Acceptability of a Mobile Clinical Decision Tool Among Emergency Department Clinicians: Development and Evaluation of The Ottawa Rules App.

BACKGROUND: The Ottawa Ankle Rules, Ottawa Knee Rule, and Canadian C-Spine Rule-together known as The Ottawa Rules-are a set of internationally validated clinical decision rules developed to decrease unnecessary diagnostic imaging in the emergency department. In this study, we sought to develop and evaluate the use of a mobile app version of The Ottawa Rules. OBJECTIVE: The primary objective of this study was to determine acceptability of The Ottawa Rules app among emergency department clinicians. The secondary objective was to evaluate the effect of publicity efforts on uptake of The Ottawa Rules app. METHODS: The Ottawa Rules app was developed and publicly released for free on iOS and Android operating systems in April 2016. Local and national news and academic media coverage coincided with app release. This study was conducted at a large tertiary trauma care center in Ottawa, Canada. The study was advertised through posters and electronically by email. Emergency department clinicians were approached in person to enroll via in-app consent for a 1-month study during which time they were encouraged to use the app when evaluating patients with suspected knee, foot, or neck injuries. A 23-question survey was administered at the end of the study period via email to determine self-reported frequency, perceived ease of use of the app, and participant Technology Readiness Index scores. RESULTS: A total of 108 emergency department clinicians completed the study including 42 nurses, 33 residents, 20 attending physicians, and 13 medical students completing emergency department rotations. The median Technology Readiness Index for this group was 3.56, indicating a moderate degree of openness for technological adoption. The majority of survey respondents indicated favorable receptivity to the app including finding it helpful to applying the rules (73/108, 67.6%), that they would recommend the app to colleagues (81/108, 75.0%), and that they would continue using the app (73/108, 67.6%). Feedback from study participants highlighted a desire for access to more clinical decision rules and a higher degree of interactivity of the app. Between April 21, 2016, and June 1, 2017, The Ottawa Rules app was downloaded approximately 4000 times across 89 countries. CONCLUSIONS: We have found The Ottawa Rules app to be an effective means to disseminate the Ottawa Ankle Rules, Ottawa Knee Rule, and Canadian C-Spine Rule among all levels of emergency department clinicians. We have been successful in monitoring uptake and access of the rules in the app as a result of our publicity efforts. Mobile technology can be leveraged to improve the accessibility of clinical decision tools to health professionals.

Gene tree distributions under the coalescent process.

Under the coalescent model for population divergence, lineage sorting can cause considerable variability in gene trees generated from any given species tree. In this paper, we derive a method for computing the distribution of gene tree topologies given a bifurcating species tree for trees with an arbitrary number of taxa in the case that there is one gene sampled per species. Applications for gene tree distributions include determining exact probabilities of topological equivalence between gene trees and species trees and inferring species trees from multiple datasets. In addition, we examine the shapes of gene tree distributions and their sensitivity to changes in branch lengths, species tree shape, and tree size. The method for computing gene tree distributions is implemented in the computer program COAL.

Variation among natural isolates of Neurospora on small spatial scales.

Although species of Neurospora are among the most studied model organisms in genetics and biochemistry, basic questions remain with respect to their ecology and population biology. In this study, we sought to clarify relationships among individuals over a small spatial scale, toward assessing both local variation and mode of colonization. Isolates of Neurospora were collected after fires in the Florida Everglades (May 1999), where abundant colonies appeared on diverse plants, including grasses and woody shrubs. Colonies were sampled in a linear fashion from two adjacent scorched sugarcane stems at one site and from a burned woody shrub at a distant second site. Species and mating types were assigned based on crossing behavior. Variation at two loci, het-c and frq, was determined by direct sequencing of PCR products. The results demonstrated substantial within- and among-species variation on a small scale, with up to three species and six different haplotypes occurring on a single stem. In total, four species and more than 10 genetically distinct individuals (haplotypes) were present across the three stems, often with multiple individuals occupying the same position. A permutation analysis revealed that individuals were not distributed randomly and that adjacent nodes on cane stems were more likely than chance to be colonized by the same haplotype. This suggests that visible eruptions of conidia on burned plants reflect substantial vegetative mycelial spread through subsurface tissues after primary colonization. Results also revealed that adjacent isolates from a single plant can possess different functional alleles at het-c, an observation meaningful in the context of the proposed role of het-c in self recognition.

Association of skirt size and postmenopausal breast cancer risk in older women: a cohort study within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

OBJECTIVES: Several studies suggest that overall and central-obesity are associated with increased breast cancer (BC) risk in postmenopausal-women. However, there are no studies investigating changes of central obesity and BC. We report on the association of BC risk with self-reported skirt size (SS; waist-circumference proxy) changes between 20s and postmenopausal-age. DESIGN: Prospective cohort-study. SETTING: UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) involving the nine trial centres in England. PARTICIPANTS: Postmenopausal-women aged >50 with no known history of BC prior to or on the day of completion of the study-entry questionnaire. INTERVENTIONS: At recruitment and at study entry, women were asked to complete a questionnaire. Women were followed-up via 'flagging' at the NHS Information Centre in England and the Hospital Episode Statistics. MAIN OUTCOME-MEASURE: Time to initial BC diagnosis. RESULTS: Between 2 January 2005 and 1 July 2010, 92,834 UKCTOCS participants (median age 64.0) completed the study-entry questionnaire. During median follow-up of 3.19 years (25th-75th centile: 2.46-3.78), 1090 women developed BC. Model adjusted analysis for potential confounders showed body mass index (BMI) at recruitment to UKCTOCS (HR for a 5 unit change=1.076, 95% CI 1.012 to 1.136), current SS at study entry (HR=1.051; 95% CI 1.014 to 1.089) and change in SS per 10 years (CSS) (HR=1.330; 95% CI 1.121 to 1.579) were associated with increased BC risk but not SS at 25 (HR=1.006; 95% CI 0.958 to 1.056). CSS was the most predictive singe adiposity measure and further analysis including both CSS and BMI in the model revealed CSS remained significant (HR=1.266; 95% CI 1.041 to 1.538) but not BMI (HR=1.037; 95% CI 0.970 to 1.109). CONCLUSIONS: CSS is associated with BC risk independent of BMI. A unit increase in UK SS (eg, 12-14) every 10-years between 25 and postmenopausal-age is associated with postmenopausal BC risk by 33%. Validation of these results could provide women with a simple and easy to understand message. TRIAL REGISTRATION NUMBER: ISRCTN22488978.

Identifying hopelessness in population research: a validation study of two brief measures of hopelessness.

OBJECTIVE: Hopelessness is an important construct in psychosocial epidemiology, but there is great pressure on the length of questionnaire measures in large-scale population and clinical studies. We examined the validity and test-retest reliability of two brief measures of hopelessness, an existing negatively worded two-item measure of hopelessness (Brief-H-Neg) and a positively worded version of the same instrument (Brief-H-Pos). DESIGN: Cohort study. SETTING: Control arm of the UK Collaborative Trial of Ovarian Cancer Screening. PARTICIPANTS: A non-clinical research-based sample of 5000 postmenopausal women selected from 56 512 participants. PRIMARY AND SECONDARY OUTCOME MEASURES: Spearman's rank correlation of brief measures of hopelessness with the Beck Hopelessness Scale (BHS). Spearman's rank correlation with the Centre for Epidemiological Studies Depression Scale (CES-D) and change in mean score on repeat testing. METHODS: Two short hopelessness measures, a negatively worded brief measure of hopelessness (Brief-H-Neg) and a positively worded brief measure of hopelessness (Brief-H-Pos), were administered by postal questionnaire to 5000 women together with the 20-item BHS and 20-item CES-D. The Brief-H-Neg and Brief-H-Pos were readministered to 500 women after a 2-week interval. RESULTS: 2413 postmenopausal women (mean age 68.9 years) completed the questionnaire. The Brief-H-Neg and Brief-H-Pos correlated 0.93 and 0.87 with the BHS after correction for attenuation and their association with the CES-D mirrored that seen with the BHS (Spearman's rank correlation 0.88 and 0.68, respectively). There was no change in mean scores on the two measures with repeat testing in the 433 women who completed them and test-retest reliability was good (intraclass correlations Brief-H-Neg 0.67 and Brief-H-Pos 0.72). CONCLUSIONS: These findings provide support for the validity of the Brief-H-Neg and Brief-H-Pos. These brief measures are likely to be useful in large population studies assessing hopelessness. TRIAL REGISTRATION NUMBER: NCT00058032.

Estimation of evolutionary parameters with phylogenetic trees.

An important issue in the phylogenetic analysis of nucleotide sequence data using the maximum likelihood (ML) method is the underlying evolutionary model employed. We consider the problem of simultaneously estimating the tree topology and the parameters in the underlying substitution model and of obtaining estimates of the standard errors of these parameter estimates. Given a fixed tree topology and corresponding set of branch lengths, the ML estimates of standard evolutionary model parameters are asymptotically efficient, in the sense that their joint distribution is asymptotically normal with the variance-covariance matrix given by the inverse of the Fisher information matrix. We propose a new estimate of this conditional variance based on estimation of the expected information using a Monte Carlo sampling (MCS) method. Simulations are used to compare this conditional variance estimate to the standard technique of using the observed information under a variety of experimental conditions. In the case in which one wishes to estimate simultaneously the tree and parameters, we provide a bootstrapping approach that can be used in conjunction with the MCS method to estimate the unconditional standard error. The methods developed are applied to a real data set consisting of 30 papillomavirus sequences. This overall method is easily incorporated into standard bootstrapping procedures to allow for proper variance estimation.

A statistical framework for combining and interpreting proteomic datasets.

MOTIVATION: To identify accurately protein function on a proteome-wide scale requires integrating data within and between high-throughput experiments. High-throughput proteomic datasets often have high rates of errors and thus yield incomplete and contradictory information. In this study, we develop a simple statistical framework using Bayes' law to interpret such data and combine information from different high-throughput experiments. In order to illustrate our approach we apply it to two protein complex purification datasets. RESULTS: Our approach shows how to use high-throughput data to calculate accurately the probability that two proteins are part of the same complex. Importantly, our approach does not need a reference set of verified protein interactions to determine false positive and false negative error rates of protein association. We also demonstrate how to combine information from two separate protein purification datasets into a combined dataset that has greater coverage and accuracy than either dataset alone. In addition, we also provide a technique for estimating the total number of proteins which can be detected using a particular experimental technique. AVAILABILITY: A suite of simple programs to accomplish some of the above tasks is available at www.unm.edu/~compbio/software/DatasetAssess

A comparison of methods for estimating the transition:transversion ratio from DNA sequences.

Estimation of the ratio of the rates of transitions to transversions (TI:TV ratio) for a collection of aligned nucleotide sequences is important because it provides insight into the process of molecular evolution and because such estimates may be used to further model the evolutionary process for the sequences under consideration. In this paper, we compare several methods for estimating the TI:TV ratio, including the pairwise method [TREE 11 (1996) 158], a modification of the pairwise method due to Ina [J. Mol. Evol. 46 (1998) 521], a method based on parsimony (TREE 11 (1996) 158), a method due to Purvis and Bromham [J. Mol. Evol. 44 (1997) 112] that uses phylogenetically independent pairs of sequences, the maximum likelihood method, and a Bayesian method [Bioinformatics 17 (2001) 754]. We examine the performance of each estimator under several conditions using both simulated and real data.

The optimal number of donor biopsy sites to evaluate liver histology for transplantation.

Macrovesicular steatosis (MaS), fibrosis, and inflammation have been associated with poor graft function after liver transplantation. We evaluated histological variation in livers to determine the optimal number of biopsies to estimate pathological characteristics in livers for transplantation. Specimens from autopsies performed during 3 months in 16- to 70-years-olds without known liver disease or drug and/or alcohol abuse were examined. Eight needle biopsies were performed, and hematoxylin and eosin-stained slides were evaluated. Percentages of MaS and microvesicular steatosis (MiS) were determined, and inflammation and fibrosis were scored as 0 to 4. MaS correlated positively with MiS, and inflammation correlated positively with fibrosis, whereas patient weight showed a significant correlation with liver weight and body mass index. No patient characteristic showed a significant correlation with histological findings. Subjects 55 years and older showed no increase in pathological findings compared with those younger than 55 years. When any site was compared with the average of the other sites, Spearman's rho correlation ranged from 0.89 to 0.95 for MaS, 0.89 to 0.94 for MiS, 0.54 to 0.80 for inflammation, and 0.66 to 0.80 for fibrosis. Two biopsies explained 95% of variations for MaS and MiS and 85% for inflammation and fibrosis. There was no significant difference between findings in the right and left lobes of livers. These findings suggest that no single site best predicts pathological findings, and there is little variation among sites. In borderline cases of MaS, significant pathological characteristics may be found in additional biopsies. Therefore, we recommend two biopsy sites to evaluate donor livers with suspicious clinical histories.