Self-Management Interventions on Students with Autism: A Meta-Analysis of Single-Subject Research

ERIC Educational Resources Information Center

Carr, Monica E.; Moore, Dennis W.; Anderson, Angelika

2014-01-01

Self-management interventions aimed at skill acquisition and/or improving behavior of students diagnosed with autism spectrum disorders were examined. Twenty-three single-subject research design studies met inclusion criteria. Quality assessment of these studies was conducted using the What Works Clearinghouse guidelines, and treatment effect…

The influence of the design matrix on treatment effect estimates in the quantitative analyses of single-subject experimental design research.

PubMed

Moeyaert, Mariola; Ugille, Maaike; Ferron, John M; Beretvas, S Natasha; Van den Noortgate, Wim

2014-09-01

The quantitative methods for analyzing single-subject experimental data have expanded during the last decade, including the use of regression models to statistically analyze the data, but still a lot of questions remain. One question is how to specify predictors in a regression model to account for the specifics of the design and estimate the effect size of interest. These quantitative effect sizes are used in retrospective analyses and allow synthesis of single-subject experimental study results which is informative for evidence-based decision making, research and theory building, and policy discussions. We discuss different design matrices that can be used for the most common single-subject experimental designs (SSEDs), namely, the multiple-baseline designs, reversal designs, and alternating treatment designs, and provide empirical illustrations. The purpose of this article is to guide single-subject experimental data analysts interested in analyzing and meta-analyzing SSED data. © The Author(s) 2014.

Unraveling of Enigmatic Hearing-Impaired GJB2 Single Heterozygotes by Massive Parallel Sequencing: DFNB1 or Not?

PubMed Central

Kim, So Young; Kim, Ah Reum; Kim, Nayoung K. D.; Lee, Chung; Kim, Min Young; Jeon, Eun-Hee; Park, Woong-Yang; Choi, Byung Yoon

2016-01-01

Abstract The molecular etiology of nonsyndromic sensorineural hearing loss (SNHL) in subjects with only one detectable autosomal recessive GJB2 mutation is unclear. Here, we report GJB2 single heterozygotes with various final genetic diagnoses and suggest appropriate diagnostic strategies. A total of 160 subjects with SNHL without phenotypic markers were screened for GJB2 mutations. Single-nucleotide variants or structural variations within the DFNB1 locus or in other deafness genes were examined by Sanger sequencing, breakpoint PCR, and targeted exome sequencing (TES) of 129 deafness genes. We identified 27 subjects with two mutations and 10 subjects with only one detectable mutation in GJB2. The detection rate of the single GJB2 mutation among the 160 SNHL subjects in the present study (6.25%) was higher than 2.58% in normal hearing controls in Korean. The DFNB1 was clearly excluded as a molecular etiology in four (40%) subjects: other recessive deafness genes (N = 3) accounted for SNHL and the causative gene for the other non-DFNB1 subject (N = 1) was not identified. The etiology of additional two subjects was potentially explained by digenic etiology (N = 2) of GJB2 with MITF and GJB3, respectively. The contribution of the single GJB2 mutation in the four remaining subjects is unclear. Comprehensive diagnostic testing including TES is prerequisite for understanding GJB2 single heterozygotes. PMID:27057829

A Meta-Analysis of Single-Subject Research on Behavioral Momentum to Enhance Success in Students with Autism

ERIC Educational Resources Information Center

Cowan, Richard J.; Abel, Leah; Candel, Lindsay

2017-01-01

We conducted a meta-analysis of single-subject research studies investigating the effectiveness of antecedent strategies grounded in behavioral momentum for improving compliance and on-task performance for students with autism. First, we assessed the research rigor of those studies meeting our inclusionary criteria. Next, in order to apply a…

Bias Corrections for Standardized Effect Size Estimates Used with Single-Subject Experimental Designs

ERIC Educational Resources Information Center

Ugille, Maaike; Moeyaert, Mariola; Beretvas, S. Natasha; Ferron, John M.; Van den Noortgate, Wim

2014-01-01

A multilevel meta-analysis can combine the results of several single-subject experimental design studies. However, the estimated effects are biased if the effect sizes are standardized and the number of measurement occasions is small. In this study, the authors investigated 4 approaches to correct for this bias. First, the standardized effect…

Comparison of Nonoverlap Methods for Identifying Treatment Effect in Single-Subject Experimental Research

ERIC Educational Resources Information Center

Rakap, Salih; Snyder, Patricia; Pasia, Cathleen

2014-01-01

Debate is occurring about which result interpretation aides focused on examining the experimental effect should be used in single-subject experimental research. In this study, we examined seven nonoverlap methods and compared results using each method to judgments of two visual analysts. The data sources for the present study were 36 studies…

Evidence-Based Communication Practices for Children with Visual Impairments and Additional Disabilities: An Examination of Single-Subject Design Studies

ERIC Educational Resources Information Center

Parker, Amy T.; Grimmett, Eric S.; Summers, Sharon

2008-01-01

This review examines practices for building effective communication strategies for children with visual impairments, including those with additional disabilities, that have been tested by single-subject design methodology. The authors found 30 studies that met the search criteria and grouped intervention strategies to align any evidence of the…

Picture Exchange Communication System with Individuals with Developmental Disabilities: A Meta-Analysis of Single Subject Studies

ERIC Educational Resources Information Center

Hart, Stephanie L.; Banda, Devender R.

2010-01-01

Picture Exchange Communication System (PECS) is a picture-based communication strategy used to teach communication skills to persons with developmental disabilities including autism. This article systematically reviews 13 published single-subject studies to examine the effectiveness of PECS, the effects of PECS on speech and problem behaviors,…

Single Subject Prediction of Brain Disorders in Neuroimaging: Promises and Pitfalls

PubMed Central

Arbabshirani, Mohammad R.; Plis, Sergey; Sui, Jing; Calhoun, Vince D.

2016-01-01

Neuroimaging-based single subject prediction of brain disorders has gained increasing attention in recent years. Using a variety of neuroimaging modalities such as structural, functional and diffusion MRI, along with machine learning techniques, hundreds of studies have been carried out for accurate classification of patients with heterogeneous mental and neurodegenerative disorders such as schizophrenia and Alzheimer's disease. More than 500 studies have been published during the past quarter century on single subject prediction focused on a multiple brain disorders. In the first part of this study, we provide a survey of more than 200 reports in this field with a focus on schizophrenia, mild cognitive impairment (MCI), Alzheimer's disease (AD), depressive disorders, autism spectrum disease (ASD) and attention-deficit hyperactivity disorder (ADHD). Detailed information about those studies such as sample size, type and number of extracted features and reported accuracy are summarized and discussed. To our knowledge, this is by far the most comprehensive review of neuroimaging-based single subject prediction of brain disorders. In the second part, we present our opinion on major pitfalls of those studies from a machine learning point of view. Common biases are discussed and suggestions are provided. Moreover, emerging trends such as decentralized data sharing, multimodal brain imaging, differential diagnosis, disease subtype classification and deep learning are also discussed. Based on this survey, there are extensive evidences showing the great potential of neuroimaging data for single subject prediction of various disorders. However, the main bottleneck of this exciting field is still the limited sample size, which could be potentially addressed by modern data sharing models such as the ones discussed in this paper. Emerging big data technologies and advanced data-intensive machine learning methodologies such as deep learning have coincided with an increasing need for accurate, robust and generalizable single subject prediction of brain disorders during an exciting time. In this report, we survey the past and offer some opinions regarding the road ahead. PMID:27012503

Single subject prediction of brain disorders in neuroimaging: Promises and pitfalls.

PubMed

Arbabshirani, Mohammad R; Plis, Sergey; Sui, Jing; Calhoun, Vince D

2017-01-15

Neuroimaging-based single subject prediction of brain disorders has gained increasing attention in recent years. Using a variety of neuroimaging modalities such as structural, functional and diffusion MRI, along with machine learning techniques, hundreds of studies have been carried out for accurate classification of patients with heterogeneous mental and neurodegenerative disorders such as schizophrenia and Alzheimer's disease. More than 500 studies have been published during the past quarter century on single subject prediction focused on a multiple brain disorders. In the first part of this study, we provide a survey of more than 200 reports in this field with a focus on schizophrenia, mild cognitive impairment (MCI), Alzheimer's disease (AD), depressive disorders, autism spectrum disease (ASD) and attention-deficit hyperactivity disorder (ADHD). Detailed information about those studies such as sample size, type and number of extracted features and reported accuracy are summarized and discussed. To our knowledge, this is by far the most comprehensive review of neuroimaging-based single subject prediction of brain disorders. In the second part, we present our opinion on major pitfalls of those studies from a machine learning point of view. Common biases are discussed and suggestions are provided. Moreover, emerging trends such as decentralized data sharing, multimodal brain imaging, differential diagnosis, disease subtype classification and deep learning are also discussed. Based on this survey, there is extensive evidence showing the great potential of neuroimaging data for single subject prediction of various disorders. However, the main bottleneck of this exciting field is still the limited sample size, which could be potentially addressed by modern data sharing models such as the ones discussed in this paper. Emerging big data technologies and advanced data-intensive machine learning methodologies such as deep learning have coincided with an increasing need for accurate, robust and generalizable single subject prediction of brain disorders during an exciting time. In this report, we survey the past and offer some opinions regarding the road ahead. Copyright © 2016 Elsevier Inc. All rights reserved.

Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

PubMed Central

Cui, Yimin; Song, Yan; Wang, Jessie; Yu, Zhigang; Schuster, Alan; Barrett, Yu Chen; Frost, Charles

2013-01-01

Background The pharmacokinetics (PK), pharmacodynamics (PD), and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio) to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9). The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. PMID:24353445

Pharmacokinetics, Pharmacodynamics and Population Pharmacokinetic/Pharmacodynamic Modelling of Bilastine, a Second-Generation Antihistamine, in Healthy Japanese Subjects.

PubMed

Togawa, Michinori; Yamaya, Hidetoshi; Rodríguez, Mónica; Nagashima, Hirotaka

2016-12-01

Bilastine is a novel second-generation antihistamine for the symptomatic treatment of allergic rhinitis and urticaria. The objective of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of bilastine following single and multiple oral doses in healthy Japanese subjects. The pharmacokinetic and pharmacodynamic profiles were compared with those reported in Caucasian subjects. In a single-blind, randomized, placebo-controlled, parallel-group, single- and multiple-ascending dose study, bilastine tablets were administered at single doses of 10, 20, and 50 mg (Part I), and once daily for 14 days at 20 and 50 mg (Part II). After single oral doses, maximum plasma concentrations (C max ) were reached at 1.0-1.5 h postdose. Plasma exposure [C max and area under the plasma concentration-time curve (AUC)] increased dose-proportionally at single doses of 10-50 mg. In repeated-dose administration, no remarkable differences were observed between Day 1 and Day 14 for C max or AUC. For inhibitory effects on wheal and flare response, bilastine 20 and 50 mg showed significant inhibition from 1.5 h after administration as compared with placebo, and the significant effect persisted for 24 h after administration. The rates of adverse events (AEs) were comparable between bilastine and placebo in both Part I and Part II. In addition, no dose- or administration period-dependent tendency of increase in rate of AEs or worsening of severity was observed. Bilastine exhibits similar single- and multiple-dose pharmacokinetic and pharmacodynamic characteristics in healthy Japanese subjects compared with those observed in Caucasian subjects in previous studies.

Daily Stress as a Trigger of Migraine Attacks: Results of Thirteen Single-Subject Studies.

ERIC Educational Resources Information Center

Kohler, Thomas; Haimerl, Christianne

1990-01-01

Six-month longitudinal study examined whether migraine attacks were preceded by or occurred on stressful days. Every evening, 13 patients completed questionnaires assessing daily stress. Analyses on single-subject level tested when attacks occurred. Increased stress was generally not found for Days 2 and 3 before an attack, but often for Day 1 and…

Differences in kinematics of single leg squatting between anterior cruciate ligament-injured patients and healthy controls.

PubMed

Yamazaki, J; Muneta, T; Ju, Y J; Sekiya, I

2010-01-01

Seventy to eighty percent of all anterior cruciate ligament (ACL) injuries are due to non-contact injury mechanisms. It has been reported that the majority of injuries due to single leg landing come from valgus positioning of the lower leg. Preventing valgus positioning during single leg landing is expected to help reduce the number of ACL injuries. We found that many ACL-deficient patients cannot perform stable single leg squatting. Therefore, we performed 3D motion analysis of the single-legged half squat for ACL-injured patients to evaluate its significance as a risk factor for ACL injuries. We evaluated the relative angles between the body, thigh, and lower leg using an electromagnetic device during single leg half squatting performed by 63 ACL-injured patients (32 males, 31 females) the day before ACL reconstruction and by 26 healthy control subjects with no knee problems. The uninjured leg of ACL-injured male subjects demonstrated significantly less external knee rotation than that of the dominant leg of the male control. The uninjured leg of ACL-injured female subjects demonstrated significantly more external hip rotation and knee flexion and less hip flexion than that of the dominant leg of the female control. Comparing injured and uninjured legs, the injured leg of male subjects demonstrated significantly less external knee and hip rotation, less knee flexion, and more knee varus than that of the uninjured leg of male subjects. The injured leg of female subjects demonstrated more knee varus than that of the uninjured leg of female subjects. Regarding gender differences, female subjects demonstrated significantly more external hip rotation and knee valgus than male subjects did in both the injured and uninjured legs (P < 0.05). The current kinematic study exhibited biomechanical characteristics of female ACL-injured subjects compared with that of control groups. Kinematic correction during single leg half squat would reduce ACL reinjury in female ACL-injured subjects.

Effect Size Calculations and Single Subject Designs

ERIC Educational Resources Information Center

Olive, Melissa L.; Smith, Benjamin W.

2005-01-01

This study compared visual analyses with five alternative methods for assessing the magnitude of effect with single subject designs. Each method was successful in detecting intervention effect. When rank ordered, each method was consistent in identifying the participants with the largest effect. We recommend the use of the standard mean difference…

Synthesis of Single-Case Experimental Data: A Comparison of Alternative Multilevel Approaches

ERIC Educational Resources Information Center

Ferron, John; Van den Noortgate, Wim; Beretvas, Tasha; Moeyaert, Mariola; Ugille, Maaike; Petit-Bois, Merlande; Baek, Eun Kyeng

2013-01-01

Single-case or single-subject experimental designs (SSED) are used to evaluate the effect of one or more treatments on a single case. Although SSED studies are growing in popularity, the results are in theory case-specific. One systematic and statistical approach for combining single-case data within and across studies is multilevel modeling. The…

Reduction of depressive symptoms in an elderly Mexican-American female with type 2 diabetes mellitus: a single-subject study.

PubMed

Haltiwanger, Emily Piven; Galindo, David

2013-03-01

The purpose of this study was to determine if occupation-based activities improve diabetes self-management and reduce depressive symptoms in an elderly Mexican-American woman with type 2 diabetes mellitus (T2DM). There have been no known studies showing occupational therapy's role in self-care management of T2DM in people with depressive symptoms. The individual in this single-subject research was evaluated using glycosylated haemoglobin blood tests, four self-reported standardized questionnaires, participant reflective logs and clinical observations following an 8-week intervention. The participant improved on all measures, which were sustained 1 month after treatment ended. Clinical implications highlight a new role for occupational therapists providing early intervention in people with diabetes and depression for secondary prevention of complications of uncontrolled diabetes. Research suggestions include multiple single-subject studies showing occupational therapy contributions. Copyright © 2012 John Wiley & Sons, Ltd.

Effect of divided attention on gait in subjects with and without cognitive impairment.

PubMed

Pettersson, Anna F; Olsson, Elisabeth; Wahlund, Lars-Olof

2007-03-01

The aim of this study was to investigate the influence of cognition on motor function using 2 simple everyday tasks, talking and walking, in younger subjects with Alzheimer's disease and mild cognitive impairment. A second aim was to evaluate reliability for the dual-task test Talking While Walking. Walking speed during single and dual task and time change between single and dual task were compared between groups. The test procedure was repeated after 1 week. Subjects with AD had lower walking speed and greater time change between single and dual task compared with healthy controls. Reliability for Talking While Walking was very good. The results show that motor function in combination with a cognitive task, as well as motor function alone, influences subjects with Alzheimer's disease in a negative way and that decreased walking speed during single- and dual-task performance may be an early symptom in Alzheimer's disease.

Effect Size Measure and Analysis of Single Subject Designs

ERIC Educational Resources Information Center

Swaminathan, Hariharan; Horner, Robert H.; Rogers, H. Jane; Sugai, George

2012-01-01

This study is aimed at addressing the criticisms that have been leveled at the currently available statistical procedures for analyzing single subject designs (SSD). One of the vexing problems in the analysis of SSD is in the assessment of the effect of intervention. Serial dependence notwithstanding, the linear model approach that has been…

Applying Generalizability Theory To Evaluate Treatment Effect in Single-Subject Research.

ERIC Educational Resources Information Center

Lefebvre, Daniel J.; Suen, Hoi K.

An empirical investigation of methodological issues associated with evaluating treatment effect in single-subject research (SSR) designs is presented. This investigation: (1) conducted a generalizability (G) study to identify the sources of systematic and random measurement error (SRME); (2) used an analytic approach based on G theory to integrate…

A Systematic Review of Training Programs for Parents of Children with Autism Spectrum Disorders: Single Subject Contributions

ERIC Educational Resources Information Center

Patterson, Stephanie Y.; Smith, Veronica; Mirenda, Pat

2012-01-01

Aim: The purpose of this systematic review was to examine research utilizing single subject research designs (SSRD) to explore the effectiveness of interventions designed to increase parents' ability to support communication and social development in children with autism spectrum disorders (ASDs). Method: Included studies were systematically…

Single Subject Research: Applications to Special Education

ERIC Educational Resources Information Center

Cakiroglu, Orhan

2012-01-01

Single subject research is a scientific research methodology that is increasingly used in the field of special education. Therefore, understanding the unique characteristics of single subject research methodology is critical both for educators and practitioners. Certain characteristics make single subject research one of the most preferred…

Cerebral activation evoked by the mirror illusion of the hand in stroke patients compared to normal subjects.

PubMed

Wang, Jing; Fritzsch, Claire; Bernarding, Johannes; Krause, Thomas; Mauritz, Karl-Heinz; Brunetti, Maddalena; Dohle, Christian

2013-01-01

Mirror therapy (MT) was found to improve motor function after stroke, but its neural mechanisms remain unclear, especially in single stroke patients. The following imaging study was designed to compare brain activation patterns evoked by the mirror illusion in single stroke patients with normal subjects. Fifteen normal volunteers and five stroke patients with severe arm paresis were recruited. Cerebral activations during movement mirroring by means of a video chain were recorded with functional magnetic resonance imaging (fMRI). Single-subject analysis was performed using SPM 8. For normal subjects, ten and thirteen subjects displayed lateralized cerebral activations evoked by the mirror illusion while moving their right and left hand respectively. The magnitude of this effect in the precuneus contralateral to the seen hand was not dependent on movement speed or subjective experience. Negative correlation of activation strength with age was found for the right hand only. The activation pattern in stroke patients is comparable to that of normal subjects and present in four out of five patients. In summary, the mirror illusion can elicit cerebral activation contralateral to the perceived hand in the majority of single normal subjects, but not in all of them. This is similar even in stroke patients with severe hemiparesis.

The Effect of a Novel form of Extended-Release Gabapentin on Pain and Sleep in Fibromyalgia Subjects: An Open-Label Pilot Study.

PubMed

North, James M; Hong, Kyung-Soo J; Rauck, Richard L

2016-07-01

We assessed the efficacy and safety of extended-release gabapentin in a 15-week, open-label, single-arm, single-center study in patients with fibromyalgia (FM). Subjects with documented diagnosis of FM were allowed to participate in the study. We opened enrollment to those who have tried and failed gabapentinoids such as gabapentin or pregabalin due to side effects. Subjects with autoimmune conditions, and or taking opioids for management of their FM pain, were excluded from the study. Subjects were given an extended-release gabapentin starter pack and treated for total of 12 weeks. The primary study endpoint of pain relief was measured using Numeric Pain Rating System (NPRS) scores, and secondary study endpoints were measured with Fibromyalgia Impact Questionnaire (FIQ), Patient's Global Impression of Change (PGIC), and Medical Outcome Sleep questionnaires (MOS). A total of 34 subjects were enrolled and 29 subjects completed the starter pack (85%). Patients reported significant pain relief on NPRS by end of 4 weeks (P < 0.0001) on NPRS. Subjects also reported similar magnitude of improvements in FM and its impact on daily life by end of 4 weeks on FIQ (P < 0.0001). Survey of MOS showed our subjects reporting improved sleep quantity (on average, 1.2 hours over baseline) with gradual and statistically significant improvement in quality. Improvements in primary and secondary measurements were reflected in PGIC, with significant improvement in patient's impression of FM by week 8. Small sample size, geographical bias, relatively short duration of treatment, and single-arm study without control group. Extended-release gabapentin relieved FM pain symptoms and improved quality-of-life for the FM subjects studied. Subjects reported improvements in both quantity and quality of sleep. © 2015 World Institute of Pain.

Single-Subject Evaluation: A Tool for Quality Assurance.

ERIC Educational Resources Information Center

Nuehring, Elane M.; Pascone, Anne B.

1986-01-01

The use of single-subject designs in peer review, in utilization review, and in other quality-assurance audits is encouraged. Presents an overview of the methodologies of single-subject designs and quality assurance, and provides examples of cases in which single-subject techniques furnished relevant quality assurance documentation. (Author/ABB)

Descriptive Analysis of Single Subject Research Designs: 1983-2007

ERIC Educational Resources Information Center

Hammond, Diana; Gast, David L.

2010-01-01

Single subject research methodology is commonly used and cited in special education courses and journals. This article reviews the types of single subject research designs published in eight refereed journals between 1983 and 2007 used to answer applied research questions. Single subject designs were categorized as withdrawal/reversal, time…

[THE MOTIVATION OF MEDICAL PERSONNEL OF MULTIFIELD HOSPITAL TO WORKING OVER STANDARDS OF SINGLE JOB POSITION].

PubMed

Khazov, M V; Romanov, S V; Abaeva, O P; Murigina, M M

2015-01-01

The article considers results of study concerning prevalence of physicians working over standards of single job position in multifield hospital, including factors motivating to extra job. The research purpose was to analyze impact of gender age structure of medical personnel of multfield public medical organization on motivation of physicians to work over standards of single job position. The objectives consisted of analyzing prevalence of over standard work of medical personnel of multifield public medical organization with consideration of social structure and studying factors motivating physicians to work over standards of single job position. The study was carried out on the basis of questionnaire survey of physicians. The results of study testify higher degree of prevalence of working over standards of single job position in modern health care. So, 64.8 ± 3.6% of respondents work subject to conditions of internal and/or external moonlighting. Moreover; one third of physicians enlisted to extra job. Among physicians males more often than females work subject to conditions of moonlighting, perform extra job, enlist to working during days off. The specialists of age group from 35 to 54 years work subject to conditions of external and internal moonlighting more often than younger physicians. Among physicians, the most significant cause of working subject to conditions of moonlighting is additional earnings. At that, every fifth physician works over standards of job position with purpose to increase one's professional competence. The study results permit concluding that aspects of social structure of modern medical staff significantly impact motivation and hence possibility of enlisting workers to work over standards of single job position.

Safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole sodium injections after single and multiple intravenous doses in healthy Chinese subjects.

PubMed

Jiao, Hui-Wen; Sun, Lu-Ning; Li, Yue-Qi; Yu, Lei; Zhang, Hong-Wen; Wang, Mei-Feng; Yu, Li-Yuan; Yuan, Zi-Qing-Yun; Xie, Li-Jun; Chen, Juan; Meng, Ling; Zhang, Xue-Hui; Wang, Yong-Qing

2018-03-01

The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole (PPZ) sodium injections following single and multiple intravenous doses in healthy Chinese subjects. The dosage groups were set as followed: 20 mg of single and multiple intravenous administration of S-(-)-PPZ, 40 mg of single and multiple intravenous administration of S-(-)-PPZ or pantoprazole, and 80 mg of single dosage group of S-(-)-PPZ. Subjects were sampled for pharmacokinetic analysis and were monitored for 24-h intragastric pH prior to and 48-h intragastric pH after administration for the pharmacodynamic study. The pharmacokinetic and pharmacodynamic parameters were compared between S-(-)-PPZ and PPZ. Safety was evaluated on the basis of adverse events, vital signs, laboratory tests, and physical examination. All adverse events were mild and of limited duration. Maximum plasma concentration and area under the concentration-time curve for S-(-)-PPZ were dose proportional over the range of 20-80 mg following a single intravenous administration. Elimination rate constant and half-life observed statistical difference from a single dose to multiple doses in 40 mg of S-(-)-PPZ groups. After administration of a single dose, the mean 24-h intragastric pH value was observed higher in 80-mg group than in 40- and 20-mg groups. Slightly increase of intragastric pH was found after a single dose of 40 mg S-(-)-PPZ than 40 mg PPZ; however, the differences were not statistically significant. Twice daily of 40 mg S-(-)-PPZ sodium injections is effective in achieving satisfying acid inhibition. Compared with plasma R-(+)-PPZ levels, most subjects presented more potent and prolonged suppression of gastric acid of S-(-)-PPZ, while a few subjects showed faster metabolic rate of S-(-)-PPZ in vivo.

The Applied Behavior Analysis Research Paradigm and Single-Subject Designs in Adapted Physical Activity Research.

PubMed

Haegele, Justin A; Hodge, Samuel Russell

2015-10-01

There are basic philosophical and paradigmatic assumptions that guide scholarly research endeavors, including the methods used and the types of questions asked. Through this article, kinesiology faculty and students with interests in adapted physical activity are encouraged to understand the basic assumptions of applied behavior analysis (ABA) methodology for conducting, analyzing, and presenting research of high quality in this paradigm. The purposes of this viewpoint paper are to present information fundamental to understanding the assumptions undergirding research methodology in ABA, describe key aspects of single-subject research designs, and discuss common research designs and data-analysis strategies used in single-subject studies.

The Effect of Pilates Exercise on Trunk and Postural Stability and Throwing Velocity in College Baseball Pitchers: Single Subject Design

PubMed Central

Howe, Katherine

2007-01-01

Background Baseball pitchers need trunk strength to maximize performance. The Pilates method of exercise is gaining popularity throughout the country as a fitness and rehabilitation method of exercise. However, very few studies exist that examine the effects of the Pilates method of exercise on trunk strength or performance. Objectives Using a single subject, multiple baseline across subjects design, this study examines the effects of the Pilates method of exercise on performance of double leg lowering, star excursion balance test, and throwing velocity in college-aged baseball pitchers. Methods A convenience sample of three college baseball pitchers served as the subjects for this single subject design study. For each subject, double leg lowering, star excursion balance test, and throwing speed were measured prior to the introduction of the intervention. When baseline test values showed consistent performance, the intervention was introduced to one subject at a time. Intervention was introduced to the other subjects over a period of 4 weeks as they also demonstrated consistent performance on the baseline tests. Intervention was continued with periodic tests for the remainder of the 10 week trial. Results Each subject improved in performance on double leg lowering (increased 24.43-32.7%) and star excursion balance test (increased 4.63-17.84%) after introduction of the intervention. Throwing speed improved in two of the three subjects (up to 5.61%). Discussion and Conclusions The Pilates method of exercise may contribute to improved performance in double leg lowering, star excursion balance tests, and throwing speed in college baseball pitchers. PMID:21522199

Quality Appraisal of Single-Subject Experimental Designs: An Overview and Comparison of Different Appraisal Tools

ERIC Educational Resources Information Center

Wendt, Oliver; Miller, Bridget

2012-01-01

Critical appraisal of the research literature is an essential step in informing and implementing evidence-based practice. Quality appraisal tools that assess the methodological quality of experimental studies provide a means to identify the most rigorous research suitable for evidence-based decision-making. In single-subject experimental research,…

Comparison of a Stimulus Equivalence Protocol and Traditional Lecture for Teaching Single-Subject Designs

ERIC Educational Resources Information Center

Lovett, Sadie; Rehfeldt, Ruth Anne; Garcia, Yors; Dunning, Johnna

2011-01-01

This study compared the effects of a computer-based stimulus equivalence protocol to a traditional lecture format in teaching single-subject experimental design concepts to undergraduate students. Participants were assigned to either an equivalence or a lecture group, and performance on a paper-and-pencil test that targeted relations among the…

When Opportunity Knocks Twice: Two-Year-Olds' Repetition of Sentence Subjects

ERIC Educational Resources Information Center

Valian, Virginia; Aubry, Stephanie

2005-01-01

Why are young children's utterances short? This elicited imitation study used a new task--double imitation--to investigate the factors that contribute to children's failure to lexicalize sentence subjects. Two-year-olds heard a triad of sentences singly and attempted to imitate each; they then again heard the same triad singly and again attempted…

The Synthesis of Single-Subject Experimental Data: Extensions of the Basic Multilevel Model

ERIC Educational Resources Information Center

Van den Noortgate, Wim; Moeyaert, Mariola; Ugille, Maaike; Beretvas, Tasha; Ferron, John

2014-01-01

Due to an increasing interest in the use of single-subject experimental designs (SSEDs), appropriate techniques are needed to analyze this type of data. The purpose of this paper proposal is to present four studies (Beretvas, Hembry, Van den Noortgate, & Ferron, 2013; Bunuan, Hembry & Beretvas, 2013; Moeyaert, Ugille, Ferron, Beretvas,…

Pennsylvania Public School Superintendent Beliefs and Practices Regarding Single Subject Acceleration in an Elementary School Setting

ERIC Educational Resources Information Center

Vizza, Jill Pinnola

2017-01-01

This study was designed to identify factors that might influence Pennsylvania public school superintendents in the decision regarding the potential use of single-subject acceleration as a practice for meeting the needs of students in the elementary setting. The research targeted public school superintendents in the Commonwealth of Pennsylvania. In…

Pharmacokinetics and Pharmacodynamics of Anacetrapib Following Single Doses in Healthy, Young Japanese and White Male Subjects.

PubMed

Krishna, Rajesh; Gheyas, Ferdous; Liu, Yang; Cote, Josee; Laterza, Omar; Ruckle, Jon L; Wagner, John A; Denker, Andrew E

2018-02-01

Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor being developed for the treatment of mixed dyslipidemia. The aim of the study was to evaluate the pharmacokinetic, pharmacodynamic, and safety characteristics of anacetrapib following single doses in healthy, young Japanese men. In a double-blind, randomized, placebo-controlled, 3-panel, single-rising-dose study, 6 healthy young Japanese male or white male subjects (aged 19 to 44 years) received single oral doses of 5 to 500 mg anacetrapib, and 2 received placebo. Plasma and urine drug concentrations were measured 0-168 hours postdose, and plasma CETP inhibition was measured 0-24 hours postdose. Urinary anacetrapib levels were all below quantitation limits. Plasma concentrations of anacetrapib increased approximately less than dose-proportionally. Consumption of a traditional Japanese breakfast prior to dosing increased the plasma pharmacokinetics of anacetrapib in Japanese subjects compared with fasted conditions, to a similar extent as in white subjects. CETP activity measured over 0-24 hours postdose resulted in significant inhibition. Anacetrapib was generally well tolerated, and there were no serious adverse experiences. No clinically meaningful differences in PK and CETP inhibition parameters were found between Japanese and white subjects. © 2017, The American College of Clinical Pharmacology.

Gender differences in asymmetrical limb support patterns between subjects with and without recurrent low back pain.

PubMed

Sung, Paul S; Zipple, J Tim; Danial, Pamela

2017-04-01

New insight regarding limb-dominance effects on temporal-spatial gait parameters is needed to further investigate subjects with recurrent low back pain (LBP). Although an asymmetrical gait pattern was found to reflect natural functional differences, there is a lack of information regarding gender differences on dominant limb support patterns in subjects with LBP. The purpose of this study was to investigate temporal-spatial gait parameters based on limb dominance and gender between subjects with and without LBP. One hundred and ten right limb dominant older adults (51 subjects with LBP and 59 control subjects) participated in the study. A three-dimensional motion capture system was utilized to measure temporal-spatial gait parameters, including initial double, single, and terminal double limb support times and walking speed. The gender differences between subjects with and without LBP were analyzed based on dominance for those parameters. Overall, limb dominance demonstrated significant differences on single and terminal double limb support times as well as walking speed. Limb dominance also demonstrated interactions on group x gender for single limb support time and walking speed. The male subjects with LBP demonstrated significantly increased single limb support times on the non-dominant limb. The significant gender and group interactions based on limb dominance account for a possible pain avoidance, asymmetrical limb support pattern. The causal pathway in dominance dependency gait by unweighted ambulation might be considered as an intervention for correcting these gait deviations in subjects with LBP. The specific modification recovery profiles of the subjects with LBP could shed light on variability of current LBP experiences of the subjects and reasons for gait deviations. Clinicians need to consider the mechanism of dominant limb dependency, which requires postural control strategies in male subjects with recurrent LBP. Copyright © 2017 Elsevier B.V. All rights reserved.

Fibrosis-Related Gene Expression in Single Ventricle Heart Disease.

PubMed

Nakano, Stephanie J; Siomos, Austine K; Garcia, Anastacia M; Nguyen, Hieu; SooHoo, Megan; Galambos, Csaba; Nunley, Karin; Stauffer, Brian L; Sucharov, Carmen C; Miyamoto, Shelley D

2017-12-01

To evaluate fibrosis and fibrosis-related gene expression in the myocardium of pediatric subjects with single ventricle with right ventricular failure. Real-time quantitative polymerase chain reaction was performed on explanted right ventricular myocardium of pediatric subjects with single ventricle disease and controls with nonfailing heart disease. Subjects were divided into 3 groups: single ventricle failing (right ventricular failure before or after stage I palliation), single ventricle nonfailing (infants listed for primary transplantation with normal right ventricular function), and stage III (Fontan or right ventricular failure after stage III). To evaluate subjects of similar age and right ventricular volume loading, single ventricle disease with failure was compared with single ventricle without failure and stage III was compared with nonfailing right ventricular disease. Histologic fibrosis was assessed in all hearts. Mann-Whitney tests were performed to identify differences in gene expression. Collagen (Col1α, Col3) expression is decreased in single ventricle congenital heart disease with failure compared with nonfailing single ventricle congenital heart disease (P = .019 and P = .035, respectively), and is equivalent in stage III compared with nonfailing right ventricular heart disease. Tissue inhibitors of metalloproteinase (TIMP-1, TIMP-3, and TIMP-4) are downregulated in stage III compared with nonfailing right ventricular heart disease (P = .0047, P = .013 and P = .013, respectively). Matrix metalloproteinases (MMP-2, MMP-9) are similar between nonfailing single ventricular heart disease and failing single ventricular heart disease, and between stage III heart disease and nonfailing right ventricular heart disease. There is no difference in the prevalence of right ventricular fibrosis by histology in subjects with single ventricular failure heart disease with right ventricular failure (18%) compared with those with normal right ventricular function (38%). Fibrosis is not a primary contributor to right ventricular failure in infants and young children with single ventricular heart disease. Additional studies are required to understand whether antifibrotic therapies are beneficial in this population. Copyright © 2017 Elsevier Inc. All rights reserved.

Marital status and sleep-disordered breathing in a sample of middle-aged French men.

PubMed

Teculescu, D; Hannhart, B; Virion, J M; Montaut-Verient, B; Michaely, J P

2004-01-01

The aim of the present study was to test the hypothesis that unmarried (single) men have more sleep-disordered breathing symptoms due to a higher prevalence of obesity and a less healthy lifestyle than men living with a partner. Men (499) aged 23-66 years completed a structured questionnaire, had standard anthropometric measurements and a simple, noninvasive nose-throat examination. Of the 499,496 subjects answered the question concerning their marital status; 86% of them were married or lived with a partner (reference group) and the other 14% had never been married, divorced, or widowed ("single" group, considered at risk). Single subjects were younger, included slightly more smokers (30 vs. 23%) and more subjects with a history of chronic bronchitis, and less frequently had a large soft palate. The prevalence of sleep-disordered symptoms was not significantly different between the two groups. However, a study involving a larger number of subjects with information regarding alcoholic consumption may be needed to further evaluate this question.

Immediate Effects of Kinesiology Taping of Quadriceps on Motor Performance after Muscle Fatigued Induction.

PubMed

Ahn, Ick Keun; Kim, You Lim; Bae, Young-Hyeon; Lee, Suk Min

2015-01-01

Objectives. The purpose of this cross-sectional single-blind study was to investigate the immediate effects of Kinesiology taping of quadriceps on motor performance after muscle fatigued induction. Design. Randomized controlled cross-sectional design. Subjects. Forty-five subjects participated in this study. Participants were divided into three groups: Kinesiology taping group, placebo taping group, and nontaping group. Methods. Subjects performed short-term exercise for muscle fatigued induction, followed by the application of each intervention. Peak torque test, one-leg single hop test, active joint position sense test, and one-leg static balance test were carried out before and after the intervention. Results. Peak torque and single-leg hopping distance were significantly increased when Kinesiology taping was applied (p < 0.05). But there were no significant effects on active joint position sense and single-leg static balance. Conclusions. We proved that Kinesiology taping is effective in restoring muscle power reduced after muscle fatigued induction. Therefore, we suggest that Kinesiology taping is beneficial for fatigued muscles.

Vaccination response to tetanus toxoid and 23-valent pneumococcal vaccines following administration of a single dose of abatacept: a randomized, open-label, parallel group study in healthy subjects

PubMed Central

Tay, Lee; Leon, Francisco; Vratsanos, George; Raymond, Ralph; Corbo, Michael

2007-01-01

The effect of abatacept, a selective T-cell co-stimulation modulator, on vaccination has not been previously investigated. In this open-label, single-dose, randomized, parallel-group, controlled study, the effect of a single 750 mg infusion of abatacept on the antibody response to the intramuscular tetanus toxoid vaccine (primarily a memory response to a T-cell-dependent peptide antigen) and the intramuscular 23-valent pneumococcal vaccine (a less T-cell-dependent response to a polysaccharide antigen) was measured in 80 normal healthy volunteers. Subjects were uniformly randomized to receive one of four treatments: Group A (control group), subjects received vaccines on day 1 only; Group B, subjects received vaccines 2 weeks before abatacept; Group C, subjects received vaccines 2 weeks after abatacept; and Group D, subjects received vaccines 8 weeks after abatacept. Anti-tetanus and anti-pneumococcal (Danish serotypes 2, 6B, 8, 9V, 14, 19F and 23F) antibody titers were measured 14 and 28 days after vaccination. While there were no statistically significant differences between the dosing groups, geometric mean titers following tetanus or pneumococcal vaccination were generally lower in subjects who were vaccinated 2 weeks after receiving abatacept, compared with control subjects. A positive response (defined as a twofold increase in antibody titer from baseline) to tetanus vaccination at 28 days was seen, however, in ≥ 60% of subjects across all treatment groups versus 75% of control subjects. Similarly, over 70% of abatacept-treated subjects versus all control subjects (100%) responded to at least three pneumococcal serotypes, and approximately 25–30% of abatacept-treated subjects versus 45% of control subjects responded to at least six serotypes. PMID:17425783

School Subject Preferences of Pupils in Single Sex and Co-educational Secondary Schools.

ERIC Educational Resources Information Center

Colley, Ann; And Others

1994-01-01

Reports on a study of school subject preference among 566 male and 567 female students in both single-sex and coeducational British secondary schools. Finds an effect of school type for younger students only. Also finds clear effects of gender with higher rankings given to mathematics and science by boys and to art by girls. (CFR)

Irregular tick-borne encephalitis vaccination schedules: the effect of a single catch-up vaccination with FSME-IMMUN. A prospective non-interventional study.

PubMed

Schosser, Rudolf; Reichert, Anja; Mansmann, Ulrich; Unger, Bernd; Heininger, Ulrich; Kaiser, Reinhard

2014-04-25

Intervals longer than recommended are frequently encountered between doses of tick borne encephalitis virus (TBE) vaccines in both residents of and travelers to endemic regions. In clinical practice the management of individuals with lapsed TBE vaccination schedules varies widely and has in common that the underlying immunological evidence is scarce. The aim of this study was to generate data reliable enough to derive practical recommendations on how to continue vaccination with FSME-IMMUN in subjects with an irregular TBE vaccination history. Antibody response to a single catch-up dose of FSME-IMMUN was assessed in 1115 adults (age ≥16 years) and 125 children (age 6-15 years) with irregular TBE vaccination histories. Subjects of all age groups developed a substantial increase in geometric mean antibody concentration after a single catch-up TBE vaccination which was consistently lower in subjects with only one previous TBE vaccination compared to subjects with two or more vaccinations. Overall, >94% of young adults and children, and >93% of elderly subjects with an irregular TBE vaccination history achieved antibody levels ≥25U/ml irrespective of the number of previous TBE vaccinations. We conclude that TBE vaccination of subjects with irregular vaccination histories should be continued as if the previous vaccinations had been administered in a regular manner, with the stage of the vaccination schedule being determined by the number of previous vaccinations. Although lapsed vaccination schedules may leave subjects temporarily with inadequate protection against TBE infection, adequate protection can quickly be re-established in >93% of the subjects by a single catch-up dose of FSME-IMMUN, irrespective of age, number of previous vaccinations, and time interval since the last vaccination. Copyright © 2014 Anja Reichert. Published by Elsevier Ltd.. All rights reserved.

Single-center evaluation of the single-dose pharmacokinetics of the angiotensin II receptor antagonist azilsartan medoxomil in renal impairment.

PubMed

Preston, Richard A; Karim, Aziz; Dudkowski, Caroline; Zhao, Zhen; Garg, Dyal; Lenz, Oliver; Sica, Domenic A

2013-05-01

Azilsartan medoxomil (AZL-M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose-dependent manner. It is a pro-drug and not detected in blood after oral administration because of rapid hydrolysis to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the major metabolite M-II and minor metabolites. The objective of this study was to determine the effect of renal impairment on the pharmacokinetics of AZL and its major metabolite. This was a single-center, open-label, phase I parallel-group study which examined the single-dose (40-mg) pharmacokinetics of AZL and M-II in 24 subjects with mild, moderate, or severe renal impairment or end-stage renal disease requiring hemodialysis (n = 6 per group), respectively, and healthy matched subjects (n = 24). Renal impairment/disease did not cause clinically meaningful increases in exposure to AZL. M-II exposure was higher in all renally impaired subjects and highest in those with severe impairment (approx fivefold higher vs. control). M-II is pharmacologically inactive; increased exposure was not considered important in dose selection for AZL-M in subjects with renal impairment. Hemodialysis did not significantly remove AZL or M-II. Renal impairment had no clinically meaningful effect on the plasma protein binding of AZL or M-II. Single doses of AZL-M 40 mg were well tolerated in all subject groups. Based on the pharmacokinetic and tolerability findings, no dose adjustment of AZL-M is required for subjects with any degree of renal impairment, including end-stage renal disease.

Pharmacokinetics, Pharmacodynamics, and Tolerability of Single and Multiple Doses of Trandolapril, an Effective Angiotensin-Converting Enzyme Inhibitor, in Healthy Chinese Subjects.

PubMed

Li, Xiaojiao; Liu, Chang; Wu, Min; Zhang, Hong; Sun, Yanfu; Cheng, Longmei; Chen, Hong; Liu, Chengjiao; Yang, Lizhi; Zhang, Qi; Cao, Yuchen; Gu, Jingkai; Ding, Yanhua

2016-08-01

Trandolapril is the pro-drug of trandolaprilat, a non-sulfhydryl angiotensin-converting enzyme inhibitor. This study was designed to assess the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of single and multiple doses of trandolapril in healthy Chinese subjects. Healthy subjects (six men and six women) were randomized into a single-dose, 3 × 3 crossover study (1-2-4 mg, 2-4-1 mg, and 4-1-2 mg), and a multiple-dose study (2 mg/day, 6 days). Serial blood and urine samples were collected after drug administration and analyzed using a validated LC-MS/MS method, and the trandolapril and trandolaprilat PK parameters were obtained. PD was evaluated by the changes in blood pressure and heart rates after dosing. Tolerability was assessed by monitoring adverse events, vital signs, ECGs, and changes in laboratory tests. In the single-dose study, trandolapril was absorbed rapidly, and peak plasma levels (C max, 1.57, 3.77, and 7.99 ng/mL) and AUCs (1.89, 3.46, and 6.47 ng/mL) were dose-dependent. The AUC0-∞ of trandolaprilat was dose-dependent, but in a non-linear fashion. The cumulative urine excretion of trandolapril and trandolaprilat was 5.51, 6.20, and 7.41 % for three doses, respectively. In the multiple-dose study, steady-state pharmacokinetics was observed; there was no trandolapril accumulation, but there was mild trandolaprilat accumulation (R = 1.67). Trandolapril was well tolerated. The most pronounced reductions in blood pressure were observed at 8 h after administration, which was later than T max. No orthostatic hypotension occurred. The pharmacokinetics and pharmacodynamics following single and multiple oral doses trandolapril in healthy Chinese subjects are similar to those observed in non-Chinese healthy subjects.

A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray.

PubMed

Stott, C G; White, L; Wright, S; Wilbraham, D; Guy, G W

2013-04-01

To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, when administered to healthy male subjects. Twelve subjects took part in this fed-fasted cross-over study and received a single dose of THC/CBD spray (4 sprays = 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments. Plasma samples were collected at designated time-points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC). Statistically significant increases in the mean area under the curve (AUC) and mean maximum plasma drug concentration (Cmax) were observed in subjects during fed conditions. Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions. A large inter-subject variability in exposure from the same dose was observed, particularly for THC. The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80-14.91 ng/ml) and lower in 5 subjects (2.81-3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97-9.34 ng/ml) observed in the fasted state. Increases in mean AUC(0-t), AUC(0-inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable. Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2-2.5 h. Only mild adverse events were reported. The THC/CBD spray was well tolerated in male subjects at a single dose of four sprays. The large inter-subject variability in exposure suggests that the changes observed are unlikely to be clinically relevant.

Implant-supported single-tooth restorations. A 12-year prospective study.

PubMed

Donati, Mauro; Ekestubbe, Annika; Lindhe, Jan; Wennström, Jan L

2016-10-01

The aim of this study was to evaluate prospectively the 12-year outcome of implant-supported single-tooth restorations. Originally 45 self-tapping Astra Tech TiOblast ® ST-implants were installed by a two-stage protocol in 40 subjects requiring single-tooth prosthetic replacement for a missing tooth. Clinical and radiologic examinations were performed at completion of the prosthetic treatment 4-7 months after implant installation surgery and after 5 and 12 years in function. At 12 years 31 patients and 35 implants were available for evaluation. The overall failure rate after 12 years was 10.3% on the subject level and 9.1% on the implant level. The mean bone loss amounted to 0.67 mm (SD 2.20) on a subject level and 0.47 mm (1.72) on an implant level. Three subjects (10%) and three implants (8.6%) were diagnosed with peri-implantitis. Five subjects had experienced technical complications; three incidences of loosening of the abutment retention screw during the first 5 years and two minor porcelain fracture of the crown (two patients) between 5- and 12-years of follow-up. The findings reported in this 12-year prospective case series suggest that the use of the Astra Tech dental implants may be a valid treatment alternative for single-tooth replacement prostheses. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic polymorphisms in ESR1 and ESR2 genes, and risk of hypospadias in a multiethnic study population.

PubMed

Choudhry, Shweta; Baskin, Laurence S; Lammer, Edward J; Witte, John S; Dasgupta, Sudeshna; Ma, Chen; Surampalli, Abhilasha; Shen, Joel; Shaw, Gary M; Carmichael, Suzan L

2015-05-01

Estrogenic endocrine disruptors acting via estrogen receptors α (ESR1) and β (ESR2) have been implicated in the etiology of hypospadias, a common congenital malformation of the male external genitalia. We determined the association of single nucleotide polymorphisms in ESR1 and ESR2 genes with hypospadias in a racially/ethnically diverse study population of California births. We investigated the relationship between hypospadias and 108 ESR1 and 36 ESR2 single nucleotide polymorphisms in 647 cases and 877 population based nonmalformed controls among infants born in selected California counties from 1990 to 2003. Subgroup analyses were performed by race/ethnicity (nonHispanic white and Hispanic subjects) and by hypospadias severity (mild to moderate and severe). Odds ratios for 33 of the 108 ESR1 single nucleotide polymorphisms had p values less than 0.05 (p = 0.05 to 0.007) for risk of hypospadias. However, none of the 36 ESR2 single nucleotide polymorphisms was significantly associated. In stratified analyses the association results were consistent by disease severity but different sets of single nucleotide polymorphisms were significantly associated with hypospadias in nonHispanic white and Hispanic subjects. Due to high linkage disequilibrium across the single nucleotide polymorphisms, haplotype analyses were conducted and identified 6 haplotype blocks in ESR1 gene that had haplotypes significantly associated with an increased risk of hypospadias (OR 1.3 to 1.8, p = 0.04 to 0.00001). Similar to single nucleotide polymorphism analysis, different ESR1 haplotypes were associated with risk of hypospadias in nonHispanic white and Hispanic subjects. No significant haplotype association was observed for ESR2. The data provide evidence that ESR1 single nucleotide polymorphisms and haplotypes influence the risk of hypospadias in white and Hispanic subjects, and warrant further examination in other study populations. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

Multi-voxel pattern analysis reveals increased memory targeting and reduced use of retrieved details during single-agenda source monitoring

PubMed Central

McDuff, Susan G. R.; Frankel, Hillary C.; Norman, Kenneth A.

2009-01-01

We used multi-voxel pattern analysis (MVPA) of fMRI data to gain insight into how subjects’ retrieval agendas influence source memory judgments (was item X studied using source Y?). In Experiment 1, we used a single-agenda test where subjects judged whether items were studied with the targeted source or not. In Experiment 2, we used a multi-agenda test where subjects judged whether items were studied using the targeted source, studied using a different source, or nonstudied. To evaluate the differences between single- and multi-agenda source monitoring, we trained a classifier to detect source-specific fMRI activity at study, and then we applied the classifier to data from the test phase. We focused on trials where the targeted source and the actual source differed, so we could use MVPA to track neural activity associated with both the targeted source and the actual source. Our results indicate that single-agenda monitoring was associated with increased focus on the targeted source (as evidenced by increased targeted-source activity, relative to baseline) and reduced use of information relating to the actual, non-target source. In the multi-agenda experiment, high-levels of actual-source activity were associated with increased correct rejections, suggesting that subjects were using recollection of actual-source information to avoid source memory errors. In the single-agenda experiment, there were comparable levels of actual-source activity (suggesting that recollection was taking place), but the relationship between actual-source activity and behavior was absent (suggesting that subjects were failing to make proper use of this information). PMID:19144851

Effect of Lower Extremity Stretching Exercises on Balance in Geriatric Population.

PubMed

Reddy, Ravi Shankar; Alahmari, Khalid A

2016-07-01

The purpose of this study was to find "Effect of lower extremity stretching exercises on balance in the geriatric population. 60 subjects (30 male and 30 female) participated in the study. The subjects underwent 10 weeks of lower limb stretching exercise program. Pre and post 10 weeks stretching exercise program, the subjects were assessed for balance, using single limb stance time in seconds and berg balance score. These outcome measures were analyzed. Pre and post lower extremity stretching on balance was analyzed using paired t test. Of 60 subjects 50 subjects completed the stretching exercise program. Paired sample t test analysis showed a significant improvement in single limb stance time (eyes open and eyes closed) (p<0.001) and berg balance score (p<0.001). Lower extremity stretching exercises enhances balance in the geriatric population and thereby reduction in the number of falls.

Pharmacokinetic characteristics of telaprevir in healthy Korean male subjects and comparisons with Japanese.

PubMed

Choi, Yewon; Yoon, Seonghae; Matsumoto, Kyoko; Ohta, Yoshiyasu; Lee, SeungHwan; Yu, Kyung-Sang; Jang, In-Jin

2018-01-01

Telaprevir, a reversible selective inhibitor of viral protease and a potential blocker of viral replication, is indicated for the treatment of hepatitis C virus genotype 1 infection. In this study, the pharmacokinetic profile, safety, and tolerability of telaprevir and the effect of food on telaprevir exposure were evaluated in healthy Korean subjects, and compared with data from a previous study in Japanese male subjects. The single ascending dose study was conducted in 3 dose-based groups (500, 750, and 1,250 mg, six subjects each) in a fasted state. In the multiple dose study, eight subjects in the fed state received 750 mg of telaprevir once on Day 1 and every 8 hours from Day 2 until the morning of Day 6. Serial blood samples for pharmacokinetic analysis were collected for up to 24 hours in the single ascending dose study and for 6 days in the multiple dose study. Individual pharmacokinetic parameters were calculated using a non-compartmental analysis method. Safety and tolerability profiles were evaluated throughout the study. Following multiple administrations of telaprevir, maximum plasma concentrations (C max ), area under the concentration-time curve (AUC 0-8 ), and C trough (concentration at 8 h after drug administration) increased by ~2.41-fold. Compared to fasted state values, mean C max and AUC 0-24 increased by 4.92- and 4.81-fold, respectively, after food intake. The C max and AUC inf of Korean subjects were 26%-34% higher than those of Japanese subjects; however, these differences were not clinically significant. All observed adverse events were mild and there was no discontinuation due to AEs. In conclusion, the telaprevir's pharmacokinetic characteristics were similar in Korean and Japanese subjects. Telaprevir was well tolerated in a single dose of up to 1,250 mg and in multiple doses of 750 mg.

The Effects of School-Based Interventions for Attention Deficit Hyperactivity Disorder: A Meta-Analysis 1996-2010

ERIC Educational Resources Information Center

DuPaul, George J.; Eckert, Tanya L.; Vilardo, Brigid

2012-01-01

A meta-analysis evaluating the effects of school-based interventions for students with attention deficit hyperactivity disorder was conducted by examining 60 outcome studies between 1996 and 2010 that yielded 85 effect sizes. Separate analyses were performed for studies employing between-subjects, within- subjects, and single-subject experimental…

An Open-Label, Phase 1 Study to Assess the Effects of Hepatic Impairment on Pomalidomide Pharmacokinetics.

PubMed

Li, Yan; Wang, Xiaomin; Liu, Liangang; Zhang, Chengyue; Gomez, Diana; Reyes, Josephine; Palmisano, Maria; Zhou, Simon

2018-05-10

Pomalidomide is an immunomodulatory drug and the dosage of 4 mg per day taken orally on days 1-21 of repeated 28-day cycles has been approved in the European Union and United States to treat patients with relapsed/refractory multiple myeloma. Because pomalidomide is extensively metabolized prior to excretion, a total of 32 subjects (8 healthy subjects in group 1; 8 subjects with severe hepatic impairment in group 2; 8 subjects with moderate hepatic impairment in group 3; and 8 subjects with mild hepatic impairment in group 4) were enrolled in a multicenter, open-label, single-dose study to assess the impact of hepatic impairment on pomalidomide exposure. Following administration of a single oral dose of 4-mg pomalidomide, the geometric mean ratios of pomalidomide total plasma exposures (AUC) were 171.5%, 157.5%, and 151.2% and the geometric mean ratios of pomalidomide plasma peak exposures (C max ) were 75.8%, 94.8%, and 94.2% for subjects with severe, moderate, or mild hepatic impairment, respectively, versus healthy subjects. Pomalidomide administered as a single oral 4-mg dose was safe and well tolerated by healthy subjects and subjects with severe, moderate, or mild hepatic impairment. Based on the pharmacokinetic results from this study, the pomalidomide prescribing information approved by the US Food and Drug Administration recommends for patients with mild or moderate hepatic impairment (Child-Pugh classes A or B), a 3-mg starting daily dose (25% dose reduction) and for patients with severe hepatic impairment (Child-Pugh class C), a 2-mg starting daily dose (50% dose reduction). © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Calibration of an In-Ear Dosimeter for a Single Hearing Protection Device

DTIC Science & Technology

2014-02-01

history of ototoxic medication use, audiological history of tinnitus , etc. A total of 54 subjects were screened to participate in this study.1 subject...was excluded from this study based on a history of seizures. 18 subjects were excluded based on hearing threshold results. 15 subjects were...Military Service: Implications for hearing loss and tinnitus ”, Washington, DC, National Academies Press. 7. United States Government Accountability Office

Subjective Happiness of Lebanese College Youth in Lebanon: Factorial Structure and Invariance of the Arabic Subjective Happiness Scale

ERIC Educational Resources Information Center

Moghnie, Lamia; Kazarian, Shahe S.

2012-01-01

The present study evaluated the subjective happiness of Lebanese college youth using a multi-item rather than a single-item subjective happiness measure. An Arabic translation of the Subjective Happiness Scale (SHS) was administered to 273 Lebanese college youth from state- and private-run higher institutions of learning, as was the Arabic Adult…

Controlling for Prior Attainment Reduces the Positive Influence that Single-Gender Classroom Initiatives Exert on High School Students' Scholastic Achievements.

PubMed

Pennington, Charlotte R; Kaye, Linda K; Qureshi, Adam W; Heim, Derek

2018-01-01

Research points to the positive impact that gender-segregated schooling and classroom initiatives exert on academic attainment. An evaluation of these studies which reveal positive effects highlights, however, that students are typically selectively assigned to single- or mixed-gender instructional settings, presenting a methodological confound. The current study controls for students' prior attainment to appraise the efficacy of a single-gender classroom initiative implemented in a co-educational high school in the United Kingdom. Secondary data analysis (using archived data) was performed on 266 middle-ability, 11-12 year-old students' standardized test scores in Languages (English, foreign language), STEM-related (Mathematics, Science, Information and Communication Technology), and Non-STEM subjects (art, music, drama). Ninety-eight students (54, 55% female) were taught in single-gender and 168 (69, 41% female) in mixed-gender classrooms. Students undertook identical tests irrespective of classroom type, which were graded in accordance with U.K national curriculum guidelines. Controlling for students' prior attainment, findings indicate that students do not appear to benefit from being taught in single-gender relative to mixed-gender classrooms in Language and STEM-related subjects. Young women benefitted from being taught in mixed-gender relative to single-gender classes for Non-STEM subjects. However, when prior ability is not controlled for, the intervention appears to be effective for all school subjects, highlighting the confounding influence of selective admissions. These findings suggest that gender-segregated classroom initiatives may not bolster students' grades. It is argued that studies that do not control for selection effects may tell us little about the effectiveness of such interventions on scholastic achievement.

Use of music during physical therapy intervention for an infant with Erb's palsy: a single-subject design.

PubMed

Rahlin, Mary; Cech, Donna; Rheault, Wendy; Stoecker, Judith

2007-01-01

Evidence supporting the use of music during pediatric physical therapy intervention is limited. The purpose of this single-subject design was to evaluate the effects of music on patient progress, the amount of crying during therapy, and parent satisfaction with physical therapy services. The subject was an infant girl with Erb's palsy who participated in this study from age 8 months to age 20 months. An A-B-A withdrawal single-subject design was used. The patient's progress was assessed by using the T.I.M.E. The amount of crying was documented in the Crying Log. A parent satisfaction questionnaire was administered three times over the course of the study. The subject's progress in the music intervention period increased on three of five primary subtests of the T.I.M.E. The amount of crying decreased and parent satisfaction increased when music was played during therapy. Music may be used by pediatric physical therapists to decrease the patient's crying, increase parent satisfaction, and possibly to increase the child's rate of progress. Further research conducted with a group of infants and toddlers may help generalize these findings to a wider patient population.

Single Stance Stability and Proprioceptive Control in Older Adults Living at Home: Gender and Age Differences

PubMed Central

Riva, Dario; Mamo, Carlo; Fanì, Mara; Saccavino, Patrizia; Rocca, Flavio; Momenté, Manuel; Fratta, Marianna

2013-01-01

In developed countries, falls in older people represent a rising problem. As effective prevention should start before the risk becomes evident, an early predictor is needed. Single stance instability would appear as a major risk factor. Aims of the study were to describe single stance stability, its sensory components, and their correlation with age and gender. A random sample of 597 older adults (319 men, 278 women) living at home, aged 65–84, was studied. Stability tests were performed with an electronic postural station. The single stance test showed the impairment of single stance stability in older individuals (75–84 yrs). The significant decline of stability in the older subjects may be explained by the impairment of proprioceptive control together with the decrease in compensatory visual stabilization and emergency responses. Younger subjects (65–74 yrs) exhibited better, but still inadequate, proprioceptive control with compensatory visual stabilization. Gender differences appeared in older subjects: women were significantly less stable than men. The measurement of the sensory components of single stance stability could aid in the early detection of a decay in antigravity movements many years before the risk of falling becomes evident. Adequate proprioceptive control could mitigate the effects of all other risks of falling. PMID:23984068

Discontinuation of orthokeratology on eyeball elongation (DOEE).

PubMed

Cho, P; Cheung, S W

2017-04-01

To evaluate and compare changes in axial elongation, over a 14-month period, in subjects who discontinued and then resumed ortho-k lens wear with those who continued to wear their lenses or spectacles following a 2-year myopia control study. This single masked, prospective study recruited subjects who had just completed a 2-year myopia control study. Ortho-k subjects were classified as Group OKc, in which subjects continued ortho-k lens wear for the duration of the study; or Group OKd in which subjects discontinued lens wear for seven months and wore single-vision spectacles (Phase I) and then resumed ortho-k lens wear for another seven months (Phase II). Spectacle-wearing control subjects from the initial myopia control study continued wearing spectacles as control subjects. Axial lengths were measured at scheduled visits using the IOLMaster. Thirteen, 16, and 15 Control, OKc, and OKd subjects, aged 8-14 years, respectively completed the study. Significant increase in axial elongation was found in OKd subjects only in Phase I but not in Phase II. On resuming lens wear, in Phase II, the rate of axial elongation was no longer significantly different from those of the Control or OKc subjects. Stopping ortho-k lens wear at or before the age of 14 years led to a more rapid increase in axial length; comparable to those wearing spectacles during the initial 2-year myopia control study, but greater than the Control and OKc group in this study. Axial elongation slowed again with resumed lens wear after six months. Copyright © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Anomalous weak values and the violation of a multiple-measurement Leggett-Garg inequality

NASA Astrophysics Data System (ADS)

Avella, Alessio; Piacentini, Fabrizio; Borsarelli, Michelangelo; Barbieri, Marco; Gramegna, Marco; Lussana, Rudi; Villa, Federica; Tosi, Alberto; Degiovanni, Ivo Pietro; Genovese, Marco

2017-11-01

Quantum mechanics presents peculiar properties that, on the one hand, have been the subject of several theoretical and experimental studies about its very foundations and, on the other hand, provide tools for developing new technologies, the so-called quantum technologies. The nonclassicality pointed out by Leggett-Garg inequalities has represented, with Bell inequalities, one of the most investigated subjects. In this article we study the connection of Leggett-Garg inequalities with a new emerging field of quantum measurement, the weak values in the case of a series of sequential measurements on a single object. In detail, we perform an experimental study of the four-time-correlator Leggett-Garg test, by exploiting single and sequential weak measurements performed on heralded single photons.

Impact of cognitive task on the posture of elderly subjects with Alzheimer's disease compared to healthy elderly subjects.

PubMed

Manckoundia, Patrick; Pfitzenmeyer, Pierre; d'Athis, Philippe; Dubost, Véronique; Mourey, France

2006-02-01

The aims of this study were to analyze the effects of cognitive task on static posture in Alzheimer's disease (AD) and in healthy elderly (HE) subjects and to evaluate whether those effects were greater in AD subjects than in HE subjects. We performed a posturographic analysis on 13 subjects with mild AD (mean age, 79.7+/-5.1 years, Mini-Mental State Examination scores between 18 and 23) and on 17 HE subjects (mean age, 78.5+/-4.4 years). After watching a video sequence, the subjects were asked to maintain a stable upright posture while standing on a force platform. Then, the postural sway was measured during the following two conditions: (1) quiet standing and (2) both standing and answering questions about the video sequence. We were interested in the center of pressure (CoP) area and path. For each group, the single task was compared to the dual task for the CoP area and path. We also compared the variability of both CoP area (variation of the CoP area between the single and the dual task) and path (variation of the CoP path between the single and the dual task) between the two groups. We showed that there was no significant difference between the single and the dual task in HE subjects concerning the CoP area and path, in contrast to the AD group, and that variability of both the CoP area and path were significantly greater in the AD subjects than in the HE subjects. This finding may contribute to the risk of falls in AD patients. Copyright (c) 2005 Movement Disorder Society.

Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of Ethanol, Diazepam, and Lithium.

PubMed

Chen, Grace; Nomikos, George G; Affinito, John; Zhao, Zhen

2016-09-01

Because the multimodal antidepressant vortioxetine is likely to be coadministered with other central nervous system (CNS)-active drugs, potential drug-drug interactions warrant examination. These studies evaluated whether there are pharmacokinetic and/or pharmacodynamic interactions between vortioxetine and ethanol, diazepam, or lithium. This series of phase I studies included healthy men and women (only men in the lithium study) aged 18-45 years. The ethanol study was a randomized, double-blind, two-parallel group, four-period crossover study in which subjects received a single dose of vortioxetine (20 or 40 mg) or placebo with or without ethanol, and the diazepam study was a randomized, double-blind, placebo-controlled, two-sequence, two-period crossover study in which subjects received a single dose of diazepam following multiple doses of vortioxetine 10 mg/day or placebo. These two studies evaluated the effect of coadministration on standardized psychomotor parameters and on selected pharmacokinetic parameters of each drug. The lithium study was a single-blind, single-sequence study evaluating the effect of multiple doses of vortioxetine 10 mg/day on the steady-state pharmacokinetics of lithium. Concomitant administration of vortioxetine and single doses of either ethanol or diazepam had no significant effect on the psychomotor performance of subjects compared with administration of ethanol or diazepam alone. Vortioxetine had no significant effect on the pharmacokinetics of ethanol, diazepam, or lithium, and ethanol had no significant effect on the pharmacokinetics of vortioxetine. Concomitant administration of these agents with vortioxetine was generally well tolerated, with no clinically relevant drug-drug pharmacokinetic or pharmacodynamic interactions identified.

Rating the methodological quality of single-subject designs and n-of-1 trials: introducing the Single-Case Experimental Design (SCED) Scale.

PubMed

Tate, Robyn L; McDonald, Skye; Perdices, Michael; Togher, Leanne; Schultz, Regina; Savage, Sharon

2008-08-01

Rating scales that assess methodological quality of clinical trials provide a means to critically appraise the literature. Scales are currently available to rate randomised and non-randomised controlled trials, but there are none that assess single-subject designs. The Single-Case Experimental Design (SCED) Scale was developed for this purpose and evaluated for reliability. Six clinical researchers who were trained and experienced in rating methodological quality of clinical trials developed the scale and participated in reliability studies. The SCED Scale is an 11-item rating scale for single-subject designs, of which 10 items are used to assess methodological quality and use of statistical analysis. The scale was developed and refined over a 3-year period. Content validity was addressed by identifying items to reduce the main sources of bias in single-case methodology as stipulated by authorities in the field, which were empirically tested against 85 published reports. Inter-rater reliability was assessed using a random sample of 20/312 single-subject reports archived in the Psychological Database of Brain Impairment Treatment Efficacy (PsycBITE). Inter-rater reliability for the total score was excellent, both for individual raters (overall ICC = 0.84; 95% confidence interval 0.73-0.92) and for consensus ratings between pairs of raters (overall ICC = 0.88; 95% confidence interval 0.78-0.95). Item reliability was fair to excellent for consensus ratings between pairs of raters (range k = 0.48 to 1.00). The results were replicated with two independent novice raters who were trained in the use of the scale (ICC = 0.88, 95% confidence interval 0.73-0.95). The SCED Scale thus provides a brief and valid evaluation of methodological quality of single-subject designs, with the total score demonstrating excellent inter-rater reliability using both individual and consensus ratings. Items from the scale can also be used as a checklist in the design, reporting and critical appraisal of single-subject designs, thereby assisting to improve standards of single-case methodology.

No differences in subjective knee function between surgical techniques of anterior cruciate ligament reconstruction at 2-year follow-up: a cohort study from the Swedish National Knee Ligament Register.

PubMed

Hamrin Senorski, Eric; Sundemo, David; Murawski, Christopher D; Alentorn-Geli, Eduard; Musahl, Volker; Fu, Freddie; Desai, Neel; Stålman, Anders; Samuelsson, Kristian

2017-12-01

The purpose of this study was to investigate how different techniques of single-bundle anterior cruciate ligament (ACL) reconstruction affect subjective knee function via the Knee injury and Osteoarthritis Outcome Score (KOOS) evaluation 2 years after surgery. It was hypothesized that the surgical techniques of single-bundle ACL reconstruction would result in equivalent results with respect to subjective knee function 2 years after surgery. This cohort study was based on data from the Swedish National Knee Ligament Register during the 10-year period of 1 January 2005 through 31 December 2014. Patients who underwent primary single-bundle ACL reconstruction with hamstrings tendon autograft were included. Details on surgical technique were collected using a web-based questionnaire comprised of essential AARSC items, including utilization of accessory medial portal drilling, anatomic tunnel placement, and visualization of insertion sites and landmarks. A repeated measures ANOVA and an additional linear mixed model analysis were used to investigate the effect of surgical technique on the KOOS 4 from the pre-operative period to 2-year follow-up. A total of 13,636 patients who had undergone single-bundle ACL reconstruction comprised the study group for this analysis. A repeated measures ANOVA determined that mean subjective knee function differed between the pre-operative time period and at 2-year follow-up (p < 0.001). No differences were found with respect to the interaction between KOOS 4 and surgical technique or gender. Additionally, the linear mixed model adjusted for age at reconstruction, gender, and concomitant injuries showed no difference between surgical techniques in KOOS 4 improvement from baseline to 2-year follow-up. However, KOOS 4 improved significantly in patients for all surgical techniques of single-bundle ACL reconstruction (p < 0.001); the largest improvement was seen between the pre-operative time period and at 1-year follow-up. Surgical techniques of primary single-bundle ACL reconstruction did not demonstrate differences in the improvement in baseline subjective knee function as measured with the KOOS 4 during the first 2 years after surgery. However, subjective knee function improved from pre-operative baseline to 2-year follow-up independently of surgical technique.

Effect of a Single Musical Cakra Activation Manoeuvre on Body Temperature: An Exploratory Study

PubMed Central

Sumathy, Sundar; Parmar, Parin N

2016-01-01

Cakra activation/balancing and music therapy are part of the traditional Indian healing system. Little is known about effect of musical (vocal) technique of cakra activation on body temperature. We conducted a single-session exploratory study to evaluate effects of a single musical (vocal) cakra activation manoeuvre on body temperature in controlled settings. Seven healthy adults performed a single musical (vocal) cakra activation manoeuvre for approximately 12 minutes in controlled environmental conditions. Pre- and post-manoeuvre body temperatures were recorded with a clinical mercury thermometer. After a single manoeuvre, increase in body temperature was recorded in all seven subjects. The range of increase in body temperature was from 0.2°F to 1.4°F; with mean temperature rise being 0.5°F and median temperature rise being 0.4°F. We conclude that a single session of musical (vocal) technique of cakra activation elevated body temperatures in all 7 subjects. Further research is required to study effects of various cakra activation techniques on body temperature and other physiological parameters. PMID:28182030

Effect of a Single Musical Cakra Activation Manoeuvre on Body Temperature: An Exploratory Study.

PubMed

Sumathy, Sundar; Parmar, Parin N

2016-01-01

Cakra activation/balancing and music therapy are part of the traditional Indian healing system. Little is known about effect of musical (vocal) technique of cakra activation on body temperature. We conducted a single-session exploratory study to evaluate effects of a single musical (vocal) cakra activation manoeuvre on body temperature in controlled settings. Seven healthy adults performed a single musical (vocal) cakra activation manoeuvre for approximately 12 minutes in controlled environmental conditions. Pre- and post-manoeuvre body temperatures were recorded with a clinical mercury thermometer. After a single manoeuvre, increase in body temperature was recorded in all seven subjects. The range of increase in body temperature was from 0.2°F to 1.4°F; with mean temperature rise being 0.5°F and median temperature rise being 0.4°F. We conclude that a single session of musical (vocal) technique of cakra activation elevated body temperatures in all 7 subjects. Further research is required to study effects of various cakra activation techniques on body temperature and other physiological parameters.

Postpolio Syndrome: Using a Single Case Study

ERIC Educational Resources Information Center

Obringer, S. John; Elrod, G. Franklin

2004-01-01

The purpose of this study was to identify the major characteristics of postpolio syndrome (PPS), investigate physical and psychological limitations, and comprehensively review current medical interventions through a single subject design. The study addresses the symptoms and characteristics, the effect on life style, and the current recommended…

Single-trial classification of auditory event-related potentials elicited by stimuli from different spatial directions.

PubMed

Cabrera, Alvaro Fuentes; Hoffmann, Pablo Faundez

2010-01-01

This study is focused on the single-trial classification of auditory event-related potentials elicited by sound stimuli from different spatial directions. Five naϊve subjects were asked to localize a sound stimulus reproduced over one of 8 loudspeakers placed in a circular array, equally spaced by 45°. The subject was seating in the center of the circular array. Due to the complexity of an eight classes classification, our approach consisted on feeding our classifier with two classes, or spatial directions, at the time. The seven chosen pairs were 0°, which was the loudspeaker directly in front of the subject, with all the other seven directions. The discrete wavelet transform was used to extract features in the time-frequency domain and a support vector machine performed the classification procedure. The average accuracy over all subjects and all pair of spatial directions was 76.5%, σ = 3.6. The results of this study provide evidence that the direction of a sound is encoded in single-trial auditory event-related potentials.

Assessment of drug-drug interaction potential between ceritinib and proton pump inhibitors in healthy subjects and in patients with ALK-positive non-small cell lung cancer.

PubMed

Lau, Yvonne Y; Gu, Wen; Lin, Tiffany; Viraswami-Appanna, Kalyanee; Cai, Can; Scott, Jeffrey W; Shi, Michael

2017-06-01

The impact of proton pump inhibitors (PPIs) on the pharmacokinetics (PK) and efficacy of ceritinib was evaluated. A healthy subject drug-drug interaction (DDI) study was conducted to assess the effect of esomeprazole on the PK of a single 750 mg dose of ceritinib. To further investigate the impact of PPIs on the PK and efficacy of ceritinib in ALK-positive cancer patients, two subgroup analyses were performed. Analysis 1 evaluated ceritinib steady-state trough concentration (C trough,ss ) and overall response rate (ORR) by concomitant use of PPIs in patients from the ASCEND-1, -2, and -3 studies; analysis 2 evaluated ceritinib single-dose and steady-state AUC 0-24h and C max by concomitant PPI use in patients from ASCEND-1 using a definition of PPI usage similar to that used in the healthy subject study. In the healthy subject study, co-administration of a single 750 mg dose of ceritinib with esomeprazole 40 mg for 6 days decreased ceritinib AUC 0-∞ by 76% and C max by 79%. However, based on subgroup analysis 1, patients had similar C trough,ss and ORR regardless of concomitant PPI usage. Based on analysis 2, co-administration of a single 750 mg ceritinib dose with PPIs for 6 days in patients suggested less effect on ceritinib exposure than that observed in healthy subjects as AUC 0-24h decreased by 30% and C max decreased by 25%. No clinically meaningful effect on steady-state exposure was observed after daily dosing. Long-term administration of ceritinib with PPIs does not adversely affect the PK and efficacy of ceritinib in ALK-positive cancer patients.

Effects of lithium carbonate on performance and biomedical functions.

DOT National Transportation Integrated Search

1977-07-01

The effects of a single 600-mg dose of lithium carbonate were evaluated in a study of 15 healthy, normal male subjects. Subjects were studied, on two occasions, by utilizing a double-blind design--once receiving the lithium carbonate and once receivi...

Reading Comprehension Interventions for Students with Autism Spectrum Disorders: A Synthesis of Research

ERIC Educational Resources Information Center

El Zein, Farah; Solis, Michael; Vaughn, Sharon; McCulley, Lisa

2014-01-01

The authors synthesized reading intervention studies conducted between 1980 and 2012 with K-12 students identified with autism spectrum disorders (ASD). Nine single-subject design studies, one quasi-experimental study, and two single-group design studies met the criteria for inclusion. Findings from the studies indicate that modifying…

Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis.

PubMed

Wang, Xiaoli; Tirucherai, Giridhar; Marbury, Thomas C; Wang, Jessie; Chang, Ming; Zhang, Donglu; Song, Yan; Pursley, Janice; Boyd, Rebecca A; Frost, Charles

2016-05-01

An open-label, parallel-group, single-dose study was conducted to assess the pharmacokinetics, pharmacodynamics, and safety of apixaban in 8 subjects with end-stage renal disease (ESRD) on hemodialysis compared with 8 subjects with normal renal function. A single oral 5-mg dose of apixaban was administered once to healthy subjects and twice to subjects with ESRD, separated by ≥7 days: 2 hours before (on hemodialysis) and immediately after a 4-hour hemodialysis session (off hemodialysis). Blood samples were collected for determination of apixaban pharmacokinetic parameters, measures of clotting (prothrombin time, international normalized ratio, activated partial thromboplastin time), and anti-factor Xa (FXa) activity. Compared with healthy subjects, apixaban Cmax and AUCinf were 10% lower and 36% higher, respectively, in subjects with ESRD off hemodialysis. Hemodialysis in subjects with ESRD was associated with reductions in apixaban Cmax and AUCinf of 13% and 14%, respectively. The percent change from baseline in clotting measures was similar in healthy subjects and subjects with ESRD, and differences in anti-FXa activity were similar to differences in apixaban concentration. A single 5-mg oral dose of apixaban was well tolerated in both groups. In conclusion, ESRD resulted in a modest increase (36%) in apixaban AUC and no increase in Cmax , and hemodialysis had a limited impact on apixaban clearance. © 2015, The American College of Clinical Pharmacology.

The pharmacokinetic and safety profiles of blonanserin in healthy Chinese volunteers after single fasting doses and single and multiple postprandial doses.

PubMed

Chen, Xia; Wang, Hongyun; Jiang, Ji; Chen, Rui; Zhou, Ying; Zhong, Wen; Liu, Hongzhong; Hu, Pei

2014-03-01

Blonanserin is a novel atypical antipsychotic drug acting as a mixed serotonin 5-HT2A and dopamine D2 receptor antagonist. This study investigated the pharmacokinetics and safety of blonanserin in healthy Chinese males. This was an open-label trial with two parts. Twenty-four subjects were enrolled in part A to receive a single fasting dose of 4 or 8 mg blonanserin (each n = 12); part B recruited 12 subjects and administered single and sequentially twice-daily multiple postprandial doses of blonanserin 2 mg for 9 days. Serial blood samples were taken for the bioassay of plasma blonanserin and its four metabolites during both sub-studies. Safety was assessed, including repeat measurements of fasting serum prolactin, insulin, triglyceride and cholesterol. Blonanserin was rapidly absorbed, accompanied with immediate plasma concentration elevation of the N-oxide form (M2) and gradual rises of the N-deethylated form (M1) and its downstream metabolites. The mean elimination half-life of blonanserin (7.7-11.9 h) was much longer than that of M2 (1.2-1.3 h) but shorter than that of M1 (26.4-31.4 h) after single fasting doses. After food intake, a single dose of 2 mg blonanserin resulted in total exposure and peak concentrations of blonanserin similar to those observed with a single fasting dose of blonanserin 4 mg. Moreover, the relationship of metabolite over parent compound ratio was different between M1 and M2 after single and multiple postprandial administrations (single dose vs multiple dose: M1, 0.33 vs 0.75; M2, 0.13 vs 0.067). Mild but transient increases of prolactin, insulin and triglyceride were observed. The pharmacokinetics of blonanserin in Chinese subjects were similar to those observed in Japanese subjects. This study suggested that food intake not only increases the bioavailability of blonanserin but differently affects the pharmacokinetics of its metabolites as well. The drug was safe and well tolerated in healthy Chinese males.

No auditory experience, no tinnitus: Lessons from subjects with congenital- and acquired single-sided deafness.

PubMed

Lee, Sang-Yeon; Nam, Dong Woo; Koo, Ja-Won; De Ridder, Dirk; Vanneste, Sven; Song, Jae-Jin

2017-10-01

Recent studies have adopted the Bayesian brain model to explain the generation of tinnitus in subjects with auditory deafferentation. That is, as the human brain works in a Bayesian manner to reduce environmental uncertainty, missing auditory information due to hearing loss may cause auditory phantom percepts, i.e., tinnitus. This type of deafferentation-induced auditory phantom percept should be preceded by auditory experience because the fill-in phenomenon, namely tinnitus, is based upon auditory prediction and the resultant prediction error. For example, a recent animal study observed the absence of tinnitus in cats with congenital single-sided deafness (SSD; Eggermont and Kral, Hear Res 2016). However, no human studies have investigated the presence and characteristics of tinnitus in subjects with congenital SSD. Thus, the present study sought to reveal differences in the generation of tinnitus between subjects with congenital SSD and those with acquired SSD to evaluate the replicability of previous animal studies. This study enrolled 20 subjects with congenital SSD and 44 subjects with acquired SSD and examined the presence and characteristics of tinnitus in the groups. None of the 20 subjects with congenital SSD perceived tinnitus on the affected side, whereas 30 of 44 subjects with acquired SSD experienced tinnitus on the affected side. Additionally, there were significant positive correlations between tinnitus characteristics and the audiometric characteristics of the SSD. In accordance with the findings of the recent animal study, tinnitus was absent in subjects with congenital SSD, but relatively frequent in subjects with acquired SSD, which suggests that the development of tinnitus should be preceded by auditory experience. In other words, subjects with profound congenital peripheral deafferentation do not develop auditory phantom percepts because no auditory predictions are available from the Bayesian brain. Copyright © 2017 Elsevier B.V. All rights reserved.

Increasing motivation in robot-aided arm rehabilitation with competitive and cooperative gameplay.

PubMed

Novak, Domen; Nagle, Aniket; Keller, Urs; Riener, Robert

2014-04-16

Several strategies have been proposed to improve patient motivation and exercise intensity during robot-aided stroke rehabilitation. One relatively unexplored possibility is two-player gameplay, allowing subjects to compete or cooperate with each other to achieve a common goal. In order to explore the potential of such games, we designed a two-player game played using two ARMin arm rehabilitation robots. The game was an air-hockey task displayed on a computer monitor and controlled using shoulder movements in the ARMin robot. Three game modes were tested: single-player (competing against computer), competitive (competing against human), and cooperative (cooperating with human against computer). All modes were played by 30 unimpaired subjects and 8 impaired chronic stroke subjects. The subjects filled out the Intrinsic Motivation Inventory questionnaire after each game mode, as well as a final questionnaire about game preferences and their personality. Nearly all unimpaired subjects preferred playing the two-player game modes to the single-player one, as they enjoyed talking and interacting with another person. However, there were two distinct player groups: one liked the competitive mode but not the cooperative mode while the other liked the cooperative but not the competitive mode. Unimpaired subjects who liked the competitive mode also put significantly more effort into it than into the other modes. Results from impaired subjects were similar, with even impaired subjects over 60 years old enjoying competitive gameplay. The subjects' personalities roughly predicted which mode they would prefer, which was especially evident in a poorly-matched impaired pair that preferred the single-player mode. Results indicate great potential for two-player rehabilitation games, in the form of greater enjoyment as well as potentially more intensive exercise compared to single-player games. However, the right game type needs to be chosen for each subject depending on skill and personality, along with selecting an appropriate co-player. Further studies with patients that are currently enrolled in rehabilitation programs are recommended, and the subjective measures used in our study should be augmented with objective measures such as electromyography.

Single visit rabies pre-exposure priming induces a robust anamnestic antibody response after simulated post-exposure vaccination: results of a dose-finding study.

PubMed

Jonker, Emile F F; Visser, Leonardus G

2017-09-01

The current standard 3-dose intramuscular rabies PrEP schedule suffers from a number of disadvantages that severely limit accessibility and availability. The cost of is often prohibitive, it requires 3 visits to the clinic, and there are regular vaccine shortages. Volunteers ( N  = 30) were randomly assigned to 4 study arms: 1 standard dose intramuscular (IM) dose of PVRV (purified Vero cell rabies vaccine, Verorab), and 1/5th, 2/5th or 3/5th- fractional intradermal (ID) dose of PVRV in a single visit. All subjects received a simulated rabies post-exposure prophylaxis (D0, D3) 1 year later. Rabies virus neutralizing antibodies (RVNA) were determined by virus neutralization microtest (FAVN) on D0, D7, D28, Y1 and Y1 + D7. 28 out of 30 subjects (93%) seroconverted 1 month after primary vaccination; 1 subject in the 1-dose IM arm and 1 in the 1/5th-fractional dose ID arm did not. After 1 year, 22 out of 30 subjects (73%) no longer had RVNA above 0.5 IU/ml, with no discernible difference between study groups. After 1 year, all 30 subjects mounted a booster response within 7 days after simulated PEP, with the highest titers found in the single dose IM group ( P  < 0.03). This dose finding study demonstrates that priming with a single dose of rabies vaccine was sufficient to induce an adequate anamnestic antibody response to rabies PEP in all subjects 1 year later, even in those in whom the RVNA threshold of 0.5 IU/ml was not reached after priming. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer's disease

PubMed Central

Jia, Jing-ying; Zhao, Qian-hua; Liu, Yun; Gui, Yu-zhou; Liu, Gang-yi; Zhu, Da-yuan; Yu, Chen; Hong, Zhen

2013-01-01

Aim: Huperzine A isolated from the Chinese herb Huperzia serrata (Thunb) Trev is a novel reversible and selective AChE inhibitor. The aim of this study was to evaluate the pharmacokinetics and tolerance of single and multiple doses of ZT-1, a novel analogue of huperzine A, in healthy Chinese subjects. Methods: This was a double-blinded, placebo-controlled, randomized, single- and multiple-dose study. For the single-dose study, 9 subjects were randomly divided into 3 groups receiving ZT-1 (0.5, 0.75 or 1 mg, po) according to a Three-way Latin Square Design. For the multiple-dose study, 9 subjects receiving ZT-1 (0.75 mg/d, po) for 8 consecutive days. In the tolerance study, 40 subjects were randomly divided into 5 groups receiving a single dose of ZT-1 (0.5, 0.75, 1, 1.25 or 1.5 mg, po). Plasma and urine concentrations of ZT-1 and Hup A were determined using LC-MS/MS. Pharmacokinetic parameters, including Cmax, AUC0–72 h and AUC0–∞ were calculated. Tolerance assessments were conducted throughout the study. Results: ZT-1 was rapidly absorbed and converted into huperzine A, thus the plasma and urine concentrations of ZT-1 were below the limit of quantification (<0.05 ng/mL). After single-dose administration of ZT-1, the mean tmax of huperzine A was 0.76–0.82 h; the AUC0–72 h and Cmax of huperzine A showed approximately dose-proportional increase over the dose range of 0.5–1 mg. After the multiple-dose administration of ZT-1, a steady-state level of huperzine A was achieved within 2 d. No serious adverse events were observed. Conclusion: ZT-1 is a pro-drug that is rapidly absorbed and converted into huperzine A, and ZT-1 is well tolerated in healthy Chinese volunteers. PMID:23624756

Girls' Participation in Physics in Single Sex Classes in Mixed Schools in Relation to Confidence and Achievement.

ERIC Educational Resources Information Center

Gillibrand, Eileen; Robinson, Peter; Brawn, Richard; Osborn, Albert

1999-01-01

Reports the findings from a three-year longitudinal case study of two single-sex General Certificate of Secondary Education (GCSE) physics classes in a mixed comprehensive school in England. Results indicate that girls who elected to study physics in single-sex classes gain confidence in the subject. This gain in confidence is associated with…

Interrater reliability levels of multiple clinical examiners in the evaluation of a schizophrenic patient: quality of life, level of functioning, and neuropsychological symptomatology.

PubMed

Cicchetti, D V; Rosenheck, R; Showalter, D; Charney, D; Cramer, J

1999-05-01

Sir Ronald Fisher used a single-subject design to derive the concepts of appropriate research design, randomization, sensitivity, and tests of statistical significance. The seminal work of Broca demonstrated that valid and generalizable findings can and have emerged from studies of a single patient in neuropsychology. In order to assess the reliability and/or validity of any clinical phenomena that derive from single subject research, it becomes necessary to apply appropriate biostatistical methodology. The authors develop just such an approach and apply it successfully to the evaluation of the functioning, quality of life, and neuropsychological symptomatology of a single schizophrenic patient.

Acute effects of unilateral whole body vibration training on single leg vertical jump height and symmetry in healthy men.

PubMed

Shin, Seungho; Lee, Kyeongjin; Song, Changho

2015-12-01

[Purpose] The aim of the present study was to investigate the acute effects of unilateral whole body vibration training on height and symmetry of the single leg vertical jump in healthy men. [Subjects] Thirty males with no history of lower limb dysfunction participated in this study. [Methods] The participants were randomly allocated to one of three groups: the unilateral vibratory stimulation group (n=10), bilateral vibratory stimulation group (n=10), and, no vibratory stimulation group (n=10). The subjects in the unilateral and bilateral stimulation groups participated in one session of whole body vibration training at 26 Hz for 3 min. The no vibratory stimulation group subjects underwent the same training for 3 min without whole body vibration. All participants performed the single leg vertical jump for each lower limb, to account for the strong and weak sides. The single leg vertical jump height and symmetry were measured before and after the intervention. [Results] The single leg vertical jump height of the weak lower limb significantly improved in the unilateral vibratory stimulation group, but not in the other groups. The single leg vertical jump height of the strong lower limb significantly improved in the bilateral vibratory stimulation group, but not in the other groups. The single leg vertical jump symmetry significantly improved in the unilateral vibratory stimulation group, but not in the other groups. [Conclusion] Therefore, the present study found that the effects of whole body vibration training were different depending on the type of application. To improve the single leg vertical jump height in the weak lower limbs as well as limb symmetry, unilateral vibratory stimulation might be more desirable.

Pharmacokinetics, Safety, and Tolerability of a Single 500-mg or 1000-mg Intravenous Dose of Dalbavancin in Healthy Japanese Subjects.

PubMed

Scoble, Patrick J; Owens, Robert C; Puttagunta, Sailaja; Yen, Mark; Dunne, Michael W

2015-12-01

Dalbavancin is a novel, once-weekly glycopeptide antibiotic approved for treatment of acute bacterial skin infections. Given the importance of understanding any pharmacokinetic variability across different patient populations, a double-blind, placebo-controlled study was conducted to evaluate the pharmacokinetics, safety, and tolerability of a single 500-mg and a single 1000-mg intravenous dose of dalbavancin in healthy Japanese subjects. Ten subjects received intravenous dalbavancin 1000 mg, five subjects received intravenous dalbavancin 500 mg, and three subjects received intravenous placebo. After a single infusion of dalbavancin, the maximal plasma concentration (C max) and area under the plasma concentration-time curve (AUC) increased in a proportional manner from 500 mg to 1000 mg (C max: 157 μg/ml and 299 μg/ml; AUClast: 10,850 μg·h/ml and 22,679 μg·h/ml, on the 500-mg and 1000-mg regimens, respectively) with low inter-subject variability. The mean terminal phase half-life (t 1/2) was 204 and 193 h after the 500-mg and 1000-mg dose, respectively. Clearance and volume of distribution were similar for the two dose concentrations. Treatment-emergent adverse events reported were considered to be of mild intensity. There were no relevant changes in laboratory values or vital signs over time in subjects in either treatment group. Overall, dalbavancin 500 mg and dalbavancin 1000 mg, administered as a single 30-min infusion, was well tolerated in this population and resulted in plasma exposures similar to those in non-Asians.

Scatter characterization and correction for simultaneous multiple small-animal PET imaging.

PubMed

Prasad, Rameshwar; Zaidi, Habib

2014-04-01

The rapid growth and usage of small-animal positron emission tomography (PET) in molecular imaging research has led to increased demand on PET scanner's time. One potential solution to increase throughput is to scan multiple rodents simultaneously. However, this is achieved at the expense of deterioration of image quality and loss of quantitative accuracy owing to enhanced effects of photon attenuation and Compton scattering. The purpose of this work is, first, to characterize the magnitude and spatial distribution of the scatter component in small-animal PET imaging when scanning single and multiple rodents simultaneously and, second, to assess the relevance and evaluate the performance of scatter correction under similar conditions. The LabPET™-8 scanner was modelled as realistically as possible using Geant4 Application for Tomographic Emission Monte Carlo simulation platform. Monte Carlo simulations allow the separation of unscattered and scattered coincidences and as such enable detailed assessment of the scatter component and its origin. Simple shape-based and more realistic voxel-based phantoms were used to simulate single and multiple PET imaging studies. The modelled scatter component using the single-scatter simulation technique was compared to Monte Carlo simulation results. PET images were also corrected for attenuation and the combined effect of attenuation and scatter on single and multiple small-animal PET imaging evaluated in terms of image quality and quantitative accuracy. A good agreement was observed between calculated and Monte Carlo simulated scatter profiles for single- and multiple-subject imaging. In the LabPET™-8 scanner, the detector covering material (kovar) contributed the maximum amount of scatter events while the scatter contribution due to lead shielding is negligible. The out-of field-of-view (FOV) scatter fraction (SF) is 1.70, 0.76, and 0.11% for lower energy thresholds of 250, 350, and 400 keV, respectively. The increase in SF ranged between 25 and 64% when imaging multiple subjects (three to five) of different size simultaneously in comparison to imaging a single subject. The spill-over ratio (SOR) increases with increasing the number of subjects in the FOV. Scatter correction improved the SOR for both water and air cold compartments of single and multiple imaging studies. The recovery coefficients for different body parts of the mouse whole-body and rat whole-body anatomical models were improved for multiple imaging studies following scatter correction. The magnitude and spatial distribution of the scatter component in small-animal PET imaging of single and multiple subjects simultaneously were characterized, and its impact was evaluated in different situations. Scatter correction improves PET image quality and quantitative accuracy for single rat and simultaneous multiple mice and rat imaging studies, whereas its impact is insignificant in single mouse imaging.

Manifestation of Coronary Atherosclerosis in Klang Valley, Malaysia: An Autopsy Study

PubMed Central

Rahimi, Razuin; Singh, Mansharan Kaur Chainchel; Noor, Norizal Mohd; Omar, Effat; Noor, Shahidan Md; Mahmood, Mohd Shah; Abdullah, Nurliza; Nawawi, Hapizah Mohd

2018-01-01

Aims: The present study aimed to determine the epidemiological aspects of medico-legal autopsies and manifestation of coronary atherosclerosis. Methods: This was a cross sectional study involving 222 cases recruited from National Institute of Forensic Medicine (NIFM) Hospital Kuala Lumpur (HKL) and Department of Forensic Medicine Hospital Sungai Buloh (HSgB) for a period of 15 months, from December 2012 to April 2014. Sociodemographic and autopsy findings, including the cause and manner of death were documented. Results: Male and female subjects aged 18–70 years were recruited. Males contributed to 86% of the total subjects and comprised 61% of young adults. Road traffic accidents were the primary cause of death, contributing almost 50% of the subjects. One third of the cases comprised of death due to natural causes, wherein almost 75% of the subjects within this category succumbed to sudden cardiac death. Coronary artery disease (CAD) contributed to 60% of the sudden cardiac death (SCD). Single and double-vessel diseases were the most common pattern of atherosclerosis. In almost 80% of CAD cases, atherosclerosis affected the left anterior descending artery (LAD). Conclusion: Cardiovascular diseases were the most significant natural cause of sudden death with a staggering figure of 75%. CAD was the single most commonly encountered pathology within the SCD. Most cases presented with single and double-vessel diseases, observed in all subjects, as well as the young adult population. PMID:29118310

Pharmacokinetics and bioequivalence of two strontium ranelate formulations after single oral administration in healthy Chinese subjects.

PubMed

Zhang, Dan; Du, Aihua; Wang, Xiaolin; Zhang, Lina; Yang, Man; Ma, Jingyi; Deng, Ming; Liu, Huichen

2018-05-08

Pharmacokinetics of exogenous strontium (Sr) and bioequivalence of a new oral formulation of strontium ranelate compared with the brand-name drug in healthy Chinese subjects was evaluated. A balanced, randomized, single-dose, two-treatment parallel study was conducted in 36 healthy Chinese subjects. Subjects were randomly allocated into two groups of 18 to receive a single oral dose of test formulation and reference formulation under a fasting state, respectively. Blood samples were collected at 19 designated time points up to 240-h post-dose. Serum concentrations of Sr were quantified by ICP-MS. A total of 36 subjects were enrolled and completed the study. Nine mild adverse events in 6 subjects were reported. The C max , AUC 0-72 h , AUC 0- t , and AUC 0-∞ of test and reference formulations shown as mean ± SD were 6.97 ± 1.78 and 6.78 ± 1.80 µg/mL, 199 ± 51 and 187 ± 38 µg·h/mL, 303 ± 89 and 278 ± 54 µg·h/mL, and 337 ± 109 and 305 ± 60 µg·h/mL, respectively. Two formulations were bioequivalent, and both were generally well tolerated.

Atomoxetine pharmacokinetics in healthy Chinese subjects and effect of the CYP2D6*10 allele.

PubMed

Cui, Yi M; Teng, Choo H; Pan, Alan X; Yuen, Eunice; Yeo, Kwee P; Zhou, Ying; Zhao, Xia; Long, Amanda J; Bangs, Mark E; Wise, Stephen D

2007-10-01

To characterize atomoxetine pharmacokinetics, explore the effect of the homozygous CYP2D6*10 genotype on atomoxetine pharmacokinetics and evaluate the tolerability of atomoxetine, in healthy Chinese subjects. Twenty-four subjects, all CYP2D6 extensive metabolizers (EM), were randomized to receive atomoxetine (40 mg qd for 3 days, then 80 mg qd for 7 days) or matching placebo (2 : 1 ratio) in a double-blind fashion. Atomoxetine serum concentrations were measured following single (40 mg) and multiple (80 mg) doses. Adverse events, clinical safety laboratory data and vital signs were assessed during the study. Atomoxetine was rapidly absorbed with median time to maximum serum concentrations of approximately 1.5 h after single and multiple doses. Atomoxetine concentrations appeared to decrease monoexponentially with a mean apparent terminal half-life (t(1/2)) of approximately 4 h. The apparent clearance, apparent volume of distribution and t(1/2) following single and multiple doses were similar, suggesting linear pharmacokinetics with respect to time. Homozygous CYP2D6*10 subjects had 50% lower clearances compared with other EM subjects, resulting in twofold higher mean exposures. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. The pharmacokinetics of atomoxetine in healthy Chinese subjects appears comparable to other ethnic populations. Multiple dosing of 80 mg qd atomoxetine was well tolerated in this study.

Three-year clinical outcome of single implant-retained mandibular overdentures--results of preliminary prospective study.

PubMed

Harder, Sönke; Wolfart, Stefan; Egert, Christopher; Kern, Matthias

2011-10-01

The aim of this preliminary prospective study was to evaluate the clinical outcome, the oral health-related quality of life (OHRQoL), and the subjective chewing ability of patients with mandibular complete dentures retained by a single implant placed in the mandible midline. Patients wearing complete dentures were treated with a single implant in the mandible, followed by relining of the dentures and incorporation of ball attachments for implant retention. Implant outcome, prosthodontic maintenance, subjective chewing ability, and the oral health impact profile of the patients were assessed at baseline and at four weeks after connecting the denture and implant. Eleven patients were enrolled in this investigation, and the mean observation period was 43.4 months (minimum period: 35, maximum period: 52 months). No implants were lost during observation period, but four dentures needed repair because of the fracture of the denture base in the midline area. A significant improvement was observed in the OHRQoL of the patients after the attachment of the mandibular dentures with a single midline implant. Furthermore, the subjective chewing ability of the patients was significantly improved after implant connection. Within the limitations of this preliminary prospective clinical study, single implant-supported mandibular overdentures were a successful treatment option for older edentulous patients who showed improvements in their OHRQoL and chewing ability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pharmacokinetic study of single- and multiple-dosing with metolazone tablets in healthy Chinese population.

PubMed

Li, Xueqing; Wang, Rutao; Liu, Yang; Liu, Yun; Zheng, Heng; Feng, Yabo; Zhao, Na; Geng, Hongbin; Zhang, Wanzhi; Wen, Aidong

2017-11-16

Metolazone is a diuretic, saluretic and antihypertensive chemical compound from the quinazoline category that possesses medicinal features similar to those of other thiazide diuretic drugs. However, the pharmacokinetics of metolazone in the Chinese population has rarely been studied. This study aimed to examine the pharmacokinetic characteristics, safety characteristic, and tolerability of metolazone in healthy Chinese subjects after single and multiple doses taken orally as well as the effects that food and gender have on oral metolazone pharmacokinetic parameters. An open-label, randomized, and single- and multiple-dosing investigation was performed in healthy Chinese subjects. The investigation included 3 study groups: the 0.5 mg, 1 mg and 2 mg dose groups were the single-dose study groups in the first stage. Eligible volunteers were randomly and orally administered a single 0.5 mg, 1 mg, or 2 mg metolazone tablet. The 0.5 mg dose group was also part of the multiple-dose study group, and the 1 mg dose group was the food-effect study group in the second stage. Human plasma samples were gathered pre-dosing and up to 48 h after dosing. The human plasma sample concentration of metolazone was quantified using a validated liquid chromatography tandem mass spectrometry method. Pharmacokinetic data were calculated by a noncompartmental analysis method using WinNonlin version 6.4. Tolerability was evaluated based on adverse events, medical examination, 12-lead ECG, and other clinical laboratory exams. Thirty eligible subjects (15 men and 15 women) were registered in our investigation and completed all of the study stages. The AUC and C max showed dose proportionality after a single dose based on the linear-regression analysis. A comparison of the pharmacokinetic data revealed that the differences between the male and female groups were not statistically significant. The t max of metolazone was increased by approximately 100% in the fed condition. Metolazone was well tolerated at the tested dose, and no adverse effects were observed. Single dosing with 0.5 mg, 1 mg, or 2 mg metolazone yielded linear plasma pharmacokinetic properties in healthy Chinese subjects. Multiple oral doses of metolazone did not display significantly different distributions or elimination characteristics from those observed for a single dose. Gender factors did not appear to influence the pharmacokinetic parameter variation of metolazone. The t max of metolazone increased in the fed condition. Metolazone was well tolerated at the tested dose in this study. This investigation is retrospectively registered at chictr.org.cn (ChiCTR-IIR-17012929, October 09 2017).

Ibrutinib does not prolong the corrected QT interval in healthy subjects: results from a thorough QT study.

PubMed

de Jong, Jan; Hellemans, Peter; Jiao, James Juhui; Huang, Yuhan; Mesens, Sofie; Sukbuntherng, Juthamas; Ouellet, Daniele

2017-12-01

Ibrutinib is an orally administered, irreversible Bruton's tyrosine kinase inhibitor for treatment of B-cell malignancy. This study evaluated the effects of single-dose ibrutinib at therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects. Part 1 used an open-label, two-period sequential design to assess the safety and pharmacokinetics of single doses of ibrutinib 840 and 1680 mg in eight subjects. Part 2 was a randomized, placebo- and positive (moxifloxacin)-controlled, double-blind, single dose, four-way cross-over study to assess the effect of ibrutinib (840 and 1680 mg) on QT/QTc interval. 64 healthy subjects were planned to be enrolled. Baseline-adjusted QT (QTc) intervals for ibrutinib and moxifloxacin (assay sensitivity) were compared to placebo using linear mixed-effect model. A concentration-QTc analysis was also conducted. No clinically relevant safety observations were noted in Part 1. During Part 2, one subject experienced Grade 4 ALT/AST elevations with ibrutinib 1680 mg, leading to study termination and limiting the enrollment to 20 subjects. Ibrutinib demonstrated dose-dependent increases in exposure. The upper bounds of the 90% CIs for the mean difference in change from baseline in QTc between ibrutinib and placebo were < 10 ms at all timepoints and at supratherapeutic C max . Moxifloxacin showed the anticipated QTc effect, confirming assay sensitivity despite the early study termination. Ibrutinib caused a concentration-dependent mild shortening of QTc and mild PR prolongation, but these effects were not considered clinically meaningful. Therapeutic and supratherapeutic concentrations of ibrutinib do not prolong the QTc interval. CLINICALTRIALS.GOV: NCT02271438.

A hierarchical model for probabilistic independent component analysis of multi-subject fMRI studies

PubMed Central

Tang, Li

2014-01-01

Summary An important goal in fMRI studies is to decompose the observed series of brain images to identify and characterize underlying brain functional networks. Independent component analysis (ICA) has been shown to be a powerful computational tool for this purpose. Classic ICA has been successfully applied to single-subject fMRI data. The extension of ICA to group inferences in neuroimaging studies, however, is challenging due to the unavailability of a pre-specified group design matrix. Existing group ICA methods generally concatenate observed fMRI data across subjects on the temporal domain and then decompose multi-subject data in a similar manner to single-subject ICA. The major limitation of existing methods is that they ignore between-subject variability in spatial distributions of brain functional networks in group ICA. In this paper, we propose a new hierarchical probabilistic group ICA method to formally model subject-specific effects in both temporal and spatial domains when decomposing multi-subject fMRI data. The proposed method provides model-based estimation of brain functional networks at both the population and subject level. An important advantage of the hierarchical model is that it provides a formal statistical framework to investigate similarities and differences in brain functional networks across subjects, e.g., subjects with mental disorders or neurodegenerative diseases such as Parkinson’s as compared to normal subjects. We develop an EM algorithm for model estimation where both the E-step and M-step have explicit forms. We compare the performance of the proposed hierarchical model with that of two popular group ICA methods via simulation studies. We illustrate our method with application to an fMRI study of Zen meditation. PMID:24033125

Pharmacokinetics and pharmacodynamics of single and multiple doses of the glucagon receptor antagonist LGD-6972 in healthy subjects and subjects with type 2 diabetes mellitus.

PubMed

Vajda, Eric G; Logan, Douglas; Lasseter, Kenneth; Armas, Danielle; Plotkin, Diane J; Pipkin, J D; Li, Yong-Xi; Zhou, Rong; Klein, David; Wei, Xiaoxiong; Dilzer, Stacy; Zhi, Lin; Marschke, Keith B

2017-01-01

To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of a novel, oral glucagon receptor antagonist, LGD-6972, in healthy subjects and subjects with type 2 diabetes (T2DM). In the single ascending dose study, LGD-6972 (2-480 mg) was administered to healthy subjects (n = 48) and T2DM subjects (n = 8). In the multiple ascending dose study, healthy subjects (n = 12) received a dose of 15 mg LGD-6972 and T2DM subjects (n = 36) received doses of 5, 10 or 15 mg of LGD-6972 daily for 14 days. LGD-6972 had linear plasma pharmacokinetics consistent with once-daily dosing that was comparable in healthy and T2DM subjects. Dose-dependent decreases in fasting plasma glucose were observed in all groups with a maximum of 3.15 mmol/L (56.8 mg/dL) on day 14 in T2DM subjects. LGD-6972 also reduced plasma glucose in the postprandial state. Dose-dependent increases in fasting plasma glucagon were observed, but glucagon levels decreased and insulin levels increased after an oral glucose load in T2DM subjects. LGD-6972 was well tolerated at the doses tested without dose-related or clinically meaningful changes in clinical laboratory parameters. No subject experienced hypoglycaemia. Inhibition of glucagon action by LGD-6972 was associated with decreases in glucose in both healthy and T2DM subjects, the magnitude of which was sufficient to predict improvement in glycaemic control with longer treatment duration in T2DM patients. The safety and pharmacological profile of LGD-6972 after 14 days of dosing supports continued clinical development. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses.

PubMed

Wach, Achim; Dembowsky, Klaus; Dale, Glenn E

2018-04-01

Murepavadin is the first in class of the outer membrane protein-targeting antibiotics (OMPTA) and a pathogen-specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targeting Pseudomonas aeruginosa Murepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A of the study was a double-blind, randomized, placebo-controlled, single-ascending-dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin, and 2 subjects were randomized to placebo. Part B was a double-blind, randomized, placebo-controlled, multiple-ascending-dose investigation in 3 sequential cohorts. After a single dose of murepavadin, the geometric mean half-life (2.52 to 5.30 h), the total clearance (80.1 to 114 ml/h/kg), and the volume of distribution (415 to 724 ml/kg) were consistent across dose levels. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Murepavadin was well tolerated, adverse events were transient and generally mild, and no dose-limiting toxicity was identified. Copyright © 2018 American Society for Microbiology.

ANATOMICAL RECONSTRUCTION OF ANTERIOR CRUCIATE LIGAMENT OF THE KNEE: DOUBLE BAND OR SINGLE BAND?

PubMed

Zanella, Luiz Antonio Zanotelli; Junior, Adair Bervig; Badotti, Augusto Alves; Michelin, Alexandre Froes; Algarve, Rodrigo Ilha; de Quadros Martins, Cesar Antonio

2012-01-01

To evaluate the double-band and single-band techniques for anatomical reconstruction of the anterior cruciate ligament of the knee and demonstrate that the double-band technique not only provides greater anterior stability but also causes less pain and a better subjective patient response. We selected 42 patients who underwent anterior cruciate ligament reconstruction, by means of either the single-band anatomical reconstruction technique, using flexor tendon grafts with two tunnels, or the double-band anatomical reconstruction technique, using four tunnels and grafts from the semitendinosus and gracilis tendons. All fixations were performed using interference screws. There was no variation in the sample. Before the operation, the objective and subjective IKDC scores, Lysholm score and length of time with the injury were evaluated. All these variables were reassessed six months later, and the KT-1000 correlation with the contralateral knee was also evaluated. There was no significant difference between the two groups in subjective evaluations, but the single-band group showed better results in relation to range of motion and objective evaluations including KT-1000 (with statistical significance). Our study demonstrated that there was no difference between the two groups in subjective evaluations, but better results were found using the single-band anatomical technique, in relation to objective evaluations.

ANATOMICAL RECONSTRUCTION OF ANTERIOR CRUCIATE LIGAMENT OF THE KNEE: DOUBLE BAND OR SINGLE BAND?

PubMed Central

Zanella, Luiz Antonio Zanotelli; Junior, Adair Bervig; Badotti, Augusto Alves; Michelin, Alexandre Froes; Algarve, Rodrigo Ilha; de Quadros Martins, Cesar Antonio

2015-01-01

Objective: To evaluate the double-band and single-band techniques for anatomical reconstruction of the anterior cruciate ligament of the knee and demonstrate that the double-band technique not only provides greater anterior stability but also causes less pain and a better subjective patient response. Methods: We selected 42 patients who underwent anterior cruciate ligament reconstruction, by means of either the single-band anatomical reconstruction technique, using flexor tendon grafts with two tunnels, or the double-band anatomical reconstruction technique, using four tunnels and grafts from the semitendinosus and gracilis tendons. All fixations were performed using interference screws. There was no variation in the sample. Before the operation, the objective and subjective IKDC scores, Lysholm score and length of time with the injury were evaluated. All these variables were reassessed six months later, and the KT-1000 correlation with the contralateral knee was also evaluated. Results: There was no significant difference between the two groups in subjective evaluations, but the single-band group showed better results in relation to range of motion and objective evaluations including KT-1000 (with statistical significance). Conclusion: Our study demonstrated that there was no difference between the two groups in subjective evaluations, but better results were found using the single-band anatomical technique, in relation to objective evaluations. PMID:27042621

Increasing motivation in robot-aided arm rehabilitation with competitive and cooperative gameplay

PubMed Central

2014-01-01

Background Several strategies have been proposed to improve patient motivation and exercise intensity during robot-aided stroke rehabilitation. One relatively unexplored possibility is two-player gameplay, allowing subjects to compete or cooperate with each other to achieve a common goal. In order to explore the potential of such games, we designed a two-player game played using two ARMin arm rehabilitation robots. Methods The game was an air-hockey task displayed on a computer monitor and controlled using shoulder movements in the ARMin robot. Three game modes were tested: single-player (competing against computer), competitive (competing against human), and cooperative (cooperating with human against computer). All modes were played by 30 unimpaired subjects and 8 impaired chronic stroke subjects. The subjects filled out the Intrinsic Motivation Inventory questionnaire after each game mode, as well as a final questionnaire about game preferences and their personality. Results Nearly all unimpaired subjects preferred playing the two-player game modes to the single-player one, as they enjoyed talking and interacting with another person. However, there were two distinct player groups: one liked the competitive mode but not the cooperative mode while the other liked the cooperative but not the competitive mode. Unimpaired subjects who liked the competitive mode also put significantly more effort into it than into the other modes. Results from impaired subjects were similar, with even impaired subjects over 60 years old enjoying competitive gameplay. The subjects’ personalities roughly predicted which mode they would prefer, which was especially evident in a poorly-matched impaired pair that preferred the single-player mode. Conclusions Results indicate great potential for two-player rehabilitation games, in the form of greater enjoyment as well as potentially more intensive exercise compared to single-player games. However, the right game type needs to be chosen for each subject depending on skill and personality, along with selecting an appropriate co-player. Further studies with patients that are currently enrolled in rehabilitation programs are recommended, and the subjective measures used in our study should be augmented with objective measures such as electromyography. PMID:24739255

Resting-state fMRI correlations: From link-wise unreliability to whole brain stability.

PubMed

Pannunzi, Mario; Hindriks, Rikkert; Bettinardi, Ruggero G; Wenger, Elisabeth; Lisofsky, Nina; Martensson, Johan; Butler, Oisin; Filevich, Elisa; Becker, Maxi; Lochstet, Martyna; Kühn, Simone; Deco, Gustavo

2017-08-15

The functional architecture of spontaneous BOLD fluctuations has been characterized in detail by numerous studies, demonstrating its potential relevance as a biomarker. However, the systematic investigation of its consistency is still in its infancy. Here, we analyze within- and between-subject variability and test-retest reliability of resting-state functional connectivity (FC) in a unique data set comprising multiple fMRI scans (42) from 5 subjects, and 50 single scans from 50 subjects. We adopt a statistical framework that enables us to identify different sources of variability in FC. We show that the low reliability of single links can be significantly improved by using multiple scans per subject. Moreover, in contrast to earlier studies, we show that spatial heterogeneity in FC reliability is not significant. Finally, we demonstrate that despite the low reliability of individual links, the information carried by the whole-brain FC matrix is robust and can be used as a functional fingerprint to identify individual subjects from the population. Copyright © 2017 Elsevier Inc. All rights reserved.

Opportunities and Challenges in Using Studies without a Control Group in Comparative Effectiveness Reviews

ERIC Educational Resources Information Center

Paulus, Jessica K.; Dahabreh, Issa J.; Balk, Ethan M.; Avendano, Esther E.; Lau, Joseph; Ip, Stanley

2014-01-01

When examining the evidence on therapeutic interventions to answer a comparative effectiveness research question, one should consider all studies that are informative on the interventions' causal effects. "Single group studies" evaluate outcomes longitudinally in cohorts of subjects who are managed with a single treatment strategy.…

Meta-Analysis of Behavioral Self-Management Interventions in Single-Case Research

ERIC Educational Resources Information Center

Briesch, Amy M.; Briesch, Jacquelyn M.

2016-01-01

The current study meta-analyzed 47 single-subject studies of behavioral self-management interventions that were published between 1971 and 2011. In addition to obtaining an overall measure of effect across all self-management studies (f = 0.93), analyses were conducted to assess whether treatment effectiveness was moderated by factors such as…

Single-Subject Experimental Research: Applications for Literacy.

ERIC Educational Resources Information Center

Neuman, Susan B., Ed.; McCormick, Sandra, Ed.

Intended as a guide for both novice and experienced researchers, this collection of articles focuses on single-subject experimental research used for investigations in literacy. The premise of the collection is that this single-subject approach allows researchers--both those from outside the classroom and teacher-researchers--to discover how an…

The Move to Faculty Middle Management Structures in Scottish Secondary Schools: A Case Study

ERIC Educational Resources Information Center

Anderson, Cherie; Nixon, Graeme

2010-01-01

This article looks at the move from a management structure based on discrete subject departments managed by subject specialist principal teachers within Scottish secondary schools towards groupings of subjects (faculties) with a single manager. This article examines the impact of this change upon the experiences of students and probationer…

Developing and Modeling 21st-Century Skills with Preservice Teachers

ERIC Educational Resources Information Center

Urbani, Jacquelyn M.; Roshandel, Shadi; Michaels, Rosemarie; Truesdell, Elizabeth

2017-01-01

This study describes a collaboration in one northern California university between three teacher education programs (multiple subject, single subject, and education specialist) that explores how and to what extent faculty are developing and modeling the 21st-century skills in preservice teachers. In addition, this study analyzes preservice…

Interdisciplinary Studies on the Combat Readiness and Health Issues Faced by Military Personnel

DTIC Science & Technology

2009-09-01

related activity in single subjects, and this facilitates clinical diagnosis in which single subjects are the focus of investigation. Methods...Good Clinical Practice Guidelines, the Declaration of Helsinki, and the U.S. Code of Federal Regulations. Written and informed consent was obtained from...S, and a temporal loading T. For two triplets: (Fa, Sa, Ta) and (Fb, Sb, Tb), we define the triplet similarity metric Cab = FTa Fb STaSb TTa

A single dose desensitization for summer hay fever. Results of a double blind study-1988.

PubMed

Fell, P; Brostoff, J

1990-01-01

A new type of desensitising vaccine, enzyme potentiated was subjected to a double-blind randomised study during the hay fever season. The vaccine is a convenient single injection given in March and the results show good protection throughout the grass pollen season.

Comparative electrophysiological study of response to botulinum toxin type B in Japanese and Caucasians.

PubMed

Arimura, Kimiyoshi; Arimura, Yumiko; Takata, Yoshiharu; Nakamura, Tomonori; Kaji, Ryuji

2008-01-30

Ethnic differences in the muscle-relaxing effect of botulinum toxin type B (BTX-B) were examined by means of electrophysiological measurements in Japanese and Caucasian volunteers. This was a randomized, single-blinded, single-center study of 24 Japanese and 24 Caucasian healthy adult male subjects in Japan. BTX-B (20 U, 100 U, or 500 U/0.2 mL) or placebo was administered to the extensor digitorum brevis (EDB) muscle in the left lower limb as a single dose (in each dose group, 6 subjects received the test drug and two received placebo). The inhibitory effect of BTX-B on the M wave amplitude of EDB muscle generated by stimulation of the deep peroneal nerve was measured frequently during 2 weeks after administration, and then at weeks 4 (day 28) and 12 (day 84). The inhibitory effect of BTX-B on the M wave amplitude of EDB muscle was dose-dependent in both Japanese and Caucasian subjects, and the dose-response curves were similar. These findings demonstrate that the muscle-relaxing effect of BTX-B in Japanese subjects is electrophysiologically similar to that in Caucasians. 2007 Movement Disorder Society

Safety and immunogenicity of ricin vaccine, RVEc™, in a Phase 1 clinical trial.

PubMed

Pittman, Phillip R; Reisler, Ronald B; Lindsey, Changhong Y; Güereña, Fernando; Rivard, Robert; Clizbe, Denise P; Chambers, Matthew; Norris, Sarah; Smith, Leonard A

2015-12-16

Ricin is a potent toxin and potential bioterrorism weapon for which no specific licensed countermeasures are available. We report the safety and immunogenicity of the ricin vaccine RVEc™ in a Phase 1 (N=30) multiple-dose, open-label, non-placebo-controlled, dose-escalating (20, 50, and 100μg), single-center study. Each subject in the 20- and 50-μg dose groups (n=10 for each group) received three injections at 4-week intervals and was observed carefully for untoward effects of the vaccine; blood was drawn at predetermined intervals after each dose for up to 1 year. RVEc™ was safe and well tolerated at the 20- and 50-μg doses. The most common adverse events were pain at the injection site and headache. Of the 10 subjects who received a single 100-μg dose, two developed elevated creatine phosphokinase levels, which resolved without sequelae. No additional doses were administered to subjects in the 100-μg group. Immunogenicity of the vaccine was evaluated by measuring antibody response using the well standardized enzyme-linked immunosorbent assay (ELISA) and toxin neutralization assay (TNA). Of the subjects in the 20- and 50-μg dose groups, 100% achieved ELISA anti-ricin IgG titers of 1:500 to 1:121,500 and 50% produced neutralizing anti-ricin antibodies measurable by TNA. Four subjects in the 50-μg group received a single booster dose of RVEc™ 20-21 months after the initial dose. The single booster was safe and well tolerated, resulting in no serious adverse events, and significantly enhanced immunogenicity of the vaccine in human subjects. Each booster recipient developed a robust anamnestic response with ELISA anti-ricin IgG titers of 1:13,500 to 1:121,500 and neutralizing antibody titers of 1:400 to 1:3200. Future studies will attempt to optimize dose, scheduling, and route of administration. This study is registered at clinicaltrials.gov (NCT01317667 and NCT01846104). Published by Elsevier Ltd.

Pharmacokinetic interaction of flecainide and paroxetine in relation to the CYP2D6*10 allele in healthy Korean subjects

PubMed Central

Lim, Kyoung Soo; Cho, Joo-Youn; Jang, In-Jin; Kim, Bo-Hyung; Kim, JaeWoo; Jeon, Ji-Young; Tae, Yu-Mi; Yi, SoJeong; Eum, SoYoung; Shin, Sang-Goo; Yu, Kyung-Sang

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT The only existing study of CYP2D6*10-associated alterations in flecainide pharmacokinetics was retrospective. Paroxetine has been known as a strong inhibitor of CYP2D6. WHAT THIS STUDY ADDS This study reports that the extent of drug interaction between flecainide and paroxetine is influenced by the CYP2D6*10 allele in healthy subjects, which is frequent in Asians. AIMS The objectives were to evaluate the effect of CYP2D6 genetic polymorphism on the pharmacokinetics of flecainide, and also on the extent of drug interaction with paroxetine as a CYP2D6 inhibitor after a single oral administration in healthy subjects. METHODS An open-label, two-period, single-sequence, cross-over study was performed in 21 healthy Korean male volunteers (seven for CYP2D6*1/*1 or *1/*2, group 1; seven for CYP2D6*1/*10, group 2; seven for CYP2D6*10/*10 or *10/*36, group 3). Subjects were administered 200 mg of flecainide on day 1. After a 7-day wash-out period, subjects were administered 20 mg of paroxetine from day 8 to 14, and 200 mg of flecainide on day 15. Blood sampling was performed up to 72 h after flecainide administration. RESULTS Terminal elimination half-life and mean residence time (MRT) were significantly different among three genotype groups after a single oral administration of flecainide (P = 0.021, 0.011, respectively). Area under the concentration–time curve, terminal elimination half-life and MRT increased significantly after paroxetine co-administration only in groups 1 and 2. CONCLUSIONS This study reports that the extent of drug interaction between flecainide and paroxetine is influenced by the CYP2D6*10 allele in healthy subjects, which is frequent in Asians. PMID:18754843

Pharmacokinetics of Tedizolid in Subjects with Renal or Hepatic Impairment

PubMed Central

Minassian, S. L.; Morris, D.; Ponnuraj, R.; Marbury, T. C.; Alcorn, H. W.; Fang, E.; Prokocimer, P.

2014-01-01

Two open-label, single-dose, parallel-group studies were conducted to characterize the pharmacokinetics of the novel antibacterial tedizolid and the safety of tedizolid phosphate, its prodrug, in renally or hepatically impaired subjects. Tedizolid pharmacokinetics in subjects with severe renal impairment without dialysis support was compared with that of matched control subjects with normal renal function. Effects of hemodialysis on tedizolid pharmacokinetics were determined in a separate cohort of subjects undergoing long-term hemodialysis. Effects of hepatic impairment on tedizolid pharmacokinetics were determined in subjects with moderate or severe hepatic impairment and compared with those of matched control subjects with normal hepatic function. Each participant received a single oral (hepatic impairment) or intravenous (renal impairment) dose of tedizolid phosphate at 200 mg; hemodialysis subjects received two doses (separated by 7 days), before and after dialysis, in a crossover fashion. The pharmacokinetics of tedizolid was similar in subjects with severe renal impairment and controls (∼8% lower area under the concentration-time curve [AUC], with a nearly identical peak concentration) and in subjects undergoing hemodialysis before and after tedizolid phosphate administration (∼9% lower AUC, with a 15% higher peak concentration); <10% of the dose was removed during 4 h of hemodialysis. Tedizolid pharmacokinetics was only minimally altered in subjects with moderate or severe hepatic impairment; the AUC was increased approximately 22% and 34%, respectively, compared with that of subjects in the control group. Tedizolid phosphate was generally well tolerated in all participants. These results suggest that tedizolid phosphate dose adjustments are not necessary in patients with any degree of renal or hepatic impairment. (This study has been registered at ClinicalTrials.gov under registration numbers NCT01452828 [renal study] and NCT01431833 [hepatic study].) PMID:25136024

Disorder-specific cognitive profiles in major depressive disorder and generalized anxiety disorder.

PubMed

Hendriks, Sanne M; Licht, Carmilla M M; Spijker, Jan; Beekman, Aartjan T F; Hardeveld, Florian; de Graaf, Ron; Penninx, Brenda W J H

2014-04-01

This investigation examines differences in cognitive profiles in subjects with major depressive disorder (MDD) and generalized anxiety disorder (GAD). Data were used from subjects with current MDD (n = 655), GAD (n = 107) and comorbid MDD/GAD (n = 266) diagnosis from the Netherlands Study of Depression and Anxiety (NESDA). The Composite Interview Diagnostic Instrument was used to diagnose MDD and GAD. Cognitive profiles were measured using the Leiden Index of Depression Sensitivity, the Anxiety Sensitivity Index, and the Penn State Worry Questionnaire. Results showed that differences in cognitive profiles between single MDD and single GAD subjects were present: scores on hopelessness/suicidality and rumination were significantly higher in MDD than GAD, whereas anxiety sensitivity for physical concerns and pathological worry were higher in GAD than MDD. The cognitive profile of comorbid MDD/GAD showed more extreme depression cognitions compared to single disorders, and a similar anxiety profile compared to single GAD subjects. Despite the commonalities in cognitive profiles in MDD and GAD, there are differences suggesting that MDD and GAD have disorder-specific cognitive profiles. Findings of this investigation give support for models like the cognitive content-specificity model and the tripartite model and could provide useful handles for treatment focus.

Effect of dietary aspartame on plasma concentrations of phenylalanine and tyrosine in normal and homozygous phenylketonuric patients.

PubMed

Mackey, S A; Berlin, C M

1992-07-01

Six normal subjects each ingested a single 12-oz can of a diet cola (Diet Coke) providing 184 mg aspartame (APM), of which 104 mg is phenylalanine (Phe), and, on another occasion, a single 12-oz can of regular cola (Coke Classic). Neither cola significantly affected plasma concentrations of Phe or tyrosine over the three-hour postingestion study period. Each of five homozygous phenylketonuric (PKU) subjects (ages 11, 16, 17, 21, and 23 years) ingested a single 12-oz can of the same diet cola. In these five subjects (three with classic PKU and two with hyperphenylalinemia), the increase in plasma Phe concentrations varied from 0.26 mg/dL to 1.77 mg/dL two or three hours after ingestion (baseline levels, 5.04 to 17.2 mg/dL). Tyrosine concentrations did not differ significantly from baseline levels. The data indicate that ingestion of dietary Phe, as supplied in a single can of diet cola, is readily handled in both normal and PKU subjects. The small increases in plasma Phe concentrations in the homozygous PKU patients are not considered clinically significant.

Single trial discrimination of individual finger movements on one hand: A combined MEG and EEG study☆

PubMed Central

Quandt, F.; Reichert, C.; Hinrichs, H.; Heinze, H.J.; Knight, R.T.; Rieger, J.W.

2012-01-01

It is crucial to understand what brain signals can be decoded from single trials with different recording techniques for the development of Brain-Machine Interfaces. A specific challenge for non-invasive recording methods are activations confined to small spatial areas on the cortex such as the finger representation of one hand. Here we study the information content of single trial brain activity in non-invasive MEG and EEG recordings elicited by finger movements of one hand. We investigate the feasibility of decoding which of four fingers of one hand performed a slight button press. With MEG we demonstrate reliable discrimination of single button presses performed with the thumb, the index, the middle or the little finger (average over all subjects and fingers 57%, best subject 70%, empirical guessing level: 25.1%). EEG decoding performance was less robust (average over all subjects and fingers 43%, best subject 54%, empirical guessing level 25.1%). Spatiotemporal patterns of amplitude variations in the time series provided best information for discriminating finger movements. Non-phase-locked changes of mu and beta oscillations were less predictive. Movement related high gamma oscillations were observed in average induced oscillation amplitudes in the MEG but did not provide sufficient information about the finger's identity in single trials. Importantly, pre-movement neuronal activity provided information about the preparation of the movement of a specific finger. Our study demonstrates the potential of non-invasive MEG to provide informative features for individual finger control in a Brain-Machine Interface neuroprosthesis. PMID:22155040

Coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone improves postprandial endothelial dysfunction in patients with borderline and stage 1 hypertension.

PubMed

Kajikawa, Masato; Maruhashi, Tatsuya; Hidaka, Takayuki; Nakano, Yukiko; Kurisu, Satoshi; Matsumoto, Takeshi; Iwamoto, Yumiko; Kishimoto, Shinji; Matsui, Shogo; Aibara, Yoshiki; Yusoff, Farina Mohamad; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Noma, Kensuke; Nakashima, Ayumu; Watanabe, Takuya; Tone, Hiroshi; Hibi, Masanobu; Osaki, Noriko; Katsuragi, Yoshihisa; Higashi, Yukihito

2018-01-12

The purpose of this study was to evaluate acute effects of coffee with a high content of chlorogenic acids and different hydroxyhydroquinone contents on postprandial endothelial dysfunction. This was a single-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 37 patients with borderline or stage 1 hypertension were randomized to two study groups. The participants consumed a test meal with a single intake of the test coffee. Subjects in the Study 1 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or placebo coffee with crossover. Endothelial function assessed by flow-mediated vasodilation and plasma concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after coffee intake. Compared with baseline values, single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone, but not coffee with a high content of chlorogenic acids and high content of hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow-mediated vasodilation and decreased circulating 8-isoprostane levels. These findings suggest that a single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone is effective for improving postprandial endothelial dysfunction. URL for Clinical Trial: https://upload.umin.ac.jp ; Registration Number for Clinical Trial: UMIN000013283.

Quantitative analysis of single- vs. multiple-set programs in resistance training.

PubMed

Wolfe, Brian L; LeMura, Linda M; Cole, Phillip J

2004-02-01

The purpose of this study was to examine the existing research on single-set vs. multiple-set resistance training programs. Using the meta-analytic approach, we included studies that met the following criteria in our analysis: (a) at least 6 subjects per group; (b) subject groups consisting of single-set vs. multiple-set resistance training programs; (c) pretest and posttest strength measures; (d) training programs of 6 weeks or more; (e) apparently "healthy" individuals free from orthopedic limitations; and (f) published studies in English-language journals only. Sixteen studies generated 103 effect sizes (ESs) based on a total of 621 subjects, ranging in age from 15-71 years. Across all designs, intervention strategies, and categories, the pretest to posttest ES in muscular strength was (chi = 1.4 +/- 1.4; 95% confidence interval, 0.41-3.8; p < 0.001). The results of 2 x 2 analysis of variance revealed simple main effects for age, training status (trained vs. untrained), and research design (p < 0.001). No significant main effects were found for sex, program duration, and set end point. Significant interactions were found for training status and program duration (6-16 weeks vs. 17-40 weeks) and number of sets performed (single vs. multiple). The data indicated that trained individuals performing multiple sets generated significantly greater increases in strength (p < 0.001). For programs with an extended duration, multiple sets were superior to single sets (p < 0.05). This quantitative review indicates that single-set programs for an initial short training period in untrained individuals result in similar strength gains as multiple-set programs. However, as progression occurs and higher gains are desired, multiple-set programs are more effective.

Event-related potential indices of workload in a single task paradigm

NASA Technical Reports Server (NTRS)

Horst, R. L.; Munson, R. C.; Ruchkin, D. S.

1984-01-01

Many previous studies of both behavioral and physiological correlates of cognitive workload have burdened subjects with a contrived secondary task in order to assess the workload of a primary task. The present study investigated event-related potential (ERP) indices of workload in a single task paradigm. Subjects monitored changing digital readouts for values that went 'out-of-bounds'. The amplitude of a long-latency positivity in the ERPs elicited by readout changes increased with the number of readouts being monitored. This effect of workload on ERPs is reported, along with plans for additional analyses to address theoretical implications.

The relative effects on math performance of single- versus multiple-ratio schedules: a case study1

PubMed Central

Lovitt, Tom C.; Esveldt, Karen A.

1970-01-01

This series of four experiments sought to assess the comparative effects of multiple- versus single-ratio schedules on a pupil's responding to mathematics materials. Experiment I, which alternated between single- and multiple-ratio contingencies, revealed that during the latter phase the subject responded at a higher rate. Similar findings were revealed by Exp. II. The third experiment, which manipulated frequency of reinforcement rather than multiple ratios, revealed that the alteration had a minimal effect on the subject's response rate. A final experiment, conducted to assess further the effects of multiple ratios, provided data similar to those of Exp. I and II. PMID:16795267

Effect of Single vs Bilateral Lung Transplantation on Plasma Surfactant Protein D Levels in Idiopathic Pulmonary Fibrosis

PubMed Central

Beers, Michael F.; Ahya, Vivek N.; Kawut, Steven M.; Sims, Karen D.; Lederer, David J.; Palmer, Scott M.; Wille, Keith; Lama, Vibha N.; Shah, Pali D.; Orens, Jonathan B.; Bhorade, Sangeeta; Crespo, Maria; Weinacker, Ann; Demissie, Ejigayehu; Bellamy, Scarlett; Christie, Jason D.; Ware, Lorraine B.

2011-01-01

Background: Serum levels of surfactant protein D (SP-D) have been suggested as reflecting epithelial damage in acute lung injury, COPD, and idiopathic pulmonary fibrosis (IPF). However, little is known about SP-D levels in the setting of lung transplantation. Methods: We examined plasma SP-D levels in 104 subjects from a prospective, multicenter cohort study of lung allograft recipients. Plasma SP-D was measured by enzyme-linked immunosorbent assay prior to transplant and daily for 3 days after transplant. Results: Subjects undergoing transplant for IPF had higher baseline SP-D levels (median, 325 ng/mL) compared with subjects with cystic fibrosis, COPD, and pulmonary hypertension (median, 100, 80, and 82 ng/mL, respectively; P = .0001). Among subjects with IPF undergoing bilateral transplant, SP-D levels declined rapidly postoperatively. In contrast, SP-D levels in subjects undergoing single lung transplant for IPF remained significantly higher than those of bilateral allograft recipients. Among subjects undergoing single lung transplant for IPF, the development of primary graft dysfunction (PGD) was associated with a subsequent rise in SP-D levels, whereas SP-D levels in IPF subjects undergoing bilateral transplant declined, even in the presence of grade 3 PGD. Importantly, single lung allograft recipients without PGD had higher postoperative SP-D levels than bilateral allograft recipients with PGD. Conclusions: Subjects undergoing lung transplant for IPF have significantly higher baseline plasma SP-D levels compared with those with other diagnoses. Plasma SP-D is likely a biomarker of the air-blood barrier integrity in the native IPF lung, but may be less useful as a biomarker of PGD after transplant. PMID:21349925

A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray.

PubMed

Stott, C G; White, L; Wright, S; Wilbraham, D; Guy, G W

2013-05-01

A Phase I study to assess the single and multipledose pharmacokinetics (PKs) and safety and tolerability of oromucosally administered Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, in healthy male subjects. Subjects received either single doses of THC/CBD spray as multiple sprays [2 (5.4 mg THC and 5.0 mg CBD), 4 (10.8 mg THC and 10.0 mg CBD) or 8 (21.6 mg THC and 20.0 mg CBD) daily sprays] or multiple doses of THC/CBD spray (2, 4 or 8 sprays once daily) for nine consecutive days, following fasting for a minimum of 10 h overnight prior to each dosing. Plasma samples were analyzed by gas chromatography-mass spectrometry for CBD, THC, and its primary metabolite 11-hydroxy-THC, and various PK parameters were investigated. Δ(9)-Tetrahydrocannabinol and CBD were rapidly absorbed following single-dose administration. With increasing single and multiple doses of THC/CBD spray, the mean peak plasma concentration (Cmax) increased for all analytes. There was evidence of dose-proportionality in the single but not the multiple dosing data sets. The bioavailability of THC was greater than CBD at single and multiple doses, and there was no evidence of accumulation for any analyte with multiple dosing. Inter-subject variability ranged from moderate to high for all PK parameters in this study. The time to peak plasma concentration (Tmax) was longest for all analytes in the eight spray group, but was similar in the two and four spray groups. THC/CBD spray was well-tolerated in this study and no serious adverse events were reported. The mean Cmax values (<12 ng/mL) recorded in this study were well below those reported in patients who smoked/inhaled cannabis, which is reassuring since elevated Cmax values are linked to significant psychoactivity. There was also no evidence of accumulation on repeated dosing.

A food effect study and dose proportionality study to assess the pharmacokinetics and safety of bardoxolone methyl in healthy volunteers.

PubMed

Teuscher, Nathan S; Kelley, Richard J; Dumas, Emily O; Klein, Cheri Enders; Awni, Walid M; Meyer, Colin J

2014-07-01

This study investigated the effect of food on the plasma pharmacokinetics of bardoxolone methyl, an antioxidant inflammation modulator, at a 20 mg dose, and the dose proportionality of bardoxolone methyl pharmacokinetics from 20 to 80 mg. It was a single-dose study conducted at a single center in 32 healthy volunteers aged 18-45 years using an amorphous spray-dried dispersion formulation of bardoxolone methyl. In Part A, 16 subjects received single 20 mg doses of bardoxolone methyl under fasting and non-fasting conditions. In Part B, 16 subjects received a single 60 or 80 mg dose of bardoxolone methyl and a matching placebo dose under fasting conditions. Blood samples for pharmacokinetic analysis were taken over 120 hours following dose administration. Single dose administration of 20, 60, and 80 mg bardoxolone methyl was safe and well-tolerated in healthy volunteers. Total bardoxolone methyl exposure was unchanged in the presence of food. However, doses of bardoxolone methyl above 20 mg appear to have a saturated dissolution or absorption process and are associated with less than proportional increases in drug exposure. © 2013, The American College of Clinical Pharmacology.

A new fully human recombinant FSH (follitropin epsilon): two phase I randomized placebo and comparator-controlled pharmacokinetic and pharmacodynamic trials.

PubMed

Abd-Elaziz, Khalid; Duijkers, Ingrid; Stöckl, Lars; Dietrich, Bruno; Klipping, Christine; Eckert, Kelvin; Goletz, Steffen

2017-08-01

What are the differences and similarities of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the novel recombinant human FSH follitropin epsilon expressed in the human cell line GlycoExpress compared with a Chinese hamster ovary (CHO) derived compound and a urinary derived product? Overall follitropin epsilon, with a fully human glycosylation, shows a comparable PK profile at single-dose as well as multiple-dose administration compared to recombinant CHO-derived FSH as well as urinary derived FSH, whereas the PD properties differ from product to product with follitropin epsilon being most active in PD parameters. Recombinant FSH produced in CHO and FSH obtained from the urine of postmenopausal women show comparable PK and PD properties. However, more recently a comparative study of a recombinant FSH produced in the human cell line PerC6 and a CHO-derived FSH preparation revealed differences in PK and PD properties of the molecule. Both studies were randomized, placebo- and comparator-controlled, single-blind phase I studies in healthy pituitary-suppressed female volunteers aged 18 and 40 years. The single-dose, dose escalation study included 19 women (April 2011 to September 2011) with three ascending dose levels per subject or placebo/comparators with a 14-day washout phase between dosings. The multiple-dose study included 57 women (October 2011 to April 2012) in five cohorts with three dose levels versus placebo and two comparators. Randomization to the respective treatment was performed after successful downregulation of the pituitary gland prior to Investigational Medicinal Product dosing. In the single-dose study, 12 subjects received follitropin epsilon (25, 75, 150 and 300 IU) in three of four possible ascending doses and seven subjects received one dose of two comparators (150 IU Bravelle and 150 IU Gonal-f) and placebo in random order in each treatment period. In the multiple-dose study, 30 subjects received follitropin epsilon (75 IU or 150 IU once daily [QD], or 150 IU every other day [QAD], 10 subjects each) and 27 subjects received 150 IU Gonal-f, 150 IU Bravelle, or placebo for 7 days (11/10/6 subjects). Blood samples for measuring PK as well as PD parameters were collected systematically before, during and after dosing. Adverse events (AEs) and other relevant safety parameters were recorded. Data were summarized using descriptive statistics. The single- and multiple-dose PK parameters maximum concentration (Cmax) and area under the concentration-time curve (AUC0-last) increased in a linear fashion with increasing dose levels of follitropin epsilon. Follitropin epsilon showed PK characteristics comparable to the comparators indicating that well established treatment schemes could be applied. There was a dose-response effect of single and multiple doses of follitropin epsilon on follicular growth, which was shown for the biomarker inhibin B as well as for the mean number and size of follicles. Multiple doses of 75 IU follitropin epsilon given daily, as well as 150 IU follitropin epsilon every second day, showed a follicle growth comparable with 150 IU Gonal-f given daily, while in case of daily administration of 150 IU Bravelle only weak follicle stimulation was observed. Multiple doses of 150 IU follitropin epsilon induced a much higher follicle growth compared to the same dose of Gonal-f. All single and multiple follitropin epsilon doses tested were safe and well tolerated, and overall there were no relevant differences between follitropin epsilon and the comparators in terms of safety. The average number of AEs increased with increasing dose levels. No clinically relevant abnormalities were reported for any of the other safety parameters assessed. No follitropin epsilon anti-drug antibodies were observed. The studies were conducted as a single-blind design. Hormone levels or other parameters assessed in serum are generally not considered as being subject to bias. Other assessments directly performed by the investigators, such as transvaginal ultrasound assessments, may have been subject to personal bias. No prospective calculations of statistical power had been made, as is common practice for first in human and early phase I studies in healthy volunteers. These early development studies showed that follitropin epsilon exhibits comparable PK characteristics, as well as inducing stronger PD effects in terms of follicle growth and serum inhibin B, than the comparators. Follitropin epsilon induced a dose-dependent increase in follicular growth. The results warrant further studies with this new fully human recombinant FSH. The studies were sponsored by GLYCOTOPE GmbH, Berlin, Germany. K.A-E. is an employee of QPS-Netherlands, B.V., which received funding for the studies from Glycotope GmbH; I.D. and C.K. are employees of Dinox B.V., which received funding for the studies from Glycotope GmbH; L.S. and S.G. are employees and shareholders of Glycotope GmbH; B.D. and K.E. are employees of Glycotope GmbH. www.clinicaltrials.gov: NCT01354886 (single-dose); NCT01477073 (multiple-dose). The single-dose trial was registered on 11 May 2011 while the multiple-dose trial was registered on 09 November 2011. First subject was enroled in the single-dose trial in 27 April 2011 and in the multiple-dose trial in 02 October 2011. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing

PubMed Central

Tsioris, Konstantinos; Gupta, Namita T.; Ogunniyi, Adebola O.; Zimnisky, Ross M.; Qian, Feng; Yao, Yi; Wang, Xiaomei; Stern, Joel N. H.; Chari, Raj; Briggs, Adrian W.; Clouser, Christopher R.; Vigneault, Francois; Church, George M.; Garcia, Melissa N.; Murray, Kristy O.; Montgomery, Ruth R.; Kleinstein, Steven H.; Love, J. Christopher

2015-01-01

West Nile virus infection (WNV) is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV - recently infected and post-convalescent subjects - and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis. The results from single-cell analysis indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects. These cells exhibited class-switched antibody isotypes. Furthermore, the results suggest that the antibody response itself does not predict the clinical severity of the disease (asymptomatic or symptomatic). Using the nucleotide coding sequences for WNV-specific antibodies derived from single cells, we revealed the ontogeny of expanded WNV-specific clones in the repertoires of recently infected subjects through NGS and bioinformatic analysis. This analysis also indicated that the humoral response to WNV did not depend on an anamnestic response, due to an unlikely previous exposure to the virus. The innovative and integrative approach presented here to analyze the evolution of neutralizing antibodies from natural infection on a single-cell and repertoire level can also be applied to vaccine studies, and could potentially aid the development of therapeutic antibodies and our basic understanding of other infectious diseases. PMID:26481611

Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing.

PubMed

Tsioris, Konstantinos; Gupta, Namita T; Ogunniyi, Adebola O; Zimnisky, Ross M; Qian, Feng; Yao, Yi; Wang, Xiaomei; Stern, Joel N H; Chari, Raj; Briggs, Adrian W; Clouser, Christopher R; Vigneault, Francois; Church, George M; Garcia, Melissa N; Murray, Kristy O; Montgomery, Ruth R; Kleinstein, Steven H; Love, J Christopher

2015-12-01

West Nile virus (WNV) infection is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV - recently infected and post-convalescent subjects - and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis. The results from single-cell analysis indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects. These cells exhibited class-switched antibody isotypes. Furthermore, the results suggest that the antibody response itself does not predict the clinical severity of the disease (asymptomatic or symptomatic). Using the nucleotide coding sequences for WNV-specific antibodies derived from single cells, we revealed the ontogeny of expanded WNV-specific clones in the repertoires of recently infected subjects through NGS and bioinformatic analysis. This analysis also indicated that the humoral response to WNV did not depend on an anamnestic response, due to an unlikely previous exposure to the virus. The innovative and integrative approach presented here to analyze the evolution of neutralizing antibodies from natural infection on a single-cell and repertoire level can also be applied to vaccine studies, and could potentially aid the development of therapeutic antibodies and our basic understanding of other infectious diseases.

Computer-based visual communication in aphasia.

PubMed

Steele, R D; Weinrich, M; Wertz, R T; Kleczewska, M K; Carlson, G S

1989-01-01

The authors describe their recently developed Computer-aided VIsual Communication (C-VIC) system, and report results of single-subject experimental designs probing its use with five chronic, severely impaired aphasic individuals. Studies replicate earlier results obtained with a non-computerized system, demonstrate patient competence with the computer implementation, extend the system's utility, and identify promising areas of application. Results of the single-subject experimental designs clarify patients' learning, generalization, and retention patterns, and highlight areas of performance difficulties. Future directions for the project are indicated.

A Study of Attitudes in an All Boys' School.

ERIC Educational Resources Information Center

Tickner, Anne-Marie

This study examined the effect of single-sex schooling on the academic and social development of boys. An extensive literature review presents the conflicting results of studies of various issues related to single-sex education. Subjects of the present study were 39 boys in a fourth grade class at a boys school and 23 boys in a fourth grade class…

Sensitivity to carbon dioxide in subjects with a single lifetime panic attack: possible clinical "bedside" predictive test for panic disorder after a first attack.

PubMed

Berzak, Elina; Reznik, Mila; Narsia, Oxana; Benjamin, Jonathan

2004-01-01

There is currently no way of knowing whether a patient who has recently had a single panic attack has incipient panic disorder. Sensitivity to carbon dioxide (CO2) is lower in healthy volunteers than in panic disorder patients. If this is also true of people who experience a single lifetime panic attack, it could be used as a prognostic test. Subjects with a single lifetime panic attack and subjects with panic disorder received an inhalation of 35% CO2. Subjects completed the panic symptoms scale (PSS), and also stated whether they considered that they had experienced an attack. None of 14 subjects with a single lifetime panic attack, compared to 7 of 17 subjects with panic disorder (P=.009), had an attack. The PSS also distinguished between the groups. The 35% CO2 challenge warrants further investigation as a predictive test after a first panic attack.

Effects of combining vertical and horizontal information into a primary flight display

NASA Technical Reports Server (NTRS)

Abbott, Terence S.; Nataupsky, Mark; Steinmetz, George G.

1987-01-01

A ground-based aircraft simulation study was conducted to determine the effects of combining vertical and horizontal flight information into a single display. Two display configurations were used in this study. The first configuration consisted of a Primary Flight Display (PFD) format and a Horizontal Situation Display (HSD) with the PFD displayed conventionally above the HSD. For the second display configuration, the HSD format was combined with the PFD format. Four subjects participated in this study. Data were collected on performance parameters, pilot-control inputs, auditory evoked response parameters (AEP), oculometer measurements (eye-scan), and heart rate. Subjective pilot opinion was gathered through questionnaire data and scorings for both the Subjective Workload Assessment Technique (SWAT) and the NASA Task Load Index (NASA-TLX). The results of this study showed that, from a performance and subjective standpoint, the combined configuration was better than the separate configuration. Additionally, both the eye-transition and eye-dwell times for the separate HSD were notably higher than expected, with a 46% increase in available visual time when going from double to single display configuration.

Effect of gemfibrozil, rifampicin, or probenecid on the pharmacokinetics of the SGLT2 inhibitor empagliflozin in healthy volunteers.

PubMed

Macha, Sreeraj; Koenen, Rüdiger; Sennewald, Regina; Schöne, Katja; Hummel, Noemi; Riedmaier, Stephan; Woerle, Hans J; Salsali, Afshin; Broedl, Uli C

2014-02-01

Empagliflozin is a potent, oral, selective inhibitor of sodium glucose cotransporter 2 in development for the treatment of type 2 diabetes mellitus. The goal of these studies was to investigate potential drug-drug interactions between empagliflozin and gemfibrozil (an organic anion-transporting polypeptide 1B1 [OATP1B1]/1B3 and organic anion transporter 3 [OAT3] inhibitor), rifampicin (an OATP1B1/1B3 inhibitor), or probenecid (an OAT3 and uridine diphosphate glucuronosyltransferase inhibitor). Two open-label, randomized, crossover studies were undertaken in healthy subjects. In the first study, 18 subjects received the following in 1 of 2 randomized treatment sequences: a single dose of empagliflozin 25 mg alone and gemfibrozil 600 mg BID for 5 days with a single dose of empagliflozin 25 mg on the third day. In the second study, 18 subjects received a single dose of empagliflozin 10 mg, a single dose of empagliflozin 10 mg coadministered with a single dose of rifampicin 600 mg, and probenecid 500 mg BID for 4 days with a single dose of empagliflozin 10 mg on the second day in 1 of 6 randomized treatment sequences. In the gemfibrozil study, 11 subjects were male, mean age was 35.1 years and mean body mass index (BMI) was 23.47 kg/m(2). In the rifampicin/probenecid study, 10 subjects were male, mean age was 32.7 years and mean BMI was 23.03 kg/m(2). Exposure to empagliflozin was increased by coadministration with gemfibrozil (AUC0-∞: geometric mean ratio [GMR], 158.50% [90% CI, 151.77-165.53]; Cmax: GMR, 115.00% [90% CI, 106.15-124.59]), rifampicin (AUC0-∞: GMR, 135.20% [90% CI, 129.58-141.06]; Cmax: GMR, 175.14% [90% CI, 160.14-191.56]), and probenecid (AUC0-∞: GMR, 153.47% [90% CI, 146.41-160.88]; Cmax: GMR, 125.60% [90% CI, 113.67-138.78]). All treatments were well tolerated. Increases in empagliflozin exposure were <2-fold, indicating that the inhibition of the OATP1B1/1B3, OAT3 transporter, and uridine diphosphate glucuronosyltransferases did not have a clinically relevant effect on empagliflozin exposure. No dose adjustments of empagliflozin were necessary when it was coadministered with gemfibrozil, rifampicin, or probenecid. ClinicalTrials.gov identifiers: NCT01301742 and NCT01634100. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Seeing without Seeing? Degraded Conscious Vision in a Blindsight Patient.

PubMed

Overgaard, Morten; Fehl, Katrin; Mouridsen, Kim; Bergholt, Bo; Cleeremans, Axel

2008-08-21

Blindsight patients, whose primary visual cortex is lesioned, exhibit preserved ability to discriminate visual stimuli presented in their "blind" field, yet report no visual awareness hereof. Blindsight is generally studied in experimental investigations of single patients, as very few patients have been given this "diagnosis". In our single case study of patient GR, we ask whether blindsight is best described as unconscious vision, or rather as conscious, yet severely degraded vision. In experiment 1 and 2, we successfully replicate the typical findings of previous studies on blindsight. The third experiment, however, suggests that GR's ability to discriminate amongst visual stimuli does not reflect unconscious vision, but rather degraded, yet conscious vision. As our finding results from using a method for obtaining subjective reports that has not previously used in blindsight studies (but validated in studies of healthy subjects and other patients with brain injury), our results call for a reconsideration of blindsight, and, arguably also of many previous studies of unconscious perception in healthy subjects.

A Cross-Correlational Analysis between Electroencephalographic and End-Tidal Carbon Dioxide Signals: Methodological Issues in the Presence of Missing Data and Real Data Results

PubMed Central

Morelli, Maria Sole; Giannoni, Alberto; Passino, Claudio; Landini, Luigi; Emdin, Michele; Vanello, Nicola

2016-01-01

Electroencephalographic (EEG) irreducible artifacts are common and the removal of corrupted segments from the analysis may be required. The present study aims at exploring the effects of different EEG Missing Data Segment (MDS) distributions on cross-correlation analysis, involving EEG and physiological signals. The reliability of cross-correlation analysis both at single subject and at group level as a function of missing data statistics was evaluated using dedicated simulations. Moreover, a Bayesian-based approach for combining the single subject results at group level by considering each subject’s reliability was introduced. Starting from the above considerations, the cross-correlation function between EEG Global Field Power (GFP) in delta band and end-tidal CO2 (PETCO2) during rest and voluntary breath-hold was evaluated in six healthy subjects. The analysis of simulated data results at single subject level revealed a worsening of precision and accuracy in the cross-correlation analysis in the presence of MDS. At the group level, a large improvement in the results’ reliability with respect to single subject analysis was observed. The proposed Bayesian approach showed a slight improvement with respect to simple average results. Real data results were discussed in light of the simulated data tests and of the current physiological findings. PMID:27809243

Assessment of the efficacy and safety of single platelet-rich plasma injection on different types and grades of facial wrinkles.

PubMed

Elnehrawy, Naema Y; Ibrahim, Zeinab A; Eltoukhy, Azza M; Nagy, Hala M

2017-03-01

Platelet-rich plasma (PRP) is considered as a growing modality for tissue regeneration and a developing research area for clinicians and researchers. PRP injection treatment provides supraphysiological concentrations of growth factors that may help in accelerated tissue remodeling and regeneration. To evaluate the efficacy and safety of single autologous PRP intradermal injection for treatment of facial wrinkles and for facial rejuvenation. A total of 20 subjects with different types of facial wrinkles were included in this study. All subjects received single PRP intradermal injection and were clinically assessed before and after treatment for a period of 8 weeks using Wrinkle Severity Rating Scale (WSRS), Skin Homogeneity and Texture (SHnT) Scale, Physician Assessment Scale, and Subject Satisfaction Scale. The mean value of WSRS reduced from 2.90 ± 0.91 before treatment to 2.10 ± 0.79 after 8 weeks of treatment. The most significant results were with younger subjects that have mild and moderate wrinkles of the nasolabial folds (NLFs). Fourteen of seventeen subjects with NLFs showed more than 25% improvement in their appearance. Side effects of PRP treatment were minimal to mild and with excellent tolerability. Single PRP intradermal injection is well tolerated and capable of rejuvenating the face and producing a significant correction of wrinkles especially the NLFs. © 2016 Wiley Periodicals, Inc.

Effect of Oral Coadministration of Ascorbic Acid with Ling Zhi Preparation on Pharmacokinetics of Ganoderic Acid A in Healthy Male Subjects: A Randomized Crossover Study

PubMed Central

Tawasri, Patcharanee; Ampasavate, Chadarat; Tharatha, Somsak

2016-01-01

The objective of this randomized, open-label, single-dose, two-phase crossover study was to determine the effect of ascorbic acid on pharmacokinetics of ganoderic acid A, an important biologically active triterpenoid compound with anticancer activities, following oral administration of water extract of fruiting bodies of Ling Zhi in 12 healthy male subjects. Each subject was randomized to receive either one of the two regimens: (1) a single dose of 3,000 mg of the Ling Zhi preparation or (2) a single dose of 3,000 mg of the Ling Zhi preparation in combination with 2,500 mg of ascorbic acid. After a washout period of at least two weeks, subjects were switched to receive the alternate regimen. Blood samples were collected in each phase immediately before dosing and at specific time points for 8 hours after dosing. Plasma ganoderic acid A concentrations were quantified using liquid chromatography-mass spectrometry (LC-MS). The pharmacokinetic parameters analyzed were maximal plasma concentration (C max), time to reach peak concentration (T max), area under the plasma concentration-time curve (AUC), and half-life (t 1/2). An oral coadministration of ascorbic acid with Ling Zhi preparation did not significantly alter the pharmacokinetic parameters of ganoderic acid A in healthy male subjects. PMID:27747224

Single Versus Multiple Parenting: Implications for Infancy.

ERIC Educational Resources Information Center

Eiduson, Bernice T.; And Others

This study, part of a naturalistic longitudinal study of infants being reared in a variety of family life styles, attempted to establish the extent to which differing parenting patterns affected early developmental outcomes. Subjects were 200 infants: 50 of single mothers who headed their family units, 50 of mothers in communal living groups, and…

Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects.

PubMed

Han, Yi; Ayalasomayajula, Surya; Pan, Wei; Yang, Fan; Yuan, Yaozong; Langenickel, Thomas; Hinder, Markus; Kalluri, Sampath; Pal, Parasar; Sunkara, Gangadhar

2017-02-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) and has been recently approved in several countries for the treatment of patients with heart failure and reduced ejection fraction. This was the first study conducted to characterise the pharmacokinetics of LCZ696 analytes (pro-drug sacubitril, active neprilysin inhibitor LBQ657 and valsartan) after single-dose administration of LCZ696 in healthy Chinese subjects. In this open-label, randomised, parallel-group study, following screening and baseline evaluation, eligible healthy subjects received single oral doses of LCZ696 50, 100, 200 or 400 mg. The pharmacokinetics, safety and tolerability of LCZ696 were assessed up to 72 h after dosing. A total of 40 healthy male subjects were enrolled, and all completed the study. Following oral administration, LCZ696 delivered systemic exposure to sacubitril, LBQ657 and valsartan with a median time to reach maximum plasma concentration (T max ) ranging from 0.50 to 1.25, 2.00 to 3.00 and 1.50 to 2.50 h, respectively, over the investigated dose range. The mean terminal elimination half-life (T 1/2 ) ranged from 0.89 to 1.35, 8.57 to 9.24 and 5.33 to 7.91 h for sacubitril, LBQ657 and valsartan, respectively. The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last ), and maximum plasma concentration (C max ) for LBQ657 increased dose proportionally over the entire dose range. Dose linear increase in the exposure was observed across the dose range for sacubitril and valsartan. LCZ696 was safe and well tolerated at all doses in this study. Adverse events of only mild intensity, which required no treatment, were reported in 6 (15 %) subjects. The pharmacokinetic profiles of LCZ696 analytes in Chinese subjects are similar to those reported previously in Caucasian subjects.

Automatic sleep stage classification using two facial electrodes.

PubMed

Virkkala, Jussi; Velin, Riitta; Himanen, Sari-Leena; Värri, Alpo; Müller, Kiti; Hasan, Joel

2008-01-01

Standard sleep stage classification is based on visual analysis of central EEG, EOG and EMG signals. Automatic analysis with a reduced number of sensors has been studied as an easy alternative to the standard. In this study, a single-channel electro-oculography (EOG) algorithm was developed for separation of wakefulness, SREM, light sleep (S1, S2) and slow wave sleep (S3, S4). The algorithm was developed and tested with 296 subjects. Additional validation was performed on 16 subjects using a low weight single-channel Alive Monitor. In the validation study, subjects attached the disposable EOG electrodes themselves at home. In separating the four stages total agreement (and Cohen's Kappa) in the training data set was 74% (0.59), in the testing data set 73% (0.59) and in the validation data set 74% (0.59). Self-applicable electro-oculography with only two facial electrodes was found to provide reasonable sleep stage information.

Single-gender mathematics and science classes and the effects on urban middle school boys and girls

NASA Astrophysics Data System (ADS)

Sudler, Dawn M.

This study compared the differences in the Criterion-Referenced Competency Test (CRCT) mathematics and science achievement scores of boys and girls in Grade 7 at two urban middle schools. The data allowed the researcher to determine to what degree boys and girls in Grade 7 differ in their mathematics and science achievements within a single-gender environment versus a coeducational learning environment. The study compared any differences between boys and girls in Grade 7 within a single-gender environment in the subjects of mathematics and science, as measured by the CRCT assessments. The study also compared differences between boys and girls in Grade 7 within a coeducational environment in the subjects of mathematics and science, as measured by the CRCT assessments. Two middle schools were used within the study. One middle school was identified as a single-gender school (Middle School A); the other was identified as a coeducational school (Middle School B). This quantitative study applied the use of a descriptive research design. In addition, CRCT scores for the subjects of mathematics and science were taken during the spring of 2008 from both middle schools. Data were measured using descriptive statistics and independent t test calculations. The frequency statistics proceeded to compare each sample performance levels. The data were described in means, standard deviations, standard error means, frequency, and percentages. This method provided an excellent description of a sample scored on the spring 2008 CRCT mathematics and science assessments.

Identification of the most significant electrode positions in electromyographic evaluation of swallowing-related movements in humans.

PubMed

Zaretsky, E; Pluschinski, P; Sader, R; Birkholz, P; Neuschaefer-Rube, C; Hey, Christiane

2017-02-01

Surface electromyography (sEMG) is a well-established procedure for recording swallowing-related muscle activities. Because the use of a large number of sEMG channels is time consuming and technically sophisticated, the aim of this study was to identify the most significant electrode positions associated with oropharyngeal swallowing activities. Healthy subjects (N = 16) were tested with a total of 42 channels placed in M. masseter, M. orbicularis oris, submental and paralaryngeal regions. Each test subject swallowed 10 ml of water five times. After having identified 16 optimal electrode positions, that is, positions with the strongest signals quantified by the highest integral values, differences to 26 other ones were determined by a Mann-Whitney U test. Kruskal-Wallis H test was utilized for the analysis of differences between single subjects, subject subgroups, and single electrode positions. Factors associated with sEMG signals were examined in a linear regression. Sixteen electrode positions were chosen by a simple ranking of integral values. These positions delivered significantly higher signals than the other 26 positions. Differences between single electrode positions and between test subjects were also significant. Sixteen most significant positions were identified which represent swallowing-related muscle potentials in healthy subjects.

Human single-neuron responses at the threshold of conscious recognition

PubMed Central

Quiroga, R. Quian; Mukamel, R.; Isham, E. A.; Malach, R.; Fried, I.

2008-01-01

We studied the responses of single neurons in the human medial temporal lobe while subjects viewed familiar faces, animals, and landmarks. By progressively shortening the duration of stimulus presentation, coupled with backward masking, we show two striking properties of these neurons. (i) Their responses are not statistically different for the 33-ms, 66-ms, and 132-ms stimulus durations, and only for the 264-ms presentations there is a significantly higher firing. (ii) These responses follow conscious perception, as indicated by the subjects' recognition report. Remarkably, when recognized, a single snapshot as brief as 33 ms was sufficient to trigger strong single-unit responses far outlasting stimulus presentation. These results suggest that neurons in the medial temporal lobe can reflect conscious recognition by “all-or-none” responses. PMID:18299568

Comparative Efficacy of a Soft Toothbrush with Tapered-tip Bristles to an ADA Reference Toothbrush on Gingival Abrasion over a 12-Week Period.

PubMed

Gallob, John; Petrone, Dolores M; Mateo, Luis R; Chaknis, Patricia; Morrison, Boyce M; Panagakos, Foti; Williams, Malcolm

2016-06-01

Evaluation of the impact of a soft toothbrush with tapered-tip (Test Toothbrush) bristles and an ADA reference toothbrush (ADA Toothbrush) on gingival abrasion over a 12-week period. This was a randomized, single-center, examiner-blind, two-cell, parallel clinical research study and used the Danser Gingival Abrasion Index to assess the level of gingival abrasion after a single brushing, as well as after six weeks and 12 weeks of twice-daily brushing. Adult male and female subjects from the Central New Jersey, USA area refrained from all oral hygiene procedures for 24 hours. They reported to the study site after refraining from eating, drinking, and smoking for four hours. Following a qualifying examination using plaque and gingivitis scores along with a baseline gingival abrasion examination, subjects were randomized into two balanced groups, each group using one of the two study toothbrushes. Subjects were instructed to brush their teeth for one minute, under supervision, with their assigned toothbrush and a commercially available fluoride toothpaste (Colgate© Cavity Protection Toothpaste), after which they were again evaluated for gingival abrasion. Subjects were dismissed from the study site with their assigned toothbrush and toothpaste, and instructed to brush twice daily at home for the next 12 weeks. The subjects were instructed to brush for one minute during each tooth brushing. The subjects reported to the study site after six weeks and 12 weeks of product use, at which time they were evaluated for gingival abrasion. Seventy-one (71) subjects complied with the protocol and completed the clinical study. The results of this study showed that the Test Toothbrush provided statistically significantly (p < 0.05) greater reductions in gingival abrasion scores as compared to the gingival abrasion scores of the ADA Toothbrush after a single tooth brushing, after six weeks, and after 12 weeks of product use (75.0%, 85.5%, 73.9%, respectively). The soft toothbrush with tapered-tip bristles produced significantly less gingival abrasion after 12 weeks of product use as compared to the ADA reference toothbrush.

The maximum single dose of resistant maltodextrin that does not cause diarrhea in humans.

PubMed

Kishimoto, Yuka; Kanahori, Sumiko; Sakano, Katsuhisa; Ebihara, Shukuko

2013-01-01

The objective of the present study was to determine the maximum dose of resistant maltodextrin (Fibersol)-2, a non-viscous water-soluble dietary fiber), that does not induce transitory diarrhea. Ten healthy adult subjects (5 men and 5 women) ingested Fibersol-2 at increasing dose levels of 0.7, 0.8, 0.9, 1.0, and 1.1 g/kg body weight (bw). Each administration was separated from the previous dose by an interval of 1 wk. The highest dose level that did not cause diarrhea in any subject was regarded as the maximum non-effective level for a single dose. The results showed that no subject of either sex experienced diarrhea at dose levels of 0.7, 0.8, 0.9, or 1.0 g/kg bw. At the highest dose level of 1.1 g/kg bw, no female subject experienced diarrhea, whereas 1 male subject developed diarrhea with muddy stools 2 h after ingestion of the test substance. Consequently, the maximum non-effective level for a single dose of the resistant maltodextrin Fibersol-2 is 1.0 g/kg bw for men and >1.1 g/kg bw for women. Gastrointestinal symptoms were gurgling sounds in 4 subjects (7 events) and flatus in 5 subjects (9 events), although no association with dose level was observed. These symptoms were mild and transient and resolved without treatment.

Identification of rs7350481 at chromosome 11q23.3 as a novel susceptibility locus for metabolic syndrome in Japanese individuals by an exome-wide association study.

PubMed

Yamada, Yoshiji; Sakuma, Jun; Takeuchi, Ichiro; Yasukochi, Yoshiki; Kato, Kimihiko; Oguri, Mitsutoshi; Fujimaki, Tetsuo; Horibe, Hideki; Muramatsu, Masaaki; Sawabe, Motoji; Fujiwara, Yoshinori; Taniguchi, Yu; Obuchi, Shuichi; Kawai, Hisashi; Shinkai, Shoji; Mori, Seijiro; Arai, Tomio; Tanaka, Masashi

2017-06-13

We have performed exome-wide association studies to identify genetic variants that influence body mass index or confer susceptibility to obesity or metabolic syndrome in Japanese. The exome-wide association study for body mass index included 12,890 subjects, and those for obesity and metabolic syndrome included 12,968 subjects (3954 individuals with obesity, 9014 controls) and 6817 subjects (3998 individuals with MetS, 2819 controls), respectively. Exome-wide association studies were performed with Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of genotypes of single nucleotide polymorphisms to body mass index was examined by linear regression analysis, and that of allele frequencies of single nucleotide polymorphisms to obesity or metabolic syndrome was evaluated with Fisher's exact test. The exome-wide association studies identified six, 11, and 40 single nucleotide polymorphisms as being significantly associated with body mass index, obesity (P <1.21 × 10-6), or metabolic syndrome (P <1.20 × 10-6), respectively. Subsequent multivariable logistic regression analysis with adjustment for age and sex revealed that three and five single nucleotide polymorphisms were related (P < 0.05) to obesity or metabolic syndrome, respectively, with one of these latter polymorphisms-rs7350481 (C/T) at chromosome 11q23.3-also being significantly (P < 3.13 × 10-4) associated with metabolic syndrome. The polymorphism rs7350481 may thus be a novel susceptibility locus for metabolic syndrome in Japanese. In addition, single nucleotide polymorphisms in three genes (CROT, TSC1, RIN3) and at four loci (ANKK1, ZNF804B, CSRNP3, 17p11.2) were implicated as candidate determinants of obesity and metabolic syndrome, respectively.

Dynamic changes of RNA-sequencing expression for precision medicine: N-of-1-pathways Mahalanobis distance within pathways of single subjects predicts breast cancer survival

PubMed Central

Piegorsch, Walter W.; Lussier, Yves A.

2015-01-01

Motivation: The conventional approach to personalized medicine relies on molecular data analytics across multiple patients. The path to precision medicine lies with molecular data analytics that can discover interpretable single-subject signals (N-of-1). We developed a global framework, N-of-1-pathways, for a mechanistic-anchored approach to single-subject gene expression data analysis. We previously employed a metric that could prioritize the statistical significance of a deregulated pathway in single subjects, however, it lacked in quantitative interpretability (e.g. the equivalent to a gene expression fold-change). Results: In this study, we extend our previous approach with the application of statistical Mahalanobis distance (MD) to quantify personal pathway-level deregulation. We demonstrate that this approach, N-of-1-pathways Paired Samples MD (N-OF-1-PATHWAYS-MD), detects deregulated pathways (empirical simulations), while not inflating false-positive rate using a study with biological replicates. Finally, we establish that N-OF-1-PATHWAYS-MD scores are, biologically significant, clinically relevant and are predictive of breast cancer survival (P < 0.05, n = 80 invasive carcinoma; TCGA RNA-sequences). Conclusion: N-of-1-pathways MD provides a practical approach towards precision medicine. The method generates the magnitude and the biological significance of personal deregulated pathways results derived solely from the patient’s transcriptome. These pathways offer the opportunities for deriving clinically actionable decisions that have the potential to complement the clinical interpretability of personal polymorphisms obtained from DNA acquired or inherited polymorphisms and mutations. In addition, it offers an opportunity for applicability to diseases in which DNA changes may not be relevant, and thus expand the ‘interpretable ‘omics’ of single subjects (e.g. personalome). Availability and implementation: http://www.lussierlab.net/publications/N-of-1-pathways. Contact: yves@email.arizona.edu or piegorsch@math.arizona.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26072495

Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects.

PubMed

Shin, Dongseong; Lee, SeungHwan; Yi, Sojeong; Yoon, Seo Hyun; Cho, Joo-Youn; Bahng, Mi Young; Jang, In-Jin; Yu, Kyung-Sang

2017-01-01

DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5) in the plasma and urine after administration of a single oral dose in healthy male subjects. A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP) enzymes on the pharmacokinetics of DA-8031 was evaluated. After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2-3 h and was eliminated with terminal elimination half-life of 17.9-28.7 h. The mean renal clearance was 3.7-5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20-80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized C max and AUC 0- t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported. In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20-80 mg. Genetic polymorphisms of CYP2D6 had an effect on the systemic exposure of DA-8031. DA-8031 was well tolerated after single doses of 80 mg or less.

Randomized trial of a comparison of the efficacy of TVT-O and single-incision tape TVT SECUR systems in the treatment of stress urinary incontinent women--2-year follow-up.

PubMed

Masata, Jaromir; Svabik, Kamil; Zvara, Karel; Drahoradova, Petra; El Haddad, Rachid; Hubka, Petr; Martan, Alois

2012-10-01

The aim of this study was to compare the efficacy of the use of tension-free vaginal tape obturator (TVT-O) and single-incision TVT SECUR, hammock and U approach (TVT-S, H and U), in the treatment of urodynamic stress urinary incontinence (SUI). This single-center randomized three-arm trial compared the objective and subjective efficacy and early failure rate of the TVT-O and TVT-S H and U approach by objective criteria (cough test) and subjective criteria using the International Consultation on Incontinence Questionnaire--Short Form (ICIQ-UI SF). The objective efficacy rate was defined as the number of patients with a negative cough stress test. Subjective cure was defined by no stress leakage of urine after surgery based on the evaluation of ICIQ-UI SH (when patients ticked "Never"/"Urine does not leak" in answer to question 6: When does urine leak?). Objective and subjective efficacy were evaluated using Last Failure Carried Forward analysis, i.e., final analysis also included patients with early failure. To describe outcome at different time points, the Last Observation Carried Forward method was also implemented. One hundred ninety-seven women with proven SUI were randomized into three groups--TVT-O (n = 68), TVT-S H (n = 64), and TVT-S U (n = 65). Each patient allocated to a treatment group received the planned surgery. There were no differences in each group in preoperative characteristics. Median follow-up after surgery was 2 years (SD, 0.8; range, 0.1 to 3.8 years). Of the subjects, 92.6% in the TVT-O group, 68.8% in the TVT-S H group, and 69.2% in the TVT-S U group had negative stress test (p < 0.001). Of the subjects, 85.3 % in the TVT-O group, 68.8% in the TVT-S H group, and 61.5% in the TVT-S U group were subjectively continent (p = 0.02). Our study demonstrated a significantly lower subjective and objective cure rate in the single-incision TVT group compared to the TVT-O group.

A population MRI brain template and analysis tools for the macaque.

PubMed

Seidlitz, Jakob; Sponheim, Caleb; Glen, Daniel; Ye, Frank Q; Saleem, Kadharbatcha S; Leopold, David A; Ungerleider, Leslie; Messinger, Adam

2018-04-15

The use of standard anatomical templates is common in human neuroimaging, as it facilitates data analysis and comparison across subjects and studies. For non-human primates, previous in vivo templates have lacked sufficient contrast to reliably validate known anatomical brain regions and have not provided tools for automated single-subject processing. Here we present the "National Institute of Mental Health Macaque Template", or NMT for short. The NMT is a high-resolution in vivo MRI template of the average macaque brain generated from 31 subjects, as well as a neuroimaging tool for improved data analysis and visualization. From the NMT volume, we generated maps of tissue segmentation and cortical thickness. Surface reconstructions and transformations to previously published digital brain atlases are also provided. We further provide an analysis pipeline using the NMT that automates and standardizes the time-consuming processes of brain extraction, tissue segmentation, and morphometric feature estimation for anatomical scans of individual subjects. The NMT and associated tools thus provide a common platform for precise single-subject data analysis and for characterizations of neuroimaging results across subjects and studies. Copyright © 2017 ElsevierCompany. All rights reserved.

Injectable percutaneous polydimethicone in the treatment of pedal keratomas: a single blind randomized trial.

PubMed

Tollafield, D R; Holdcroft, D J; Singh, R; Haque, M S

2001-01-01

Thirty-one subjects who presented with plantar (metatarsal lesions only 21 out of 31 patients completed the study) completed a single blind injection of 350-centistroke polydimethicone or saline over a 6 to 9-month period. The injectable silicone conformed to European Economic Community standards and was accepted by the Medical Devices Agency (UK). The subjects were equally divided between male and female. Two randomly divided groups received silicone (n = 16) and sterile saline (n = 15). Total volumes used were not identical between the groups of subjects (p = .05), although the maximum volume was no greater than 1.5 ml in any subject. The effectiveness of the injection was reviewed using a Harris-Beath ink mat, visual analogue scale, alteration in frequency of treatment, and subjective analysis of reduction in lesions before and after by color photography. Essential histopathology was undertaken on 11 subjects. Granulomatous reactions were only positively identified in one case. Nine matched pairs showed no statistically significant difference between the two treatments (p = .082) using parametric and nonparametric tests. This study found no evidence to show that small quantities of medically prepared liquid silicone caused adverse reactions, although two cases were more sensitive after injection of silicone.

A double-blind, randomized, placebo-controlled, single-dose study of the cyclooxygenase-2 inhibitor, GW406381, as a treatment for acute migraine.

PubMed

Wentz, A L; Jimenez, T B; Dixon, R M; Aurora, S K; Gold, M

2008-04-01

The objective of the present study was to explore the clinical efficacy and tolerability of GW406381, a cyclooxygenase-2 (COX-2) inhibitor with relatively high CNS penetration, in acute migraine. This was a double-blind, single-dose study of GW406381 compared with placebo and naproxen sodium compared with placebo (protocol number CXA20008). Three hundred and thirty-seven subjects were randomized 1:1:1 to GW406381 (70 mg), naproxen sodium (825 mg), or placebo for the treatment of one migraine headache of moderate or severe intensity in a potential 8-week period. The primary end-point was the proportion of subjects with headache relief [reduction in headache severity score from pre-dose 2 (moderate) or 3 (severe) to 0 (no pain) or 1 (mild)] at 2 h post-dose for GW406381 compared with placebo. Significantly higher proportions of subjects treated with GW406381 (50%, P = 0.032) or naproxen sodium (56%, P = 0.005) than with placebo (35%) reported headache relief at 2 h post-dose. Additional significant benefits were observed on many secondary outcomes, including proportions of subjects pain-free, for both GW406381 and naproxen sodium treatment compared with placebo. Both active treatments were well tolerated. Single-dose GW406381 (70 mg) and naproxen sodium (825 mg) were effective and well tolerated in the treatment of acute migraine.

Age-related degeneration in leg-extensor muscle-tendon units decreases recovery performance after a forward fall: compensation with running experience.

PubMed

Karamanidis, Kiros; Arampatzis, Adamantios

2007-01-01

The goals of this study were to investigate whether the lower muscle-tendon units (MTUs) capacities in older affect their ability to recover balance with a single-step after a fall, and to examine whether running experience enhances and protects this motor skill in young and old adults. The investigation was conducted on 30 older and 19 younger divided into two subgroups: runners versus non-active. In previous studies we documented that the older had lower leg extensor muscle strength and tendon stiffness while running had no effect on MTUs capacities. The current study examined recovery mechanics of the same individuals after an induced forward fall. Younger were better able to recover balance with a single-step compared to older (P < 0.001); this ability was associated with a more effective body configuration at touchdown (more posterior COM position relative to the recovery foot, P <0.001). MTUs capacities classified 88.6% of the subjects into single- or multiple-steppers. Runners showed a superior ability to recover balance with a single-step (P < 0.001) compared to non-active subjects due to a more effective mechanical response during the stance phase (greater knee joint flexion, P <0.05). We concluded that the age-related degeneration of the MTUs significantly diminished the older adults' ability to restore balance with a single-step. Running seems to enhance and protect this motor skill. We suggested that runners, due to their running experience, could update the internal representation of mechanisms responsible for the control of dynamic stability during a forward fall and, thus, were able to restore balance more often with a single-step compared to the non-active subjects.

Ultrasonic propulsion of kidney stones: preliminary results of human feasibility study.

PubMed

Bailey, Michael; Cunitz, Bryan; Dunmire, Barbrina; Paun, Marla; Lee, Franklin; Ross, Susan; Lingeman, James; Coburn, Michael; Wessells, Hunter; Sorensen, Mathew; Harper, Jonathan

2014-09-03

One in 11 Americans has experienced kidney stones, with a 50% average recurrence rate within 5-10 years. Ultrasonic propulsion (UP) offers a potential method to expel small stones or residual fragments before they become a recurrent problem. Reported here are preliminary findings from the first investigational use of UP in humans. The device uses a Verasonics ultrasound engine and Philips HDI C5-2 probe to generate real-time B-mode imaging and targeted "push" pulses on demand. There are three arms of the study: de novo stones, post-lithotripsy fragments, and the preoperative setting. A pain questionnaire is completed prior to and following the study. Movement is classified based on extent. Patients are followed for 90 days. Ten subjects have been treated to date: three de novo , five post-lithotripsy, and two preoperative. None of the subjects reported pain associated with the treatment or a treatment related adverse event, beyond the normal discomfort of passing a stone. At least one stone was moved in all subjects. Three of five post-lithotripsy subjects passed a single or multiple stones within 1-2 weeks following treatment; one subject passed two (1-2 mm) fragments before leaving clinic. In the pre-operative studies we successfully moved 7 - 8 mm stones. In four subjects, UP revealed multiple stone fragments where the clinical image and initial ultrasound examination indicated a single large stone.

Thematic versus Subject-Based Curriculum Delivery and Achievement Goals: Findings from a Single-School Study

ERIC Educational Resources Information Center

Putwain, Dave; Whiteley, Helen; Caddick, Lee

2011-01-01

Background: It has been claimed that thematic or integrated approaches to curriculum delivery offer a range of advantages over subject-based modes of delivery including improved pupil motivation. Purpose: This study put claims regarding pupil motivation to the test, using the achievement goals framework. This contemporary approach to understanding…

Single-trial laser-evoked potentials feature extraction for prediction of pain perception.

PubMed

Huang, Gan; Xiao, Ping; Hu, Li; Hung, Yeung Sam; Zhang, Zhiguo

2013-01-01

Pain is a highly subjective experience, and the availability of an objective assessment of pain perception would be of great importance for both basic and clinical applications. The objective of the present study is to develop a novel approach to extract pain-related features from single-trial laser-evoked potentials (LEPs) for classification of pain perception. The single-trial LEP feature extraction approach combines a spatial filtering using common spatial pattern (CSP) and a multiple linear regression (MLR). The CSP method is effective in separating laser-evoked EEG response from ongoing EEG activity, while MLR is capable of automatically estimating the amplitudes and latencies of N2 and P2 from single-trial LEP waveforms. The extracted single-trial LEP features are used in a Naïve Bayes classifier to classify different levels of pain perceived by the subjects. The experimental results show that the proposed single-trial LEP feature extraction approach can effectively extract pain-related LEP features for achieving high classification accuracy.

Single-trial classification of motor imagery differing in task complexity: a functional near-infrared spectroscopy study

PubMed Central

2011-01-01

Background For brain computer interfaces (BCIs), which may be valuable in neurorehabilitation, brain signals derived from mental activation can be monitored by non-invasive methods, such as functional near-infrared spectroscopy (fNIRS). Single-trial classification is important for this purpose and this was the aim of the presented study. In particular, we aimed to investigate a combined approach: 1) offline single-trial classification of brain signals derived from a novel wireless fNIRS instrument; 2) to use motor imagery (MI) as mental task thereby discriminating between MI signals in response to different tasks complexities, i.e. simple and complex MI tasks. Methods 12 subjects were asked to imagine either a simple finger-tapping task using their right thumb or a complex sequential finger-tapping task using all fingers of their right hand. fNIRS was recorded over secondary motor areas of the contralateral hemisphere. Using Fisher's linear discriminant analysis (FLDA) and cross validation, we selected for each subject a best-performing feature combination consisting of 1) one out of three channel, 2) an analysis time interval ranging from 5-15 s after stimulation onset and 3) up to four Δ[O2Hb] signal features (Δ[O2Hb] mean signal amplitudes, variance, skewness and kurtosis). Results The results of our single-trial classification showed that using the simple combination set of channels, time intervals and up to four Δ[O2Hb] signal features comprising Δ[O2Hb] mean signal amplitudes, variance, skewness and kurtosis, it was possible to discriminate single-trials of MI tasks differing in complexity, i.e. simple versus complex tasks (inter-task paired t-test p ≤ 0.001), over secondary motor areas with an average classification accuracy of 81%. Conclusions Although the classification accuracies look promising they are nevertheless subject of considerable subject-to-subject variability. In the discussion we address each of these aspects, their limitations for future approaches in single-trial classification and their relevance for neurorehabilitation. PMID:21682906

Pharmacokinetics of the BCL-2 Inhibitor Venetoclax in Healthy Chinese Subjects.

PubMed

Cheung, Tommy T; Salem, Ahmed Hamed; Menon, Rajeev M; Munasinghe, Wijith P; Bueno, Orlando F; Agarwal, Suresh K

2018-05-01

Venetoclax has been approved in the United States, Europe, Canada, and Australia for appropriate patients with difficult-to-treat chronic lymphocytic leukemia (CLL). The objective of this phase 1 study was to evaluate the pharmacokinetics of venetoclax in Chinese subjects to inform the dose selection of venetoclax in a phase 2 study of patients with relapsed/refractory (R/R) CLL in China. Twelve healthy first-generation Han Chinese subjects received a single 100-mg dose of venetoclax following a low-fat breakfast. Pharmacokinetic parameters were estimated using noncompartmental methods. After a single dose of venetoclax in healthy Chinese subjects, the median time to peak concentration was 6 hours (range, 4 to 6 hours), and the mean ± SD C max , AUC inf , and terminal half-life were 1.0 ± 0.32 μg/mL, 12.6 ± 5.4 μg·h/mL, and 18.4 ± 2.97 hours, respectively. On average, venetoclax C max and AUC inf values were 94% and 66% higher, respectively, in Chinese subjects compared with those observed historically for non-Asian subjects receiving the same dose. Based on these pharmacokinetic results and the established exposure-response relationship of venetoclax in non-Asian CLL subjects, a 400-mg once-daily dosage regimen was selected for evaluating the venetoclax pharmacokinetics, efficacy, and safety in the venetoclax phase 2 open-label study in Chinese subjects with R/R CLL. © 2017, The American College of Clinical Pharmacology.

Case study: videogame distraction reduces behavioral distress in a preschool-aged child undergoing repeated burn dressing changes: a single-subject design.

PubMed

Sil, Soumitri; Dahlquist, Lynnda M; Burns, Andrew J

2013-04-01

This single-subject design study evaluated the feasibility and efficacy of passive and interactive videogame distraction on behavioral distress for a preschool-aged child receiving repeated burn dressing changes. A 4-year-old girl underwent 3 baseline and 10 videogame distraction sessions (5 passive and 5 interactive) using a restricted alternating treatments design. Observed behavioral distress was coded, and parents and nurses rated the child's distress and cooperative behavior. Relative to baseline, behavioral distress decreased and cooperative behavior increased immediately after the onset of videogame distraction. Single Case Randomization Tests revealed significantly lower behavioral distress and greater cooperation during interactive videogame distraction relative to passive videogame distraction. Interactive videogame distraction appears to be a feasible and effective pain management strategy for a preschool-aged child undergoing repeated painful medical procedures.

Reference values for fatigued versus non-fatigued limb symmetry index measured by a newly designed single-leg hop test battery in healthy subjects: a pilot study.

PubMed

Leister, Iris; Mattiassich, Georg; Kindermann, Harald; Ortmaier, Reinhold; Barthofer, Jürgen; Vasvary, Imre; Katzensteiner, Klaus; Stelzhammer, Christine; Kulnik, Stefan Tino

2018-01-01

There is sparse evidence for return to sport criteria after knee injury. Functional performance deficits, particularly in fatigued muscular condition, should be verified prior to the attempt to return to high-risk pivoting sports. The purpose of this study was to generate reference values for the limb symmetry index (LSI) of healthy subjects in fatigued and non-fatigued muscular condition in a newly designed test battery. Forty-two healthy subjects [22 females, 20 males; mean (SD) age 30.4 (6.6) years] were evaluated using a test battery consisting of an isometric strength test, a series of five single-leg hop tests and an integrated fatigue protocol. Subjective physical activity was assessed with the Tegner Activity Scale (TAS). The cut-off values for healthy subjects were calculated considering the fifth percentile as the minimum reference value for the LSI and single-leg hop distance. The mean (SD) overall LSI was 98.8% (4.6). No significant gender or age specific differences in limb symmetry were observed. The comparison of the non-fatigued LSI with the overall LSI revealed no clinically relevant change due to muscular fatigue. Repeated measures ANOVA revealed a significant within effect on fatigue/non-fatigue condition ( F (1,38)  = 18.000; p  < 0.001, η 2  = 0.321) on absolute single-leg hop distance. Moreover, a significant between effect on the TAS-parameter ( F (1,38)  = 5.928; p  = 0.020, η 2  = 0.135 between: TAS ≤ 5/TAS > 5) and on gender ( F (1,38)  = 23.956; p  < 0.001, η 2  = 0.387) could be detected. The absolute jumping distance in the single-leg hop for distance was significantly reduced due to fatigue. No clinically relevant effect of muscular fatigue was observed on limb symmetry in our study sample. Gender and physical activity are important factors to be considered when interpreting reference values.

Host Th1/Th2 immune response to Taenia solium cyst antigens in relation to cyst burden of neurocysticercosis.

PubMed

Tharmalingam, J; Prabhakar, A T; Gangadaran, P; Dorny, P; Vercruysse, J; Geldhof, P; Rajshekhar, V; Alexander, M; Oommen, A

2016-10-01

Neurocysticercosis (NCC), Taenia solium larval infection of the brain, is an important cause of acquired seizures in endemic countries, which relate to number, location and degenerating cysts in the brain. Multicyst infections are common in endemic countries although single-cyst infection prevails in India. Single-cyst infections in an endemic country suggest a role for host immunity limiting the infection. This study examined ex vivo CD4(+) T cells and in vitro Th1 and Th2 cytokine responses to T. solium cyst antigens of peripheral blood mononuclear cells of healthy subjects from endemic and nonendemic regions and of single- and multicyst-infected patients for association with cyst burden of NCC. T. solium cyst antigens elicited a Th1 cytokine response in healthy subjects of T. solium-endemic and T. solium-non-endemic regions and those with single-cyst infections and a Th2 cytokine response from subjects with multicyst neurocysticercosis. Multicyst neurocysticercosis subjects also exhibited low levels of effector memory CD4(+) T cells. Th1 cytokine response of T. solium exposure and low infectious loads may aid in limiting cyst number. Th2 cytokines and low effector T cells may enable multiple-cyst infections to establish and persist. © 2016 John Wiley & Sons Ltd.

Pharmacokinetics After Single Ascending Dose, Food Effect, and Safety of Sacubitril/Valsartan (LCZ696), an Angiotensin Receptor and Neprilysin Inhibitor, in Healthy Japanese Subjects.

PubMed

Akahori, Mizuki; Ayalasomayajula, Surya; Langenickel, Thomas; Pal, Parasar; Zhou, Wei; Sunkara, Gangadhar

2017-06-01

LCZ696 (sacubitril/valsartan) is a novel angiotensin receptor neprilysin inhibitor (ARNI) that has been developed for treatment of heart failure patients with reduced ejection fraction and approved in the US, Europe, and many other countries. This randomized, placebo-controlled study was conducted in healthy Japanese male subjects (N = 50) to assess the pharmacokinetics and safety of single ascending oral doses (20-600 mg) of LCZ696. Food effect was also evaluated following administration of 200 mg dose. Plasma and urine samples from 40 subjects receiving LCZ696 were collected to assess pharmacokinetics of LCZ696 analytes (sacubitril, sacubitrilat, and valsartan). Following single oral dose administration of LCZ696, sacubitril and valsartan rapidly appeared in systemic circulation with a dose-linear increase in the exposure to the LCZ696 analytes. Of the administered dose, approximately 0.85 %, 54.0 %, and 8.19 % of sacubitril, sacubitrilat, and valsartan, respectively, were recovered in urine. Food reduced AUC of sacubitril, sacubitrilat, and valsartan by 21, 8, and 40 %, respectively, and C max by 72, 27, and 51 %, respectively. Single oral doses of up to 600 mg of LCZ696 were safe and generally well tolerated in healthy Japanese male subjects.

Establishing Interventions via a Theory-Driven Single Case Design Research Cycle

ERIC Educational Resources Information Center

Kilgus, Stephen P.; Riley-Tillman, T. Chris; Kratochwill, Thomas R.

2016-01-01

Recent studies have suggested single case design (SCD) intervention research is subject to publication bias, wherein studies are more likely to be published if they possess large or statistically significant effects and use rigorous experimental methods. The nature of SCD and the purposes for which it might be used could suggest that large effects…

Interventions to Support Social Interaction in Children with Autism Spectrum Disorders: A Systematic Review of Single Case Studies

ERIC Educational Resources Information Center

Ozuna, Jennifer; Mavridis, Alexis; Hott, Brittany L.

2015-01-01

Social interaction is a core deficit in individuals with autism spectrum disorder (ASD). Therefore, parents and teachers need effective interventions to support students with ASD. This synthesis provides a quantitative analysis of single-subject studies that examine interventions to support social interactions in children with ASD. Results suggest…

21 CFR 320.31 - Applicability of requirements regarding an “Investigational New Drug Application.”

Code of Federal Regulations, 2010 CFR

2010-04-01

... patients where either the maximum single or total daily dose exceeds that specified in the labeling of the... application. (2) A multiple-dose study in normal subjects or patients where either the single or total daily... conducting the study, including any contract research organization, shall retain reserve samples of any test...

Student and Teacher Perceptions of a Single-Sex Middle School Learning Environment.

ERIC Educational Resources Information Center

Smith, Nancy

A study of a single-sex learning environment was conducted in a public school, Edward Hand Middle School in Lancaster, Pennsylvania; sixth, seventh, and eighth grade students were grouped homogeneously by sex for all major subjects for a period of one semester and grouped heterogeneously for one semester. The study examined the effects that the…

Improving Treatment Plan Implementation in Schools: A Meta-Analysis of Single Subject Design Studies

ERIC Educational Resources Information Center

Noell, George H.; Gansle, Kristin A.; Mevers, Joanna Lomas; Knox, R. Maria; Mintz, Joslyn Cynkus; Dahir, Amanda

2014-01-01

Twenty-nine peer-reviewed journal articles that analyzed intervention implementation in schools using single-case experimental designs were meta-analyzed. These studies reported 171 separate data paths and provided 3,991 data points. The meta-analysis was accomplished by fitting data extracted from graphs in mixed linear growth models. This…

Play Caging Benefits the Behavior of Singly Housed Laboratory Rhesus Macaques (Macaca mulatta)

PubMed Central

Griffis, Caroline M; Martin, Allison L; Perlman, Jaine E; Bloomsmith, Mollie A

2013-01-01

This study addresses a recommendation in The Guide for the Care and Use of Laboratory Animals to provide singly housed nonhuman primates with intermittent access to large, enriched (play) caging. Research on the potential benefits of this type of caging is limited. The present study examines the effects of play caging on behavior, activity, and enrichment use. Singly housed, adult male, rhesus macaques (n = 10) underwent a baseline phase in their home cages, a 2-wk treatment phase with housing in play cages, and a posttreatment phase after returning to their home cages. Each subject underwent focal behavioral observations (n = 10; duration 30 min each) during each study phase, for a total of 150 h of data collection. Results showed increases in locomotion and enrichment use and a trend toward decreased abnormal behavior while subjects were in the play cage, with the durations of these behaviors returning to baseline levels after treatment. Anxiety-related behaviors decreased between the treatment and posttreatment phases but not between baseline and treatment, suggesting that outside factors may have influenced the decline. During the treatment phase, subjects spent more time in the upper quadrants of the play caging and preferred a mirror and forage boards as forms of enrichment. The greatest behavioral improvement occurred during the first week in the play cage. This study provides evidence to support the benefits of play caging for singly housed rhesus macaques. PMID:24041207

Platelet Aggregation Inhibitory Effects and Pharmacokinetics of Prasugrel Used in Combination With Aspirin in Healthy Japanese Subjects.

PubMed

Umemura, Kazuo; Ikeda, Yasuhiko; Matsushima, Nobuko; Kondo, Kazunao

2017-07-01

We evaluated the pharmacokinetics and pharmacodynamics of prasugrel used in combination with aspirin in healthy Japanese subjects. All subjects received aspirin 100 mg/day. Subsequently, in the single-administration study, 23 subjects also received prasugrel 20 or 30 mg, and in the multiple-administration study, 20 subjects received a loading dose of prasugrel 20 or 30 mg on day 1, followed by a maintenance dose of prasugrel 5 or 7.5 mg/day, respectively, on days 2-5. In both studies, the plasma concentration of the active metabolite of prasugrel, R-138727, reached a maximum 0.5 hours after administration and rapidly decreased within 4 hours. In the single-administration study, the inhibitory effect on adenosine diphosphate-induced platelet aggregation was significantly higher in the prasugrel 20- and 30-mg groups than in the placebo group at all times (1-144 hours) after administration. In the multiple-administration study, a similar antiplatelet effect was found after both the loading dose and the maintenance dose and was maintained for 3-6 days after the last administration. There were study drug-related adverse events; however, all were mild, and none was clinically significant. © 2016 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Case Series Investigations in Cognitive Neuropsychology

PubMed Central

Schwartz, Myrna F.; Dell, Gary S.

2011-01-01

Case series methodology involves the systematic assessment of a sample of related patients, with the goal of understanding how and why they differ from one another. This method has become increasingly important in cognitive neuropsychology, which has long been identified with single-subject research. We review case series studies dealing with impaired semantic memory, reading, and language production, and draw attention to the affinity of this methodology for testing theories that are expressed as computational models and for addressing questions about neuroanatomy. It is concluded that case series methods usefully complement single-subject techniques. PMID:21714756

The risk of umbilical hernia and other complications with laparoendoscopic single-site surgery.

PubMed

Gunderson, Camille C; Knight, Jason; Ybanez-Morano, Jessica; Ritter, Carol; Escobar, Pedro F; Ibeanu, Okechukwu; Grumbine, Francis C; Bedaiwy, Mohamed A; Hurd, William W; Fader, Amanda Nickles

2012-01-01

To estimate the risk of umbilical hernia and other latent complications in women who underwent laparoendoscopic single-site surgery (LESS) for a gynecologic indication. Retrospective, nonrandomized clinical study (Canadian Task Force classification II-2). Four tertiary care academic medical centers. Women undergoing LESS for a benign or malignant gynecologic indication from 2009 to 2011. A total of 211 women underwent LESS via a single 1.5- to 2.0-cm umbilical incision. All surgeries were performed by advanced gynecologic laparoscopists. Incisions were repaired with a running, delayed absorbable suture. Subject demographics and clinical variables were collected and surgical outcomes analyzed. Median age and body mass index were 45 years and 30 kg/m(2), respectively. Approximately half of study subjects underwent a hysterectomy with or without salpingo-oophorectomy, and 15% had a diagnosis of cancer. Overall, 0.9% of women were diagnosed with a preoperative umbilical hernia, and 2.4% of women experienced a major perioperative complication. After a median postoperative follow-up time of 16 months, 2.4% had development of an umbilical hernia. However, 4/5 of these women had significant risk factors for fascial weakening independent of LESS, including requirement for a second abdominal surgery in 1 subject and a cancer diagnosis with postoperative chemotherapy administration in 2 subjects. When these subjects deemed "high risk" for incisional disruption were excluded from the analysis, the umbilical hernia rate was 0.5% (1/207). On univariable analysis, obesity was the only factor associated with complications (p = .04). When performed by advanced laparoscopic surgeons, laparoendoscopic single-site gynecologic surgery is associated with a low risk of major adverse events. Additionally, the overall umbilical hernia rate was 2.4% and was lower (0.5%) in subjects without significant comorbidities. Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.

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.

A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab

PubMed Central

Kaur, Primal; Chow, Vincent; Zhang, Nan; Moxness, Michael; Kaliyaperumal, Arunan; Markus, Richard

2017-01-01

Objective To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501. Methods Randomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed concentration (Cmax). Secondary end points included safety and immunogenicity. Results AUCinf and Cmax were similar across the three groups. Geometrical mean ratio (GMR) of AUCinf was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of Cmax was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUCinf and Cmax were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups. Conclusions Results of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups. Trial registration number EudraCT number 2012-000785-37; Results. PMID:27466231

Phase I clinical studies of the advanced glycation end-product (AGE)-breaker TRC4186: safety, tolerability and pharmacokinetics in healthy subjects.

PubMed

Chandra, Kumar P; Shiwalkar, Ajay; Kotecha, Jignesh; Thakkar, Purav; Srivastava, Ambrish; Chauthaiwale, Vijay; Sharma, Sanjay K; Cross, Maurice R; Dutt, Chaitanya

2009-01-01

Advanced glycation end-products (AGEs) have been implicated in the pathogenesis of diabetic complications through a variety of mechanisms including endothelial dysfunction and structural abnormalities in the vasculature and myocardium. Reducing the AGEs burden and their ensuing pro-inflammatory, pro-oxidative and pro-coagulant effect with associated dysfunctional proteins in various target tissues may retard the progression of and even reverse diabetic macro- and microvascular complications. Pyridinium, 3-[[2-(methylsulfonyl) hydrazino] carbonyl]-1-[2-oxo-2-2-thienyl) ethyl]-chloride (TRC4186) has demonstrated AGE-breaking activities in in vitro experiments and improvement in the endothelial and myocardial function in animal models of diabetes mellitus with reduction of AGEs accumulation in tissues over time. The safety of TRC4186 has been established in in vitro and in vivo preclinical studies. Thus, this drug is being developed for the treatment of complications associated with diabetes. This investigation set out to evaluate the safety, tolerability and pharmacokinetics of TRC4186 in healthy human subjects after single and multiple ascending doses, fixed doses in elderly male and female subjects, and with food and different formulations of the compound. Four studies were conducted during phase I clinical development of TRC4186. These were: (i) a randomized, double-blind, placebo-controlled, single-dose, dose-ascending study in healthy male subjects with doses of TRC4186 ranging from 250 to 2500 mg administered as an oral solution (total six doses); (ii) a randomized, double-blind, placebo-controlled, multiple-dose, dose-ascending study in healthy male subjects with three doses of TRC4186 ranging from 500 to 2000 mg twice daily for 6 days with a final single dose on day 7; (iii) a randomized, open-label, three-way crossover study to assess the effect of food (fasted vs fed) and formulation (solution vs tablet) with TRC4186 500 mg; (iv) a randomized, double-blind, placebo-controlled, single-dose, dose-ascending study in elderly male and female subjects at a dose of TRC4186 500 mg followed by TRC4186 1000 mg after a 7-day washout period. The safety and tolerability of TRC4186 were assessed by considering adverse events (AEs), ECG findings, vital signs and laboratory investigation results. TRC4186 was rapidly absorbed, with maximum plasma concentrations (C(max)) attained within 1-4 hours. C(max) and area under the plasma concentration-time curve (AUC) were dose proportional over the range 250-2500 mg for a single dose and 500-2000 mg for multiple doses with twice-daily administration. Steady-state conditions were attained within 6 days at different dose levels. C(max) and AUC were not affected by age, sex, race or type of formulation. The tablet formulation of TRC4186 was bioequivalent with the solution form of the drug under fasting conditions and systemic availability of the tablet formulation was reduced by 40% when administered under fed conditions. Terminal elimination and renal clearance in the elderly male (age 69.1 +/- 6.0 years) were not significantly different compared with younger subjects (age 31 +/- 8.6 years). TRC4186 was safe and well tolerated when administered orally with either a single or multiple doses across the different ages, sexes, races and formulations studied. A dose-proportional increase in plasma TRC4186 concentration was seen, with steady state being achieved within 6 days.

Retention of the "first-trial effect" in gait-slip among community-living older adults.

PubMed

Liu, Xuan; Bhatt, Tanvi; Wang, Shuaijie; Yang, Feng; Pai, Yi-Chung Clive

2017-02-01

"First-trial effect" characterizes the rapid adaptive behavior that changes the performance outcome (from fall to non-fall) after merely a single exposure to postural disturbance. The purpose of this study was to investigate how long the first-trial effect could last. Seventy-five (≥ 65 years) community-dwelling older adults, who were protected by an overhead full body harness system, were retested for a single slip 6-12 months after their initial exposure to a single gait-slip. Subjects' body kinematics that was used to compute their proactive (feedforward) and reactive (feedback) control of stability was recorded by an eight-camera motion analysis system. We found the laboratory falls of subjects on their retest slip were significantly lower than that on the novel initial slip, and the reactive stability of these subjects was also significantly improved. However, the proactive stability of subjects remains unchanged between their initial slip and retest slip. The fall rates and stability control had no difference among the 6-, 9-, and 12-month retest groups, which indicated a maximum retention on 12 months after a single slip in the laboratory. These results highlighted the importance of the "first-trial effect" and suggested that perturbation training is effective for fall prevention, with lower trial doses for a long period (up to 1 year). Therefore, single slip training might benefit those older adults who could not tolerate larger doses in reality.

Pharmacokinetic profiles of repaglinide in elderly subjects with type 2 diabetes.

PubMed

Hatorp, V; Huang, W C; Strange, P

1999-04-01

Pharmacokinetic profiles of single- and multiple-dose regimens of repaglinide were evaluated in 12 elderly subjects with type 2 diabetes. On day 1, following a 10-hour fast, subjects received a single 2-mg dose of repaglinide. Starting on day 2 and continuing for 7 days, each subject received a 2-mg dose of repaglinide 15 minutes before each of the three main meals. On day 9, subjects received a single 2-mg dose of repaglinide. Pharmacokinetic profiles, including area under the curve (AUC), log(AUC), maximal concentration (Cmax), log(Cmax), time to maximal concentration (Tmax), and half-life (T(1/2)), were determined at completion of the single- and multiple-dose regimens (days 1 and 9, respectively). Trough repaglinide values were collected on days 2 through 7. The mean log(AUC) values after multiple dosing were significantly higher than the values obtained after a single dose. The mean values for log(Cmax), and Tmax were comparable after each dosing regimen. The T(1/2) of repaglinide after multiple dosing was 1.7 hours. The trough values for repaglinide were low. No hypoglycemic events were reported. The pharmacokinetic profiles of repaglinide after single- and multiple-dose regimens were similar, and repaglinide was well tolerated by elderly subjects with type 2 diabetes.

Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan.

PubMed

Mikamo, Hiroshige; Matsumizu, Miyako; Nakazuru, Yoshiomi; Okayama, Akifumi; Nagashima, Masahito

2015-07-01

Vulvovaginal candidiasis is the second most common cause of vaginal infections following bacterial vaginosis. For the treatment of vulvovaginal candidiasis, antifungal agents are used either as topical (vaginal tablets and cream) or oral formulations. A single oral 150 mg dose of fluconazole has been recommended as the standard therapy for uncomplicated, acute vulvovaginal candidiasis in global guidelines; however, in Japan oral fluconazole therapy has not been approved. We conducted a phase 3 study to evaluate the efficacy and safety of a single oral 150 mg dose of fluconazole in Japanese subjects with vulvovaginal candidiasis for regulatory submission. A total of 157 subjects received a single oral 150 mg dose of fluconazole. Candida species (104 strains) were identified by fungal culture from 102 subjects at baseline, including Candida albicans (100 strains). The efficacy rate for the therapeutic outcome (assessed based on a comprehensive evaluation of the clinical and mycological efficacy in each subject) was 74.7% (74/99) on Day 28 in the modified Intent-To-Treat (m-ITT) population. Concerning the clinical and mycological efficacy on Day 28 in the m-ITT population, the cure, cure or improvement, and eradication rates were 81.6%, 95.9%, and 85.9%, respectively. The most common treatment-related adverse events were diarrhea and nausea (1.9% for each). No clinically significant safety issues were reported. A single oral 150 mg dose of fluconazole demonstrated excellent therapeutic efficacy and was well tolerated in Japanese subjects with vulvovaginal candidiasis. NCT01806623. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Word and Number Reading in the Brain: Evidence from a Voxel-Based Lesion-Symptom Mapping Study

ERIC Educational Resources Information Center

Piras, Fabrizio; Marangolo, Paola

2009-01-01

The high incidence of number transcoding deficits in aphasic subjects suggests there is a strong similarity between language and number domains. However, recent single case studies of subjects who showed a dissociation between word and number word transcoding led us to hypothesize that the two types of stimuli are represented independently in the…

Effects of Extended-Release Niacin and Extended-Release Niacin/Laropiprant on the Pharmacokinetics of Simvastatin in Healthy Subjects.

PubMed

Lauring, Brett; Dishy, Victor; De Kam, Pieter-Jan; Crumley, Tami; Wenning, Larissa; Liu, Fang; Sisk, Christine; Wagner, John; Lai, Eseng

2015-01-01

The use of multiple lipid-modifying agents with different mechanisms of action is often required to regulate lipid levels in patients with dyslipidemia. During combination therapy, alterations in the pharmacokinetics of any of the drugs used and their metabolites may occur. Three separate open-label, randomized, crossover studies evaluated the potential for pharmacokinetic interaction between extended-release niacin (with and without concomitant laropiprant) and simvastatin in healthy subjects. Study 1 used single doses of extended-release niacin and simvastatin; study 2 used multiple-dose coadministration of extended-release niacin/laropiprant and simvastatin in healthy subjects; and study 3 used single doses of both extended-release niacin and the coadministration of extended-release niacin/laropiprant and simvastatin in healthy Chinese subjects. During each treatment period, plasma samples were collected predose and at prespecified postdose time points for pharmacokinetic analyses. The safety and tolerability of simvastatin with and without coadministered extended-release niacin (or extended-release niacin/laropiprant) were assessed by clinical evaluation of adverse experiences. In 2 studies in healthy subjects, modest increases in exposure to simvastatin acid (by ∼60%) by extended-release niacin and extended-release niacin/laropiprant were observed. Based on the clinical experience with simvastatin, these effects are not believed to be clinically meaningful. In the third study on healthy Chinese subjects, no statistically meaningful increases in exposure to simvastatin by extended-release niacin and extended-release niacin/laropiprant were observed. In all populations examined in these studies, the coadministration of extended-release niacin and simvastatin was generally well tolerated.

Intake occasion affects the serum cholesterol lowering of a plant sterol-enriched single-dose yoghurt drink in mildly hypercholesterolaemic subjects.

PubMed

Doornbos, A M E; Meynen, E M; Duchateau, G S M J E; van der Knaap, H C M; Trautwein, E A

2006-03-01

To determine the impact of intake occasion (with or without a meal), and product fat level on the cholesterol-lowering efficacy of a plant sterol (PS)-enriched (3 g/day) single-dose yoghurt drink. Double-blind, randomized, placebo-controlled, parallel study with a 4 weeks run-in and 4 weeks intervention period. Subjects recruited from the general community. A total of 184 moderate hypercholesterolaemic subjects (81 men and 103 women) (age 57+/-2 years) completed the study. The study product was a 100-g single-dose yoghurt drink with or without added PS in the form of PS esters. The subjects were randomly assigned to one of five 4-week treatments: (i) drink A (0.1% dairy fat, 2.2% total fat) with a meal, (ii) drink A without a meal, (iii) drink B (1.5% dairy fat, 3.3% total fat) with a meal, (iv) drink B without a meal and (v) placebo drink with a meal. LDL-cholesterol (LDL-C) was significantly lowered when the single-dose drink was taken with a meal independent of its fat content (drink A: -9.5% (P<0.001, 95% CI: -13.8 to -5.2); drink B: -9.3% (P<0.001, 95% CI: -13.7 to -4.9)) as compared to placebo. When consumed without a meal, LDL-C was also significantly decreased (drink A: -5.1% (P<0.05, 95% CI: -9.4 to -0.8); drink B: -6.9% (P<0.01, 95% CI: -11.3 to -2.5) as compared to placebo, however the effect was significantly smaller as compared to the intake with a meal. These results indicate that a PS-ester-enriched single-dose yoghurt drink effectively reduces LDL-C irrespective of the fat content of the product. A substantially larger decrease in serum cholesterol concentration was achieved when the single-dose drink was consumed with a meal emphasizing the importance of the intake occasion for optimal cholesterol-lowering efficacy. Unilever Research and Development, Vlaardingen, The Netherlands.

A Comparison of Single-Gender Classes and Traditional, Coeducational Classes on Student Academic Achievement, Discipline Referrals, and Attitudes toward Subjects

ERIC Educational Resources Information Center

Smith, Debra Messenger

2010-01-01

In recent years, there has been a resurgence of interest in single gender education. Emerging science has proven that boys and girls learn differently. This study compared fifth grade single-gender classes to fifth grade traditional, coeducational classes in the same urban middle school. The following were compared: students' academic achievement;…

The influence of an auditory-memory attention-demanding task on postural control in blind persons.

PubMed

Melzer, Itshak; Damry, Elad; Landau, Anat; Yagev, Ronit

2011-05-01

In order to evaluate the effect of an auditory-memory attention-demanding task on balance control, nine blind adults were compared to nine age-gender-matched sighted controls. This issue is particularly relevant for the blind population in which functional assessment of postural control has to be revealed through "real life" motor and cognitive function. The study aimed to explore whether an auditory-memory attention-demanding cognitive task would influence postural control in blind persons and compare this with blindfolded sighted persons. Subjects were instructed to minimize body sway during narrow base upright standing on a single force platform under two conditions: 1) standing still (single task); 2) as in 1) while performing an auditory-memory attention-demanding cognitive task (dual task). Subjects in both groups were required to stand blindfolded with their eyes closed. Center of Pressure displacement data were collected and analyzed using summary statistics and stabilogram-diffusion analysis. Blind and sighted subjects had similar postural sway in eyes closed condition. However, for dual compared to single task, sighted subjects show significant decrease in postural sway while blind subjects did not. The auditory-memory attention-demanding cognitive task had no interference effect on balance control on blind subjects. It seems that sighted individuals used auditory cues to compensate for momentary loss of vision, whereas blind subjects did not. This may suggest that blind and sighted people use different sensorimotor strategies to achieve stability. Copyright © 2010 Elsevier Ltd. All rights reserved.

Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model

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

Yamamoto, Tokihiro, E-mail: toyamamoto@ucdavis.edu

Purpose: Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging. Methods: Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those twomore » CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t-test. Results: The mean TRE (and standard deviation) was 0.6 ± 0.7 mm (smaller than the voxel dimension) for DIR between pre contrast and postcontrast end-inspiratory CT image data sets. No singularities were observed in the displacement vector fields. The mean HU enhancement (and standard deviation) was 37.3 ± 10.5 HU for normal lung subjects and 30.7 ± 13.5 HU for diseased lung subjects. Spatial heterogeneity of regional perfusion was found to be higher for diseased lung subjects than for normal lung subjects, i.e., a mean coefficient of variation of 2.06 vs 1.59 (p = 0.07). The average gravitationally directed gradient was strong and significant (R{sup 2} = 0.99, p < 0.01) for normal lung dogs, whereas it was moderate and nonsignificant (R{sup 2} = 0.61, p = 0.12) for diseased lung dogs. Conclusions: This canine study demonstrated the accuracy of DIR with subvoxel TREs on average, higher spatial heterogeneity of regional perfusion for diseased lung subjects than for normal lung subjects, and a strong gravitationally directed gradient for normal lung subjects, providing proof-of-principle for single-energy CT pulmonary perfusion imaging. Further studies such as comparison with other perfusion imaging modalities will be necessary to validate the physiological significance.« less

Subject Choice and Occupational Aspirations among Pupils at Girls' Schools

ERIC Educational Resources Information Center

Francis, Becky; Hutchings, Merryn; Archer, Louise; Amelling, Lindsay

2003-01-01

Various studies have found that British girls' curriculum subject preferences and future aspirations have changed and diversified in recent years. Other work has suggested that girls educated in single-sex schools might have a different (perhaps less gender-stereotypical) experience of education in comparison with their contemporaries at…

Comparison of single-microphone noise reduction schemes: can hearing impaired listeners tell the difference?

PubMed

Huber, Rainer; Bisitz, Thomas; Gerkmann, Timo; Kiessling, Jürgen; Meister, Hartmut; Kollmeier, Birger

2018-06-01

The perceived qualities of nine different single-microphone noise reduction (SMNR) algorithms were to be evaluated and compared in subjective listening tests with normal hearing and hearing impaired (HI) listeners. Speech samples added with traffic noise or with party noise were processed by the SMNR algorithms. Subjects rated the amount of speech distortions, intrusiveness of background noise, listening effort and overall quality, using a simplified MUSHRA (ITU-R, 2003 ) assessment method. 18 normal hearing and 18 moderately HI subjects participated in the study. Significant differences between the rating behaviours of the two subject groups were observed: While normal hearing subjects clearly differentiated between different SMNR algorithms, HI subjects rated all processed signals very similarly. Moreover, HI subjects rated speech distortions of the unprocessed, noisier signals as being more severe than the distortions of the processed signals, in contrast to normal hearing subjects. It seems harder for HI listeners to distinguish between additive noise and speech distortions or/and they might have a different understanding of the term "speech distortion" than normal hearing listeners have. The findings confirm that the evaluation of SMNR schemes for hearing aids should always involve HI listeners.

Who is the research subject in cluster randomized trials in health research?

PubMed Central

2011-01-01

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the CRT is to be set on a firm ethical foundation. This paper addresses the first of the questions posed, namely, who is the research subject in a CRT in health research? The identification of human research subjects is logically prior to the application of protections as set out in research ethics and regulation. Aspects of CRT design, including the fact that in a single study the units of randomization, experimentation, and observation may differ, complicate the identification of human research subjects. But the proper identification of human research subjects is important if they are to be protected from harm and exploitation, and if research ethics committees are to review CRTs efficiently. We examine the research ethics literature and international regulations to identify the core features of human research subjects, and then unify these features under a single, comprehensive definition of human research subject. We define a human research subject as any person whose interests may be compromised as a result of interventions in a research study. Individuals are only human research subjects in CRTs if: (1) they are directly intervened upon by investigators; (2) they interact with investigators; (3) they are deliberately intervened upon via a manipulation of their environment that may compromise their interests; or (4) their identifiable private information is used to generate data. Individuals who are indirectly affected by CRT study interventions, including patients of healthcare providers participating in knowledge translation CRTs, are not human research subjects unless at least one of these conditions is met. PMID:21791064

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram.

PubMed

Klein, N; Sacher, J; Geiss-Granadia, T; Attarbaschi, T; Mossaheb, N; Lanzenberger, R; Pötzi, C; Holik, A; Spindelegger, C; Asenbaum, S; Dudczak, R; Tauscher, J; Kasper, S

2006-10-01

Escitalopram is a dual serotonin reuptake inhibitor (SSRI) approved for the treatment of depression and anxiety disorders. It is the S-enantiomer of citalopram, and is responsible for the serotonin reuptake activity, and thus for its pharmacological effects. Previous studies pointed out that clinically efficacious doses of other SSRIs produce an occupancy of the serotonin reuptake transporter (SERT) of about 80% or more. The novel radioligand [123I]ADAM and single photon emission computer tomography (SPECT) were used to measure midbrain SERT occupancies for different doses of escitalopram and citalopram. Twenty-five healthy subjects received a single dose of escitalopram [5 mg (n=5), 10 mg (n=5), and 20 mg (n=5)] or citalopram [(10 mg (n=5) and 20 mg (n=5)]. Midbrain SERT binding was measured with [(123)I]ADAM and SPECT on two study days, once without study drug and once 6 h after single dose administration of the study drug. The ratio of midbrain-cerebellum/cerebellum was the outcome measure (V3") for specific binding to SERT in midbrain. Subsequently, SERT occupancy levels were calculated using the untreated baseline level for each subject. An Emax model was used to describe the relationship between S-citalopram concentrations and SERT occupancy values. Additionally, four subjects received placebo to determine test-retest variability. Single doses of 5, 10, or 20 mg escitalopram led to a mean SERT occupancy of 60+/-6, 64+/-6, and 75+/-5%, respectively. SERT occupancies for subjects treated with single doses of 10 and 20 mg citalopram were 65+/-10 and 70+/-6%, respectively. A statistically significant difference was found between SERT occupancies after application of 10 and 20 mg escitalopram, but not for 10 and 20 mg citalopram. There was no statistically significant difference between the SERT occupancies of either 10 mg citalopram or 10 mg escitalopram, or between 20 mg citalopram and 20 mg escitalopram. Emax was slightly higher after administration of citalopram (84%) than escitalopram (79%). In the test-retest study, a mean SERT "occupancy" of 4% was found after administration of placebo, the intraclass correlation coefficient was 0.92, and the repeatability coefficient was 0.25. SPECT and [123I]ADAM were used to investigate SERT occupancies after single doses of escitalopram or citalopram. The test-retest study revealed good reproducibility of SERT quantification. Similar SERT occupancies were found after administration of equal doses (in respect to mg) of escitalopram and citalopram, giving indirect evidence for a fractional blockade of SERT by the inactive R-citalopram.

Influence of hepatic impairment on the pharmacokinetics and safety profile of dapagliflozin: an open-label, parallel-group, single-dose study.

PubMed

Kasichayanula, Sreeneeranj; Liu, Xiaoni; Zhang, Weijiang; Pfister, Marc; LaCreta, Frank P; Boulton, David W

2011-11-01

Dapagliflozin, a selective inhibitor of renal sodium glucose co-transporter 2, is under development for the treatment of type 2 diabetes mellitus. Dapagliflozin elimination is primarily via glucuronidation to an inactive metabolite, dapagliflozin 3-O-glucuronide. Pharmacokinetic studies are recommended in subjects with impaired hepatic function if hepatic metabolism accounts for a substantial portion of the absorbed drug. The purpose of our study was to compare the pharmacokinetics of dapagliflozin in patients with mild, moderate, or severe hepatic impairment (HI) with healthy subjects. This was an open-label, parallel-group study in male or female patients with mild, moderate, or severe HI (6 per group according to Child-Pugh classification) and in 6 healthy control subjects. The control subjects were matched to the combined HI group for age (±10 years), weight (±20%), sex, and smoking status, with no deviations from normal in medical history, physical examination, ECG, or laboratory determinations. All participants received a single 10-mg oral dose of dapagliflozin, and the pharmacokinetics of dapagliflozin and dapagliflozin 3-O-glucuronide were characterized. Dapagliflozin tolerability was also assessed throughout the study. Demographic characteristics and baseline physical measurements (weight, height, and body mass index) were similar among the 18 patients in the HI groups (58-126 kg; 151.2-190.0 cm, and 31.5-37.7 kg/m(2), respectively) and the healthy subject group (65.0-102.6 kg; 166.0-184.0 cm, and 23.3-34.3 kg/m(2), respectively). In those with mild, moderate, or severe HI, dapagliflozin mean C(max) values were 12% lower and 12% and 40% higher than healthy subjects, respectively. Mean dapagliflozin AUC(0-∞) values were 3%, 36%, and 67% higher compared with healthy subjects, respectively. Dapagliflozin 3-O-glucuronide mean C(max) values were 4% and 58% higher and 14% lower in those with mild, moderate, or severe HI compared with healthy subjects, respectively, and mean dapagliflozin 3-O-glucuronide AUC(0-∞) values were 6%, 100%, and 30% higher compared with healthy subjects, respectively. These values were highly dependent on the calculated creatinine clearance of each group. All adverse events were mild or moderate, with no imbalance in frequency between groups. Compared with healthy subjects, systemic exposure to dapagliflozin in subjects with HI was correlated with the degree of HI. Single 10-mg doses of dapagliflozin were generally well tolerated by participants in this study. Due to the higher dapagliflozin exposures in patients with severe HI, the benefit:risk ratio should be individually assessed because the long-term safety profile and efficacy of dapagliflozin have not been specifically studied in this population. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

The Effectiveness of Single-Gender Eighth-Grade English, History, Mathematics and Science Classes

ERIC Educational Resources Information Center

Roth, Douglas Jeffrey

2009-01-01

Purpose, scope, and method of study. The purpose of this study was to compare the effectiveness of eighth-grade single-gender classes with coed classes across subject area, gender, at-risk status, and socioeconomic status (SES). The sample was drawn from one school, DeSoto West Junior High School, where enrollment averages 80% African American,…

Single-Center Evaluation of the Pharmacokinetics and Safety of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Mild to Moderate Hepatic Impairment.

PubMed

Dudkowski, Caroline; Karim, Aziz; Zhao, Zhen; Alonso, Alberto B; Garg, Dyal; Preston, Richard A

2018-01-01

Azilsartan medoxomil (AZL-M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose-dependent manner. It is a prodrug that is not detected in blood after its oral administration because of its rapid hydrolysis to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the major metabolite, M-II, and minor metabolites. The objective of this study was to determine the effect of mild to moderate hepatic impairment on the pharmacokinetics of AZL and its major metabolite. This was a single-center, open-label, phase 1 parallel-group study that examined the single-dose (day 1) and multiple-dose (days 4-8) - 40 mg - pharmacokinetics of AZL and M-II in 16 subjects with mild and moderate hepatic impairment by Child-Pugh classification (n = 8 per group) and subjects (n = 16) matched based on age, sex, race, weight, and smoking status. Mild or moderate hepatic impairment did not cause clinically meaningful increases in exposure to AZL and M-II. Mild or moderate hepatic impairment had no clinically meaningful effect on the plasma protein binding of AZL and M-II. Single and multiple doses of AZL-M 40 mg were well tolerated in all subject groups. Based on the pharmacokinetic and tolerability findings, no dose adjustment of AZL-M is required for subjects with mild and moderate hepatic impairment. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Case Study: Videogame Distraction Reduces Behavioral Distress in a Preschool-Aged Child Undergoing Repeated Burn Dressing Changes: A Single-Subject Design

PubMed Central

Sil, Soumitri; Burns, Andrew J.

2013-01-01

Objective This single-subject design study evaluated the feasibility and efficacy of passive and interactive videogame distraction on behavioral distress for a preschool-aged child receiving repeated burn dressing changes. Method A 4-year-old girl underwent 3 baseline and 10 videogame distraction sessions (5 passive and 5 interactive) using a restricted alternating treatments design. Observed behavioral distress was coded, and parents and nurses rated the child’s distress and cooperative behavior. Results Relative to baseline, behavioral distress decreased and cooperative behavior increased immediately after the onset of videogame distraction. Single Case Randomization Tests revealed significantly lower behavioral distress and greater cooperation during interactive videogame distraction relative to passive videogame distraction. Conclusions Interactive videogame distraction appears to be a feasible and effective pain management strategy for a preschool-aged child undergoing repeated painful medical procedures. PMID:23248343

Structural, mechanical, electrical and optical properties of a new lithium boro phthalate NLO crystal synthesized by a slow evaporation method

NASA Astrophysics Data System (ADS)

Mohanraj, K.; Balasubramanian, D.; Jhansi, N.

2017-11-01

A new non-linear optical (NLO) single crystal of lithium boro phthalate (LiBP) was grown by slow solvent evaporation technique. The powder sample was subjected to powder X-ray diffraction (PXRD) to find its crystalline nature and the crystal structure of the grown crystal was determined using single crystal X-ray (SXRD) diffraction analysis. The Fourier Transform Infrared (FTIR) spectrum was recorded for grown crystal to identify the various functional groups present in the compound. The mechanical property of the LiBP single crystal was studied using Vickers microhardness tester. The dielectric constant and dielectric loss measurements were carried out for the grown crystal at various temperatures. The grown crystal was subjected to UV-Visible Spectral Studies to analyze the linear optical behavior of the grown crystal. The Kurtz-Perry Powder technique was employed to measure the Second Harmonic Generation efficiency of the grown crystal.

Video game-based exercises for balance rehabilitation: a single-subject design.

PubMed

Betker, Aimee L; Szturm, Tony; Moussavi, Zahra K; Nett, Cristabel

2006-08-01

To investigate whether coupling foot center of pressure (COP)-controlled video games to standing balance exercises will improve dynamic balance control and to determine whether the motivational and challenging aspects of the video games would increase a subject's desire to perform the exercises and complete the rehabilitation process. Case study, pre- and postexercise. University hospital outpatient clinic. A young adult with excised cerebellar tumor, 1 middle-aged adult with single right cerebrovascular accident, and 1 middle-aged adult with traumatic brain injury. A COP-controlled, video game-based exercise system. The following were calculated during 12 different tasks: the number of falls, range of COP excursion, and COP path length. Postexercise, subjects exhibited a lower fall count, decreased COP excursion limits for some tasks, increased practice volume, and increased attention span during training. The COP-controlled video game-based exercise regime motivated subjects to increase their practice volume and attention span during training. This in turn improved subjects' dynamic balance control.

A double blind parallel group placebo controlled comparison of sedative and mnesic effects of etifoxine and lorazepam in healthy subjects [corrected].

PubMed

Micallef, J; Soubrouillard, C; Guet, F; Le Guern, M E; Alquier, C; Bruguerolle, B; Blin, O

2001-06-01

This paper describes the psychomotor and mnesic effects of single oral doses of etifoxine (50 and 100 mg) and lorazepam (2 mg) in healthy subjects. Forty-eight healthy subjects were included in this randomized double blind, placebo controlled parallel group study [corrected]. The effects of drugs were assessed by using a battery of subjective and objective tests that explored mood and vigilance (Visual Analog Scale), attention (Barrage test), psychomotor performance (Choice Reaction Time) and memory (digit span, immediate and delayed free recall of a word list). Whereas vigilance, psychomotor performance and free recall were significantly impaired by lorazepam, neither dosage of etifoxine (50 and 100 mg) produced such effects. These results suggest that 50 and 100 mg single dose of etifoxine do not induce amnesia and sedation as compared to lorazepam.

Are Infants' Theory-of-Mind Abilities Well Integrated? Implicit Understanding of Intentions, Desires, and Beliefs

ERIC Educational Resources Information Center

Yott, Jessica; Poulin-Dubois, Diane

2016-01-01

The development of theory of mind (ToM) in infancy has been mainly documented through studies conducted on a single age group with a single task. Very few studies have examined ToM abilities other than false belief, and very few studies have used a within-subjects design. During 2 testing sessions, infants aged 14 and 18 months old were…

Distributed Representation of Visual Objects by Single Neurons in the Human Brain

PubMed Central

Valdez, André B.; Papesh, Megan H.; Treiman, David M.; Smith, Kris A.; Goldinger, Stephen D.

2015-01-01

It remains unclear how single neurons in the human brain represent whole-object visual stimuli. While recordings in both human and nonhuman primates have shown distributed representations of objects (many neurons encoding multiple objects), recordings of single neurons in the human medial temporal lobe, taken as subjects' discriminated objects during multiple presentations, have shown gnostic representations (single neurons encoding one object). Because some studies suggest that repeated viewing may enhance neural selectivity for objects, we had human subjects discriminate objects in a single, more naturalistic viewing session. We found that, across 432 well isolated neurons recorded in the hippocampus and amygdala, the average fraction of objects encoded was 26%. We also found that more neurons encoded several objects versus only one object in the hippocampus (28 vs 18%, p < 0.001) and in the amygdala (30 vs 19%, p < 0.001). Thus, during realistic viewing experiences, typical neurons in the human medial temporal lobe code for a considerable range of objects, across multiple semantic categories. PMID:25834044

Cognitive workload modulation through degraded visual stimuli: a single-trial EEG study

NASA Astrophysics Data System (ADS)

Yu, K.; Prasad, I.; Mir, H.; Thakor, N.; Al-Nashash, H.

2015-08-01

Objective. Our experiments explored the effect of visual stimuli degradation on cognitive workload. Approach. We investigated the subjective assessment, event-related potentials (ERPs) as well as electroencephalogram (EEG) as measures of cognitive workload. Main results. These experiments confirm that degradation of visual stimuli increases cognitive workload as assessed by subjective NASA task load index and confirmed by the observed P300 amplitude attenuation. Furthermore, the single-trial multi-level classification using features extracted from ERPs and EEG is found to be promising. Specifically, the adopted single-trial oscillatory EEG/ERP detection method achieved an average accuracy of 85% for discriminating 4 workload levels. Additionally, we found from the spatial patterns obtained from EEG signals that the frontal parts carry information that can be used for differentiating workload levels. Significance. Our results show that visual stimuli can modulate cognitive workload, and the modulation can be measured by the single trial EEG/ERP detection method.

Gender differences in rotation of the shank during single-legged drop landing and its relation to rotational muscle strength of the knee.

PubMed

Kiriyama, Shinya; Sato, Haruhiko; Takahira, Naonobu

2009-01-01

Increased shank rotation during landing has been considered to be one of the factors for noncontact anterior cruciate ligament injuries in female athletes. There have been no known gender differences in rotational knee muscle strength, which is expected to inhibit exaggerated shank rotation. Women have less knee external rotator strength than do men. Lower external rotator strength is associated with increased internal shank rotation at the time of landing. Controlled laboratory study. One hundred sixty-nine healthy young subjects (81 female and 88 male; age, 17.0 +/- 1.0 years) volunteered to participate in this study. The subjects performed single-legged drop landings from a 20-cm height. Femoral and shank kinematics were measured using a 3D optoelectronic tracking system during the drop landings, and then the joint angles around the knee (flexion/extension, valgus/varus, and internal/external rotation) were calculated. The maximal isometric rotational muscle strength of the knee was measured at 30 degrees of knee flexion in a supine position using a dynamometer. The female subjects had significantly less external shank rotation strength than did the male subjects (P < .001). Female subjects also exhibited significantly greater peak shank internal rotation angles than did males during landing (P < .05). Moderate but significant association was found between the maximum shank external rotation strength and the peak shank internal rotation angle during landing (r = -0.322, P < .01). Female subjects tended to have poor shank external rotator strength. This may lead to large shank internal rotation movement during the single-legged drop landing. Improving strength training of the external rotator muscle may help decrease the rates of anterior cruciate ligament injury in female athletes.

Analysis of the impact of a cognitive task on the posture of elderly subjects with depression compared with healthy elderly subjects.

PubMed

Casteran, Matthieu; Putot, Alain; Pfitzenmeyer, François; Thomas, Elizabeth; Manckoundia, Patrick

2016-11-01

While previous studies have demonstrated that depressive elderly subjects (DES) experience difficulties in the processing of simultaneous cognitive tasks, few have examined the coupling of cognitive tasks with seemingly 'automatic' tasks, such as standing upright. Current patient management focuses on pharmacological treatments and cognitive-behavioral therapies. Healthy elderly (HES) and non-treated DES were included. Postural sway in DES was compared with that in HES while in single-task and dual-task conditions. The single-task consisted of standing upright. For the dual-task, the subjects recalled various items from memory or counted while standing upright. Postural sway was evaluated by computing the center of pressure (CoP) area and path length. DES showed greater postural sway than HES in all conditions. The HES showed a greater CoP area in the dual-task than in the single-task conditions. In DES, the CoP area in the single-task condition was similar to that in the dual-task condition. The greater postural sway observed in DES may be a cause of a greater risk of falls. We showed that even seemingly automatic tasks, such as maintaining an upright posture, are affected by depression. These results are important for the management of DES. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Subject-based discriminative sparse representation model for detection of concealed information.

PubMed

Akhavan, Amir; Moradi, Mohammad Hassan; Vand, Safa Rafiei

2017-05-01

The use of machine learning approaches in concealed information test (CIT) plays a key role in the progress of this neurophysiological field. In this paper, we presented a new machine learning method for CIT in which each subject is considered independent of the others. The main goal of this study is to adapt the discriminative sparse models to be applicable for subject-based concealed information test. In order to provide sufficient discriminability between guilty and innocent subjects, we introduced a novel discriminative sparse representation model and its appropriate learning methods. For evaluation of the method forty-four subjects participated in a mock crime scenario and their EEG data were recorded. As the model input, in this study the recurrence plot features were extracted from single trial data of different stimuli. Then the extracted feature vectors were reduced using statistical dependency method. The reduced feature vector went through the proposed subject-based sparse model in which the discrimination power of sparse code and reconstruction error were applied simultaneously. Experimental results showed that the proposed approach achieved better performance than other competing discriminative sparse models. The classification accuracy, sensitivity and specificity of the presented sparsity-based method were about 93%, 91% and 95% respectively. Using the EEG data of a single subject in response to different stimuli types and with the aid of the proposed discriminative sparse representation model, one can distinguish guilty subjects from innocent ones. Indeed, this property eliminates the necessity of several subject EEG data in model learning and decision making for a specific subject. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effectiveness of the Instructional Programs Based on Self-Management Strategies in Acquisition of Social Skills by the Children with Intellectual Disabilities

ERIC Educational Resources Information Center

Avcioglu, Hasan

2012-01-01

The purpose of this study is to evaluate the effectiveness of self-management skills training program, based on self-control strategies, on students with intellectual disabilities. A multiple-probe design across subjects single-subject research methodology was used in this study. Nine students with intellectual disabilities, whose ages are between…

The Effect of an Enrichment Reading Program on the Cognitive Processes and Neural Structures of Children Having Reading Difficulties

ERIC Educational Resources Information Center

Kuruyer, Hayriye Gül; Akyol, Hayati; Karli Oguz, Kader; Has, Arzu Ceylan

2017-01-01

The main purpose of the current study is to explain the effect of an enrichment reading program on the cognitive processes and neural structures of children experiencing reading difficulties. The current study was carried out in line with a single-subject research method and the between-subjects multiple probe design belonging to this method. This…

Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

PubMed

Krishnaswami, Sriram; Boy, Mary; Chow, Vincent; Chan, Gary

2015-03-01

Tofacitinib is an oral Janus kinase inhibitor. This randomized, double-blind, parallel-group, placebo-controlled study was the first evaluation of tofacitinib in humans. The objectives were to characterize the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics of escalating single tofacitinib doses in healthy subjects. Tofacitinib (0.1, 0.3, 1, 3, 10, 30, 60, and 100 mg) or placebo was administered as oral powder for constitution. For each dose, 7-9 subjects were randomized to tofacitinib and 3-5 subjects to placebo. Ninety-five males and females (age range 19-45) completed the study. Forty-nine treatment-emergent all-causality adverse events (AEs) were observed; nausea and headache were the most frequently reported. Tofacitinib PK was characterized by rapid absorption (time to peak serum concentration [Tmax ] 0.5-1 hour), rapid elimination (mean terminal half-lives 2.3-3.1 hours), and dose-proportional systemic exposures (peak serum concentration [Cmax ] and area under the serum concentration-time curve from time zero to infinity [AUC0-∞ ]). No appreciable correlation was observed between tofacitinib dose and lymphocyte subset counts. Single-dose tofacitinib up to 100 mg in healthy subjects had a safety profile of mostly mild AEs, and no deaths, serious AEs, severe AEs or discontinuations due to AEs. © 2014, The American College of Clinical Pharmacology.

First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica.

PubMed

Rolan, Paul E; O'Neill, Gilmore; Versage, Eve; Rana, Jitesh; Tang, Yongqiang; Galluppi, Gerald; Aycardi, Ernesto

2015-01-01

To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica. This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28. Beyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was rapidly distributed, with a prolonged terminal elimination phase. These data support the development of BG00010 for the treatment of neuropathic pain. ClinicalTrials.gov NCT00961766.

A comparison of muscular activity during single and double mouse clicks.

PubMed

Thorn, Stefan; Forsman, Mikael; Hallbeck, Susan

2005-05-01

Work-related musculoskeletal disorders (WMSDs) in the neck/shoulder region and the upper extremities are a common problem among computer workers. Occurrences of motor unit (MU) double discharges with very short inter-firing intervals (doublets) have been hypothesised as a potential additional risk for overuse of already exhausted fibres during long-term stereotyped activity. Doublets are reported to be present during double-click mouse work tasks. A few comparative studies have been carried out on overall muscle activities for short-term tasks with single types of actions, but none on occurrences of doublets during double versus single clicks. The main purpose of this study was to compare muscle activity levels of single and double mouse clicks during a long-term combined mouse/keyboard work task. Four muscles were studied: left and right upper trapezius, right extensor digitorum communis (EDC) and right flexor carpi ulnaris. Additionally, MU activity was analysed through intramuscular electromyography in the EDC muscle for a selection of subjects. The results indicate that double clicking produces neither higher median or 90th percentile levels in the trapezius and EDC muscles, nor a higher disposition for MU doublets, than does single clicking. Especially for the 90th percentile levels, the indications are rather the opposite (in the EDC significantly higher during single clicks in 8 of 11 subjects, P < 0.05). Although it cannot be concluded from the present study that double clicks are harmless, there were no signs that double clicks during computer work generally constitute a larger risk factor for WMSDs than do single clicks.

[Pharmacokinetics of digoxin in hyperthyroidism. Effect of methimazole].

PubMed

Izbicka, Maria; Gasińska, Teresa; Dec, Renata

2010-01-01

Cardiovascular abnormalities may be the only manifestations of overt hyperthyroidism. In patients with heart failure and atrial fibrillation digoxin can be beneficial in controlling the symptoms and signs, but hyperthyroid patients show an impaired response or even resistance to digoxin treatment. The aim of the study is to establish: 1. Are there any differences in the pharmacokinetics of a single oral dose of digoxin between hypertyroid and euthyroid patients? 2. Does simultaneous administration of digoxin and methimazole affect the pharmacokinetics of a single oral dose of dogoxin? 3. Does methimazole-induced euthyroidism change the pharmacokinetics of a single oral dose of digoxin? The subject of the study were 28 patients with hyperthyroidism and 15 healthy persons. We evaluated the pharmacokinetics of a single oral dose of digoxin. Moreover we evaluated pharmacokinetics of a single dose of digoxin after simultaneous administration of digoxin and methimazole in 12 patients and 12 methimazole treated patients werere-assessed once they had become euthyroid. Hyperthyroid patients showed significantly lower serum digoxin concentrations, shorter T1/2 beta and a significantly smaller area under the concentration curve (AUC) that the control group. Administration of methimazole did not affect digoxin pharmacokinetics. In hyperthyroid patients: 1. the pharmacokinetics of a single oral dose of digoxin does differ from that observed in healthy subjects. 2.methimazole do not alter digoxin pharmacokinetics.

Effects of training and detraining on the static and dynamic balance in elderly fallers and non-fallers: a pilot study.

PubMed

Toulotte, Claire; Thevenon, Andre; Fabre, Claudine

2006-01-30

The aim of this study was to evaluate the effects of training based on static and dynamic balance in single and dual task conditions in order to analyse the effects of detraining on static and dynamic balance in healthy elderly fallers and non-fallers. A group of 16 subjects were trained: eight fallers aged 71.1 +/- 5.0 years and eight non-fallers aged 68.4 +/- 4.5 years. The subjects were evaluated 3 months before the training period, 2 days before the training period, 2 days after the end of the training period and 3 months after the training period. All subjects performed a unipedal test with eyes open and eyes closed. Gait parameters were analysed under single-task and dual motor-task conditions. This study demonstrated a loss of physical capacities over 3 months for stride time, single support time for fallers in both conditions. Physical training significantly improves static and dynamic balance under single and dual task conditions. Lastly, after 3 months of detraining, a loss of the physical training effects were measured for fallers and non-fallers on the different walking parameters in the two conditions and on the unipedal tests. The absence of stimulation before the trained period shows a negative effect of ageing on walking and falls whereas training permits an improvement in static balance and the pattern of walking under single and dual task conditions, which could be due to an increase in muscular strength and a better division of attention. On the other hand, 3 months of detraining inhibited the effects of training, which showed the speed of the decline caused by 'natural' ageing.

Multiclass classification of obstructive sleep apnea/hypopnea based on a convolutional neural network from a single-lead electrocardiogram.

PubMed

Urtnasan, Erdenebayar; Park, Jong-Uk; Lee, Kyoung-Joung

2018-05-24

In this paper, we propose a convolutional neural network (CNN)-based deep learning architecture for multiclass classification of obstructive sleep apnea and hypopnea (OSAH) using single-lead electrocardiogram (ECG) recordings. OSAH is the most common sleep-related breathing disorder. Many subjects who suffer from OSAH remain undiagnosed; thus, early detection of OSAH is important. In this study, automatic classification of three classes-normal, hypopnea, and apnea-based on a CNN is performed. An optimal six-layer CNN model is trained on a training dataset (45,096 events) and evaluated on a test dataset (11,274 events). The training set (69 subjects) and test set (17 subjects) were collected from 86 subjects with length of approximately 6 h and segmented into 10 s durations. The proposed CNN model reaches a mean -score of 93.0 for the training dataset and 87.0 for the test dataset. Thus, proposed deep learning architecture achieved a high performance for multiclass classification of OSAH using single-lead ECG recordings. The proposed method can be employed in screening of patients suspected of having OSAH. © 2018 Institute of Physics and Engineering in Medicine.

21 CFR 320.26 - Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Guidelines on the design of a single-dose in vivo bioavailability or bioequivalence study. 320.26 Section 320.26 Food and Drugs FOOD AND DRUG ADMINISTRATION... test product and the reference material should be administered to subjects in the fasting state, unless...

Mixed Schools versus Single-Sex Schools: Are There Differences in the Academic Results for Boys and Girls in Catalonia?

ERIC Educational Resources Information Center

Garcia-Gracia, Maribel; Donoso Vázquez, Trinidad

2016-01-01

This study carries out a comparative analysis of achievement according to gender between mixed and single-sex schools in the region of Catalonia, Spain, for the subjects of Spanish, Catalan, English and Mathematics. After a brief contextualisation, a review of the main findings from international studies on differences in results for mixed schools…

A Language Training Strategy for Teaching Young Language-Delayed Children a Functional Syntactical Form.

ERIC Educational Resources Information Center

Hester, Peggy; Hendrickson, Jo

A modeling procedure involving dynamic interactions was used to train three language-delayed preschool children to emit five-element syntactic responses. A single-subject multiple baseline design using within- and across-subject replication was employed to study the acquisition of expanded "agent-action-object" sentences and the…

Aging and Cortical Mechanisms of Speech Perception in Noise

ERIC Educational Resources Information Center

Wong, Patrick C. M.; Jin, James Xumin; Gunasekera, Geshri M.; Abel, Rebekah; Lee, Edward R.; Dhar, Sumitrajit

2009-01-01

Spoken language processing in noisy environments, a hallmark of the human brain, is subject to age-related decline, even when peripheral hearing might be intact. The present study examines the cortical cerebral hemodynamics (measured by fMRI) associated with such processing in the aging brain. Younger and older subjects identified single words in…

A Decade of Literacy Research in the "Journal of Educational Research".

ERIC Educational Resources Information Center

Knudson, Ruth E.; Theurer, Joan Leikam; Boyd-Batstone, Paul

A total of 378 articles were published in the "Journal of Educational Research" from 1990-1999. Ninety-seven (26%) focused on literacy. Information was categorized for each article with respect to authors' gender, multiple versus single authorship, study design, use of statistics, age of subjects, number of subjects, and kind of…

Prevalence of Multiply Controlled Problem Behavior

ERIC Educational Resources Information Center

Beavers, Gracie A.; Iwata, Brian A.

2011-01-01

We examined articles in the "Journal of Applied Behavior Analysis" in which results of functional analyses indicated that problem behavior was maintained by multiple sources of reinforcement. Data for 88 (16.9%) of 521 subjects reported in 168 studies met the criteria for multiple control. Data for 11 subjects (2.1%) involved a single response…

Subjective perception of natural scenes: the role of color

NASA Astrophysics Data System (ADS)

Bianchi-Berthouze, Nadia

2003-01-01

The subjective perception of colors has been extensively studied, with a focus on single colors or on combinations of a few colors. Not much has been done, however, to understand the subjective perception of colors in other contexts, where color is not a single feature. This is what the Kansei community in Japan has set itself to, by exploring subjective experiences of perceptions, and colors in particular, given its obvious influence on humans' emotional changes. The motivation is to create computational models of user visual perceptions, so that computers can be endowed with the ability to personalize visual aspects of their computational task, according to their user. Such a capability is hypothesized to be very important in fields such as printing, information search, design support, advertisement, etc. In this paper, we present our experimental results in the study of color as a contextual feature of images, rather than in isolation. The experiments aim at understanding the mechanisms linked to the personal perception of colors in complex images, and to understand the formation of color categories when labeling experiences related to color perception.

Evidence for a pharmacokinetic interaction between eslicarbazepine and rosuvastatin: Potential effects on xenobiotic transporters.

PubMed

Gidal, Barry E; Mintzer, Scott; Schwab, Matthias; Schutz, Ralph; Kharidia, Jahnavi; Blum, David; Grinnell, Todd; Sunkaraneni, Soujanya

2017-09-01

Patients with partial-onset seizures and comorbid cardiovascular disease may concomitantly receive eslicarbazepine acetate (ESL), an antiepileptic drug, and rosuvastatin, an HMG-CoA reductase inhibitor. This study evaluated the effect of multiple-dose ESL on the pharmacokinetic (PK) parameters of a single dose of rosuvastatin in healthy subjects. This was a Phase I, single-center, fixed-sequence, open-label study. Healthy subjects received two treatments, in sequence. Treatment A: a single 40mg oral dose of rosuvastatin on Day 1, followed by a washout period (Days 1-4); treatment B: titration of ESL (400-800mg once daily) on Days 5-18, followed by ESL 1200mg once daily on Days 19-35, with a single dose of rosuvastatin (40mg) on Day 32. Subjects then entered a 2-week follow-up period. Plasma concentrations of rosuvastatin were quantified for PK analyses. Safety and tolerability were assessed throughout the study. Thirty-three healthy subjects were enrolled and 30 completed the study. Mean rosuvastatin (standard deviation) t 1/2 was similar when rosuvastatin was used concomitantly with ESL and when it was used alone (26.5 [16.3]h, and 22.4 [9.5]h, respectively). The geometric least squares mean ratios (90% confidence intervals) of rosuvastatin exposure levels between rosuvastatin used concomitantly with ESL and rosuvastatin used alone were as follows: C max , 64.0% (55.9-73.3%); AUC (0-∞) , 63.0% (57.1-69.4%); and AUC (0-last) , 60.9% (55.2-67.1%). Concomitant use of ESL and rosuvastatin was generally well tolerated. Rosuvastatin exposure was 36-39% lower with steady-state administration of ESL, potentially due to reduced oral bioavailability of rosuvastatin. Consequently, when rosuvastatin is used with ESL, a rosuvastatin dose adjustment may be necessary if a clinically significant change in lipids is noted. Copyright © 2017. Published by Elsevier B.V.

A review of technology-based interventions to teach academic skills to students with autism spectrum disorder.

PubMed

Knight, Victoria; McKissick, Bethany R; Saunders, Alicia

2013-11-01

A comprehensive review of the literature was conducted for articles published between 1993 and 2012 to determine the degree to which technology-based interventions can be considered an evidence-based practice to teach academic skills to individuals with Autism Spectrum Disorder (ASD). Criteria developed by Horner et al. (Except Child 71:165-178, 2005) and Gersten et al. (Except Child 71:149-164, 2005) were used to determine the quality of single-subject research studies and group experimental research studies respectively. A total of 29 [Corrected] studies met inclusion criteria. Of these studies, only three single-subject studies and no group studies met criteria for quality or acceptable studies. Taken together, the results suggest that practitioners should use caution when teaching academic skills to individuals with ASD using technology-based interventions. Limitations and directions for future research are discussed.

Reduction of non-adherent behaviour in a Mexican-American adolescent with type 2 diabetes.

PubMed

Piven, Emily; Duran, Rene

2014-03-01

This single-subject research aimed to evaluate the effect of occupation-based activities to improve diabetes self-management skills in a non-adherent 19-year-old Mexican-American adolescent transitioning to young adulthood. Using a pre-test/post-test design, the subject's performance was re-evaluated with five standardized measures following an 8-week intervention. The subject made major improvements on the Diabetes Self-Efficacy Scale, Exercise Behaviour and in goal attainment of targeted behaviours on the basis of the Canadian Occupational Performance Measure. The Adapted Intrusiveness Rating Scale and the Social/Role Activities Limitations Scale revealed increased intrusiveness of diabetes in his life, once he finally embraced his need to prioritize diabetes self-care. The study illuminated how a culturally sensitive, occupation-based early intervention might potentially prevent or reduce debilitating complications in adulthood. The value of this study is its contribution to body of diabetes literature on the role of occupational therapist in secondary prevention with Mexican-Americans. Research suggestions included expansion of single-subject design with larger samples and higher-level research studies with adolescents from various cultural backgrounds. Copyright © 2014 John Wiley & Sons, Ltd.

Bioavailability of two oral suspension and two oral tablet formulations of acyclovir 400 mg: two single-dose, open-label, randomized, two-period crossover comparisons in healthy Mexican adult subjects.

PubMed

Palma-Aguirre, Jose Antonio; Absalón-Reyes, Jose Antonio; Novoa-Heckel, Germán; de Lago, Alberto; Oliva, Iván; Rodríguez, Zulema; González-de la Parra, Mario; Burke-Fraga, Victoria; Namur, Salvador

2007-06-01

Acyclovir is an important antiviral drug, used extensively for treatment of herpes simplex and varicella zoster. Six oral generic formulations of acyclovir are available in Mexico; however, a literature search failed to identify data information concerning the bioavailability of these formulations in the Mexican population. The aim of these 2 studies was to compare the bioavailability of 4 oral formulations of acyclovir 400 mg--2 tablet formulations and 2 suspension formulations--with their corresponding listed drug references in Mexico (a list issued by Mexican Health Authorities). Two separate, single-dose, open-label, randomized, 2-period crossover studies were conducted at the Centro de Estudios Científicos y Clínicos Pharma, S.A. de C.V. (clinical unit), Mexico City, Mexico. For each study, a different set of eligible subjects were selected. They included healthy Mexican volunteers of either sex. For each study, subjects were randomly assigned to receive 1 test formulation of acyclovir 400 mg followed by the reference formulation, or vice versa, with a 1-week washout period between doses. After a 12-hour (overnight) fast, subjects received a single 400-mg dose (tablet or 10-mL suspension) of the corresponding formulation. For the analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2, 3, 4, 6, 8, 12, and 24 hours after dosing. The formulations were considered bioequivalent if the natural logarithm (ln)-transformed ratios of Cmax and AUC were within the predetermined equivalence range of 80% to 125% and if P

Evaluation of the single-dose pharmacokinetics of bilastine in subjects with various degrees of renal insufficiency.

PubMed

Lasseter, Kenneth C; Sologuren, Ander; La Noce, Anna; Dilzer, Stacy C

2013-09-01

Bilastine is a novel second-generation H1 antihistamine, which has not shown sedative or cardiotoxic effects in clinical trials and in post-marketing experience so far, developed for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It has recently been granted marketing authorization for these therapeutic indications in adults and adolescents at a once-daily oral dose of 20 mg in several European countries. This study was conducted to determine the pharmacokinetics of bilastine at a single oral dose of 20 mg in renally impaired subjects. The need for a dose adjustment in patients with renal insufficiency was assessed by comparing the exposure to bilastine in these subjects with the estimated exposure of a dose corresponding to the safety margin. The study was an open-label, single-dose, parallel-group study of the pharmacokinetics and safety of a single dose of bilastine. The study was conducted as an in-patient setting at a clinical pharmacology facility. A total of 24 male or female subjects aged 18-80 years were to be enrolled in four groups of six subjects each. The groups were as follows: (1) healthy [glomerular filtration rate (GFR) >80 mL/min/1.73 m(2)]; (2) mild renal insufficiency (GFR 50-80 mL/min/1.73 m(2)); (3) moderate renal insufficiency (GFR 30-50 mL/min/1.73 m(2)); and (4) severe renal insufficiency (GFR ≤30 mL/min/1.73 m(2)). A single 20 mg bilastine tablet was administered in a fasted state. Blood and urine samples were collected from pre-dose up to 72 h post-dose for bilastine pharmacokinetic analysis. Pharmacokinetic results were summarized using appropriate descriptive statistics. There was a clear trend of increasing area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C(max)) through the groups 1-4. The mean AUC from time zero to infinity (AUC(∞)) ranged from 737.4 to 1708.5 ng·h/mL in healthy subjects and severely impaired subjects, respectively. No significant differences among groups in median time to reach Cmax (tmax) or in the mean terminal disposition rate constants for bilastine were found. Renal and plasma clearance paralleled GFR. In all groups of renally impaired subjects the corresponding 90 % confidence interval of both AUC(∞) and AUC from time zero to time of last measurable plasma concentration (AUC(last)) were not within the 0.8-1.25 interval, indicating that bioequivalence between groups could not be demonstrated. The majority of bilastine was excreted within the first 12 h, and elimination was essentially complete by 72 h. An oral dose of bilastine (20 mg) was well-tolerated in renal insufficiency, despite the increase in exposure. The oral plasma clearance to renal clearance ratio [(CL(P)/F)/CL(R)] was approximately equal in the different groups, suggesting that renal excretion was the main elimination route for bilastine, and no alternative elimination routes were used even in severe renal insufficiency. Although exposure to bilastine was higher in renally impaired subjects, it remained well within the safety margins, thus allowing the conclusion that a 20-mg daily dose can be safely administered to subjects with different degrees of renal insufficiency without the need for dose adjustments.

Alzheimer Disease and Behavioral Variant Frontotemporal Dementia: Automatic Classification Based on Cortical Atrophy for Single-Subject Diagnosis.

PubMed

Möller, Christiane; Pijnenburg, Yolande A L; van der Flier, Wiesje M; Versteeg, Adriaan; Tijms, Betty; de Munck, Jan C; Hafkemeijer, Anne; Rombouts, Serge A R B; van der Grond, Jeroen; van Swieten, John; Dopper, Elise; Scheltens, Philip; Barkhof, Frederik; Vrenken, Hugo; Wink, Alle Meije

2016-06-01

Purpose To investigate the diagnostic accuracy of an image-based classifier to distinguish between Alzheimer disease (AD) and behavioral variant frontotemporal dementia (bvFTD) in individual patients by using gray matter (GM) density maps computed from standard T1-weighted structural images obtained with multiple imagers and with independent training and prediction data. Materials and Methods The local institutional review board approved the study. Eighty-four patients with AD, 51 patients with bvFTD, and 94 control subjects were divided into independent training (n = 115) and prediction (n = 114) sets with identical diagnosis and imager type distributions. Training of a support vector machine (SVM) classifier used diagnostic status and GM density maps and produced voxelwise discrimination maps. Discriminant function analysis was used to estimate suitability of the extracted weights for single-subject classification in the prediction set. Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were calculated for image-based classifiers and neuropsychological z scores. Results Training accuracy of the SVM was 85% for patients with AD versus control subjects, 72% for patients with bvFTD versus control subjects, and 79% for patients with AD versus patients with bvFTD (P ≤ .029). Single-subject diagnosis in the prediction set when using the discrimination maps yielded accuracies of 88% for patients with AD versus control subjects, 85% for patients with bvFTD versus control subjects, and 82% for patients with AD versus patients with bvFTD, with a good to excellent AUC (range, 0.81-0.95; P ≤ .001). Machine learning-based categorization of AD versus bvFTD based on GM density maps outperforms classification based on neuropsychological test results. Conclusion The SVM can be used in single-subject discrimination and can help the clinician arrive at a diagnosis. The SVM can be used to distinguish disease-specific GM patterns in patients with AD and those with bvFTD as compared with normal aging by using common T1-weighted structural MR imaging. (©) RSNA, 2015.

A standardized mean difference effect size for multiple baseline designs across individuals.

PubMed

Hedges, Larry V; Pustejovsky, James E; Shadish, William R

2013-12-01

Single-case designs are a class of research methods for evaluating treatment effects by measuring outcomes repeatedly over time while systematically introducing different condition (e.g., treatment and control) to the same individual. The designs are used across fields such as behavior analysis, clinical psychology, special education, and medicine. Emerging standards for single-case designs have focused attention on methods for summarizing and meta-analyzing findings and on the need for effect sizes indices that are comparable to those used in between-subjects designs. In the previous work, we discussed how to define and estimate an effect size that is directly comparable to the standardized mean difference often used in between-subjects research based on the data from a particular type of single-case design, the treatment reversal or (AB)(k) design. This paper extends the effect size measure to another type of single-case study, the multiple baseline design. We propose estimation methods for the effect size and its variance, study the estimators using simulation, and demonstrate the approach in two applications. Copyright © 2013 John Wiley & Sons, Ltd.

GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects.

PubMed

Spreen, William; Ford, Susan L; Chen, Shuguang; Wilfret, David; Margolis, David; Gould, Elizabeth; Piscitelli, Stephen

2014-12-15

GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from <8% to 28% of corresponding plasma concentrations. These data suggest 744 LA injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

A randomized, single-blind, single-dose study evaluating the pharmacokinetic equivalence of proposed biosimilar ABP 980 and trastuzumab in healthy male subjects.

PubMed

Hanes, Vladimir; Chow, Vincent; Zhang, Nan; Markus, Richard

2017-05-01

This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 980 and trastuzumab in healthy males. In this single-blind study, 157 healthy males were randomized 1:1:1 to a single 6 mg/kg intravenous infusion of ABP 980, FDA-licensed trastuzumab [trastuzumab (US)], or EU-authorized trastuzumab [trastuzumab (EU)]. Primary endpoints were area under the serum concentration-time curve from time 0 to infinity (AUC inf ) and maximum observed serum concentration (C max ). To establish equivalence, the geometric mean ratio (GMR) and 90% confidence interval (CI) for C max and AUC inf had to be within the equivalence criteria of 0.80-1.25. The GMRs and 90% CIs for C max and AUC inf , respectively, were: 1.04 (0.99-1.08) and 1.06 (1.00-1.12) for ABP 980 versus trastuzumab (US); 0.99 (0.95-1.03) and 1.00 (0.95-1.06) for ABP 980 versus trastuzumab (EU); and 0.96 (0.92-1.00) and 0.95 (0.90-1.01) for trastuzumab (US) versus trastuzumab (EU). All comparisons were within the equivalence criteria of 0.80-1.25. Treatment-emergent adverse events (TEAEs) were reported in 84.0, 75.0, and 78.2 of subjects in the ABP 980, trastuzumab (US), and trastuzumab (EU) groups, respectively. There were no deaths or TEAEs leading to study discontinuation and no binding or neutralizing anti-drug anti-bodies were detected. This study demonstrated the PK similarity of ABP 980 to both trastuzumab (US) and trastuzumab (EU), and of trastuzumab (US) to trastuzumab (EU). No differences in safety and tolerability between treatments were noted; no subject tested positive for binding anti-bodies.

Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects

PubMed Central

Frost, Charles; Wang, Jessie; Nepal, Sunil; Schuster, Alan; Barrett, Yu Chen; Mosqueda-Garcia, Rogelio; Reeves, Richard A; LaCreta, Frank

2013-01-01

Aims To evaluate apixaban single dose safety, tolerability, pharmacokinetics and pharmacodynamics and assess the effect of food on apixaban pharmacokinetics. Methods A double-blind, placebo-controlled, single ascending-dose, first-in-human study assessed apixaban safety, pharmacokinetics and pharmacodynamics in healthy subjects randomized to oral apixaban (n = 43; 0.5–2.5 mg as solution or 5–50 mg as tablets) or placebo (n = 14) under fasted conditions. An open label, randomized, two treatment crossover study investigated apixaban pharmacokinetics/pharmacodynamics in healthy subjects (n = 21) administered apixaban 10 mg in fasted and fed states. Both studies measured apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT) or a modified PT (mPT). Results In the single ascending-dose study increases in apixaban exposure appeared dose-proportional. Median tmax occurred 1.5–3.3 h following oral administration. Mean terminal half-life ranged between 3.6 and 6.8 h following administration of solution doses ≤2.5 mg and between 11.1 and 26.8 h for tablet doses ≥5 mg. Concentration-related changes in pharmacodynamic assessments were observed. After a 50 mg dose, peak aPTT, INR and mPT increased by 1.2-, 1.6- and 2.9-fold, respectively, from baseline. In the food effect study: 90% confidence intervals of geometric mean ratios of apixaban Cmax and AUC in a fed vs. fasted state were within the predefined no effect (80–125%) range. Apixaban half-life was approximately 11.5 h. The effect of apixaban on INR, PT and aPTT was comparable following fed and fasted administration. Conclusions Single doses of apixaban were well tolerated with a predictable pharmacokinetic/pharmacodynamic profile and a half-life of approximately 12 h. Apixaban can be administered with or without food. PMID:22759198

N-of-1-pathways MixEnrich: advancing precision medicine via single-subject analysis in discovering dynamic changes of transcriptomes.

PubMed

Li, Qike; Schissler, A Grant; Gardeux, Vincent; Achour, Ikbel; Kenost, Colleen; Berghout, Joanne; Li, Haiquan; Zhang, Hao Helen; Lussier, Yves A

2017-05-24

Transcriptome analytic tools are commonly used across patient cohorts to develop drugs and predict clinical outcomes. However, as precision medicine pursues more accurate and individualized treatment decisions, these methods are not designed to address single-patient transcriptome analyses. We previously developed and validated the N-of-1-pathways framework using two methods, Wilcoxon and Mahalanobis Distance (MD), for personal transcriptome analysis derived from a pair of samples of a single patient. Although, both methods uncover concordantly dysregulated pathways, they are not designed to detect dysregulated pathways with up- and down-regulated genes (bidirectional dysregulation) that are ubiquitous in biological systems. We developed N-of-1-pathways MixEnrich, a mixture model followed by a gene set enrichment test, to uncover bidirectional and concordantly dysregulated pathways one patient at a time. We assess its accuracy in a comprehensive simulation study and in a RNA-Seq data analysis of head and neck squamous cell carcinomas (HNSCCs). In presence of bidirectionally dysregulated genes in the pathway or in presence of high background noise, MixEnrich substantially outperforms previous single-subject transcriptome analysis methods, both in the simulation study and the HNSCCs data analysis (ROC Curves; higher true positive rates; lower false positive rates). Bidirectional and concordant dysregulated pathways uncovered by MixEnrich in each patient largely overlapped with the quasi-gold standard compared to other single-subject and cohort-based transcriptome analyses. The greater performance of MixEnrich presents an advantage over previous methods to meet the promise of providing accurate personal transcriptome analysis to support precision medicine at point of care.

Functional performance testing of the hip in athletes: a systematic review for reliability and validity.

PubMed

Kivlan, Benjamin R; Martin, Robroy L

2012-08-01

The purpose of this study was to systematically review the literature for functional performance tests with evidence of reliability and validity that could be used for a young, athletic population with hip dysfunction. A search of PubMed and SPORTDiscus databases were performed to identify movement, balance, hop/jump, or agility functional performance tests from the current peer-reviewed literature used to assess function of the hip in young, athletic subjects. The single-leg stance, deep squat, single-leg squat, and star excursion balance tests (SEBT) demonstrated evidence of validity and normative data for score interpretation. The single-leg stance test and SEBT have evidence of validity with association to hip abductor function. The deep squat test demonstrated evidence as a functional performance test for evaluating femoroacetabular impingement. Hop/Jump tests and agility tests have no reported evidence of reliability or validity in a population of subjects with hip pathology. Use of functional performance tests in the assessment of hip dysfunction has not been well established in the current literature. Diminished squat depth and provocation of pain during the single-leg balance test have been associated with patients diagnosed with FAI and gluteal tendinopathy, respectively. The SEBT and single-leg squat tests provided evidence of convergent validity through an analysis of kinematics and muscle function in normal subjects. Reliability of functional performance tests have not been established on patients with hip dysfunction. Further study is needed to establish reliability and validity of functional performance tests that can be used in a young, athletic population with hip dysfunction. 2b (Systematic Review of Literature).

Temporal reliability of ultra-high field resting-state MRI for single-subject sensorimotor and language mapping.

PubMed

Branco, Paulo; Seixas, Daniela; Castro, São Luís

2018-03-01

Resting-state fMRI is a well-suited technique to map functional networks in the brain because unlike task-based approaches it requires little collaboration from subjects. This is especially relevant in clinical settings where a number of subjects cannot comply with task demands. Previous studies using conventional scanner fields have shown that resting-state fMRI is able to map functional networks in single subjects, albeit with moderate temporal reliability. Ultra-high resolution (7T) imaging provides higher signal-to-noise ratio and better spatial resolution and is thus well suited to assess the temporal reliability of mapping results, and to determine if resting-state fMRI can be applied in clinical decision making including preoperative planning. We used resting-state fMRI at ultra-high resolution to examine whether the sensorimotor and language networks are reliable over time - same session and one week after. Resting-state networks were identified for all subjects and sessions with good accuracy. Both networks were well delimited within classical regions of interest. Mapping was temporally reliable at short and medium time-scales as demonstrated by high values of overlap in the same session and one week after for both networks. Results were stable independently of data quality metrics and physiological variables. Taken together, these findings provide strong support for the suitability of ultra-high field resting-state fMRI mapping at the single-subject level. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A Single Subject Evaluation of the K-P Diet for Hyperkinesis.

ERIC Educational Resources Information Center

Burlton-Bennet, Jocelyn A.; Robinson, Viviane M. J.

1987-01-01

A single subject ABAB design was employed to determine the effectiveness of the Feingold Kaiser Permanente (K-P) diet in the treatment of a six-year-old hyperkinetic male. Results indicated the K-P diet was effective in controlling the subject's hyperkinesis, nutritionally adequate, and moderately difficult to implement. (Author/DB)

Methods for forming particles from single source precursors

DOEpatents

Fox, Robert V [Idaho Falls, ID; Rodriguez, Rene G [Pocatello, ID; Pak, Joshua [Pocatello, ID

2011-08-23

Single source precursors are subjected to carbon dioxide to form particles of material. The carbon dioxide may be in a supercritical state. Single source precursors also may be subjected to supercritical fluids other than supercritical carbon dioxide to form particles of material. The methods may be used to form nanoparticles. In some embodiments, the methods are used to form chalcopyrite materials. Devices such as, for example, semiconductor devices may be fabricated that include such particles. Methods of forming semiconductor devices include subjecting single source precursors to carbon dioxide to form particles of semiconductor material, and establishing electrical contact between the particles and an electrode.

Therapeutic riding followed by rhythmic auditory stimulation to improve balance and gait in a subject with orthopedic pathologies.

PubMed

Ungermann, Cathryn M; Gras, Laura Z

2011-12-01

The study objectives were to investigate the effect of therapeutic riding with a subject who had an orthopedic diagnosis. This is a single-subject case report. The study was conducted at an equestrian facility with an indoor riding arena. The subject was a 59-year-old woman with grade I spondylolisthesis at L4/L5 and multilevel lumbar spinal stenosis in central and foraminal canals. The subject had an anterior cervical fusion of C3-C7. The subject has been ambulating with a straight cane due to her history of frequent falls. Gait, agility, strength, range of motion, and balance testing were performed. The subject had impairments of bilateral lower extremities with an ataxic gait pattern and was at risk for continued falls according to the balance measures. The intervention comprised therapeutic riding sessions 3 times a week for 20 minutes for 4 weeks. Each riding session was immediately followed by a 10-minute independent walking program with a metronome for rhythmic auditory stimulation. The outcome measures were as follows: Manual muscle testing and range of motion of the lower extremities, Gait Speed Test, Dynamic Gait Index, Four-Square Step Test, Chair Stand Test, Single Leg Stance. Improvements were seen in lower extremity strength and range of motion and balance. The subject improved on balance scores, placing her out of the risk for falls category. Therapeutic riding followed by rhythmic auditory stimulation improved lower extremity range of motion, strength, and balance with this subject.

MiSight Assessment Study Spain (MASS). A 2-year randomized clinical trial.

PubMed

Ruiz-Pomeda, Alicia; Pérez-Sánchez, Belén; Valls, Isabel; Prieto-Garrido, Francisco Luis; Gutiérrez-Ortega, Ramón; Villa-Collar, César

2018-05-01

To compare myopia progression in children randomized to MiSight contact lenses (CLs) versus children corrected with single-vision spectacles (SV) over a 2-year period. Subjects aged 8 to 12 with myopia (-0.75 to -4.00 D sphere) and astigmatism (< -1.00 D cylinder) were assigned to the lens study group (MiSight) or the control group (single vision). Measurements of visual acuity and subjective refraction were taken at 6-month intervals, and axial length, anterior chamber, corneal power, and cycloplegic autorefraction were measured at the baseline, 12-month, and 24-month visits. Eighty-nine subjects were recruited. Forty-fix children were assigned to the MiSight group, and 33 to the single-vision spectacle group. In total, 74 children completed the clinical trial, with the following parameters at the beginning of the study: n =  41 in the MiSight group (age: 11.01 ± 1.23 years, spherical equivalent: -2.16 ± 0.94 D, gender: male: 21, female: 20) and n = 33 in the single-vision group (age: 10.12 ± 1.38 years, spherical equivalent: -1.75 ± 0.94 D, gender: male: 12, female: 21). After 2 years of follow-up, myopia progressed slowly in the MiSight group compared to the control group (0.45 D vs 0.74 D, p < 0.001) and there was less axial elongation in the MiSight group compared to the single-vision group (0.28 mm vs 0.44 mm, p < 0.001). Therefore, use of MiSight CLs produced lower myopia progression (39.32%) and lower axial growth of the eye (36.04%) at 2 years compared to spectacle use. MiSight contact lens wear reduces axial elongation and myopia progression in comparison to distance single-vision spectacles in children. ClinicalTrials.gov Identifier: NCT01917110.

Gender differences in colour naming performance for gender specific body shape images.

PubMed

Elliman, N A; Green, M W; Wan, W K

1998-03-01

Males are increasingly subjected to pressures to conform to aesthetic body stereotypes. There is, however, comparatively little published research on the aetiology of male body shape concerns. Two experiments are presented, which investigate the relationship between gender specific body shape concerns and colour-naming performance. Each study comprised a between subject design, in which each subject was tested on a single occasion. A pictorial version of a modified Stroop task was used in both studies. Subjects colour-named gender specific obese and thin body shape images and semantically homogeneous neutral images (birds) presented in a blocked format. The first experiment investigated female subjects (N = 68) and the second investigated males (N = 56). Subjects also completed a self-report measure of eating behaviour. Currently dieting female subjects exhibited significant colour-naming differences between obese and neutral images. A similar pattern of colour-naming performance was found to be related to external eating in the male subjects.

Prescriptions of Chinese herbal medicine for constipation under the national health insurance in Taiwan.

PubMed

Jong, Maw-Shiou; Hwang, Shinn-Jang; Chen, Yu-Chun; Chen, Tzeng-Ji; Chen, Fun-Jou; Chen, Fang-Pey

2010-07-01

Constipation is a common gastrointestinal problem worldwide. The aim of this study was to determine the frequency of use and prescriptive patterns of Chinese herbal medicine (CHM) in treating constipation by analyzing the claims data of traditional Chinese medicine (TCM) from the National Health Insurance (NHI) in Taiwan. The computerized claims dataset of the TCM office visits and the corresponding prescription files in 2004 compiled by the NHI Research Institute in Taiwan were linked and processed. Visit files with the single diagnostic coding of constipation (ICD-9-CM code 564.0) were extracted to analyze the frequency and pattern of corresponding CHM prescriptions. The association rule was applied to analyze the co-prescription of CHM in treating constipation. There were 152,564 subjects who visited TCM clinics only for constipation in Taiwan during 2004 and received a total of 387,268 CHM prescriptions. Subjects between 20 and 29 years of age comprised the largest number of those treated (25.5%). Female subjects used CHM for constipation more frequently than male subjects (female:male = 3.31:1). There was an average of 4.6 items of single Chinese herbs or formula in a single prescription for constipation. Ma-zi-renwan was the most commonly prescribed herbal formula, while Da-huang (Rheum palmatum) was the most commonly used single Chinese herb. According to the association rule, the most common prescribed pattern of 2-drug combination of CHM for treating constipation was Ban-xia-xie-xin-tang plus Ma-zi-ren-wan, while the 3-drug combination of CHM was Fang-feng-tong-sheng-san, Rheum palmatum and Ma-zi-ren-wan. This study showed the pattern of single Chinese herbs or herbal formulae used in treating constipation in Taiwan. Further clinical trials are needed to evaluate the efficacy and safety of these CHMs in treating constipation. 2010 Elsevier. Published by Elsevier B.V. All rights reserved.

Validating the Vocabulary Levels Test with Fourth and Fifth Graders to Identify Students At-Risk in Vocabulary Development Using a Quasiexperimental Single Group Design

ERIC Educational Resources Information Center

Dunn, Suzanna

2012-01-01

This quasiexperimental single group design study investigated the validity of the Vocabulary Levels Test (VLT) to identify fourth and fifth grade students who are at-risk in vocabulary development. The subjects of the study were 88 fourth and fifth grade students at one elementary school in Washington State. The Group Reading Assessment and…

Effects of night time road traffic noise—an overview of laboratory and field studies on noise dose and subjective noise sensitivity

NASA Astrophysics Data System (ADS)

Öhrström, E.; Rylander, R.; Björkman, M.

1988-12-01

This paper presents an overview of research on sleep and noise at the Department of Environmental Hygiene, University of Gothenburg. Different methods were developed to study primary and after effects of night time road traffic noise on sleep. Three one-week laboratory experiments were undertaken to study the relevance of different noise descriptors— Leq, maximum peak noise level and number of events with high peak noise levels—for sleep disturbance effects. The noise exposure was either single noise evenys or a continuous, even road traffic noise. It was concluded that Leq was not related to sleep disturbance effects. Peak noise levels were significantly related to subjective sleep quality and body movements. Results from a third continuing study showed that there is a threshold for effects of the number of single noise events on sleep quality. Habituation to noise among subjects with differing noise sensitivity was studied in a two-week experiment. A significant noise effect on subjective sleep quality was found among sensitive subjects only. No habituation was seen for the negative influence of noise on sleep quality, mood and performance. Long-term effects of road traffic noise were also investigated in a field survey among 106 individuals. This study revealed the presence of a decrease in sleep quality as well as psycho-social effects on tiredness and mood, together with increased reports of headaches and nervous stomach. As in the laboratory study, sensitive individuals were more affected by noise than less sensitive individuals.

Pharmacokinetics and Safety of a Single Oral Dose of Mirogabalin in Japanese Subjects With Varying Degrees of Renal Impairment.

PubMed

Kato, Manabu; Tajima, Naoyuki; Shimizu, Takako; Sugihara, Masahiro; Furihata, Kenichi; Harada, Kazuhiro; Ishizuka, Hitoshi

2018-01-01

Mirogabalin (DS-5565) is a novel preferentially selective α 2 δ-1 ligand being developed for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia. The current multicenter open-label study determined the effect of varying degrees of renal impairment on the pharmacokinetics and safety of a single dose of mirogabalin 5 mg in Japanese subjects. A total of 30 subjects (6 subjects per renal function category [normal, mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]) were enrolled and completed the study. The AUC last increased with severity of renal impairment; the geometric least-squares mean ratios of AUC last compared with subjects with normal renal function were 1.3, 1.9, 3.6, and 5.3 for patients with mild, moderate, and severe impairment and ESRD, respectively. In accordance with this AUC last increase, apparent total body clearance (CL/F), renal clearance (CLr), and the cumulative percentage of mirogabalin dose excreted into urine all decreased with severity of renal impairment. There were no deaths and no severe treatment-related adverse events (TEAEs), serious TEAEs, or TEAEs resulting in study discontinuation. Mirogabalin was well tolerated in Japanese subjects with normal renal function and those with mild to severe renal impairment. It was also tolerated in subjects with ESRD but with a higher incidence of TEAEs. The most frequently reported TEAEs were dizziness (ESRD, n = 3), somnolence (ESRD, n = 2), and vomiting (ESRD, n = 2). Based on these data, a mirogabalin dose adjustment will be considered in Japanese subjects with moderate to severe renal impairment and those with ESRD. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

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.

Vitamin K absorption and kinetics in human subjects after consumption of 13C-labeled phylloquinone from kale

USDA-ARS?s Scientific Manuscript database

The absorption and plasma elimination of vitamin K was investigated by uniformly labeling phylloquinone in kale with carbon-13 and feeding the kale to study subjects. Seven healthy volunteers ingested a single 400 g serving of kale with 30 g vegetable oil. The kale provided 156 nmol of phylloquino...

The Development of Anaphora Resolution at the Syntax-Discourse Interface: Pronominal Subjects in Greek Learners of Spanish

ERIC Educational Resources Information Center

Lozano, Cristóbal

2018-01-01

This study explores the development of anaphora resolution (AR) in late sequential bilinguals, namely, adult Greek learners of Spanish at three proficiency levels (intermediate, lower advanced, upper advanced). The use of an overt/null pronominal subject anaphor is investigated in three discourse contexts: topic-continuity (a single antecedent…

Analysis and visualization of single-trial event-related potentials

NASA Technical Reports Server (NTRS)

Jung, T. P.; Makeig, S.; Westerfield, M.; Townsend, J.; Courchesne, E.; Sejnowski, T. J.

2001-01-01

In this study, a linear decomposition technique, independent component analysis (ICA), is applied to single-trial multichannel EEG data from event-related potential (ERP) experiments. Spatial filters derived by ICA blindly separate the input data into a sum of temporally independent and spatially fixed components arising from distinct or overlapping brain or extra-brain sources. Both the data and their decomposition are displayed using a new visualization tool, the "ERP image," that can clearly characterize single-trial variations in the amplitudes and latencies of evoked responses, particularly when sorted by a relevant behavioral or physiological variable. These tools were used to analyze data from a visual selective attention experiment on 28 control subjects plus 22 neurological patients whose EEG records were heavily contaminated with blink and other eye-movement artifacts. Results show that ICA can separate artifactual, stimulus-locked, response-locked, and non-event-related background EEG activities into separate components, a taxonomy not obtained from conventional signal averaging approaches. This method allows: (1) removal of pervasive artifacts of all types from single-trial EEG records, (2) identification and segregation of stimulus- and response-locked EEG components, (3) examination of differences in single-trial responses, and (4) separation of temporally distinct but spatially overlapping EEG oscillatory activities with distinct relationships to task events. The proposed methods also allow the interaction between ERPs and the ongoing EEG to be investigated directly. We studied the between-subject component stability of ICA decomposition of single-trial EEG epochs by clustering components with similar scalp maps and activation power spectra. Components accounting for blinks, eye movements, temporal muscle activity, event-related potentials, and event-modulated alpha activities were largely replicated across subjects. Applying ICA and ERP image visualization to the analysis of sets of single trials from event-related EEG (or MEG) experiments can increase the information available from ERP (or ERF) data. Copyright 2001 Wiley-Liss, Inc.

Normal and obsessional jealousy: a study of a population of young adults.

PubMed

Marazziti, Donatella; Di Nasso, Elena; Masala, Irene; Baroni, Stefano; Abelli, Marianna; Mengali, Francesco; Mungai, Francesco; Rucci, Paola

2003-05-01

Jealousy is a heterogenous emotion ranging from normality to pathology. Several problems still exist in the distinction between normal and pathological jealousy. With the present study, we aimed to contribute to the definition of the boundary between obsessional and normal jealousy by means of a specific self-report questionnaire developed by us. The questionnaire called "Questionnaire on the Affective Relationships" (QAR) and consisting of 30 items, was administered to 400 university students of both sexes and to 14 outpatients affected by obsessive-compulsive disorder (OCD) whose main obsession was jealousy. The total scores and single items were analysed and compared. Two hundred and forty-five, approximately 61% of the questionnaires, were returned. The statistical analyses showed that patients with OCD had higher total scores than healthy subjects; in addition, it was possible to identify an intermediate group of subjects, corresponding to 10% of the total, who were concerned by jealousy thoughts around the partner, but at a lower degree than patients, and that we called "healthy jealous subjects" because they had no other psychopathological trait. Significant differences were also observed for single items in the three groups. Our study showed that 10% of a population of university students, albeit normal, have jealousy thoughts around the partner, as emerged by the specific questionnaire developed by us. This instrument permitted to clearly distinguish these subjects from patients with OCD and healthy subjects with no jealousy concern.

Assessment of the abuse liability of a dual orexin receptor antagonist: a crossover study of almorexant and zolpidem in recreational drug users.

PubMed

Cruz, Hans G; Hoever, Petra; Chakraborty, Bijan; Schoedel, Kerri; Sellers, Edward M; Dingemanse, Jasper

2014-04-01

Dual orexin receptor antagonists (DORAs) enable initiation and maintenance of sleep in patients with primary insomnia. Blockade of the orexin system has shown reduction of drug-seeking behavior in animal studies, supporting the role of orexin antagonism as a novel approach for treating substance abuse. Since hypnotics are traditionally associated with misuse, a lack of abuse liability of DORAs would offer significant benefits over current therapies for sleep disorders. In this randomized, crossover, proof-of-concept study, single oral doses of the DORA almorexant (200, 400, and 1,000 mg) were administered to healthy subjects with previous non-therapeutic experience with central nervous system depressants and were compared with placebo and single oral doses of zolpidem (20 and 40 mg), a benzodiazepine-like drug. Subjective measures of abuse potential (visual analog scales [VAS], Addiction Research Center Inventory, and Subjective Drug Value) and objective measures (divided attention [DA]) were evaluated over 24 h post-dose in 33 evaluable subjects. Drug Liking VAS peak effect (E max; primary endpoint) was significantly higher for all doses of almorexant and zolpidem compared with placebo (p<0.001). Almorexant 200 mg showed significantly less 'Drug Liking' than both zolpidem doses (p<0.01), and almorexant 400 mg had smaller effects than zolpidem 20 mg (p<0.05), while almorexant 1,000 mg was not different from either zolpidem dose. Results were similar for other subjective measures, although almorexant generally showed smaller negative and perceptual effects compared with zolpidem. Almorexant also showed less cognitive impairment compared with zolpidem on most DA endpoints. This study in humans investigating single doses of almorexant is the first to explore and show abuse liability of a DORA, a class of compounds that is not only promising for the treatment of sleep disorders, but also of addiction.

Effect of ice massage on lower extremity functional performance and weight discrimination ability in collegiate footballers.

PubMed

Sharma, Geeta; Noohu, Majumi Mohamad

2014-09-01

Cryotherapy, in the form of ice massge is used to reduce inflammation after acute musculoskeletal injury or trauma. The potential negative effects of ice massage on proprioception are unknown, despite equivocal evidence supporting its effectiveness. The purpose of the study was to test the influence of cooling on weight discrimination ability and hence the performance in footballers. The study was of same subject experimental design (pretest-posttest design). Thirty male collegiate football players, whose mean age was 21.07 years, participated in the study. The participants were assessed for two functional performance tests, single leg hop test and crossed over hop test and weight discrimination ability before and after ice massage for 5 minutes on hamstrings muscle tendon. Pre cooling scores of Single Leg Hop Test of the dominant leg in the subjects was 166.65 (± 10.16) cm and post cooling scores of the dominant leg was 167.25 (± 11.77) cm. Pre cooling scores of Crossed Over Hop Test of the dominant leg in the subjects was 174.14 (± 8.60) cm and post cooling scores of the dominant leg was 174.45 (± 9.28) cm. Pre cooling scores of Weight Discrimination Differential Threshold of the dominant leg in the subjects was 1.625 ± 1.179 kg compared with post cooling scores of the dominant leg 1.85 (± 1.91) kg. Pre cooling scores of single leg hop and crossed over hop test of the dominant leg in the subjects compared with post cooling scores of the dominant leg showed no significant differences and it was also noted that the weight discrimination ability (weight discrimination differential threshold) didn't show any significant difference. All the values are reported as mean ± SD. This study provides additional evidence that proprioceptive acuity in the hamstring muscles (biceps femoris) remains largely unaffected after ice application to the hamstrings tendon (biceps femoris).

Bioequivalence study of two imatinib formulations after single-dose administration in healthy Korean male volunteers.

PubMed

Jung, J A; Kim, N; Yang, J-S; Kim, T-e; Kim, J-R; Song, G-S; Kim, H; Ko, J W; Huh, W

2014-12-01

Imatinib mesylate is effective for chronic myeloid leukaemia and gastrointestinal tumours. We aimed to evaluate the pharmacokinetics of a 200-mg imatinib tablet compared to 2×100-mg imatinib tablets in order to meet the regulatory requirements for marketing in Korea.An open-label, randomized, single-dose, 2-period, 2-treatment cross-over study was conducted in 28 healthy Korean male volunteers. Subjects were administered a 200-mg imatinib tablet and 2×100-mg imatinib tablets under a fasting state according to a randomly assigned order with a 2-week wash-out period. Serial blood samples were collected up to 72 h post-dose. The pharmacokinetic parameters were calculated using non-compartmental methods.A total of 28 subjects were enrolled and 23 subjects completed the study. There were no serious adverse events during the study. 23 mild to moderate adverse events were reported (11 events with 200-mg imatinib vs. 12 events with 2×100-mg imatinib) and subjects recovered without sequelae. The Cmax value was 922.8±318.8 μg/L at 3.15 h for 200-mg imatinib tablet, and 986.3±266.0 μg/L at 2.91 h for the 2×100-mg imatinib tablet. The AUClast of 200-mg and 2×100-mg tablets were 13 084.3±39.1 and 14 131.7±3 826.2 h · μg/L, respectively. The geometric mean ratios (90% confidence intervals) for Cmax and AUClast were 0.9121 (0.8188, 1.0161) and 0.9558 (0.8685, 1.0519), respectively.A newly developed 200-mg imatinib tablet was bioequivalent to 2×100-mg imatinib tablets in healthy Korean subjects. A single-dose of either of the 2 formulations was generally well tolerated. © Georg Thieme Verlag KG Stuttgart · New York.

Storytelling in the early bereavement period to reduce emotional distress among surrogates involved in a decision to limit life support in the ICU: A pilot feasibility trial

PubMed Central

Barnato, Amber E.; Schenker, Yael; Tiver, Greer; Dew, Mary Amanda; Arnold, Robert M.; Nunez, Eduardo R.; Reynolds, Charles F.

2017-01-01

Background Surrogate decision makers involved in decisions to limit life support for an incapacitated patient in the ICU have high rates of adverse emotional health outcomes distinct from normal processes of grief and bereavement. Narrative self-disclosure (storytelling) reduces emotional distress after other traumatic experiences. Objective To assess the feasibility, acceptability, and tolerability of storytelling among bereaved surrogates involved in a decision to limit life support in the ICU. Methods We conducted a pilot single-blind trial of storytelling among bereaved surrogates from 5 ICUs across 3 hospitals within a single health system between June 2013 and November 2014. Both storytelling and control conditions involved printed bereavement materials and follow-up assessments. Storytelling involved a single 1–2 hour home or telephone visit by a trained interventionist who elicited the surrogate’s story. The primary outcomes were feasibility (rates of enrollment, intervention receipt, 3- and 6-month follow up), acceptability (closed and open-ended end-of-study feedback at 6 months), and tolerability (acute mental health services referral). Results Of 53 eligible surrogates, 32 (60%) consented to treatment allocation. Surrogates’ mean age was 55.5 (SD=11.8) and they were making decisions for their parent (47%) spouse (28%), sibling (13%), child (3%) or other relation (8%). We allocated 14 to control and 18 to storytelling, 17/18 (94%) received storytelling, 14/14 (100%) and 13/14 (94%) control subjects and 16/18 (89%) and 17/18 (94%) storytelling subjects completed their 3- and 6-month telephone assessments. At 6-months, 9/13 (69%) control participants and 16/17 (94%) storytelling subjects reported feeling “better” or “much better,” and none felt “much worse”. One (8%) control subject and 1 (6%) storytelling subject said the study was burdensome, and 1 (8%) control subject wished they had not participated. No subjects required acute mental health services referral. Conclusion A clinical trial of storytelling in this study population is feasible, acceptable, and tolerable. PMID:27618273

Storytelling in the Early Bereavement Period to Reduce Emotional Distress Among Surrogates Involved in a Decision to Limit Life Support in the ICU: A Pilot Feasibility Trial.

PubMed

Barnato, Amber E; Schenker, Yael; Tiver, Greer; Dew, Mary Amanda; Arnold, Robert M; Nunez, Eduardo R; Reynolds, Charles F

2017-01-01

Surrogate decision makers involved in decisions to limit life support for an incapacitated patient in the ICU have high rates of adverse emotional health outcomes distinct from normal processes of grief and bereavement. Narrative self-disclosure (storytelling) reduces emotional distress after other traumatic experiences. We sought to assess the feasibility, acceptability, and tolerability of storytelling among bereaved surrogates involved in a decision to limit life support in the ICU. Pilot single-blind trial. Five ICUs across three hospitals within a single health system between June 2013 and November 2014. Bereaved surrogates of ICU patients. Storytelling and control conditions involved printed bereavement materials and follow-up assessments. Storytelling involved a single 1- to 2-hour home or telephone visit by a trained interventionist who elicited the surrogate's story. The primary outcomes were feasibility (rates of enrollment, intervention receipt, 3- and 6-mo follow-up), acceptability (closed and open-ended end-of-study feedback at 6 mo), and tolerability (acute mental health services referral). Of 53 eligible surrogates, 32 (60%) consented to treatment allocation. Surrogates' mean age was 55.5 (SD, 11.8), and they were making decisions for their parent (47%), spouse (28%), sibling (13%), child (3%), or other relation (8%). We allocated 14 to control and 18 to storytelling, 17 of 18 (94%) received storytelling, 14 of 14 (100%) and 13 of 14 (94%) control subjects and 16 of 18 (89%) and 17 of 18 (94%) storytelling subjects completed their 3- and 6-month telephone assessments. At 6 months, nine of 13 control participants (69%) and 16 of 17 storytelling subjects (94%) reported feeling "better" or "much better," and none felt "much worse." One control subject (8%) and one storytelling subject (6%) said that the study was burdensome, and one control subject (8%) wished they had not participated. No subjects required acute mental health services referral. A clinical trial of storytelling in this study population is feasible, acceptable, and tolerable.

Teaching Science Courses In and Out of Area of Specialisation in a Single-Sex/Co-Educational Schools.

ERIC Educational Resources Information Center

Ogunsola-Bandele, Mercy F.

This study examined the differences and similarities experienced by secondary school science teachers when teaching science within and outside their area of specialization in single sex and co-educational schools. Interviews were conducted and audio taped for six experienced science teachers on their qualification, classes/subjects taught and…

Rural Mid-Life Single Adult Families: Male/Female Similarities and Differences.

ERIC Educational Resources Information Center

Lingren, Herbert G.; And Others

The study examined data from rural midlife singles concerning: (1) their socio-demographic characteristics; (2) their life satisfactions and happiness with their rural lifestyle; (3) their self-image and self-esteem; (4) their coping strategies; and (5) their social support systems. Subjects were 76 men and 149 women between the ages of 35 and 59…

Single-dose pharmacokinetics of repaglinide in subjects with chronic liver disease.

PubMed

Hatorp, V; Walther, K H; Christensen, M S; Haug-Pihale, G

2000-02-01

Repaglinide is a novel insulin secretagogue developed in response to the need for a fast-acting, oral prandial glucose regulator for the treatment of type 2 (non-insulin-dependent) diabetes mellitus. Repaglinide is metabolized mainly in the liver; its pharmacokinetics may therefore be altered by hepatic dysfunction. This open, parallel-group study compared the pharmacokinetics and tolerability of a single 4 mg dose of repaglinide in healthy subjects (n = 12) and patients with chronic liver disease (CLD) (n = 12). Values for AUC and Cmax were significantly higher in CLD patients compared with healthy subjects, and the MRT was prolonged in CLD patients. Values for tmax did not differ between the groups, but t1/2 was significantly prolonged in CLD patients compared with previously determined values in healthy subjects. AUC was inversely correlated with caffeine clearance in CLD patients but not in healthy subjects. Blood glucose profiles were similar in both groups. Adverse events (principally hypoglycemia) were similar in the two groups; none was serious. Repaglinide clearance is significantly reduced in patients with hepatic impairment; the agent should be used with caution in this group.

Time Independent Functional task Training: a case study on the effect of inter-joint coordination driven haptic guidance in stroke therapy.

PubMed

Brokaw, Elizabeth B; Murray, Theresa M; Nef, Tobias; Lum, Peter S; Brokaw, Elizabeth B; Nichols, Diane; Holley, Rahsaan J

2011-01-01

After a stroke abnormal joint coordination of the arm may limit functional movement and recovery. To aid in training inter-joint movement coordination a haptic guidance method for functional driven rehabilitation after stroke called Time Independent Functional Training (TIFT) has been developed for the ARMin III robot. The mode helps retraining inter-joint coordination during functional movements, such as putting an object on a shelf, pouring from a pitcher, and sorting objects into bins. A single chronic stroke subject was tested for validation of the modality. The subject was given 1.5 hrs of robotic therapy twice a week for 4 weeks. The therapy and the results of training the single stroke subject are discussed. The subject showed a decrease in training joint error for the sorting task across training sessions and increased self-selected movement time in training. In kinematic reaching analysis the subject showed improvements in range of motion and joint coordination in a reaching task, as well as improvements in supination-pronation range of motion at the wrist. © 2011 IEEE

Developing a 'personalome' for precision medicine: emerging methods that compute interpretable effect sizes from single-subject transcriptomes.

PubMed

Vitali, Francesca; Li, Qike; Schissler, A Grant; Berghout, Joanne; Kenost, Colleen; Lussier, Yves A

2017-12-18

The development of computational methods capable of analyzing -omics data at the individual level is critical for the success of precision medicine. Although unprecedented opportunities now exist to gather data on an individual's -omics profile ('personalome'), interpreting and extracting meaningful information from single-subject -omics remain underdeveloped, particularly for quantitative non-sequence measurements, including complete transcriptome or proteome expression and metabolite abundance. Conventional bioinformatics approaches have largely been designed for making population-level inferences about 'average' disease processes; thus, they may not adequately capture and describe individual variability. Novel approaches intended to exploit a variety of -omics data are required for identifying individualized signals for meaningful interpretation. In this review-intended for biomedical researchers, computational biologists and bioinformaticians-we survey emerging computational and translational informatics methods capable of constructing a single subject's 'personalome' for predicting clinical outcomes or therapeutic responses, with an emphasis on methods that provide interpretable readouts. (i) the single-subject analytics of the transcriptome shows the greatest development to date and, (ii) the methods were all validated in simulations, cross-validations or independent retrospective data sets. This survey uncovers a growing field that offers numerous opportunities for the development of novel validation methods and opens the door for future studies focusing on the interpretation of comprehensive 'personalomes' through the integration of multiple -omics, providing valuable insights into individual patient outcomes and treatments. © The Author 2017. Published by Oxford University Press.

Esthetic evaluation of single-tooth implants in the anterior mandible.

PubMed

Hof, Markus; Tepper, Gabor; Koller, Barbara; Krainhöfner, Martin; Watzek, Georg; Pommer, Bernhard

2014-09-01

Single-tooth replacement of anterior mandibular teeth is frequently complicated by insufficient bucco-lingual bone width and limited mesio-distal space available for implant placement. The aim of the present study was to assess implant esthetics in the partially edentulous anterior mandible. Esthetic evaluation of 43 anterior mandibular single-tooth implants in 15 women and 28 men was performed using esthetic indices (PES = Pink Esthetic Score, PI = Papilla Index, SES = Subjective Esthetic Score) as well as subjective patients' Visual Analogue Scale (VAS) ratings. Clinical and radiological parameters (implant and crown dimensions, pocket depth, bleeding on probing, plaque, keratinized mucosa, marginal bone level, and distance to adjacent teeth) were tested for influence. Implant esthetics were judged satisfactory (PES ≤10) in 42% of implants compared with a patient satisfaction rate of 87%. Correlation between objective indices (PES/PI: rs  = 0.62, PES/SES: rs  = -0.73, PI/SES: rs  = -0.48) was highly significant (P ≤ 0.001); however, no association to subjective patients' ratings could be observed. Type of prosthetic restoration (single crown vs. tulip-shaped double crowns), mesio-distal crown width as well as anatomic crown length significantly affected esthetic scores. Patients' judgment, by contrast, could not be associated to any prognostic factor. Subjective patient satisfaction with implant esthetics in the partially edentulous anterior mandible is high, however, remains hard to predict or objectively quantify. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab.

PubMed

Kaur, Primal; Chow, Vincent; Zhang, Nan; Moxness, Michael; Kaliyaperumal, Arunan; Markus, Richard

2017-03-01

To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501. Randomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC inf ) and the maximum observed concentration (C max ). Secondary end points included safety and immunogenicity. AUC inf and C max were similar across the three groups. Geometrical mean ratio (GMR) of AUC inf was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of C max was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUC inf and C max were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups. Results of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups. EudraCT number 2012-000785-37; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Double-layer versus single-layer bone-patellar tendon-bone anterior cruciate ligament reconstruction: a prospective randomized study with 3-year follow-up.

PubMed

Mei, Xiaoliang; Zhang, Zhenxiang; Yang, Jingwen

2016-12-01

To evaluate the clinical results of a randomized controlled trial of single-layer versus double-layer bone-patellar tendon-bone (BPTB) anterior cruciate ligament (ACL) reconstruction. Fifty-eight subjects who underwent primary ACL reconstruction with a BPTB allograft were prospectively randomized into two groups: single-layer reconstruction (n = 31) and double-layer reconstruction (n = 27). The following evaluation methods were used: clinical examination, KT-1000 arthrometer measurement, muscle strength, Tegner activity score, Lysholm score, subjective rating scale regarding patient satisfaction and sports performance level, graft retear, contralateral ACL tear, and additional meniscus surgery. Forty-eight subjects (24 in single-layer group and 24 in double-layer group) who were followed up for 3 years were evaluated. Preoperatively, there were no differences between the groups. At 3-year follow-up, the Lachman and pivot-shift test results were better in the double-layer group (P = 0.019 and P < 0.0001, respectively). KT measurements were better in the double-layer group (mean 2.9 versus 1.5 mm; P = 0.0025). The Tegner score was also better in the double-layer group (P = 0.024). There were no significant differences in range of motion, muscle strength, Lysholm score, subjective rating scale, graft retear, and secondary meniscal tear. In ACL reconstruction, double-layer BPTB reconstruction was significantly better than single-layer reconstruction regarding anterior and rotational stability at 3-year follow-up. The results of KT measurements and the Lachman and pivot-shift tests were significantly better in the double-layer group, whereas there was no difference in the anterior drawer test results. The Tegner score was also better in the double-layer group; however, there were no differences in the other subjective findings.

Safety, Tolerability and Pharmacokinetics of Single Doses of Oxytocin Administered via an Inhaled Route in Healthy Females: Randomized, Single-blind, Phase 1 Study.

PubMed

Fernando, Disala; Siederer, Sarah; Singh, Sunita; Schneider, Ian; Gupta, Ashutosh; Powell, Marcy; Richards, Duncan; McIntosh, Michelle P; Lambert, Peter; Fowles, Susan

2017-08-01

The utility of intramuscular (IM) oxytocin for the prevention of postpartum hemorrhage in resource-poor settings is limited by the requirement for temperature-controlled storage and skilled staff to administer the injection. We evaluated the safety, tolerability and pharmacokinetics (PK) of a heat-stable, inhaled (IH) oxytocin formulation. This phase 1, randomized, single-center, single-blind, dose-escalation, fixed-sequence study (NCT02542813) was conducted in healthy, premenopausal, non-pregnant, non-lactating women aged 18-45years. Subjects initially received IM oxytocin 10 international units (IU) on day 1, IH placebo on day 2, and IH oxytocin 50μg on day 3. Subjects were then randomized 4:1 using validated GSK internal software to IH placebo or ascending doses of IH oxytocin (200, 400, 600μg). PK was assessed by comparing systemic exposure (maximum observed plasma concentration, area under the concentration-time curve, and plasma concentrations at 10 and 30min post dose) for IH versus IM oxytocin. Adverse events (AEs), spirometry, laboratory tests, vital signs, electrocardiograms, physical examinations, and cardiac telemetry were assessed. Subjects were recruited between September 14, 2015 and October 12, 2015. Of the 16 subjects randomized following initial dosing, 15 (IH placebo n=3; IH oxytocin n=12) completed the study. IH (all doses) and IM oxytocin PK profiles were comparable in shape. However, systemic exposure with IH oxytocin 400μg most closely matched IM oxytocin 10IU. Systemic exposure was approximately dose proportional for IH oxytocin. No serious AEs were reported. No clinically significant findings were observed for any safety parameters. These data suggest that similar oxytocin systemic exposure can be achieved with IM and IH administration routes, and no safety concerns were identified with either route. The inhalation route may offer the opportunity to increase access to oxytocin for women giving birth in resource-poor settings. Copyright © 2017. Published by Elsevier B.V.

Convolutional neural networks for event-related potential detection: impact of the architecture.

PubMed

Cecotti, H

2017-07-01

The detection of brain responses at the single-trial level in the electroencephalogram (EEG) such as event-related potentials (ERPs) is a difficult problem that requires different processing steps to extract relevant discriminant features. While most of the signal and classification techniques for the detection of brain responses are based on linear algebra, different pattern recognition techniques such as convolutional neural network (CNN), as a type of deep learning technique, have shown some interests as they are able to process the signal after limited pre-processing. In this study, we propose to investigate the performance of CNNs in relation of their architecture and in relation to how they are evaluated: a single system for each subject, or a system for all the subjects. More particularly, we want to address the change of performance that can be observed between specifying a neural network to a subject, or by considering a neural network for a group of subjects, taking advantage of a larger number of trials from different subjects. The results support the conclusion that a convolutional neural network trained on different subjects can lead to an AUC above 0.9 by using an appropriate architecture using spatial filtering and shift invariant layers.

Difference of motor overflow depending on the impaired or unimpaired hand in stroke patients.

PubMed

Kim, Yushin; Kim, Woo-Sub; Shim, Jae Kun; Suh, Dong Won; Kim, TaeYeong; Yoon, BumChul

2015-02-01

The aim of this study was to investigate the patterns of contralateral motor overflow (i.e. mirror movement) between the homologous body parts on the right and left side, in stroke patients during single-finger and multi-finger maximum force production tasks. Forty subjects, including stroke (n=20) and normal subjects (n=20), participated in this study. The stroke subjects maximally pressed force sensors with their fingers in a flexed position using a single (index, middle, ring, or little) or all fingers (all 4 fingers) using the impaired (IH) or unimpaired (UIH) hand, while the non-patient subjects used their right hands for the same tasks. The maximal voluntary forces in the ipsilateral and unintended pressing forces of each contralateral finger were recorded during the tasks. The magnitude of motor overflow to the contralateral side was calculated using the index of contralateral independence (CI). During the single finger tasks, the finger CI was significantly decreased in the UIH (91%) compared with that in the IH (99%) or normal hands (99%). Likewise, the multiple finger tasks showed that the CI was significantly lower in the UIH (84%) compared with that in the IH (96%) or normal hands (99%). However, the maximal forces were significantly lower in the IH relative to those in the UIH and normal hands. These data demonstrate that stroke patients have greater motor overflow from the UIH to the IH. Copyright © 2014 Elsevier B.V. All rights reserved.

Safety, Tolerability and Pharmacokinetics of the Serotonin 5-HT6 Receptor Antagonist, SUVN-502, in Healthy Young Adults and Elderly Subjects.

PubMed

Nirogi, Ramakrishna; Mudigonda, Koteshwara; Bhyrapuneni, Gopinadh; Muddana, Nageswara Rao; Goyal, Vinod Kumar; Pandey, Santosh Kumar; Palacharla, Raghava Choudary

2018-05-01

SUVN-502, a selective 5-HT6 receptor antagonist, was found to be active in preclinical models of cognitive deterioration suggesting a potential role in the treatment of dementia related to Alzheimer's disease. The objective of this study was to characterize the safety, tolerability and pharmacokinetics of SUVN-502 in healthy young adults and elderly subjects following single and multiple oral doses. Single doses (5, 15, 50, 100 and 200 mg SUVN-502) and multiple doses (50, 100 and 130 mg SUVN-502 once daily for 7 days) were evaluated in healthy young adults and multiple doses (50 and 100 mg SUVN-502 once daily for 14 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food, gender and age on SUVN-502 pharmacokinetics (100 mg single dose) was evaluated using an open-label, two-period, randomized, fed and fasted in a crossover design. SUVN-502 and M1 (major metabolite of SUVN-502) were monitored using validated analytical methods. SUVN-502 is safe and well tolerated up to the highest tested single dose of 200 mg in healthy young adults and multiple doses up to 130 mg for 7 days and 100 mg for 14 days in healthy young adults and elderly subjects, respectively. Exposures of SUVN-502 and M1 were more than dose-proportional over the evaluated dose range. Food and gender did not have a clinically meaningful effect on SUVN-502 exposure. The mean SUVN-502 total (AUC 0-∞ , and AUC 0-last ) and peak exposures (C max ) were 2.9- and 2.2-fold higher, respectively, in elderly subjects compared to young subjects. Steady-state was achieved for SUVN-502 and M1 within 7 days after once-daily dosing of SUVN-502. SUVN-502 exhibited an acceptable safety, tolerability and pharmacokinetic profile in healthy young adults and elderly subjects. Based on the above results, 50 and 100 mg once-daily doses of SUVN-502 were advanced to Phase 2 evaluation in patients with moderate AD.

Randomized, open-label, single-dose, crossover, relative bioavailability study in healthy adults, comparing the pharmacokinetics of rabeprazole granules administered using soft food or infant formula as dosing vehicle versus suspension.

PubMed

Thyssen, An; Solanki, Bhavna; Treem, William

2012-07-01

A sprinkle capsule formulation containing enteric-coated, delayed-release rabeprazole granules is being developed for the treatment of children with gastrointestinal reflux disease. The granules are designed to be mixed with vehicles that facilitate delivery to children, who may be unable to swallow solid formulations. The primary objective of this study-conducted on the sponsor's initiative-was to compare the bioavailability of rabeprazole granules when mixed with various dosing vehicles (small amount of soft food or infant formula) with that of a rabeprazole suspension with inactive vehicle granules (reference), to determine which dosing vehicle can be used to deliver rabeprazole in children. Tolerability was also assessed. This single-center, single-dose, randomized, open-label, 5-period crossover study was conducted in 35 healthy adult subjects. In a randomized sequence, fasting subjects received a single dose of 10-mg rabeprazole granules per treatment period, mixed with small amounts of 1 of 5 dosing vehicles (a strawberry-flavored suspension of rabeprazole granules with inactive vehicle granules reconstituted with water, yogurt [1 tablespoon], applesauce [1 tablespoon], or infant formula [5 mL], or a suspension of rabeprazole granules with inactive vehicle tablet reconstituted with water). Full plasma pharmacokinetic (PK) profiles of rabeprazole and its thioether metabolite were collected; concentrations were estimated via LC-MS/MS. PK properties were estimated using noncompartmental methods; 90% CIs around least squares mean test-to-reference ratios were calculated for C(max) and AUC values. All treatment-emergent adverse events (TEAEs) were recorded and assessed for severity (mild, moderate, or severe) and relationship to study drug. A total of 35 subjects were enrolled (mean age, 38 years; 54.3% female; 100% white; mean weight, 71.4 kg). Thirty-four subjects completed the study. Rabeprazole and rabeprazole thioether plasma PK properties were comparable between all of the dosing vehicles tested. Median T(max) was 2.5 to 3.0 hours, and mean elimination half-life was 1.27 to 1.43 hours. The 90%CIs for the least squares mean ratios for rabeprazole and rabeprazole thioether exposure were within the 80% to 125% bioequivalence limits for all relevant comparisons. All TEAEs were of mild or moderate intensity, with headache being the most commonly reported; 21 subjects (60%) experienced TEAEs during the study. No deaths or serious AEs were reported during the study; 1 subject experienced a TEAE (urinary tract infection) that led to the discontinuation of treatment. In these healthy adult subjects, the bioavailability of rabeprazole granules was comparable between all of the dosing vehicles tested, and rabeprazole was well tolerated. Soft food suitable for young children or infant formula may be appropriate for use as dosing vehicles for rabeprazole granules. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

The effects of display-control I/O, compatibility, and integrality on dual-task performance and subjective workload

NASA Technical Reports Server (NTRS)

Tsang, Pamela S.; Hart, Sandra G.; Vidulich, Michael A.

1987-01-01

The utility of speech technology was evaluated in terms of three dual task principles: resource competition between the time shared tasks, stimulus central processing response compatibility, and task integrality. Empirical support for these principles was reviewed. Two studies investigating the interactive effects of the three principles were described. Objective performance and subjective workload ratings for both single and dual tasks were examined. It was found that the single task measures were not necessarily good predictors for the dual task measures. It was shown that all three principles played an important role in determining an optimal task configuration. This was reflected in both the performance measures and the subjective measures. Therefore, consideration of all three principles is required to insure proper use of speech technology in a complex environment.

Evidence-based practice: a quality indicator analysis of peer-tutoring in adapted physical education.

PubMed

Kalef, Laura; Reid, Greg; Macdonald, Cathy

2013-09-01

The purpose of the research was to conduct a quality indicator analysis of studies investigating peer-tutoring for students with a disability in adapted physical education. An electronic search was conducted among English journals published from 1960 to November 2012. Databases included ERIC, PsycINFO, and SPORTDiscus. Fifteen research studies employing group-experimental (Gersten et al., 2005) or single-subject designs (Horner et al., 2005) met inclusion criteria. Each study was assessed for the presence and clarity of quality indicators. Group designs met an average of 62.5% essential and 69% desirable indicators. An average of 80% of indicators was present for single-subject designs. Results suggest claims of peer-tutoring being an evidence-based practice are premature. Recommendations for clarifying and applying the quality indicators are offered. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of Age, Sex, and Race on the Safety and Pharmacokinetics of Single and Multiple Doses of Azilsartan Medoxomil in Healthy Subjects.

PubMed

Harrell, Robert E; Karim, Aziz; Zhang, Wencan; Dudkowski, Caroline

2016-05-01

Azilsartan medoxomil (AZL-M) is an angiotensin II receptor blocker approved to treat hypertension. After oral dosing, AZL-M is quickly hydrolyzed to azilsartan (AZL). The aims of this study were to assess the effects of age, sex, and race on the pharmacokinetics of AZL-M in healthy subjects, as well as safety and tolerability. Sixty-one healthy adults were enrolled in this phase I, single-blind, randomized placebo-controlled study (placebo control was for assessment of safety/tolerability only). Subjects were stratified by age (18-45 vs. 65-85 years), sex, and race (black vs. white) and given oral AZL-M 60 mg (3 × 20 mg capsules) or placebo as a single dose (Day 1) and consecutive daily doses (Days 4-8) (6:2 ratio for AZL-M:placebo per group). Pharmacokinetics were evaluated (AZL-M patients only) on Days 1-3 and 8-9 and safety/tolerability was monitored. Age, sex, and race had no clinically meaningful effect on AZL exposures after single or multiple dosing. Pharmacokinetic parameters remained similar between Days 1 and 8 for each age, sex, and race subgroup. The frequency of adverse events was similar for AZL-M (32%) and placebo (29%). No discontinuations or serious adverse events occurred. Based on these pharmacokinetic and safety/tolerability findings, no AZL-M dose adjustments are required based on age, sex, or race (black/white).

Subjective aggression during alcohol and cannabis intoxication before and after aggression exposure.

PubMed

De Sousa Fernandes Perna, E B; Theunissen, E L; Kuypers, K P C; Toennes, S W; Ramaekers, J G

2016-09-01

Alcohol and cannabis use have been implicated in aggression. Alcohol consumption is known to facilitate aggression, whereas a causal link between cannabis and aggression has not been clearly demonstrated. This study investigated the acute effects of alcohol and cannabis on subjective aggression in alcohol and cannabis users, respectively, following aggression exposure. Drug-free controls served as a reference. It was hypothesized that aggression exposure would increase subjective aggression in alcohol users during alcohol intoxication, whereas it was expected to decrease subjective aggression in cannabis users during cannabis intoxication. Heavy alcohol (n = 20) and regular cannabis users (n = 21), and controls (n = 20) were included in a mixed factorial study. Alcohol and cannabis users received single doses of alcohol and placebo or cannabis and placebo, respectively. Subjective aggression was assessed before and after aggression exposure consisting of administrations of the point-subtraction aggression paradigm (PSAP) and the single category implicit association test (SC-IAT). Testosterone and cortisol levels in response to alcohol/cannabis treatment and aggression exposure were recorded as secondary outcome measures. Subjective aggression significantly increased following aggression exposure in all groups while being sober. Alcohol intoxication increased subjective aggression whereas cannabis decreased the subjective aggression following aggression exposure. Aggressive responses during the PSAP increased following alcohol and decreased following cannabis relative to placebo. Changes in aggressive feeling or response were not correlated to the neuroendocrine response to treatments. It is concluded that alcohol facilitates feelings of aggression whereas cannabis diminishes aggressive feelings in heavy alcohol and regular cannabis users, respectively.

Parametric mapping using spectral analysis for 11C-PBR28 PET reveals neuroinflammation in mild cognitive impairment subjects.

PubMed

Fan, Zhen; Dani, Melanie; Femminella, Grazia D; Wood, Melanie; Calsolaro, Valeria; Veronese, Mattia; Turkheimer, Federico; Gentleman, Steve; Brooks, David J; Hinz, Rainer; Edison, Paul

2018-07-01

Neuroinflammation and microglial activation play an important role in amnestic mild cognitive impairment (MCI) and Alzheimer's disease. In this study, we investigated the spatial distribution of neuroinflammation in MCI subjects, using spectral analysis (SA) to generate parametric maps and quantify 11 C-PBR28 PET, and compared these with compartmental and other kinetic models of quantification. Thirteen MCI and nine healthy controls were enrolled in this study. Subjects underwent 11 C-PBR28 PET scans with arterial cannulation. Spectral analysis with an arterial plasma input function was used to generate 11 C-PBR28 parametric maps. These maps were then compared with regional 11 C-PBR28 V T (volume of distribution) using a two-tissue compartment model and Logan graphic analysis. Amyloid load was also assessed with 18 F-Flutemetamol PET. With SA, three component peaks were identified in addition to blood volume. The 11 C-PBR28 impulse response function (IRF) at 90 min produced the lowest coefficient of variation. Single-subject analysis using this IRF demonstrated microglial activation in five out of seven amyloid-positive MCI subjects. IRF parametric maps of 11 C-PBR28 uptake revealed a group-wise significant increase in neuroinflammation in amyloid-positive MCI subjects versus HC in multiple cortical association areas, and particularly in the temporal lobe. Interestingly, compartmental analysis detected group-wise increase in 11 C-PBR28 binding in the thalamus of amyloid-positive MCI subjects, while Logan parametric maps did not perform well. This study demonstrates for the first time that spectral analysis can be used to generate parametric maps of 11 C-PBR28 uptake, and is able to detect microglial activation in amyloid-positive MCI subjects. IRF parametric maps of 11 C-PBR28 uptake allow voxel-wise single-subject analysis and could be used to evaluate microglial activation in individual subjects.

Distributed representation of visual objects by single neurons in the human brain.

PubMed

Valdez, André B; Papesh, Megan H; Treiman, David M; Smith, Kris A; Goldinger, Stephen D; Steinmetz, Peter N

2015-04-01

It remains unclear how single neurons in the human brain represent whole-object visual stimuli. While recordings in both human and nonhuman primates have shown distributed representations of objects (many neurons encoding multiple objects), recordings of single neurons in the human medial temporal lobe, taken as subjects' discriminated objects during multiple presentations, have shown gnostic representations (single neurons encoding one object). Because some studies suggest that repeated viewing may enhance neural selectivity for objects, we had human subjects discriminate objects in a single, more naturalistic viewing session. We found that, across 432 well isolated neurons recorded in the hippocampus and amygdala, the average fraction of objects encoded was 26%. We also found that more neurons encoded several objects versus only one object in the hippocampus (28 vs 18%, p < 0.001) and in the amygdala (30 vs 19%, p < 0.001). Thus, during realistic viewing experiences, typical neurons in the human medial temporal lobe code for a considerable range of objects, across multiple semantic categories. Copyright © 2015 the authors 0270-6474/15/355180-07$15.00/0.

Pharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: Results of a double-blind randomized clinical trial

PubMed Central

Flanigan, Kevin M.; Voit, Thomas; Rosales, Xiomara Q.; Servais, Laurent; Kraus, John E.; Wardell, Claire; Morgan, Allison; Dorricott, Susie; Nakielny, Joanna; Quarcoo, Naashika; Liefaard, Lia; Drury, Tom; Campion, Giles; Wright, Padraig

2014-01-01

Duchenne muscular dystrophy (DMD) is a progressive, lethal neuromuscular disorder caused by the absence of dystrophin protein due to mutations of the dystrophin gene. Drisapersen is a 2′-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. This study assessed safety, tolerability, and pharmacokinetics of drisapersen after a single subcutaneous administration in non-ambulatory subjects. Eligible subjects were non-ambulant boys aged ≥9 years, in wheelchairs for ≥1 to ≤4 years, with a diagnosis of DMD resulting from a mutation correctable by drisapersen treatment. Four dose cohorts were planned (3, 6, 9 and 12 mg/kg), but study objectives were met with the 9 mg/kg dose. Less than proportional increase in exposure was demonstrated over the 3–9 mg/kg dose range, though post hoc analysis showed dose proportionality was more feasible over the 3–6 mg/kg range. Single doses of drisapersen at 3 and 6 mg/kg did not result in significant safety or tolerability concerns; however, at the 9 mg/kg dose, pyrexia and transient elevations in inflammatory parameters were seen. The maximum tolerated dose of 6 mg/kg drisapersen was identified for further characterization in multiple dose studies in the non-ambulant DMD population. PMID:24321374

The effect of talocrural joint manipulation on range of motion at the ankle.

PubMed

Fryer, Gary A; Mudge, Jacob M; McLaughlin, Patrick A

2002-01-01

To determine whether a single high-velocity, low-amplitude thrust manipulation to the talocrural joint altered ankle range of motion. A randomized, controlled and blinded study. Asymptomatic male and female volunteers (N = 41). Subjects were randomly assigned into either an experimental group (n = 20) or a control group (n = 21). Both ankles of subjects in the experimental group were manipulated by using a single high-velocity, low-amplitude thrust to the talocrural joint. Pretest and posttest measurements of passive dorsiflexion range of motion were taken. No significant changes in dorsiflexion range of motion were detected between manipulated ankles and those of control subjects. A significantly greater pretest dorsiflexion range of motion existed in those ankles in which manipulation produced an audible cavitation. Manipulation of the ankle does not increase dorsiflexion range of motion in asymptomatic subjects. Ankles that displayed a greater pretest range of dorsiflexion were more likely to cavitate, raising the possibility that ligament laxity may be associated with the tendency for ankles to cavitate.

Combining features from ERP components in single-trial EEG for discriminating four-category visual objects.

PubMed

Wang, Changming; Xiong, Shi; Hu, Xiaoping; Yao, Li; Zhang, Jiacai

2012-10-01

Categorization of images containing visual objects can be successfully recognized using single-trial electroencephalograph (EEG) measured when subjects view images. Previous studies have shown that task-related information contained in event-related potential (ERP) components could discriminate two or three categories of object images. In this study, we investigated whether four categories of objects (human faces, buildings, cats and cars) could be mutually discriminated using single-trial EEG data. Here, the EEG waveforms acquired while subjects were viewing four categories of object images were segmented into several ERP components (P1, N1, P2a and P2b), and then Fisher linear discriminant analysis (Fisher-LDA) was used to classify EEG features extracted from ERP components. Firstly, we compared the classification results using features from single ERP components, and identified that the N1 component achieved the highest classification accuracies. Secondly, we discriminated four categories of objects using combining features from multiple ERP components, and showed that combination of ERP components improved four-category classification accuracies by utilizing the complementarity of discriminative information in ERP components. These findings confirmed that four categories of object images could be discriminated with single-trial EEG and could direct us to select effective EEG features for classifying visual objects.

A systematic review of training programs for parents of children with autism spectrum disorders: single subject contributions.

PubMed

Patterson, Stephanie Y; Smith, Veronica; Mirenda, Pat

2012-09-01

The purpose of this systematic review was to examine research utilizing single subject research designs (SSRD) to explore the effectiveness of interventions designed to increase parents' ability to support communication and social development in children with autism spectrum disorders (ASDs). Included studies were systematically assessed for methodological quality (Logan et al., 2008; Smith et al., 2007) and intervention effects. Data examining participant characteristics, study methodology, outcomes, and analysis were systematically extracted. Eleven SSRD parent-training intervention studies examining 44 participants with ASD were included. Overall, the studies were of moderate quality and reported increases in parent skills and child language and communication outcomes. The results supported by improvement rate difference (IRD) analysis indicated several interventions demonstrated positive effects for both parent and child outcomes. However, limited generalization and follow-up data suggested only one intervention demonstrated parents' accurate and ongoing intervention implementation beyond training.

Grey matter networks in people at increased familial risk for schizophrenia.

PubMed

Tijms, Betty M; Sprooten, Emma; Job, Dominic; Johnstone, Eve C; Owens, David G C; Willshaw, David; Seriès, Peggy; Lawrie, Stephen M

2015-10-01

Grey matter brain networks are disrupted in schizophrenia, but it is still unclear at which point during the development of the illness these disruptions arise and whether these can be associated with behavioural predictors of schizophrenia. We investigated if single-subject grey matter networks were disrupted in a sample of people at familial risk of schizophrenia. Single-subject grey matter networks were extracted from structural MRI scans of 144 high risk subjects, 32 recent-onset patients and 36 healthy controls. The following network properties were calculated: size, connectivity density, degree, path length, clustering coefficient, betweenness centrality and small world properties. People at risk of schizophrenia showed decreased path length and clustering in mostly prefrontal and temporal areas. Within the high risk sample, the path length of the posterior cingulate cortex and the betweenness centrality of the left inferior frontal operculum explained 81% of the variance in schizotypal cognitions, which was previously shown to be the strongest behavioural predictor of schizophrenia in the study. In contrast, local grey matter volume measurements explained 48% of variance in schizotypy. The present results suggest that single-subject grey matter networks can quantify behaviourally relevant biological alterations in people at increased risk for schizophrenia before disease onset. Copyright © 2015 Elsevier B.V. All rights reserved.

Gender differences in human single neuron responses to male emotional faces.

PubMed

Newhoff, Morgan; Treiman, David M; Smith, Kris A; Steinmetz, Peter N

2015-01-01

Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus (n = 270), anterior cingulate cortex (n = 256), and ventromedial prefrontal cortex (n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% (n = 15∕66) of neurons in men were significantly affected by facial emotion, vs. 8% (n = 6∕76) of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two (p < 0.01). These results show specific differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala.

Variance in direct exposure measures of typing force and wrist kinematics across hours and days among office computer workers.

PubMed

Asundi, Krishna; Johnson, Peter W; Dennerlein, Jack T

2012-01-01

To determine the number of direct measurements needed to obtain a representative estimate of typing force and wrist kinematics, continuous measures of keyboard reaction force and wrist joint angle were collected at the workstation of 22 office workers while they completed their own work over three days, six hours per day. Typing force and wrist kinematics during keyboard, mouse and idle activities were calculated for each hour of measurement along with variance in measurements between subjects and between day and hour within subjects. Variance in measurements between subjects was significantly greater than variance in measurements between days and hours within subjects. Therefore, we concluded a single, one-hour period of continuous measures is sufficient to identify differences in typing force and wrist kinematics between subjects. Within subjects, day and hour of measurement had a significant effect on some measures and thus should be accounted for when comparing measures within a subject. The dose response relationship between exposure to computer related biomechanical risk factors and musculoskeletal disorders is poorly understood due to the difficulty and cost of direct measures. This study demonstrates a single hour of direct continuous measures is sufficient to identify differences in wrist kinematics and typing force between individuals.

Diversity of human small intestinal Streptococcus and Veillonella populations.

PubMed

van den Bogert, Bartholomeus; Erkus, Oylum; Boekhorst, Jos; de Goffau, Marcus; Smid, Eddy J; Zoetendal, Erwin G; Kleerebezem, Michiel

2013-08-01

Molecular and cultivation approaches were employed to study the phylogenetic richness and temporal dynamics of Streptococcus and Veillonella populations in the small intestine. Microbial profiling of human small intestinal samples collected from four ileostomy subjects at four time points displayed abundant populations of Streptococcus spp. most affiliated with S. salivarius, S. thermophilus, and S. parasanguinis, as well as Veillonella spp. affiliated with V. atypica, V. parvula, V. dispar, and V. rogosae. Relative abundances varied per subject and time of sampling. Streptococcus and Veillonella isolates were cultured using selective media from ileostoma effluent samples collected at two time points from a single subject. The richness of the Streptococcus and Veillonella isolates was assessed at species and strain level by 16S rRNA gene sequencing and genetic fingerprinting, respectively. A total of 160 Streptococcus and 37 Veillonella isolates were obtained. Genetic fingerprinting differentiated seven Streptococcus lineages from ileostoma effluent, illustrating the strain richness within this ecosystem. The Veillonella isolates were represented by a single phylotype. Our study demonstrated that the small intestinal Streptococcus populations displayed considerable changes over time at the genetic lineage level because only representative strains of a single Streptococcus lineage could be cultivated from ileostoma effluent at both time points. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Safety and immunogenicity of a single dose 23-valent pneumococcal polysaccharide vaccine in Russian subjects.

PubMed

Ciprero, Karen; Zykov, Kirill A; Briko, Nikolay I; Shekar, Tulin; Sterling, Tina M; Bitieva, Elizaveta; Stek, Jon E; Musey, Luwy

2016-08-02

Pneumococcal infection is a major cause of pneumonia, bacteremia, and meningitis. Incidence of pneumococcal disease (PD) varies worldwide. The 23-valent pneumococcal polysaccharide vaccine (PPV23) displays an acceptable safety profile and has been demonstrated cost-effective in reducing burden of PD. Approximately 100 subjects from the Russian Federation who were either 2 to 49 y of age with increased risk for PD or ≥50 years of age were enrolled into the study (NCT01734239) to receive a single dose of PPV23 administered intramuscularly. Each subject was followed for local and systemic adverse events (AEs) for 5 and 14 days, respectively. Serious AEs were collected for 28 d postvaccination. Blood samples were collected immediately prior to vaccination and 28 d postvaccination for the measurement of IgG to serotypes 1, 6B, 14, 19F, and 23F. High proportion of subjects had ≥2 -fold increase in IgG following receipt of PPV23. Rates were 92.0%, 83.0%, 89.0%, 81%, 84% for serotypes 1, 6B, 14, 19F, and 23F, respectively. Similar rates of responders and increases in the magnitude of immune responses were observed in both age groups (2-49, ≥50 ). PPV23 was generally safe and well tolerated. Injection site and systemic AEs were reported by 14.7% and 18.6% of study subjects, respectively. PPV23 is generally safe, well tolerated, and highly immunogenic when given as a single dose to Russian individuals 50 y of age and older, as well as Russian individuals 2 to 49 y of age who are at high risk for PD.

Safety and immunogenicity of meningococcal ACWY CRM197-conjugate vaccine in children, adolescents and adults in Russia.

PubMed

Ilyina, Natalia; Kharit, Susanna; Namazova-Baranova, Leila; Asatryan, Asmik; Benashvili, Mayya; Tkhostova, Elmira; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

2014-01-01

Neisseria meningitidis is the leading cause of bacterial invasive infections in people aged <15 years in the Russian Federation. The aim of this phase III, multicenter, open-label study was to assess the immunogenicity and safety of the quadrivalent meningococcal CRM197-conjugate vaccine MenACWY when administered to healthy Russian subjects aged 2 years and above. A total of 197 subjects were immunized with a single dose of the vaccine, and serogroup-specific serum bactericidal activity was measured pre and 1-month post-vaccination with human complement (hSBA) serum titers. Regardless of baseline serostatus, 1 month after a single dose of MenACWY-CRM197 85% (95%CI, 79-90%) of subjects showed serologic response against serogroup A, 74% (67-80%) against serogroup C, 60% (53-67%) against serogroup W, and 83% (77-88%) against serogroup Y. The percentage of subjects with hSBA titers ≥ 1:8 1 month after vaccination was 89% (83-93%) against serogroup A, 84% (78-89%) against serogroup C, 97% (93-99%) against serogroup W, and 88% (82-92%) against serogroup Y. Comparable results were obtained across all subjects: children (2 to 10 years), adolescents (11 to 17 years), and adults (≥18 years). The MenACWY-CRM197 vaccine showed an acceptable safety profile and was well tolerated across all age groups, with no serious adverse events or deaths reported during the study. In conclusion, a single dose of meningococcal MenACWY-CRM197 vaccine is immunogenic and has an acceptable safety profile, provides a broad protection against the most frequent epidemic serogroups, and is a suitable alternative to currently available unconjugated monovalent or bivalent polysaccharide vaccines in Russia.

Genetic Structures of Copy Number Variants Revealed by Genotyping Single Sperm

PubMed Central

Luo, Minjie; Cui, Xiangfeng; Fredman, David; Brookes, Anthony J.; Azaro, Marco A.; Greenawalt, Danielle M.; Hu, Guohong; Wang, Hui-Yun; Tereshchenko, Irina V.; Lin, Yong; Shentu, Yue; Gao, Richeng; Shen, Li; Li, Honghua

2009-01-01

Background Copy number variants (CNVs) occupy a significant portion of the human genome and may have important roles in meiotic recombination, human genome evolution and gene expression. Many genetic diseases may be underlain by CNVs. However, because of the presence of their multiple copies, variability in copy numbers and the diploidy of the human genome, detailed genetic structure of CNVs cannot be readily studied by available techniques. Methodology/Principal Findings Single sperm samples were used as the primary subjects for the study so that CNV haplotypes in the sperm donors could be studied individually. Forty-eight CNVs characterized in a previous study were analyzed using a microarray-based high-throughput genotyping method after multiplex amplification. Seventeen single nucleotide polymorphisms (SNPs) were also included as controls. Two single-base variants, either allelic or paralogous, could be discriminated for all markers. Microarray data were used to resolve SNP alleles and CNV haplotypes, to quantitatively assess the numbers and compositions of the paralogous segments in each CNV haplotype. Conclusions/Significance This is the first study of the genetic structure of CNVs on a large scale. Resulting information may help understand evolution of the human genome, gain insight into many genetic processes, and discriminate between CNVs and SNPs. The highly sensitive high-throughput experimental system with haploid sperm samples as subjects may be used to facilitate detailed large-scale CNV analysis. PMID:19384415

QT effect of semagacestat at therapeutic and supratherapeutic doses.

PubMed

Zhang, Wei; Ayan-Oshodi, Mosun; Willis, Brian A; Annes, William; Hall, Stephen D; Chiesa, Joseph; Seger, Mary

2012-04-01

This thorough QT/ QT interval corrected for heart rate (QTc) study was designed to assess the potential of semagacestat, a functional gamma-secretase inhibitor, to delay cardiac repolarization. In this Phase I, single-dose, randomized, 4-period crossover study, semagacestat was compared with placebo in 54 healthy male and female subjects between the ages of 19 and 63 years, inclusive. Each study period included single oral-dose administrations of semagacestat 140 mg, semagacestat 280 mg, moxifloxacin 400 mg, or placebo. Study subjects and the investigator were blinded to the identity of semagacestat and placebo; however, moxifloxacin was administered as open-label. Moxifloxacin was compared with placebo for assay sensitivity analysis. Pharmacokinetic parameters were also assessed. For each QTc, the upper bound of the 2-sided 90% confidence interval (CI) for the least squares mean difference between semagacestat (at both the 140- and 280-mg dose levels) and placebo was < 10 msec at all time points, and thus, within the limits set for clinical relevance in regulatory guidelines. The results of this study indicate that single doses of 140 and 280 mg semagacestat did not prolong QTc to a clinically significant degree.

A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response

PubMed Central

Adamson, Britt; Norman, Thomas M.; Jost, Marco; Cho, Min Y.; Nuñez, James K.; Chen, Yuwen; Villalta, Jacqueline E.; Gilbert, Luke A.; Horlbeck, Max A.; Hein, Marco Y.; Pak, Ryan A.; Gray, Andrew N.; Gross, Carol A.; Dixit, Atray; Parnas, Oren; Regev, Aviv; Weissman, Jonathan S.

2016-01-01

SUMMARY Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured. We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. Two genome-scale CRISPR interference (CRISPRi) screens identified genes whose repression perturbs ER homeostasis. Subjecting ~100 hits to Perturb-seq enabled high-precision functional clustering of genes. Single-cell analyses decoupled the three UPR branches, revealed bifurcated UPR branch activation among cells subject to the same perturbation, and uncovered differential activation of the branches across hits, including an isolated feedback loop between the translocon and IRE1α. These studies provide insight into how the three sensors of ER homeostasis monitor distinct types of stress and highlight the ability of Perturb-seq to dissect complex cellular responses. PMID:27984733

A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

PubMed

Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

2015-06-25

Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

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

Pharmacokinetics of Caffeine following a Single Administration of Coffee Enema versus Oral Coffee Consumption in Healthy Male Subjects

PubMed Central

Tosri, Nisanuch; Rojanasthien, Noppamas; Srichairatanakool, Somdet; Sangdee, Chaichan

2013-01-01

The objective of this study was to determine the pharmacokinetics of caffeine after single administration of a coffee enema versus coffee consumed orally in healthy male subjects. The study design was an open-label, randomized two-phase crossover study. Eleven healthy subjects were randomly assigned either to receive 500 mL of coffee enema for 10 minutes or to consume 180 mL of ready-to-drink coffee beverage. After a washout period of at least 10 days, all the subjects were switched to receive the alternate coffee procedure. Blood samples were collected immediately before and at specific time points until 12 hours after coffee administration in each phase. The mean caffeine content in both the coffee solution prepared for the coffee enema and the ready-to-drink coffee beverage was not statistically different. The C max and AUC of caffeine obtained from the coffee enema were about 3.5 times significantly less than those of the coffee consumed orally, despite having slightly but statistically faster T max. The t 1/2 of caffeine obtained following both coffee procedures did not statistically differ. In summary, the relative bioavailability of caffeine obtained from the coffee enema was about 3.5 times significantly less than those of the coffee consumed orally. PMID:23533801

Prevalence and predictors of stress disorders following two earthquakes.

PubMed

Yuan, Kang Chuan; Ruo Yao, Zhao; Zhen Yu, Shi; Xu Dong, Zhao; Jian Zhong, Yang; Edwards, Jason Glen; Edwards, Glen David

2013-09-01

Studies about stress disorders following a disaster have mainly been based on single-event trauma with little emphasis on multiple traumas. This study investigated the prevalence and predictors of stress disorders following two earthquakes in China. Subjects were randomly sampled from 11 villages in rural China. A total of 624 subjects were administered with the 12-item General Health Questionnaire (GHQ-12), Symptom Checklist -90-R (SCL-90-R), Coping Style Scale and Social Support Rating Scale. This was followed by a structural clinical interview using the Chinese translation of the Structured Clinical Interview for Diagnostic and Statistical Manual (DSM)-IV-TR axis 1 disorders (SCID-I-P) for acute stress disorder (ASD) and post-traumatic stress disorder (PTSD). The prevalence of ASD and PTSD was 15% and 29%, respectively. Regression analysis indicated that high intensity of trauma exposure, lower educational level, subjective feeling of economic status and psychological stress after the first earthquake significantly predicted the outcome of PTSD. The study suggested that the prevalence of stress disorders in two earthquakes were higher than that experienced in a single disaster. The intensity of trauma exposure, low educational level, bad subjective feeling of economic status, and psychological stress after the first earthquake could be used to identify survivors at risk of developing PTSD in two earthquakes.

Lower extremity neuromuscular compensations during instrumented single leg hop testing 2-10 years following ACL reconstruction.

PubMed

Nyland, John; Wera, Jeff; Klein, Scott; Caborn, David N M

2014-12-01

This study compared lower extremity EMG activation and sagittal plane kinematics of subjects at a minimum of 2 years post-successful ACL reconstruction and rehabilitation during instrumented single leg hop testing. Comparisons were made based on subject responses to the following question, "compared to prior to your knee injury how capable are you now in performing sports activities"? Group 1=very capable, Group 2=capable, and Group 3=not capable. In addition to EMG (1000 Hz) and kinematic (60 Hz) data, subjective knee function, internal health locus of control, sports activity characteristics (intensity, frequency) pre-knee injury, and at follow-up were also compared. Group 3 had lower perceived knee function, decreased perceived sports intensity, and more subjects with decreased sports activity intensity by two levels compared to pre-injury values. Perceived function scores, anterior laxity measurements and grades were similar between groups. During single leg hop propulsion and landing Group 1 (very capable) had greater involved lower extremity gluteus maximus and medial hamstring activation amplitudes than Group 3 (not capable). Perceived sports capability was related to better subjective knee function, and higher perceived sports activity intensity. Neuromuscular compensations suggesting a hip bias with increased gluteus maximus and medial hamstring activation were identified at the involved lower extremity among most subjects who perceived high perceived sports capability compared to pre-injury status. These compensations may be related to a permanent neurosensory deficit, and its influence on afferent pathway changes that influence CNS sensorimotor re-organization. Copyright © 2014 Elsevier B.V. All rights reserved.

FUNCTIONAL PERFORMANCE TESTING OF THE HIP IN ATHLETES: A SYSTEMATIC REVIEW FOR RELIABILITY AND VALIDITY

PubMed Central

Martin, RobRoy L.

2012-01-01

Purpose/Background: The purpose of this study was to systematically review the literature for functional performance tests with evidence of reliability and validity that could be used for a young, athletic population with hip dysfunction. Methods: A search of PubMed and SPORTDiscus databases were performed to identify movement, balance, hop/jump, or agility functional performance tests from the current peer-reviewed literature used to assess function of the hip in young, athletic subjects. Results: The single-leg stance, deep squat, single-leg squat, and star excursion balance tests (SEBT) demonstrated evidence of validity and normative data for score interpretation. The single-leg stance test and SEBT have evidence of validity with association to hip abductor function. The deep squat test demonstrated evidence as a functional performance test for evaluating femoroacetabular impingement. Hop/Jump tests and agility tests have no reported evidence of reliability or validity in a population of subjects with hip pathology. Conclusions: Use of functional performance tests in the assessment of hip dysfunction has not been well established in the current literature. Diminished squat depth and provocation of pain during the single-leg balance test have been associated with patients diagnosed with FAI and gluteal tendinopathy, respectively. The SEBT and single-leg squat tests provided evidence of convergent validity through an analysis of kinematics and muscle function in normal subjects. Reliability of functional performance tests have not been established on patients with hip dysfunction. Further study is needed to establish reliability and validity of functional performance tests that can be used in a young, athletic population with hip dysfunction. Level of Evidence: 2b (Systematic Review of Literature) PMID:22893860

Spatiotemporal analysis of single-trial EEG of emotional pictures based on independent component analysis and source location

NASA Astrophysics Data System (ADS)

Liu, Jiangang; Tian, Jie

2007-03-01

The present study combined the Independent Component Analysis (ICA) and low-resolution brain electromagnetic tomography (LORETA) algorithms to identify the spatial distribution and time course of single-trial EEG record differences between neural responses to emotional stimuli vs. the neutral. Single-trial multichannel (129-sensor) EEG records were collected from 21 healthy, right-handed subjects viewing the emotion emotional (pleasant/unpleasant) and neutral pictures selected from International Affective Picture System (IAPS). For each subject, the single-trial EEG records of each emotional pictures were concatenated with the neutral, and a three-step analysis was applied to each of them in the same way. First, the ICA was performed to decompose each concatenated single-trial EEG records into temporally independent and spatially fixed components, namely independent components (ICs). The IC associated with artifacts were isolated. Second, the clustering analysis classified, across subjects, the temporally and spatially similar ICs into the same clusters, in which nonparametric permutation test for Global Field Power (GFP) of IC projection scalp maps identified significantly different temporal segments of each emotional condition vs. neutral. Third, the brain regions accounted for those significant segments were localized spatially with LORETA analysis. In each cluster, a voxel-by-voxel randomization test identified significantly different brain regions between each emotional condition vs. the neutral. Compared to the neutral, both emotional pictures elicited activation in the visual, temporal, ventromedial and dorsomedial prefrontal cortex and anterior cingulated gyrus. In addition, the pleasant pictures activated the left middle prefrontal cortex and the posterior precuneus, while the unpleasant pictures activated the right orbitofrontal cortex, posterior cingulated gyrus and somatosensory region. Our results were well consistent with other functional imaging studies, while revealed temporal dynamics of emotional processing of specific brain structure with high temporal resolution.

Videotaped Self-Modeling as a Technique for Training Preschoolers with Autism in Social-Communicative Functioning.

ERIC Educational Resources Information Center

Neisworth, John T.; Wert, Barbara Yingling

This report discusses findings of a study that investigated the effectiveness of video self-modeling (VSM) for increasing request communication of children with autism. A single subject design using multiple baselines across subjects was used. Four participants (ages 4-6) with autism were taped in the home setting for the purpose of creating VSM…

Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Adv. Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With DLBCL

ClinicalTrials.gov

2018-05-31

B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

Faster Horses...An Analysis of Country-Western Music.

ERIC Educational Resources Information Center

Lippard, Paula

This paper reports on a study of the content of the lyrics of 100 country-western songs. It presents findings concerning the primary subject matter of the songs, female and male roles portrayed, and the value system implicit in the song lyrics. Among the findings were that the single most-valued subject in country-western music is romantic love;…

Life Satisfaction, Self-Esteem, and Subjective Age in Women across the Life Span

ERIC Educational Resources Information Center

Borzumato-Gainey, Christine; Kennedy, Alison; McCabe, Beth; Degges-White, Suzanne

2009-01-01

A study of 320 women, ages 21 to 69, explored the relations among relationship status, subjective age, self-esteem, and life satisfaction. Women in married or partnered relationships had higher levels of life satisfaction than did single women. Women in their 30s and 40s had significantly lower levels of life satisfaction than did other age…

Validation of Static and Dynamic Balance Assessment Using Microsoft Kinect for Young and Elderly Populations.

PubMed

Eltoukhy, Moataz A; Kuenze, Christopher; Oh, Jeonghoon; Signorile, Joseph F

2018-01-01

Reduction in balance is an indicator of fall risk, and therefore, an accurate and cost-effective balance assessment tool is essential for prescribing effective postural control strategies. This study established the validity of the Kinect v2 sensor in assessing center of mass (CoM) excursion and velocity during single-leg balance and voluntary ankle sway tasks among young and elderly subjects. We compared balance outcome measures (anteroposterior (AP) and mediolateral (ML) CoM excursion and velocity and average sway length) to a traditional three-dimensional motion analysis system. Twenty subjects (10 young: age = y, height cm, weight kg; 10 elderly: age y, height cm, weight kg), with no history of lower extremity injury, participated in this study. Subjects performed six randomized trials; four single-leg stand (SLS) and two ankle sway trials. SLS and voluntary ankle sway trials showed that consistency (ICC(2, k)) and agreement (ICC(3, k)) for all variables when all subjects were considered, as well as when the elderly and young groups were analyzed separately. Concordance between systems ranged from poor to nearly perfect depending on the group, task, and variable assessed.

Single Dose and Repeat Once-Daily Dose Safety, Tolerability and Pharmacokinetics of Valbenazine in Healthy Male Subjects.

PubMed

Luo, Rosa; Bozigian, Haig; Jimenez, Roland; Loewen, Gordon; O'Brien, Christopher F

2017-08-01

Valbenazine (VBZ) is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia. The safety, tolerability and pharmacokinetics of VBZ following single and repeat once-daily (QD) dosing were evaluated in 2 randomized, single-center, double-blind studies in healthy male subjects. In the first study, 2 cohorts of 8 subjects were administered single doses (SD) of placebo (PBO; N = 2/period) or VBZ (N = 6/period; 1, 2, 5, or 12.5 mg for Cohort 1 and 12.5, 25, 50, or 75 mg for Cohort 2) using a sequential escalation scheme. The second study consisted of 2 phases. In the initial phase, subjects were administered SD PBO (N = 2/period) or VBZ (N = 6/period; 75, 100, 125 or 150 mg) with sequential escalation. In the second phase, subjects received PBO, or 50 or 100 mg VBZ (N = 4:8:8) QD for 8 days (Cohort 1) or PBO or 50 mg VBZ (N = 6:6) QD for 8 days (Cohort 2). For both studies, plasma concentrations of VBZ and its active metabolite, NBI-98782, were determined. Safety was assessed throughout the studies. PK parameters were determined using noncompartmental methods. In both studies, VBZ was rapidly absorbed with peak concentrations typically observed within 1.5 hours. Peak NBI-98782 concentrations were typically observed at 4.0 to 9.0 hours. Terminal elimination half-life for both VBZ and NBI-98782 was ~20 hours. Across the 1 to 150 mg SD range evaluated across the studies, VBZ and NBI-98782 C max and AUC increased dose-proportionally from 50 to 150 mg and more than dose-proportionally from 1 to 50 mg. QD VBZ and NBI-98782 C max and AUC parameters were also dose-proportional between the 50 and 100 mg doses. Steady-state for both analytes appeared to be achieved by Day 8. The accumulation index was ~1.5 for VBZ and ~2.5 for NBI-98782. Peak to trough fluctuation was approximately 250% for VBZ and 70% for NBI-98782. Across both studies, NBI-98782 exposure was approximately 20%-30% that of VBZ based on molar ratios. In the first study, the maximum-tolerated dose was not achieved; headache (2 events) was the only treatment-emergent adverse event (TEAE) reported by more than one subject. In the second study, fatigue (4 events) was the only TEAE reported by more than one subject following SD VBZ. Following QD VBZ, the TEAEs of fatigue, insomnia, disturbance in attention, and nervousness were dose-dependent; the latter three TEAEs were considered dose-limiting. Subject withdrawals due to TEAEs were 1 each for PBO and 50 mg VBZ QD, and 3 for 100 mg VBZ QD. Clinically relevant effects on laboratory parameters, vital signs or ECGs were limited to increased CPK (SD: 1 each for 5 mg VBZ and PBO), ALT (QD: 1 each for 50 and 100 mg VBZ and PBO), and triglycerides (QD: 1 each for 50 mg VBZ and PBO). VBZ has an acceptable safety profile and predictable pharmacokinetics that result in stable concentrations of active compounds with low peak-to-trough fluctuation following once-daily dosing.

Single Dose and Repeat Once-Daily Dose Safety, Tolerability and Pharmacokinetics of Valbenazine in Healthy Male Subjects

PubMed Central

Luo, Rosa; Bozigian, Haig; Jimenez, Roland; Loewen, Gordon; O’Brien, Christopher F.

2017-01-01

Valbenazine (VBZ) is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia. The safety, tolerability and pharmacokinetics of VBZ following single and repeat once-daily (QD) dosing were evaluated in 2 randomized, single-center, double-blind studies in healthy male subjects. In the first study, 2 cohorts of 8 subjects were administered single doses (SD) of placebo (PBO; N = 2/period) or VBZ (N = 6/period; 1, 2, 5, or 12.5 mg for Cohort 1 and 12.5, 25, 50, or 75 mg for Cohort 2) using a sequential escalation scheme. The second study consisted of 2 phases. In the initial phase, subjects were administered SD PBO (N = 2/period) or VBZ (N = 6/period; 75, 100, 125 or 150 mg) with sequential escalation. In the second phase, subjects received PBO, or 50 or 100 mg VBZ (N = 4:8:8) QD for 8 days (Cohort 1) or PBO or 50 mg VBZ (N = 6:6) QD for 8 days (Cohort 2). For both studies, plasma concentrations of VBZ and its active metabolite, NBI-98782, were determined. Safety was assessed throughout the studies. PK parameters were determined using noncompartmental methods. In both studies, VBZ was rapidly absorbed with peak concentrations typically observed within 1.5 hours. Peak NBI-98782 concentrations were typically observed at 4.0 to 9.0 hours. Terminal elimination half-life for both VBZ and NBI-98782 was ~20 hours. Across the 1 to 150 mg SD range evaluated across the studies, VBZ and NBI-98782 Cmax and AUC increased dose-proportionally from 50 to 150 mg and more than dose-proportionally from 1 to 50 mg. QD VBZ and NBI-98782 Cmax and AUC parameters were also dose-proportional between the 50 and 100 mg doses. Steady-state for both analytes appeared to be achieved by Day 8. The accumulation index was ~1.5 for VBZ and ~2.5 for NBI-98782. Peak to trough fluctuation was approximately 250% for VBZ and 70% for NBI-98782. Across both studies, NBI-98782 exposure was approximately 20%–30% that of VBZ based on molar ratios. In the first study, the maximum-tolerated dose was not achieved; headache (2 events) was the only treatment-emergent adverse event (TEAE) reported by more than one subject. In the second study, fatigue (4 events) was the only TEAE reported by more than one subject following SD VBZ. Following QD VBZ, the TEAEs of fatigue, insomnia, disturbance in attention, and nervousness were dose-dependent; the latter three TEAEs were considered dose-limiting. Subject withdrawals due to TEAEs were 1 each for PBO and 50 mg VBZ QD, and 3 for 100 mg VBZ QD. Clinically relevant effects on laboratory parameters, vital signs or ECGs were limited to increased CPK (SD: 1 each for 5 mg VBZ and PBO), ALT (QD: 1 each for 50 and 100 mg VBZ and PBO), and triglycerides (QD: 1 each for 50 mg VBZ and PBO). VBZ has an acceptable safety profile and predictable pharmacokinetics that result in stable concentrations of active compounds with low peak-to-trough fluctuation following once-daily dosing. PMID:28839339

Persistency and flexibility of complex brain networks underlie dual-task interference.

PubMed

Alavash, Mohsen; Hilgetag, Claus C; Thiel, Christiane M; Gießing, Carsten

2015-09-01

Previous studies on multitasking suggest that performance decline during concurrent task processing arises from interfering brain modules. Here, we used graph-theoretical network analysis to define functional brain modules and relate the modular organization of complex brain networks to behavioral dual-task costs. Based on resting-state and task fMRI we explored two organizational aspects potentially associated with behavioral interference when human subjects performed a visuospatial and speech task simultaneously: the topological overlap between persistent single-task modules, and the flexibility of single-task modules in adaptation to the dual-task condition. Participants showed a significant decline in visuospatial accuracy in the dual-task compared with single visuospatial task. Global analysis of topological similarity between modules revealed that the overlap between single-task modules significantly correlated with the decline in visuospatial accuracy. Subjects with larger overlap between single-task modules showed higher behavioral interference. Furthermore, lower flexible reconfiguration of single-task modules in adaptation to the dual-task condition significantly correlated with larger decline in visuospatial accuracy. Subjects with lower modular flexibility showed higher behavioral interference. At the regional level, higher overlap between single-task modules and less modular flexibility in the somatomotor cortex positively correlated with the decline in visuospatial accuracy. Additionally, higher modular flexibility in cingulate and frontal control areas and lower flexibility in right-lateralized nodes comprising the middle occipital and superior temporal gyri supported dual-tasking. Our results suggest that persistency and flexibility of brain modules are important determinants of dual-task costs. We conclude that efficient dual-tasking benefits from a specific balance between flexibility and rigidity of functional brain modules. © 2015 Wiley Periodicals, Inc.

Pharmacokinetics of a New Orally Disintegrating Tablet Formulation of Aripiprazole 15 mg Administered Without Water in Healthy Middle-aged Korean Subjects.

PubMed

Kim, Yunjeong; Jeon, Ji-Young; Chung, Young-Chul; Kim, Min-Gul

2015-12-01

The main objective of this study was to compare the pharmacokinetic properties and relative bioavailability of two 15-mg aripiprazole formulations (an orally disintegrating tablet [ODT] as the test drug and a conventional tablet as the reference drug) in healthy middle-aged Korean subjects. This study was conducted in a population of healthy middle-aged Korean subjects as a randomized, open-label, single-dose, 2-sequence, 2-period crossover trial. After administration of a single dose of a 15-mg aripiprazole standard tablet with 240 mL water or an aripiprazole 15-mg ODT without water, blood samples were collected at specific time intervals from 0 to 240 hours. Concentrations of aripiprazole in plasma were analyzed by using a LC-MS/MS method of detection. Data on the pharmacokinetic parameters were recorded, and the 90% CIs of the ratios of the geometric means of the parameters were determined from the logarithmically transformed data by using an ANOVA model. Thirty-nine healthy middle-aged Korean subjects were enrolled (mean age, 52.7 years; mean height, 167 cm; mean weight, 67.6 kg); 33 participants completed the study (29 male subjects and 4 female subjects). The 90% CIs of the geometric means ratio (test drug/reference drug) of Cmax, AUC0-last, and AUC0-∞ values were 0.95 to 1.14, 0.98 to 1.09, and 0.97 to 1.08, respectively. All of the subjects who experienced adverse events recovered without sequelae, and no serious adverse events were observed. The aripiprazole pharmacokinetics was similar for the ODT and standard tablet of 15-mg aripiprazole in these healthy middle-aged Korean subjects. The aripiprazole ODT formulation is therefore expected to offer a convenient alternative for patients who have difficulty swallowing tablets without water. The study was registered at http://cris.nih.go.kr (registration number: KCT0001677). Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

The Impact of Single-Sex and Coeducational Schooling on Participation and Achievement in Science: A 10-Year Perspective.

ERIC Educational Resources Information Center

McEwen, Alex; Knipe, Damian; Gallagher, Tony

1997-01-01

Examines the impact of government science education policy through the uptake of science A level subjects and patterns of attainment among boys and girls. Whereas recent evidence from Britain has been popularly interpreted as showing the educational advantage of single-sex schooling, the evidence of this study suggests that pupils are more likely…

Effect of Training Japanese L1 Speakers in the Production of American English /r/ Using Spectrographic Visual Feedback

ERIC Educational Resources Information Center

Patten, Iomi; Edmonds, Lisa A.

2015-01-01

The present study examines the effects of training native Japanese speakers in the production of American /r/ using spectrographic visual feedback. Within a modified single-subject design, two native Japanese participants produced single words containing /r/ in a variety of positions while viewing live spectrographic feedback with the aim of…

Using Extensible Markup Language (XML) for the Single Source Delivery of Educational Resources by Print and Online: A Case Study

ERIC Educational Resources Information Center

Walsh, Lucas

2007-01-01

This article seeks to provide an introduction to Extensible Markup Language (XML) by looking at its use in a single source publishing approach to the provision of teaching resources in both hardcopy and online. Using the development of the International Baccalaureate Organisation's online Economics Subject Guide as a practical example, this…

Delafloxacin Pharmacokinetics in Subjects With Varying Degrees of Renal Function

PubMed Central

Hoover, Randall K.; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K.; Quintas, Megan

2017-01-01

Abstract Delafloxacin, a fluoroquinolone, has activity against gram‐positive organisms including methicillin‐resistant Staphylococcus aureus and fluoroquinolone‐susceptible and –resistant gram‐negative organisms. This study was conducted to determine delafloxacin pharmacokinetics after a single intravenous infusion or oral dose administration in subjects with varying degrees of renal function. The study was an open‐label, parallel‐group crossover study in subjects with normal renal function or with mild, moderate, or severe renal impairment. Subjects received 300 mg delafloxacin intravenously, placebo intravenously, and 400 mg delafloxacin orally in 3 periods separated by ≥14‐day washouts. Blood and urine pharmacokinetic parameters were calculated using noncompartmental methods. Delafloxacin total clearance decreased with decreasing renal function, with a corresponding increase in AUC0–∞. After intravenous administration, mean total clearance was 13.7 and 7.07 L/h, and mean AUC0–∞ was 22.6 and 45.0 μg·h/mL in normal and severe renal subjects, respectively. Mean renal clearance as determined by urinary excretion was 6.03 and 0.44 L/h in normal and severe renal impairment subjects, respectively. Total clearance exhibited linear relationships to eGFR and CLCR. Similar observations were found after oral administration of delafloxacin. Single doses of delafloxacin 300 mg intravenously and 400 mg orally were well tolerated in all groups. In conclusion, renal insufficiency has an effect on delafloxacin clearance; a dosing adjustment for intravenous dosing is warranted for patients with severe renal impairment (eGFR < 30 mL/min). PMID:29251785

Disrupted modular organization of resting-state cortical functional connectivity in U.S. military personnel following concussive ‘mild’ blast-related traumatic brain injury†

PubMed Central

Han, Kihwan; Mac Donald, Christine L.; Johnson, Ann M.; Barnes, Yolanda; Wierzechowski, Linda; Zonies, David; Oh, John; Flaherty, Stephen; Fang, Raymond; Raichle, Marcus E.; Brody, David L.

2013-01-01

Blast-related traumatic brain injury (TBI) has been one of the “signature injuries” of the wars in Iraq and Afghanistan. However, neuroimaging studies in concussive ‘mild’ blast-related TBI have been challenging due to the absence of abnormalities in computed tomography or conventional magnetic resonance imaging (MRI) and the heterogeneity of the blast-related injury mechanisms. The goal of this study was to address these challenges utilizing single-subject, module-based graph theoretic analysis of resting-state functional MRI (fMRI) data. We acquired 20 minutes of resting-state fMRI in 63 U.S. military personnel clinically diagnosed with concussive blast-related TBI and 21 U.S. military controls who had blast exposures but no diagnosis of TBI. All subjects underwent an initial scan within 90 days post-injury and 65 subjects underwent a follow-up scan 6 to 12 months later. A second independent cohort of 40 U.S. military personnel with concussive blast-related TBI patients served as a validation dataset. The second independent cohort underwent an initial scan within 30 days post-injury. 75% of scans were of good quality, with exclusions primarily due to excessive subject motion. Network analysis of the subset of these subjects in the first cohort with good quality scans revealed spatially localized reductions in participation coefficient, a measure of between-module connectivity, in the TBI patients relative to the controls at the time of the initial scan. These group differences were less prominent on the follow-up scans. The 15 brain areas with the most prominent reductions in participation coefficient were next used as regions of interest (ROIs) for single-subject analyses. In the first TBI cohort, more subjects than would be expected by chance (27/47 versus 2/47 expected, p < 0.0001) had 3 or more brain regions with abnormally low between-module connectivity relative to the controls on the initial scans. On the follow-up scans, more subjects than expected by chance (5/37, p = 0.044) but fewer subjects than on the initial scans had 3 or more brain regions with abnormally low between-module connectivity. Analysis of the second TBI cohort validation dataset with no free parameters provided a partial replication; again more subjects than expected by chance (8/31, p = 0.006) had 3 or more brain regions with abnormally low between-module connectivity on the initial scans, but the numbers were not significant (2/27, p = 0.276) on the follow-up scans. A single-subject, multivariate analysis by probabilistic principal component analysis of the between-module connectivity in the 15 identified ROIs, showed that 31/47 subjects in the first TBI cohort were found to be abnormal relative to the controls on the initial scans. In the second TBI cohort, 9/31 patients were found to be abnormal in identical multivariate analysis with no free parameters. Again, there were not substantial differences on the follow-up scans. Taken together, these results indicate that single-subject, module-based graph theoretic analysis of resting-state fMRI provides potentially useful information for concussive blast-related TBI if high quality scans can be obtained. The underlying biological mechanisms and consequences of disrupted between-module connectivity are unknown, thus further studies are required. PMID:23968735

Speech intelligibility and subjective benefit in single-sided deaf adults after cochlear implantation.

PubMed

Finke, Mareike; Strauß-Schier, Angelika; Kludt, Eugen; Büchner, Andreas; Illg, Angelika

2017-05-01

Treatment with cochlear implants (CIs) in single-sided deaf individuals started less than a decade ago. CIs can successfully reduce incapacitating tinnitus on the deaf ear and allow, so some extent, the restoration of binaural hearing. Until now, systematic evaluations of subjective CI benefit in post-lingually single-sided deaf individuals and analyses of speech intelligibility outcome for the CI in isolation have been lacking. For the prospective part of this study, the Bern Benefit in Single-Sided Deafness Questionnaire (BBSS) was administered to 48 single-sided deaf CI users to evaluate the subjectively perceived CI benefit across different listening situations. In the retrospective part, speech intelligibility outcome with the CI up to 12 month post-activation was compared between 100 single-sided deaf CI users and 125 bilaterally implanted CI users (2nd implant). The positive median ratings in the BBSS differed significantly from zero for all items suggesting that most individuals with single-sided deafness rate their CI as beneficial across listening situations. The speech perception scores in quiet and noise improved significantly over time in both groups of CI users. Speech intelligibility with the CI in isolation was significantly better in bilaterally implanted CI users (2nd implant) compared to the scores obtained from single-sided deaf CI users. Our results indicate that CI users with single-sided deafness can reach open set speech understanding with their CI in isolation, encouraging the extension of the CI indication to individuals with normal hearing on the contralateral ear. Compared to the performance reached with bilateral CI users' second implant, speech reception threshold are lower, indicating an aural preference and dominance of the normal hearing ear. The results from the BBSS propose good satisfaction with the CI across several listening situations. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacokinetic Profiles of Ticagrelor Orodispersible Tablets in Healthy Western and Japanese Subjects.

PubMed

Teng, Renli; Hammarberg, Maria; Carlson, Glenn F; Bokelund-Singh, Sara; Ruderfelt, Terese; Blychert, Eva

2017-11-01

Ticagrelor is an antiplatelet agent for patients with acute coronary syndrome or a history of myocardial infarction. Two studies compared pharmacokinetic profiles of orodispersible (OD) ticagrelor tablets versus immediate-release (IR) tablets in Western and Japanese subjects. Both studies were open-label, randomized, crossover, single-center trials. Thirty-six healthy subjects (94% white, 6% other race; Western study NCT02400333) and 42 Japanese healthy subjects (Japanese study NCT02436577) received a single 90-mg ticagrelor dose as an OD tablet [with/without water, and via a nasogastric tube (Western study only)], and an IR tablet; washout between treatments was ≥7 days. Assessments included ticagrelor and AR-C124910XX (active metabolite) plasma concentrations for pharmacokinetic analyses, and safety evaluations. In the Western study, the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for ticagrelor and AR-C124910XX maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) were within the acceptance interval (80%-125%) for OD tablets (with/without water, via a nasogastric tube) versus the IR tablet; except for an ~15% lowering of ticagrelor C max (90% CI: 76.77%-93.78%) for the OD tablet taken with water. In the Japanese study, 90% CIs of the GMRs for AUC and C max of both ticagrelor and AR-C124910XX were all within the acceptance intervals for the OD (with/without water) versus IR tablet. No new safety issues were identified. Ticagrelor administered as an OD tablet to Western (without water, and via a nasogastric tube) and Japanese (with/without water) subjects was bioequivalent to the IR tablet.

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.

Karyopathological traits of thyrocytes and exposure to radioiodines in Belarusian children and adolescents following the accident at the Chernobyl nuclear power plant.

PubMed

Nadyrov, Eldar; Rozhko, Alexander; Kravtsov, Viacheslav; Mabuchi, Kiyohiko; Hatch, Maureen; Nakamura, Nori; Nikonovich, Sergey; Aleksanin, Sergey

2012-05-01

The Belarus-American (BelAm) thyroid study cohort consists of persons who were 0-18 years of age at the time of exposure to radioactive iodine fallout from the 1986 Chernobyl nuclear power plant accident and who have undergone serial thyroid screenings with referral for fine-needle aspiration biopsy (FNAB) using standardized criteria. We investigated thyrocyte nuclear abnormalities in cytological samples from FNABs in 75 BelAm subjects with single and multiple thyroid nodules and 47 nodular goiter patients from Leningrad, Russia, unexposed to Chernobyl fallout. Nuclear abnormalities examined included internuclear chromosome bridges and derivative nuclei with broken bridges (i.e., "tailed" nuclei), which are formed from dicentric and ring chromosomes and thus may be cellular markers of radiation exposure. Among subjects with single-nodular goiter, thyrocytes with bridges were present in 86.8% of the exposed BelAm cohort compared with 27.0% of unexposed controls. The average frequency of thyrocytes with bridges and with tailed nuclei was also significantly higher in the BelAm subjects than in controls. Among subjects with multinodular goiters, thyrocytes with bridges were present in 75.7% of exposed BelAm patients compared with 16.7% of unexposed controls; thyrocytes with tailed nuclei were observed in all of the BelAm subjects but in only 40% of controls, and the mean frequencies of bridges and tailed nuclei were significantly higher in the exposed group. Unusually, long bridges were detected in 29% of BelAm patients with single-nodular goiters and 35% of those with multinodular goiters, while no such abnormalities were observed among patients from the Leningrad region. In the exposed subjects from BelAm, we also found positive correlations between their estimated dose of Iodine-131 from Chernobyl fallout and the frequency of tailed nuclei (p = 0.008) and bridges (p = 0.09). Further study is needed to confirm that these phenomena represent consequences of radiation exposure in the human organism.

Single low-dose rHuIL-12 safely triggers multilineage hematopoietic and immune-mediated effects

PubMed Central

2014-01-01

Background Recombinant human interleukin 12 (rHuIL-12) regulates hematopoiesis and cell-mediated immunity. Based on these hematopoietic and immunomodulatory activities, a recombinant human IL-12 (rHuIL-12) is now under development to address the unmet need for a medical countermeasure against the hematopoietic syndrome of the acute radiation syndrome (HSARS) that occurs in individuals exposed to lethal radiation, and also to serve as adjuvant therapy that could provide dual hematopoietic and immunotherapeutic benefits in patients with cancer receiving chemotherapy. We sought to demonstrate in healthy subjects the safety of rHuIL-12 at single, low doses that are appropriate for use as a medical countermeasure for humans exposed to lethal radiation and as an immunomodulatory anti-cancer agent. Methods Two placebo-controlled, double-blinded studies assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of rHuIL-12. The first-in-human (FIH) dose-escalation study randomized subjects to single subcutaneous injections of placebo or rHuIL-12 at 2, 5, 10, and 20 μg doses. Due to toxicity, dose was reduced to 15 μg and then to 12 μg. The phase 1b expansion study randomized subjects to the highest safe and well tolerated dose of 12 μg. Results Thirty-two subjects were enrolled in the FIH study: 4 active and 2 placebo at rHuIL-12 doses of 2, 5, 10, 12, and 15 μg; 1 active and 1 placebo at 20 μg. Sixty subjects were enrolled in the expansion study: 48 active and 12 placebo at 12 μg dose of rHuIL-12. In both studies, the most common adverse events (AEs) related to rHuIL-12 were headache, dizziness, and chills. No immunogenicity was observed. Elimination of rHuIL-12 was biphasic, suggesting significant distribution into extravascular spaces. rHuIL-12 triggered transient changes in neutrophils, platelets, reticulocytes, lymphocytes, natural killer cells, and CD34+ hematopoietic progenitor cells, and induced increases in interferon-γ and C-X-C motif chemokine 10. Conclusion A single low dose of rHuIl-12 administered subcutaneously can elicit hematological and immune-mediated effects without undue toxicity. The safety and the potent multilineage hematopoietic/immunologic effects triggered by low-dose rHuIL-12 support the development of rHuIL-12 both as a radiation medical countermeasure and as adjuvant immunotherapy for cancer. Trial registration ClinicalTrials.gov: NCT01742221 PMID:24725395

Role of Colgate Total toothpaste in helping control plaque and gingivitis.

PubMed

Rover, Jo-Ann; Leu-Wai-See, Petal

2014-06-01

To assess the anti-plaque and anti-gingivitis effects of a dentifrice containing 0.3% triclosan, 2% copolymer and 0.243% (1,100 ppm) sodium fluoride in subjects with moderate plaque-induced gingivitis. This was a single center, monadic study. Subjects had at least 20 teeth remaining in the functional dentition, excluding third molars. Following a baseline examination for plaque, gingival inflammation and bleeding, 75 qualified healthy adult males and females, ages 18-70 were selected to participate in the study. Dental prophylaxis was performed and subjects were provided with two tubes of toothpaste (Colgate Total) and a soft-bristle toothbrush (Colgate Wave Toothbrush). The subjects were instructed to brush twice daily using a modified Bass brushing technique. At the end of the 6- to 8-week period subjects returned for collection of clinical and subjective data. 75 subjects completed the study. Both clinical and subjective reductions were significant. The results showed statistically significant reductions in plaque index, gingival inflammation and bleeding on probing. The overall conclusion was that Colgate Total was a comprehensive dentifrice that produced a significant reduction in gingivitis, plaque, and bleeding.

Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers.

PubMed

Gelal, Ayse; Guven, Hulya; Balkan, Dilara; Artok, Levent; Benowitz, Neal L

2003-09-01

The present study was undertaken to determine whether a single oral dose of menthol affects the metabolism of caffeine, a cytochrome P(450) 1A2 (CYP1A2) substrate, and pharmacological responses to caffeine in people. Eleven healthy female subjects participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of caffeine (200 mg) in coffee taken together with a single oral dose of menthol (100 mg) or placebo capsules. Serum caffeine concentrations and cardiovascular and subjective parameters were measured throughout the study. Co-administration of menthol resulted in an increase of caffeine t(max) values from 43.6+/-20.6 min (mean+/-SD) to 76.4+/-28.0 min ( P<0.05). The C(max) values of caffeine were lower in the menthol phase than in the placebo phase, but this effect was not statistically significant ( P=0.06). (AUC)(0-24), (AUC)(0- infinity ), terminal half-life and oral clearance were not affected by menthol. Only nine subjects' cardiovascular data were included in the analysis because of technical problems during the measurements. After caffeine, heart rate decreased in both treatment phases. The maximum decrease in heart rate was less in the menthol phase (-8.9+/-3.9 beats/min) than in the placebo phase (-13.1+/-2.1 beats/min) ( P=0.024). There were no statistically significant differences in systolic and diastolic blood pressures between the two treatments. We conclude that a single oral dose of pure menthol (100 mg) delays caffeine absorption and blunts the heart-rate slowing effect of caffeine, but does not affect caffeine metabolism. The possibility that menthol slows the absorption of other drugs should be considered.

A Phase 1, Single-center, Double-blind, Placebo-controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Clinical Effects, and Pharmacokinetics-Pharmacodynamics of Intravenous Cyclopropyl-methoxycarbonylmetomidate (ABP-700) after a Single Ascending Bolus Dose.

PubMed

Struys, Michel M R F; Valk, Beatrijs I; Eleveld, Douglas J; Absalom, Anthony R; Meyer, Peter; Meier, Sascha; den Daas, Izaak; Chou, Thomas; van Amsterdam, Kai; Campagna, Jason A; Sweeney, Steven P

2017-07-01

Cyclopropyl-methoxycarbonylmetomidate (ABP-700) is a new "soft" etomidate analog. The primary objectives of this first-in-human study were to describe the safety and efficacy of ABP-700 and to determine its maximum tolerated dose. Secondary objectives were to characterize the pharmacokinetics of ABP-700 and its primary metabolite (cyclopropyl-methoxycarbonyl acid), to assess the clinical effects of ABP-700, and to investigate the dose-response and pharmacokinetic/pharmacodynamic relationships. Sixty subjects were divided into 10 cohorts and received an increasing, single bolus of either ABP-700 or placebo. Safety was assessed by clinical laboratory evaluations, infusion-site reactions, continuous monitoring of vital signs, physical examination, adverse event monitoring, and adrenocorticotropic hormone stimulation testing. Clinical effects were assessed with modified observer's assessment of alertness/sedation and Bispectral Index monitoring. Pharmacokinetic parameters were calculated. Stopping criteria were met at 1.00 mg/kg dose. No serious adverse events were reported. Adverse events were dose-dependent and comprised involuntary muscle movement, tachycardia, and ventilatory effects. Adrenocorticotropic hormone stimulation evoked a physiologic cortisol response in all subjects, no different from placebo. Pharmacokinetics were dose-proportional. A three-compartment pharmacokinetic model described the data well. A rapid onset of anesthesia/sedation after bolus administration and also a rapid recovery were observed. A quantitative concentration-effect relationship was described for the modified observer's assessment of alertness/sedation and Bispectral Index. This first-in-human study of ABP-700 shows that ABP-700 was safe and well tolerated after single-bolus injections up to 1.00 mg/kg. Bolus doses of 0.25 and 0.35 mg/kg were found to provide the most beneficial clinical effect versus side-effect profile.

Support and Development of Workflow Protocols for High Throughput Single-Lap-Joint Testing-Experimental

DTIC Science & Technology

2013-04-01

preparation, and presence of an overflow fillet for a high strength epoxy and ductile methacylate adhesive. A unique feature of this study was the...of expanding adhesive joint test configurations as part of the GEMS program. 15. SUBJECT TERMS single lap joint, adhesion, aluminum, epoxy ... epoxy and ductile methacylate adhesive. A unique feature of this study was the use of untrained GEMS (Gains in the Education of Mathematics and Sci

Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard gel: a new formulation for "dual protection" contraception.

PubMed

Sitruk-Ware, Regine; Brache, Vivian; Maguire, Robin; Croxatto, Horacio; Kumar, Narender; Kumar, Sushma; Montero, Juan Carlos; Salvatierra, Ana Maria; Phillips, David; Faundes, Anibal

2007-06-01

The study was conducted to assess levonorgestrel (LNG) serum levels achieved after a single administration of two different doses of Carraguard vaginal gel containing LNG (CARRA/LNG), designed for use as microbicide and contraceptive for potential dual protection. This was a randomized double-blind pharmacokinetic study conducted in 12 subjects enrolled at two centers. Each subject received a single vaginal administration of CARRA/LNG containing either 0.75 or 1.5 mg LNG per 4 mL of gel on Days 10-12 of the menstrual cycle. LNG serum levels were measured at 0, 1, 2, 4, 8 and 12 h after administration and for the following 7 days. LH and progesterone (for a preliminary evaluation of effect on the ovarian function) as well as SHBG were measured in the daily samples. Serum LNG maximum concentrations (Cmax) were 14.1+/-2.1 and 11.7+/-2.7 nmol/L and Tmax was 12.0 and 6.0 h for the low and high dose, respectively, with large intersubject variability within the first 48 h. Mean levels at 96 h were 10% of Cmax. Differences in AUC between both doses were not statistically significant. SHBG levels decreased approximately 25% by Day 4 after administration. Luteal activity was observed in 3/6 and 5/6 of the subjects in the low- and high-dose group, respectively. This study demonstrates that the CARRA/LNG gel can sustain elevated serum levels of the contraceptive steroid for up to 96 h after a single application. The serum levels attained with the 0.75-mg formulation are in the range expected to perturb the ovulatory process as observed in some subjects. The lack of correlation between the administered dose and serum concentrations of the steroid may be related to a rate-limiting absorption of LNG from the vaginal mucosa. The results reported here suggest that the CARRA/LNG formulation has good potential to become a dual-protection method, possibly preventing conception and sexually transmitted infections.

Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard® gel: a new formulation for “dual protection” contraception

PubMed Central

Sitruk-Ware, R; Brache, V; Maguire, R; Croxatto, H; Kumar, N; Kumar, S; Montero, JC; Salvatierra, AM; Phillips, D; Faundes, A

2007-01-01

Objective: The study was conducted to assess levonorgestrel (LNG) serum levels achieved after a single administration of two different doses of Carraguard vaginal gel containing LNG (CARRA/LNG), designed for use as microbicide and contraceptive for potential dual-protection. Materials and methods: This was a randomized double-blind pharmacokinetic study conducted in 12 subjects enrolled at two centers. Each subject received a single vaginal administration of CARRA/LNG containing either 0.75 or 1.5 mg LNG per 4 mL of gel on day 10-12 of the menstrual cycle. LNG serum levels were measured at 0, 1, 2, 4, 8 and 12 h after administration and for the following seven days. LH and progesterone (for a preliminary evaluation of effect on the ovarian function) as well as SHBG were measured in the daily samples. Results: Serum LNG maximum concentrations (Cmax) were 14.1 ± 5.1 and 11.7 ± 6.5 nmol/L and Tmax was 12.0 and 6.0 h for the low and high dose, respectively, with large intersubject variability within the first 48 h. Mean levels at 96 h were 10% of Cmax. Differences in AUC between both doses were not statistically significant. SHBG levels decreased approximately 25% by day 4 after administration. Luteal activity was observed in 3/6 and 5/6 of the subjects in the low and high dose group, respectively. Conclusion: This study demonstrates that the CARRA/LNG gel can sustain elevated serum levels of the contraceptive steroid for up to 96 h after a single application. The serum levels attained with the 0.75 mg formulation are in the range expected to perturb the ovulatory process as observed in some subjects. The lack of correlation between the administered dose and serum concentrations of the steroid may be related to a rate-limiting absorption of LNG from the vaginal mucosa. The results reported here suggest that the CARRA/LNG formulation has good potential to become a dual-protection method, possibly preventing conception and sexually transmitted infections. PMID:17519152

Binocular adaptive optics visual simulator.

PubMed

Fernández, Enrique J; Prieto, Pedro M; Artal, Pablo

2009-09-01

A binocular adaptive optics visual simulator is presented. The instrument allows for measuring and manipulating ocular aberrations of the two eyes simultaneously, while the subject performs visual testing under binocular vision. An important feature of the apparatus consists on the use of a single correcting device and wavefront sensor. Aberrations are controlled by means of a liquid-crystal-on-silicon spatial light modulator, where the two pupils of the subject are projected. Aberrations from the two eyes are measured with a single Hartmann-Shack sensor. As an example of the potential of the apparatus for the study of the impact of the eye's aberrations on binocular vision, results of contrast sensitivity after addition of spherical aberration are presented for one subject. Different binocular combinations of spherical aberration were explored. Results suggest complex binocular interactions in the presence of monochromatic aberrations. The technique and the instrument might contribute to the better understanding of binocular vision and to the search for optimized ophthalmic corrections.

Efficacy of Bone-Anchored Hearing Aids in Single-Sided Deafness: A Systematic Review.

PubMed

Kim, Gaeun; Ju, Hyun Mi; Lee, Sun Hee; Kim, Hee-Soon; Kwon, Jeong A; Seo, Young Joon

2017-04-01

Bone-anchored hearing aids (BAHAs) have been known to partially restore some of the functions lost in subjects with single-sided deafness (SSD). Our aims in this systemic review were to analyze the present capabilities of BAHAs in the context of SSD, and to evaluate the efficacy of BAHAs in improving speech recognition in noisy conditions, sound localization, and subjective outcomes. A systematic search was undertaken until August 2015 by two independent reviewers, with disagreements resolved by consensus. Among 286 references, we analyzed 14 studies that used both subjective and objective indicators to assess the capabilities of a total of 296 patients in the unaided and aided situations. Although there was "no benefit" of BAHA implantation for sound localization, BAHAs certainly improved subjects' speech discrimination in noisy circumstances. In the six studies that dealt with sound localization, no significant difference was found after the implantation. Twelve studies showed the benefits of BAHAs for speech discrimination in noise. Regarding subjective outcomes of using the prosthesis in patients with SSD (abbreviated profile of hearing aid benefit [APHAB] and the Glasgow hearing aid benefit profile [GHABP], etc.), we noticed an improvement in the quality of life. This systematic review has indicated that BAHAs may successfully rehabilitate patients with SSD by alleviating the hearing handicap to a certain degree, which could improve patients' quality of life. This report has presented additional evidence of effective auditory rehabilitation for SSD and will be helpful to clinicians counseling patients regarding treatment options for SSD.

[Effects of training on static and dynamic balance in elderly subjects who have had a fall or not].

PubMed

Toulotte, C; Thévenon, A; Fabre, C

2004-11-01

To evaluate the effects of a physical training program on static and dynamic balance during single and dual task conditions in elderly subjects who have had a fall or not. Two groups, comprising a total of 33 elderly subjects, were trained: 16 who had a fall were 69.2 +/- 5.0 years old and 17 who had not had a fall were 67.3 +/- 3.8 years. All subjects underwent an unipedal test with eyes open and eyes closed, followed by gait assessment during single and dual motor task conditions, before and after a physical training program. All subjects showed a significant decrease, by six times for subjects who had fallen and four times by those who had not, in the number of touch-downs in the unipedal test with eyes open (P < 0.05), and by 2.5 and 2 times, respectively, with eyes closed (P < 0.05) after the training program. All subjects showed a significant increase in speed (P < 0.05), cadence (P < 0.05) and stride length (P < 0.05) and a significant decrease in the single support time (P < 0.05) and stride time (P < 0.05) in gait assessment during single and dual task conditions after the training program. During the training program, no subjects fell. The physical training program improved static balance and quality of gait in elderly subjects who had had a fall and those who had not, which could contribute to minimizing and/or retarding the effects of aging and maintaining physical independence.

A randomized phase I study of methanesulfonyl fluoride, an irreversible cholinesterase inhibitor, for the treatment of Alzheimer's disease

PubMed Central

Moss, Donald E; Fariello, Ruggero G; Sahlmann, Jörg; Sumaya, Isabel; Pericle, Federica; Braglia, Enrico

2013-01-01

Aims To ascertain the tolerability profile of single and repeated oral doses of methanesulfonyl fluoride (MSF, SNX-001) in healthy aged subjects, and to determine the degree of erythrocyte acetylcholinesterase (AChE) inhibition induced by MSF after single and repeated oral doses. Methods To calculate properly the kinetics and the duration of AChE inhibition, the effects of MSF were also studied in rodents. These experiments suggested that MSF administered three times per week should provide safe and efficacious AChE inhibition. In a randomized placebo-controlled phase I study, 3.6 mg, 7.2 mg or 10.8 mg MSF were then orally administered to 27 consenting healthy volunteers (aged 50 to 72 years). After a single dose phase and a 1 week wash-out period, the subjects received the same doses three times per week for 2 weeks. Results Twenty-two out of the 27 subjects completed the study. Four patients withdrew due to adverse events (AEs) and one for non-compliance. Erythrocyte AChE was inhibited by a total of 33%, 46%, and 62% after 2 weeks of 3.6 mg, 7.2 mg and 10.8 mg MSF, respectively. No serious AEs occurred. The most frequent AEs were headache (27%), nausea (11%) and diarrhoea (8%). Conclusions MSF proved to be well tolerated even with repeated oral dosing. It is estimated that MSF provided a degree of AChE inhibition that should effectively enhance memory. This molecule deserves to be tested for efficacy in a pilot randomized controlled study in patients with Alzheimer's disease. PMID:23116458

A single session, group study of exposure and Eye Movement Desensitization and Reprocessing in treating Posttraumatic Stress Disorder among Vietnam War veterans: preliminary data.

PubMed

Rogers, S; Silver, S M; Goss, J; Obenchain, J; Willis, A; Whitney, R L

1999-01-01

This report summarizes data gathered thus far from an ongoing study. Two groups (total N = 12) of Vietnam War veterans diagnosed with Posttraumatic Stress Disorder (PTSD) received a single session of exposure or Eye Movement Desensitization and Reprocessing (EMDR) focusing on the veterans' most distressing war experience. Group assignment was random, treatment providers were blind to assessment data, and the pre- and posttreatment assessor was blind to treatment assignment. Both groups showed improvement on the Impact of Event Scale. EMDR treatment resulted in greater positive changes in within-session Subjective Units of Discomfort levels and on self-monitored severity of intrusive recollection. A trend toward decreased heart rate reactivity was observed in both groups. Results must be considered carefully due to the small number of subjects used in the study.

Histologic improvement in photodamage after 12 months of treatment with tretinoin emollient cream (0.02%).

PubMed

Kircik, Leon H

2012-09-01

Topical retinoids, such as tretinoin, have been established as the gold standard for the treatment of photodamaged skin. This was a single-center, open-label, single-group, observational histologic subanalysis of 3 of 19 patients participating in a study of the efficacy and safety of tretinoin emollient cream 0.02% for the treatment of moderate to severe facial photodamage. Subjects were female, 18 years of age or older, and instructed to apply tretinoin 0.02% to the treatment areas for 12 months. Histology was undertaken using facial photographs and 2-mm biopsies of the lateral canthus area that were obtained from 3 subjects at baseline and 12 months. Histopathologic analyses revealed evidence of extensive solar elastosis at baseline for 2 of the 3 subjects who were white, with moderate elastosis observed for the third subject who was African American. Histologic improvements in photodamage following 12 months of treatment with tretinoin 0.02% were observed for each subject. Improvements included smoothing of the epidermis, a slightly thinner keratin layer, and thin, comparatively straight elastic and collagen fibers in the mid- to deep-dermal layer. The histologic changes in all subjects could be attributed to a remodeling (elastin) or repair (collagen) process that affected the connective tissue fibers in all layers of the dermis. These results suggest that tretinoin 0.02% may be an effective treatment for photodamage, and additional evaluation is warranted in future studies.

Bioavailability of oral carisoprodol 250 and 350 mg and metabolism to meprobamate: A single-dose crossover study

PubMed Central

Simon, Steve; D’Andrea, Carrie; Wheeler, William J.; Sacks, Harry

2010-01-01

Background: Carisoprodol is a skeletal muscle relaxant indicated for use in the treatment of acute, painful musculoskeletal conditions. Two randomized, controlled clinical trials have reported that carisoprodol 250 mg QID was equally effective as and better tolerated than carisoprodol 350 mg QID. Objectives: The primary objective of the current study was to determine the relative bioavailability of carisoprodol and its metabolite, meprobamate, with singledose administration of 250- and 350-mg tablets. A secondary objective of the study was to determine whether lowering the carisoprodol dose would decrease plasma meprobamate concentrations. Methods: This single-dose, randomized, open-label, crossover study enrolled healthy volunteers. Each dose was administered with water in the morning; after a 7-day washout, subjects received the alternate dose. Blood samples were drawn at prespecified times over a 48-hour period. For tolerability assessment, subjects underwent a physical examination, including 12-lead ECG. Results: A total of 24 subjects were enrolled (12 men, 12 women; mean age, 22.8 years). The dose-adjusted AUC0−∞ values for carisoprodol were 5.29 μg/mL/h with the 250-mg tablet and 5.75 μg/mL/h with the 350-mg tablet (relative bioavailability, 92%). The mean (SD) Cmax values of carisoprodol and meprobamate after administration of the 250-mg carisoprodol tablet were 1.24 (0.49) and 1.84 (0.31) μg/mL, respectively, compared with 1.78 (0.97) and 2.46 (0.47) μg/mL with the 350-mg tablet. AUC0−∞ was dose proportional, and the apparent t1/2 values at the terminal phase were 1.74 hours with the 250-mg tablet and 1.96 hours with the 350-mg tablet. There were 3 mild adverse events considered possibly treatment related (weakness, dizziness, and drowsiness); these were reported in 2 subjects with 350-mg carisoprodol. Conclusions: In this small study in healthy fasting subjects, the exposure to carisoprodol and meprobamate was dose proportional between the single 250- and 350-mg doses. Both doses were generally well tolerated. PMID:24683250

Pharmacokinetics and Safety of Momelotinib in Subjects With Hepatic or Renal Impairment.

PubMed

Xin, Yan; Kawashima, Jun; Weng, Winnie; Kwan, Ellen; Tarnowski, Thomas; Silverman, Jeffrey A

2018-04-01

Momelotinib is a Janus kinase 1/2 inhibitor in clinical development for the treatment of myelofibrosis. Two phase 1 open-label, parallel-group, adaptive studies were conducted to evaluate the pharmacokinetics of a single 200-mg oral dose of momelotinib in subjects with hepatic or renal impairment compared with healthy matched control subjects with normal hepatic or renal function. Plasma pharmacokinetics of momelotinib and its major active metabolite, M21, were evaluated, and geometric least-squares mean ratios (GMRs) and associated 90% confidence intervals (CIs) for impaired versus each control group were calculated for plasma exposures (area under concentration-time curve from time 0 to ∞ [AUC ∞ ] and maximum concentration) of momelotinib and M21. There was no clinically significant difference in plasma exposures of momelotinib and M21 between subjects with moderate or severe renal impairment or moderate hepatic impairment and healthy control subjects. Compared with healthy control subjects, momelotinib AUC ∞ was increased (GMR, 197%; 90%CI, 129%-301%), and M21 AUC ∞ was decreased (GMR, 52%; 90%CI, 34%-79%) in subjects with severe hepatic impairment. The safety profile following a single dose of momelotinib was similar between subjects with hepatic or renal dysfunction and healthy control subjects. These pharmacokinetic and safety results indicate that dose adjustment is not necessary for momelotinib in patients with renal impairment or mild to moderate hepatic impairment. In patients with severe hepatic impairment, however, the dose of momelotinib should be reduced. © 2017, The American College of Clinical Pharmacology.

[Statistical analysis of body and lung mass of animals subjected to a single experimental insufflation of soil dust and electro-energetic ashes].

PubMed

Matysiak, W; Królikowska-Prasał, I; Staszyc, J; Kifer, E; Romanowska-Sarlej, J

1989-01-01

The studies were performed on 44 white female Wistar rats which were intratracheally administered the suspension of the soil dust and the electro-energetic ashes. The electro-energetic ashes were collected from 6 different local heat and power generating plants while the soil dust from several random places of our country. The statistical analysis of the body and the lung mass of the animals subjected to the single dust and ash insufflation was performed. The applied variants proved the statistically significant differences between the body and the lung mass. The observed differences are connected with the kinds of dust and ash used in the experiment.

Onset of action of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg in subjects aged 12 years with moderate to severe seasonal allergic rhinitis: a pooled analysis of two single-dose, randomized, double-blind, placebo-controlled allergen exposure unit studies.

PubMed

Berkowitz, Robert B; McCafferty, Frank; Lutz, Cheryl; Bazelmans, Donna; Godfrey, Penny; Meeves, Suzanne; Liao, Yuning; Georges, George

2006-10-01

The onset of action of antihistamine-decongestant combinations is an important factor in the treatment of subjects with seasonal allergic rhinitis (SAR). This was a pooled analysis of 2 published studies with identical designs investigating the onset of action of the combination of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg (FEX60/PSE120) in subjects with moderate to severe SAR. Subjects aged 12 years received single doses of FEX60/PSE120 or placebo in 2 randomized, double-blind, placebo-controlled, parallel-group, allergen exposure unit studies and recorded their SAR symptoms on diary cards before dosing, at 15-minute intervals for 2 hours after dosing, and at 30-minute intervals for the next 4 hours. The primary efficacy end point was onset of action, assessed in terms of absolute change in the major symptom complex (MSC) score, which was the sum of scores for the individual symptoms of stuffy nose, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, and sneezing. Secondary end points included the absolute and percent change in the total symptom complex (TSC) score (the sum of the MSC score plus the scores for nose blowing, sniffles, postnasal drip, and cough) and individual symptom scores. Treatment-emergent adverse events (TEAEs) were recorded. Analyses were performed on the modified intention-to-treat (mITT) population, which included all subjects who were randomized to treatment and took the single dose of study medication according to the protocol. A total of 1693 subjects were screened in the 2 studies, and 786 were randomized (298 in study 1, 488 in study 2). Two subjects withdrew from study 2; therefore, the mITT population consisted of 784 subjects. Subjects' mean age was 33.4 years, and 64.4% were female. The onset of action of FEX60/PSE120 was 45 minutes; the least squares mean (SD) treatment difference in the change from baseline in absolute MSC score was 0.8 (0.31) (95% CI, 0.2-1.4; P = 0.008). All subsequent changes from baseline in MSC scores were statistically significant for FEX60/PSE120 compared with placebo (P < 0.001). The absolute and percent change in TSC score and the percent change in MSC score were significantly decreased at all time points from 45 minutes after dosing for FEX60/PSE120 compared with placebo (all, P < 0.05). Individual symptoms (mean of hours 1 to 5) also were significantly improved with FEX60/PSE120 compared with placebo (all, P < 0.05). TEAEs were reported by 2.3% (9/391) and 4.3% (17/393) of subjects receiving FEX60/PSE120 and placebo, respectively. The most commonly occurring TEAS in the FEX60/PSE120 and placebo groups was somnolence (n = 4 and n = 6, respectively). In this pooled analysis of 2 allergen exposure unit studies, FEX60/PSE120 had an onset of action of 45 minutes and a sustained effect throughout the 6-hour study period in subjects with moderate to severe SAR.

Alternating treatments design: one strategy for comparing the effects of two treatments in a single subject.

PubMed Central

Barlow, D H; Hayes, S C

1979-01-01

A little used and often confused design, capable of comparing two treatments within a single subject, has been termed, variously, a multielement baseline design, a multiple schedule design, and a randomization design. The background of these terms is reviewed, and a new, more descriptive term, Alternating Treatments Design, is proposed. Critical differences between this design and a Simultaneous Treatment Design are outlined, and experimental questions answerable by each design are noted. Potential problems with multiple treatment interference in this procedure are divided into sequential confounding, carryover effects, and alternation effects and the importance of these issues vis-a-vis other single-case experimental designs is considered. Methods of minimizing multiple treatment interference as well as methods of studying these effects are outlined. Finally, appropriate uses of Alternating Treatments Designs are described and discussed in the context of recent examples. PMID:489478

Sex and the (older) single girl: experiences of sex and dating in later life.

PubMed

Fileborn, Bianca; Thorpe, Rachel; Hawkes, Gail; Minichiello, Victor; Pitts, Marian

2015-04-01

This study explored the sexual subjectivities of older Australian women. In this article we present findings from 15 qualitative interviews with Australian women aged 55-81 who were single at the time of interview. The majority of these women were single following divorce or separation, with a smaller number of women who were widowed or never in a long-term relationship. We found that these women's sexual desire and sexual activity were fluid and diverse across their life course. Although some participants desired a romantic or sexual relationship, they were also protective of their independence and reluctant to re-enter into a relationship in later life. Our findings indicate that these women's sexual subjectivities were shaped by dominant norms of ageing, sex, and gender. At the same time, older women are challenging and resisting these norms, and beginning to renegotiate sexuality in later life. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship of extinction to perceptual thresholds for single stimuli.

PubMed

Meador, K J; Ray, P G; Day, L J; Loring, D W

2001-04-24

To demonstrate the effects of target stimulus intensity on extinction to double simultaneous stimuli. Attentional deficits contribute to extinction in patients with brain lesions, but extinction (i.e., masking) can also be produced in healthy subjects. The relationship of extinction to perceptual thresholds for single stimuli remains uncertain. Brief electrical pulses were applied simultaneously to the left and right index fingers of 16 healthy volunteers (8 young and 8 elderly adults) and 4 patients with right brain stroke (RBS). The stimulus to be perceived (i.e., target stimulus) was given at the lowest perceptual threshold to perceive any single stimulus (i.e., Minimal) and at the threshold to perceive 100% of single stimuli. The mask stimulus (i.e., stimulus given to block the target) was applied to the contralateral hand at intensities just below discomfort. Extinction was less for target stimuli at 100% than Minimal threshold for healthy subjects. Extinction of left targets was greater in patients with RBS than elderly control subjects. Left targets were extinguished less than right in healthy subjects. In contrast, the majority of left targets were extinguished in patients with RBS even when right mask intensity was reduced below right 100% threshold for single stimuli. RBS patients had less extinction for right targets despite having greater left mask - threshold difference than control subjects. In patients with RBS, right "targets" at 100% threshold extinguished left "masks" (20%) almost as frequently as left masks extinguished right targets (32%). Subtle changes in target intensity affect extinction in healthy adults. Asymmetries in mask and target intensities (relative to single-stimulus perceptual thresholds) affect extinction in RBS patients less for left targets but more for right targets as compared with control subjects.

Arterial blood pressure response to heavy resistance exercise.

PubMed

MacDougall, J D; Tuxen, D; Sale, D G; Moroz, J R; Sutton, J R

1985-03-01

The purpose of this study was to record the blood pressure response to heavy weight-lifting exercise in five experienced body builders. Blood pressure was directly recorded by means of a capacitance transducer connected to a catheter in the brachial artery. Intrathoracic pressure with the Valsalva maneuver was recorded as mouth pressure by having the subject maintain an open glottis while expiring against a column of Hg during the lifts. Exercises included single-arm curls, overhead presses, and both double- and single-leg presses performed to failure at 80, 90, 95, and 100% of maximum. Systolic and diastolic blood pressures rose rapidly to extremely high values during the concentric contraction phase for each lift and declined with the eccentric contraction. The greatest peak pressures occurred during the double-leg press where the mean value for the group was 320/250 mmHg, with pressures in one subject exceeding 480/350 mmHg. Peak pressures with the single-arm curl exercise reached a mean group value of 255/190 mmHg when repetitions were continued to failure. Mouth pressures of 30-50 Torr during a single maximum lift, or as subjects approached failure with a submaximal weight, indicate that a portion of the observed increase in blood pressure was caused by a Valsalva maneuver. It was concluded that when healthy young subjects perform weight-lifting exercises the mechanical compression of blood vessels combines with a potent pressor response and a Valsalva response to produce extreme elevations in blood pressure. Pressures are extreme even when exercise is performed with a relatively small muscle mass.

The Effects of Test Trial and Processing Level on Immediate and Delayed Retention

ERIC Educational Resources Information Center

Chang, Sau Hou

2017-01-01

The purpose of the present study was to investigate the effects of test trial and processing level on immediate and delayed retention. A 2 × 2 × 2 mixed ANOVAs was used with two between-subject factors of test trial (single test, repeated test) and processing level (shallow, deep), and one within-subject factor of final recall (immediate,…

Evidence-Based Practice for Nurses and Healthcare Professionals (Third edition) Barker Janet Linsley Paul Kane Ros Evidence-Based Practice for Nurses and Healthcare Professionals (Third edition) 240pp £22.99 Sage 9781473925038 1473925037 [Formula: see text].

PubMed

2016-11-16

This book provides a complete primer on the subject of evidence-based practice in health care. As an introductory single textbook, it is especially useful for nurses undertaking academic study, or who are new to the subject.

Safety and Immunogenicity of a rAd35-EnvA Prototype HIV-1 Vaccine in Combination with rAd5-EnvA in Healthy Adults (VRC 012).

PubMed

Crank, Michelle C; Wilson, Eleanor M P; Novik, Laura; Enama, Mary E; Hendel, Cynthia S; Gu, Wenjuan; Nason, Martha C; Bailer, Robert T; Nabel, Gary J; McDermott, Adrian B; Mascola, John R; Koup, Richard A; Ledgerwood, Julie E; Graham, Barney S

2016-01-01

VRC 012 was a Phase I study of a prototype recombinant adenoviral-vector serotype-35 (rAd35) HIV vaccine, the precursor to two recently published clinical trials, HVTN 077 and 083. On the basis of prior evaluation of multiclade rAd5 HIV vaccines, Envelope A (EnvA) was selected as the standard antigen for a series of prototype HIV vaccines to compare various vaccine platforms. In addition, prior studies of rAd5-vectored vaccines suggested pre-existing human immunity may be a confounding factor in vaccine efficacy. rAd35 is less seroprevalent across human populations and was chosen for testing alone and in combination with a rAd5-EnvA vaccine in the present two-part phase I study. First, five subjects each received a single injection of 109, 1010, or 1011 particle units (PU) of rAd35-EnvA in an open-label, dose-escalation study. Next, 20 Ad5/Ad35-seronegative subjects were randomized to blinded, heterologous prime-boost schedules combining rAd5-EnvA and rAd35-EnvA with a three month interval. rAd35-EnvA was given at 1010 or 1011 PU to ten subjects each; all rAd5-EnvA injections were 1010 PU. EnvA-specific immunogenicity was assessed four weeks post-injection. Solicited reactogenicity and clinical safety were followed after each injection. Vaccinations were well tolerated at all dosages. Antibody responses measured by ELISA were detected at 4 weeks in 30% and 50% of subjects after single doses of 1010 or 1011 PU rAd35, respectively, and in 89% after a single rAd5-EnvA 1010 PU injection. EnvA-specific IFN-γ ELISpot responses were detected at four weeks in 0%, 70%, and 50% of subjects after the respective rAd35-EnvA dosages compared to 89% of subjects after rAd5. T cell responses were higher after a single rAd5-EnvA 1010 PU injection than after a single rAd35-EnvA 1010 PU injection, and humoral responses were low after a single dose of either vector. Of those completing the vaccine schedule, 100% of rAd5-EnvA recipients and 90% of rAd35-EnvA recipients had both T cell and humoral responses after boosting with the heterologous vector. ELISpot response magnitude was similar in both regimens and comparable to a single dose of rAd5. A trend toward more robust CD8 T cell responses using rAd5-EnvA prime and rAd35-EnvA boost was observed. Humoral response magnitude was also similar after either heterologous regimen, but was several fold higher than after a single dose of rAd5. Adverse events (AEs) related to study vaccines were in general mild and limited to one episode of hematuria, Grade two. Activated partial thromboplastin time (aPTT) AEs were consistent with an in vitro effect on the laboratory assay for aPTT due to a transient induction of anti-phospholipid antibody, a phenomenon that has been reported in other adenoviral vector vaccine trials. Limitations of the rAd vaccine vectors, including the complex interactions among pre-existing adenoviral immunity and vaccine-induced immune responses, have prompted investigators to include less seroprevalent vectors such as rAd35-EnvA in prime-boost regimens. The rAd35-EnvA vaccine described here was well tolerated and immunogenic. While it effectively primed and boosted antibody responses when given in a reciprocal prime-boost regimen with rAd5-EnvA using a three-month interval, it did not significantly improve the frequency or magnitude of T cell responses above a single dose of rAd5. The humoral and cellular immunogenicity data reported here may inform future vaccine and study design. ClinicalTrials.gov NCT00479999.

Pharmacokinetic profile of dextromethorphan hydrobromide in a syrup formulation in children and adolescents.

PubMed

Guenin, Eric; Armogida, Marianna; Riff, Dennis

2014-09-01

Dextromethorphan hydrobromide (DM) is a widely used antitussive. This study determined, for the first time, the basic pharmacokinetic profile of DM and its active metabolite, dextrorphan (DP) in children and adolescents. Thirty-eight male and female subjects at risk for developing an upper respiratory tract infection (URTI), or symptomatic with cough due to URTI, were enrolled in this single-dose, open-label study: ages 2-5 years (Group A, n = 8), 6-11 years (Group B, n = 17), 12-17 years (Group C, n = 13). Subjects were genotyped for cytochrome P450 (CYP) 2D6 polymorphisms and characterized as poor (PM) or non-poor metabolizers (non-PM). Groups A and B were dosed using an age-weight dosing schedule (DM range 7.5-24.75 mg); a 30-mg dose was used for Group C. Average exposures to total DP increased as age group increased, and average exposure to DM was highest in the adolescent group. One subject in that group was a PM. The terminal half-life (t ½) values were longer in the adolescent group due in part to the single PM subject. No relationship between body weight and pharmacokinetic parameters was noted. This is the first evaluation of the pharmacokinetic characteristics of DM in children and adolescents. A single dose of DM in this population was safe, and well tolerated at all doses tested. The data are used to model and compare pediatric DM exposures with those of adults.

The effect of local cryotherapy on subjective and objective recovery characteristics following an exhaustive jump protocol

PubMed Central

Hohenauer, Erich; Clarys, Peter; Baeyens, Jean-Pierre; Clijsen, Ron

2016-01-01

The purpose of this controlled trial was to investigate the effects of a single local cryotherapy session on the recovery characteristics over a period of 72 hours. Twenty-two young and healthy female (n=17; mean age: 21.9±1.1 years) and male (n=5;mean age: 25.4±2.8 years) adults participated in this study. Following an exhaustive jump protocol (3×30 countermovement jumps), half of the participants received either a single local cryotherapy application (+8°C) or a single local thermoneutral application (+32°C) of 20-minute duration using two thigh cuffs. Subjective measures of recovery (delayed-onset muscle soreness and ratings of perceived exertion) and objective measures of recovery (vertical jump performance and peak power output) were assessed immediately following the postexercise applications (0 hours) and at 24 hours, 48 hours, and 72 hours after the jump protocol. Local cryotherapy failed to significantly affect any subjective recovery variable during the 72-hour recovery period (P>0.05). After 72 hours, the ratings of perceived exertion were significantly lower in the thermoneutral group compared to that in the cryotherapy group (P=0.002). No significant differences were observed between the cryotherapy and the thermoneutral groups with respect to any of the objective recovery variables. In this experimental study, a 20-minute cryotherapy cuff application failed to demonstrate a positive effect on any objective measures of recovery. The effects of local thermoneutral application on subjective recovery characteristics were superior when compared to the effects of local cryotherapy application at 72 hours postapplication. PMID:27579000

A randomized control hands-on defibrillation study-Barrier use evaluation.

PubMed

Wampler, David; Kharod, Chetan; Bolleter, Scotty; Burkett, Alison; Gabehart, Caitlin; Manifold, Craig

2016-06-01

Chest compressions and defibrillation are the only therapies proven to increase survival in cardiac arrest. Historically, rescuers must remove hands to shock, thereby interrupting chest compressions. This hands-off time results in a zero blood flow state. Pauses have been associated with poorer neurological recovery. This was a blinded randomized control cadaver study evaluating the detection of defibrillation during manual chest compressions. An active defibrillator was connected to the cadaver in the sternum-apex configuration. The sham defibrillator was not connected to the cadaver. Subjects performed chest compressions using 6 barrier types: barehand, single and double layer nitrile gloves, firefighter gloves, neoprene pad, and a manual chest compression/decompression device. Randomized defibrillations (10 per barrier type) were delivered at 30 joules (J) for bare hand and 360J for all other barriers. After each shock, the subject indicated degree of sensation on a VAS scale. Ten subjects participated. All subjects detected 30j shocks during barehand compressions, with only 1 undetected real shock. All barriers combined totaled 500 shocks delivered. Five (1%) active shocks were detected, 1(0.2%) single layer of Nitrile, 3(0.6%) with double layer nitrile, and 1(0.2%) with the neoprene barrier. One sham shock was reported with the single layer nitrile glove. No shocks were detected with fire gloves or compression decompression device. All shocks detected barely perceptible (0.25(±0.05)cm on 10cm VAS scale). Nitrile gloves and neoprene pad prevent (99%) responder's detection of defibrillation of a cadaver. Fire gloves and compression decompression device prevented detection. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effect of local cryotherapy on subjective and objective recovery characteristics following an exhaustive jump protocol.

PubMed

Hohenauer, Erich; Clarys, Peter; Baeyens, Jean-Pierre; Clijsen, Ron

2016-01-01

The purpose of this controlled trial was to investigate the effects of a single local cryotherapy session on the recovery characteristics over a period of 72 hours. Twenty-two young and healthy female (n=17; mean age: 21.9±1.1 years) and male (n=5;mean age: 25.4±2.8 years) adults participated in this study. Following an exhaustive jump protocol (3×30 countermovement jumps), half of the participants received either a single local cryotherapy application (+8°C) or a single local thermoneutral application (+32°C) of 20-minute duration using two thigh cuffs. Subjective measures of recovery (delayed-onset muscle soreness and ratings of perceived exertion) and objective measures of recovery (vertical jump performance and peak power output) were assessed immediately following the postexercise applications (0 hours) and at 24 hours, 48 hours, and 72 hours after the jump protocol. Local cryotherapy failed to significantly affect any subjective recovery variable during the 72-hour recovery period (P>0.05). After 72 hours, the ratings of perceived exertion were significantly lower in the thermoneutral group compared to that in the cryotherapy group (P=0.002). No significant differences were observed between the cryotherapy and the thermoneutral groups with respect to any of the objective recovery variables. In this experimental study, a 20-minute cryotherapy cuff application failed to demonstrate a positive effect on any objective measures of recovery. The effects of local thermoneutral application on subjective recovery characteristics were superior when compared to the effects of local cryotherapy application at 72 hours postapplication.

Creating single-subject design graphs in Microsoft Excel 2007.

PubMed

Dixon, Mark R; Jackson, James W; Small, Stacey L; Horner-King, Mollie J; Lik, Nicholas Mui Ker; Garcia, Yors; Rosales, Rocio

2009-01-01

Over 10 years have passed since the publication of Carr and Burkholder's (1998) technical article on how to construct single-subject graphs using Microsoft Excel. Over the course of the past decade, the Excel program has undergone a series of revisions that make the Carr and Burkholder paper somewhat difficult to follow with newer versions. The present article provides task analyses for constructing various types of commonly used single-subject design graphs in Microsoft Excel 2007. The task analyses were evaluated using a between-subjects design that compared the graphing skills of 22 behavior-analytic graduate students using Excel 2007 and either the Carr and Burkholder or newly developed task analyses. Results indicate that the new task analyses yielded more accurate and faster graph construction than the Carr and Burkholder instructions.

CREATING SINGLE-SUBJECT DESIGN GRAPHS IN MICROSOFT EXCELTM 2007

PubMed Central

Dixon, Mark R; Jackson, James W; Small, Stacey L; Horner-King, Mollie J; Lik, Nicholas Mui Ker; Garcia, Yors; Rosales, Rocio

2009-01-01

Over 10 years have passed since the publication of Carr and Burkholder's (1998) technical article on how to construct single-subject graphs using Microsoft Excel. Over the course of the past decade, the Excel program has undergone a series of revisions that make the Carr and Burkholder paper somewhat difficult to follow with newer versions. The present article provides task analyses for constructing various types of commonly used single-subject design graphs in Microsoft Excel 2007. The task analyses were evaluated using a between-subjects design that compared the graphing skills of 22 behavior-analytic graduate students using Excel 2007 and either the Carr and Burkholder or newly developed task analyses. Results indicate that the new task analyses yielded more accurate and faster graph construction than the Carr and Burkholder instructions. PMID:19949515

Effect of Low- and High-Fat Meals on the Pharmacokinetics of Venetoclax, a Selective First-in-Class BCL-2 Inhibitor.

PubMed

Salem, Ahmed Hamed; Agarwal, Suresh K; Dunbar, Martin; Nuthalapati, Silpa; Chien, David; Freise, Kevin J; Wong, Shekman L

2016-11-01

Venetoclax is a selective, first-in-class, B-cell lymphoma-2 inhibitor that has demonstrated clinical efficacy in several hematological malignancies. Two studies evaluated the relative bioavailability of venetoclax in healthy subjects: (1) a bioequivalence study to compare the bioavailability of the film-coated tablet with that of an earlier uncoated tablet and (2) a food effect study to evaluate the effect of food on venetoclax pharmacokinetics. Both studies were open-label, single-dose, crossover studies. In the bioequivalence study, 15 subjects received a single dose of venetoclax 50 mg under nonfasting conditions, in each of 2 periods; one period used the uncoated tablet, and the other used the film-coated tablet. In the food effect study, 24 subjects received a single dose of venetoclax film-coated 100-mg tablet under fasting conditions, after a low-fat breakfast or after a high-fat breakfast in different periods. The venetoclax film-coated tablet was bioequivalent to the uncoated tablet, which indicates that the film coating does not affect bioavailability. The median T max of venetoclax was delayed by about 2 hours when administered with food. Compared with fasting conditions, C max and AUC increased by approximately 3.4-fold following a low-fat breakfast. High-fat meals increased C max and AUC by approximately 50% relative to low-fat meals. The mean terminal half-life was comparable between the high-fat meal and fasting conditions (19.1 versus 16.1 hours). Based on these results and the venetoclax exposure-response profile, venetoclax should be administered with food and without specific recommendations for fat content to ensure adequate and consistent bioavailability. © 2016, The American College of Clinical Pharmacology.

Relative Incidence of Phlebitis Caused by Continuous Intravenous Infusion of Cephapirin and Cephalothin

PubMed Central

Lane, A. Z.; Taggart, J. G.; Iles, R. L.

1972-01-01

In a single-blinded study, two groups of 10 healthy subjects were given cephapirin or cephalothin by continuous intravenous infusion for 5 days, 0.5 g every 6 hr for the first day and then 1.0 g every 6 hr for 4 days. Eight of the cephalothin subjects and two of the cephapirin subjects developed phlebitis. Phlebitis was more severe in the cephalothin group and developed more rapidly, necessitating vein changes six times more often than in the cephapirin group. The less irritating properties of cephapirin demonstrated in this study indicate it may be the more useful cephalosporin analogue for intravenous therapy. PMID:4790563

Method for exploratory cluster analysis and visualisation of single-trial ERP ensembles.

PubMed

Williams, N J; Nasuto, S J; Saddy, J D

2015-07-30

The validity of ensemble averaging on event-related potential (ERP) data has been questioned, due to its assumption that the ERP is identical across trials. Thus, there is a need for preliminary testing for cluster structure in the data. We propose a complete pipeline for the cluster analysis of ERP data. To increase the signal-to-noise (SNR) ratio of the raw single-trials, we used a denoising method based on Empirical Mode Decomposition (EMD). Next, we used a bootstrap-based method to determine the number of clusters, through a measure called the Stability Index (SI). We then used a clustering algorithm based on a Genetic Algorithm (GA) to define initial cluster centroids for subsequent k-means clustering. Finally, we visualised the clustering results through a scheme based on Principal Component Analysis (PCA). After validating the pipeline on simulated data, we tested it on data from two experiments - a P300 speller paradigm on a single subject and a language processing study on 25 subjects. Results revealed evidence for the existence of 6 clusters in one experimental condition from the language processing study. Further, a two-way chi-square test revealed an influence of subject on cluster membership. Our analysis operates on denoised single-trials, the number of clusters are determined in a principled manner and the results are presented through an intuitive visualisation. Given the cluster structure in some experimental conditions, we suggest application of cluster analysis as a preliminary step before ensemble averaging. Copyright © 2015 Elsevier B.V. All rights reserved.

Abnormal behavior and associated risk factors in captive baboons (Papio hamadryas spp.).

PubMed

Lutz, Corrine K; Williams, Priscilla C; Sharp, R Mark

2014-04-01

Abnormal behavior, ranging from motor stereotypies to self-injurious behavior, has been documented in captive nonhuman primates, with risk factors including nursery rearing, single housing, and veterinary procedures. Much of this research has focused on macaque monkeys; less is known about the extent of and risk factors for abnormal behavior in baboons. Because abnormal behavior can be indicative of poor welfare, either past or present, the purpose of this study was to survey the presence of abnormal behavior in captive baboons and to identify potential risk factors for these behaviors with an aim of prevention. Subjects were 144 baboons (119 females, 25 males) aged 3-29 (median = 9.18) years temporarily singly housed for research or clinical reasons. A 15-min focal observation was conducted on each subject using the Noldus Observer® program. Abnormal behavior was observed in 26% of the subjects, with motor stereotypy (e.g., pace, rock, swing) being the most common. Motor stereotypy was negatively associated with age when first singly housed (P < 0.005) while self-directed behavior (e.g., hair pull, self-bite) was positively associated with the lifetime number of days singly housed (P < 0.05) and the average number of blood draws per year (P < 0.05). In addition, abnormal appetitive behavior was associated with being male (P < 0.05). Although the baboons in this study exhibited relatively low levels of abnormal behavior, the risk factors for these behaviors (e.g., social restriction, routine veterinary procedures, and sex) appear to remain consistent across primate species. © 2013 Wiley Periodicals, Inc.

Recruitment methods for intervention research in bereavement-related depression. Five years' experience.

PubMed

Schlernitzauer, M; Bierhals, A J; Geary, M D; Prigerson, H G; Stack, J A; Miller, M D; Pasternak, R E; Reynolds, C F

1998-01-01

The authors compared various strategies for recruiting elderly subjects with bereavement-related depression into a randomized clinical trial. Over 5 years, they empaneled 65 patients from a total of 441 subjects screened (14.7%). Response to media advertisements was the single most effective strategy (54% of subjects). Another effective, but labor-intensive, strategy was using letters to bereaved spouses found through newspaper obituaries (14%); another 14% were referred by friends who had seen study advertisements. Information letters to healthcare providers yielded no study participants. Pathways to study participation did not differ as a function of race or gender and did not influence study retention or remission rates. Our experience suggests that successful intake depends on a personal mode of recruitment.

Development of Advanced Technologies for Complete Genomic and Proteomic Characterization of Quantized Human Tumor Cells

DTIC Science & Technology

2015-09-01

glioblastoma . We have successfully established several patient-derived cell lines from glioblastoma tumors and further established a number of...and single-cell technologies. Although the focus of this research is glioblastoma , the proposed tools are generally applicable to all cancer-based...studies. 15. SUBJECT TERMS Human cohorts, Glioblastoma , Genomic, Proteomic, Single-cell technologies, Hypothesis-driven, integrative systems approach

The Effect of Child-Centered Play Therapy on the Externalizing Behaviors of Low Income Male Preschoolers during Group Instructional Time and Center Time: A Single-Case Design Study

ERIC Educational Resources Information Center

Phipps, Christa Brown

2017-01-01

Low income male preschoolers with externalizing behaviors have continued behavior issues throughout elementary school, middle school, high school, and into adulthood and create stress for their teachers. Because of this, it is important to detect externalizing behaviors early and implement an appropriate intervention. A single subject reversal…

Dynamic and functional balance tasks in subjects with persistent whiplash: a pilot trial.

PubMed

Stokell, Raina; Yu, Annie; Williams, Katrina; Treleaven, Julia

2011-08-01

Disturbances in static balance have been demonstrated in subjects with persistent whiplash. Some also report loss of balance and falls. These disturbances may contribute to difficulties in dynamic tasks. The aim of this study was to determine whether subjects with whiplash had deficits in dynamic and functional balance tasks when compared to a healthy control group. Twenty subjects with persistent pain following a whiplash injury and twenty healthy controls were assessed in single leg stance with eyes open and closed, the step test, Fukuda stepping test, tandem walk on a firm and soft surface, Singleton test with eyes open and closed, a stair walking test and the timed 10 m walk with and without head movement. Subjects with whiplash demonstrated significant deficits (p < 0.01) in single leg stance with eyes closed, the step test, tandem walk on a firm and soft surface, stair walking and the timed 10 m walk with and without head movement when compared to the control subjects. Specific assessment and rehabilitation directed towards improving these deficits may need to be considered in the management of patients with persistent whiplash if these results are confirmed in a larger cohort. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Radiofrequency Coblation Versus Intramural Bipolar Cautery for the Treatment of Inferior Turbinate Hypertrophy.

PubMed

Shah, Anil N; Brewster, Douglas; Mitzen, Kelly; Mullin, David

2015-09-01

Compare intramural bipolar electrocautery and radiofrequency coblation in the treatment of inferior turbinate hypertrophy with regards to objective and subjective improvement in nasal obstruction, rate and type of complications, experience during the procedure, and rate of recovery. Prospective, single-blinded study. Single tertiary medical center from 2008 to 2010. Forty-one adult patients with inferior turbinate hypertrophy refractory to medical management were treated with radiofrequency coblation in one nostril and intramural bipolar cautery in the other. Subjective and objective data, including use of a Visual Analog Scale (VAS) for subjective outcomes, acoustic rhinometry, and nasal endoscopy, were then obtained from each patient comparing the 2 techniques. Radiofrequency coblation was significantly less painful than intramural bipolar cautery during the procedure (P = .03) and during the early postoperative period (P < .02) and produced less crusting at 3 weeks (P = .009). Both interventions were similar in subjective and objective improvements in nasal obstruction as measured by acoustic rhinometry and subjective VAS outcomes. Radiofrequency coblation seems to offer an equivalent alternative to bipolar electrocautery for the treatment of inferior turbinate hypertrophy with less discomfort during the procedure and early post-operative period. © The Author(s) 2015.

Relative bioavailability of generic and branded 250-mg and 500-mg oral chlorphenesin carbamate tablets in healthy Korean volunteers: a single-dose, randomized-sequence, open-label, two-period crossover trial.

PubMed

Yu, Ji-young; Song, Hyun Ho; Kim, Bo Gyeom; Park, Hyeon Ju; Choi, Kwang Sik; Kwon, Young Ee

2009-11-01

Chlorphenesin carbamate is a skeletal muscle relaxant approved in Korea for use in the treatment of pain and discomfort related to skeletal muscle trauma and inflammation. The aim of this study was to assess the bioequivalence of a generic formulation of chlorphenesin carbamate at doses of 250 and 500 mg and 2 branded formulations of the same doses in healthy Korean adults. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Korean male and female volunteers. Subjects were assigned to receive, in a randomized sequence, a single dose of the generic (test) and branded (reference) formulations of chlorphenesin carbamate at a dose of 250 or 500 mg. Blood samples were drawn at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 9, 12, and 15 hours after administration. Pharmacokinetic properties (C(max), T(max), AUC(0-t) AUC(0-infinity), t(1/2), and ke) were determined using HPLC. The formulations were to be considered bioequivalent if the 90% CIs of the treatment ratios of the geometric means of C(max) and AUC(0-t) were within a predetermined range of log 0.80 to log 1.25 based on regulatory criteria. Tolerability was assessed by monitoring for adverse events (AEs) on physical examination and/or e-mail and personal interview at the beginning and end of each study period. Twenty-eight subjects (22 men, 6 women) received chlorphenesin carbamate at the 250-mg dose, and 24 male subjects received the 500-mg dose. The mean (SD) ages of the subjects were 24.0 (2.6) and 24.0 (1.9) years in the 250- and 500-mg groups, respectively. No significant differences were found between the test and reference formulations (90% CIs: C(max), 1.0048-1.1153 with the 250-mg dose and 0.9630-1.1189 with the 500-mg dose; AUC(0-t), 0.9882-1.0546 and 0.9842-1.0578, respectively). No clinically significant AEs (upper gastric pain, abdominal bloating, pyrexia, edema, nausea, heartburn, constipation, headache, dizziness, drowsiness, or fatigue) were reported throughout the study. In this single-dose study in these healthy Korean subjects, the generic and branded formulations of chlorphenesin carbamate 250 and 500 mg met the regulatory criteria for bioequivalence. All formulations were well tolerated. Copyright 2009 Excerpta Medica Inc. All rights reserved.

Gender differences in human single neuron responses to male emotional faces

PubMed Central

Newhoff, Morgan; Treiman, David M.; Smith, Kris A.; Steinmetz, Peter N.

2015-01-01

Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus (n = 270), anterior cingulate cortex (n = 256), and ventromedial prefrontal cortex (n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% (n = 15∕66) of neurons in men were significantly affected by facial emotion, vs. 8% (n = 6∕76) of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two (p < 0.01). These results show specific differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala. PMID:26441597

Methods of forming semiconductor devices and devices formed using such methods

DOEpatents

Fox, Robert V; Rodriguez, Rene G; Pak, Joshua

2013-05-21

Single source precursors are subjected to carbon dioxide to form particles of material. The carbon dioxide may be in a supercritical state. Single source precursors also may be subjected to supercritical fluids other than supercritical carbon dioxide to form particles of material. The methods may be used to form nanoparticles. In some embodiments, the methods are used to form chalcopyrite materials. Devices such as, for example, semiconductor devices may be fabricated that include such particles. Methods of forming semiconductor devices include subjecting single source precursors to carbon dioxide to form particles of semiconductor material, and establishing electrical contact between the particles and an electrode.

Randomized study on the effect of single-implant versus two-implant retained overdentures on implant loss and muscle activity: a 12-month follow-up report.

PubMed

Alqutaibi, A Y; Kaddah, A F; Farouk, M

2017-06-01

The objective was to evaluate and compare single- and two-implant retained overdentures for the rehabilitation of the edentulous mandible. Fifty-six edentulous subjects were eligible for inclusion. Using a random sampling system, a single implant or two implants were placed in the mandible. After 3 months, locator attachments were connected to the implants and the denture delivered with the retentive components incorporated in the denture base. Implant failure and muscle activity were evaluated at the 3-, 6-, and 12-month follow-up examinations. The study sample comprised 56 patients (32 male, 24 female), with a mean age of 58.2 years. A total of 84 implants were placed (28 in the single-implant group and 56 in the two-implant group). All patients completed the 12 months of follow-up. No significant differences were found between subjects in the two groups with respect to implant failure. With regard to improvements in muscle activity, the two-implant group showed statistically significant but perhaps not clinically important differences. Single-implant mandibular overdentures may be suggested as an alternative treatment modality for the rehabilitation of edentulous patients who cannot afford the cost of a two-implant overdenture. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Multibreath alveolar oxygen tension imaging.

PubMed

Clapp, Justin; Hamedani, Hooman; Kadlecek, Stephen; Xin, Yi; Shaghaghi, Hoora; Siddiqui, Sarmad; Rossman, Milton D; Rizi, Rahim R

2016-10-01

This study tested the ability of a multibreath hyperpolarized HP (3) He MRI protocol to increase the accuracy of regional alveolar oxygen tension (PA O2 ) measurements by lessening the influence of gas-flow artifacts. Conventional single-breath PA O2 measurement has been susceptible to error induced by intervoxel gas flow, particularly when used to study subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD). Both single-breath and multibreath PA O2 imaging schemes were implemented in seven human subjects (one healthy, three asymptomatic smokers, and three COPD). The number and location of voxels with nonphysiologic PA O2 values generated by intervoxel gas flow were compared between the two protocols. The multibreath scheme resulted in a significantly lower total percentage of nonphysiologic PA O2 values (6.0%) than the single-breath scheme (13.7%) (P = 0.006). PA O2 maps showed several patterns of gas-flow artifacts that were present in the single-breath protocol but mitigated by the multibreath approach. Multibreath imaging also allowed for the analysis of slow-filling areas that presented no signal after a single breath. A multibreath approach enhances the accuracy and completeness of noninvasive PA O2 measurement by significantly lessening the proportion of nonphysiologic values generated by intervoxel gas flow. Magn Reson Med 76:1092-1101, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

m-Trifluoromethyl-diphenyl Diselenide Regulates Prefrontal Cortical MOR and KOR Protein Levels and Abolishes the Phenotype Induced by Repeated Forced Swim Stress in Mice.

PubMed

Rosa, Suzan Gonçalves; Pesarico, Ana Paula; Martini, Franciele; Nogueira, Cristina Wayne

2018-04-05

The present study aimed to investigate the m-trifluoromethyl-diphenyl diselenide [(m-CF 3 -PhSe) 2 ] effects on prefrontal cortical MOR and KOR protein levels and phenotype induced by repeated forced swim stress (FSS) in mice. Adult Swiss mice were subjected to repeated FSS sessions, and after that, they performed the spontaneous locomotor/exploratory activity, tail suspension, and splash tests. (m-CF 3 -PhSe) 2 (0.1 to 5 mg/kg) was administered to mice 30 min before the first FSS session and 30 min before the subsequent repeated FSS. (m-CF 3 -PhSe) 2 abolished the phenotype induced by repeated FSS in mice. In addition, a single FSS session increased μ but reduced δ-opioid receptor contents, without changing the κ content. Mice subjected to repeated FSS had an increase in the μ content when compared to those of naïve group or subjected to single FSS. Repeated FSS induced an increase of δ-opioid receptor content compared to those mice subjected to single FSS. However, the δ-opioid receptor contents were lower than those found in the naïve group. The mice subjected to repeated FSS showed an increase in the κ-opioid receptor content when compared to that of the naïve mice. (m-CF 3 -PhSe) 2 regulated the protein contents of μ and κ receptors in mice subjected to repeated FSS. These findings demonstrate that (m-CF 3 -PhSe) 2 was effective to abolish the phenotype induced by FSS, which was accompanied by changes in the contents of cortical μ- and κ-opioid receptors.

Grand average ERP-image plotting and statistics: A method for comparing variability in event-related single-trial EEG activities across subjects and conditions

PubMed Central

Delorme, Arnaud; Miyakoshi, Makoto; Jung, Tzyy-Ping; Makeig, Scott

2014-01-01

With the advent of modern computing methods, modeling trial-to-trial variability in biophysical recordings including electroencephalography (EEG) has become of increasingly interest. Yet no widely used method exists for comparing variability in ordered collections of single-trial data epochs across conditions and subjects. We have developed a method based on an ERP-image visualization tool in which potential, spectral power, or some other measure at each time point in a set of event-related single-trial data epochs are represented as color coded horizontal lines that are then stacked to form a 2-D colored image. Moving-window smoothing across trial epochs can make otherwise hidden event-related features in the data more perceptible. Stacking trials in different orders, for example ordered by subject reaction time, by context-related information such as inter-stimulus interval, or some other characteristic of the data (e.g., latency-window mean power or phase of some EEG source) can reveal aspects of the multifold complexities of trial-to-trial EEG data variability. This study demonstrates new methods for computing and visualizing grand ERP-image plots across subjects and for performing robust statistical testing on the resulting images. These methods have been implemented and made freely available in the EEGLAB signal-processing environment that we maintain and distribute. PMID:25447029

The Effects of Test Trial and Processing Level on Immediate and Delayed Retention.

PubMed

Chang, Sau Hou

2017-03-01

The purpose of the present study was to investigate the effects of test trial and processing level on immediate and delayed retention. A 2 × 2 × 2 mixed ANOVAs was used with two between-subject factors of test trial (single test, repeated test) and processing level (shallow, deep), and one within-subject factor of final recall (immediate, delayed). Seventy-six college students were randomly assigned first to the single test (studied the stimulus words three times and took one free-recall test) and the repeated test trials (studied the stimulus words once and took three consecutive free-recall tests), and then to the shallow processing level (asked whether each stimulus word was presented in capital letter or in small letter) and the deep processing level (whether each stimulus word belonged to a particular category) to study forty stimulus words. The immediate test was administered five minutes after the trials, whereas the delayed test was administered one week later. Results showed that single test trial recalled more words than repeated test trial in immediate final free-recall test, participants in deep processing performed better than those in shallow processing in both immediate and delayed retention. However, the dominance of single test trial and deep processing did not happen in delayed retention. Additional study trials did not further enhance the delayed retention of words encoded in deep processing, but did enhance the delayed retention of words encoded in shallow processing.

The Effects of Test Trial and Processing Level on Immediate and Delayed Retention

PubMed Central

Chang, Sau Hou

2017-01-01

The purpose of the present study was to investigate the effects of test trial and processing level on immediate and delayed retention. A 2 × 2 × 2 mixed ANOVAs was used with two between-subject factors of test trial (single test, repeated test) and processing level (shallow, deep), and one within-subject factor of final recall (immediate, delayed). Seventy-six college students were randomly assigned first to the single test (studied the stimulus words three times and took one free-recall test) and the repeated test trials (studied the stimulus words once and took three consecutive free-recall tests), and then to the shallow processing level (asked whether each stimulus word was presented in capital letter or in small letter) and the deep processing level (whether each stimulus word belonged to a particular category) to study forty stimulus words. The immediate test was administered five minutes after the trials, whereas the delayed test was administered one week later. Results showed that single test trial recalled more words than repeated test trial in immediate final free-recall test, participants in deep processing performed better than those in shallow processing in both immediate and delayed retention. However, the dominance of single test trial and deep processing did not happen in delayed retention. Additional study trials did not further enhance the delayed retention of words encoded in deep processing, but did enhance the delayed retention of words encoded in shallow processing. PMID:28344679

Single wheel hub motor failures and their impact on vehicle and driver behaviour

NASA Astrophysics Data System (ADS)

Wanner, Daniel; Kreußlein, Maria; Augusto, Bruno; Drugge, Lars; Stensson Trigell, Annika

2016-10-01

This research work studies the impact of single wheel hub motor failures on the dynamic behaviour of electric vehicles and the corresponding driver reactions. An experimental study in a moving-base driving simulator is conducted to analyse the influence of single wheel hub motor failures for motorway speeds. Driver reaction times are derived from the measured data and discussed in their experimental context. The failure is rated objectively on the dynamic behaviour of the vehicle and compared to the subjective evaluation. Findings indicate that critical traffic situations impairing traffic safety can occur for motorway speeds. Clear counteractions by the drivers had to be taken.

A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles

PubMed Central

Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F.; Hamaoka, Takafumi

2015-01-01

Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously. PMID:26109079

Childhood trauma and adult prostitution behavior in a multiethnic heterosexual drug-using population.

PubMed

Medrano, Martha A; Hatch, John P; Zule, William A; Desmond, David P

2003-05-01

A cross-sectional study of the association between severity of childhood trauma and adult prostitution behaviors was conducted among 676 heterosexual drug addicts in San Antonio, Texas. Three hundred and fifty eight women and 338 men taking part in a national multisite program for AIDS prevention research completed the Childhood Trauma Questionnaire as part of a comprehensive risk behavior assessment. Women addicts in the sample were less educated, more likely to be in a common-law relationship, living with someone of the opposite sex or separated, and had lower incomes in comparison to men addicts. Among male subjects,higher educational levels and older age were positively associated with prostitution activities. Single female subjects were three times more likely to engage in selling sex than married subjects. Single women with higher incomes were more likely to be prostituting than single women with lower incomes. Black women reporting severe degrees of emotional abuse, emotional neglect, or physical neglect were more likely to engage in prostitution behavior than Hispanic or white women with similar levels of trauma. Black men with a history of childhood physical abuse were more likely to use prostitutes than Hispanic or white men.

Preparation and characterization of the magnetic superconductor EuSr2RuCu2O8-δ (RuEu-1212) by partial melting

NASA Astrophysics Data System (ADS)

Yamaki, K.; Kitagawa, N.; Funahashi, S.; Bamba, Y.; Irie, A.

2018-07-01

In this study, fine single crystals of the magnetic superconductor EuSr2RuCu2O8-δ (RuEu-1212) were successfully prepared using the partial melting technique. The obtained single crystals had a cubic shape, which coincides with the results of previous studies of RuGd-1212 single crystals. The single crystals had a typical length of 20-30 μm and the diffraction pattern observed from a sample prepared by partial melting was consistent with patterns of previously reported polycrystalline RuEu-1212 samples. A sample subjected to prolonged sintering, which consisted of a large number of combined micro single crystals prepared by partial melting, exhibited a superconducting transition with Tc-onset of 30.9 K and Tc-zero of 10.5 K.

Absorption, distribution, metabolism and excretion (ADME) of the ALK inhibitor alectinib: results from an absolute bioavailability and mass balance study in healthy subjects.

PubMed

Morcos, Peter N; Yu, Li; Bogman, Katrijn; Sato, Mika; Katsuki, Hisakazu; Kawashima, Kosuke; Moore, David J; Whayman, Matt; Nieforth, Keith; Heinig, Katja; Guerini, Elena; Muri, Dieter; Martin-Facklam, Meret; Phipps, Alex

2017-03-01

1. Alectinib is a highly selective, central nervous system-active small molecule anaplastic lymphoma kinase inhibitor. 2. The absolute bioavailability, metabolism, excretion and pharmacokinetics of alectinib were studied in a two-period single-sequence crossover study. A 50 μg radiolabelled intravenous microdose of alectinib was co-administered with a single 600 mg oral dose of alectinib in the first period, and a single 600 mg/67 μCi oral dose of radiolabelled alectinib was administered in the second period to six healthy male subjects. 3. The absolute bioavailability of alectinib was moderate at 36.9%. Geometric mean clearance was 34.5 L/h, volume of distribution was 475 L and the hepatic extraction ratio was low (0.14). 4. Near-complete recovery of administered radioactivity was achieved within 168 h post-dose (98.2%) with excretion predominantly in faeces (97.8%) and negligible excretion in urine (0.456%). Alectinib and its major active metabolite, M4, were the main components in plasma, accounting for 76% of total plasma radioactivity. In faeces, 84% of dose was excreted as unchanged alectinib with metabolites M4, M1a/b and M6 contributing to 5.8%, 7.2% and 0.2% of dose, respectively. 5. This novel study design characterised the full absorption, distribution, metabolism and excretion properties in each subject, providing insight into alectinib absorption and disposition in humans.

Comparison of the efficacy of tension-free vaginal tape obturator (TVT-O) and single-incision tension-free vaginal tape (Ajust™) in the treatment of female stress urinary incontinence: a 1-year follow-up randomized trial.

PubMed

Masata, Jaromir; Svabik, Kamil; Zvara, Karel; Hubka, Petr; Toman, Ales; Martan, Alois

2016-10-01

The aim of this study was to compare the efficacy of the tension-free vaginal tape obturator (TVT-O) and single-incision tension-free vaginal tape (Ajust™) in the treatment of stress urinary incontinence in a randomized two-arm study with a 1-year follow-up. This single-centre randomized trial compared the objective and subjective cure rates of TVT-O and Ajust using objective criteria (cough test) and subjective criteria (International Consultation on Incontinence Questionnaire short form, ICIQ-UI SF). The objective cure rate was defined as the number of patients with a negative cough stress test. Subjective cure was defined as no stress leakage of urine after surgery based on the ICIQ-UI SF. The primary outcome was to establish differences in objective and subjective cure rates between the TVT-O and Ajust groups. We also compared postoperative pain profiles using a visual analogue scale (VAS), improvement in quality of life using the ICIQ- UI SF and the Incontinence Quality of Life questionnaire, and overall satisfaction with the surgical procedure using a VAS and a five-item Likert scale. Inclusion criteria were age over 18 years, signed informed consent, and urodynamic stress urinary incontinence. Following a power calculation, 50 patients were enrolled into each group (Ajust and TVT-O). The mean follow-up after surgery was 445 days (SD 157.6 days) in the TVT-O group and 451.8 days (SD 127.6 days) in the Ajust group (p = 76.6 %). At 1 year, 47 patients were evaluated in the TVT-O group and 49 in the Ajust group. No differences in subjective cure rates or objective cure rates were observed. In the Ajust and TVT-O groups, the rates for no subjective stress leakage were 89.8 % and 91.5 %, respectively (p = 1.0, OR 1.22, 95 % CI 0.24 - 6.58), and the rates for a negative stress test were 89.8 % and 87.2 %, respectively (p = 0.76, OR 0.77, 95 % CI 0.17 - 3.32). In the Ajust group two patients reported de novo pain during sexual intercourse. After a 1-year-follow-up, no significant differences were found with regard to subjective and objective outcomes between the single-incision tape Ajust and TVT-O.

Comparative Efficacy of a Soft Toothbrush with Tapered-tip Bristles and an ADA Reference Toothbrush on Established Gingivitis and Supragingival Plaque over a 12-Week Period.

PubMed

Gallob, John; Petrone, Dolores M; Mateo, Luis R; Chaknis, Patricia; Morrison, Boyce M; Williams, Malcolm; Panagakos, Foti

2016-06-01

Evaluation of the efficacy of a soft toothbrush with tapered-tip bristles (Test Toothbrush) and an ADA reference soft toothbrush (ADA Toothbrush) on established gingivitis and supragingival plaque over a 12-week period. This randomized, single-center, examiner-blind, two-cell, parallel clinical research study assessed plaque removal by the comparison of pre- to- post-brushing after a single use, and again after six- and 12-weeks' use, using the Quigley-Hein Plaque Index, Turesky Modification. The study also assessed gingivitis after six weeks and 12 weeks using the Löe & Silness Gingival Index. Adult male and female subjects from the Central New Jersey, USA area refrained from all oral hygiene procedures for 24 hours. They reported to the study site after refraining from eating, drinking, and smoking for four hours. Subjects had the study procedure explained to them both orally and by written instructions. Subjects then gave written consent to participate before entry into the study. Following an examination for plaque (pre-brushing) and gingivitis (baseline), the subjects were randomized into two balanced groups, each group assigned to one of the two study toothbrushes. Subjects were instructed to brush their teeth for one minute under supervision with their assigned toothbrush and a commercially available fluoride toothpaste (Colgate© Cavity Protection Toothpaste), after which they were again evaluated for plaque (post-brushing). Subjects were dismissed from the study site with their assigned toothbrush and toothpaste, and instructed to brush twice daily at home for the next 12 weeks. The subjects were instructed to brush for one minute during each tooth brushing. The subjects reported to the study site after six weeks and 12 weeks of product use, at which time they were evaluated for plaque and gingivitis. Seventy-one (71) subjects complied with the protocol and completed the clinical study. Compared to the ADA Toothbrush, the Test Toothbrush provided statistically significantly (p < 0.05) greater reductions of 71.1% in whole mouth plaque index scores, 43.8% in plaque severity index scores, and 81.3% in interproximal sites plaque scores after a single tooth brushing. After six weeks' use, the Test Toothbrush provided statistically significantly (p < 0.05) greater reductions of 700% in whole mouth gingival index scores, 700% in gingivitis severity index scores, and 400% in interproximal sites gingival scores compared to the ADA Toothbrush. Also after six weeks' use, the Test Toothbrush provided statistically significantly (p < 0.05) greater reductions of 188.9% in whole mouth plaque index scores, 165% in plaque severity index scores, and 203% in interproximal sites plaque scores compared to the ADA Toothbrush. After 12 weeks' use, the Test Toothbrush provided statistically significantly (p < 0.05) greater reductions of 266.7% in whole mouth gingival index scores, 300% in gingivitis severity index scores, and 250% in interproximal sites gingival scores compared to the ADA Toothbrush. Also after 12 weeks' use, the Test Toothbrush provided statistically significantly (p < 0.05) greater reductions of 158.1% in whole mouth plaque index scores, 143.5% in plaque severity index scores, and 145.4% in interproximal sites plaque scores compared to the ADA Toothbrush. This study demonstrated that a soft toothbrush with tapered-tip bristles provided a significantly greater reduction in supragingival plaque after a single tooth brushing, as well as after six and 12 weeks of twice-daily use, compared to the ADA Toothbrush. After six and 12 weeks of twice-daily use, it also provided a significantly greater reduction in gingivitis as compared to the ADA Toothbrush.

Delafloxacin Pharmacokinetics in Subjects With Varying Degrees of Renal Function.

PubMed

Hoover, Randall K; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K; Quintas, Megan; Cammarata, Sue K

2018-04-01

Delafloxacin, a fluoroquinolone, has activity against gram-positive organisms including methicillin-resistant Staphylococcus aureus and fluoroquinolone-susceptible and -resistant gram-negative organisms. This study was conducted to determine delafloxacin pharmacokinetics after a single intravenous infusion or oral dose administration in subjects with varying degrees of renal function. The study was an open-label, parallel-group crossover study in subjects with normal renal function or with mild, moderate, or severe renal impairment. Subjects received 300 mg delafloxacin intravenously, placebo intravenously, and 400 mg delafloxacin orally in 3 periods separated by ≥14-day washouts. Blood and urine pharmacokinetic parameters were calculated using noncompartmental methods. Delafloxacin total clearance decreased with decreasing renal function, with a corresponding increase in AUC 0-∞ . After intravenous administration, mean total clearance was 13.7 and 7.07 L/h, and mean AUC 0-∞ was 22.6 and 45.0 μg·h/mL in normal and severe renal subjects, respectively. Mean renal clearance as determined by urinary excretion was 6.03 and 0.44 L/h in normal and severe renal impairment subjects, respectively. Total clearance exhibited linear relationships to eGFR and CL CR . Similar observations were found after oral administration of delafloxacin. Single doses of delafloxacin 300 mg intravenously and 400 mg orally were well tolerated in all groups. In conclusion, renal insufficiency has an effect on delafloxacin clearance; a dosing adjustment for intravenous dosing is warranted for patients with severe renal impairment (eGFR < 30 mL/min). © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Rilonacept in the treatment of subacromial bursitis: A randomized, non-inferiority, unblinded study versus triamcinolone acetonide.

PubMed

Carroll, Matthew B; Motley, Spencer A; Wohlford, Susanna; Ramsey, Bryan C

2015-12-01

Subacromial bursitis is caused by inflammation of the bursa that separates the superior surface of the supraspinatus tendon from the overlying coraco-acromial ligament and acromion. While multiple cytokines are implicated, interleukin-1 beta appears to play a prominent role. Rilonacept, an interleukin-1 trap, may be an alternative to corticosteroid injection for the management of this condition. This single center, randomized, non-inferiority, unblinded study recruited 33 subjects over 9 months. Twenty subjects received 160mg intrabursal injection of rilonacept and 13 received a 6mL mixture of lidocaine, bupivacaine, and 80mg triamcinolone acetonide. QuickDASH, subject reported pain, and adverse events were recorded at time of injection, 2 days later, 2 weeks later, and 4 weeks later. Primary outcome was improvement in QuickDASH 4 weeks post-injection. Secondary outcomes were improvement in subject reported pain and occurrence of adverse events at 4 weeks. Both study groups were equally matched for age, gender, ethnicity, and site of bursa injection. Both medications demonstrated a statistically significant improvement in QuickDASH 4 weeks post-injection, but triamcinolone acetonide injection offered greater improvement (P=0.004). Both medications demonstrated improvement in subject reported pain but between group comparison at 4 weeks showed that triamcinolone was superior (P=0.044). No statistically significant differences in adverse events were noted between groups, but subjects who received rilonacept experienced more episodes of diarrhea and headache. While improvement in QuickDASH and pain was noted with a single intrabursal injection of rilonacept at 4 weeks, injection with triamcinolone acetonide was more efficacious. This trial was registered with www.clinicaltrials.gov (NCT01830699). Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Split-face comparison between single-band and dual-band pulsed light technology for treatment of photodamage.

PubMed

Varughese, Neal; Keller, Lauren; Goldberg, David J

2016-08-01

Intense pulsed light (IPL) has a well-recognized role in the treatment of photodamaged skin. To assess the safety and efficacy of a novel single-band IPL handpiece versus dual-band IPL handpiece in the treatment of photodamage. This was a prospective, single-center split-face study with 20 enrolled participants. Three treatments, 21 days apart, were administered to the subjects and follow-up was performed for 20 weeks. The left side of the face was treated with the single-band handpiece. The right side of the face was treated with the dual-band handpiece. Blinded investigators assessed the subjects' skin texture, pigmented components of photodamage, and presence of telangiectasia both before and after treatment, utilizing a five-point scale. Pigmented components of photodamage, skin texture, and presence of telangiectasias on the left and right side of the face were improved at the end of treatment. At 20-week follow-up, the side treated with single-band handpiece showed improvement in telangiectasia and pigmentation that was statistically superior to the contralateral side treated with the dual-band handpiece. Both devices equally improved textural changes. No adverse effects were noted with either device. Both single-band and dual-band IPL technology are safe and effective in the treatment of photodamaged facial skin. IPL treatment with a single-band handpiece yielded results comparable or superior to dual-band technology.

Frequency, probability, and prediction: easy solutions to cognitive illusions?

PubMed

Griffin, D; Buehler, R

1999-02-01

Many errors in probabilistic judgment have been attributed to people's inability to think in statistical terms when faced with information about a single case. Prior theoretical analyses and empirical results imply that the errors associated with case-specific reasoning may be reduced when people make frequentistic predictions about a set of cases. In studies of three previously identified cognitive biases, we find that frequency-based predictions are different from-but no better than-case-specific judgments of probability. First, in studies of the "planning fallacy, " we compare the accuracy of aggregate frequency and case-specific probability judgments in predictions of students' real-life projects. When aggregate and single-case predictions are collected from different respondents, there is little difference between the two: Both are overly optimistic and show little predictive validity. However, in within-subject comparisons, the aggregate judgments are significantly more conservative than the single-case predictions, though still optimistically biased. Results from studies of overconfidence in general knowledge and base rate neglect in categorical prediction underline a general conclusion. Frequentistic predictions made for sets of events are no more statistically sophisticated, nor more accurate, than predictions made for individual events using subjective probability. Copyright 1999 Academic Press.

Single-trial EEG RSVP classification using convolutional neural networks

NASA Astrophysics Data System (ADS)

Shamwell, Jared; Lee, Hyungtae; Kwon, Heesung; Marathe, Amar R.; Lawhern, Vernon; Nothwang, William

2016-05-01

Traditionally, Brain-Computer Interfaces (BCI) have been explored as a means to return function to paralyzed or otherwise debilitated individuals. An emerging use for BCIs is in human-autonomy sensor fusion where physiological data from healthy subjects is combined with machine-generated information to enhance the capabilities of artificial systems. While human-autonomy fusion of physiological data and computer vision have been shown to improve classification during visual search tasks, to date these approaches have relied on separately trained classification models for each modality. We aim to improve human-autonomy classification performance by developing a single framework that builds codependent models of human electroencephalograph (EEG) and image data to generate fused target estimates. As a first step, we developed a novel convolutional neural network (CNN) architecture and applied it to EEG recordings of subjects classifying target and non-target image presentations during a rapid serial visual presentation (RSVP) image triage task. The low signal-to-noise ratio (SNR) of EEG inherently limits the accuracy of single-trial classification and when combined with the high dimensionality of EEG recordings, extremely large training sets are needed to prevent overfitting and achieve accurate classification from raw EEG data. This paper explores a new deep CNN architecture for generalized multi-class, single-trial EEG classification across subjects. We compare classification performance from the generalized CNN architecture trained across all subjects to the individualized XDAWN, HDCA, and CSP neural classifiers which are trained and tested on single subjects. Preliminary results show that our CNN meets and slightly exceeds the performance of the other classifiers despite being trained across subjects.

Identifying Evidence-Based Special Education Interventions from Single-Subject Research

ERIC Educational Resources Information Center

Freeman, Jennifer; Sugai, George

2013-01-01

Special educators are required to use evidence-based academic and behavioral interventions in their classrooms (U.S. Department of Education, 2010). No rigorous and comprehensive database currently exists to support educators. Within the field of special education, single-subject research is the primary research methodology (Horner, Carr, Halle,…

The Utility of Single Subject Design Research

ERIC Educational Resources Information Center

Bennett, Kyle D.

2016-01-01

Single subject design (SSD) research is a quantitative approach used to investigate basic and applied research questions. It has been used for decades to examine issues of social importance such as those related to general and special education strategies, therapeutic approaches in mental health, community health practices, safety, and business…

Single-Subject Research in Gifted Education

ERIC Educational Resources Information Center

Simonsen, Brandi; Little, Catherine A.

2011-01-01

Single-subject research (SSR) is an experimental research tradition that is well established in other fields (e.g., special education, behavior analysis) but has rarely been applied to topics in gifted education. In this Methodological Brief, Brandi Simonsen and Catherine A. Little from the University of Connecticut highlight the key features of…

Single-Subject Experimental Design for Evidence-Based Practice

ERIC Educational Resources Information Center

Byiers, Breanne J.; Reichle, Joe; Symons, Frank J.

2012-01-01

Purpose: Single-subject experimental designs (SSEDs) represent an important tool in the development and implementation of evidence-based practice in communication sciences and disorders. The purpose of this article is to review the strategies and tactics of SSEDs and their application in speech-language pathology research. Method: The authors…

Parallel Treatments Design: A Nested Single Subject Design for Comparing Instructional Procedures.

ERIC Educational Resources Information Center

Gast, David L.; Wolery, Mark

1988-01-01

This paper describes the parallel treatments design, a nested single subject experimental design that combines two concurrently implemented multiple probe designs, allows control for effects of extraneous variables through counterbalancing, and replicates its effects across behaviors. Procedural guidelines for the design's use and issues related…

Do Functional Behavioral Assessments Improve Intervention Effectiveness for Students with ADHD? A Single-Subject Meta-Analysis

ERIC Educational Resources Information Center

Miller, Faith G.

2011-01-01

The primary purpose of this quantitative synthesis of single-subject research was to investigate the relative effectiveness of function-based and non-function-based behavioral interventions for students diagnosed with attention-deficit/hyperactivity disorder. In addition, associations between various participant, assessment, and intervention…

Human joint motion estimation for electromyography (EMG)-based dynamic motion control.

PubMed

Zhang, Qin; Hosoda, Ryo; Venture, Gentiane

2013-01-01

This study aims to investigate a joint motion estimation method from Electromyography (EMG) signals during dynamic movement. In most EMG-based humanoid or prosthetics control systems, EMG features were directly or indirectly used to trigger intended motions. However, both physiological and nonphysiological factors can influence EMG characteristics during dynamic movements, resulting in subject-specific, non-stationary and crosstalk problems. Particularly, when motion velocity and/or joint torque are not constrained, joint motion estimation from EMG signals are more challenging. In this paper, we propose a joint motion estimation method based on muscle activation recorded from a pair of agonist and antagonist muscles of the joint. A linear state-space model with multi input single output is proposed to map the muscle activity to joint motion. An adaptive estimation method is proposed to train the model. The estimation performance is evaluated in performing a single elbow flexion-extension movement in two subjects. All the results in two subjects at two load levels indicate the feasibility and suitability of the proposed method in joint motion estimation. The estimation root-mean-square error is within 8.3% ∼ 10.6%, which is lower than that being reported in several previous studies. Moreover, this method is able to overcome subject-specific problem and compensate non-stationary EMG properties.

Unidirectional growth, rocking curve, linear and nonlinear optical properties of LPHCl single crystals

NASA Astrophysics Data System (ADS)

Kumar, P. Ramesh; Gunaseelan, R.; Raj, A. Antony; Selvakumar, S.; Sagayaraj, P.

2012-06-01

Nonlinear optical amino-acid single crystal of L-phenylalanine hydrochloride (LPHCl) was successfully grown by unidirectional Sankaranarayanan-Ramasamy (SR) method under ambient conditions for the first time. The grown single crystal was subjected to different characterization analyses in order to find out its suitability for device fabrication. The crystalline perfection was evaluated using high-resolution X-ray diffractometry. It is evident from the optical absorption study that crystal has excellent transmission in the entire visible region with its lower cut off wavelength around 290 nm.

Control of Echolalic Speech in Psychotic Children

ERIC Educational Resources Information Center

Carr, Edward G.; And Others

1975-01-01

Immediate echolalia (repeating what someone has just said) was studied in a series of replicated single-subject designs across six schizophrenic and five normal children (all ranging in age from 2 to 15 years). (Author/SBH)

The nutritional status and dietary adequacy of single homeless women and their children in shelters.

PubMed Central

Drake, M A

1992-01-01

Data were collected on the nutrient intake and nutritional status of 96 single mothers and their 192 dependent children who had been displaced from their homes. The objective of the study was to provide information on the dietary adequacy of a newly identified subgroup of homeless persons, single women and their dependent children. Once situated in temporary housing, those participating in the study indicated that they believed that they were receiving sufficient food. However, a nutrient analysis found that the study subjects in all age groups were consuming less than 50 percent of the 1989 Recommended Dietary Allowances (RDA) for iron, magnesium, zinc, and folic acid. Adults were consuming less than 50 percent of the RDA for calcium. The type and amounts of fats consumed were in higher than desirable quantities for a significant number of subjects of all ages. The health risk factors of iron deficiency anemia, obesity, and hypercholesterolemia were prevalent. The findings indicate a need to examine and remedy nutrient intake deficiencies among single women who are heads of household and their dependent children in temporary housing situations. Diet-related conditions found included low nutrient intakes that may affect child growth and development, risk factors associated with chronic disease, and lack of appropriate foods and knowledge of food preparation methods in shelter situations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1594741

"The Road Less Traveled": Combining Disability Studies and Quantitative Analysis with Medium and Large Data Sets

ERIC Educational Resources Information Center

Cosier, Meghan

2012-01-01

Historically, researchers focused on individuals with severe disabilities have utilized single-subject research methodologies to study the application of the behavioral theory to learning. In contrast, disability studies scholars have primarily used qualitative research methodologies to study quality of life or policy issues related to individuals…

Demonstration of Protein-Based Human Identification Using the Hair Shaft Proteome

PubMed Central

Leppert, Tami; Anex, Deon S.; Hilmer, Jonathan K.; Matsunami, Nori; Baird, Lisa; Stevens, Jeffery; Parsawar, Krishna; Durbin-Johnson, Blythe P.; Rocke, David M.; Nelson, Chad; Fairbanks, Daniel J.; Wilson, Andrew S.; Rice, Robert H.; Woodward, Scott R.; Bothner, Brian; Hart, Bradley R.; Leppert, Mark

2016-01-01

Human identification from biological material is largely dependent on the ability to characterize genetic polymorphisms in DNA. Unfortunately, DNA can degrade in the environment, sometimes below the level at which it can be amplified by PCR. Protein however is chemically more robust than DNA and can persist for longer periods. Protein also contains genetic variation in the form of single amino acid polymorphisms. These can be used to infer the status of non-synonymous single nucleotide polymorphism alleles. To demonstrate this, we used mass spectrometry-based shotgun proteomics to characterize hair shaft proteins in 66 European-American subjects. A total of 596 single nucleotide polymorphism alleles were correctly imputed in 32 loci from 22 genes of subjects’ DNA and directly validated using Sanger sequencing. Estimates of the probability of resulting individual non-synonymous single nucleotide polymorphism allelic profiles in the European population, using the product rule, resulted in a maximum power of discrimination of 1 in 12,500. Imputed non-synonymous single nucleotide polymorphism profiles from European–American subjects were considerably less frequent in the African population (maximum likelihood ratio = 11,000). The converse was true for hair shafts collected from an additional 10 subjects with African ancestry, where some profiles were more frequent in the African population. Genetically variant peptides were also identified in hair shaft datasets from six archaeological skeletal remains (up to 260 years old). This study demonstrates that quantifiable measures of identity discrimination and biogeographic background can be obtained from detecting genetically variant peptides in hair shaft protein, including hair from bioarchaeological contexts. PMID:27603779

Periapical healing outcome following single visit endodontic treatment in patients with type 2 diabetes mellitus

PubMed Central

Nayak, Moksha; Babshet, Medha

2016-01-01

Background The prevalence of apical periodontitis in diabetes mellitus patients is high. The altered immunity in diabetes affects the healing process of periapical tissue. Single visit endodontic treatment has shown to increase the periapical healing rate with better patient compliance. Hence the present study aims at evaluating the clinical and radiographic healing outcome of single visit endodontic treatment, in type 2 diabetes mellitus patients with periapical disease. Material and Methods Eighty patients with periapical disease were divided into 2 groups of 40 each: Group I, Control subjects and Group II, Type 2 diabetics. Glycosylated hemoglobin levels were assessed preoperatively and at follow up intervals in diabetics. Pre-operative assessment of periapical status was done using CPDR (Clinical periapical diagnosis of root), QLDR (Qualitative radiographic diagnosis of tooth) and QTDR (Quantitative radiographic diagnosis of tooth) criteria. Postoperative healing was evaluated following single-visit endodontic treatment by Strindberg criteria. Results Group 2 subjects had chronic and exacerbating lesions with significantly larger lesions (p=0.029). 100 % clinical healing outcome in diabetic group was seen in two months. Group 2 showed 85% success in one year on radiographic evaluation. Poor controlled diabetics showed failure compared to fair and good controlled. Conclusions Type 2 diabetics had chronic and larger sized lesions when compared to control subjects. The periapical lesions in patients with poor diabetic control showed failure. The clinical and radiographic healing outcome of single visit endodontic therapy was delayed in diabetic patients. Key words:Apical periodontitis, diabetes mellitus type 2, endodontics, periapical lesion, strindberg criteria. PMID:27957260

Topical nasal decongestant oxymetazoline (0.05%) provides relief of nasal symptoms for 12 hours.

PubMed

Druce, H M; Ramsey, D L; Karnati, S; Carr, A N

2018-05-22

Nasal congestion, often referred to as stuffy nose or blocked nose is one of the most prevalent and bothersome symptoms of an upper respiratory tract infection. Oxymetazoline, a widely used intranasal decongestant, offers fast symptom relief, but little is known about the duration of effect. The results of 2 randomized, double-blind, vehicle-controlled, single-dose, parallel, clinical studies (Study 1, n=67; Study 2, n=61) in which the efficacy of an oxymetazoline (0.05% Oxy) nasal spray in patients with acute coryzal rhinitis was assessed over a 12-hour time-period. Data were collected on both subjective relief of nasal congestion (6-point nasal congestion scale) and objective measures of nasal patency (anterior rhinomanometry) in both studies. A pooled study analysis showed statistically significant changes from baseline in subjective nasal congestion for 0.05% oxymetazoline and vehicle at each hourly time-point from Hour 1 through Hour 12 (marginally significant at Hour 11). An objective measure of nasal flow was statistically significant at each time-point up to 12 hours. Adverse events on either treatment were infrequent. The number of subjects who achieved an improvement in subjective nasal congestion scores of at least 1.0 was significantly higher in the Oxy group vs. vehicle at all hourly time-points on a 6-point nasal congestion scale. This study shows for the first time, that oxymetazoline provides both statistically significant and clinically meaningful relief of nasal congestion and improves nasal airflow for up to 12 hours following a single dose.

A randomised clinical study to evaluate experimental children's toothpastes in an in-situ palatal caries model in children aged 11-14 years.

PubMed

Newby, Evelyn E; Martinez-Mier, Esperanza A; Hara, Anderson; Lippert, Frank; Kelly, Sue A; Fleming, Nancy; Butler, Andrew; Bosma, Mary Lynn; Zero, Domenick T

2013-12-01

To compare three children's sodium fluoride toothpastes to placebo with respect to enamel remineralisation potential, enamel fluoride uptake and net acid resistance using an in situ palatal caries model in children aged 11-14 years following a single brushing. This was a randomised, single blind (laboratory analyst), single-centre, four-treatment, crossover study with a 7-day washout period between treatments. The treatments were 1,426 ppm fluoride, 1,000 ppm fluoride, 500 ppm fluoride and 0 ppm fluoride (placebo) toothpaste (NaF/silica). A custom made in situ palatal appliance was used by each subject in all treatment periods. At each of the four treatment visits subjects wore the appliance containing four partially demineralised human enamel specimens for 5 minutes and then brushed their teeth using a standardised procedure for 60 seconds under supervision using 1.0 g (±0.1 g) of their assigned toothpaste. After 4 hours the appliance was removed and enamel specimen recovered. This process was repeated until all subjects completed all four study treatment visits. Recovered enamel specimens were analysed for per cent surface microhardness recovery (%SMHR; Knoop) and enamel fluoride uptake (EFU; microdrill biopsy). Subsequently, specimens were demineralised in vitro to determine their % net acid resistance (%NAR; Knoop). All three fluoride toothpastes demonstrated significantly greater %SMHR, EFU and %NAR compared with 0 ppm F toothpaste. The model demonstrated a dose response over the range 0 to 1,426 ppm fluoride for %SMHR, EFU and %NAR. There was no significant difference between 500 ppm F and 1,000 ppm F for %SMHR and between 1,000 ppm F and 1,426 ppm F for %SMHR, EFU and %NAR. The present in situ study demonstrated that the children's fluoride toothpastes tested are capable of delivering cariostatic amounts of fluoride to early caries lesions following a single brushing. © 2013 FDI World Dental Federation.

A pilot study on seborrheic dermatitis using pramiconazole as a potent oral anti-Malassezia agent.

PubMed

Piérard, Gérald E; Ausma, Jannie; Henry, Frédérique; Vroome, Valérie; Wouters, Luc; Borgers, Marcel; Cauwenbergh, Geert; Piérard-Franchimont, Claudine

2007-01-01

Seborrheic dermatitis is considered to be a Malassezia-driven disease. Little objective information is available so far from biometrological quantitative assessments of this skin condition. Pramiconazole is a novel triazole with potent in vitro antifungal activity, especially against Malassezia spp. To study the sequential effects of pramiconazole on Malassezia, inflammation and epidermal changes. This study was performed in 2 groups of subjects suffering from seborrheic dermatitis. The first group (n = 17) remained untreated and was used as control. Clinical, mycological and biometrological assessments were performed at inclusion and during the following 2 weeks. The second group of subjects (n = 10) received a single 200-mg oral dose of pramiconazole at inclusion. Clinical, mycological and biometrological evaluations were performed before and during 1 month following the single antifungal intake. For both parts of the study, several parameters were assessed including yeast density, desquamation, erythema, itching and sebum excretion. In the control group, no significant changes were observed in any of the parameters during the observation period. The findings were markedly different in the pramiconazole-treated subjects. The yeast density was significantly improved on days 3, 7 and 28. Desquamation, erythema, itching, and the global clinical evaluation as assessed by the patients and investigators became significantly improved on days 7 and 28. A trend in decrease of scaliness was noted. No effect on sebum excretion was evidenced. In conclusion, a single 200-mg dose of pramiconazole exhibitsin vivo efficacy in controlling some important clinical aspects of seborrheic dermatitis. Following a reduction in the number of yeasts on day 3, a decrease in the severity of clinical signs and symptoms occurred from day 7 onwards. Sebum excretion appeared uninvolved in the clearing process of seborrheic dermatitis. A single 200-mg dose of pramiconazole appears to abate seborrheic dermatitis. The density in Malassezia present on lesional skin is first decreased, followed by clearing of the clinical signs. Copyright 2007 S. Karger AG, Basel.

Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies).

PubMed

Teramoto, Tamio; Kobayashi, Masahiko; Uno, Kiyoko; Takagi, Yoshiharu; Matsuoka, Osamu; Sugimoto, Masayuki; Inoue, Satoshi; Minami, Fumiko; Baccara-Dinet, Marie Thérèse

2016-07-01

We assessed the safety and tolerability of ascending single doses of alirocumab in healthy Japanese subjects and evaluated the effect of alirocumab at 3 doses (50, 75, 150 mg) on low-density lipoprotein cholesterol (LDL-C) reduction in patients with primary hypercholesterolemia on atorvastatin. A randomized, single ascending-dose study of alirocumab (100, 150, 250, or 300 mg) or placebo (3:1 ratio), administered subcutaneously, was conducted in 32 healthy Japanese men. The phase 2, randomized, double-blind, placebo-controlled, parallel-group study was performed in patients with primary hypercholesterolemia (defined as calculated LDL-C ≥100 mg/dl [2.6 mmol/l]) who were on a stable dose of atorvastatin (5 to 20 mg). Patients were randomized to alirocumab (50, 75, or 150 mg) or placebo (in single 1.0-ml injection volumes) administered every 2 weeks (Q2W) for 12 weeks; the primary outcome was the mean percent change in calculated LDL-C from baseline to week 12. Single subcutaneous administration of alirocumab in healthy subjects was well tolerated over 15 weeks and resulted in highest mean percent reductions in LDL-C from baseline of approximately 40% to 60%. In the multiple-dose study, least-square mean (SE) changes in calculated LDL-C concentrations from baseline to week 12 were -54.8% (3.1%) for alirocumab 50 mg, -62.3% (3.1%) for alirocumab 75 mg, and -71.7% (3.1%) for alirocumab 150 mg, with a least-square mean (SE) difference versus placebo of -52.2% (4.3%), -59.6% (4.3%), and -69.1% (4.3%), respectively (all p <0.0001). In conclusion, alirocumab was well tolerated and significantly reduced LDL-C concentrations in Japanese patients with primary hypercholesterolemia on atorvastatin. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Hearing history influences voice gender perceptual performance in cochlear implant users.

PubMed

Kovačić, Damir; Balaban, Evan

2010-12-01

The study was carried out to assess the role that five hearing history variables (chronological age, age at onset of deafness, age of first cochlear implant [CI] activation, duration of CI use, and duration of known deafness) play in the ability of CI users to identify speaker gender. Forty-one juvenile CI users participated in two voice gender identification tasks. In a fixed, single-interval task, subjects listened to a single speech item from one of 20 adult male or 20 adult female speakers and had to identify speaker gender. In an adaptive speech-based voice gender discrimination task with the fundamental frequency difference between the voices as the adaptive parameter, subjects listened to a pair of speech items presented in sequential order, one of which was always spoken by an adult female and the other by an adult male. Subjects had to identify the speech item spoken by the female voice. Correlation and regression analyses between perceptual scores in the two tasks and the hearing history variables were performed. Subjects fell into three performance groups: (1) those who could distinguish voice gender in both tasks, (2) those who could distinguish voice gender in the adaptive but not the fixed task, and (3) those who could not distinguish voice gender in either task. Gender identification performance for single voices in the fixed task was significantly and negatively related to the duration of deafness before cochlear implantation (shorter deafness yielded better performance), whereas performance in the adaptive task was weakly but significantly related to age at first activation of the CI device, with earlier activations yielding better scores. The existence of a group of subjects able to perform adaptive discrimination but unable to identify the gender of singly presented voices demonstrates the potential dissociability of the skills required for these two tasks, suggesting that duration of deafness and age of cochlear implantation could have dissociable effects on the development of different skills required by CI users to identify speaker gender.

A focused exercise regimen improves clinical measures of balance in patients with peripheral neuropathy.

PubMed

Richardson, J K; Sandman, D; Vela, S

2001-02-01

To determine the effect of a specific exercise regimen on clinical measures of postural stability and confidence in a population with peripheral neuropathy (PN). Prospective, controlled, single blind study. Outpatient clinic of a university hospital. Twenty subjects with diabetes mellitus and electrodiagnostically confirmed PN. Ten subjects underwent a 3-week intervention exercise regimen designed to increase rapidly available distal strength and balance. The other 10 subjects performed a control exercise regimen. Unipedal stance time, functional reach, tandem stance time, and score on the activities-specific balance and confidence (ABC) scale. The intervention subjects, but not the control subjects, showed significant improvement in all 3 clinical measures of balance and nonsignificant improvement on the ABC scale. A brief, specific exercise regimen improved clinical measures of balance in patients with diabetic PN. Further studies are needed to determine if this result translates into a lower fall frequency in this high-risk population.

The application of statistical parametric mapping to 123I-FP-CIT SPECT in dementia with Lewy bodies, Alzheimer's disease and Parkinson's disease.

PubMed

Colloby, Sean J; O'Brien, John T; Fenwick, John D; Firbank, Michael J; Burn, David J; McKeith, Ian G; Williams, E David

2004-11-01

Dopaminergic loss can be visualised using (123)I-FP-CIT single photon emission computed tomography (SPECT) in several disorders including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Most previous SPECT studies have adopted region of interest (ROI) methods for analysis, which are subjective and operator-dependent. The purpose of this study was to investigate differences in striatal binding of (123)I-FP-CIT SPECT using the automated technique of statistical parametric mapping (SPM99) in subjects with DLB, Alzheimer's disease (AD), PD and healthy age-matched controls. This involved spatial normalisation of each subject's image to a customised template, followed by smoothing and intensity normalisation of each image to its corresponding mean occipital count per voxel. Group differences were assessed using a two-sample t test. Applying a height threshold of P

Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A.

PubMed

Coyle, T E; Reding, M T; Lin, J C; Michaels, L A; Shah, A; Powell, J

2014-04-01

BAY 94-9027 is a B-domain-deleted recombinant factor VIII (rFVIII) with site-specific attachment of poly(ethylene glycol) that has shown an extended half-life in animal models of hemophilia. To assess the pharmacokinetics and safety of BAY 94-9027 after single and repeated administration in subjects with severe hemophilia A. This 8-week, prospective, multicenter, open-label, phase I trial was conducted in 14 subjects aged 21–58 years with FVIII of < 1%, ≥ 150 days of exposure to FVIII, and no history of FVIII inhibitors. After a ≥ 3-day washout, subjects received a single dose of sucrose-formulated rFVIII (rFVIII-FS) (cohort 1 [n = 7], 25 IU kg−1; cohort 2 [n = 7], 50 IU kg−1) for a 48-h pharmacokinetic (PK) study. After another ≥ 3-day washout, cohort 1 received twice-weekly BAY 94-9027 at 25 IU kg−1 (16 doses), and cohort 2 received once-weekly BAY 94-9027 at 60 IU kg−1 (nine doses). A 168-h PK study was performed after the first and last BAY 94-9027 doses. BAY 94-9027 showed equivalent recovery and an improved PK profile vs. rFVIII-FS, with a half-life of ~ 19 h (vs. ~ 13.0 h for rFVIII-FS). BAY 94-9027 was well tolerated, and no immunogenicity was observed. This phase I study demonstrates that BAY 94-9027 has an extended half-life in subjects with hemophilia A and, after multiple dosing, was well tolerated with no immunogenicity during the 8-week trial. A phase III study in a larger number of subjects is underway to fully characterize how this prolonged half-life will permit less frequent prophylaxis dosing for patients with hemophilia.

Dose-escalation of human anti-interferon-α receptor monoclonal antibody MEDI-546 in subjects with systemic sclerosis: a phase 1, multicenter, open label study

PubMed Central

2014-01-01

Introduction Type I interferons (IFNs) are implicated in the pathogenesis of systemic sclerosis (SSc). MEDI-546 is an investigational human monoclonal antibody directed against the type I IFN receptor. This Phase 1 study evaluated the safety/tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of single and multiple intravenous doses of MEDI-546 in adults with SSc. Methods Subjects (≥18 years) with SSc were enrolled in an open-label, dose-escalation study to receive single (0.1, 0.3, 1.0, 3.0, 10.0, or 20.0 mg/kg), or 4 weekly intravenous doses (0.3, 1.0, or 5.0 mg/kg/week) of MEDI-546. Subjects were followed for 12 weeks. Safety assessments included adverse events (AEs), laboratory results, and viral monitoring. Blood samples were collected from all subjects for determination of PK, presence of anti-drug antibodies (ADAs), and expression of type I IFN-inducible genes. Results Of 34 subjects (mean age 47.4 years), 32 completed treatment and 33 completed the study. Overall, 148 treatment-emergent AEs (TEAEs) were reported (68.9% mild, 27.7% moderate). TEAEs included one grade 1 infusion reaction (5.0 mg/kg/week multiple dose). Of 4 treatment-emergent serious AEs (skin ulcer, osteomyelitis, vertigo, and chronic myelogenous leukemia (CML)), only CML (1.0 mg/kg/week multiple dose) was considered possibly treatment-related. MEDI-546 exhibited non-linear PK at lower doses. ADAs were detected in 5 subjects; no apparent impact on PK was observed. Peak inhibition of the type I IFN signature in whole blood was achieved within 1 day and in skin after 7 days. Conclusion The safety/tolerability, PK, and PD profiles observed in this study support further clinical development of MEDI-546. Trial Registration ClinicalTrials.gov NCT00930683 PMID:24559157

Volume measurements of individual muscles in human quadriceps femoris using atlas-based segmentation approaches.

PubMed

Le Troter, Arnaud; Fouré, Alexandre; Guye, Maxime; Confort-Gouny, Sylviane; Mattei, Jean-Pierre; Gondin, Julien; Salort-Campana, Emmanuelle; Bendahan, David

2016-04-01

Atlas-based segmentation is a powerful method for automatic structural segmentation of several sub-structures in many organs. However, such an approach has been very scarcely used in the context of muscle segmentation, and so far no study has assessed such a method for the automatic delineation of individual muscles of the quadriceps femoris (QF). In the present study, we have evaluated a fully automated multi-atlas method and a semi-automated single-atlas method for the segmentation and volume quantification of the four muscles of the QF and for the QF as a whole. The study was conducted in 32 young healthy males, using high-resolution magnetic resonance images (MRI) of the thigh. The multi-atlas-based segmentation method was conducted in 25 subjects. Different non-linear registration approaches based on free-form deformable (FFD) and symmetric diffeomorphic normalization algorithms (SyN) were assessed. Optimal parameters of two fusion methods, i.e., STAPLE and STEPS, were determined on the basis of the highest Dice similarity index (DSI) considering manual segmentation (MSeg) as the ground truth. Validation and reproducibility of this pipeline were determined using another MRI dataset recorded in seven healthy male subjects on the basis of additional metrics such as the muscle volume similarity values, intraclass coefficient, and coefficient of variation. Both non-linear registration methods (FFD and SyN) were also evaluated as part of a single-atlas strategy in order to assess longitudinal muscle volume measurements. The multi- and the single-atlas approaches were compared for the segmentation and the volume quantification of the four muscles of the QF and for the QF as a whole. Considering each muscle of the QF, the DSI of the multi-atlas-based approach was high 0.87 ± 0.11 and the best results were obtained with the combination of two deformation fields resulting from the SyN registration method and the STEPS fusion algorithm. The optimal variables for FFD and SyN registration methods were four templates and a kernel standard deviation ranging between 5 and 8. The segmentation process using a single-atlas-based method was more robust with DSI values higher than 0.9. From the vantage of muscle volume measurements, the multi-atlas-based strategy provided acceptable results regarding the QF muscle as a whole but highly variable results regarding individual muscle. On the contrary, the performance of the single-atlas-based pipeline for individual muscles was highly comparable to the MSeg, thereby indicating that this method would be adequate for longitudinal tracking of muscle volume changes in healthy subjects. In the present study, we demonstrated that both multi-atlas and single-atlas approaches were relevant for the segmentation of individual muscles of the QF in healthy subjects. Considering muscle volume measurements, the single-atlas method provided promising perspectives regarding longitudinal quantification of individual muscle volumes.

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks.

PubMed

Ilfeld, Brian M; Viscusi, Eugene R; Hadzic, Admir; Minkowitz, Harold S; Morren, Michael D; Lookabaugh, Janice; Joshi, Girish P

2015-01-01

Liposome bupivacaine (Exparel) is a multivesicular liposomal formulation of bupivacaine currently approved in the United States for single-dose administration into the surgical site to provide postsurgical analgesia. This retrospective analysis examined safety data from clinical trials involving the off-label use of this formulation in peripheral nerve blocks. Data from 6 controlled (phases I-III) studies were compiled involving single-injection ankle, femoral nerve, and intercostal nerve blocks (2 each). Adverse events (AEs) were monitored for 1 to 30 days after study drug administration. Of 575 subjects, 335 received liposome bupivacaine (2-310 mg), 33 received bupivacaine HCl (75-125 mg), and 207 received normal saline (placebo). Overall, 76% of subjects receiving liposome bupivacaine experienced 1 or more AEs compared with 61% receiving bupivacaine HCl and 76% receiving placebo. The most frequently reported AEs among subjects receiving liposome bupivacaine were nausea, pyrexia, pruritus, constipation, and vomiting. The most common treatment-related AE was hypesthesia among subjects treated with liposome bupivacaine or bupivacaine HCl. Incidence of nervous system AEs for liposome bupivacaine, bupivacaine HCl, and placebo was 21%, 27%, and 21%, respectively. Similarly, incidence of cardiac AEs was 9%, 0%, and 12%, respectively. At least 1 serious AE occurred in 8% of subjects receiving liposome bupivacaine compared with 10% of those receiving placebo (none assessed by investigators as related to study medication). Liposome bupivacaine has a similar safety and side effect profile to bupivacaine HCl and normal saline, suggesting that most of the more common AEs are related to either opioid rescue or the surgical procedure itself.

The transition to increased automaticity during finger sequence learning in adult males who stutter.

PubMed

Smits-Bandstra, Sarah; De Nil, Luc; Rochon, Elizabeth

2006-01-01

The present study compared the automaticity levels of persons who stutter (PWS) and persons who do not stutter (PNS) on a practiced finger sequencing task under dual task conditions. Automaticity was defined as the amount of attention required for task performance. Twelve PWS and 12 control subjects practiced finger tapping sequences under single and then dual task conditions. Control subjects performed the sequencing task significantly faster and less variably under single versus dual task conditions while PWS' performance was consistently slow and variable (comparable to the dual task performance of control subjects) under both conditions. Control subjects were significantly more accurate on a colour recognition distracter task than PWS under dual task conditions. These results suggested that control subjects transitioned to quick, accurate and increasingly automatic performance on the sequencing task after practice, while PWS did not. Because most stuttering treatment programs for adults include practice and automatization of new motor speech skills, findings of this finger sequencing study and future studies of speech sequence learning may have important implications for how to maximize stuttering treatment effectiveness. As a result of this activity, the participant will be able to: (1) Define automaticity and explain the importance of dual task paradigms to investigate automaticity; (2) Relate the proposed relationship between motor learning and automaticity as stated by the authors; (3) Summarize the reviewed literature concerning the performance of PWS on dual tasks; and (4) Explain why the ability to transition to automaticity during motor learning may have important clinical implications for stuttering treatment effectiveness.

Quantifying gait patterns in Parkinson's disease

NASA Astrophysics Data System (ADS)

Romero, Mónica; Atehortúa, Angélica; Romero, Eduardo

2017-11-01

Parkinson's disease (PD) is constituted by a set of motor symptoms, namely tremor, rigidity, and bradykinesia, which are usually described but not quantified. This work proposes an objective characterization of PD gait patterns by approximating the single stance phase a single grounded pendulum. This model estimates the force generated by the gait during the single support from gait data. This force describes the motion pattern for different stages of the disease. The model was validated using recorded videos of 8 young control subjects, 10 old control subjects and 10 subjects with Parkinson's disease in different stages. The estimated force showed differences among stages of Parkinson disease, observing a decrease of the estimated force for the advanced stages of this illness.

The NASA earth resources spectral information system: A data compilation

NASA Technical Reports Server (NTRS)

Leeman, V.; Earing, D.; Vincent, R. K.; Ladd, S.

1971-01-01

The NASA Earth Resources Spectral Information System and the information contained therein are described. It contains an ordered, indexed compilation of natural targets in the optical region from 0.3 to 45.0 microns. The data compilation includes approximately 100 rock and mineral, 2600 vegetation, 1000 soil, and 60 water spectral reflectance, transmittance, and emittance curves. Most of the data have been categorized by subject, and the curves in those subject areas have been plotted on a single graph. Those categories with too few curves and miscellaneous categories have been plotted as single-curve graphs. Each graph, composite of single, is fully titled to indicate curve source and is indexed by subject to facilitate user retrieval.

Enhancement of in vitro interleukin-2 production in normal subjects following a single spinal manipulative treatment

PubMed Central

Teodorczyk-Injeyan, Julita A; Injeyan, H Stephen; McGregor, Marion; Harris, Glen M; Ruegg, Richard

2008-01-01

Background Increasing evidence supports somato-visceral effects of manual therapies. We have previously demonstrated that a single spinal manipulative treatment (SMT) accompanied by audible release has an inhibitory effect on the production of proinflammatory cytokines in asymptomatic subjects. The purpose of this study is to report on SMT-related changes in the production of the immunoregulatory cytokine interleukin 2 (IL-2) and to investigate whether such changes might differ with respect to the treatment approach related to the presence or absence of an audible release (joint cavitation). Methods Of 76 asymptomatic subjects, 29 received SMT with cavitation (SMT-C), 23 were treated with SMT without cavitation (SMT-NC) and 24 comprised the venipuncture control (VC) group. The SMT-C and SMT-NC subjects received a single, similar force high velocity low amplitude manipulation, in the upper thoracic spine. However, in SMT-NC subjects, positioning and line of drive were not conducive to cavitation. Blood and serum samples were obtained before and then at 20 and 120 min post-intervention. The production of IL-2 in peripheral blood mononuclear cell cultures was induced by activation for 48 hr with Staphylococcal protein A (SPA) and, in parallel preparations, with the combination of phorbol ester (TPA) and calcium ionophore. The levels of IL-2 in culture supernatants and serum were assessed by specific immunoassays. Results Compared with VC and their respective baselines, SPA-induced secretion of IL-2 increased significantly in cultures established from both SMT-C and SMT-NC subjects at 20 min post-intervention. At 2 hr post-treatment, significant elevation of IL-2 synthesis was still apparent in preparations from SMT-treated groups though it became somewhat attenuated in SMT-NC subjects. Conversely, IL-2 synthesis induced by TPA and calcium ionophore was unaltered by either type of SMT and was comparable to that in VC group at all time points. No significant alterations in serum-associated IL-2 levels were observed in any of the study groups. Conclusion The present study demonstrates that, the in vitro T lymphocyte response to a conventional mitogen (SPA), as measured by IL-2 synthesis, can become enhanced following SMT. Furthermore, within a period of time following the manipulative intervention, this effect may be independent of joint cavitation. Thus the results of this study suggest that, under certain physiological conditions, SMT might influence IL-2-regulated biological responses. PMID:18507834

Factors Impacting Growth in Infants with Single Ventricle Physiology: A Report from Pediatric Heart Network Infant Single Ventricle Trial

PubMed Central

Williams, Richard V.; Zak, Victor; Ravishankar, Chitra; Altmann, Karen; Anderson, Jeffrey; Atz, Andrew M.; Dunbar-Masterson, Carolyn; Ghanayem, Nancy; Lambert, Linda; Lurito, Karen; Medoff-Cooper, Barbara; Margossian, Renee; Pemberton, Victoria L.; Russell, Jennifer; Stylianou, Mario; Hsu, Daphne

2011-01-01

Objectives To describe growth patterns in infants with single ventricle physiology and determine factors influencing growth. Study design Data from 230 subjects enrolled in the Pediatric Heart Network Infant Single Ventricle Enalapril Trial were used to assess factors influencing change in weight-for-age z-score (Δz) from study enrollment (0.7 ± 0.4 months) to pre-superior cavopulmonary connection (SCPC) (5.1 ± 1.8 months, period 1), and pre-SCPC to final study visit (14.1 ± 0.9 months, period 2). Predictor variables included patient characteristics, feeding regimen, clinical center, and medical factors during neonatal (period 1) and SCPC hospitalizations (period 2). Univariate regression analysis was performed, followed by backward stepwise regression and bootstrapping reliability to inform a final multivariable model. Results Weights were available for 197/230 subjects for period 1 and 173/197 for period 2. For period 1, greater gestational age, younger age at study enrollment, tube feeding at neonatal discharge, and clinical center were associated with a greater negative Δz (poorer growth) in multivariable modeling (adjusted R2 = 0.39, p < 0.001). For period 2, younger age at SCPC and greater daily caloric intake were associated with greater positive Δz (better growth) (R2 = 0.10, p = 0.002). Conclusions Aggressive nutritional support and earlier SCPC are modifiable factors associated with a favorable change in weight-for-age z-score. PMID:21784436

Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking.

PubMed

Kosobud, Ann E K; Wetherill, Leah; Plawecki, Martin H; Kareken, David A; Liang, Tiebing; Nurnberger, John L; Windisch, Kyle; Xuei, Xiaoling; Edenberg, Howard J; Foroud, Tatiana M; O'Connor, Sean J

2015-07-01

Subjective perceptions of alcohol intoxication are associated with altered risk for alcohol abuse and dependence. Acute adaptation of these perceptions may influence such risk and may involve genes associated with pleasant perceptions or the relief of anxiety. This study assessed the effect of variation in the GABAA receptor genes GABRG1 and GABRA2 and recent drinking history on the acute adaptation of subjective responses to alcohol. One hundred and thirty-two nondependent moderate to heavy drinkers, aged 21 to 27, participated in 2 single-blind, counterbalanced sessions, approximately 1 week apart. One session was an intravenous alcohol "clamp," during which breath alcohol concentration was held steady at 60 mg/dl (60 mg%) for 3 hours, and the other an identical session using saline infusion. Subjective perceptions of Intoxication, Enjoyment, Stimulation, Relaxation, Anxiety, Tiredness, and Estimated Number of Drinks were acquired before (baseline), and during the first and final 45 minutes of the clamp. A placebo-adjusted index of the subject's acute adaptation to alcohol was calculated for each of the 7 subjective measures and used in a principal component analysis to create a single aggregate estimate for each subject's adaptive response to alcohol. Analysis of covariance tested whether GABRA2 and GABRG1 single nucleotide polymorphism (SNP) genotypes, gender, placebo session, family history of alcoholism, recent drinking history, and the genotype × recent drinking history interaction significantly predicted the adaptive response. Recent drinking history (p = 0.01), and recent drinking history × genotype interaction (p = 0.01) were significantly associated with acute adaptation of the subjective responses to alcohol for the GABRA2 SNP rs279858. Higher recent drinking was found to be associated with reduced acute tolerance to positive, stimulating effects of alcohol in carriers of the rs279858 risk allele. We postulate that the GABRA2 effect on alcohol dependence may, in part, be due to its effect on subjective responses to alcohol. Copyright © 2015 by the Research Society on Alcoholism.

Long-lasting changes in brain activation induced by a single REAC technology pulse in Wi-Fi bands. Randomized double-blind fMRI qualitative study.

PubMed

Rinaldi, Salvatore; Mura, Marco; Castagna, Alessandro; Fontani, Vania

2014-07-11

The aim of this randomized double-blind study was to evaluate in healthy adult subjects, with functional magnetic resonance imaging (fMRI), long lasting changes in brain activation patterns following administration of a single, 250 milliseconds pulse emitted with radio-electric asymmetric conveyer (REAC) technology in the Wi-Fi bands. The REAC impulse was not administered during the scan, but after this, according to a protocol that has previously been demonstrated to be effective in improving motor control and postural balance, in healthy subjects and patients. The study was conducted on 33 healthy volunteers, performed with a 1.5 T unit while operating a motor block task involving cyclical and alternating flexion and extension of one leg. Subsequently subjects were randomly divided into a treatment and a sham treatment control group. Repeated fMRI examinations were performed following the administration of the REAC pulse or sham treatment. The Treated group showed cerebellar and ponto-mesencephalic activation components that disappeared in the second scan, while these activation components persisted in the Sham group. This study shows that a very weak signal, such as 250 milliseconds Wi-Fi pulse, administered with REAC technology, could lead to lasting effects on brain activity modification.

A Single Nucleotide Polymorphism in 3′-Untranslated Region Contributes to the Regulation of Toll-like Receptor 4 Translation*

PubMed Central

Sato, Kayo; Yoshimura, Atsutoshi; Kaneko, Takashi; Ukai, Takashi; Ozaki, Yukio; Nakamura, Hirotaka; Li, Xinyue; Matsumura, Hiroyoshi; Hara, Yoshitaka; Ogata, Yorimasa

2012-01-01

We have previously shown that a single nucleotide polymorphism rs11536889 in the 3′-untranslated region (UTR) of TLR4 was associated with periodontitis. In this study the effects of this single nucleotide polymorphism on Toll-like receptor (TLR) 4 expression were investigated. Monocytes from subjects with the C/C genotype expressed higher levels of TLR4 on their surfaces than those from subjects with the other genotypes. Peripheral blood mononuclear cells (PBMCs) from the C/C and G/C subjects secreted higher levels of IL-8 in response to lipopolysaccharide (LPS), a TLR4 ligand, than the cells from the G/G subjects. However, there was no significant difference in TLR4 mRNA levels in PBMCs from the subjects with each genotype. After stimulation with tripalmitoylated CSK4 (Pam3CSK4), TLR4 mRNA levels increased in PBMCs from both the C/C and G/G subjects, whereas TLR4 protein levels increased in PBMCs from the C/C but not G/G subjects. Transient transfection of a series of chimeric luciferase constructs revealed that a fragment of 3′-UTR containing rs11536889 G allele, but not C allele, suppressed luciferase activity induced by LPS or IL-6. Two microRNAs, hsa-miR-1236 and hsa-miR-642a, were predicted to bind to rs11536889 G allele. Inhibition of these microRNAs reversed the suppressed luciferase activity. These microRNA inhibitors also up-regulated endogenous TLR4 protein on THP-1 cells (the G/G genotype) after LPS stimulation. Furthermore, mutant microRNAs that bind to the C allele inhibited the luciferase activity of the construct containing the C allele. These results indicate that genetic variation of rs11536889 contributes to translational regulation of TLR4, possibly by binding to microRNAs. PMID:22661708

Pharmacokinetics of betamethasone after single-dose intramuscular administration of betamethasone phosphate and betamethasone acetate to healthy subjects.

PubMed

Salem, Isam I; Najib, Naji M

2012-01-01

Betamethasone is used for its antiinflammatory and immunosuppressive effects in disorders of many organ systems. However, the pharmacokinetic properties of betamethasone in plasma after intramuscular injection of betamethasone sodium phosphate and betamethasone acetate dual-acting suspension need further investigation. The main aim of this study was to determine the pharmacokinetic parameters of betamethasone, betamethasone acetate, and betamethasone phosphate after the administration of a single intramuscular dose of the dual-acting suspension to healthy human volunteers. Two different studies were conducted in healthy males. Volunteers were judged healthy based on their medical history, physical examination, and laboratory test results. Before confinement, all volunteers were tested for freedom from alcohol and drugs of abuse. Following a 10-hour overnight fasting, a single dose of 1 mL of the dual-acting suspension containing 3 mg of betamethasone phosphate and 3 mg of betamethasone acetate was administered by intramuscular injection. Blood sampling covered 48 hours. The plasma samples obtained in the second study were stabilized to enable pharmacokinetic profiling of betamethasone esters. Twenty-four healthy males with mean (SD) age of 27 (6.62) years participated in each study. No incidences of serious adverse events were recorded during the studies. Six mild adverse events were reported in 2 subjects in the second study. One subject suffered from pain at the injection site and insomnia, and another subject complained of heartburn and drowsiness. Betamethasone phosphate appeared to be readily absorbed with a mean AUC(0-t) of 96.01 ng/h/mL and an AUC(0-∞) of 97.96 (23.38) ng/h/mL. Betamethasone peak plasma concentration reached a mean t(½) of 12.92 hours. Betamethasone acetate was not detected in the volunteers' plasma in either study (total of 2208 plasma samples). The observed pharmacokinetic parameters suggested that the acetate ester, and not the phosphate ester, of betamethasone acts as a prodrug or reservoir for betamethasone, conferring on it sustained- and extended-release characteristics. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Public awareness of warning symptoms, risk factors, and treatment of stroke in northwest India.

PubMed

Pandian, Jeyaraj D; Jaison, Ashish; Deepak, Sukhbinder S; Kalra, Guneet; Shamsher, Shivali; Lincoln, Douglas J; Abraham, George

2005-03-01

This study assessed public awareness of warning symptoms, risk factors, and treatment of stroke in Ludhiana, Punjab, North West India. A hospital-based survey was conducted between February 2002 and September 2002 by the Stroke section of Christian Medical College. The study subjects were relatives of patients without history of stroke, attending the outpatient department of the hospital. Trained medical students, interns, and a nurse interviewed subjects using a structured, pretested, open-ended questionnaire. Nine hundred forty-two individuals were interviewed during the study period (56.4% men, mean age 40.1 years, age range 15 to 80 years). Forty-five percent of the subjects did not recognize the brain as the affected organ in stroke. In the multivariate analysis, higher education (P<0.001; odds ratio 2.6; 95%, CI 1.8 to 3.8) and upper socioeconomic status (P<0.005; odds ratio 1.6; CI, 1.1 to 2.2) correlated with a better knowledge of which organ was affected in stroke. Twenty-three percent of the participants did not know a single warning symptom of stroke. Twenty-one percent of the subjects could not identify even a single risk factor for stroke. Seven percent of the study population believed that oil massage would improve stroke victims. A small proportion of subjects believed in witchcraft, faith healing, homeopathic, and ayurvedic treatment (3%). This hospital-based survey reveals a better awareness of stroke warning signs and risk factors. However, knowledge regarding the organ involved, etiology, and treatment of stroke is lacking. Considerable education is needed to increase public awareness in modern concepts of stroke treatment.

Phase 1 Study of CK-301 as a Single Agent in Subjects With Advanced Cancers

ClinicalTrials.gov

2018-01-02

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Malignant Mesothelioma, Advanced; Head and Neck Cancer; Melanoma; Merkel Cell Carcinoma; Renal Cell Carcinoma; Urothelial Carcinoma; Classical Hodgkin Lymphoma

Using Self-Experimentation and Single-Subject Methodology to Promote Critical Thinking

ERIC Educational Resources Information Center

Cowley, Brian J.; Lindgren, Ann; Langdon, David

2006-01-01

Critical thinking is often absent from classroom endeavor because it is hard to define (Gelder, 2005) or is difficult to assess (Bissell & Lemons, 2006). Critical thinking is defined as application, analysis, synthesis, and evaluation (Browne & Minnick, 2005). This paper shows how self-experimentation and single-subject methodology can be used to…

Single-Sex Schooling in Trinidad and Tobago: a Holistic Exploration

ERIC Educational Resources Information Center

Blair, Erik

2013-01-01

Single-sex schooling has been proposed as a way of addressing the disengagement of boys; the disproportion of gender in certain subjects; stereotyped gender images, and the labelling of some subjects as "masculine" or "feminine". However, there exists no clear research evidence to support such claims. Despite the lack of…

Does My Program Really Make a Difference? Program Evaluation Utilizing Aggregate Single-Subject Data

ERIC Educational Resources Information Center

Burns, Catherine E.

2015-01-01

In the current climate of increasing fiscal and clinical accountability, information is required about overall program effectiveness using clinical data. These requests present a challenge for programs utilizing single-subject data due to the use of highly individualized behavior plans and behavioral monitoring. Subsequently, the diversity of the…

Do Functional Behavioral Assessments Improve Intervention Effectiveness for Students Diagnosed with ADHD? A Single-Subject Meta-Analysis

ERIC Educational Resources Information Center

Miller, Faith G.; Lee, David L.

2013-01-01

The primary purpose of this quantitative synthesis of single-subject research was to investigate the relative effectiveness of function-based and non-function-based behavioral interventions for students diagnosed with attention-deficit/hyperactivity disorder. In addition, associations between various participant, assessment, and intervention…

Hierarchical Linear Modeling Meta-Analysis of Single-Subject Design Research

ERIC Educational Resources Information Center

Gage, Nicholas A.; Lewis, Timothy J.

2014-01-01

The identification of evidence-based practices continues to provoke issues of disagreement across multiple fields. One area of contention is the role of single-subject design (SSD) research in providing scientific evidence. The debate about SSD's utility centers on three issues: sample size, effect size, and serial dependence. One potential…

Photonic-plasmonic hybrid single-molecule nanosensor measures the effect of fluorescent labels on DNA-protein dynamics

PubMed Central

Liang, Feng; Guo, Yuzheng; Hou, Shaocong; Quan, Qimin

2017-01-01

Current methods to study molecular interactions require labeling the subject molecules with fluorescent reporters. However, the effect of the fluorescent reporters on molecular dynamics has not been quantified because of a lack of alternative methods. We develop a hybrid photonic-plasmonic antenna-in-a-nanocavity single-molecule biosensor to study DNA-protein dynamics without using fluorescent labels. Our results indicate that the fluorescein and fluorescent protein labels decrease the interaction between a single DNA and a protein due to weakened electrostatic interaction. Although the study is performed on the DNA-XPA system, the conclusion has a general implication that the traditional fluorescent labeling methods might be misestimating the molecular interactions. PMID:28560341

Crystal growth and characterization of semi organic nonlinear optical (NLO) piperazinium tetrachlorozincate monohydrate (PTCZ) single crystal

NASA Astrophysics Data System (ADS)

Karuppasamy, P.; Pandian, Muthu Senthil; Ramasamy, P.

2018-04-01

The semi-organic single crystal of piperazinium tetrachlorozincate monohydrate (PTCZ) was successfully grown by slow evaporation solution technique (SEST). The grown crystal was subjected to the single crystal XRD studies for confirming the unit cell parameters. The optical quality of the grown crystal was identified by the UV-Vis NIR spectrum analysis and the optical band gap energy was calculated. The photoconductivity study reveals that the grown crystal has positive photoconductive nature. The mechanical stability of the grown crystal was analyzed using Vickers microhardness analyzer. The third-order nonlinear optical properties such as nonlinear refractive index (n2), absorption co-efficient (β) and susceptibility (χ(3)) were studied by Z-scan technique at 640 nm using solid state laser.

Single-accelerometer-based daily physical activity classification.

PubMed

Long, Xi; Yin, Bin; Aarts, Ronald M

2009-01-01

In this study, a single tri-axial accelerometer placed on the waist was used to record the acceleration data for human physical activity classification. The data collection involved 24 subjects performing daily real-life activities in a naturalistic environment without researchers' intervention. For the purpose of assessing customers' daily energy expenditure, walking, running, cycling, driving, and sports were chosen as target activities for classification. This study compared a Bayesian classification with that of a Decision Tree based approach. A Bayes classifier has the advantage to be more extensible, requiring little effort in classifier retraining and software update upon further expansion or modification of the target activities. Principal components analysis was applied to remove the correlation among features and to reduce the feature vector dimension. Experiments using leave-one-subject-out and 10-fold cross validation protocols revealed a classification accuracy of approximately 80%, which was comparable with that obtained by a Decision Tree classifier.

User-oriented evaluation of mechanical single-channel axial pipettes.

PubMed

Sormunen, Erja; Nevala, Nina

2013-09-01

Hand tools should be designed so that they are comfortable to use, fit the hand and are user-oriented. Six different manual, single-channel axial pipettes were evaluated for such objective outcomes as muscular activity, wrist postures and efficiency, as well as for subjective outcomes concerning self-assessed features of pipette usability and musculoskeletal strain. Ten experienced laboratory employees volunteered for the study. The results showed that light and short pipettes with better tool comfort resulted in reduced muscular activity and perceived musculoskeletal strain when they were compared with a long and heavy pipette. There were no differences in the efficiency between the different pipettes. Combining both the objective and subjective measures enabled a broader evaluation of product usability. The results of this study can be used both in product development and as information on which to base the purchase of new pipettes for laboratory work. Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.

A review of the efficacy of the picture exchange communication system intervention.

PubMed

Preston, Deborah; Carter, Mark

2009-10-01

The Picture Exchange Communication System (PECS) is a communication program that has become widely used, especially with children with autism. This paper reports the results of a review of the empirical literature on PECS. A descriptive review is provided of the 27 studies identified, which included randomized controlled trials (RCTs), other group designs and single subject studies. For 10 appropriate single subject designs the percentage of nonoverlapping data (PND) and percentage exceeding median (PEM) metrics were examined. While there are few RCTs, on balance, available research provides preliminary evidence that PECS is readily learned by most participants and provides a means of communication for individuals with little or no functional speech. Very limited data suggest some positive effect on both social-communicative and challenging behaviors, while effects on speech development remain unclear. Directions for future research are discussed including the priority need for further well-conducted RCTs.

The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study

PubMed Central

Fair, Damien A.; Choi, Alexander H.; Dosenbach, Yannic B.L.; Coalson, Rebecca S.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

2009-01-01

Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we use an event-related design, which allowed us to isolate trial related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single-subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. PMID:19819000

Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist Elagolix

PubMed Central

Struthers, R. Scott; Nicholls, Andrew J.; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S. C.; Bozigian, Haig P.

2009-01-01

Context: Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist. Objective: Our objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single-dose and 7-d elagolix administration to healthy premenopausal women. Design: This was a first-in-human, double-blind, placebo-controlled, single- and multiple-dose study with sequential dose escalation. Participants: Fifty-five healthy, regularly cycling premenopausal women participated. Interventions: Subjects were administered a single oral dose of 25–400 mg or placebo. In a second arm of the study, subjects received placebo or 50, 100, or 200 mg once daily or 100 mg twice daily for 7 d. Treatment was initiated on d 7 (±1) after onset of menses. Main Outcome Measures: Safety, tolerability, pharmacokinetics, and serum LH, FSH, and estradiol concentrations were assessed. Results: Elagolix was well tolerated and rapidly bioavailable after oral administration. Serum gonadotropins declined rapidly. Estradiol was suppressed by 24 h in subjects receiving at least 50 mg/d. Daily (50–200 mg) or twice-daily (100 mg) administration for 7 d maintained low estradiol levels (17 ± 3 to 68 ± 46 pg/ml) in most subjects during late follicular phase. Effects of the compound were rapidly reversed after discontinuation. Conclusions: Oral administration of a nonpeptide GnRH antagonist, elagolix, suppressed the reproductive endocrine axis in healthy premenopausal women. These results suggest that elagolix may enable dose-related pituitary and gonadal suppression in premenopausal women as part of treatment strategies for reproductive hormone-dependent disease states. PMID:19033369

Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix.

PubMed

Struthers, R Scott; Nicholls, Andrew J; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S C; Bozigian, Haig P

2009-02-01

Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist. Our objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single-dose and 7-d elagolix administration to healthy premenopausal women. This was a first-in-human, double-blind, placebo-controlled, single- and multiple-dose study with sequential dose escalation. Fifty-five healthy, regularly cycling premenopausal women participated. Subjects were administered a single oral dose of 25-400 mg or placebo. In a second arm of the study, subjects received placebo or 50, 100, or 200 mg once daily or 100 mg twice daily for 7 d. Treatment was initiated on d 7 (+/-1) after onset of menses. Safety, tolerability, pharmacokinetics, and serum LH, FSH, and estradiol concentrations were assessed. Elagolix was well tolerated and rapidly bioavailable after oral administration. Serum gonadotropins declined rapidly. Estradiol was suppressed by 24 h in subjects receiving at least 50 mg/d. Daily (50-200 mg) or twice-daily (100 mg) administration for 7 d maintained low estradiol levels (17 +/- 3 to 68 +/- 46 pg/ml) in most subjects during late follicular phase. Effects of the compound were rapidly reversed after discontinuation. Oral administration of a nonpeptide GnRH antagonist, elagolix, suppressed the reproductive endocrine axis in healthy premenopausal women. These results suggest that elagolix may enable dose-related pituitary and gonadal suppression in premenopausal women as part of treatment strategies for reproductive hormone-dependent disease states.

The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study.

PubMed

Fair, Damien A; Choi, Alexander H; Dosenbach, Yannic B L; Coalson, Rebecca S; Miezin, Francis M; Petersen, Steven E; Schlaggar, Bradley L

2010-08-01

Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon is accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we used an event-related design, which allowed us to isolate trial-related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial-related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. 2009 Elsevier Inc. All rights reserved.

An EPAS1 haplotype is associated with high altitude polycythemia in male Han Chinese at the Qinghai-Tibetan plateau.

PubMed

Chen, Yu; Jiang, Chunhua; Luo, Yongjun; Liu, Fuyu; Gao, Yuqi

2014-12-01

Hemoglobin concentration at high altitude is considered an important marker of high altitude adaptation, and native Tibetans in the Qinghai-Tibetan plateau show lower hemoglobin concentrations than Han people who have emigrated from plains areas. Genetic studies revealed that EPAS1 plays a key role in high altitude adaptation and is associated with the low hemoglobin concentration in Tibetans. Three single nucleotide polymorphisms (rs13419896, rs4953354, rs1868092) of noncoding regions in EPAS1 exhibited significantly different allele frequencies in the Tibetan and Han populations and were associated with low hemoglobin concentrations in Tibetans. To explore the hereditary basis of high altitude polycythemia (HAPC) and investigate the association between EPAS1 and HAPC in the Han population, these 3 single nucleotide polymorphisms were assessed in 318 male Han Chinese HAPC patients and 316 control subjects. Genotyping was performed by high resolution melting curve analysis. The G-G-G haplotype of rs13419896, rs4953354, and rs1868092 was significantly more frequent in HAPC patients than in control subjects, whereas no differences in the allele or genotype frequencies of the 3 single nucleotide polymorphisms were found between HAPC patients and control subjects. Moreover, genotypes of rs1868092 (AA) and rs4953354 (GG) that were not observed in the Chinese Han in the Beijing population were found at frequencies of 1.6% and 0.9%, respectively, in our study population of HAPC patients and control subjects. Carriers of this EPAS1 haplotype (G-G-G, rs13419896, rs4953354, and rs1868092) may have a higher risk for HAPC. These results may contribute to a better understanding of the pathogenesis of HAPC in the Han population. Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Changes in accommodation and ocular aberration with simultaneous vision multifocal contact lenses.

PubMed

Ruiz-Alcocer, Javier; Madrid-Costa, David; Radhakrishnan, Hema; Ferrer-Blasco, Teresa; Montés-Micó, Robert

2012-09-01

The aim of this study was to evaluate ocular aberration changes through different simultaneous vision multifocal contact lenses (CLs). Eighteen young-adult subjects with a mean age of 29.8±2.11 years took part. Changes in accommodative response, spherical aberration (C(4)(0)), horizontal coma (C(3)(1)), vertical coma (C(3)(-1)), and root mean square (RMS) of higher-order aberrations (HOAs, third to sixth orders) were evaluated. Measurements were obtained with a distance-single vision CL and 2 aspheric multifocal CLs of simultaneous focus center-near design (PureVision Low Add and PureVision High Add) for 2 accommodative stimuli (-2.50 and -4.00 D). All measurements were performed monocularly with a Hartmann-Shack aberrometer (IRX-3; Imagine Eyes, Orsay, France). No statistically significant differences were found in accommodative responses to -2.50- and -4.00-D stimuli between the single vision CL and the 2 multifocal CLs. Spherical aberration was found to decrease and become more negative with accommodation for both stimuli with all three CLs. Horizontal coma decreased significantly with accommodation (-2.5- and -4.00-D stimuli) for the distance-single vision CLs (P=0.002 and P=0.003). No differences were found in vertical coma Zernike coefficients. The RMS of HOAs was found to decrease only with the single vision CLs for both stimuli (P<0.01). Data obtained in this study suggest that in young subjects, the multifocal CLs studied do not induce large changes in accommodative response compared with the distance-single vision CLs. Spherical aberration reduced significantly with accommodation.

The perception of visual images encoded in musical form: a study in cross-modality information transfer.

PubMed Central

Cronly-Dillon, J; Persaud, K; Gregory, R P

1999-01-01

This study demonstrates the ability of blind (previously sighted) and blindfolded (sighted) subjects in reconstructing and identifying a number of visual targets transformed into equivalent musical representations. Visual images are deconstructed through a process which selectively segregates different features of the image into separate packages. These are then encoded in sound and presented as a polyphonic musical melody which resembles a Baroque fugue with many voices, allowing subjects to analyse the component voices selectively in combination, or separately in sequence, in a manner which allows a subject to patch together and bind the different features of the object mentally into a mental percept of a single recognizable entity. The visual targets used in this study included a variety of geometrical figures, simple high-contrast line drawings of man-made objects, natural and urban scenes, etc., translated into sound and presented to the subject in polyphonic musical form. PMID:10643086

Effects of single antegrade hot shot in comparison with no hot shot administration during coronary artery bypass grafting

PubMed Central

Mirmohammadsadeghi, Pouya; Mirmohammadsadeghi, Mohsen

2015-01-01

BACKGROUND Superior results will be achieved from cardiac surgery by minimizing the effect of ischemia/reperfusion injury during cross-clamping of the aorta. Different cardioplegia solutions have been introduced, but the optimum one is still ambiguous. The aim of this study is to determine the effect of single antegrade hot shot terminal warm blood cardioplegia (TWBC) on patients who had undergone coronary artery bypass grafting (CABG). METHODS In total, 2488 patients who had CABG surgery in Sina Hospital, Isfahan, Iran, from 2003 to 2011 were enrolled in this case-control study. They were divided into two groups, those who received cold cardioplegia only and those who received a hot shot following cold cardioplegia. Demographics, and clinical data, such as; premature atrial contraction (PAC) arrhythmia, diabetes treatment, and left ventricular ejection fraction (EF), were collected and logistic regression analysis was used to analyze the data. RESULTS There were significant differences found between subjects receiving antegrade hot shot based on direct current (DC) shocks, with regard to; female, EF levels, diabetes treatment (P < 0.050). Those who did not receive the hot shot and were not diabetic received more DC shock (P = 0.019). The prevalence of subjects who did no need DC shock was significantly higher among male subjects who had good EF and acceptable diabetic treatment. Multiple logistic regression showed that PAC arrhythmia did not have a significant effect on receiving DC shock during CAGB [0.84 (0.25, 2.85), (P = 0.780)]. Having poor EF increased the risk of receiving DC shock among subjects by 2.81 [(1.69, 4.69), (P ≤ 0.001)] (P < 0.001). Among the diabetic subjects, receiving insulin decreased the risk of receiving DC shock by 0.54 (0.29, 0.98) (P = 0.042). CONCLUSION It was concluded that single antegrade hot shot following cold cardioplegia was not particularly effective in the CABG group. TWBC will decrease the need for DC shock. PMID:26405451

Effects of single antegrade hot shot in comparison with no hot shot administration during coronary artery bypass grafting.

PubMed

Mirmohammadsadeghi, Pouya; Mirmohammadsadeghi, Mohsen

2015-05-01

Superior results will be achieved from cardiac surgery by minimizing the effect of ischemia/reperfusion injury during cross-clamping of the aorta. Different cardioplegia solutions have been introduced, but the optimum one is still ambiguous. The aim of this study is to determine the effect of single antegrade hot shot terminal warm blood cardioplegia (TWBC) on patients who had undergone coronary artery bypass grafting (CABG). In total, 2488 patients who had CABG surgery in Sina Hospital, Isfahan, Iran, from 2003 to 2011 were enrolled in this case-control study. They were divided into two groups, those who received cold cardioplegia only and those who received a hot shot following cold cardioplegia. Demographics, and clinical data, such as; premature atrial contraction (PAC) arrhythmia, diabetes treatment, and left ventricular ejection fraction (EF), were collected and logistic regression analysis was used to analyze the data. There were significant differences found between subjects receiving antegrade hot shot based on direct current (DC) shocks, with regard to; female, EF levels, diabetes treatment (P < 0.050). Those who did not receive the hot shot and were not diabetic received more DC shock (P = 0.019). The prevalence of subjects who did no need DC shock was significantly higher among male subjects who had good EF and acceptable diabetic treatment. Multiple logistic regression showed that PAC arrhythmia did not have a significant effect on receiving DC shock during CAGB [0.84 (0.25, 2.85), (P = 0.780)]. Having poor EF increased the risk of receiving DC shock among subjects by 2.81 [(1.69, 4.69), (P ≤ 0.001)] (P < 0.001). Among the diabetic subjects, receiving insulin decreased the risk of receiving DC shock by 0.54 (0.29, 0.98) (P = 0.042). It was concluded that single antegrade hot shot following cold cardioplegia was not particularly effective in the CABG group. TWBC will decrease the need for DC shock.

Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects.

PubMed

Krösser, S; Tillner, J; Fluck, M; Ungethüm, W; Wolna, P; Kovar, A

2007-05-01

Sarizotan is a 5-HTIA receptor agonist with high affinity for D3 and D4 receptors. Here we report the pharmacokinetic and tolerability results from four Phase 1 studies. Two single-dose (5 -25 mg, n = 25, 0.5 - 5 mg, n = 16) and two multiple-dose (10 and 20 mg b.i.d., n = 30, 5 mg b.i.d., n = 12) studies with orally administered sarizotan HCl were carried out in healthy subjects. Plasma sarizotan HCl concentrations were measured using a validated HPLC method and fluorescence or MS/MS detection. Pharmacokinetic parameters were obtained using standard non-compartmental methods. Sarizotan was rapidly absorbed, group-median times to reach maximum concentration (tmax) ranged from 0.5 -2.25 h after single doses and during steady state. Maximum plasma concentration (Cmax) and tmax were slightly dependent on formulation and food intake, whereas area under the curve (AUC) was unaffected by these factors. AUC and Cmax increased dose-proportionally over the tested dose range. Independently of dose and time, sarizotan HCl plasma concentrations declined polyexponentially with a terminal elimination half-life (t1/2) of 5 - 7 h. Accumulation factors corresponded to t1/2 values, and steady state was reached within 24 h. Plasma metabolite concentrations were considerably lower than those of the parent drug. The ratio metabolite AUC : parent drug AUC was time- and dose-independent for all three metabolites suggesting that the metabolism of sarizotan is non-saturable in the tested dose range. The pharmacokinetics of sarizotan were dose-proportional and time-independent for the dose range 0.5 -25 mg). The drug was well-tolerated by healthy subjects up to a single dose of 20 mg.

Enhanced disease characterization through multi network functional normalization in fMRI.

PubMed

Çetin, Mustafa S; Khullar, Siddharth; Damaraju, Eswar; Michael, Andrew M; Baum, Stefi A; Calhoun, Vince D

2015-01-01

Conventionally, structural topology is used for spatial normalization during the pre-processing of fMRI. The co-existence of multiple intrinsic networks which can be detected in the resting brain are well-studied. Also, these networks exhibit temporal and spatial modulation during cognitive task vs. rest which shows the existence of common spatial excitation patterns between these identified networks. Previous work (Khullar et al., 2011) has shown that structural and functional data may not have direct one-to-one correspondence and functional activation patterns in a well-defined structural region can vary across subjects even for a well-defined functional task. The results of this study and the existence of the neural activity patterns in multiple networks motivates us to investigate multiple resting-state networks as a single fusion template for functional normalization for multi groups of subjects. We extend the previous approach (Khullar et al., 2011) by co-registering multi group of subjects (healthy control and schizophrenia patients) and by utilizing multiple resting-state networks (instead of just one) as a single fusion template for functional normalization. In this paper we describe the initial steps toward using multiple resting-state networks as a single fusion template for functional normalization. A simple wavelet-based image fusion approach is presented in order to evaluate the feasibility of combining multiple functional networks. Our results showed improvements in both the significance of group statistics (healthy control and schizophrenia patients) and the spatial extent of activation when a multiple resting-state network applied as a single fusion template for functional normalization after the conventional structural normalization. Also, our results provided evidence that the improvement in significance of group statistics lead to better accuracy results for classification of healthy controls and schizophrenia patients.

Predictive parameters for return to pre-injury level of sport 6 months following anterior cruciate ligament reconstruction surgery.

PubMed

Müller, Ulrike; Krüger-Franke, Michael; Schmidt, Michael; Rosemeyer, Bernd

2015-12-01

The aim of the study was to find predictive parameters for a successful resumption of pre-injury level of sport 6 months post anterior cruciate ligament (ACL) reconstruction. In a prospective study, 40 patients with a ruptured ACL were surgically treated with semitendinosus tendon autograft. Six months after surgery, strength of knee extensors and flexors, four single-leg hop tests, Anterior Cruciate Ligament-Return to Sport after Injury Scale (ACL-RSI), subjective International Knee Documentation Committee (IKDC) 2000 and the Tampa Scale of Kinesiophobia-11 (TSK-11) were assessed. Seven months post-operatively, a standardized interview was conducted to identify "return to sport" (RS) and "non-return to sport" (nRS) patients. Logistic regression and "Receiver Operating Characteristic" (ROC) analyses were used to determine predictive parameters. No significant differences could be detected between RS and nRS patients concerning socio-demographic data, muscle tests, square hop and TSK-11. In nRS patients, the Limb Symmetry Index (LSI) of single hop for distance (p = 0.005), crossover hop (p = 0.008) and triple hop (p = 0.001) were significantly lower, in addition to the ACL-RSI (p = 0.013) and IKDC 2000 (p = 0.037). The cut-off points for LSI single hop for distance were 75.4 % (sensitivity 0.74; specificity 0.88), and for ACL-RSI 51.3 points (sensitivity 0.97; specificity 0.63). Logistic regression distinguished between RS and nRS subjects (sensitivity 0.97; specificity 0.63). The single hop for distance and ACL-RSI were found to be the strongest predictive parameters, assessing both the objective functional and the subjective psychological aspects of returning to sport. Both tests may help to identify patients at risk of not returning to pre-injury sport. II.

Monitoring driver fatigue using a single-channel electroencephalographic device: A validation study by gaze-based, driving performance, and subjective data.

PubMed

Morales, José M; Díaz-Piedra, Carolina; Rieiro, Héctor; Roca-González, Joaquín; Romero, Samuel; Catena, Andrés; Fuentes, Luis J; Di Stasi, Leandro L

2017-12-01

Driver fatigue can impair performance as much as alcohol does. It is the most important road safety concern, causing thousands of accidents and fatalities every year. Thanks to technological developments, wearable, single-channel EEG devices are now getting considerable attention as fatigue monitors, as they could help drivers to assess their own levels of fatigue and, therefore, prevent the deterioration of performance. However, the few studies that have used single-channel EEG devices to investigate the physiological effects of driver fatigue have had inconsistent results, and the question of whether we can monitor driver fatigue reliably with these EEG devices remains open. Here, we assessed the validity of a single-channel EEG device (TGAM-based chip) to monitor changes in mental state (from alertness to fatigue). Fifteen drivers performed a 2-h simulated driving task while we recorded, simultaneously, their prefrontal brain activity and saccadic velocity. We used saccadic velocity as the reference index of fatigue. We also collected subjective ratings of alertness and fatigue, as well as driving performance. We found that the power spectra of the delta EEG band showed an inverted U-shaped quadratic trend (EEG power spectra increased for the first hour and half, and decreased during the last thirty minutes), while the power spectra of the beta band linearly increased as the driving session progressed. Coherently, saccadic velocity linearly decreased and speeding time increased, suggesting a clear effect of fatigue. Subjective data corroborated these conclusions. Overall, our results suggest that the TGAM-based chip EEG device is able to detect changes in mental state while performing a complex and dynamic everyday task as driving. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacokinetics, safety and tolerability of mipomersen in healthy Japanese volunteers and comparison with Western subjects.

PubMed

Li, Zhaoyang; Hard, Marjie L; Andersen, Grit; Pabst, Günther; Wagener, Gilbert; Singh, Tejdip; Chin, Wai; Culm-Merdek, Kerry; Boltje, Ingrid; von Moltke, Lisa L

2014-04-01

To characterize the safety, tolerability, pharmacokinetics (PK) and dose proportionality of mipomersen after single subcutaneous (SC) administration to Japanese healthy subjects; and to compare the PK profiles of Japanese and Western subjects. 20 healthy first-generation Japanese male subjects were enrolled into one of three treatment cohorts (50, 100 and 200 mg SC) in a dose-escalation design. Within each cohort, subjects were randomized in a 4 : 1 ratio to receive mipomersen or placebo. Mipomersen was absorbed rapidly after SC administration; median tmax varied between 2 and 3 hours. After reaching peak levels, plasma concentrations of mipomersen decayed multiphasically with an initial distribution t1/2 in several hours and a terminal t1/2 of 261 - 393 hours. Mean Cmax increased in a dose-linear manner while all mean AUC from time 0 to different cut points increased slightly more than dose proportionally. Although mean terminal t1/2 varied in the dose range tested, it did not show dose-dependence. The PK profiles of mipomersen in Japanese subjects are similar to those observed in Western subjects. A single SC dose of 50 mg, 100 mg and 200 mg mipomersen was well tolerated by male Japanese subjects. Single SC doses of 50 - 200 mg were safe and well tolerated when administered to Japanese subjects. Comparison of PK between Japanese and Western subjects does not support any need for dose adjustment in Japanese population in future clinical development.

75 FR 9247 - Single Family Mortgage Insurance Premium, Single Family

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-01

... is soliciting public comments on the subject proposal. Lenders use the Single Family Premium... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5376-N-13] Single Family Mortgage Insurance Premium, Single Family AGENCY: Office of the Chief Information Officer, HUD. ACTION: Notice...

Leg kinematics and kinetics in landing from a single-leg hop for distance. A comparison between dominant and non-dominant leg.

PubMed

van der Harst, J J; Gokeler, A; Hof, A L

2007-07-01

Anterior cruciate ligament (ACL) deficiency can be a major problem for athletes and subsequent reconstruction of the ACL may be indicated if a conservative regimen has failed. After ACL reconstruction signs of abnormality in the use of the leg remain for a long time. It is expected that the landing after a single-leg hop for distance (horizontal hop) might give insight in the differences in kinematics and kinetics between uninjured legs and ACL-reconstructed legs. Before the ACL-reconstructed leg can be compared with the contralateral leg, knowledge of differences between legs of uninjured subjects is needed. Kinematic and kinetic variables of both legs were measured with an optoelectronic system and a force plate and calculated by inverse dynamics. The dominant leg (the leg with biggest horizontal hop distance) and the contralateral leg of nine uninjured subjects were compared. No significant differences were found in most of the kinematic and kinetic variables between dominant leg and contralateral leg of uninjured subjects. Only hop distance and hip extension angles differed significantly. This study suggests that there are no important differences between dominant leg and contralateral leg in healthy subjects. As a consequence, the uninvolved leg of ACL-reconstructed patients can be used as a reference. The observed variables of this study can be used as a reference of normal values and normal differences between legs in healthy subjects.

The effects of single-session music therapy interventions on the observed and self-reported levels of pain control, physical comfort, and relaxation of hospice patients.

PubMed

Krout, R E

2001-01-01

This article describes the process and results of a three-month music therapy clinical effectiveness study conducted with terminally ill patients. The purpose of this study was to quantify and evaluate the effectiveness of single-session music therapy interventions with hospice patients in three patient problem areas: pain control; physical comfort; and relaxation. Data from a total of 90 sessions conducted with a total of 80 subjects served by Hospice of Palm Beach County, Florida, were included in the study. Music therapy services were provided by five board-certified music therapists and one music therapist eligible for board certification. The subjects in this study were receiving regularly scheduled music therapy services from the hospice organization. The study used both behavioral observation and subject's self-reporting as methods of data reporting and recording. Subjects were observed for, or self-reported, their levels of pain control, physical comfort, and relaxation, both before and after each music therapy session. The subjects were served in the environments where music therapy services would normally be delivered (i.e., home, hospital, nursing home, or inpatient acute-care unit of the hospice organization). Music therapy services included live active and passive music-based experiences. These were designed to build and to establish rapport with patient or family, to facilitate family interaction and patient control, to provide support and comfort, to facilitate relaxation, to enable reminiscence and life review, to provide a frame-work for spiritual exploration and validation, and to encourage the identification and expression of feelings of anticipatory mourning and grief. A total of six hypotheses stated that there would be significant pre- to postsession differences in each of the three variables: pain control, physical comfort, and relaxation, as measured during two different session and data collection scenarios. These scenarios included the independent observation and recording of the three subject variables and the subject's self-report of each variable. Reliability correlation coefficients were calculated for each of the different session and data-collection scenarios to help assess the correlation between primary and reliability observers. Pearson product moment correlations indicated reliability agreement coefficients of r = .85 and r = .90. One-tailed t-tests were performed on the collected data for subject pain control, physical comfort, and relaxation. Results of the t-tests were significant at the p < or = .001 (for observed pain control, physical comfort, and relaxation) and p < or = 005 (for self-reported pain control, physical comfort, and relaxation) levels. These results suggest that single-session music therapy interventions appear to be effective in increasing subject pain control, physical comfort, and relaxation during both data collection scenarios. Based on the results of these tests of the analyzed data, the hypotheses were all accepted. Tables illustrate pre- to post-session changes in levels of all three variables from both session and data-collection scenarios. Copies of the data-collection forms are also included in the Appendix. The discussion section addresses limitations of this study and suggestions for future studies.

Drug Delivery and Transport into the Central Circulation: An Example of Zero-Order In vivo Absorption of Rotigotine from a Transdermal Patch Formulation.

PubMed

Cawello, Willi; Braun, Marina; Andreas, Jens-Otto

2018-01-13

Pharmacokinetic studies using deconvolution methods and non-compartmental analysis to model clinical absorption of drugs are not well represented in the literature. The purpose of this research was (1) to define the system of equations for description of rotigotine (a dopamine receptor agonist delivered via a transdermal patch) absorption based on a pharmacokinetic model and (2) to describe the kinetics of rotigotine disposition after single and multiple dosing. The kinetics of drug disposition was evaluated based on rotigotine plasma concentration data from three phase 1 trials. In two trials, rotigotine was administered via a single patch over 24 h in healthy subjects. In a third trial, rotigotine was administered once daily over 1 month in subjects with early-stage Parkinson's disease (PD). A pharmacokinetic model utilizing deconvolution methods was developed to describe the relationship between drug release from the patch and plasma concentrations. Plasma-concentration over time profiles were modeled based on a one-compartment model with a time lag, a zero-order input (describing a constant absorption via skin into central circulation) and first-order elimination. Corresponding mathematical models for single- and multiple-dose administration were developed. After single-dose administration of rotigotine patches (using 2, 4 or 8 mg/day) in healthy subjects, a constant in vivo absorption was present after a minor time lag (2-3 h). On days 27 and 30 of the multiple-dose study in patients with PD, absorption was constant during patch-on periods and resembled zero-order kinetics. Deconvolution based on rotigotine pharmacokinetic profiles after single- or multiple-dose administration of the once-daily patch demonstrated that in vivo absorption of rotigotine showed constant input through the skin into the central circulation (resembling zero-order kinetics). Continuous absorption through the skin is a basis for stable drug exposure.

Effects of low to moderate acute doses of pramipexole on impulsivity and cognition in healthy volunteers.

PubMed

Hamidovic, Ajna; Kang, Un Jung; de Wit, Harriet

2008-02-01

The neurotransmitter dopamine is integrally involved in the rewarding effects of drugs, and it has also been thought to mediate impulsive behaviors in animal models. Most of the studies of drug effects on impulsive behaviors in humans have involved drugs with complex actions on different transmitter systems and different receptor subtypes. The present study was designed to characterize the effect of single doses of pramipexole, a D2/D3 agonist, on measures of cognitive and impulsive behavior, as well as on mood in healthy volunteers. Healthy men and women (N = 10) received placebo and 2 doses of pramipexole, 0.25 and 0.50 mg, in a within-subject, double-blinded study. Outcome measures included changes in cognitive performance, assessed by the Automated Neuropsychological Assessment Metrics, several behavioral measures related to impulsive behavior, including the Balloon Analogue Risk Task, Delay Discounting Task, Go/No-Go Task, Card Perseveration Task, and subjective ratings of mood assessed by Addiction Research Center Inventory, Profile of Mood States, and Drug Effects Questionnaire. Pramipexole decreased positive ratings of mood (euphoria, intellectual efficiency, and energy) and increased both subjectively reported sedation and behavioral sedation indicated by impaired cognitive performance on several measures of the Automated Neuropsychological Assessment Metrics. Single low to medium doses of this drug did not produce a decrease in impulsive responding on behavioral measures included in this study. The sedative-like effects observed in this study may reflect presynaptic actions of the drug. Higher doses with postsynaptic actions may be needed to produce either behavioral or subjective stimulant-like effects.

78 FR 46994 - Proposed Collection; 60-Day Comment Request: National Institute of Mental Health Recruitment and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... Project Clearance Liaison, Science Policy and Evaluation Branch, OSPPC, NIMH, NIH, Neuroscience Center... NIMH-sponsored clinical research studies that plan to enroll 150 or more human subjects in a single study. Clinical studies can have difficulty recruiting, and accurate and timely reporting is the best...

Systematic review of communication partner training in aphasia: methodological quality.

PubMed

Cherney, Leora R; Simmons-Mackie, Nina; Raymer, Anastasia; Armstrong, Elizabeth; Holland, Audrey

2013-10-01

Twenty-three studies identified from a previous systematic review examining the effects of communication partner training on persons with aphasia and their communication partners were evaluated for methodological quality. Two reviewers rated the studies on defined methodological quality criteria relevant to each study design. There were 11 group studies, seven single-subject participant design studies, and five qualitative studies. Quality scores were derived for each study. The mean inter-rater reliability of scores for each study design ranged from 85-93%, with Cohen's Kappa indicating substantial agreement between raters. Methodological quality of research on communication partner training in aphasia was highly varied. Overall, group studies employed the least rigorous methodology as compared to single subject and qualitative research. Only two of 11 group studies complied with more than half of the quality criteria. No group studies reported therapist blinding and only one group study reported participant blinding. Across all types of studies, the criterion of treatment fidelity was most commonly omitted. Failure to explicitly report certain methodological quality criteria may account for low ratings. Using methodological rating scales specific to the type of study design may help improve the methodological quality of aphasia treatment studies, including those on communication partner training.

Functional Assessment of the Vanderbilt Multigrasp Myoelectric Hand: A Continuing Case Study

PubMed Central

Dalley, Skyler A.; Bennett, Daniel A.; Goldfarb, Michael

2015-01-01

This paper presents a case study involving the functional assessment of the Vanderbilt Multigrasp (VMG) hand prosthesis on a single transradial amputee subject. In particular, a transradial amputee subject performed the Southampton Hand Assessment Procedure (SHAP) using the hand prosthesis and multigrasp myoelectric controller in a series of experimental sessions occurring over a multi-week time span. The subject’s index of function (IoF) improved with each session, although essentially plateaued after the fourth session, resulting in a IoF score of 87, which compares favorably to SHAP scores published in previous studies. PMID:25571412

Acute and Chronic Noradrenergic Effects on Cortical Excitability in Healthy Humans

PubMed Central

Kuo, Hsiao-I; Paulus, Walter; Batsikadze, Giorgi; Jamil, Asif; Kuo, Min-Fang

2017-01-01

Abstract Background Noradrenaline is a major neuromodulator in the central nervous system, and it is involved in the pathophysiology of diverse neuropsychiatric diseases. Previous transcranial magnetic stimulation studies suggested that acute application of selective noradrenaline reuptake inhibitors enhances cortical excitability in the human brain. However, other, such like clinical effects, usually require prolonged noradrenaline reuptake inhibitor treatment, which might go along with different physiological effects. Methods The purpose of this study was to investigate the acute and chronic effects of the selective noradrenaline reuptake inhibitor reboxetine on cortical excitability in healthy humans in a double-blind, placebo-controlled, randomized crossover study. Sixteen subjects were assessed with different transcranial magnetic stimulation measurements: motor thresholds, input-output curve, short-latency intracortical inhibition and intracortical facilitation, I-wave facilitation, and short-interval afferent inhibition before and after placebo or reboxetine (8 mg) single-dose administration. Afterwards, the same subjects took reboxetine (8 mg/d) consecutively for 21 days. During this period (subjects underwent 2 experimental sessions with identical transcranial magnetic stimulation measures under placebo or reboxetine), transcranial magnetic stimulation measurements were assessed before and after drug intake. Results Both single-dose and chronic administration of reboxetine increased cortical excitability; increased the slope of the input-output curve, intracortical facilitation, and I-wave facilitation; but decreased short-latency intracortical inhibition and short-interval afferent inhibition. Moreover, chronic reboxetine showed a larger enhancement of intracortical facilitation and I-wave facilitation compared with single-dose application. Conclusions The results show physiological mechanisms of noradrenergic enhancement possibly underlying the functional effects of reboxetine regarding acute and chronic application. PMID:28430976

Predictors of subjective health status 10 years post-PCI.

PubMed

van den Berge, Jan C; Dulfer, Karolijn; Utens, Elisabeth M W J; Hartman, Eline M J; Daemen, Joost; van Geuns, Robert J; van Domburg, Ron T

2016-06-01

Subjective health status is an increasingly important parameter to assess the effect of percutaneous coronary intervention (PCI) in clinical practice. Aim of this study was to determine medical and psychosocial predictors of poor subjective health status over a 10 years' post-PCI period. We included a series of consecutive PCI patients (n = 573) as part of the RESEARCH registry, a Dutch single-center retrospective cohort study. These patients completed the 36-item Short-Form Health Survey (SF-36) at baseline and 10 years post-PCI. We found 6 predictors of poor subjective health status 10 years post-PCI: SF-36 at baseline, age, previous PCI, obesity, acute myocardial infarction as indication for PCI, and diabetes mellitus (arranged from most to least numbers of sub domains). SF-36 scores at baseline, age, and previous PCI were significant predictors of subjective health status 10 years post-PCI. Specifically, the SF-36 score at baseline was an important predictor. Thus assessment of subjective health status at baseline is useful as an indicator to predict long-term subjective health status. Subjective health status becomes better by optimal medical treatment, cardiac rehabilitation and psychosocial support. This is the first study determining predictors of subjective health status 10 years post-PCI.

Fitting a single-phase model to the post-exercise changes in heart rate and oxygen uptake.

PubMed

Stupnicki, R; Gabryś, T; Szmatlan-Gabryś, U; Tomaszewski, P

2010-01-01

The kinetics of post-exercise heart rate (HR) and oxygen consumption (EPOC) was studied in 10 elite cyclists subjected to four laboratory cycle ergometer maximal exercises lasting 30, 90, 180 or 360 s. Heart rate and oxygen uptake (VO2) were recorded over a period of 6 min after the exercise. By applying the logit transformation to the recorded variables and relating them to the decimal logarithm of the recovery time, uniform single-phase courses of changes were shown for both variables in all subjects and exercises. This enabled computing half-recovery times (t(1/2)) for both variables. Half-time for VO2 negatively correlated with square root of exercise duration (within-subject r = -0.629, p < 0.001), the total post-exercise oxygen uptake till t(1/2) was thus constant irrespectively of exercise intensity. The method is simple and enables reliable comparisons of various modes of exercise with respect to the rate of recovery.

The acute effects of ethanol on acetanilide disposition in normal subjects, and in patients with liver disease.

PubMed Central

McKay, J; Rawlings, M D; Cobden, I; James, O F

1982-01-01

1 The effects of single doses (25 g and 50 g) oral ethanol on the disposition of acetanilide (50 mg/kg metabolic active mass) has been studied in normal subjects, and in patients with chronic non-alcoholic liver disease. 2 In normal subjects, ethanol produced a dose-dependent increase in acetanilide half-life, and a decrease in acetenilide clearance. There was a significant correlation (rs = 0.71, P less than 0.01) between the 90 min blood ethanol concentration and the reduction in acetanilide clearance. 3 In patients with liver disease, ethanol produced a similar proportional change in acetanilide half-life and clearance, but these were less consistent. Moreover, liver disease itself was associated with an increase in acetenilide half-life, and a reduction in clearance. 4 It is concluded that single oral doses of ethanol, comparable to those consumed during social drinking, may inhibit some forms of microsomal oxidation and thus have important clinical implications. PMID:7138735

The acute effects of ethanol on acetanilide disposition in normal subjects, and in patients with liver disease.

PubMed

McKay, J; Rawlings, M D; Cobden, I; James, O F

1982-10-01

1 The effects of single doses (25 g and 50 g) oral ethanol on the disposition of acetanilide (50 mg/kg metabolic active mass) has been studied in normal subjects, and in patients with chronic non-alcoholic liver disease. 2 In normal subjects, ethanol produced a dose-dependent increase in acetanilide half-life, and a decrease in acetenilide clearance. There was a significant correlation (rs = 0.71, P less than 0.01) between the 90 min blood ethanol concentration and the reduction in acetanilide clearance. 3 In patients with liver disease, ethanol produced a similar proportional change in acetanilide half-life and clearance, but these were less consistent. Moreover, liver disease itself was associated with an increase in acetenilide half-life, and a reduction in clearance. 4 It is concluded that single oral doses of ethanol, comparable to those consumed during social drinking, may inhibit some forms of microsomal oxidation and thus have important clinical implications.

Cerebral blood flow changes during sodium-lactate-induced panic attacks

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

Stewart, R.S.; Devous, M.D. Sr.; Rush, A.J.

1988-04-01

Dynamic single-photon emission computed axial tomography (CAT) with inhaled xenon-133 was used to measure regional cerebral blood flow in 10 drug-free patients with DSM-III-diagnosed panic disorder and in five normal control subjects. All subjects underwent regional cerebral blood flow studies while at rest or during normal saline infusion and during sodium lactate infusion. Six of the 10 patients and none of the control subjects experienced lactate-induced panic attacks. Lactate infusion markedly raised hemispheric blood flow levels in both control subjects and patients who did not panic. Patients who did panic experienced either a minimal increase or a decrease in hemisphericmore » blood flow.« less

Performance and brain electrical activity during prolonged confinement.

PubMed

Lorenz, B; Lorenz, J; Manzey, D

1996-01-01

A subset of the AGARD-STRES battery including memory search, unstable tracking, and a combination of both tasks (dual-task), was applied repeatedly to the four chamber crew members before, during, and after the 60-day isolation period of EXEMSI. Five ground control group members served as a control group. A subjective state questionnaire was also included. The results were subjected to a quantitative single-subject analysis. Electroencephalograms (EEG) were recorded to permit correlation of changes in task performance with changes in the physiological state. Evaluation of the EEG focused on spectral parameters of spontaneous EEG waves. No physiological data were collected from the control group. Significant decrements in tracking ability were observed in the chamber crew. The time course of these effects followed a triphasic pattern with initial deterioration, intermediate recovery to pre-isolation baseline scores after the first half of the isolation period, and a second deterioration towards the end. None of the control group subjects displayed such an effect. Memory search (speed and accuracy) was only occasionally impaired during isolation, but the control group displayed a similar pattern of changes. It is suggested that a state of decreased alertness causes tracking deterioration, which leads to a reduced efficiency of sustained cue utilization. The assumption of low alertness was further substantiated by higher fatigue ratings by the chamber crew compared to those of the control group. Analysis of the continuous EEG recordings revealed that only two subjects produced reliable alpha wave activity (8-12 Hz) over Pz and, to a much smaller extent, Fz-theta wave activity (5-7 Hz) during task performance. In both subjects Pz-alpha power decreased consistently under task conditions involving single-task and dual-task tracking. Fz-theta activity was increased more by single-task and dual-task memory search than by single-task tracking. The alpha attenuation appears to be associated with an increasing demand on perceptual cue utilization required by the tracking performance. In one subject marked attenuation of alpha power occurred during the first half of the confinement period, where he also scored the highest fatigue ratings. A striking increase in fronto-central theta activity was observed in the same subject after six weeks of isolation. The change was associated with an efficient rather than a degraded task performance, and a high rating of the item "concentrated" and a low rating of the item "fatigued." This finding supports the hypothesis that the activation state associated with increased fronto-central theta activity accompanies efficient performance of demanding mental tasks. The usefulness of standardized laboratory tasks as monitoring instruments is demonstrated by the direct comparability with results of studies obtained from other relevant research applications using the same tasks. The feasibility of a self-administered integrated psychophysiological assessment of the individual state was illustrated by the nearly complete collection of data. The large number of individual data collected over the entire period permitted application of quantitative single-subject analysis, allowing reliable determination of changes in the individual state in the course of time. It thus appears that this assessment technique can be adapted for in-flight monitoring of astronauts during prolonged spaceflights. Parallel EEG recording can provide relevant supplementary information for diagnosing the individual activation state associated with task performance. The existence of large individual differences in the generation of task-sensitive EEG rhythms forms an important issue for further studies.

Comparison of fMRI paradigms assessing visuospatial processing: Robustness and reproducibility

PubMed Central

Herholz, Peer; Zimmermann, Kristin M.; Westermann, Stefan; Frässle, Stefan; Jansen, Andreas

2017-01-01

The development of brain imaging techniques, in particular functional magnetic resonance imaging (fMRI), made it possible to non-invasively study the hemispheric lateralization of cognitive brain functions in large cohorts. Comprehensive models of hemispheric lateralization are, however, still missing and should not only account for the hemispheric specialization of individual brain functions, but also for the interactions among different lateralized cognitive processes (e.g., language and visuospatial processing). This calls for robust and reliable paradigms to study hemispheric lateralization for various cognitive functions. While numerous reliable imaging paradigms have been developed for language, which represents the most prominent left-lateralized brain function, the reliability of imaging paradigms investigating typically right-lateralized brain functions, such as visuospatial processing, has received comparatively less attention. In the present study, we aimed to establish an fMRI paradigm that robustly and reliably identifies right-hemispheric activation evoked by visuospatial processing in individual subjects. In a first study, we therefore compared three frequently used paradigms for assessing visuospatial processing and evaluated their utility to robustly detect right-lateralized brain activity on a single-subject level. In a second study, we then assessed the test-retest reliability of the so-called Landmark task–the paradigm that yielded the most robust results in study 1. At the single-voxel level, we found poor reliability of the brain activation underlying visuospatial attention. This suggests that poor signal-to-noise ratios can become a limiting factor for test-retest reliability. This represents a common detriment of fMRI paradigms investigating visuospatial attention in general and therefore highlights the need for careful considerations of both the possibilities and limitations of the respective fMRI paradigm–in particular, when being interested in effects at the single-voxel level. Notably, however, when focusing on the reliability of measures of hemispheric lateralization (which was the main goal of study 2), we show that hemispheric dominance (quantified by the lateralization index, LI, with |LI| >0.4) of the evoked activation could be robustly determined in more than 62% and, if considering only two categories (i.e., left, right), in more than 93% of our subjects. Furthermore, the reliability of the lateralization strength (LI) was “fair” to “good”. In conclusion, our results suggest that the degree of right-hemispheric dominance during visuospatial processing can be reliably determined using the Landmark task, both at the group and single-subject level, while at the same time stressing the need for future refinements of experimental paradigms and more sophisticated fMRI data acquisition techniques. PMID:29059201

The effect of labetalol and propranolol on the pressor response to sexual arousal in women.

PubMed Central

Riley, A J; Riley, E J

1981-01-01

1 The effect of a single oral dose of labetalol (100 mg), propranolol (80 mg) and placebo on the pressor response to sexual autostimulation has been studied in six female volunteers. 2 Labetalol but not propranolol significantly reduced the increase in blood pressure that occurred at orgasm. 3 The subjective features of the sexual response were assessed by each subject using visual analogue scales. 4 Subjects reported a significant reduction in vaginal lubrication with labetalol compared to both placebo and propranolol. 5 No other effects were noted. PMID:7295463

Transferring and generalizing deep-learning-based neural encoding models across subjects.

PubMed

Wen, Haiguang; Shi, Junxing; Chen, Wei; Liu, Zhongming

2018-08-01

Recent studies have shown the value of using deep learning models for mapping and characterizing how the brain represents and organizes information for natural vision. However, modeling the relationship between deep learning models and the brain (or encoding models), requires measuring cortical responses to large and diverse sets of natural visual stimuli from single subjects. This requirement limits prior studies to few subjects, making it difficult to generalize findings across subjects or for a population. In this study, we developed new methods to transfer and generalize encoding models across subjects. To train encoding models specific to a target subject, the models trained for other subjects were used as the prior models and were refined efficiently using Bayesian inference with a limited amount of data from the target subject. To train encoding models for a population, the models were progressively trained and updated with incremental data from different subjects. For the proof of principle, we applied these methods to functional magnetic resonance imaging (fMRI) data from three subjects watching tens of hours of naturalistic videos, while a deep residual neural network driven by image recognition was used to model visual cortical processing. Results demonstrate that the methods developed herein provide an efficient and effective strategy to establish both subject-specific and population-wide predictive models of cortical representations of high-dimensional and hierarchical visual features. Copyright © 2018 Elsevier Inc. All rights reserved.

Single visit nonsurgical endodontic therapy for periapical cysts: A clinical study

PubMed Central

Maity, Ipsita; Meena, N.; Kumari, R. Anitha

2014-01-01

Aims: The aim of this study was to assess the outcome of single sitting root canal treatment (RCT) of asymptomatic teeth with periapical cysts. Materials and Methods: Ten maxillary anterior teeth showing periapical lesion on the radiograph was further screened by ultrasound with color power Doppler (CPD) for confirmation of a cyst. The average dimension of the lesions ranged from 1.3 to 1.9 cm. Single sitting RCT was performed on all the selected teeth. Postoperative healing was monitored at regular interval of 3 months, 6 months, and 1 year by using subjective feedback, radiograph, and ultrasound with CPD study. Results: Eight among the ten cases showed either signs of complete healing or healing in progress by the end of 6-12 months. Conclusions: It was observed that single sitting nonsurgical endodontic management of asymptomatic teeth with periapical cyst confirmed by ultrasound was successful in selected cases. PMID:24963246

Single visit nonsurgical endodontic therapy for periapical cysts: A clinical study.

PubMed

Maity, Ipsita; Meena, N; Kumari, R Anitha

2014-04-01

The aim of this study was to assess the outcome of single sitting root canal treatment (RCT) of asymptomatic teeth with periapical cysts. Ten maxillary anterior teeth showing periapical lesion on the radiograph was further screened by ultrasound with color power Doppler (CPD) for confirmation of a cyst. The average dimension of the lesions ranged from 1.3 to 1.9 cm. Single sitting RCT was performed on all the selected teeth. Postoperative healing was monitored at regular interval of 3 months, 6 months, and 1 year by using subjective feedback, radiograph, and ultrasound with CPD study. Eight among the ten cases showed either signs of complete healing or healing in progress by the end of 6-12 months. It was observed that single sitting nonsurgical endodontic management of asymptomatic teeth with periapical cyst confirmed by ultrasound was successful in selected cases.

Continuous Classroom Assessment at Primary Level

ERIC Educational Resources Information Center

Ali, Imtiaz; Shah, Syed Manzoor Hussein; Gujjar, Aijaz Ahmed

2014-01-01

This study was designed to analyze the continuous classroom assessment at primary level in Pakistan. Findings of the study revealed that the students' achievement of single class teacher in the subject of English, General science, Urdu and mathematics were almost on average and rubric observation during continuous classroom assessment ranked…

The Long Game: Five Years of Simulating the Middle East

ERIC Educational Resources Information Center

Hardy, Mat; Totman, Sally

2017-01-01

Scholarly literature attesting to the benefits of role play in teaching international relations or political science subjects is abundant and universally positive. However, despite many case studies presenting snapshots of single examples, long term data concerning a role play exercise is difficult to find. This study presents student feedback…

Vitamin concentrations in human milk vary with time within feed, circadian rhythm, and single-dose supplementation

USDA-ARS?s Scientific Manuscript database

Importance: Human milk is the subject of many nutrition studies but methods for representative sample collection are not established. Our recently improved, validated methods for analyzing micronutrients in human milk now enable systematic study of factors affecting their concentration. Objective...

The Experimental Study of Cultural Transmission: A Pilot Study on When and Who People Copy

DTIC Science & Technology

2012-08-01

Shepard & Metzler [49], and allows trials of different difficulty to be generated. In each trial, subjects received a single visual presentation of an...and the Evolutionary Process. Chicago University Press: Chicago . Cavalli-Sforza LL, Feldman MW. 1981. Cultural Transmission and Evolution : A

AAC Interventions for Autism: A Research Summary

ERIC Educational Resources Information Center

Nunes, Debora R. P.

2008-01-01

Fifty-six studies from 1980 to 2007 involving the use of augmentative and alternative communication (AAC) by individuals with autism were reviewed. The majority of the studies used single-subject research designs and emphasized language production skills. Many investigations were held in artificial language learning settings, and a few involved…

Implementation of Apple's iPad as an Instructional Tool in the Elementary Language Arts Classroom: A Phenomenological Case Study

ERIC Educational Resources Information Center

Kolarcik, Tiffany Nicole

2013-01-01

This study explored how elementary educators implement iPad devices as instructional tools to enhance their language arts instruction. The study used a phenomenological qualitative design with a single-subject case study design coupled with an embedded rubric component. The researcher conducted in-depth, semi-structured interviews, classroom…

Effects of listening to pleasant music on chronic unilateral neglect: a single-subject study.

PubMed

Tsai, Pei-Luen; Chen, Mei-Ching; Huang, Yu-Ting; Lin, Keh-Chung

2013-01-01

Recent studies suggest that the positive emotion induced by pleasant music may improve cognitive functions. We used the single-subject design to study whether listening to preferred music may reduce unilateral neglect in two participants with post-stroke neglect. These participants were instructed to listen to their preferred music every day for 5 weeks, followed by 2 weeks of follow-up assessment. Outcome measures involved the Star Cancellation Test, the Line Bisection Test, and the visual exploration task. A combination of visual analysis and the two-standard-deviation band method was used for data analysis. Both participants showed significant intervention-related improvements on all outcome measures except the Line Bisection Test, on which one participant showed no improvement. The therapeutic effects were maintained during the follow-up phase. The findings suggest that positive emotion, evoked by preferred music, may be used to ameliorate unilateral neglect. Further research using controlled trials is warranted to validate the findings.

Bayesian model reduction and empirical Bayes for group (DCM) studies

PubMed Central

Friston, Karl J.; Litvak, Vladimir; Oswal, Ashwini; Razi, Adeel; Stephan, Klaas E.; van Wijk, Bernadette C.M.; Ziegler, Gabriel; Zeidman, Peter

2016-01-01

This technical note describes some Bayesian procedures for the analysis of group studies that use nonlinear models at the first (within-subject) level – e.g., dynamic causal models – and linear models at subsequent (between-subject) levels. Its focus is on using Bayesian model reduction to finesse the inversion of multiple models of a single dataset or a single (hierarchical or empirical Bayes) model of multiple datasets. These applications of Bayesian model reduction allow one to consider parametric random effects and make inferences about group effects very efficiently (in a few seconds). We provide the relatively straightforward theoretical background to these procedures and illustrate their application using a worked example. This example uses a simulated mismatch negativity study of schizophrenia. We illustrate the robustness of Bayesian model reduction to violations of the (commonly used) Laplace assumption in dynamic causal modelling and show how its recursive application can facilitate both classical and Bayesian inference about group differences. Finally, we consider the application of these empirical Bayesian procedures to classification and prediction. PMID:26569570

Cybernetics and Rhetoric: Freshman English in an Overdetermined World

ERIC Educational Resources Information Center

Comprone, Joseph

1975-01-01

Argues that freshman composition courses should incorporate the study of communications systems (Cybernetics) and the idea that a situation or subject cannot be explained by a single series of logical steps (Overdetermination) as part of their rationale. (RB)

Bioavailability of two oral-tablet and two oral-suspension formulations of naproxen sodium/paracetamol (acetaminophen): single-dose, randomized, open-label, two-period crossover comparisons in healthy Mexican adult subjects.

PubMed

Palma-Aguirre, Jose Antonio; Villalpando-Hernández, Jorge; Novoa-Heckel, Germán; Oliva, Iván; Cariño, Lizbeth; López-Bojórquez, Ericka; Burke-Fraga, Victoria; Namur, Salvador; González-de la Parra, Mario

2009-02-01

Naproxen sodium/paracetamol (acetaminophen) is a combination for the treatment of symptomatic pain and fever marketed both as a prescription and an over-the-counter product in Mexico. The aim of these 2 studies was to compare the bioavailability and to determine the bioequivalence of 2 test formulations (an oral-tablet formulation containing the combination of naproxen sodium/paracetamol 275/300 mg and an oral-suspension formulation containing the combination of naproxen sodium/paracetamol 375/300 mg per 15 mL) with their corresponding listed reference-drug formulations in Mexico (a list issued by Mexican health authorities). Two separate, single-dose, randomized, open-label, 2-period crossover, postmarketing studies were conducted. For each study, a different set of eligible subjects was selected comprising healthy Mexican adults of either sex, and subjects were randomly assigned to receive 1 test formulation of the combination of naproxen sodium/paracetamol followed by the corresponding reference-drug formulation, or vice versa, with a 1-week washout period between doses. After a 12-hour overnight fast, subjects received a single dose of naproxen sodium/paracetamol 275/300-mg tablet or naproxen sodium/paracetamol 375/300 mg per 15 mL suspension, depending on the study. For the analysis of pharmacokinetic parameters, including C(max), AUC from time 0 (baseline) to 48 hours (AUC(0-48)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and at 0.16, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours after administration. The formulations were considered bioequivalent if the geometric mean ratios (test/reference) of the C(max) and AUC were within the predetermined range of 80% to 125%. Tolerability was determined by clinical assessment, monitoring vital signs, laboratory analysis results, and subject interviews regarding adverse events. A total of 26 subjects (15 men, 11 women; mean [SD] age, 29 [8] years [range, 20-50 years]; weight, 63.1 [9] kg [range, 51.4-84.4 kg]; height, 164 [9] cm [range, 149-179 cm]; and body mass index [BMI], 23.53 [2.18] kg/m(2) [range, 18.54-26.82 kg/m(2)]) were enrolled to receive the suspension-dosage formulation; 13 subjects received the suspension-test formulation first. A total of 26 subjects (13 men, 13 women; mean [SD] age, 29 [8] years [range, 18-43 years]; weight, 64.3 [7.7] kg [range, 50.6-80.7 kg]; height, 165 [9] cm [range, 151-181 cm]; and BMI, 23.64 [2.43] kg/m(2) [range, 18.02-26.42 kg/m(2)]) were enrolled to receive the tablet-dosage formulation; 13 subjects received the tablet-test formulation first. No significant period or sequence effects were detected based on analysis of variance. For the suspension-dosage formulation, the 90% CIs for naproxen C(max), AUC(0-48), and AUC(0-infinity) were 93.06% to 104.00%, 93.50% to 98.44%, and 92.14% to 98.99%, respectively, and were 90.09% to 105.90%, 88.58% to 99.34%, and 91.43% to 101.55%, respectively, for paracetamol. For the tablet-dosage formulation, the 90% CIs for naproxen C(max), AUC(0-48), and AUC(0-infinity) were 102.83% to 117.15%, 96.59% to 104.26%, and 96.01% to 102.90%, respectively, and were 94.04% to 121.09%, 95.48% to 105.64%, and 96.64% to 105.42%, respectively, for paracetamol. In these 2 small studies in healthy Mexican adult subjects, a single dose of naproxen sodium/paracetamol 275/300 mg of the test formulation of the tablet-dosage formulation or a single dose of naproxen sodium/paracetamol 375/300 mg per 15 mL of the test formulation of the suspension-dosage formulation was found to be bioequivalent to the corresponding reference formulations according to the regulatory definition of bioequivalence based on the rate and extent of absorption. All formulations were generally well tolerated.

[The enhancement of human thermal resistance by the single use of bemitil and fenibut].

PubMed

Makarov, V I; Tiurenkov, I N; Klauchek, S V; Nalivaĭko, I Iu; Antipova, A Iu

1997-01-01

The authors studied the effect of single intake of bymetil (0.5 g) and phenibut (0.25 g) on the thermal state, gas-energy exchange, blood oxygenation, working capacity, and the subjective status of man in intensive physical exertion in isolating means of individual protection. The drugs under study increased thermal resistance, promoted normal supply of the organism with oxygen, and provided the maintenance of man's high working capacity under conditions which lead to his overheating. The best protective effects was produced in this case with phenibut.

Single-dose evaluation of safety, tolerability and pharmacokinetics of newly formulated hydromorphone immediate-release and hydrophilic matrix extended-release tablets in healthy Japanese subjects without co-administration of an opioid antagonist.

PubMed

Toyama, Kaoru; Uchida, Naoki; Ishizuka, Hitoshi; Sambe, Takehiko; Kobayashi, Shinichi

2015-09-01

This single dose, open-label study investigated the safety, tolerability and pharmacokinetics of single oral doses of newly formulated immediate-release (IR) and hydrophilic matrix extended-release (ER) hydromorphone tablets in healthy Japanese subjects without co-administration of an opioid antagonist under fasting and fed conditions. Plasma and urinary concentrations of hydromorphone and metabolites were measured by liquid-chromatography tandem mass-spectroscopy. Following administration of the ER tablet, plasma concentrations of hydromorphone slowly increased with a median tmax of 5.0 h and the Cmax decreased to 37% of the IR tablet, while the AUC0-inf was comparable with that of the IR tablet when administered at the same dose. The degree of fluctuation in the plasma concentration for the ER tablet was much lower than that of the IR tablet and certain levels of plasma concentrations were maintained after 24 h of ER dosing. The AUC0-inf and Cmax increased with food for both IR and ER tablets. The AUC0-inf of hydromorphone-3-glucoside was one-tenth of that of hydromorphone-3-glucuronide. A single oral administration of the hydromorphone tablets would be well-tolerated in healthy Japanese subjects despite a lack of co-administration of an opioid antagonist and the newly developed ER hydromorphone tablets may have the appropriate PK characteristics for once-daily dosing. © 2015, The American College of Clinical Pharmacology.

Effect of a Motivational Interviewing-Based Health Coaching on Quality of Life in Subjects With COPD.

PubMed

Rehman, Hamid; Karpman, Craig; Vickers Douglas, Kristin; Benzo, Roberto P

2017-08-01

Improving quality of life (QOL) is a key goal in the care of patients with COPD. Pulmonary rehabilitation (PR) has clearly been shown to improve QOL, but is not accessible to many eligible patients. There is a need for alternative programs designed to improve patient well-being that are accessible to all patients with COPD. Our goal was to pilot test a simple, telephone-based health-coaching intervention that was recently shown to decrease readmission among hospitalized COPD patients and stable COPD patients eligible for PR. Subjects received a 3-month intervention consisting of 10 health-coaching telephone calls based on motivational interviewing principles. Outcome measures included dyspnea level, measured by the modified Medical Research Council scale, and QOL, measured by the Chronic Respiratory Questionnaire and a single-item general self-rated health status. Fifty subjects with moderate to severe COPD were enrolled in the study. Forty-four subjects (86%) completed the study intervention. Dyspnea measured by the modified Medical Research Council score improved significantly after the intervention ( P = .002). The domains of fatigue, emotional function, and mastery on the Chronic Respiratory Disease Questionnaire and the single-item QOL question also improved significantly after the 3 months of health coaching ( P = .001, P = .001, P = .007, and P = .03, respectively). Thirty-six (71%) subjects had a clinically meaningful improvement in at least 1 study end point (either in the severity of dyspnea or a domain of QOL). Thirty subjects (58%) had an improvement of ≥0.5 points, the minimum clinically important difference in at least 1 component of the Chronic Respiratory Disease Questionnaire. A telephone-delivered motivational interviewing-based coaching program for COPD patients is a feasible, well-accepted (by both participants and providers), simple, and novel intervention to improve the well-being of patients with COPD. This pilot study provides insight into a possible alternative to a conventional PR program for patients with limited access to that program. Copyright © 2017 by Daedalus Enterprises.

Immunogenicity and safety of a single dose of a CRM-conjugated meningococcal ACWY vaccine in children and adolescents aged 2-18 years in Taiwan: results of an open label study.

PubMed

Huang, Li-Min; Chiu, Nan-Chang; Yeh, Shu-Jen; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

2014-09-08

MenACWY-CRM (Menveo®, Novartis Vaccines, Siena, Italy) is a quadrivalent meningococcal conjugate vaccine developed to help prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W, and Y. It is approved within the European Union in persons >2 years of age and in persons from 2 months to 55 years of age in the United States, among other countries. Little is known about the immunogenicity and safety of this vaccine in Taiwanese children >2 years and adolescents. This study assessed the immunogenicity and safety of a single injection of MenACWY-CRM vaccine in Taiwanese subjects aged 2-18 years old. In this phase III, multicentre, open-label study 341 subjects received one dose of MenACWY-CRM. Immunogenicity measures were rates of seroresponse (defined as the proportion of subjects with a postvaccination hSBA ≥1:8 if the prevaccination (baseline) titre was <1:4, or at least a fourfold higher hSBA titre than baseline if the prevaccination titre was ≥1:4), percentages of subjects with serum bactericidal activity (hSBA) ≥1:8 for serogroups A, C, W and Y and hSBA geometric mean titres (GMTs). Local and systemic reactions and all adverse events (AEs) were recorded for 7 days, and medically attended AEs for 1 month post-vaccination. Seroresponse rates after MenACWY-CRM vaccination at Day 29 for the serogroups A, C, W, and Y were 83%, 93%, 50%, and 65%, respectively. At Day 29 the percentages of subjects with hSBA ≥1:8 against all four serogroups A, C, W and Y were: 83%, 96%, 96% and 82%, respectively. GMTs against all serogroups rose by ≥7-fold from baseline to Day 29. The vaccine was well tolerated. A single dose of MenACWY-CRM demonstrated a robust immune response, and an acceptable safety profile in Taiwanese children and adolescents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Single and Combined Effects of Air, Road, and Rail Traffic Noise on Sleep and Recuperation

PubMed Central

Basner, Mathias; Müller, Uwe; Elmenhorst, Eva-Maria

2011-01-01

Study Objective: Traffic noise disturbs sleep and may impair recuperation. There is limited information on single and combined effects of air, road, and rail traffic noise on sleep and recuperation. Design: Repeated measures. Setting: Polysomnographic laboratory study. Participants: 72 healthy subjects, mean ± standard deviation 40 ± 13 years, range 18-71 years, 32 male. Interventions: Exposure to 40, 80, or 120 rail, road, and/or air traffic noise events. Measurement and Results: Subjects were investigated for 11 consecutive nights, which included 8 noise exposure nights and one noise-free control night. Noise effects on sleep structure and continuity were subtle, even in nights with combined exposure, most likely because of habituation and an increase in arousal thresholds both within and across nights. However, cardiac arousals did not habituate across nights. Noise exposure significantly affected subjective assessments of sleep quality and recuperation, whereas objective performance was unaffected, except for a small increase in mean PVT reaction time (+4 ms, adjusted P < 0.05). Road traffic noise led to the strongest changes in sleep structure and continuity, whereas subjective assessments of sleep were worse after nights with air and rail traffic noise exposure. In contrast to daytime annoyance, cortical arousal probabilities and cardiac responses were significantly lower for air than for road and rail traffic noise (all P < 0.0001). These differences were explained by sound pressure level rise time and high frequency (> 3 kHz) noise event components. Conclusions: Road, rail, and air traffic noise differentially affect objective and subjective assessments of sleep. Differences in the degree of noise-induced sleep fragmentation between traffic modes were explained by the specific spectral and temporal composition of noise events, indicating potential targets for active and passive noise control. Field studies are needed to validate our findings in a setting with higher ecologic validity. Citation: Basner M; Müller U; Elmenhorst EM. Single and combined effects of air, road, and rail traffic noise on sleep and recuperation. SLEEP 2011;34(1):11-23. PMID:21203365

The effect of music on repetitive disruptive vocalizations of persons with dementia.

PubMed

Casby, J A; Holm, M B

1994-10-01

This study examined the effect of classical music and favorite music on the repetitive disruptive vocalizations of long-term-care facility (LTCF) residents with dementia of the Alzheimer's type (DAT). Three subjects diagnosed with DAT who had a history of repetitive disruptive vocalizations were selected for the study. Three single-subject withdrawal designs (ABA, ACA, and ABCA) were used to assess subjects' repetitive disruptive vocalizations during each phase: no intervention (A); relaxing, classical music (B); and favorite music (C). Classical music and favorite music significantly decreased the number of vocalizations in two of the three subjects (p < .05). These findings support a method that was effective in decreasing the disruptive vocalization pattern common in those with DAT in the least restrictive manner, as mandated by the Omnibus Budget Reconciliation Act of 1987.

An Evaluation of a Computer-Based Training on the Visual Analysis of Single-Subject Data

ERIC Educational Resources Information Center

Snyder, Katie

2013-01-01

Visual analysis is the primary method of analyzing data in single-subject methodology, which is the predominant research method used in the fields of applied behavior analysis and special education. Previous research on the reliability of visual analysis suggests that judges often disagree about what constitutes an intervention effect. Considering…

Durations of Recognition for Single Letters, with and without Visual Masking, by Dyslexics and Normal Readers.

ERIC Educational Resources Information Center

Grosser, George S.; Trzeciak, Gerda M.

1981-01-01

Two sets of letters, those subject to reversal/rotation and others, were tachistoscopically presented singly to normal readers and dyslexic children. The data support the hypothesis that letters subject to reversal have no special relation to dyslexia. The view that dyslexia is a developmental anomaly was supported. (Author/AL)

Creating Single-Subject Design Graphs in Microsoft Excel[TM] 2007

ERIC Educational Resources Information Center

Dixon, Mark R.; Jackson, James W.; Small, Stacey L.; Horner-King, Mollie J.; Mui Ker Lik, Nicholas; Garcia, Yors; Rosales, Rocio

2009-01-01

Over 10 years have passed since the publication of Carr and Burkholder's (1998) technical article on how to construct single-subject graphs using Microsoft Excel. Over the course of the past decade, the Excel program has undergone a series of revisions that make the Carr and Burkholder paper somewhat difficult to follow with newer versions. The…

A Field-Tested Task Analysis for Creating Single-Subject Graphs Using Microsoft[R] Office Excel

ERIC Educational Resources Information Center

Lo, Ya-yu; Konrad, Moira

2007-01-01

Creating single-subject (SS) graphs is challenging for many researchers and practitioners because it is a complex task with many steps. Although several authors have introduced guidelines for creating SS graphs, many users continue to experience frustration. The purpose of this article is to minimize these frustrations by providing a field-tested…

Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate.

PubMed

De Jongh, Cindy M; Verberk, Maarten M; Withagen, Carien E T; Jacobs, John J L; Rustemeyer, Thomas; Kezic, Sanja

2006-06-01

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.

Electronic Cigarette Topography in the Natural Environment

PubMed Central

Morabito, P. N.; Roundtree, K. A.

2015-01-01

This paper presents the results of a clinical, observational, descriptive study to quantify the use patterns of electronic cigarette users in their natural environment. Previously published work regarding puff topography has been widely indirect in nature, and qualitative rather than quantitative, with the exception of three studies conducted in a laboratory environment for limited amounts of time. The current study quantifies the variation in puffing behaviors among users as well as the variation for a given user throughout the course of a day. Puff topography characteristics computed for each puffing session by each subject include the number of subject puffs per puffing session, the mean puff duration per session, the mean puff flow rate per session, the mean puff volume per session, and the cumulative puff volume per session. The same puff topography characteristics are computed across all puffing sessions by each single subject and across all subjects in the study cohort. Results indicate significant inter-subject variability with regard to puffing topography, suggesting that a range of representative puffing topography patterns should be used to drive machine-puffed electronic cigarette aerosol evaluation systems. PMID:26053075

Electronic Cigarette Topography in the Natural Environment.

PubMed

Robinson, R J; Hensel, E C; Morabito, P N; Roundtree, K A

2015-01-01

This paper presents the results of a clinical, observational, descriptive study to quantify the use patterns of electronic cigarette users in their natural environment. Previously published work regarding puff topography has been widely indirect in nature, and qualitative rather than quantitative, with the exception of three studies conducted in a laboratory environment for limited amounts of time. The current study quantifies the variation in puffing behaviors among users as well as the variation for a given user throughout the course of a day. Puff topography characteristics computed for each puffing session by each subject include the number of subject puffs per puffing session, the mean puff duration per session, the mean puff flow rate per session, the mean puff volume per session, and the cumulative puff volume per session. The same puff topography characteristics are computed across all puffing sessions by each single subject and across all subjects in the study cohort. Results indicate significant inter-subject variability with regard to puffing topography, suggesting that a range of representative puffing topography patterns should be used to drive machine-puffed electronic cigarette aerosol evaluation systems.

Treating Acute Insomnia: A Randomized Controlled Trial of a “Single-Shot” of Cognitive Behavioral Therapy for Insomnia

PubMed Central

Ellis, Jason G.; Cushing, Toby; Germain, Anne

2015-01-01

Study Objectives: Despite considerable evidence supporting cognitive behavioral therapy for insomnia (CBT-I) for chronic insomnia, it remains untested within the context of acute insomnia. This study examined the efficacy of a single session of CBT-I, with an accompanying self-help pamphlet, for individuals with acute insomnia. Design: A pragmatic parallel group randomized controlled trial. Setting: Community. Participants: Forty adults (mean age 32.9 ± 13.72 y) with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) defined insomnia disorder, except a self-reported duration of less than 3 mo (i.e., acute insomnia), who reported no previous exposure to CBT-I and were not currently taking medication for sleep. Interventions: A single 60- to 70-min session of CBT-I (n = 20), with an accompanying self-help pamphlet, or wait list control group (n = 20). All subjects were offered a full individual course of CBT-I on completion of the study, regardless of group allocation. Measurements and Results: Subjects completed sleep diaries and the Insomnia Severity Index (ISI) pretreatment and 1 mo following treatment. There were no between-group differences on baseline ISI scores or subjective sleep continuity. The intervention group reported significantly lower ISI scores than controls (t(38) 2.24, P < 0.05) at follow-up. Further, using proposed ISI scores for identifying insomnia caseness (i.e., ≥ 10), 60% of those in the CBT-I group had remitted by 1 mo compared to 15% of those in the control group. Conclusions: This single session of cognitive behavioral therapy for insomnia (CBT-I) is sufficiently efficacious for a significant proportion of those with acute insomnia. The results are discussed in terms of integrating this brief form of CBT-I into the “stepped care” model of insomnia. Trial Registration: Testing the efficacy of an early intervention for acute insomnia (SRCTN05891695) http://www.controlled-trials.com/ISRCTN05891695. Citation: Ellis JG, Cushing T, Germain A. Treating acute insomnia: a randomized controlled trial of a “single-shot” of cognitive behavioral therapy for insomnia. SLEEP 2015;38(6):971–978. PMID:25515106

Short-term effect of a new mouthrinse formulation on oral malodour after single use in vivo: a comparative, randomized, single-blind, parallel-group clinical study.

PubMed

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

2010-09-01

This study aimed to compare a new chlorhexidine (CHX)-free mouthrinse containing amine fluoride/stannous fluoride (ASF) against a benchmark containing CHX with respect to their effect on oral malodour after single use. A total of 42 male and female subjects with an intraoral cause of bad breath, each with an organoleptic rating (OR) of at least 2 and a total volatile sulfur compound (VSC) concentration higher than 130 ppb, participated in the study. Subjects were allocated to one of three treatment groups (i.e. CHX-free ASF mouthrinse, CHX benchmark mouthrinse or water) according to a randomization list. Participants received written instructions on precautions to be taken for optimal breath analysis. Eight trained and qualified odour judges assessed the subjects' malodour by OR at baseline and 30 min and 4 h after single use of the mouthrinses. Additionally, VSC levels were measured at baseline and 4 h after using the mouthrinse. Treatment with water alone led already to some reduction in OR with mean differences to baseline of -1.13 at 30 min and -0.64, 4 h after treatment. Both CHX-free ASF product (-1.51) and CHX (-1.48) provided a significantly stronger OR reduction than water at 30 min (p < 0.05). Only CHX-free ASF treatment showed a sustained benefit in terms of significantly better OR reduction after 4 h (-1.17, p < 0.05), whereas CHX (-0.81) was not significantly different from water (-0.64, p = 0.517). Both ASF (-90.9%) and CHX (-81.6%) reduced VSC levels significantly stronger than water (-53.5%; p < 0.001). OR and VSC readings in the group using the CHX mouthrinse did not differ significantly from those in the group using the CHX-free ASF formulation. The newly developed CHX-free ASF mouthrinse significantly reduced oral malodour after single use, both in terms of OR and VSC levels. Efficacy was comparable to that of the CHX benchmark product.

Trunk, pelvis, hip, and knee kinematics, hip strength, and gluteal muscle activation during a single-leg squat in males and females with and without patellofemoral pain syndrome.

PubMed

Nakagawa, Theresa H; Moriya, Erika T U; Maciel, Carlos D; Serrão, Fábio V

2012-06-01

Controlled laboratory study using a cross-sectional design. To determine whether there are any differences between the sexes in trunk, pelvis, hip, and knee kinematics, hip strength, and gluteal muscle activation during the performance of a single-leg squat in individuals with patellofemoral pain syndrome (PFPS) and control participants. Though there is a greater incidence of PFPS in females, PFPS is also quite common in males. Trunk kinematics may affect hip and knee function; however, there is a lack of studies of the influence of the trunk in individuals with PFPS. Eighty subjects were distributed into 4 groups: females with PFPS, female controls, males with PFPS, and male controls. Trunk, pelvis, hip, and knee kinematics and gluteal muscle activation were evaluated during a single-leg squat. Hip abduction and external rotation eccentric strength was measured on an isokinetic dynamometer. Group differences were assessed using a 2-way multivariate analysis of variance (sex by PFPS status). Compared to controls, subjects with PFPS had greater ipsilateral trunk lean (mean ± SD, 9.3° ± 5.3° versus 6.7° ± 3.0°; P = .012), contralateral pelvic drop (10.3° ± 4.7° versus 7.4° ± 3.8°; P = .003), hip adduction (14.8° ± 7.8° versus 10.8° ± 5.6°; P<.0001), and knee abduction (9.2° ± 5.0° versus 5.8° ± 3.4°; P<.0001) when performing a single-leg squat. Subjects with PFPS also had 18% less hip abduction and 17% less hip external rotation strength. Compared to female controls, females with PFPS had more hip internal rotation (P<.05) and less muscle activation of the gluteus medius (P = .017) during the single-leg squat. Despite many similarities in findings for males and females with PFPS, there may be specific sex differences that warrant consideration in future studies and when clinically evaluating and treating females with PFPS.

When the Single Matters more than the Group (II): Addressing the Problem of High False Positive Rates in Single Case Voxel Based Morphometry Using Non-parametric Statistics.

PubMed

Scarpazza, Cristina; Nichols, Thomas E; Seramondi, Donato; Maumet, Camille; Sartori, Giuseppe; Mechelli, Andrea

2016-01-01

In recent years, an increasing number of studies have used Voxel Based Morphometry (VBM) to compare a single patient with a psychiatric or neurological condition of interest against a group of healthy controls. However, the validity of this approach critically relies on the assumption that the single patient is drawn from a hypothetical population with a normal distribution and variance equal to that of the control group. In a previous investigation, we demonstrated that family-wise false positive error rate (i.e., the proportion of statistical comparisons yielding at least one false positive) in single case VBM are much higher than expected (Scarpazza et al., 2013). Here, we examine whether the use of non-parametric statistics, which does not rely on the assumptions of normal distribution and equal variance, would enable the investigation of single subjects with good control of false positive risk. We empirically estimated false positive rates (FPRs) in single case non-parametric VBM, by performing 400 statistical comparisons between a single disease-free individual and a group of 100 disease-free controls. The impact of smoothing (4, 8, and 12 mm) and type of pre-processing (Modulated, Unmodulated) was also examined, as these factors have been found to influence FPRs in previous investigations using parametric statistics. The 400 statistical comparisons were repeated using two independent, freely available data sets in order to maximize the generalizability of the results. We found that the family-wise error rate was 5% for increases and 3.6% for decreases in one data set; and 5.6% for increases and 6.3% for decreases in the other data set (5% nominal). Further, these results were not dependent on the level of smoothing and modulation. Therefore, the present study provides empirical evidence that single case VBM studies with non-parametric statistics are not susceptible to high false positive rates. The critical implication of this finding is that VBM can be used to characterize neuroanatomical alterations in individual subjects as long as non-parametric statistics are employed.

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers.

PubMed

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J; Brown, Powel H; Dannenberg, Andrew J; Szabo, Eva

2012-09-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. Published by Elsevier Inc.

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers

PubMed Central

Mohebati, Arash; Knutson, Allison; Zhou, Xi Kathy; Smith, Judith J.; Brown, Powel H.; Dannenberg, Andrew J.; Szabo, Eva

2012-01-01

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. PMID:22771576

New Developments in Robotics and Single-site Gynecologic Surgery.

PubMed

Matthews, Catherine A

2017-06-01

Within the last 10 years there have been significant advances in minimal-access surgery. Although no emerging technology has demonstrated improved outcomes or fewer complications than standard laparoscopy, the introduction of the robotic surgical platform has significantly lowered abdominal hysterectomy rates. While operative time and cost were higher in robotic-assisted procedures when the technology was first introduced, newer studies demonstrate equivalent or improved robotic surgical efficiency with increased experience. Single-port hysterectomy has not improved postoperative pain or subjective cosmetic results. Emerging platforms with flexible, articulating instruments may increase the uptake of single-port procedures including natural orifice transluminal endoscopic cases.

Carryover effect of hip and knee exercises program on functional performance in individuals with patellofemoral pain syndrome

PubMed Central

Ahmed Hamada, Hamada; Hussein Draz, Amira; Koura, Ghada Mohamed; Saab, Ibtissam M.

2017-01-01

[Purpose] This study was carried out to investigate the carryover effect of hip and knee exercises program on functional performance (single legged hop test as functional performance test and Kujala score for functional activities). [Subjects and Methods] Thirty patients with patellofemoral pain syndrome were randomly assigned into two equal groups. Group (A) consisted of 15 patients undergoing hip strengthening exercises for four weeks then measuring all variables followed by additional four weeks of knee exercises program then measuring all variables again. Group (B): consisted of 15 patients undergoing knee exercises program for four weeks then measuring all variables followed by additional four weeks of hip strengthening exercises then measuring all variables. Functional abilities and knee muscles performance were assessed using Kujala questionnaire and single legged hop test respectively pre and after the completion of the first 4 weeks then after 8 weeks for both groups. [Results] Significantly increase in Kujala questionnaire in group A compared with group B was observed. While, there were significant increase in single legged hop performance test in group B compared with group A. [Conclusion] Starting with hip exercises improve the performance of subjects more than functional activities while starting with knee exercises improve the functional activities of subjects more than performance. PMID:28878459

Carryover effect of hip and knee exercises program on functional performance in individuals with patellofemoral pain syndrome.

PubMed

Ahmed Hamada, Hamada; Hussein Draz, Amira; Koura, Ghada Mohamed; Saab, Ibtissam M

2017-08-01

[Purpose] This study was carried out to investigate the carryover effect of hip and knee exercises program on functional performance (single legged hop test as functional performance test and Kujala score for functional activities). [Subjects and Methods] Thirty patients with patellofemoral pain syndrome were randomly assigned into two equal groups. Group (A) consisted of 15 patients undergoing hip strengthening exercises for four weeks then measuring all variables followed by additional four weeks of knee exercises program then measuring all variables again. Group (B): consisted of 15 patients undergoing knee exercises program for four weeks then measuring all variables followed by additional four weeks of hip strengthening exercises then measuring all variables. Functional abilities and knee muscles performance were assessed using Kujala questionnaire and single legged hop test respectively pre and after the completion of the first 4 weeks then after 8 weeks for both groups. [Results] Significantly increase in Kujala questionnaire in group A compared with group B was observed. While, there were significant increase in single legged hop performance test in group B compared with group A. [Conclusion] Starting with hip exercises improve the performance of subjects more than functional activities while starting with knee exercises improve the functional activities of subjects more than performance.

Novice drivers' performance after different alcohol dosages and placebo in the divided-attention steering simulator (DASS).

PubMed

Verster, Joris C; Wester, Anne E; Goorden, Maartje; van Wieringen, Jan-Peter; Olivier, Berend; Volkerts, Edmund R

2009-05-01

The divided-attention steering simulator (DASS) is designed to measure lane-keeping (i.e., a tracking task using a steering wheel) while performing a secondary visual task (responding to digits that appear in the corners of the computer screen). Some studies have already used the DASS, but the magnitude of impairment is difficult to interpret because reference values are lacking. To examine the magnitude of impairment after administration of four different dosages of alcohol and placebo. Thirty-two healthy young adults participated in this randomized, single-blind crossover trial. Subjects received alcohol to gain a blood alcohol concentration (BAC) of 0.02%, 0.05%, 0.08%, and 0.10% or alcohol-placebo. Sixteen subjects performed a 30-min test in DASS (dual-task condition). Outcome measures were steering error, reaction time, and percentage of errors. Sixteen other subjects performed the test without performing the secondary peripheral task (single-task condition). Twenty-eight subjects (novice drivers; drivers' license up to 5 years) were included in the analyses. Dose-dependent impairment was found in both the single-task condition (F ((4,11)) = 10.86, p < 0.001) and the dual-task condition (F ((4,9)) = 5.58, p < 0.015). Performance at all BAC levels differed significantly (p < 0.05) from alcohol-placebo, except BAC 0.02%. With increasing BAC levels, subjects made more errors and reacted slower on the peripheral visual search task, but these effects did not reach significance. With increasing BAC, dose-dependent impairment was found. The DASS seems to be a suitable divided-attention task that is useful in psychopharmacological research and training of novice drivers.

Acute Effects of Different Types of Resistance Training on Cardiac Autonomic Modulation in COPD.

PubMed

Vanderlei, Franciele M; Zandonadi, Fernando; de Lima, Fabiano Franciso; Silva, Bruna S A; Freire, Ana Paula C F; Ramos, Dionei; Ramos, Ercy Mara C

2018-05-22

An exercise modality that has been gaining significant importance in the rehabilitation of subjects with COPD is resistance training. When considering that patients with COPD present alterations in autonomic cardiac modulation caused by the disease itself, it is necessary to investigate the behavior of the autonomic nervous system in relation to this type of exercise. Thus, the objective of this study was to compare the acute effects of resistance training with elastic tubes, elastic bands, and conventional weightlifitng on the behavior of cardiac autonomic modulation in post-exercise recovery in subjects with COPD. Thirty-four subjects with COPD performed an single session of resistance training divided according to the therapeutic resource used: elastic tubes ( n = 10), elastic bands ( n = 11), and conventional bodybuilding ( n = 13). For analysis of cardiac autonomic modulation, the heart rate was obtained beat to beat at rest and immediately after the end of the session for 60 min in a seated position. Heart rate variability indices were obtained in the time and frequency domains. The 3 therapeutic resource types used in the single session of resistance training promoted changes in heart rate variability linear indices in the time and frequency domains; however, post-exercise recovery time was similar for all protocols performed. After single resistance training the elastic tubes group presented a minimum alteration in the post-exercise recovery of cardiac autonomic modulation in the subjects with COPD; however, at 5 min after exercising, the subjects with COPD had already recovered. Therefore, if the purpose of the training is to restore autonomic cardiac modulation, the use of elastic tubes is suggested, when considering their low cost and versatility. Copyright © 2018 by Daedalus Enterprises.

Is there a difference between the effects of single and triple indirect moxibustion stimulations on skin temperature changes of the posterior trunk surface?

PubMed

Mori, Hidetoshi; Kuge, Hiroshi; Tanaka, Tim Hideaki; Taniwaki, Eiichi; Ohsawa, Hideo

2011-06-01

To determine whether any difference exists in responses to indirect moxibustion (IM) relative to thermal stimulation duration. In experiment 1, 9 subjects attended two experimental sessions consisting of single stimulation with IM or triple stimulation with IM, using a crossover design. A K-type thermocouple temperature probe was fixed on the skin surface at the GV14 acupuncture point. IM stimulation was administered to the top of the probe in order to measure the temperature curve. In addition, each subject evaluated his or her subjective feeling of heat on a visual analogue scale after each stimulation. Experiment 2 was conducted on 42 participants, divided into three groups according to the envelope allocation method: single stimulation with IM (n=20), triple stimulation with IM (n=11) and a control group (n=11). A thermograph was used to obtain the skin temperature on the posterior trunk of the participant. To analyse skin temperature, four arbitrary frames (the scapular, interscapular, lumbar and vertebral regions) were made on the posterior trunk. In experiment 1, no significant difference in maximum temperature was found in IM and subjective feeling of heat intensity between single and triple stimulation with IM. In experiment 2, increases in skin temperature occurred on the posterior trunk, but no differences in skin temperature occurred between the groups receiving single and triple stimulation with IM. No difference exists in the skin temperature response to moxibustion between the single and triple stimulation with IM.

The Lack of Effect of Food on the Pharmacokinetics of ZX008 (Fenfluramine Oral Solution): Results of a Single-dose, Two-period Crossover Study.

PubMed

Gammaitoni, Arnold; Smith, Steven; Boyd, Brooks

2018-06-22

Fenfluramine is being developed as a low-dose adjunctive treatment for seizures in patients with Dravet syndrome and other epileptic encephalopathies, including Lennox-Gastaut syndrome. Most patients with Dravet syndrome receive multiple antiepileptic drugs, making it challenging for caregivers to track correct administration times. The present Phase I study was conducted to determine the effect of food on the pharmacokinetic properties of fenfluramine. Healthy nonsmoking subjects aged 18 to 50years were enrolled in an open-label, crossover, Phase I pharmacokinetic and safety profile study and received 2 single 0.8-mg/kg doses of ZX008 (fenfluramine hydrochloride oral solution), 1 after a 10-hour overnight fast and the other 30 minutes after the start of consumption of a high-fat breakfast, in a randomly assigned order. A washout period of at least 9days separated the 2 treatment periods. Venous blood samples were taken before each dose and periodically for 72hours after each dose for determination of concentrations of fenfluramine and its active metabolite norfenfluramine. Plasma pharmacokinetic parameters were estimated for each subject by noncompartmental analysis. In the 13 subjects completing both treatment periods, food had no effect on the rate or extent of absorption and bioavailability of fenfluramine as assessed by fed vs fasted adjusted geometric mean observed plasma C max (59.1vs 56.7 ng/mL; NS) and AUC 0-∞ (1640vs 1600 ng · h/mL; NS). Additionally, there was no impact of food on systemic exposure of norfenfluramine. Seven subjects reported at least 1 treatment-emergent adverse event; all treatment-emergent adverse events were mild in severity. The bioequivalence and tolerability of single 0.8-mg/kg oral doses of ZX008 in the fed and fasted states support ZX008 administration without regard to meals. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Esophageal transit and in vivo disintegration of branded risedronate sodium tablets and two generic formulations of alendronic acid tablets: a single-center, single-blind, six-period crossover study in healthy female subjects.

PubMed

Perkins, Alan C; Blackshaw, P Elaine; Hay, Peter D; Lawes, Simon C; Atherton, Clare T; Dansereau, Richard J; Wagner, Leigh K; Schnell, Dan J; Spiller, Robin C

2008-05-01

Delayed esophageal transit or disintegration of oral bisphosphonate tablets before they enter the stomach may be of concern with respect to iatrogenic complications among patients receiving longterm treatment. Different formulations of generic bisphosphonate tablets meeting regulatory requirements may have substantial differences in pharmaceutical attributes from the branded product that may result in different characteristics during esophageal transit. The primary objective of this study was to evaluate and compare esophageal transit times and in vivo disintegration of 3 bisphosphonate formulations, one branded and the others generic, that are commercially available in Canada and the United Kingdom. This was a single-center, randomized, singleblind, 6-period crossover study in healthy postmenopausal women aged >50 years. Each subject received a single oral dose of a branded risedronate sodium 35-mg tablet and 2 generic formulations of alendronic acid 70-mg tablets (Novopharm Limited, Toronto, Canada, and Teva UK Limited, Morley, United Kingdom) in both the erect and semisupine (45 degrees ) positions. Although the products are labeled to be taken in the erect position, the semisupine position was included to simulate dosing in bedridden patients. Subjects took tablets with 30 mL of water in the morning after an overnight fast. The tablets were radiolabeled with technetium-99m ion-exchange resins to enable visualization and measurement of esophageal transit time and disintegration using a gamma camera. Dynamic scintigraphic images were obtained for a total of 10 minutes: 2 images per second for the first 30 seconds and 1 image every 15 seconds for 9.5 minutes. This was a mechanistic study and tolerability was not assessed. The study was conducted in 20 healthy white female subjects with a mean age of 62 years (range, 51-77 years). The effect of body position was statistically significant (P = 0.043), with the estimated hazard ratio (HR) of 0.74 indicating longer transit time in the semisupine position relative to the erect position. There was a statistically significant difference in transit time among the 3 types of tablets (P = 0.007), with the Novopharm tablet (HR = 0.59; P < 0.001) and Teva tablet (HR = 0.71; P = 0.042) having longer transit times compared with the risedronate tablet. In 4 instances, the Novopharm tablet disintegrated and dispersed in the esophagus, once in the erect position and 3 times in the semisupine position. In these healthy female subjects, esophageal transit was delayed when the tablets were given in the semisupine position. The branded risedronate tablet had a significantly faster transit time than the 2 generic formulations of alendronate tested.

Two Randomized Clinical Studies to Confirm Differential Plaque Removal by Sodium Bicarbonate Dentifrices in a Single Timed Brushing Model.

PubMed

Mason, Stephen; Karwal, Ritu; Bosma, Mary Lynn

2017-09-01

This study evaluated and compared plaque removal efficacy of commercially available dentifrices containing sodium bicarbonate (NaHCO3) to those without NaHCO3 in a single timed brushing clinical study model. Two randomized, examiner-blind, three-period, three-treatment, crossover studies were performed in adults with a mean Turesky modification of the Quigley-Hein Plaque Index (TPI) score of = 2.00. In Study 1, 60 subjects were randomized to commercially available dentifrices containing: (i) 67% NaHCO3 plus 1425 ppm fluoride (F) as sodium fluoride (NaF); (ii) 45% NaHCO3 plus 1425 ppm F as NaF; or (iii) 0% NaHCO3 plus silica and 1450 ppm F as NaF. In Study 2, 55 subjects were randomized to commercially available dentifrices containing: (i) 67% NaHCO3 plus 1425 ppm F as NaF; (ii) 0% NaHCO3 plus silica and 1400 ppm F as amine F/stannous F; or (iii) 0% NaHCO3 plus chlorhexidine/aluminum lactate and silica with 1360 ppm F as aluminum F. In both studies, subjects brushed their teeth for one timed minute under supervised conditions. Plaque was assessed pre- and post-brushing according to a six-site modification of the TPI. Mean TPI score was analyzed using an analysis of covariance model with treatment and study period as fixed effects, subject as a random variable, and pre-brushing score as a covariate. In both studies, mean TPI score decreased in all groups post-brushing compared with pre-brushing. In Study 1, statistically significant improvements in mean TPI score were reported with the 67% and 45% NaHCO3 dentifrices compared with the 0% NaHCO3 dentifrice (p = 0.0003 and p = 0.0005, respectively). In Study 2, improvements in mean TPI score were statistically significantly greater with the 67% NaHCO3 dentifrice compared with both 0% NaHCO3 dentifrices (p < 0.0001 for both comparisons). All dentifrices were generally well tolerated. A single timed brushing with commercially available dentifrices containing 67% or 45% NaHCO3 exerted a significantly greater effect on plaque removal than commercially available dentifrices without NaHCO3.

Studentized continuous wavelet transform (t-CWT) in the analysis of individual ERPs: real and simulated EEG data

PubMed Central

Real, Ruben G. L.; Kotchoubey, Boris; Kübler, Andrea

2014-01-01

This study aimed at evaluating the performance of the Studentized Continuous Wavelet Transform (t-CWT) as a method for the extraction and assessment of event-related brain potentials (ERP) in data from a single subject. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the t-CWT were assessed and compared to a variety of competing procedures using simulated EEG data at six low signal-to-noise ratios. Results show that the t-CWT combines high sensitivity and specificity with favorable PPV and NPV. Applying the t-CWT to authentic EEG data obtained from 14 healthy participants confirmed its high sensitivity. The t-CWT may thus be well suited for the assessment of weak ERPs in single-subject settings. PMID:25309308

Studentized continuous wavelet transform (t-CWT) in the analysis of individual ERPs: real and simulated EEG data.

PubMed

Real, Ruben G L; Kotchoubey, Boris; Kübler, Andrea

2014-01-01

This study aimed at evaluating the performance of the Studentized Continuous Wavelet Transform (t-CWT) as a method for the extraction and assessment of event-related brain potentials (ERP) in data from a single subject. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the t-CWT were assessed and compared to a variety of competing procedures using simulated EEG data at six low signal-to-noise ratios. Results show that the t-CWT combines high sensitivity and specificity with favorable PPV and NPV. Applying the t-CWT to authentic EEG data obtained from 14 healthy participants confirmed its high sensitivity. The t-CWT may thus be well suited for the assessment of weak ERPs in single-subject settings.

Matching Automatic Gain Control Across Devices in Bimodal Cochlear Implant Users.

PubMed

Veugen, Lidwien C E; Chalupper, Josef; Snik, Ad F M; Opstal, A John van; Mens, Lucas H M

2016-01-01

The purpose of this study was to improve bimodal benefit in listeners using a cochlear implant (CI) and a hearing aid (HA) in contralateral ears, by matching the time constants and the number of compression channels of the automatic gain control (AGC) of the HA to the CI. Equivalent AGC was hypothesized to support a balanced loudness for dynamically changing signals like speech and improve bimodal benefit for speech understanding in quiet and with noise presented from the side(s) at 90 degree. Fifteen subjects participated in the study, all using the same Advanced Bionics Harmony CI processor and HA (Phonak Naida S IX UP). In a 3-visit crossover design with 4 weeks between sessions, performance was measured using a HA with a standard AGC (syllabic multichannel compression with 1 ms attack time and 50 ms release time) or an AGC that was adjusted to match that of the CI processor (dual AGC broadband compression, 3 and 240 msec attack time, 80 and 1500 msec release time). In all devices, the AGC was activated above the threshold of 63 dB SPL. The authors balanced loudness across the devices for soft and loud input sounds in 3 frequency bands (0 to 548, 548 to 1000, and >1000 Hz). Speech understanding was tested in free field in quiet and in noise for three spatial speaker configurations, with target speech always presented from the front. Single-talker noise was either presented from the CI side or the HA side, or uncorrelated stationary speech-weighted noise or single-talker noise was presented from both sides. Questionnaires were administered to assess differences in perception between the two bimodal fittings. Significant bimodal benefit over the CI alone was only found for the AGC-matched HA for the speech tests with single-talker noise. Compared with the standard HA, matched AGC characteristics significantly improved speech understanding in single-talker noise by 1.9 dB when noise was presented from the HA side. AGC matching increased bimodal benefit insignificantly by 0.6 dB when noise was presented from the CI implanted side, or by 0.8 (single-talker noise) and 1.1 dB (stationary noise) in the more complex configurations with two simultaneous maskers from both sides. In questionnaires, subjects rated the AGC-matched HA higher than the standard HA for understanding of one person in quiet and in noise, and for the quality of sounds. Listening to a slightly raised voice, subjects indicated increased listening comfort with matched AGCs. At the end of the study, 9 of 15 subjects preferred to take home the AGC-matched HA, 1 preferred the standard HA and 5 subjects had no preference. For bimodal listening, the AGC-matched HA outperformed the standard HA in speech understanding in noise tasks using a single competing talker and it was favored in questionnaires and in a subjective preference test. When noise was presented from the HA side, AGC matching resulted in a 1.9 dB SNR additional benefit, even though the HA was at the least favorable SNR side in this speaker configuration. Our results possibly suggest better binaural processing for matched AGCs.

Pharmacokinetic comparison of sustained- and immediate-release oral formulations of cilostazol in healthy Korean subjects: a randomized, open-label, 3-part, sequential, 2-period, crossover, single-dose, food-effect, and multiple-dose study.

PubMed

Lee, Donghwan; Lim, Lay Ahyoung; Jang, Seong Bok; Lee, Yoon Jung; Chung, Jae Yong; Choi, Jong Rak; Kim, Kiyoon; Park, Jin Woo; Yoon, Hosang; Lee, Jaeyong; Park, Min Soo; Park, Kyungsoo

2011-12-01

A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower C(max) and a similar AUC to the immediate-release (IR) formulation. The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, 3-part, sequential, open-label, 2-period crossover study. Each part consisted of different subjects between the ages of 19 and 55 years. In part 1, each subject received a single dose of SR (200 mg × 1 tablet, once daily) and IR (100 mg × 2 tablets, BID) formulations of cilostazol orally 7 days apart in a fasted state. In part 2, each subject received a single dose of the SR (200 mg × 1 tablet, once daily) formulation of cilostazol 7 days apart in a fasted and a fed state. In part 3, each subject received multiple doses of the 2 formulations for 8 consecutive days 21 days apart. Blood samples were taken for 72 hours after the dose. Cilostazol pharmacokinetics were determined for both the parent drug and its metabolites (OPC-13015 and OPC-13213). Adverse events were evaluated through interviews and physical examinations. Among the 92 enrolled subjects (66 men, 26 women; part 1, n = 26; part 2, n = 26; part 3, n = 40), 87 completed the study. In part 1, all the primary pharmacokinetic parameters satisfied the criterion for assumed bioequivalence both in cilostazol and its metabolites, yielding 90% CI ratios of 0.9624 to 1.2323, 0.8873 to 1.1208, and 0.8919 to 1.1283 for C(max) and 0.8370 to 1.0134, 0.8204 to 0.9807, and 0.8134 to 0.9699 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213, respectively. In part 2, food intake increased C(max) and AUC significantly (P < 0.0001), yielding geometric mean ratios of 3.2879, 2.9894, and 3.0592 for C(max) and 1.7001, 1.7689, and 1.6976 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213. In part 3, only the C(ssmax) of clilostazol in the reference formulation did not satisfy the criterion for assumed bioequivalence, yielding 90% CI ratios of 1.2693 to 1.4238 and 1.2038 to 1.3441, respectively. When each dose was normalized, the C(max) for the SR formulation was significantly lower (P < 0.005 for cilostazol). Headache was the most frequently noted adverse effect (part 1, a total of 14 subjects with the IR formulation and 14 with the SR formulation; part 2, a total of 10 without food and 23 with a high-fat meal; part 3, a total of 10 with the IR formulation and 24 with the SR formulation), followed by nausea (part 1, none; part 2, only 1 without food and 3 with a high-fat meal; part 3, a total of 3 with the IR formulation and 3 with the SR formulation), and then dizziness (parts 1 and 2, none; part 3, a total of 4 with the IR formulation and 5 with the SR formulation). All other AEs, including fever, cough, vomiting, palpitation, diarrhea, and epigastric pain, occurred in <3 subjects. These findings suggest that in this select group of healthy Korean volunteers, the SR formulation of cilostazol was not significantly different in AUC compared with that of the IR formulation, although it did display a significantly lower C(max) per dose in both the single- and multiple-dose groups. Food significantly increased the bioavailability of the SR formulation. The cilostazol SR and IR formulations were well tolerated in all parts of the study, with no serious adverse events reported. ClinicalTrials.gov identifier: NCT01455558. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

Effect of squatting velocity on hip muscle latency in women with patellofemoral pain syndrome.

PubMed

Orozco-Chavez, Ignacio; Mendez-Rebolledo, Guillermo

2018-03-01

[Purpose] Neuromuscular activity has been evaluated in patellofemoral pain syndrome but movement velocity has not been considered. The aim was to determine differences in onset latency of hip and knee muscles between individuals with and without patellofemoral pain syndrome during a single leg squat, and whether any differences are dependent on movement velocity. [Subjects and Methods] Twenty-four females with patellofemoral pain syndrome and 24 healthy females participated. Onset latency of gluteus maximus, anterior and posterior gluteus medius, rectus femoris, vastus medialis, vastus lateralis and biceps femoris during a single leg squat at high and low velocity were evaluated. [Results] There was an interaction between velocity and diagnosis for posterior gluteus medius. Healthy subjects showed a later posterior gluteus medius onset latency at low velocity than high velocity; and also later than patellofemoral pain syndrome subjects at low velocity and high velocity. [Conclusion] Patellofemoral pain syndrome subjects presented an altered latency of posterior gluteus medius during a single leg squat and did not generate adaptations to velocity variation, while healthy subjects presented an earlier onset latency in response to velocity increase.

Artifact removal in the context of group ICA: a comparison of single-subject and group approaches

PubMed Central

Du, Yuhui; Allen, Elena A.; He, Hao; Sui, Jing; Wu, Lei; Calhoun, Vince D.

2018-01-01

Independent component analysis (ICA) has been widely applied to identify intrinsic brain networks from fMRI data. Group ICA computes group-level components from all data and subsequently estimates individual-level components to recapture inter-subject variability. However, the best approach to handle artifacts, which may vary widely among subjects, is not yet clear. In this work, we study and compare two ICA approaches for artifacts removal. One approach, recommended in recent work by the Human Connectome Project, first performs ICA on individual subject data to remove artifacts, and then applies a group ICA on the cleaned data from all subjects. We refer to this approach as Individual ICA based artifacts Removal Plus Group ICA (IRPG). A second proposed approach, called Group Information Guided ICA (GIG-ICA), performs ICA on group data, then removes the group-level artifact components, and finally performs subject-specific ICAs using the group-level non-artifact components as spatial references. We used simulations to evaluate the two approaches with respect to the effects of data quality, data quantity, variable number of sources among subjects, and spatially unique artifacts. Resting-state test-retest datasets were also employed to investigate the reliability of functional networks. Results from simulations demonstrate GIG-ICA has greater performance compared to IRPG, even in the case when single-subject artifacts removal is perfect and when individual subjects have spatially unique artifacts. Experiments using test-retest data suggest that GIG-ICA provides more reliable functional networks. Based on high estimation accuracy, ease of implementation, and high reliability of functional networks, we find GIG-ICA to be a promising approach. PMID:26859308