Within-subject Differences Research Articles

Flicker light-induced retinal vasodilation is unaffected by inhibition of epoxyeicosatrienoic acids and prostaglandins in humans.

To investigate the role of epoxyeicosatrienoic acids (EETs) and prostaglandins (PGs) in retinal blood vessel calibers and vasodilation during flicker light stimulation in humans. Twelve healthy nonsmokers participated in a balanced crossover study. Oral fluconazole 400 mg and dispersible aspirin 600 mg were used to inhibit production of EETs and PGs, respectively. Retinal imaging was performed 1 hour after drug ingestion with the Dynamic Vessel Analyzer. Resting calibers of selected vessel segments were recorded in measurement units (MU). Maximum percentage dilations during flicker stimulation were calculated from baseline calibers. We then studied six participants each after fluconazole and aspirin ingestions at 30-minute intervals for 2 hours. Within-subject differences were assessed by ANOVA and Dunnett-adjusted pairwise comparisons with significance taken at P < 0.05. In crossover study participants, mean (SD) arteriole and venule dilations without drug administration were 4.4% (2.0%) and 4.6% (1.7%), respectively. Neither drug affected vasodilation during flicker stimulation. Mean (SD) resting arteriole and venule calibers on no-drug visits were 119.6 (10.6) MU and 145.7 (17.0) MU, respectively. Fluconazole reduced mean (±95% CI) resting venule calibers by 5.1 (4.3) MU. In repeated measures participants, neither drug affected vasodilations, but fluconazole reduced resting venule calibers over 2 hours (P < 0.001). Epoxyeicosatrienoic acids and prostaglandins are unlikely to be primary mediators of flicker light-induced retinal vasodilation in humans. However, EETs may play a role in the regulation of retinal vascular tone and blood flow under resting physiological conditions.

A recommended analysis for 2 × 2 crossover trials with baseline measurements.

In many two-period, two-treatment (2 × 2) crossover trials, for each subject, a continuous response of interest is measured before and after administration of the assigned treatment within each period. The resulting data are typically used to test a null hypothesis involving the true difference in treatment response means. We show that the power achieved by different statistical approaches is greatly influenced by (i) the 'structure' of the variance-covariance matrix of the vector of within-subject responses and (ii) how the baseline (i.e., pre-treatment) responses are accounted for in the analysis. For (ii), we compare different approaches including ignoring one or both period baselines, using a common change from baseline analysis (which we advise against), using functions of one or both baselines as period-specific or period-invariant covariates, and doing joint modeling of the post-baseline and baseline responses with corresponding mean constraints for the latter. Based on theoretical arguments and simulation-based type I error rate and power properties, we recommend an analysis of covariance approach that uses the within-subject difference in treatment responses as the dependent variable and the corresponding difference in baseline responses as a covariate. Data from three clinical trials are used to illustrate the main points.

The (lack of) effect of alprazolam on eating behavior in anorexia nervosa: a preliminary report.

Anxiety is a prominent symptom in anorexia nervosa (AN), and higher pre-meal anxiety has been associated with lower caloric intake. Yet, the causal relationship has not been assessed. We proposed that reducing anxiety with a short acting benzodiazepine would increase caloric intake among individuals with AN. In a randomized, double-blind, placebo controlled cross-over study, we administered alprazolam 0.75 mg to inpatients with AN (n = 17) and assessed caloric intake in a laboratory test meal. Within-subject differences in caloric intake, anxiety, and fatigue were compared between alprazolam and placebo days. Caloric intake did not differ on alprazolam versus placebo (t(15) = 1.72, p = .11). Alprazolam did not reduce anxiety, but was associated with increased fatigue. This study was not able to evaluate the causal role of anxiety in meal intake among individuals with AN, as alprazolam did not alter anxiety symptoms. These data further suggest that the therapeutic role for short-acting benzodiazepines in AN is likely limited.

Flicker-induced retinal arteriole dilation is reduced by ambient lighting.

To investigate the impact of ambient room lighting on the magnitude of flicker light-induced retinal vasodilations in healthy individuals. Twenty healthy nonsmokers participated in a balanced 2 × 2 crossover study. Retinal vascular imaging was performed with the dynamic vessel analyzer under reduced or normal ambient lighting, then again after 20 minutes under the alternate condition. Baseline calibers of selected arteriole and venule segments were recorded in measurement units. Maximum percentage dilations from baseline during 20 seconds of luminance flicker were calculated from the mean of three measurement cycles. Within-subject differences were assessed by repeated measures analysis of variance with the assumption of no carryover effects and pairwise comparisons from the fitted model. Mean (SD) maximum arteriole dilations during flicker stimulation under reduced and normal ambient lighting were 4.8% (2.3%) and 4.1% (1.9%), respectively (P = 0.019). Maximum arteriole dilations were (mean ± 95% confidence interval) 0.7% ± 0.6% lower under normal ambient lighting compared with reduced lighting. Ambient lighting had no significant effect on maximum venular dilations during flicker stimulation or on the baseline calibers of arterioles or venules. Retinal arteriole dilation in response to luminance flicker stimulation is reduced under higher ambient lighting conditions. Reduced responses with higher ambient lighting may reflect reduced contrast between the ON and OFF flicker phases. Although it may not always be feasible to conduct studies under reduced lighting conditions, ambient lighting levels should be consistent to ensure that comparisons are valid.

Heart rate variability and swimming.

Professionals in the domain of swimming have a strong interest in implementing research methods in evaluating and improving training methods to maximize athletic performance and competitive outcome. Heart rate variability (HRV) has gained attention in research on sport and exercise to assess autonomic nervous system activity underlying physical activity and sports performance. Studies on swimming and HRV are rare. This review aims to summarize the current evidence on the application of HRV in swimming research and draws implications for future research. A systematic search of databases (PubMed via MEDLINE, PSYNDEX and Embase) according to the PRISMA statement was employed. Studies were screened for eligibility on inclusion criteria: (a) empirical investigation (HRV) in humans (non-clinical); (b) related to swimming; (c) peer-reviewed journal; and (d) English language. The search revealed 194 studies (duplicates removed), of which the abstract was screened for eligibility. Fourteen studies meeting the inclusion criteria were included in the review. Included studies broadly fell into three classes: (1) control group designs to investigate between-subject differences (i.e. swimmers vs. non-swimmers, swimmers vs. other athletes); (2) repeated measures designs on within-subject differences of interventional studies measuring HRV to address different modalities of training or recovery; and (3) other studies, on the agreement of HRV with other measures. The feasibility and possibilities of HRV within this particular field of application are well documented within the existing literature. Future studies, focusing on translational approaches that transfer current evidence in general practice (i.e. training of athletes) are needed.

Induced α rhythms track the content and quality of visual working memory representations with high temporal precision.

Past work has suggested that neuronal oscillations coordinate the cellular assemblies that represent items in working memory (WM). In line with this hypothesis, we show that the spatial distribution of power in the alpha frequency band (8-12 Hz) can be used to decode the content and quality of the representations stored in visual WM. We acquired EEG data during an orientation WM task, and used a forward encoding model of orientation selectivity to reconstruct orientation-specific response profiles (termed channel tuning functions, or CTFs) that tracked the orientation of the memorandum during both encoding and delay periods of the trial. Critically, these EEG-based CTFs were robust predictors of both between- and within-subject differences in mnemonic precision, showing that EEG-based CTFs provide a sensitive measure of the quality of sensory population codes. Experiments 2 and 3 established that these EEG-based CTFs are contingent on the voluntary storage goals of the observer. When observers were given a postsample cue to store or drop the memorandum, the resulting CTF was sustained in the "store" condition and rapidly eliminated following the "drop" cue. When observers were instructed to store one of two simultaneously presented stimuli, only the stored item was represented in a sustained fashion throughout the delay period. These findings suggest that the oscillatory activity in the alpha frequency band plays a central role in the active storage of information in visual WM, and demonstrate a powerful approach for tracking the precision of on-line memories with high temporal resolution.

Ability tilt on the SAT and ACT predicts specific abilities and college majors

This research examined the validity of ability tilt, measured as within-subject differences in math and verbal scores on the SAT and ACT. Tilt scores were correlated with academic abilities (math and verbal) and college majors (STEM and humanities), both drawn from the National Longitudinal Survey of Youth. Math tilt (math>verbal) correlated positively with math ability and negatively with verbal ability, whereas verbal tilt (verbal>math) showed the opposite pattern. In addition, math tilt was associated with STEM majors (e.g., science and math), whereas verbal tilt was associated with humanities majors (e.g., English and history). Both math and verbal tilt were unrelated to non-academic abilities (speed and shop) and g. The results support niche-picking and investment theories, in which investment in one area (math) means less investment in competing areas (verbal).

Neurobehavioral Effects of Aspartame Consumption

Despite its widespread use, the artificial sweetener aspartame remains one of the most controversial food additives, due to mixed evidence on its neurobehavioral effects. Healthy adults who consumed a study-prepared high-aspartame diet (25 mg/kg body weight/day) for 8 days and a low-aspartame diet (10 mg/kg body weight/day) for 8 days, with a 2-week washout between the diets, were examined for within-subject differences in cognition, depression, mood, and headache. Measures included weight of foods consumed containing aspartame, mood and depression scales, and cognitive tests for working memory and spatial orientation. When consuming high-aspartame diets, participants had more irritable mood, exhibited more depression, and performed worse on spatial orientation tests. Aspartame consumption did not influence working memory. Given that the higher intake level tested here was well below the maximum acceptable daily intake level of 40-50 mg/kg body weight/day, careful consideration is warranted when consuming food products that may affect neurobehavioral health.

Isotonic resistance jaw exercise alters jaw muscle coordination during jaw movements

The aim was to investigate the effects of isotonic resistance exercise on the electro-myographic (EMG) activity of the jaw muscles during standardised jaw movements. In 12 asymptomatic adults surface EMG activity was recorded from the anterior temporalis and masseter muscles bilaterally and the right anterior digastric muscle during right lateral jaw movements that tracked a target. Participants were randomly assigned to a Control group or an Exercise group. Jaw movement and EMG activity were collected (i) at baseline, before the exercise task (pre-exercise); (ii) immediately after the exercise task (isotonic resistance at 60% MVC against right lateral jaw movements); (iii) after 4 weeks of a home-based exercise programme; and, (iv) at 8-weeks follow-up. There were no significant within-subject or between-group differences in the velocity and amplitude of the right lateral jaw movements either within or between data collection sessions (P > 0.05). However, over the 8 weeks of the study, three of the tested EMG variables (EMG Duration, Time to Peak EMG from EMG Onset, and Time to Peak EMG activity relative to Movement Onset) showed significant (P < 0.05) differences in the five tested muscles. Many of the significant changes occurred in the Control group, while the Exercise group tended to maintain the majority of the tested variables at pre-exercise baseline values. The data suggest a level of variability between recording sessions in the recruitment patterns of some of the muscles of mastication for the production of the same right lateral jaw movement and that isotonic resistance exercise may reduce this variability.

Comparison of the Hedonic General Labeled Magnitude Scale with the Hedonic 9‐Point Scale

The hedonic 9-point scale was designed to compare palatability among different food items; however, it has also been used occasionally to compare individuals and groups. Such comparisons can be invalid because scale labels (for example, "like extremely") can denote systematically different hedonic intensities across some groups. Addressing this problem, the hedonic general Labeled Magnitude Scale (gLMS) frames affective experience in terms of the strongest imaginable liking/disliking of any kind, which can yield valid group comparisons of food palatability provided extreme hedonic experiences are unrelated to food. For each scale, 200 panelists rated affect for remembered food products (including favorite and least favorite foods) and sampled foods; they also sampled taste stimuli (quinine, sucrose, NaCl, citric acid) and rated their intensity. Finally, subjects identified experiences representing the endpoints of the hedonic gLMS. Both scales were similar in their ability to detect within-subject hedonic differences across a range of food experiences, but group comparisons favored the hedonic gLMS. With the 9-point scale, extreme labels were strongly associated with extremes in food affect. In contrast, gLMS data showed that scale extremes referenced nonfood experiences. Perceived taste intensity significantly influenced differences in food liking/disliking (for example, those experiencing the most intense tastes, called supertasters, showed more extreme liking and disliking for their favorite and least favorite foods). Scales like the hedonic gLMS are suitable for across-group comparisons of food palatability.

Balance Ability and Proprioception after Single-Bundle, Single-Bundle Augmentation, and Double-Bundle ACL Reconstruction

Purpose. The present study sought to determine the influences of single-bundle (SB), single-bundle augmentation (SBA), and double-bundle (DB) reconstructions on balance ability and proprioceptive function. Methods. 67 patients who underwent a single- or double-bundle ACL reconstruction or a SBA using multistranded autologous hamstring tendons were included in this study with a 1-year follow-up. Body sway and knee kinesthesia (using the threshold to detect passive motion test (TTDPM)) were measured to indicate balance ability and proprioceptive function, respectively. Additionally, within-subject differences in anterior-posterior stability of the tibia and lower extremity muscle strength were evaluated before and after surgery. Results. At 6 and 12 months after surgery, DB reconstruction resulted in better balance and proprioceptive function than SB reconstruction (P < 0.05). Although no significant difference was observed in balance ability or proprioceptive function between the SBA and DB reconstructions, knee stability was significantly better with SBA and DB reconstructions than SB reconstruction (P < 0.05). No significant differences were found in quadriceps and hamstrings strength among the three reconstruction techniques. Conclusions. Our findings consider that joint stability, proprioceptive function, and balance ability were superior with SBA and DB reconstructions compared to SB reconstruction at 6 and 12 months after surgery.

Same Traits, Different Variance

Personality trait questionnaires are regularly used in individual differences research to examine personality scores between participants, although trait researchers tend to place little value on intra-individual variation in item ratings within a measured trait. The few studies that examine variability indices have not considered how they are related to a selection of psychological outcomes, so we recruited 160 participants (age M = 24.16, SD = 9.54) who completed the IPIP-HEXACO personality questionnaire and several outcome measures. Heterogenous within-subject differences in item ratings were found for every trait/facet measured, with measurement error that remained stable across the questionnaire. Within-subject standard deviations, calculated as measures of individual variation in specific item ratings within a trait/facet, were related to outcomes including life satisfaction and depression. This suggests these indices represent valid constructs of variability, and that researchers administering behavior statement trait questionnaires with outcome measures should also apply item-level variability indices.

Vein Visualization

Background We investigated the patient characteristic factors that correlate with identification of i.v. cannulation sites with normal eyesight. We evaluated a new infrared vein finding (VF) technology device in identifying i.v. cannulation sites. Methods Each subject underwent two observations: one using the conventional method (CM) of normal, unassisted eyesight and the other with the infrared VF device, VueTek's Veinsite™ (VF). A power analysis for moderate effect size (β=0.95) required 54 samples for within-subject differences. Results Patient characteristic profiles were obtained from 384 subjects (768 observations). Our sample population exhibited an overall average of 5.8 [95% confidence interval (CI) 5.4–6.2] veins using CM. As a whole, CM vein visualization were less effective among obese [4.5 (95% CI 3.8–5.3)], African-American [4.6 (95% CI 3.6–5.5 veins)], and Asian [5.1 (95% CI 4.1–6.0)] subjects. Next, the VF technology identified an average of 9.1 (95% CI 8.6–9.5) possible cannulation sites compared with CM [average of 5.8 (95% CI 5.4–6.2)]. Seventy-six obese subjects had an average of 4.5 (95% CI 3.8–5.3) and 8.2 (95% CI 7.4–9.1) veins viewable by CM and VF, respectively. In dark skin subjects, 9.1 (95% CI 8.3–9.9) veins were visible by VF compared with 5.4 (95% CI 4.8–6.0) with CM. Conclusions African-American or Asian ethnicity, and obesity were associated with decreased vein visibility. The visibility of veins eligible for cannulation increased for all subgroups using a new infrared device.

Altitude training and haemoglobin mass from the optimised carbon monoxide rebreathing method determined by a meta-analysis

ObjectiveTo characterise the time course of changes in haemoglobin mass (Hbmass) in response to altitude exposure.MethodsThis meta-analysis uses raw data from 17 studies that used carbon monoxide rebreathing to determine...

Longitudinal pilot‐study of Sustained Attention to Response Task and P300 in manifest and pre‐manifest Huntington's disease

Earlier research has found cross-sectional attentional control deficits in manifest Huntington's disease (HD) using neuropsychological testing combined with simultaneous P300 registration. In the current pilot-study, we investigate attentional control in pre-manifest and manifest HD over a 3-year follow-up period. Five manifest HD (MHD), 9 pre-manifest HD (PMHD), and 12 control subjects were included. Sustained Attention to Response task (SART) and P300 registration resulted in number of errors, reaction time (RT), and P300 amplitude and latency. RT change patterns surrounding No-go trials were also investigated. Within-subject differences were tested using paired-samples t-tests and between-group results with ANCOVA on delta scores (follow-up--baseline scores). Manifest HD made more errors and were slower than controls and PMHD. Longitudinally, MHD showed an overall RT increase and a specific slowing on trials preceding a correct No-go trial (within-group effects). The latter was also seen in PMHD. P300 latency prolongation was found for controls on No-go and for MHD on Go trials. On specific trials surrounding both correct and incorrect No-go trials, MHD became significantly slower over time than controls and PMHD (between-group effects). Over 3-years, MHD subjects became slower on the SART and showed a prolongation of P300 latency on specific SART trials. Specific slowing of performance over time was also seen in PMHD, suggestive of compensatory mechanisms in this group.

Test–retest reliability of structural brain networks from diffusion MRI

Structural brain networks constructed from diffusion MRI (dMRI) and tractography have been demonstrated in healthy volunteers and more recently in various disorders affecting brain connectivity. However, few studies have addressed the reproducibility of the resulting networks. We measured the test–retest properties of such networks by varying several factors affecting network construction using ten healthy volunteers who underwent a dMRI protocol at 1.5T on two separate occasions.Each T1-weighted brain was parcellated into 84 regions-of-interest and network connections were identified using dMRI and two alternative tractography algorithms, two alternative seeding strategies, a white matter waypoint constraint and three alternative network weightings. In each case, four common graph-theoretic measures were obtained. Network properties were assessed both node-wise and per network in terms of the intraclass correlation coefficient (ICC) and by comparing within- and between-subject differences.Our findings suggest that test–retest performance was improved when: 1) seeding from white matter, rather than grey; and 2) using probabilistic tractography with a two-fibre model and sufficient streamlines, rather than deterministic tensor tractography. In terms of network weighting, a measure of streamline density produced better test–retest performance than tract-averaged diffusion anisotropy, although it remains unclear which is a more accurate representation of the underlying connectivity. For the best performing configuration, the global within-subject differences were between 3.2% and 11.9% with ICCs between 0.62 and 0.76. The mean nodal within-subject differences were between 5.2% and 24.2% with mean ICCs between 0.46 and 0.62. For 83.3% (70/84) of nodes, the within-subject differences were smaller than between-subject differences. Overall, these findings suggest that whilst current techniques produce networks capable of characterising the genuine between-subject differences in connectivity, future work must be undertaken to improve network reliability.

A Phase 2a Multicenter, Double-Blind, Placebo-Controlled, Crossover Trial to Investigate the Efficacy, Safety, and Toleration of CP-866,087 (a High-Affinity Mu-Opioid Receptor Antagonist) in Premenopausal Women Diagnosed with Female Sexual Arousal Disorder (FSAD)

Female sexual arousal disorder (FSAD) is a condition that can affect women of all ages and have a significant negative impact on emotional well-being. The aim of this study is to prospectively evaluate the effects of CP-866,087, a selective mu-opioid receptor antagonist, in premenopausal women with FSAD. The study included 51 women (20-45 years of age) with FSAD. All women received placebo and two of three planned doses of CP-866,087 (1, 3, and 10 mg) for 6 weeks in each of three double-blind treatment periods. Efficacy was determined through a series of measures to assess sexual functioning, sexual activity, sexual distress, and perceived meaningful benefit as a result of treatment. In addition, a semi-structured exit interview was conducted at the end of the fourth treatment period or withdrawal to provide a more in-depth, qualitative description of the participants' symptoms, response to treatment, and treatment satisfaction to augment the quantitative assessments. The within-subject differences from placebo in the change from baseline were compared across a range of measures of sexual function. Summary statistics and 90% confidence intervals were calculated. A qualitative analysis of the exit interview was conducted based on grounded theory methods. Although improvements were seen with CP-866,087 in the key efficacy end points, there was no clinical treatment benefit over placebo. The exit interview analysis suggested that being part of the study and taking positive action to search for a solution to the women's sexual disorder may have been a significant factor in the behavioral changes that were seen, as opposed to the drug treatment itself. Discerning the potential benefit of pharmacotherapy in a heterogeneous condition such as FSAD is challenging. Participation in a clinical trial combined with a commitment to actively engage in sexual activity may in itself create an environment that is conducive to symptom improvement.

Salivary alpha-Amylase and Cortisol Responsiveness Following Electrical Stimulation Stress in Patients with the Generalized Type of Social Anxiety Disorder

Social anxiety disorder is believed to be a stress-induced disease. Although it can be inferred from the symptoms during attacks that there exists some abnormality of autonomic nervous system in any of the stress systems in social anxiety disorder, little evidence has been reported. This study focused on comparing the reactivity of 2 stress systems, the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis in patients with social anxiety disorder. 32 patients with the generalized type of social anxiety disorder were compared with 80 age- and gender-matched controls. We collected saliva samples from patients and controls before and after electrical stimulation to measure the concentrations of salivary alpha-amylase (sAA) and salivary cortisol. Profile of Mood State (POMS) and State-Trait Anxiety Inventory (STAI) scores and Heart Rate Variability (HRV) were also determined following stimulation. SAA in patients displayed a significantly higher level at baseline and a significantly larger response to electrical stimulation as compared to controls, whereas no group differences were seen in any HRV. Neither within-subject nor group differences were seen in salivary cortisol levels. These results suggest that SAD patients displayed enhanced ANS (but not HPA axis) activity vs. healthy controls.

Changes in QuantiFERON®-TB Gold In-Tube results during treatment for tuberculous infection

Randomised trial comparing 9 months of isoniazid with 4 months of rifampicin for the treatment of high-risk tuberculin skin test positive subjects in Rio de Janeiro, Brazil. To compare QuantiFERON®-TB Gold In-Tube (QFT-GIT) responses before and 1, 4 and 9 months after starting treatment for latent tuberculous infection (LTBI) according to adherence to one of the two regimens. Participants in the trial were invited to undergo serial QFT-GIT. Within-subject differences at different time points were analysed as quantitative responses and categorised as positive or negative using different cut-off points. Of 215 participants, 118 completed treatment, of whom 58 underwent all three tests; and 97 did not complete treatment, of whom 10 underwent all tests. After 1 month of treatment, there was no significant difference in QFT-GIT response between the groups. After 4 and 9 months, reversions were more frequent in non-adherent subjects. Marked within-subject fluctuations were observed. No cut-off point could be established at which QFT-GIT responses were consistently positive or associated with adherence or type of treatment. Frequent within-subject variability in QFT-GIT responses, not associated with LTBI treatment, makes it difficult for clinicians to interpret QFT-GIT conversions and reversions.

Processing load during listening: The influence of task characteristics on the pupil response

This study examined the magnitude of the pupillary response evoked by a number of tasks varying in the nature and complexity of the auditory and linguistic information provided. The tasks comprised passive listening, anticipation to verbally responding to a prompt signal, auditory detection, and the identification of meaningful words. Performance in the auditory detection and identification tasks was matched at 79% correct. In all, 42 normally hearing adults (aged 18–44 years, mean age 25.5 years) from three different sites (Amsterdam, Cologne, and Warsaw) participated. During each condition, the pupil diameter was measured. A Repeated Measures ANOVA was conducted to examine within and between subject (site) differences in the pupil response over 8 time intervals during the four conditions. The maximum mean pupil dilation was largest in the words-in-noise identification task (0.13 mm) and differed significantly from the maximum mean dilation in the noise-in-noise-detection task. The latter did not differ significantly from the pupil response during passive listening to noise and an answer prompt. No significant differences between sites were observed. Task evoked pupillary responses to theory-based measures of linguistic processing are robust, reliable, and sensitive to differences in task demands. Word-in-noise identification requires more processing load than nonspeech detection. To obtain information about within-subject differences in auditory processing, examination of both processing load and behavioural performance is recommended. Methodological implications are discussed.