Mixed-effects Analysis Of Variance Model Research Articles

Effects of the Brief Simha Kriya Breathing Practice for Health Care Workers During the COVID-19 Pandemic.

Introduction: During the COVID-19 pandemic, health care workers (HCWs) experienced increased anxiety, depression, loneliness, and other mental health issues. HCWs need additional resources to cope with the mental health impact of their work. Yoga techniques could be helpful strategies to manage different stressors during times of uncertainty. Methods: This prospective, single-arm, trial examined the effects of a brief pranayama yoga practice on the wellbeing of HCWs during the height of COVID-19. HCWs were recruited through announcements and institutional websites at a large major cancer center in the southern United States. A short, prerecorded, 5-min breathwork video intervention called "Simha Kriya" was provided to participants, and they were encouraged to practice one to two times daily for 4 weeks. Participants completed self-report instruments at baseline and weeks 1 and 4, including: (1) Perceived Stress Scale (PSS); (2) Brief Resilient Coping Scale (BRCS); and (3) a questionnaire assessing the experience of COVID-19 among HCWs that had five subscales. HCWs also conducted a measure of breath holding time. Paired sample t-tests and mixed-effects analysis of variance models examined changes over time. Results: One hundred participants consented to the study, with 88 female, 60 white, 39 worked remotely, and 27 were clinical staff. Sixty-nine participants provided data at week 1 and 56 at week 4. Participants' adherence to the breathing exercises between weeks 1 and 4 was similar, with a mean of six times per week. At week 4, there were significant decreases in the COVID-19 Distress score (p < 0.0001) and COVID-19 Disruption (p = 0.013), yet no changes in the PSS. There were also significant increases in COVID-19 Stress Management (p = 0.0001) and BRCS scores (p = 0.012), but no changes in Perceived Benefits of COVID-19 and no changes in breath holding time. Discussion: Brief yoga-based breathing practices helped reduce pandemic-specific stress, improved resilience, and stress management skills in HCWs. Trial Registration Number: NCT04482647.

High preoperative bradykinin level is a risk factor for severe postoperative hypoxaemia in acute aortic dissection surgery.

What is the central question of this study? Hypoxaemia can lead to increased postoperative mortality in patients: what are the independent risk factors for severe hypoxaemia after acute Stanford type A aortic dissection? What is the main finding and its importance? Severe postoperative hypoxaemia was found in 36.4% of patients, and it was determined that high preoperative bradykinin levels and increased BMI were independent predictors of severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. For obese patients with high preoperative bradykinin levels, more attention should be paid to preventing severe postoperative hypoxaemia. Severe hypoxaemia after cardiac surgery is associated with serious complications and a high risk of mortality. The purpose of this study is to investigate the independent risk factors of severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. We collected 77 patients with acute Stanford type A aortic dissection who underwent surgical treatment. The primary outcome was severe postoperative hypoxaemia (PaO2 /FiO2 ≤100mmHg), and a multivariate logistic regression analysis was performed to assess the independent predictors of risk for this. A mixed-effects analysis of variance model and a receiver operating characteristic (ROC) curve were generated to evaluate the predictive probabilities of risk factors for severe postoperative hypoxaemia. A total of 36.4% of patients developed severe postoperative hypoxaemia. The multivariate logistic regression analysis identified high preoperative bradykinin level (odds ratio (OR)=55.918, P<0.001) and increased body mass index (BMI; OR=1.292, P=0.032) as independent predictors of severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. The mixed-effect analysis of variance model and ROC curve indicated that high preoperative bradykinin level and BMI were significant predictors of severe postoperative hypoxaemia (area under the ROC curve=0.834 and 0.764, respectively). High preoperative bradykinin levels and obesity were independent risk factors for severe postoperative hypoxaemia in patients with acute Stanford type A aortic dissection. For obese patients with high levels of bradykinin before surgery, clinicians should actively take measures to block bradykinin-mediated inflammatory reactions.

Tedizolid vs Linezolid for the Treatment of Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients

BackgroundTreatment options for nontuberculous mycobacteria (NTM) infections are limited by the pathogen’s intrinsic resistance profile and toxicities. Tedizolid and linezolid display in vitro activity against NTM species. However, safety data and treatment outcomes are limited in the solid organ transplant (SOT) population.MethodsThis was a single-center retrospective cohort study of adult SOT recipients receiving linezolid or tedizolid for an NTM infection from January 1, 2010, to August 31, 2019. The primary outcome compared the hematologic safety profiles of tedizolid vs linezolid. We also described nonhematological adverse drug events (ADEs) and therapy discontinuation rates. In an exploratory analysis, we assessed symptomatic microbiologic and clinical outcomes in those receiving tedizolid or linezolid for at least 4 weeks.ResultsTwenty-four patients were included (15 tedizolid, 9 linezolid). No differences were identified comparing the effects of tedizolid vs linezolid on platelet counts, absolute neutrophil counts (ANCs), and hemoglobin over 7 weeks using mixed-effects analysis of variance models. ANC was significantly decreased in both groups after 7 weeks of therapy (P = .04). Approximately 20% of patients in each arm discontinued therapy due to an ADE. Seven of 12 (58%) and 2 of 3 (67%) patients were cured or clinically cured with tedizolid- and linezolid-containing regimens, respectively.ConclusionsThis study suggests no significant safety benefit of tedizolid over linezolid for the treatment of NTM infections in SOT recipients. Tedizolid or linezolid-containing regimens demonstrated a potential benefit in symptomatic and microbiologic improvement. Larger cohorts are needed to further delineate the comparative role of linezolid and tedizolid for the treatment of NTM infections in SOT recipients.

0673 Effects Of Solriamfetol On Driving Performance In Participants With Excessive Daytime Sleepiness Associated With Obstructive Sleep Apnea

Abstract Introduction Excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA) is associated with an increased risk of driving accidents. Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved in the US (Sunosi®) for EDS associated with OSA (37.5-150 mg/day). This study evaluated solriamfetol’s effects on on-road driving performance in participants with EDS associated with OSA. Methods In each period of this randomized, double-blind, placebo-controlled, crossover study (NCT 02806895; EudraCT 2015-003930-28), driving performance during an on-road driving test was assessed at 2 hours and 6 hours postdose following 7 days of treatment with solriamfetol (150mg/day × 3, then 300mg/day × 4) or placebo. The primary endpoint—standard deviation of lateral position (SDLP), a measure of “weaving,” at 2 hours postdose—was compared between solriamfetol and placebo per time point using a repeated mixed-effects analysis of variance model. Results The study included 34 participants. Baseline characteristics reflected the broader OSA population (88% male; mean age=52 years; mean Epworth Sleepiness Scale score=14.4). SDLP at 2 hours postdose was statistically significantly lower following solriamfetol (least squares [LS] mean [standard error; SE], 18.83cm [0.63]) compared with placebo (19.92cm [0.63]): LS mean difference, -1.08cm; 95% confidence interval (CI), -1.85, -0.32; P=0.0062 (incomplete driving tests: solriamfetol, n=1; placebo, n=4), indicating better performance with solriamfetol. At 6 hours postdose, SDLP following solriamfetol (LS mean[SE], 19.24cm [0.63]) was statistically significantly lower compared with placebo (20.04cm [0.63]): LS mean difference, -0.80cm; 95% CI, -1.58, -0.03; P=0.0432 (incomplete driving tests: solriamfetol, n=3; placebo, n=7). Common adverse events (≥5%) with solriamfetol were headache, nausea, insomnia, dizziness, and agitation. Conclusion Solriamfetol (300mg/day) improved SDLP, an important measure of driving performance, at 2 and 6 hours in participants with EDS associated with OSA. Support Jazz Pharmaceuticals

Comparison of the Effectiveness of Online Homework With Handwritten Homework in Electrical and Computer Engineering Classes

Contribution: This article compares the predictive performance of the scores on WeBWorK homework (online) with those of standard handwritten homework. The comparison is done across six undergraduate electrical engineering classes where each of the nine instructors have used both homework modalities. Background: Online homework systems have been used for many years, but analysis of their effectiveness is mixed. Previous work has been limited to a small number of classes in a wide variety of disciplines. This article has a larger number of classes and instructors than previous studies. The classes cover many basic topic areas in electrical and computer engineering, so is directly applicable to the audience of these transactions. Research Question: What is the effect of online homework compared to traditional handwritten homework on the performance of the students on the final exams in selected ECE classes? Methodology: Mixed-effects analysis of variance models are used to determine the predictive ability of performance on homework of the two modalities on the performance on the final exams. The data are limited to classes where the instructors have taught the class using both modalities. These models incorporate the effect of modalities for each instructor and the effect of the modalities across all classes. Findings: The result is that there is no significant statistical difference in the two modalities to predict final exam scores. This indicates that the advantages of using the automated online system can be obtained with no detrimental effect on the students’ learning.

Decreased Injection Site Pain Associated with Phosphate-Free Etanercept Formulation in Rheumatoid Arthritis or Psoriatic Arthritis Patients: A Randomized Controlled Trial.

IntroductionEtanercept, a tumor necrosis factor inhibitor, is used to treat rheumatoid arthritis (RA) and psoriatic arthritis (PsA), and is administered via subcutaneous injection. Injection site pain (ISP) associated with subcutaneous administration may affect compliance or hinder initiation of prescribed medications. To improve the patient experience, a new phosphate-free formulation of etanercept was evaluated for reduced ISP associated with administration.MethodsThis phase 3b, multicenter, randomized, double-blind, cross-over study compared the prior formulation of etanercept to a phosphate-free formulation. Etanercept-naïve adults with RA or PsA indicated for treatment with etanercept were eligible. Patients were randomized (1:1) to receive both etanercept formulations (50 mg) in one of two crossover sequences: prior formulation followed by phosphate-free formulation (sequence AB) or phosphate-free formulation followed by prior formulation (sequence BA) at visits 1 week apart. Patients self-reported ISP using a fit-for-purpose 100-mm visual analog scale within 30 s after injection. Safety outcomes included incidence of treatment-emergent adverse events. Mixed-effects analysis of variance model was used to assess ISP, with treatment, study period, sequence, and disease indication as fixed-effect covariates and patient-within-sequence as random effect.ResultsA total of 111 patients enrolled (56 sequence AB; 55 sequence BA). Mean ISP score for prior formulation was 23.1 mm and for phosphate-free formulation was 19.1 mm (mean difference − 4 mm; 95% confidence interval: − 8.0, 0.0; P = 0.048). Patients with the highest ISP scores from the prior formulation (by quartile cut points) had the largest reduction in pain with phosphate-free formulation. Injection site reactions were few in number and similar between formulations; no new safety signals were observed.ConclusionsThe new phosphate-free formulation of etanercept had statistically significantly lower mean pain scores than the prior formulation, with largest pain reductions observed among patients who reported highest pain with the prior formulation.Trial RegistrationClinicalTrials.gov: NCT02986139.FundingAmgen Inc, Thousand Oaks, CA USA.

Assignment of Opsonic Values to Pneumococcal Reference Serum 007sp for Use in Opsonophagocytic Assays for 13 Serotypes.

Opsonophagocytic assays (OPAs) are routinely used for assessing the immunogenicity of pneumococcal vaccines, with OPA data often being utilized for licensure of new vaccine formulations. However, no reference serum for pneumococcal OPAs is available, making evaluation of data among different laboratories difficult. This international collaboration was initiated to (i) assign consensus opsonic indexes (OIs) to FDA pneumococcal reference serum lot 007sp (here referred to as 007sp) and a panel of serum samples used for calibration of the OPA and (ii) determine if the normalization of the OPA results obtained with test samples to those obtained with 007sp decreases the variability in OPA results among laboratories. To meet these goals, six participating laboratories tested a panel of serum samples in five runs for 13 serotypes. For each serum sample, consensus OIs were obtained using a mixed-effects analysis of variance model. For the calibration serum samples, normalized consensus values were also determined on the basis of the results obtained with 007sp. For each serotype, the overall reduction in interlaboratory variability was calculated by comparing the coefficients of variation of the unadjusted and the normalized values. Normalization of the results substantially reduced the interlaboratory variability, ranging from a 15% reduction in variability for serotype 9V to a 64% reduction for serotype 7F. Normalization also increased the proportion of data within 2-fold of the consensus value from approximately 70% (average for all serotypes) to >90%. On the basis of the data obtained in this study, pneumococcal reference standard lot 007sp will likely be a useful reagent for the normalization of pneumococcal OPA results from different laboratories. The data also support the use of the 16 FDA serum samples used for calibration of the OPA as part of the initial evaluation of new assays or periodic assessment of established assays.

Interobserver Variability of Radiographic Pulmonary Nodule Diameter Measurements in Dogs and Cats

The purpose of this study was to determine the interobserver variability of radiographic pulmonary nodule diameter measurements among readers with varying levels of experience. Because interobserver variability may lead to inaccurate estimations of nodule growth on repeat radiographic assessment, an incorrect presumption of malignant etiology or misclassification of tumor response to treatment may result. The maximum diameters of 47 pulmonary nodules from 22 dogs and 7 cats were measured. Measurements were performed using one digital thoracic radiographic projection by eight clinicians. The eight clinicians included two interns, two residents, two board-certified veterinary specialists, and two board-certified veterinary radiologists. A mixed-effect analysis of variance model was used to evaluate the contribution of reader, experience level, patient, nodule, and nodule size to the overall variability in mean pulmonary nodule diameter. The interobserver variability in diameter measurement for any given nodule was 16%, and experience level and nodule size classification did not contribute to measurement variability. Linear measurements of the diameter of a pulmonary nodule can vary significantly among a group of clinicians; however, depending on the criteria used to evaluate nodule growth or tumor response, the 16% interobserver variability reported here is likely not clinically significant.

Inter- and Intraobserver Reliability of Two-dimensional CT Scan for Total Knee Arthroplasty Component Malrotation

Rotational malalignment of total knee arthroplasty (TKA) has been correlated with patellofemoral maltracking, knee instability, and stiffness. CT is the most accurate method to assess rotational alignment of prosthetic components after TKA, but inter- and intraobserver reliability of CT scans for this use has not been well documented. The objective of this study was to determine the inter- and intraobserver reliability and the repeatability of the measurement of TKA component rotation using two-dimensional CT scans. Fifty-two CT scans of TKAs being evaluated for revision surgery were measured by three different physicians. An orthopaedic resident and attending measured the same scans twice (more than 2 weeks apart) and a musculoskeletal radiologist measured them once. To assess interobserver reliability, intraclass correlation coefficients (ICCs) with two-way mixed-effects analysis of variance models as well as 95% confidence intervals for each were done. The repeatability coefficient was calculated as well, which is defined as the difference in measurements that include 95% of the values. This indicates the magnitude of variability among measurements in the same scale, which in this study is degrees. The interobserver ICC measurement for the femoral component was 0.386 (poor), and it was 0.670 (good) for the tibial component. The interobserver ICC for the combined rotation measurements was 0.617 (good). The intraobserver ICC for the femoral component was 0.606 (good), and it was 0.809 (very good) for the tibial component. The intraobserver ICC for combined rotation was 0.751 (good). The intraobserver repeatability coefficient for the femoral component was 0.49°, 10.64° for the tibial component, and 12.29° for combined rotation. In this study, the inter- and intraobserver reliability, and the repeatability, of TKA component rotation were variable. This raises concern about whether CT scan is diagnostic in the assessment of component malrotation after TKA.

Bone mineral apposition rates at early implantation times around differently prepared titanium surfaces: a study in beagle dogs

This study evaluated the bone mineral apposition rate (MAR) at the bone-implant interface region of alumina-blasted/acid-etched (AB/AE), plasma-sprayed hydroxyapatite (PSHA), and nanometric-scale bioceramic-coated surfaces at early implantation times in a dog tibia model.Implants (n = 12 per group) with three different surfaces-AB/AE, PSHA, and a bioceramic coating in the 300- to 500-nm thickness range-were placed bilaterally along the proximal tibiae of six male beagles. Implants remained for 3 and 5 weeks in vivo. Ten and 2 days prior to euthanization, calcein green and oxytetracycline were administered for bone labeling. Following euthanization, the limbs were retrieved by sharp dissection and the implants and bone were processed nondecalcified into ~30-Μm-thick sections along the implant long axis. MAR was measured by the distance between bone labels over time at the interface region (to 0.5 mm from the implant surface) and at regions > 3 mm from the implant surface (remote site). A generalized linear mixed-effects analysis of variance model was conducted with significance levels set at .05.Irrespective of implant surface, the MAR at the interface region was significantly higher than the MAR at the remote site. Significant MAR differences in the interface region were observed between the different surfaces (PSHA > AB/AE > nano).Bone kinetics during early healing stages were influenced by implant surface modifications.

Foot Kinematics During a Bilateral Heel Rise Test in Participants With Stage II Posterior Tibial Tendon Dysfunction

Experimental laboratory study using a cross-sectional design. To compare foot kinematics, using 3-dimensional tracking methods, during a bilateral heel rise between participants with posterior tibial tendon dysfunction (PTTD) and participants with a normal medial longitudinal arch (MLA). The bilateral heel rise test is commonly used to assess patients with PTTD; however, information about foot kinematics during the test is lacking. Forty-five individuals volunteered to participate, including 30 patients diagnosed with unilateral stage II PTTD (mean +/- SD age, 59.8 +/- 11.1 years; body mass index, 29.9 +/- 4.8 kg/m2) and 15 controls (mean +/- SD age, 56.5 +/- 7.7 years; body mass index, 30.6 +/- 3.6 kg/m2). Foot kinematic data were collected during a bilateral heel rise task from the calcaneus (hindfoot), first metatarsal, and hallux, using an Optotrak motion analysis system and Motion Monitor software. A 2-way mixed-effects analysis of variance model, with normalized heel height as a covariate, was used to test for significant differences between the normal MLA and PTTD groups. The patients in the PTTD group exhibited significantly greater ankle plantar flexion (mean difference between groups, 7.3 degrees ; 95% confidence interval [CI]: 5.1 degrees to 9.5 degrees ), greater first metatarsal dorsiflexion (mean difference between groups, 9.0 degrees ; 95% CI: 3.7 degrees to 14.4 degrees ), and less hallux dorsiflexion (mean difference, 6.7 degrees ; 95% CI: 1.7 degrees to 11.8 degrees ) compared to controls. At peak heel rise, hindfoot inversion was similar (P = .130) between the PTTD and control groups. Except for hindfoot eversion/inversion, the differences in foot kinematics in participants with stage II PTTD, when compared to the control group, mainly occur as an offset, not an alteration in shape, of the kinematic patterns.

Psychrobacter arcticus 273-4 Uses Resource Efficiency and Molecular Motion Adaptations for Subzero Temperature Growth

Permafrost soils are extreme environments that exert low-temperature, desiccation, and starvation stress on bacteria over thousands to millions of years. To understand how Psychrobacter arcticus 273-4 survived for >20,000 years in permafrost, transcriptome analysis was performed during growth at 22 degrees C, 17 degrees C, 0 degrees C, and -6 degrees C using a mixed-effects analysis of variance model. Genes for transcription, translation, energy production, and most biosynthetic pathways were downregulated at low temperatures. Evidence of isozyme exchange was detected over temperature for D-alanyl-D-alanine carboxypeptidases (dac1 and dac2), DEAD-box RNA helicases (csdA and Psyc_0943), and energy-efficient substrate incorporation pathways for ammonium and acetate. Specific functions were compensated by upregulation of genes at low temperature, including genes for the biosynthesis of proline, tryptophan, and methionine. RNases and peptidases were generally upregulated at low temperatures. Changes in energy metabolism, amino acid metabolism, and RNase gene expression were consistent with induction of a resource efficiency response. In contrast to results observed for other psychrophiles and mesophiles, only clpB and hsp33 were upregulated at low temperature, and there was no upregulation of other chaperones and peptidyl-prolyl isomerases. relA, csdA, and dac2 knockout mutants grew more slowly at low temperature, but a dac1 mutant grew more slowly at 17 degrees C. The combined data suggest that the basal biological machinery, including translation, transcription, and energy metabolism, is well adapted to function across the growth range of P. arcticus from -6 degrees C to 22 degrees C, and temperature compensation by gene expression was employed to address specific challenges to low-temperature growth.

Observer reliability of three-dimensional cephalometric landmark identification on cone-beam computerized tomography

To evaluate reliability in 3-dimensional (3D) landmark identification using cone-beam computerized tomography (CBCT). Twelve presurgery CBCTs were randomly selected from 159 orthognathic surgery patients. Three observers independently repeated 3 times the identification of 30 landmarks in the sagittal, coronal, and axial slices. A mixed-effects analysis of variance model estimated the intraclass correlations (ICC) and assessed systematic bias. The ICC was >0.9 for 86% of intraobserver assessments and 66% of interobserver assessments. Only 1% of intraobserver and 3% of interobserver coefficients were <0.45. The systematic difference among observers was greater in X and Z than in Y dimensions, but the maximum mean difference was quite small. Overall, the intra- and interobserver reliability was excellent. Three-dimensional landmark identification using CBCT can offer consistent and reproducible data if a protocol for operator training and calibration is followed. This is particularly important for landmarks not easily specified in all 3 planes of space.

Time to deterioration in dimensions of health-related quality of life (HRQL) for patients with recurrent glioblastoma multiforme (GBM): Results from the randomized, phase III trial of enzastaurin (ENZ) versus lomustine (CCNU)

2040 Background: One goal of therapy for recurrent GBM is to delay worsening in HRQL, with interventions expected to have greatest impact on physical and functional domains. HRQL assessment in recurrent GBM has been limited by deterioration of patient (pt) status. We report HRQL results from a multinational phase III trial. Methods: Pts with recurrent GBM were randomized 2:1 to ENZ 500 mg daily or CCNU 100–130 mg/m2 every 6 weeks. Pts and proxies completed the 50-item Functional Assessment of Cancer Therapy - Brain (FACT-Br) (version 4) prior to randomization, approximately every 3 weeks while on therapy and then 30 days after discontinuation. Time to deterioration (TtD) for each pt was defined as an 11-point decrease in the 148-point Trial Outcome Index (TOI; physical and functional well-being plus brain tumor-specific concerns) or death. Only pts with baseline FACT-Br data were included in the analysis. Proxy data were used when pts were unable to complete the FACT-Br and if there were sufficient dyad data to establish an imputation pattern. TtD was analyzed using Kaplan-Meier methods. To assess differences between arms in TOI subscales, change from baseline was analyzed with a mixed-effects analysis of variance model. Results: Enrollment was terminated after an interim analysis. Of 266 randomized pts, 159 / 174 (91%) ENZ and 82 / 92 (89%) CCNU pts were analyzed for TtD. Baseline scores for TOI were not statistically different between arms (p=0.638). Pt compliance for completing the FACT-Br on-study over the first 6 months was 77% for ENZ and 78% for CCNU; use of proxy data increased compliance to 79% and 81%, respectively. Median TtD was 2.27 months for ENZ and 2.33 months for CCNU with 6-month rates of 18% and 29%, respectively (hazard ratio = 1.12 [95% CI: 0.77–1.63]; log-rank p-value = 0.54; 47% censoring). There were no differences between arms in change from baseline in physical and functional well-being or in brain tumor-specific concerns (p>0.05). Conclusions: Assessment of HRQL is feasible in pts with recurrent GBM. No difference in time that physical and functional domains of HRQL were maintained was detected between ENZ and CCNU. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly, MGI Pharma, Pfizer Oncology, Schering-Plough Eli Lilly Eli Lilly, Merck, Pfizer Oncology, Schering-Plough Eli Lilly Schering-Plough

Using Theater to Teach Clinical Empathy: A Pilot Study

Clinical empathy, a critical skill for the doctor-patient relationship, is infrequently taught in graduate medical education. No study has tested if clinical empathy can be taught effectively. To assess whether medicine residents can learn clinical empathy techniques from theater professors. A controlled trial of a clinical empathy curriculum taught and assessed by 4 theater professors. Virginia Commonwealth University, Richmond, Virginia, a large urban university and health system. Twenty Internal Medicine residents: 14 in the intervention group, 6 in the control group. Six hours of classroom instruction and workshop time with professors of theater. Scores derived from an instrument with 6 subscores designed to measure empathy in real-time patient encounters. Baseline comparisons were made using two-sample T tests. A mixed-effects analysis of variance model was applied to test for significance between the control and intervention groups. The intervention group demonstrated significant improvement (p < or = .011) across all 6 subscores between pre-intervention and post-intervention observations. Compared to the control group, the intervention group had better posttest scores in 5 of 6 subscores (p < or = .01). The study was neither randomized nor blinded. Collaborative efforts between the departments of theater and medicine are effective in teaching clinical empathy techniques.

Functional mapping of human sensorimotor cortex with electrocorticographic spectral analysis. II. Event-related synchronization in the gamma band.

It has been shown in animals that neuronal activity in the 'gamma band' (>30 Hz) is associated with cortical activation and may play a role in multi-regional and multi-modal integration of cortical processing. Studies of gamma activity in human scalp EEG have typically focused on event-related synchronization (ERS) in the 40 Hz band. To assess further the gamma band ERS further, as an index of cortical activation and as a tool for human functional brain mapping, we recorded subdural electrocorticographic (ECoG) signals in five clinical subjects while they performed visual-motor decision tasks designed to activate the representations of different body parts in sensorimotor cortex. ECoG spectral analysis utilized a mixed-effects analysis of variance model in which within-trial temporal dependencies were accounted for. Taking an exploratory approach, we studied gamma ERS in 10-Hz-wide bands (overlapping by 5 Hz) ranging from 30 to 100 Hz, and compared these findings with changes in the alpha (8-13 Hz) and beta (15-25 Hz) bands. Gamma ERS (observed in three out of subjects) occurred in two broad bands-'low gamma' included the 35-45 and 40-50 Hz bands, and 'high gamma' the 75-85, 80-90, 85-95 and 90-100 Hz bands. The temporal and spatial characteristics of low and high gamma ERS were distinct, suggesting relatively independent neurophysiological mechanisms. Low gamma ERS often began after onset of the motor response and was sustained through much of it, in parallel with event-related desynchronization (ERD) in the alpha band. High gamma ERS often began during, or slightly before, the motor response and was transient, ending well before completion of the motor response. These temporal differences in low and high gamma suggest different functional associations with motor performance. Compared with alpha and beta ERD, the topographical patterns of low and high gamma ERS were more discrete and somatotopically specific and only occurred over contralateral sensorimotor cortex during unilateral limb movements (alpha and beta ERD were also observed ipsilaterally). Maps of sensorimotor function inferred from gamma ERS were consistent with maps generated by cortical electrical stimulation for clinical purposes. In addition, different task conditions in one subject produced consistent differences in both motor response latencies and onset latency of gamma ERS, particularly high gamma ERS. Compared with alpha and beta ERD, the topography of gamma ERS is more consistent with traditional maps of sensorimotor functional anatomy. In addition, gamma ERS may provide complementary information about cortical neurophysiology that is useful for mapping brain function in humans.

Estimating Treatment Means in a Mixed-Effect ANOVA Model for Bioequivalence Studies

In order to establish bioequivalence between two formulations in a crossover trial, it is common to assume a mixed-effect analysis of variance (ANOVA) model and perform two one-sided tests. When the analysis is done on the untransformed data, the numerators of the test statistics are not, in general, treatment contrasts. Consequently, the standard errors of the numerators are difficult to compute. The usual practice is to approximate these with the standard errors of treatment contrasts (the "usual approximation"). This paper examines the goodness of this approximation. We present a few technical issues involved in analyzing the untransformed data with a mixed-effect ANOVA model, and state a parametric definition for the terminology "treatment means." The best linear unbiased estimator (BLUE) for the treatment means is derived, as well as its covariance matrix. Due to the presence of the intersubject variability, the variances and covariances of the BLUE of the treatment means are much larger than is commonly believed. A simulation study shows that these larger-than-expected variances/covariances may widen the usual approximate 90% confidence interval by as much as 10%.