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1.
Surg Endosc ; 38(4): 2240-2251, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38503906

ABSTRACT

BACKGROUND AND PURPOSE: Emergency colectomies are associated with a higher risk of complications compared to elective ones. A critical assessment of complications occurring beyond post-operative day 30 (POD30) is lacking. This study aimed to assess the readmission rate and factors associated with readmission 6-months following emergency colectomy. METHODS: A retrospective cohort study of adult patients who underwent emergency colectomy (2010-2018) was performed using the Nationwide Readmissions Database. The cohort was divided into two groups: (i) no readmission and (ii) emergency readmission(s) for complications related to colectomy (defined using ICD-9/10 codes). Readmissions were categorized as either "early" (POD0-30) or "late" (> POD30). Differences between groups were described and multivariable regression controlling for relevant covariates defined a priori were used to identify factors associated with timing of readmission and cost. RESULTS: Of 141,481 eligible cases, 13.22% (n = 18,699) were readmitted within 6-months of emergency colectomy for colectomy-related complications, 61.63% of which were "late" readmissions (> POD30). The most common reasons for "late" readmission were for bleeding, gastrointestinal, and infectious complications (20.80%, 25.30%, and 32.75%, respectively). On multiple logistic regression, female gender (OR 1.12; 95%CI 1.04-1.21), open procedures (OR 1.12, 95%CI 1.011-1.24), and sigmoidectomies (OR 1.51, 95%CI 1.39-1.65, relative to right hemicolectomies) were the strongest predictors of "late" readmission. On multiple linear regression, "late" readmissions were associated with a $1717.09 USD (95%CI $1717.05-$1717.12) increased cost compared to "early" readmissions. DISCUSSION: The majority of colectomy-related readmissions following emergency colectomy occur beyond POD30 and are associated with cases that are of overall higher morbidity, as well as open sigmoidectomies. Given the associated increased cost of care, mitigation of such readmissions by close follow-up prior to and beyond POD30 is advisable.


Subject(s)
Patient Readmission , Postoperative Complications , Adult , Humans , Female , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Follow-Up Studies , Risk Factors , Colectomy/adverse effects , Colectomy/methods
2.
Can J Public Health ; 114(2): 195-206, 2023 04.
Article in English | MEDLINE | ID: mdl-36763331

ABSTRACT

OBJECTIVES: With increased bicycle use during the COVID-19 pandemic and growing availability of bicycle-sharing programs in Montreal, we hypothesize helmet use has decreased. The aim of this study was to evaluate helmet use and proper fit among Montreal cyclists during the pandemic relative to historical data. METHODS: Nine observers collected data on bike type, gender, helmet use, and ethnicity using the iHelmet© app at 18 locations across the island of Montreal from June to September 2021. Proper helmet wear was assessed at one busy location. Multiple logistic regression was used to identify factors associated with helmet wear and results were compared to a historical study. RESULTS: Of the 2200 cyclists observed, 1109 (50.4%) wore a helmet. Males (OR = 0.78, 95%CI = 0.65-0.95), young adults (OR = 0.65, 95%CI = 0.51-0.84), visible minorities (OR = 0.38, 95%CI = 0.28-0.53), and bike-share users (OR = 0.21, 95%CI = 0.15-0.28) were less likely to be wearing a helmet, whereas children (OR = 3.92, 95%CI = 2.17-7.08) and cyclists using racing bicycles (OR = 3.84, 95%CI = 2.62-5.62) were more likely to be wearing a helmet. The majority (139/213; 65.3%) of assessed cyclists wore properly fitting helmets. Children had the lowest odds of having a properly fitted helmet (OR = 0.13, 95%CI = 0.04-0.41). Compared to 2011, helmet use during the pandemic increased significantly (1109/2200 (50.4%) vs. 2192/4789 (45.8%); p = 0.032). CONCLUSION: Helmet use among Montreal cyclists was associated with age, gender, ethnicity, and type of bicycle. Children were least likely to have a properly fitted helmet. The recent increase in popularity of cycling and expansion of bicycle-sharing programs reinforce the need for bicycle helmet awareness initiatives, legislation, and funding prioritization.


RéSUMé: OBJECTIF: Avec la popularité grandissante du vélo durant la pandémie COVID-19 et l'expansion du vélopartage à Montréal, nous croyons que le port du casque a diminué. L'objectif de cette étude était d'évaluer l'utilisation du casque et le port adéquat parmi les cyclistes montréalais et de comparer nos résultats avec des données historiques. MéTHODE: Neuf observateurs, stationnés à 18 emplacements, ont recueilli les informations suivantes en utilisant l'application mobile iHelmet© : type de vélo, sexe, origine ethnique et port du casque. Le port adéquat du casque a été observé à un endroit. L'association de chaque variable avec le port et le port adéquat a été fait par régression multivariable et comparé à des données historiques. RéSULTATS: Des 2 200 cyclistes observés, 1 109 (50,4 %) portaient un casque. Les enfants (OR = 3,92, IC95% = 2,17­7,08) et les cyclistes de performance (OR = 3,84, IC95% = 2,62­5,62) portaient le casque plus fréquemment tandis que les hommes (OR = 0,78, IC95% = 0,65­0,95), les jeunes adultes (OR = 0,65, IC95% = 0,51­0,84), les minorités visibles (OR = 0,38, IC95% = 0,28­0,53), et les utilisateurs de vélopartage (OR = 0,21, IC95% = 0,15­0,28) le portaient moins. La majorité (139/213; 65,3 %) des casques étaient portés adéquatement. Les enfants étaient plus à risque de porter un casque mal ajusté (OR = 0,13, IC95% = 0,04­0,41). L'utilisation d'un casque chez les cyclistes montréalais a augmenté significativement depuis 2011 (1 109/2 200 (50,4 %) c. 2 192/4 789 (45,8 %); p = 0,032). CONCLUSION: Le port du casque à vélo à Montréal est associé à l'âge, le sexe, l'origine ethnique et le type de vélo. Les enfants sont plus à risque de mal porter un casque. Des stratégies de promotion ainsi que la législation peuvent favoriser des comportements sécuritaires à vélo.


Subject(s)
COVID-19 , Craniocerebral Trauma , Male , Child , Young Adult , Humans , Head Protective Devices , Bicycling , Cross-Sectional Studies , Pandemics , COVID-19/epidemiology , COVID-19/prevention & control
3.
Surg Endosc ; 37(1): 669-682, 2023 01.
Article in English | MEDLINE | ID: mdl-36195816

ABSTRACT

BACKGROUND: Early ileostomy closure (EIC), ≤ 2 weeks from creation, is a relatively new practice. Multiple studies have demonstrated that this approach is safe, feasible, and cost-effective. Despite the demonstrated benefits, this is neither routine practice, nor has it been studied, in North America. This study aimed to assess patient and surgeon perspectives about EIC. METHODS: A mixed-methods, cross-sectional study of patients and surgeons was performed. Rectal cancer survivors from a single institution who underwent restorative proctectomy with diverting loop ileostomy and subsequent closure within the last 5 years were contacted. North American surgeons with high rectal cancer volumes (> 20 cases/year) were included. Surveys (patients) and semi-structured interviews (surgeons) were conducted. Analysis employed descriptive statistics and thematic analysis, respectively. RESULTS: Forty-eight patients were surveyed (mean age 65.1 ± 11.8 years; 54.2% male). Stoma closure occurred after a median of 7.7 months (IQR 4.8-10.9) and 50.0% (24) found it "difficult" or "very difficult" to live with their stoma. Patients considered improvement in quality of life and quicker return to normal function the most important advantages of EIC, whereas the idea of two operations in two weeks being too taxing on the body was deemed the biggest disadvantage. Most patients (35, 72.9%) would have opted for EIC. Surgeon interviews (15) revealed 4 overarching themes: (1) there are many benefits to EIC; (2) specific patient characteristics would make EIC an appropriate option; (3) many barriers to implementing EIC exist; and (4) many logistical hurdles need to be addressed for successful implementation. Most surgeons (12, 80.0%) would "definitely want to participate" in a North American randomized-controlled trial (RCT) on EIC for rectal cancer patients. CONCLUSIONS: Implementing EIC poses many logistical challenges. Both patients and surgeons are interested in further exploring EIC and believe it warrants a North American RCT to motivate a change in practice.


Subject(s)
Proctectomy , Rectal Neoplasms , Surgeons , Male , Humans , Middle Aged , Aged , Female , Ileostomy/methods , Postoperative Complications , Rectal Neoplasms/surgery , Proctectomy/methods
4.
Ann Thorac Surg ; 115(1): 200-208, 2023 01.
Article in English | MEDLINE | ID: mdl-35926638

ABSTRACT

BACKGROUND: Surgery, as part of a multimodal approach, offers the greatest chance of cure for esophageal cancer. However, esophagectomy is often perceived as having a lasting impact on quality of life (QOL), biasing some physicians and patients toward nonoperative management. A comprehensive understanding of the dynamic changes in patient-centered outcomes is therefore important for decision making. Our objective was to determine the long-term QOL after esophagectomy. METHODS: Data were obtained from a prospectively collected (2006-2015) esophagectomy database at a high-volume center, and patients surviving 3 or more years were identified. Health-related QOL was evaluated using the Functional Assessment of Cancer Therapy-Esophageal Module (FACT-E) at diagnosis and every 3 to 6 months, and was stratified according to operative approach, stage, and complications. In addition, QOL scores were compared with normative population values. RESULTS: Of 480 patients, 47% (n = 226) survived 3 or more years and 70% (158 of 226) completed the health-related QOL assessments. Time of follow-up was 5.1 ± 2.8 years. After a reduction at 1 to 3 months, FACT-E increased from a baseline of 126 (95% CI, 121-131) to 133 (95% CI, 127-139) at 12 months, and to 147 (95% CI, 142-153) by 5 years. There was no difference in long-term FACT-E with respect to the surgical approach, clinical and pathologic stage, or postoperative complications. At long-term follow-up (more than 3 years), QOL did not differ significantly from the normative population reference values. CONCLUSIONS: The long-term QOL of esophagectomy patients surviving at least 3 years is improved when compared with the time of diagnosis and does not differ from the general population.


Subject(s)
Esophageal Neoplasms , Quality of Life , Humans , Esophagectomy/methods , Esophageal Neoplasms/surgery , Outcome Assessment, Health Care
5.
Eur J Trauma Emerg Surg ; 48(1): 315-319, 2022 Feb.
Article in English | MEDLINE | ID: mdl-33398439

ABSTRACT

PURPOSE: Hemodynamically unstable trauma patients who would benefit from angioembolization (AE) typically also require emergent surgery for their injuries. The critical decision of transferring a patient to the operating room versus the interventional radiology (IR) suite can be bypassed with the advent of intra-operative AE (IOAE). Previously limited by the availability of costly rooms termed RAPTOR (resuscitation with angiography, percutaneous techniques and open repair) suites, it has been suggested that using C-arm digital subtraction angiography (DSA) is a comparable alternative. This case series aims to establish the feasibility and safety of IOAE. METHODS: We conducted a retrospective analysis of all trauma patients at our level 1 trauma center who underwent IOAE with a concomitant surgical intervention from January 2011 to May 2019. Descriptive analyses were conducted. RESULTS: A total of 49 patients (80% male, 44 ± 17 years, 92% blunt) underwent IOAE using the C-arm DSA during the study period. All but one patient underwent exploratory laparotomy, 56% of which underwent an additional surgical procedure (ex. exploratory thoracotomy, orthopedic). Either Gelfoam® (Pfizer, New York, USA) (90%), coils (2.0%), or a combination (8.2%) were used for embolization. Internal iliac embolization was performed in 88% of cases (59% bilateral). IOAE was successful in all but four cases (8.2%) and thirty-day mortality was 31%. CONCLUSION: IOAE appears to be a feasible and safe management option in severe trauma patients with the advantage of concurrent operative intervention and ongoing active resuscitation with good success in hemorrhage control.


Subject(s)
Embolization, Therapeutic , Wounds, Nonpenetrating , Angiography, Digital Subtraction , Feasibility Studies , Female , Humans , Male , Retrospective Studies , Trauma Centers , Wounds, Nonpenetrating/therapy
6.
Colorectal Dis ; 23(6): 1507-1514, 2021 06.
Article in English | MEDLINE | ID: mdl-33423346

ABSTRACT

AIM: The objectives of this project were (1) to compare time to readiness for discharge by set criteria and actual length of stay (LOS) in a newly implemented colorectal enhanced recovery pathway and (2) to identify reasons for delayed hospital discharge. METHOD: We conducted a prospective cohort study of 73 adult patients (age 67 ± 14 years, 56% men, 51% laparoscopic, 13% stoma creation) undergoing elective colorectal surgery in a university hospital with a recently implemented recovery pathway (<2 years). Time to readiness for discharge (oral intake, flatus, pain control, ability to walk, and no complications) was compared to actual LOS using a correlation-adjusted log-rank test. The treating team was interviewed, and thematic analysis was used to identify reasons for patients remaining in hospital after discharge criteria (DC) were achieved. RESULTS: Median LOS was 6 (4-8) days and median time to readiness for discharge was 5 (3-8) days (P < 0.001). Twenty-eight patients (37%) remained in hospital after DC were achieved. Although some delayed discharges were medically justified (e.g., workup [13%] or treatment of complications not captured by DC [2.6%]), unnecessary hospital stays were common (e.g., perceived need for observation [16%], or patients not willing to be discharged [11%]). CONCLUSIONS: Unnecessary hospital stays were common within a recently implemented enhanced recovery pathway and represent a target for quality improvement. Efforts should be directed at optimizing patient education regarding discharge expectations, early consultation of the discharge planning team and improving discharge decision-making using standardized DC.


Subject(s)
Colorectal Surgery , Digestive System Surgical Procedures , Adult , Aged , Aged, 80 and over , Female , Humans , Length of Stay , Male , Middle Aged , Patient Discharge , Postoperative Complications , Prospective Studies
7.
J Obstet Gynaecol Can ; 42(8): 984-1000, 2020 Aug.
Article in English | MEDLINE | ID: mdl-31882284

ABSTRACT

Intrauterine adhesions (IUAs) are a result of trauma to the basalis layer of the endometrium and may lead to clinical sequelae such as miscarriage, infertility, and menstrual irregularities. Hysteroscopy is recognized as the gold standard in diagnosis and management, although the optimal treatment after surgical intervention remains unclear. This review aimed to provide an update on the treatment options available after hysteroscopic adhesiolysis and to facilitate clinical management of patients with IUAs. To avoid duplicating previous work, the review focused on studies that compared various adjunctive postoperative treatments in patients receiving hormone therapy. Of 548 studies, 15 papers fit our criteria that compared post-resection treatment options in women with IUAs. Meta-analysis of the use of Foley catheter or amnion graft as an adjunctive therapy after adhesiolysis failed to show a statistical difference (odds ratio 1.55; 95% confidence interval 0.60-3.99). Meta-analysis could not be done for the 13 remaining studies as a result of extensive heterogeneity, bias, or non-comparable end points. The lack of a universal classification system for IUAs and the use of variable outcomes to measure the success of adjunctive treatment pose challenges in generating standard treatment recommendations. This review calls for the development of a universal classification system and studies with consistent parameters and end points to allow for the generation of standard treatment guidelines. On the basis of the available evidence, recommendation of specific adjunctive treatments after hysteroscopic adhesiolysis is unjustified.


Subject(s)
Hysteroscopy/methods , Tissue Adhesions/surgery , Uterine Diseases/surgery , Female , Humans , Hysteroscopy/adverse effects , Pregnancy , Tissue Adhesions/complications , Uterine Diseases/complications
8.
J Pediatr Surg ; 55(3): 493-512, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31839371

ABSTRACT

PURPOSE: Low- and middle-income countries (LMICs) have only 19% of the global surgical workforce yet see 80% of worldwide deaths from noncommunicable diseases. We aimed to interrogate the correlation between pediatric surgical workforce density (PSWD) and survival from pediatric surgical conditions worldwide. METHODS: A systematic review of online databases identified outcome studies for key pediatric surgical conditions (gastroschisis, esophageal atresia, intestinal atresia, and typhoid perforation) as well as PSWD data across low-income (LICs), middle-income (MICs), and high-income countries (HICs). PSWD was expressed as the number of PSs/million children under 15 years of age and we correlated this to surgical outcomes for our case series. RESULTS: PSWD ranged between zero (Burundi, The Gambia, and Mauritania) and 125.2 (Poland) across 86 countries. Outcomes for at least one condition were obtained in 61 countries: 50 outcomes in HICs, 52 in MICs and 8 in LICs. The mean survival in our case series was 42.3%, 69.4% and 91.6% for LICs, MICs, and HICs, respectively. A PSWD ≥4 PSs/million children under 15 years of age significantly correlated to odds of survival ≥80% (OR 16.8, p < 0.0001, 95% CI 5.66-49.88). Specifically in the studied LICs and MICs, increasing the PSWD to 4 would require training 1427 additional surgeons. CONCLUSION: Using a novel approach, we have established a benchmark for the scale-up of pediatric surgical workforce, which may support broader efforts to reduce childhood deaths from congenital disease. LEVELS OF EVIDENCE: 2c - Outcomes Research.


Subject(s)
Pediatrics/organization & administration , Surgeons/statistics & numerical data , Surgical Procedures, Operative , Workforce/statistics & numerical data , Adolescent , Child , Child, Preschool , Digestive System Abnormalities/surgery , Humans , Infant , Infant, Newborn , Poverty , Surgical Procedures, Operative/mortality , Surgical Procedures, Operative/statistics & numerical data , Treatment Outcome
9.
J Pediatr Surg ; 54(5): 925-931, 2019 May.
Article in English | MEDLINE | ID: mdl-30786991

ABSTRACT

PURPOSE: Effective antenatal counseling in congenital diaphragmatic hernia (CDH) relies on proper measurement of prognostic indices. This quality initiative audited the accuracy of prenatal imaging with postnatal outcomes at two tertiary pediatric referral centers. METHODS: Prenatal lung-head ratio (LHR) and total fetal lung volume (TFLV) for CDH patients treated between 2006 and 2017 were retrieved. Study inclusion required at least one LHR or TFLV measurement between 24 and 32 weeks gestational age. Postnatal outcomes [mortality, extracorporeal life support (ECLS) need, patch repair, persistent pulmonary hypertension, oxygen requirement at 28 days] were abstracted from the Canadian Pediatric Surgery Network (CAPSNet) database and local chart review. Univariate and descriptive analyses were conducted. RESULTS: Eighty-two of 121 eligible CDH patients (68%) were included. Overall mortality, ECLS rates, and patch repair were 33%, 12.5%, and 45%, respectively. Lower LHR values correlated with increased rates of each outcome and persisted despite multiple measurements. Values obtained were higher than those in published schemata. LHR values >45% were most associated with survival, avoidance of ECLS, and primary repair. TFLV values only correlated with mortality and patch repair. CONCLUSIONS: This audit confirms that LHR and TFLV values predict CDH outcomes. However, absolute values obtained require careful interpretation and internal review. LEVEL OF EVIDENCE: IV.


Subject(s)
Extracorporeal Membrane Oxygenation , Hernias, Diaphragmatic, Congenital/diagnostic imaging , Hernias, Diaphragmatic, Congenital/mortality , Canada/epidemiology , Directive Counseling , Female , Gestational Age , Head/anatomy & histology , Head/diagnostic imaging , Hernias, Diaphragmatic, Congenital/surgery , Humans , Infant, Newborn , Lung/diagnostic imaging , Lung/pathology , Lung Volume Measurements , Male , Organ Size , Prognosis , Survival Rate , Ultrasonography, Prenatal
10.
BMC Med Genomics ; 9: 19, 2016 Apr 11.
Article in English | MEDLINE | ID: mdl-27067391

ABSTRACT

BACKGROUND: Sequencing of both healthy and disease singletons yields many novel and low frequency variants of uncertain significance (VUS). Complete gene and genome sequencing by next generation sequencing (NGS) significantly increases the number of VUS detected. While prior studies have emphasized protein coding variants, non-coding sequence variants have also been proven to significantly contribute to high penetrance disorders, such as hereditary breast and ovarian cancer (HBOC). We present a strategy for analyzing different functional classes of non-coding variants based on information theory (IT) and prioritizing patients with large intragenic deletions. METHODS: We captured and enriched for coding and non-coding variants in genes known to harbor mutations that increase HBOC risk. Custom oligonucleotide baits spanning the complete coding, non-coding, and intergenic regions 10 kb up- and downstream of ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, and TP53 were synthesized for solution hybridization enrichment. Unique and divergent repetitive sequences were sequenced in 102 high-risk, anonymized patients without identified mutations in BRCA1/2. Aside from protein coding and copy number changes, IT-based sequence analysis was used to identify and prioritize pathogenic non-coding variants that occurred within sequence elements predicted to be recognized by proteins or protein complexes involved in mRNA splicing, transcription, and untranslated region (UTR) binding and structure. This approach was supplemented by in silico and laboratory analysis of UTR structure. RESULTS: 15,311 unique variants were identified, of which 245 occurred in coding regions. With the unified IT-framework, 132 variants were identified and 87 functionally significant VUS were further prioritized. An intragenic 32.1 kb interval in BRCA2 that was likely hemizygous was detected in one patient. We also identified 4 stop-gain variants and 3 reading-frame altering exonic insertions/deletions (indels). CONCLUSIONS: We have presented a strategy for complete gene sequence analysis followed by a unified framework for interpreting non-coding variants that may affect gene expression. This approach distills large numbers of variants detected by NGS to a limited set of variants prioritized as potential deleterious changes.


Subject(s)
Breast Neoplasms/genetics , DNA, Intergenic/genetics , Genetic Predisposition to Disease , Inheritance Patterns/genetics , Mutation/genetics , Ovarian Neoplasms/genetics , Base Sequence , Exons/genetics , Female , Humans , Information Theory , Molecular Sequence Data , Nucleic Acid Conformation , Polymorphism, Single Nucleotide/genetics , Protein Binding/genetics , Protein Isoforms/genetics , RNA Splice Sites/genetics , Sequence Alignment , Sequence Analysis, DNA , Sequence Deletion/genetics , Untranslated Regions/genetics
11.
Hum Mutat ; 37(7): 640-52, 2016 07.
Article in English | MEDLINE | ID: mdl-26898890

ABSTRACT

BRCA1 and BRCA2 testing for hereditary breast and ovarian cancer (HBOC) does not identify all pathogenic variants. Sequencing of 20 complete genes in HBOC patients with uninformative test results (N = 287), including noncoding and flanking sequences of ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51B, STK11, TP53, and XRCC2, identified 38,372 unique variants. We apply information theory (IT) to predict and prioritize noncoding variants of uncertain significance in regulatory, coding, and intronic regions based on changes in binding sites in these genes. Besides mRNA splicing, IT provides a common framework to evaluate potential affinity changes in transcription factor (TFBSs), splicing regulatory (SRBSs), and RNA-binding protein (RBBSs) binding sites following mutation. We prioritized variants affecting the strengths of 10 splice sites (four natural, six cryptic), 148 SRBS, 36 TFBS, and 31 RBBS. Three variants were also prioritized based on their predicted effects on mRNA secondary (2°) structure and 17 for pseudoexon activation. Additionally, four frameshift, two in-frame deletions, and five stop-gain mutations were identified. When combined with pedigree information, complete gene sequence analysis can focus attention on a limited set of variants in a wide spectrum of functional mutation types for downstream functional and co-segregation analysis.


Subject(s)
Gene Regulatory Networks , Genetic Variation , Hereditary Breast and Ovarian Cancer Syndrome/genetics , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Female , Genetic Predisposition to Disease , Humans , Middle Aged , Nucleic Acid Conformation , RNA Splicing , RNA, Messenger/chemistry , RNA, Messenger/genetics , Sequence Analysis, DNA
12.
Radiat Prot Dosimetry ; 159(1-4): 95-104, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24757176

ABSTRACT

We present a prototype software system with sufficient capacity and speed to estimate radiation exposures in a mass casualty event by counting dicentric chromosomes (DCs) in metaphase cells from many individuals. Top-ranked metaphase cell images are segmented by classifying and defining chromosomes with an active contour gradient vector field (GVF) and by determining centromere locations along the centreline. The centreline is extracted by discrete curve evolution (DCE) skeleton branch pruning and curve interpolation. Centromere detection minimises the global width and DAPI-staining intensity profiles along the centreline. A second centromere is identified by reapplying this procedure after masking the first. Dicentrics can be identified from features that capture width and intensity profile characteristics as well as local shape features of the object contour at candidate pixel locations. The correct location of the centromere is also refined in chromosomes with sister chromatid separation. The overall algorithm has both high sensitivity (85 %) and specificity (94 %). Results are independent of the shape and structure of chromosomes in different cells, or the laboratory preparation protocol followed. The prototype software was recoded in C++/OpenCV; image processing was accelerated by data and task parallelisation with Message Passaging Interface and Intel Threading Building Blocks and an asynchronous non-blocking I/O strategy. Relative to a serial process, metaphase ranking, GVF and DCE are, respectively, 100 and 300-fold faster on an 8-core desktop and 64-core cluster computers. The software was then ported to a 1024-core supercomputer, which processed 200 metaphase images each from 1025 specimens in 1.4 h.


Subject(s)
Automation, Laboratory/methods , Centromere , Chromosome Aberrations/radiation effects , Chromosomes, Human/radiation effects , Cytogenetic Analysis/methods , Radiation Monitoring/methods , Algorithms , Dose-Response Relationship, Radiation , Humans , Software
13.
F1000Res ; 3: 282, 2014.
Article in English | MEDLINE | ID: mdl-25717368

ABSTRACT

The interpretation of genomic variants has become one of the paramount challenges in the post-genome sequencing era. In this review we summarize nearly 20 years of research on the applications of information theory (IT) to interpret coding and non-coding mutations that alter mRNA splicing in rare and common diseases. We compile and summarize the spectrum of published variants analyzed by IT, to provide a broad perspective of the distribution of deleterious natural and cryptic splice site variants detected, as well as those affecting splicing regulatory sequences. Results for natural splice site mutations can be interrogated dynamically with Splicing Mutation Calculator, a companion software program that computes changes in information content for any splice site substitution, linked to corresponding publications containing these mutations. The accuracy of IT-based analysis was assessed in the context of experimentally validated mutations. Because splice site information quantifies binding affinity, IT-based analyses can discern the differences between variants that account for the observed reduced (leaky) versus abolished mRNA splicing. We extend this principle by comparing predicted mutations in natural, cryptic, and regulatory splice sites with observed deleterious phenotypic and benign effects. Our analysis of 1727 variants revealed a number of general principles useful for ensuring portability of these analyses and accurate input and interpretation of mutations. We offer guidelines for optimal use of IT software for interpretation of mRNA splicing mutations.

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