Citations

AbstractVariable tumor cellularity can limit sensitivity and precision in comparative genomics because differences in tumor content can result in misclassifying truncal mutations as region‐specific private mutations in stroma‐rich regions, especially when studying tissue specimens of mediocre tumor cellularity such as lung adenocarcinomas (LUADs). To address this issue, we refined a nuclei flow‐sorting approach by sorting nuclei based on ploidy and the LUAD lineage marker thyroid transcription factor 1 and applied this method to investigate genome‐wide somatic copy number aberrations (SCNAs) and mutations of 409 cancer genes in 39 tumor populations obtained from 16 primary tumors and 21 matched metastases. This approach increased the mean tumor purity from 54% (range 7–89%) of unsorted material to 92% (range 79–99%) after sorting. Despite this rise in tumor purity, we detected limited genetic heterogeneity between primary tumors and their metastases. In fact, 88% of SCNAs and 80% of mutations were propagated from primary tumors to metastases and low allele frequency mutations accounted for much of the mutational heterogeneity. Even though the presence of SCNAs indicated a history of chromosomal instability (CIN) in all tumors, metastases did not have more SCNAs than primary tumors. Moreover, tumors with biallelic TP53 or ATM mutations had high numbers of SCNAs, yet they were associated with a low interlesional genetic heterogeneity. The results of our study thus provide evidence that most macroevolutionary events occur in primary tumors before metastatic dissemination and advocate for a limited degree of CIN over time and space in this cohort of LUADs. Sampling of primary tumors thus may suffice to detect most mutations and SCNAs. In addition, metastases but not primary tumors had seeded additional metastases in three of four patients; this provides a genomic rational for surgical treatment of such oligometastatic LUADs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Studying voice production during running speech can provide new knowledge about the mechanisms of voice production with and without disorder. Laryngeal high-speed videoendoscopy (HSV) systems are powerful tools for studying laryngeal function and, if coupled with flexible fiberoptic endoscopes, they can provide unique possibilities to measure vocal fold vibration with high temporal resolution during connected speech. Hence, we can measure the non-stationary behaviors of the vocal folds, such as the glottal attack and offset times in running speech. In this study, a custom-built flexible fiberoptic HSV system was used to record a “Rainbow Passage” production from a vocally normal female. Automated temporal and spatial segmentation algorithms were developed to determine the time stamps of the vibrating vocal folds and the edges of the vocal folds during phonation. The glottal attack time and offset times were then measured from the temporally and spatially segmented HSV images. The amplification ratio was computed during the phonation onset and the damping ratio was calculated at the offset of sustained portion of phonation. These measures can be used to describe the laryngeal mechanisms of voice production in connected speech.

Bilateral oophorectomy in premenopausal women is a unique condition causing the abrupt and premature loss of ovarian hormones, primarily estrogen. Bilateral oophorectomy causes an alteration of several fundamental aging processes at the cellular, tissue, organ, and system levels, leading to multimorbidity, frailty, and reduced survival. However, many questions remain unanswered.

AbstractObjectiveAcute myeloid leukemia (AML) can be subtyped based on recurrent cytogenetic and molecular genetic abnormalities with diagnostic and prognostic significance. Although cytogenetic characterization classically involves conventional chromosome and/or fluorescence in situ hybridization (FISH) assays, limitations of these techniques include poor resolution and the inability to precisely identify breakpoints.MethodWe evaluated whether an NGS‐based methodology that detects structural abnormalities and copy number changes using mate pair sequencing (MPseq) can enhance the diagnostic yield for patients with AML.ResultsUsing 68 known abnormal and 20 karyotypically normal AML samples, each recurrent primary AML‐specific abnormality previously identified in the abnormal samples was confirmed using MPseq. Importantly, in eight cases with abnormalities that could not be resolved by conventional cytogenetic studies, MPseq was utilized to molecularly define eight recurrent AML‐fusion events. In addition, MPseq uncovered two cryptic abnormalities that were missed by conventional cytogenetic studies. Thus, MPseq improved the diagnostic yield in the detection of AML‐specific structural rearrangements in 10/88 (11%) of cases analyzed.ConclusionUtilization of MPseq represents a precise, molecular‐based technique that can be used as an alternative to conventional cytogenetic studies for newly diagnosed AML patients with the potential to revolutionize the diagnosis of hematologic malignancies.

Objective: With advancements in surgical equipment and procedures, human–system interactions in operating rooms affect surgeon workload and performance. Workload was measured across surgical specialties using surveys to identify potential predictors of high workload for future performance improvement. Summary Background Data: Surgical instrumentation and technique advancements have implications for surgeon workload and human–systems interactions. To understand and improve the interaction of components in the work system, NASA-Task Load Index can measure workload across various fields. Baseline workload measurements provide a broad overview of the field and identify areas most in need of improvement. Methods: Surgeons were administered a modified NASA-Task Load Index survey (0 = low, 20 = high) following each procedure. Patient and procedural factors were retrieved retrospectively. Results: Thirty-four surgeons (41% female) completed 662 surgery surveys (M = 14.85, SD = 7.94), of which 506 (76%) have associated patient and procedural data. Mental demand (M = 7.7, SD = 5.56), physical demand (M = 7.0, SD = 5.66), and effort (M = 7.8, SD = 5.77) were the highest rated workload subscales. Surgeons reported difficulty levels higher than expected for 22% of procedures, during which workload was significantly higher ( P < 0.05) and procedural durations were significantly longer ( P > 0.001). Surgeons reported poorer perceived performance during cases with unexpectedly high difficulty ( P < 0.001). Conclusions: When procedural difficulty is greater than expected, there are negative implications for mental and physical demand that result in poorer perceived performance. Investigations are underway to identify patient and surgical variables associated with unexpected difficulty and high workload. Future efforts will focus on re-engineering the surgical planning process and procedural environment to optimize workload and performance for improved surgical care.