Systematic Individualized Narrative Language Intervention on the Personal Narratives of Children with Autism

ERIC Educational Resources Information Center

Petersen, Douglas B.; Brown, Catherine L.; Ukrainetz, Teresa A.; Wise, Christine; Spencer, Trina D.

2014-01-01

Purpose: The purpose of this study was to investigate the effect of an individualized, systematic language intervention on the personal narratives of children with autism. Method: A single-subject, multiple-baseline design across participants and behaviors was used to examine the effect of the intervention on language features of personal…

Effect Size in Clinical Phonology

ERIC Educational Resources Information Center

Gierut, Judith A.; Morrisette, Michele L.

2011-01-01

The purpose of this article is to motivate the use of effect size (ES) for single-subject research in clinical phonology, with an eye towards meta-analyses of treatment effects for children with phonological disorders. Standard mean difference (SMD) is introduced and illustrated as one ES well suited to the multiple baseline (MBL) design and…

Effectiveness of a Computer-Assisted Intervention for Young Children with Attention and Reading Problems

ERIC Educational Resources Information Center

Walcott, Christy M.; Marett, Katherine; Hessel, Amanda B.

2014-01-01

Children who are significantly inattentive and poor early readers require intervention, and traditional tutoring approaches may not be effective with this group. Using a single-subject, multiple-baseline-across-participants design, Study 1 examines whether a computer-assisted reading intervention increases performance for three first-grade…

A Community-Based Early Intervention Program for Toddlers with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Rollins, Pamela Rosenthal; Campbell, Michelle; Hoffman, Renee Thibodeau; Self, Kayli

2016-01-01

This study examined Pathways Early Autism Intervention, a community-based, parent-mediated, intensive behavioral and developmental intervention program for children with autism spectrum disorders that could be used as a model for state-funded early intervention programs. A single-subject, multiple-baseline, across-participants design was used.…

Ameliorating the English Reading Comprehension of Spanish-Speaking ELLs through a Reciprocal Teaching Intervention

ERIC Educational Resources Information Center

Ramos, Jose A.

2012-01-01

Through a single-subject multiple-baseline across-participants design, the present study examined the effects of Reciprocal Teaching (RT) instruction and Spanish use on the cognitive strategy use and English reading comprehension of four, 4th grade Spanish-speaking bilingual students that are "good" decoders but "poor"…

Efficacy of a Brief Relaxation Training Intervention for Pediatric Recurrent Abdominal Pain

ERIC Educational Resources Information Center

Bell, Katrina M.; Meadows, Elizabeth A.

2013-01-01

This study is a preliminary investigation of the efficacy of a brief intervention for recurrent abdominal pain (RAP) via a multiple baseline across subjects design. The intervention consisted of a single 1-hour session including psychoeducation and coaching of breathing retraining; the length, duration, and content of the intervention were…

Exploring inter-task transfer following a CO-OP approach with four children with DCD: A single subject multiple baseline design.

PubMed

Capistran, Julie; Martini, Rose

2016-10-01

Cognitive Orientation to daily Occupational Performance (CO-OP) approach has been shown to be effective for improving the performance of tasks worked on in therapy and the use of cognitive strategies. No study to date seems to have explored its effectiveness for improving performance of untrained tasks (inter-task transfer) in children with Developmental Coordination Disorder (DCD). This study aimed to determine whether CO-OP leads to improved performance in an untrained task. A single-subject design with multiple baselines across skills was adopted, with three replications. Four children with DCD (7-12years) received 10 sessions of CO-OP intervention where each child worked on three tasks during therapy sessions and a fourth task was identified, but not worked on, to verify inter-task transfer. Task performance was rated over four phases (baseline, intervention, post-intervention, follow-up) using the Performance Quality Rating Scale (PQRS-OD). Graphed data was statistically analyzed using a two or three standard deviation band method. Significant improvement was obtained for 11 of 12 tasks worked on during therapy and for two of the four untrained tasks. These results indicate that the effectiveness of CO-OP to improve untrained tasks in children merit further exploration. Copyright © 2016 Elsevier B.V. All rights reserved.

Repeated readings and science: Fluency with expository passages

NASA Astrophysics Data System (ADS)

Kostewicz, Douglas E.

The current study investigated the effects of repeated readings to a fluency criterion (RRFC) for seven students with disabilities using science text. The study employed a single subject design, specifically, two multiple probe multiple baselines across subjects, to evaluate the effects of the RRFC intervention. Results indicated that students met criterion (200 or more correct words per minute with 2 or fewer errors) on four consecutive passages. A majority of students displayed accelerations to correct words per minute and decelerations to incorrect words per minute on successive initial, intervention readings suggesting reading transfer. Students' reading scores during posttest and maintenance out performed pre-test and baseline readings provided additional measures of reading transfer. For a relationship to comprehension, students scored higher on oral retell measures after meeting criterion as compared to initial readings. Overall, the research findings suggested that the RRFC intervention improves science reading fluency for students with disabilities, and may also indirectly benefit comprehension.

The Treatment of Maladaptive Shame in Borderline Personality Disorder: A Pilot Study of "Opposite Action"

ERIC Educational Resources Information Center

Rizvi, Shireen L.; Linehan, Marsha M.

2005-01-01

This study sought to pilot test a short-term intervention for maladaptive shame in borderline personality disorder (BPD) based on the skill of "opposite action" from dialectical behavior therapy. Five women with BPD were treated with the intervention using a single-subject, multiple-baseline design. Results indicate that, although state ratings of…

Development of a Theoretically Based Treatment for Sentence Comprehension Deficits in Individuals with Aphasia

ERIC Educational Resources Information Center

Kiran, Swathi; Caplan, David; Sandberg, Chaleece; Levy, Joshua; Berardino, Alex; Ascenso, Elsa; Villard, Sarah; Tripodis, Yorghos

2012-01-01

Purpose: Two new treatments, 1 based on sentence to picture matching (SPM) and the other on object manipulation (OM), that train participants on the thematic roles of sentences using pictures or by manipulating objects were piloted. Method: Using a single-subject multiple-baseline design, sentence comprehension was trained on the affected sentence…

The Impact of Tier 2 Mathematics Instruction on Second Graders with Mathematics Difficulties

ERIC Educational Resources Information Center

Dennis, Minyi Shih; Bryant, Brian R.; Drogan, Robin

2015-01-01

Although research on Tier 2 interventions for early mathematics is accumulating, such efforts remain far behind those for reading, especially regarding specific features such as the ideal time to begin an intervention. The present study investigated the effectiveness of a Tier 2 intervention using a single subject multiple baseline, across-groups…

Improving Preschoolers' Theory of Mind Skills with Digital Games: A Training Study

ERIC Educational Resources Information Center

Nikolayev, Mariya

2015-01-01

This single-subject research study examined functional relation between digital games enriched with voice-overs and theory of mind (ToM) when game play was either followed or not followed by a discussion focused on the game's content. The study employed multiple baseline design across participants to evaluate the effects of games with mental state…

The Role of Program Consistency in a Summer Therapeutic Camp for Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Quinn, Colleen; Nowosielski, Ashley; Kitchen, Tom; Belfiore, Phillip J.

2014-01-01

Although evidenced-based practices, delivered with procedural integrity are increasingly common in the field of autism, generalizing those practices to less traditional settings is not. The present study, conducted at a summer therapeutic camp used a single subject multiple baseline across participants research design to evaluate the effects of…

An Investigation of the Additive Benefits of Parent Dialogic Reading Techniques in Older Preschool Children

ERIC Educational Resources Information Center

Switalski, Sarah O'Neill

2012-01-01

This study examined the additive benefit of parent dialogic reading techniques in older, high-risk preschool children using multiple baseline design across participants, a single subject research design, as was as well as pre-test and post-test measures. Five preschoolers age-eligible to begin kindergarten the following school year participated.…

Using Incremental Rehearsal to Teach Letter Sounds to English Language Learners

ERIC Educational Resources Information Center

Rahn, Naomi L.; Wilson, Jennifer; Egan, Andrea; Brandes, Dana; Kunkel, Amy; Peterson, Meredith; McComas, Jennifer

2015-01-01

This study examined the effects of incremental rehearsal (IR) on letter sound expression for one kindergarten and one first grade English learner who were below district benchmark for letter sound fluency. A single-subject multiple-baseline design across sets of unknown letter sounds was used to evaluate the effect of IR on letter-sound expression…

Intensive Voice Treatment (LSVT LOUD) for Children with Spastic Cerebral Palsy and Dysarthria

ERIC Educational Resources Information Center

Fox, Cynthia Marie; Boliek, Carol Ann

2012-01-01

Purpose: The purpose of this study was to examine the effects of an intensive voice treatment (Lee Silverman Voice Treatment, commonly known as LSVT LOUD) for children with spastic cerebral palsy (CP) and dysarthria. Method: A nonconcurrent multiple baseline single-subject design with replication across 5 children with spastic CP was used.…

Cognitive-Behavioral Therapy for Comorbid Generalized Anxiety Disorder and Panic Disorder with Agoraphobia

ERIC Educational Resources Information Center

Labrecque, Joane; Dugas, Michel J.; Marchand, Andre; Letarte, Andree

2006-01-01

The goal of this study was to evaluate the efficacy of a cognitive-behavioral treatment package for comorbid generalized anxiety disorder (GAD) and panic disorder with agoraphobia (PDA). A single-case, multiple-baseline, across-subjects design was used with 3 primary GAD patients with secondary PDA. The efficacy of the treatment was evaluated with…

Increased statistical power with combined independent randomization tests used with multiple-baseline design.

PubMed

Tyrrell, Pascal N; Corey, Paul N; Feldman, Brian M; Silverman, Earl D

2013-06-01

Physicians often assess the effectiveness of treatments on a small number of patients. Multiple-baseline designs (MBDs), based on the Wampold-Worsham (WW) method of randomization and applied to four subjects, have relatively low power. Our objective was to propose another approach with greater power that does not suffer from the time requirements of the WW method applied to a greater number of subjects. The power of a design that involves the combination of two four-subject MBDs was estimated using computer simulation and compared with the four- and eight-subject designs. The effect of a delayed linear response to treatment on the power of the test was also investigated. Power was found to be adequate (>80%) for a standardized mean difference (SMD) greater than 0.8. The effect size associated with 80% power from combined tests was smaller than that of the single four-subject MBD (SMD=1.3) and comparable with the eight-subject MBD (SMD=0.6). A delayed linear response to the treatment resulted in important reductions in power (20-35%). By combining two four-subject MBD tests, an investigator can detect better effect sizes (SMD=0.8) and be able to complete a comparatively timelier and feasible study. Copyright © 2013 Elsevier Inc. All rights reserved.

Improving the Comprehension of Students with Significant Developmental Disabilities: Systematic Instruction on the Steps for Completing and Using a Graphic Organizer

ERIC Educational Resources Information Center

Britt, Alexander P.

2015-01-01

A single-subject, multiple-baseline across participants design was used to examine the functional relation between systematic instruction and the ability to complete a graphic organizer and recall facts about informational texts by students with significant development disabilities. Four high school students enrolled in an adapted academic program…

The Utilization of an iPad for Increasing Work-Related Behaviors in Adults with Disabilities

ERIC Educational Resources Information Center

Jones, Sarah; Bucholz, Jessica L.

2014-01-01

The purpose of this study was to investigate the effectiveness of an iPad to increase work related behaviors for one adult with disabilities in a vocational setting. A multiple baseline across behaviors single subject research design was used to determine if an iPad helped to increase independence in three identified behaviors, which included…

Teaching the Imitation and Spontaneous Use of Descriptive Gestures in Young Children with Autism Using a Naturalistic Behavioral Intervention

ERIC Educational Resources Information Center

Ingersoll, Brooke; Lewis, Elizabeth; Kroman, Emily

2007-01-01

Children with autism exhibit deficits in the imitation and spontaneous use of descriptive gestures. Reciprocal Imitation Training (RIT), a naturalistic imitation intervention, has been shown to increase object imitation skills in young children with autism. A single-subject, multiple-baseline design across five young children with autism was used…

The Effect of Educational Software, Video Modelling and Group Discussion on Social-Skill Acquisition among Students with Mild Intellectual Disabilities

ERIC Educational Resources Information Center

Hetzroni, Orit E.; Banin, Irit

2017-01-01

Background: People with intellectual and developmental disabilities (IDD) often demonstrate difficulties in social skills. The purpose of this study was to examine the effects of a comprehensive intervention program on the acquisition of social skills among students with mild IDD. Method: Single subject multiple baseline design across situations…

Acquisition and Generalization of the Picture Exchange Communication System Behaviors across Settings, Persons, and Stimulus Classes with Three Students with Autism

ERIC Educational Resources Information Center

Dogoe, Maud S.; Banda, Devender R.; Lock, Robin H.

2010-01-01

This study examined the acquisition and generalization of requesting behaviors learned through PECS with three children with autism. A single-subject multiple baseline across participants design was used to determine the effects of PECS. Results indicated that all three participants acquired PECS skills for requesting and generalized the skills…

Effects of Constant Time Delay Procedure on the Halliwick's Method of Swimming Rotation Skills for Children with Autism

ERIC Educational Resources Information Center

Yilmaz, Ilker; Konukman, Ferman; Birkan, Binyamin; Ozen, Arzu; Yanardag, Mehmet; Camursoy, Ilhan

2010-01-01

Effects of a constant time delay procedure on the Halliwick's method of swimming rotation skills (i.e., vertical and lateral rotation) for children with autism were investigated. A single subject multiple baseline model across behaviors with probe conditions was used. Participants were three boys, 8-9 years old. Data were collected over a 10-week…

The Effects of Point-of-View Video Modeling on Symbolic Play Actions and Play-Associated Language Utterances in Preschoolers with Autism

ERIC Educational Resources Information Center

Bonnet, Lauren Kravetz

2012-01-01

This single-subject research study was designed to examine the effects of point-of-view video modeling (POVM) on the symbolic play actions and play-associated language of four preschool students with autism. A multiple baseline design across participants was conducted in order to evaluate the effectiveness of using POVM as an intervention for…

An Examination of the Effects of a Social Communication Intervention on the Play Behaviors of Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Walberg, Jennifer Loncola; Craig-Unkefer, Lesley A.

2010-01-01

This study examined the effect of a social-communication intervention on the play behaviors of children with autism. Six children between the ages of five and eight participated in this study that employed a single-subject, multiple baseline design. Children recruited from an urban Midwestern public school system participated in an intervention…

Therapeutic Horseback Riding Outcomes of Parent-Identified Goals for Children with Autism Spectrum Disorder: An ABA′ Multiple Case Design Examining Dosing and Generalization to the Home and Community

PubMed Central

Baird, Joanne M.; Kim, Young Joo; Rajora, Kuwar B.; D’Silva, Delma; Podolinsky, Lin; Mazefsky, Carla; Minshew, Nancy

2014-01-01

We examined whether different doses of therapeutic riding influenced parent-nominated target behaviors of children with autism spectrum disorder (ASD) (a) during the session (b) at home, and (c) in the community. We used a single subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5 times/week. Three boys with ASD, 6–8 years of age participated, and counts of target behaviors were collected in each setting and phase of the study. Compared to Baseline, 70 % of the target behaviors were better during Intervention and improvement was retained in 63 % of the behaviors during Withdrawal. Increased doses of therapeutic riding were significant for magnitude of change, and the effect of the therapeutic riding sessions generalized to home and community. PMID:24091469

Effects of virtual reality training with modified constraint-induced movement therapy on upper extremity function in acute stage stroke: a preliminary study.

PubMed

Ji, Eun-Kyu; Lee, Sang-Heon

2016-11-01

[Purpose] The purpose of this study was to investigate the effects of virtual reality training combined with modified constraint-induced movement therapy on upper extremity motor function recovery in acute stage stroke patients. [Subjects and Methods] Four acute stage stroke patients participated in the study. A multiple baseline single subject experimental design was utilized. Modified constraint-induced movement therapy was used according to the EXplaining PLastICITy after stroke protocol during baseline sessions. Virtual reality training with modified constraint-induced movement therapy was applied during treatment sessions. The Manual Function Test and the Box and Block Test were used to measure upper extremity function before every session. [Results] The subjects' upper extremity function improved during the intervention period. [Conclusion] Virtual reality training combined with modified constraint-induced movement is effective for upper extremity function recovery in acute stroke patients.

Teaching Young People Who Are Blind and Have Autism to Make Requests Using a Variation on the Picture Exchange Communication System with Tactile Symbols: A Preliminary Investigation

ERIC Educational Resources Information Center

Lund, Shelley K.; Troha, Jeanette M.

2008-01-01

This study used a single-subject multiple baseline across participants design to evaluate the effectiveness of a modified picture exchange communication system (PECS) teaching protocol with tactile symbols. Three students (two male, one female) aged 12-17 years who had autism and were blind participated in the study. The instructional program…

On Internal Validity in Multiple Baseline Designs

ERIC Educational Resources Information Center

Pustejovsky, James E.

2014-01-01

Single-case designs are a class of research designs for evaluating intervention effects on individual cases. The designs are widely applied in certain fields, including special education, school psychology, clinical psychology, social work, and applied behavior analysis. The multiple baseline design (MBD) is the most frequently used single-case…

Design-Comparable Effect Sizes in Multiple Baseline Designs: A General Modeling Framework

ERIC Educational Resources Information Center

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

2014-01-01

In single-case research, the multiple baseline design is a widely used approach for evaluating the effects of interventions on individuals. Multiple baseline designs involve repeated measurement of outcomes over time and the controlled introduction of a treatment at different times for different individuals. This article outlines a general…

The Contributions of Eye Contact and Contingent Praise to Effective Instruction Delivery in Compliance Training

ERIC Educational Resources Information Center

Everett, Gregory E.; Olmi, D. Joe; Edwards, Ron P.; Tingstrom, Daniel H.

2005-01-01

The present study, using a multiple baseline across subjects design for two children and a nonconcurrent multiple baseline across subjects design for two additional children, evaluated whether the addition of eye contact and then contingent praise for compliance (CP) would lead to increases in childhood compliance for both statement and question…

Supporting First-Grade Writers Who Fail to Learn: Multiple Single-Case Evaluation of a Response to Intervention Approach

ERIC Educational Resources Information Center

Arrimada, María; Torrance, Mark; Fidalgo, Raquel

2018-01-01

We report a multiple-baseline single-case study, based in the response to intervention framework, evaluating transcription-only and transcription-and-planning interventions for young, struggling writers. In a baseline phase, 8 classes of Spanish children at the start of their first year of primary (elementary) education completed short, probe…

A comparison of between- and within-subjects imitation designs.

PubMed

Kressley, Regina A; Knopf, Monika

2006-12-01

Two experimental methods, which have dominated the study of declarative memory in preverbal children with imitation tasks, namely the deferred imitation and elicited imitation paradigm, differ in the amount of physical contact with test stimuli afforded infants prior to a test for long-term recall. The current study assessed effects of pre- and post-demonstration contact with test stimuli on deferred imitation of novel, single-step unrelated actions with multiple objects by 8(1/2)- and 10(1/2)-month-old infants (N=50). The rate of target action completion after a delay remained consistent at both ages across different conditions of prior contact with test stimuli. This study shows that a within-subjects baseline appraisal is valid within certain experimental parameters and offers a more economical alternative. The results show furthermore that different experimental designs utilized to assess deferred imitation are highly comparable for the first year despite differences in determining baseline.

The effects of response cost and response restriction on a multiple-response repertoire with humans

PubMed Central

Crosbie, John

1993-01-01

In two experiments a multiple-response repertoire of four free-operant responses was developed with university students as subjects using monetary gain as reinforcement. Following baseline, one of the responses was reduced either by making monetary loss contingent upon it (response cost) or by removing it from the repertoire (response restriction). In Experiment 1 a multielement baseline design was employed in which baseline and restriction or response-cost contingencies alternated semirandomly every 3 minutes. In Experiment 2 a reversal design was employed (i.e., baseline, restriction or response cost, then baseline), and each response required a different amount of effort. Both experiments had the following results: (a) The target response decreased substantially; (b) most nontarget responses increased, and the rest remained near their baseline levels; and (c) no support was found for Dunham's hierarchical, most frequent follower, or greatest temporal similarity rules. For several subjects, the least probable responses during baseline increased most, and the most probable responses increased least. Furthermore, in Experiment 2, responses with the lowest frequency of reinforcement increased most (for all 7 subjects), and those with the greatest frequency of reinforcement increased least (for 5 subjects). PMID:16812683

Eye Movement Desensitisation and Reprocessing Therapy for Posttraumatic Stress Disorder in a Child and an Adolescent with Mild to Borderline Intellectual Disability: A Multiple Baseline across Subjects Study

ERIC Educational Resources Information Center

Mevissen, Liesbeth; Didden, Robert; Korzilius, Hubert; de Jongh, Ad

2017-01-01

Background: This study explored the effectiveness of eye movement desensitisation and reprocessing (EMDR) therapy for post-traumatic stress disorder (PTSD) in persons with mild to borderline intellectual disability (MBID) using a multiple baseline across subjects design. Methods: One child and one adolescent with MBID, who met diagnostic criteria…

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.

Treatment of visual neglect in elderly patients with stroke: a single-subject series using either a scanning and cueing strategy or a left-limb activation strategy.

PubMed

Bailey, Maggie J; Riddoch, M Jane; Crome, Peter

2002-08-01

The presence of unilateral visual neglect (UVN) may adversely affect functional recovery, and rehabilitation strategies that are practical for use in clinical settings are needed. The purpose of this study was to evaluate the use of 2 approaches to reduce UVN in people who have had strokes. Seven elderly patients with stroke and severe left UVN, aged 60 to 85 years, were recruited from a stroke rehabilitation unit. A nonconcurrent, multiple-baselines-across-subjects approach, with an A-B-A treatment-withdrawal single-subject experimental design, was used. Five subjects received a scanning and cueing approach, and 2 subjects received a contralesional limb activation approach, for 10 one-hour sessions. In the former approach, active scanning to the left was encouraged by the therapist, using visual and verbal cues and a mental imagery technique, during reading and copying tasks and simple board games. In the latter approach, functional and goal-oriented left upper-limb activities in neglected hemispace were encouraged. Unilateral visual neglect was examined by a masked (blinded) examiner throughout all phases using the Star Cancellation Test, the Line Bisection Test, and the Baking Tray Task. Data were analyzed using visual and inferential statistical techniques. Both subjects who received limb activation and 3 of the 5 subjects who received scanning and cueing showed a reduction in UVN in one or more tests. This improvement was maintained during the withdrawal phase. Both approaches had a positive effect of reducing aspects of UVN in some subjects relative to no-treatment baselines. However, causality cannot be assured in the absence of controls. The approaches are practical for use in rehabilitation settings. These procedures warrant further replication across subjects, settings, and therapists.

Effects of exposure in single and multiple contexts on fear renewal: The moderating role of threat-specific and nonspecific emotionality.

PubMed

Olatunji, Bunmi O; Tomarken, Andrew; Wentworth, Brian; Fritzsche, Laura

2017-03-01

The current study examines effects of exposure in multiple contexts on fear reduction and renewal and the moderating effect of baseline threat-specific and nonspecific emotionality. Snake-fearful participants received a negative or neutral emotion induction and were randomized to video exposure to a snake in a single context, multiple context, or a no exposure control group. Anxiety in response to video presentations of a snake was significantly reduced in the two exposure groups compared to the control group, especially among those with heightened baseline threat-specific emotionality as indicated by snake anxiety ratings at baseline. Although the two exposure groups did not differ in responding when confronted with a novel snake, both exposure groups reported significantly lower snake anxiety and arousal than the control group. Subsequent analysis did show that compared to controls, the single context group demonstrated greater increase in anxiety and arousal from post-exposure to exposure to the novel snake among those with heightened snake anxiety at baseline. Furthermore, the multiple context group was less avoidant and less fearful than the single context group on a post-exposure behavioral test. The study used an analogue exposure paradigm with an analogue sample and findings may not be generalizable to a clinical population. These findings suggest that baseline threat-specific emotionality influences fear reduction and renewal. The benefits of exposure in multiple contexts are discussed in relation to a distinct pattern of symptom change that is in line with an inhibitory learning approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Functional Mobility Skills Training for Adults with Severe Multiple Disabilities

ERIC Educational Resources Information Center

Whinnery, Stacie B.; Whinnery, Keith W.

2011-01-01

This study investigated the effects of a functional mobility program on the functional standing and walking skills of five adults with developmental disabilities. The Mobility Opportunities Via Education (MOVE) Curriculum was implemented using a multiple-baseline across subjects design. Repeated measures were taken during baseline, intervention…

Single Case Evaluation of an Intensive Cognitive Behavioral Treatment for Generalized Social Anxiety Disorder

PubMed Central

Stoddard, Jill A.; Rosellini, Anthony J.; Hofmann, Stefan G.

2008-01-01

The present study investigated the efficacy of an 8-day, 6-session, intensive individual cognitive behavioral therapy protocol for social anxiety disorder using a multiple baseline across subjects design with 1, 2, and 3 months follow-up assessments. Participants were 5 outpatients with generalized social anxiety disorder. The intervention had variable effects on clinician-rated and self-report measures of anxiety and depression. The results question the efficacy of intensive psychotherapy as a general therapeutic strategy for social anxiety disorder. Directions for future research are discussed. PMID:19169365

Visual Analysis of Multiple Baseline across Participants Graphs when Change Is Delayed

ERIC Educational Resources Information Center

Lieberman, Rebecca G.; Yoder, Paul J.; Reichow, Brian; Wolery, Mark

2010-01-01

A within-subjects group experimental design was used to test whether three manipulated characteristics of multiple baseline across participants (MBL-P) data showing at least a month delayed change in slope affected experts' inference of a functional relation and agreement on this judgment. Thirty-six experts completed a survey composed of 16 MBL-P…

Cumulative Effects of Concussion History on Baseline Computerized Neurocognitive Test Scores: Systematic Review and Meta-analysis.

PubMed

Alsalaheen, Bara; Stockdale, Kayla; Pechumer, Dana; Giessing, Alexander; He, Xuming; Broglio, Steven P

It is unclear whether individuals with a history of single or multiple clinically recovered concussions exhibit worse cognitive performance on baseline testing compared with individuals with no concussion history. To analyze the effects of concussion history on baseline neurocognitive performance using a computerized neurocognitive test. PubMed, CINAHL, and psycINFO were searched in November 2015. The search was supplemented by a hand search of references. Studies were included if participants completed the Immediate Post-concussion Assessment and Cognitive Test (ImPACT) at baseline (ie, preseason) and if performance was stratified by previous history of single or multiple concussions. Systematic review and meta-analysis. Level 2. Sample size, demographic characteristics of participants, as well as performance of participants on verbal memory, visual memory, visual-motor processing speed, and reaction time were extracted from each study. A random-effects pooled meta-analysis revealed that, with the exception of worsened visual memory for those with 1 previous concussion (Hedges g = 0.10), no differences were observed between participants with 1 or multiple concussions compared with participants without previous concussions. With the exception of decreased visual memory based on history of 1 concussion, history of 1 or multiple concussions was not associated with worse baseline cognitive performance.

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.

Nonstationary multivariate modeling of cerebral autoregulation during hypercapnia.

PubMed

Kostoglou, Kyriaki; Debert, Chantel T; Poulin, Marc J; Mitsis, Georgios D

2014-05-01

We examined the time-varying characteristics of cerebral autoregulation and hemodynamics during a step hypercapnic stimulus by using recursively estimated multivariate (two-input) models which quantify the dynamic effects of mean arterial blood pressure (ABP) and end-tidal CO2 tension (PETCO2) on middle cerebral artery blood flow velocity (CBFV). Beat-to-beat values of ABP and CBFV, as well as breath-to-breath values of PETCO2 during baseline and sustained euoxic hypercapnia were obtained in 8 female subjects. The multiple-input, single-output models used were based on the Laguerre expansion technique, and their parameters were updated using recursive least squares with multiple forgetting factors. The results reveal the presence of nonstationarities that confirm previously reported effects of hypercapnia on autoregulation, i.e. a decrease in the MABP phase lead, and suggest that the incorporation of PETCO2 as an additional model input yields less time-varying estimates of dynamic pressure autoregulation obtained from single-input (ABP-CBFV) models. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Comparison of Objective and Subjective Changes Induced by Multiple-Pinhole Glasses and Single-Pinhole Glasses

PubMed Central

2017-01-01

Multiple-pinhole (MPH) glasses are currently sold in many countries with unproven advertisements; however, their objective and subjective effects have not been investigated. Therefore, to investigate the effects of MPH glasses excluding the single-pinhole (SPH) effect, we compared the visual functional changes, reading speed, and ocular discomfort after reading caused by MPH and SPH glasses. Healthy 36 participants with a mean age of 33.1 years underwent examinations of pupil size, visual acuity (VA), depth of focus (DOF), and near point accommodation (NPA); tests for visual field (VF), contrast sensitivity (CS), stereopsis, and reading speed; and a survey of ocular discomfort after reading. Both types of pinhole glasses enlarged pupil diameter and improved VA, DOF, and NPA. However, CS, stereopsis, and VF parameters deteriorated. In comparison with SPH glasses, MPH glasses induced smaller pupil dilation (5.3 and 5.9 mm, P < 0.001) and showed better VF parameters with preserved peripheral VF. However, no significant difference was observed for VA, DOF, NPA, stereopsis, and CS. Reading speed using pinhole glasses was significantly slower than baseline; SPH glasses showed the slowest reading speed. Both types of glasses caused significant ocular discomfort after reading compared with baseline, and symptoms were worst with MPH glasses. In conclusion, both types of pinhole glasses had positive effects due to the pinhole effect; however, they had negative effects on VF, CS, stereopsis, reading speed, and ocular discomfort. In spite of the increased luminance and preserved peripheral VF with MPHs, these glasses caused more severe ocular discomfort than SPH glasses. This clinical trial was registered at www.ClinicalTrials.gov (Identifier: NCT02572544). PMID:28378561

Critical evaluation of the effect of valerian extract on sleep structure and sleep quality.

PubMed

Donath, F; Quispe, S; Diefenbach, K; Maurer, A; Fietze, I; Roots, I

2000-03-01

A carefully designed study assessed the short-term (single dose) and long-term (14 days with multiple dosage) effects of a valerian extract on both objective and subjective sleep parameters. The investigation was performed as a randomised, double-blind, placebo-controlled, cross-over study. Sixteen patients (4 male, 12 female) with previously established psychophysiological insomnia (ICSD-code 1.A.1.), and with a median age of 49 (range: 22 to 55), were included in the study. The main inclusion criteria were reported primary insomnia according to ICSD criteria, which was confirmed by polysomnographic recording, and the absence of acute diseases. During the study, the patients underwent 8 polysomnographic recordings: i.e., 2 recordings (baseline and study night) at each time point at which the short and long-term effects of placebo and valerian were tested. The target variable of the study was sleep efficiency. Other parameters describing objective sleep structure were the usual features of sleep-stage analysis, based on the rules of Rechtschaffen and Kales (1968), and the arousal index (scored according to ASDA criteria, 1992) as a sleep microstructure parameter. Subjective parameters such as sleep quality, morning feeling, daytime performance, subjectively perceived duration of sleep latency, and sleep period time were assessed by means of questionnaires. After a single dose of valerian, no effects on sleep structure and subjective sleep assessment were observed. After multiple-dose treatment, sleep efficiency showed a significant increase for both the placebo and the valerian condition in comparison with baseline polysomnography. We confirmed significant differences between valerian and placebo for parameters describing slow-wave sleep. In comparison with the placebo, slow-wave sleep latency was reduced after administration of valerian (21.3 vs. 13.5 min respectively, p<0.05). The SWS percentage of time in bed (TIB) was increased after long-term valerian treatment, in comparison to baseline (9.8 vs. 8.1% respectively, p<0.05). At the same time point, a tendency for shorter subjective sleep latency, as well as a higher correlation coefficient between subjective and objective sleep latencies, were observed under valerian treatment. Other improvements in sleep structure - such as an increase in REM percentage and a decrease in NREM1 percentage - took place simultaneously under placebo and valerian treatment. A remarkable finding of the study was the extremely low number of adverse events during the valerian treatment periods (3 vs. 18 in the placebo period). In conclusion, treatment with a herbal extract of radix valerianae demonstrated positive effects on sleep structure and sleep perception of insomnia patients, and can therefore be recommended for the treatment of patients with mild psychophysiological insomnia.

Conceptually based vocabulary intervention: second graders' development of vocabulary words.

PubMed

Dimling, Lisa M

2010-01-01

An instructional strategy was investigated that addressed the needs of deaf and hard of hearing students through a conceptually based sign language vocabulary intervention. A single-subject multiple-baseline design was used to determine the effects of the vocabulary intervention on word recognition, production, and comprehension. Six students took part in the 30-minute intervention over 6-8 weeks, learning 12 new vocabulary words each week by means of the three intervention components: (a) word introduction, (b) word activity (semantic mapping), and (c) practice. Results indicated that the vocabulary intervention successfully improved all students' recognition, production, and comprehension of the vocabulary words and phrases.

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.

Prolonged-release fampridine treatment improved subject-reported impact of multiple sclerosis: Item-level analysis of the MSIS-29.

PubMed

Gasperini, Claudio; Hupperts, Raymond; Lycke, Jan; Short, Christine; McNeill, Manjit; Zhong, John; Mehta, Lahar R

2016-11-15

Prolonged-release (PR) fampridine is approved to treat walking impairment in persons with multiple sclerosis (MS); however, treatment benefits may extend beyond walking. MOBILE was a phase 2, 24-week, double-blind, placebo-controlled exploratory study to assess the impact of 10mg PR-fampridine twice daily versus placebo on several subject-assessed measures. This analysis evaluated the physical and psychological health outcomes of subjects with progressing or relapsing MS from individual items of the Multiple Sclerosis Impact Scale (MSIS-29). PR-fampridine treatment (n=68) resulted in greater improvements from baseline in the MSIS-29 physical (PHYS) and psychological (PSYCH) impact subscales, with differences of 89% and 148% in mean score reduction from baseline (n=64) at week 24 versus placebo, respectively. MSIS-29 item analysis showed that a higher percentage of PR-fampridine subjects had mean improvements in 16/20 PHYS and 6/9 PSYCH items versus placebo after 24weeks. Post hoc analysis of the 12-item Multiple Sclerosis Walking Scale (MSWS-12) improver population (≥8-point mean improvement) demonstrated differences in mean reductions from baseline of 97% and 111% in PR-fampridine MSIS-29 PHYS and PSYCH subscales versus the overall placebo group over 24weeks. A higher percentage of MSWS-12 improvers treated with PR-fampridine showed mean improvements in 20/20 PHYS and 8/9 PSYCH items versus placebo at 24weeks. In conclusion, PR-fampridine resulted in physical and psychological benefits versus placebo, sustained over 24weeks. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

FIVE-YEAR OUTCOMES OF INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH PATHOLOGIC MYOPIA.

PubMed

Onishi, Yuka; Yokoi, Tae; Kasahara, Kaori; Yoshida, Takeshi; Nagaoka, Natsuko; Shinohara, Kosei; Kaneko, Yuichiro; Suga, Mitsuki; Uramoto, Kengo; Ohno-Tanaka, Akiko; Ohno-Matsui, Kyoko

2018-05-03

To determine the 5-year outcome of intravitreal ranibizumab (IVR) for myopic choroidal neovascularization (CNV). We retrospectively analyzed the medical records of 51 eyes of 51 consecutive patients with myopic CNV who had been treated with IVR with a minimum follow-up period of 5 years after the initial IVR injection. The factors that predicted the best-corrected visual acuity (BCVA) at 5 years after IVR were determined by multiple regression analysis. The mean age of the subjects was 63.6 years, and the mean axial length was 29.4 mm. The mean number of IVR was 1.6, and 34 eyes (66.7%) had only a single IVR. At the baseline and at the 1-year, 2-year, 4-year, and 5-year period, the mean BCVAs were 20/49, 20/37, 20/41, 20/45, and 20/42, respectively. Stepwise multiple regression analysis showed that the BCVA at 5-year period was significantly correlated with the baseline BCVA, the number of IVR injections, and the size of the CNV-related macular atrophy. Intravitreal ranibizumab provide a 5-year visual benefit in eyes with myopic CNV compared with the natural course. A lack of enlargement of the CNV-related macular atrophy, a better baseline BCVA, and a minimum number of IVR injections were associated with better visual outcomes.

Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study

PubMed Central

Porter, Danielle P.; Daeumer, Martin; Thielen, Alexander; Chang, Silvia; Martin, Ross; Cohen, Cal; Miller, Michael D.; White, Kirsten L.

2015-01-01

At Week 96 of the Single-Tablet Regimen (STaR) study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF) developed resistance mutations compared to those treated with efavirenz (EFV)/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq) was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33), as well as baseline samples from control subjects with virologic response (n = 118). Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20%) were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study. PMID:26690199

Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study.

PubMed

Porter, Danielle P; Daeumer, Martin; Thielen, Alexander; Chang, Silvia; Martin, Ross; Cohen, Cal; Miller, Michael D; White, Kirsten L

2015-12-07

At Week 96 of the Single-Tablet Regimen (STaR) study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF) developed resistance mutations compared to those treated with efavirenz (EFV)/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq) was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33), as well as baseline samples from control subjects with virologic response (n = 118). Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20%) were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.

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

The recolonization hypothesis in a full-mouth or multiple-session treatment protocol: a blinded, randomized clinical trial.

PubMed

Zijnge, Vincent; Meijer, Henriette F; Lie, Mady-Ann; Tromp, Jan A H; Degener, John E; Harmsen, Hermie J M; Abbas, Frank

2010-06-01

To test recolonization of periodontal lesions after full-mouth scaling and root planing (FM-SRP) or multiple session-SRP (MS-SRP) in a randomized clinical trial and whether FM-SRP and MS-SRP result in different clinical outcomes. Thirty-nine subjects were randomly assigned to FM-SRP or MS-SRP groups. At baseline and after 3 months, probing pocket depth (PPD), plaque index (PlI) and bleeding on probing (BoP) were recorded. At baseline, immediately after treatment, after 1, 2, 7, 14 and 90 days, paper point samples from a single site from the maxillary right quadrant were collected for microbiological analysis of five putative pathogens by polymerase chain reaction. FM-SRP and MS-SRP resulted in significant reductions in PPD, BoP and PlI and the overall detection frequencies of the five species after 3 months without significant differences between treatments. Compared with MS-SRP, FM-SRP resulted in less recolonization of the five species, significantly for Treponema denticola, in the tested sites. FM-SRP and MS-SRP result in overall clinically and microbiologically comparable outcomes where recolonization of periodontal lesions may be better prevented by FM-SRP.

The effect of the Nintendo Wii Fit on balance control and gross motor function of children with spastic hemiplegic cerebral palsy.

PubMed

Jelsma, Jennifer; Pronk, Marieke; Ferguson, Gillian; Jelsma-Smit, Dorothee

2013-01-01

To study the impact of training using the Nintendo Wii Fit in 14 children with spastic hemiplegic cerebral palsy. A single-subject single blinded design with multiple subjects and baselines was utilised. Interactive video gaming (IVG) in lieu of regular physiotherapy was given for 3 weeks. Outcome measures included modified balance and running speed and agility (RSA) scales of the Bruininks-Oserestky test of Motor Performance 2 and the timed up and down stairs (TUDS). Balances score improved significantly (F(2, 26) = 9.8286, p = 0.001). Changes over time in the RSA (F(2, 26) = 0.86198, p = 0.434) and the TUDS (F(2, 26) = 1.3862, p = 0.268) were not significant. Ten children preferred the intervention to conventional physiotherapy. Most children preferred the IVG but as the effect did not carry over into function, IVG should not be used in place of conventional therapy and further research is needed into its use as an adjunct to therapy.

The Small Aircraft Transportation System Higher Volume Operations (SATS HVO) Flight Experiment

NASA Technical Reports Server (NTRS)

Williams, Daniel M.; Murdoch, Jennifer L.; Adams, Catherine H.

2005-01-01

This paper provides a summary of conclusions from the Small Aircraft Transportation System (SATS) Higher Volume Operations (HVO) Flight Experiment which NASA conducted to determine pilot acceptability of the HVO concept for normal conditions. The SATS HVO concept improves efficiency at non-towered, non-radar airports in Instrument Meteorological Conditions (IMC) while achieving a level of safety equal to today s system. Reported are results from flight experiment data that indicate that the SATS HVO concept is viable. The success of the SATS HVO concept is based on acceptable pilot workload, performance, and subjective criteria when compared to the procedural control operations in use today at non-towered, non-radar controlled airfields in IMC. The HVO Flight Experiment, flown on NASA's Cirrus SR22, used a subset of the HVO Simulation Experiment scenarios and evaluation pilots in order to validate the simulation experiment results. HVO and Baseline (today s system) scenarios flown included: single aircraft arriving for a GPS non-precision approach; aircraft arriving for the approach with multiple traffic aircraft; and aircraft arriving for the approach with multiple traffic aircraft and then conducting a missed approach. Results reveal that all twelve low-time instrument-rated pilots preferred SATS HVO when compared to current procedural separation operations. These pilots also flew the HVO procedures safely and proficiently without additional workload in comparison to today s system (Baseline). Detailed results of pilot flight technical error, and their subjective assessments of workload and situation awareness are presented in this paper.

An Examination of Fluoxetine for the Treatment of Selective Mutism Using a Nonconcurrent Multiple-Baseline Single-Case Design Across 5 Cases.

PubMed

Barterian, Justin A; Sanchez, Joel M; Magen, Jed; Siroky, Allison K; Mash, Brittany L; Carlson, John S

2018-01-01

This study examined the utility of fluoxetine in the treatment of 5 children, aged 5 to 14 years, diagnosed with selective mutism who also demonstrated symptoms of social anxiety. A nonconcurrent, randomized, multiple-baseline, single-case design with a single-blind placebo-controlled procedure was used. Parents and the study psychiatrist completed multiple methods of assessment including Direct Behavior Ratings and questionnaires. Treatment outcomes were evaluated by calculating effect sizes for each participant as an individual and for the participants as a group. Information regarding adverse effects with an emphasis on behavioral disinhibition and ratings of parental acceptance of the intervention was gathered. All 5 children experienced improvement in social anxiety, responsive speech, and spontaneous speech with medium to large effect sizes; however, children still met criteria for selective mutism at the end of the study. Adverse events were minimal, with only 2 children experiencing brief occurrences of minor behavioral disinhibition. Parents found the treatment highly acceptable.

Modeling Rabbit Responses to Single and Multiple Aerosol ...

EPA Pesticide Factsheets

Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

Predictive Utility of Marketed Volumetric Software Tools in Subjects at Risk for Alzheimer's: Do Regions Outside the Hippocampus Matter?

PubMed Central

Tanpitukpongse, Teerath P.; Mazurowski, Maciej A.; Ikhena, John; Petrella, Jeffrey R.

2016-01-01

Background and Purpose To assess prognostic efficacy of individual versus combined regional volumetrics in two commercially-available brain volumetric software packages for predicting conversion of patients with mild cognitive impairment to Alzheimer's disease. Materials and Methods Data was obtained through the Alzheimer's Disease Neuroimaging Initiative. 192 subjects (mean age 74.8 years, 39% female) diagnosed with mild cognitive impairment at baseline were studied. All had T1WI MRI sequences at baseline and 3-year clinical follow-up. Analysis was performed with NeuroQuant® and Neuroreader™. Receiver operating characteristic curves assessing the prognostic efficacy of each software package were generated using a univariable approach employing individual regional brain volumes, as well as two multivariable approaches (multiple regression and random forest), combining multiple volumes. Results On univariable analysis of 11 NeuroQuant® and 11 Neuroreader™ regional volumes, hippocampal volume had the highest area under the curve for both software packages (0.69 NeuroQuant®, 0.68 Neuroreader™), and was not significantly different (p > 0.05) between packages. Multivariable analysis did not increase the area under the curve for either package (0.63 logistic regression, 0.60 random forest NeuroQuant®; 0.65 logistic regression, 0.62 random forest Neuroreader™). Conclusion Of the multiple regional volume measures available in FDA-cleared brain volumetric software packages, hippocampal volume remains the best single predictor of conversion of mild cognitive impairment to Alzheimer's disease at 3-year follow-up. Combining volumetrics did not add additional prognostic efficacy. Therefore, future prognostic studies in MCI, combining such tools with demographic and other biomarker measures, are justified in using hippocampal volume as the only volumetric biomarker. PMID:28057634

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.

Spelling on the fly: investigating a pentop computer to improve the spelling skills of three elementary students with disabilities.

PubMed

Doughty, Teresa Taber; Bouck, Emily C; Bassette, Laura; Szwed, Kathryn; Flanagan, Sara

2013-01-01

The purpose of this study was to examine the effects of a pentop computer and accompanying spelling software on the spelling accuracy and academic engagement behavior in three elementary students with disabilities who were served in a resource room setting. Using a multiple baseline across students single subject research design, researchers determined student use of the pentop computer--the FLYPen--and its spelling software may serve as an equivalent intervention to traditional spelling instruction. While academic engagement performance increased considerably for students when using the FLYPen, results indicated little to no improvement over traditional instruction in spelling accuracy. Implications and suggestions for future research are presented.

Production of graphic symbol sentences by individuals with aphasia: efficacy of a computer-based augmentative and alternative communication intervention.

PubMed

Koul, Rajinder; Corwin, Melinda; Hayes, Summer

2005-01-01

The study employed a single-subject multiple baseline design to examine the ability of 9 individuals with severe Broca's aphasia or global aphasia to produce graphic symbol sentences of varying syntactical complexity using a software program that turns a computer into a speech output communication device. The sentences ranged in complexity from simple two-word phrases to those with morphological inflections, transformations, and relative clauses. Overall, results indicated that individuals with aphasia are able to access, manipulate, and combine graphic symbols to produce phrases and sentences of varying degrees of syntactical complexity. The findings are discussed in terms of the clinical and public policy implications.

A therapeutic skating intervention for children with autism spectrum disorder.

PubMed

Casey, Amanda Faith; Quenneville-Himbeault, Gabriel; Normore, Alexa; Davis, Hanna; Martell, Stephen G

2015-01-01

The purpose of this study was to evaluate the effects of a highly structured therapeutic skating intervention on motor outcomes and functional capacity in 2 boys with autism spectrum disorder aged 7 and 10 years. This multiple-baseline, single-subject study assigned participants to three 1-hour skating sessions per week for 12 weeks focusing on skill and motor development. Multiple data points assessed (a) fidelity to the intervention and (b) outcomes measures including the Pediatric Balance Scale, Timed Up and Go, floor to stand, Six-Minute Walk Test, goal attainment, and weekly on-ice testing. Improvements were found in balance, motor behavior, and functional capacity by posttest with gains remaining above pretest levels at follow-up. Therapeutic skating may produce physical benefits for children with autism spectrum disorder and offer a viable, inexpensive community-based alternative to other forms of physical activity.

Pharmacodynamic Effects of Single and Multiple Doses of Empagliflozin in Patients With Type 2 Diabetes.

PubMed

Heise, Tim; Jordan, Jens; Wanner, Christoph; Heer, Martina; Macha, Sreeraj; Mattheus, Michaela; Lund, Søren S; Woerle, Hans J; Broedl, Uli C

2016-10-01

Our aim was to investigate the effects of the sodium glucose cotransporter 2 inhibitor empagliflozin on urinary and serum glucose and electrolytes, urinary volume, osmolality, and the renin-angiotensin system in patients with type 2 diabetes. In an open-label study, 22 patients receiving metformin (median age 56 years; range 40-65 years) received empagliflozin 25 mg once daily for 5 days. Food, fluid, and sodium intake were standardized for 3 days before and during treatment. Twenty patients completed treatment. After single and multiple doses of empagliflozin, mean (SE) changes from baseline in 24-hour urinary glucose excretion were 463.3 (57.3) mmol/d and 599.5 (60.0) mmol/d, respectively (83.5 [10.3] g/d and 108.0 [10.8] g/d, respectively) (both P < 0.001), and in fasting serum glucose concentration were -1.8 (0.4) mmol/L and -1.1 (0.3) mmol/L, respectively (both P < 0.001). After a single dose, mean (SE) change from baseline in urine sodium excretion was 45.3 (9.6) mmol/d (P < 0.001), and in urine volume was 341.0 (140.5) g/d (P = 0.025), but there were no changes compared with baseline in either parameter after multiple doses. There were no changes in plasma renin or serum aldosterone with single or multiple doses of empagliflozin. There was a nonsignificant reduction in weight after a single dose of empagliflozin and a mean (SE) change of -1.4 (0.5) kg after multiple doses (P = 0.020). Empagliflozin 25 mg increased urinary glucose excretion and decreased serum glucose and weight with transient natriuresis and increases in urine volume, without significant changes in the renin-angiotensin system. Clinicaltrials.gov Identifier: NCT01276288. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose.

PubMed

Ero, Michael Penfield; Ng, Connie M; Mihailovski, Tamara; Harvey, Nathaniel R; Lewis, Brad Howard

2013-01-01

Nattokinase is a serine protease and is derived from natto, a traditional Japanese, fermented, soybean food meal. Multiple authors have described the significant fibrinolytic, antithrombotic, and antihypertensive effects of natto. Nattokinase has been growing in popularity for use as a dietary supplement for the benefit of cardiovascular health. Little is known regarding the pharmacokinetic and pharmacodynamic properties of this enzyme, and the bioavailability of nattokinase is currently unknown. This study intended to (1) detect nattokinase directly and immunologically, (2) show that nattokinase and/or its metabolites were detectable in human blood following ingestion of a commercial preparation, and (3) chart a pharmacokinetic dosing effect for nattokinase. The research team designed the pilot study as an in vivo, human clinical trial. Healthy human subjects responded to an advertisement and were screened. Subjects who satisfied both inclusion and exclusion criteria were enrolled into the study. Subjects were then instructed to orally ingest a single capsule containing a known concentration of nattokinase immediately following a baseline blood draw. Subsequent blood draws occurred over a 24-h period. This study was conducted in Oakland, California, at a clinical reference laboratory and was performed with the approval of an institutional review board (IRB) to ensure that appropriate ethical standards were met. Eleven healthy participants (five male, six female, ages 21-65), who met eligibility criteria, were enrolled. Administration of nattokinase occurred orally with the ingestion of a single daily dose (2000 FU) of nattokinase. Capsules, each containing approximately 100 mg of nattokinase, in softgel form (NSK-SD, Japan Bio Science Laboratory, Osaka, Japan), were used in the study. Baseline blood samples were collected, and participants were observed swallowing a single capsule of the nattokinase supplement before returning at 2, 4, 8, 12, 24, and 48 h post ingestion for subsequent blood draws. The presence of nattokinase in serum was measured by an enzyme-linked immunosorbent assay (ELISA), using a rabbit, polyclonal, antinattokinase-capture antibody. A pharmacokinetic pattern was observed for nattokinase between baseline and 48 h postdose. Peak serum levels of nattokinase were observed at approximately 13.3 h ± 2.5 h (mean ± standard error) postdose. Statistically significant increases in binding were detectable from baseline when comparing averaged data at time points t = 2 h-t = 24 h. These results provided the first evidence that nattokinase can be measured directly in the blood of humans. The results further suggest that a larger, more extensive, pharmacokinetic study of nattokinase is warranted. Additionally, looking for intact enzyme and bioactive nattokinase peptides should be a consideration for future studies investigating the pharmacokinetic profile of nattokinase.

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.

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.

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.

Teaching young people who are blind and have autism to make requests using a variation on the picture exchange communication system with tactile symbols: a preliminary investigation.

PubMed

Lund, Shelley K; Troha, Jeanette M

2008-04-01

This study used a single-subject multiple baseline across participants design to evaluate the effectiveness of a modified picture exchange communication system (PECS) teaching protocol with tactile symbols. Three students (two male, one female) aged 12-17 years who had autism and were blind participated in the study. The instructional program involved three phases. First, each participant learned to exchange a tactile symbol with his/her communication partner to request a preferred item/activity. Second, the distance between the communication partner and the participant was increased. Third, the participants were required to discriminate between two dissimilar tactile symbols. One out of three participants completed all phases of the instructional program. Although the other two participants did not complete the program, they demonstrated improvement from baseline responding rates. This study provided preliminary results that using tactile symbols with strategies from PECS may be an effective method to teach requesting to youth who are blind and have autism.

An intensive virtual reality program improves functional balance and mobility of adolescents with cerebral palsy.

PubMed

Brien, Marie; Sveistrup, Heidi

2011-01-01

To examine functional balance and mobility in adolescents with cerebral palsy classified at Gross Motor Function Classification System (GMFCS) level I following an intensive short-duration virtual reality (VR) intervention. Single-subject, multiple-baseline design with 4 adolescents. Outcomes included the Community Balance and Mobility Scale (CB&M), the 6-Minute Walk Test (6MWT), the Timed Up and Down Stairs, and the Gross Motor Function Measure Dimension E. Assessments were recorded 3 to 6 times at baseline, 5 times during intervention, and 4 times at follow-up. Daily 90-minute VR intervention was completed for 5 consecutive days. Visual, statistical, and clinical significance analyses were used. Statistically significant improvements were shown in all adolescents on CB&M and 6MWT. True change was recorded in all for the CB&M and in 3 for the 6MWT. Functional balance and mobility in adolescents with cerebral palsy classified at GMFCS level I improve with intense, short duration VR intervention, and changes are maintained at 1-month posttraining.

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.

Multiple Acquisition InSAR Analysis: Persistent Scatterer and Small Baseline Approaches

NASA Astrophysics Data System (ADS)

Hooper, A.

2006-12-01

InSAR techniques that process data from multiple acquisitions enable us to form time series of deformation and also allow us to reduce error terms present in single interferograms. There are currently two broad categories of methods that deal with multiple images: persistent scatterer methods and small baseline methods. The persistent scatterer approach relies on identifying pixels whose scattering properties vary little with time and look angle. Pixels that are dominated by a singular scatterer best meet these criteria; therefore, images are processed at full resolution to both increase the chance of there being only one dominant scatterer present, and to reduce the contribution from other scatterers within each pixel. In images where most pixels contain multiple scatterers of similar strength, even at the highest possible resolution, the persistent scatterer approach is less optimal, as the scattering characteristics of these pixels vary substantially with look angle. In this case, an approach that interferes only pairs of images for which the difference in look angle is small makes better sense, and resolution can be sacrificed to reduce the effects of the look angle difference by band-pass filtering. This is the small baseline approach. Existing small baseline methods depend on forming a series of multilooked interferograms and unwrapping each one individually. This approach fails to take advantage of two of the benefits of processing multiple acquisitions, however, which are usually embodied in persistent scatterer methods: the ability to find and extract the phase for single-look pixels with good signal-to-noise ratio that are surrounded by noisy pixels, and the ability to unwrap more robustly in three dimensions, the third dimension being that of time. We have developed, therefore, a new small baseline method to select individual single-look pixels that behave coherently in time, so that isolated stable pixels may be found. After correction for various error terms, the phase values of the selected pixels are unwrapped using a new three-dimensional algorithm. We apply our small baseline method to an area in southern Iceland that includes Katla and Eyjafjallajökull volcanoes, and retrieve a time series of deformation that shows transient deformation due to intrusion of magma beneath Eyjafjallajökull. We also process the data using the Stanford method for persistent scatterers (StaMPS) for comparison.

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

Teaching Students with Cognitive Impairment Chained Mathematical Task of Decimal Subtraction Using Simultaneous Prompting

ERIC Educational Resources Information Center

Rao, Shaila; Kane, Martha T.

2009-01-01

This study assessed effectiveness of simultaneous prompting procedure in teaching two middle school students with cognitive impairment decimal subtraction using regrouping. A multiple baseline, multiple probe design replicated across subjects successfully taught two students with cognitive impairment at middle school level decimal subtraction…

A Randomized, Double-Blind Study Assessing Changes in Cognitive Function in Indian School Children Receiving a Combination of Bacopa monnieri and Micronutrient Supplementation vs. Placebo

PubMed Central

Mitra-Ganguli, Tora; Kalita, Soumik; Bhushan, Sakshi; Stough, Con; Kean, James; Wang, Nan; Sethi, Vidhu; Khadilkar, Anuradha

2017-01-01

Several studies have indicated a chronic cognitive enhancing effect of Bacopa monnieri across different ages and cognitive impairment associated with vitamin and mineral deficiencies in children. Therefore, we investigated the effects of 4-month supplementation with a combination of B. monnieri extract and multiple micronutrients on cognitive functions in Indian school children aged 7–12 years. This was a randomized, double-blind, parallel design, single-center study in which 300 children were randomized to receive a beverage either fortified with B. monnieri and multiple micronutrients (“fortified”) or a non-fortified isocaloric equivalent (“control”) twice-daily for 4 months. Cognitive function was assessed by the Cambridge Neuropsychological Automated Test Battery (CANTAB) administered at baseline, Day 60 and Day 121. The primary endpoint was change in short-term memory (working memory) from baseline in subjects receiving “fortified” vs. “control” beverages after 4 months. Secondary endpoints included sustained attention, episodic memory, and executive function. The “fortified” beverage did not significantly improve short-term memory or any of the secondary outcomes tested relative to the “control” beverage. However, the spatial working memory “strategy” score showed significant improvement on Day 60 (difference between groups in change from baseline: −0.55; p < 0.05), but not on Day 121 due to the active intervention. Study products were well-tolerated. Reasons for these unexpected findings are discussed. PMID:29204115

Systematic individualized narrative language intervention on the personal narratives of children with autism.

PubMed

Petersen, Douglas B; Brown, Catherine L; Ukrainetz, Teresa A; Wise, Christine; Spencer, Trina D; Zebre, Jennifer

2014-01-01

The purpose of this study was to investigate the effect of an individualized, systematic language intervention on the personal narratives of children with autism. A single-subject, multiple-baseline design across participants and behaviors was used to examine the effect of the intervention on language features of personal narratives. Three 6- to 8-year-old boys with autism participated in 12 individual intervention sessions that targeted 2-3 story grammar elements (e.g., problem, plan) and 3-4 linguistic complexity elements (e.g., causal subordination, adverbs) selected from each participant's baseline performance. Intervention involved repeated retellings of customized model narratives and the generation of personal narratives with a systematic reduction of visual and verbal scaffolding. Independent personal narratives generated at the end of each baseline, intervention, and maintenance session were analyzed for presence and sophistication of targeted features. Graphical and statistical results showed immediate improvement in targeted language features as a function of intervention. There was mixed evidence of maintenance 2 and 7 weeks after intervention. Children with autism can benefit from an individualized, systematic intervention targeting specific narrative language features. Greater intensity of intervention may be needed to gain enduring effects for some language features.

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

A Fast Radio Burst Search Method for VLBI Observation

NASA Astrophysics Data System (ADS)

Liu, Lei; Tong, Fengxian; Zheng, Weimin; Zhang, Juan; Tong, Li

2018-02-01

We introduce the cross-spectrum-based fast radio burst (FRB) search method for Very Long Baseline Interferometer (VLBI) observation. This method optimizes the fringe fitting scheme in geodetic VLBI data post-processing, which fully utilizes the cross-spectrum fringe phase information and therefore maximizes the power of single-pulse signals. Working with cross-spectrum greatly reduces the effect of radio frequency interference compared with using auto-power spectrum. Single-pulse detection confidence increases by cross-identifying detections from multiple baselines. By combining the power of multiple baselines, we may improve the detection sensitivity. Our method is similar to that of coherent beam forming, but without the computational expense to form a great number of beams to cover the whole field of view of our telescopes. The data processing pipeline designed for this method is easy to implement and parallelize, which can be deployed in various kinds of VLBI observations. In particular, we point out that VGOS observations are very suitable for FRB search.

Donepezil improved memory in multiple sclerosis in a randomized clinical trial.

PubMed

Krupp, L B; Christodoulou, C; Melville, P; Scherl, W F; MacAllister, W S; Elkins, L E

2004-11-09

To determine the effect of donepezil in treating memory and cognitive dysfunction in multiple sclerosis (MS). This single-center double-blind placebo-controlled clinical trial evaluated 69 MS patients with cognitive impairment who were randomly assigned to receive a 24-week treatment course of either donepezil (10 mg daily) or placebo. Patients underwent neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in verbal learning and memory on the Selective Reminding Test (SRT). Secondary outcomes included other tests of cognitive function, patient-reported change in memory, and clinician-reported impression of cognitive change. Donepezil-treated patients showed significant improvement in memory performance on the SRT compared to placebo (p = 0.043). The benefit of donepezil remained significant after controlling for various covariates including age, Expanded Disability Status Scale, baseline SRT score, reading ability, MS subtype, and sex. Donepezil-treated patients did not show significant improvements on other cognitive tests, but were more than twice as likely to report memory improvement than those in the placebo group (p = 0.006). The clinician also reported cognitive improvement in almost twice as many donepezil vs placebo patients (p = 0.036). No serious adverse events related to study medication occurred, although more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams (p = 0.010). Donepezil improved memory in MS patients with initial cognitive impairment in a single center clinical trial. A larger multicenter investigation of donepezil in MS is warranted in order to more definitively assess the efficacy of this intervention.

Single-donor islet transplantation and long-term insulin independence in select patients with type 1 diabetes mellitus.

PubMed

Al-Adra, David P; Gill, Richdeep S; Imes, Sharleen; O'Gorman, Doug; Kin, Tatsuya; Axford, Sara J; Shi, Xinzhe; Senior, Peter A; Shapiro, A M James

2014-11-15

Islet transplantation is a recognized treatment option for select patients with type I diabetes mellitus. However, islet infusions from multiple donors are often required to achieve insulin independence. Ideally, insulin independence would be achieved routinely with only a single donor. Identification of factors associated with insulin independence after single-donor islet transplantation may help to select recipient-donor combinations with the highest probability of success. Subjects undergoing islet transplantation at a single center (Edmonton, Canada) between March 1999 and August 2013 were included. Recipient, donor, and transplant characteristics were collected and compared between recipients who became insulin independent after one islet transplantation and those who did not. Thirty-one patients achieved insulin independence after a single-donor islet transplantation, and 149 did not. Long-term insulin-free survival was not different between the groups. Factors significantly associated with single-donor success included recipient age, insulin requirement at baseline, donor weight, donor body mass index, islet transplant mass, and peritransplant heparin and insulin administration. On multivariate analysis, pretransplantation daily insulin requirements, the use of peritransplantation heparin and insulin infusions, and islet transplant mass remained significant. We have identified clinically relevant differences defining the achievement of insulin independence after single-donor transplantation. Based on these differences, a preoperative insulin requirement of less than 0.6 U/kg per day and receiving more than 5,646 islet equivalents (IEQ)/kg have a sensitivity of 84% and 71% and specificity of 50% and 50%, respectively, for insulin independence after single-donor islet transplantation. With ideal patient selection, this finding could potentially increase single-donor transplantation success and may be especially relevant for presensitized subjects or those who may subsequently require renal replacement.

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

Feasibility and potential effectiveness of a non-pharmacological multidisciplinary care programme for persons with generalised osteoarthritis: a randomised, multiple-baseline single-case study

PubMed Central

Kwakkenbos, Linda; Rietveld, Leonie; den Broeder, Alfons A; de Bie, Rob A; van den Ende, Cornelia H M

2012-01-01

Objectives To evaluate the feasibility and potential effectiveness of a 12-week, non-pharmacological multidisciplinary intervention in patients with generalised osteoarthritis (GOA). Design A randomised, concurrent, multiple-baseline single-case design. During the baseline period, the intervention period and the postintervention period, all participants completed several health outcomes twice a week on Visual Analogue Scales. Setting Rheumatology outpatient department of a specialised hospital in the Netherlands. Participants 1 man and four women (aged 51–76 years) diagnosed with GOA. Primary outcome measures To assess feasibility, the authors assessed the number of dropouts and adverse events, adherence rates and patients' satisfaction. Secondary outcome measures To assess the potential effectiveness, the authors assessed pain and self-efficacy using visual data inspection and randomisation tests. Results The intervention was feasible in terms of adverse events (none) and adherence rate but not in terms of participants' satisfaction with the intervention. Visual inspection of the data and randomisation testing demonstrated no effects on pain (p=0.93) or self-efficacy (p=0.85). Conclusions The results of the present study indicate that the proposed intervention for patients with GOA was insufficiently feasible and effective. The data obtained through this multiple-baseline study have highlighted several areas in which the therapy programme can be optimised. PMID:22815466

The effect of antacid on salivary pH in patients with and without dental erosion after multiple acid challenges.

PubMed

Dhuhair, Sarah; Dennison, Joseph B; Yaman, Peter; Neiva, Gisele F

2015-04-01

To evaluate the effect of antacid swish in the salivary pH values and to monitor the pH changes in subjects with and without dental erosion after multiple acid challenge tests. 20 subjects with tooth erosion were matched in age and gender with 20 healthy controls according to specific inclusion/exclusion criteria. Baseline measures were taken of salivary pH, buffering capacity and salivary flow rate using the Saliva Check System. Subjects swished with Diet Pepsi three times at 10-minute intervals. Changes in pH were monitored using a digital pH meter at 0-, 5-, and 10- minute intervals and at every 5 minutes after the third swish until pH resumed baseline value or 45 minutes relapse. Swishing regimen was repeated on a second visit, followed by swishing with sugar-free liquid antacid (Mylanta Supreme). Recovery times were also recorded. Data was analyzed using independent t-tests, repeated measures ANOVA, and Fisher's exact test (α= 0.05). Baseline buffering capacity and flow rate were not significantly different between groups (P= 0.542; P= 0.2831, respectively). Baseline salivary pH values were similar between groups (P= 0.721). No significant differences in salivary pH values were found between erosion and non-erosion groups in response to multiple acid challenges (P= 0.695) or antacid neutralization (P= 0.861). Analysis of salivary pH recovery time revealed no significant differences between groups after acid challenges (P= 0.091) or after the use of antacid (P= 0.118). There was a highly significant difference in the survival curves of the two groups on Day 2, with the non-erosion group resolving significantly faster than the erosion group (P= 0.0086).

Anterior Segment Imaging Predicts Incident Gonioscopic Angle Closure.

PubMed

Baskaran, Mani; Iyer, Jayant V; Narayanaswamy, Arun K; He, Yingke; Sakata, Lisandro M; Wu, Renyi; Liu, Dianna; Nongpiur, Monisha E; Friedman, David S; Aung, Tin

2015-12-01

To investigate the incidence of gonioscopic angle closure after 4 years in subjects with gonioscopically open angles but varying degrees of angle closure detected on anterior segment optical coherence tomography (AS OCT; Visante; Carl Zeiss Meditec, Dublin, CA) at baseline. Prospective, observational study. Three hundred forty-two subjects, mostly Chinese, 50 years of age or older, were recruited, of whom 65 were controls with open angles on gonioscopy and AS OCT at baseline, and 277 were cases with baseline open angles on gonioscopy but closed angles (1-4 quadrants) on AS OCT scans. All subjects underwent gonioscopy and AS OCT at baseline (horizontal and vertical single scans) and after 4 years. The examiner performing gonioscopy was masked to the baseline and AS OCT data. Angle closure in a quadrant was defined as nonvisibility of the posterior trabecular meshwork by gonioscopy and visible iridotrabecular contact beyond the scleral spur in AS OCT scans. Gonioscopic angle closure in 2 or 3 quadrants after 4 years. There were no statistically significant differences in age, ethnicity, or gender between cases and controls. None of the control subjects demonstrated gonioscopic angle closure after 4 years. Forty-eight of the 277 subjects (17.3%; 95% confidence interval [CI], 12.8-23; P < 0.0001) with at least 1 quadrant of angle closure on AS OCT at baseline demonstrated gonioscopic angle closure in 2 or more quadrants, whereas 28 subjects (10.1%; 95% CI, 6.7-14.6; P < 0.004) demonstrated gonioscopic angle closure in 3 or more quadrants after 4 years. Individuals with more quadrants of angle closure on baseline AS OCT scans had a greater likelihood of gonioscopic angle closure developing after 4 years (P < 0.0001, chi-square test for trend for both definitions of angle closure). Anterior segment OCT imaging at baseline predicts incident gonioscopic angle closure after 4 years among subjects who have gonioscopically open angles and iridotrabecular contact on AS OCT at baseline. Copyright © 2015 American Academy of Ophthalmology. All rights reserved.

STAR 3 randomized controlled trial to compare sensor-augmented insulin pump therapy with multiple daily injections in the treatment of type 1 diabetes: research design, methods, and baseline characteristics of enrolled subjects.

PubMed

Davis, Stephen N; Horton, Edward S; Battelino, Tadej; Rubin, Richard R; Schulman, Kevin A; Tamborlane, William V

2010-04-01

Sensor-augmented pump therapy (SAPT) integrates real-time continuous glucose monitoring (RT-CGM) with continuous subcutaneous insulin infusion (CSII) and offers an alternative to multiple daily injections (MDI). Previous studies provide evidence that SAPT may improve clinical outcomes among people with type 1 diabetes. Sensor-Augmented Pump Therapy for A1c Reduction (STAR) 3 is a multicenter randomized controlled trial comparing the efficacy of SAPT to that of MDI in subjects with type 1 diabetes. Subjects were randomized to either continue with MDI or transition to SAPT for 1 year. Subjects in the MDI cohort were allowed to transition to SAPT for 6 months after completion of the study. SAPT subjects who completed the study were also allowed to continue for 6 months. The primary end point was the difference between treatment groups in change in hemoglobin A1c (HbA1c) percentage from baseline to 1 year of treatment. Secondary end points included percentage of subjects with HbA1c < or =7% and without severe hypoglycemia, as well as area under the curve of time spent in normal glycemic ranges. Tertiary end points include percentage of subjects with HbA1c < or =7%, key safety end points, user satisfaction, and responses on standardized assessments. A total of 495 subjects were enrolled, and the baseline characteristics similar between the SAPT and MDI groups. Study completion is anticipated in June 2010. Results of this randomized controlled trial should help establish whether an integrated RT-CGM and CSII system benefits patients with type 1 diabetes more than MDI.

AUTOGENIC THERAPY IN TENSION HEADACHE

PubMed Central

Amruthraj, Brunda; Mishra, H.; Kumaraiah, V.

1987-01-01

SUMMARY Ten subjects diagnosed as Psychalgia were taken for study. A multiple baseline design was adapted and clients were subjected to 30 sessions of autogenic training. They were assessed using physiological (EMG and thermal change) and behavioural measures (Visual analogue scale and behavioural symptom checklist). Findings revealed autogenic therapy to be effective in reducing tension headache. PMID:21927245

Diagnostic transitions in mild cognitive impairment subtypes.

PubMed

Forlenza, Orestes Vicente; Diniz, Breno Satler; Nunes, Paula Villela; Memória, Claudia Maia; Yassuda, Monica Sanches; Gattaz, Wagner Farid

2009-12-01

At least for a subset of patients, the clinical diagnosis of mild cognitive impairment (MCI) may represent an intermediate stage between normal aging and dementia. Nevertheless, the patterns of transition of cognitive states between normal cognitive aging and MCI to dementia are not well established. In this study we address the pattern of transitions between cognitive states in patients with MCI and healthy controls, prior to the conversion to dementia. 139 subjects (78% women, mean age, 68.5 +/- 6.1 years; mean educational level, 11.7 +/- 5.4 years) were consecutively assessed in a memory clinic with a standardized clinical and neuropsychological protocol, and classified as cognitively healthy (normal controls) or with MCI (including subtypes) at baseline. These subjects underwent annual reassessments (mean duration of follow-up: 2.7 +/- 1.1 years), in which cognitive state was ascertained independently of prior diagnoses. The pattern of transitions of the cognitive state was determined by Markov chain analysis. The transitions from one cognitive state to another varied substantially between MCI subtypes. Single-domain MCI (amnestic and non-amnestic) more frequently returned to normal cognitive state upon follow-up (22.5% and 21%, respectively). Among subjects who progressed to Alzheimer's disease (AD), the most common diagnosis immediately prior conversion was multiple-domain MCI (85%). The clinical diagnosis of MCI and its subtypes yields groups of patients with heterogeneous patterns of transitions between one given cognitive state to another. The presence of more severe and widespread cognitive deficits, as indicated by the group of multiple-domain amnestic MCI may be a better predictor of AD than single-domain amnestic or non-amnestic deficits. These higher-risk individuals could probably be the best candidates for the development of preventive strategies and early treatment for the disease.

Positive Association of Vitamin E Supplementation with Hemoglobin Levels in Mildly Anemic Healthy Pakistani Adults.

PubMed

Jilani, Tanveer; Azam, Iqbal; Moiz, Bushra; Mehboobali, Naseema; Perwaiz Iqbal, Mohammad

2015-01-01

Hemoglobin levels slightly below the lower limit of normal are common in adults in the general population in developing countries. A few human studies have suggested the use of antioxidant vitamins in the correction of mild anemia. The objective of the present study was to investigate the association of vitamin E supplementation in mildly anemic healthy adults with post-supplemental blood hemoglobin levels in the general population of Karachi, Pakistan. In a single-blinded and placebo-controlled randomized trial, 124 mildly anemic subjects from the General Practitioners' Clinics and personnel of the Aga Khan University were randomized into intervention (n = 82) and control (n = 42) group. In the intervention group, each subject was given vitamin E (400 mg) everyday for a period of three months, while control group subjects received a placebo. Eighty six subjects completed the trial. Fasting venous blood was collected at baseline and after three months of supplementation. Hemoglobin levels and serum/plasma concentrations of vitamin E, vitamin B12, folate, ferritin, serum transferrin receptor (sTfR), glucose, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, creatinine, total-antioxidant-status and erythropoietin were measured and analyzed using repeated measures ANOVA and multiple linear regression. The adjusted regression coefficients (β) and standard error [SE(β)] of the significant predictors of post-supplemental hemoglobin levels were serum concentration of vitamin E (0.983[0.095]), gender (- 0.656[0.244]), sTfR (- 0.06[0.02]) and baseline hemoglobin levels (0.768[0.077]). The study showed a positive association between vitamin E supplementation and enhanced hemoglobin levels in mildly anemic adults.

Relationship between sleep and pain in adolescents with juvenile primary fibromyalgia syndrome.

PubMed

Olsen, Margaret N; Sherry, David D; Boyne, Kathleen; McCue, Rebecca; Gallagher, Paul R; Brooks, Lee J

2013-04-01

To investigate sleep quality in adolescents with juvenile primary fibromyalgia syndrome (JPFS) and determine whether sleep abnormalities, including alpha-delta sleep (ADS), correlate with pain intensity. We hypothesized that successful treatment for pain with exercise therapy would reduce ADS and improve sleep quality. Single-center preintervention and postintervention (mean = 5.7 ± 1.0 weeks; range = 4.0-7.3 weeks) observational study. Ten female adolescents (mean age = 16.2 ± 0.65 SD yr) who met criteria for JPFS and completed treatment. Multidisciplinary pain treatment, including intensive exercise therapy. Pain and disability were measured by a pain visual analog scale (VAS) and the functional disability inventory. Subjective sleep measures included a sleep VAS, an energy VAS, and the School Sleep Habits Survey. Objective sleep measures included actigraphy, polysomnography (PSG), and the Multiple Sleep Latency Test. Baseline PSG was compared with that of healthy age- and sex-matched control patients. At baseline, patients had poorer sleep efficiency, more arousals/awakenings, and more ADS (70.3% of total slow wave sleep [SWS] versus 21.9% SWS, P = 0.002) than controls. ADS was unrelated to pain, disability, or subjective sleep difficulty. After treatment, pain decreased (P = 0.000) and subjective sleep quality improved (P = 0.008). Objective sleep quality, including the amount of ADS, did not change. Although perceived sleep quality improved in adolescents with JPFS after treatment, objective measures did not. Our findings do not suggest exercise therapy for pain improves sleep by reducing ADS, nor do they support causal relationships between ADS and chronic pain or subjective sleep quality.

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.

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

Flight crew sleep during multiple layover polar flights

NASA Technical Reports Server (NTRS)

Sasaki, Mitsuo; Kurosaki, Yuko S.; Spinweber, Cheryl L.; Graeber, R. C.; Takahashi, Toshiharu

1993-01-01

This study investigated changes in sleep after multiple transmeridian flights. The subjects were 12 B747 airline pilots operating on the following polar flight: Tokyo (TYO)-Anchorage (ANC)-London (LON)-Anchorage-Tokyo. Sleep polysmonograms were recorded on two baseline nights (B1, B2), during layovers, and, after returning to Tokyo, two recovery nights were recorded (R1, R2). In ANC (outbound), total sleep time was reduced and, sleep efficiency was low (72.0 percent). In London, time in bed increased slightly, but sleep efficiency was still reduced. On return to ANC (inbound), there was considerable slow wave sleep rebound and multiple awakenings reduced sleep efficiency to 76.8 percent. Sleep efficiency on R2 was significantly lower than on B1 but not different from R1. To sum up, sleep of aircrews flying multiple transmeridian flights is disrupted during layovers and this effect persists during the two recovery nights. As a result, there is a marked cumulative sleep loss during multilegs polar route trip in comparison to single leg flights. These findings suggest that following such extensive transmeridian trips, crews should have at least three nights of recovery sleep in their home time zone before returning to duty.

Stress, Behavior, and Children and Youth Who Are Deafblind

ERIC Educational Resources Information Center

Nelson, Catherine; Greenfield, Robin G.; Hyte, Holly A.; Shaffer, Jason P.

2013-01-01

Children and youth who are deafblind with multiple disabilities have several identified risk factors for experiencing toxic levels of stress, and such stress is known to impair physical, mental, and emotional health. This single-case multiple baseline study examined the frequency and duration of behaviors thought to indicate stress, the duration…

Teaching Children with Language-Learning Disabilities to Plan and Revise Compare-Contrast Texts

ERIC Educational Resources Information Center

Shen, Mei; Troia, Gary A.

2018-01-01

This study used a multiple-probe, multiple-baseline single-case design to investigate the efficacy of planning, and then revising strategy instruction using self-regulated strategy development on the compare-contrast writing performance of three late elementary students with language-learning disabilities. After receiving the planning instruction,…

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.

Limits in feature-based attention to multiple colors.

PubMed

Liu, Taosheng; Jigo, Michael

2017-11-01

Attention to a feature enhances the sensory representation of that feature. Although much has been learned about the properties of attentional modulation when attending to a single feature, the effectiveness of attending to multiple features is not well understood. We investigated this question in a series of experiments using a color-detection task while varying the number of attended colors in a cueing paradigm. Observers were shown either a single cue, two cues, or no cue (baseline) before detecting a coherent color target. We measured detection threshold by varying the coherence level of the target. Compared to the baseline condition, we found consistent facilitation of detection performance in the one-cue and two-cue conditions, but performance in the two-cue condition was lower than that in the one-cue condition. In the final experiment, we presented a 50% valid cue to emulate the situation in which observers were only able to attend a single color in the two-cue condition, and found equivalent detection thresholds with the standard two-cue condition. These results indicate a limit in attending to two colors and further imply that observers could effectively attend a single color at a time. Such a limit is likely due to an inability to maintain multiple active attentional templates for colors.

Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects.

PubMed

Nugent, Allison C; Ballard, Elizabeth D; Gould, Todd D; Park, Lawrence T; Moaddel, Ruin; Brutsche, Nancy E; Zarate, Carlos A

2018-02-27

Ketamine's mechanism of action was assessed using gamma power from magnetoencephalography (MEG) as a proxy measure for homeostatic balance in 35 unmedicated subjects with major depressive disorder (MDD) and 25 healthy controls enrolled in a double-blind, placebo-controlled, randomized cross-over trial of 0.5 mg/kg ketamine. MDD subjects showed significant improvements in depressive symptoms, and healthy control subjects exhibited modest but significant increases in depressive symptoms for up to 1 day after ketamine administration. Both groups showed increased resting gamma power following ketamine. In MDD subjects, gamma power was not associated with the magnitude of the antidepressant effect. However, baseline gamma power was found to moderate the relationship between post-ketamine gamma power and antidepressant response; specifically, higher post-ketamine gamma power was associated with better response in MDD subjects with lower baseline gamma, with an inverted relationship in MDD subjects with higher baseline gamma. This relationship was observed in multiple regions involved in networks hypothesized to be involved in the pathophysiology of MDD. This finding suggests biological subtypes based on the direction of homeostatic dysregulation and has important implications for inferring ketamine's mechanism of action from studies of healthy controls alone.

The Effects of a Self-Monitoring Package on Homework Completion and Accuracy of Students with Disabilities in an Inclusive General Education Classroom

ERIC Educational Resources Information Center

Falkenberg, Carol Ann; Barbetta, Patricia M.

2013-01-01

This study used a multiple baseline design across subjects to investigate the effects of a self-monitoring package on the math and spelling homework completion and accuracy rates of four fourth-grade students (two boys and two girls) with disabilities in an inclusive general education classroom. Throughout baseline and intervention, participants…

Repaglinide pharmacokinetics in healthy young adult and elderly subjects.

PubMed

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

1999-04-01

In this open-label, single-center, pharmacokinetic study of repaglinide, 12 healthy volunteers (6 men, 6 women) were enrolled in each of 2 groups (total, 24 volunteers). One group consisted of young adult subjects (18 to 40 years), and the other group consisted of elderly subjects (> or = 65 years). On day 1, after a 10-hour fast, all 24 subjects received a single 2-mg dose of repaglinide. Starting on day 2 and continuing for 7 days, subjects received a 2-mg dose of repaglinide 15 minutes before each of 3 meals. On day 9, subjects received a single 2-mg dose of repaglinide. Pharmacokinetic profiles, including area under the curve, maximum concentration (Cmax), time to Cmax, and half-life, were determined at completion of the single-dose and multiple-dose regimens (days 1 and 9, respectively). Trough repaglinide values were collected on days 2 through 7 to assess steady state. The single-dose and multiple-dose pharmacokinetic variables of serum repaglinide were not significantly different between young adult and elderly subjects. Repaglinide was well tolerated in both groups. Hypoglycemic events occurred in 5 young adult and 5 elderly subjects. This study demonstrates that the pharmacokinetics of repaglinide are similar in healthy young adult and elderly subjects.

Dextromethorphan/Quinidine in Migraine Prophylaxis: An Open-label Observational Clinical Study.

PubMed

Berkovich, Regina R; Sokolov, Alexey Y; Togasaki, Daniel M; Yakupova, Aida A; Cesar, Paul-Henry; Sahai-Srivastava, Soma

This study aimed to assess potential efficacy and safety of dextromethorphan/quinidine (DMQ) in prophylactic treatment of migraine in patients with multiple sclerosis (MS) with superimposed pseudobulbar affect (PBA). Multiple sclerosis patients with superimposed PBA and comorbid migraine were enrolled into this open-label observational study at the University of Southern California Comprehensive MS Center. The baseline characteristics included, among other data, frequency and severity of acute migraine attacks and use of migraine relievers. The DMQ was used exclusively per its primary indication - PBA symptoms control - 20/10 mg orally, twice a day for the mean of 4.5 months (the shortest exposure registered was 3 months and the longest, 6 months). To determine whether treatment caused an effect on migraine frequency and severity, the baseline and posttreatment values were compared using nonparametric sign test. Thirty-three MS subjects with PBA, who also suffered from migraines, were identified. Twenty-nine subjects had improvement in headache frequency, 4 had no change, and none had worsening (P < 0.001 as compared with the baseline). Twenty-eight subjects had improvement in headache severity, 5 had no change, and none had worsening (P < 0.001). Our pilot study results provide evidence that DMQ shows promise as a candidate for larger clinical studies evaluating its efficacy for the prevention of migraine headaches.

Individuals with Single Versus Multiple Suicide Attempts Over 10 Years of Prospective Follow-Up

PubMed Central

Boisseau, Christina L.; Yen, Shirley; Markowitz, John C.; Grilo, Carlos M.; Sanislow, Charles A.; Shea, M. Tracie; Zanarini, Mary C.; Skodol, Andrew E.; Gunderson, John G.; Morey, Leslie C.; McGlashan, Thomas H.

2012-01-01

Background The study attempted to identify characteristics that differentiate multiple suicide attempters from single attempters in individuals with personality disorders (PDs) and/or major depression. Method Participants were 431 participants enrolled in the Collaborative Longitudinal Study of Personality Disorders from July 1996 to June 2008. Suicide attempts were assessed with the Longitudinal Interval Follow-up Evaluation at 6 and 12 months, then yearly through 10 years. Logistic regression was used to compare single attempters to multiple attempters on Axis I and II psychiatric disorders and personality trait variables. Results Twenty-one percent of participants attempted suicide during the 10 years of observation, with 39 (9.0%) reporting a single suicide attempt and 54 (12.5%) reporting multiple suicide attempts. Although no significant differences in were found in baseline Axis I disorders, multiple attempters were significantly more likely to meet criteria for borderline personality disorder and to have higher impulsivity scores than single attempters. Conclusion These results underscore the importance of considering both personality disorders and traits in the assessment of suicidality. PMID:22995448

Using Clickers to Increase On-Task Behaviors of Middle School Students with Behavior Problems

ERIC Educational Resources Information Center

Xin, Joy F.; Johnson, Mary L.

2015-01-01

This study examined the effect of using a remote device, a Clicker, on the on-task behavior of middle school students with behavior problems. Five students with behavior problems participated in the study. A single-subject research design with ABAB (phase A: baseline 1, phase B: intervention 1, phase A: baseline 2, phase B: intervention 2) phases…

Predictive Utility of Marketed Volumetric Software Tools in Subjects at Risk for Alzheimer Disease: Do Regions Outside the Hippocampus Matter?

PubMed

Tanpitukpongse, T P; Mazurowski, M A; Ikhena, J; Petrella, J R

2017-03-01

Alzheimer disease is a prevalent neurodegenerative disease. Computer assessment of brain atrophy patterns can help predict conversion to Alzheimer disease. Our aim was to assess the prognostic efficacy of individual-versus-combined regional volumetrics in 2 commercially available brain volumetric software packages for predicting conversion of patients with mild cognitive impairment to Alzheimer disease. Data were obtained through the Alzheimer's Disease Neuroimaging Initiative. One hundred ninety-two subjects (mean age, 74.8 years; 39% female) diagnosed with mild cognitive impairment at baseline were studied. All had T1-weighted MR imaging sequences at baseline and 3-year clinical follow-up. Analysis was performed with NeuroQuant and Neuroreader. Receiver operating characteristic curves assessing the prognostic efficacy of each software package were generated by using a univariable approach using individual regional brain volumes and 2 multivariable approaches (multiple regression and random forest), combining multiple volumes. On univariable analysis of 11 NeuroQuant and 11 Neuroreader regional volumes, hippocampal volume had the highest area under the curve for both software packages (0.69, NeuroQuant; 0.68, Neuroreader) and was not significantly different ( P > .05) between packages. Multivariable analysis did not increase the area under the curve for either package (0.63, logistic regression; 0.60, random forest NeuroQuant; 0.65, logistic regression; 0.62, random forest Neuroreader). Of the multiple regional volume measures available in FDA-cleared brain volumetric software packages, hippocampal volume remains the best single predictor of conversion of mild cognitive impairment to Alzheimer disease at 3-year follow-up. Combining volumetrics did not add additional prognostic efficacy. Therefore, future prognostic studies in mild cognitive impairment, combining such tools with demographic and other biomarker measures, are justified in using hippocampal volume as the only volumetric biomarker. © 2017 by American Journal of Neuroradiology.

Single-Trial Normalization for Event-Related Spectral Decomposition Reduces Sensitivity to Noisy Trials

PubMed Central

Grandchamp, Romain; Delorme, Arnaud

2011-01-01

In electroencephalography, the classical event-related potential model often proves to be a limited method to study complex brain dynamics. For this reason, spectral techniques adapted from signal processing such as event-related spectral perturbation (ERSP) – and its variant event-related synchronization and event-related desynchronization – have been used over the past 20 years. They represent average spectral changes in response to a stimulus. These spectral methods do not have strong consensus for comparing pre- and post-stimulus activity. When computing ERSP, pre-stimulus baseline removal is usually performed after averaging the spectral estimate of multiple trials. Correcting the baseline of each single-trial prior to averaging spectral estimates is an alternative baseline correction method. However, we show that this method leads to positively skewed post-stimulus ERSP values. We eventually present new single-trial-based ERSP baseline correction methods that perform trial normalization or centering prior to applying classical baseline correction methods. We show that single-trial correction methods minimize the contribution of artifactual data trials with high-amplitude spectral estimates and are robust to outliers when performing statistical inference testing. We then characterize these methods in terms of their time–frequency responses and behavior compared to classical ERSP methods. PMID:21994498

Efficacy of the Fun For Wellness Online Intervention to Promote Multidimensional Well-Being: a Randomized Controlled Trial.

PubMed

Myers, Nicholas D; Prilleltensky, Isaac; Prilleltensky, Ora; McMahon, Adam; Dietz, Samantha; Rubenstein, Carolyn L

2017-11-01

Subjective well-being refers to people's level of satisfaction with life as a whole and with multiple dimensions within it. Interventions that promote subjective well-being are important because there is evidence that physical health, mental health, substance use, and health care costs may be related to subjective well-being. Fun For Wellness (FFW) is a new online universal intervention designed to promote growth in multiple dimensions of subjective well-being. The purpose of this study was to provide an initial evaluation of the efficacy of FFW to increase subjective well-being in multiple dimensions in a universal sample. The study design was a prospective, double-blind, parallel group randomized controlled trial. Data were collected at baseline and 30 and 60 days-post baseline. A total of 479 adult employees at a major university in the southeast of the USA were enrolled. Recruitment, eligibility verification, and data collection were conducted online. Measures of interpersonal, community, occupational, physical, psychological, economic (i.e., I COPPE), and overall subjective well-being were constructed based on responses to the I COPPE Scale. A two-class linear regression model with complier average causal effect estimation was imposed for each dimension of subjective well-being. Participants who complied with the FFW intervention had significantly higher subjective well-being, as compared to potential compliers in the Usual Care group, in the following dimensions: interpersonal at 60 days, community at 30 and 60 days, psychological at 60 days, and economic at 30 and 60 days. Results from this study provide some initial evidence for both the efficacy of, and possible revisions to, the FFW intervention.

The effects of workstation changes and behavioral interventions on safe typing postures in an office.

PubMed

Gravina, Nicole; Lindstrom-Hazel, Debra; Austin, John

2007-01-01

The purpose of the present study was to determine the effectiveness of an ergonomic and behavioral safety intervention for improving participants' safe typing postures in a library office setting. A single-subject multiple baseline design across five participants was employed to evaluate the effects of the four independent variables (workstation adjustment, equipment trial (rollermouse mouse alternative), peer observations, and graphic feedback). Six participant postures were observed repeatedly while participants worked at their workstations throughout the study. Each of the interventions resulted in improvements in safety for more than one posture compared to the previous phase. Results of the study indicate that a comprehensive ergonomic program that includes a workstation adjustment and a behavioral safety approach may be helpful to produce maximum improvements in employees' safe ergonomic postures.

Using the Virtual Reality-Cognitive Rehabilitation Approach to Improve Contextual Processing in Children with Autism

PubMed Central

Reid, Denise

2013-01-01

Background. This pilot study investigated the efficacy of a novel virtual reality-cognitive rehabilitation (VR-CR) intervention to improve contextual processing of objects in children with autism. Previous research supports that children with autism show deficits in contextual processing, as well as deficits in its elementary components: abstraction and cognitive flexibility. Methods. Four children with autism participated in a multiple-baseline, single-subject study. The children were taught how to see objects in context by reinforcing attention to pivotal contextual information. Results. All children demonstrated statistically significant improvements in contextual processing and cognitive flexibility. Mixed results were found on the control test and changes in context-related behaviours. Conclusions. Larger-scale studies are warranted to determine the effectiveness and usability in comprehensive educational programs. PMID:24324379

Wii-habilitation as balance therapy for children with acquired brain injury.

PubMed

Tatla, Sandy K; Radomski, Anna; Cheung, Jessica; Maron, Melissa; Jarus, Tal

2014-02-01

To evaluate the effectiveness of the Nintendo Wii compared to traditional balance therapy in improving balance, motivation, and functional ability in children undergoing acute rehabilitation after brain injury. A non-concurrent, randomized multiple baseline single-subject research design was used with three participants. Data were analyzed by visual inspection of trend lines. Daily Wii balance training was equally motivating to traditional balance therapy for two participants and more motivating for one participant. While improvements in dynamic balance were observed, the results for static balance remain inconclusive. All participants demonstrated improvements in functional ability. Wii balance therapy is a safe, feasible, and motivating intervention for children undergoing acute rehabilitation after an acquired brain injury. Further research to examine the effectiveness of Wii balance therapy in this population is warranted.

Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity.

PubMed

Dantoft, Thomas Meinertz; Skovbjerg, Sine; Andersson, Linus; Claeson, Anna-Sara; Lind, Nina; Nordin, Steven; Brix, Susanne

2015-01-01

Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology. The aim of this study was to examine baseline and low dose n-butanol-induced upper airway inflammatory response profiles in MCS subjects versus healthy controls. Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained. The physiological and psychophysical measurements during the n-butanol exposure session verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences. We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes.

Double-blind, Placebo-controlled Study Assessing the Effect of Chocolate Consumption in Subjects with a History of Acne Vulgaris.

PubMed

Caperton, Caroline; Block, Samantha; Viera, Martha; Keri, Jonette; Berman, Brian

2014-05-01

To assess the effect of chocolate on acne exacerbation in males between the ages of 18 and 35 with a history of acne vulgaris. Double-blind, placebo-controlled, randomized, controlled trial. Single-site, outpatient, research, clinical facility at an academic research institution. Fourteen men between the ages of 18 and 35 were assigned to swallow capsules filled with either unsweetened 100-percent cocoa, hydrolyzed gelatin powder, or a combination of the two, at baseline. Lesions were assessed and photographs were taken at baseline, Day 4, and Day 7. Of the 14 subjects, 13 completed this Institutional Review Board approved study. A statistically significant increase in the mean number of total acneiform lesions (comedones, papules, pustules, nodules) was detected on both Day 4 (p=0.006) and Day 7 (p=0.043) compared to baseline. A small-strength positive Pearson's correlation coefficient existed between the amount of chocolate each subject consumed and the number of lesions each subject developed between baseline and Day 4 (r=0.250), while a medium-strength positive correlation existed between baseline and Day 7 (r=0.314). No serious adverse events occurred. It appears that in acne-prone, male individuals, the consumption of chocolate correlates to an increase in the exacerbation of acne.

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.

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.

The Effects of Self-Regulated Strategy Development on the Writing of Expository Essays for Adults with Written Expression Difficulties: Preparing for the GED

ERIC Educational Resources Information Center

Berry, Ann Bassett; Mason, Linda H.

2012-01-01

A multiple-probe, multiple-baseline, across-subjects design was used to examine the writing performance of four low-achieving adult students with and without disabilities enrolled in general equivalency diploma (GED) preparatory classes. Students' writing was evaluated before instruction and after self-regulated strategy development (SRSD)…

Effects of Neoprene Wrist/Hand Splints on Handwriting for Students with Joint Hypermobility Syndrome: A Single System Design Study

ERIC Educational Resources Information Center

Frohlich, Lauren; Wesley, Alison; Wallen, Margaret; Bundy, Anita

2012-01-01

Purpose: Pain associated with hypermobility of wrist and hand joints can contribute to decreased handwriting output. This study examined the effectiveness of a neoprene wrist/hand splint in reducing pain and increasing handwriting speed and endurance for students with joint hypermobility syndrome. Methods: Multiple baseline, single system design…

Formative Assessment Using Direct Behavior Ratings: Evaluating Intervention Effects of Daily Behavior Report Cards

ERIC Educational Resources Information Center

Sims, Wesley A.; Riley-Tillman, Chris; Cohen, Daniel R.

2017-01-01

This study examined the treatment sensitivity of "Direct Behavior Rating-Single Item Scales" (DBR-SIS) in response to an evidence-based intervention delivered in a single-case, multiple-baseline design. DBR-SIS was used as a formative assessment in conjunction with a frequently used intervention in schools, a Daily Behavior Report Card…

Enhancing conversation skills in patients with Alzheimer's disease using a prosthetic memory aid.

PubMed

Bourgeois, M S

1990-01-01

The effectiveness of teaching Alzheimer's disease subjects to use a prosthetic memory aid when conversing with familiar partners was evaluated. Effects of the training of three topics by caregivers was assessed in daily probes with the experimenter and twice weekly probes with a familiar conversational partner. All 3 subjects learned to use the memory aid with both conversational partners and improved the quality of their conversational content. Subjects made significantly more statements of fact and fewer ambiguous utterances after training on each topic according to a multiple baseline design. All subjects also generated novel, untrained statements in conversations with both partners. Treatment effects were maintained at high levels throughout training and at 3- and 6-week follow-up sessions. Naive judges rated baseline and posttreatment conversational samples as significantly improved on all eight conversational dimensions.

Masked Visual Analysis: Minimizing Type I Error in Visually Guided Single-Case Design for Communication Disorders

PubMed Central

Hitchcock, Elaine R.; Ferron, John

2017-01-01

Purpose Single-case experimental designs are widely used to study interventions for communication disorders. Traditionally, single-case experiments follow a response-guided approach, where design decisions during the study are based on participants' observed patterns of behavior. However, this approach has been criticized for its high rate of Type I error. In masked visual analysis (MVA), response-guided decisions are made by a researcher who is blinded to participants' identities and treatment assignments. MVA also makes it possible to conduct a hypothesis test assessing the significance of treatment effects. Method This tutorial describes the principles of MVA, including both how experiments can be set up and how results can be used for hypothesis testing. We then report a case study showing how MVA was deployed in a multiple-baseline across-subjects study investigating treatment for residual errors affecting rhotics. Strengths and weaknesses of MVA are discussed. Conclusions Given their important role in the evidence base that informs clinical decision making, it is critical for single-case experimental studies to be conducted in a way that allows researchers to draw valid inferences. As a method that can increase the rigor of single-case studies while preserving the benefits of a response-guided approach, MVA warrants expanded attention from researchers in communication disorders. PMID:28595354

Masked Visual Analysis: Minimizing Type I Error in Visually Guided Single-Case Design for Communication Disorders.

PubMed

Byun, Tara McAllister; Hitchcock, Elaine R; Ferron, John

2017-06-10

Single-case experimental designs are widely used to study interventions for communication disorders. Traditionally, single-case experiments follow a response-guided approach, where design decisions during the study are based on participants' observed patterns of behavior. However, this approach has been criticized for its high rate of Type I error. In masked visual analysis (MVA), response-guided decisions are made by a researcher who is blinded to participants' identities and treatment assignments. MVA also makes it possible to conduct a hypothesis test assessing the significance of treatment effects. This tutorial describes the principles of MVA, including both how experiments can be set up and how results can be used for hypothesis testing. We then report a case study showing how MVA was deployed in a multiple-baseline across-subjects study investigating treatment for residual errors affecting rhotics. Strengths and weaknesses of MVA are discussed. Given their important role in the evidence base that informs clinical decision making, it is critical for single-case experimental studies to be conducted in a way that allows researchers to draw valid inferences. As a method that can increase the rigor of single-case studies while preserving the benefits of a response-guided approach, MVA warrants expanded attention from researchers in communication disorders.

Use of virtual reality in rehabilitation of movement in children with hemiplegia--a multiple case study evaluation.

PubMed

Green, Dido; Wilson, Peter H

2012-01-01

To evaluate the feasibility and therapeutic effect of engaging children of differing neuromotor and cognitive ability in a virtual reality (VR) tabletop workspace designed to improve upper-limb function. Single-subject experimental design with multiple baselines was employed. Four children with hemiplegia participated in VR-based training between nine and 19, 30-minute sessions, over three-four weeks. Outcomes were assessed from the perspective of the International Classification of Functioning, Disability and Health; considering body function, activity performance and participation. Upper-limb performance was assessed using system-measured variables (speed, trajectory and accuracy) and standardized tests. Trend analyses were employed to determine trends on system variables between baseline phase and treatment phases. Standardised measures were compared between pre- and post-training. Two children made progress across system variables with some translation to daily activities. Performance of the other two children was more variable, however, they engaged positively with the system by the end of the treatment phase. The VR (RE-ACTION) system shows promise as an engaging rehabilitation tool to improve upper-limb function of children with hemiplegia, across ability levels. Trade-offs between kinematic variables should be considered when measuring improvements in movement skill. Larger trials are warranted to evaluate effects of augmented feedback, intensity and duration of training, and interface type to optimise the system's effectiveness.

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.

EAT-UP™ Family-Centered Feeding Intervention to Promote Food Acceptance and Decrease Challenging Behaviors: A Single-Case Experimental Design Replicated across Three Families of Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Cosbey, Joanna; Muldoon, Deirdre

2017-01-01

This study evaluated the effectiveness of a family-centered feeding intervention, Easing Anxiety Together with Understanding and Perseverance (EAT-UP™), for promoting food acceptance of children with autism spectrum disorder at home. A concurrent multiple-baseline design was used with systematic replication across three families. Baseline was…

Phase delaying the human circadian clock with a single light pulse and moderate delay of the sleep/dark episode: no influence of iris color.

PubMed

Canton, Jillian L; Smith, Mark R; Choi, Ho-Sun; Eastman, Charmane I

2009-07-17

Light exposure in the late evening and nighttime and a delay of the sleep/dark episode can phase delay the circadian clock. This study assessed the size of the phase delay produced by a single light pulse combined with a moderate delay of the sleep/dark episode for one day. Because iris color or race has been reported to influence light-induced melatonin suppression, and we have recently reported racial differences in free-running circadian period and circadian phase shifting in response to light pulses, we also tested for differences in the magnitude of the phase delay in subjects with blue and brown irises. Subjects (blue-eyed n = 7; brown eyed n = 6) maintained a regular sleep schedule for 1 week before coming to the laboratory for a baseline phase assessment, during which saliva was collected every 30 minutes to determine the time of the dim light melatonin onset (DLMO). Immediately following the baseline phase assessment, which ended 2 hours after baseline bedtime, subjects received a 2-hour bright light pulse (~4,000 lux). An 8-hour sleep episode followed the light pulse (i.e. was delayed 4 hours from baseline). A final phase assessment was conducted the subsequent night to determine the phase shift of the DLMO from the baseline to final phase assessment.Phase delays of the DLMO were compared in subjects with blue and brown irises. Iris color was also quantified from photographs using the three dimensions of red-green-blue color axes, as well as a lightness scale. These variables were correlated with phase shift of the DLMO, with the hypothesis that subjects with lighter irises would have larger phase delays. The average phase delay of the DLMO was -1.3 +/- 0.6 h, with a maximum delay of ~2 hours, and was similar for subjects with blue and brown irises. There were no significant correlations between any of the iris color variables and the magnitude of the phase delay. A single 2-hour bright light pulse combined with a moderate delay of the sleep/dark episode delayed the circadian clock an average of ~1.5 hours. There was no evidence that iris color influenced the magnitude of the phase shift. Future studies are needed to replicate our findings that iris color does not impact the magnitude of light-induced circadian phase shifts, and that the previously reported differences may be due to race.

Localizing gravitational wave sources with single-baseline atom interferometers

NASA Astrophysics Data System (ADS)

Graham, Peter W.; Jung, Sunghoon

2018-02-01

Localizing sources on the sky is crucial for realizing the full potential of gravitational waves for astronomy, astrophysics, and cosmology. We show that the midfrequency band, roughly 0.03 to 10 Hz, has significant potential for angular localization. The angular location is measured through the changing Doppler shift as the detector orbits the Sun. This band maximizes the effect since these are the highest frequencies in which sources live for several months. Atom interferometer detectors can observe in the midfrequency band, and even with just a single baseline they can exploit this effect for sensitive angular localization. The single-baseline orbits around the Earth and the Sun, causing it to reorient and change position significantly during the lifetime of the source, and making it similar to having multiple baselines/detectors. For example, atomic detectors could predict the location of upcoming black hole or neutron star merger events with sufficient accuracy to allow optical and other electromagnetic telescopes to observe these events simultaneously. Thus, midband atomic detectors are complementary to other gravitational wave detectors and will help complete the observation of a broad range of the gravitational spectrum.

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.

Self-Administered Cued Naming Therapy: A Single-Participant Investigation of a Computer-Based Therapy Program Replicated in Four Cases

ERIC Educational Resources Information Center

Ramsberger, Gail; Marie, Basem

2007-01-01

Purpose: This study examined the benefits of a self-administered, clinician-guided, computer-based, cued naming therapy. Results of intense and nonintense treatment schedules were compared. Method: A single-participant design with multiple baselines across behaviors and varied treatment intensity for 2 trained lists was replicated over 4…

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.

How stigma impacts on people with psychosis: The mediating effect of self-esteem and hopelessness on subjective recovery and psychotic experiences.

PubMed

Vass, Victoria; Morrison, Anthony P; Law, Heather; Dudley, James; Taylor, Pamela; Bennett, Kate M; Bentall, Richard P

2015-12-15

This study aimed to examine how stigma impacts on symptomatic and subjective recovery from psychosis, both concurrently and longitudinally. We also aimed to investigate whether self-esteem and hopelessness mediated the observed associations between stigma and outcomes. 80 service-users with psychosis completed symptom (Positive and Negative Syndrome Scale) and subjective recovery measures (Process of Recovery Questionnaire) at baseline and 6-months later, and also completed the King Stigma Scale, the Self-Esteem Rating Scale and the Beck Hopelessness Scale at baseline. In cross sectional regression and multiple mediation analyses of the baseline data, we found that stigma predicted both symptomatic and subjective recovery, and the effects of stigma on these outcomes were mediated by hopelessness and self-esteem. When the follow-up data were examined, stigma at baseline continued to predict recovery judgements and symptoms. However, self-esteem only mediated the effect of stigma on PANSS passive social withdrawal. Self-esteem and hopelessness should be considered in interventions to reduce the effects of stigma. Interventions that address the current and long-term effects of stigma may positively affect outcome for people being treated for psychosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Long-Term Changes in Adiposity and Glycemic Control Are Associated With Past Adenovirus Infection

PubMed Central

Lin, Wan-Yu; Dubuisson, Olga; Rubicz, Rohina; Liu, Nianjun; Allison, David B.; Curran, Joanne E.; Comuzzie, Anthony G.; Blangero, John; Leach, Charles T.; Göring, Harald; Dhurandhar, Nikhil V.

2013-01-01

OBJECTIVE Ad36, a human adenovirus, increases adiposity but improves glycemic control in animal models. Similarly, natural Ad36 infection is cross-sectionally associated with greater adiposity and better glycemic control in humans. This study compared longitudinal observations in indices of adiposity (BMI and body fat percentage) and glycemic control (fasting glucose and insulin) in Ad36-infected versus uninfected adults. RESEARCH DESIGN AND METHODS Baseline sera from Hispanic men and women (n = 1,400) were screened post hoc for the presence of Ad36-specific antibodies. Indices of adiposity and glycemic control at baseline and at ∼10 years past the baseline were compared between seropositive and seronegative subjects, with adjustment for age and sex. In addition to age and sex, indices of glycemic control were adjusted for baseline BMI and were analyzed only for nondiabetic subjects. RESULTS Seropositive subjects (14.5%) had greater adiposity at baseline, compared with seronegative subjects. Longitudinally, seropositive subjects showed greater adiposity indices but lower fasting insulin levels. Subgroup analyses revealed that Ad36-seropositivity was associated with better baseline glycemic control and lower fasting insulin levels over time in the normal-weight group (BMI ≤25 kg/m2) and longitudinally, with greater adiposity in the overweight (BMI 25–30 kg/m2) and obese (BMI >30 kg/m2) men. Statistically, the differences between seropositive and seronegative individuals were modest in light of the multiple tests performed. CONCLUSIONS This study strengthens the plausibility that in humans, Ad36 increases adiposity and attenuates deterioration of glycemic control. Panoptically, the study raises the possibility that certain infections may modulate obesity or diabetes risk. A comprehensive understanding of these under-recognized factors is needed to effectively combat such metabolic disorders. PMID:23160725

Clinical evaluation of the efficacy of an in-office desensitizing paste containing 8% arginine and calcium carbonate in providing instant and lasting relief of dentin hypersensitivity.

PubMed

Schiff, Thomas; Delgado, Evaristo; Zhang, Yun Po; Cummins, Diane; DeVizio, William; Mateo, Luis R

2009-03-01

To determine the efficacy of an in-office desensitizing paste containing 8% arginine and calcium carbonate relative to that of a commercially-available pumice prophylaxis paste in reducing dentin hypersensitivity instantly after a single application following a dental scaling procedure and to establish the duration of sensitivity relief over a period of 4 weeks and 12 weeks. This was a single-center, parallel group, double-blind, stratified clinical study conducted in San Francisco, California, USA. Qualifying adult male and female subjects who presented two hypersensitive teeth with a tactile hypersensitivity score (Yeaple Probe) between 10-50 grams of force and an air blast hypersensitivity score of 2 or 3 (Schiff Cold Air Sensitivity Scale) were stratified according to their baseline hypersensitivity scores and randomly assigned within strata to one of two treatment groups: (1) A Test Paste, a desensitizing paste containing 8% arginine and calcium carbonate (Colgate-Palmolive Co); and (2) A Control Paste, Nupro pumice prophylaxis paste (Dentsply Professional). Subjects received a professionally-administered scaling procedure, after which they were re-examined for tactile and air blast dentin hypersensitivity (Post-Scaling Examinations). The assigned pastes were then applied as the final step to the professional dental cleaning procedure. Tactile and air blast dentin hypersensitivity examinations were again performed immediately after paste application. Subjects were provided with a commercially-available non-desensitizing dentifrice containing 0.243% sodium fluoride (Crest Cavity Protection, Procter & Gamble Co.) and an adult soft-bristled toothbrush and were instructed to brush their teeth for 1 minute, twice daily at home using only the toothbrush and dentifrice provided, for the next 12 weeks. Subjects returned to the testing facility 4 and 12 weeks after the single application of Test or Control paste, having refrained from all oral hygiene procedures and chewing gum for 8 hours and from eating and drinking for 4 hours, prior to each follow-up visit. Assessments of tactile and air blast hypersensitivity, and examinations of oral soft and hard tissue were repeated at these 4- and 12-week examinations. 68 subjects completed the 12-week study. No statistically significant differences from baseline scores were indicated at the Post-Scaling Examinations for either the Test Paste or Control Paste groups. Immediately following product application and 4 weeks after product application, subjects assigned to the Test Paste group exhibited statistically significant improvements from baseline with respect to baseline-adjusted mean air blast (44.1% and 45.9% respectively) and mean tactile hypersensitivity scores (156.2% and 170.3% respectively). At the same time points, subjects assigned to the Control Paste group exhibited statistically significant improvements from baseline with respect to baseline-adjusted mean air blast (15.1% and 8.9% respectively) and mean tactile hypersensitivity scores (43.1% and 8.3% respectively). Immediately following application of the assigned paste and 4 weeks later, the Test Paste group demonstrated statistically significant reductions in dentin hypersensitivity with respect to baseline-adjusted mean air blast (34.1% and 40.6% respectively) and mean tactile hypersensitivity scores (79.0% and 149.6% respectively), compared to the Control Paste group. No statistically significant differences were exhibited between paste groups at the Post-Scaling and 12-week examinations with respect to mean tactile and baseline-adjusted mean air blast hypersensitivity scores.

OpT2mise: a randomized controlled trial to compare insulin pump therapy with multiple daily injections in the treatment of type 2 diabetes-research design and methods.

PubMed

Aronson, Ronnie; Cohen, Ohad; Conget, Ignacio; Runzis, Sarah; Castaneda, Javier; de Portu, Simona; Lee, Scott; Reznik, Yves

2014-07-01

In insulin-requiring type 2 diabetes patients, current insulin therapy approaches such as basal-alone or basal-bolus multiple daily injections (MDI) have not consistently provided achievement of optimal glycemic control. Previous studies have suggested a potential benefit of continuous subcutaneous insulin infusion (CSII) in these patients. The OpT2mise study is a multicenter, randomized, trial comparing CSII with MDI in a large cohort of subjects with evidence of persistent hyperglycemia despite previous MDI therapy. Subjects were enrolled into a run-in period for optimization of their MDI insulin regimen. Subjects showing persistent hyperglycemia (glycated hemoglobin [HbA1c] ≥8% and ≤12%) were then randomly assigned to CSII or continuing an MDI regimen for a 6-month phase followed by a single crossover of the MDI arm, switching to CSII. The primary end point is the between-group difference in mean change in HbA1c from baseline to 6 months. Secondary end points include change in mean 24-h glucose values, area under the curve and time spent in hypoglycemia and hyperglycemia, measures of glycemic excursions, change in postprandial hyperglycemia, and evaluation of treatment satisfaction. Safety end points include hypoglycemia, hospital admissions, and emergency room visits. When subject enrollment was completed in May 2013, 495 subjects had been enrolled in the study. The study completion for the primary end point is expected in January 2014. OpT2mise will represent the largest studied homogeneous cohort of type 2 diabetes patients with persistent hyperglycemia despite optimized MDI therapy. OpT2mise will help define the role of CSII in insulin intensification and define its safety, rate of hypoglycemia, patient adherence, and patient satisfaction.

Label-aligned Multi-task Feature Learning for Multimodal Classification of Alzheimer’s Disease and Mild Cognitive Impairment

PubMed Central

Zu, Chen; Jie, Biao; Liu, Mingxia; Chen, Songcan

2015-01-01

Multimodal classification methods using different modalities of imaging and non-imaging data have recently shown great advantages over traditional single-modality-based ones for diagnosis and prognosis of Alzheimer’s disease (AD), as well as its prodromal stage, i.e., mild cognitive impairment (MCI). However, to the best of our knowledge, most existing methods focus on mining the relationship across multiple modalities of the same subjects, while ignoring the potentially useful relationship across different subjects. Accordingly, in this paper, we propose a novel learning method for multimodal classification of AD/MCI, by fully exploring the relationships across both modalities and subjects. Specifically, our proposed method includes two subsequent components, i.e., label-aligned multi-task feature selection and multimodal classification. In the first step, the feature selection learning from multiple modalities are treated as different learning tasks and a group sparsity regularizer is imposed to jointly select a subset of relevant features. Furthermore, to utilize the discriminative information among labeled subjects, a new label-aligned regularization term is added into the objective function of standard multi-task feature selection, where label-alignment means that all multi-modality subjects with the same class labels should be closer in the new feature-reduced space. In the second step, a multi-kernel support vector machine (SVM) is adopted to fuse the selected features from multi-modality data for final classification. To validate our method, we perform experiments on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database using baseline MRI and FDG-PET imaging data. The experimental results demonstrate that our proposed method achieves better classification performance compared with several state-of-the-art methods for multimodal classification of AD/MCI. PMID:26572145

Gut microbiota in MS: possible influence of immunomodulators

PubMed Central

Cantarel, Brandi L.; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z.; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M.; Mowry, Ellen M.

2015-01-01

Objectives Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in multiple sclerosis patients and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Methods Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Multiple sclerosis patients were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5,000 IU/day) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. Results While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in multiple sclerosis patients. Glatiramer acetate-treated MS subjects showed differences in community composition compared to untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and Other Clostridiales. Compared to the other groups, untreated multiple sclerosis subjects had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. Conclusions While overall bacterial communities were similar, specific operational taxonomic units differed between healthy and multiple sclerosis subjects. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results. PMID:25775034

Feeding the brain - The effects of micronutrient interventions on cognitive performance among school-aged children: A systematic review of randomized controlled trials.

PubMed

Lam, Long Fung; Lawlis, Tanya R

2017-08-01

Micronutrients are essential for brain development with deficiencies in specific nutrients linked to impaired cognitive function. Interventions are shown to be beneficial to children's mental development, particularly in subjects who were micronutrient-deficient at baseline but results on healthy subjects remain inconsistent. This systematic review evaluated the effect of micronutrient inventions on different cognitive domains. Studies conducted in both developing and developed countries, and trials that investigate the effect of both single and multiple micronutrient intervention were reviewed. Systematic searches of Medline, CINAHL Plus and Academic Search database were undertaken to identify trials published after year 2000. Randomized controlled trials (RCTs) that evaluate the effect of micronutrients on cognitive performance or academic performance among children aged 4-18 years were included. 19 trials were identified from 18 articles. The major cognitive outcomes assessed included fluid intelligence, crystallized intelligence, short-term memory, long-term memory, cognitive processing speed, attention and concentration, and school performance. Eight of ten trials assessing fluid intelligence reported significant positive effects of micronutrient supplementation among micronutrient-deficient children, especially those who were iron-deficient or iodine-deficient at baseline. The effects of micronutrient interventions on other domains were inconsistent. Improvement in fluid intelligence among micronutrient-deficient children was consistently reported. Further research is needed to provide more definite evidence on the beneficial effects of micronutrient inventions on other cognitive domains and the effects in healthy subjects. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Flight crew sleep during multiple layover polar flights.

PubMed

Sasaki, M; Kurosaki, Y S; Spinweber, C L; Graeber, R C; Takahashi, T

1993-07-01

This study investigated changes in sleep after multiple transmeridian flights. The subjects were 12 B747 airline pilots operating on the following polar flight: Tokyo (TYO)-Anchorage (ANC)-London (LON)-Anchorage-Tokyo. Sleep polysomnograms were recorded on two baseline nights (B1, B2), during layovers, and, after returning to Tokyo, two recovery nights were recorded (R1, R2). In ANC (outbound), total sleep time (TST) was reduced and, sleep efficiency was low (72.0%). In London, time in bed (TIB) increased slightly, but sleep efficiency was still reduced. On return to ANC (inbound), there was considerable slow wave sleep (SWS) rebound and multiple awakenings reduced sleep efficiency to 76.8%. Sleep efficiency on R2 was significantly lower than on B1 (t-test, p < 0.05) but not different from R1. To sum up, sleep of aircrews flying multiple transmeridian flights is disrupted during layovers and this effect persists during the two recovery nights. As a result, there is a marked cumulative sleep loss during multi-legs polar route trip in comparison to single leg flights. These findings suggest that following such extensive transmeridian trips, crews should have at least three nights of recovery sleep in their home time zone before returning to duty.

Acute effects of a single warm-water bath on serum adiponectin and leptin levels in healthy men: A pilot study

NASA Astrophysics Data System (ADS)

Shimodozono, Megumi; Matsumoto, Shuji; Ninomiya, Koji; Miyata, Ryuji; Ogata, Atsuko; Etoh, Seiji; Watanabe, Satoshi; Kawahira, Kazumi

2012-09-01

To preliminarily assess the acute effects of a single warm -water bath (WWB) on serum adipokine activity, we measured serum adiponectin, leptin and other metabolic profiles before, immediately after and 30 minutes after WWB in seven healthy male volunteers (mean age, 39.7 ± 6.0 years; mean body mass index, 21.6 ± 1.8 kg/m2). The subjects were immersed in tap water at 41°C for 10 minutes. Two weeks later, the same subjects underwent a single WWB with a bath additive that included inorganic salts and carbon dioxide (WWB with ISCO2) by the same protocol as for the first WWB. Leptin levels significantly increased immediately after WWB with tap water and ISCO2 (both P < 0.05), and remained significantly higher than those at baseline even 30 minutes after WWB with tap water ( P < 0.05). Adiponectin levels showed a slight, but not significant, increase both immediately after and 30 minutes after WWB with tap water or ISCO2. Some parameters, such as serum total cholesterol, red blood cell count, hemoglobin and hematocrit significantly increased immediately after WWB with tap water or ISCO2 (all P < 0.05), but they all returned to the baseline levels 30 minutes after bathing under both conditions. The sublingual temperature rose significantly after 10 minutes of WWB with tap water (0.96 ± 0.16°C relative to baseline, P < 0.01) and after the same duration of WWB with ISCO2 (1.24 ± 0.34°C relative to baseline, P < 0.01). These findings suggest that a single WWB at 41°C for 10 minutes may modulate leptin and adiponectin profiles in healthy men.

Strategies for longitudinal neuroimaging studies of overt language production.

PubMed

Meltzer, Jed A; Postman-Caucheteux, Whitney A; McArdle, Joseph J; Braun, Allen R

2009-08-15

Longitudinal fMRI studies of language production are of interest for evaluating recovery from post-stroke aphasia, but numerous methodological issues remain unresolved, particularly regarding strategies for evaluating single subjects at multiple timepoints. To address these issues, we studied overt picture naming in eleven healthy subjects, scanned four times each at one-month intervals. To evaluate the natural variability present across repeated sessions, repeated scans were directly contrasted in a unified statistical framework on a per-voxel basis. The effect of stimulus familiarity was evaluated using explicitly overtrained pictures, novel pictures, and untrained pictures that were repeated across sessions. For untrained pictures, we found that activation declined across multiple sessions, equally for both novel and repeated stimuli. Thus, no repetition priming for individual stimuli at one-month intervals was found, but rather a general effect of task habituation was present. Using a set of overtrained pictures identical in each session, no decline was found, but activation was minimized and produced less consistent patterns across participants, as measured by intra-class correlation coefficients. Subtraction of a baseline task, in which subjects produced a stereotyped utterance to scrambled pictures, resulted in specific activations in the left inferior frontal gyrus and other language areas for untrained items, while overlearned stimuli relative to pseudo pictures activated only the fusiform gyrus and supplementary motor area. These findings indicate that longitudinal fMRI is an effective means of detecting changes in neural activation magnitude over time, as long as the effect of task habituation is taken into account.

Double-blind, Placebo-controlled Study Assessing the Effect of Chocolate Consumption in Subjects with a History of Acne Vulgaris

PubMed Central

Caperton, Caroline; Block, Samantha; Viera, Martha; Keri, Jonette

2014-01-01

Objective: To assess the effect of chocolate on acne exacerbation in males between the ages of 18 and 35 with a history of acne vulgaris. Design: Double-blind, placebo-controlled, randomized, controlled trial. Setting: Single-site, outpatient, research, clinical facility at an academic research institution. Participants: Fourteen men between the ages of 18 and 35 were assigned to swallow capsules filled with either unsweetened 100-percent cocoa, hydrolyzed gelatin powder, or a combination of the two, at baseline. Measurements: Lesions were assessed and photographs were taken at baseline, Day 4, and Day 7. Results: Of the 14 subjects, 13 completed this Institutional Review Board approved study. A statistically significant increase in the mean number of total acneiform lesions (comedones, papules, pustules, nodules) was detected on both Day 4 (p=0.006) and Day 7 (p=0.043) compared to baseline. A small-strength positive Pearson’s correlation coefficient existed between the amount of chocolate each subject consumed and the number of lesions each subject developed between baseline and Day 4 (r=0.250), while a medium-strength positive correlation existed between baseline and Day 7 (r=0.314). No serious adverse events occurred. Conclusion: It appears that in acne-prone, male individuals, the consumption of chocolate correlates to an increase in the exacerbation of acne. PMID:24847404

Effectiveness of the California Tri-Pull Taping method for shoulder subluxation poststroke: a single-subject ABA design.

PubMed

Hayner, Kate A

2012-01-01

I evaluated the effectiveness of the California Tri-Pull Taping method for clients with poststroke inferior shoulder subluxation of the glenohumeral joint. Ten participants were followed for 9 wk using an interrupted time series quasi-experimental single-subject ABA design to examine shoulder pain, activities of daily living (ADL) function, active range of motion, tape comfort, and subluxation. The California Tri-Pull Taping method decreased inferior subluxation significantly from baseline to intervention but not at postintervention. Active range of motion was significantly increased in shoulder flexion and abduction between the baseline and intervention and the intervention and postintervention phases. Functional ADL scores were significant. The taping was reported to be comfortable. No significant difference in pain was found. This intervention is a promising adjunct to the management of the hemiplegic subluxed shoulder that warrants further research. Copyright © 2012 by the American Occupational Therapy Association, Inc.

Repeated stool sampling and use of multiple techniques enhance the sensitivity of helminth diagnosis: a cross-sectional survey in southern Lao People's Democratic Republic.

PubMed

Sayasone, Somphou; Utzinger, Jürg; Akkhavong, Kongsap; Odermatt, Peter

2015-01-01

Intestinal parasitic infections are common in Lao People's Democratic Republic (Lao PDR). We investigated the accuracy of the Kato-Katz (KK) technique in relation to varying stool sampling efforts, and determined the effect of the concurrent use of a quantitative formalin-ethyl acetate concentration technique (FECT) for helminth diagnosis and appraisal of concomitant infections. The study was carried out between March and May 2006 in Champasack province, southern Lao PDR. Overall, 485 individuals aged ≥6 months who provided three stool samples were included in the final analysis. All stool samples were subjected to the KK technique. Additionally, one stool sample per individual was processed by FECT. Diagnosis was done under a light microscope by experienced laboratory technicians. Analysis of three stool samples with KK plus a single FECT was considered as diagnostic 'gold' standard and resulted in prevalence estimates of hookworm, Opisthorchis viverrini, Ascaris lumbricoides, Trichuris trichiura and Schistosoma mekongi infection of 77.9%, 65.0%, 33.4%, 26.2% and 24.3%, respectively. As expected, a single KK and a single FECT missed a considerable number of infections. While our diagnostic 'gold' standard produced similar results than those obtained by a mathematical model for most helminth infections, the 'true' prevalence predicted by the model for S. mekongi (28.1%) was somewhat higher than after multiple KK plus a single FECT (24.3%). In the current setting, triplicate KK plus a single FECT diagnosed helminth infections with high sensitivity. Hence, such a diagnostic approach might be utilised for generating high-quality baseline data, assessing anthelminthic drug efficacy and rigorous monitoring of community interventions. Copyright © 2014 Elsevier B.V. All rights reserved.

Cerebral dopaminergic and glutamatergic transmission relate to different subjective responses of acute alcohol intake: an in vivo multimodal imaging study.

PubMed

Leurquin-Sterk, Gil; Ceccarini, Jenny; Crunelle, Cleo Lina; Weerasekera, Akila; de Laat, Bart; Himmelreich, Uwe; Bormans, Guy; Van Laere, Koen

2018-05-01

Converging preclinical evidence links extrastriatal dopamine release and glutamatergic transmission via the metabotropic glutamate receptor 5 (mGluR5) to the rewarding properties of alcohol. To date, human evidence is lacking on how and where in the brain these processes occur. Mesocorticolimbic dopamine release upon intravenous alcohol administration and mGluR5 availability were measured in 11 moderate social drinkers by single-session [ 18 F]fallypride and [ 18 F]FPEB positron emission tomography, respectively. Additionally, baseline and postalcohol glutamate and glutamine levels in the anterior cingulate cortex (ACC) were measured by using proton-magnetic resonance spectroscopy. To investigate differences in reward domains linked to both neurotransmitters, regional imaging data were related to subjective alcohol responses. Alcohol induced significant [ 18 F]fallypride displacement in the prefrontal cortex (PFC), temporal and parietal cortices and thalamus (P < 0.05, corrected for multiple comparisons). Dopamine release in the ACC and orbitofrontal and ventromedial PFCs were correlated with subjective 'liking' and 'wanting' effects (P < 0.05). In contrast, baseline mGluR5 availability was positively correlated with the 'high' effect of alcohol in dorsolateral, ventrolateral and ventromedial PFCs and in the medial temporal lobe, thalamus and caudate nucleus (P < 0.05). Although neither proton-magnetic resonance spectroscopy glutamate nor glutamine levels were affected by alcohol, baseline ACC glutamate levels were negatively associated with the alcohol 'liking' effect (P < 0.003). These data reveal new mechanistic understanding and differential neurobiological underpinnings of the effects of acute alcohol consumption on human behavior. Specifically, prefrontal dopamine release may encode alcohol 'liking' and 'wanting' effects in specific areas underlying value processing and motivation, whereas mGluR5 availability in distinct prefrontal-temporal-subcortical regions is more related to the alcohol 'high' effect. © 2017 Society for the Study of Addiction.

Physical Fitness Measures as Potential Markers of Low Cognitive Function in Japanese Community-Dwelling Older Adults without Apparent Cognitive Problems.

PubMed

Narazaki, Kenji; Matsuo, Eri; Honda, Takanori; Nofuji, Yu; Yonemoto, Koji; Kumagai, Shuzo

2014-09-01

Detecting signs of cognitive impairment as early as possible is one of the most urgent challenges in preventive care of dementia. It has still been unclear whether physical fitness measures can serve as markers of low cognitive function, a sign of cognitive impairment, in older people free from dementia. The aim of the present study was to examine an association between each of five physical fitness measures and global cognition in Japanese community-dwelling older adults without apparent cognitive problems. The baseline research of the Sasaguri Genkimon Study was conducted from May to August 2011 in Sasaguri town, Fukuoka, Japan. Of the 2,629 baseline subjects who were aged 65 years or older and not certified as individuals requiring nursing care by the town, 1,552 participants without apparent cognitive problems (Mini-Mental State Examination score ≥24) were involved in the present study (59.0% of the baseline subjects, median age: 72 years, men: 40.1%). Global cognitive function was measured by the Japanese version of the Montreal Cognitive Assessment. Handgrip strength, leg strength, sit-to-stand rate, gait speed, and one-leg stand time were examined as physical fitness measures. In multiple linear regression analyses, each of the five physical fitness measures was positively associated with the Montreal Cognitive Assessment score after adjusting for age and sex (p < 0.001). These associations were preserved after additional adjustment for years of formal education, body mass index, and other confounding factors (p < 0.001). The present study first demonstrated the associations between multiple aspects of physical fitness and global cognitive function in Japanese community-dwelling older people without apparent cognitive problems. These results suggest that each of the physical fitness measures has a potential as a single marker of low cognitive function in older populations free from dementia and thereby can be useful in community-based preventive care of dementia. Key pointsThere is a great need for identifying lifestyle-related markers which help detect subtle cognitive impairment in the preclinical or earlier phase of dementia.In the present study, each of the five physical fitness measures employed was linearly and positively associated with the Montreal Cognitive Assessment score in the present older adults without apparent cognitive problems, after adjusting for age, sex, education, body mass index, and other confounding factors.The results suggest the potential of each physical fitness measure as a single lifestyle-related marker of low cognitive function in the population, which can be useful in community-based preventive care of dementia.

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

Behavioral and neurochemical consequences of multiple MDMA administrations in the rat: role of individual differences in anxiety-related behavior.

PubMed

Ludwig, V; Mihov, Y; Schwarting, R K W

2008-05-16

Using the elevated plus-maze (EPM), Wistar rats can be distinguished into high (HA) or low anxiety (LA) subjects. These differences seem to reflect traits, since HA and LA rats vary also in other anxiety-dependent tasks, neurochemical mechanisms, and psychopharmacological reactivity, including lasting consequences after single treatment with 3,4-methylenedioxymethamphetamine (MDMA). Here, we tested whether multiple MDMA treatments also have subject-dependent effects. Based on routine EPM screening, male Wistar rats were divided into HA and LA sub-groups, which received five (i.e. multiple) daily injections of MDMA (5 mg/kg) or saline, followed by a test battery, including a challenge test with MDMA, a retest in the EPM, a novel-object test, and a final neurochemical analysis. Acutely, MDMA led to comparable hyperactivity in HA and LA rats. After multiple MDMA, behavioral sensitization was observed, especially in LA rats. Open arm time during the EPM retest (min 0-5) correlated with that of the initial one only in those rats, which had received a single injection of MDMA. Rats with multiple MDMA, especially LA-rats, showed more open-arm time and locomotion during the subsequent 5-10 min of the retest. In a novel-object test, rats with multiple MDMA, again especially LA subjects, showed more exploratory bouts towards the novel object. Neurochemically, multiple MDMA led to moderately lower serotonin in the ventral striatum, and higher dopamine levels in the frontal cortex as compared to single MDMA; these effects were also moderated by subject-dependent factors. Our data show that low-dosed multiple MDMA can lead to behavioral sensitization and outlasting consequences, which affect behavior in the EPM and a novel object task. Detecting such sequels partly requires consideration of individual differences.

Method for Visually Integrating Multiple Data Acquisition Technologies for Real Time and Retrospective Analysis

NASA Technical Reports Server (NTRS)

Bogart, Edward H. (Inventor); Pope, Alan T. (Inventor)

2000-01-01

A system for display on a single video display terminal of multiple physiological measurements is provided. A subject is monitored by a plurality of instruments which feed data to a computer programmed to receive data, calculate data products such as index of engagement and heart rate, and display the data in a graphical format simultaneously on a single video display terminal. In addition live video representing the view of the subject and the experimental setup may also be integrated into the single data display. The display may be recorded on a standard video tape recorder for retrospective analysis.

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…

Development of a single-meal fish consumption advisory for methyl mercury

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

Ginsberg, G.L.; Toal, B.F.

2000-02-01

Methyl mercury (meHg) contamination of fish is the leading cause of fish consumption advisories in the US. These advisories have focused upon repeated or chronic exposure, whereas risks during pregnancy may also exist from a single-meal exposure if the fish tissue concentration is high enough. In this study, acute exposure to meHg from a single fish meal was analyzed by using the one-compartment meHg biokinetic model to predict maternal hair concentrations. These concentrations were evaluated against the mercury hair concentration corresponding to the US Environmental Protection Agency's reference dose (RfD), which is intended to protect against neurodevelopmental effects. The one-compartmentmore » model was validated against blood concentrations from three datasets in which human subjects ingested meHg in fish, either as a single meal or multiple meals. Model simulations of the single-meal scenario at different fish meHg concentrations found that concentrations of 2.0 ppm or higher can be associated with maternal hair concentrations elevated above the RfD level for days to weeks during gestation. A single-meal fish concentration cutoff of {ge} 2.0 ppm is an important consideration, especially because this single high exposure event might be in addition to a baseline meHg body burden from other types of fish consumption. This type of single-meal advisory requires that fish sampling programs provide data for individual rather than composited fish, and take into account seasonal differences that may exist in fish concentrations.« less

Effects of rehabilitative horse riding on the Sit-to-Stand action of the adolescent with brain lesions.

PubMed

Lee, Jang Won; Han, A-Reum; Kim, Kihong

2014-02-01

The purpose of this study was to investigate the balance abilities of the adolescent girl with brain lesions by Sit-to-Stand (STS) action analysis before and after the rehabilitative horse riding of 16 week program. The subject aged 16 yr old who had the disabilities of spasticity and hemiplegia was recruited with the consent approval. The equilibrium abilities of the subject were tested by Sit-to-Stand examination with Weight Transfer Time (WTT), Mean Rising Index (MRI), Mean Weight Asymmetry (MWA), Max Trunk Flexion Velocity (MTFV), and Max Trunk Extension Velocity (MTEV). Research was designed by AB single subject study with baseline of 3 times of measurement and rehabilitative horse riding treatments. In the results, the enhancement of the subject's equilibrium ability was shown from the comparisons between baseline and treatment by the STS test that WTT was 2.37 sec faster, MRI was 6.64 N/kg higher, and MWA was 8.12% lower, and MTFV was 0.57°/sec larger than all those means of baseline. It suggested that the subject showed her enhanced balance ability while in sitting and standing after the rehabilitative horse riding treatments.

Multimodal lung cancer screening using the ITALUNG biomarker panel and low dose computed tomography. Results of the ITALUNG biomarker study.

PubMed

Carozzi, Francesca Maria; Bisanzi, Simonetta; Carrozzi, Laura; Falaschi, Fabio; Lopes Pegna, Andrea; Mascalchi, Mario; Picozzi, Giulia; Peluso, Marco; Sani, Cristina; Greco, Luana; Ocello, Cristina; Paci, Eugenio

2017-07-01

Asymptomatic high-risk subjects, randomized in the intervention arm of the ITALUNG trial (1,406 screened for lung cancer), were enrolled for the ITALUNG biomarker study (n = 1,356), in which samples of blood and sputum were analyzed for plasma DNA quantification (cut off 5 ng/ml), loss of heterozygosity and microsatellite instability. The ITALUNG biomarker panel (IBP) was considered positive if at least one of the two biomarkers included in the panel was positive. Subjects with and without lung cancer diagnosis at the end of the screening cycle with LDCT (n = 517) were evaluated. Out of 18 baseline screen detected lung cancer cases, 17 were IBP positive (94%). Repeat screen-detected lung cancer cases were 18 and 12 of them positive at baseline IBP test (66%). Interval cancer cases (2-years) and biomarker tests after a suspect Non Calcific Nodule follow-up were investigated. The single test versus multimodal screening measures of accuracy were compared in a simulation within the screened ITALUNG intervention arm, considering screen-detected and interval cancer cases. Sensitivity was 90% at baseline screening. Specificity was 71 and 61% for LDCT and IBP as baseline single test, and improved at 89% with multimodal, combined screening. The positive predictive value was 4.3% for LDCT at baseline and 10.6% for multimodal screening. Multimodal screening could improve the screening efficiency at baseline and strategies for future implementation are discussed. If IBP was used as primary screening test, the LDCT burden might decrease of about 60%. © 2017 UICC.

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…

Multiple fMRI system-level baseline connectivity is disrupted in patients with consciousness alterations.

PubMed

Demertzi, Athena; Gómez, Francisco; Crone, Julia Sophia; Vanhaudenhuyse, Audrey; Tshibanda, Luaba; Noirhomme, Quentin; Thonnard, Marie; Charland-Verville, Vanessa; Kirsch, Murielle; Laureys, Steven; Soddu, Andrea

2014-03-01

In healthy conditions, group-level fMRI resting state analyses identify ten resting state networks (RSNs) of cognitive relevance. Here, we aim to assess the ten-network model in severely brain-injured patients suffering from disorders of consciousness and to identify those networks which will be most relevant to discriminate between patients and healthy subjects. 300 fMRI volumes were obtained in 27 healthy controls and 53 patients in minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/UWS) and coma. Independent component analysis (ICA) reduced data dimensionality. The ten networks were identified by means of a multiple template-matching procedure and were tested on neuronality properties (neuronal vs non-neuronal) in a data-driven way. Univariate analyses detected between-group differences in networks' neuronal properties and estimated voxel-wise functional connectivity in the networks, which were significantly less identifiable in patients. A nearest-neighbor "clinical" classifier was used to determine the networks with high between-group discriminative accuracy. Healthy controls were characterized by more neuronal components compared to patients in VS/UWS and in coma. Compared to healthy controls, fewer patients in MCS and VS/UWS showed components of neuronal origin for the left executive control network, default mode network (DMN), auditory, and right executive control network. The "clinical" classifier indicated the DMN and auditory network with the highest accuracy (85.3%) in discriminating patients from healthy subjects. FMRI multiple-network resting state connectivity is disrupted in severely brain-injured patients suffering from disorders of consciousness. When performing ICA, multiple-network testing and control for neuronal properties of the identified RSNs can advance fMRI system-level characterization. Automatic data-driven patient classification is the first step towards future single-subject objective diagnostics based on fMRI resting state acquisitions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Localizing gravitational wave sources with single-baseline atom interferometers

DOE PAGES

Graham, Peter W.; Jung, Sunghoon

2018-01-31

Localizing sources on the sky is crucial for realizing the full potential of gravitational waves for astronomy, astrophysics, and cosmology. Here in this paper, we show that the midfrequency band, roughly 0.03 to 10 Hz, has significant potential for angular localization. The angular location is measured through the changing Doppler shift as the detector orbits the Sun. This band maximizes the effect since these are the highest frequencies in which sources live for several months. Atom interferometer detectors can observe in the midfrequency band, and even with just a single baseline they can exploit this effect for sensitive angular localization.more » The single-baseline orbits around the Earth and the Sun, causing it to reorient and change position significantly during the lifetime of the source, and making it similar to having multiple baselines/detectors. For example, atomic detectors could predict the location of upcoming black hole or neutron star merger events with sufficient accuracy to allow optical and other electromagnetic telescopes to observe these events simultaneously. Thus, midband atomic detectors are complementary to other gravitational wave detectors and will help complete the observation of a broad range of the gravitational spectrum.« less

Localizing gravitational wave sources with single-baseline atom interferometers

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

Graham, Peter W.; Jung, Sunghoon

Localizing sources on the sky is crucial for realizing the full potential of gravitational waves for astronomy, astrophysics, and cosmology. Here in this paper, we show that the midfrequency band, roughly 0.03 to 10 Hz, has significant potential for angular localization. The angular location is measured through the changing Doppler shift as the detector orbits the Sun. This band maximizes the effect since these are the highest frequencies in which sources live for several months. Atom interferometer detectors can observe in the midfrequency band, and even with just a single baseline they can exploit this effect for sensitive angular localization.more » The single-baseline orbits around the Earth and the Sun, causing it to reorient and change position significantly during the lifetime of the source, and making it similar to having multiple baselines/detectors. For example, atomic detectors could predict the location of upcoming black hole or neutron star merger events with sufficient accuracy to allow optical and other electromagnetic telescopes to observe these events simultaneously. Thus, midband atomic detectors are complementary to other gravitational wave detectors and will help complete the observation of a broad range of the gravitational spectrum.« less

Need for recovery from work related fatigue and its role in the development and prediction of subjective health complaints

PubMed Central

Sluiter, J; de Croon, E M; Meijman, T; Frings-Dresen, M

2003-01-01

Aims: To present the available empirical evidence for the assumed position of the concept of work related fatigue as: (1) short term effect of the working day; and (2) an intermediate variable between work demands and the development of subjective health complaints and sickness absence. Methods: Results from six single occupation studies, conducted between 1996 and 2002, are presented. Work demands (working hours, decision latitude, break control/autonomy, and mental, emotional, and physical demands) were assessed through validated scales. Work related fatigue was represented and assessed by means of the need for recovery after working time scale in all studies. Subjective health complaints and duration of sickness absence were quantified with the same instruments in most studies as well. Both cross sectional studies (four) as well as prospective studies (two; up to two years follow up) were performed. Cross sectional data of 3820 workers, in total, were available. Prospective data were accessible for 1200 workers in industry and health care. Models were tested with stepwise multiple regression analyses. Results: Strong associations between work demands and need for necovery were found in different occupations. The variance explained in need for recovery by work demands, age, and (baseline) need for recovery ranged between 14% and 48% in both types of studies. The amount of explained variance by work demands, age, and (baseline) need for recovery in subjective health complaints ranged between 24% and 58% in the different occupations. The prospective data showed the prognostic value of need for recovery in relation to subjective health complaints (in terms of psychosomatic complaints, emotional exhaustion, or sleep problems) and duration of future sickness absence. Conclusions: The hypothesised role for work related fatigue as a link in the causal string of events, that is assumed to exist between repeated adverse work demands and the development of work related stress reactions, (psychological) overload and, eventually, health problems, was confirmed. PMID:12782749

No effect on QT intervals of mipomersen, a 2'-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects.

PubMed

Yu, Rosie Z; Gunawan, Rudy; Li, Zhaoyang; Mittleman, Robert S; Mahmood, Asif; Grundy, John S; Singleton, Walter; Geary, Richard; Wang, Yanfeng

2016-03-01

The aim of this study to evaluate the effect of mipomersen on QT intervals in a phase I dose escalation, placebo-controlled study, and a thorough QT (tQT) study in healthy subjects. In the initial phase I study, 29 healthy subjects received either single or multiple (for 4 weeks) ascending doses of mipomersen (50-400 mg) administered subcutaneously (SC) or via a 2-h intravenous (IV) infusion, and 7 subjects received placebo. In the confirmative tQT study, 58 healthy subjects received placebo, 400 mg IV moxifloxacin, 200 mg SC, or 200 mg IV of mipomersen in a double-blind, 4-way crossover design with a minimum 5-day washout between treatments. ECG measurements were performed at baseline and selected time points (including Tmax). The correlation between QTcF intervals corrected for baseline and time-matched placebo when available with PK plasma exposure was evaluated by linear regression analysis. In the phase I study, no positive correlation between the PK exposure and ∆QTcF or ∆∆QTcF was observed within the wide dose or exposure range tested. Similar results were observed in the tQT study, where the predicted ΔΔQTcF and its upper bound of the 90% CI at Cmax of therapeutic and supratherapeutic dose were approximately -1.7 and 2.9 ms, respectively. Mipomersen showed no effect on QT intervals in both the phase I dose escalation study and the tQT study. These results support the proposal that QT assessment can be made in a phase I dose escalation study, and no tQT study may be necessary if the phase I dose escalation study showed a negative QT effect.

Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study.

PubMed

Dalbeth, Nicola; Saag, Kenneth G; Palmer, William E; Choi, Hyon K; Hunt, Barbara; MacDonald, Patricia A; Thienel, Ulrich; Gunawardhana, Lhanoo

2017-12-01

To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline -0.43 versus -0.07; P <0.001), decreased the overall incidence of gout flares (29.3% versus 41.4%; P < 0.05), and improved serum UA control (62.8% versus 5.7%; P < 0.001). No major safety concerns were reported. Urate-lowering therapy with febuxostat improved magnetic resonance imaging-determined synovitis and reduced the incidence of gout flares in subjects with early gout. © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

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.

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…

Research Strategies in Higher Education.

ERIC Educational Resources Information Center

Semb, George

The present paper outlines two alternative strategies for evaluating teaching effectiveness. These are: (1) within-subject reversal designs, and (2) multiple baseline testing procedures. Each design is discussed in terms of its application to research problems in higher education. In reversal designs, the student is exposed to different teaching…

Evaluation of attention training and metacognitive facilitation to improve reading comprehension in aphasia.

PubMed

Lee, Jaime B; Moore Sohlberg, McKay

2013-05-01

This pilot study investigated the impact of direct attention training combined with metacognitive facilitation on reading comprehension in individuals with aphasia. A single-subject, multiple baseline design was employed across 4 participants to evaluate potential changes in reading comprehension resulting from an 8-week intervention using Attention Process Training-3 (APT-3). The primary outcome measure was a maze reading task. Pre- and posttesting included attention and reading comprehension measures. Visual inspection of graphed performance data across conditions was used as the primary method of analysis. Treatment effect sizes were calculated for changes in reading comprehension probes from baseline to maintenance phases. Two of the study's 4 participants demonstrated improvements in maze reading, with corresponding effect sizes that were small in magnitude according to benchmarks for aphasia treatment research. All 4 participants made improvements on select standardized measures of attention. Interventions that include a metacognitive component with direct attention training may elicit improvements in participants' attention and allocation of resources. Maze passage reading is a repeated measure that appears sensitive to treatment-related changes in reading comprehension. Issues for future research related to measurement, candidacy, and clinical delivery are discussed.

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.

Physical activity in the elderly is associated with improved executive function and processing speed: the LADIS Study.

PubMed

Frederiksen, Kristian Steen; Verdelho, Ana; Madureira, Sofia; Bäzner, Hansjörg; O'Brien, John T; Fazekas, Franz; Scheltens, Philip; Schmidt, Reinhold; Wallin, Anders; Wahlund, Lars-Olof; Erkinjunttii, Timo; Poggesi, Anna; Pantoni, Leonardo; Inzitari, Domenico; Waldemar, Gunhild

2015-07-01

Physical activity reduces the risk of cognitive decline but may affect cognitive domains differently. We examined whether physical activity modifies processing speed, executive function and memory in a population of non-dementia elderly subjects with age-related white matter changes (ARWMC). Data from the Leukoaraiosis And DISability (LADIS) study, a multicenter, European prospective cohort study aimed at examining the role of ARWMC in transition to disability, was used. Subjects in the LADIS study were clinically assessed yearly for 3 years including MRI at baseline and 3-year follow-up. Physical activity was assessed at baseline, and cognitive compound scores at baseline and 3-year assessment were used. Two-hundred-eighty-two subjects (age, y (mean (SD)): 73.1 (± 5.1); gender (f/m): 164/118); MMSE (mean (SD)): 28.3 (± 1.7)) who had not progressed to MCI or dementia, were included. Multiple variable linear regression analysis with baseline MMSE, education, gender, age, stroke, diabetes and ARWMC rating as covariates revealed that physical activity was associated with better scores at baseline and 3-year follow-up for executive function (baseline: β: 0.39, 95% CI: 0.13-0.90, p = 0.008; follow-up: β: 0.24, 95% CI: 0.10-0.38, p = 0.001) and processing speed (baseline: β: 0.48, 95% CI: 0.14-0.89, p = 0.005; follow-up: β: 0.15, 95% CI: 0.02-0.29, p = 0.02) but not memory. When including baseline cognitive score as a covariate in the analysis of 3-year follow-up scores, executive function remained significant (β: 0.11, 95% CI: 0-0.22, p = 0.04). Our findings confirm previous findings of a positive effect of physical activity on cognitive functions in elderly subjects, and further extends these by showing that the association is also present in patients with ARWMC. Copyright © 2014 John Wiley & Sons, Ltd.

Characterization of the disposition of fostamatinib in Japanese subjects including pharmacokinetic assessment in dry blood spots: results from two phase I clinical studies.

PubMed

Martin, Paul; Cheung, S Y Amy; Yen, Mark; Han, David; Gillen, Michael

2016-01-01

The aims of the present study were to characterize the pharmacokinetics of fostamatinib in two phase I studies in healthy Japanese subjects after single- and multiple-dose administration, and to evaluate the utility of dried blood spot (DBS) sampling. In study A, 40 Japanese and 16 white subjects were randomized in a double-blind parallel group study consisting of seven cohorts, which received either placebo or a fostamatinib dose between 50 and 200 mg after single and multiple dosing. Pharmacokinetics of R406 (active metabolite of fostamatinib) in plasma and urine was assessed, and safety was intensively monitored. Study B was an open-label study that assessed fostamatinib 100 and 200 mg in 24 Japanese subjects. In addition to plasma and urine sampling (as for study A), pharmacokinetics was also assessed in blood. Mean maximum plasma concentration (C max) and area under total plasma concentration–time curve (AUC) increased with increasing dose in Japanese subjects. Steady state was achieved in 5–7 days for all doses. C max and AUC were both higher in Japanese subjects administered a 150-mg single dose than in white subjects. This difference was maintained for steady state exposure by day 10. Overall, R406 blood concentrations were consistent and ∼2.5-fold higher than in plasma. Minimal (<0.1 %) R406 was excreted in urine. Fostamatinib was well tolerated at all doses. Fostamatinib pharmacokinetics following single- and multiple-dose administration was approximately dose proportional at all doses ≤150 mg and greater than dose proportional at 200 mg in Japanese subjects. Japanese subjects administered fostamatinib 150 mg had higher exposure than white subjects. R406 could be measured in DBS samples and distributed into red blood cells, and DBS sampling was a useful method for assessing R406 pharmacokinetics.

Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome

PubMed Central

Politis, Marios; Su, Paul; Turkheimer, Federico E.; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Waldman, Adam; Reynolds, Richard; Nicholas, Richard; Piccini, Paola

2015-01-01

The most accurate predictor of the subsequent development of multiple sclerosis in clinically isolated syndrome is the presence of lesions at magnetic resonance imaging. We used in vivo positron emission tomography with 11C-(R)-PK11195, a biomarker of activated microglia, to investigate the normal-appearing white matter and grey matter of subjects with clinically isolated syndrome to explore its role in the development of multiple sclerosis. Eighteen clinically isolated syndrome and eight healthy control subjects were recruited. Baseline assessment included: history, neurological examination, expanded disability status scale, magnetic resonance imaging and PK11195-positron emission tomography scans. All assessments except the PK11195-positron emission tomography scan were repeated over 2 years. SUPERPK methodology was used to measure the binding potential relative to the non-specific volume, BPND. We show a global increase of normal-appearing white matter PK11195 BPND in clinically isolated syndrome subjects compared with healthy controls (P = 0.014). Clinically isolated syndrome subjects with T2 magnetic resonance imaging lesions had higher PK11195 BPND in normal-appearing white matter (P = 0.009) and their normal-appearing white matter PK11195 BPND correlated with the Expanded Disability Status Scale (P = 0.007; r = 0.672). At 2 years those who developed dissemination in space or multiple sclerosis, had higher PK11195 BPND in normal-appearing white matter at baseline (P = 0.007 and P = 0.048, respectively). Central grey matter PK11195 BPND was increased in subjects with clinically isolated syndrome compared to healthy controls but no difference was found in cortical grey matter PK11195 BPND. Microglial activation in clinically isolated syndrome normal-appearing white matter is diffusely increased compared with healthy control subjects and is further increased in those who have magnetic resonance imaging lesions. Furthermore microglial activation in clinically isolated syndrome normal-appearing white matter is also higher in those subjects who developed multiple sclerosis at 2 years. Our finding, if replicated in a larger study, could be of prognostic value and aid early treatment decisions in clinically isolated syndrome. PMID:25416179

Mechanistic correlates of clinical responses to omalizumab in the setting of oral immunotherapy for milk allergy.

PubMed

Frischmeyer-Guerrerio, Pamela A; Masilamani, Madhan; Gu, Wenjuan; Brittain, Erica; Wood, Robert; Kim, Jennifer; Nadeau, Kari; Jarvinen, Kirsi M; Grishin, Alexander; Lindblad, Robert; Sampson, Hugh A

2017-10-01

In our recent clinical trial, the addition of omalizumab to oral immunotherapy (OIT) for milk allergy improved safety, but no significant clinical benefit was detected. We sought to investigate mechanisms by which omalizumab modulates immunity in the context of OIT and to identify baseline biomarkers that predict subgroups of patients most likely to benefit from omalizumab. Blood was obtained at baseline and multiple time points during a placebo-controlled trial of OIT for milk allergy in which subjects were randomized to receive omalizumab or placebo. Immunologic outcomes included measurement of basophil CD63 expression and histamine release and casein-specific CD4 + regulatory T-cell proliferation. Biomarkers were analyzed in relationship to measurements of safety and efficacy. Milk-induced basophil CD63 expression was transiently reduced in whole blood samples from both omalizumab- and placebo-treated subjects. However, IgE-dependent histamine release increased in washed cell preparations from omalizumab- but not placebo-treated subjects. No increase in regulatory T-cell frequency was evident in either group. Subjects with lower rates of adverse reactions, regardless of arm, experienced better clinical outcomes. Pre-OIT basophil reactivity positively associated with occurrence of symptoms during OIT, whereas the baseline milk IgE/total IgE ratio correlated with the likelihood of achieving sustained unresponsiveness. A combination of baseline basophil and serologic biomarkers defined a subset of patients in which adjunctive therapy with omalizumab was associated with attainment of sustained unresponsiveness and a reduction in adverse reactions. Combining omalizumab therapy with milk OIT led to distinct alterations in basophil reactivity but not T-cell responses. Baseline biomarkers can identify subjects most likely to benefit from adjunctive therapy with omalizumab. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

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

PubMed

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

2015-05-01

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

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.

Effects of a short burst of gait training with body weight-supported treadmill training for a person with chronic stroke: a single-subject study.

PubMed

Combs, Stephanie A; Miller, Ellen Winchell

2011-04-01

The purpose of this study was to investigate the effects of a short-burst dose of intense gait training with body weight-supported treadmill training (BWSTT) on walking speed, endurance, and quality of life of a participant with chronic stroke. A single-subject experimental (A-B-A-A) design with immediate and 3-month retention phases was used. The participant was a 66-year-old woman, 1 year after left cerebrovascular accident. Repeated baseline walking performance was established during 2 weeks of testing using the comfortable 10-meter walk test (CWT) and the 6-minute walk test (6MWT). The Stroke Impact Scale (SIS) was measured one time during baseline. Baseline testing was followed by ten 30-minute sessions of BWSTT over a 2-week duration. Retention testing was conducted immediately and 3 months following the intervention. Statistically significant improvements from baseline with the CWT and the 6MWT were achieved and maintained by the participant across all subsequent measurement phases. Improvements considered to be clinically meaningful changes in the SIS domains of strength and mobility achieved immediately after the intervention were not maintained at 3-month retention testing. For the participant in this study, the short-burst dosage of BWSTT provided a feasible and effective means for improving goal-oriented functional walking ability.

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.

Physiological, biochemical, and multiple-task-performance responses to different alterations of the wake-sleep cycle.

DOT National Transportation Integrated Search

1976-11-01

Three groups, each comprising five healthy, male, paid volunteers (ages 21 to 30), were studied for 11 days. Baseline data were collected for 3 days, during which subjects adhered to a day/night routine. On the fourth day each group took a 'flight' i...

Virtual-Reality-Based Social Interaction Training for Children with High-Functioning Autism

ERIC Educational Resources Information Center

Ke, Fengfeng; Im, Tami

2013-01-01

Employing the multiple-baseline across-subjects design, the authors examined the implementation and potential effect of a virtual-reality-based social interaction program on the interaction and communication performance of children with high functioning autism. The data were collected via behavior observation and analysis, questionnaires, and…

The influence of talker and foreign-accent variability on spoken word identification.

PubMed

Bent, Tessa; Holt, Rachael Frush

2013-03-01

In spoken word identification and memory tasks, stimulus variability from numerous sources impairs performance. In the current study, the influence of foreign-accent variability on spoken word identification was evaluated in two experiments. Experiment 1 used a between-subjects design to test word identification in noise in single-talker and two multiple-talker conditions: multiple talkers with the same accent and multiple talkers with different accents. Identification performance was highest in the single-talker condition, but there was no difference between the single-accent and multiple-accent conditions. Experiment 2 further explored word recognition for multiple talkers in single-accent versus multiple-accent conditions using a mixed design. A detriment to word recognition was observed in the multiple-accent condition compared to the single-accent condition, but the effect differed across the language backgrounds tested. These results demonstrate that the processing of foreign-accent variation may influence word recognition in ways similar to other sources of variability (e.g., speaking rate or style) in that the inclusion of multiple foreign accents can result in a small but significant performance decrement beyond the multiple-talker effect.

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.

Multi-template tensor-based morphometry: Application to analysis of Alzheimer's disease

PubMed Central

Koikkalainen, Juha; Lötjönen, Jyrki; Thurfjell, Lennart; Rueckert, Daniel; Waldemar, Gunhild; Soininen, Hilkka

2012-01-01

In this paper methods for using multiple templates in tensor-based morphometry (TBM) are presented and comparedtothe conventional single-template approach. TBM analysis requires non-rigid registrations which are often subject to registration errors. When using multiple templates and, therefore, multiple registrations, it can be assumed that the registration errors are averaged and eventually compensated. Four different methods are proposed for multi-template TBM. The methods were evaluated using magnetic resonance (MR) images of healthy controls, patients with stable or progressive mild cognitive impairment (MCI), and patients with Alzheimer's disease (AD) from the ADNI database (N=772). The performance of TBM features in classifying images was evaluated both quantitatively and qualitatively. Classification results show that the multi-template methods are statistically significantly better than the single-template method. The overall classification accuracy was 86.0% for the classification of control and AD subjects, and 72.1%for the classification of stable and progressive MCI subjects. The statistical group-level difference maps produced using multi-template TBM were smoother, formed larger continuous regions, and had larger t-values than the maps obtained with single-template TBM. PMID:21419228

Comparison of the root canal debridement ability of two single file systems with a conventional multiple rotary system in long oval-shaped root canals: In vitro study.

PubMed

Khoshbin, Elham; Shokri, Abbas; Donyavi, Zakieh; Shahriari, Shahriar; Salehimehr, Golsa; Farhadian, Maryam; Kavandi, Zeinab

2017-08-01

This study sought to compare the root canal debridement ability of Neolix, Reciproc and ProTaper rotary systems in long oval-shaped root canals. Eighty five extracted single-rooted human teeth with long oval-shaped single root canals were selected and divided into three experimental groups(n=25) and one control group (n= 10). Root canals were filled with Vitapex radiopaque contrast medium and prepared with Neolix, Reciproc or ProTaper systems. The control group only received irrigation. Digital radiographs were obtained at baseline and postoperatively and subjected to digital subtraction. The percentage of reduction in contrast medium was quantified at 0-5 mm and 5-10 mm distances from the apex. The data were analyzed using one-way ANOVA and t-test. The mean percentage of the contrast medium removed was not significantly different in the 0-5mm segment among the three groups ( P =0.6). In the 5-10mm segment a significant difference was found in this regard among the ProTaper and Reciproc groups ( P =0.02) and the highest mean percentage of contrast medium was removed by ProTaper. But, difference between ProTaper and Neolix as well as Neolix and Reciproc was not significant. In Neolix ( P =0.024) and Reciproc ( P =0.002) systems, the mean percentage of the contrast medium removed from the 0-5mm segment was significantly greater than that in 5-10mm segment; however, this difference was not significant in ProTaper group ( P =0.069). Neolix single-file system may be a suitable alternative to ProTaper multiple-file system in debridement of long oval shaped canals. Key words: Root Canal Preparation, Debridement, Root Canal Therapy.

Comparative Markedness and Induced Opacity*

PubMed Central

Dinnsen, Daniel A.; Gierut, Judith A.; Farris-Trimble, Ashley W.

2011-01-01

Results are reported from a descriptive and experimental study that was intended to evaluate comparative markedness (McCarthy 2002, 2003) as an amendment to optimality theory. Two children (aged 4;3 and 4;11) with strikingly similar, delayed phonologies presented with two independent, interacting error patterns of special interest, i.e., Deaffrication ([tɪn] ‘chin’) and Consonant Harmony ([ɡɔɡ] ‘dog’) in a feeding interaction ([kik] ‘cheek’). Both children were enrolled in a counterbalanced treatment study employing a multiple base-line single-subject experimental design, which was intended to induce a grandfather effect in one case ([dɔɡ] ‘dog’ and [kik] ‘cheek’) and a counterfeeding interaction in the other ([ɡɔɡ] ‘dog’ and [tik] ‘cheek’). The results were largely supportive of comparative markedness, although some anomalies were observed. The clinical implications of these results are also explored. PMID:21666872

Increasing money-counting skills with a student with brain injury: skill and performance deficits.

PubMed

Fienup, Daniel M; Mudgal, Dipti; Pace, Gary

2013-01-01

Two studies examined the effectiveness of interventions designed to increase money-counting skills of a student with brain injury. Both skill and performance hypotheses were examined. Single subject designs were used to evaluate interventions, including a multiple-baseline across counting paper and coin money (study 1) and a changing criterion design (study 2). In study 1, it was hypothesized that the student had a skill deficit; thus, the participant was taught organizational strategies for counting money. In study 2, a performance deficit was hypothesized and the effects of contingent rewards were evaluated. In study 1, organizational strategies increased organized counting of money, but did not affect counting accuracy. In study 2, contingent rewards increased accurate money counting. When dealing with multi-step behaviours, different components of behaviour can be controlled by different variables, such as skill and performance deficits. Effective academic interventions may need to consider both types of deficits.

Relationship between Risk Factor Control and Compliance with a Lifestyle Modification Program in the Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis Trial.

PubMed

Turan, Tanya N; Al Kasab, Sami; Nizam, Azhar; Lynn, Michael J; Harrell, Jamie; Derdeyn, Colin P; Fiorella, David; Janis, L Scott; Lane, Bethany F; Montgomery, Jean; Chimowitz, Marc I

2018-03-01

Lifestyle modification programs have improved the achievement of risk factor targets in a variety of clinical settings, including patients who have previously suffered a stroke or transient ischemic attack and those with multiple risk factors. Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) was the first vascular disease prevention trial to provide a commercially available lifestyle modification program to enhance risk factor control. We sought to determine the relationship between compliance with this program and risk factor control in SAMMPRIS. SAMMPRIS aggressive medical management included a telephonic lifestyle modification program provided free of charge to all subjects (n = 451) during their participation in the study. Subjects with fewer than 3 expected lifestyle-coaching calls were excluded from these analyses. Compliant subjects (n = 201) had  greater than or equal to 78.5% of calls (median % of completed/expected calls). Noncompliant subjects (n = 200) had less than 78.5% of calls or refused to participate. Mean risk factor values or % in-target for each risk factor was compared between compliant versus noncompliant subjects, using t tests and chi-square tests. Risk factor changes from baseline to follow-up were compared between the groups to account for baseline differences. Compliant subjects had better risk factor control throughout follow-up for low-density lipoprotein, systolic blood pressure (SBP), hemoglobin A1c (HgA1c), non-high-density lipoprotein, nonsmoking, and exercise than noncompliant subjects, but there was no difference for body mass index. After adjusting for baseline differences between the groups, compliant subjects had a greater change from baseline than noncompliant subjects for SBP did at 24 months and HgA1c at 6 months. SAMMPRIS subjects who were compliant with the lifestyle modification program had better risk factor control during the study for almost all risk factors. Published by Elsevier Inc.

Crew performance monitoring: Putting some feeling into it

NASA Astrophysics Data System (ADS)

Pattyn, N.; Migeotte, P.-F.; Morais, J.; Soetens, E.; Cluydts, R.; Kolinsky, R.

2009-08-01

Two hypotheses have been invoked so far to explain performance decrements in space: the microgravity hypothesis and the multiple stressors hypothesis. Furthermore, previous investigations of cognitive performance did not specifically target executive functions. The aim of this study was to investigate the impact of operational stress on cognitive control, towards both neutral and emotionally loaded material, using both psychometric and physiological indicators (autonomic nervous system activity computed through cardio-respiratory recordings). We applied the same design in a study on student pilots (N=12) in baseline conditions and right before a major evaluation flight and on astronauts (N=3) before, during and after a short-duration spaceflight. To address the problem of scarcity of subjects, we applied analytical methods derived from neuropsychology: comparing each astronaut treated as a single subject to a group of carefully matched controls (N=13). Results from both student pilots and astronauts showed that operational stress resulted in failing cognitive control, especially on emotionally loaded material that was relevant to the subjects' current concern. This impaired cognitive control was associated with a decreased physiological reactivity during mental tasks. Furthermore, for astronauts, this performance decrement appeared on the last data-collection before launch and lasted for the two in-flight measurements. These results thus allow us to conclude that: (i) performance testing including an emotional dimension seems more sensitive to operational stress, (ii) decreased heart rate reactivity was associated with impaired cognitive control and (iii) microgravity is not the sole causal factor of potential performance decrements in space, which are more likely due to the combination of multiple stressors.

An Open-Label Exploratory Study with Memantine: Correlation between Proton Magnetic Resonance Spectroscopy and Cognition in Patients with Mild to Moderate Alzheimer's Disease

PubMed Central

Gordon, Marc L.; Kingsley, Peter B.; Goldberg, Terry E.; Koppel, Jeremy; Christen, Erica; Keehlisen, Lynda; Kohn, Nina; Davies, Peter

2012-01-01

Aim To characterize progression of Alzheimer's disease (AD) using proton magnetic resonance spectroscopy (1H MRS). Methods Eleven subjects with mild to moderate AD underwent neurocognitive testing and single-voxel 1H MRS from the precuneus and posterior cingulate region at baseline, after 24 weeks of monotherapy with a cholinesterase inhibitor, and after another 24 weeks of combination therapy with open-label memantine and a cholinesterase inhibitor. Baseline metabolites [N-acetylaspartate (NAA), myo-inositol (mI), choline (Cho), and creatine (Cr)] and their ratios in AD subjects were compared with those of an age-matched control group of 28 cognitively normal subjects. Results AD subjects had significantly higher mI/Cr and lower NAA, NAA/Cr, NAA/Cho, and NAA/mI. Baseline Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores significantly correlated with NAA/Cr, mI/Cr, and NAA/mI. There was an increase in mI and a decrease in NAA/mI, but no significant change in other metabolites or ratios, or neurocognitive measures, when memantine was added to a cholinesterase inhibitor. Conclusion Metabolite ratios significantly differed between AD and control subjects. Baseline metabolite ratios correlated with function (ADCS-ADL). There was an increase in mI and a decrease in NAA/mI, but no changes in other metabolites, ratios, or cognitive measures, when memantine was added to a cholinesterase inhibitor. PMID:22962555

A Novel Study Paradigm for Long-term Prevention Trials in Alzheimer Disease: The Placebo Group Simulation Approach (PGSA): Application to MCI data from the NACC database.

PubMed

Berres, M; Kukull, W A; Miserez, A R; Monsch, A U; Monsell, S E; Spiegel, R

2014-01-01

The PGSA (Placebo Group Simulation Approach) aims at avoiding problems of sample representativeness and ethical issues typical of placebo-controlled secondary prevention trials with MCI patients. The PGSA uses mathematical modeling to forecast the distribution of quantified outcomes of MCI patient groups based on their own baseline data established at the outset of clinical trials. These forecasted distributions are then compared with the distribution of actual outcomes observed on candidate treatments, thus substituting for a concomitant placebo group. Here we investigate whether a PGSA algorithm that was developed from the MCI population of ADNI 1*, can reliably simulate the distribution of composite neuropsychological outcomes from a larger, independently selected MCI subject sample. Data available from the National Alzheimer's Coordinating Center (NACC) were used. We included 1523 patients with single or multiple domain amnestic mild cognitive impairment (aMCI) and at least two follow-ups after baseline. In order to strengthen the analysis and to verify whether there was a drift over time in the neuropsychological outcomes, the NACC subject sample was split into 3 subsamples of similar size. The previously described PGSA algorithm for the trajectory of a composite neuropsychological test battery (NTB) score was adapted to the test battery used in NACC. Nine demographic, clinical, biological and neuropsychological candidate predictors were included in a mixed model; this model and its error terms were used to simulate trajectories of the adapted NTB. The distributions of empirically observed and simulated data after 1, 2 and 3 years were very similar, with some over-estimation of decline in all 3 subgroups. The by far most important predictor of the NTB trajectories is the baseline NTB score. Other significant predictors are the MMSE baseline score and the interactions of time with ApoE4 and FAQ (functional abilities). These are essentially the same predictors as determined for the original NTB score. An algorithm comprising a small number of baseline variables, notably cognitive performance at baseline, forecasts the group trajectory of cognitive decline in subsequent years with high accuracy. The current analysis of 3 independent subgroups of aMCI patients from the NACC database supports the validity of the PGSA longitudinal algorithm for a NTB. Use of the PGSA in long-term secondary AD prevention trials deserves consideration.

Neuropsychological Performance and Subjective Symptom Reporting in Military Service Members With a History of Multiple Concussions: Comparison With a Single Concussion, Posttraumatic Stress Disorder, and Orthopedic Trauma.

PubMed

Cooper, Douglas B; Curtiss, Glenn; Armistead-Jehle, Patrick; Belanger, Heather G; Tate, David F; Reid, Matthew; Bowles, Amy O; Velez, Carmen S; Kennedy, Jan E; Vanderploeg, Rodney D

To examine differences in objective neurocognitive performance and subjective cognitive symptoms in individuals with a history of a single concussion, multiple concussions, orthopedic injuries, and posttraumatic stress disorder (PTSD). Participants included 116 military service members who sustained a mild traumatic brain injury (mTBI) during combat deployment. Subjects were subdivided into groups based on concussion frequency: a single concussion (n = 42), 2 concussions (n = 21), and 3 or more concussions (n = 53). Eighty-one subjects sustained an orthopedic injury (n = 60) during deployment or were diagnosed with PTSD (n = 21), but had no history of mTBI. Subjects completed a battery of neuropsychological tests and self-report measures of postconcussive symptoms, PTSD symptoms, and psychopathology. No differences were found among the concussion groups on a composite neuropsychological measure. The PTSD group had the highest number of symptom complaints, with the 2-concussion and 3-plus-concussion groups being most similar to the PTSD group. The concussion groups showed a nonsignificant pattern of increasing distress with increasing number of concussions. The current findings are consistent with meta-analytic results showing no differential effect on neuropsychological functioning due to multiple concussions. Results also support the burden of adversity hypothesis suggesting increasing symptom levels with increasing psychological or physically traumatic exposures.

Improved Topographic Mapping Through Multi-Baseline SAR Interferometry with MAP Estimation

NASA Astrophysics Data System (ADS)

Dong, Yuting; Jiang, Houjun; Zhang, Lu; Liao, Mingsheng; Shi, Xuguo

2015-05-01

There is an inherent contradiction between the sensitivity of height measurement and the accuracy of phase unwrapping for SAR interferometry (InSAR) over rough terrain. This contradiction can be resolved by multi-baseline InSAR analysis, which exploits multiple phase observations with different normal baselines to improve phase unwrapping accuracy, or even avoid phase unwrapping. In this paper we propose a maximum a posteriori (MAP) estimation method assisted by SRTM DEM data for multi-baseline InSAR topographic mapping. Based on our method, a data processing flow is established and applied in processing multi-baseline ALOS/PALSAR dataset. The accuracy of resultant DEMs is evaluated by using a standard Chinese national DEM of scale 1:10,000 as reference. The results show that multi-baseline InSAR can improve DEM accuracy compared with single-baseline case. It is noteworthy that phase unwrapping is avoided and the quality of multi-baseline InSAR DEM can meet the DTED-2 standard.

Pharmacokinetics of Mirabegron, a β3-Adrenoceptor Agonist for Treatment of Overactive Bladder, in Healthy East Asian Subjects.

PubMed

Iitsuka, Hiromi; van Gelderen, Marcel; Katashima, Masataka; Takusagawa, Shin; Sawamoto, Taiji

2015-05-01

The objective of these studies was to evaluate the pharmacokinetic profile, safety, and tolerability of mirabegron, a β3-adrenoceptor agonist for the treatment of overactive bladder, including food effects (low- or high-fat meals) and sex, in healthy East Asian subjects. In total, 5 pharmacokinetic studies of mirabegron were conducted in healthy East Asian subjects. Food effects were assessed in 3 randomized, single-dose studies in young Japanese male subjects (study 1), male and female subjects (study 2), and young Taiwanese male and female subjects (study 3). In the other 2 single- and multiple-dose studies in young Chinese male and female subjects (study 4 and study 5), mirabegron was administered as a single dose under fasted conditions. After the washout period, mirabegron was administered once daily under fed conditions for 8 days. Pharmacokinetic parameters were determined using noncompartmental methods. Safety and tolerability assessments included physical examinations, vital signs, 12-lead ECG, clinical laboratory tests (biochemistry, hematology, and urinalysis), and adverse event monitoring. After administration of single oral doses of mirabegron, exposure under fed conditions was lower than under fasted conditions in Japanese and Taiwanese subjects. In Japanese subjects, a greater reduction in mirabegron Cmax and AUC0-∞ was observed after a low-fat meal compared with a high-fat meal. In Chinese subjects, Cmax was reached at approximately 4.0 hours after single oral doses. Mirabegron accumulated 2- to 3-fold on once-daily dosing of multiple-dose relative to single-dose data. Steady state was reached within 7 days. After administration of mirabegron, mean values for Cmax and AUC in female subjects were higher than those in male subjects. Mirabegron was well tolerated in Japanese, Taiwanese, and Chinese subjects. Our studies confirm the higher exposure levels of mirabegron in female compared with male East Asian subjects as found earlier in Western subjects. Furthermore, the effects of food on the pharmacokinetic profiles appeared to be similar among the 3 populations tested in our studies. The findings suggest that there are no significant pharmacokinetic differences among the Japanese, Taiwanese, and Chinese populations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The Caterpillar Game: A Classroom Management System

ERIC Educational Resources Information Center

Floress, Margaret T.; Rock, Angela L.; Hailemariam, Assegedech

2017-01-01

A single-case experimental design was used to evaluate the effects of the Caterpillar Game, a classroom management system, on disruptive behavior in a general education first grade classroom. A multiple baseline design across settings was used to evaluate changes in student disruptive behavior and teacher praise. When the Caterpillar Game was…

Evaluating a Tacit Knowledge Sharing Initiative: A Case Study

ERIC Educational Resources Information Center

Gubbins, Claire; Corrigan, Siobhan; Garavan, Thomas N.; O'Connor, Christy; Leahy, Damien; Long, David; Murphy, Eamonn

2012-01-01

Purpose: This paper aims to present a case study illustrating the issues involved in the tacit knowledge conversion process and to determine whether such conversion delivers value to the organisation in terms of business value and return on investment (ROI). Design/methodology/approach: A single-case multiple baseline participants experimental…

Impact of baseline body mass index status on glucose lowering and weight change during sitagliptin treatment for type 2 diabetics.

PubMed

Chen, Jung-Fu; Chang, Chih-Min; Kuo, Ming-Chun; Tung, Shih-Chen; Tsao, Cheng-Feng; Tsai, Chia-Jen

2016-10-01

This study was designed to evaluate the efficacy of sitagliptin in Taiwanese diabetic subjects with different baseline BMI status. This was a single-center, hospital-based, retrospective chart review in subjects (n=1874) with type 2 diabetes who received sitagliptin. Subjects were classified into subgroups depending upon their baseline BMI by Taiwan national weight classification: normal (BMI<24kg/m(2)) (n=504), overweight (BMI: 24-27kg/m(2)) (n=615), and obese (BMI⩾27kg/m(2)) (n=755). Changes in HbA1c and weight were evaluated over a 12month treatment period. For all three groups, the HbA1c levels declined over the first three months by about 8%, and subsequently plateaued for the next nine months. Obese subjects were slower in reducing HbA1c compared with normal and overweight subjects (P<0.05), but at nine months the reduction was similar across groups. Mean body weight increased over the first nine months of sitagliptin therapy in subjects with normal BMI (57.12-58.30kg), but there was no change in mean body weight in the overweight group. After three months the obese groups had significantly greater loss in body weight compared with the normal group. Baseline BMI status may influence the reduction of HbA1c levels within the first six months of sitagliptin therapy and affect weight change after three months. Being obese was associated with an initial lag in HbA1c reduction and greater weight loss compared with normal and overweight subjects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Subjective burden among spousal and adult-child informal caregivers of older adults: results from a longitudinal cohort study.

PubMed

Oldenkamp, Marloes; Hagedoorn, Mariët; Slaets, Joris; Stolk, Ronald; Wittek, Rafael; Smidt, Nynke

2016-12-07

Pressures on informal caregivers are likely to increase due to increasing life expectancy and health care costs, which stresses the importance of prevention of subjective burden. The present study examined the correlates of overall subjective burden and multiple burden dimensions among spousal and adult-child caregivers of Dutch older adults, both cross-sectional and longitudinal (12-months follow-up). In 2010 and 2011 baseline and follow-up data was collected in a sample of informal caregivers and care recipients in the Northern provinces of the Netherlands. Subjective burden included 7 burden dimensions and a summary score for overall subjective burden, based on the Care-Related Quality of Life Instrument (CarerQoL-7D). Objective stressors were the time investment in caregiving (hours of household care, personal care, practical care) and the health situation of the care recipient, including multimorbidity, functional limitations (Katz Index of Independence Basic Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL), and cognitive functioning problems (EQ-5D + C). Correlates of subjective burden were evaluated with linear and logistic regression analyses. The sample consisted of 356 caregivers at baseline (43% spousal, 57% adult-child caregivers), and 158 caregivers at follow-up (45% spousal, 55% adult-child caregivers). At baseline and follow-up, spousal caregivers experienced a higher overall subjective burden, and reported more often mental health problems, physical health problems, and problems with combining daily activities, compared to adult-child caregivers. For spousal caregivers, a poorer health situation of the care recipient was associated with higher subjective burden, while adult-child caregivers reported higher levels of subjective burden when their time investment in caregiving was high. Subjective burden at follow-up was mainly explained by baseline subjective burden. These results indicate that for effective caregiver support, it is crucial to take the type of care relationship into account, since the level and correlates of overall subjective burden and burden dimensions varied for spousal and adult-child caregivers. In addition, reducing subjective burden will also positively impact the subjective burden over time.

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.

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.

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.

A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MS.

PubMed

Freedman, M S; Bar-Or, A; Oger, J; Traboulsee, A; Patry, D; Young, C; Olsson, T; Li, D; Hartung, H-P; Krantz, M; Ferenczi, L; Verco, T

2011-10-18

To evaluate the efficacy and safety of MBP8298 in subjects with secondary progressive multiple sclerosis (SPMS) who express human leukocyte antigen (HLA) haplotype DR2 or DR4 (DR2(+) or DR4(+)). This multicenter randomized 2-year, double-blind, placebo-controlled study included 612 subjects with a diagnosis of SPMS and an Expanded Disability Status Scale (EDSS) score of 3.5-6.5, stratified according to baseline EDSS score (3.5-5.0, or 5.5-6.5) and HLA haplotype (DR2(+) or DR4(+), or DR2(-)/DR4(-)). Upon entry of 100 DR2(-)/DR4(-) subjects, further study enrollment was limited to DR2(+) or DR4(+) subjects. Subjects were randomly assigned to either 500 mg MBP8298 or placebo, given by IV injection once every 6 months for 2 years. The primary outcome measure was time to progression by ≥1.0 EDSS point (or 0.5 point if baseline EDSS was 5.5 or higher), confirmed 6 months later. Secondary outcomes included mean change in EDSS, mean change in Multiple Sclerosis Functional Composite, MRI changes, annualized relapse rate, and quality of life. There were no significant differences between treatment groups in either the primary or secondary endpoints. MBP8298 was well tolerated in all treated subjects with no safety issues identified. In the population studied, treatment with MBP8298 did not provide a clinical benefit compared to placebo. This study provides Class 1 evidence that MBP8298 is not effective in patients with SPMS who are HLA DR2(+) or DR4(+).

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.

The sustained effect (12 months) of a single-dose vectored thermal pulsation procedure for meibomian gland dysfunction and evaporative dry eye.

PubMed

Blackie, Caroline A; Coleman, Christy A; Holland, Edward J

2016-01-01

To evaluate the sustained effect (up to 1 year) of a single, 12-minute vectored thermal pulsation (VTP) treatment in improving meibomian gland function and dry eye symptoms in patients with meibomian gland dysfunction and evaporative dry eye. The prospective, multicenter, open-label clinical trial included 200 subjects (400 eyes) who were randomized to a single VTP treatment (treatment group) or twice-daily, 3-month, conventional warm compress and eyelid hygiene therapy (control group). Control group subjects received crossover VTP treatment at 3 months (crossover group). Effectiveness measures of meibomian gland secretion (MGS) and dry eye symptoms were evaluated at baseline and 1, 3, 6, 9, and 12 months. Subjects with inadequate symptom relief could receive additional meibomian gland dysfunction therapy after 3 (treatment group) and 6 months (crossover group). At 3 months, the treatment group had greater mean improvement in MGS (P<0.0001) and dry eye symptoms (P=0.0068), compared to controls. At 12 months, 86% of the treatment group had received only one VTP treatment, and sustained a mean improvement in MGS from 6.4±3.7 (baseline) to 17.3±9.1 (P<0.0001) and dry eye symptoms from 44.1±20.4 to 21.6±21.3 (P<0.0001); 89% of the crossover group had received only one VTP treatment with sustained mean improvement in MGS from 6.3±3.6 to 18.4±11.1 (P<0.0001) and dry eye symptoms from 49.1±21.0 to 24.0±23.2 (P<0.0001). Greater mean improvement in MGS was associated with less severe baseline MGS (P=0.0017) and shorter duration of time between diagnosis and treatment (P=0.0378). A single VTP treatment can deliver a sustained mean improvement in meibomian gland function and mean reduction in dry eye symptoms, over 12 months. A single VTP treatment provides significantly greater mean improvement in meibomian gland function and dry eye symptoms as compared to a conventional, twice-daily, 3-month regimen. Early VTP intervention for meibomian gland dysfunction is associated with improved treatment outcomes.

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.

An Inverse U-Shaped Curve of Resting-State Networks in Individuals at High Risk of Alzheimer's Disease.

PubMed

Ye, Qing; Chen, Haifeng; Su, Fan; Shu, Hao; Gong, Liang; Xie, Chunming; Zhou, Hong; Bai, Feng

Higher functional connectivity (FC) in resting-state networks has been shown in individuals at risk of Alzheimer's disease (AD) by many studies. However, the longitudinal trajectories of the FC remain unknown. The present 35-month follow-up study aimed to explore longitudinal changes in higher FC in multiple resting-state networks in subjects with the apolipoprotein E ε4 allele (ApoE4) and/or amnestic mild cognitive impairment (aMCI). Fifty-one subjects with aMCI and 64 cognitively normal (CN) subjects underwent neuropsychological tests and resting-state functional magnetic resonance imaging (fMRI) scans twice from April 2011 to June 2015. Subjects were divided into 4 groups according to diagnosis and ApoE4 status. The CN non-ApoE4 group served as a control group, and other groups served as AD risk groups. The cross-sectional and longitudinal patterns of multiple resting-state networks, including default mode network, hippocampus network, executive control network, and salience network, were explored by comparing FC data between groups and between time points, respectively. At baseline, compared with the control group, the AD risk groups showed higher FC with 8 regions in multiple networks. At follow-up, 6 of the regions displayed longitudinally decreased FC in AD risk groups. In contrast, the FC with all of these regions was maintained in the control group. Notably, among the 3 risk groups, most of the higher FC at baseline (5 of the 8 regions) and longitudinally decreased FC at follow-up (4 of the 6 regions) were shown in the aMCI ApoE4 group. Higher resting-state FC is followed by a decline in subjects at AD risk, and this inverse U-shaped trajectory is more notable in subjects with higher risk. © Copyright 2018 Physicians Postgraduate Press, Inc.

Volume reduction of benign thyroid nodules 3 months after a single treatment with high-intensity focused ultrasound (HIFU).

PubMed

Korkusuz, Huedayi; Fehre, Niklas; Sennert, Michael; Happel, Christian; Grünwald, Frank

2015-01-01

High-intensity focused ultrasound (HIFU) is a promising, non-invasive technique in treating benign thyroid nodules (TNs). The aim of this study was to evaluate the efficacy of HIFU to induce clinically meaningful shrinkage in benign predominantly solid TNs and to identify variables that influence or predict the magnitude of TN volume reduction. For each of ten subjects, HIFU treatment was conducted on a single nodule. Nodular volume was measured sonographically at baseline and at 3 months post-procedure. Nodular function and early treatment assessment was done scintigraphically. Median nodular volume reduction was 0.7 ml absolute and 48.8% relative to pre-interventional size (p < 0.05). Absolute shrinkage was negatively correlated with the average treatment depth (τ = -0.61, p < 0.05). Absolute nodular volume was positively correlated with the scintigraphic nodular uptake reduction (τ = 0.66, p < 0.05). HIFU treatment of benign predominantly solid TNs appears to be safe and effective for inducing nodular shrinkage. Despite potential for improvement, a single treatment session with HIFU is already a viable alternative to more standard methods. The feasibility of multiple HIFU treatments requires further investigation. Due to the small sample size, the findings of this analysis need conformation by larger studies.

Using Self-Instruction to Teach Counseling Skills to School Psychology Students: An Efficacy Study

ERIC Educational Resources Information Center

Loe, Scott A.; Jones, W. Paul; Crank, Joe N.; Krach, S. Kathleen

2009-01-01

Counseling is highly valued by school psychology faculty and practitioners but represents a small area of concentration within many graduate training programs, often comprised only of two or three survey courses without a supervised practicum experience. This multiple baseline, across subjects, study involving nine school psychology trainees…

Cognitive-Behavior Therapy for Vietnamese Refugees with PTSD and Comorbid Panic Attacks

ERIC Educational Resources Information Center

Hinton, Devon E.; Safren, Steven A.; Pollack, Mark H.; Tran, Minh

2006-01-01

For Vietnamese refugees, we describe (a) how headache- and orthostasis-focused panic attacks are generated, (b) a culturally sensitive treatment for PTSD with comorbid headache- and orthostasis-focused panic attacks, and (c) the outcome of a treatment series. In a multiple-baseline, across-subjects design (N = 3), all patients demonstrated…

Eye movement desensitisation and reprocessing therapy for posttraumatic stress disorder in a child and an adolescent with mild to borderline intellectual disability: A multiple baseline across subjects study.

PubMed

Mevissen, Liesbeth; Didden, Robert; Korzilius, Hubert; de Jongh, Ad

2017-12-01

This study explored the effectiveness of eye movement desensitisation and reprocessing (EMDR) therapy for post-traumatic stress disorder (PTSD) in persons with mild to borderline intellectual disability (MBID) using a multiple baseline across subjects design. One child and one adolescent with MBID, who met diagnostic criteria for PTSD according to a PTSD clinical interview (i.e., ADIS-C PTSD section), adapted and validated for this target group, were offered four sessions of EMDR. PTSD symptoms were measured before, during and after EMDR, and at six weeks follow-up. For both participants, number of PTSD symptoms decreased in response to treatment and both no longer met PTSD criteria at post-treatment. This result was maintained at 6-week follow-up. The results of this study add further support to the notion that EMDR can be an effective treatment for PTSD in children and adolescents with MBID. Replication of this study in larger samples and using a randomized controlled design is warranted. © 2017 John Wiley & Sons Ltd.

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

ECL-IAA and ECL-GADA Can Identify High-Risk Single Autoantibody-Positive Relatives in the TrialNet Pathway to Prevention Study.

PubMed

Steck, Andrea K; Fouts, Alexandra; Miao, Dongmei; Zhao, Zhiyuan; Dong, Fran; Sosenko, Jay; Gottlieb, Peter; Rewers, Marian J; Yu, Liping

2016-07-01

Relatives with single positive islet autoantibodies have a much lower risk of progression to diabetes than those with multiple autoantibodies. TrialNet subjects positive for single autoantibody to insulin (mIAA) (n = 50) or single autoantibody to glutamic acid decarboxylase (GADA) (n = 50) were analyzed using new electrochemiluminescence (ECL) assays (ECL-IAA and ECL-GADA, respectively) at their initial visit and longitudinally over time. Affinity assays were performed on a subset of single autoantibody-positive subjects at initial and most recent visits. After a mean follow-up of 5.3 years, 20 subjects developed type 1 diabetes. Among either single GADA or single mIAA subjects, those who were positive in the ECL assay showed higher affinity at the initial visit, and affinity results stayed consistent over time. No converting events from low to high or high to low affinity were seen over time. Confirmed positivity for ECL is associated with high affinity and can help staging of risk for type 1 diabetes in single autoantibody-positive subjects.

Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

PubMed

Fleming, J O; Isaak, A; Lee, J E; Luzzio, C C; Carrithers, M D; Cook, T D; Field, A S; Boland, J; Fabry, Z

2011-06-01

Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

A generalized least squares regression approach for computing effect sizes in single-case research: application examples.

PubMed

Maggin, Daniel M; Swaminathan, Hariharan; Rogers, Helen J; O'Keeffe, Breda V; Sugai, George; Horner, Robert H

2011-06-01

A new method for deriving effect sizes from single-case designs is proposed. The strategy is applicable to small-sample time-series data with autoregressive errors. The method uses Generalized Least Squares (GLS) to model the autocorrelation of the data and estimate regression parameters to produce an effect size that represents the magnitude of treatment effect from baseline to treatment phases in standard deviation units. In this paper, the method is applied to two published examples using common single case designs (i.e., withdrawal and multiple-baseline). The results from these studies are described, and the method is compared to ten desirable criteria for single-case effect sizes. Based on the results of this application, we conclude with observations about the use of GLS as a support to visual analysis, provide recommendations for future research, and describe implications for practice. Copyright © 2011 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

A randomized trial of peer coach and office staff support to reduce coronary heart disease risk in African-Americans with uncontrolled hypertension.

PubMed

Turner, Barbara J; Hollenbeak, Christopher S; Liang, Yuanyuan; Pandit, Kavita; Joseph, Shelly; Weiner, Mark G

2012-10-01

Adopting features of the Chronic Care Model may reduce coronary heart disease risk and blood pressure in vulnerable populations. We evaluated a peer and practice team intervention on reduction in 4-year coronary heart disease risk and systolic blood pressure. A single blind, randomized, controlled trial in two adjacent urban university-affiliated primary care practices. Two hundred eighty African-American subjects aged 40 to 75 with uncontrolled hypertension. Three monthly calls from trained peer patients with well-controlled hypertension and, on alternate months, two practice staff visits to review a personalized 4-year heart disease risk calculator and slide shows about heart disease risks. All subjects received usual physician care and brochures about healthy cooking and heart disease. Change in 4-year coronary heart disease risk (primary) and change in systolic blood pressure, both assessed at 6 months. At baseline, the 136 intervention and 144 control subjects' mean 4-year coronary heart disease risk did not differ (intervention=5.8 % and control=6.4 %, P=0.39), and their mean systolic blood pressure was the same (140.5 mmHg, p=0.83). Endpoint data for coronary heart disease were obtained for 69 % of intervention and 82 % of control subjects. After multiple imputation for missing endpoint data, the reduction in risk among all 280 subjects favored the intervention, but was not statistically significant (difference -0.73 %, 95 % confidence interval: -1.54 % to 0.09 %, p=0.08). Among the 247 subjects with a systolic blood pressure endpoint (85 % of intervention and 91 % of control subjects), more intervention than control subjects achieved a >5 mmHg reduction (61 % versus 45 %, respectively, p=0.01). After multiple imputation, the absolute reduction in systolic blood pressure was also greater for the intervention group (difference -6.47 mmHg, 95 % confidence interval: -10.69 to -2.25, P=0.003). One patient died in each study arm. Peer patient and office-based behavioral support for African-American patients with uncontrolled hypertension did not result in a significantly greater reduction in coronary heart disease risk but did significantly reduce systolic blood pressure.

A Comparison of Structurally Connected and Multiple Spacecraft Interferometers

NASA Technical Reports Server (NTRS)

Surka, Derek M.; Crawley, Edward F.

1996-01-01

Structurally connected and multiple spacecraft interferometers are compared in an attempt to establish the maximum baseline (referred to as the "cross-over baseline") for which it is preferable to operate a single-structure interferometer in space rather than an interferometer composed of numerous, smaller spacecraft. This comparison is made using the total launched mass of each configuration as the comparison metric. A framework of study within which structurally connected and multiple spacecraft interferometers can be compared is presented in block diagram form. This methodology is then applied to twenty-two different combinations of trade space parameters to investigate the effects of different orbits, orientations, truss materials, propellants, attitude control actuators, onboard disturbance sources, and performance requirements on the cross-over baseline. Rotating interferometers and the potential advantages of adding active structural control to the connected truss of the structurally connected interferometer are also examined. The minimum mass design of the structurally connected interferometer that meets all performance-requirements and satisfies all imposed constraints is determined as a function of baseline. This minimum mass design is then compared to the design of the multiple spacecraft interferometer. It is discovered that the design of the minimum mass structurally connected interferometer that meets all performance requirements and constraints in solar orbit is limited by the minimum allowable aspect ratio, areal density, and gage of the struts. In the formulation of the problem used in this study, there is no advantage to adding active structural control to the truss for interferometers in solar orbit. The cross-over baseline for missions of practical duration (ranging from one week to thirty years) in solar orbit is approximately 400 m for non-rotating interferometers and 650 m for rotating interferometers.

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

Single-unit muscle sympathetic nervous activity and its relation to cardiac noradrenaline spillover

PubMed Central

Lambert, Elisabeth A; Schlaich, Markus P; Dawood, Tye; Sari, Carolina; Chopra, Reena; Barton, David A; Kaye, David M; Elam, Mikael; Esler, Murray D; Lambert, Gavin W

2011-01-01

Abstract Recent work using single-unit sympathetic nerve recording techniques has demonstrated aberrations in the firing pattern of sympathetic nerves in a variety of patient groups. We sought to examine whether nerve firing pattern is associated with increased noradrenaline release. Using single-unit muscle sympathetic nerve recording techniques coupled with direct cardiac catheterisation and noradrenaline isotope dilution methodology we examined the relationship between single-unit firing patterns and cardiac and whole body noradrenaline spillover to plasma. Participants comprised patients with hypertension (n = 6), depression (n = 7) and panic disorder (n = 9) who were drawn from our ongoing studies. The patient groups examined did not differ in their single-unit muscle sympathetic nerve firing characteristics nor in the rate of spillover of noradrenaline to plasma from the heart. The median incidence of multiple spikes per beat was 9%. Patients were stratified according to the firing pattern: low level of incidence (less than 9% incidence of multiple spikes per beat) and high level of incidence (greater than 9% incidence of multiple spikes per beat). High incidence of multiple spikes within a cardiac cycle was associated with higher firing rates (P < 0.0001) and increased probability of firing (P < 0.0001). Whole body noradrenaline spillover to plasma and (multi-unit) muscle sympathetic nerve activity in subjects with low incidence of multiple spikes was not different to that of those with high incidence of multiple spikes. In those with high incidence of multiple spikes there occurred a parallel activation of the sympathetic outflow to the heart, with cardiac noradrenaline spillover to plasma being two times that of subjects with low nerve firing rates (11.0 ± 1.5 vs. 22.0 ± 4.5 ng min−1, P < 0.05). This study indicates that multiple within-burst firing and increased single-unit firing rates of the sympathetic outflow to the skeletal muscle vasculature is associated with high cardiac noradrenaline spillover. PMID:21486790

A daily skincare regimen with a unique ceramide and filaggrin formulation rapidly improves chronic xerosis, pruritus, and quality of life in older adults.

PubMed

Chang, Anne Lynn S; Chen, Suephy C; Osterberg, Lars; Brandt, Staci; von Grote, Erika C; Meckfessel, Matthew H

A skin care regimen which significantly improved atopic dermatitis and pruritus was evaluated for its efficacy and acceptability in senior subjects diagnosed with xerosis who also suffer from pruritus. This was an open-label, single-center study, designed to evaluate the daily use of a skin care regimen for 15 days. Assessments were made at baseline, day 8 and day 15 for visual skin dryness, transepidermal water loss (TEWL), hydration, desquamation, subject-perceived itch and quality of life (QoL). Twenty-five subjects, ages 60-73 years, had significantly improved skin visual dryness, hydration, desquamation, itch and QoL at days 8 and 15, relative to baseline (P < .05). TEWL was improved, though not significantly. Subjects expressed a high degree of satisfaction with the results. This regimen provides geriatric patients with an easily incorporated skin routine to help improve a common symptom of aging skin which negatively affects QoL. Copyright © 2017 Elsevier Inc. All rights reserved.

Multi-task linear programming discriminant analysis for the identification of progressive MCI individuals.

PubMed

Yu, Guan; Liu, Yufeng; Thung, Kim-Han; Shen, Dinggang

2014-01-01

Accurately identifying mild cognitive impairment (MCI) individuals who will progress to Alzheimer's disease (AD) is very important for making early interventions. Many classification methods focus on integrating multiple imaging modalities such as magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET). However, the main challenge for MCI classification using multiple imaging modalities is the existence of a lot of missing data in many subjects. For example, in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, almost half of the subjects do not have PET images. In this paper, we propose a new and flexible binary classification method, namely Multi-task Linear Programming Discriminant (MLPD) analysis, for the incomplete multi-source feature learning. Specifically, we decompose the classification problem into different classification tasks, i.e., one for each combination of available data sources. To solve all different classification tasks jointly, our proposed MLPD method links them together by constraining them to achieve the similar estimated mean difference between the two classes (under classification) for those shared features. Compared with the state-of-the-art incomplete Multi-Source Feature (iMSF) learning method, instead of constraining different classification tasks to choose a common feature subset for those shared features, MLPD can flexibly and adaptively choose different feature subsets for different classification tasks. Furthermore, our proposed MLPD method can be efficiently implemented by linear programming. To validate our MLPD method, we perform experiments on the ADNI baseline dataset with the incomplete MRI and PET images from 167 progressive MCI (pMCI) subjects and 226 stable MCI (sMCI) subjects. We further compared our method with the iMSF method (using incomplete MRI and PET images) and also the single-task classification method (using only MRI or only subjects with both MRI and PET images). Experimental results show very promising performance of our proposed MLPD method.

Multi-Task Linear Programming Discriminant Analysis for the Identification of Progressive MCI Individuals

PubMed Central

Yu, Guan; Liu, Yufeng; Thung, Kim-Han; Shen, Dinggang

2014-01-01

Accurately identifying mild cognitive impairment (MCI) individuals who will progress to Alzheimer's disease (AD) is very important for making early interventions. Many classification methods focus on integrating multiple imaging modalities such as magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET). However, the main challenge for MCI classification using multiple imaging modalities is the existence of a lot of missing data in many subjects. For example, in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, almost half of the subjects do not have PET images. In this paper, we propose a new and flexible binary classification method, namely Multi-task Linear Programming Discriminant (MLPD) analysis, for the incomplete multi-source feature learning. Specifically, we decompose the classification problem into different classification tasks, i.e., one for each combination of available data sources. To solve all different classification tasks jointly, our proposed MLPD method links them together by constraining them to achieve the similar estimated mean difference between the two classes (under classification) for those shared features. Compared with the state-of-the-art incomplete Multi-Source Feature (iMSF) learning method, instead of constraining different classification tasks to choose a common feature subset for those shared features, MLPD can flexibly and adaptively choose different feature subsets for different classification tasks. Furthermore, our proposed MLPD method can be efficiently implemented by linear programming. To validate our MLPD method, we perform experiments on the ADNI baseline dataset with the incomplete MRI and PET images from 167 progressive MCI (pMCI) subjects and 226 stable MCI (sMCI) subjects. We further compared our method with the iMSF method (using incomplete MRI and PET images) and also the single-task classification method (using only MRI or only subjects with both MRI and PET images). Experimental results show very promising performance of our proposed MLPD method. PMID:24820966

Gut microbiota in multiple sclerosis: possible influence of immunomodulators.

PubMed

Cantarel, Brandi L; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M; Mowry, Ellen M

2015-06-01

Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer acetate-treated patients with multiple sclerosis showed differences in community composition compared with untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. While overall bacterial communities were similar, specific operational taxonomic units differed between healthy controls and patients with multiple sclerosis. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results.

Trade Study of Multiple Thruster Options for the Mars Airplane Concept

NASA Technical Reports Server (NTRS)

Kuhl, Christopher A.; Gayle, Steven W.; Hunter, Craig A.; Kenney, Patrick S.; Scola, Salvatore; Paddock, David A.; Wright, Henry S.; Gasbarre, Joseph F.

2009-01-01

A trade study was performed at NASA Langley Research Center under the Planetary Airplane Risk Reduction (PARR) project (2004-2005) to examine the option of using multiple, smaller thrusters in place of a single large thruster on the Mars airplane concept with the goal to reduce overall cost, schedule, and technical risk. The 5-lbf (22N) thruster is a common reaction control thruster on many satellites. Thousands of these types of thrusters have been built and flown on numerous programs, including MILSTAR and Intelsat VI. This study has examined the use of three 22N thrusters for the Mars airplane propulsion system and compared the results to those of the baseline single thruster system.

Hydra multiple head star sensor and its in-flight self-calibration of optical heads alignment

NASA Astrophysics Data System (ADS)

Majewski, L.; Blarre, L.; Perrimon, N.; Kocher, Y.; Martinez, P. E.; Dussy, S.

2017-11-01

HYDRA is EADS SODERN new product line of APS-based autonomous star trackers. The baseline is a multiple head sensor made of three separated optical heads and one electronic unit. Actually the concept which was chosen offers more than three single-head star trackers working independently. Since HYDRA merges all fields of view the result is a more accurate, more robust and completely autonomous multiple-head sensor, releasing the AOCS from the need to manage the outputs of independent single-head star trackers. Specific to the multiple head architecture and the underlying data fusion, is the calibration of the relative alignments between the sensor optical heads. The performance of the sensor is related to its estimation of such alignments. HYDRA design is first reminded in this paper along with simplification it can bring at system level (AOCS). Then self-calibration of optical heads alignment is highlighted through descriptions and simulation results, thus demonstrating the performances of a key part of HYDRA multiple-head concept.

Effective seat-to-head transmissibility in whole-body vibration: Effects of posture and arm position

NASA Astrophysics Data System (ADS)

Rahmatalla, Salam; DeShaw, Jonathan

2011-12-01

Seat-to-head transmissibility is a biomechanical measure that has been widely used for many decades to evaluate seat dynamics and human response to vibration. Traditionally, transmissibility has been used to correlate single-input or multiple-input with single-output motion; it has not been effectively used for multiple-input and multiple-output scenarios due to the complexity of dealing with the coupled motions caused by the cross-axis effect. This work presents a novel approach to use transmissibility effectively for single- and multiple-input and multiple-output whole-body vibrations. In this regard, the full transmissibility matrix is transformed into a single graph, such as those for single-input and single-output motions. Singular value decomposition and maximum distortion energy theory were used to achieve the latter goal. Seat-to-head transmissibility matrices for single-input/multiple-output in the fore-aft direction, single-input/multiple-output in the vertical direction, and multiple-input/multiple-output directions are investigated in this work. A total of ten subjects participated in this study. Discrete frequencies of 0.5-16 Hz were used for the fore-aft direction using supported and unsupported back postures. Random ride files from a dozer machine were used for the vertical and multiple-axis scenarios considering two arm postures: using the armrests or grasping the steering wheel. For single-input/multiple-output, the results showed that the proposed method was very effective in showing the frequencies where the transmissibility is mostly sensitive for the two sitting postures and two arm positions. For multiple-input/multiple-output, the results showed that the proposed effective transmissibility indicated higher values for the armrest-supported posture than for the steering-wheel-supported posture.

The Caterpillar Game: A SW-PBIS Aligned Classroom Management System

ERIC Educational Resources Information Center

Floress, Margaret T.; Jacoby, Amber L.

2017-01-01

The Caterpillar Game is a classroom management system that is aligned with School-wide Positive Behavioral Interventions and Supports standards. A single-case, multiple-baseline design was used to evaluate the effects of the Caterpillar Game on disruptive student behavior and teacher praise. Three classrooms were included in the study (preschool,…

Precision of Curriculum-Based Measurement Reading Data: Considerations for Multiple-Baseline Designs

ERIC Educational Resources Information Center

Klingbeil, David A.; Van Norman, Ethan R.; Nelson, Peter M.

2017-01-01

Single-case designs provide an established technology for evaluating the effects of academic interventions. Researchers interested in studying the long-term effects of reading interventions often use curriculum-based measures of reading (CBM-R) as they possess many of the desirable characteristics for use in a time-series design. The reliability…

A Pilot Study of Integrated Listening Systems for Children with Sensory Processing Problems

ERIC Educational Resources Information Center

Schoen, Sarah A.; Miller, Lucy J.; Sullivan, Jillian

2015-01-01

This pilot study explored the effects of Integrated Listening Systems (iLs) Focus Series on individualized parent goals for children with sensory processing impairments. A nonconcurrent multiple baseline, repeated measure across participants, single-case study design was employed (n = 7). The 40-session intervention was delivered at home and in…

Coaching Preservice Teachers to Teach Play Skills to Children with Disabilities

ERIC Educational Resources Information Center

Barton, Erin E.; Chen, Ching-I; Pribble, Lois; Pomes, Maria; Kim, Young-Ah

2013-01-01

The purpose of this article is to describe two studies that examined the effects of training and coaching on preservice teachers' implementation of an intervention focused on teaching play to young children with disabilities. A multiple-baseline across teachers single-case research design was used to systematically examine the relation between…

Coaching Teachers to Support Child Communication across Daily Routines in Early Head Start Classrooms

ERIC Educational Resources Information Center

Friedman, Mollie; Woods, Juliann

2015-01-01

This study investigates the use of a situated coaching protocol in Early Head Start (EHS) classrooms to increase teachers' use of communication facilitation strategies with children identified with delays during typical play and caregiving routines. A single-case, multiple baseline design across 3 EHS teachers and children with communication…

Guidelines for the Clinical Evaluation of Psychoactive Drugs in Infants and Children.

ERIC Educational Resources Information Center

Food and Drug Administration (DHEW), Washington, DC.

These guidelines are intended to help those who design and conduct investigations of psychopharmacologic agents in children. A progression of studies in four phases is advocated. First, early short term studies should establish single and multiple dose safety baselines. Second, early pilot efficacy studies may be initiated jointly with longer…

Repeated Reading, Turn Taking, and Augmentative and Alternative Communication (AAC)

ERIC Educational Resources Information Center

Edmister, Evette; Wegner, Jane

2015-01-01

This single participant multiple baseline research design measured the effects of repeatedly reading narrative books to children who used voice output augmentative communication devices to communicate. The study sought to determine if there was a difference observed in the number of turns taken when reading stories repeatedly. Three girls ranging…

A Writing Intervention to Teach Simple Sentences and Descriptive Paragraphs to Adolescents with Writing Difficulties

ERIC Educational Resources Information Center

Datchuk, Shawn M.; Kubina, Richard M., Jr.

2017-01-01

The present study used a multiple-baseline, single-case experimental design to investigate the effects of a multicomponent intervention on construction of simple sentences and word sequences. The intervention entailed sequential delivery of sentence instruction and frequency building to a performance criterion and paragraph instruction.…

A Standardized Mean Difference Effect Size for Multiple Baseline Designs across Individuals

ERIC Educational Resources Information Center

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

2013-01-01

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…

Stimulus Generalization of Parenting Skills during Parent-Child Interaction Therapy

ERIC Educational Resources Information Center

Naik-Polan, Anjali T.; Budd, Karen S.

2008-01-01

This study investigated the generalization of parenting skills to the home from PCIT delivered in a community mental health setting with four urban, low-income, single mothers at risk for child maltreatment. Using a multiple baseline design and direct observation in the home, the research examined changes in positive attention skills (praise,…

Video Modeling for Children and Adolescents with Autism Spectrum Disorder: A Meta-Analysis

ERIC Educational Resources Information Center

Thompson, Teresa Lynn

2014-01-01

The objective of this research was to conduct a meta-analysis to examine existing research studies on video modeling as an effective teaching tool for children and adolescents diagnosed with Autism Spectrum Disorder (ASD). Study eligibility criteria included (a) single case research design using multiple baselines, alternating treatment designs,…

Liposomal bupivacaine as a single-injection peripheral nerve block: a dose-response study.

PubMed

Ilfeld, Brian M; Malhotra, Nisha; Furnish, Timothy J; Donohue, Michael C; Madison, Sarah J

2013-11-01

Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration of <24 hours. A liposomal bupivacaine formulation (EXPAREL, Pacira Pharmaceuticals, Inc., San Diego, CA), releasing bupivacaine over 96 hours, recently gained Food and Drug Administration approval exclusively for wound infiltration but not peripheral nerve blocks. Bilateral single-injection femoral nerve blocks were administered in healthy volunteers (n = 14). For each block, liposomal bupivacaine (0-80 mg) was mixed with normal saline to produce 30 mL of study fluid. Each subject received 2 different doses, 1 on each side, applied randomly in a double-masked fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. There were statistically significant dose responses in MVIC (0.09%/mg, SE = 0.03, 95% confidence interval [CI], 0.04-0.14, P = 0.002) and tolerance to cutaneous current (-0.03 mA/mg, SE = 0.01, 95% CI, -0.04 to -0.02, P < 0.001), however, in the opposite direction than expected (the higher the dose, the lower the observed effect). This inverse relationship is biologically implausible and most likely due to the limited sample size and the subjective nature of the measurement instruments. While peak effects occurred within 24 hours after block administration in 75% of cases (95% CI, 43%-93%), block duration usually lasted much longer: for bupivacaine doses >40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 hours in 100% of subjects (95% CI, 56%-100%). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI, 54%-100%). Motor block duration was not correlated with bupivacaine dose (0.06 hour/mg, SE = 0.14, 95% CI, -0.27 to 0.39, P = 0.707). The results of this investigation suggest that deposition of a liposomal bupivacaine formulation adjacent to the femoral nerve results in a partial sensory and motor block of >24 hours for the highest doses examined. However, the high variability of block magnitude among subjects and inverse relationship of dose and response magnitude attests to the need for a phase 3 study with a far larger sample size, and that these results should be viewed as suggestive, requiring confirmation in a future trial.

Liposomal Bupivacaine as a Single-Injection Peripheral Nerve Block: A Dose-Response Study

PubMed Central

Ilfeld, Brian M.; Malhotra, Nisha; Furnish, Timothy J.; Donohue, Michael C.; Madison, Sarah J.

2013-01-01

Background Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration less than 24 hours. A liposomal bupivacaine formulation (EXPAREL®, Pacira Pharmaceuticals, Inc., San Diego, California), releasing bupivacaine over 96 hours, recently gained Food and Drug Administration approval exclusively for wound infiltration, but not peripheral nerve blocks. Methods Bilateral single-injection femoral nerve blocks were administered in healthy volunteers (n=14). For each block, liposomal bupivacaine (0–80 mg) was mixed with normal saline to produce 30 mL of study fluid. Each subject received two different doses, one on each side, applied randomly in a double-masked fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. Results There were statistically significant dose responses in MVIC (0.09% / mg, SE = 0.03, 95% CI 0.04 to 0.14, p = 0.002) and tolerance to cutaneous current (−0.03 mA / mg, SE = 0.01, 95% CI −0.04 to 0.02, p < 0.001), however, in the opposite direction than expected (the higher the dose, the lower the observed effect). This inverse relationship is biologically implausible, and most likely due to the limited sample size and the subjective nature of the measurement instruments. While peak effects occurred within 24 hours after block administration in 75% of cases (95% CI 43 to 93%), block duration usually lasted much longer: for bupivacaine doses above 40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 h in 100% of subjects (95% CI 56 to 100). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI 54 to 100%). Motor block duration was not correlated with bupivacaine dose (0.06 h/mg, SE = 0.14, 95% CI −0.27 to 0.39, p = 0.707). Conclusions The results of this investigation suggest that deposition of a liposomal bupivacaine formulation adjacent to the femoral nerve results in a partial sensory and motor block of more than 24 hours for the highest doses examined. However, the high variability of block magnitude among subjects and inverse relationship of dose and response magnitude attests to the need for a Phase 3 study with a far larger sample size, and these results should be viewed as suggestive, requiring confirmation in a future trial. PMID:24108252

Group selection for adaptation to multiple-hen cages: humoral immune response.

PubMed

Hester, P Y; Muir, W M; Craig, J V

1996-11-01

A selected line of White Leghorns, which has shown improved survivability and reduced feather loss in large multiple-hen cages, was evaluated for humoral immune response to SRBC under both stressed and unstressed conditions. Three lines of chickens (selected, control, and commercial) were housed in either single- (1 hen) or multiple-hen cages (12 hens, social competition) and subjected to a cold ambient temperature (0 C) at 33 wk of age and to two heating episodes (38 C) at 44 wk of age. Each hen was challenged intravenously with 1 mL of a 7% saline suspension of SRBC at the time that cold exposure was initiated. Hens subjected to high ambient temperatures had been exposed previously to a cold temperature, but were not challenged with SRBC until 16 to 18 h following the end of the second heating episode. Exposure to cold caused immunosuppression in single-caged hens, but not in hens in colony cages. Single- vs colony-caged hens of the control environment challenged with SRBC at 33 wk of age had similar primary hemagglutinin responses to SRBC. Hens subjected to heat experienced immunosuppression at 9 and 12 d following challenge to SRBC when compared to the controls. Hens of multiple-bird cages challenged with antigen at 44 wk of age had a significantly lower hemagglutinin response to SRBC than those reared in single-bird cages. The three lines of genetic stock had similar primary hemagglutinin responses to SRBC; the interactions of genetic stock with cage size or environmental temperature were not significant. It was concluded that genetically selecting hens for survival in multiple-hen cages did not affect their humoral immune response to SRBC.

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).

Improved A1C by switching to continuous subcutaneous insulin infusion from injection insulin therapy in type 2 diabetes: A retrospective claims analysis.

PubMed

Lynch, Peter; Riedel, Aylin Altan; Samant, Navendu; Fan, Ying; Peoples, Tim; Levinson, Jenifer; Lee, Scott W

2010-12-01

This study was a real-world, retrospective evaluation of the clinical effectiveness of switching to continuous subcutaneous insulin infusion (CSII) among managed care enrollees with type 2 diabetes for whom multiple daily injections (MDI) had presumably failed. Administrative claims with integrated A1C values from a large and geographically diverse health plan were analyzed. Statistically significant A1C reductions (from the baseline period to follow-up period, mean follow-up 17 months) were achieved with CSII. Among subjects using a long-acting and rapid-acting insulin regimen at baseline, A1C decreased to mean follow-up A1C by 0.8% and to minimum follow-up A1C by 1.2% (p<0.001). The proportion of subjects at target (A1C<7%) increased significantly from baseline to follow-up (8.4-22.9% [using mean A1C] and 32.8% [using minimum A1C]; both p<0.001). The rate of severe hypoglycemic events was similar from baseline to follow-up. CSII was associated with significant reductions in A1C without an increase in hypoglycemic events in insulin-taking people with type 2 diabetes, including subjects previously using a long-acting and rapid-acting insulin regimen. Copyright © 2010 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

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.

Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome.

PubMed

Giannetti, Paolo; Politis, Marios; Su, Paul; Turkheimer, Federico E; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Waldman, Adam; Reynolds, Richard; Nicholas, Richard; Piccini, Paola

2015-01-01

The most accurate predictor of the subsequent development of multiple sclerosis in clinically isolated syndrome is the presence of lesions at magnetic resonance imaging. We used in vivo positron emission tomography with (11)C-(R)-PK11195, a biomarker of activated microglia, to investigate the normal-appearing white matter and grey matter of subjects with clinically isolated syndrome to explore its role in the development of multiple sclerosis. Eighteen clinically isolated syndrome and eight healthy control subjects were recruited. Baseline assessment included: history, neurological examination, expanded disability status scale, magnetic resonance imaging and PK11195-positron emission tomography scans. All assessments except the PK11195-positron emission tomography scan were repeated over 2 years. SUPERPK methodology was used to measure the binding potential relative to the non-specific volume, BPND. We show a global increase of normal-appearing white matter PK11195 BPND in clinically isolated syndrome subjects compared with healthy controls (P = 0.014). Clinically isolated syndrome subjects with T2 magnetic resonance imaging lesions had higher PK11195 BPND in normal-appearing white matter (P = 0.009) and their normal-appearing white matter PK11195 BPND correlated with the Expanded Disability Status Scale (P = 0.007; r = 0.672). At 2 years those who developed dissemination in space or multiple sclerosis, had higher PK11195 BPND in normal-appearing white matter at baseline (P = 0.007 and P = 0.048, respectively). Central grey matter PK11195 BPND was increased in subjects with clinically isolated syndrome compared to healthy controls but no difference was found in cortical grey matter PK11195 BPND. Microglial activation in clinically isolated syndrome normal-appearing white matter is diffusely increased compared with healthy control subjects and is further increased in those who have magnetic resonance imaging lesions. Furthermore microglial activation in clinically isolated syndrome normal-appearing white matter is also higher in those subjects who developed multiple sclerosis at 2 years. Our finding, if replicated in a larger study, could be of prognostic value and aid early treatment decisions in clinically isolated syndrome. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of Online Augmented Kinematic and Perceptual Feedback on Treatment of Speech Movements in Apraxia of Speech

PubMed Central

McNeil, M.R.; Katz, W.F.; Fossett, T.R.D.; Garst, D.M.; Szuminsky, N.J.; Carter, G.; Lim, K.Y.

2010-01-01

Apraxia of speech (AOS) is a motor speech disorder characterized by disturbed spatial and temporal parameters of movement. Research on motor learning suggests that augmented feedback may provide a beneficial effect for training movement. This study examined the effects of the presence and frequency of online augmented visual kinematic feedback (AVKF) and clinician-provided perceptual feedback on speech accuracy in 2 adults with acquired AOS. Within a single-subject multiple-baseline design, AVKF was provided using electromagnetic midsagittal articulography (EMA) in 2 feedback conditions (50 or 100%). Articulator placement was specified for speech motor targets (SMTs). Treated and baselined SMTs were in the initial or final position of single-syllable words, in varying consonant-vowel or vowel-consonant contexts. SMTs were selected based on each participant's pre-assessed erred productions. Productions were digitally recorded and online perceptual judgments of accuracy (including segment and intersegment distortions) were made. Inter- and intra-judge reliability for perceptual accuracy was high. Results measured by visual inspection and effect size revealed positive acquisition and generalization effects for both participants. Generalization occurred across vowel contexts and to untreated probes. Results of the frequency manipulation were confounded by presentation order. Maintenance of learned and generalized effects were demonstrated for 1 participant. These data provide support for the role of augmented feedback in treating speech movements that result in perceptually accurate speech production. Future investigations will explore the independent contributions of each feedback type (i.e. kinematic and perceptual) in producing efficient and effective training of SMTs in persons with AOS. PMID:20424468

Adolescents with Asperger Syndrome Can Use a Mindfulness-Based Strategy to Control Their Aggressive Behavior

ERIC Educational Resources Information Center

Singh, Nirbhay N.; Lancioni, Giulio E.; Singh, Angela D. A.; Winton, Alan S. W.; Singh, Ashvind N. A.; Singh, Judy

2011-01-01

Children and adolescents with Asperger syndrome occasionally exhibit aggressive behavior against peers and parents. In a multiple baseline design across subjects, three adolescents with Asperger syndrome were taught to use a mindfulness-based procedure called "Meditation on the Soles of the Feet" to control their physical aggression in the family…

The Effects of Cooperative Learning on the Classroom Participation of Students Placed at Risk for Societal Failure

ERIC Educational Resources Information Center

Drakeford, William

2012-01-01

A multiple baseline design across two subjects was used to determine the effectiveness of cooperative learning techniques on increasing student participation. The study was conducted on two male secondary students attending the upward bound pre-college program. Each student worked in small groups with specific roles, and two observers documented…

Longitudinal changes in airway remodeling and air trapping in severe asthma

PubMed Central

Witt, Chad A.; Sheshadri, Ajay; Carlstrom, Luke; Tarsi, Jaime; Kozlowski, James; Wilson, Brad; Gierada, David; Hoffman, Eric; Fain, Sean; Cook-Granroth, Janice; Sajol, Geneline; Sierra, Oscar; Giri, Tusar; O'Neil, Michael; Zheng, Jie; Schechtman, Kenneth B.; Bacharier, Leonard B.; Jarjour, Nizar; Busse, William; Castro, Mario

2014-01-01

Rationale and Objectives Previous cross-sectional studies have demonstrated that airway wall thickness and air trapping are greater in subjects with severe asthma than in those with mild-to-moderate asthma. However, a better understanding of how airway remodeling and lung density change over time is needed. This study aims to evaluate predictors of airway wall remodeling and change in lung function and lung density over time in severe asthma. Materials and Methods Phenotypic characterization and quantitative multidetector computed tomography (MDCT) of the chest was performed at baseline and ∼2.6 years later in 38 participants with asthma (severe n=24, mild-moderate n=14) and 9 normal controls from the Severe Asthma Research Program. Results Subjects with severe asthma had a significant decline in post-bronchodilator FEV1% predicted over time (p = <0.001). Airway wall thickness measured by MDCT was increased at multiple airway generations in severe asthma compared to mild-to-moderate asthma (wall area percent (WA%): p <0.05) and normals (p <0.05) at baseline and year 2. Over time, there was an increase in WA% and wall thickness (WT%) in all subjects (p = 0.030 and 0.009 respectively) with no change in emphysema-like lung or air trapping. Baseline pre-bronchodilator FEV1% inversely correlated with WA% and WT% (both p = <0.05). In a multivariable regression model, baseline WA%, race and healthcare utilization were predictors of subsequent airway remodeling. Conclusions Severe asthma subjects have a greater decline in lung function over time than normal subjects or those with mild-to-moderate asthma. MDCT provides a noninvasive measure of airway wall thickness that may predict subsequent airway remodeling. PMID:25018070

The implications of autoantibodies to a single islet antigen in relatives with normal glucose tolerance: development of other autoantibodies and progression to type 1 diabetes.

PubMed

Bingley, Polly J; Boulware, David C; Krischer, Jeffrey P

2016-03-01

Autoantibodies directed at single islet autoantigens are associated with lower overall risk of type 1 diabetes than multiple autoantibodies, but individuals with one autoantibody may progress to higher risk categories. We examined the characteristics of this progression in relatives followed prospectively in the TrialNet Pathway to Prevention. The study population comprised 983 relatives who were single autoantibody positive with normal baseline glucose tolerance (median age 16.2 years). Samples were screened for antibodies to GAD, insulinoma-associated antigen 2 (IA-2) and insulin, and all positive samples tested for antibodies to zinc transporter 8 and islet cell antibodies. Antibodies to at least one additional islet autoantigen appeared in 118 of 983 relatives (overall 5 year risk 22%, 95% CI [17.9, 26.1]). At baseline, antibodies to GAD alone (68%) were more frequent than antibodies to insulin (26%) or IA-2 (6%), but all were associated with a similar risk of developing additional autoantibodies. Risk was associated with younger age (p = 0.002) and HLA class II genotype, but was similar in high and intermediate genetic risk groups (p = 0.65). Relatives who became multiple autoantibody positive during the follow-up had increased risk of developing diabetes comparable with the risk in relatives with multiple autoantibodies at study entry. Progression of islet autoimmunity in single autoantibody positive relatives in late childhood/adult life is associated with a predominance of autoantibodies to GAD and a distinct HLA risk profile. This heterogeneity in type 1 diabetes autoimmunity has potentially important implications for disease prevention.

Efficacy of cognitive-behavioral therapy for insomnia associated with traumatic brain injury: a single-case experimental design.

PubMed

Ouellet, Marie-Christine; Morin, Charles M

2007-12-01

To test the efficacy of a cognitive-behavioral therapy (CBT) for insomnia in persons having sustained traumatic brain injury (TBI). Single-case design with multiple baselines across participants. Outpatient rehabilitation center. Eleven subjects having sustained mild to severe TBI who developed insomnia after the injury. Eight-week CBT for insomnia including stimulus control, sleep restriction, cognitive restructuring, sleep hygiene education, and fatigue management. Total wake time, sleep efficiency, and diagnostic criteria. Visual analyses, corroborated by intervention time series analyses and t tests, revealed clinically and statistically significant reductions in total wake time and sleep efficiency for 8 (73%) of 11 participants. An average reduction of 53.9% in total wake time was observed across participants from pre- to post-treatment. Progress was in general well maintained at the 1-month and 3-month follow-ups. The average sleep efficiency augmented significantly from pretreatment (77.2%) to post-treatment (87.9%), and also by the 3-month follow-up (90.9%). Improvements in sleep were accompanied by a reduction in symptoms of general and physical fatigue. The results of this study show that psychologic interventions for insomnia are a promising therapeutic avenue for TBI survivors.

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.

Multiple Image Arrangement for Subjective Quality Assessment

NASA Astrophysics Data System (ADS)

Wang, Yan; Zhai, Guangtao

2017-12-01

Subjective quality assessment serves as the foundation for almost all visual quality related researches. Size of the image quality databases has expanded from dozens to thousands in the last decades. Since each subjective rating therein has to be averaged over quite a few participants, the ever-increasing overall size of those databases calls for an evolution of existing subjective test methods. Traditional single/double stimulus based approaches are being replaced by multiple image tests, where several distorted versions of the original one are displayed and rated at once. And this naturally brings upon the question of how to arrange those multiple images on screen during the test. In this paper, we answer this question by performing subjective viewing test with eye tracker for different types arrangements. Our research indicates that isometric arrangement imposes less duress on participants and has more uniform distribution of eye fixations and movements and therefore is expected to generate more reliable subjective ratings.

Schema therapy for chronic depression: Results of a multiple single case series.

PubMed

Renner, Fritz; Arntz, Arnoud; Peeters, Frenk P M L; Lobbestael, Jill; Huibers, Marcus J H

2016-06-01

The aim of this study was to test the effects of individual schema therapy (ST) for patients with chronic depression. Using a multiple-baseline single case series design, patients with chronic major depressive disorder (N = 25) first entered a 6-24 weeks baseline phase; this phase functioned as a no-treatment control condition. Then, patients started a 12 week exploration phase during which symptoms and underlying schemas were explored; this phase functioned as an attention control condition. Next, patients received up to 65 sessions of individual ST. The Beck Depression Inventory II (BDI-II) and the Quick Inventory of Depressive Symptomatology (QIDS) were the primary outcome measures. The BDI-II was assessed once a week during all phases of the study resulting in 100 repeated assessments per participant on average. Mixed regression analysis was used to contrast change in symptoms during the intervention with change in symptoms during the baseline and exploration control phases. When compared to the no-treatment control period, the intervention had a significant, large effect on depressive symptoms (Cohen's d BDI-II = 1.30; Cohen's d QIDS = 1.22). Effects on secondary continuous outcomes were moderate to large. The small sample size and lack of a control group. These findings provide evidence that ST might be an effective treatment for patients with chronic depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Drug Use and Multiple Sex Partners among Homeless Ex-Offenders: Secondary Findings from an Experimental Study

PubMed Central

Nyamathi, Adeline M.; Zhang, Sheldon; Wall, Sarah; Hall, Elizabeth A.; Salem, Benissa E.; Farabee, David; Faucette, Mark; Yadav, Kartik

2016-01-01

Background Transitioning into society after release from incarceration presents real challenges for male offenders; in California, up to 60% return to prison within three years following release. The risk for ongoing drug use and having sex with multiple sex partners is a significant challenge for ex-offenders preparing to enter the community. Objectives The aims are to describe drug use and sexual behavior (sex with multiple partners) prior to incarceration and six and 12 months following study enrollment using data obtained as part of a randomized controlled trial (RCT). Methods This is a planned secondary analysis of data obtained as part of an RCT designed to study the effects of intensive peer coaching and nurse case management, intensive peer coaching, and brief nurse counseling on hepatitis A and B vaccination adherence compared to a usual care control treatment that also included brief peer coaching and brief nurse counseling. Self-report data from subjects enrolled at one residential drug treatment facility in Los Angeles were captured at three time points: baseline, and six- and 12-month follow up. Results Findings showed substantive and significant reductions in drug use and engaging in sex with multiple partners six months following enrollment into the study compared to the baseline data, but results did not differ by study condition. At 12-month follow up, drug use and sex with multiple partners increased, but remained less than at baseline levels. Discussion Sustaining reductions in drug use and engaging in sex with multiple partners remains a challenge following incarceration. PMID:27124254

Multiocular image sensor with on-chip beam-splitter and inner meta-micro-lens for single-main-lens stereo camera.

PubMed

Koyama, Shinzo; Onozawa, Kazutoshi; Tanaka, Keisuke; Saito, Shigeru; Kourkouss, Sahim Mohamed; Kato, Yoshihisa

2016-08-08

We developed multiocular 1/3-inch 2.75-μm-pixel-size 2.1M- pixel image sensors by co-design of both on-chip beam-splitter and 100-nm-width 800-nm-depth patterned inner meta-micro-lens for single-main-lens stereo camera systems. A camera with the multiocular image sensor can capture horizontally one-dimensional light filed by both the on-chip beam-splitter horizontally dividing ray according to incident angle, and the inner meta-micro-lens collecting the divided ray into pixel with small optical loss. Cross-talks between adjacent light field images of a fabricated binocular image sensor and of a quad-ocular image sensor are as low as 6% and 7% respectively. With the selection of two images from one-dimensional light filed images, a selective baseline for stereo vision is realized to view close objects with single-main-lens. In addition, by adding multiple light field images with different ratios, baseline distance can be tuned within an aperture of a main lens. We suggest the electrically selective or tunable baseline stereo vision to reduce 3D fatigue of viewers.

Manifold Regularized Multitask Feature Learning for Multimodality Disease Classification

PubMed Central

Jie, Biao; Zhang, Daoqiang; Cheng, Bo; Shen, Dinggang

2015-01-01

Multimodality based methods have shown great advantages in classification of Alzheimer’s disease (AD) and its prodromal stage, that is, mild cognitive impairment (MCI). Recently, multitask feature selection methods are typically used for joint selection of common features across multiple modalities. However, one disadvantage of existing multimodality based methods is that they ignore the useful data distribution information in each modality, which is essential for subsequent classification. Accordingly, in this paper we propose a manifold regularized multitask feature learning method to preserve both the intrinsic relatedness among multiple modalities of data and the data distribution information in each modality. Specifically, we denote the feature learning on each modality as a single task, and use group-sparsity regularizer to capture the intrinsic relatedness among multiple tasks (i.e., modalities) and jointly select the common features from multiple tasks. Furthermore, we introduce a new manifold-based Laplacian regularizer to preserve the data distribution information from each task. Finally, we use the multikernel support vector machine method to fuse multimodality data for eventual classification. Conversely, we also extend our method to the semisupervised setting, where only partial data are labeled. We evaluate our method using the baseline magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), and cerebrospinal fluid (CSF) data of subjects from AD neuroimaging initiative database. The experimental results demonstrate that our proposed method can not only achieve improved classification performance, but also help to discover the disease-related brain regions useful for disease diagnosis. PMID:25277605

ECL-IAA and ECL-GADA Can Identify High-Risk Single Autoantibody-Positive Relatives in the TrialNet Pathway to Prevention Study

PubMed Central

Fouts, Alexandra; Miao, Dongmei; Zhao, Zhiyuan; Dong, Fran; Sosenko, Jay; Gottlieb, Peter; Rewers, Marian J.

2016-01-01

Abstract Background: Relatives with single positive islet autoantibodies have a much lower risk of progression to diabetes than those with multiple autoantibodies. Materials and Methods: TrialNet subjects positive for single autoantibody to insulin (mIAA) (n = 50) or single autoantibody to glutamic acid decarboxylase (GADA) (n = 50) were analyzed using new electrochemiluminescence (ECL) assays (ECL-IAA and ECL-GADA, respectively) at their initial visit and longitudinally over time. Affinity assays were performed on a subset of single autoantibody-positive subjects at initial and most recent visits. Results: After a mean follow-up of 5.3 years, 20 subjects developed type 1 diabetes. Among either single GADA or single mIAA subjects, those who were positive in the ECL assay showed higher affinity at the initial visit, and affinity results stayed consistent over time. No converting events from low to high or high to low affinity were seen over time. Conclusions: Confirmed positivity for ECL is associated with high affinity and can help staging of risk for type 1 diabetes in single autoantibody-positive subjects. PMID:26991969

State Insurance Mandates and Multiple Birth Rates After In Vitro Fertilization.

PubMed

Provost, Meredith P; Thomas, Samantha M; Yeh, Jason S; Hurd, William W; Eaton, Jennifer L

2016-12-01

To examine the association between state-mandated insurance coverage for in vitro fertilization (IVF) and the incidence of multiple birth while controlling for differences in baseline patient characteristics. We conducted a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System from 2007 to 2011 to examine the association between state-mandated insurance coverage for IVF and the incidence of multiple birth while controlling for differences in baseline patient characteristics. Analyses were stratified according to patient age and day of embryo transfer (3 or 5). Of the 173,968 cycles included in the analysis, 45,011 (25.9%) were performed in mandated states and 128,957 (74.1%) in nonmandated states. The multiple birth rate was significantly lower in mandated states (29.0% compared with 32.8%, adjusted odds ratio [OR] 0.87, 99.95% confidence interval [CI] 0.80-0.94). After stratification, this association remained statistically significant only in women younger than 35 years old who underwent transfer on day 5 (33.1% compared with 38.6%, adjusted OR 0.81, 99.95% CI 0.71-0.92). Among women younger than 35 years with day 5 transfer, the elective single embryo transfer rate was significantly higher in mandated states (21.8% compared with 13.1%, adjusted OR 2.36, 99.95% CI 2.09-2.67). State-mandated insurance coverage for IVF is associated with decreased odds of multiple birth. This relationship is driven by increased use of elective single embryo transfer among young women undergoing day 5 transfer.

Embedding Individualized Social Goals into Routine Activities in Inclusive Early Childhood Classrooms

ERIC Educational Resources Information Center

Macy, Marisa G.; Bricker, Diane D.

2007-01-01

This study examined the effectiveness of embedding children's social goals into routine activities within inclusive preschool classroom settings. An AB (i.e. baseline and intervention) single-subject design was used across three male participants with identified disabilities. Three student-teachers, enrolled in a master's program at a university,…

Benign multiple sclerosis: physical and cognitive impairment follow distinct evolutions.

PubMed

Gajofatto, A; Turatti, M; Bianchi, M R; Forlivesi, S; Gobbin, F; Azzarà, A; Monaco, S; Benedetti, M D

2016-03-01

Benign multiple sclerosis (BMS) definitions rely on physical disability level but do not account sufficiently for cognitive impairment which, however, is not rare. To study the evolution of physical disability and cognitive performance of a group of patients with BMS followed at an University Hospital Multiple Sclerosis Center. A consecutive sample of 24 BMS cases (diagnosis according to 2005 McDonald's criteria, relapsing-remitting course, disease duration ≥ 10 years, and expanded disability status scale [EDSS] score ≤ 2.0) and 13 sex- and age-matched non-BMS patients differing from BMS cases for having EDSS score 2.5-5.5 were included. Main outcome measures were as follows: (i) baseline and 5-year follow-up cognitive impairment defined as failure of at least two tests of the administered neuropsychological battery; (ii) EDSS score worsening defined as confirmed increase ≥ 1 point (or 0.5 point if baseline EDSS score = 5.5). At inclusion, BMS subjects were 41 ± 8 years old and had median EDSS score 1.5 (range 0-2), while non-BMS patients were 46 ± 8 years old and had median EDSS score 3.0 (2.5-5.5). At baseline 16% of patients in both groups were cognitively impaired. After 5 years, EDSS score worsened in 8% of BMS and 46% of non-BMS patients (P = 0.008), while the proportion of cognitively impaired subjects increased to 25% in both groups. Patients with BMS had better physical disability outcome at 5 years compared to non-BMS cases. However, cognitive impairment frequency and decline over time appeared similar. Neuropsychological assessment is essential in patients with BMS given the distinct pathways followed by disease progression in cognitive and physical domains. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of an artificially lengthened vocal tract on the glottal closed quotient in untrained male voices

NASA Astrophysics Data System (ADS)

Gaskill, Christopher Somers

The use of hard-walled narrow tubes, often called resonance tubes, for the purpose of voice therapy and voice training has a historical precedent and some theoretical support, but the mechanism of any potential benefit from the application of this technique has remained poorly understood. Fifteen vocally untrained male participants produced a series of spoken /a / vowels at a modal pitch and constant loudness, followed by a minute of repeated phonation into a hard-walled glass tube at the same pitch and loudness targets. The tube parameters and tube phonation task criteria were selected according to theoretical calculations predicting an increase in the acoustic load such that phonation would occur under conditions of near-maximum inertive reactance. Following tube phonation, each participant repeated a similar series of spoken /a/ vowels. Electroglottography (EGG) was used to measure the glottal closed quotient (CQ) during each phase of the experiment. A single-subject, multiple-baseline design with direct replication across subjects was used to identify any changes in CQ across the phases of the experiment. Single-subject analysis using the method of Statistical Process Control (SPC) revealed statistically significant changes in CQ during tube phonation, but with no discernable pattern across the 15 participants. These results indicate that the use of resonance tubes can have a distinct effect on glottal closure, but the mechanism behind this change remains unclear. The implication is that vocal loading techniques such as this need to be studied further with specific attention paid to the underlying mechanism of any measured changes in glottal behavior, and especially to the role of instruction and feedback in the therapeutic and pedagogical application of these techniques.

A Multiple-Sequence Variant of the Multiple-Baseline Design: A Strategy for Analysis of Sequence Effects and Treatment Comparison.

ERIC Educational Resources Information Center

Noell, George H.; Gresham, Frank M.

2001-01-01

Describes design logic and potential uses of a variant of the multiple-baseline design. The multiple-baseline multiple-sequence (MBL-MS) consists of multiple-baseline designs that are interlaced with one another and include all possible sequences of treatments. The MBL-MS design appears to be primarily useful for comparison of treatments taking…

Increasing Self-Regulation and Classroom Participation of a Child Who Is Deafblind

ERIC Educational Resources Information Center

Nelson, Catherine; Hyte, Holly A.; Greenfield, Robin

2015-01-01

Self regulation has been identified as essential to school success. However, for a variety of reasons, its development may be compromised in children and youth who are deafblind. A single-case multiple baseline study of a child who was deafblind examined the effects of three groups of evidence-based interventions on variables thought to be…

Supporting Early Childhood Educators' Use of Embedded Communication Strategies by Providing Feedback via Bug-in-Ear Technology

ERIC Educational Resources Information Center

Riggie, Jennifer

2013-01-01

The purpose of this study was to examine the relationship between coaching provided with bug-in-ear technology, the frequency of the early childhood educators' use of targeted communication strategies and children's expressive communication. Four multiple-baseline single-case design experiments were completed to evaluate these relationships.…

Learning with Technology: Video Modeling with Concrete-Representational-Abstract Sequencing for Students with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Yakubova, Gulnoza; Hughes, Elizabeth M.; Shinaberry, Megan

2016-01-01

The purpose of this study was to determine the effectiveness of a video modeling intervention with concrete-representational-abstract instructional sequence in teaching mathematics concepts to students with autism spectrum disorder (ASD). A multiple baseline across skills design of single-case experimental methodology was used to determine the…

The Evaluation of a Personal Narrative Language Intervention for School-Age Children with Down Syndrome

ERIC Educational Resources Information Center

Finestack, Lizbeth; O'Brien, Katy H.; Hyppa-Martin, Jolene; Lyrek, Kristen A.

2017-01-01

The purpose of this study was to evaluate the feasibility of an intervention focused on improving personal narrative skills of school-age children with Down syndrome (DS) using an approach involving visual supports. Four females with DS, ages 10 through 15 years, participated in this multiple baseline across participants single-subject…

Efficacy of Cognitive-Behavioral Therapy for Comorbid Panic Disorder with Agoraphobia and Generalized Anxiety Disorder

ERIC Educational Resources Information Center

Labrecque, Joane; Marchand, Andre; Dugas, Michel J.; Letarte, Andree

2007-01-01

The goal of this study was to evaluate the efficacy of cognitive-behavioral therapy for comorbid panic disorder with agoraphobia (PDA) and generalized anxiety disorder (GAD) by combining treatment strategies for both disorders. A single-case, multiple-baseline design across participants was used. Three participants with primary PDA and secondary…

The effects of mands and models on the speech of unresponsive language-delayed preschool children.

PubMed

Warren, S F; McQuarter, R J; Rogers-Warren, A K

1984-02-01

The effects of the systematic use of mands (non-yes/no questions and instructions to verbalize), models (imitative prompts), and specific consequent events on the productive verbal behavior of three unresponsive, socially isolate, language-delayed preschool children were investigated in a multiple-baseline design within a classroom free play period. Following a lengthy intervention condition, experimental procedures were systematically faded out to check for maintenance effects. The treatment resulted in increases in total verbalizations and nonobligatory speech (initiations) by the subjects. Subjects also became more responsive in obligatory speech situations. In a second free play (generalization) setting, increased rates of total child verbalizations and nonobligatory verbalizations were observed for all three subjects, and two of the three subjects were more responsive compared to their baselines in the first free play setting. Rate of total teacher verbalizations and questions were also higher in this setting. Maintenance of the treatment effects was shown during the fading condition in the intervention setting. The subjects' MLUs (mean length of utterance) increased during the intervention condition when the teacher began prompting a minimum of two-word utterances in response to a mand or model.

COMT Val(158)Met genotype determines the direction of cognitive effects produced by catechol-O-methyltransferase inhibition.

PubMed

Farrell, Sarah M; Tunbridge, Elizabeth M; Braeutigam, Sven; Harrison, Paul J

2012-03-15

Catechol-O-methyltransferase (COMT) metabolizes dopamine. The COMT Val(158)Met polymorphism influences its activity, and multiple neural correlates of this genotype on dopaminergic phenotypes, especially working memory, have been reported. COMT activity can also be regulated pharmacologically by COMT inhibitors. The inverted-U relationship between cortical dopamine signaling and working memory predicts that the effects of COMT inhibition will differ according to COMT genotype. Thirty-four COMT Met(158)Met (Met-COMT) and 33 COMT Val(158)Val (Val-COMT) men were given a single 200-mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a randomized, double-blind, between-subjects design. They completed the N-back task of working memory and a gambling task. In the placebo group, Met-COMT subjects outperformed Val-COMT subjects on the 2- back, and they were more risk averse. Tolcapone had opposite effects in the two genotype groups: it worsened N-back performance in Met-COMT subjects but enhanced it in Val-COMT subjects. Tolcapone made Met-COMT subjects less risk averse but Val-COMT subjects more so. In both tasks, tolcapone reversed the baseline genotype differences. Depending on genotype, COMT inhibition can enhance or impair working memory and increase or decrease risky decision making. To our knowledge, the data are the clearest demonstration to date that the direction of effect of a drug can be influenced by a polymorphism in its target gene. The results support the inverted-U model of dopamine function. The findings are of translational relevance, because COMT inhibitors are used in the adjunctive treatment of Parkinson's disease and are under evaluation in schizophrenia and other disorders. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Health among Swedish employees and financial situation, education, and managerial responsibility: a longitudinal study.

PubMed

Runeson, Roma; Vingård, Eva; Lampa, Erik; Wahlstedt, Kurt

2012-11-01

The present study is part of a 3-year longitudinal study on work and health among employees in the public sector in Sweden. The aim was to study associations between self-rated health (SRH) and financial situation, education, and managerial responsibility. Of the 9003 employees, 7533 answered the baseline questionnaires (84%). Altogether 9373 subjects received the follow-up questionnaire, and 6617 subjects responded (71%). In total 4240 completed the questionnaire on both occasions, and this group comprised the study population. SRH consisted of the response to a single question: 'In general, would you say your health is excellent, very good, good, poor, or very poor?' The health was investigated in terms of the development of health status in the 3-year follow-up. The exposure factors were: financial situation, education, and managerial responsibility. Odds ratios were analysed using logistic regressions. Good financial situation and further education were predictors in maintaining good health and in avoiding poor health. The analysis also indicated the following determinants of sustained good SRH: having a good financial situation (OR 1.99 at baseline and OR 1.87 at follow-up), having a further education compared to lower education (OR 1.17 at baseline), and not having a worsening financial situation between baseline and follow-up (OR 0.53). Financial situation and educational level were important factors that influence the subjective perception of health.

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.

Increased Behavioral Economic Demand and Craving for Alcohol following a Laboratory Alcohol Challenge

PubMed Central

Amlung, Michael; McCarty, Kayleigh N.; Morris, David H.; Tsai, Chia-Lin; McCarthy, Denis M.

2015-01-01

Background and aims Although increases in subjective alcohol craving have been observed following moderate doses of alcohol (e.g., priming effects), the effects of alcohol consumption on behavioral economic demand for alcohol are largely unstudied. This study examined the effects of alcohol intoxication on alcohol demand and craving. Design A between-subjects design in which participants were randomly assigned to either an alcohol (n = 31), placebo (n = 29) or control (n = 25) condition. Setting A laboratory setting at the University of Missouri, USA. Participants Eighty-five young adult moderate drinkers were recruited from the University of Missouri and surrounding community. Measurements Change in demand for alcohol across time was measured using three single items: alcohol consumption at no cost (i.e., intensity), maximum price paid for a single drink (i.e., breakpoint), and total amount spent on alcohol (i.e., Omax). Alcohol demand at baseline was also assessed using an alcohol purchase task (APT). Craving was assessed using a single visual analog scale item. Findings In the alcohol group compared with the combined non-alcohol groups, intensity, breakpoint, and craving increased from baseline to the ascending limb and decreased thereafter (ps < 0.05; Omax p = 0.06). Change in craving following alcohol consumption was significantly associated with change in each of the demand indices (ps < 0.0001). Finally, the demand single items were associated with corresponding indices from the APT (ps < 0.01). Conclusions Alcohol demand increases following intoxication, in terms of both the maximum amount people are willing to pay for one drink and the number of drinks people would consume if drinks were free. Behavioral economic measures of alcohol value can complement subjective craving as measures of moment-to-moment fluctuations in drinking motivation following intoxication. PMID:25732875

An innovative training program based on virtual reality and treadmill: effects on gait of persons with multiple sclerosis.

PubMed

Peruzzi, Agnese; Zarbo, Ignazio Roberto; Cereatti, Andrea; Della Croce, Ugo; Mirelman, Anat

2017-07-01

In this single blind randomized controlled trial, we examined the effect of a virtual reality-based training on gait of people with multiple sclerosis. Twenty-five individuals with multiple sclerosis with mild to moderate disability were randomly assigned to either the control group (n = 11) or the experimental group (n = 14). The subjects in the control group received treadmill training. Subjects in the experimental group received virtual reality based treadmill training. Clinical measures and gait parameters were evaluated. Subjects in both the groups significantly improved the walking endurance and speed, cadence and stride length, lower limb joint ranges of motion and powers, during single and dual task gait. Moreover, subjects in the experimental group also improved balance, as indicated by the results of the clinical motor tests (p < 0.05). Between-group comparisons revealed that the experimental group improved significantly more than control group in hip range of motion and hip generated power at terminal stance at post-training. Our results support the perceived benefits of training programs that incorporate virtual reality to improve gait measures in individuals with multiple sclerosis. Implication of rehabilitation Gait deficits are common in multiple sclerosis (85%) and worsen during dual task activities. Intensive and progressive treadmill training, with and without virtual reality, is effective on dual task gait in persons with multiple sclerosis. Virtual reality-based treadmill training requiring obstacle negotiation increases the range of motion and the power generated at the hip, consequently allowing longer stride length and, consequently, higher gait speed.

Treatment of giant intradural (perimedullary) arteriovenous fistulas.

PubMed

Halbach, V V; Higashida, R T; Dowd, C F; Fraser, K W; Edwards, M S; Barnwell, S L

1993-12-01

Ten patients with giant intradural spinal arteriovenous fistulas (perimedullary Types II and III) were treated with embolization alone (three patients) or in combination with surgery (seven patients). Their ages at the time of treatment ranged from 2 to 40 years, with a mean of 19.5 years. The indications for treatment included progressive myelopathy in five patients, spinal subarachnoid hemorrhage in four, and acute paraplegia in one. Associated conditions included Rendu-Osler-Weber syndrome in two patients, and Cobb's syndrome in two patients. In one patient, the cause of the fistula may have been related to epidural anesthesia traumatizing a low tethered cord. Angiographically, the fistulas were subclassified in three groups: a single-hole fistula supplied by a single feeding medullary artery (three patients); a single-hole fistula supplied by multiple medullary arteries (three patients); and multiple separate fistulas supplied by multiple medullary arteries (four patients). Eight patients were classified as perimedullary Type III and two as perimedullary Type II. Embolic agents were delivered from transarterial routes in 14 procedures and transvenous routes in 2 procedures. A total of 16 embolizations and 8 operations were performed in 10 patients. Seven patients were cured of their fistula (as demonstrated by angiography), two patients had 5% residual filling and are scheduled for future therapy. One refused a follow-up angiographic examination. Complications related to embolization included rupture of the anterior spinal artery by a detachable balloon, resulting in transient worsening of paraplegia with recovery to baseline. Transient worsening of symptoms after surgery was common, but all patients returned to baseline or better. Dramatic improvement was observed in four patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple sclerosis and employment: Associations of psychological factors and work instability.

PubMed

Wicks, Charlotte Rose; Ward, Karl; Stroud, Amanda; Tennant, Alan; Ford, Helen L

2016-10-12

People with multiple sclerosis often stop working earlier than expected. Psychological factors may have an impact on job retention. Investigation may inform interventions to help people stay in work. To investigate the associations between psychological factors and work instability in people with multiple sclerosis. A multi-method, 2-phased study. Focus groups were held to identify key themes. Questionnaire packs using validated scales of the key themes were completed at baseline and at 8-month follow-up. Four key psychological themes emerged. Out of 208 study subjects 57.2% reported medium/high risk of job loss, with marginal changes at 8 months. Some psychological variables fluctuated significantly, e.g. depression fell from 24.6% to 14.5%. Work instability and anxiety and depression were strongly correlated (χ2 p < 0.001). Those with probable depression at baseline had 7.1 times increased odds of medium/high work instability, and baseline depression levels also predicted later work instability (Hosmer-Lemeshow test 0.899; Nagelkerke R Square 0.579). Psychological factors fluctuated over the 8-month follow-up period. Some psychological variables, including anxiety and depression, were significantly associated with, and predictive of, work instability. Longitudinal analysis should further identify how these psychological attributes impact on work instability and potential job loss in the longer term.

The Efficacy of Noncontingent Escape for Decreasing Children's Disruptive Behavior during Restorative Dental Treatment

ERIC Educational Resources Information Center

O'Callaghan, Patrick M.; Allen, Keith D.; Powell, Shawn; Salama, Fouad

2006-01-01

We evaluated the effectiveness of a dentist-implemented behavioral intervention in which brief escape from dental treatment was provided on a regular basis, independent of the child's behavior. Within a multiple baseline design across subjects, 5 children, ages 4 to 7 years, were provided with temporary escape from dental treatment on a fixed-time…

Promoting Imitation in Young Children with Autism: A Comparison of Reciprocal Imitation Training and Video Modeling

ERIC Educational Resources Information Center

Cardon, Teresa A.; Wilcox, M. Jeanne

2011-01-01

The inability to imitate is a salient diagnostic marker for autism. It has been suggested that for children with autism, imitation may be a prerequisite skill that can assist in the development of various skills. Using a multiple baseline design across subjects, the purpose of this research was to determine if two interventions, reciprocal…

Contingency Contracting and Its Impact on the Use of Punctuation Skills by Fifth Graders with Learning Disabilities

ERIC Educational Resources Information Center

Grünke, Matthias; Coeppicus, Christin

2017-01-01

The purpose of this study was to assess the effectiveness of contingency contracting on the percentage of correctly used punctuation marks in free writing tasks. Participants were three 11-year-old boys with learning disabilities (LD). A multiple-baseline across-subjects design was employed to test our prediction that the students would show…

Self-Monitoring of Attention versus Self-Monitoring of Academic Performance: Effects among Students with ADHD in the General Education Classroom

ERIC Educational Resources Information Center

Harris, Karen R.; Friedlander, Barbara Danoff; Saddler, Bruce; Frizzelle, Remedios; Graham, Steve

2005-01-01

A counterbalanced, multiple-baseline, across-subjects design was used to determine if attention and performance monitoring had differential effects on the on-task and spelling study behavior of 6 elementary students with attention-deficit/hyperactivity disorder (ADHD) in the general education classroom. Both self-monitoring of attention and…

Filtering for networked control systems with single/multiple measurement packets subject to multiple-step measurement delays and multiple packet dropouts

NASA Astrophysics Data System (ADS)

Moayedi, Maryam; Foo, Yung Kuan; Chai Soh, Yeng

2011-03-01

The minimum-variance filtering problem in networked control systems, where both random measurement transmission delays and packet dropouts may occur, is investigated in this article. Instead of following the many existing results that solve the problem by using probabilistic approaches based on the probabilities of the uncertainties occurring between the sensor and the filter, we propose a non-probabilistic approach by time-stamping the measurement packets. Both single-measurement and multiple measurement packets are studied. We also consider the case of burst arrivals, where more than one packet may arrive between the receiver's previous and current sampling times; the scenario where the control input is non-zero and subject to delays and packet dropouts is examined as well. It is shown that, in such a situation, the optimal state estimate would generally be dependent on the possible control input. Simulations are presented to demonstrate the performance of the various proposed filters.

The problem of isotopic baseline: Reconstructing the diet and trophic position of fossil animals

NASA Astrophysics Data System (ADS)

Casey, Michelle M.; Post, David M.

2011-05-01

Stable isotope methods are powerful, frequently used tools which allow diet and trophic position reconstruction of organisms and the tracking of energy sources through ecosystems. The majority of ecosystems have multiple food sources which have distinct carbon and nitrogen isotopic signatures despite occupying a single trophic level. This difference in the starting isotopic composition of primary producers sets up an isotopic baseline that needs to be accounted for when calculating diet or trophic position using stable isotopic methods. This is particularly important when comparing animals from different regions or different times. Failure to do so can cause erroneous estimations of diet or trophic level, especially for organisms with mixed diets. The isotopic baseline is known to vary seasonally and in concert with a host of physical and chemical variables such as mean annual rainfall, soil maturity, and soil pH in terrestrial settings and lake size, depth, and distance from shore in aquatic settings. In the fossil record, the presence of shallowing upward suites of rock, or parasequences, will have a considerable impact on the isotopic baseline as basin size, depth and distance from shore change simultaneously with stratigraphic depth. For this reason, each stratigraphic level is likely to need an independent estimation of baseline even within a single outcrop. Very little is known about the scope of millennial or decadal variation in isotopic baseline. Without multi-year data on the nature of isotopic baseline variation, the impacts of time averaging on our ability to resolve trophic relationships in the fossil record will remain unclear. The use of a time averaged baseline will increase the amount of error surrounding diet and trophic position reconstructions. Where signal to noise ratios are low, due to low end member disparity (e.g., aquatic systems), or where the observed isotopic shift is small (≤ 1‰) the error introduced by time averaging may severely inhibit the scope of one's interpretations and limit the types of questions one can reliably answer. In situations with strong signal strength, resulting from high amounts of end member disparity (e.g., terrestrial settings), this additional error maybe surmountable. Baseline variation that is adequately characterized can be dealt with by applying multiple end-member mixing models.

The Effect of Educational Software, Video Modelling and Group Discussion on Social-Skill Acquisition Among Students with Mild Intellectual Disabilities.

PubMed

Hetzroni, Orit E; Banin, Irit

2017-07-01

People with intellectual and developmental disabilities (IDD) often demonstrate difficulties in social skills. The purpose of this study was to examine the effects of a comprehensive intervention program on the acquisition of social skills among students with mild IDD. Single subject multiple baseline design across situations was used for teaching five school-age children with mild IDD social skills embedded in school-based situations. Results demonstrate that the intervention program that included video modelling and games embedded with group discussions and simulations increased the level and use of adequate social behaviours within the school's natural environment. Results demonstrate the unique attribution of a comprehensive interactive program for acquisition and transfer of participants' social skills such as language pragmatics and social rules within the school environment. Group discussions and simulations were beneficial and enabled both group and personalized instruction through the unique application of the program designed for the study. © 2016 John Wiley & Sons Ltd.

Effect of Knee Orthoses on Hamstring Contracture in Children With Cerebral Palsy: Multiple Single-Subject Study.

PubMed

Laessker-Alkema, Kristina; Eek, Meta Nyström

2016-01-01

To examine the effect of knee orthoses on extensibility of the hamstrings in children with spastic cerebral palsy (CP). The short-term effects of knee orthoses on passive range of motion (ROM), spasticity, and gross motor function of the hamstrings. Ten children with spastic CP, aged 5 to 14 years, at Gross Motor Function Classification System levels I to V, were followed. The orthoses were worn for a minimum of 30 minutes day, 5 days per week, during the intervention period of 8 weeks. Visual analysis using the Two Standard Deviation Band Method supported improvements in passive ROM for all 20 hamstring muscles and in 12 of 14 knee extension measurements. Analyses with the Wilcoxon signed rank test confirm the individual results and support a significant increase in hamstring muscles (P = .005) and knee extension (right: P =.028; left: P =.018) compared with baseline. In children with spastic CP, 8 weeks of treatment with knee orthoses can improve extensibility of the hamstrings.

Effects of a Single Night of Postpartum Sleep on Childless Women’s Daytime Functioning

PubMed Central

McBean, Amanda L.; Kinsey, Steven G.; Montgomery-Downs, Hawley E.

2017-01-01

Study Objectives The maternal postpartum period is characterized by sleep fragmentation, which is associated with daytime impairment, mental health disturbances, and changes in melatonin patterns. In addition to sleep fragmentation, women undergo a complex set of physiological and environmental changes upon entering the postpartum period, confounding our understanding of effects of postpartum sleep disturbance. The primary study aim was to understand the basic impact of a single night of postpartum-like sleep fragmentation on sleep architecture, nocturnal melatonin levels, mood, daytime sleepiness, and neurobehavioral performance. Measurements and Results For one week prior to entry into the laboratory, eleven healthy nulliparous women kept a stable sleep-wake schedule (verified via actigraphy). Participants contributed three consecutive nights of laboratory overnight polysomnography: (1) a habituation/sleep disorder screening night; (2) a baseline night; and (3) a sleep fragmentation night, when participants were awakened three times for ~30 min each. Self-reported sleep quality and mood (Profile of Mood States Survey) both decreased significantly after sleep fragmentation compared to baseline measurements. Unexpectedly, daytime sleepiness (Multiple Sleep Latency Test) decreased significantly after sleep fragmentation. Experimental fragmentation had no significant effect on time spent in nocturnal sleep stages, urinary 6-sulphatoxymelatonin concentration, or psychomotor vigilance test performance. Participants continued to provide actigraphy data, and daily PVTs and self-reported sleep quality assessments at home for one week following sleep fragmentation; these assessments did not differ from baseline values. Conclusions While there were no changes in measured physiological components of a single night of postpartum-like experimental sleep fragmentation, there were decreases in self-reported measures of mood and sleep quality. Future research should examine the effects of multiple nights of modeling postpartum-like sleep fragmentation on objective measures of sleep and daytime functioning. PMID:26776447

The sustained effect (12 months) of a single-dose vectored thermal pulsation procedure for meibomian gland dysfunction and evaporative dry eye

PubMed Central

Blackie, Caroline A; Coleman, Christy A; Holland, Edward J

2016-01-01

Purpose To evaluate the sustained effect (up to 1 year) of a single, 12-minute vectored thermal pulsation (VTP) treatment in improving meibomian gland function and dry eye symptoms in patients with meibomian gland dysfunction and evaporative dry eye. Methods The prospective, multicenter, open-label clinical trial included 200 subjects (400 eyes) who were randomized to a single VTP treatment (treatment group) or twice-daily, 3-month, conventional warm compress and eyelid hygiene therapy (control group). Control group subjects received crossover VTP treatment at 3 months (crossover group). Effectiveness measures of meibomian gland secretion (MGS) and dry eye symptoms were evaluated at baseline and 1, 3, 6, 9, and 12 months. Subjects with inadequate symptom relief could receive additional meibomian gland dysfunction therapy after 3 (treatment group) and 6 months (crossover group). Results At 3 months, the treatment group had greater mean improvement in MGS (P<0.0001) and dry eye symptoms (P=0.0068), compared to controls. At 12 months, 86% of the treatment group had received only one VTP treatment, and sustained a mean improvement in MGS from 6.4±3.7 (baseline) to 17.3±9.1 (P<0.0001) and dry eye symptoms from 44.1±20.4 to 21.6±21.3 (P<0.0001); 89% of the crossover group had received only one VTP treatment with sustained mean improvement in MGS from 6.3±3.6 to 18.4±11.1 (P<0.0001) and dry eye symptoms from 49.1±21.0 to 24.0±23.2 (P<0.0001). Greater mean improvement in MGS was associated with less severe baseline MGS (P=0.0017) and shorter duration of time between diagnosis and treatment (P=0.0378). Conclusion A single VTP treatment can deliver a sustained mean improvement in meibomian gland function and mean reduction in dry eye symptoms, over 12 months. A single VTP treatment provides significantly greater mean improvement in meibomian gland function and dry eye symptoms as compared to a conventional, twice-daily, 3-month regimen. Early VTP intervention for meibomian gland dysfunction is associated with improved treatment outcomes. PMID:27555745

Acute Modafinil Effects on Attention and Inhibitory Control in Methamphetamine-Dependent Humans*

PubMed Central

Dean, Andy C.; Sevak, Rajkumar J.; Monterosso, John R.; Hellemann, Gerhard; Sugar, Catherine A.; London, Edythe D.

2011-01-01

Objective: Individuals who are methamphetamine dependent exhibit higher rates of cognitive dysfunction than healthy people who do not use methamphetamine, and this dysfunction may have a negative effect on the success of behavioral treatments for the disorder. Therefore, a medication that improves cognition, such as modafinil (Provigil), may serve as a useful adjunct to behavioral treatments for methamphetamine dependence. Although cognitive-enhancing effects of modafinil have been reported in several populations, little is known about the effects of modafinil in methamphetamine-dependent individuals. We thus sought to evaluate the effects of modafinil on the cognitive performance of methamphetamine-dependent and healthy individuals. Method: Seventeen healthy subjects and 24 methamphetamine-dependent subjects participated in this randomized, double-blind, placebo-controlled, crossover study. Effects of modafinil (200 mg, single oral dose) were assessed on participants’ performance on tests of inhibitory control, working memory, and processing speed/attention. Results: Across subjects, modafinil improved performance on a test of sustained attention, with no significant improvement on any other cognitive tests. However, within the methamphetamine-dependent group only, participants with a high baseline frequency of methamphetamine use demonstrated a greater effect of modafinil on tests of inhibitory control and processing speed than those participants with low baseline use of methamphetamine. Conclusions: Although modafinil produced limited effects across all participants, methamphetamine-dependent participants with a high baseline use of methamphetamine demonstrated significant cognitive improvement on modafinil relative to those with low baseline methamphetamine use. These results add to the findings from a clinical trial that suggested that modafinil may be particularly useful in methamphetamine-dependent subjects who use the drug frequently. PMID:22051208

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9

PubMed Central

Fitzgerald, Kevin; White, Suellen; Borodovsky, Anna; Bettencourt, Brian R.; Strahs, Andrew; Clausen, Valerie; Wijngaard, Peter; Horton, Jay D.; Taubel, Jorg; Brooks, Ashley; Fernando, Chamikara; Kauffman, Robert S.; Kallend, David; Vaishnaw, Akshay; Simon, Amy

2018-01-01

BACKGROUND Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin–kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol. METHODS In this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated. RESULTS The most common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level, which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a least-squares mean reduction of 59.7% from baseline to day 84). CONCLUSIONS In this phase 1 trial, no serious adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam Pharmaceuticals and the Medicines Company; ClinicalTrials.gov number, NCT02314442.) PMID:27959715

Lower brain-derived neurotrophic factor levels associated with worsening fatigue in prostate cancer patients during repeated stress from radiation therapy.

PubMed

Saligan, L N; Lukkahatai, N; Holder, G; Walitt, B; Machado-Vieira, R

2016-12-01

Fatigue during cancer treatment is associated with depression. Neurotrophic factors play a major role in depression and stress and might provide insight into mechanisms of fatigue. This study investigated the association between plasma concentrations of three neurotrophic factors (BDNF, brain-derived neurotrophic factor; GDNF, glial-derived neurotrophic factor; and SNAPIN, soluble N-ethylmaleimide sensitive fusion attachment receptor-associated protein) and initial fatigue intensification during external beam radiation therapy (EBRT) in euthymic non-metastatic prostate cancer men. Fatigue, as measured by the 13-item Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and plasma neurotrophic factors were collected at baseline (prior to EBRT) and mid-EBRT. Subjects were categorized into fatigue and no fatigue groups using a > 3-point change in FACT-F scores between the two time points. Multiple linear regressions analysed the associations between fatigue and neurotrophic factors. FACT-F scores of 47 subjects decreased from baseline (43.95 ± 1.3) to mid-EBRT (38.36 ± 1.5, P < 0.001), indicating worsening fatigue. SNAPIN levels were associated with fatigue scores (r s = 0.43, P = 0.005) at baseline. A significant decrease of BDNF concentration (P = 0.008) was found in fatigued subjects during EBRT (n = 39). Baseline SNAPIN and decreasing BDNF levels may influence worsening fatigue during EBRT. Further investigations are warranted to confirm their role in the pathophysiology and therapeutics of fatigue.

Baseline and changes in serum uric acid independently predict 11-year incidence of metabolic syndrome among community-dwelling women.

PubMed

Kawamoto, R; Ninomiya, D; Kasai, Y; Senzaki, K; Kusunoki, T; Ohtsuka, N; Kumagi, T

2018-02-19

Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. In women, increased serum uric acid (SUA) levels are associated with MetS and its components. However, whether baseline and changes in SUA predict incidence of MetS and its components remains unclear. The subjects comprised 407 women aged 71 ± 8 years from a rural village. We have identified participants who underwent a similar examination 11 years ago, and examined the relationship between baseline and changes in SUA, and MetS based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report. Of these subjects, 83 (20.4%) women at baseline and 190 (46.7%) women at follow-up had MetS. Multiple linear regression analysis was performed to evaluate the contribution of each confounding factor for MetS; both baseline and changes in SUA as well as history of cardiovascular disease, low-density lipoprotein cholesterol, and estimated glomerular filtration ratio (eGFR) were independently and significantly associated with the number of MetS components during an 11-year follow-up. The adjusted odds ratios (ORs) (95% confidence interval) for incident MetS across tertiles of baseline SUA and changes in SUA were 1.00, 1.47 (0.82-2.65), and 3.11 (1.66-5.83), and 1.00, 1.88 (1.03-3.40), and 2.49 (1.38-4.47), respectively. In addition, the combined effect between increased baseline and changes in SUA was also a significant and independent determinant for the accumulation of MetS components (F = 20.29, p < 0.001). The ORs for incident MetS were significant only in subjects with age ≥ 55 years, decline in eGFR, and no baseline MetS. These results suggested that combined assessment of baseline and changes in SUA levels provides increased information for incident MetS, independent of other confounding factors in community-dwelling women.

One session treatment for pediatric blood-injection-injury phobia: A controlled multiple baseline trial.

PubMed

Oar, Ella L; Farrell, Lara J; Waters, Allison M; Conlon, Elizabeth G; Ollendick, Thomas H

2015-10-01

The present study evaluated the effectiveness of a modified One Session Treatment (OST), which included an e-therapy homework maintenance program over 4 weeks for Blood-Injection-Injury (BII) phobia in children and adolescents. Using a single case, non-concurrent multiple-baseline design, 24 children and adolescents (8-18 years; 7 males, 17 females) with a primary diagnosis of BII phobia were randomly assigned to a one, two or three week baseline prior to receiving OST. Primary outcome measures included diagnostic severity, diagnostic status, and child and parent fear ratings. Secondary outcome measures included avoidance during behavioural avoidance tasks (BAT), global functioning and self and parent reported anxiety, fear and depression. Efficacy was assessed at post-treatment, 1-month, and 3-month follow-up. BII symptoms and diagnostic severity remained relatively stable during the baseline periods and then significantly improved following implementation of the intervention. Treatment response was supported by changes across multiple measures, including child, parent and independent clinician ratings. At post-treatment 8 of the 24 (33.33%) children were BII diagnosis free. Treatment gains improved at follow-ups with 14 (58.33%) children diagnosis free at 1-month follow-up and 15 (62.5%) diagnosis free at 3-month follow-up. Preliminary findings support the effectiveness of a modified OST approach for BII phobic youth with treatment outcomes improving over follow-up intervals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Apathy in late-life depression: common, persistent, and disabling.

PubMed

Yuen, Genevieve S; Bhutani, Saumya; Lucas, Bryony J; Gunning, Faith M; AbdelMalak, Bassem; Seirup, Joanna K; Klimstra, Sibel A; Alexopoulos, George S

2015-05-01

The aims of this study were to examine: (1) the relationship between apathy and disability in late-life depression, and (2) the functional significance of improvement in apathy following escitalopram treatment in terms of its relationship to disability. Subjects were 71 non-demented elderly with non-psychotic major depression. After a 2-week single-blind placebo period, subjects who had Hamilton Depression Rating Scale (HDRS) ≥ 18 received escitalopram 10 mg daily for 12 weeks. Apathy and disability were assessed with the Apathy Evaluation Scale (AES) and the World Health Organization Disability Assessment Scale II (WHODAS), respectively. These measures and the HDRS were administered at baseline and again following 12 weeks of treatment. At baseline, 38% of depressed subjects had significant apathy (AES ≥ 36.5). Severity of apathy at baseline significantly correlated with severity of disability. In a multivariate regression model, baseline severity of apathy, but not the overall depressive syndrome (HDRS), significantly correlated with baseline disability. Following escitalopram treatment, improvement in apathy significantly correlated with improvement in disability measures, while change in the rest of the depressive syndrome did not. The overall change in apathy and disability in response to escitalopram treatment was significant but small. Apathy is common in late-life depression and is associated with disability above and beyond the influence of other depressive symptoms. Given the strong relationship between apathy and disability, understanding the neurobiology of apathy and developing treatments for apathy may improve the functional outcomes of late-life depression. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Dolphin-Assisted Therapy as a Verbal Operant Condition for Children with Autism

ERIC Educational Resources Information Center

Terrasi, Renee Marie

2007-01-01

This study examined the effects of Dolphin-Assisted Therapy (DAT) as a reinforcer for verbal operant production in children with Autism Spectrum Disorder. Three children who attended a dolphin therapy program participated in this single subject research study. Baseline data was collected for each child via a video tape provided by parents and…

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers

PubMed Central

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-01-01

Aim The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Methods Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. Results ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Conclusions Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. PMID:23016924

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers.

PubMed

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-05-01

The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. © 2012 Abbott Laboratories. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Depression and fatigue in patients with multiple sclerosis.

PubMed

Greeke, Emily E; Chua, Alicia S; Healy, Brian C; Rintell, David J; Chitnis, Tanuja; Glanz, Bonnie I

2017-09-15

Previous research has examined the components of depression and fatigue in multiple sclerosis (MS), but the findings have been inconsistent. The aim of this study was to explore the associations between overall and subscale scores of the Center for Epidemiologic Studies-Depression Scale (CES-D) and the Modified Fatigue Impact Scale (MFIS) as well as the longitudinal changes in scores in a large cohort of MS patients. MS subjects who completed a battery of patient reported outcome (PRO) measures including the CES-D and MFIS (N=435) were included in our analysis. At the first available MFIS measurement, Pearson's correlation coefficient was used to estimate the association between the CES-D and MFIS in terms of both total scores and subscale scores. In addition, the longitudinal change in each total score and subscale score was estimated using a linear mixed model, and the association between the measures in terms of longitudinal change was estimated using Pearson's correlation coefficient and linear mixed models. At baseline, 15% of subjects were classified as high on both depression and fatigue scales, 16% were classified as high on the fatigue scale only, and 9% were classified as high on the depression scale only. There was a high correlation between CES-D and MFIS total scores (r=0.62). High correlations were also observed between the somatic and retarded activity subscales of the CES-D and each of the MFIS subscales (r≥0.60). In terms of longitudinal change, the change over the first year between the CES-D and MFIS total scores showed a moderate correlation (r=0.49). Subjects with high fatigue scores but low depression scores at baseline were more likely than subjects with low baseline fatigue and depression scores to develop high depression scores at follow-up. Our study demonstrated that depression and fatigue in MS share several features and have a similar longitudinal course. But using cut-off scores to define depression and fatigue, our study also found that non-depressed subjects with high fatigue may be at a greater risk for developing depression. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effects of a Peer-Mediated Reading Intervention on Juvenile Offenders' Main Idea Statements about Informational Text

ERIC Educational Resources Information Center

Wexler, Jade; Reed, Deborah K.; Barton, Erin E.; Mitchell, Marisa; Clancy, Erin

2018-01-01

Many youth in the juvenile justice system with or at risk for emotional and behavioral disorders struggle with reading. A multiple-baseline-across-participants single-case research design was used to examine the relationship between a supplemental peer-mediated reading intervention and juvenile offenders' generation of main idea statements about…

Effectiveness of Video Self-Modeling to Promote Social Initiations by 3-Year-Olds with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Buggey, Tom

2012-01-01

Video Self-Modeling (VSM) provides individuals the opportunity to view themselves performing a task beyond their present functioning level through the careful editing of videos. In this study, a single-case multiple-baseline design was used to determine whether VSM would facilitate social initiations across three young children (M = 3 years 10…

Progress Monitoring Using Direct Behavior Rating Single Item Scales in a Multiple-Baseline Design Study of the Daily Report Card Intervention

ERIC Educational Resources Information Center

Fabiano, Gregory A.; Pyle, Kellina; Kelty, Mary Bridget; Parham, Brittany R.

2017-01-01

Direct behavior rating (DBR) may be a viable assessment for documenting current areas of impaired functioning and progress monitoring students' response to a behavioral intervention. Challenging behaviors are often addressed in general education settings using interventions such as the daily report card (DRC). To best implement and monitor such…

Effect of glatiramer acetate three-times weekly on the evolution of new, active multiple sclerosis lesions into T1-hypointense "black holes": a post hoc magnetic resonance imaging analysis.

PubMed

Zivadinov, Robert; Dwyer, Michael; Barkay, Hadas; Steinerman, Joshua R; Knappertz, Volker; Khan, Omar

2015-03-01

Conversion of active lesions to black holes has been associated with disability progression in subjects with relapsing-remitting multiple sclerosis (RRMS) and represents a complementary approach to evaluating clinical efficacy. The objective of this study was to assess the conversion of new active magnetic resonance imaging (MRI) lesions, identified 6 months after initiating treatment with glatiramer acetate 40 mg/mL three-times weekly (GA40) or placebo, to T1-hypointense black holes in subjects with RRMS. Subjects received GA40 (n = 943) or placebo (n = 461) for 12 months. MRI was obtained at baseline and Months 6 and 12. New lesions were defined as either gadolinium-enhancing T1 or new T2 lesions at Month 6 that were not present at baseline. The adjusted mean numbers of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a negative binomial model; adjusted proportions of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a logistic regression model. Of 1,292 subjects with complete MRI data, 433 (50.3 %) GA-treated and 247 (57.2 %) placebo-treated subjects developed new lesions at Month 6. Compared with placebo, GA40 significantly reduced the mean number (0.31 versus 0.45; P = .0258) and proportion (15.8 versus 19.6 %; P = .006) of new lesions converting to black holes. GA significantly reduced conversion of new active lesions to black holes, highlighting the ability of GA40 to prevent tissue damage in RRMS.

Imagery Rescripting for Body Dysmorphic Disorder: A Multiple-Baseline Single-Case Experimental Design.

PubMed

Willson, Rob; Veale, David; Freeston, Mark

2016-03-01

Individuals with body dysmorphic disorder (BDD) often experience negative distorted images of their appearance, and research suggests these may be linked to memories of adverse events such as bullying or teasing. This study evaluates imagery rescripting (ImR) as an intervention for BDD. In this article, we present a multiple-baseline single-case experimental design testing imagery rescripting as a brief, stand-alone intervention, with six individuals with BDD that related to aversive memories. The impact of the intervention was assessed by self-reported daily measures of symptom severity (preoccupation with appearance, appearance-related checking behaviors, appearance-related distress, and strength of belief that their main problem is their appearance) and standardized clinician ratings of BDD severity (Yale-Brown Obsessive Compulsive Scale modified for BDD). Four out of six of the participants responded positively to the intervention, with clinically meaningful improvement in symptomatology. Overall response was rapid; improvements began within the first week post-ImR intervention. From a small sample it is cautiously concluded that imagery rescripting may show promise as a module in cognitive-behavioral therapy for BDD, and is worthy of further investigation. Copyright © 2015. Published by Elsevier Ltd.

Tumor Cell Gene Expression Changes Following Short-term In vivo Exposure to Single Agent Chemotherapeutics are Related to Survival in Multiple Myeloma

PubMed Central

Burington, Bart; Barlogie, Bart; Zhan, Fenghuang; Crowley, John; Shaughnessy, John D.

2013-01-01

Changes in global gene expression patterns in tumor cells following in vivo therapy may vary by treatment and provide added or synergistic prognostic power over pretherapy gene expression profiles (GEP). This molecular readout of drug-cell interaction may also point to mechanisms of action/resistance. In newly diagnosed patients with multiple myeloma (MM), microarray data were obtained on tumor cells prior to and 48 hours after in vivo treatment using dexamethasone (n = 45) or thalidomide (n = 42); in the case of relapsed MM, microarray data were obtained prior to (n = 36) and after (n = 19) lenalidomide administration. Dexamethasone and thalidomide induced both common and unique GEP changes in tumor cells. Combined baseline and 48-hour changes in GEP in a subset of genes, many related to oxidative stress and cytoskeletal dynamics, were predictive of outcome in newly diagnosed MM patients receiving tandem transplants. Thalidomide-altered genes also changed following lenalidomide exposure and predicted event-free and overall survival in relapsed patients receiving lenalidomide as a single agent. Combined with baseline molecular features, changes in GEP following short-term single-agent exposure may help guide treatment decisions for patients with MM. Genes whose drug-altered expression were found to be related to survival may point to molecular switches related to response and/or resistance to different classes of drugs. PMID:18676754

Engaging Preschool Children with Severe and Multiple Disabilities Using Books and iPad Apps

ERIC Educational Resources Information Center

Kemp, Coral; Stephenson, Jennifer; Cooper, Megan; Hodge, Kerry

2016-01-01

A single subject multiple treatment design was used to compare the engagement of 3 preschool children with severe and multiple disabilities, using 2 different stimuli: picture books and iPad apps matched for theme and content. Two of the 3 children had diagnoses of autism spectrum disorder in addition to their other disabilities. Sessions for each…

Safety of an alkalinizing buffer designed for inhaled medications in humans.

PubMed

Davis, Michael D; Walsh, Brian K; Dwyer, Scott T; Combs, Casey; Vehse, Nico; Paget-Brown, Alix; Pajewski, Thomas; Hunt, John F

2013-07-01

Airway acidification plays a role in disorders of the pulmonary tract. We hypothesized that the inhalation of alkalinized glycine buffer would measurably alkalinize the airways without compromising lung function or causing adverse events. We evaluated the safety of an inhaled alkaline glycine buffer in both healthy subjects and in subjects with stable obstructive airway disease. This work includes 2 open-label safety studies. The healthy controls were part of a phase 1 safety study of multiple inhalations of low-dose alkaline glycine buffer; nebulized saline was used as a comparator in 8 of the healthy controls. Subsequently, a phase 2 study in subjects with stable obstructive airway disease was completed using a single nebulized higher-dose strategy of the alkaline inhalation. We studied 20 non-smoking adults (10 healthy controls and 10 subjects with obstructive airway disease), both at baseline and after inhalation of alkaline buffer. We used spirometry and vital signs as markers of clinical safety. We used changes in fraction of exhaled nitric oxide (NO) and exhaled breath condensate (EBC) pH as surrogate markers of airway pH modification. Alkaline glycine inhalation was tolerated by all subjects in both studies, with no adverse effects on spirometric parameters or vital signs. Airway alkalinization was confirmed by a median increase in EBC pH of 0.235 pH units (IQR 0.56-0.03, P = .03) in subjects after inhalation of the higher-dose alkaline buffer (2.5 mL of 100 mmol/L glycine). Alkalinization of airway lining fluid is accomplished with inhalation of alkaline glycine buffer and causes no adverse effects on pulmonary function or vital signs.

Feasibility of the Nintendo WiiFit™ for improving walking in individuals with a lower limb amputation.

PubMed

Imam, Bita; Miller, William C; McLaren, Linda; Chapman, Paul; Finlayson, Heather

2013-01-01

To evaluate the feasibility of the Nintendo WiiFit™ as an adjunct to usual therapy in individuals with a lower limb amputation. The study was a Multiple Baseline (AB) Single Subject Research Design. Subjects were ≥19 years old, had their first unilateral transtibial or transfemoral amputation  ≤12 months ago, and were participating in prosthetic training. WiiFit training was provided for 30 min, 5 times a week, for a minimum of 2 and a maximum of 6 weeks in addition to usual therapy. Feasibility indicators were safety, post-intervention fatigue and pain levels, adherence, and subject's acceptability of the program as measured by the Short Feedback Questionnaire-modified (SFQ-M). The primary clinical outcome was walking capacity assessed by the 2 Minute Walk Test (2MWT). The secondary clinical outcomes were the Short Physical Performance Battery, L-test, and Activities-Specific Balance Confidence. Subjects (4 transtibial; 2 transfemoral) had a median age of 48.5 years (range = 45-59 years). No adverse events associated with the intervention occurred. Median pain and fatigue levels were 1.3 (range = 0.5-3.5) and 3.1 (range = 1.4-4.1), respectively. Median adherence was 80%. Subjects found the WiiFit enjoyable and acceptable (median SFQ-M = 35). Five subjects showed statistical improvement on the 2MWT and four on the secondary outcomes (p < 0.05). The WiiFit intervention was found to be feasible in individuals with unilateral lower limb amputation. This research provides the foundation for future clinical research investigating the use of the WiiFit as a viable adjunctive therapy to improve outcomes in individuals with unilateral lower limb amputation who are participating in prosthetic training.

An evaluation of 1-day disposable contact lens wear in a population of allergy sufferers.

PubMed

Hayes, Valérie Y; Schnider, Cristina M; Veys, Jane

2003-06-01

This was a multi-site, 128-subject, bilateral crossover study to evaluate subjective comfort and slit-lamp findings with 1-day disposable contact lenses in a population of allergy sufferers during periods when allergen levels were elevated. The study involved 1-month of single-use daily wear with a 1-day disposable test lens (1. DAY ACUVUE Brand Contact Lenses, Johnson & Johnson Vision Care) and 1-month of daily wear with subjects' habitual lenses replaced to their usual replacement schedule. Pollen and mould counts were obtained for each site 1 week prior to the study and twice weekly throughout the study period. Subjective comfort and slit-lamp findings were recorded at baseline and after 1-month's wear of each modality. Sixty-seven percent of subjects agreed that the 1-day disposable lenses provided improved comfort when compared to the lenses they wore prior to the study, compared with 18% agreeing that the new pair of habitual lenses provided improved comfort. The 1-day disposable lenses showed greater improvement in slit-lamp findings from baseline than new habitual lenses. The use of 1-day disposable lenses is an effective strategy for managing allergy-suffering contact lens wearers.

Neuroimaging findings in cryptogenic stroke patients with and without patent foramen ovale.

PubMed

Thaler, David E; Ruthazer, Robin; Di Angelantonio, Emanuele; Di Tullio, Marco R; Donovan, Jennifer S; Elkind, Mitchell S V; Griffith, John; Homma, Shunichi; Jaigobin, Cheryl; Mas, Jean-Louis; Mattle, Heinrich P; Michel, Patrik; Mono, Marie-Luise; Nedeltchev, Krassen; Papetti, Federica; Serena, Joaquín; Weimar, Christian; Kent, David M

2013-03-01

Patent foramen ovale (PFO) and cryptogenic stroke are commonly associated but some PFOs are incidental. Specific radiological findings associated with PFO may be more likely to indicate a PFO-related cause. We examined whether specific radiological findings are associated with PFO among subjects with cryptogenic stroke and known PFO status. We analyzed the Risk of Paradoxical Embolism(RoPE) Study database of subjects with cryptogenic stroke and known PFO status, for associations between PFO and: (1) index stroke seen on imaging, (2) index stroke size, (3) index stroke location, (4) multiple index strokes, and (5) prior stroke on baseline imaging. We also compared imaging with purported high-risk echocardiographic features. Subjects (N=2680) were significantly more likely to have a PFO if their index stroke was large (odds ratio [OR], 1.36; P=0.0025), seen on index imaging (OR, 1.53; P=0.003), and superficially located (OR, 1.54; P<0.0001). A prior stroke on baseline imaging was associated with not having a PFO (OR, 0.66; P<0.0001). Finding multiple index strokes was unrelated to PFO status (OR, 1.21; P=0.161). No echocardiographic variables were related to PFO status. This is the largest study to report the radiological characteristics of patients with cryptogenic stroke and known PFO status. Strokes that were large, radiologically apparent, superficially located, or unassociated with prior radiological infarcts were more likely to be PFO-associated than were unapparent, smaller, or deep strokes, and those accompanied by chronic infarcts. There was no association between PFO and multiple acute strokes nor between specific echocardiographic PFO features with neuroimaging findings.

EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

PubMed Central

Berlin, Michael S; Rowe-Rendleman, Cheryl; Ahmed, Ike; Ross, Douglas T; Fujii, Akifumi; Ouchi, Takafumi; Quach, Christine; Wood, Andrew; Ward, Caroline L

2016-01-01

Background/aims The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering. Methods This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability. Results Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of −7.4 mm Hg (−30.8%) for AM dosing and −9.1 mm Hg, (−38.0%) for PM dosing; after 14 days, mean reduction in IOP was −6.8 mm Hg (−28.6%) for AM dosing and −7.5 mm Hg (−31.0%) for PM dosing. Conclusions PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP. Trial registration number NCT01670266. PMID:26453641

Communication partner training of enrolled nurses working in nursing homes with people with communication disorders caused by stroke or Parkinson's disease.

PubMed

Eriksson, Karin; Forsgren, Emma; Hartelius, Lena; Saldert, Charlotta

2016-01-01

To evaluate the effect of a communication partner training programme directed to enrolled nurses working with people with communication disorders in nursing homes, using an individualised approach. Five dyads consisting of a person with stroke-induced aphasia (n = 4) or Parkinson's disease (PD) (n = 1) living in different nursing homes and his/her enrolled nurse participated in the study, which had a replicated single-subject design with multiple baselines across individuals. The main element of the intervention was supervised analysis of video-recorded natural interaction in everyday nursing situations and the formulation of individual goals to change particular communicative strategies. Outcome was measured via blinded assessments of filmed natural interaction obtained at baseline, intervention and follow-up and showed an increased use of the target communicative strategies. Subjective measures of goal attainment by the enrolled nurses were consistent with these results. Measures of perceived functional communication on behalf of the persons with communication disorders were mostly positive; four of five participants with communication disorders and two of five enrolled nurses reported improved functional communication after intervention. The use of an individualised communication partner training programme led to significant changes in natural interaction, which contributes importantly to a growing body of knowledge regarding communication partner training. Communication partner training can improve the communicative environment of people with communication disorders. For people with communication disorders who live in institutions, the main conversation partner is likely to be a professional caretaker. An individualised approach for communication partner training that focussed on specific communication patterns was successful in increasing the use of supportive strategies that enrolled nurses used in natural interaction with persons with communication disorders. The training also positively affected the perceived functional communication of the persons with communication disorders.

A Prospective Observational Comparison Between Arm and Wrist Blood Pressure During Scheduled Cesarean Delivery.

PubMed

Sebbag, Ilana; Massey, Simon R; Albert, Arianne Y K; Dube, Alison; Gunka, Vit; Douglas, M Joanne

2015-09-01

Shivering is common during cesarean delivery (CD) under neuraxial anesthesia and may disrupt the measurement of noninvasive blood pressure (BP). BP measured at the wrist may be less affected by shivering. There have been no studies comparing trends in BP measured on the upper arm and wrist. We hypothesized that wrist systolic blood pressure (sBP) would accurately trend with upper arm sBP measurements (agree within a limit of ±10%) in parturients undergoing elective CD under spinal anesthesia or combined spinal-epidural anesthesia. After initiation of spinal anesthesia, BP measurements were obtained simultaneously from the upper arm and wrist on opposite arms. The interval between measurements was 1 to 2 minutes, and data were collected for 20 minutes or until delivery. The primary outcome was agreement in dynamic changes in sBP measurements between the upper arm and the wrist. Bland-Altman plots indicating the levels of agreement between the methods were drawn for baseline measurements, over multiple measurements, and over multiple measurements on percentage change from baseline. Forty-nine patients were recruited and completed the study. The wrist sBP tended to overestimate the upper sBP for both baseline data (sBP bias = 13.4 mm Hg; 95% confidence interval = +10.4 to +16.4 mm Hg) and data obtained over multiple measurements (sBP bias = 12.8 mm Hg; 95% confidence interval = +9.3 to +16.3 mm Hg). For change in sBP from baseline over multiple measurements, the mean difference between the wrist and the arm sBP was -0.2 percentage points (99% limits of agreement -25 to +25 percentage points). The wrist measurement overestimated the reading relative to the upper arm measurement for multiple measurements over time. However, when the time series for each subject was examined for percentage change from baseline, the 2 methods mirrored each other in most cases. Nevertheless, our hypothesis was rejected as the limits of agreement were higher than ±10%. This finding suggests that wrist BP may not be an accurate method of detecting hypotension or hypertension during spinal or combined spinal-epidural anesthesia for CD.

Impact of Multiple Complex Plaques on Short-and Long-Term Clinical in Patients Presenting with ST-Segment Elevation Myocardial Infarction (From the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Trial)

PubMed Central

Keeley, Ellen C.; Mehran, Roxana; Brener, Sorin J.; Witzenbichler, Bernhard; Guagliumi, Giulio; Dudek, Dariusz; Kornowski, Ran; Dressler, Ovidiu; Fahy, Martin; Xu, Ke; Grines, Cindy L.; Stone, Gregg W.

2014-01-01

It is not known whether the extent and severity of non-culprit coronary lesions correlate with outcomes in patients with STEMI referred for primary PCI. We sought to quantify complex plaques in ST-segment elevation myocardial infarction (STEMI) patients referred for primary percutaneous coronary intervention (PCI) and to determine their effect on short- and long-term clinical outcomes by examining the core laboratory database for plaque analysis from the HORIZONS-AMI study. Baseline demographic, angiographic, and procedural details were compared between patients with single vs. multiple complex plaques undergoing single vessel PCI. Multivariable analysis was performed for predictors of long-term major adverse cardiac events (MACE), a combined end point of death, reinfarction, ischemic target vessel revascularization, or stroke, and for death alone. Single vessel PCI was performed in 3,137 patients (87%): 2,174 (69%) had multiple complex plaques and 963 (31%) had a single complex plaque. Compared to those with a single complex plaque, patients with multiple complex plaques were older (p<0.0001) and had more comorbidities. The presence of multiple complex plaques was an independent predictor of 3-year MACE (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.26–1.98, p<0.0001), and death alone (HR: 1.68; 95% CI: 1.05–2.70, p=0.03). In conclusion, multiple complex plaques are present in the majority of STEMI patients undergoing primary PCI and their presence is an independent predictor of short- and long-term MACE, including death. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) PMID:24703369

Multibaseline gravitational wave radiometry

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

Talukder, Dipongkar; Bose, Sukanta; Mitra, Sanjit

2011-03-15

We present a statistic for the detection of stochastic gravitational wave backgrounds (SGWBs) using radiometry with a network of multiple baselines. We also quantitatively compare the sensitivities of existing baselines and their network to SGWBs. We assess how the measurement accuracy of signal parameters, e.g., the sky position of a localized source, can improve when using a network of baselines, as compared to any of the single participating baselines. The search statistic itself is derived from the likelihood ratio of the cross correlation of the data across all possible baselines in a detector network and is optimal in Gaussian noise.more » Specifically, it is the likelihood ratio maximized over the strength of the SGWB and is called the maximized-likelihood ratio (MLR). One of the main advantages of using the MLR over past search strategies for inferring the presence or absence of a signal is that the former does not require the deconvolution of the cross correlation statistic. Therefore, it does not suffer from errors inherent to the deconvolution procedure and is especially useful for detecting weak sources. In the limit of a single baseline, it reduces to the detection statistic studied by Ballmer [Classical Quantum Gravity 23, S179 (2006).] and Mitra et al.[Phys. Rev. D 77, 042002 (2008).]. Unlike past studies, here the MLR statistic enables us to compare quantitatively the performances of a variety of baselines searching for a SGWB signal in (simulated) data. Although we use simulated noise and SGWB signals for making these comparisons, our method can be straightforwardly applied on real data.« less

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.

A single-dose, crossover, placebo- and moxifloxacin-controlled study to assess the effects of neratinib (HKI-272) on cardiac repolarization in healthy adult subjects.

PubMed

Hug, Bruce; Abbas, Richat; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

2010-08-01

Neratinib is an orally administered, small-molecule, irreversible pan-ErbB inhibitor in development for the treatment of ErbB2-positive breast cancer. This study assessed the effects of therapeutic and supratherapeutic neratinib concentrations on cardiac repolarization, in accordance with current regulatory guidance. This was a two-part study in healthy subjects. In part 1, subjects were randomized to receive placebo, 400 mg moxifloxacin, or 240 mg neratinib (therapeutic dose) following a high-fat meal. In part 2, after a washout period, subjects received placebo plus 400 mg ketoconazole or 240 mg neratinib plus ketoconazole (supratherapeutic dose). ANOVA was used to compare the baseline-adjusted QTc interval for neratinib with that of placebo (reference), and for neratinib plus ketoconazole with that of placebo plus ketoconazole (reference). Pharmacokinetic/pharmacodynamic analyses and categorical summaries of interval data were done. Assay sensitivity was evaluated by the effect of moxifloxacin on QTc compared with placebo. Sixty healthy subjects were enrolled in this study. The upper bounds of the 90% confidence interval for baseline-adjusted QTcN (population-specific corrected QT) were 450 milliseconds or change from baseline >30 milliseconds. Moxifloxacin produced a significant increase in QTcN compared with placebo (P < 0.05). Therapeutic and supratherapeutic plasma concentrations of neratinib do not prolong the QTc interval in healthy subjects. (c) 2010 AACR.

Differences in Postprandial Lipid Response to Breast- or Formula-feeding in 8-Week-Old Infants.

PubMed

Teller, Inga C; Schoen, Stefanie; van de Heijning, Bert; van der Beek, Eline M; Sauer, Pieter J J

2017-04-01

Lipids play important roles in infant growth and development. In this exploratory observational single-center study, we investigated postmeal responses of infants to dietary lipids and differences between breast-feeding (BF) and formula-feeding (FF). Two capillary blood samples were collected from each subject, before and randomly assigned at either 30, 60, 90, 120, 180, or 240 minutes after their respective feeding, followed by measurement of lipid-related plasma parameter concentrations using enzyme-linked immunosorbent assay-based or combined enzymatic and colorimetric methods. The intermeal interval before testing was shorter in the BF (182.91 ± 22.85 minutes, n = 33) versus FF group (214.1 ± 30.76 minutes, n = 34); BF subjects fed 5 minutes longer (BF 20.27 ± 7.7 minutes; FF 14.82 ± 3.57 minutes). Composite postmeal concentration profiles were generated from 59 plasma sample pairs with sufficient volume (BF = 30): triglyceride (TG) baselines were not different. A TG difference was indicated for BF over FF subjects at 30 minutes, for FF over BF subjects at 60 minutes when corrected for baseline. TG responses in both groups appeared and seemed to clear much faster than those reported for adults. The TG:apolipoprotein B48 (ApoB48) ratio suggests that chylomicrons in BF subjects may carry a higher fat load (P < 0.05), compensated by a higher chylomicron number in FF subjects (P < 0.05). Cholesterol in BF subjects was higher and showed an increase after feeding when corrected for baseline. Our results indicate that lipids from either BF or FF may be handled differently in young healthy infants.

Recruitment factors which affect the outcome of a seasonal allergic rhinitis trial.

PubMed

Sharma, Shilpy; Vasnani, Raj; De Tineo, Marcella; Du, Gaixin; Pinto, Jayant M; Baroody, Fuad M; Naclerio, Robert M

2011-01-01

Although intranasal corticosteroids (INSs) are the first-line treatment for seasonal allergic rhinitis (SAR), some patients do not respond adequately, reflecting biological heterogeneity or confounding conditions. The objective of this study was to determine what recruitment factors identify SAR subjects who will be unresponsive to mometasone furoate (MF). We performed a 2-week, double-blind, placebo-controlled, parallel study on 40 subjects with SAR. Each subject underwent a decongestant test using oxymetazoline. Baseline nasal symptoms, nasal peak inspiratory flow (NPIF) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores were recorded. Next, subjects were randomized to either 200 μg of MF or placebo. Symptom diaries and NPIF measurements were completed twice daily. After 2 weeks, subjects repeated the RQLQ and the global assessment of symptoms. There was a significant reduction in symptoms in the MF group compared with placebo (p ≤ 0.05) in patients with baseline total symptom scores of ≥6. Multivariate analysis showed that treatment (MF versus placebo; p = 0.049) and amount of decongestion (percent change in NPIF after oxymetazoline; p = 0.008) predicted the improvement in total nasal symptoms. In clinical trials, SAR subjects must report multiple symptoms to be responsive to treatment with INSs. Our results also support the use of the decongestant test for choice of appropriate study volunteers, both to ensure participation of potentially responsive subjects and to eliminate those with confounding issues.

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…

Association of Scavenger Receptor Class B Type I Polymorphisms with Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Naj, Adam C.; West, Michael; Rich, Stephen S.; Post, Wendy; Kao, W.H. Linda; Wasserman, Bruce A.; Herrington, David M.; Rodriguez, Annabelle

2012-01-01

Background Little is known regarding the association of scavenger receptor class B type I (SCARB1) single nucleotide polymorphisms (SNPs) and subclinical atherosclerosis (SCA), particularly in subjects of different racial/ethnic backgrounds. We examined this relationship in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods and Results Forty-three SCARB1 tagging SNPs were genotyped. Baseline examinations included fasting lipids and SCA phenotypes (coronary artery calcium [CAC], and common and internal carotid artery thickness [CCIMT and ICIMT]). Examining SNP associations with different SCA phenotypes across multiple racial/ethnic groups with adjustment for multiple covariates, we found the C allele of SNP rs10846744 was associated with higher CCIMT in African American (P=0.03), Chinese (P=0.02), European American (P=0.05), and Hispanic participants (P=0.03), and was strongly associated in pooled analyses (P=0.0002). The results also showed that the association of this SNP with CCIMT was independent of lipids and other well-established cardiovascular risk factors. Stratifying by sex, there appeared to be a strong association of rs10846744 with CCIMT in females, but no genotype-sex interactions were observed. Conclusions Variation in SCARB1 at rs10846744 was significantly associated with CCIMT across racial/ethnic groups in MESA. PMID:20160195

Modelling the immunological response to a tetravalent dengue vaccine from multiple phase-2 trials in Latin America and South East Asia.

PubMed

Dorigatti, Ilaria; Aguas, Ricardo; Donnelly, Christl A; Guy, Bruno; Coudeville, Laurent; Jackson, Nicholas; Saville, Melanie; Ferguson, Neil M

2015-07-17

The most advanced dengue vaccine candidate is a live-attenuated recombinant vaccine containing the four dengue viruses on the yellow fever vaccine backbone (CYD-TDV) developed by Sanofi Pasteur. Several analyses have been published on the safety and immunogenicity of the CYD-TDV vaccine from single trials but none modelled the heterogeneity observed in the antibody responses elicited by the vaccine. We analyse the immunogenicity data collected in five phase-2 trials of the CYD-TDV vaccine. We provide a descriptive analysis of the aggregated datasets and fit the observed post-vaccination PRNT50 titres against the four dengue (DENV) serotypes using multivariate regression models. We find that the responses to CYD-TDV are principally predicted by the baseline immunological status against DENV, but the trial is also a significant predictor. We find that the CYD-TDV vaccine generates similar titres against all serotypes following the third dose, though DENV4 is immunodominant after the first dose. This study contributes to a better understanding of the immunological responses elicited by CYD-TDV. The recent availability of phase-3 data is a unique opportunity to further investigate the immunogenicity and efficacy of the CYD-TDV vaccine, especially in subjects with different levels of pre-existing immunity against DENV. Modelling multiple immunological outcomes with a single multivariate model offers advantages over traditional approaches, capturing correlations between response variables, and the statistical method adopted in this study can be applied to a variety of infections with interacting strains. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3 study.

PubMed

Mohan, Vadrevu Krishna; Varanasi, Vineeth; Singh, Anit; Pasetti, Marcela F; Levine, Myron M; Venkatesan, Ramasamy; Ella, Krishna M

2015-08-01

Enteric fever caused by Salmonella Typhi remains a major public health problem in developing countries. Typbar-TCV is a single-dose typhoid Vi polysaccharide-tetanus toxoid conjugate vaccine for persons ≥6 months of age. Six hundred fifty-four healthy subjects aged 2-45 years enrolled in a double-blind, randomized controlled trial (RCT) received a single dose of Typbar-TCV or comparator "Vi polysaccharide" (Typbar), and 327 healthy subjects aged 6-23 months received a single dose of Typbar-TCV in an open-label trial (OLT); both received single- or multidose presentations from different lots. After 2 years, subsets in each group received a booster dose. The primary objective included analysis of geometric mean titer (GMTs) and 4-fold rise of anti-Vi serum immunoglobulin G (IgG) enzyme-linked immunosorbent assay titers over baseline (seroconversion [SCN]) 42 days after immunization. Typbar-TCV recipients in the RCT attained higher anti-Vi IgG GMTs 42 days after immunization (SCN, 97%; GMT, 1293 [95% confidence interval {CI}, 1153-1449]) than recipients of Typbar (SCN, 93%; GMT, 411 [95% CI, 359-471]) (P < .001). Typbar-TCV was highly immunogenic in the OLT (SCN, 98%; GMT, 1937 [95% CI, 1785-2103]). Two years after vaccination, anti-Vi titers remained higher in Typbar-TCV subjects (GMT, 82 [95% CI, 73-92]); and exhibited higher avidity (geometric mean avidity index [GMAI], 60%) than in Typbar recipients (GMT, 46 [95% CI, 40-53]; GMAI 46%) in the RCT (P < .001). OLT Typbar-TCV recipients achieved GMT of 48 (95% CI, 42-55) and GMAI of 57%. Typbar-TCV induced multiple IgG subclasses and strong booster responses in all ages. No serious vaccine-attributable adverse events were observed. Single-dose Typbar-TCV is well tolerated and induces robust and long-lasting serum anti-Vi IgG across age groups. CTRI/2011/08/001957, CTRI/2014/01/004341. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Differential rate in decline in ovarian reserve markers in women with polycystic ovary syndrome compared with control subjects: results of a longitudinal study.

PubMed

Ahmad, Asima K; Kao, Chia-Ning; Quinn, Molly; Lenhart, Nikolaus; Rosen, Mitchell; Cedars, Marcelle I; Huddleston, Heather

2018-03-01

To estimate rates of ovarian aging in polycystic ovary syndrome (PCOS) subjects versus a community control population. Longitudinal. Tertiary academic center. PCOS subjects diagnosed according to the 2004 Rotterdam criteria were systematically enrolled in a PCOS cohort study. The comparison control subjects were from the Ovarian Aging study, a prospective longitudinal study of ovarian aging in healthy women with regular menstrual cycles. Clinical data collection over two study visits. Antral follicle count (AFC), ovarian volume (OV), and antimüllerian hormone level (AMH). PCOS subjects were found to have higher baseline values for all ovarian reserve markers compared with control subjects. Univariate models indicated that, compared with control subjects, PCOS patients experienced significantly faster rates of decline for both AFC and AMH. Change in OV did not differ significantly. To account for potential confounder effects, multiple analysis of covariance models were evaluated for the best fit, considering age, body mass index, and baseline ovarian reserve markers. Adjusted models demonstrated that PCOS patients do not experience a significant difference in AFC decline compared with control subjects, but they do experience a faster rate of decline in AMH (P<.01) and slower rate of decline in OV (P<.01). Ovarian aging in PCOS is characterized by a more rapid decline in AMH and a slower decline in OV compared with control subjects. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Patients Using an Online Forum for Reporting Progress When Engaging With a Six-Week Exercise Program for Knee Conditioning: Feasibility Study.

PubMed

Bright, Philip; Hambly, Karen

2018-04-26

The use of electronic health (eHealth) and Web-based resources for patients with knee pain is expanding. Padlet is an online noticeboard that can facilitate patient interaction by posting virtual “sticky notes.” The primary aim of this study was to determine feasibility of patients in a 6-week knee exercise program using Padlet as an online forum for self-reporting on outcome progression. Undergraduate manual therapy students were recruited as part of a 6-week study into knee conditioning. Participants were encouraged to post maximum effort readings from quadriceps and gluteal home exercises captured from standard bathroom scales on a bespoke Padlet. Experience and progression reporting were encouraged. Posted data were analyzed for association between engagement, entry frequency, and participant characteristics. Individual data facilitated single-subject, multiple-baseline analysis using statistical process control. Experiential narrative was analyzed thematically. Nineteen participants were recruited (47%, 9/19 female); ages ranged from 19 to 53 years. Twelve individuals (63%) opted to engage with the forum (range 4-40 entries), with five (42%) reporting across all 6 weeks. Gender did not influence reporting (odds ratio [OR] 0.76, 95% CI 0.06-6.93). No significant difference manifested between body mass index and engagement P=.46); age and entry frequency did not correlate (R 2 =.054, 95% CI –0.42 to 0.51, P=.83). Statistically significant conditioning profiles arose in single participants. Themes of pain, mitigation, and response were inducted from the experiences posted. Patients will engage with an online forum for reporting progress when undertaking exercise programs. In contrast to related literature, no significant association was found with reporting and gender, age, or body mass index. Individual posted data allowed multiple-baseline analysis and experiential induction from participants. Conditioning responses were evident on visual inspection. The importance of individualized visual data to patients and the role of forums in monitoring patients’ progress in symptomatic knee pain populations need further consideration. ©Philip Bright, Karen Hambly. Originally published in JMIR Rehabilitation and Assistive Technology (http://rehab.jmir.org), 26.04.2018.

California sea lion (Zalophus californianus) aerial hearing sensitivity measured using auditory steady-state response and psychophysical methods.

PubMed

Mulsow, Jason; Finneran, James J; Houser, Dorian S

2011-04-01

Although electrophysiological methods of measuring the hearing sensitivity of pinnipeds are not yet as refined as those for dolphins and porpoises, they appear to be a promising supplement to traditional psychophysical procedures. In order to further standardize electrophysiological methods with pinnipeds, a within-subject comparison of psychophysical and auditory steady-state response (ASSR) measures of aerial hearing sensitivity was conducted with a 1.5-yr-old California sea lion. The psychophysical audiogram was similar to those previously reported for otariids, with a U-shape, and thresholds near 10 dB re 20 μPa at 8 and 16 kHz. ASSR thresholds measured using both single and multiple simultaneous amplitude-modulated tones closely reproduced the psychophysical audiogram, although the mean ASSR thresholds were elevated relative to psychophysical thresholds. Differences between psychophysical and ASSR thresholds were greatest at the low- and high-frequency ends of the audiogram. Thresholds measured using the multiple ASSR method were not different from those measured using the single ASSR method. The multiple ASSR method was more rapid than the single ASSR method, and allowed for threshold measurements at seven frequencies in less than 20 min. The multiple ASSR method may be especially advantageous for hearing sensitivity measurements with otariid subjects that are untrained for psychophysical procedures.

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

PubMed

Goadsby, P J; Grosberg, B M; Mauskop, A; Cady, R; Simmons, K A

2014-10-01

We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Increasing Social Interactions Using Prompts and Rewards for Adolescents with ASD in an Ice Hockey Practice Context

ERIC Educational Resources Information Center

Beiers, Kevin; Derby, K. Mark; McLaughlin, T. F.

2016-01-01

We evaluated the effects of using prompts and reinforcement procedures to increase the social interaction of two children with autism (ASD). This study took place during the context of a hockey practice. Two adolescent participants were evaluated using an ABAB single subject reversal design. Baseline data were collected prior to and after the…

Analysis of Performance on Cognitive Test Measures Before, During, and After 6 Months of Hearing Aid Use: A Single-Subject Experimental Design.

PubMed

Desjardins, Jamie L

2016-06-01

The present study examined the effect of hearing aid use on cognitive test performance using a single-subject treatment design. Six participants 54 to 64 years old with sensorineural hearing loss were fitted with hearing aids. Participants used the hearing aids for approximately 8 hr each day for the duration of the study. A battery of cognitive tests was administered to participants during baseline (pre-hearing aid fitting), treatment (hearing aid use), and withdrawal (post-hearing aid use) study phases over a period of 6 months of hearing aid use. All participants showed significant improvements in performance on the cognitive test measures with hearing aid use. The most significant treatment effects were evidenced at 2 to 4 weeks of hearing aid use on the Listening Span Test and an auditory selective attention task. In many cases, cognitive performance scores returned to baseline levels after the participant stopped using the hearing aids. The findings from this study are consistent with the hypothesis that hearing aid use may improve cognitive performance by improving audibility and decreasing the cognitive load of the listening task.

Prospective study of telomere length and LINE-1 methylation in peripheral blood cells: the role of B vitamins supplementation.

PubMed

Pusceddu, Irene; Herrmann, Markus; Kirsch, Susanne H; Werner, Christian; Hübner, Ulrich; Bodis, Marion; Laufs, Ulrich; Wagenpfeil, Stefan; Geisel, Jürgen; Herrmann, Wolfgang

2016-08-01

Deficiencies of folate, vitamins B12 and D are common age-related conditions. Vitamin B12 and folate are necessary for DNA methylation. Telomeres appear to be regulated by DNA methylation. Here, we study the effect of B vitamins supplementation on telomere length and global DNA methylation in a prospective study. In total, 60 elderly subjects were supplemented for 1 year with either vitamin B12, B6, folate, vitamin D and calcium (group A n = 31) or only vitamin D and calcium (group B n = 29). LINE-1 methylation, relative telomere length (T/S), vitamin B12, folate, homocysteine (tHcy) , 5-methyltetrahydrofolate (5-methylTHF), S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), cystathionine and vitamin D were quantified before and after supplementation. At baseline, tHcy was high, vitamin D was low, and T/S did not differ between groups A and B. Vitamin supplementation increased LINE-1 methylation in group A at site 317 but reduced LINE-1 methylation in group B at site 327. There was no correlation between T/S and LINE-1 methylation at baseline. Multiple backward regression analysis revealed baseline tHcy and 5-methylTHF are significant predictors of T/S. After supplementation in group B but not in group A, LINE-1 methylation correlated inversely with T/S, and LINE-1 methylation variation was an independent predictor of T/S variation. B vitamins decreased tHcy significantly in group A. Multiple backward regression analysis showed 5-methylTHF in group A and tHcy in group B were significant predictors for LINE-1 methylation. At baseline, the lower LINE-1 methylation observed in subjects with 5-methylTHF >10 nmol/l was in agreement with a reduced methyl group transfer due to a lower SAM formation. In group B, an increase in telomere length was correlated with lower LINE-1 methylation. Subjects with hyperhomocysteinemia >12 µmol/L had compared to those with normal tHcy a reduced LINE-1 methylation accompanied by a higher SAM and SAH (that inhibits demethylation of SAM) as well as lower 5-methylTHF. Additionally, subjects with tHcy > 12 µmol/L had longer telomeres when compared with subjects having tHcy < 12 µmol/L. The results suggest a possible effect of B vitamins for telomere biology in blood cells. Suboptimal B vitamins status and hyperhomocysteinemia are associated with altered DNA methylation and telomere length. These data have to be confirmed in future studies.

Longitudinal performance of plasma neurofilament light and tau in professional fighters: The Professional Fighters Brain Health Study.

PubMed

Bernick, Charles; Zetterberg, Henrik; Shan, Guogen; Banks, Sarah; Blennow, Kaj

2018-04-02

The objective of this study is to evaluate longitudinal change in plasma neurofilament light (NF-L) and tau levels in relationship to clinical and radiological measures in professional fighters. Participants (active and retired professional fighters and control group) underwent annual blood sampling, 3 Tesla MRI brain imaging, computerized cognitive testing, and assessment of exposure to head trauma. Plasma tau and NF-L concentrations were measured using Simoa assays. Multiple linear regression models were used to compare the difference across groups in regard to baseline measurements, while mixed linear models was used for the longitudinal data with multiple measurements for each participant. Plasma samples were available on 471 participants. Baseline NF-L measures differed across groups (F_3,393=6.99, p=0.0001), with the active boxers having the highest levels. Higher NF-L levels at baseline were correlated with lower baseline MRI regional volumes and lower cognitive scores. The number of sparring rounds completed by the active fighters was correlated with NF-L (95% CI 0.0116-0.4053, p=0.0381), but not tau, levels. Among 126 subjects having multiple yearly samples, there was a significant difference in average yearly percentage change in tau across groups (F_3,83=3.87, p=0.0121).). We conclude that plasma NF-L and tau behave differently in a group of active and retired fighters; NF-L better reflects acute exposure whereas the role of plasma tau levels in signifying chronic change in brain structure over time requires further study.

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.

Effect of Multiple Dietary Supplement Containing Lutein, 
Astaxanthin, Cyanidin-3-Glucoside, and DHA on Accommodative Ability

PubMed Central

Kono, Keiko; Shimizu, Yoshiki; Takahashi, Satomi; Matsuoka, Sayuri; Yui, Kei

2014-01-01

Objective The study aimed to verify that ingestion of multiple dietary supplement containing lutein, astaxanthin, cyanidin-3-glucoside and docosahexaenoic acid (DHA) would improve accommodative ability of aged and older subjects who were aware of eye strain on a daily basis. Methods A randomized double-blind placebo-controlled parallel group comparison study was conducted for 48 participants aged 45 to 64 years who complained of eye strain. The subjects took multiple dietary supplement containing 10 mg of lutein, 20 mg of bilberry extract and 26.5 mg of black soybean hull extract (a total of 2.3 mg of cyanidin-3-glucoside in both extracts), 4 mg of astaxanthin, and 50 mg of DHA (test supplement) or placebo for four consecutive weeks. Near-point accommodation (NPA) and subjective symptoms were evaluated both before and after four weeks’ intake. Results The variation of the NPA of both eyes from baseline to 4 weeks’ post-intake in the test supplement group was significantly higher than in the placebo group (1.321±0.394 diopter (D) in the test supplement group and 0.108±0.336 D in the placebo group, p=0.023). The multiple dietary supplement group showed improvement in the NPA. Regarding subjective symptoms, significant improvement of “stiff shoulders or neck” and “blurred vision” was also found in the test supplement group compared to the placebo group (p<0.05). There were no safety concerns in this study. Conclusion This study shows that multiple dietary supplement containing lutein, astaxanthin, cyanidin-3-glucoside, and DHA has effect to improve accommodative ability and subjective symptoms related to eye fatigue.

Evaluation of the effectiveness and efficiency of two stimulus prompt strategies with severely handicapped students.

PubMed Central

Steege, M W; Wacker, D P; McMahon, C M

1987-01-01

In this study we compared the effectiveness and efficiency of two treatment packages that used stimulus prompt sequences and task analyses for teaching community living skills to severely handicapped students. Four severely and multiply handicapped students were trained to perform four tasks: (a) making toast, (b) making popcorn, (c) operating a clothes dryer, and (d) operating a washing machine. Following baseline, each student was exposed to two types of training procedures, each involving a task analysis of the target behavior. Training Procedure 1 (Traditional) utilized a least-to-most restrictive prompt sequence. Training Procedure 2 (Prescriptive) utilized ongoing behavioral assessment data to identify discriminative stimuli. The assessment data were used to prescribe instructional prompts across successive training trials. Performance on the tasks was evaluated within a combination multiple baseline (across subjects) and probe (across tasks) design. Training conditions were counterbalanced across subjects and tasks. Results indicated that both training procedures were equally effective in increasing independent task acquisition for subjects on all tasks; however, the prescriptive procedure was the more efficient procedure. PMID:3667479

Multiple skin neoplasms in subjects under 40 years of age in Goiania, Brazil

PubMed Central

Pereira, Samir; Curado, Maria Paula; Ribeiro, Ana Maria Quinteiro

2015-01-01

OBJECTIVE To describe the trend for malignant skin neoplasms in subjects under 40 years of age in a region with high ultraviolet radiation indices. METHODS A descriptive epidemiological study on melanoma and nonmelanoma skin cancers that was conducted in Goiania, Midwest Brazil, with 1,688 people under 40 years of age, between 1988 and 2009. Cases were obtained from Registro de Câncer de Base Populacional de Goiânia (Goiania’s Population-Based Cancer File). Frequency, trends, and incidence of cases with single and multiple lesions were analyzed; transplants and genetic skin diseases were found in cases with multiple lesions. RESULTS Over the period, 1,995 skin cancer cases were observed to found, of which 1,524 (90.3%) cases had single lesions and 164 (9.7%) had multiple lesions. Regarding single lesions, incidence on men was observed to have risen from 2.4 to 3.1/100,000 inhabitants; it differed significantly for women, shifting from 2.3 to 5.3/100,000 (Annual percentage change – [APC] 3.0%, p = 0.006). Regarding multiple lesions, incidence on men was observed to have risen from 0.30 to 0.98/100,000 inhabitants; for women, it rose from 0.43 to 1.16/100,000 (APC 8.6%, p = 0.003). Genetic skin diseases or transplants were found to have been correlated with 10.0% of cases with multiple lesions – an average of 5.1 lesions per patient. The average was 2.5 in cases without that correlation. CONCLUSIONS Skin cancer on women under 40 years of age has been observed to be increasing for both cases with single and multiple lesions. It is not unusual to find multiple tumors in young people – in most cases, they are not associated with genetic skin diseases or transplants. It is necessary to avoid excessive exposure to ultraviolet radiation from childhood. PMID:26465667

A Hough Transform Global Probabilistic Approach to Multiple-Subject Diffusion MRI Tractography

PubMed Central

Aganj, Iman; Lenglet, Christophe; Jahanshad, Neda; Yacoub, Essa; Harel, Noam; Thompson, Paul M.; Sapiro, Guillermo

2011-01-01

A global probabilistic fiber tracking approach based on the voting process provided by the Hough transform is introduced in this work. The proposed framework tests candidate 3D curves in the volume, assigning to each one a score computed from the diffusion images, and then selects the curves with the highest scores as the potential anatomical connections. The algorithm avoids local minima by performing an exhaustive search at the desired resolution. The technique is easily extended to multiple subjects, considering a single representative volume where the registered high-angular resolution diffusion images (HARDI) from all the subjects are non-linearly combined, thereby obtaining population-representative tracts. The tractography algorithm is run only once for the multiple subjects, and no tract alignment is necessary. We present experimental results on HARDI volumes, ranging from simulated and 1.5T physical phantoms to 7T and 4T human brain and 7T monkey brain datasets. PMID:21376655

Family Implementation of Positive Behavior Support for a Child with Autism: Longitudinal, Single-Case, Experimental, and Descriptive Replication and Extension

ERIC Educational Resources Information Center

Lucyshyn, Joseph M.; Albin, Richard W.; Horner, Robert H.; Mann, Jane C.; Mann, James A.; Wadsworth, Gina

2007-01-01

This study examined the efficacy, social validity, and durability of a positive behavior support (PBS) approach with the family of a girl with autism and severe problem behavior. The study was conducted across a 10-year period beginning when the child was 5 years old. A multiple baseline across family routines design evaluated the functional…

A Randomized Controlled Clinical Trial to Evaluate Extrinsic Stain Removal of a Whitening Dentifrice.

PubMed

Terézhalmy, Géza; He, Tao; Anastasia, Mary Kay; Eusebio, Rachelle

2016-12-01

To evaluate the extrinsic stain removal efficacy of a new whitening dentifrice containing sodium hexametaphosphate (SHMP) over a two-week period. This study used a controlled and randomized, examiner-blind, single-center, two-treatment, parallel group design. Subjects with visible extrinsic dental stain on facial surfaces of their anterior teeth, and meeting all study criteria, were entered into the trial. The test group received the whitening dentifrice with sodium fluoride and SHMP and an ADA reference soft manual toothbrush. Subjects in the control group received a dental prophylaxis after the initial examination at Baseline and were instructed to use their usual oral hygiene products at home. Subjects returned at Day 3 and Week 2 for re-evaluation of extrinsic dental stain. Extrinsic stain was measured using the Interproximal Modified Lobene (IML) Stain Index; safety was assessed based on clinical examination. Fifty subjects (mean age 32.0 years) completed the study, with 25 in each group. Statistically significant reductions in composite stain for whole tooth, as well as interproximal, gingival, and body surfaces were observed for both groups at Day 3 and Week 2 (p < 0.0001) with no significant differences between the two groups (p > 0.3). At Day 3, median percent reductions in composite IML stain from Baseline were 98% for the prophylaxis group and 100% for the test dentifrice group. At Week 2, median percent reductions in composite IML stain were 100% compared to Baseline for both groups. No adverse events were reported for either group. The whitening dentifrice demonstrated a statistically significant reduction in IML stain after three days and two weeks of use relative to baseline. Stain reduction with the toothpaste was comparable to a dental prophylaxis.

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

Improving Feeding Skills and Mealtime Behaviors in Children and Youth with Disabilities

ERIC Educational Resources Information Center

Bailey, Rita L.; Angell, Maureen E.

2005-01-01

A single-subject multiple treatment design counterbalanced across nine participants with moderate to severe and multiple disabilities was used to determine the efficacy of a school-based multi-treatment package (a combined dysphagia treatment and positive reinforcement behavior management program) for children and youth (ages 4-17) with feeding…

The immediate effect of individual manipulation techniques on pulmonary function measures in persons with chronic obstructive pulmonary disease

PubMed Central

Noll, Donald R; Johnson, Jane C; Baer, Robert W; Snider, Eric J

2009-01-01

Background The use of manipulation has long been advocated in the treatment of chronic obstructive pulmonary disease (COPD), but few randomized controlled clinical trials have measured the effect of manipulation on pulmonary function. In addition, the effects of individual manipulative techniques on the pulmonary system are poorly understood. Therefore, the purpose of this study was to determine the immediate effects of four osteopathic techniques on pulmonary function measures in persons with COPD relative to a minimal-touch control protocol. Methods Persons with COPD aged 50 and over were recruited for the study. Subjects received five, single-technique treatment sessions: minimal-touch control, thoracic lymphatic pump (TLP) with activation, TLP without activation, rib raising, and myofascial release. There was a 4-week washout period between sessions. Protocols were given in random order until all five techniques had been administered. Pulmonary function measures were obtained at baseline and 30-minutes posttreatment. For the actual pulmonary function measures and percent predicted values, Wilcoxon signed rank tests were used to test within-technique changes from baseline. For the percent change from baseline, Friedman tests were used to test for between-technique differences. Results Twenty-five subjects were enrolled in the study. All four tested osteopathic techniques were associated with adverse posttreatment changes in pulmonary function measures; however, different techniques changed different measures. TLP with activation increased posttreatment residual volume compared to baseline, while TLP without activation did not. Side effects were mild, mostly posttreatment chest wall soreness. Surprisingly, the majority of subjects believed they could breathe better after receiving osteopathic manipulation. Conclusion In persons with COPD, TLP with activation, TLP without activation, rib raising, and myofascial release mildly worsened pulmonary function measures immediately posttreatment relative to baseline measurements. The activation component of the TLP technique appears to increase posttreatment residual volume. Despite adverse changes in pulmonary function measures, persons with COPD subjectively reported they benefited from osteopathic manipulation. PMID:19814829

The immediate effect of individual manipulation techniques on pulmonary function measures in persons with chronic obstructive pulmonary disease.

PubMed

Noll, Donald R; Johnson, Jane C; Baer, Robert W; Snider, Eric J

2009-10-08

The use of manipulation has long been advocated in the treatment of chronic obstructive pulmonary disease (COPD), but few randomized controlled clinical trials have measured the effect of manipulation on pulmonary function. In addition, the effects of individual manipulative techniques on the pulmonary system are poorly understood. Therefore, the purpose of this study was to determine the immediate effects of four osteopathic techniques on pulmonary function measures in persons with COPD relative to a minimal-touch control protocol. Persons with COPD aged 50 and over were recruited for the study. Subjects received five, single-technique treatment sessions: minimal-touch control, thoracic lymphatic pump (TLP) with activation, TLP without activation, rib raising, and myofascial release. There was a 4-week washout period between sessions. Protocols were given in random order until all five techniques had been administered. Pulmonary function measures were obtained at baseline and 30-minutes posttreatment. For the actual pulmonary function measures and percent predicted values, Wilcoxon signed rank tests were used to test within-technique changes from baseline. For the percent change from baseline, Friedman tests were used to test for between-technique differences. Twenty-five subjects were enrolled in the study. All four tested osteopathic techniques were associated with adverse posttreatment changes in pulmonary function measures; however, different techniques changed different measures. TLP with activation increased posttreatment residual volume compared to baseline, while TLP without activation did not. Side effects were mild, mostly posttreatment chest wall soreness. Surprisingly, the majority of subjects believed they could breathe better after receiving osteopathic manipulation. In persons with COPD, TLP with activation, TLP without activation, rib raising, and myofascial release mildly worsened pulmonary function measures immediately posttreatment relative to baseline measurements. The activation component of the TLP technique appears to increase posttreatment residual volume. Despite adverse changes in pulmonary function measures, persons with COPD subjectively reported they benefited from osteopathic manipulation.

Test-retest reliability and task order effects of emotional cognitive tests in healthy subjects.

PubMed

Adams, Thomas; Pounder, Zoe; Preston, Sally; Hanson, Andy; Gallagher, Peter; Harmer, Catherine J; McAllister-Williams, R Hamish

2016-11-01

Little is known of the retest reliability of emotional cognitive tasks or the impact of using different tasks employing similar emotional stimuli within a battery. We investigated this in healthy subjects. We found improved overall performance in an emotional attentional blink task (EABT) with repeat testing at one hour and one week compared to baseline, but the impact of an emotional stimulus on performance was unchanged. Similarly, performance on a facial expression recognition task (FERT) was better one week after a baseline test, though the relative effect of specific emotions was unaltered. There was no effect of repeat testing on an emotional word categorising, recall and recognition task. We found no difference in performance in the FERT and EABT irrespective of task order. We concluded that it is possible to use emotional cognitive tasks in longitudinal studies and combine tasks using emotional facial stimuli in a single battery.

Single-Trial Classification of Multi-User P300-Based Brain-Computer Interface Using Riemannian Geometry.

PubMed

Korczowski, L; Congedo, M; Jutten, C

2015-08-01

The classification of electroencephalographic (EEG) data recorded from multiple users simultaneously is an important challenge in the field of Brain-Computer Interface (BCI). In this paper we compare different approaches for classification of single-trials Event-Related Potential (ERP) on two subjects playing a collaborative BCI game. The minimum distance to mean (MDM) classifier in a Riemannian framework is extended to use the diversity of the inter-subjects spatio-temporal statistics (MDM-hyper) or to merge multiple classifiers (MDM-multi). We show that both these classifiers outperform significantly the mean performance of the two users and analogous classifiers based on the step-wise linear discriminant analysis. More importantly, the MDM-multi outperforms the performance of the best player within the pair.

Oral supplementation with L‐homoarginine in young volunteers

PubMed Central

Atzler, Dorothee; Schönhoff, Mirjam; Cordts, Kathrin; Ortland, Imke; Hoppe, Julia; Hummel, Friedhelm C.; Gerloff, Christian; Jaehde, Ulrich; Jagodzinski, Annika; Böger, Rainer H.; Choe, Chi‐un

2016-01-01

Aims Low blood concentrations of the naturally occurring amino acid L‐homoarginine (L‐hArg) are related to impaired cardiovascular outcome and mortality in humans and animals. L‐hArg is a weak substrate of nitric oxide synthase and an inhibitor of arginases in vitro. The aim of our study was to obtain kinetic and dynamic data after oral L‐hArg supplementation. Methods In a double‐blind, randomized, placebo‐controlled crossover study, 20 young volunteers received 125 mg L‐hArg once daily for 4 weeks. Kinetic parameters (C max, T max and AUC0‐24h) were calculated after ingestion of single and multiple doses of oral supplementation as primary endpoint. Secondary endpoints that were evaluated were routine laboratory, L‐arginine, asymmetric dimethylarginine (ADMA), pulse wave velocity (PWV), augmentation index (AIx), flow‐mediated vasodilatation (FMD), corticospinal excitability, i.e. motor threshold (MT), and cortical excitability, i.e. intracortical inhibition (ICI) and facilitation (ICF). Results One hour after ingestion (T max), L‐hArg increased the baseline L‐hArg plasma concentration (2.87 ± 0.91 μmol l−1, mean ± SD) by 8.74 ± 4.46 [95% confidence intervals 6.65; 10.9] and 17.3 ± 4.97 [14.9; 19.6] μmol l−1 (C max), after single and multiple doses, respectively. Once‐only and 4 weeks of supplementation resulted in AUCs0‐24h of 63.5 ± 28.8 [50.0; 76.9] and 225 ± 78.5 [188; 2624] μmol l−1*h, for single and multiple doses, respectively. Routine laboratory parameters, L‐arginine, ADMA, PWV, AIx, FMD, MT, ICI and ICF did not change by L‐hArg supplementation compared to baseline. Conclusion Once daily orally applied 125 mg L‐hArg raises plasma L‐hArg four‐ and sevenfold after single dose and 4 weeks of supplementation, respectively, and is safe and well tolerated in young volunteers. PMID:27434056

In vivo single-shot three-dimensionally localized multiple quantum spectroscopy of GABA in the human brain with improved spectral selectivity

NASA Astrophysics Data System (ADS)

Choi, In-Young; Lee, Sang-Pil; Shen, Jun

2005-01-01

A single-shot multiple quantum filtering method is developed that uses two double-band frequency selective pulses for enhanced spectral selectivity in combination with a slice-selective 90°, a slice-selective universal rotator 90°, and a spectral-spatial pulse composed of two slice-selective universal rotator 45° pulses for single-shot three-dimensional localization. The use of this selective multiple quantum filtering method for C3 and C4 methylene protons of GABA resulted in improved spectral selectivity for GABA and effective suppression of overlapping signals such as creatine and glutathione in each single scan, providing reliable measurements of the GABA doublet in all subjects. The concentration of GABA was measured to be 0.7 ± 0.2 μmol/g (means ± SD, n = 15) in the fronto-parietal region of the human brain in vivo.

Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study.

PubMed

Rapaport, M H; Nierenberg, A A; Schettler, P J; Kinkead, B; Cardoos, A; Walker, R; Mischoulon, D

2016-01-01

This study explores whether inflammatory biomarkers act as moderators of clinical response to omega-3 (n-3) fatty acids in subjects with major depressive disorder (MDD). One hundred fifty-five subjects with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD, a baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) score ⩾ 15 and baseline biomarker data (interleukin (IL)-1ra, IL-6, high-sensitivity C-reactive protein (hs-CRP), leptin and adiponectin) were randomized between 18 May 2006 and 30 June 2011 to 8 weeks of double-blind treatment with eicosapentaenoic acid (EPA)-enriched n-3 1060 mg day(-1), docosahexaenoic acid (DHA)-enriched n-3 900 mg day(-1) or placebo. Outcomes were determined using mixed model repeated measures analysis for 'high' and 'low' inflammation groups based on individual and combined biomarkers. Results are presented in terms of standardized treatment effect size (ES) for change in HAM-D-17 from baseline to treatment week 8. Although overall treatment group differences were negligible (ES=-0.13 to +0.04), subjects with any 'high' inflammation improved more on EPA than placebo (ES=-0.39) or DHA (ES=-0.60) and less on DHA than placebo (ES=+0.21); furthermore, EPA-placebo separation increased with increasing numbers of markers of high inflammation. Subjects randomized to EPA with 'high' IL-1ra or hs-CRP or low adiponectin ('high' inflammation) had medium ES decreases in HAM-D-17 scores vs subjects 'low' on these biomarkers. Subjects with 'high' hs-CRP, IL-6 or leptin were less placebo-responsive than subjects with low levels of these biomarkers (medium to large ES differences). Employing multiple markers of inflammation facilitated identification of a more homogeneous cohort of subjects with MDD responding to EPA vs placebo in our cohort. Studies are needed to replicate and extend this proof-of-concept work.

The Effect of High Versus Low Teacher Affect and Passive Versus Active Student Activity During Music Listening on Preschool Children's Attention, Piece Preference, Time Spent Listening, and Piece Recognition.

ERIC Educational Resources Information Center

Sims, Wendy L.

1986-01-01

Small-group listening lessons and subsequent individual posttests were used to judge 94 three- through five-year-old subjects' attention, paired-comparison piece preference, time spent listening, and piece recognition. Research procedures included a modified multiple baseline design and split-screen video taping of instructional sessions.…

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…

The Effectiveness of Vowel Production Training with Real-Time Spectrographic Displays for Children with Profound Hearing Impairment.

NASA Astrophysics Data System (ADS)

Ertmer, David Joseph

1994-01-01

The effectiveness of vowel production training which incorporated direct instruction in combination with spectrographic models and feedback was assessed for two children who exhibited profound hearing impairment. A multiple-baseline design across behaviors, with replication across subjects was implemented to determine if vowel production accuracy improved following the introduction of treatment. Listener judgments of vowel correctness were obtained during the baseline, training, and follow-up phases of the study. Data were analyzed through visual inspection of changes in levels of accuracy, changes in trends of accuracy, and changes in variability of accuracy within and across phases. One subject showed significant improvement of all three trained vowel targets; the second subject for the first trained target only (Kolmogorov-Smirnov Two Sample Test). Performance trends during training sessions suggest that continued treatment would have resulted in further improvement for both subjects. Vowel duration, fundamental frequency, and the frequency locations of the first and second formants were measured before and after training. Acoustic analysis revealed highly individualized changes in the frequency locations of F1 and F2. Vowels which received the most training were maintained at higher levels than those which were introduced later in training, Some generalization of practiced vowel targets to untrained words was observed in both subjects. A bias towards judging productions as "correct" was observed for both subjects during self-evaluation tasks using spectrographic feedback.

SMS text messaging as a means of increasing recall of therapy goals in brain injury rehabilitation: a single-blind within-subjects trial.

PubMed

Culley, Campbell; Evans, Jonathan J

2010-01-01

A single-blind within-subjects trial was used to test the efficacy of sending SMS text messages to patients with a traumatic brain injury as a means of improving their recall of rehabilitation goals. Eleven participants were recruited from two community-based rehabilitation centres and were sent text messages relating to three randomly selected goals from a selection of six current goals three times per day for 14 days. Participants' recall of their rehabilitation goals was assessed at baseline, seven days, and 14 days via free recall and cued recall procedures. Results showed that goals in the "text" condition were recalled better than goals in the "no text" condition. Practical applications and extensions are discussed.

Long-term (12-month) improvement in meibomian gland function and reduced dry eye symptoms with a single thermal pulsation treatment.

PubMed

Greiner, Jack V

2013-08-01

To determine the 1-year post-treatment dry eye status of subjects with meibomian gland dysfunction and dry eye symptoms after receiving a single LipiFlow Thermal Pulsation System treatment. Single-centre, prospective, observational, open-label, 1-month-registered clinical trial with a 1-year follow-up examination. Patients with evaporative dry eye disease with meibomian gland dysfunction and dry eye symptoms who had participated in the registered 1-month clinical trial. Eighteen of 30 subjects initially enrolled were able to return for a 1-year follow-up. Both eyes of all patients were treated with a single 12-min treatment using the LipiFlow Thermal Pulsation System. Meibomian gland function, tear break-up time and dry eye symptoms were measured. Data are presented for pretreatment (baseline), and 1-month and 1-year post-treatment. Meibomian gland secretion scores, and tear break-up time and dry eye symptoms. Significant improvement in meibomian gland secretion scores from baseline measurements (4.0 ± 3.4) to 1-month post-treatment (11.3 ± 4.7; P < 0.0005) was maintained at 1-year (7.3 ± 4.6; P < 0.05). Baseline tear break-up time (4.9 ± 3.0) was significantly increased at 1-month (9.5 ± 6.9; P < 0.05); however, this improvement was no longer evident at 1-year post-treatment (6.0 ± 4.4). The significant improvement in symptom scores on Ocular Surface Disease Index and Standard Patient Evaluation of Eye Dryness questionnaires observed at 1-month (P < 0.0005) was maintained at 1-year (Ocular Surface Disease Index [P < 0.05]; Standard Patient Evaluation of Eye Dryness [P < 0.0005]). A single 12-min treatment with the Lipi Flow Thermal Pulsation System offers an effective treatment for evaporative dry eye and meibomian gland dysfunction resulting in significant and sustained improvement in signs and symptoms for up to 1 year. © 2012 The Author. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

Feasibility of the Nintendo WiiFit™ for improving walking in individuals with a lower limb amputation

PubMed Central

Imam, Bita; McLaren, Linda; Chapman, Paul; Finlayson, Heather

2013-01-01

Objectives: To evaluate the feasibility of the Nintendo WiiFit™ as an adjunct to usual therapy in individuals with a lower limb amputation. Methods: The study was a Multiple Baseline (AB) Single Subject Research Design. Subjects were ≥19 years old, had their first unilateral transtibial or transfemoral amputation  ≤12 months ago, and were participating in prosthetic training. WiiFit training was provided for 30 min, 5 times a week, for a minimum of 2 and a maximum of 6 weeks in addition to usual therapy. Feasibility indicators were safety, post-intervention fatigue and pain levels, adherence, and subject’s acceptability of the program as measured by the Short Feedback Questionnaire–modified (SFQ-M). The primary clinical outcome was walking capacity assessed by the 2 Minute Walk Test (2MWT). The secondary clinical outcomes were the Short Physical Performance Battery, L-test, and Activities-Specific Balance Confidence. Results: Subjects (4 transtibial; 2 transfemoral) had a median age of 48.5 years (range = 45–59 years). No adverse events associated with the intervention occurred. Median pain and fatigue levels were 1.3 (range = 0.5–3.5) and 3.1 (range = 1.4–4.1), respectively. Median adherence was 80%. Subjects found the WiiFit enjoyable and acceptable (median SFQ-M = 35). Five subjects showed statistical improvement on the 2MWT and four on the secondary outcomes (p < 0.05). Conclusion: The WiiFit intervention was found to be feasible in individuals with unilateral lower limb amputation. This research provides the foundation for future clinical research investigating the use of the WiiFit as a viable adjunctive therapy to improve outcomes in individuals with unilateral lower limb amputation who are participating in prosthetic training. PMID:26770676

A survey of stellar families: Multiplicity of solar-type stars

NASA Astrophysics Data System (ADS)

Raghavan, Deepak

I present the results of a comprehensive assessment of companions to 454 solar- type stars within 25 pc. New observational aspects of this work include surveys for (1) very close companions with long-baseline interferometry at the Center for High Angular Resolution Astronomy (CHARA) Array, (2) close companions with speckle interferometry, and (3) wide proper motion companions identified by blinking multi-epoch archival images. I have also obtained and included unpublished results from extensive radial velocity monitoring programs. The many sources utilized enable a thorough evaluation of stellar and brown dwarf companions. The results presented here include eight new companion discoveries, four of which are wide common proper motion pairs discovered by blinking archival images, and four more are from the spectroscopic data. The overall observed fractions of single, double, triple, and higher order systems are 57%±3%, 33%±2%, 8%±1%, and 3%±1%, respectively, counting all stellar and brown dwarf companions. The incompleteness analysis indicates that only a few undiscovered companions remain in this well-studied sample, showing that a majority of the solar-type stars are single. Bluer, more massive stars are more likely to have companions than redder, less massive ones. I confirm earlier expectations that more active stars are more likely to have companions. A preliminary, but important indication is that brown dwarfs, like planets, prefer stars with higher metallicity, tentatively suggesting that brown dwarfs may form like planets when they are companions to stars. The period distribution is unimodal and roughly Gaussian with peak and median values of about 300 years. The period-eccentricity relation shows a roughly flat distribution beyond the circularization limit of about 12 days. The mass- ratio distribution shows a clear discontinuity near a value of one, indicating a preference for twins, which are not confined to short orbital periods, suggesting that stars form by multiple formation mechanisms. The ratio of planet hosts among single, binary, and multiple systems are statistically indistinguishable, suggesting that planets are as likely to form around single stars as they are around components of binary or multiple systems at sufficiently wide separations. INDEX WORDS: Stellar multiplicity, Binary stars, Solar-type stars, Solar neighborhood, Exoplanet systems, Brown dwarfs, Survey, Long baseline interferometry, Radial velocity

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…

Individual differences in the cortisol-awakening response during the first two years of shift work: A longitudinal study in novice police officers.

PubMed

Lammers-van der Holst, Heidi M; Kerkhof, Gerard A

2015-01-01

Cortisol acts as a critical biological intermediary through which chronic stressors like shift work impact upon multiple physiological, neuro-endocrine and hormonal functions. Therefore, the cortisol awakening response (CAR) is suggested as a prime index of shift work tolerance. Repeated assessments of the CAR (calculated as MnInc) in a group of 25 young novice police officers showed that in the interval between about 4 and 14 months after transitioning from regular day work to rotating shift work, mean values began to rise from baseline to significantly higher levels at about 14 months after they commenced shift work. Visual inspection of the individual trends revealed that a subgroup of 10 subjects followed a monotonically rising trend, whereas another 14 subjects, after an initial rise from about 4-14 months, reverted to a smaller, baseline level cortisol response at about 20 months after the start of shift work. If the initial increase in the cortisol response marks the development of a chronic stress response, the subsequent reversal to baseline levels in the subgroup of 14 participants might be indicative of a process of recovery, possibly the development of shift work tolerance.

Strategies to exclude subjects who conceal and fabricate information when enrolling in clinical trials.

PubMed

Devine, Eric G; Peebles, Kristina R; Martini, Valeria

2017-03-01

Clinical trials within the US face an increasing challenge with the recruitment of quality candidates. One readily available group of subjects that have high rates of participation in clinical research are subjects who enroll in multiple trials for the purpose of generating income through study payments. Aside from issues of safety and generalizability, evidence suggests that these subjects employ methods of deception to qualify for the strict entrance criteria of some studies, including concealing information and fabricating information. Including these subjects in research poses a significant risk to the integrity of data quality and study designs. Strategies to limit enrollment of subjects whose motivation is generating income have not been systematically addressed in the literature. The present paper is intended to provide investigators with a range of strategies for developing and implementing a study protocol with protections to minimize the enrollment of subjects whose primary motivation for enrolling is to generate income. This multifaceted approach includes recommendations for advertising strategies, payment strategies, telephone screening strategies, and baseline screening strategies. The approach also includes recommendations for attending to inconsistent study data and subject motivation. Implementing these strategies may be more or less important depending upon the vulnerability of the study design to subject deception. Although these strategies may help researchers exclude subjects with a higher rate of deceptive practices, widespread adoption of subject registries would go a long way to decrease the chances of subjects enrolling in multiple studies or more than once in the same study.

Efficacy of single-agent bortezomib vs. single-agent thalidomide in patients with relapsed or refractory multiple myeloma: a systematic comparison

PubMed Central

Prince, H Miles; Adena, Michael; Smith, Dell Kingsford; Hertel, Judy

2007-01-01

Objective: To conduct a systematic review of the efficacy of single-agent bortezomib vs. single-agent thalidomide in patients with relapsed/refractory multiple. Methods: Publications in English from 1966 to June 2005 (MEDLINE, EMBASE, Cochrane library), publication reference lists, Janssen-Cilag data-on-file and abstracts from recent multiple myeloma conferences were reviewed. Prospective studies containing at least a single arm of either treatment group with n ≥ 30 were included. Studies adding dexamethasone for non-responders were excluded. Statistical pooling was performed for response rate and overall survival. Results: One bortezomib study (n = 333, NEJM 2005, 352; 2487–98) and 15 thalidomide (n = 1007) studies met these criteria and were included. Patient baseline characteristics including age, gender, IgG:IgA, disease duration and beta-2 microglobulin were well matched except that 48% of bortezomib patients had received prior thalidomide. Response rate, defined as serum M-protein reduction ≥ 50%, was 53% for patients receiving bortezomib vs. 32% for thalidomide (P < 0.001, n = 10 studies). Response rate determined by European Group for Blood and Marrow Transplantation (EBMT) criteria was 41% for patients receiving bortezomib vs. 22% for thalidomide (P < 0.001, n = 4 studies). Conclusion: Bortezomib was associated with a significantly higher response rate and complete remission rate using both M-protein and EBMT criteria. PMID:17608711

Setting Single or Multiple Goals for Diet and Physical Activity Behaviors Improves Cardiovascular Disease Risk Factors in Adults With Type 2 Diabetes: A Pragmatic Pilot Randomized Trial.

PubMed

Swoboda, Christine M; Miller, Carla K; Wills, Celia E

2016-08-01

The purpose of this study was to evaluate a 4-month telephone-based goal-setting and decision support intervention among adults with type 2 diabetes mellitus (T2DM) and multiple risk factors for cardiovascular disease (CVD). A randomized pretest-posttest control group design was employed. Overweight or obese adults aged 40 to 75 years with T2DM and ≥1 additional CVD risk factor were provided with individualized CVD risk information. At baseline and each biweekly telephone call, the multiple-goal group self-selected both diet- and physical activity-related goals, the single goal group set a single goal, and the control group received information about community health resources. Dietary intake was assessed via a food frequency questionnaire, physical activity via questionnaire, and A1C and blood lipids via fasting fingerstick sample. Between-group differences for clinical (ie, A1C, blood pressure, and blood lipids), physical activity, and dietary variables were evaluated using Kruskal-Wallis, Mann-Whitney U, analysis of variance, and t tests. From pre- to postintervention, the single-goal group demonstrated significant improvement in systolic blood pressure and intake of servings of fruits, vegetables, and refined grains (all P < .05). The multiple-goal group reported significant reduction in percent energy from total, saturated, monounsaturated, and trans fat intake and significant increase in leisure time walking (all P < .05). A multiple-goal approach over 4 months can improve dietary and physical activity outcomes, while a single-goal approach may facilitate improvement in one behavioral domain. Additional research is needed to evaluate maintenance of the achieved changes. © 2016 The Author(s).

Evaluation of the efficacy, tolerability, and safety of an over-the-counter acne regimen containing benzoyl peroxide and salicylic acid in subjects with acne.

PubMed

Kircik, Leon H; Gwazdauskas, Jennifer; Butners, Victoria; Eastern, Joseph; Green, Lawrence J

2013-03-01

Benzoyl peroxide (BPO) is a widely used over-the-counter (OTC) topical acne treatment often used in combination with salicylic acid (SA) to achieve better comedone control than that achieved with BPO alone. MaxClarity™ is an OTC acne treatment system comprising BPO and SA in an aqueous foam delivery vehicle, VersaFoam AF™. This paper describes 2 open-label, single-arm studies conducted to assess the efficacy, safety, tolerability, and patient preference of MaxClarity in the treatment of mild, moderate, and severe acne. Subjects applied MaxClarity twice daily for 8 weeks in study 402 and for 12 weeks in study 405. Reductions in all lesion types were seen throughout both studies. At week 8 (study 402), there was a mean reduction from baseline of -56.9 ± 32.7% in total lesions in subjects with mild, moderate, or severe acne. At week 12 (study 405), there was a reduction from baseline of -61.6 ± 22.0% in total lesions in subjects with moderate or severe acne. Overall, both studies demonstrated that MaxClarity is a generally well tolerated and effective treatment for mild, moderate, and severe acne.

Including persistency of impairment in mild cognitive impairment classification enhances prediction of 5-year decline.

PubMed

Vandermorris, Susan; Hultsch, David F; Hunter, Michael A; MacDonald, Stuart W S; Strauss, Esther

2011-02-01

Although older adults with Mild Cognitive Impairment (MCI) show elevated rates of conversion to dementia as a group, heterogeneity of outcomes is common at the individual level. Using data from a prospective 5-year longitudinal investigation of cognitive change in healthy older adults (N = 262, aged 64-92 years), this study addressed limitations in contemporary MCI identification procedures which rely on single occasion assessment ("Single-Assessment [SA] MCI") by evaluating an alternate operational definition of MCI requiring evidence of persistent cognitive impairment over multiple-testing sessions ("Multiple-Assessment [MA] MCI"). As hypothesized, prevalence of SA-MCI exceeded that of MA-MCI. Further, the MA-MCI groups showed lower baseline cognitive and functional performance and steeper cognitive decline compared with Control and SA-MCI group. Results are discussed with reference to retest effects and clinical implications.

A randomized controlled trial of single versus multiple health behavior change: promoting physical activity and nutrition among adolescents.

PubMed

Prochaska, Judith J; Sallis, James F

2004-05-01

Targeting multiple behaviors for change may provide significant health benefits. This study compared interventions targeting physical activity and nutrition (PAN) concurrently versus physical activity (PA) alone. Adolescents (N=138) were randomized to the PAN or PA intervention or control condition (n=46 per group). Primary outcomes were change in PA accelerometer and 3-day dietary recording from baseline to 3-month follow-up. The PAN and PA interventions were efficacious in supporting boys' (p<.001) but not girls' (p=.663) PA relative to the control condition. Dietary change was minimal. Although the findings do not reveal a decrement to PA promotion when a nutrition intervention was added, neither do they reveal any additional benefit. More studies comparing single versus multibehavioral interventions are needed. ((c) 2004 APA, all rights reserved)

Dual wing, swept forward swept rearward wing, and single wing design optimization for high performance business airplanes

NASA Technical Reports Server (NTRS)

Rhodes, M. D.; Selberg, B. P.

1982-01-01

An investigation was performed to compare closely coupled dual wing and swept forward swept rearward wing aircraft to corresponding single wing 'baseline' designs to judge the advantages offered by aircraft designed with multiple wing systems. The optimum multiple wing geometry used on the multiple wing designs was determined in an analytic study which investigated the two- and three-dimensional aerodynamic behavior of a wide range of multiple wing configurations in order to find the wing geometry that created the minimum cruise drag. This analysis used a multi-element inviscid vortex panel program coupled to a momentum integral boundary layer analysis program to account for the aerodynamic coupling between the wings and to provide the two-dimensional aerodynamic data, which was then used as input for a three-dimensional vortex lattice program, which calculated the three-dimensional aerodynamic data. The low drag of the multiple wing configurations is due to a combination of two dimensional drag reductions, tailoring the three dimensional drag for the swept forward swept rearward design, and the structural advantages of the two wings that because of the structural connections permitted higher aspect ratios.

The Effect of Contingent Reinforcement on Target Variables in Outpatient Psychotherapy for Depression: A Successful and Unsuccessful Case Using Functional Analytic Psychotherapy

ERIC Educational Resources Information Center

Kanter, Jonathan W.; Landes, Sara J.; Busch, Andrew M.; Rusch, Laura C.; Brown, Keri R.; Baruch, David E.; Holman, Gareth I.

2006-01-01

The current study investigated a behavior-analytic treatment, functional analytic psychotherapy (FAP), for outpatient depression utilizing two single-subject A/A+B designs. The baseline condition was cognitive behavioral therapy. Results demonstrated treatment success in 1 client after the addition of FAP and treatment failure in the 2nd. This…

TSH increment and the risk of incident type 2 diabetes mellitus in euthyroid subjects.

PubMed

Jun, Ji Eun; Jin, Sang-Man; Jee, Jae Hwan; Bae, Ji Cheol; Hur, Kyu Yeon; Lee, Moon-Kyu; Kim, Sun Wook; Kim, Jae Hyeon

2017-03-01

Thyroid function is known to influence glucose metabolism, and thyroid-stimulating hormone is the most useful parameter in screening for thyroid dysfunction. Therefore, the aim of this study was to investigate the incidence of type 2 diabetes according to baseline thyroid-stimulating hormone level and thyroid-stimulating hormone change in euthyroid subjects. We identified and enrolled 17,061 euthyroid subjects without diabetes among participants who had undergone consecutive thyroid function tests between 2006 and 2012 as a part of yearly health check-up program. Thyroid-stimulating hormone changes were determined by subtracting baseline thyroid-stimulating hormone level from thyroid-stimulating hormone level at 1 year before diagnosis of diabetes or at the end of follow-up in subjects who did not develope diabetes. During 84,595 person-years of follow-up, there were 956 new cases of type 2 diabetes. Cox proportional hazards models showed the risk of incident type 2 diabetes was significantly increased with each 1 μIU/mL increment in TSH after adjustment for multiple confounding factors (hazard ratio = 1.13, 95% confidence interval: 1.07-1.20, P < 0.001). Compared with individuals in the lowest tertile (-4.08 to 0.34 μIU/mL), those in the highest thyroid-stimulating hormone change tertile (0.41-10.84 μIU/mL) were at greater risk for incident type 2 diabetes (hazard ratio = 1.25, 95% confidence interval: 1.05-1.48, P for trend = 0.011). However, baseline thyroid-stimulating hormone level and tertile were not associated with the risk for diabetes. Prominent increase in thyroid-stimulating hormone concentration can be an additional risk factor for the development of type 2 diabetes in euthyroid subjects.

Implementation and Performance of Factorized Back projection on Low-Cost Commercial-Off-the-Shelf Hardware

DTIC Science & Technology

performance on a low cost, low size, weight, and power (SWAP) computer : a Raspberry Pi Model B. For a comparison of performance, a baseline implementation...improvement factor of 2-3 compared to filtered backprojection. Execution on a single Raspberry Pi is too slow for real-time imaging. However, factorized...backprojection is easily parallelized, and we include a discussion of parallel implementation across multiple Pis .

Effects of the Practiced Routines Parent Training Program on Behavioral Strategy Use, Parental Well-Being, and Child Challenging Behavior in Parents of Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Raulston, Tracy Jane

2017-01-01

In this study, a concurrent randomized multiple baseline across three parent-child dyads single-case design was employed to evaluate the effects of a brief three-week parent training program, titled Practiced Routines. The Practiced Routines parent training program included positive behavior supports (PBS) and mindfulness strategies within the…

Extended H2 synthesis for multiple degree-of-freedom controllers

NASA Technical Reports Server (NTRS)

Hampton, R. David; Knospe, Carl R.

1992-01-01

H2 synthesis techniques are developed for a general multiple-input-multiple-output (MIMO) system subject to both stochastic and deterministic disturbances. The H2 synthesis is extended by incorporation of anticipated disturbances power-spectral-density information into the controller-design process, as well as by frequency weightings of generalized coordinates and control inputs. The methodology is applied to a simple single-input-multiple-output (SIMO) problem, analogous to the type of vibration isolation problem anticipated in microgravity research experiments.

Long-term natalizumab treatment is associated with sustained improvements in quality of life in patients with multiple sclerosis.

PubMed

Foley, John F; Nair, Kavita V; Vollmer, Timothy; Stephenson, Judith J; Niecko, Timothy; Agarwal, Sonalee S; Watson, Crystal

2017-01-01

Multiple sclerosis (MS) patients experience lower health-related quality of life (HRQoL) than the general population. In clinical trials, natalizumab significantly improved HRQoL and reduced relapse rates and disability progression in patients with relapsing MS. In a 1-year analysis of patients included in the current study, HRQoL improvement occurred within 3 months of natalizumab initiation and continued for 1 year thereafter. However, natalizumab's long-term efficacy in improving HRQoL has not been studied. In this longitudinal, observational, single-arm US study, HRQoL and treatment satisfaction were evaluated in MS patients receiving intravenous natalizumab 300 mg every 4 weeks in clinical settings. Patients completed surveys at baseline and every 6 months for 3 years and reported the following measures: Short Form-12 Version 2 (SF-12v2), Multiple Sclerosis Impact Scale (MSIS-29), and Treatment Satisfaction Questionnaire for Medication. In this study, 120 patients completed ≥3 years of natalizumab treatment. Significant HRQoL improvements were evident from baseline to year 3 by increases in SF-12v2 Physical Component Summary (PCS) and Mental Component Summary scores ( P <0.01) and decreases in MSIS-29 physical and psychological scores ( P <0.0001). Patients with less physical disability (baseline Disease Steps [DS] 0-2) had significant improvement from baseline to year 3 in SF-12v2 PCS ( P <0.05) and MSIS-29 physical scores ( P <0.05). Physical HRQoL outcomes in patients with baseline DS 3-6 remained stable over 3 years. Treatment satisfaction increased significantly from baseline to year 1 ( P <0.0001) and was maintained in the following 2 years. Patients reported physical and psychological HRQoL improvements over 3 years of natalizumab treatment, supporting the long-term efficacy of natalizumab in real-world settings. Lower baseline disease activity and earlier treatment were related to better outcomes, indicating the importance of starting natalizumab early in the disease course. Treatment satisfaction increased after natalizumab initiation and remained high over 3 years of treatment.

Magnetic MIMO Signal Processing and Optimization for Wireless Power Transfer

NASA Astrophysics Data System (ADS)

Yang, Gang; Moghadam, Mohammad R. Vedady; Zhang, Rui

2017-06-01

In magnetic resonant coupling (MRC) enabled multiple-input multiple-output (MIMO) wireless power transfer (WPT) systems, multiple transmitters (TXs) each with one single coil are used to enhance the efficiency of simultaneous power transfer to multiple single-coil receivers (RXs) by constructively combining their induced magnetic fields at the RXs, a technique termed "magnetic beamforming". In this paper, we study the optimal magnetic beamforming design in a multi-user MIMO MRC-WPT system. We introduce the multi-user power region that constitutes all the achievable power tuples for all RXs, subject to the given total power constraint over all TXs as well as their individual peak voltage and current constraints. We characterize each boundary point of the power region by maximizing the sum-power deliverable to all RXs subject to their minimum harvested power constraints. For the special case without the TX peak voltage and current constraints, we derive the optimal TX current allocation for the single-RX setup in closed-form as well as that for the multi-RX setup. In general, the problem is a non-convex quadratically constrained quadratic programming (QCQP), which is difficult to solve. For the case of one single RX, we show that the semidefinite relaxation (SDR) of the problem is tight. For the general case with multiple RXs, based on SDR we obtain two approximate solutions by applying time-sharing and randomization, respectively. Moreover, for practical implementation of magnetic beamforming, we propose a novel signal processing method to estimate the magnetic MIMO channel due to the mutual inductances between TXs and RXs. Numerical results show that our proposed magnetic channel estimation and adaptive beamforming schemes are practically effective, and can significantly improve the power transfer efficiency and multi-user performance trade-off in MIMO MRC-WPT systems.

Self-Monitoring Checklists for Inquiry Problem-Solving: Functional Problem-Solving Methods for Students with Intellectual Disability

ERIC Educational Resources Information Center

Miller, Bridget; Taber-Doughty, Teresa

2014-01-01

Three students with mild to moderate intellectual and multiple disability, enrolled in a self-contained functional curriculum class were taught to use a self-monitoring checklist and science notebook to increase independence in inquiry problem-solving skills. Using a single-subject multiple-probe design, all students acquired inquiry…

Strengthening transversus abdominis in pregnancy related pelvic pain: the pressure biofeedback stabilization training.

PubMed

Rajalakshmi, Dharmarajan; Senthil Kumar, N Sundaramurthy

2012-05-28

Pregnancy related pelvic pain (PRPP) refers to musculoskeletal type of persistent posterior pelvic pain during and after pregnancy with feature of reduced endurance capacity for standing, walking and sitting which leads to severe discomfort and considerable impairment of daily activities. To test the effect of pressure biofeedback stabilizer training, on the pain and dysfunction of a thirty year old subject who presented with PRPP. Single case design. Oswestry pain and disability index, TrA efficacy. An initial assessment was followed by treatment sessions which consist of 2 phases (Phase A & Phase B). The baseline phase (A) consists of conventional therapeutic exercises while the intervention phase (B) consists of pressure biofeedback training in conjunction with the conventional therapeutic exercises. The study data demonstrated that the subject showed minimal improvement in pain, disability and TrA efficacy during the baseline phase and shown a steady improvement in all these variables during the intervention phase. Core muscle performance (TrA) can be retrained with pressure biofeedback stabilization training program in subject with PRPP thereby reducing pain and disability.

A Developmental Neuroscience of Borderline Pathology: Emotion Dysregulation and Social Baseline Theory

PubMed Central

Hughes, Amy E.; Crowell, Sheila E.; Uyeji, Lauren; Coan, James A.

2011-01-01

Theoretical and empirical research has linked poor emotion regulation abilities with dysfunctional frontolimbic circuitry. Consistent with this, research on borderline personality disorder (BPD) finds that frontolimbic dysfunction is a predominant neural substrate underlying the disorder. Emotion regulation is profoundly compromised in BPD. However, BPD is also associated with broad impairment across multiple domains, including impulse control, interpersonal relationships, and cognitive functioning. To date, BPD research has focused largely on single areas of dysfunction, failing to account for overlap at either the biological or behavioral levels of analysis. We examine the literature on frontolimbic dysfunction in BPD within the context of Coan’s social baseline theory. Social baseline theory proposes that healthy human functioning is dependent upon adequate social support and that, at baseline, biological systems are adapted to operate interdependently rather than independently. The social baseline perspective is particularly useful for understanding borderline personality development because the impulsive and emotionally dysregulated behaviors common among those with BPD occur almost invariably within an interpersonal context. We discuss clinical and research implications of this work. PMID:21845379

Primary prevention of overweight in children and adolescents: a meta-analysis of the effectiveness of interventions aiming to decrease sedentary behaviour

PubMed Central

2012-01-01

The objectives of this meta-analysis were to provide an overview of the evidence regarding the effects of interventions, implemented in the school- and general population setting, aiming to prevent excessive sedentary behaviour in children and adolescents on (1) the amount of sedentary behaviour and (2) BMI. Differences in effects on sedentary behaviour and BMI between single health behaviour interventions (sedentary behaviour only) and multiple health behaviour interventions were explored. A literature search was conducted in PubMed, EMBASE, Web of Science, PsycINFO and Cochrane Database of Systematic Reviews. Thirty-four (R)CT studies evaluating 33 general population interventions, published between 1990 and April 2011, aiming to decrease sedentary behaviour in normal weight children or adolescents (0–18 years) were included. Intervention duration ranged from 7 days to 4 years. Mean change in sedentary behaviour and BMI from baseline to post-intervention was calculated using a random effects model. Results showed significant decreases for the amount of sedentary behaviour and BMI. For sedentary behaviour the post-intervention mean difference was −17.95 min/day (95%CI:-26.61;–9.28); the change-from-baseline mean difference was −20.44 min/day (95%CI:-30.69;–10.20). For BMI the post-intervention mean difference was −0.25 kg/m² (95%CI:-0.40;–0.09); the change-from-baseline mean difference was −0.14 kg/m² (95%CI:-0.23;–0.05). No differences were found between single and multiple health behaviour interventions. Interventions in the school- and general population setting aiming to reduce only sedentary behaviour and interventions targeting multiple health behaviours can result in significant decreases in sedentary behaviour. Studies need to increase follow-up time to estimate the sustainability of the intervention effects found. PMID:22640437

Pharmacokinetics and safety of vitamin E δ-tocotrienol after single and multiple doses in healthy subjects with measurement of vitamin E metabolites.

PubMed

Mahipal, Amit; Klapman, Jason; Vignesh, Shivakumar; Yang, Chung S; Neuger, Anthony; Chen, Dung-Tsa; Malafa, Mokenge P

2016-07-01

Vitamin E delta-tocotrienol (VEDT) has demonstrated chemopreventive and antineoplastic activity in preclinical models. The aim of our study was to determine the safety and pharmacokinetics of VEDT and its metabolites after single- and multiple-dose administrations in healthy subjects. Thirty-six subjects received from 100 to 1600 mg of oral VEDT as a single dose or twice daily for 14 consecutive days. A 3 + 3 dose escalation design was utilized. Pharmacokinetic data were derived from high-performance liquid chromatography (HPLC) assays. Serial blood and urine samples were collected before and during VEDT administration, with serum and urine metabolites assessed using HPLC. No drug-related adverse events were observed. Pharmacokinetic parameters for single and multiple doses were, respectively, as follows (shown as range): time to maximum concentration of 4-9.3 and 4.7-7.3 h, maximum concentration of 795.6-3742.6 and 493.3-3746 ng/mL, half-life of 1.7-5.9 and 2.3-6.9 h, and 0-12 h area under the curve of 4518.7-20,781.4 and 1987.7-22,171.2 ng h/mL. Plasma tocotrienols were significantly increased after VEDT administration, indicating oral bioavailability of VEDT in humans. Plasma and urine levels of metabolites, δ-carboxyethyl hydroxychroman, and δ-carboxymethylbutyl hydroxychroman were elevated after VEDT administration in a dose-dependent manner and were 30-60 times significantly higher than δ-tocotrienol levels. VEDT can be safely administered at doses up to 1600 mg twice daily. Plasma VEDT concentrations were comparable to those obtained in VEDT-treated mice in which tumor growth was delayed. Our results suggest that VEDT can be safely consumed by healthy subjects and achieve bioactive levels, supporting the investigation of VEDT for chemoprevention.

Effect of Contralateral Strength Training on Muscle Weakness in People With Multiple Sclerosis: Proof-of-Concept Case Series.

PubMed

Manca, Andrea; Cabboi, Maria Paola; Ortu, Enzo; Ginatempo, Francesca; Dragone, Daniele; Zarbo, Ignazio Roberto; de Natale, Edoardo Rosario; Mureddu, Giovanni; Bua, Guido; Deriu, Franca

2016-06-01

The contralateral strength training (CST) effect is a transfer of muscle performance to the untrained limb following training of the contralateral side. The aim of this study was to explore, in individuals with multiple sclerosis (MS) presenting marked lower limb strength asymmetry, the effectiveness of CST on management of muscle weakness of the more-affected limb following training of the less-affected limb. A single-subject research design was used. Eight individuals with MS underwent 16 to 18 high-intensity training sessions of the less-affected ankle dorsiflexor muscles. The primary outcome measure of this single-system case series was maximal strength expressed as peak moment and maximal work. Secondary outcome measures were: Six-Minute-Walk Test, Timed "Up & Go" Test, 10-Meter Timed Walk Test, and Multiple Sclerosis Quality of Life-54 questionnaire. After the 6-week intervention, the contralateral more affected (untrained) limb showed a 22% to 24% increase in maximal strength. From pretest-posttest measurements, participants also performed significantly better on the clinical and functional secondary outcome measures. At the 12-week follow-up, the strength levels of the weaker untrained limb remained significantly superior to baseline levels in the majority (5 out of 8) of the outcome parameters. Considering the design used, the absence of a control group, and the sample size, these findings should be cautiously generalized and will need confirmation in a properly planned randomized controlled trial. The present proof-of-concept study shows, for the first time, the occurrence of the CST effect on muscle performance of ankle dorsiflexor muscles in people with MS. These preliminary findings reveal new potential implications for CST as a promising rehabilitation approach to those conditions where unilateral muscle weakness does not allow or makes difficult performing conventional strength training of the weaker limb. © 2016 American Physical Therapy Association.

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...

Benefits and Drawbacks of Using Multiple Instructors to Teach Single Courses

ERIC Educational Resources Information Center

Jones, Francis; Harris, Sara

2012-01-01

We set out to identify the benefits and drawbacks of using more than one instructor to teach single section science courses at a large research university. Nine courses were investigated involving widely differing subjects and levels. Teaching models included: sequential teaching with two to six instructors each covering only their own modules,…

Acute effects of single and multiple level thoracic manipulations on chronic mechanical neck pain: a randomized controlled trial

PubMed Central

Puntumetakul, Rungthip; Suvarnnato, Thavatchai; Werasirirat, Phurichaya; Uthaikhup, Sureeporn; Yamauchi, Junichiro; Boucaut, Rose

2015-01-01

Background Thoracic spine manipulation has become a popular alternative to local cervical manipulative therapy for mechanical neck pain. This study investigated the acute effects of single-level and multiple-level thoracic manipulations on chronic mechanical neck pain (CMNP). Methods Forty-eight patients with CMNP were randomly allocated to single-level thoracic manipulation (STM) at T6–T7 or multiple-level thoracic manipulation (MTM), or to a control group (prone lying). Cervical range of motion (CROM), visual analog scale (VAS), and the Thai version of the Neck Disability Index (NDI-TH) scores were measured at baseline, and at 24-hour and at 1-week follow-up. Results At 24-hour and 1-week follow-up, neck disability and pain levels were significantly (P<0.05) improved in the STM and MTM groups compared with the control group. CROM in flexion and left lateral flexion were increased significantly (P<0.05) in the STM group when compared with the control group at 1-week follow-up. The CROM in right rotation was increased significantly after MTM compared to the control group (P<0.05) at 24-hour follow-up. There were no statistically significant differences in neck disability, pain level at rest, and CROM between the STM and MTM groups. Conclusion These results suggest that both single-level and multiple-level thoracic manipulation improve neck disability, pain levels, and CROM at 24-hour and 1-week follow-up in patients with CMNP. PMID:25624764

Long-term follow-up of echolalia and question answering.

PubMed

Foxx, R M; Faw, G D

1990-01-01

A long-term follow-up of echolalia and correct question answering was conducted for 6 subjects from three previously published studies. The follow-up periods ranged from 26 to 57 months. In a training site follow-up, subjects were exposed to baseline/posttraining conditions in which the original trainer and/or a novel person(s) presented trained and untrained questions. Four subjects displayed echolalia below baseline levels, and another did so in some assessments. Overall, echolalia was lower than in baseline in 80.6% of the follow-ups. Five subjects displayed correct responding above baseline levels. No clear differences were noted in correct responding or echolalia between the trainer and novel-person presentations or between trained and untrained questions. In a follow-up in a natural environment conducted by a novel person, lower than baseline levels of echolalia were displayed by 3 subjects; 2 subjects displayed lower than baseline levels in some assessments. Two subjects consistently displayed correct responding above baseline, and 3 did so occasionally. Issues related to the study of maintenance are discussed.

Long-term follow-up of echolalia and question answering.

PubMed Central

Foxx, R M; Faw, G D

1990-01-01

A long-term follow-up of echolalia and correct question answering was conducted for 6 subjects from three previously published studies. The follow-up periods ranged from 26 to 57 months. In a training site follow-up, subjects were exposed to baseline/posttraining conditions in which the original trainer and/or a novel person(s) presented trained and untrained questions. Four subjects displayed echolalia below baseline levels, and another did so in some assessments. Overall, echolalia was lower than in baseline in 80.6% of the follow-ups. Five subjects displayed correct responding above baseline levels. No clear differences were noted in correct responding or echolalia between the trainer and novel-person presentations or between trained and untrained questions. In a follow-up in a natural environment conducted by a novel person, lower than baseline levels of echolalia were displayed by 3 subjects; 2 subjects displayed lower than baseline levels in some assessments. Two subjects consistently displayed correct responding above baseline, and 3 did so occasionally. Issues related to the study of maintenance are discussed. PMID:2249974

An Open Label Clinical Trial of a Peptide Treatment Serum and Supporting Regimen Designed to Improve the Appearance of Aging Facial Skin.

PubMed

Draelos, Zoe Diana; Kononov, Tatiana; Fox, Theresa

2016-09-01

A 14-week single-center clinical usage study was conducted to test the efficacy of a peptide treatment serum and supporting skincare regimen in 29 women with mild to moderately photodamaged facial skin. The peptide treatment serum contained gamma-aminobutyric acid (GABA) and various peptides with neurotransmitter inhibiting and cell signaling properties. It was hypothesized that the peptide treatment serum would ameliorate eye and facial expression lines including crow's feet and forehead lines. The efficacy of the supporting skincare regimen was also evaluated. An expert investigator examined the subjects at rest and at maximum smile. Additionally, the subjects completed self-assessment questionnaires. At week 14, the expert investigator found a statistically significant improvement in facial lines, facial wrinkles, eye lines, and eye wrinkles at rest when compared to baseline results. The expert investigator also found statistically significant improvement at week 14 in facial lines, eye lines, and eye wrinkles when compared to baseline results at maximum smile. In addition, there was continued highly statistically significant improvement in smoothness, softness, firmness, radiance, luminosity, and overall appearance at rest when compared to baseline results at the 14-week time point. The test regimen was well perceived by the subjects for efficacy and product attributes. The products were well tolerated with no adverse events.

J Drugs Dermatol. 2016;15(9):1100-1106.

Analysis of the Physiological and Molecular Responses of Dunaliella salina to Macronutrient Deprivation

PubMed Central

Lv, Hexin; Cui, Xianggan; Wahid, Fazli; Xia, Feng; Zhong, Cheng; Jia, Shiru

2016-01-01

The halotolerant chlorophyte Dunaliella salina can accumulate up to 10% of its dry weight as β-carotene in chloroplasts when subjected to adverse conditions, including nutrient deprivation. However, the mechanisms of carotenoid biosynthesis are poorly understood. Here, the physiological and molecular responses to the deprivation of nitrogen (-N), sulfur (-S), phosphorus (-P) and different combinations of those nutrients (-N-P, -N-S, -P-S and -N-P-S) were compared to gain insights into the underlying regulatory mechanisms of carotenoid biosynthesis. The results showed that both the growth and photosynthetic rates of cells were decreased during nutrient deprivation, accompanied by lipid globule accumulation and reduced chlorophyll levels. The SOD and CAT activities of the cells were altered during nutrient deprivation, but their responses were different. The total carotenoid contents of cells subjected to multiple nutrient deprivation were higher than those of cells subjected to single nutrient deprivation and non-stressed cells. The β-carotene contents of cells subjected to -N-P, -N-S and -N-P-S were higher than those of cells subjected to single nutrient deprivation. Cells subjected to sulfur deprivation accumulated more lutein than cells subjected to nitrogen and phosphorous deprivation. In contrast, no cumulative effects of nutrient deprivation on the transcription of genes in the carotenogenic pathway were observed because MEP and carotenogenic pathway genes were up-regulated during single nutrient deprivation but were downregulated during multiple nutrient deprivation. Therefore, we proposed that the carotenoid biosynthesis pathway of D. salina is regulated at both the transcriptional and posttranscriptional levels and that a complex crosstalk occurs at the physiological and molecular levels in response to the deprivation of different nutrients. PMID:27023397

A single-bout of one-hour spinning exercise increases troponin T in healthy subjects.

PubMed

Duttaroy, Smita; Thorell, Daniel; Karlsson, Lena; Börjesson, Mats

2012-02-01

While long-term endurance exercise is known to increase cardiac biomarkers, only a few studies on short-term exercise and these markers have been reported. The aim of this study was to investigate the acute effects of a one-hour bicycle spinning on cardiac biomarkers in healthy individuals. Serum levels of high-sensitive troponin T (TnT), creatinine kinase MB fraction (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatinine kinase (CK) and myoglobin were measured at baseline, 1 and 24 hour after one hour of spinning exercise in ten healthy and fit (age 31.0 ± 6.6 years) individuals. TnT doubled one hour post-exercise (All values ≤ 5 - 9.7 ± 6.0 ng/L, p < 0.001). Two individuals had TnT levels above upper reference limit, URL (20.7 and 20.2 ng/L, URL = 12 ng/L). Myoglobin levels increased 72% one hour post-exercise (38 ± 20 - 66 ± 41 mg/L, p < 0.02). TnT and myoglobin levels returned to baseline 24 hour post-exercise. Serum levels of CK-MB, NT-proBNP and CK were not significantly changed. A single-bout of one-hour bicycle spinning transiently increases TnT and myoglobin in healthy subjects. Some subjects even have TnT release above URL. Thus, recently performed exercise also of short duration should be taken into consideration in the evaluation of acute chest pain with release of cardiac TnT.

Multi-Domain Transfer Learning for Early Diagnosis of Alzheimer's Disease.

PubMed

Cheng, Bo; Liu, Mingxia; Shen, Dinggang; Li, Zuoyong; Zhang, Daoqiang

2017-04-01

Recently, transfer learning has been successfully applied in early diagnosis of Alzheimer's Disease (AD) based on multi-domain data. However, most of existing methods only use data from a single auxiliary domain, and thus cannot utilize the intrinsic useful correlation information from multiple domains. Accordingly, in this paper, we consider the joint learning of tasks in multi-auxiliary domains and the target domain, and propose a novel Multi-Domain Transfer Learning (MDTL) framework for early diagnosis of AD. Specifically, the proposed MDTL framework consists of two key components: 1) a multi-domain transfer feature selection (MDTFS) model that selects the most informative feature subset from multi-domain data, and 2) a multi-domain transfer classification (MDTC) model that can identify disease status for early AD detection. We evaluate our method on 807 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using baseline magnetic resonance imaging (MRI) data. The experimental results show that the proposed MDTL method can effectively utilize multi-auxiliary domain data for improving the learning performance in the target domain, compared with several state-of-the-art methods.

Communication about emotions during storybook reading: Effects of an instruction programme for children with Down syndrome.

PubMed

Na, Ji Young; Wilkinson, Krista M

2017-08-07

Children with Down syndrome often have more restricted emotion expression and recognition skills than their peers who are developing typically, and potentially fewer opportunities to learn these skills. This study investigated the effect of the Strategies for Talking about Emotions as PartnerS (STEPS) programme on parents' provision of opportunities for emotion communication using visual communication supports. The study used a single-subject multiple-baseline across participants design with three parent-child dyads. Shared book reading was used as the context for parent instruction and data collection. Parents increased their use of the emotion communication strategies immediately following an instructional session, and continued to use them for the remaining phases of the study. In turn, the children participated more actively in the discussion by making comments about emotions when parents provided more opportunities. The STEPS instructional programme is effective for improving parents' provision of opportunities for discussing emotions during storybook reading with children who have Down syndrome. All parents indicated that they would use the strategy during future reading activities. This paper discusses the results of the study and directions for future research.

Multi-Domain Transfer Learning for Early Diagnosis of Alzheimer’s Disease

PubMed Central

Cheng, Bo; Liu, Mingxia; Li, Zuoyong

2017-01-01

Recently, transfer learning has been successfully applied in early diagnosis of Alzheimer’s Disease (AD) based on multi-domain data. However, most of existing methods only use data from a single auxiliary domain, and thus cannot utilize the intrinsic useful correlation information from multiple domains. Accordingly, in this paper, we consider the joint learning of tasks in multi-auxiliary domains and the target domain, and propose a novel Multi-Domain Transfer Learning (MDTL) framework for early diagnosis of AD. Specifically, the proposed MDTL framework consists of two key components: 1) a multi-domain transfer feature selection (MDTFS) model that selects the most informative feature subset from multi-domain data, and 2) a multidomain transfer classification (MDTC) model that can identify disease status for early AD detection. We evaluate our method on 807 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database using baseline magnetic resonance imaging (MRI) data. The experimental results show that the proposed MDTL method can effectively utilize multi-auxiliary domain data for improving the learning performance in the target domain, compared with several state-of-the-art methods. PMID:27928657

Effects of computer-based graphic organizers to solve one-step word problems for middle school students with mild intellectual disability: A preliminary study.

PubMed

Sheriff, Kelli A; Boon, Richard T

2014-08-01

The purpose of this study was to examine the effects of computer-based graphic organizers, using Kidspiration 3© software, to solve one-step word problems. Participants included three students with mild intellectual disability enrolled in a functional academic skills curriculum in a self-contained classroom. A multiple probe single-subject research design (Horner & Baer, 1978) was used to evaluate the effectiveness of computer-based graphic organizers to solving mathematical one-step word problems. During the baseline phase, the students completed a teacher-generated worksheet that consisted of nine functional word problems in a traditional format using a pencil, paper, and a calculator. In the intervention and maintenance phases, the students were instructed to complete the word problems using a computer-based graphic organizer. Results indicated that all three of the students improved in their ability to solve the one-step word problems using computer-based graphic organizers compared to traditional instructional practices. Limitations of the study and recommendations for future research directions are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional brain imaging of a complex navigation task following one night of total sleep deprivation

NASA Technical Reports Server (NTRS)

Strangman, Gary; Thompson, John H.; Strauss, Monica M.; Marshburn, Thomas H.; Sutton, Jeffrey P.

2006-01-01

Study Objectives: To assess the cerebral effects associated with sleep deprivation in a simulation of a complex, real-world, high-risk task. Design and Interventions: A two-week, repeated measures, cross-over experimental protocol, with counterbalanced orders of normal sleep (NS) and total sleep deprivation (TSD). Setting: Each subject underwent functional magnetic resonance imaging (fMRI) while performing a dual-joystick, 3D sensorimotor navigation task (simulated orbital docking). Scanning was performed twice per subject, once following a night of normal sleep (NS), and once following a single night of total sleep deprivation (TSD). Five runs (eight 24s docking trials each) were performed during each scanning session. Participants: Six healthy, young, right-handed volunteers (2 women; mean age 20) participated. Measurements and Results: Behavioral performance on multiple measures was comparable in the two sleep conditions. Neuroimaging results within sleep conditions revealed similar locations of peak activity for NS and TSD, including left sensorimotor cortex, left precuneus (BA 7), and right visual areas (BA 18/19). However, cerebral activation following TSD was substantially larger and exhibited higher amplitude modulations from baseline. When directly comparing NS and TSD, most regions exhibited TSD>NS activity, including multiple prefrontal cortical areas (BA 8/9,44/45,47), lateral parieto-occipital areas (BA 19/39, 40), superior temporal cortex (BA 22), and bilateral thalamus and amygdala. Only left parietal cortex (BA 7) demonstrated NS>TSD activity. Conclusions: The large network of cerebral differences between the two conditions, even with comparable behavioral performance, suggests the possibility of detecting TSD-induced stress via functional brain imaging techniques on complex tasks before stress-induced failures.

Within-day variability on short and long walking tests in persons with multiple sclerosis.

PubMed

Feys, Peter; Bibby, Bo; Romberg, Anders; Santoyo, Carme; Gebara, Benoit; de Noordhout, Benoit Maertens; Knuts, Kathy; Bethoux, Francois; Skjerbæk, Anders; Jensen, Ellen; Baert, Ilse; Vaney, Claude; de Groot, Vincent; Dalgas, Ulrik

2014-03-15

To compare within-day variability of short (10 m walking test at usual and fastest speed; 10MWT) and long (2 and 6-minute walking test; 2MWT/6MWT) tests in persons with multiple sclerosis. Observational study. MS rehabilitation and research centers in Europe and US within RIMS (European network for best practice and research in MS rehabilitation). Ambulatory persons with MS (Expanded Disability Status Scale 0-6.5). Subjects of different centers performed walking tests at 3 time points during a single day. 10MWT, 2MWT and 6MWT at fastest speed and 10MWT at usual speed. Ninety-five percent limits of agreement were computed using a random effects model with individual pwMS as random effect. Following this model, retest scores are with 95% certainty within these limits of baseline scores. In 102 subjects, within-day variability was constant in absolute units for the 10MWT, 2MWT and 6MWT at fastest speed (+/-0.26, 0.16 and 0.15m/s respectively, corresponding to +/-19.2m and +/-54 m for the 2MWT and 6MWT) independent on the severity of ambulatory dysfunction. This implies a greater relative variability with increasing disability level, often above 20% depending on the applied test. The relative within-day variability of the 10MWT at usual speed was +/-31% independent of ambulatory function. Absolute values of within-day variability on walking tests at fastest speed were independent of disability level and greater with short compared to long walking tests. Relative within-day variability remained overall constant when measured at usual speed. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

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.

eNOS Glu298Asp polymorphism and hypertension in a cohort study in Japanese.

PubMed

Kishimoto, Takuji; Misawa, Yumiko; Kaetu, Akihiko; Nagai, Maria; Osaki, Yoneatsu; Okamoto, Mikizoh; Yoshida, Soiti; Kurosawa, Yoichi; Fukumoto, Soji

2004-11-01

Some recent case-control association studies have suggested negative and positive relationship between Glu298Asp (the substitution of aspartic acid for glutamic acid at amino acid position 298) polymorphism of the endothelial nitric oxide synthase (eNOS) gene and hypertension. To investigate whether the Glu298Asp polymorphism of the eNOS gene affects the incidence of hypertension, a retrospective cohort study was performed. The baseline data among Japanese workers in Shimane Prefecture, Japan, were obtained at regular health examination in 1992, and a retrospective cohort study was performed to analyze the influence of Glu298Asp polymorphism on the incidence of hypertension in 1998. The incidences of Glu298Glu, Glu298Asp, and Asp298Asp genotypes in the subjects were 86.4%, 12.6% and 1.1%, respectively. The risk ratios of Glu298Asp and Asp298Asp against Glu298Glu for the incidence of hypertension by single variance analysis were 0.830 in total subjects [95% confidence interval (CI) 0.474-1.452], 0.596 in subjects 20-39 years old (95% CI; 0.207-1.717), and 0.915 in subjects 40-59 years old (95% CI; 0.464-1.805). The risk ratios of Glu298Asp and Asp298Asp against Glu298Glu for the incidence of hypertension by multiple variance analysis adjusted for sex, BMI, serum total cholesterol, serum high-density lipoprotein (HDL) cholesterol, fasting glucose, cigarette smoking, drinking habits, eating habits, and exercise in 1992 were 0.750 in total subjects (95% CI; 0.421-1.335), 0.505 in subjects 20-39 years old (95% CI; 0.170-1.496), and 0.873 in subjects 40-59 years old (95% CI; 0.434-1.757). These results suggested no association between the Glu298Asp gene polymorphism and the incidence of hypertension in this selected population.

Single versus multiple sets of resistance exercise: a meta-regression.

PubMed

Krieger, James W

2009-09-01

There has been considerable debate over the optimal number of sets per exercise to improve musculoskeletal strength during a resistance exercise program. The purpose of this study was to use hierarchical, random-effects meta-regression to compare the effects of single and multiple sets per exercise on dynamic strength. English-language studies comparing single with multiple sets per exercise, while controlling for other variables, were considered eligible for inclusion. The analysis comprised 92 effect sizes (ESs) nested within 30 treatment groups and 14 studies. Multiple sets were associated with a larger ES than a single set (difference = 0.26 +/- 0.05; confidence interval [CI]: 0.15, 0.37; p < 0.0001). In a dose-response model, 2 to 3 sets per exercise were associated with a significantly greater ES than 1 set (difference = 0.25 +/- 0.06; CI: 0.14, 0.37; p = 0.0001). There was no significant difference between 1 set per exercise and 4 to 6 sets per exercise (difference = 0.35 +/- 0.25; CI: -0.05, 0.74; p = 0.17) or between 2 to 3 sets per exercise and 4 to 6 sets per exercise (difference = 0.09 +/- 0.20; CI: -0.31, 0.50; p = 0.64). There were no interactions between set volume and training program duration, subject training status, or whether the upper or lower body was trained. Sensitivity analysis revealed no highly influential studies, and no evidence of publication bias was observed. In conclusion, 2 to 3 sets per exercise are associated with 46% greater strength gains than 1 set, in both trained and untrained subjects.

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.

UNIX programmer`s environment and configuration control

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

Arnold, T.R.; Wyatt, P.W.

1993-12-31

A package of UNIX utilities has been developed which unities the advantages of the public domain utility ``imake`` and a configuration control system. The ``imake`` utility is portable It allows a user to make Makefiles on a wide variety of platforms without worrying about the machine-dependent idiosyncracies of the UNIX utility ``make.`` Makefiles are a labor-saving device for compiling and linking complicated programs, and ``imake`` is a labor-saving device for making Makefiles, as well as other useful software (like a program`s internal dependencies on included files). This ``Environment,`` which has been developed around ``imake,`` allows a programmer to manage amore » complicated project consisting of multiple executables which may each link with multiple user-created libraries. The configuration control aspect consists of a directory hierarchy (a baseline) which is mirrored in a developer`s workspace. The workspace includes a minimum of files copied from the baseline; it employs soft links into the baseline wherever possible. The utilities are a multi-tiered suite of Bourne shells to copy or check out sources, check them back in, import new sources (sources which are not in the baseline) and link them appropriately, create new low-level directories and link them, compare with the baseline, update Makefiles with minimal effort, and handle dependencies. The directory hierarchy utilizes a single source repository, which is mirrored in the baseline and in a workspace for a several platform architectures. The system was originally written to support C code on Sun-4`s and RS6000`s. It has now been extended to support FORTRAN as well as C on SGI and Cray YMP platforms as well as Sun-4`s and RS6000`s.« less

Gender classification under extended operating conditions

NASA Astrophysics Data System (ADS)

Rude, Howard N.; Rizki, Mateen

2014-06-01

Gender classification is a critical component of a robust image security system. Many techniques exist to perform gender classification using facial features. In contrast, this paper explores gender classification using body features extracted from clothed subjects. Several of the most effective types of features for gender classification identified in literature were implemented and applied to the newly developed Seasonal Weather And Gender (SWAG) dataset. SWAG contains video clips of approximately 2000 samples of human subjects captured over a period of several months. The subjects are wearing casual business attire and outer garments appropriate for the specific weather conditions observed in the Midwest. The results from a series of experiments are presented that compare the classification accuracy of systems that incorporate various types and combinations of features applied to multiple looks at subjects at different image resolutions to determine a baseline performance for gender classification.

Comparison of Interferometric Time-Series Analysis Techniques with Implications for Future Mission Design

NASA Astrophysics Data System (ADS)

Werner, C. L.; Wegmuller, U.; Strozzi, T.; Wiesmann, A.

2006-12-01

Principle contributors to the noise in differential SAR interferograms are temporal phase stability of the surface, geometry relating to baseline and surface slope, and propagation path delay variations due to tropospheric water vapor and the ionosphere. Time series analysis of multiple interferograms generated from a stack of SAR SLC images seeks to determine the deformation history of the surface while reducing errors. Only those scatterers within a resolution element that are stable and coherent for each interferometric pair contribute to the desired deformation signal. Interferograms with baselines exceeding 1/3 the critical baseline have substantial geometrical decorrelation for distributed targets. Short baseline pairs with multiple reference scenes can be combined using least-squares estimation to obtain a global deformation solution. Alternately point-like persistent scatterers can be identified in scenes that do not exhibit geometrical decorrelation associated with large baselines. In this approach interferograms are formed from a stack of SAR complex images using a single reference scene. Stable distributed scatter pixels are excluded however due to the presence of large baselines. We apply both point- based and short-baseline methodologies and compare results for a stack of fine-beam Radarsat data acquired in 2002-2004 over a rapidly subsiding oil field near Lost Hills, CA. We also investigate the density of point-like scatters with respect to image resolution. The primary difficulty encountered when applying time series methods is phase unwrapping errors due to spatial and temporal gaps. Phase unwrapping requires sufficient spatial and temporal sampling. Increasing the SAR range bandwidth increases the range resolution as well as increasing the critical interferometric baseline that defines the required satellite orbital tube diameter. Sufficient spatial sampling also permits unwrapping because of the reduced phase/pixel gradient. Short time intervals further reduce the differential phase due to deformation when the deformation is continuous. Lower frequency systems (L- vs. C-Band) substantially improve the ability to unwrap the phase correctly by directly reducing both interferometric phase amplitude and temporal decorrelation.

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.

Multiple-Baseline Detection of a Geostationary Satellite with the Navy Precision Optical Interferometer

DTIC Science & Technology

2015-01-01

Multiple-baseline detection of a geostationary satellite with the Navy Precision Optical Interferometer J. Thomas Armstronga, Ellyn K. Bainesa...observations of a geostationary satellite using the Navy Precision Optical Inter- ferometer (NPOI) during the glint season of March 2015. We succeeded in...the second night. These baseline lengths correspond to a resolution of ∼4 m at geostationary altitude. This is the first multiple-baseline

Long-term outcomes of acute ischemic stroke patients treated with endovascular thrombectomy: A real-world experience.

PubMed

Zhao, Wenbo; Shang, Shuyi; Li, Chuanhui; Wu, Longfei; Wu, Chuanjie; Chen, Jian; Song, Haiqing; Zhang, Hongqi; Zhang, Yunzhou; Duan, Jiangang; Feng, Wuwei; Ji, Xunming

2018-07-15

Long-term follow-up of large trials have confirmed the superiority of endovascular thrombectomy (ET) for treating acute ischemic stroke (AIS). However, it is still unknown whether these results can be generalized to clinical practice. In this study, we aimed to determine the long-term outcomes of AIS post-ET in the real-world clinical practice. This observational study is based on a single-center prospective registry study. AIS patients were treated with second-generation stent retrievers from December 2012 to April 2016. The primary outcome was modified Ranks scale (mRS) at the time of the latest assessment. Favorable outcome was defined as mRS scores 0-2, and the unfavorable outcome was defined as mRS scores 3-6. Eighty-nine AIS subjects with large artery occlusion in anterior circulation undergoing ET were eligible for analysis. Median follow-up duration was 20 months (interquartile range 6-32), and 47 subjects (53%) achieved favorable outcome whereas 17 subjects (19%) were functional dependence and 25 subjects (28%) died. Independent predicators for long-term unfavorable outcome were higher baseline National Institutes of Health Stroke Scale (NIHSS) score (odd ratio:1.21;95% confidence interval 1.09-1.35; p < 0.001) and symptomatic intracerebral hemorrhage (sICH) (odd ratio:16.45;95% confidence interval 1.34-193.44; p = 0.026). More subjects of large-artery-atherosclerosis underwent permanent intracranial stenting (22%vs.10%) as compared with those of cardioembolism, while subjects of cardioembolism were more likely to experience sICH (13%vs.8%) and died (32%vs.16%). Over half of AIS patients can achieve favorable long-term outcomes post-ET. Higher baseline NIHSS scores and sICH are independently associated with unfavorable outcome. Overall, clinical practice in this single canter can replicate the long-term outcomes from the published endovascular clinical trials. Copyright © 2018 Elsevier B.V. All rights reserved.

Single-dose FTY720 pharmacokinetics, food effect, and pharmacological responses in healthy subjects

PubMed Central

Kovarik, John M; Schmouder, Robert; Barilla, Denise; Wang, Yibin; Kraus, Gerolf

2004-01-01

Aims FTY720 is a sphingosine-1-phosphate receptor agonist that redirects lymphocytes from the circulation to lymph nodes without impairing lymphocyte function. It is being developed as an immunomodulator for the prevention of acute rejection after organ transplantation. This study was performed to provide guidance on administration with respect to meals and to measure pharmacologic responses in healthy subjects. Methods In this randomized, two-period, crossover study, 14 healthy subjects received placebo on day −1 of each period with baseline circadian measurements of lymphocyte count and heart rate. Subjects subsequently received a single 1 mg oral dose of FTY720 on day 1 under fasting conditions and after a high fat meal. Blood FTY720 concentrations, lymphocyte count, and supine heart rate were assessed over an 8 day period after each FTY720 dose. The effect of food on FTY720 pharmacokinetics was assessed by standard bioequivalence testing. Results Both the peak concentration (0.65 ± 0.17 vs 0.64 ± 0.18 ng ml−1) and total exposure (AUC 149 ± 65 vs 139 ± 43 ng ml−1 h) did not differ significantly between fasting and fed states, respectively. The corresponding fed/fasting ratios and 90% confidence intervals were 1.00 (0.86, 1.17) for Cmax and 0.98 (0.86, 1.11) for AUC. Under both treatment conditions peripheral blood lymphocyte count decreased from baseline by 38 ± 9% over the first 2 days postdose and then increased towards predose values over the subsequent week. Whereas a circadian rhythm in supine heart rate was preserved in the presence of FTY720, the heart rate vs time curve was shifted downwards by 10% over the first day postdose and then recovered to prestudy values by days 3–5 postdose. These changes were asymptomatic. Conclusions Single 1 mg doses of FTY720 were well tolerated in healthy subjects and elicited a moderate decrease in peripheral blood lymphocyte count and a transient decrease in heart rate consistent with its pharmacological mode of action. FTY720 may be administered without regard to the timing of meals or their fat content. PMID:15089811

Housing First improves subjective quality of life among homeless adults with mental illness: 12-month findings from a randomized controlled trial in Vancouver, British Columbia.

PubMed

Patterson, Michelle; Moniruzzaman, Akm; Palepu, Anita; Zabkiewicz, Denise; Frankish, Charles J; Krausz, Michael; Somers, Julian M

2013-08-01

This study used an experimental design to examine longitudinal changes in subjective quality of life (QoL) among homeless adults with mental illness after assignment to different types of supported housing or to treatment as usual (TAU, no housing or supports through the study). We hypothesized that subjective QoL would improve over time among participants assigned to supported housing as compared to TAU, regardless of the type of supported housing received or participants' level of need. Participants (n = 497) were stratified by level of need ("high" or "moderate") and randomly assigned to Housing First (HF) in scattered-site apartments, HF in a congregate setting (high needs only), or TAU. Linear mixed-effects regression was used to model the association between study arm and self-reported QoL at baseline and at 6 and 12 months post-baseline by need level. Based on the adjusted overall score on the QoL measure, participants randomized to HF reported significantly greater overall QoL as compared to TAU, regardless of need level or type of supported housing at both 6 and 12 months post-baseline. Scores on the safety and living situation subscales were significantly greater for both high and moderate need participants assigned to supported housing regardless of type at both 6 and 12 months post-baseline as compared to TAU. Despite multiple health and social challenges faced by homeless individuals with mental illness, HF in both scattered-site and congregate models results in significantly greater perceived QoL as compared to individuals who do not receive HF even after a relatively short period of time.

A Hough transform global probabilistic approach to multiple-subject diffusion MRI tractography.

PubMed

Aganj, Iman; Lenglet, Christophe; Jahanshad, Neda; Yacoub, Essa; Harel, Noam; Thompson, Paul M; Sapiro, Guillermo

2011-08-01

A global probabilistic fiber tracking approach based on the voting process provided by the Hough transform is introduced in this work. The proposed framework tests candidate 3D curves in the volume, assigning to each one a score computed from the diffusion images, and then selects the curves with the highest scores as the potential anatomical connections. The algorithm avoids local minima by performing an exhaustive search at the desired resolution. The technique is easily extended to multiple subjects, considering a single representative volume where the registered high-angular resolution diffusion images (HARDI) from all the subjects are non-linearly combined, thereby obtaining population-representative tracts. The tractography algorithm is run only once for the multiple subjects, and no tract alignment is necessary. We present experimental results on HARDI volumes, ranging from simulated and 1.5T physical phantoms to 7T and 4T human brain and 7T monkey brain datasets. Copyright © 2011 Elsevier B.V. All rights reserved.

Microprocessor-based cardiotachometer

NASA Technical Reports Server (NTRS)

Crosier, W. G.; Donaldson, J. A.

1981-01-01

Instrument operates reliably even with stress-test electrocardiogram (ECG) signals subject to noise, baseline wandering, and amplitude change. It records heart rate from preamplified, single-lead ECG input signal and produces digital and analog heart-rate outputs which are fed elsewhere. Analog hardware processes ECG input signal, producing 10-ms pulse for each heartbeat. Microprocessor analyzes resulting pulse train, identifying irregular heartbeats and maintaining stable output during lead switching. Easily modified computer program provides analysis.

Clinical Assessment of Immediate and Long-Term Effects of a Two-Step Topical Hyaluronic Acid Lip Treatment.

PubMed

Makino, Elizabeth T; Tan, Priscilla; Qian, Kun; Babcock, Michael; Mehta, Rahul C

2017-04-01

Key features of lip aging include loss of volume, color, and definition as well as increases in lines/wrinkles and uneven skin texture. A single-center, open-label clinical study was conducted to assess the efficacy and tolerability of a novel, topical two-step lip treatment (HA5 LS) in female subjects presenting with mild to moderate lip dryness and mild to severe lip condition. Subjects were instructed to apply HA5 LS at least three times a day to ensure coverage 8 hours a day for four weeks. Clinical assessments for efficacy and tolerability were conducted at baseline, baseline post-application, week 2, and week 4. Standardized digital photography, subject self-assessment questionnaires, and instrumentation measurements for skin hydration (corneometer) and lip plumpness (digital caliper) were also conducted. Thirty-six female subjects aged 22-40 years enrolled in the study. HA5 LS provided instant and long term effects, achieving significant improvements in all clinical grading parameters including lip texture, color, definition/contour, scaling, cupping, lines/wrinkles, lip plumpness, and overall lip condition from baseline post-application to week 4 (all P less than equal to .001; Wilcoxon signed-rank test). Instrumentation measurements for hydration and digital caliper at weeks 2 and 4 were also significant (all P less than equal to .032; paired t-test). HA5 LS was also well-tolerated and highly-rated by subjects throughout the study duration. Results from this study suggest that HA5 LS addresses the key features of lip aging, providing both instant and long-term benefits.

J Drugs Dermatol. 2017;16(4):366-371.

Resource utilization with insulin pump therapy for type 2 diabetes mellitus.

PubMed

Lynch, Peter M; Riedel, Aylin Altan; Samant, Navendu; Fan, Ying; Peoples, Tim; Levinson, Jennifer; Lee, Scott W

2010-01-01

To evaluate the effects of switching from multiple daily injection (MDI) therapy to insulin pump therapy, also called continuous subcutaneous insulin infusion (CSII), on antidiabetic drug and healthcare resource utilization. This study was a retrospective analysis of administrative claims data from a large geographically diverse health plan in the United States from January 1, 2005, through April 30, 2008. Changes in antidiabetic drug use, antidiabetic drug switching and augmentation, and healthcare utilization during the baseline period and after CSII initiation were assessed using paired t test. There were 3649 possible subjects, of whom 943 met the criteria for analysis. The mean number of antidiabetic drugs used decreased by 46% after CSII initiation, and the mean reduction in antidiabetic drug utilization was 0.67; both were statistically significant. More than one-third of subjects who were taking antidiabetic drugs before CSII initiation discontinued oral therapy after CSII initiation. The number of subjects using multiple antidiabetic drugs significantly decreased after CSII initiation by 58%, and rates of switching or augmenting significantly decreased from 42% at baseline to 25% after CSII initiation.The rates of emergency department visits and inpatient admissions significantly decreased, and the rate of ambulatory visits significantly increased. CSII was associated with significant decreases in antidiabetic drug and healthcare resource utilization, contributing to stability of care. The evidence from this study indicates that CSII should be considered as an option for patients with type 2 diabetes mellitus who are using MDI and are experiencing a high degree of antidiabetic drug and healthcare resource utilization.

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.

Abdominal adiposity is the main determinant of the C-reactive response to injury in subjects undergoing inguinal hernia repair

PubMed Central

2013-01-01

Background Obesity and serum C-reactive protein (CRP) (a sensitive marker of inflammatory activity) are associated with most chronic diseases. Abdominal adiposity along with age is the strongest determinant of baseline CRP levels in healthy subjects. The mechanism of the association of serum CRP with disease is uncertain. We hypothesized that baseline serum CRP is a marker of inflammatory responsiveness to injury and that abdominal adiposity is the main determinant of this responsiveness. We studied the effect of abdominal adiposity, age and other environmental risk factors for chronic disease on the CRP response to a standardised surgical insult, unilateral hernia repair to not only test this hypothesis but to inform the factors which must be taken into account when assessing systemic inflammatory responses to surgery. Methods 102 male subjects aged 24-94 underwent unilateral hernia repair by a single operator. CRP was measured at 0, 6, 24 and 48 hrs. Response was defined as the peak CRP adjusted for baseline CRP. Results Age and waist:hip ratio (WHR) were associated both with basal CRP and CRP response with similar effect sizes after adjustment for a wide-range of covariates. The adjusted proportional difference in CRP response per 10% increase in WHR was 1.50 (1.17-1.91) p = 0.0014 and 1.15(1.00-1.31) p = 0.05 per decade increase in age. There was no evidence of important effects of other environmental cardiovascular risk factors on CRP response. Conclusion Waist:hip ratio and age need to be considered when studying the inflammatory response to surgery. The finding that age and waist:hip ratio influence baseline and post-operative CRP levels to a similar extent suggests that baseline CRP is a measure of inflammatory responsiveness to casual stimuli and that higher age and obesity modulate the generic excitability of the inflammatory system leading to both higher baseline CRP and higher CRP response to surgery. The mechanism for the association of baseline CRP and waist:hip ratio to chronic disease outcomes could be through this increase in inflammatory system excitability. PMID:23391158

Quantifying the test-retest reliability of cerebral blood flow measurements in a clinical model of on-going post-surgical pain: A study using pseudo-continuous arterial spin labelling.

PubMed

Hodkinson, Duncan J; Krause, Kristina; Khawaja, Nadine; Renton, Tara F; Huggins, John P; Vennart, William; Thacker, Michael A; Mehta, Mitul A; Zelaya, Fernando O; Williams, Steven C R; Howard, Matthew A

2013-01-01

Arterial spin labelling (ASL) is increasingly being applied to study the cerebral response to pain in both experimental human models and patients with persistent pain. Despite its advantages, scanning time and reliability remain important issues in the clinical applicability of ASL. Here we present the test-retest analysis of concurrent pseudo-continuous ASL (pCASL) and visual analogue scale (VAS), in a clinical model of on-going pain following third molar extraction (TME). Using ICC performance measures, we were able to quantify the reliability of the post-surgical pain state and ΔCBF (change in CBF), both at the group and individual case level. Within-subject, the inter- and intra-session reliability of the post-surgical pain state was ranked good-to-excellent (ICC > 0.6) across both pCASL and VAS modalities. The parameter ΔCBF (change in CBF between pre- and post-surgical states) performed reliably (ICC > 0.4), provided that a single baseline condition (or the mean of more than one baseline) was used for subtraction. Between-subjects, the pCASL measurements in the post-surgical pain state and ΔCBF were both characterised as reliable (ICC > 0.4). However, the subjective VAS pain ratings demonstrated a significant contribution of pain state variability, which suggests diminished utility for interindividual comparisons. These analyses indicate that the pCASL imaging technique has considerable potential for the comparison of within- and between-subjects differences associated with pain-induced state changes and baseline differences in regional CBF. They also suggest that differences in baseline perfusion and functional lateralisation characteristics may play an important role in the overall reliability of the estimated changes in CBF. Repeated measures designs have the important advantage that they provide good reliability for comparing condition effects because all sources of variability between subjects are excluded from the experimental error. The ability to elicit reliable neural correlates of on-going pain using quantitative perfusion imaging may help support the conclusions derived from subjective self-report.

A randomized comparative trial of continued abacavir/lamivudine plus efavirenz or replacement with efavirenz/emtricitabine/tenofovir DF in hypercholesterolemic HIV-1 infected individuals.

PubMed

Moyle, Graeme J; Orkin, Chloe; Fisher, Martin; Dhar, Jyoti; Anderson, Jane; Wilkins, Edmund; Ewan, Jacqueline; Ebrahimi, Ramin; Wang, Hui

2015-01-01

Drug choice and metabolic changes with antiretroviral therapy contribute to cardiovascular risk in persons with HIV-1 infection. A randomized, 12 week, open-label, comparative study of the impact on lipids of continuation of abacavir/lamivudine (ABC/3TC) plus efavirenz (EFV) or replacement with the single tablet regimen of EFV/emtricitabine/tenofovir DF (EFV/FTC/TDF) in hypercholesterolaemic subjects on successful antiretroviral therapy, with a 12-week extension with all subjects on EFV/FTC/TDF. 157 subjects received study drug, 79 switched to EFV/FTC/TDF and 78 subjects continued ABC/3TC+EFV. At Week 12, 73 subjects on ABC/3TC+EFV switched to EFV/FTC/TDF. The switch was well tolerated and no subject experienced viral rebound. Median baseline fasting total cholesterol was 6.32 mmol/L. 12 weeks following switch, the difference in the means (LSM) between treatment groups (EFV/FTC/TDF minus ABC/3TC+EFV) in total cholesterol change from baseline was -0.74 mmol/l (95% CI -1.00, -0.47, p < 0.001). The median change from baseline in total cholesterol following switch in the EFV/FTC/TDF arm was -0.86 mmol/l (p < 0.001) compared with +0.01 mmol/l (p = 0.45) in the continuation arm at Week 12. Significant (p < 0.001) differences between treatment groups following switch were seen for all lipid fractions from baseline to Week 12: LDL cholesterol (-0.47 mmol/L [-0.70, -0.25]), HDL cholesterol (-0.15 mmol/L [-0.21, -0.08]), triglycerides (-0.43 mmol/L [-0.75, -0.11]), and non HDL cholesterol (-0.56 mmol/L [-0.80, -0.31]). In the extension phase, similar declines in total cholesterol were observed with a median change from Week 12 to Week 24 of -0.73 mmol/L (p < 0.001). Switching from ABC/3TC+EFV to EFV/FTC/TDF in persons with hypercholesterolemia maintains virological control and significantly improves key lipid parameters. ClinicalTrials.gov NCT00615810.

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

Does robot-assisted gait training ameliorate gait abnormalities in multiple sclerosis? A pilot randomized-control trial.

PubMed

Straudi, S; Benedetti, M G; Venturini, E; Manca, M; Foti, C; Basaglia, N

2013-01-01

Gait disorders are common in multiple sclerosis (MS) and lead to a progressive reduction of function and quality of life. Test the effects of robot-assisted gait rehabilitation in MS subjects through a pilot randomized-controlled study. We enrolled MS subjects with Expanded Disability Status Scale scores within 4.5-6.5. The experimental group received 12 robot-assisted gait training sessions over 6 weeks. The control group received the same amount of conventional physiotherapy. Outcomes measures were both biomechanical assessment of gait, including kinematics and spatio-temporal parameters, and clinical test of walking endurance (six-minute walk test) and mobility (Up and Go Test). 16 subjects (n = 8 experimental group, n = 8 control group) were included in the final analysis. At baseline the two groups were similar in all variables, except for step length. Data showed walking endurance, as well as spatio-temporal gait parameters improvements after robot-assisted gait training. Pelvic antiversion and reduced hip extension during terminal stance ameliorated after aforementioned intervention. Robot-assisted gait training seems to be effective in increasing walking competency in MS subjects. Moreover, it could be helpful in restoring the kinematic of the hip and pelvis.

Scalable multi-sample single-cell data analysis by Partition-Assisted Clustering and Multiple Alignments of Networks

PubMed Central

Samusik, Nikolay; Wang, Xiaowei; Guan, Leying; Nolan, Garry P.

2017-01-01

Mass cytometry (CyTOF) has greatly expanded the capability of cytometry. It is now easy to generate multiple CyTOF samples in a single study, with each sample containing single-cell measurement on 50 markers for more than hundreds of thousands of cells. Current methods do not adequately address the issues concerning combining multiple samples for subpopulation discovery, and these issues can be quickly and dramatically amplified with increasing number of samples. To overcome this limitation, we developed Partition-Assisted Clustering and Multiple Alignments of Networks (PAC-MAN) for the fast automatic identification of cell populations in CyTOF data closely matching that of expert manual-discovery, and for alignments between subpopulations across samples to define dataset-level cellular states. PAC-MAN is computationally efficient, allowing the management of very large CyTOF datasets, which are increasingly common in clinical studies and cancer studies that monitor various tissue samples for each subject. PMID:29281633

Coffee and Green Tea Consumption and Subsequent Risk of Malignant Lymphoma and Multiple Myeloma in Japan: The Japan Public Health Center-based Prospective Study.

PubMed

Ugai, Tomotaka; Matsuo, Keitaro; Sawada, Norie; Iwasaki, Motoki; Yamaji, Taiki; Shimazu, Taichi; Sasazuki, Shizuka; Inoue, Manami; Kanda, Yoshinobu; Tsugane, Shoichiro

2017-08-01

Background: The aim of this study was to investigate the association of coffee and green tea consumption and the risk of malignant lymphoma and multiple myeloma in a large-scale population-based cohort study in Japan. Methods: In this analysis, a total of 95,807 Japanese subjects (45,937 men and 49,870 women; ages 40-69 years at baseline) of the Japan Public Health Center-based Prospective Study who completed a questionnaire about their coffee and green tea consumption were followed up until December 31, 2012, for an average of 18 years. HRs and 95% confidence intervals were estimated using a Cox regression model adjusted for potential confounders as a measure of association between the risk of malignant lymphoma and multiple myeloma associated with coffee and green tea consumption at baseline. Results: During the follow-up period, a total of 411 malignant lymphoma cases and 138 multiple myeloma cases were identified. Overall, our findings showed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma for both sexes. Conclusions: In this study, we observed no significant association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma. Impact: Our results do not support an association between coffee or green tea consumption and the risk of malignant lymphoma or multiple myeloma. Cancer Epidemiol Biomarkers Prev; 26(8); 1352-6. ©2017 AACR . ©2017 American Association for Cancer Research.

Mission control of multiple unmanned aerial vehicles: a workload analysis.

PubMed

Dixon, Stephen R; Wickens, Christopher D; Chang, Dervon

2005-01-01

With unmanned aerial vehicles (UAVs), 36 licensed pilots flew both single-UAV and dual-UAV simulated military missions. Pilots were required to navigate each UAV through a series of mission legs in one of the following three conditions: a baseline condition, an auditory autoalert condition, and an autopilot condition. Pilots were responsible for (a) mission completion, (b) target search, and (c) systems monitoring. Results revealed that both the autoalert and the autopilot automation improved overall performance by reducing task interference and alleviating workload. The autoalert system benefited performance both in the automated task and mission completion task, whereas the autopilot system benefited performance in the automated task, the mission completion task, and the target search task. Practical implications for the study include the suggestion that reliable automation can help alleviate task interference and reduce workload, thereby allowing pilots to better handle concurrent tasks during single- and multiple-UAV flight control.

Peripheral arterial stiffness is associated with higher baseline plasma uric acid: A prospective cohort study.

PubMed

Ding, Xiaohan; Ye, Ping; Wang, Xiaona; Cao, Ruihua; Yang, Xu; Xiao, Wenkai; Zhang, Yun; Bai, Yongyi; Wu, Hongmei

2017-03-01

This prospective cohort study aimed at identifying association between uric acid (UA) and peripheral arterial stiffness. A prospective cohort longitudinal study was performed according to an average of 4.8 years' follow-up. The demographic data, anthropometric parameters, peripheral arterial stiffness (carotid-radial pulse-wave velocity, cr-PWV) and biomarker variables including UA were examined at both baseline and follow-up. Pearson's correlations were used to identify the associations between UA and peripheral arterial stiffness. Further logistic regressions were employed to determine the associations between UA and arterial stiffness. At the end of follow-up, 1447 subjects were included in the analyses. At baseline, cr-PWV ( r  = 0.200, p  < 0.001) was closely associated with UA. Furthermore, the follow-up cr-PWV ( r  = 0.145, p  < 0.001) was also strongly correlated to baseline UA in Pearson's correlation analysis. Multiple regressions also indicated the association between follow-up cr-PWV ( β  = 0.493, p  = 0.013) and baseline UA level. Logistic regressions revealed that higher baseline UA level was an independent predictor of arterial stiffness severity assessed by cr-PWV at follow-up cross-section. Peripheral arterial stiffness is closely associated with higher baseline UA level. Furthermore, a higher baseline UA level is an independent risk factor and predictor for peripheral arterial stiffness.

Self-refraction, ready-made glasses and quality of life among rural myopic Chinese children: a non-inferiority randomized trial.

PubMed

Zhou, Zhongqiang; Chen, Tingting; Jin, Ling; Zheng, Dongxing; Chen, Shangji; He, Mingguang; Silver, Josh; Ellwein, Leon; Moore, Bruce; Congdon, Nathan G

2017-09-01

To study, for the first time, the effect of wearing ready-made glasses and glasses with power determined by self-refraction on children's quality of life. This is a randomized, double-masked non-inferiority trial. Children in grades 7 and 8 (age 12-15 years) in nine Chinese secondary schools, with presenting visual acuity (VA) ≤6/12 improved with refraction to ≥6/7.5 bilaterally, refractive error ≤-1.0 D and <2.0 D of anisometropia and astigmatism bilaterally, were randomized to receive ready-made spectacles (RM) or identical-appearing spectacles with power determined by: subjective cycloplegic retinoscopy by a university optometrist (U), a rural refractionist (R) or non-cycloplegic self-refraction (SR). Main study outcome was global score on the National Eye Institute Refractive Error Quality of Life-42 (NEI-RQL-42) after 2 months of wearing study glasses, comparing other groups with the U group, adjusting for baseline score. Only one child (0.18%) was excluded for anisometropia or astigmatism. A total of 426 eligible subjects (mean age 14.2 years, 84.5% without glasses at baseline) were allocated to U [103 (24.2%)], RM [113 (26.5%)], R [108 (25.4%)] and SR [102 (23.9%)] groups, respectively. Baseline and endline score data were available for 398 (93.4%) of subjects. In multiple regression models adjusting for baseline score, older age (p = 0.003) and baseline spectacle wear (p = 0.016), but not study group assignment, were significantly associated with lower final score. Quality of life wearing ready-mades or glasses based on self-refraction did not differ from that with cycloplegic refraction by an experienced optometrist in this non-inferiority trial. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Role of Anti-Inflammatory Cytokines on Muscle Mass and Performance Changes in Elderly Men and Women.

PubMed

Rossi, A P; Budui, S; Zoico, E; Caliari, C; Mazzali, G; Fantin, F; D'Urbano, M; Paganelli, R; Zamboni, M

2017-01-01

Investigate the presence of a correlation between systemic inflammatory profile of community-dwelling individuals and the loss of muscular mass and performance in old age over a 4.5y follow-up, focusing on the role of anti-inflammatory cytokines in muscular changes in elderly. Longitudinal clinical study. Subjects were randomly selected from lists of 11 general practitioners in the city of Verona, Italy. The study included 120 subjects, 92 women and 28 men aged 72.27±2.06 years and with BMI of 26.52±4.07 kg/m2 at baseline. Six minutes walking test (6MWT), appendicular and leg fat free mass (FFM) as measured with Dual Energy X-ray absorptiometry, were obtained at baseline and after 4.5 years (4.5y) of mean follow-up. Height, weight, body mass index (BMI), and circulating levels of TNFα, IL-4, IL-10, and IL-13 were evaluated at baseline. A significant reduction of appendicular FFM, leg FFM and 6MWT performance (all p<0.001) was observed after 4.5 y follow-up. In a stepwise regression model, considering appendicular FFM decline as dependent variable, lnIL-4, BMI, baseline appendicular FFM, lnTNFα and lnIL-13 were significant predictors of appendicular FFM decline explaining 30.8% of the variance. While building a stepwise multiple regression considering leg FFM as a dependent variable, lnIL-4, BMI and leg FFM were significant predictors of leg FFM decline and explained 27.4% of variance. When considering 6MWT decline as a dependent variable, baseline 6MWT, lnIL-13 and lnTNFα were significant predictors of 6MWT decline to explain 22.9% of variance. Our study suggest that higher serum levels of anti-inflammatory markers, and in particular IL-4 and IL-13, may play a protective role on FFM and performance maintenance in elderly subjects.

A Randomized Trial of Soft Multifocal Contact Lenses for Myopia Control: Baseline Data and Methods.

PubMed

Walline, Jeffrey J; Gaume Giannoni, Amber; Sinnott, Loraine T; Chandler, Moriah A; Huang, Juan; Mutti, Donald O; Jones-Jordan, Lisa A; Berntsen, David A

2017-09-01

The Bifocal Lenses In Nearsighted Kids (BLINK) study is the first soft multifocal contact lens myopia control study to compare add powers and measure peripheral refractive error in the vertical meridian, so it will provide important information about the potential mechanism of myopia control. The BLINK study is a National Eye Institute-sponsored, double-masked, randomized clinical trial to investigate the effects of soft multifocal contact lenses on myopia progression. This article describes the subjects' baseline characteristics and study methods. Subjects were 7 to 11 years old, had -0.75 to -5.00 spherical component and less than 1.00 diopter (D) astigmatism, and had 20/25 or better logMAR distance visual acuity with manifest refraction in each eye and with +2.50-D add soft bifocal contact lenses on both eyes. Children were randomly assigned to wear Biofinity single-vision, Biofinity Multifocal "D" with a +1.50-D add power, or Biofinity Multifocal "D" with a +2.50-D add power contact lenses. We examined 443 subjects at the baseline visits, and 294 (66.4%) subjects were enrolled. Of the enrolled subjects, 177 (60.2%) were female, and 200 (68%) were white. The mean (± SD) age was 10.3 ± 1.2 years, and 117 (39.8%) of the eligible subjects were younger than 10 years. The mean spherical equivalent refractive error, measured by cycloplegic autorefraction was -2.39 ± 1.00 D. The best-corrected binocular logMAR visual acuity with glasses was +0.01 ± 0.06 (20/21) at distance and -0.03 ± 0.08 (20/18) at near. The BLINK study subjects are similar to patients who would routinely be eligible for myopia control in practice, so the results will provide clinical information about soft bifocal contact lens myopia control as well as information about the mechanism of the treatment effect, if one occurs.

Targeting Treatments to Improve Cognitive Function in Mood Disorder: Suggestions From Trials Using Erythropoietin.

PubMed

Miskowiak, Kamilla Woznica; Rush, A John; Gerds, Thomas A; Vinberg, Maj; Kessing, Lars V

2016-12-01

There is no established efficacious treatment for cognitive dysfunction in unipolar and bipolar disorder. This may be partially due to lack of consensus regarding the need to screen for cognitive impairment in cognition trials or which screening criteria to use. We have demonstrated in 2 randomized placebo-controlled trials that 8 weeks of erythropoietin (EPO) treatment has beneficial effects on verbal memory across unipolar and bipolar disorder, with 58% of EPO-treated patients displaying a clinically relevant memory improvement as compared to 15% of those treated with placebo. We reassessed the data from our 2 EPO trials conducted between September 2009 and October 2012 to determine whether objective performance-based memory impairment or subjective self-rated cognitive impairment at baseline was related to the effect of EPO on cognitive function as assessed by Rey Auditory Verbal Learning Test (RAVLT) total recall with multiple logistic regression adjusted for diagnosis, age, gender, symptom severity, and education levels. We included 79 patients with an ICD-10 diagnosis of unipolar or bipolar disorder, of whom 39 received EPO and 40 received placebo (saline). For EPO-treated patients with objective memory dysfunction at baseline (n = 16) (defined as RAVLT total recall ≤ 43), the odds of a clinically relevant memory improvement were increased by a factor of 290.6 (95% CI, 2.7-31,316.4; P = .02) compared to patients with no baseline impairment (n = 23). Subjective cognitive complaints (measured with the Cognitive and Physical Functioning Questionnaire) and longer illness duration were associated with small increases in patients' chances of treatment efficacy on memory (53% and 16% increase, respectively; P ≤ .04). Diagnosis, gender, age, baseline depression severity, and number of mood episodes did not significantly change the chances of EPO treatment success (P ≥ .06). In the placebo-treated group, the odds of memory improvement were not significantly different for patients with or without objectively defined memory dysfunction (P ≥ .59) or subjective complaints at baseline (P ≥ .06). Baseline objectively assessed memory impairments and-to a lesser degree-subjective cognitive complaints increased the chances of treatment efficacy on cognition in unipolar and bipolar disorder. ClinicalTrials.gov identifier: NCT00916552. © Copyright 2016 Physicians Postgraduate Press, Inc.

Investigations of Multiple Swirl-Venturi Fuel Injector Concepts: Recent Experimental Optical Measurement Results for 1-Point, 7-Point, and 9-Point Configurations

NASA Technical Reports Server (NTRS)

Hicks, Yolanda R.; Anderson, Robert C.; Tedder, Sarah A.; Tacina, Kathleen M.

2015-01-01

This paper presents results obtained during testing in optically-accessible, JP8-fueled, flame tube combustors using swirl-venturi lean direct injection (LDI) research hardware. The baseline LDI geometry has 9 fuel/air mixers arranged in a 3 x 3 array within a square chamber. 2-D results from this 9-element array are compared to results obtained in a cylindrical combustor using a 7-element array and a single element. In each case, the baseline element size remains the same. The effect of air swirler angle, and element arrangement on the presence of a central recirculation zone are presented. Only the highest swirl number air swirler produced a central recirculation zone for the single element swirl-venturi LDI and the 9-element LDI, but that same swirler did not produce a central recirculation zone for the 7-element LDI, possibly because of strong interactions due to element spacing within the array.

Promoting imitation in young children with autism: a comparison of reciprocal imitation training and video modeling.

PubMed

Cardon, Teresa A; Wilcox, M Jeanne

2011-05-01

The inability to imitate is a salient diagnostic marker for autism. It has been suggested that for children with autism, imitation may be a prerequisite skill that can assist in the development of various skills. Using a multiple baseline design across subjects, the purpose of this research was to determine if two interventions, reciprocal imitation training and video modeling were effective in promoting imitation acquisition in young children with autism. Six boys were matched across various features (i.e., age, language, autism severity) and randomly placed in a treatment condition. Results indicated that all six participants increased their imitation skills to varying degrees in both conditions, and imitation maintained and generalized at higher than baseline levels post treatment.

Development of the Complex General Linear Model in the Fourier Domain: Application to fMRI Multiple Input-Output Evoked Responses for Single Subjects

PubMed Central

Rio, Daniel E.; Rawlings, Robert R.; Woltz, Lawrence A.; Gilman, Jodi; Hommer, Daniel W.

2013-01-01

A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function. PMID:23840281

Development of the complex general linear model in the Fourier domain: application to fMRI multiple input-output evoked responses for single subjects.

PubMed

Rio, Daniel E; Rawlings, Robert R; Woltz, Lawrence A; Gilman, Jodi; Hommer, Daniel W

2013-01-01

A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.

Assessment of abuse liability of Tramadol among experienced drug users: Double-blind crossover randomized controlled trial.

PubMed

Das, Mrinmay; Jain, Raka; Dhawan, Anju; Kaur, Amandeep

Tramadol is a widely used opioid analgesic. Different preclinical, clinical, and postmarketing surveillance studies show conflicting results regarding abuse potential of this drug. A randomized double-blind complete crossover study was conducted at National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi. Total subjects were 10, comprising total 120 observations (each subject assessed at baseline, 5, 45, and 240 minutes). Subjects with history of substance abuse were included after detoxification and informed consent. Assessment was done using modified single dose opiate questionnaire, morphine benzedrine group (MBG), pentobarbital chlorpromazine alcohol group (PCAG), and two bipolar visual analogue scales (VAS) after administration of three drugs-Tramadol (100 mg), Buprenorphine (0.6 mg), and Placebo (Normal Saline) intramuscularly, at 5-day interval. In intra-group analysis, there was statistically significant increase in scores of all four scales from baseline to all three time points after Tramadol and Buprenorphine administration. In inter-group analysis, statistically higher scores were seen for Buprenorphine in comparison to Tramadol at 5, 45, and 240 minutes for MBG scale; the score was significantly higher for Buprenorphine in VAS for pleasurable effect at 45 and 240 minutes, but not at baseline and 5 minutes. There was no significant difference in score at any point of time between Tramadol and Buprenorphine in PCAG scale and VAS for sedative/alertness effect. The scores were statistically insignificant in case of Placebo. All the subjects liked Buprenorphine most and then Tramadol followed by Placebo. Tramadol has abuse potential (even in therapeutic doses) more than Placebo but less than or comparable to Buprenorphine.

Clinical characteristics of African Americans vs Caucasian Americans with multiple sclerosis.

PubMed

Cree, B A C; Khan, O; Bourdette, D; Goodin, D S; Cohen, J A; Marrie, R A; Glidden, D; Weinstock-Guttman, B; Reich, D; Patterson, N; Haines, J L; Pericak-Vance, M; DeLoa, C; Oksenberg, J R; Hauser, S L

2004-12-14

African American (AA) individuals are thought to develop multiple sclerosis (MS) less frequently than Caucasian American (CA) individuals. To compare the clinical characteristics of AA and CA patients with MS. The clinical features of MS were compared in a large retrospective cohort of AA (n = 375) and CA (n = 427) subjects. The proportion of women to men was similar in AA and CA subjects (81% [AA] vs 77% [CA]; p = 0.122). There were no differences in the proportions of subjects with relapsing-remitting, secondary progressive, primary progressive, and progressive relapsing MS. The median time to diagnosis was 1 year after symptom onset in AA subjects and 2 years after symptom onset in CA subjects (p = 0.0013). The age at onset was approximately 2.5 years later in AA than CA subjects (33.7 vs 31.1 years; p = 0.0001). AA subjects presented with multisite signs and symptoms at disease onset more often than CA subjects (p = 0.018). Clinical involvement restricted to the optic nerves and spinal cord (opticospinal MS) occurred in 16.8% of AA patients compared with 7.9% of CA patients (p < 0.001). Transverse myelitis also occurred more frequently in AA subjects (28 vs 18%; p = 0.001). Survival analysis revealed that AA subjects were at higher risk for development of ambulatory disability than CA subjects. After adjusting for baseline variations and differences in therapeutic interventions, AAs were at 1.67-fold greater risk for requiring a cane to ambulate than CA patients (p < 0.001). There was a trend suggesting that AAs were also at greater risk for development of wheelchair dependency (p = 0.099). Adjusted Cox proportional hazard models showed that this effect was in part attributable to the older age at onset in AAs (p < 0.001). Compared with multiple sclerosis (MS) in Caucasian Americans, African American patients with MS have a greater likelihood of developing opticospinal MS and transverse myelitis and have a more aggressive disease course.

Risk for switch from unipolar to bipolar disorder in youth with ADHD: a long term prospective controlled study.

PubMed

Biederman, Joseph; Petty, Carter R; Byrne, Deirdre; Wong, Patricia; Wozniak, Janet; Faraone, Stephen V

2009-12-01

To investigate whether ADHD is a risk factor for switches from unipolar to bipolar disorder over time. Data from two large controlled longitudinal family studies of boys and girls with and without ADHD and their siblings were used. Subjects (n=168) were followed prospectively and blindly over an average follow-up period of 7 years. Comparisons were made between youth with unipolar major depression who did and did not switch to full or subthreshold BP-I disorder at the follow-up assessment. Subjects were assessed at baseline and follow-up on multiple domains of functioning. Positive family history of parental psychiatric disorders was also compared between groups. ADHD was associated with a significantly higher risk for switches from unipolar to bipolar disorder (28% versus 6%; z=2.80, p=0.005). In subjects with ADHD, switches from unipolar to bipolar disorder were predicted by baseline comorbid conduct disorder, school behavior problems, and a positive family history of parental mood disorder. Psychosis was an exclusionary criterion in the original ascertainment of the studies of ADHD probands, so we were unable to test this as a predictor of switching to BPD. ADHD is a risk factor for switches from unipolar to bipolar disorder, and switches could be predicted by the presence of baseline conduct disorder, school behavior problems, and a positive family history of a mood disorder in a parent. These characteristics can aid clinicians in their treatment of youth with MDD.

Biopsychosocial Factors Associated with Foot and Ankle Pain and Injury in Irish Dance: A Prospective Study.

PubMed

Cahalan, Roisin; Purtill, Helen; O'Sullivan, Kieran

2017-06-01

Foot and ankle pain/injury (FAPI) is the most common musculoskeletal problem suffered in Irish dancing. A prospective examination of risk factors for FAPI in this cohort has never been performed. Prospective study over 1-year. 85 elite adult Irish dancers were screened at baseline for biopsychosocial factors and followed up prospectively each month for 1 year to evaluate FAPI rates and potential risk factors. Subjects who suffered from multiple incidences of FAPI (with no pain/injury reported elsewhere in the body) or at least one moderate episode of FAPI were allocated to the foot/ankle-injured (FAI) group (n=28, 25 F/3 M). Subjects reporting no pain/injury or only one minor FAPI were allocated to the non-injured group (n=21, 14 F/7 M). Baseline differences in variables between groups were tested with the independent samples t-test, Mann-Whitney U-test for skewed data, and Fisher's exact test for categorical variables. Baseline factors significantly associated with the FAI group included failing to always perform a warm-up (p=0.042), lower levels of energy (p=0.013), and more bothersome pain (p=0.021). Subjects also scored worse on two dimensions of the Athletic Coping Skills Inventory: i.e., coping with adversity (p=0.035) and goal setting and mental preparation (p=0.009). Several biopsychosocial factors appear to be associated with FAPI in Irish dancers. Biopsychosocial screening protocols and prevention strategies may best identify and support at-risk dancers.

"You Can't Always Get What You Want": A Novel Research Paradigm to Explore the Relationship between Multiple Intentions and Behaviours.

PubMed

Sniehotta, Falko F; Presseau, Justin; Allan, Julia; Araújo-Soares, Vera

2016-07-01

Research investigating cognitive moderators of the intention-behaviour relationship and psychological consequences of failure to enact intentions is usually conducted in a single-behaviour paradigm. A multiple-behaviour paradigm is introduced which overcomes bias inherent to single-behaviour designs and allows testing of novel hypotheses. Two exploratory studies illustrate the utility of this new paradigm by investigating the role of cognitive predictors and psychological correlates of intention-behaviour relationships. The proposed method involves measuring multiple intentions across common areas of life activity at baseline and corresponding behaviours at follow-up. In two studies, 51 intentions and behaviours were assessed (49 by self-report, 2 objectively). In Study 1, participants (n = 126) also completed self-reported measures of everyday cognitive failures and dysexecutive behaviours, crystallised intelligence (Mill Hill Vocabulary Scale) at baseline and Quality of Life (QoL; follow-up). In Study 2, objective executive function measures (Stroop, Go/NoGo task and Word Fluency test) were completed by N = 30 participants. The total number of intentions, cognitive, and QoL measures were unrelated to the percentage of intentions enacted. Crystallised intelligence was related to successful intention implementation and problems with emotion regulation were associated with forming fewer intentions and with fewer failed intentions. QoL was strongly related with more intentions, regardless of whether or not these were implemented. Study 2 showed that cognitive flexibility (word fluency) and task errors, rather than Stroop effect and Go/No-Go performance were related, to intention-behaviour congruence. Intention-behaviour relationships might be better understood when considering the multiple intentions and behaviours that people are engaged in at once at any one point in time. A multiple-behaviour paradigm suggests novel hypotheses. Preliminary findings reported here require replication. Anticipated applications of the paradigm are outlined and discussed. © 2016 The Authors. Applied Psychology: Health and Well-Being published by John Wiley & Sons Ltd on behalf of International Association of Applied Psychology.

Estimation of a Nonlinear Intervention Phase Trajectory for Multiple-Baseline Design Data

ERIC Educational Resources Information Center

Hembry, Ian; Bunuan, Rommel; Beretvas, S. Natasha; Ferron, John M.; Van den Noortgate, Wim

2015-01-01

A multilevel logistic model for estimating a nonlinear trajectory in a multiple-baseline design is introduced. The model is applied to data from a real multiple-baseline design study to demonstrate interpretation of relevant parameters. A simple change-in-levels (?"Levels") model and a model involving a quadratic function…

Effects of video modeling on social initiations by children with autism.

PubMed

Nikopoulos, Christos K; Keenan, Michael

2004-01-01

We examined the effects of a video modeling intervention on social initiation and play behaviors with 3 children with autism using a multiple baseline across subjects design. Each child watched a videotape showing a typically developing peer, and the experimenter engaged in a simple social interactive play using one toy. For all children, social initiation and reciprocal play skills were enhanced, and these effects were maintained at 1- and 3-month follow-up periods.

The use of self-modeling to improve the swimming performance of spina bifida children.

PubMed Central

Dowrick, P W; Dove, C

1980-01-01

The use of edited videotape replay (which showed only "positive" behaviors) to improve the water skills of three spina bifida children, aged 5 to 10 years was examined. A multiple baseline across subjects design was used, and behavioral changes were observed to occur in close association with intervention. One child was given successive reapplications of videotaped self-modeling with continuing improvements. It appears that a useful practical technique has been developed. PMID:6988381

Effects of video modeling on social initiations by children with autism.

PubMed Central

Nikopoulos, Christos K; Keenan, Michael

2004-01-01

We examined the effects of a video modeling intervention on social initiation and play behaviors with 3 children with autism using a multiple baseline across subjects design. Each child watched a videotape showing a typically developing peer, and the experimenter engaged in a simple social interactive play using one toy. For all children, social initiation and reciprocal play skills were enhanced, and these effects were maintained at 1- and 3-month follow-up periods. PMID:15154221

Basal and induced NO formation in the pharyngo-oral tract influences estimates of alveolar NO levels.

PubMed

Malinovschi, Andrei; Janson, Christer; Holm, Lena; Nordvall, Lennart; Alving, Kjell

2009-02-01

The present study analyzed how models currently used to distinguish alveolar from bronchial contribution to exhaled nitric oxide (NO) are affected by manipulation of NO formation in the pharyngo-oral tract. Exhaled NO was measured at multiple flow rates in 15 healthy subjects in two experiments: 1) measurements at baseline and 5 min after chlorhexidine (CHX) mouthwash and 2) measurements at baseline, 60 min after ingestion of 10 mg NaNO(3)/kg body wt, and 5 min after CHX mouthwash. Alveolar NO concentration (Calv(NO)) and bronchial flux (J'aw(NO)) were calculated by using the slope-intercept model with or without adjustment for trumpet shape of airways and axial diffusion (TMAD). Salivary nitrate and nitrite were measured in the second experiment. Calv(NO) [median (range)] was reduced from 1.16 ppb (0.77, 1.96) at baseline to 0.84 ppb (0.57, 1.48) 5 min after CHX mouthwash (P < 0.001). The TMAD-adjusted Calv(NO) value after CHX mouthwash was 0.50 ppb (0, 0.85). The nitrate load increased J'aw(NO) from 32.2 nl/min (12.2, 60.3) to 57.1 nl/min (22.0, 119) in all subjects and Calv(NO) from 1.47 ppb (0.73, 1.95) to 1.87 ppb (10.85, 7.20) in subjects with high nitrate turnover (>10-fold increase of salivary nitrite after nitrate load). CHX mouthwash reduced Calv(NO) levels to 1.15 ppb (0.72, 2.07) in these subjects with high nitrate turnover. All these results remained consistent after TMAD adjustment. We conclude that estimated alveolar NO concentration is affected by pharyngo-oral tract production of NO in healthy subjects, with a decrease after CHX mouthwash. Moreover, unknown ingestion of dietary nitrate could significantly increase estimated alveolar NO in subjects with high nitrate turnover, and this might be falsely interpreted as a sign of peripheral inflammation. These findings were robust for TMAD.

Effect of aquatic exercise training on fatigue and health-related quality of life in patients with multiple sclerosis.

PubMed

Kargarfard, Mehdi; Etemadifar, Masoud; Baker, Peter; Mehrabi, Maryam; Hayatbakhsh, Reza

2012-10-01

To examine the effectiveness of aquatic exercise training on fatigue and health-related quality of life (HRQOL) in women with multiple sclerosis (MS). Randomized controlled trial, 4-week and 8-week follow-up. Referral center of a multiple sclerosis society. Women (N=32) diagnosed with relapsing-remitting MS (mean age ± SD, 32.6±8.0y) were recruited into this study. After undergoing baseline testing by a neurologist, participants were randomly assigned to either an intervention (aquatic exercise) or a control group. The intervention consisted of 8 weeks supervised aquatic exercise in a swimming pool (3 times a week, each session lasting 60min). At baseline, 4 weeks, and 8 weeks, fatigue and HRQOL were assessed by a blind assessor using the Modified Fatigue Impact Scale and the Multiple Sclerosis Quality of Life-54 questionnaire, respectively. A mixed-model approach to repeated-measures analysis of variance was used to detect within- and between-subject effects. Findings are based on 21 patients (10 from the exercise group and 11 from the control group) who had data available on outcomes. There was no significant difference between the 2 groups at the baseline. Patients in the aquatic exercise group showed significant improvements in fatigue and subscores of HRQOL after 4 and 8 weeks compared with the control group. Results obtained from the intention-to-treat analysis were consistent with those of per-protocol analysis. The findings suggest that aquatic exercise training can effectively improve fatigue and HRQOL of patients with MS and should be considered in the management of this relatively common public health problem. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Eye Movement in Response to Single and Multiple Targets

DTIC Science & Technology

1985-02-01

pursuit control system. METHOD The SVFB technique was described in detail elsewhere (Zeevi et al., 1979). Displaying, to the subject, the point of gaze , in...34 The subject was presented with his point of gaze using the unconditioned SVFB signal (gain = 1, eccentric bias = 0). The SVFB signal was locked on the...superimposing the SVFB on the target, is gazing away from it and thus achieves eccentric fixation (Zeevi et al., 1979). As the subject moves from one

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.

Binary variable multiple-model multiple imputation to address missing data mechanism uncertainty: Application to a smoking cessation trial

PubMed Central

Siddique, Juned; Harel, Ofer; Crespi, Catherine M.; Hedeker, Donald

2014-01-01

The true missing data mechanism is never known in practice. We present a method for generating multiple imputations for binary variables that formally incorporates missing data mechanism uncertainty. Imputations are generated from a distribution of imputation models rather than a single model, with the distribution reflecting subjective notions of missing data mechanism uncertainty. Parameter estimates and standard errors are obtained using rules for nested multiple imputation. Using simulation, we investigate the impact of missing data mechanism uncertainty on post-imputation inferences and show that incorporating this uncertainty can increase the coverage of parameter estimates. We apply our method to a longitudinal smoking cessation trial where nonignorably missing data were a concern. Our method provides a simple approach for formalizing subjective notions regarding nonresponse and can be implemented using existing imputation software. PMID:24634315

Low cost solar array project cell and module formation research area: Process research of non-CZ silicon material

NASA Technical Reports Server (NTRS)

1981-01-01

Liquid diffusion masks and liquid applied dopants to replace the CVD Silox masking and gaseous diffusion operations specified for forming junctions in the Westinghouse baseline process sequence for producing solar cells from dendritic web silicon were investigated. The baseline diffusion masking and drive processes were compared with those involving direct liquid applications to the dendritic web silicon strips. Attempts were made to control the number of variables by subjecting dendritic web strips cut from a single web crystal to both types of operations. Data generated reinforced earlier conclusions that efficiency levels at least as high as those achieved with the baseline back junction formation process can be achieved using liquid diffusion masks and liquid dopants. The deliveries of dendritic web sheet material and solar cells specified by the current contract were made as scheduled.

A single digital droplet PCR assay to detect multiple KIT exon 11 mutations in tumor and plasma from patients with gastrointestinal stromal tumors.

PubMed

Boonstra, Pieter A; Ter Elst, Arja; Tibbesma, Marco; Bosman, Lisette J; Mathijssen, Ron; Atrafi, Florence; van Coevorden, Frits; Steeghs, Neeltje; Farag, Sheima; Gelderblom, Hans; van der Graaf, Winette T A; Desar, Ingrid M E; Maier, Jacqueline; Overbosch, Jelle; Suurmeijer, Albert J H; Gietema, Jourik; Schuuring, Ed; Reyners, Anna K L

2018-03-02

Gastrointestinal stromal tumors (GISTs) are characterized by oncogenic KIT mutations that cluster in two exon 11 hotspots. The aim of this study was to develop a single, sensitive, quantitative digital droplet PCR (ddPCR) assay for the detection of common exon 11 mutations in both GIST tumor tissue and in circulating tumor DNA (ctDNA) isolated from GIST patients' plasma. A ddPCR assay was designed using two probes that cover both hotspots. Available archival FFPE tumor tissue from 27 consecutive patients with known KIT exon 11 mutations and 9 randomly selected patients without exon 11 mutations were tested. Plasma samples were prospectively collected in a multicenter bio-databank from December 2014. ctDNA was analyzed of 22 patients with an exon 11 mutation and a baseline plasma sample. The ddPCR assay detected the exon 11 mutation in 21 of 22 tumors with exon 11 mutations covered by the assay. Mutations in ctDNA were detected at baseline in 13 of 14 metastasized patients, but in only 1 of 8 patients with localized disease. In serial plasma samples from 11 patients with metastasized GIST, a decrease in mutant droplets was detected during treatment. According to RECIST 1.1, 10 patients had radiological treatment response and one patient stable disease. A single ddPCR assay for the detection of multiple exon 11 mutations in ctDNA is a feasible, promising tool for monitoring treatment response in patients with metastasized GIST and should be further evaluated in a larger cohort.

Subjective, but not Objective, Lingering Effects of Multiple Past Concussions in Adolescents

PubMed Central

McKay, Carly D.; Mrazik, Martin; Barlow, Karen M.; Meeuwisse, Willem H.; Emery, Carolyn A.

2013-01-01

Abstract The existing literature on lingering effects from concussions in children and adolescents is limited and mixed, and there are no clear answers for patients, clinicians, researchers, or policy makers. The purpose of this study was to examine whether there are lingering effects of past concussions in adolescent athletes. Participants in this study included 643 competitive Bantam and Midget hockey players (most elite 20% by division of play) between 13 and 17 years of age (mean age=15.5, SD=1.2). Concussion history at baseline assessment was retrospectively documented using a pre-season questionnaire (PSQ), which was completed at home by parents and players in advance of baseline testing. Players with English as a second language, self-reported attention or learning disorders, a concussion within 6 months of baseline, or suspected invalid test profiles were excluded from these analyses. Demographically adjusted standard scores for the five composites/domains and raw symptom ratings from the brief Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) computerized battery were analyzed. Adolescent athletes with one or two or more prior concussions did not have significantly worse neurocognitive functioning on ImPACT than did those with no previous concussions. There were significantly more symptoms reported in those with two or more prior concussions than in those with no or one prior concussion. Adolescents with multiple previous concussions had higher levels of baseline symptoms, but there were not group differences in neurocognitive functioning using this brief computerized battery. PMID:23560947

Subjective, but not objective, lingering effects of multiple past concussions in adolescents.

PubMed

Brooks, Brian L; McKay, Carly D; Mrazik, Martin; Barlow, Karen M; Meeuwisse, Willem H; Emery, Carolyn A

2013-09-01

The existing literature on lingering effects from concussions in children and adolescents is limited and mixed, and there are no clear answers for patients, clinicians, researchers, or policy makers. The purpose of this study was to examine whether there are lingering effects of past concussions in adolescent athletes. Participants in this study included 643 competitive Bantam and Midget hockey players (most elite 20% by division of play) between 13 and 17 years of age (mean age=15.5, SD=1.2). Concussion history at baseline assessment was retrospectively documented using a pre-season questionnaire (PSQ), which was completed at home by parents and players in advance of baseline testing. Players with English as a second language, self-reported attention or learning disorders, a concussion within 6 months of baseline, or suspected invalid test profiles were excluded from these analyses. Demographically adjusted standard scores for the five composites/domains and raw symptom ratings from the brief Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) computerized battery were analyzed. Adolescent athletes with one or two or more prior concussions did not have significantly worse neurocognitive functioning on ImPACT than did those with no previous concussions. There were significantly more symptoms reported in those with two or more prior concussions than in those with no or one prior concussion. Adolescents with multiple previous concussions had higher levels of baseline symptoms, but there were not group differences in neurocognitive functioning using this brief computerized battery.

Higher serotonin transporter occupancy after multiple dose administration of escitalopram compared to citalopram: an [123I]ADAM SPECT study.

PubMed

Klein, Nikolas; Sacher, Julia; Geiss-Granadia, Thomas; Mossaheb, Nilufar; Attarbaschi, Trawat; Lanzenberger, Rupert; Spindelegger, Christoph; Holik, Alexander; Asenbaum, Susanne; Dudczak, Robert; Tauscher, Johannes; Kasper, Siegfried

2007-04-01

Previous studies have investigated the occupancy of the serotonin reuptake transporter (SERT) after clinical doses of citalopram and other selective serotonin reuptake inhibitors. In the present study, the occupancies of SERT after multiple doses of escitalopram and citalopram were compared using the radioligand [(123)I]ADAM and single photon emission computed tomography (SPECT). Fifteen healthy subjects received escitalopram 10 mg/day (n = 6) or citalopram 20 mg/day (n = 9) for a total of 10 days. SERT occupancies in midbrain were determined with SPECT and [(123)I]ADAM at three different time points: at baseline (no medication) and at 6 and 54 h after last drug intake. At 6 h after the last dose, mean SERT occupancies were 81.5 +/- 5.4% (mean+/-SD) for escitalopram and 64.0 +/- 12.7% for citalopram (p < 0.01). At 54 h after the last dose, mean SERT occupancies were 63.3 +/- 12.1% for escitalopram and 49.0 +/- 11.7% for citalopram (p < 0.05). The plasma concentrations of the S-enantiomer were of the same magnitude in both substances. For both drugs, the elimination rate of the S-enantiomer in plasma was markedly higher than the occupancy decline rate in the midbrain. The significantly higher occupancy of SERT after multiple doses of escitalopram compared to citalopram indicates an increased inhibition of SERT by escitalopram. The results can also be explained by an attenuating effect of R-citalopram on the occupancy of S-citalopram at the SERT.

Effects on Cognition of Stereotactic Lesional Surgery For the Treatment of Tremor in Multiple Sclerosis

PubMed Central

Jahanshahi, Marjan; Pieter, Socorro; Alusi, Sundus H.; Jones, Catherine R. G.; Glickman, Scott; Stein, John; Aziz, Tipu; Bain, Peter G.

2008-01-01

Objective: To assess the effect of stereotactic lesional surgery for treatment of tremor in multiple sclerosis on cognition. Methods: Eleven patients (3 males, 8 females) with multiple sclerosis participated in the study. Six subjects comprised the surgical group and five the matched control group. All patients were assessed at baseline and three months using a neuropsychological test battery that included measures of intellectual ability, memory, language, perception and executive function. Results: There were no significant differences between the surgical and control groups and no change from pre to post testing except for a decline in scores on the Mini-Mental State Examination (MMSE), WAIS-R Digit Span and Verbal Fluency in the surgical group. Conclusions: The results indicate that stereotactic lesional surgery does not result in major cognitive impairment in multiple sclerosis. However, the decline in MMSE scores, digit span and verbal fluency require further investigation in a larger sample. PMID:19491469

Multiple-electrode radiofrequency ablation: simultaneous production of separate zones of coagulation in an in vivo porcine liver model.

PubMed

Laeseke, Paul F; Sampson, Lisa A; Haemmerich, Dieter; Brace, Chris L; Fine, Jason P; Frey, Tina M; Winter, Thomas C; Lee, Fred T

2005-12-01

A multiple-electrode radiofrequency (RF) system was developed based on switching between electrodes that allows for the simultaneous use of as many as three electrically independent electrodes. The purpose of this study was to determine if each multiple-electrode ablation zone is identical to an ablation zone created with conventional single-electrode mode. Nine female domestic pigs (mean weight, 90 kg) were used for this study. A prototype monopolar multiple-electrode RF ablation system was created with use of an RF generator and an electronic switching algorithm. A maximum of three electrodes can be used simultaneously by switching between electrodes at each impedance spike (30 omega greater than baseline levels). A total of 39 zones of ablation were created at open laparotomy in pig livers with use of a conventional single electrode (n = 9), two single electrodes simultaneously (n = 6 ablations; 12 ablation zones), or three single electrodes simultaneously (n = 6 ablations; 18 ablation zones). RF electrodes were spaced in separate lobes of the liver when multiple zones of coagulation were created simultaneously. Animals were euthanized after RF ablation, livers were removed, and ablation zones were sectioned and measured. Zones of coagulation created simultaneously with two or three electrodes were equivalent to ablation zones created with use of conventional single-electrode ablation. No significant differences were observed among control animals treated with a single electrode, those with two separate zones of ablation created simultaneously, and those with three simultaneously created ablation zones in terms of mean (+/-SD) minimum diameter (1.6 cm +/- 0.6, 1.6 cm +/- 0.5, and 1.7 cm +/- 0.4, respectively), maximum diameter (2.0 cm +/- 0.5, 2.3 cm +/- 0.5, 2.2 cm +/- 0.5, respectively), and volume (6.7 cm3 +/- 3.7, 7.4 cm3 +/- 3.8, and 7.8 cm3 +/- 3.9; P > .30, analysis of variance, pairwise t-test comparisons). A rapid-switching multiple-electrode RF system was able to simultaneously create as many as three separate ablation zones of equivalent size compared with single-electrode controls. This system would allow physicians to simultaneously treat multiple tumors, substantially reducing procedure time and anesthesia risk.

Social roles among recruits in Switzerland: Do social roles relate to alcohol use and does role change have an impact?

PubMed

Kuntsche, Sandra; Astudillo, Mariana; Gmel, Gerhard

2016-03-01

Young men are likely to report high levels of alcohol use. Previous studies found a reduction in alcohol use when adopting adult social roles. This study examines the frequency of parenthood, partnership and stable employment among young men in Switzerland. It tests whether the alcohol use of those with adult social roles differs from those without and whether changes in social roles relate to changes in alcohol use. Data was available from 5025 men (20.0 years) at baseline (August 2010 to November 2011) and 15 months later. Changes in social roles and their impact on alcohol use were examined in multiple regression models. At baseline, 15.8% had a job and 4.9% a stable partner, and 1.5% had a child or were expecting one (30.5%, 6.1% and 2.2% at follow-up). Having a partner was associated with a significant decrease in annual frequency of drinking and weekly risky single-occasion drinking (RSOD) at follow-up. A higher number of social roles at follow-up was associated with a significant decrease in weekly RSOD. Apart from a significant decrease in weekly RSOD among those remaining in a stable partnership, role development was not found to have significant effects on alcohol use between baseline and follow-up. In Switzerland, an early engagement in permanent social roles is uncommon. Nevertheless, holding single or multiple social roles was commonly associated with reduced alcohol use, although not always significantly so. In western European countries, the engagement in adult social roles is postponed to later ages. Copyright © 2015. Published by Elsevier Ltd.

Birth Weight Is Associated With the IGF-1 Response to GH in Children: Programming of the Anabolic Action of GH?

PubMed

Donzeau, Aurélie; Bouhours-Nouet, Natacha; Fauchard, Mathilde; Decrequy, Anne; Mathieu, Elisabeth; Boux de Casson, Florence; Gascoin, Geraldine; Coutant, Régis

2015-08-01

Intrauterine programming of the somatotropic axis has been hypothesized in cases of intrauterine growth retardation. The objective of the study was to study the effects of birth weight and body composition on GH sensitivity. This was a cross-sectional study with a single GH administration to assess GH sensitivity. The study was conducted at the Department of Pediatric Endocrinology of an academic medical center. One hundred normal short children aged from 4 to 17 years old (44 girls, 56 boys) separated into four groups: early childhood (aged 4-8 y, n = 14), late childhood (aged 9-12 y, pubertal stage 1, n = 30), early puberty (aged 10-15 y, stage 2, n = 32), and midpuberty (aged 12-17 y, stages 3 and 4, n = 24). Serum IGF-1 at baseline and 24 hours after a single administration of GH (2 mg/m(2)) were measured. δIGF-1 significantly increased across the groups (P < .0001) with no gender difference, whereas the percentage of change in IGF-1 was similar (47% ± 32%). Independent predictors of δIGF-1 were birth weight SD score, fat percentage, fasting insulin (all positive predictors), and free fatty acids (negative predictor), with age, puberty, and baseline IGF-1 as adjusting variables (multiple R = 0.73, P < .0001). Independent predictors of the percentage of change in IGF-1 were birth weight SD score, fat percentage, and baseline IGF-1 (multiple R = 0.43, P < .001). This study suggests that in cases of low birth weight, intrauterine programming of GH sensitivity may be an adaptation to an expected poor postnatal nutritional environment, serving to restrict the anabolic action of GH. Conversely, postnatal excess energy stores may promote the anabolic action of GH.

Using virtual reality to distinguish subjects with multiple- but not single-domain amnestic mild cognitive impairment from normal elderly subjects.

PubMed

Mohammadi, Alireza; Kargar, Mahmoud; Hesami, Ehsan

2018-03-01

Spatial disorientation is a hallmark of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease. Our aim was to use virtual reality to determine the allocentric and egocentric memory deficits of subjects with single-domain aMCI (aMCIsd) and multiple-domain aMCI (aMCImd). For this purpose, we introduced an advanced virtual reality navigation task (VRNT) to distinguish these deficits in mild Alzheimer's disease (miAD), aMCIsd, and aMCImd. The VRNT performance of 110 subjects, including 20 with miAD, 30 with pure aMCIsd, 30 with pure aMCImd, and 30 cognitively normal controls was compared. Our newly developed VRNT consists of a virtual neighbourhood (allocentric memory) and virtual maze (egocentric memory). Verbal and visuospatial memory impairments were also examined with Rey Auditory-Verbal Learning Test and Rey-Osterrieth Complex Figure Test, respectively. We found that miAD and aMCImd subjects were impaired in both allocentric and egocentric memory, but aMCIsd subjects performed similarly to the normal controls on both tasks. The miAD, aMCImd, and aMCIsd subjects performed worse on finding the target or required more time in the virtual environment than the aMCImd, aMCIsd, and normal controls, respectively. Our findings indicated the aMCImd and miAD subjects, as well as the aMCIsd subjects, were more impaired in egocentric orientation than allocentric orientation. We concluded that VRNT can distinguish aMCImd subjects, but not aMCIsd subjects, from normal elderly subjects. The VRNT, along with the Rey Auditory-Verbal Learning Test and Rey-Osterrieth Complex Figure Test, can be used as a valid diagnostic tool for properly distinguishing different forms of aMCI. © 2018 Japanese Psychogeriatric Society.

Influence of drive and timing mechanisms on breathing pattern and ventilation during mental task performance.

PubMed

Wientjes, C J; Grossman, P; Gaillard, A W

1998-09-01

Assessment of multiple respiratory measures may provide insight into how behavioral demands affect the breathing pattern. This is illustrated by data from a study among 44 subjects, in which tidal volume, respiration rate, minute ventilation and indices of central drive and timing mechanisms were assessed via inductive plethysmography, in addition to end-tidal PCO2. After a baseline, three conditions of a memory comparison task were presented. The first two conditions differed only with regard to the presence or absence of feedback of performance (NFB and FB). In the third 'all-or-nothing' (AON) condition, subjects only received a monetary bonus, if their performance exceeded that of the previous two conditions. Minute ventilation increased from baseline to all task conditions, and from NFB and FB to AON. Respiration rate increased in all task conditions, but there were no differences between task conditions. Tidal volume decreased during NFB, but was equal to baseline during FB and AON. Of the respiratory control indices, inspiratory flow rate covaried much more closely with minute ventilation than duty cycle. The task performance induced a minor degree of hyperventilation. The discussion focusses on how behavioral demands affect respiratory control processes to produce alterations in breathing pattern and ventilation.

The Use of Correctional “NO!” Approach to Reduce Destructive Behavior on Autism Student of CANDA Educational Institution in Surakarta

NASA Astrophysics Data System (ADS)

Anggraini, N.

2017-02-01

This research aims to reduce the destructive behavior such as throwing the learning materials on autism student by using correctional “NO!” approach in CANDA educational institution Surakarta. This research uses Single Subject Research (SSR) method with A-B design, it is baseline and intervention. Subject of this research is one autism student of CANDA educational institution named G.A.P. Data were collected through recording in direct observation in the form of recording events at the time of implementation baseline and intervention. Data were analyzed by simple descriptive statistical analysis and is displayed in graphical form. Based on the result of data analysis, it could be concluded that destructive behavior such as throwing the learning material on autism student was significantly reduced after given an intervention. Based on the research results, using correctional “NO!” approach can be used by teacher or therapist to reduce the destructive behavior on autism student.

Two Seating Systems' Effects on an Adolescent With Cerebral Palsy and Severe Scoliosis.

PubMed

Lephart, Kim; Kaplan, Sandra L

2015-01-01

To compare physiological functioning, communication switch activation, and response accuracy in a 19-year-old young man with quadriplegic cerebral palsy and neurological scoliosis using 2 seating systems within the school setting. Prospective single-subject alternating treatment design with 2 conditions: baseline phase with standard planar inserts (A1), custom-molded back with original seat (B), and return to baseline (A2). Measures included oxygen saturation (SaO2), heart rate (HR), respiration rate (RR), body temperature (BT), processing time to activate switches, and response accuracy. SaO2 levels increased from "distressed" to "normal"; variability decreased. HR, RR, and BT fluctuations decreased with the custom-molded back. Processing time decreased with increased variability, affected by subject's motivation; accuracy improved slightly. Reported social approachability and student-initiated communication increased. SaO2 increased and HR, RR, and BT fluctuations decreased with a custom-molded back. Graphing data may help determine seating effect with complex clients.

Neuroimaging-Aided Prediction of the Effect of Methylphenidate in Children with Attention-Deficit Hyperactivity Disorder: A Randomized Controlled Trial.

PubMed

Ishii-Takahashi, Ayaka; Takizawa, Ryu; Nishimura, Yukika; Kawakubo, Yuki; Hamada, Kasumi; Okuhata, Shiho; Kawasaki, Shingo; Kuwabara, Hitoshi; Shimada, Takafumi; Todokoro, Ayako; Igarashi, Takashi; Watanabe, Kei-Ichiro; Yamasue, Hidenori; Kato, Nobumasa; Kasai, Kiyoto; Kano, Yukiko

2015-11-01

Although methylphenidate hydrochloride (MPH) is a first-line treatment for children with attention-deficit hyperactivity disorder (ADHD), the non-response rate is 30%. Our aim was to develop a supplementary neuroimaging biomarker for predicting the clinical effect of continuous MPH administration by using near-infrared spectroscopy (NIRS). After baseline assessment, we performed a double-blind, placebo-controlled, crossover trial with a single dose of MPH, followed by a prospective 4-to-8-week open trial with continuous MPH administration, and an ancillary 1-year follow-up. Twenty-two drug-naïve and eight previously treated children with ADHD (NAÏVE and NON-NAÏVE) were compared with 20 healthy controls (HCs) who underwent multiple NIRS measurements without intervention. We tested whether NIRS signals at the baseline assessment or ΔNIRS (single dose of MPH minus baseline assessment) predict the Clinical Global Impressions-Severity (CGI-S) score after 4-to-8-week or 1-year MPH administration. The secondary outcomes were the effect of MPH on NIRS signals after single-dose, 4-to-8-week, and 1-year administration. ΔNIRS significantly predicted CGI-S after 4-to-8-week MPH administration. The leave-one-out classification algorithm had 81% accuracy using the NIRS signal. ΔNIRS also significantly predicted CGI-S scores after 1 year of MPH administration. For secondary analyses, NAÏVE exhibited significantly lower prefrontal activation than HCs at the baseline assessment, whereas NON-NAÏVE and HCs showed similar activation. A single dose of MPH significantly increased activation compared with the placebo in NAÏVE. After 4-to-8-week administration, and even after MPH washout following 1-year administration, NAÏVE demonstrated normalized prefrontal activation. Supplementary NIRS measurements may serve as an objective biomarker for clinical decisions and monitoring concerning continuous MPH treatment in children with ADHD.

Effects of caffeine on mood and performance: a study of realistic consumption.

PubMed

Brice, Carolyn F; Smith, Andrew P

2002-11-01

There is a vast literature on the behavioural effects of caffeine. Many of the studies have involved single administration of a large dose of caffeine that is not representative of the way in which caffeine is usually ingested. Further information is required, therefore, on the behavioural effects of realistic patterns of consumption. The present study aimed to determine whether a realistic drinking regime (multiple small doses - 4 x 65 mg over a 5-h period) produced the same effects as a single large dose (200 mg). The smaller doses were selected so that the amount of caffeine present in the body after 5 h would be equivalent to that found with the single dose. A double-blind, placebo-controlled, within-subjects experiment was, therefore, carried out. The participants ( n=24) attended for four sessions. Each session started with a baseline measurement of mood and performance at 0930 hours. On two of the sessions, coffee was then consumed at 1000, 1100, 1200 and 1300 hours. In one of these sessions 65 mg caffeine was added to the de-caffeinated coffee. In the other two sessions, the participants consumed coffee at 1300 hours and 200 mg caffeine was added in one of the sessions. The volunteers completed the battery of tests again at 1500 hours. The results showed that in both consumption regimes caffeine led to increased alertness and anxiety and improved performance on simple and choice reactive tasks, a cognitive vigilance task, a task requiring sustained response and a dual task involving tracking and target detection. These results suggest that previous findings from studies using a large single dose may be applicable to normal patterns of caffeine consumption.

The effects of a standardized belly dance program on perceived pain, disability, and function in women with chronic low back pain.

PubMed

Castrillon, Tabitha; Hanney, William J; Rothschild, Carey E; Kolber, Morey J; Liu, Xinliang; Masaracchio, Michael

2017-01-01

An alternative approach to facilitate movement and control through the trunk and pelvis is belly dancing. Investigations of belly dancing mechanics indicate similar muscular activation patterns of those known to influence chronic low back pain (cLBP). However, no documented studies have examined its effectiveness as a treatment for cLBP. The purpose of this study was to investigate the influence of a standardized belly dance program in women with cLBP. A single subject design was used to evaluate weekly outcomes during a three-week baseline period, six-week belly dance program, and again at a two-month follow-up. Outcome measures for pain, disability, function, and fear-avoidance beliefs were utilized. Two subjects completed the program. No significant differences were noted during the baseline assessment period. At two months, subject one demonstrated change scores of -1.12, -1%, and 2.2 for pain, disability, and function respectively while subject two demonstrated change scores of 5.4, 5%, and 1.1 for pain, disability, and function, respectively. Subject one showed a clinically significant change score for both fear avoidance of work and physical activity, with score changes of 4 and 3.3, respectively. The results of this study suggest a standardized belly dance program may positively influence pain and function in women with cLBP.

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.

Effect of Pet Insects on the Psychological Health of Community-Dwelling Elderly People: A Single-Blinded, Randomized, Controlled Trial.

PubMed

Ko, Hae-Jin; Youn, Chang-Ho; Kim, Seong-Hyun; Kim, So-Yun

2016-01-01

There is evidence that animal-assisted therapy has positive effects on mental health, especially in elderly people. Caring for insects is easy, relatively inexpensive, and does not require much space. The aim of this 8-week randomized, controlled, single-blinded study was to investigate the effect of pet insects on the psychological health of community-dwelling elderly people. Elderly subjects (≥65 years old) attending a community center in Daegu, Korea, were enrolled in the study between April and May 2014 and randomized at a 1:1 ratio to receive insect therapy and health advice or only health advice. The insect group received 5 crickets in a cage with sufficient fodder and a detailed instruction manual. At baseline and at 8 weeks, all subjects underwent psychometric tests via a direct interview [Beck Anxiety Inventory, Geriatric Depression Scale (GDS-15), Mini-Mental State Examination (MMSE), 36-Item Short Form Health Survey, Insomnia Severity Index, Fatigue Severity Scale, and Brief Encounter Psychosocial Instrument] and laboratory analyses of inflammatory and oxidative stress markers (erythrocyte sedimentation rate, high-sensitivity C-reactive protein, biological antioxidant potential, and derivatives of reactive oxygen metabolites). The insect-caring (n = 46) and control (n = 48) groups did not differ in baseline characteristics. The insect-caring group had significantly lower GDS-15 scores at week 8 (3.20 vs. 4.90, p = 0.004) and, after adjustment for baseline values, a significantly greater change in GDS-15 scores relative to baseline (-1.12 vs. 0.20, p = 0.011). They also had a significantly greater change in MMSE scores relative to baseline (1.13 vs. 0.31, p = 0.045). The two groups did not differ in terms of other psychometric and laboratory tests. No serious risks or adverse events were reported. Caring for insects, which is cost-effective and safe, was associated with a small to medium positive effect on depression and cognitive function in community-dwelling elderly people. © 2015 S. Karger AG, Basel.

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.

Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program.

PubMed

Moore, Allan F; Jablonski, Kathleen A; McAteer, Jarred B; Saxena, Richa; Pollin, Toni I; Franks, Paul W; Hanson, Robert L; Shuldiner, Alan R; Knowler, William C; Altshuler, David; Florez, Jose C

2008-09-01

Genome-wide association scans (GWASs) have identified novel diabetes-associated genes. We evaluated how these variants impact diabetes incidence, quantitative glycemic traits, and response to preventive interventions in 3,548 subjects at high risk of type 2 diabetes enrolled in the Diabetes Prevention Program (DPP), which examined the effects of lifestyle intervention, metformin, and troglitazone versus placebo. We genotyped selected single nucleotide polymorphisms (SNPs) in or near diabetes-associated loci, including EXT2, CDKAL1, CDKN2A/B, IGF2BP2, HHEX, LOC387761, and SLC30A8 in DPP participants and performed Cox regression analyses using genotype, intervention, and their interactions as predictors of diabetes incidence. We evaluated their effect on insulin resistance and secretion at 1 year. None of the selected SNPs were associated with increased diabetes incidence in this population. After adjustments for ethnicity, baseline insulin secretion was lower in subjects with the risk genotype at HHEX rs1111875 (P = 0.01); there were no significant differences in baseline insulin sensitivity. Both at baseline and at 1 year, subjects with the risk genotype at LOC387761 had paradoxically increased insulin secretion; adjustment for self-reported ethnicity abolished these differences. In ethnicity-adjusted analyses, we noted a nominal differential improvement in beta-cell function for carriers of the protective genotype at CDKN2A/B after 1 year of troglitazone treatment (P = 0.01) and possibly lifestyle modification (P = 0.05). We were unable to replicate the GWAS findings regarding diabetes risk in the DPP. We did observe genotype associations with differences in baseline insulin secretion at the HHEX locus and a possible pharmacogenetic interaction at CDKNA2/B.

The Effects of Direct Instruction Flashcards and Rewards with Math Facts at School and in the Home: Acquisition and Maintenance

ERIC Educational Resources Information Center

Mann, Zennetta; McLaughlin, T. F.; Williams, Randy Lee; Derby, K. Mark; Everson, Mary

2012-01-01

The purpose of the present study was to evaluate the effects of Direct Instruction (DI) flashcard procedure, combined with strategies and rewards on multiplication fact accuracy of two elementary school-age students. A single subject replication design across three and four sets of multiplication facts was used to evaluate outcomes. The results…

Cognitive impairment at diagnosis predicts 10-year multiple sclerosis progression.

PubMed

Moccia, Marcello; Lanzillo, Roberta; Palladino, Raffaele; Chang, Kiara Chu-Mei; Costabile, Teresa; Russo, Cinzia; De Rosa, Anna; Carotenuto, Antonio; Saccà, Francesco; Maniscalco, Giorgia Teresa; Brescia Morra, Vincenzo

2016-04-01

Cognitive impairment occurs from the early phases of multiple sclerosis (MS), and more frequently affects secondary progressive (SP) subjects than relapsing-remitting (RR). To investigate relationships between cognitive dysfunctions in newly diagnosed RRMS, and long-term MS-related outcomes. The present 10-year retrospective longitudinal study included 155 RRMS subjects, tested with the Rao Brief Repeatable Battery at MS diagnosis. The reaching of Expanded Disability Status Scale (EDSS) 4.0, and the SP conversion were recorded. 67 subjects (43.2%) reached EDSS 4.0, and 34 subjects (21.9%) converted to SP during a follow-up period of 10.0±1.8 years. Subjects with cognitive impairment at diagnosis had a rate of reaching EDSS 4.0 more than three times greater (p<0.001; HR=3.183), and a rate of SP conversion more than two times greater, as compared to cognitively preserved subjects (p=0.008; HR=2.535). In particular, better scores in the Selective Reminding Test-Delayed Recall and in the Symbol Digit Modalities Test at baseline were associated with lower SP conversion rates during the follow-up period (p=0.018; HR=0.835; and p=0.001; HR=0.941, respectively). Cognitive impairment, with particular involvement of processing speed and memory, predicts disability progression and SP conversion in newly diagnosed RRMS, highlighting the importance of cognitive assessment from the beginning of MS. © The Author(s), 2015.

The effects of sleep extension on the athletic performance of collegiate basketball players.

PubMed

Mah, Cheri D; Mah, Kenneth E; Kezirian, Eric J; Dement, William C

2011-07-01

To investigate the effects of sleep extension over multiple weeks on specific measures of athletic performance as well as reaction time, mood, and daytime sleepiness. Stanford Sleep Disorders Clinic and Research Laboratory and Maples Pavilion, Stanford University, Stanford, CA. Eleven healthy students on the Stanford University men's varsity basketball team (mean age 19.4 ± 1.4 years). Subjects maintained their habitual sleep-wake schedule for a 2-4 week baseline followed by a 5-7 week sleep extension period. Subjects obtained as much nocturnal sleep as possible during sleep extension with a minimum goal of 10 h in bed each night. Measures of athletic performance specific to basketball were recorded after every practice including a timed sprint and shooting accuracy. Reaction time, levels of daytime sleepiness, and mood were monitored via the Psychomotor Vigilance Task (PVT), Epworth Sleepiness Scale (ESS), and Profile of Mood States (POMS), respectively. Total objective nightly sleep time increased during sleep extension compared to baseline by 110.9 ± 79.7 min (P < 0.001). Subjects demonstrated a faster timed sprint following sleep extension (16.2 ± 0.61 sec at baseline vs. 15.5 ± 0.54 sec at end of sleep extension, P < 0.001). Shooting accuracy improved, with free throw percentage increasing by 9% and 3-point field goal percentage increasing by 9.2% (P < 0.001). Mean PVT reaction time and Epworth Sleepiness Scale scores decreased following sleep extension (P < 0.01). POMS scores improved with increased vigor and decreased fatigue subscales (P < 0.001). Subjects also reported improved overall ratings of physical and mental well-being during practices and games. Improvements in specific measures of basketball performance after sleep extension indicate that optimal sleep is likely beneficial in reaching peak athletic performance.

Sleep breathing disorders and cognitive function in the elderly: an 8-year follow-up study. the proof-synapse cohort.

PubMed

Martin, Magali Saint; Sforza, Emilia; Roche, Frédéric; Barthélémy, Jean Claude; Thomas-Anterion, Catherine

2015-02-01

Sleep breathing disorder (SBD) may be an important factor in age-related cognitive decline. In a cohort of healthy elderly subjects, we performed an 8-y longitudinal study to assess whether changes in cognitive function occur in untreated elderly patients with SBD and without dementia and the factors implicated in these changes. A population-based longitudinal study. Clinical research settings. A total of 559 participants of the PROOF study aged 67 y at the study entry and free from neurological disorders were examined. N/A. Abnormal breathing events were defined by an apnea-hypopnea index (AHI) > 15. The raw cognitive data and averaged Z-scores for the attentional, executive, and memory functions were collected at the baseline and follow-up. At baseline, AHI > 15 was found in 54% of subjects with 18% having an AHI > 30. At follow-up, the presence of abnormal breathing events was associated with a slight but significant decline in the attentional domain (P = 0.01), which was more evident in the subjects with an AHI > 30 (P = 0.004). No significant changes over time were observed in the executive and memory functions. Several indices of chronic hypoxemia, defined either as a cumulative peripheral oxygen saturation (SpO2) < 90% or a minimal SpO2, accounted for portions of the variance in the decline in attention. All observed effects were small, accounting for 4-7% of variance in multivariate models. In healthy elderly subjects, various components of sleep breathing disorder at baseline were associated with small changes in selected cognitive functions specific to the attention domain after controlling for multiple comorbidities, such as sleepiness, hypertension, diabetes, anxiety, and depression. ClinicalTrials.gov identifiers NCT 00759304 and NCT 00766584. © 2015 Associated Professional Sleep Societies, LLC.

Post-traumatic stress disorder in U.S. soldiers with post-traumatic headache.

PubMed

Rosenthal, Jacqueline F; Erickson, Jay C

2013-01-01

To determine the impact of post-traumatic stress disorder (PTSD) on headache characteristics and headache prognosis in U.S. soldiers with post-traumatic headache. PTSD and post-concussive headache are common conditions among U.S. Army personnel returning from deployment. The impact of comorbid PTSD on the characteristics and outcomes of post-traumatic headache has not been determined in U.S. Army soldiers. A retrospective cohort study was conducted among 270 consecutive U.S. Army soldiers diagnosed with post-traumatic headache at a single Army neurology clinic. All subjects were screened for PTSD at baseline using the PTSD symptom checklist. Headache frequency and characteristics were determined for post-traumatic headache subjects with and without PTSD at baseline. Headache measures were reassessed 3 months after the baseline visit, and were compared between groups with and without PTSD. Of 270 soldiers with post-traumatic headache, 105 (39%) met screening criteria for PTSD. There was no significant difference between subjects with PTSD and those without PTSD with regard to headache frequency (17.2 vs 15.7 headache days per month; P = .15) or chronic daily headache (58.1% vs 52.1%; P = .34). Comorbid PTSD was associated with higher headache-related disability as measured by the Migraine Disability Assessment Score. Three months after the baseline neurology clinic visit, the number of subjects with at least 50% reduction in headache frequency was similar among post-traumatic headache cases with and without PTSD (25.9% vs 26.8%). PTSD is prevalent among U.S. Army soldiers with post-traumatic headache. Comorbid PTSD is not associated with more frequent headaches or chronic daily headache in soldiers evaluated at a military neurology clinic for chronic post-traumatic headache. Comorbid PTSD does not adversely affect short-term headache outcomes, although prospective controlled trials are needed to better assess this relationship. © 2013 American Headache Society.

Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study.

PubMed

Tran, Jonathan Q; Hartung, Jeffrey P; Olson, Allan D; Mendzelevski, Boaz; Timony, Gregg A; Boehm, Marcus F; Peach, Robert J; Gujrathi, Sheila; Frohna, Paul A

2018-03-01

Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double-blind, placebo-controlled, positive-controlled, parallel-group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2 mg over 14 days) or placebo (for 14 days). A single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17. The primary end point was the time-matched, placebo-corrected, baseline-adjusted mean QTcF (ΔΔQTcF). A total of 113/124 (91.1%) subjects completed the study. The upper limits of the 2-sided 90% confidence intervals for ΔΔQTcF for both ozanimod 1 and 2 mg were below the 10-millisecond regulatory threshold. No QTcF >480 milliseconds or postdose change in QTcF of >60 milliseconds was observed. There was no evidence of a positive relationship between concentrations of ozanimod and its active metabolites and ΔΔQTcF. Although ozanimod blunted the observed diurnal increase in heart rate, excursions below predose heart rates were no greater than with placebo. Results demonstrate that ozanimod does not prolong the QTc interval or cause clinically significant bradycardia, supporting ozanimod's evolving favorable cardiac safety profile. © 2017 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Emixustat Hydrochloride for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Clinical Trial.

PubMed

Rosenfeld, Philip J; Dugel, Pravin U; Holz, Frank G; Heier, Jeffrey S; Pearlman, Joel A; Novack, Roger L; Csaky, Karl G; Koester, John M; Gregory, Jeffrey K; Kubota, Ryo

2018-04-28

To determine whether emixustat hydrochloride (emixustat) reduces the rate of enlargement of geographic atrophy (GA) compared with placebo in subjects with age-related macular degeneration (AMD) and to evaluate the safety and tolerability of emixustat over 24 months of treatment. Multicenter, randomized, double-masked, placebo-controlled, phase 2b/3 clinical trial. Patients with GA secondary to AMD, a visual acuity score of at least 35 letters, and GA with a total area of 1.25 to 18 mm 2 were enrolled. Subjects were randomized (1:1:1:1) to emixustat 2.5 mg, 5 mg, 10 mg, or placebo, administered orally once daily for 24 months. Visits included screening, baseline, and months 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, and 25. The primary efficacy end point was the mean annual growth rate of total GA area in the study eye, as measured by a central reading center using fundus autofluorescence (FAF) images. The change from baseline in normal luminance best-corrected visual acuity (NL-BCVA) was a secondary efficacy end point. Of 508 randomized subjects, 320 completed the study. Demographics and baseline characteristics were comparable between treatment groups. On average, GA lesions in the study eye grew at a similar rate in each group (emixustat: 1.69 to 1.84 mm 2 /year; placebo: 1.69 mm 2 /year; P ≥ 0.81). Changes in NL-BCVA were also comparable between groups. Subjects with a larger low luminance deficit (LLD) at baseline (≥20 letters) demonstrated a more rapid growth of GA over 24 months. No relationship was observed between the risk-allele status of the AMD-associated single-nucleotide polymorphisms tested and the growth rate of GA. The most common adverse events in emixustat-treated subjects were delayed dark adaptation (55%), chromatopsia (18%), visual impairment (15%), and erythropsia (15%). Emixustat did not reduce the growth rate of GA in AMD. The most common adverse events were ocular in nature and likely related to the drug's mechanism of action. Data gained from this study over a 2-year period add to the understanding of the natural history of GA and the baseline characteristics affecting the growth rate of GA. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Daily Goals Formulation and Enhanced Visualization of Mechanical Ventilation Variance Improves Mechanical Ventilation Score.

PubMed

Walsh, Brian K; Smallwood, Craig; Rettig, Jordan; Kacmarek, Robert M; Thompson, John; Arnold, John H

2017-03-01

The systematic implementation of evidence-based practice through the use of guidelines, checklists, and protocols mitigates the risks associated with mechanical ventilation, yet variation in practice remains prevalent. Recent advances in software and hardware have allowed for the development and deployment of an enhanced visualization tool that identifies mechanical ventilation goal variance. Our aim was to assess the utility of daily goal establishment and a computer-aided visualization of variance. This study was composed of 3 phases: a retrospective observational phase (baseline) followed by 2 prospective sequential interventions. Phase I intervention comprised daily goal establishment of mechanical ventilation. Phase II intervention was the setting and monitoring of daily goals of mechanical ventilation with a web-based data visualization system (T3). A single score of mechanical ventilation was developed to evaluate the outcome. The baseline phase evaluated 130 subjects, phase I enrolled 31 subjects, and phase II enrolled 36 subjects. There were no differences in demographic characteristics between cohorts. A total of 171 verbalizations of goals of mechanical ventilation were completed in phase I. The use of T3 increased by 87% from phase I. Mechanical ventilation score improved by 8.4% in phase I and 11.3% in phase II from baseline ( P = .032). The largest effect was in the low risk V T category, with a 40.3% improvement from baseline in phase I, which was maintained at 39% improvement from baseline in phase II ( P = .01). mechanical ventilation score was 9% higher on average in those who survived. Daily goal formation and computer-enhanced visualization of mechanical ventilation variance were associated with an improvement in goal attainment by evidence of an improved mechanical ventilation score. Further research is needed to determine whether improvements in mechanical ventilation score through a targeted, process-oriented intervention will lead to improved patient outcomes. (ClinicalTrials.gov registration NCT02184208.). Copyright © 2017 by Daedalus Enterprises.

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…

Steady-state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol XL.

PubMed

Barilla, Denise; Prasad, Pratapa; Hubert, Martine; Gumbhir-Shah, Kavita

2004-03-01

This was an open-label, randomized, three-period, three-treatment, multiple dose, crossover study in 12 healthy male and female subjects. This study evaluated single dose and steady-state pharmacokinetics of fluvastatin following single and multiple dose administrations of a new extended release fluvastatin 8 h matrix tablet, Lescol XL 80 mg and 160 mg doses once a day. The study also included a twice a day administration of an immediate release (IR) form of fluvastatin capsule, Lescol, for comparative purposes. All doses were administered for 7 days. The safety and tolerability were also assessed. The pharmacokinetics of fluvastatin were evaluated on days 1 and 7 following each treatment. Fluvastatin systemic exposure was 50% less when administered as Lescol XL 80 mg qd compared with Lescol IR 40 mg bid. Conversely, fluvastatin systemic exposure was 22% higher when administered as Lescol XL 160 mg qd compared with Lescol IR 40 mg bid. Single doses of Lescol XL 80 mg and 160 mg were dose proportional but, deviation (30%) from dose proportionality was observed for the Lescol XL 160 mg at steady-state. There appeared to be moderate (20%-40%) accumulation of serum fluvastatin maximal concentrations and exposure after multiple doses of Lescol XL tablets. Both Lescol XL 80 mg and 160 mg showed delayed absorption and longer apparent elimination half-life compared with fluvastatin IR capsule. Single and multiple doses of fluvastatin were generally well tolerated in this healthy volunteer population. Adverse event profiles were consistent with the published safety profile of the marketed formulations. Aside from one incidence of creatine phosphokinase (CPK) elevation (following Lescol XL 160 mg qd treatment), there were no safety concerns with any of the treatments when administered acutely (7 days). Copyright 2004 John Wiley & Sons, Ltd.

Blockade of the High-Affinity Interleukin-2 Receptors with Daclizumab High-Yield Process: Pharmacokinetic/Pharmacodynamic Analysis of Single- and Multiple-Dose Phase I Trials.

PubMed

Minocha, Mukul; Tran, Jonathan Q; Sheridan, James P; Othman, Ahmed A

2016-01-01

Daclizumab high-yield process (DAC HYP) is a humanized monoclonal antibody that selectively blocks the α-subunit (CD25) of the high-affinity interleukin-2 receptors, and has shown robust efficacy as a treatment for multiple sclerosis (MS). This work quantitatively characterized the relationship between DAC HYP serum concentrations and saturation of CD25 expressed on antigen-rich target T cells in blood. Serial pharmacokinetic and 968 CD25 measurements from three double-blind, randomized, placebo-controlled, phase I studies of DAC HYP (50-300 mg subcutaneous and 200-400 mg intravenous doses or placebo) in healthy volunteers (n = 95) were analyzed using nonlinear mixed-effects modeling. CD25 occupancy was determined using flow cytometry and a fluorescently-labeled DAC HYP-competing antibody. CD25 occupancy was described using a direct inhibitory sigmoidal maximum effect (E max) model (where DAC HYP fully inhibited CD25 labeling with competing antibody). Two IC50 (serum concentration corresponding to 50 % of maximal inhibition) parameters were used to describe rapid CD25 saturation at initiation of dosing and apparently slower desaturation during DAC HYP washout. Parameter estimates (95 % bootstrap confidence intervals) were: baseline CD25 labeling, 47 % (45-48); DAC HYP IC50(saturation), 0.023 µg/mL (0.005-0.073); IC50(desaturation) 0.86 µg/mL (0.74-0.98); Hill coefficient 5.6 (4.3-6.8). Based on the developed model, the 150 mg monthly subcutaneous regimen of DAC HYP in subjects with MS is predicted to saturate CD25 on target effector T cells within a few hours of dosing and maintain CD25 saturation during the entire dosing interval. Free CD25 levels return to baseline within 4-6 months of the last DAC HYP dose.

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.

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.

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).

Tailor-made rehabilitation approach using multiple types of hybrid assistive limb robots for acute stroke patients: A pilot study.

PubMed

Fukuda, Hiroyuki; Morishita, Takashi; Ogata, Toshiyasu; Saita, Kazuya; Hyakutake, Koichi; Watanabe, Junko; Shiota, Etsuji; Inoue, Tooru

2016-01-01

This article investigated the feasibility of a tailor-made neurorehabilitation approach using multiple types of hybrid assistive limb (HAL) robots for acute stroke patients. We investigated the clinical outcomes of patients who underwent rehabilitation using the HAL robots. The Brunnstrom stage, Barthel index (BI), and functional independence measure (FIM) were evaluated at baseline and when patients were transferred to a rehabilitation facility. Scores were compared between the multiple-robot rehabilitation and single-robot rehabilitation groups. Nine hemiplegic acute stroke patients (five men and four women; mean age 59.4 ± 12.5 years; four hemorrhagic stroke and five ischemic stroke) underwent rehabilitation using multiple types of HAL robots for 19.4 ± 12.5 days, and 14 patients (six men and eight women; mean age 63.2 ± 13.9 years; nine hemorrhagic stroke and five ischemic stroke) underwent rehabilitation using a single type of HAL robot for 14.9 ± 8.9 days. The multiple-robot rehabilitation group showed significantly better outcomes in the Brunnstrom stage of the upper extremity, BI, and FIM scores. To the best of the authors' knowledge, this is the first pilot study demonstrating the feasibility of rehabilitation using multiple exoskeleton robots. The tailor-made rehabilitation approach may be useful for the treatment of acute stroke.

Common Genetic Variant Risk Score Is Associated With Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study.

PubMed

Strauss, David G; Vicente, Jose; Johannesen, Lars; Blinova, Ksenia; Mason, Jay W; Weeke, Peter; Behr, Elijah R; Roden, Dan M; Woosley, Ray; Kosova, Gulum; Rosenberg, Michael A; Newton-Cheh, Christopher

2017-04-04

Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known. We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs. Genetic analysis of 22 subjects was performed in a secondary analysis of a randomized, double-blind, placebo-controlled, crossover trial of 3 QT-prolonging drugs with 15 time-matched QT and plasma drug concentration measurements. Subjects received single doses of dofetilide, quinidine, ranolazine, and placebo. The outcome was the correlation between a genetic QT score comprising 61 common genetic variants and the slope of an individual subject's drug-induced increase in heart rate-corrected QT (QTc) versus drug concentration. The genetic QT score was correlated with drug-induced QTc prolongation. Among white subjects, genetic QT score explained 30% of the variability in response to dofetilide ( r =0.55; 95% confidence interval, 0.09-0.81; P =0.02), 23% in response to quinidine ( r =0.48; 95% confidence interval, -0.03 to 0.79; P =0.06), and 27% in response to ranolazine ( r =0.52; 95% confidence interval, 0.05-0.80; P =0.03). Furthermore, the genetic QT score was a significant predictor of drug-induced torsade de pointes in an independent sample of 216 cases compared with 771 controls ( r 2 =12%, P =1×10 -7 ). We demonstrate that a genetic QT score comprising 61 common genetic variants explains a significant proportion of the variability in drug-induced QT prolongation and is a significant predictor of drug-induced torsade de pointes. These findings highlight an opportunity for recent genetic discoveries to improve individualized risk-benefit assessment for pharmacological therapies. Replication of these findings in larger samples is needed to more precisely estimate variance explained and to establish the individual variants that drive these effects. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01873950. © 2017 American Heart Association, Inc.

Baseline Vascular Cognitive Impairment Predicts the Course of Apathetic Symptoms After Stroke: The CASPER Study.

PubMed

Douven, Elles; Köhler, Sebastian; Schievink, Syenna H J; van Oostenbrugge, Robert J; Staals, Julie; Verhey, Frans R J; Aalten, Pauline

2018-03-01

To examine the influence of vascular cognitive impairment (VCI) on the course of poststroke depression (PSD) and poststroke apathy (PSA). Included were 250 stroke patients who underwent neuropsychological and neuropsychiatric assessment 3 months after stroke (baseline) and at a 6- and 12-month follow-up after baseline. Linear mixed models tested the influence of VCI in at least one cognitive domain (any VCI) or multidomain VCI (VCI in multiple cognitive domains) at baseline and domain-specific VCI at baseline on levels of depression and apathy over time, with random effects for intercept and slope. Almost half of the patients showed any VCI at baseline, and any VCI was associated with increasing apathy levels from baseline to the 12-month follow-up. Patients with multidomain VCI had higher apathy scores at the 6- and 12-month follow-up compared with patients with VCI in a single cognitive domain. Domain-specific analyses showed that impaired executive function and slowed information processing speed went together with increasing apathy levels from baseline to 6- and 12-month follow-up. None of the cognitive variables predicted the course of depressive symptoms. Baseline VCI is associated with increasing apathy levels from baseline to the chronic stroke phase, whereas no association was found between baseline VCI and the course of depressive symptoms. Health professionals should be aware that apathy might be absent early after stroke but may evolve over time in patients with VCI. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Multilevel Analysis of Multiple-Baseline Data Evaluating Precision Teaching as an Intervention for Improving Fluency in Foundational Reading Skills for at Risk Readers

ERIC Educational Resources Information Center

Brosnan, Julie; Moeyaert, Mariola; Brooks Newsome, Kendra; Healy, Olive; Heyvaert, Mieke; Onghena, Patrick; Van den Noortgate, Wim

2018-01-01

In this article, multiple-baseline across participants designs were used to evaluate the impact of a precision teaching (PT) program, within a Tier 2 Response to Intervention framework, targeting fluency in foundational reading skills with at risk kindergarten readers. Thirteen multiple-baseline design experiments that included participation from…

Carotid intima-media thickness is associated with the progression of cognitive impairment in older adults.

PubMed

Moon, Jae Hoon; Lim, Soo; Han, Ji Won; Kim, Kyoung Min; Choi, Sung Hee; Park, Kyong Soo; Kim, Ki Woong; Jang, Hak Chul

2015-04-01

We investigated the association between cardiovascular risk factors, including carotid intima-media thickness (CIMT), and future risk of mild cognitive impairment (MCI) and dementia in elderly subjects. We conducted a population-based prospective study as a part of the Korean Longitudinal Study on Health and Aging. Our study included 348 participants who were nondemented at the baseline (mean age, 71.7±6.3 years) and underwent cognitive evaluation at the 5-year follow-up. Baseline cardiovascular risk factors were compared according to the development of MCI or dementia during the study period. At the baseline evaluation, 278 subjects were cognitively normal and 70 subjects had MCI. Diagnoses of cognitive function either remained unchanged or improved during the study period in 292 subjects (nonprogression group), whereas 56 subjects showed progression of cognitive impairment to MCI or dementia (progression group). The progression group exhibited a higher prevalence of hypertension and greater CIMT compared with the nonprogression group. Other baseline cardiovascular risk factors, including sex, body mass index, diabetes mellitus, insulin resistance, total cholesterol, waist-to-hip ratio, visceral fat, pulse wave velocity, and ankle-brachial index, were not significantly different between 2 groups. The association between greater baseline CIMT and the progression of cognitive impairment was maintained after adjustment for conventional baseline risk factors of cognitive impairment. Greater baseline CIMT was also independently associated with the development of MCI in the subjects whose baseline cognitive function was normal. Greater baseline CIMT was independently associated with the risk of cognitive impairment, such as MCI and dementia in elderly subjects. © 2015 American Heart Association, Inc.

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

Observational Model for Precision Astrometry with the Space Interferometry Mission

NASA Technical Reports Server (NTRS)

Turyshev, Slava G.; Milman, Mark H.

2000-01-01

The Space Interferometry Mission (SIM) is a space-based 10-m baseline Michelson optical interferometer operating in the visible waveband that is designed to achieve astrometric accuracy in the single digits of the microarcsecond domain. Over a narrow field of view SIM is expected to achieve a mission accuracy of 1 microarcsecond. In this mode SIM will search for planetary companions to nearby stars by detecting the astrometric "wobble" relative to a nearby reference star. In its wide-angle mode, SIM will provide 4 microarcsecond precision absolute position measurements of stars, with parallaxes to comparable accuracy, at the end of its 5-year mission. The expected proper motion accuracy is around 3 microarcsecond/year, corresponding to a transverse velocity of 10 m/ s at a distance of 1 kpc. The basic astrometric observable of the SIM instrument is the pathlength delay. This measurement is made by a combination of internal metrology measurements that determine the distance the starlight travels through the two arms of the interferometer, and a measurement of the white light stellar fringe to find the point of equal pathlength. Because this operation requires a non-negligible integration time, the interferometer baseline vector is not stationary over this time period, as its absolute length and orientation are time varying. This paper addresses how the time varying baseline can be "regularized" so that it may act as a single baseline vector for multiple stars, as required for the solution of the astrometric equations.

Prevalence and predictors of healthcare utilization among older people (60+): focusing on ADL dependency and risk of depression.

PubMed

Sandberg, Magnus; Kristensson, Jimmie; Midlöv, Patrik; Fagerström, Cecilia; Jakobsson, Ulf

2012-01-01

The aim of this study was to investigate healthcare utilization patterns over a six-year period among older people (60+), classified as dependent/independent in Activities of Daily Living (ADL) and/or at/not at risk of depression and to identify healthcare utilization predictors. A sample (n=1402) comprising ten age cohorts aged between 60 and 96 years was drawn from the Swedish National study on Aging and Care (SNAC). Baseline data were collected between 2001 and 2003. Number and length of hospital stays were collected for six years after baseline year. Group differences and mean changes over time were investigated. Healthcare utilization predictors were explored using multiple linear regression analysis. The results revealed that 21-24% had at least one hospital stay in the six years after baseline, 29-37% among ADL dependent subjects and 24-33% among those at risk of depression. There was a significant increase of hospital stays in all groups over time. ADL-dependent subjects and those at risk of depression had significant more hospital stays, except for those at/not at risk of depression in years 2, 4 and 5. The healthcare utilization predictors 5-6 years after baseline were mainly age, previous healthcare utilization and various symptoms and, in 1-2 and 3-4 years after baseline, age, various diagnostic groups and various physical variables. Thus healthcare utilization patterns seem to be similar for the different groups, but it is difficult to find universal predictors. This suggests that different variables should be considered, including both ADL and psychosocial variables, when trying to identify future healthcare users. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performance.

PubMed

Pejovic, Slobodanka; Basta, Maria; Vgontzas, Alexandros N; Kritikou, Ilia; Shaffer, Michele L; Tsaoussoglou, Marina; Stiffler, David; Stefanakis, Zacharias; Bixler, Edward O; Chrousos, George P

2013-10-01

One workweek of mild sleep restriction adversely impacts sleepiness, performance, and proinflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation, and stress hormones, 30 healthy young men and women (mean age ± SD, 24.7 ± 3.5 yr; mean body mass index ± SD, 23.6 ± 2.4 kg/m(2)) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8 h/night), followed by 6 sleep restriction nights (6 h/night) and 3 recovery nights (10 h/night)]. Twenty-four-hour profiles of circulating IL-6 and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after 1 wk of sleep restriction), and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared with baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one work week of mild sleep restriction on daytime sleepiness, fatigue, and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown.

Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performance

PubMed Central

Pejovic, Slobodanka; Basta, Maria; Kritikou, Ilia; Shaffer, Michele L.; Tsaoussoglou, Marina; Stiffler, David; Stefanakis, Zacharias; Bixler, Edward O.; Chrousos, George P.

2013-01-01

One workweek of mild sleep restriction adversely impacts sleepiness, performance, and proinflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation, and stress hormones, 30 healthy young men and women (mean age ± SD, 24.7 ± 3.5 yr; mean body mass index ± SD, 23.6 ± 2.4 kg/m2) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8 h/night), followed by 6 sleep restriction nights (6 h/night) and 3 recovery nights (10 h/night)]. Twenty-four-hour profiles of circulating IL-6 and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after 1 wk of sleep restriction), and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared with baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one work week of mild sleep restriction on daytime sleepiness, fatigue, and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown. PMID:23941878

Diagnostic Instability and Reversals of Chronic Obstructive Pulmonary Disease Diagnosis in Individuals with Mild to Moderate Airflow Obstruction.

PubMed

Aaron, Shawn D; Tan, Wan C; Bourbeau, Jean; Sin, Don D; Loves, Robyn H; MacNeil, Jenna; Whitmore, George A

2017-08-01

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive disease, and reversal of COPD diagnosis is thought to be uncommon. To determine whether a spirometric diagnosis of mild or moderate COPD is subject to variability and potential error. We examined two prospective cohort studies that enrolled subjects with mild to moderate post-bronchodilator airflow obstruction. The Lung Health Study (n = 5,861 subjects; study duration, 5 yr) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study (n = 1,551 subjects; study duration, 4 yr) were examined to determine frequencies of (1) diagnostic instability, represented by how often patients initially met criteria for a spirometric diagnosis of COPD but then crossed the diagnostic threshold to normal and then crossed back to COPD over a series of annual visits, or vice versa; and (2) diagnostic reversals, defined as how often an individual's COPD diagnosis at the study outset reversed to normal by the end of the study. Diagnostic instability was common and occurred in 19.5% of the Lung Health Study subjects and 6.4% of the CanCOLD subjects. Diagnostic reversals of COPD from the beginning to the end of the study period occurred in 12.6% and 27.2% of subjects in the Lung Health Study and CanCOLD study, respectively. The risk of diagnostic instability was greatest for subjects whose baseline FEV 1 /FVC value was closest to the diagnostic threshold, and the risk of diagnostic reversal was greatest for subjects who quit smoking during the study. A single post-bronchodilator spirometric assessment may not be reliable for diagnosing COPD in patients with mild to moderate airflow obstruction at baseline.

Workplace bullying and mental distress - a prospective study of Norwegian employees.

PubMed

Finne, Live Bakke; Knardahl, Stein; Lau, Bjørn

2011-07-01

Using a prospective design, the objective of this study was to determine the relationship between workplace bullying and mental distress. Altogether, 1971 Norwegian employees, recruited from 20 organizations, answered questions regarding workplace bullying and mental distress at both baseline and follow-up. Baseline data were gathered between 2004-2006, and follow-up data were gathered between 2006-2009. The time-lag between baseline and follow-up was approximately two years for all the respondents in all the organizations. The factors measured in the study were individual characteristics, mental distress measured with the Hopkins Symptom Checklist (HSCL-10), self-reported workplace bullying measured with a single item from the General Nordic Questionnaire for Psychological and Social Factors at Work (QPSNordic) and job demands and job control assessed by QPSNordic. A multiple linear regression analysis adjusted for mental distress, sex, age, job demands and job control at baseline [β=0.05, 95% confidence interval (95% CI) 0.03-0.17] and a repeated measures ANOVA adjusted for sex and age [F(3,1965)=38.37; partial η (2)=0.06] showed that workplace bullying predicted mental distress. Furthermore, a multiple binary logistic regression analysis adjusted for bullying, sex, age, job demands and job control at baseline [odds ratio (OR) 2.30, 95% CI 1.43-3.69] showed that mental distress was a predictor of bullying. We found support for the notion that self-reported workplace bullying is a predictor of mental distress two years later. Bullying had an independent effect on mental distress after adjusting for job demands and job control. Mental distress was also found to be a predictor of bullying, indicating that the reverse relationship is also important.

Space Systems - Safety and Compatibility of Materials - Method to Determine the Ignition Susceptibility of Materials or Components to Particle Impact

NASA Technical Reports Server (NTRS)

Hirsch, David B.

2011-01-01

The scope of this International Technical Specification is to provide a method to determine the ignition susceptibility of materials and components to particle impact. The method can be used to determine the conditions at which ignition and consumption of a specimen material occurs when impacted by single or multiple particles entrained in a flow of gaseous oxygen (GOX). Alternatively, the method can be used to determine if a specific material or component is subject to ignition and sustained combustion in a given flow environment when impacted by single or multiple particles entrained in a flow of GOX.

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

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.

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.

Best (but oft-forgotten) practices: the multiple problems of multiplicity-whether and how to correct for many statistical tests.

PubMed

Streiner, David L

2015-10-01

Testing many null hypotheses in a single study results in an increased probability of detecting a significant finding just by chance (the problem of multiplicity). Debates have raged over many years with regard to whether to correct for multiplicity and, if so, how it should be done. This article first discusses how multiple tests lead to an inflation of the α level, then explores the following different contexts in which multiplicity arises: testing for baseline differences in various types of studies, having >1 outcome variable, conducting statistical tests that produce >1 P value, taking multiple "peeks" at the data, and unplanned, post hoc analyses (i.e., "data dredging," "fishing expeditions," or "P-hacking"). It then discusses some of the methods that have been proposed for correcting for multiplicity, including single-step procedures (e.g., Bonferroni); multistep procedures, such as those of Holm, Hochberg, and Šidák; false discovery rate control; and resampling approaches. Note that these various approaches describe different aspects and are not necessarily mutually exclusive. For example, resampling methods could be used to control the false discovery rate or the family-wise error rate (as defined later in this article). However, the use of one of these approaches presupposes that we should correct for multiplicity, which is not universally accepted, and the article presents the arguments for and against such "correction." The final section brings together these threads and presents suggestions with regard to when it makes sense to apply the corrections and how to do so. © 2015 American Society for Nutrition.

Framing effects in choices between multioutcome life-expectancy lotteries.

PubMed

Bernstein, L M; Chapman, G B; Elstein, A S

1999-01-01

To explore framing or editing effects and a method to debias framing in a clinical context. Clinical scenarios using multioutcome life-expectancy lotteries of equal value required choices between two supplementary drugs that either prolonged or shortened life from the 20-year beneficial effect of a baseline drug. The effects of these supplementary drugs were presented in two conditions, using a between-subjects design. In segregated editing (n = 116) the effects were presented separately from the effects of the baseline drug. In integrated editing (n = 100), effects of supplementary and baseline drugs were combined in the lottery presentation. Each subject responded to 30 problems. To explore one method of debiasing, another 100 subjects made choices after viewing both segregated and integrated editings of 20 problems (dual framing). Statistically significant preference reversals between segregated and integrated editing of pure lotteries occurred only when one framing placed outcomes in the gain domain, and the other framing placed them in the loss domain. When both editings resulted in gain-domain outcomes only, there was no framing effect. There was a related relationship of framing-effect shifts from losses to gains in mixed-lottery-choice problems. Responses to the dual framing condition did not consistently coincide with responses to either single framing. In some situations, dual framing eliminated or lessened framing effects. The results support two components of prospect theory, coding outcomes as gains or losses from a reference point, and an s-shaped utility function (concave in gain, convex in loss domains). Presenting both alternative editings of a complex situation prior to choice more fully informs the decision maker and may help to reduce framing effects. Given the extent to which preferences shift in response to alternative presentations, it is unclear which choice represents the subject's "true preferences."

Regulation of oxidative stress in response to acute aerobic and resistance exercise in HIV-infected subjects: a case-control study.

PubMed

Deresz, L F; Sprinz, E; Kramer, A S; Cunha, G; de Oliveira, A R; Sporleder, H; de Freitas, D R J; Lazzarotto, A R; Dall'Ago, P

2010-11-01

Human immunodeficiency virus (HIV)-infected subjects have increased levels of oxidative stress which could impair immunological function and therefore contribute to the progression of AIDS. These characteristics are usually evaluated at rest and responses to exercise have yet to be evaluated. The aim of the present study was to assess the effect of a bout of aerobic exercise followed by resistance exercises on antioxidant system in HIV-infected and non-HIV subjects. There were included 14 cases (HIV-positive) and 14 controls (HIV-negative). The exercise protocol consisted of a single session of 20 minutes on a cycloergometer followed by a set of six resistance exercises. The activity of glutathione S-transferase (GST) and catalase were measured in plasma samples, total glutathione (TGSH) and thiobarbituric acid reactive substances (TBARS) were measured in erythrocytes. T CD4+ cells, T CD8+, viral load, complete blood count, and white blood count were also assessed. All measurements were performed at three times: baseline, after aerobic exercise, and after resistance exercises. At baseline, the HIV group had lower GST activity than controls, but after the exercise session GST values were similar in both groups. Compared to the control group TGSH was significantly lower in the HIV group at baseline, after aerobic and resistance exercises. The control group presented higher TBARS values after aerobic exercise compared to the HIV group. The neutrophil count was lower in the HIV group after aerobic and resistance exercises. These data indicate that HIV-infected subjects had lower antioxidant activity at rest. Physical exercise stimulated the enzymatic activity similarly in both groups.

Association of subjective memory complaints with subsequent cognitive decline in community-dwelling elderly individuals with baseline cognitive impairment.

PubMed

Schofield, P W; Marder, K; Dooneief, G; Jacobs, D M; Sano, M; Stern, Y

1997-05-01

The validity of subjective memory complaints has been questioned by clinical studies that have shown little relationship between memory complaints and objective memory performance. These studies often have been cross-sectional in design, have excluded individuals with cognitive impairment, or have lacked a comparison group. The authors conducted a study that attempted to avoid these limitations. Memory complaints of 364 nondemented, community-dwelling elderly individuals were recorded as present or absent at the baseline evaluation. After 1 year, 169 subjects were reevaluated. Standardized neurologic and neuropsychological evaluations were used at each assessment to classify subjects as normal or cognitively impaired. At baseline, 31% of the normal subjects and 47% of those with cognitive impairment had memory complaints. Subjects with memory complaints had higher Hamilton depression scale scores than subjects without memory complaints but equivalent scores on a measure of total recall. At follow-up, multivariate analyses showed that subjects with baseline memory complaints had significantly greater decline in memory and cognition than subjects without memory complaints. Secondary analyses showed this effect to be confined to subjects with baseline cognitive impairment. Memory complaints may lack validity in subjects with normal cognition, but in nondemented individuals with cognitive impairment, memory complaints may predict subsequent cognitive decline.

[Predictors of social isolation among older people living in urban area: a prospective study].

PubMed

Ejiri, Manami; Kawai, Hisashi; Fujiwara, Yoshinori; Ihara, Kazushige; Hirano, Hirohiko; Kojima, Motonaga; Obuchi, Shuichi

2018-01-01

Objectives　We aimed to investigate the predictors of social isolation among older people living in urban area.Methods　A mail survey was sent out to 7,015 elderly subjects living in nine districts of Itabashi ward. At baseline (2012), 3,696 subjects and at follow-up (2014) 2,375 replied to the self-administered questionnaire. We defined social isolation as seeing friends or relatives less than two or three times a month. Gender, age, self-rated health, present illnesses, instrumental activities of daily living (IADL), frequency of going out, frequency of social participation, family structure, and perceived financial status were also investigated. A t-test, a chi-square test, and logistic regression analysis were conducted to examine the predictors of social isolation in a follow-up study.Results　Of the 1,791 subjects who were analyzed for social isolation, 348 (19.4%) were found to be socially isolated in 2014. A multiple logistic regression analysis showed that men (adjusted odds ratio, 1.88; 95% confidence interval, 1.41-2.50) were significantly more likely to be isolated than women. Being older (1.03, 1.01-1.06) was also a significant predictor of isolation. Subjects who participated in group activities one to three times a month (1.62, 1.04-2.53) were significantly more likely to be isolated than those who participated in them more than once a week. Subjects who rated their financial status as low (1.67, 1.20-2.32) were more likely to be isolated than those who rated it as high. Subjects who were isolated (10.24, 7.60-13.81), and those who did not respond to questions about isolation (8.15, 3.76-17.67), were significantly more likely to be isolated than those who were not isolated at baseline. Among the subjects who were not isolated at baseline, being male (2.39, 1.57-3.64) and lower self-rated health (3.99, 1.33-11.94) were predictors of social isolation.Conclusion　Participation in social activities is effective in preventing social isolation among elderly men living in urban area.

Rainbow: a tool for large-scale whole-genome sequencing data analysis using cloud computing.

PubMed

Zhao, Shanrong; Prenger, Kurt; Smith, Lance; Messina, Thomas; Fan, Hongtao; Jaeger, Edward; Stephens, Susan

2013-06-27

Technical improvements have decreased sequencing costs and, as a result, the size and number of genomic datasets have increased rapidly. Because of the lower cost, large amounts of sequence data are now being produced by small to midsize research groups. Crossbow is a software tool that can detect single nucleotide polymorphisms (SNPs) in whole-genome sequencing (WGS) data from a single subject; however, Crossbow has a number of limitations when applied to multiple subjects from large-scale WGS projects. The data storage and CPU resources that are required for large-scale whole genome sequencing data analyses are too large for many core facilities and individual laboratories to provide. To help meet these challenges, we have developed Rainbow, a cloud-based software package that can assist in the automation of large-scale WGS data analyses. Here, we evaluated the performance of Rainbow by analyzing 44 different whole-genome-sequenced subjects. Rainbow has the capacity to process genomic data from more than 500 subjects in two weeks using cloud computing provided by the Amazon Web Service. The time includes the import and export of the data using Amazon Import/Export service. The average cost of processing a single sample in the cloud was less than 120 US dollars. Compared with Crossbow, the main improvements incorporated into Rainbow include the ability: (1) to handle BAM as well as FASTQ input files; (2) to split large sequence files for better load balance downstream; (3) to log the running metrics in data processing and monitoring multiple Amazon Elastic Compute Cloud (EC2) instances; and (4) to merge SOAPsnp outputs for multiple individuals into a single file to facilitate downstream genome-wide association studies. Rainbow is a scalable, cost-effective, and open-source tool for large-scale WGS data analysis. For human WGS data sequenced by either the Illumina HiSeq 2000 or HiSeq 2500 platforms, Rainbow can be used straight out of the box. Rainbow is available for third-party implementation and use, and can be downloaded from http://s3.amazonaws.com/jnj_rainbow/index.html.