namely, the continuous real time 13C breath test (BreathID system: Exalenz Bioscience Ltd., Israel). Eight healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted overnight and were randomly assigned to receive 50mg itopride following a test meal (200 kcal per 200mL, containing 100mg 13C acetate), or the test meal alone. Under both conditions, gastric emptying was monitored for 4 hours after administration of the test meal by the 13C-acetic acid breath test performed continually using the BreathID system. Using Oridion Research Software (beta version), the time required for emptying of 50% of the labeled meal (T 1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (T lag), the gastric emptying coefficient (GEC), and the regression-estimated constants (beta and kappa) were calculated. The parameters measured under the two conditions were compared using the Wilcoxon's signed-rank test. No significant differences in the calculated parameters, namely, the T 1/2, T lag, GEC, beta or kappa, were observed between the two test conditions, namely, administration of a test meal+itopride and administration of the test meal alone. The present study revealed that postprandial itopride intake had no significant influence on the rate of gastric emptying. Recently, several studies have shown that itopride may be effective in the treatment of patients with functional dyspepsia. Our results suggest that the efficacy of itopride in patients with functional dyspepsia may be based on its effect of improving functions other than the rate of gastric emptying, such as the activities at neuronal sites, brain-gut correlation, visceral hypersensitivity, gastric accommodation and distension-induced adaptation.

Electromagnetic pump stator frame having power crossover struts

DOEpatents

Fanning, Alan W.; Olich, Eugene E.

1995-01-01

A stator frame for an electromagnetic pump includes a casing joined to a hub by a plurality of circumferentially spaced apart struts. At least one electrically insulated power crossover lead extends through the hub, through a crossover one of the struts, and through the casing for carrying electrical current therethrough.

50 CFR 660.320 - Open access fishery-crossover provisions.

Code of Federal Regulations, 2010 CFR

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. (b...

50 CFR 660.320 - Open access fishery-crossover provisions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 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. (b...

Determination of Effective Crossover Location and Dimensions for Branched Detonation in a Pulsed Detonation Engine

DTIC Science & Technology

2012-03-22

location is varied from the aft end of the detonation tube to the middle of the detonation tube while the crossover width is varied from 2.5 in to 0.5...the other end where the tube is connected to a source of fuel, oxidizer, and ignition .7 The engine cycle is divided into three equal phases: fill...location and width of the crossover duct for hydrogen, ethylene and an n-alkane. The crossover location is varied from the aft end of the

Spin crossover in (Mg,Fe3+)(Si,Fe3+)O3 bridgmanite: effects of disorder, iron concentration, and temperature

NASA Astrophysics Data System (ADS)

Shukla, Gaurav; Wentzcovitch, Renata

The spin crossover of iron in Fe3+-bearing bridgmanite, the most abundant mineral of the Earth's lower mantle, is by now a well-established phenomenon, though several aspects of this crossover remain unclear. Here we investigate effects of disorder, iron concentration, and temperature on this crossover using ab initio LDA + USC calculations. Disorder and concentration effects are addressed using complete statistical samplings of coupled substituted configurations up to 80 atoms supercells, while the vibrational effects using the quasiharmonic approximation. Our calculated compression curves for iron-free and iron-bearing bridgmanite compare well with the latest experimental measurements. The comparison also suggests that in a closed system, Fe2+ present in the sample may transform into Fe3+ by introduction of Mg and O vacancies with increasing pressure. As in the spin crossover in ferropericlase, this crossover in bridgmanite is accompanied by a clear volume reduction and an anomalous softening of the bulk modulus throughout the crossover pressure range. Though the concentration of [Fe3+]Si in bridgmanite may be small, related elastic anomalies may impact the interpretation of radial and lateral velocity structures of the Earth's lower mantle. This research was supported primarily by NSF Grant EAR 1348066. Computations are performed at the Minnesota Supercomputing Institute (MSI).

A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness.

PubMed

Golier, Julia A; Caramanica, Kimberly; Michaelides, Andreas C; Makotkine, Iouri; Schmeidler, James; Harvey, Philip D; Yehuda, Rachel

2016-02-01

No pharmacological treatments have been demonstrated to effectively treat chronic multisymptom illness (CMI) in Gulf War veterans (GWV). This study assessed the effect of the glucocorticoid receptor antagonist mifepristone in GWV with CMI. A randomized, double-blind, cross-over trial of mifepristone, with two six-week treatment phases separated by a one-month washout period, was conducted at a Veterans Affairs (VA) hospital between 2008 and 2011. Participants were randomized to receive either 200mg of mifepristone per day or matched placebo first. The primary clinical outcome measure was change in self-reported physical health. Neurocognitive functioning and self-reported measures of depression, PTSD, and fatigue were secondary outcomes. Sixty-five participants enrolled, of whom 36 were randomized and 32 (mean age, 49.1 (7.2) years) completed the study. Physical and mental health status and neurocognitive functioning were poor at baseline. Mifepristone treatment was not associated with improvement in self-reported physical health (p=0.838) or in other self-reported measures of mental health. Mifepristone treatment was significantly associated with improvements in verbal learning (p=0.008, d=0.508), in the absence of improvement in other cognitive measures (working memory (p=0.914), visual learning (p=0.643) and a global composite measure (p=0.937). Baseline morning cortisol levels and lysozyme IC50-DEX, a measure of peripheral glucocorticoid sensitivity, displayed a significant relationship with endpoint verbal learning scores (p=0.012 and p=0.007, respectively). The magnitude of cortisol change during treatment mediated the improvement in verbal learning. This study was negative for the primary and secondary clinical outcomes. However, the data suggest a moderate dose of mifepristone may have circumscribed cognitive-enhancing effects in CMI. Further study is warranted to determine whether and through which mechanisms mifepristone treatment can yield clinically meaningful improvement in cognitive function in CMI or other neuropsychiatric conditions associated with HPA axis dysregulation. Published by Elsevier Ltd.

Laboratory- and community-based health outcomes in people with transtibial amputation using crossover and energy-storing prosthetic feet: A randomized crossover trial

PubMed Central

Morgan, Sara J.; McDonald, Cody L.; Halsne, Elizabeth G.; Cheever, Sarah M.; Salem, Rana; Kramer, Patricia A.

2018-01-01

Contemporary prosthetic feet are generally optimized for either daily or high-level activities. Prosthesis users, therefore, often require multiple prostheses to participate in activities that span a range of mobility. Crossover feet (XF) are designed to increase the range of activities that can be performed with a single prosthesis. However, little evidence exists to guide clinical prescription of XF relative to traditional energy storing feet (ESF). The objective of this study was to assess the effects of XF and ESF on health outcomes in people with transtibial amputation. A randomized crossover study was conducted to assess changes in laboratory-based (endurance, perceived exertion, walking performance) and community-based (step activity and self-reported mobility, fatigue, balance confidence, activity restrictions, and satisfaction) outcomes. Twenty-seven participants were fit with XF and ESF prostheses with standardized sockets, interfaces, and suspensions. Participants were not blinded to the intervention, and wore each prosthesis for one month while their steps were counted with an activity monitor. After each accommodation period, participants returned for data collection. Endurance and perceived exertion were measured with the Six-Minute Walk Test and Borg-CR100, respectively. Walking performance was measured using an electronic walkway. Self-reported mobility, fatigue, balance confidence, activity restrictions, and satisfaction were measured with survey instruments. Participants also reported foot preferences upon conclusion of the study. Differences between feet were assessed with a crossover analysis. While using XF, users experienced improvements in most community-based outcomes, including mobility (p = .001), fatigue (p = .001), balance confidence (p = .005), activity restrictions (p = .002), and functional satisfaction (p < .001). Participants also exhibited longer sound side steps in XF compared to ESF (p < .001). Most participants (89%) reported an overall preference for XF; others (11%) reported no preference. Results indicate that XF may be a promising alternative to ESF for people with transtibial amputation who engage in a range of mobility activities. Trial registration: ClinicalTrials.gov NCT02440711 PMID:29414988

Modafinil In Debilitating fatigue After Stroke (MIDAS): study protocol for a randomised, double-blinded, placebo-controlled, crossover trial.

PubMed

Lillicrap, Thomas; Krishnamurthy, Venkatesh; Attia, John; Nilsson, Michael; Levi, Christopher R; Parsons, Mark W; Bivard, Andrew

2016-08-17

Fatigue is a common symptom in stroke survivors for which there is currently no proven therapy. Modafinil is a wakefulness-promoting agent with established benefits in other disease models. We aim to test if modafinil will improve patient's self-reported fatigue scores when compared to placebo and if therapy results in increased quality of life. MIDAS is a phase II, single-centre, prospective, double-blinded, randomised, crossover trial of modafinil for the treatment of persistent fatigue in survivors of ischaemic stroke. The inclusion criteria will require an average score of 12 or more across all domains of the Multi-dimensional Fatigue Inventory (MFI-20) and the diagnosis of a stroke more than 6 months prior. Patients will be randomised 1:1 to receive either modafinil 200 mg daily or placebo for a period of 6 weeks, after which a crossover will occur where patients who are on modafinil will begin taking placebo and vice versa. The primary outcome will be improvement in fatigue as measured by the MFI-20. Secondary outcomes will include changes in the Fatigue Severity Scale, improved cognition measured using the Montreal Cognitive Assessment, improvement in mood as determined by the Depression, Anxiety and Stress Scale and improvement in each patient's stroke-specific quality of life score. All participants will also undergo magnetic resonance imaging (MRI) at baseline, crossover and study conclusion to measure cerebral blood flow on arterial spin labelling and brain activity on resting state functional MRI. This study will comply with the CONSORT guidelines. The projected sample size requirement is 36 participants in a crossover trial giving a power of 80 % and a type-1 error rate of 0.05. MIDAS seeks to enhance the quality of life in stroke survivors by assisting or resolving stroke-associated fatigue. ACTRN12615000350527 , registered on the 17 April 2015. Protocol version 3, approved 16 June 2015.

A crossover-crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and serum reproductive hormones in men.

PubMed

Nassan, Feiby L; Coull, Brent A; Skakkebaek, Niels E; Andersson, Anna-Maria; Williams, Michelle A; Mínguez-Alarcón, Lidia; Krawetz, Stephen A; Hall, Janet E; Hait, Elizabeth J; Korzenik, Joshua R; Ford, Jennifer B; Moss, Alan C; Hauser, Russ

2018-01-01

Phthalates, such as dibutyl phthalate (DBP), are endocrine disruptors used in some medication coatings e.g., mesalamine to treat inflammatory bowel disease (IBD). Taking advantage of different mesalamine formulations with/without DBP, we assessed whether DBP from mesalamine (>1000x background) altered serum hormones. Men (N=73) with IBD participated in a crossover-crossback prospective study and provided up to 6 serum samples (2:baseline, 2:crossover, 2:crossback). Men on non-DBP mesalamine (background) at baseline crossed-over for 4 months to DBP-mesalamine (high) and then crossed-back for 4 months to non-DBP mesalamine (B 1 HB 2 -arm) and vice versa for men on DBP-mesalamine at baseline (H 1 BH 2 -arm). We divided H 1 BH 2 -arm at the median (H 1 <3yrs or H 1 ≥3yrs). We estimated crossover and crossback % changes in serum reproductive hormones using multivariable linear mixed effect models. When B 1 HB 2 -arm (26 men,134 samples) crossed-over, luteinizing hormone decreased 13.9% (95% confidence interval(CI): -23.6,-3.0) and testosterone, inhibin-B, and follicle-stimulating hormone (FSH) marginally decreased; after crossback all increased 8-14%. H 1 BH 2 -arm, H 1 ≥3yrs (25 men,107samples) had no changes at crossover or crossback whereas in H 1 BH 2 -arm,H 1 <3yrs (22 men,100 samples) after crossover, inhibin-B increased 13.2% (CI: 4.2,22.9), FSH decreased 9.9% (CI: -17.9,-1.1) and after crossback, inhibin-B further increased 11.3%, and FSH marginally increased. High-DBP exposure may disrupt pituitary-gonadal hormones that largely reversed after exposure removal, but only in men with no or short previous high-exposure history. Paradoxically, men with longer duration of high-DBP exposure, exposure removal did not change hormone levels, suggesting that long-term high-DBP exposure may alter the pituitary-gonadal axis and make it insensitive to exposure changes. Copyright © 2017 Elsevier Inc. All rights reserved.

12-month blood pressure results of catheter-based renal artery denervation for resistant hypertension: the SYMPLICITY HTN-3 trial.

PubMed

Bakris, George L; Townsend, Raymond R; Flack, John M; Brar, Sandeep; Cohen, Sidney A; D'Agostino, Ralph; Kandzari, David E; Katzen, Barry T; Leon, Martin B; Mauri, Laura; Negoita, Manuela; O'Neill, William W; Oparil, Suzanne; Rocha-Singh, Krishna; Bhatt, Deepak L

2015-04-07

Results of the SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial confirmed the safety but not the efficacy of renal denervation for treatment-resistant hypertension at 6 months post procedure. This study sought to analyze the 12-month SYMPLICITY HTN-3 results for the original denervation group, the sham subjects who underwent denervation after the 6-month endpoint (crossover group), and the sham subjects who did not undergo denervation after 6 months (non-crossover group). Eligible subjects were randomized 2:1 to denervation or sham procedure. Subjects were unblinded to their treatment group after the 6-month primary endpoint was ascertained; subjects in the sham group meeting eligibility requirements could undergo denervation. Change in blood pressure (BP) at 12 months post randomization (6 months for crossover subjects) was analyzed. The 12-month follow-up was available for 319 of 361 denervation subjects and 48 of 101 non-crossover subjects; 6-month denervation follow-up was available for 93 of 101 crossover subjects. In denervation subjects, the 12-month office systolic BP (SBP) change was greater than that observed at 6 months (-15.5 ± 24.1 mm Hg vs. -18.9 ± 25.4 mm Hg, respectively; p = 0.025), but the 24-h SBP change was not significantly different at 12 months (p = 0.229). The non-crossover group office SBP decreased by -32.9 ± 28.1 mm Hg at 6 months, but this response regressed to -21.4 ± 19.9 mm Hg (p = 0.01) at 12 months, increasing to 11.5 ± 29.8 mm Hg. These data support no further reduction in office or ambulatory BP after 1-year follow-up. Loss of BP reduction in the non-crossover group may reflect decreased medication adherence or other related factors. (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Opposite effects of cannabis and cocaine on performance monitoring.

PubMed

Spronk, Desirée B; Verkes, Robbert J; Cools, Roshan; Franke, Barbara; Van Wel, Janelle H P; Ramaekers, Johannes G; De Bruijn, Ellen R A

2016-07-01

Drug use is often associated with risky and unsafe behavior. However, the acute effects of cocaine and cannabis on performance monitoring processes have not been systematically investigated. The aim of the current study was to investigate how administration of these drugs alters performance monitoring processes, as reflected in the error-related negativity (ERN), the error positivity (Pe) and post-error slowing. A double-blind placebo-controlled randomized three-way crossover design was used. Sixty-one subjects completed a Flanker task while EEG measures were obtained. Subjects showed diminished ERN and Pe amplitudes after cannabis administration and increased ERN and Pe amplitudes after administration of cocaine. Neither drug affected post-error slowing. These results demonstrate diametrically opposing effects on the early and late phases of performance monitoring of the two most commonly used illicit drugs of abuse. Conversely, the behavioral adaptation phase of performance monitoring remained unaltered by the drugs. Copyright © 2016. Published by Elsevier B.V.

Safety of HTX-019 (intravenous aprepitant) and fosaprepitant in healthy subjects.

PubMed

Ottoboni, Tom; Lauw, Michael; Keller, Mary Rose; Cravets, Matt; Manhard, Kimberly; Clendeninn, Neil; Quart, Barry

2018-06-06

Evaluate safety of HTX-019, a novel polysorbate 80- and synthetic surfactant-free intravenous formulation of neurokinin 1 receptor antagonist aprepitant for chemotherapy-induced nausea and vomiting. Two open-label, randomized, two-way crossover studies evaluated treatment-emergent adverse events (TEAEs) in 200 healthy subjects. Subjects received HTX-019 130 mg (30-min infusion) and fosaprepitant 150 mg (20- or 30-min infusion), with ≥7-day washout between doses. Less than or equal to 30 min after start of infusion, TEAEs occurred in 5 (3%) HTX-019 and 30 (15%) fosaprepitant recipients. No HTX-019 recipients had infusion-site adverse events, versus 15 (8%) fosaprepitant recipients. Treatment-related dyspnea occurred in one HTX-019 and six fosaprepitant recipients. No severe/serious TEAEs occurred; all TEAEs resolved. HTX-019 may provide a safer aprepitant formulation than fosaprepitant for chemotherapy-induced nausea and vomiting prevention.

Impact of spherical nanoparticles on nematic order parameters

NASA Astrophysics Data System (ADS)

Kyrou, C.; Kralj, S.; Panagopoulou, M.; Raptis, Y.; Nounesis, G.; Lelidis, I.

2018-04-01

We study experimentally the impact of spherical nanoparticles on the orientational order parameters of a host nematic liquid crystal. We use spherical core-shell quantum dots that are surface functionalized to promote homeotropic anchoring on their interface with the liquid crystal host. We show experimentally that the orientational order may be strongly affected by the presence of spherical nanoparticles even at low concentrations. The orientational order of the composite system is probed by means of polarized micro-Raman spectroscopy and by optical birefringence measurements as function of temperature and concentration. Our data show that the orientational order depends on the concentration in a nonlinear way, and the existence of a crossover concentration χc≈0.004 pw . It separates two different regimes exhibiting pure-liquid crystal like (χ <χc ) and distorted-nematic ordering (χ >χc ), respectively. In the latter phase the degree of ordering is lower with respect to the pure-liquid crystal nematic phase.

Do Surrogate Endpoints Better Correlate with Overall Survival in Studies That Did Not Allow for Crossover or Reported Balanced Postprogression Treatments? An Application in Advanced Non-Small Cell Lung Cancer.

PubMed

Hashim, Mahmoud; Pfeiffer, Boris M; Bartsch, Robert; Postma, Maarten; Heeg, Bart

2018-01-01

In previous studies, correlation between overall survival (OS) and surrogate endpoints like objective response rate (ORR) or progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) was poor. This can be biased by crossover and postprogression treatments. To evaluate the relationship between these two surrogate endpoints and OS in advanced NSCLC studies that did not allow for crossover or reported balanced post-progression treatments. A systematic review in patients with advanced NSCLC receiving second- and further-line therapy was performed. The relationship between the absolute difference in ORR or median PFS (mPFS) and the absolute difference in median OS (mOS) was assessed using the correlation coefficient (R) and weighted regression models. The analysis was repeated in predefined data cuts based on crossover and balance of postprogression treatments. When the upper limit of R's 95% confidence interval (CI) was more than 0.7, the surrogate threshold effect (STE) was estimated. In total, 146 randomized clinical trials (43,061 patients) were included. The mean ORR, mPFS, and mOS were 12.2% ± 11.2%, 3.2 ± 1.3 months, and 9.6 ± 4.1 months, respectively. The correlation coefficients of ORR and mPFS were 0.181 (95% CI 0.016-0.337) and 0.254 (95% CI 0.074-0.418), respectively, with mOS. Nevertheless, in trials that did not allow crossover and reported balanced postprogression treatments, the correlation coefficients of ORR and mPFS were 0.528 (95% CI 0.081-0.798) and 0.778 (95% CI 0.475-0.916), respectively, with mOS. On the basis of STE estimation, in trials showing significant treatment effect size of 41.0% or more ORR or 4.15 or more mPFS months, OS benefit can be expected with sufficient certainty. Crossover and postprogression treatments may bias the relationship between surrogate endpoints and OS. Presented STE calculation can be used to interpret treatment effect on either ORR or PFS when used as primary endpoints. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Active cycle of breathing technique for cystic fibrosis.

PubMed

Mckoy, Naomi A; Wilson, Lisa M; Saldanha, Ian J; Odelola, Olaide A; Robinson, Karen A

2016-07-05

People with cystic fibrosis experience chronic airway infections as a result of mucus build up within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (also known as ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review. To compare the clinical effectiveness of the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 25 April 2016. Randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. Two review authors independently screened each article, abstracted data and assessed the risk of bias of each study. Our search identified 62 studies, of which 19 (440 participants) met the inclusion criteria. Five randomised controlled studies (192 participants) were included in the meta-analysis; three were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 22.33 years). In 13 studies, follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis.Included studies compared the active cycle of breathing technique with autogenic drainage, airway oscillating devices, high frequency chest compression devices, conventional chest physiotherapy, and positive expiratory pressure. Preference of technique varied: more participants preferred autogenic drainage over the active cycle of breathing technique; more preferred the active cycle of breathing technique over airway oscillating devices; and more were comfortable with the active cycle of breathing technique versus high frequency chest compression. No significant difference was seen in quality of life, sputum weight, exercise tolerance, lung function, or oxygen saturation between the active cycle of breathing technique and autogenic drainage or between the active cycle of breathing technique and airway oscillating devices. There was no significant difference in lung function and the number of pulmonary exacerbations between the active cycle of breathing technique alone or in conjunction with conventional chest physiotherapy. All other outcomes were either not measured or had insufficient data for analysis. There is insufficient evidence to support or reject the use of the active cycle of breathing technique over any other airway clearance therapy. Five studies, with data from eight different comparators, found that the active cycle of breathing technique was comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of the active cycle of breathing technique on outcomes important for people with cystic fibrosis such as quality of life and preference.

Application of Liquid Chromatography-Tandem Mass Spectrometry To Determine Urinary Concentrations of Five Commonly Used Low-Calorie Sweeteners: A Novel Biomarker Approach for Assessing Recent Intakes?

PubMed

Logue, Caomhan; Dowey, Le Roy C; Strain, J J; Verhagen, Hans; McClean, Stephen; Gallagher, Alison M

2017-06-07

Although the use of low-calorie sweeteners (LCSs) is widespread, methods of assessing consumption within free-living populations have inherent limitations. Five commonly consumed LCSs, namely, acesulfame-K, saccharin, sucralose, cyclamate, and steviol glycosides, are excreted via the urine, and therefore a urinary biomarker approach may provide more objective LCS intake data. A LC-ESI-MS/MS method of simultaneously determining acesulfame-K, saccharin, sucralose, cyclamate, and the excretory metabolite of steviol glycosides, steviol glucuronide, in human urine was developed and validated. Linearity was observed over a concentration range of 10-1000 ng/mL with coefficients of determination ranging from 0.9969 to 0.9997. Accuracy ranged from 92 to 104%, and intrabatch and interday precisions were within acceptable limits with %CV below 8% for all compounds. A double-blind, randomized crossover dose-response study was conducted to assess the usefulness of urinary LCS excretions (from both fasting spot and a full 24-h urine collection) for investigating recent intakes. Both modes of sampling were useful for distinguishing between the three short-term intakes of acesulfame-K, saccharin, cyclamates, and steviol glycosides (p < 0.001), whereas for sucralose, urinary concentrations were useful for distinguishing between low (0.1% ADI) and high doses (10% ADI) only (p < 0.001). In summary, this biomarker approach may be useful for assessing intakes of five commonly consumed LCSs.

Digoxin: use pattern in Estonia and bioavailability of the local market leader.

PubMed

Pähkla, R; Irs, A; Oselin, K; Rootslane, L

1999-10-01

In comparison with neighbouring Scandinavian countries, the use of digoxin in Estonia is high. The present study was carried out to determine the use pattern of digoxin in Estonia and bioavailability of the local market leader preparation in comparison with Lanoxin. Drug use data were evaluated from the annual reports of wholesale companies. For the bioequivalence study, a single-blind cross-over randomised two-way single-dose comparative bioavailability study was performed using 14 healthy volunteers. Digoxin concentrations in serum samples and urine were measured by chemiluminescent competitive immunoassay. The use of digoxin in Estonia has increased by 35% during the period 1994-97. The steady market leader was the local generic drug. No statistically significant differences were found in any pharmacokinetic parameter between the generic preparation and Lanoxin. All parameters showed considerable variability. The total amount of drug excreted was the parameter with lowest inter- individual variation. The present study indicates that the generic digoxin preparation studied is bioequivalent to Lanoxin. The increasing use of digoxin in Estonia is not caused by low bioavailability of the local market leader but by therapeutic traditions.

Crossover of exhaustion between dentists and dental nurses.

PubMed

Hakanen, Jari J; Perhoniemi, Riku; Bakker, Arnold B

2014-04-01

The aim of this study was to investigate the conditions under which job-related exhaustion may transmit (cross over) from dentists to dental nurses and vice versa. We conducted a cross-sectional survey study among 470 Finnish dentist-dental nurse dyads and used moderated structural equation modelling analyses. We found no support for the direct crossover of exhaustion from one work partner to the other. Instead, we found that exhaustion transferred from dentists to dental nurses only when collaboration was frequent and dental nurses perceived the collaboration as friendly or consisting of mutual feedback. In contrast, dentists were not affected by dental nurses' exhaustion. These results indicate that exhaustion can be contagious in work dyads and may be fuelled by positive and frequent interpersonal relationships when the partner who is higher in the hierarchy has high (versus low) levels of exhaustion. Thus, interpersonal and hierarchical relationships among work partners may play an important role in the crossover process. Limitations and implications are mentioned. © 2013 John Wiley & Sons, Ltd.

Patient profiling can identify patients with adult spinal deformity (ASD) at risk for conversion from nonoperative to surgical treatment: initial steps to reduce ineffective ASD management.

PubMed

Passias, Peter G; Jalai, Cyrus M; Line, Breton G; Poorman, Gregory W; Scheer, Justin K; Smith, Justin S; Shaffrey, Christopher I; Burton, Douglas C; Fu, Kai-Ming G; Klineberg, Eric O; Hart, Robert A; Schwab, Frank; Lafage, Virginie; Bess, Shay

2018-02-01

Non-operative management is a common initial treatment for patients with adult spinal deformity (ASD) despite reported superiority of surgery with regard to outcomes. Ineffective medical care is a large source of resource drain on the health system. Characterization of patients with ASD likely to elect for operative treatment from non-operative management may allow for more efficient patient counseling and cost savings. This study aimed to identify deformity and disability characteristics of patients with ASD who ultimately convert to operative treatment compared with those who remain non-operative and those who initially choose surgery. A retrospective review was carried out. A total of 510 patients with ASD (189 non-operative, 321 operative) with minimum 2-year follow-up comprised the patient sample. Oswestry Disability Index (ODI), Short-Form 36 Health Assessment (SF-36), Scoliosis Research Society questionnaire (SRS-22r), and spinopelvic radiographic alignment were the outcome measures. Demographic, radiographic, and patient-reported outcome measures (PROMs) from a cohort of patients with ASD prospectively enrolled into a multicenter database were evaluated. Patients were divided into three treatment cohorts: Non-operative (NON=initial non-operative treatment and remained non-operative), Operative (OP=initial operative treatment), and Crossover (CROSS=initial non-operative treatment with subsequent conversion to operative treatment). NON and OP groups were propensity score-matched (PSM) to CROSS for baseline demographics (age, body mass index, Charlson Comorbidity Index). Time to crossover was divided into early (<1 year) and late (>1 year). Outcome measures were compared across and within treatment groups at four time points (baseline, 6 weeks, 1 year, and 2 years). Following PSM, 118 patients were included (NON=39, OP=38, CROSS=41). Crossover rate was 21.7% (41/189). Mean time to crossover was 394 days. All groups had similar baseline sagittal alignment, but CROSS had larger pelvic incidence and lumbar lordosis (PI-LL) mismatch than NON (11.9° vs. 3.1°, p=.032). CROSS and OP had similar baseline PROM scores; however, CROSS had worse baseline ODI, PCS, SRS-22r (p<.05). At time of crossover, CROSS had worse ODI (35.7 vs. 27.8) and SRS Satisfaction (2.6 vs. 3.3) compared with NON (p<.05). Alignment remained similar for CROSS from baseline to conversion; however, PROMs (ODI, PCS, SRS Activity/Pain/Total) worsened (p<.05). Early and late crossover evaluation demonstrated CROSS-early (n=25) had worsening ODI, SRS Activity/Pain at time of crossover (p<.05). From time of crossover to 2-year follow-up, CROSS-early had less SRS Appearance/Mental improvement compared with OP. Both CROSS-early/late had worse baseline, but greater improvements, in ODI, PCS, SRS Pain/Total compared with NON (p<.05). Baseline alignment and disability parameters increased crossover odds-Non with Schwab T/L/D curves and ODI≥40 (odds ratio [OR]: 3.05, p=.031), and Non with high PI-LL modifier grades ("+"/'++') and ODI≥40 (OR: 5.57, p=.007) were at increased crossover risk. High baseline and increasing disability over time drives conversion from non-operative to operative ASD care. CROSS patients had similar spinal deformity but worse PROMs than NON. CROSS achieved similar 2-year outcome scores as OP. Profiling at first visit for patients at risk of crossover may optimize physician counseling and cost savings. Copyright © 2017. Published by Elsevier Inc.

Effects of the interaction range on structural phases of flexible polymers.

PubMed

Gross, J; Neuhaus, T; Vogel, T; Bachmann, M

2013-02-21

We systematically investigate how the range of interaction between non-bonded monomers influences the formation of structural phases of elastic, flexible polymers. Massively parallel replica-exchange simulations of a generic, coarse-grained model, performed partly on graphics processing units and in multiple-gaussian modified ensembles, pave the way for the construction of the structural phase diagram, parametrized by interaction range and temperature. Conformational transitions between gas-like, liquid, and diverse solid (pseudo) phases are identified by microcanonical statistical inflection-point analysis. We find evidence for finite-size effects that cause the crossover of "collapse" and "freezing" transitions for very short interaction ranges.

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

PubMed

Bro, S; Rasmussen, R A; Handberg, J; Olgaard, K; Feldt-Rasmussen, B

1998-02-01

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 outcome measurements were plasma ionized calcium levels, plasma phosphate levels, plasma intact parathyroid hormone (PTH) levels, requirements for supplemental aluminum-aminoacetate therapy, patient tolerance, and cost of therapy. Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months. All had previously tolerated therapy with calcium carbonate. Of the 19 patients included, 10 completed both treatment arms. After 12 weeks of therapy, the mean (+/-SEM) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm (4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL; P = 0.004), whereas the mean plasma phosphate (4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL) and PTH levels (266+/-125 pg/mL v 301+/-148 pg/mL) did not differ significantly between the two treatment arms. Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment, while two patients needed this supplement when treated with calcium carbonate. Five of 17 (29%) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance (anorexia, vomiting, diarrhea, general uneasiness), whereas the remaining 12 patients did not experience any side effects at all. The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms; four of them had received treatment with cimetidine or omeprazol before inclusion into the study. Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium carbonate (US$6.00/d v US$0.65/d). Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia. However, care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort. Due to the high cost of the therapy, calcium ketoglutarate should be used only for selected patients.

Magnetic-field-temperature phase diagram of alternating ferrimagnetic chains: Spin-wave theory from a fully polarized vacuum

NASA Astrophysics Data System (ADS)

da Silva, W. M.; Montenegro-Filho, R. R.

2017-12-01

Quantum critical (QC) phenomena can be accessed by studying quantum magnets under an applied magnetic field (B ). The QC points are located at the end points of magnetization plateaus and separate gapped and gapless phases. In one dimension, the low-energy excitations of the gapless phase form a Luttinger liquid (LL), and crossover lines bound insulating (plateau) and LL regimes, as well as the QC regime. Alternating ferrimagnetic chains have a spontaneous magnetization at T =0 and gapped excitations at zero field. Besides the plateau at the fully polarized (FP) magnetization, due to the gap there is another magnetization plateau at the ferrimagnetic (FRI) magnetization. We develop spin-wave theories to study the thermal properties of these chains under an applied magnetic field: one from the FRI classical state and another from the FP state, comparing their results with quantum Monte Carlo data. We deepen the theory from the FP state, obtaining the crossover lines in the T vs B low-T phase diagram. In particular, from local extreme points in the susceptibility and magnetization curves, we identify the crossover between an LL regime formed by excitations from the FRI state to another built from excitations of the FP state. These two LL regimes are bounded by an asymmetric domelike crossover line, as observed in the phase diagram of other quantum magnets under an applied magnetic field.

Study of. lambda. parameters and crossover phenomena in SU(N) x SU(N) sigma models in two dimensions

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

Shigemitsu, J; Kogut, J B

1981-01-01

The spin system analogues of recent studies of the string tension and ..lambda.. parameters of SU(N) gauge theories in 4 dimensions are carried out for the SU(N) x SU(N) and O(N) models in 2 dimensions. The relations between the ..lambda.. parameters of both the Euclidean and Hamiltonian formulation of the lattice models and the ..lambda.. parameter of the continuum models are obtained. The one loop finite renormalization of the speed of light in the lattice Hamiltonian formulations of the O(N) and SU(N) x SU(N) models is calculated. Strong coupling calculations of the mass gaps of these spin models are donemore » for all N and the constants of proportionality between the gap and the ..lambda.. parameter of the continuum models are obtained. These results are contrasted with similar calculations for the SU(N) gauge models in 3+1 dimensions. Identifying suitable coupling constants for discussing the N ..-->.. infinity limits, the numerical results suggest that the crossover from weak to strong coupling in the lattice O(N) models becomes less abrupt as N increases while the crossover for the SU(N) x SU(N) models becomes more abrupt. The crossover in SU(N) gauge theories also becomes more abrupt with increasing N, however, at an even greater rate than in the SU(N) x SU(N) spin models.« less

Assessment of NHTSA’s Report “Relationships Between Fatality Risk, Mass, and Footprint in Model Year 2000-2007 Passenger Cars and LTVs”

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

Wenzel, Tom

2012-08-01

NHTSA recently completed a logistic regression analysis updating its 2003 and 2010 studies of the relationship between vehicle mass and US fatality risk per vehicle mile traveled (VMT). The new study updates the previous analyses in several ways: updated FARS data from 2002 to 2008 for MY00 to MY07 vehicles are used; induced exposure data from police reported crashes in several additional states are added; a new vehicle category for car-based crossover utility vehicles (CUVs) and minivans is created; crashes with other light-duty vehicles are divided into two groups based on the crash partner vehicle’s weight, and a category formore » all other fatal crashes is added; and new control variables for new safety technologies and designs, such as electronic stability controls (ESC), side airbags, and methods to meet voluntary agreement to improve light truck compatibility with cars, are included.« less

Integrating In Vitro, Modeling, and In Vivo Approaches to Investigate Warfarin Bioequivalence

PubMed Central

Wen, H; Fan, J; Vince, B; Li, T; Gao, W; Kinjo, M; Brown, J; Sun, W; Jiang, W; Lionberger, R

2017-01-01

We demonstrate the use of modeling and simulation to investigate bioequivalence (BE) concerns raised about generic warfarin products. To test the hypothesis that the loss of isopropyl alcohol and slow dissolution in acidic pH has significant impact on the pharmacokinetics of warfarin sodium tablets, we conducted physiologically based pharmacokinetic absorption modeling and simulation using formulation factors or in vitro dissolution profiles as input parameters. Sensitivity analyses indicated that warfarin pharmacokinetics was not sensitive to solubility, particle size, density, or dissolution rate in pH 4.5, but was affected by dissolution rate in pH 6.8 and potency. Virtual BE studies suggested that stressed warfarin sodium tablets with slow dissolution rate in pH 4.5 but having similar dissolution rate in pH 6.8 would be bioequivalent to the unstressed warfarin sodium tablets. A four‐way, crossover, single‐dose BE study in healthy subjects was conducted to test the same hypothesis and confirmed the simulation conclusion. PMID:28379643

Assessment of NHTSA’s Report “Relationships Between Fatality Risk, Mass, and Footprint in Model Year 2000-2007 Passenger Cars and LTVs”

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

Wenzel, Tom

2011-09-01

NHTSA recently completed a logistic regression analysis updating its 2003 and 2010 studies of the relationship between vehicle mass and US fatality risk per vehicle mile traveled (VMT). The new study updates the previous analyses in several ways: updated FARS data from 2002 to 2008 for MY00 to MY07 vehicles are used; induced exposure data from police reported crashes in several additional states are added; a new vehicle category for car-based crossover utility vehicles (CUVs) and minivans is created; crashes with other light-duty vehicles are divided into two groups based on the crash partner vehicle’s weight, and a category formore » all other fatal crashes is added; and new control variables for new safety technologies and designs, such as electronic stability controls (ESC), side airbags, and methods to meet voluntary agreement to improve light truck compatibility with cars, are included.« less

An Analysis of the Relationship between Casualty Risk Per Crash and Vehicle Mass and Footprint for Model Year 2000-2007 Light-Duty Vehicles

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

Wenzel, Tom

2012-08-01

NHTSA recently completed a logistic regression analysis (Kahane 2012) updating its 2003 and 2010 studies of the relationship between vehicle mass and US fatality risk per vehicle mile traveled (VMT). The new study updates the previous analyses in several ways: updated FARS data for 2002 to 2008 involving MY00 to MY07 vehicles are used; induced exposure data from police reported crashes in several additional states are added; a new vehicle category for car-based crossover utility vehicles (CUVs) and minivans is created; crashes with other light-duty vehicles are divided into two groups based on the crash partner vehicle’s weight, and amore » category for all other fatal crashes is added; and new control variables for new safety technologies and designs, such as electronic stability controls (ESC), side airbags, and methods to meet voluntary agreement to improve light truck compatibility with cars, are included.« less

An interdisciplinary approach to mapping through scientific cartography, design and artistic expression

NASA Astrophysics Data System (ADS)

Gardener, Joanna; Cartwright, William; Duxbury, Lesley

2018-05-01

This paper reports on the initial findings of an interdisciplinary study exploring perceptions of space and place through alternate ways of mapping. The research project aims to bring depth and meaning to places by utilising a combination of diverse influences and responses, including emotional, sensory, memory and imaginary. It investigates mapping from a designer's perspective, with further narration from both the cartographic science and fine art perspectives. It examines the role of design and artistic expression in the cartographic process, and its capacity to effect and transform the appearance, reading and meaning of the final cartographic outcome (Robinson 2010). The crossover between the cartographic sciences and the work of artists who explore space and place enables an interrogation of where these fields collide or alternatively merge, in order to challenge the definition of a map. By exploring cartography through the overlapping of the distinct fields of science and art, this study challenges and questions the tipping point of when a map ceases to be a map and becomes art.

Interference-mediated synaptonemal complex formation with embedded crossover designation

PubMed Central

Zhang, Liangran; Espagne, Eric; de Muyt, Arnaud; Zickler, Denise; Kleckner, Nancy E.

2014-01-01

Biological systems exhibit complex patterns at length scales ranging from the molecular to the organismic. Along chromosomes, events often occur stochastically at different positions in different nuclei but nonetheless tend to be relatively evenly spaced. Examples include replication origin firings, formation of chromatin loops along chromosome axes and, during meiosis, localization of crossover recombination sites (“crossover interference”). We present evidence in the fungus Sordaria macrospora that crossover interference is part of a broader pattern that includes synaptonemal complex (SC) nucleation. This pattern comprises relatively evenly spaced SC nucleation sites, among which a subset are crossover sites that show a classical interference distribution. This pattern ensures that SC forms regularly along the entire length of the chromosome as required for the maintenance of homolog pairing while concomitantly having crossover interactions locally embedded within the SC structure as required for both DNA recombination and structural events of chiasma formation. This pattern can be explained by a threshold-based designation and spreading interference process. This model can be generalized to give diverse types of related and/or partially overlapping patterns, in two or more dimensions, for any type of object. PMID:25380597

Statistical power analysis of cardiovascular safety pharmacology studies in conscious rats.

PubMed

Bhatt, Siddhartha; Li, Dingzhou; Flynn, Declan; Wisialowski, Todd; Hemkens, Michelle; Steidl-Nichols, Jill

2016-01-01

Cardiovascular (CV) toxicity and related attrition are a major challenge for novel therapeutic entities and identifying CV liability early is critical for effective derisking. CV safety pharmacology studies in rats are a valuable tool for early investigation of CV risk. Thorough understanding of data analysis techniques and statistical power of these studies is currently lacking and is imperative for enabling sound decision-making. Data from 24 crossover and 12 parallel design CV telemetry rat studies were used for statistical power calculations. Average values of telemetry parameters (heart rate, blood pressure, body temperature, and activity) were logged every 60s (from 1h predose to 24h post-dose) and reduced to 15min mean values. These data were subsequently binned into super intervals for statistical analysis. A repeated measure analysis of variance was used for statistical analysis of crossover studies and a repeated measure analysis of covariance was used for parallel studies. Statistical power analysis was performed to generate power curves and establish relationships between detectable CV (blood pressure and heart rate) changes and statistical power. Additionally, data from a crossover CV study with phentolamine at 4, 20 and 100mg/kg are reported as a representative example of data analysis methods. Phentolamine produced a CV profile characteristic of alpha adrenergic receptor antagonism, evidenced by a dose-dependent decrease in blood pressure and reflex tachycardia. Detectable blood pressure changes at 80% statistical power for crossover studies (n=8) were 4-5mmHg. For parallel studies (n=8), detectable changes at 80% power were 6-7mmHg. Detectable heart rate changes for both study designs were 20-22bpm. Based on our results, the conscious rat CV model is a sensitive tool to detect and mitigate CV risk in early safety studies. Furthermore, these results will enable informed selection of appropriate models and study design for early stage CV studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Compressed exponential relaxation in liquid silicon: Universal feature of the crossover from ballistic to diffusive behavior in single-particle dynamics

NASA Astrophysics Data System (ADS)

Morishita, Tetsuya

2012-07-01

We report a first-principles molecular-dynamics study of the relaxation dynamics in liquid silicon (l-Si) over a wide temperature range (1000-2200 K). We find that the intermediate scattering function for l-Si exhibits a compressed exponential decay above 1200 K including the supercooled regime, which is in stark contrast to that for normal "dense" liquids which typically show stretched exponential decay in the supercooled regime. The coexistence of particles having ballistic-like motion and those having diffusive-like motion is demonstrated, which accounts for the compressed exponential decay in l-Si. An attempt to elucidate the crossover from the ballistic to the diffusive regime in the "time-dependent" diffusion coefficient is made and the temperature-independent universal feature of the crossover is disclosed.

Inequity in work and intimate relationships: a Spillover-Crossover model.

PubMed

Bakker, Arnold B; Petrou, Paraskevas; Tsaousis, Ioannis

2012-01-01

This study among 267 Greek teachers and their partners tested and expanded the recently proposed Spillover-Crossover model (SCM) of well-being. Accordingly, experiences built up at work spill over to the home domain, and then influence the partner. The authors integrated equity theory in the model by formulating hypotheses about exchange in interpersonal relationships. Structural equation modeling analyses supported the spillover hypothesis that teachers who lose their work engagement as a result of an inequitable relationship with their students invest less in the relationship with their partner. In addition, the results supported the crossover hypothesis that teachers' relationship investments, in turn, show a negative relationship with inequity in the intimate relationship as perceived by the partner; and inequity in the intimate relationship contributed to partner depression. The findings are discussed in light of the SCM of well-being.

Homing by path integration when a locomotion trajectory crosses itself.

PubMed

Yamamoto, Naohide; Meléndez, Jayleen A; Menzies, Derek T

2014-01-01

Path integration is a process with which navigators derive their current position and orientation by integrating self-motion signals along a locomotion trajectory. It has been suggested that path integration becomes disproportionately erroneous when the trajectory crosses itself. However, there is a possibility that this previous finding was confounded by effects of the length of a traveled path and the amount of turns experienced along the path, two factors that are known to affect path integration performance. The present study was designed to investigate whether the crossover of a locomotion trajectory truly increases errors of path integration. In an experiment, blindfolded human navigators were guided along four paths that varied in their lengths and turns, and attempted to walk directly back to the beginning of the paths. Only one of the four paths contained a crossover. Results showed that errors yielded from the path containing the crossover were not always larger than those observed in other paths, and the errors were attributed solely to the effects of longer path lengths or greater degrees of turns. These results demonstrated that path crossover does not always cause significant disruption in path integration processes. Implications of the present findings for models of path integration are discussed.

The assessment of health policy changes using the time-reversed crossover design.

PubMed Central

Sollecito, W A; Gillings, D B

1986-01-01

The time-reversed crossover design is a quasi-experimental design which can be applied to evaluate the impact of a change in health policy on a large population. This design makes use of separate sampling and analysis strategies to improve the validity of conclusions drawn from such an evaluation. The properties of the time-reversed crossover design are presented including the use of stratification on outcome in the sampling stage, which is intended to improve external validity. It is demonstrated that, although this feature of the design introduces internal validity threats due to regression toward the mean in extreme-outcome strata, these effects can be measured and eliminated from the test of significance of treatment effects. Methods for within- and across-stratum estimation and hypothesis-testing are presented which are similar to those which have been developed for the traditional two-period crossover design widely used in clinical trials. The procedures are illustrated using data derived from a study conducted by the United Mine Workers of America Health and Retirement Funds to measure the impact of cost-sharing on health care utilization among members of its health plan. PMID:3081465

Test equality in binary data for a 4 × 4 crossover trial under a Latin-square design.

PubMed

Lui, Kung-Jong; Chang, Kuang-Chao

2016-10-15

When there are four or more treatments under comparison, the use of a crossover design with a complete set of treatment-receipt sequences in binary data is of limited use because of too many treatment-receipt sequences. Thus, we may consider use of a 4 × 4 Latin square to reduce the number of treatment-receipt sequences when comparing three experimental treatments with a control treatment. Under a distribution-free random effects logistic regression model, we develop simple procedures for testing non-equality between any of the three experimental treatments and the control treatment in a crossover trial with dichotomous responses. We further derive interval estimators in closed forms for the relative effect between treatments. To evaluate the performance of these test procedures and interval estimators, we employ Monte Carlo simulation. We use the data taken from a crossover trial using a 4 × 4 Latin-square design for studying four-treatments to illustrate the use of test procedures and interval estimators developed here. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Pressure and Temperature Sensors Using Two Spin Crossover Materials.

PubMed

Jureschi, Catalin-Maricel; Linares, Jorge; Boulmaali, Ayoub; Dahoo, Pierre Richard; Rotaru, Aurelian; Garcia, Yann

2016-02-02

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.

Reports show fewer pallets entering landfills

Treesearch

Robert J. Bush; Philip A. Araman

2010-01-01

Information from a series of Virginia Tech studies reveals current trends in core utilization by the pallet industry. The most recent report released this year studied trends from 2006. Virginia Tech researchers compared these results to five previous studies going all the way back to 1992.

Impact of antimicrobial wipes compared with hypochlorite solution on environmental surface contamination in a health care setting: A double-crossover study.

PubMed

Siani, Harsha; Wesgate, Rebecca; Maillard, Jean-Yves

2018-05-11

Antimicrobial wipes are increasingly used in health care settings. This study evaluates, in a clinical setting, the efficacy of sporicidal wipes versus a cloth soaked in a 1,000 ppm chlorine solution. A double-crossover study was performed on 2 different surgical and cardiovascular wards in a 1,000-bed teaching hospital over 29 weeks. The intervention period that consisted of surface decontamination with the preimpregnated wipe or cloth soaked in chlorine followed a 5-week baseline assessment of microbial bioburden on surfaces. Environmental samples from 11 surfaces were analyzed weekly for their microbial content. A total of 1,566 environmental samples and 1,591 ATP swabs were analyzed during the trial. Overall, there were significant differences in the recovery of total aerobic bacteria (P < .001), total anaerobic bacteria (P < .001), and ATP measurement (P < .001) between wards and between the different parts of the crossover study. Generally, the use of wipes produced the largest reduction in the total aerobic and anaerobic counts when compared with the baseline data or the use of 1,000 ppm chlorine. Collectively, the introduction of training plus daily wipe disinfection significantly reduced multidrug-resistant organisms recovered from surfaces. Reversion to using 1,000 ppm chlorine resulted in the number of sites positive for multidrug-resistant organisms rising again. This double-crossover study is the first controlled field trial comparison of using preimpregnated wipes versus cotton cloth dipped into a bucket of hypochlorite to decrease surface microbial bioburden. The results demonstrate the superiority of the preimpregnated wipes in significantly decreasing microbial bioburden from high-touch surfaces. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Melatonin improves sleep in children with epilepsy: randomized, double-blind cross-over study

PubMed Central

Jain, Sejal V; Horn, Paul S; Simakajornboon, Narong; Beebe, Dean W; Holland, Katherine; Byars, Anna W; Glauser, Tracy A

2015-01-01

Objective Insomnia, especially maintenance insomnia is widely prevalent in epilepsy. Although melatonin is commonly used, limited data address its efficacy. We performed a randomized, double-blind, placebo-controlled, cross-over study to identify the effects of melatonin on sleep and seizure control in children with epilepsy. Methods Eleven pre-pubertal, developmentally normal children aged 6–11 years with epilepsy were randomized by software algorithm to receive placebo or 9 mg sustained release melatonin for 4 weeks, followed by a 1-week washout and 4-week crossover condition. The pharmacy performed blinding; patients, parents and study staff other than a statistician were blinded. Primary outcomes were sleep onset latency and wakefulness after sleep onset (WASO) measured on polysomnography. Secondary outcomes included seizure frequency, epileptiform spike density per hour of sleep on EEG and reaction time measures on psychomotor vigilance task. Statistical tests appropriate for cross-over designs were used for analysis. Results Data were analyzed from ten subjects who completed the study. Melatonin decreased sleep latency (Mean difference (MD): 11.4 min, p= 0.02) and WASO (MD 22 min, p=0.04) as compared to placebo. No worsening of spike density or seizure frequency was seen. Additionally, Slow-wave sleep duration and REM latency were increased with melatonin and REM sleep duration was decreased. These changes were statistically significant. Worsening of headache was noted in one subject with migraine on melatonin. Conclusion Sustained-release melatonin resulted in statistically significant decreases in sleep latency and WASO. No clear effects on seizures were observed but the study was too small to allow any conclusions to be drawn in this regard. PMID:25862116

RELIABILITY AND VALIDITY OF FUNCTIONAL PERFORMANCE TESTS IN DANCERS WITH HIP DYSFUNCTION

PubMed Central

Carcia, Christopher R.; Clemente, F. Richard; Phelps, Amy L.; Martin, RobRoy L.

2013-01-01

Study Design: Quasi-experimental, repeated measures. Purpose/Background: Functional performance tests that identify hip joint impairments and assess the effect of intervention have not been adequately described for dancers. The purpose of this study was to examine the reliability and validity of hop and balance tests among a group of dancers with musculoskeletal pain in the hip region. Methods: Nineteen female dancers (age: 18.90±1.11 years; height: 164.85±6.95 cm; weight: 60.37±8.29 kg) with unilateral hip pain were assessed utilizing the cross-over reach, medial triple hop, lateral triple hop, and cross-over hop tests on two occasions, 2 days apart. Test-retest reliability and comparisons between the involved and uninvolved side for each respective test were determined. Results: Intra-class correlation coefficients for the functional performance tests ranged from 0.89-0.96. The cross-over reach test had a SEM of 2.79 cm and a MDC of 7.73 cm. The medial and lateral triple hop tests had SEM values of 7.51 cm and 8.17 cm, and MDC values of 20.81 cm and 22.62 cm, respectively. The SEM was 0.15 seconds and the MDC was 0.42 seconds for the cross-over hop test. Performance on the medial triple hop test was significantly less on the involved side (370.21±38.26 cm) compared to the uninvolved side (388.05±41.49 cm); t(18) = −4.33, p<0.01. The side-to-side comparisons of the cross-over reach test (involved mean=61.68±10.9 cm; uninvolved mean=61.69±8.63 cm); t(18) = −0.004, p=0.99, lateral triple hop test (involved mean=306.92±35.79 cm; uninvolved mean=310.68±24.49 cm); t(18) = −0.55, p=0.59, and cross-over hop test (involved mean=2.49±0.34 seconds; uninvolved mean= 2.61±0.42 seconds; t(18) = −1.84, p=0.08) were not statistically different between sides. Conclusion: The functional performance tests used in this study can be reliably performed on dancers with unilateral hip pain. The medial triple hop test was the only functional performance test with evidence of validity in side-to-side comparisons. These results suggest that the medial triple hop test may be a reliable and valid functional performance test to assess impairments related to hip pain among dancers. Level of Evidence: 3b. Non-consecutive cohort study PMID:24175123

Five Ways to Try if our Believe about the Truth is Right, That you can Do using Stuff you have at Home, done in five minutes.

NASA Astrophysics Data System (ADS)

Hut, R.

2015-12-01

The best way to know if what you believe about the world is true, is by trying stuff out. I will try five things, using stuff you have at home, all in a total of five minutes. Do you want to know how big grey animals clean their teeth? Come to this talk! Fire needs air, right? Do you want to know how to put out a fire using a part of the air? Come to this talk! Do you like this: https://youtu.be/Hek0gUiWESU moving picture but think that I use hard to understand words? Than come and watch me try those five things in five minutes!

Neurobehavioral toxicity of cadmium sulfate to the planarian Dugesia dorotocephala

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

Grebe, E.; Schaeffer, D.J.

1991-05-01

The authors are developing bioassays which use planarians (free-living platyhelminthes) for the rapid determination of various types of toxicity, including acute mortality, tumorigenicity, and short-term neurobehavioral responses. Their motivation for using these animals is due to their importance as components of the aquatic ecology of unpolluted streams their sensitivity to low concentrations of environmental toxicants and the presence of a sensitive neurological system with a true brain which allows for complex social behavior. A previous paper described the results of a neurobehavioral bioassay using phenol in a crossover study. This paper reports a similar crossover study using cadmium sulfate.

Pharmacokinetics of three formulations of ondansetron hydrochloride in healthy volunteers: 24-mg oral tablet, rectal suppository, and i.v. infusion.

PubMed

VanDenBerg, C M; Kazmi, Y; Stewart, J; Weidler, D J; Tenjarla, S N; Ward, E S; Jann, M W

2000-06-01

The absolute bioavailability and pharmacokinetics of three formulations of ondansetron hydrochloride 24 mg--an oral tablet, an intravenous solution, and an extemporaneous rectal suppository--were studied. Twelve healthy, nonsmoking volunteers (six men and six women) were given ondansetron in a study with a three-way cross-over design. All subjects received each dosage form on the same day in the following order: oral tablet, rectal suppository, and intravenous infusion. Administrations were separated by one week. Blood sampling times varied, depending on the administration route. Mean absolute bioavailability for the oral tablet and the rectal suppository differed significantly. Absorption of ondansetron was prolonged when it was administered as the rectal suppository. Absolute bioavailability for the 24-mg tablet was similar to that for other tablet strengths in previous studies. All subjects completed the study without significant adverse effects. Absorption of ondansetron from the rectal suppository was prolonged compared with the oral tablet and the i.v. infusion. Bioavailability for the 24-mg suppository formulation was considerably lower than for the 24-mg tablet.

Association of daily asthma emergency department visits and hospital admissions with ambient air pollutants among the pediatric Medicaid population in Detroit: time-series and time-stratified case-crossover analyses with threshold effects.

PubMed

Li, Shi; Batterman, Stuart; Wasilevich, Elizabeth; Wahl, Robert; Wirth, Julie; Su, Feng-Chiao; Mukherjee, Bhramar

2011-11-01

Asthma morbidity has been associated with ambient air pollutants in time-series and case-crossover studies. In such study designs, threshold effects of air pollutants on asthma outcomes have been relatively unexplored, which are of potential interest for exploring concentration-response relationships. This study analyzes daily data on the asthma morbidity experienced by the pediatric Medicaid population (ages 2-18 years) of Detroit, Michigan and concentrations of pollutants fine particles (PM2.5), CO, NO2 and SO2 for the 2004-2006 period, using both time-series and case-crossover designs. We use a simple, testable and readily implementable profile likelihood-based approach to estimate threshold parameters in both designs. Evidence of significant increases in daily acute asthma events was found for SO2 and PM2.5, and a significant threshold effect was estimated for PM2.5 at 13 and 11 μg m(-3) using generalized additive models and conditional logistic regression models, respectively. Stronger effect sizes above the threshold were typically noted compared to standard linear relationship, e.g., in the time series analysis, an interquartile range increase (9.2 μg m(-3)) in PM2.5 (5-day-moving average) had a risk ratio of 1.030 (95% CI: 1.001, 1.061) in the generalized additive models, and 1.066 (95% CI: 1.031, 1.102) in the threshold generalized additive models. The corresponding estimates for the case-crossover design were 1.039 (95% CI: 1.013, 1.066) in the conditional logistic regression, and 1.054 (95% CI: 1.023, 1.086) in the threshold conditional logistic regression. This study indicates that the associations of SO2 and PM2.5 concentrations with asthma emergency department visits and hospitalizations, as well as the estimated PM2.5 threshold were fairly consistent across time-series and case-crossover analyses, and suggests that effect estimates based on linear models (without thresholds) may underestimate the true risk. Copyright © 2011 Elsevier Inc. All rights reserved.

Assessment of the effects of atmospheric oil pollution in post war Kuwait.

PubMed

Coombe, M D; Drysdale, S F

1993-10-01

A prospective study was undertaken to assess and monitor the effects of oil pollution in soldiers exposed in Kuwait in 1991 after Op Granby. One hundred and twenty five soldiers were monitored over a five month period by measurement of Forced Expiratory Volume (in one second) (FEV1) and Forced Vital Capacity (FVC). Although no demonstrable changes were observed, this study has gone some way to filling the gap in research in this environmentally sensitive field.