A Single-Cell Atlas of Small Airway Disease in Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.

Rationale: Emerging data demonstrate that the smallest conducting airways, terminal bronchioles, are the early site of tissue destruction in chronic obstructive pulmonary disease (COPD) and are reduced by as much as 41% by the time someone is diagnosed with mild (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1) COPD. Objectives: To develop a single-cell atlas that describes the structural, cellular, and extracellular matrix alterations underlying terminal bronchiole loss in COPD. Methods: This cross-sectional study of 262 lung samples derived from 34 ex-smokers with normal lung function (n = 10) or GOLD stage 1 (n = 10), stage 2 (n = 8), or stage 4 (n = 6) COPD was performed to assess the morphology, extracellular matrix, single-cell atlas, and genes associated with terminal bronchiole reduction using stereology, micro-computed tomography, nonlinear optical microscopy, imaging mass spectrometry, and transcriptomics. Measurements and Main Results: The lumen area of terminal bronchioles progressively narrows with COPD severity as a result of the loss of elastin fibers within alveolar attachments, which was observed before microscopic emphysematous tissue destruction in GOLD stage 1 and 2 COPD. The single-cell atlas of terminal bronchioles in COPD demonstrated M1-like macrophages and neutrophils located within alveolar attachments and associated with the pathobiology of elastin fiber loss, whereas adaptive immune cells (naive, CD4, and CD8 T cells, and B cells) are associated with terminal bronchiole wall remodeling. Terminal bronchiole pathology was associated with the upregulation of genes involved in innate and adaptive immune responses, the interferon response, and the degranulation of neutrophils. Conclusions: This comprehensive single-cell atlas highlights terminal bronchiole alveolar attachments as the initial site of tissue destruction in centrilobular emphysema and an attractive target for disease modification.

Multitasking Induced Contextual Blindness.

OBJECTIVE: To examine the impact of secondary task performance on contextual blindness arising from the suppression and masking of temporal and spatial sequence learning. BACKGROUND: Dual-task scenarios can lead to a diminished ability to use environmental cues to guide attention, a phenomenon that is related to multitasking-induced inattentional blindness. This research aims to extend the theoretical understanding of how secondary tasks can impair attention and memory processes in sequence learning and access. METHOD: We conducted three experiments. In Experiment 1, we used a serial reaction time task to investigate the impact of a secondary tone counting task on temporal sequence learning. In Experiment 2, we used a contextual cueing task to examine the effects of dual-task performance on spatial cueing. In Experiment 3, we integrated and extended these concepts to a simulated driving task. RESULTS: Across the experiments, the performance of a secondary task consistently suppressed (all experiments) and masked task learning (experiments 1 and 3). In the serial response and spatial search tasks, dual-task conditions reduced the accrual of sequence knowledge and impaired knowledge expression. In the driving simulation, similar patterns of learning suppression from multitasking were also observed. CONCLUSION: The findings suggest that secondary tasks can significantly suppress and mask sequence learning in complex tasks, leading to a form of contextual blindness characterized by impairments in the ability to use environmental cues to guide attention and anticipate future events. APPLICATION: These findings have implications for both skill acquisition and skilled performance in complex domains such as driving, aviation, manufacturing, and human-computer interaction.

This Is Your Brain on Autopilot 2.0: The Influence of Practice on Driver Workload and Engagement During On-Road, Partially Automated Driving.

OBJECTIVE: This on-road study employed behavioral and neurophysiological measurement techniques to assess the influence of six weeks of practice driving a Level 2 partially automated vehicle on driver workload and engagement. BACKGROUND: Level 2 partial automation requires a driver to maintain supervisory control of the vehicle to detect "edge cases" that the automation is not equipped to handle. There is mixed evidence regarding whether drivers can do so effectively. There is also an open question regarding how practice and familiarity with automation influence driver cognitive states over time. METHOD: Behavioral and neurophysiological measures of driver workload and visual engagement were recorded from 30 participants at two testing sessions-with a six-week familiarization period in-between. At both testing sessions, participants drove a vehicle with partial automation engaged (Level 2) and not engaged (Level 0) on two interstate highways while reaction times to the detection response task (DRT) and neurophysiological (EEG) metrics of frontal theta and parietal alpha were recorded. RESULTS: DRT results demonstrated that partially automated driving placed more cognitive load on drivers than manual driving and six weeks of practice decreased driver workload-though only when the driving environment was relatively simple. EEG metrics of frontal theta and parietal alpha showed null effects of partial automation. CONCLUSION: Driver workload was influenced by level of automation, specific highway characteristics, and by practice over time, but only on a behavioral level and not on a neural level. APPLICATION: These findings expand our understanding of the influence of practice on driver cognitive states under Level 2 partial automation.

This Is Your Brain on Autopilot: Neural Indices of Driver Workload and Engagement During Partial Vehicle Automation.

OBJECTIVE: This research explores the effect of partial vehicle automation on neural indices of mental workload and visual engagement during on-road driving. BACKGROUND: There is concern that the introduction of automated technology in vehicles may lead to low driver stimulation and subsequent disengagement from the driving environment. Simulator-based studies have examined the effect of automation on a driver's cognitive state, but it is unknown how the conclusions translate to on-road driving. Electroencephalographic (EEG) measures of frontal theta and parietal alpha can provide insight into a driver's mental workload and visual engagement while driving under various conditions. METHOD: EEG was recorded from 71 participants while driving on the roadway. We examined two age cohorts, on two different highway configurations, in four different vehicles, with partial vehicle automation both engaged and disengaged. RESULTS: Analysis of frontal theta and parietal alpha power revealed that there was no change in mental workload or visual engagement when driving manually compared with driving under partial vehicle automation. CONCLUSION: Drivers new to the technology remained engaged with the driving environment when operating under partial vehicle automation. These findings suggest that the concern surrounding driver disengagement under vehicle automation may need to be tempered, at least for drivers new to the experience. APPLICATION: These findings expand our understanding of the effects of partial vehicle automation on drivers' cognitive states.

The molecular and cellular mechanisms associated with the destruction of terminal bronchioles in COPD.

RATIONALE: Peripheral airway obstruction is a key feature of chronic obstructive pulmonary disease (COPD), but the mechanisms of airway loss are unknown. This study aims to identify the molecular and cellular mechanisms associated with peripheral airway obstruction in COPD. METHODS: Ten explanted lung specimens donated by patients with very severe COPD treated by lung transplantation and five unused donor control lungs were sampled using systematic uniform random sampling (SURS), resulting in 240 samples. These samples were further examined by micro-computed tomography (CT), quantitative histology and gene expression profiling. RESULTS: Micro-CT analysis showed that the loss of terminal bronchioles in COPD occurs in regions of microscopic emphysematous destruction with an average airspace size of ≥500 and <1000 µm, which we have termed a "hot spot". Based on microarray gene expression profiling, the hot spot was associated with an 11-gene signature, with upregulation of pro-inflammatory genes and downregulation of inhibitory immune checkpoint genes, indicating immune response activation. Results from both quantitative histology and the bioinformatics computational tool CIBERSORT, which predicts the percentage of immune cells in tissues from transcriptomic data, showed that the hot spot regions were associated with increased infiltration of CD4 and CD8 T-cell and B-cell lymphocytes. INTERPRETATION: The reduction in terminal bronchioles observed in lungs from patients with COPD occurs in a hot spot of microscopic emphysema, where there is upregulation of IFNG signalling, co-stimulatory immune checkpoint genes and genes related to the inflammasome pathway, and increased infiltration of immune cells. These could be potential targets for therapeutic interventions in COPD.

Small Airway Reduction and Fibrosis Is an Early Pathologic Feature of Idiopathic Pulmonary Fibrosis.

Rationale: To improve disease outcomes in idiopathic pulmonary fibrosis (IPF), it is essential to understand its early pathophysiology so that it can be targeted therapeutically. Objectives: Perform three-dimensional assessment of the IPF lung microstructure using stereology and multiresolution computed tomography (CT) imaging. Methods: Explanted lungs from patients with IPF (n = 8) and donor control subjects (n = 8) were inflated with air and frozen. CT scans were used to assess large airways. Unbiased, systematic uniform random samples (n = 8/lung) were scanned with microCT for stereological assessment of small airways (count number, and measure airway wall and lumen area) and parenchymal fibrosis (volume fraction of tissue, alveolar surface area, and septal wall thickness). Measurements and Main Results: The total number of airways on clinical CT was greater in IPF lungs than control lungs (P < 0.01), owing to an increase in the wall (P < 0.05) and lumen area (P < 0.05) resulting in more visible airways with a lumen larger than 2 mm. In IPF tissue samples without microscopic fibrosis, assessed by the volume fraction of tissue using microCT, there was a reduction in the number of the terminal (P < 0.01) and transitional (P < 0.001) bronchioles, and an increase in terminal bronchiole wall area (P < 0.001) compared with control lungs. In IPF tissue samples with microscopic parenchymal fibrosis, terminal bronchioles had increased airway wall thickness (P < 0.05) and dilated airway lumens (P < 0.001) leading to honeycomb cyst formations. Conclusions: This study has important implications for the current thinking on how the lung tissue is remodeled in IPF and highlights small airways as a potential target to modify IPF outcomes.

Physicians' and Attorneys' Beliefs and Attitudes Related to the Brain Disease Model of Addiction.

BACKGROUND AND OBJECTIVES: Addiction is increasingly considered a chronic, relapsing brain disease; however, many scholars still disagree with the brain disease model of addiction. We set out to provide evidence of attorneys' and physicians' beliefs regarding the model. First, we asked the following question: do attorneys and physicians affirm the full brain disease model, or its modified form, or do they believe that addiction is driven by deficits in self-control or moral weakness? Second, we evaluated the extent to which such beliefs correspond to attitudes toward individuals with substance use disorders (SUDs). METHODS: A questionnaire was sent to resident physicians (N = 301) and criminal defense attorneys (N = 483) practicing in the United States. It was comprised of (i) an attitudes measure, (ii) a measure regarding conceptions of addiction, and (iii) demographic questions. RESULTS: Attorneys were more likely to believe that individuals with SUDs had "practically no choice" about whether to seek and use, whereas physicians were more likely to believe that such individuals had "genuine choice." For both groups of participants, the rejection of the full brain disease model of addiction was associated with more negative attitudes toward individuals with SUDs. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These results represent an important advance, as past research has neglected attorneys' attitudes and is inconclusive regarding the manner in which beliefs about the brain disease model of addiction are related to attitudes toward individuals with SUDs. Educating practitioners regarding this relationship would raise awareness regarding when and to what extent stigma is likely to be present, which may in turn provide a foundation from which to address stigma. (Am J Addict 2020;00:00-00).

Visual and Cognitive Demands of CarPlay, Android Auto, and Five Native Infotainment Systems.

OBJECTIVE: The present research compared and contrasted the workload associated with using in-vehicle information systems commonly available in five different automotive original equipment manufacturers (OEMs) with that of CarPlay and Android Auto when used in the same vehicles. BACKGROUND: A growing trend is to provide access to portable smartphone-based systems (e.g., CarPlay and Android Auto) that support an expansion of various in-vehicle infotainment system features and functions. METHOD/RESULTS: The study involved on-road testing of 24 participants in each configuration of five vehicles crossed with the three different infotainment systems: the embedded portion of the native OEM systems, CarPlay, and Android Auto. Our analysis found that workload was significantly greater for the embedded portion of the native OEM systems than for CarPlay and Android Auto. The strengths and weaknesses of each CarPlay and Android Auto traded off in such a way that the overall demand associated with using the two systems did not differ. CONCLUSION: CarPlay and Android Auto provided more functionality and resulted in lower levels of workload than the embedded portion of the native OEM infotainment systems. APPLICATION: Potential applications of this research include refinements to CarPlay and Android Auto to address variations in workload as a function of task type, the modality of interaction, and OEM implementation of the system.

Attitudes toward defendants with substance-related charges: An analysis of a national sample of criminal defense attorneys.

BACKGROUND AND OBJECTIVES: While a large percentage of criminal offenders suffer from substance use disorders (SUDs), virtually nothing is known about the attitudes criminal defense attorneys possess toward their clients who are facing substance-related charges. This is a serious concern, as the burden of steering individuals with SUDs into treatment often falls to criminal defense attorneys. The goal of this study was to examine the attitudes of criminal defense attorneys toward individuals who have been accused of drug crimes. METHODS: A questionnaire was sent to criminal defense attorneys (N = 1,933) from all 50 U.S. states and the District of Columbia. It was comprised of (i) demographic information and (ii) a version of the 11-item Medical Condition Regard Scale (MCRS). RESULTS: Criminal defense attorneys held generally positive attitudes toward clients with substance-related charges, but there was a significant divergence in attitudes between private and public attorneys, with the latter showing both greater familiarity with and better attitudes toward this same group of clients. These differences were impactful: worse attitudes toward clients strongly correlated with greater predictions that the clients would reoffend. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Given the magnitude of the incarcerated population with SUDs and the centrality of defense attorneys in the treatment process, especially its initiation, the divergence in attitudes between private and public criminal defense attorneys is concerning. There is a clear need for increased collaboration between physicians and attorneys, with an aim of increasing the number of individuals with SUDs receiving proper treatment (Am J Addict 2018;XX:1-7).

Micro-Computed Tomography Comparison of Preterminal Bronchioles in Centrilobular and Panlobular Emphysema.

RATIONALE: Very little is known about airways that are too small to be visible on thoracic multidetector computed tomography but larger than the terminal bronchioles. OBJECTIVES: To examine the structure of preterminal bronchioles located one generation proximal to terminal bronchioles in centrilobular and panlobular emphysema. METHODS: Preterminal bronchioles were identified by backtracking from the terminal bronchioles, and their centerlines were established along the entire length of their lumens. Multiple cross-sectional images perpendicular to the centerline were reconstructed to evaluate the bronchiolar wall and lumen, and the alveolar attachments to the outer airway walls in relation to emphysematous destruction in 28 lung samples from six patients with centrilobular emphysema, 20 lung samples from seven patients with panlobular emphysema associated with alpha-1 antitrypsin deficiency, and 47 samples from seven control (donor) lungs. MEASUREMENTS AND MAIN RESULTS: The preterminal bronchiolar length, wall volume, total volume (wall + lumen), lumen circularity, and number of alveolar attachments were reduced in both centrilobular and panlobular emphysema compared with control lungs. In contrast, thickening of the wall and narrowing of the lumen were more severe and heterogeneous in centrilobular than in panlobular emphysema. The bronchiolar lumen was narrower in the middle than at both ends, and the decreased number of alveolar attachments was associated with increased wall thickness in centrilobular emphysema. CONCLUSIONS: These results provide new information about small airways pathology in centrilobular and panlobular emphysema and show that these changes affect airways that are not visible with thoracic multidetector computed tomography scans but located proximal to the terminal bronchioles in chronic obstructive pulmonary disease.