Exome resequencing and GWAS for growth, ecophysiology, and chemical and metabolomic composition of wood of Populus trichocarpa.

BackgroundPopulus trichocarpa is an important forest tree species for the generation of lignocellulosic ethanol. Understanding the genomic basis of biomass production and chemical composition of wood is fundamental in supporting genetic improvement programs. Considerable variation has been observed in this species for complex traits related to growth, phenology, ecophysiology and wood chemistry. Those traits are influenced by both polygenic control and environmental effects, and their genome architecture and regulation are only partially understood. Genome wide association studies (GWAS) represent an approach to advance that aim using thousands of single nucleotide polymorphisms (SNPs). Genotyping using exome capture methodologies represent an efficient approach to identify specific functional regions of genomes underlying phenotypic variation.ResultsWe identified 813 K SNPs, which were utilized for genotyping 461 P. trichocarpa clones, representing 101 provenances collected from Oregon and Washington, and established in California. A GWAS performed on 20 traits, considering single SNP-marker tests identified a variable number of significant SNPs (p-value < 6.1479E-8) in association with diameter, height, leaf carbon and nitrogen contents, and δ15N. The number of significant SNPs ranged from 2 to 220 per trait. Additionally, multiple-marker analyses by sliding-windows tests detected between 6 and 192 significant windows for the analyzed traits. The significant SNPs resided within genes that encode proteins belonging to different functional classes as such protein synthesis, energy/metabolism and DNA/RNA metabolism, among others.ConclusionsSNP-markers within genes associated with traits of importance for biomass production were detected. They contribute to characterize the genomic architecture of P. trichocarpa biomass required to support the development and application of marker breeding technologies

“Be patient, dear mother … wait for me”: the neo-infirmity film, female illness and contemporary cinema

In social reality, illness and death occur in myriad ways, yet Hollywood films have historically preferred spectacular, violent death over realist depictions of the terminal stages of life. Yet an ever-growing number of popular films, which I term neo-infirmity films, incorporate episodes of women characters debilitated by illness or injury. Operating at the intersection of melodrama and realism, the scenes are instrumental in staging contemporary cinema's gender politics. I argue that women's deathbed and hospital-bed scenes in contemporary cinema validate anew the maternal role and the figure of the mother, transporting the woman-centered discursive space of melodrama into narrative terrain often hostile to women's presence. Through this relocation, the films emphasize her importance to sons in particular (and less often to daughters, husbands, and the larger family unit). Many such scenes simultaneously undermine women's agency, reducing mothers to principally symbolic, literally immobile roles. Ailing women can become catalysts for male psychological transformation occurring through grief, action, or both in combination. In all, such scenes speak to continued ambivalence surrounding women's representation in popular cinema, and to continued patrolling of the boundaries of female power. This essay compares selected texts from contemporary Hollywood cinema, alongside three parallel discourses that also deploy melodramatic modes of articulation: nonfiction amateur video as relayed via television news programs, international art cinema, and US independent cinema. Arguing for homologies across multiple fields of textual production, I seek through this comparison to generate insights into the cultural work done by filmic representation

Determining the Quantitative Principles of T Cell Response to Antigenic Disparity in Stem Cell Transplantation

Alloreactivity compromising clinical outcomes in stem cell transplantation is observed despite HLA matching of donors and recipients. This has its origin in the variation between the exomes of the two, which provides the basis for minor histocompatibility antigens (mHA). The mHA presented on the HLA class I and II molecules and the ensuing T cell response to these antigens results in graft vs. host disease. In this paper, results of a whole exome sequencing study are presented, with resulting alloreactive polymorphic peptides and their HLA class I and HLA class II (DRB1) binding affinity quantified. Large libraries of potentially alloreactive recipient peptides binding both sets of molecules were identified, with HLA-DRB1 generally presenting a greater number of peptides. These results are used to develop a quantitative framework to understand the immunobiology of transplantation. A tensor-based approach is used to derive the equations needed to determine the alloreactive donor T cell response from the mHA-HLA binding affinity and protein expression data. This approach may be used in future studies to simulate the magnitude of expected donor T cell response and determine the risk for alloreactive complications in HLA matched or mismatched hematopoietic cell and solid organ transplantation

Ambulatory Clinic Exam Room Design with respect to Computing Devices: A Laboratory Simulation Study

Background—Challenges persist regarding how to integrate computing effectively into the exam room, while maintaining patient-centered care. Purpose—Our objective was to evaluate a new exam room design with respect to the computing layout, which included a wall-mounted monitor for ease of (re)-positioning. Methods—In a lab-based experiment, 28 providers used prototypes of the new and older “legacy” outpatient exam room layouts in a within-subject comparison using simulated patient encounters. We measured efficiency, errors, workload, patient-centeredness (proportion of time the provider was focused on the patient), amount of screen sharing with the patient, workflow integration, and provider situation awareness. Results—There were no statistically significant differences between the exam room layouts for efficiency, errors, or time spent focused on the patient. However, when using the new layout providers spent 75% more time in screen sharing activities with the patient, had 31% lower workload, and gave higher ratings for situation awareness (14%) and workflow integration (17%). Conclusions—Providers seemed to be unwilling to compromise their focus on the patient when the computer was in a fixed position in the corner of the room and, as a result, experienced greater workload, lower situation awareness, and poorer workflow integration when using the old “legacy” layout. A thoughtful design of the exam room with respect to the computing may positively impact providers’ workload, situation awareness, time spent in screen sharing activities, and workflow integration

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans

Publisher Correction: Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

The original version of this article contained an error in the name of the author Ramachandran S. Vasan, which was incorrectly given as Vasan S. Ramachandran. This has now been corrected in both the PDF and HTML versions of the article

Diagnosing and managing sleep apnea in patients with chronic cerebrovascular disease: a randomized trial of a home-based strategy

Background Obstructive sleep apnea is common and associated with poor outcomes after stroke or transient ischemic attack (TIA). We sought to determine whether the intervention strategy improved sleep apnea detection, obstructive sleep apnea (OSA) treatment, and hypertension control among patients with chronic cerebrovascular disease and hypertension. Methods In this randomized controlled strategy trial intervention, patients received unattended polysomnography at baseline, and patients with OSA (apnea-hypopnea index ≥5 events/h) received auto-titrating continuous positive airway pressure (CPAP) for up to 1 year. Control patients received usual care and unattended polysomnography at the end of the study, to identify undiagnosed OSA. Both groups received 24-h blood pressure assessments at baseline and end of the study. “Excellent” CPAP adherence was defined as cumulative use of ≥4 h/night for ≥70% of the nights. Results Among 225 randomized patients (115 control; 110 intervention), 61.9% (120/194) had sleep apnea. The strategy successfully diagnosed sleep apnea with 97.1% (102/105) valid studies; 90.6% (48/53, 95% CI 82.7–98.4%) of sleep apnea was undiagnosed among control patients. The intervention improved long-term excellent CPAP use: 38.6% (22/57) intervention versus 0% (0/2) control (p < 0.0001). The intervention did not improve hypertension control in this population with well-controlled baseline blood pressure: intervention, 132.7 mmHg (±standard deviation, 14.1) versus control, 133.8 mmHg (±14.0) (adjusted difference, −1.1 mmHg, 95% CI (−4.2, 2.0)), p = 0.48). Conclusions Patients with cerebrovascular disease and hypertension have a high prevalence of OSA. The use of portable polysomnography, and auto-titrating CPAP in the patients’ homes, improved both the diagnosis and the treatment for sleep apnea compared with usual care but did not lower blood pressure

Ambulatory Clinic Exam Room Design with respect to Computing Devices: A Laboratory Simulation Study

OCCUPATIONAL APPLICATIONS When comparing a typical exam room layout to the Department of Veterans Affairs (VA's) new exam room design, with respect to the exam room computing, primary care providers experienced significantly less mental workload and greater situation awareness when using the new exam room design. Further, providers rated the new exam room layout significantly higher in terms of being integrated with their clinical workflow and spent significantly more time in screen sharing activities with the patient. A more thoughtful design of the exam room layout with respect to the placement and physical design of the computing set-up may reduce provider cognitive effort and enhance aspects of patient centeredness by viewing the computer and electronic health record (EHR) it displays as an important mediator between provider and patient. This was achieved by using an all-in-one computer attached to a wall mount that moves the monitor along three axes, allowing for optimal screen positioning and adjustable depending upon the scenario. TECHNICAL ABSTRACT Background: Challenges persist regarding how to integrate computing effectively into the exam room, while maintaining patient-centered care. Purpose: Our objective was to evaluate a new exam room design with respect to the computing layout, which included a wall-mounted monitor for ease of (re)-positioning. Methods: In a lab-based experiment, 28 providers used prototypes of the new and older "legacy" outpatient exam room layouts in a within-subject comparison using simulated patient encounters. We measured efficiency, errors, workload, patient-centeredness (proportion of time the provider was focused on the patient), amount of screen sharing with the patient, workflow integration, and provider situation awareness. Results: There were no statistically significant differences between the exam room layouts for efficiency, errors, or time spent focused on the patient. However, when using the new layout providers spent 75% more time in screen sharing activities with the patient, had 31% lower workload, and gave higher ratings for situation awareness (14%) and workflow integration (17%). Conclusions: Providers seemed to be unwilling to compromise their focus on the patient when the computer was in a fixed position in the corner of the room and, as a result, experienced greater workload, lower situation awareness, and poorer workflow integration when using the old "legacy" layout. A thoughtful design of the exam room with respect to the computing may positively impact providers' workload, situation awareness, time spent in screen sharing activities, and workflow integration.Agency for Health care Research and Quality (AHRQ), U.S. Department of Health and Human Services [1R03HS024488-01A1]12 month embargo; published online: 8 June 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Rare Copy Number Variants in \u3cem\u3eNRXN1\u3c/em\u3e and \u3cem\u3eCNTN6\u3c/em\u3e Increase Risk for Tourette Syndrome

Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (\u3c 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (\u3e 1 Mb), singleton events (OR = 2.28, 95% CI [1.39–3.79], p = 1.2 × 10−3) and known, pathogenic CNVs (OR = 3.03 [1.85–5.07], p = 1.5 × 10−5). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR = 20.3, 95% CI [2.6–156.2]; CNTN6 duplications, OR = 10.1, 95% CI [2.3–45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS