A cost-effective sequencing method for genetic studies combining high-depth whole exome and low-depth whole genome.

Whole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high-depth WGS, most large-scale genetic association studies use genotyping arrays or high-depth whole exome sequencing (WES). Here we propose a cost-effective method which we call "Whole Exome Genome Sequencing" (WEGS), that combines low-depth WGS and high-depth WES with up to 8 samples pooled and sequenced simultaneously (multiplexed). We experimentally assess the performance of WEGS with four different depth of coverage and sample multiplexing configurations. We show that the optimal WEGS configurations are 1.7-2.0 times cheaper than standard WES (no-plexing), 1.8-2.1 times cheaper than high-depth WGS, reach similar recall and precision rates in detecting coding variants as WES, and capture more population-specific variants in the rest of the genome that are difficult to recover when using genotype imputation methods. We apply WEGS to 862 patients with peripheral artery disease and show that it directly assesses more known disease-associated variants than a typical genotyping array and thousands of non-imputable variants per disease-associated locus.

Validation and reliability testing of a rating scale for objective assessment of performance in laparoscopic appendicectomy surgery.

BACKGROUNDS: To achieve a competency-based training paradigm, the ability to obtain reliable and valid quantitative assessments of intraoperative performance is required. Through this, weaknesses can be identified and practiced, and competency assessed. This study aimed to determine the validity and reliability an objective evaluation tool for assessment of performance in laparoscopic appendicectomy (LA). METHODS: A prospective single-blinded observational study design was used. Videos of inexperienced (performed <10 LAs) and experienced (performed >100 LAs) surgeons performing LA surgery were collected. Surgical performance during each recording was rated by two independent, blinded expert surgeons using the LA Rating Scale (LARS) and the modified Objective Structured Assessment of Technical Skill (OSATS) scale. RESULTS: The intraclass correlation coefficient (ICC) for LARS was 0.95 (95%CI 0.83-0.98). The ICC for each step ranged from 0.48 to 0.90, and the test-retest ICC for LARS was 0.91 (95%CI 0.69-0.98). Significant differences (P < 0.001) between median performance scores as rated by LARS were observed between the inexperienced and experienced surgeons. A Spearman's correlation coefficient of 0.87 (P < 0.001) was observed between LARS performance scores and modified OSATS scores. CONCLUSION: LARS demonstrated excellent inter-rater and test-retest reliability, and construct and concurrent validity and can be used to quantitatively evaluate performance during LA. This can potentially allow specific weaknesses to be identified and improved upon through deliberate practice. Progress can be tracked through re-evaluation and scores of expert surgeons can be used as performance goals for credentialing in LA.

Assessment of age in ulcerative colitis patients with ileal pouch creation - an evaluation of outcomes.

INTRODUCTION: The aim of the study was to determine if age at the creation of an ileal pouchanal anastomosis (IPAA) has an impact on the outcomes in patients with ulcerative colitis (UC). MATERIALS AND METHODS: A retrospective review of all patients who underwent IPAA for UC from 1999 to 2011 was performed. Long-term functional outcome was assessed using both the Cleveland Clinic and St Mark's incontinence scores. RESULTS: Eighty-nine patients, with a median age of 46 (range, 16 to 71) years, formed the study group. The median duration of disease prior to their pouch surgery was 7 (0.5 to 39) years. There were 57 (64%) patients who were aged ≤50 years old and 32 (36%) who were >50 years old. Fifty-seven (64%) patients developed perioperative complications of which 51 (89.5%) were minor. High ileostomy output (n = 21, 23.6%) and urinary symptoms (n = 13, 14.6%) were the most commonly encountered complications. The older patients were more likely to have an ASA score ≥3 and a longer length of stay. Although there was a higher incidence of complications in the older group of patients, the difference was not statistically significant. There were no significant differences in the incidence of severe complications. Forty-nine (55%) patients completed our questionnaire on the evaluation of their functional outcomes. There were no significant differences in the Cleveland Clinic and St Mark's incontinence scores between the older (n = 19, 38.8%) and younger (n = 30, 61.2%) patients. There were also no significant differences in the frequency of bowel movements during the day or overnight after sleep between the 2 groups. CONCLUSION: IPAA procedure for patients with UC can be safely performed. Long-term functional outcome is not significantly influenced by the age at which the IPAA was created.