Swedish Interactive Threshold Algorithm (SITA) Faster is the most recent and fastest testing algorithm for the evaluation of Humphrey visual fields (VF). However, existing evidence suggests that ...there are some differences in global measures of VF loss in eyes transitioning from SITA Standard to the newer SITA Faster. These differences may be relevant, especially in glaucoma, where VF changes over time influence clinical decisions around treatment. Furthermore, characterization of differences in localizable VF loss patterns between algorithms, rather than global summary measures, can be important for clinician interpretation when transitioning testing strategies. In this study, we determined the effect of transitioning from SITA Standard to SITA Faster on VF loss patterns in glaucomatous eyes undergoing longitudinal VF testing in a real-world clinical setting. Archetypal analysis was used to derive composition weights of 16 clinically relevant VF patterns (i.e., archetypes (AT)) from patient VFs. We found switching from SITA Standard to SITA Faster was associated with less preservation of VF loss (i.e., abnormal AT 2-4, 6-9, 11, 13, 14) relative to successive SITA Standard exams (P value < 0.01) and was associated with relatively greater preservation of AT 1, the normal VF (P value < 0.01). Eyes that transition from SITA Standard to SITA Faster in a real-world clinical setting have an increased likelihood of preserving patterns reflecting a normal VF and lower tendency to preserve patterns reflecting abnormal VF as compared to consecutive SITA Standard exams in the same eye.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of ...early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.
ABSTRACT Randomization-based inference using the Fisher randomization test allows for the computation of Fisher-exact P-values, making it an attractive option for the analysis of small, randomized ...experiments with non-normal outcomes. Two common test statistics used to perform Fisher randomization tests are the difference-in-means between the treatment and control groups and the covariate-adjusted version of the difference-in-means using analysis of covariance. Modern computing allows for fast computation of the Fisher-exact P-value, but confidence intervals have typically been obtained by inverting the Fisher randomization test over a range of possible effect sizes. The test inversion procedure is computationally expensive, limiting the usage of randomization-based inference in applied work. A recent paper by Zhu and Liu developed a closed form expression for the randomization-based confidence interval using the difference-in-means statistic. We develop an important extension of Zhu and Liu to obtain a closed form expression for the randomization-based covariate-adjusted confidence interval and give practitioners a sufficiency condition that can be checked using observed data and that guarantees that these confidence intervals have correct coverage. Simulations show that our procedure generates randomization-based covariate-adjusted confidence intervals that are robust to non-normality and that can be calculated in nearly the same time as it takes to calculate the Fisher-exact P-value, thus removing the computational barrier to performing randomization-based inference when adjusting for covariates. We also demonstrate our method on a re-analysis of phase I clinical trial data.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, OILJ, SBCE, SBMB, UPUK
With the advent of precision oncology, there is an urgent need to develop improved methods for rapidly detecting responses to targeted therapies. Here, we have developed an ultrasensitive measure of ...cell-free tumor load using targeted and whole-genome sequencing approaches to assess responses to tyrosine kinase inhibitors in patients with advanced lung cancer. Analyses of 28 patients treated with anti-EGFR or HER2 therapies revealed a bimodal distribution of cell-free circulating tumor DNA (ctDNA) after therapy initiation, with molecular responders having nearly complete elimination of ctDNA (>98%). Molecular nonresponders displayed limited changes in ctDNA levels posttreatment and experienced significantly shorter progression-free survival (median 1.6 vs. 13.7 months,
< 0.0001; HR = 66.6; 95% confidence interval, 13.0-341.7), which was detected on average 4 weeks earlier than CT imaging. ctDNA analyses of patients with radiographic stable or nonmeasurable disease improved prediction of clinical outcome compared with CT imaging. These analyses provide a rapid approach for evaluating therapeutic response to targeted therapies and have important implications for the management of patients with cancer and the development of new therapeutics.
Cell-free tumor load provides a novel approach for evaluating longitudinal changes in ctDNA during systemic treatment with tyrosine kinase inhibitors and serves an unmet clinical need for real-time, noninvasive detection of tumor response to targeted therapies before radiographic assessment.
.
Using GitHub Classroom To Teach Statistics Fiksel, Jacob; Jager, Leah R.; Hardin, Johanna S. ...
Journal of statistics education,
01/2019, Volume:
27, Issue:
2
Journal Article
Peer reviewed
Open access
Git and GitHub are common tools for keeping track of multiple versions of data analytic content, which allow for more than one person to simultaneously work on a project. GitHub Classroom aims to ...provide a way for students to work on and submit their assignments via Git and GitHub, giving teachers an opportunity to facilitate the integration of these version control tools into their undergraduate statistics courses. In the Fall 2017 semester, we implemented GitHub Classroom in two educational settings-an introductory computational statistics lab and a more advanced computational statistics course. We found many educational benefits of implementing GitHub Classroom, such as easily providing coding feedback during assignments and making students more confident in their ability to collaborate and use version control tools for future data science work. To encourage and ease the transition into using GitHub Classroom, we provide free and publicly available resources-both for students to begin using Git/GitHub and for teachers to use GitHub Classroom for their own courses.
Compositional data are common in many fields, both as outcomes and predictor variables. The inventory of models for the case when both the outcome and predictor variables are compositional is ...limited, and the existing models are often difficult to interpret in the compositional space, due to their use of complex log‐ratio transformations. We develop a transformation‐free linear regression model where the expected value of the compositional outcome is expressed as a single Markov transition from the compositional predictor. Our approach is based on estimating equations thereby not requiring complete specification of data likelihood and is robust to different data‐generating mechanisms. Our model is simple to interpret, allows for 0s and 1s in both the compositional outcome and covariates, and subsumes several interesting subcases of interest. We also develop permutation tests for linear independence and equality of effect sizes of two components of the predictor. Finally, we show that despite its simplicity, our model accurately captures the relationship between compositional data using two datasets from education and medical research.
Full text
Available for:
BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Quantification learning is the task of prevalence estimation for a test population using predictions from a classifier trained on a different population. Quantification methods assume that the ...sensitivities and specificities of the classifier are either perfect or transportable from the training to the test population. These assumptions are inappropriate in the presence of dataset shift, when the misclassification rates in the training population are not representative of those for the test population. Quantification under dataset shift has been addressed only for single-class (categorical) predictions and assuming perfect knowledge of the true labels on a small subset of the test population. We propose generalized Bayes quantification learning (GBQL) that uses the entire compositional predictions from probabilistic classifiers and allows for uncertainty in true class labels for the limited labeled test data. Instead of positing a full model, we use a model-free Bayesian estimating equation approach to compositional data using Kullback-Leibler loss-functions based only on a first-moment assumption. The idea will be useful in Bayesian compositional data analysis in general as it is robust to different generating mechanisms for compositional data and allows 0's and 1's in the compositional outputs thereby including categorical outputs as a special case. We show how our method yields existing quantification approaches as special cases. Extension to an ensemble GBQL that uses predictions from multiple classifiers yielding inference robust to inclusion of a poor classifier is discussed. We outline a fast and efficient Gibbs sampler using a rounding and coarsening approximation to the loss functions. We establish posterior consistency, asymptotic normality and valid coverage of interval estimates from GBQL, which to our knowledge are the first theoretical results for a quantification approach in the presence of local labeled data. We also establish finite sample posterior concentration rate. Empirical performance of GBQL is demonstrated through simulations and analysis of real data with evident dataset shift.
Supplementary materials
for this article are available online.
Full text
Available for:
BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Cell-free DNA in the blood provides a non-invasive diagnostic avenue for patients with cancer
. However, characteristics of the origins and molecular features of cell-free DNA are poorly understood. ...Here we developed an approach to evaluate fragmentation patterns of cell-free DNA across the genome, and found that profiles of healthy individuals reflected nucleosomal patterns of white blood cells, whereas patients with cancer had altered fragmentation profiles. We used this method to analyse the fragmentation profiles of 236 patients with breast, colorectal, lung, ovarian, pancreatic, gastric or bile duct cancer and 245 healthy individuals. A machine learning model that incorporated genome-wide fragmentation features had sensitivities of detection ranging from 57% to more than 99% among the seven cancer types at 98% specificity, with an overall area under the curve value of 0.94. Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases. Combining our approach with mutation-based cell-free DNA analyses detected 91% of patients with cancer. The results of these analyses highlight important properties of cell-free DNA and provide a proof-of-principle approach for the screening, early detection and monitoring of human cancer.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Risk factors for progression of coronavirus disease 2019 (COVID-19) to severe disease or death are underexplored in U.S. cohorts.
To determine the factors on hospital admission that are predictive of ...severe disease or death from COVID-19.
Retrospective cohort analysis.
Five hospitals in the Maryland and Washington, DC, area.
832 consecutive COVID-19 admissions from 4 March to 24 April 2020, with follow-up through 27 June 2020.
Patient trajectories and outcomes, categorized by using the World Health Organization COVID-19 disease severity scale. Primary outcomes were death and a composite of severe disease or death.
Median patient age was 64 years (range, 1 to 108 years); 47% were women, 40% were Black, 16% were Latinx, and 21% were nursing home residents. Among all patients, 131 (16%) died and 694 (83%) were discharged (523 63% had mild to moderate disease and 171 20% had severe disease). Of deaths, 66 (50%) were nursing home residents. Of 787 patients admitted with mild to moderate disease, 302 (38%) progressed to severe disease or death: 181 (60%) by day 2 and 238 (79%) by day 4. Patients had markedly different probabilities of disease progression on the basis of age, nursing home residence, comorbid conditions, obesity, respiratory symptoms, respiratory rate, fever, absolute lymphocyte count, hypoalbuminemia, troponin level, and C-reactive protein level and the interactions among these factors. Using only factors present on admission, a model to predict in-hospital disease progression had an area under the curve of 0.85, 0.79, and 0.79 at days 2, 4, and 7, respectively.
The study was done in a single health care system.
A combination of demographic and clinical variables is strongly associated with severe COVID-19 disease or death and their early onset. The COVID-19 Inpatient Risk Calculator (CIRC), using factors present on admission, can inform clinical and resource allocation decisions.
Hopkins inHealth and COVID-19 Administrative Supplement for the HHS Region 3 Treatment Center from the Office of the Assistant Secretary for Preparedness and Response.
PDF
