Faculty Bibliography

Rationale: SPIROMICS is a prospective cohort study that has enrolled 2,981 participants across four strata (Never smokers, Smokers without COPD, Mild/Moderate COPD, and Severe COPD) with the goals of identifying new COPD subgroups and intermediate markers of disease progression. Individuals with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) experience impaired quality of life and more frequent exacerbations (Omachi 2012, Zeidler 2018). COPD severity also associates with CT scan-based emphysema and alterations in airway wall dimensions (Han 2009). We hypothesize that lung function and lung structure influence the risk of sleep apnea among current and former smokers.
Method(s): We calculated two OSA risk scores, the Berlin Sleep Questionnaire (BSQ, OSA high-risk cutoff >=2 positive categories) and the DOISNORE50 (Disease[Atrial Fibrillation/stroke/hypertension], Observed apnea, Insomnia, Snoring, Neck circumference[>17inches males,>16inches females], Obesity[BMI>32], R[Are you male?], Excessive daytime sleepiness, >=50years age) score (OSA high-risk cutoff >=6), in 1,767 current and former smokers with available data from SPIROMICS. Regression models included age, sex, smoking status/pack-years, BMI, height, and study site.
Result(s): The study cohort had a mean age of 63 years, BMI of 28 kg/m2, and FEV1 of 74.8% predicted. The majority were male (55%), white (77%), former smokers (59%), and had COPD (63%). A high-risk OSA score was reported in 36% and 61% of participants using DOISNORE50 and BSQ, respectively. There was a 9% increased odds of a high-risk DOISNORE50 score (OR=1.09, 95%CI:1.03-1.14) and a nominally increased odds of a high-risk BSQ score for every 10% decrease in FEV1% predicted (OR=1.04, 95%CI:0.998-1.09). Individuals with a high-risk of OSA based on DOISNORE50 had higher CT-based measures of functional small airways disease (PRM-fSAD, OR=1.10, 95%CI:1.02-1.20, p=0.02), mean segmental % wall area (OR=1.06, 95%CI:1.01-1.11, p=0.02), tracheal % wall area (T%WA, OR=1.05, 95%CI:1.01-1.10, p=0.01), and lower measures of dysanapsis (OR0.85 95%CI:0.74-0.98, p=0.02), but only T%WA associated with a high-risk BSQ score (OR=1.05, 95%CI:1.01-1.06, p=0.007). Lung function-OSA risk associations persisted after additionally adjusting for lung structure measurements (%emphysema, %air-trapping, PRM-fSAD, mean segmental wall area, tracheal % wall area, dysanapsis) for DOISNORE50 (OR=1.12, 95%CI: 1.03-1.22) and BSQ (OR=1.09, 95%CI: 1.01-1.18).
Conclusion(s): We confirm that lower lung function independently associates with having a high-risk for OSA based on the DOISNORE50 score in current and former smokers. Lung structural elements, especially dysanapsis, functional small airways disease, and tracheal % wall area had strong effects on OSA risk, but did not completely mediate the association between lung function and OSA risk

RATIONALE: The GOLD report recommends considering blood eosinophil counts <100 cells/muM (BEClow) as a predictor of poor response to inhaled corticosteroids (ICS). Using SPIROMICS cohort data we evaluated clinical characteristics of BEClow individuals with COPD in comparison to those without low BEC (BEC100+) and searched for unique predictors of exacerbations.
Method(s): 1414 COPD subjects from the SPIROMICS cohort not taking ICS or oral steroids at enrollment into the study were evaluated for a variety of outcomes using multivariate and longitudinal analysis.
Result(s): We identified 485 BEClow individuals with 61 classified as GOLD group D COPD and 929 individuals with BEC100+ with 124 classified as Group D. Characterization of individuals as BEClow was reproducible based on 6-week retesting in repeatability substudy (N=53, ICC of 0.78) and over one-year follow up (N=1136, ICC of 0.71). BEClow was composed of more current smokers, with less frequent reported history of childhood asthma or use of LAMA, and lower plasma fibrinogen in comparison to BEC100+. In Group D patients with BEClow, current smokers were also more prevalent than among those with BEC100+ (47% vs. 31%, P=0.048). These differences were not observed in multivariable models adjusted for standard demographic variables. BEClow individuals showed faster rate of decline of FEV1 (slope-0.046 vs.-0.038 P<0.00001) but in longitudinal analysis there was no difference in acute exacerbations (AE) over the course of the study (P=0.223), rate of ICS initiation throughout the study (2.5% (12) in BEClow vs 4.4% (41) in BEC100+ P=0.0714), or mortality (7.8% (38) vs 8.4% (78) P=0.79). Focused analysis of Group D individuals showed similar findings. Besides FEV1 and exacerbation history as established predictors of future AE in BEClow group, being non-Caucasian was associated with lower risk of AE (OR 0.40 (95%CI 0.21-0.76) P=0.006), while childhood asthma, a predictor of AE in BEC100+ group, was not (OR 0.72 (95%CI 0.24-2.20) P=0.56).
Conclusion(s): BEClow individuals represent a heterogeneous cohort characterized by higher prevalence of current smokers and worse decline in lung function in both Group D and overall COPD in comparison to those with non-low blood eosinophil counts. Nevertheless, the BEClow group was not different in terms of occurrence of exacerbations, initiation of ICS, or survival. Our findings highlight the known interactions between low blood eosinophil counts, responsiveness to ICS in terms of preventing exacerbations, and smoking status, emphasizing the importance of adequate interpretation of the role of BEC in the evaluation and management of COPD

Humans imitate patently irrelevant actions known as overimitation, and rather than decreasing with age, overimitation increases with age. Whereas most overimitation research has focused on social factors associated with overimitation, comparatively little is known about the cognitive- and task-specific features that influence overimitation. Specifically, developmental contrasts between imitation and overimitation are confounded by the addition of irrelevant actions to causally necessary actions, increasing sequence length, cognitive load, and processing costs-variables known to be age dependent. We constructed a novel puzzle box task such that a four-step imitation, four-step overimitation, and two-step efficient sequence could be demonstrated using the same apparatus on video. In Experiments 1 and 2, 2.5- to 5-year-olds randomly assigned to imitation and overimitation groups performed significantly more target actions than baseline control groups. Rates of imitation and overimitation increased as a function of age, with older preschoolers outperforming younger preschoolers in both conditions. In Experiment 3, preschoolers were shown a video of an efficient two-step demonstration prior to testing. After they responded, they were shown a four-step overimitation video and were tested on the same puzzle box. Children imitated the efficient demonstration, but after watching the overimitation video, they also overimitated the irrelevant actions. Once again, older children overimitated more than younger children. Together, results show that preschoolers are faithful, flexible, and persistent overimitators. The fidelity and flexibility of overimitation are constrained not only by social factors but also by basic cognitive processes that vary across age groups. As these constraints diminish, overimitation and flexible (optimal) imitation increases.

Bilingual infants from 6- to 24-months of age are more likely to generalize, flexibly reproducing actions on novel objects significantly more often than age-matched monolingual infants are. In the current study, we examine whether the addition of novel verbal labels enhances memory generalization in a perceptually complex imitation task. We hypothesized that labels would provide an additional retrieval cue and aid memory generalization for bilingual infants. Specifically, we hypothesized that bilinguals might be more likely than monolinguals to map multiple perceptual features onto a novel label and therefore show enhanced generalization. Eighty-seven 18-month-old monolingual and bilingual infants were randomly assigned to one of two experimental conditions or a baseline control condition. In the experimental conditions, either no label or a novel label was added during demonstration and again at the beginning of the test session. After a 24-hr delay, infants were tested with the same stimulus set to test cued recall and with a perceptually different but functionally equivalent stimulus set to test memory generalization. Bilinguals performed significantly above baseline on both cued recall and memory generalization in both experimental conditions, whereas monolinguals performed significantly above baseline only on cued recall in both experimental conditions. These findings show a difference between monolinguals and bilinguals in memory generalization and suggest that generalization differences between groups may arise from visual perceptual processing rather than linguistic processing. A video abstract of this article can be viewed at https://youtu.be/yXB4pM3fF2k.

The use of global, standardized instruments is conventional among clinicians and researchers interested in assessing neurocognitive development. Exclusively relying on these tests for evaluating effects may underestimate or miss specific effects on early cognition. The goal of this review is to identify alternative measures for possible inclusion in future clinical trials and interventions evaluating early neurocognitive development. The domains included for consideration are attention, memory, executive function, language, and socioemotional development. Although domain-based tests are limited, as psychometric properties have not yet been well-established, this review includes tasks and paradigms that have been reliably used across various developmental psychology laboratories.

Bilingual advantages in memory flexibility, indexed using a memory generalization task, have been reported (Brito & Barr, 2012; 2014), and the present study examines what factors may influence memory performance. The first experiment examines the role of language similarity; bilingual 18-month-old infants exposed to two similar languages (Spanish-Catalan) or two more different (English-Spanish) languages were tested on a memory generalization task and compared to monolingual 18-month-olds. The second experiment compares performance by trilingual 18-month-olds to monolingual and bilingual infants' performance from the first experiment. The bilingual advantage in memory flexibility was robust; both bilingual groups outperformed the monolingual groups, with no significant differences between bilingual groups. Interestingly, an advantage was not found for infants exposed to three languages. These findings demonstrate early emerging differences in memory flexibility, and have important implications for our understanding of how early environmental variations shape the trajectory of memory development.

STUDY OBJECTIVE: To compare the outcome of robotic-assisted laparoscopy vs conventional laparoscopy in the management of ovarian masses. DESIGN: Retrospective cohort (Canadian Task Force classification II-3). SETTING: Academic medical centre in the northeast United States. PATIENTS: Retrospective medical record review of 71 consecutive patients with presumed benign ovarian masses. INTERVENTION: Robotic-assisted laparoscopy in 30 patients with presumed benign ovarian masses was compared with conventional laparoscopy in 41 patients. MEASUREMENTS AND MAIN RESULTS: Operative outcomes including operative time, estimated blood loss, length of hospital stay, and complications were recorded. Standard statistical analysis was used to compare the outcomes in the 2 groups. Mean (SD) operative time in the robotic group was 1.95 (0.63) hours, which was significantly longer than in the conventional laparoscopic group, 1.28 (0.83) hours (p = .04). Estimated blood loss in the robotic group was 74.52 (56.23) mL, which was not significantly different from that in the conventional laparoscopic group, 55.97 (49.18) mL. There were no significant differences in length of hospital stay between the robotic and conventional laparoscopic groups: 1.20 (0.78) days and 1.48 (0.63). Conversion to laparotomy was not necessary in either group of patients. Intraoperative and postoperative complications were similar between the 2 groups. CONCLUSION: Robotic-assisted laparoscopy is a safe and efficient technique for management of various types of ovarian masses. However, conventional laparoscopy is preferred for management of ovarian masses because of shorter operative time. Prospective studies are needed to evaluate the outcomes of robotic-assisted laparoscopic management of benign and malignant ovarian neoplasms.